Study Findings

Have you ever wondered how your participation impacts others? Below is a list of publications that have been made possible thanks to volunteers like you.
Search findings by publication, study, or institution
Arizona State University
  • The moderating impact of neighborhood walkability on mHealth interventions to increase moderate to vigorous physical activity for insufficiently active adults in a randomized trial.
    The international journal of behavioral nutrition and physical activity (2023)
    McEntee ML, Hurley JC, Phillips CB, Hooker SP, Todd M, Frank LD, Adams MA. The moderating impact of neighborhood walkability on mHealth interventions to increase moderate to vigorous physical activity for insufficiently active adults in a randomized trial. Int J Behav Nutr Phys Act. 2023 Aug 15; 20(1):97.
    Abstract: Ecological models suggest that interventions targeting specific behaviors are most effective when supported by the environment. This study prospectively examined the interactions between neighborhood walkability and an mHealth intervention in a large-scale, adequately powered trial to increase moderate-to-vigorous physical activity (MVPA). Healthy, insufficiently active adults (N = 512) were recruited purposefully from census block groups ranked on walkability (high/low) and socioeconomic status (SES, high/low). Participants were block-randomized in groups of four to WalkIT Arizona, a 12-month, 2 × 2 factorial trial evaluating adaptive versus static goal setting and immediate versus delayed financial reinforcement delivered via text messages. Participants wore ActiGraph GT9X accelerometers daily for one year. After recruitment, a walkability index was calculated uniquely for every participant using a 500-m street network buffer. Generalized linear mixed-effects hurdle models tested for interactions between walkability, intervention components, and phase (baseline vs. intervention) on: (1) likelihood of any (versus no) MVPA and (2) daily MVPA minutes, after adjusting for accelerometer wear time, neighborhood SES, and calendar month. Neighborhood walkability was probed at 5th, 25th, 50th, 75th, and 95th percentiles to explore the full range of effects. Adaptive goal setting was more effective in increasing the likelihood of any MVPA and daily MVPA minutes, especially in lower walkable neighborhoods, while the magnitude of intervention effect declined as walkability increased. Immediate reinforcement showed a greater increase in any and daily MVPA compared to delayed reinforcement, especially relatively greater in higher walkable neighborhoods. Results partially supported the synergy hypotheses between neighborhood walkability and PA interventions and suggest the potential of tailoring interventions to individuals' neighborhood characteristics. Preregistered at clinicaltrials.gov (NCT02717663).

    Abstract Summary: Scientists did a study to see if a neighborhood that's easy to walk in and a phone app could help people exercise more. They looked at 512 adults who didn't move around much and lived in different kinds of neighborhoods. Some neighborhoods were easy to walk in, and some were not. They also looked at whether the neighborhoods were rich or not so rich. The study lasted a year, and people got text messages with goals for walking. Some got goals that changed, and some got the same goals. They also got rewards—some right away and some later. The researchers found that changing goals helped people in less walkable places exercise more. Getting rewards right away helped too, especially in places that were already good for walking. This study shows that making exercise plans that fit where people live can help them be more active.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Adaptive Goals and Reinforcement Timing to Increase Physical Activity in Adults: A Factorial Randomized Trial.
    American journal of preventive medicine (2022)
    Adams MA, Todd M, Angadi SS, Hurley JC, Stecher C, Berardi V, Phillips CB, McEntee ML, Hovell MF, Hooker SP. Adaptive Goals and Reinforcement Timing to Increase Physical Activity in Adults: A Factorial Randomized Trial. Am J Prev Med. 2022 Feb; 62(2):e57-e68.
    Abstract: Potent lifestyle interventions to increase moderate-to-vigorous physical activity are urgently needed for population-level chronic disease prevention. This trial tested the independent and joint effects of a mobile health system automating adaptive goal setting and immediate financial reinforcement for increasing daily walking among insufficiently active adults. Participants were randomized into a 2 (adaptive versus static goal setting) X 2 (immediate versus delayed financial incentive timing) condition factorial trial to increase walking. Participants (N=512 adults) were recruited between 2016 and 2018 and were 64.5% female, aged 18-60 years, 18.8% Hispanic, 6.1% African American, and 83% White. Principles of reinforcement and behavioral economics directed intervention design. Participants wore accelerometers daily (133,876 day-level observations) that remotely measured moderate-to-vigorous physical activity bout minutes of ≥3 minutes/day for 1 year. Primary outcomes were between-condition differences in (1) engaging ≥1 bout of moderate-to-vigorous physical activity on each day and (2) on days with ≥1 bout, daily total moderate-to-vigorous physical activity minutes. Mixed-effects hurdle models tested treatment group X phase (time) interactions using an intent-to-treat approach in 2021. Engaging in any ambulatory moderate-to-vigorous physical activity was greater for Adaptive than for Static Goal groups (OR=2.34, 95% CI=2.10, 2.60 vs OR=1.66, 95% CI=1.50, 1.84; p<0.001) and for Immediate than for Static Reinforcement groups (OR=2.16 95% CI=1.94, 2.40 vs OR=1.77, 95% CI=1.59, 1.97; p<0.01). The Immediate Reinforcement group increased by 16.54 moderate-to-vigorous physical activity minutes/day, whereas the Delayed Reinforcement group increased by 9.91 minutes/day (p<0.001). The combined Adaptive Goals + Immediate Reinforcement group increased by 16.52 moderate-to-vigorous physical activity minutes/day, significantly more than that of either Delayed Reinforcement group. This study offers automated and scalable-behavior change strategies for increasing walking among adults most at-risk for chronic diseases attributed to sedentary lifestyles. This study is registered at www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT02717663).

    Abstract Summary: Scientists did a study to help adults walk more because walking a lot can keep people from getting sick with long-term diseases. They used a phone app to set walking goals and gave people money right away or later when they walked enough. They had 512 grown-ups wear step-counting gadgets for a year to see how much they walked. They found that changing the walking goals to be harder or easier helped people walk more, and giving money right away helped even more. When they did both—changing goals and giving money right away—people walked the most. This study shows that using phone apps and rewards can make people walk more, which is good for their health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of Goal Type and Reinforcement Type on Self-Reported Domain-Specific Walking Among Inactive Adults: 2×2 Factorial Randomized Controlled Trial.
    JMIR formative research (2020)
    McEntee ML, Cantley A, Foreman E, Berardi V, Phillips CB, Hurley JC, Hovell MF, Hooker S, Adams MA. Effects of Goal Type and Reinforcement Type on Self-Reported Domain-Specific Walking Among Inactive Adults: 2×2 Factorial Randomized Controlled Trial. JMIR Form Res. 2020 Dec 4; 4(12):e19863.
    Abstract: WalkIT Arizona was a 2×2 factorial trial examining the effects of goal type (adaptive versus static) and reinforcement type (immediate versus delayed) to increase moderate to vigorous physical activity (MVPA) among insufficiently active adults. The 12-month intervention combined mobile health (mHealth) technology with behavioral strategies to test scalable population-health approaches to increasing MVPA. Self-reported physical activity provided domain-specific information to help contextualize the intervention effects. The aim of this study was to report on the secondary outcomes of self-reported walking for transportation and leisure over the course of the 12-month WalkIT intervention. A total of 512 participants aged 19 to 60 years (n=330 [64.5%] women; n=425 [83%] Caucasian/white, n=96 [18.8%] Hispanic/Latinx) were randomized into interventions based on type of goals and reinforcements. The International Physical Activity Questionnaire-long form assessed walking for transportation and leisure at baseline, and at 6 months and 12 months of the intervention. Negative binomial hurdle models were used to examine the effects of goal and reinforcement type on (1) odds of reporting any (versus no) walking/week and (2) total reported minutes of walking/week, adjusted for neighborhood walkability and socioeconomic status. Separate analyses were conducted for transportation and leisure walking, using complete cases and multiple imputation. All intervention groups reported increased walking at 12 months relative to baseline. Effects of the intervention differed by domain: a significant three-way goal by reinforcement by time interaction was observed for total minutes of leisure walking/week, whereas time was the only significant factor that contributed to transportation walking. A sensitivity analysis indicated minimal differences between complete case analysis and multiple imputation. This study is the first to report differential effects of adaptive versus static goals for self-reported walking by domain. Results support the premise that individual-level PA interventions are domain- and context-specific and may be helpful in guiding further intervention refinement. Preregistered at clinicaltrials.gov: (NCT02717663) https://clinicaltrials.gov/ct2/show/NCT02717663. RR2-10.1016/j.cct.2019.05.001.

    Abstract Summary: Scientists did a study called WalkIT Arizona to see if different types of goals and rewards would help people who don't move a lot to be more active. They used technology and special plans to see if they could get more people to walk as part of their daily life or for fun. They had 512 grown-ups, mostly women and white people, try this out for a year. They checked how much these people walked for getting places or just for fun at the start, in the middle, and at the end of the study. They found that everyone walked more by the end of the study. But the way people walked for fun changed more than the way they walked to get places. This shows that when we try to get people to walk more, we need to think about why they are walking. This can help us make better plans to get more people moving. The study was registered and anyone can look it up online to learn more.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Boston University
  • Amyloid PET across the cognitive spectrum in former professional and college American football players: findings from the DIAGNOSE CTE Research Project.
    Alzheimer's research & therapy (2023)
    Stern RA, Trujillo-Rodriguez D, Tripodis Y, Pulukuri SV, Alosco ML, Adler CH, Balcer LJ, Bernick C, Baucom Z, Marek KL, McClean MD, Johnson KA, McKee AC, Stein TD, Mez J, Palmisano JN, Cummings JL, Shenton ME, Reiman EM, DIAGNOSE CTE Research Project Inve. Amyloid PET across the cognitive spectrum in former professional and college American football players: findings from the DIAGNOSE CTE Research Project. Alzheimers Res Ther. 2023 Oct 5; 15(1):166.
    Abstract: Exposure to repetitive head impacts (RHI) in American football players can lead to cognitive impairment and dementia due to neurodegenerative disease, particularly chronic traumatic encephalopathy (CTE). The pathognomonic lesion of CTE consists of perivascular aggregates of hyper-phosphorylated tau in neurons at the depths of cortical sulci. However, it is unclear whether exposure to RHI accelerates amyloid-β (Aβ) plaque formation and increases the risk for Alzheimer's disease (AD). Although the Aβ neuritic plaques characteristic of AD are observed in a minority of later-stage CTE cases, diffuse plaques are more common. This study examined whether former professional and college American football players, including those with cognitive impairment and dementia, have elevated neuritic Aβ plaque density, as measured by florbetapir PET. Regardless of cognitive and functional status, elevated levels of florbetapir uptake were not expected. We examined 237 men ages 45-74, including 119 former professional (PRO) and 60 former college (COL) football players, with and without cognitive impairment and dementia, and 58 same-age men without a history of contact sports or TBI (unexposed; UE) and who denied cognitive or behavioral symptoms at telephone screening. Former players were categorized into four diagnostic groups: normal cognition, subjective memory impairment, mild cognitive impairment, and dementia. Positive florbetapir PET was defined by cortical-cerebellar average SUVR of ≥ 1.10. Multivariable linear regression and analysis of covariance (ANCOVA) compared florbetapir average SUVR across diagnostic and exposure groups. Multivariable logistic regression compared florbetapir positivity. Race, education, age, and APOE4 were covariates. There were no diagnostic group differences either in florbetapir average SUVR or the proportion of elevated florbetapir uptake. Average SUVR means also did not differ between exposure groups: PRO-COL (p = 0.94, 95% C.I. = [- 0.033, 0.025]), PRO-UE (p = 0.40, 95% C.I. = [- 0.010, 0.029]), COL-UE (p = 0.36, 95% CI = [0.0004, 0.039]). Florbetapir was not significantly associated with years of football exposure, cognition, or daily functioning. Cognitive impairment in former American football players is not associated with PET imaging of neuritic Aβ plaque deposition. These findings are inconsistent with a neuropathological diagnosis of AD in individuals with substantial RHI exposure and have both clinical and medico-legal implications. NCT02798185.

    Abstract Summary: Scientists wanted to see if playing American football, which can cause lots of hits to the head, might make players more likely to get a brain problem called Alzheimer's disease when they get older. Alzheimer's disease can make it hard for people to remember things and take care of themselves. The researchers used a special brain scan to look for signs of Alzheimer's in former professional and college football players, some of whom were having memory problems, and compared them to men who never played contact sports. They checked 237 men between 45 and 74 years old. The brain scans did not show more signs of Alzheimer's in the football players, even in those who played a lot or had memory issues. This means that the memory problems in these football players might not be caused by Alzheimer's. This is important for doctors to know when they are trying to help players who have memory problems after many hits to the head. It also matters for legal reasons, like when players need to prove their health problems are because of football.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Initial assessment of the feasibility and efficacy of a scalable digital CBT for generalized anxiety and associated health behaviors in a cardiovascular disease population.
    Contemporary clinical trials (2023)
    Parsons EM, Hiserodt M, Otto MW. Initial assessment of the feasibility and efficacy of a scalable digital CBT for generalized anxiety and associated health behaviors in a cardiovascular disease population. Contemp Clin Trials. 2023 Jan; 124:107018.
    Abstract: Generalized anxiety disorder (GAD) is a significant yet modifiable risk factor for worse cardiovascular disease (CVD) outcomes. The treatment of GAD in an accessible manner represents an unmet need in CVD, given that patients with CVD experience numerous barriers to in-person treatment engagement. This paper presents the rationale and design for an investigation of a strategy to enhance care for patients with CVD by introducing a scalable, affordable, and system-friendly digital intervention that targets a prominent modifiable risk factor (generalized anxiety and associated worry) for negative health behaviors in CVD. In the context of a randomized clinical trial design, we describe an experimental medicine approach for evaluating the degree to which a digital cognitive behavior therapy (dCBT), relative to a waitlist control group, engages anxiety and worry outcomes in a sample of 90 adults who have experienced an acute CVD event and who have comorbid GAD symptoms. We also investigate the degree to which dCBT leads to greater changes in GAD symptoms compared to the control condition and whether reductions in these symptoms are associated with corresponding reductions in cardiac anxiety and cardiac health behaviors (including smoking, physical activity, heart-healthy diet, and medication adherence). We propose that by targeting GAD symptoms in CVD in a way that does not tax ongoing medical care provision, we have the potential to improve the uptake of effective care and address both GAD and associated health behaviors.

    Abstract Summary: Doctors found that people with a lot of worry and anxiety, especially about their health, might have more heart problems. They think helping these people worry less could make their hearts healthier. So, they're trying out a new way to help using computers and the internet, which is easier for people to use than going to the doctor's office. They're testing this idea with 90 adults who have heart problems and also worry a lot. These adults will try a special computer program that teaches them how to worry less. The doctors will see if the people who use the program start to worry less and if that helps them do better things for their hearts, like eating healthy, exercising, and taking their medicine. If it works, this could be a new way to help lots of people with heart problems and anxiety feel better without making their regular doctor visits harder.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Developing methods to detect and diagnose chronic traumatic encephalopathy during life: rationale, design, and methodology for the DIAGNOSE CTE Research Project.
    Alzheimer's research & therapy (2021)
    Alosco ML, Mariani ML, Adler CH, Balcer LJ, Bernick C, Au R, Banks SJ, Barr WB, Bouix S, Cantu RC, Coleman MJ, Dodick DW, Farrer LA, Geda YE, Katz DI, Koerte IK, Kowall NW, Lin AP, Marcus DS, Marek KL, McClean MD, McKee AC, Mez J, Palmisano JN, Peskind ER. Developing methods to detect and diagnose chronic traumatic encephalopathy during life: rationale, design, and methodology for the DIAGNOSE CTE Research Project. Alzheimers Res Ther. 2021 Aug 12; 13(1):136.
    Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that has been neuropathologically diagnosed in brain donors exposed to repetitive head impacts, including boxers and American football, soccer, ice hockey, and rugby players. CTE cannot yet be diagnosed during life. In December 2015, the National Institute of Neurological Disorders and Stroke awarded a seven-year grant (U01NS093334) to fund the "Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project." The objectives of this multicenter project are to: develop in vivo fluid and neuroimaging biomarkers for CTE; characterize its clinical presentation; refine and validate clinical research diagnostic criteria (i.e., traumatic encephalopathy syndrome [TES]); examine repetitive head impact exposure, genetic, and other risk factors; and provide shared resources of anonymized data and biological samples to the research community. In this paper, we provide a detailed overview of the rationale, design, and methods for the DIAGNOSE CTE Research Project. The targeted sample and sample size was 240 male participants, ages 45-74, including 120 former professional football players, 60 former collegiate football players, and 60 asymptomatic participants without a history of head trauma or participation in organized contact sports. Participants were evaluated at one of four U.S. sites and underwent the following baseline procedures: neurological and neuropsychological examinations; tau and amyloid positron emission tomography; magnetic resonance imaging and spectroscopy; lumbar puncture; blood and saliva collection; and standardized self-report measures of neuropsychiatric, cognitive, and daily functioning. Study partners completed similar informant-report measures. Follow-up evaluations were intended to be in-person and at 3 years post-baseline. Multidisciplinary diagnostic consensus conferences are held, and the reliability and validity of TES diagnostic criteria are examined. Participant enrollment and all baseline evaluations were completed in February 2020. Three-year follow-up evaluations began in October 2019. However, in-person evaluation ceased with the COVID-19 pandemic, and resumed as remote, 4-year follow-up evaluations (including telephone-, online-, and videoconference-based cognitive, neuropsychiatric, and neurologic examinations, as well as in-home blood draw) in February 2021. Findings from the DIAGNOSE CTE Research Project should facilitate detection and diagnosis of CTE during life, and thereby accelerate research on risk factors, mechanisms, epidemiology, treatment, and prevention of CTE. NCT02798185.

    Abstract Summary: Scientists are studying a brain disease called Chronic Traumatic Encephalopathy (CTE) that can happen to people who have had many head injuries, like football players or boxers. Right now, doctors can't tell if someone has CTE until after they've passed away. A big research project called DIAGNOSE CTE is trying to find ways to spot CTE in people while they are still alive. They are looking at 240 men, some who played football and some who didn't, to see if they can find signs of CTE using special brain scans, tests, and collecting things like blood and saliva. They started checking these men in 2015 and will keep doing it for a few years. The goal is to learn how to tell if someone has CTE early, which could help find ways to treat or prevent the disease in the future.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Using Health Information Technology to Engage African American Women on Nutrition and Supplement Use During the Preconception Period.
    Frontiers in endocrinology (2020)
    Gardiner P, Bickmore T, Yinusa-Nyahkoon L, Reichert M, Julce C, Sidduri N, Martin-Howard J, Woodhams E, Aryan J, Zhang Z, Fernandez J, Loafman M, Srinivasan J, Cabral H, Jack BW. Using Health Information Technology to Engage African American Women on Nutrition and Supplement Use During the Preconception Period. Front Endocrinol (Lausanne). 2020; 11:571705.
    Abstract: Healthy nutrition and appropriate supplementation during preconception have important implications for the health of the mother and newborn. The best way to deliver preconception care to address health risks related to nutrition is unknown. We conducted a secondary analysis of data from a randomized controlled trial designed to study the impact of conversational agent technology in 13 domains of preconception care among 528 non-pregnant African American and Black women. This analysis is restricted to those 480 women who reported at least one of the ten risks related to nutrition and dietary supplement use. An online conversational agent, called "Gabby", assesses health risks and delivers 12 months of tailored dialogue for over 100 preconception health risks, including ten nutrition and supplement risks, using behavioral change techniques like shared decision making and motivational interviewing. The control group received a letter listing their preconception risks and encouraging them to talk to a health care provider. After 6 months, women using Gabby (a) reported progressing forward on the stage of change scale for, on average, 52.9% (SD, 35.1%) of nutrition and supplement risks compared to 42.9% (SD, 35.4) in the control group (IRR 1.22, 95% CI 1.03-1.45, P = 0.019); and (b) reported achieving the action and maintenance stage of change for, on average, 52.8% (SD 37.1) of the nutrition and supplement risks compared to 42.8% (SD, 37.9) in the control group (IRR 1.26, 96% CI 1.08-1.48, P = 0.004). For subjects beginning the study at the contemplation stage of change, intervention subjects reported progressing forward on the stage of change scale for 75.0% (SD, 36.3%) of their health risks compared to 52.1% (SD, 47.1%) in the control group (P = 0.006). The scalability of Gabby has the potential to improve women's nutritional health as an adjunct to clinical care or at the population health level. Further studies are needed to determine if improving nutrition and supplement risks can impact clinical outcomes including optimization of weight. ClinicalTrials.gov, identifier NCT01827215.

    Abstract Summary: Scientists did a study to see if a computer program named "Gabby" could help women eat better and take the right vitamins before they get pregnant. They looked at 480 women who had some eating or vitamin habits that could be better. Half of the women talked to Gabby for a year, and the other half got a letter telling them to talk to a doctor. After 6 months, the women who used Gabby were doing better at eating right and taking vitamins than the women who just got a letter. The study shows that Gabby might help lots of women be healthier, especially before having a baby. More research is needed to see if this really helps women and babies stay healthy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Improving the health of young African American women in the preconception period using health information technology: a randomised controlled trial.
    The Lancet. Digital health (2020)
    Jack BW, Bickmore T, Yinusa-Nyahkoon L, Reichert M, Julce C, Sidduri N, Martin-Howard J, Zhang Z, Woodhams E, Fernandez J, Loafman M, Cabral HJ. Improving the health of young African American women in the preconception period using health information technology: a randomised controlled trial. Lancet Digit Health. 2020 Sep; 2(9):e475-e485.
    Abstract: Preconception care focuses on improving women's health before pregnancy as a means to improve their health and future pregnancy outcomes. How to effectively deliver such care is unknown. The aim of this research was to assess the impact of an embodied conversational agent system on preconception risks among African American and Black women. We did an open-label, randomised controlled trial of women aged 18-34 years, self-identified as African American or Black, or both, and not pregnant, recruited from 35 states in the USA. Sealed allocation envelopes (in permuted blocks of six and eight, prepared using a random number generator) were opened after enrolment. Intervention participants received an online conversational agent called Gabby that assessed 102 preconception risks and delivered 12 months of tailored dialogue using synthesised speech, non-verbal behaviour, visual aids, and health behaviour change techniques such as motivational interviewing. The control group received a letter listing their preconception risks and encouraging them to talk with a clinician. The primary outcome was the proportion of identified risks at the action or maintenance stage of change at months 6 and 12. The study is registered with ClinicalTrials.gov, NCT01827215. From March 11, 2014, through July 8, 2018, 528 women recruited from 35 states and 242 cities across the USA received the Gabby intervention (n=262) or were assigned to the control group (n=266). Participants identified a mean of 21 preconception risks per woman (SD 9·9). In the intention-to-treat analysis, at 6 months, intervention women reported reaching the action or maintenance stage of change for 50·0% (SD 28·9) of those preconception risks identified compared with 42·7% (28·3) in the control group (incidence rate ratio 1·16, 95% CI 1·07-1·26; p=0·0004). This result persisted at 12 months. The Gabby system has the potential to improve women's preconception health. Further research is needed to determine if improving preconception risks impacts outcomes such as preterm delivery. National Institute for Minority Health and Health Disparities.

    Abstract Summary: Scientists wanted to see if a special computer program could help African American and Black women get healthier before they have babies, which can make them and their future babies healthier. They tested a program called Gabby that talks to women about their health and gives advice for a whole year. They compared it to just giving women a letter about their health. They found that the women who talked to Gabby were better at taking care of their health risks after 6 months and even after 12 months. This means Gabby could help lots of women get healthier before they have babies, but the scientists say they need to do more research to be sure.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Case Western Reserve University
  • The Pharmacogenomics of Bipolar Disorder study (PGBD): identification of genes for lithium response in a prospective sample.
    BMC psychiatry (2016)
    Oedegaard KJ, Alda M, Anand A, Andreassen OA, Balaraman Y, Berrettini WH, Bhattacharjee A, Brennand KJ, Burdick KE, Calabrese JR, Calkin CV, Claasen A, Coryell WH, Craig D, DeModena A, Frye M, Gage FH, Gao K, Garnham J, Gershon E, Jakobsen P, Leckband SG,. The Pharmacogenomics of Bipolar Disorder study (PGBD): identification of genes for lithium response in a prospective sample. BMC Psychiatry. 2016 May 5; 16:129.
    Abstract: Bipolar disorder is a serious and common psychiatric disorder characterized by manic and depressive mood switches and a relapsing and remitting course. The cornerstone of clinical management is stabilization and prophylaxis using mood-stabilizing medications to reduce both manic and depressive symptoms. Lithium remains the gold standard of treatment with the strongest data for both efficacy and suicide prevention. However, many patients do not respond to this medication, and clinically there is a great need for tools to aid the clinician in selecting the correct treatment. Large genome wide association studies (GWAS) investigating retrospectively the effect of lithium response are in the pipeline; however, few large prospective studies on genetic predictors to of lithium response have yet been conducted. The purpose of this project is to identify genes that are associated with lithium response in a large prospective cohort of bipolar patients and to better understand the mechanism of action of lithium and the variation in the genome that influences clinical response. This study is an 11-site prospective non-randomized open trial of lithium designed to ascertain a cohort of 700 subjects with bipolar I disorder who experience protocol-defined relapse prevention as a result of treatment with lithium monotherapy. All patients will be diagnosed using the Diagnostic Interview for Genetic Studies (DIGS) and will then enter a 2-year follow-up period on lithium monotherapy if and when they exhibit a score of 1 (normal, not ill), 2 (minimally ill) or 3 (mildly ill) on the Clinical Global Impressions of Severity Scale for Bipolar Disorder (CGI-S-BP Overall Bipolar Illness) for 4 of the 5 preceding weeks. Lithium will be titrated as clinically appropriate, not to exceed serum levels of 1.2 mEq/L. The sample will be evaluated longitudinally using a wide range of clinical scales, cognitive assessments and laboratory tests. On relapse, patients will be discontinued or crossed-over to treatment with valproic acid (VPA) or treatment as usual (TAU). Relapse is defined as a DSM-IV manic, major depressive or mixed episode or if the treating physician decides a change in medication is clinically necessary. The sample will be genotyped for GWAS. The outcome for lithium response will be analyzed as a time to event, where the event is defined as clinical relapse, using a Cox Proportional Hazards model. Positive single nucleotide polymorphisms (SNPs) from past genetic retrospective studies of lithium response, the Consortium on Lithium Genetics (ConLiGen), will be tested in this prospective study sample; a meta-analysis of these samples will then be performed. Finally, neurons will be derived from pluripotent stem cells from lithium responders and non-responders and tested in vivo for response to lithium by gene expression studies. SNPs in genes identified in these cellular studies will also be tested for association to response. Lithium is an extraordinarily important therapeutic drug in the clinical management of patients suffering from bipolar disorder. However, a significant proportion of patients, 30-40 %, fail to respond, and there is currently no method to identify the good lithium responders before initiation of treatment. Converging evidence suggests that genetic factors play a strong role in the variation of response to lithium, but only a few genes have been tested and the samples have largely been retrospective or quite small. The current study will collect an entirely unique sample of 700 patients with bipolar disorder to be stabilized on lithium monotherapy and followed for up to 2 years. This study will produce useful information to improve the understanding of the mechanism of action of lithium and will add to the development of a method to predict individual response to lithium, thereby accelerating recovery and reducing suffering and cost. ClinicalTrials.gov Identifier: NCT01272531 Registered: January 6, 2011.

    Abstract Summary: Doctors want to help people with bipolar disorder, a condition where people feel very high and very low in mood. They use a medicine called lithium to make the mood stable, but it doesn't work for everyone. The study is trying to find out why some people get better with lithium and others don't. They are looking at the genes of 700 people with bipolar disorder who are taking lithium to see if their genes can tell us who will get better. They will watch these people for 2 years and also do some tests on cells in the lab to learn more about how lithium works. This research might help doctors know in advance if lithium will work for a person, which could help people feel better faster and save money.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Children's National Hospital
  • Cardiometabolic Risk and Body Composition in Youth With Down Syndrome.
    Pediatrics (2019)
    Magge SN, Zemel BS, Pipan ME, Gidding SS, Kelly A. Cardiometabolic Risk and Body Composition in Youth With Down Syndrome. Pediatrics. 2019 Aug; 144(2):.
    Abstract: Whether BMI captures adiposity and cardiometabolic risk in Down syndrome (DS), a condition associated with obesity, short stature, and altered body proportions, is not known. We compared cardiometabolic risk measures in youth with DS and typically developing matched controls. Youth with ( = 150) and without ( = 103) DS of comparable age (10-20 years), sex, race, ethnicity, and BMI percentile underwent whole-body dual-energy X-ray absorptiometry, fasting glucose, insulin, lipids, lipoprotein particles, inflammatory factors, and when BMI percentile ≥85, an oral glucose tolerance test. Sixty-four percent of youth with DS had BMI percentile ≥85. Among these, no difference in glucose, insulin, or insulin resistance was detected, but prediabetes was more prevalent with DS (26.4% vs 10.3%; = .025) after adjustment for demographics, pubertal status, and BMI score (odds ratio = 3.2; = .026). Among all participants, those with DS had higher low-density lipoprotein cholesterol (median 107 [interquartile range 89-128] vs 88.5 [79-103] mg/dL; < .00005), triglycerides (89.5 [73-133] vs 71.5 [56-104] mg/dL; < .00005), non-high-density lipoprotein cholesterol (non-HDL-C; 128 [104-153] vs 107 [92-123] mg/dL; < .00005), and triglycerides/HDL-C (2.2 [1.6-3.4] vs 1.7 [1.1-2.5] mg/dL; = .0003) and lower levels of HDL-C (41 [36.5-47] vs 45 [37-53] mg/dL; = .012). DS youth had higher high-sensitivity C-reactive protein, interleukin-6, small low-density lipoprotein particles (LDL-P), and total LDL-P, but similar LDL-P size. Youth with DS had less visceral fat (VFAT), fat mass, and lean mass for BMI score, but greater VFAT at higher fat mass. However, VFAT did not fully explain the increased prevalence of dyslipidemia or prediabetes in youth with DS. Despite similar insulin resistance, youth with DS had greater prevalence of dyslipidemia and prediabetes than typically developing youth, which was not fully explained by VFAT.

    Abstract Summary: Scientists wanted to see if Body Mass Index (BMI) is a good way to tell if young people with Down syndrome (DS) might have heart or sugar problems, since they often have different body shapes and can be overweight. They looked at 150 young people with DS and 103 without, who were all similar in age, gender, and BMI. They checked their body fat, sugar levels, and other health signs. They found that kids with DS were more likely to have higher bad cholesterol and sugar problems, even though their bodies resisted insulin the same way as kids without DS. Kids with DS also had more fat around their belly, but this didn't fully explain why they had more health issues. So, even if kids with DS and without DS have the same BMI, those with DS might still have a higher chance of getting heart and sugar problems.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Cross-Sectional Study of Arterial Stiffness in Adolescents with Down Syndrome.
    The Journal of pediatrics (2019)
    Kelly A, Magge SN, Walega R, Cochrane C, Pipan ME, Zemel BS, Cohen MS, Gidding SS, Townsend R. Cross-Sectional Study of Arterial Stiffness in Adolescents with Down Syndrome. J Pediatr. 2019 Sep; 212:79-86.e1.
    Abstract: To test whether youth with Down syndrome have aortic stiffness indices, as measured by pulse wave velocity (PWV), that differ from youth without Down syndrome and to compare reference-based age-adjusted (age-PWV-Z) and height-adjusted (Ht-PWV-Z) in youth with and without Down syndrome. Cross-sectional study of PWV in 129 adolescents with Down syndrome and 97 youth of comparable age, sex, race/ethnicity, and body mass index (BMI). PWV, age-PWV-Z, and Ht-PWV-Z were compared. Regression models were developed to test for associations with PWV. Youth with Down syndrome and controls were comparable in BMI-Z (1.4 [-1.5 to 2.8] vs 1.2 [-2.0 to 2.8], P = .57) but not Ht-Z (-2.3 [-4.7 to 0.8] vs 0.4 [-2.0 to 2.6], P < .0001). PWV (m/s, 5.0 [3.1-7.9] vs 5.0 [3.6-8.0], P = .5) and mean arterial pressure (MAP, mm Hg) (78 [61-102] vs 74 [64-97], P = .09) were not different between groups. In adjusted analyses confined to Down syndrome, PWV was associated only with BMI, but not age, black race, or MAP (R = 0.11). In contrast, BMI, age, black race, and MAP were all positively associated with and better explained PWV in controls (R = 0.50). PWV was not associated with height in youth with or without Down syndrome. Although age-PWV-Z was not different in Down syndrome (-0.36 [-2.93 to 3.49]) vs -0.15 [-2.32 to 3.22]), Ht-PWV-Z was greater in Down syndrome (0.32 [-2.28 to 4.07] vs -0.08 [-2.64 to 2.64], P = .002), and Ht-PWV-Z was greater than age-PWV-Z in Down syndrome (P < .0001). The lack of relationship of PWV, an independent predictor of adult cardiovascular events, with its traditional determinants including MAP suggests Down syndrome-specific phenomena may alter such relationships in this population. In youth with Down syndrome, Ht-adjusted PWV may overestimate aortic stiffness. Clinicaltrials.gov: NCT01821300.

    Abstract Summary: Scientists wanted to see if teenagers with Down syndrome have different levels of stiffness in their big body artery compared to other kids. They checked this by measuring the speed of blood pulse waves in 129 teenagers with Down syndrome and 97 other kids who were similar in age, gender, race, and body size. They found that both groups had similar pulse wave speeds and blood pressure. However, when they looked closer, they noticed that in kids with Down syndrome, body size was the only thing linked to pulse wave speed, not age, race, or blood pressure like in other kids. Also, when they adjusted the pulse wave speed for height, it seemed like kids with Down syndrome had stiffer arteries than they actually did. This study is important because it shows that doctors might need to check heart health differently in kids with Down syndrome.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Relationships of Body Composition to Cardiac Structure and Function in Adolescents With Down Syndrome are Different than in Adolescents Without Down Syndrome.
    Pediatric cardiology (2019)
    Kelly A, Gidding SS, Walega R, Cochrane C, Clauss S, Townsend RR, Xanthopoulos M, Pipan ME, Zemel BS, Magge SN, Cohen MS. Relationships of Body Composition to Cardiac Structure and Function in Adolescents With Down Syndrome are Different than in Adolescents Without Down Syndrome. Pediatr Cardiol. 2019 Feb; 40(2):421-430.
    Abstract: Median survival in Down syndrome (DS) is 60 years, but cardiovascular disease risk and its markers such as left ventricular mass (LVM) have received limited attention. In youth, LVM is typically scaled to height as a surrogate for lean body mass (LBM), the strongest predictor of LVM, but whether this algorithm applies to DS, a condition which features short stature, is unknown. To examine the relationships of LVM and function with height, LBM, and moderate-to-vigorous physical activity(MVPA) in DS, DS youth aged 10-20 years, and age-, sex-, BMI-, race-matched nonDS controls underwent echocardiography for LVM, ejection fraction (EF), and left ventricular diastolic function (measured as E/E'); dual-energy X-ray absorptiometry (DXA)-measured LBM; accelerometry for MVPA. (DS vs. nonDS median [min-max]): DS had lower height (cm) (144.5 [116.7-170.3] vs. 163.3 [134.8-186.7]; p < 0.0001); LBM (kg) (33.48 [14.5-62.3] vs 41.8 [18.07-72.46], p < 0.0001); and LVM (g) (68.3 [32.1-135] vs 94.0 [43.9-164.6], p < 0.0001); similar EF (%) (65 [54-77] vs 64 [53-77], p = 0.59); and higher E/E' (8.41 [5.54-21.4] vs 5.81 [3.44-9.56], p < 0.0001). In height-adjusted models, LVM was lower in DS (β = - 7.7, p = 0.02). With adjustment for LBM, LVM was even lower in DS (β = - 15.1, p < 0.0001), a finding not explained by MVPA. E/E' remained higher in DS after adjustment for age, height, HR, SBP, and BMI (β = 2.6, p < 0.0001). DS was associated with stiffer left ventricles and lower LVM, the latter magnified with LBM adjustment. Scaling to height, the traditional approach for assessing LVM in youth, may underestimate LVM differences in DS. Whether lower LVM and diastolic function are intrinsic to DS, pathologic, or protective remains unknown.Clinical Trial Registration: NCT01821300.

    Abstract Summary: Scientists did a study to learn about heart health in young people with Down syndrome (DS), who usually live to be about 60 years old. They wanted to see if the size of the heart's main pumping chamber and how well it works are different in kids with DS compared to kids without DS. They looked at 10 to 20-year-olds, measuring their heart size, muscle mass, and how much they move around. They found that kids with DS are shorter, have less muscle, and their hearts are smaller and stiffer than kids without DS. Usually, doctors measure heart size based on height, but this might not work well for kids with DS because they are often shorter. This study helps us understand that kids with DS might need different ways to check their heart health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Caregiver-Reported Quality of Life in Youth with Down Syndrome.
    The Journal of pediatrics (2017)
    Xanthopoulos MS, Walega R, Xiao R, Prasad D, Pipan MM, Zemel BS, Berkowitz RI, Magge SN, Kelly A. Caregiver-Reported Quality of Life in Youth with Down Syndrome. J Pediatr. 2017 Oct; 189:98-104.e1.
    Abstract: To describe caregiver-reported quality of life (QOL) in youth with Down syndrome (DS) and to examine the role of obesity on QOL. Caregivers of youth with and without DS aged 10 through 20 years completed questionnaires examining QOL (Pediatric Quality of Life Questionnaire) and weight-related QOL (Impact of Weight on Quality of Life - Kids). Age- and sex-specific z scores were generated for body mass index. Obesity was defined as a body mass index ≥95th percentile for age and sex. Caregiver-reported Total QOL, Physical Health, and Psychosocial Health summary scores were all lower in the DS group compared with the non-DS controls (P < .001). Social and School Functioning were also lower (P < .001), but Emotional Functioning did not differ between DS and non-DS groups (P = .31). Physical Functioning (P = .003) and Total scores (P = .03) differed between youth without DS with and without obesity, but no differences were reported between youth with DS with and without obesity. On the Impact of Weight on Quality of Life - Kids, caregivers of youth with DS reported greater Body Esteem (P = .020) and Social Life scores (P = .03) than caregivers of non-DS youth. Caregivers of youth with obesity, regardless of DS status, reported significantly lower weight-specific QOL scores than caregivers of youth without obesity. Caregivers reported lower QOL in youth with DS compared with youth without DS with the exception of emotional functioning. Obesity influences most domains of weight-related QOL in youth with and without DS; therefore, providers should address weight concerns in youth with obesity even in the presence of DS. NCT01821300.

    Abstract Summary: Researchers wanted to find out how kids with Down syndrome (DS) feel about their lives, and if being overweight affects their happiness. They asked parents of kids aged 10 to 20, both with and without Down syndrome, to fill out surveys about their kids' quality of life and how their weight might impact it. They found that parents said kids with Down syndrome didn't feel as good about their physical health and social life as other kids. However, their feelings weren't different when it came to emotions. For kids without Down syndrome, being overweight made them feel worse about their physical health and overall life. But for kids with Down syndrome, being overweight didn't change how they felt. Parents of kids with Down syndrome thought their kids felt better about their bodies and social life than parents of kids without Down syndrome. But all parents agreed that being overweight made kids feel worse about weight-related life quality. The study shows that doctors should help kids with obesity to feel better about themselves, even if they have Down syndrome.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Children\'s Hospital and Research Center at Oakland
  • Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults.
    Journal of the American Heart Association (2021)
    Ferrell M, Bazeley P, Wang Z, Levison BS, Li XS, Jia X, Krauss RM, Knight R, Lusis AJ, Garcia-Garcia JC, Hazen SL, Tang WHW. Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults. J Am Heart Assoc. 2021 Nov 2; 10(21):e021934.
    Abstract: Background Trimethylamine--oxide (TMAO) is a small molecule derived from the metabolism of dietary nutrients by gut microbes and contributes to cardiovascular disease. Plasma TMAO increases following consumption of red meat. This metabolic change is thought to be partly because of the expansion of gut microbes able to use nutrients abundant in red meat. Methods and Results We used data from a randomized crossover study to estimate the degree to which TMAO can be estimated from fecal microbial composition. Healthy participants received a series of 3 diets that differed in protein source (red meat, white meat, and non-meat), and fecal, plasma, and urine samples were collected following 4 weeks of exposure to each diet. TMAO was quantitated in plasma and urine, while shotgun metagenomic sequencing was performed on fecal DNA. While the cai gene cluster was weakly correlated with plasma TMAO (rho=0.17, =0.0007), elastic net models of TMAO were not improved by abundances of bacterial genes known to contribute to TMAO synthesis. A global analysis of all taxonomic groups, genes, and gene families found no meaningful predictors of TMAO. We postulated that abundances of known genes related to TMAO production do not predict bacterial metabolism, and we measured choline- and carnitine-trimethylamine lyase activity during fecal culture. Trimethylamine lyase genes were only weakly correlated with the activity of the enzymes they encode. Conclusions Fecal microbiome composition does not predict systemic TMAO because, in this case, gene copy number does not predict bacterial metabolic activity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01427855.

    Abstract Summary: Scientists did a study to see if the tiny living things in our guts (microbes) can tell us how much of a certain molecule, called TMAO, is in our blood. TMAO can be bad for our hearts, and it goes up when we eat red meat. They had healthy people eat different kinds of food, like red meat, white meat, and vegetarian food, for four weeks. They then checked their poop, blood, and pee. They were looking for special parts of the microbes (genes) that might make TMAO. But they found that even if they saw these parts, it didn't really help them guess how much TMAO would be in the blood. They also tried to see if these genes were active in the poop, but that didn't work well either. So, they learned that just because the genes are there, it doesn't mean they can tell how much TMAO will be in someone's body. This is important because it helps us understand that it's not so simple to predict heart disease risk by looking at gut microbes.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of red meat, white meat, and nonmeat protein sources on atherogenic lipoprotein measures in the context of low compared with high saturated fat intake: a randomized controlled trial.
    The American journal of clinical nutrition (2019)
    Bergeron N, Chiu S, Williams PT, M King S, Krauss RM. Effects of red meat, white meat, and nonmeat protein sources on atherogenic lipoprotein measures in the context of low compared with high saturated fat intake: a randomized controlled trial. Am J Clin Nutr. 2019 Jul 1; 110(1):24-33.
    Abstract: Dietary recommendations to limit red meat are based on observational studies linking intake to cardiovascular disease (CVD) risk together with the potential of its saturated fatty acid (SFA) content to raise low-density lipoprotein (LDL) cholesterol. However, the relation of white meat to CVD risk, and the effects of dietary protein source on lipoprotein particle subfractions, have not been extensively evaluated. We tested whether levels of atherogenic lipids and lipoproteins differed significantly following consumption of diets with high red meat content compared with diets with similar amounts of protein derived from white meat or nonmeat sources, and whether these effects were modified by concomitant intake of high compared with low SFAs. Generally healthy men and women, 21-65 y, body mass index 20-35 kg/m2, were randomly assigned to 1 of 2 parallel arms (high or low SFA) and within each, allocated to red meat, white meat, and nonmeat protein diets consumed for 4 wk each in random order. The primary outcomes were LDL cholesterol, apolipoprotein B (apoB), small + medium LDL particles, and total/high-density lipoprotein cholesterol. Analysis included participants who completed all 3 dietary protein assignments (61 for high SFA; 52 for low SFA). LDL cholesterol and apoB were higher with red and white meat than with nonmeat, independent of SFA content (P < 0.0001 for all, except apoB: red meat compared with nonmeat [P = 0.0004]). This was due primarily to increases in large LDL particles, whereas small + medium LDL and total/high-density lipoprotein cholesterol were unaffected by protein source (P = 0.10 and P = 0.51, respectively). Primary outcomes did not differ significantly between red and white meat. Independent of protein source, high compared with low SFA increased LDL cholesterol (P = 0.0003), apoB (P = 0.0002), and large LDL (P = 0.0002). The findings are in keeping with recommendations promoting diets with a high proportion of plant-based food but, based on lipid and lipoprotein effects, do not provide evidence for choosing white over red meat for reducing CVD risk. This trial was registered at Clinicaltrials.gov as NCT01427855.

    Abstract Summary: This study looked at how eating different types of meat affects our heart health. They had healthy adults eat diets high in red meat, white meat, or non-meat proteins for four weeks each. They found that both red and white meat raised levels of certain fats in the blood that can lead to heart disease, more than non-meat proteins did. This was true no matter how much saturated fat was in the diet. This means that eating more plant-based foods might be better for our hearts, and that white meat isn't necessarily better than red meat for heart health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Cincinnati Children's Hospital Medical Center
  • Education and electronic medical records and genomics network, challenges, and lessons learned from a large-scale clinical trial using polygenic risk scores.
    Genetics in medicine : official journal of the American College of Medical Genetics (2023)
    Connolly JJ, Berner ES, Smith M, Levy S, Terek S, Harr M, Karavite D, Suckiel S, Holm IA, Dufendach K, Nelson C, Khan A, Chisholm RL, Allworth A, Wei WQ, Bland HT, Clayton EW, Soper ER, Linder JE, Limdi NA, Miller A, Nigbur S, Bangash H, Hamed M, Sherafat. Education and electronic medical records and genomics network, challenges, and lessons learned from a large-scale clinical trial using polygenic risk scores. Genet Med. 2023 Sep; 25(9):100906.
    Abstract: Polygenic risk scores (PRS) have potential to improve health care by identifying individuals that have elevated risk for common complex conditions. Use of PRS in clinical practice, however, requires careful assessment of the needs and capabilities of patients, providers, and health care systems. The electronic Medical Records and Genomics (eMERGE) network is conducting a collaborative study which will return PRS to 25,000 pediatric and adult participants. All participants will receive a risk report, potentially classifying them as high risk (∼2-10% per condition) for 1 or more of 10 conditions based on PRS. The study population is enriched by participants from racial and ethnic minority populations, underserved populations, and populations who experience poorer medical outcomes. All 10 eMERGE clinical sites conducted focus groups, interviews, and/or surveys to understand educational needs among key stakeholders-participants, providers, and/or study staff. Together, these studies highlighted the need for tools that address the perceived benefit/value of PRS, types of education/support needed, accessibility, and PRS-related knowledge and understanding. Based on findings from these preliminary studies, the network harmonized training initiatives and formal/informal educational resources. This paper summarizes eMERGE's collective approach to assessing educational needs and developing educational approaches for primary stakeholders. It discusses challenges encountered and solutions provided.

    Abstract Summary: Scientists are doing a big study to see if special scores called "Polygenic risk scores" (PRS) can help doctors figure out who might get certain health problems. They're going to tell 25,000 kids and grown-ups if they have a high chance of getting any of 10 different health issues. They're making sure to include people from different backgrounds and those who usually don't get as much medical help. The team talked to lots of people – those who might get their PRS, doctors, and the study team – to learn what they need to know about these scores. They found out that people need more tools and teaching to really understand and use these scores well. The study is making special training and learning stuff to help everyone involved. They're sharing what they learned about teaching people about PRS and how to make it easier for everyone to use. This could help make health care better for lots of people by catching health problems early.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Returning integrated genomic risk and clinical recommendations: The eMERGE study.
    Genetics in medicine : official journal of the American College of Medical Genetics (2023)
    Linder JE, Allworth A, Bland HT, Caraballo PJ, Chisholm RL, Clayton EW, Crosslin DR, Dikilitas O, DiVietro A, Esplin ED, Forman S, Freimuth RR, Gordon AS, Green R, Harden MV, Holm IA, Jarvik GP, Karlson EW, Labrecque S, Lennon NJ, Limdi NA, Mittendorf KF,. Returning integrated genomic risk and clinical recommendations: The eMERGE study. Genet Med. 2023 Apr; 25(4):100006.
    Abstract: Assessing the risk of common, complex diseases requires consideration of clinical risk factors as well as monogenic and polygenic risks, which in turn may be reflected in family history. Returning risks to individuals and providers may influence preventive care or use of prophylactic therapies for those individuals at high genetic risk. To enable integrated genetic risk assessment, the eMERGE (electronic MEdical Records and GEnomics) network is enrolling 25,000 diverse individuals in a prospective cohort study across 10 sites. The network developed methods to return cross-ancestry polygenic risk scores, monogenic risks, family history, and clinical risk assessments via a genome-informed risk assessment (GIRA) report and will assess uptake of care recommendations after return of results. GIRAs include summary care recommendations for 11 conditions, education pages, and clinical laboratory reports. The return of high-risk GIRA to individuals and providers includes guidelines for care and lifestyle recommendations. Assembling the GIRA required infrastructure and workflows for ingesting and presenting content from multiple sources. Recruitment began in February 2022. Return of a novel report for communicating monogenic, polygenic, and family history-based risk factors will inform the benefits of integrated genetic risk assessment for routine health care.

    Abstract Summary: Doctors want to know if understanding a person's family health history and their own unique genes can help prevent diseases. They are studying 25,000 people from different backgrounds to see if sharing this information with patients and doctors helps them make better health choices. They made special reports that include a person's gene information, family health history, and tips for staying healthy. They are checking if people follow these health tips after getting their reports. This study started in February 2022 and might show that knowing about your genes and family health can help keep you healthy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Shortened Sleep Duration Causes Sleepiness, Inattention, and Oppositionality in Adolescents With Attention-Deficit/Hyperactivity Disorder: Findings From a Crossover Sleep Restriction/Extension Study.
    Journal of the American Academy of Child and Adolescent Psychiatry (2019)
    Becker SP, Epstein JN, Tamm L, Tilford AA, Tischner CM, Isaacson PA, Simon JO, Beebe DW. Shortened Sleep Duration Causes Sleepiness, Inattention, and Oppositionality in Adolescents With Attention-Deficit/Hyperactivity Disorder: Findings From a Crossover Sleep Restriction/Extension Study. J Am Acad Child Adolesc Psychiatry. 2019 Apr; 58(4):433-442.
    Abstract: Although poor sleep is often reported in adolescents with attention-deficit/hyperactivity disorder (ADHD), prior studies have been correlational. This study investigated whether sleep duration is causally linked to sleepiness, inattention, and behavioral functioning in adolescents with ADHD. A total of 72 adolescents (aged 14-17 years) entered a 3-week sleep protocol using an experimental crossover design. The protocol included a phase stabilization week, followed in randomized counterbalanced order by 1 week of sleep restriction (6.5 hours) and 1 week of sleep extension (9.5 hours). Sleep was monitored with actigraphy and daily sleep diaries, with laboratory visits at the end of each week. Analyses included 48 adolescents who had complete actigraphy data and successfully completed the sleep protocol (defined a priori as obtaining ≥1 hour actigraphy-measured sleep duration during extension compared to restriction). Parent and adolescent ratings of daytime sleepiness, ADHD symptoms, sluggish cognitive tempo (SCT), and oppositional behaviors were the primary measures. The A-X Continuous Performance Test (CPT) was a secondary measure. Compared to the extended sleep week, parents reported more inattentive and oppositional symptoms during the restricted sleep week. Both parents and adolescents reported more SCT symptoms and greater daytime sleepiness during restriction compared to extension. Adolescents reported less hyperactivity-impulsivity during sleep restriction than extension. No effects were found for parent-reported hyperactivity-impulsivity, adolescent-reported ADHD inattention, or CPT performance. This study provides the first evidence that sleep duration is a causal contributor to daytime behaviors in adolescents with ADHD. Sleep may be an important target for intervention in adolescents with ADHD. Cognitive and Behavioral Effects of Sleep Restriction in Adolescents With ADHD; https://clinicaltrials.gov/; NCT02732756.

    Abstract Summary: Scientists did a study to see if not getting enough sleep really does make teenagers with ADHD feel sleepier and have more trouble paying attention and behaving. They had 72 teenagers follow a special sleep plan for 3 weeks, where they sometimes got only 6.5 hours of sleep and other times got 9.5 hours. They used sleep trackers and had the teens visit a lab to check on things. They found out that when the teens didn't sleep much, they felt sleepier, had a harder time paying attention, and were more likely to act out, according to their parents. The teens themselves also felt more tired and slow when they didn't get enough sleep. But, interestingly, they didn't feel as hyper. This study shows that getting enough sleep is really important for teenagers with ADHD and could help them do better during the day.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Cleveland Clinic
  • Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response.
    Journal of psychiatric research (2019)
    Koirala P, Hu B, Altinay M, Li M, DiVita AL, Bryant KA, Karne HS, Fiedorowicz JG, Anand A. Sub-threshold bipolar disorder in medication-free young subjects with major depression: Clinical characteristics and antidepressant treatment response. J Psychiatr Res. 2019 Mar; 110:1-8.
    Abstract: This study, for the first time, compared illness and antidepressant response characteristics of young subjects with major depression (MDD) at low (LRMDD) or high-risk (HRMDD) for developing bipolar disorder with characteristics of young bipolar (BPD) subjects and healthy controls (HC). One hundred and six young (15-30 yr), medication-free subjects MDD subjects (HRMDD, N = 51; LRMDD, N = 55) were compared with 32 BPD (Type I: 14; Type II: 18) as well as 49 HC subjects. Baseline illness characteristics and frequency of comorbid conditions were examined using Analysis of Variance and Cochran-Armitage trend test. Additionally, in MDD subjects, the effect of open-label antidepressant treatment for up to 24 months with periodic assessments was compared between HRMDD and LRMDD groups for treatment response, remission and (hypo)mania switch while controlling for attrition. Significant gradation from LRMDD to HRMDD to BPD groups was found for increasing occurrence of alcohol dependence (p = 0.006), comorbid PTSD (p = 0.006), borderline personality traits (p = 0.001), and occurrence of melancholic features (p < 0.005). Antidepressant treatment response was similar between the two groups except that for the 12-month period HRMDD showed a trend for a lower response. Switch to (hypo)mania was infrequent in both groups though the HRMDD showed a higher occurrence of spikes in (hypo)mania symptoms (>25% increase in YMRS scores)(p = 0.04). Findings of the study indicate that a substantial proportion of young MDD subjects share BPD illness characteristics. These HRMDD subjects, if treated with antidepressants, need to be monitored for development of BPD. NCT01811147.

    Abstract Summary: Scientists did a study to learn more about young people with a big kind of sadness called major depression. They wanted to see if these young people were at low or high risk of getting bipolar disorder, which is when someone's mood can change a lot. They also looked at young people with bipolar disorder and young people without any mood problems. They had 106 young people with depression and 32 with bipolar disorder, plus 49 healthy young people. They checked how often the young people had other problems like drinking too much alcohol, being very scared because of a past scary event, having trouble with relationships, and feeling extra sad. They also gave medicine to the depressed young people for up to two years to see if it helped them feel better and if it made their moods swing a lot. They found that the more at risk the young people were for bipolar disorder, the more other problems they had. The medicine helped both low and high-risk groups, but the high-risk group didn't do quite as well after a year and sometimes had bigger mood swings. This study is important because it shows that doctors need to watch young people with depression carefully, especially if they are at high risk for bipolar disorder, when they give them medicine to help with their sadness.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Columbia University
  • Mobile health (m-health) smartphone interventions for adolescents and adults with overweight or obesity.
    The Cochrane database of systematic reviews (2024)
    Metzendorf MI, Wieland LS, Richter B. Mobile health (m-health) smartphone interventions for adolescents and adults with overweight or obesity. Cochrane Database Syst Rev. 2024 Feb 20; 2(2):CD013591.
    Abstract: Obesity is considered to be a risk factor for various diseases, and its incidence has tripled worldwide since 1975. In addition to potentially being at risk for adverse health outcomes, people with overweight or obesity are often stigmatised. Behaviour change interventions are increasingly delivered as mobile health (m-health) interventions, using smartphone apps and wearables. They are believed to support healthy behaviours at the individual level in a low-threshold manner. To assess the effects of integrated smartphone applications for adolescents and adults with overweight or obesity. We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, and LILACS, as well as the trials registers ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform on 2 October 2023 (date of last search for all databases). We placed no restrictions on the language of publication. Participants were adolescents and adults with overweight or obesity. Eligible interventions were integrated smartphone apps using at least two behaviour change techniques. The intervention could target physical activity, cardiorespiratory fitness, weight loss, healthy diet, or self-efficacy. Comparators included no or minimal intervention (NMI), a different smartphone app, personal coaching, or usual care. Eligible studies were randomised controlled trials of any duration with a follow-up of at least three months. We used standard Cochrane methodology and the RoB 2 tool. Important outcomes were physical activity, body mass index (BMI) and weight, health-related quality of life, self-efficacy, well-being, change in dietary behaviour, and adverse events. We focused on presenting studies with medium- (6 to < 12 months) and long-term (≥ 12 months) outcomes in our summary of findings table, following recommendations in the core outcome set for behavioural weight management interventions. We included 18 studies with 2703 participants. Interventions lasted from 2 to 24 months. The mean BMI in adults ranged from 27 to 50, and the median BMI z-score in adolescents ranged from 2.2 to 2.5. Smartphone app versus no or minimal intervention Thirteen studies compared a smartphone app versus NMI in adults; no studies were available for adolescents. The comparator comprised minimal health advice, handouts, food diaries, smartphone apps unrelated to weight loss, and waiting list. Measures of physical activity: at 12 months' follow-up, a smartphone app compared to NMI probably reduces moderate to vigorous physical activity (MVPA) slightly (mean difference (MD) -28.9 min/week (95% confidence interval (CI) -85.9 to 28; 1 study, 650 participants; moderate-certainty evidence)). We are very uncertain about the results of estimated energy expenditure and cardiorespiratory fitness at eight months' follow-up. A smartphone app compared with NMI probably results in little to no difference in changes in total activity time at 12 months' follow-up and leisure time physical activity at 24 months' follow-up. Anthropometric measures: a smartphone app compared with NMI may reduce BMI (MD of BMI change -2.6 kg/m, 95% CI -6 to 0.8; 2 studies, 146 participants; very low-certainty evidence) at six to eight months' follow-up, but the evidence is very uncertain. At 12 months' follow-up, a smartphone app probably resulted in little to no difference in BMI change (MD -0.1 kg/m, 95% CI -0.4 to 0.3; 1 study; 650 participants; moderate-certainty evidence). A smartphone app compared with NMI may result in little to no difference in body weight change (MD -2.5 kg, 95% CI -6.8 to 1.7; 3 studies, 1044 participants; low-certainty evidence) at 12 months' follow-up. At 24 months' follow-up, a smartphone app probably resulted in little to no difference in body weight change (MD 0.7 kg, 95% CI -1.2 to 2.6; 1 study, 245 participants; moderate-certainty evidence). A smartphone app compared with NMI may result in little to no difference in self-efficacy for a physical activity score at eight months' follow-up, but the results are very uncertain. A smartphone app probably results in little to no difference in quality of life and well-being at 12 months (moderate-certainty evidence) and in little to no difference in various measures used to inform dietary behaviour at 12 and 24 months' follow-up. We are very uncertain about adverse events, which were only reported narratively in two studies (very low-certainty evidence). Smartphone app versus another smartphone app Two studies compared different versions of the same app in adults, showing no or minimal differences in outcomes. One study in adults compared two different apps (calorie counting versus ketogenic diet) and suggested a slight reduction in body weight at six months in favour of the ketogenic diet app. No studies were available for adolescents. Smartphone app versus personal coaching Only one study compared a smartphone app with personal coaching in adults, presenting data at three months. Two studies compared these interventions in adolescents. A smartphone app resulted in little to no difference in BMI z-score compared to personal coaching at six months' follow-up (MD 0, 95% CI -0.2 to 0.2; 1 study; 107 participants). Smartphone app versus usual care Only one study compared an app with usual care in adults but only reported data at three months on participant satisfaction. No studies were available for adolescents. We identified 34 ongoing studies. The available evidence is limited and does not demonstrate a clear benefit of smartphone applications as interventions for adolescents or adults with overweight or obesity. While the number of studies is growing, the evidence remains incomplete due to the high variability of the apps' features, content and components, which complicates direct comparisons and assessment of their effectiveness. Comparisons with either no or minimal intervention or personal coaching show minor effects, which are mostly not clinically significant. Minimal data for adolescents also warrants further research. Evidence is also scarce for low- and middle-income countries as well as for people with different socio-economic and cultural backgrounds. The 34 ongoing studies suggest sustained interest in the topic, with new evidence expected to emerge within the next two years. In practice, clinicians and healthcare practitioners should carefully consider the potential benefits, limitations, and evolving research when recommending smartphone apps to adolescents and adults with overweight or obesity.

    Abstract Summary: Scientists wanted to see if smartphone apps help teenagers and grown-ups who weigh more than is healthy. They looked at studies where people used apps to try to be more active, eat better, or feel more confident about exercising. They compared people who used these apps to those who didn't or who got other kinds of help. They found 18 studies with 2,703 people. The studies lasted from 2 to 24 months. The results showed that using an app might help a little with exercise and weight, but they weren't sure. The apps didn't seem to change how much people weighed or how they felt about their lives after a year. They also didn't know if the apps caused any problems. Some studies compared different apps or apps with personal coaching, but they didn't find big differences. There weren't many studies on teenagers or on people from poorer countries or different backgrounds. Right now, there are 34 more studies being done, so soon they'll know more. For now, doctors should think carefully before suggesting these apps because the benefits aren't clear yet.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Time-restricted eating to improve cardiometabolic health: The New York Time-Restricted EATing randomized clinical trial - Protocol overview.
    Contemporary clinical trials (2022)
    Santos-Báez LS, Garbarini A, Shaw D, Cheng B, Popp CJ, Manoogian ENC, Panda S, Laferrère B. Time-restricted eating to improve cardiometabolic health: The New York Time-Restricted EATing randomized clinical trial - Protocol overview. Contemp Clin Trials. 2022 Sep; 120:106872.
    Abstract: Re-aligning eating patterns with biological rhythm can reduce the burden of metabolic syndrome in older adults with overweight or obesity. Time-restricted eating (TRE) has been shown to result in weight loss and improved cardiometabolic health while being less challenging than counting calories. The New York Time-Restricted EATing study (NY-TREAT) is a two-arm, randomized clinical trial (RCT) that aims to examine the efficacy and sustainability of TRE (eating window ≤10 h/day) vs. a habitual prolonged eating window (HABIT, ≥14 h/day) in metabolically unhealthy midlife adults (50-75 years) with overweight or obesity and prediabetes or type 2 diabetes (T2D). Our primary hypothesis is that the TRE will result in greater weight loss compared to HABIT at 3 months. The efficacy of the TRE intervention on body weight, fat mass, energy expenditure, and glucose is tested at 3 months, and the sustainability of its effect is measured at 12 months, with ambulatory assessments of sleep and physical activity (ActiGraph), eating pattern (smartphone application), and interstitial glucose (continuous glucose monitoring). The RCT also includes state-of-the-art measurements of body fat (quantitative magnetic resonance), total energy expenditure (doubly-labelled water), insulin secretion, insulin resistance, and glucose tolerance. Adherence to self-monitoring and reduced eating window are monitored remotely in real-time. This RCT will provide further insight into the effects of TRE on cardiometabolic health in individuals with high metabolic risk. Sixty-two participants will be enrolled, and with estimated 30% attrition, 42 participants will return at 12 months. This protocol describes the design, interventions, methods, and expected outcomes. Clinical trial registration:NCT04465721 IRB: AAAS7791.

    Abstract Summary: Scientists are doing a study to see if eating for only 10 hours a day can help older people who are a bit too heavy and have health problems like high blood sugar or diabetes. They are comparing this to people who eat over a longer time, like 14 hours a day. They think that eating for less time each day might help people lose weight after 3 months. They will check on things like how much body fat and sugar in the blood the people have, and they will keep an eye on how well they stick to the eating plan. They will also see if the good changes last for a whole year. This study could teach us if eating for a shorter time each day is good for people's health, especially for those who have a higher chance of getting heart disease or diabetes. They plan to have 62 people in the study, but they expect that some might not finish, so they hope to have at least 42 people at the end of the year.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime.
    BMC women's health (2020)
    Palacios S, Colli E, Regidor PA. Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime. BMC Womens Health. 2020 Oct 2; 20(1):218.
    Abstract: A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4 mg in a regimen 24/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks. Three European and American multicenter clinical trials have been conducted in more than 2500 patients and more than 25,000 cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9%) had a risk factor for VTE, while in the European studies, 261 patients (16.6%) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated. No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and/or 85 to 90 mm HG and no influence on ECG parameters were observed. The introduction of a new estrogen-free contraceptive with 4 mg of non-micronized drospirenone in a 24/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors. EudraCT registration numbers: 2010-021787-15 & 2011-002396-42 . Clincaltrials.gov: NCT02269241 .

    Abstract Summary: Doctors did a big study on a new birth control pill that doesn't have estrogen in it. This pill has something called drospirenone. They wanted to make sure it works well and is safe for the heart. Over 2500 women tried this new pill, and it worked really well to prevent pregnancy. They also checked to see if it caused any blood clot problems or changed the heart's health, and it didn't. Even women who usually have a higher chance of heart problems were safe taking it. This is good news because now women have another choice for birth control that's safe for their hearts.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Use of a urine anastrozole assay to determine treatment discontinuation among women with hormone-sensitive breast cancer: a pilot study.
    Journal of oncology practice (2012)
    Clarke Hillyer G, Neugut AI, Crew KD, Kalinsky K, Maurer MA, Rotsides DZ, Danaceau J, Hershman DL. Use of a urine anastrozole assay to determine treatment discontinuation among women with hormone-sensitive breast cancer: a pilot study. J Oncol Pract. 2012 Sep; 8(5):e100-4.
    Abstract: Multiple studies have shown that adherence to adjuvant hormonal therapy in women with breast cancer is suboptimal. Measurements of compliance with self-report, pill counts, and/or pharmacy records are susceptible to bias. We assessed the feasibility of using a urine anastrozole assay as an objective biomarker of nonadherence to anastrozole treatment. We recruited consecutive postmenopausal women, age ≥ 18 years, with hormone-sensitive nonmetastatic breast cancer who were prescribed anastrozole at least 3 months before enrollment. Each completed a short survey to gather information on demographics, anastrozole compliance history, and self-reported medication history, tumor characteristics, and treatment received. A single, random 15-mL urine sample was collected and tested for the presence of anastrozole using a previously validated assay. Patients were told they were part of a study to determine if anastrozole could be detected in the urine. Among 96 participants, mean age was 63.7 years (range, 51 to 70 years). The population was diverse, with 56.5% white, 57.6% US born, 59.8% unemployed, and 56.6% college educated. Prior treatment included chemotherapy (50%) and/or radiotherapy (58.7%). Mean duration of anastrozole treatment was 2.2 years (standard deviation, 1.6). Four participants reported nonadherence and declined to submit urine samples, and two had no detectable level of anastrozole (six of 96; 6.3%). Detectable levels among adherent women ranged from 49.3 to 632.8 ng/mL. We demonstrated that collection of urine to measure anastrozole levels is feasible and reliable. Identifying biomarkers to measure adherence is critical for studies investigating interventions to improve hormonal therapy compliance.

    Abstract Summary: Scientists did a study to see if they could use a special test on pee to check if women with a certain kind of breast cancer were taking their medicine like they should. They asked women who were supposed to take a medicine called anastrozole to give a pee sample and answer some questions. They found that most women had the medicine in their pee, but a few didn't, which meant they might not be taking their medicine right. This pee test could be a good way to make sure patients are following their treatment plan, which is important for their health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Duke University
  • The effects of psychotherapy for anhedonia on subcortical brain volumes measured with ultra-high field MRI.
    Journal of affective disorders (2024)
    Gibson K, Cernasov P, Styner M, Walsh EC, Kinard JL, Kelley L, Bizzell J, Phillips R, Pfister C, Scott M, Freeman L, Pisoni A, Nagy GA, Oliver JA, Smoski M, Dichter G. The effects of psychotherapy for anhedonia on subcortical brain volumes measured with ultra-high field MRI. J Affect Disord. 2024 May 28; :.
    Abstract: Anhedonia is a transdiagnostic symptom often resistant to treatment. The identification of biomarkers sensitive to anhedonia treatment will aid in the evaluation of novel anhedonia interventions. This is an exploratory analysis of changes in subcortical brain volumes accompanying psychotherapy in a transdiagnostic anhedonic sample using ultra-high field (7-Tesla) MRI. Outpatients with clinically impairing anhedonia (n = 116) received Behavioral Activation Treatment for Anhedonia, a novel psychotherapy, or Mindfulness-Based Cognitive Therapy (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Subcortical brain volumes were estimated via the MultisegPipeline, and regions of interest were the amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus. Bivariate mixed effects models estimated pre-treatment relations between anhedonia severity and subcortical brain volumes, change over time in subcortical brain volumes, and associations between changes in subcortical brain volumes and changes in anhedonia symptoms. As reported previously (Cernasov et al., 2023), both forms of psychotherapy resulted in equivalent and significant reductions in anhedonia symptoms. Pre-treatment anhedonia severity and subcortical brain volumes were not related. No changes in subcortical brain volumes were observed over the course of treatment. Additionally, no relations were observed between changes in subcortical brain volumes and changes in anhedonia severity over the course of treatment. This trial included a modest sample size and did not have a waitlist-control condition or a non-anhedonic comparison group. In this exploratory analysis, psychotherapy for anhedonia was not accompanied by changes in subcortical brain volumes, suggesting that subcortical brain volumes may not be a candidate biomarker sensitive to response to psychotherapy.

    Abstract Summary: Scientists did a study to see if therapy could help people who don't feel pleasure, a problem called anhedonia. They used a special brain scanner to look at parts of the brain deep inside the head in 116 people. These people tried two kinds of talking therapies to see if they would start feeling better. The researchers checked if the size of certain brain areas changed with therapy and if these changes were linked to people feeling less anhedonia. They found that even though people felt better after therapy, the sizes of those brain parts didn't change. This means that the size of these brain parts might not be a good way to tell if therapy is working for anhedonia.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Parsing within & between-person dynamics of therapy homework completion and clinical symptoms in two cognitive behavioral treatments for adults with anhedonia.
    Behaviour research and therapy (2023)
    Cernasov PM, Kinard JL, Walsh E, Kelley L, Phillips R, Pisoni A, Arnold M, Lowery SC, Ammirato M, Nagy GA, Oliver JA, Haworth K, Daughters SB, Dichter GS, Smoski M. Parsing within & between-person dynamics of therapy homework completion and clinical symptoms in two cognitive behavioral treatments for adults with anhedonia. Behav Res Ther. 2023 Jul; 166:104322.
    Abstract: Homework is a key theoretical component of cognitive-behavioral therapies, however, the effects of homework on clinical outcomes have largely been evaluated between-persons rather than within-persons. The effects of homework completion on treatment response were examined in a randomized trial comparing Behavioral Activation Treatment for Anhedonia (BATA, n = 38), a novel psychotherapy, to Mindfulness-Based Cognitive Therapy (MBCT, n=35). The primary endpoint was consummatory reward sensitivity, measured weekly by the Snaith Hamilton Pleasure Scale (SHAPS), up to 15 weeks. Multilevel models evaluated change in SHAPS scores over time and the effects of clinician-reported and participant-reported homework. BATA and MBCT resulted in significant, equivalent reductions in SHAPS scores. Unexpectedly, participants who completed greater mean total amounts of homework did not improve at a faster rate (i.e., no between-person effect). However, sessions with greater than average participant-reported homework completion were associated with greater than average reductions in SHAPS scores (i.e., a within-person effect). For clinician-reported homework, this effect was only evident within the BATA condition. This study shows psychotherapy homework completion relates to symptomatic improvement in cognitive-behavioral treatments for anhedonia when session-to-session changes are examined within-person. On the contrary, we found no evidence that total homework completion predicted greater improvements between-person. When possible, psychotherapy researchers should evaluate their constructs of interest across multiple sessions (not just pre/post) to allow more direct tests of hypotheses predicted by theoretical models of individual change processes.

    Abstract Summary: Scientists did a study to see if doing homework from therapy helps people feel more joy in life. They had two groups: one did an activity-focused therapy, and the other did a mindfulness therapy. They checked how much pleasure people felt every week for 15 weeks. They found that both therapies helped people feel better, but the amount of homework didn't always make a big difference. If someone did more homework than usual for them, they felt even better after that session, but doing a lot of homework overall didn't mean they felt better than others. This was especially true for the activity-focused therapy. The study tells us that for people getting therapy, it might help to focus on doing homework for each session rather than worrying about doing a lot of homework all the time.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Learning in a Virtual Environment to Improve Type 2 Diabetes Outcomes: Randomized Controlled Trial.
    JMIR formative research (2023)
    Johnson CM, D'Eramo Melkus G, Reagan L, Pan W, Amarasekara S, Pereira K, Hassell N, Nowlin S, Vorderstrasse A. Learning in a Virtual Environment to Improve Type 2 Diabetes Outcomes: Randomized Controlled Trial. JMIR Form Res. 2023 Apr 20; 7:e40359.
    Abstract: Given the importance of self-management in type 2 diabetes mellitus (T2DM), a major aspect of health is providing diabetes self-management education and support. Known barriers include access, availability, and the lack of follow through on referral to education programs. Virtual education and support have increased in use over the last few years. The purpose of the Diabetes Learning in a Virtual Environment (LIVE) study was to compare the effects of the LIVE intervention (educational 3D world) to a diabetes self-management education and support control website on diet and physical activity behaviors and behavioral and metabolic outcomes in adults with T2DM over 12 months. The LIVE study was a 52-week multisite randomized controlled trial with longitudinal repeated measures. Participants were randomized to LIVE (n=102) or a control website (n=109). Both contained the same educational materials, but the virtual environment was synchronous and interactive, whereas the control was a flat website. Data were collected at baseline and 3, 6, and 12 months using surveys and clinical, laboratory, and Fitbit measures. Descriptive statistics included baseline characteristics and demographics. The effects of the intervention were initially examined by comparing the means and SDs of the outcomes across the 4 time points between study arms, followed by multilevel modeling on trajectories of the outcomes over the 12 months. This trial included 211 participants who consented. The mean age was 58.85 (SD 10.1) years, and a majority were White (127/211, 60.2%), non-Hispanic (198/211, 93.8%), married (107/190, 56.3%), and female (125/211, 59.2%). Mean hemoglobin A (HbA) level at baseline was 7.64% (SD 1.79%) and mean BMI was 33.51 (SD 7.25). We examined weight loss status versus randomized group, where data with no weight change were eliminated, and the LIVE group experienced significantly more weight loss than the control group (P=.04). There were no significant differences between groups in changes in physical activity and dietary outcomes (all P>.05), but each group showed an increase in physical activity. Both groups experienced a decrease in mean HbA level, systolic and diastolic blood pressure, cholesterol, and triglycerides over the course of 12 months of study participation, including those participants whose baseline HbA level was 8.6% or higher. This study confirmed that there were minor positive changes on glycemic targets in both groups over the 12-month study period; however, the majority of the participants began with optimal HbA levels. We did find clinically relevant metabolic changes in those who began with an HbA level >8.6% in both groups. This study provided a variety of resources to our participants in both study groups, and we conclude that a toolkit with a variety of services would be helpful to improving self-care in the future for persons with T2DM. ClinicalTrials.gov NCT02040038; https://clinicaltrials.gov/ct2/show/NCT02040038.

    Abstract Summary: Doctors wanted to see if a special online 3D world could help adults with type 2 diabetes take better care of themselves compared to a regular website with the same information. They had 211 people join the study and split them into two groups. One group used the 3D world, and the other group used the regular website. They checked on the participants after 3, 6, and 12 months to see how they were doing with their eating, exercise, and health numbers like blood sugar and cholesterol. After a year, they found that the people using the 3D world lost a bit more weight than the other group, but both groups got more active and had better health numbers. This was especially true for people who started with higher blood sugar levels. The study showed that having different kinds of help, like the 3D world and the website, can make it easier for people with diabetes to take care of their health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Longitudinal associations between perceived stress and anhedonia during psychotherapy.
    Journal of affective disorders (2023)
    Phillips R, Walsh E, Jensen T, Nagy G, Kinard J, Cernasov P, Smoski M, Dichter G. Longitudinal associations between perceived stress and anhedonia during psychotherapy. J Affect Disord. 2023 Jun 1; 330:206-213.
    Abstract: Chronic stress alters reward sensitivity and contributes to the emergence of anhedonia. In clinical samples, the perception of stress is a strong predictor of anhedonia. While there is substantial evidence demonstrating psychotherapy reduces perceived stress, little is known regarding the effects of treatment-related decreases in perceived stress on anhedonia. The current study investigated reciprocal relations between perceived stress and anhedonia using a cross-lagged panel model approach in a 15-week clinical trial examining the effects of Behavioral Activation Treatment for Anhedonia (BATA), a novel psychotherapy to treat anhedonia, compared to a Mindfulness-Based Cognitive Therapy (MBCT) comparison intervention (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Treatment completers (n = 72) experienced significant reductions in anhedonia (M = -8.94, SD = 5.66) on the Snaith-Hamilton Pleasure Scale (t(71) = 13.39, p < .0001), and significant reductions in perceived stress (M = -3.71, SD = 3.88) on the Perceived Stress Scale (t(71) = 8.11, p < .0001) following treatment. Across all treatment-seeking participants (n = 87), a longitudinal autoregressive cross-lagged model revealed significant paths showing that higher levels of perceived stress at treatment Week 1 predicted reductions in anhedonia at treatment Week 4; lower levels of perceived stress at Week 8 predicted reductions in anhedonia at Week 12. Anhedonia did not significantly predict perceived stress at any stage of treatment. This study showed specific timing and directional effects of perceived stress on anhedonia during psychotherapy treatment. Individuals with relatively high perceived stress at the start of treatment were more likely to report relatively lower anhedonia a few weeks into treatment. At mid-treatment, individuals with low perceived stress were more likely to report lower anhedonia towards the end of treatment. These results demonstrate that early treatment components reduce perceived stress, thus allowing for downstream changes in hedonic functioning during mid-late treatment. The findings presented here suggest it will be critically important for future clinical trials evaluating novel interventions for anhedonia to measure stress levels repeatedly, as an important mechanism of change. Development of a Novel Transdiagnostic Intervention for Anhedonia - R61 Phase. TRIAL URL: https://clinicaltrials.gov/ct2/show/NCT02874534. NCT02874534.

    Abstract Summary: Scientists did a study to see if a new kind of therapy could help people who don't feel pleasure from things they used to enjoy, a problem called anhedonia. They also wanted to know if feeling less stressed out could make people feel more pleasure again. They had 72 people try two different therapies for 15 weeks. They found that both therapies helped people feel less stressed and more able to enjoy things. They also learned that if people felt less stressed at the beginning of therapy, they were more likely to start enjoying things a few weeks later. This study tells us that it's really important to check how stressed someone is when they're getting treatment for not feeling pleasure, because feeling less stressed can help them get better.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The Preventing Alzheimer's with Cognitive Training (PACT) randomized clinical trial.
    Contemporary clinical trials (2022)
    Nicholson JS, Hudak EM, Phillips CB, Chanti-Ketterl M, O'Brien JL, Ross LA, Lister JJ, Burke JR, Potter G, Plassman BL, Woods AJ, Krischer J, Edwards JD. The Preventing Alzheimer's with Cognitive Training (PACT) randomized clinical trial. Contemp Clin Trials. 2022 Dec; 123:106978.
    Abstract: To address the rising prevalence of Alzheimer's disease and related dementias, effective interventions that can be widely disseminated are warranted. The Preventing Alzheimer's with Cognitive Training study (PACT) investigates a commercially available computerized cognitive training program targeting improved Useful Field of View Training (UFOVT) performance. The primary goal is to test the effectiveness of UFOVT to reduce incidence of clinically defined mild cognitive impairment (MCI) or dementia with a secondary objective to examine if effects are moderated by plasma β-amyloid level or apolipoprotein E e4 (APOE e4) allele status. This multisite study utilizes a randomized, controlled experimental design with blinded assessors and investigators. Individuals who are 65 years of age and older are recruited from the community. Eligible participants who demonstrate intact cognitive status (Montreal Cognitive Assessment score > 25) are randomized and asked to complete 45 sessions of either a commercially available computerized-cognitive training program (UFOVT) or computerized games across 2.5 years. After three years, participants are screened for cognitive decline. For those demonstrating decline or who are part of a random subsample, a comprehensive neuropsychological assessment is completed. Those who perform below a pre-specified level are asked to complete a clinical evaluation, including an MRI, to ascertain clinical diagnosis of normal cognition, MCI, or dementia. Participants are asked to provide blood samples for analyses of Alzheimer's disease related biomarkers. The PACT study addresses the rapidly increasing prevalence of dementia. Computerized cognitive training may provide a non-pharmaceutical option for reducing incidence of MCI or dementia to improve public health. The PACT study is registered at http://Clinicaltrials.govNCT03848312.

    Abstract Summary: Scientists are studying a computer program to see if it can help older people's brains stay sharp and possibly prevent memory problems like Alzheimer's disease. People who are 65 or older and still have good thinking skills can join the study. They will either play special brain-training games or other computer games for a while. After three years, the researchers will check to see if their brains are still working well. They will also look at their blood to find clues about brain health. This study is important because it might give us a new way to keep our brains healthy without using medicine.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Interventions for interpersonal communication about end of life care between health practitioners and affected people.
    The Cochrane database of systematic reviews (2022)
    Ryan RE, Connolly M, Bradford NK, Henderson S, Herbert A, Schonfeld L, Young J, Bothroyd JI, Henderson A. Interventions for interpersonal communication about end of life care between health practitioners and affected people. Cochrane Database Syst Rev. 2022 Jul 8; 7(7):CD013116.
    Abstract: Communication about end of life (EoL) and EoL care is critically important for providing quality care as people approach death. Such communication is often complex and involves many people (patients, family members, carers, health professionals). How best to communicate with people in the period approaching death is not known, but is an important question for quality of care at EoL worldwide. This review fills a gap in the evidence on interpersonal communication (between people and health professionals) in the last year of life, focusing on interventions to improve interpersonal communication and patient, family member and carer outcomes. To assess the effects of interventions designed to improve verbal interpersonal communication about EoL care between health practitioners and people affected by EoL. We searched CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL from inception to July 2018, without language or date restrictions. We contacted authors of included studies and experts and searched reference lists to identify relevant papers. We searched grey literature sources, conference proceedings, and clinical trials registries in September 2019. Database searches were re-run in June 2021 and potentially relevant studies listed as awaiting classification or ongoing. This review assessed the effects of interventions, evaluated in randomised and quasi-randomised trials, intended to enhance interpersonal communication about EoL care between patients expected to die within 12 months, their family members and carers, and health practitioners involved in their care. Patients of any age from birth, in any setting or care context (e.g. acute catastrophic injury, chronic illness), and all health professionals involved in their care were eligible. All communication interventions were eligible, as long as they included interpersonal interaction(s) between patients and family members or carers and health professionals. Interventions could be simple or complex, with one or more communication aims (e.g. to inform, skill, engage, support). Effects were sought on outcomes for patients, family and carers, health professionals and health systems, including adverse (unintended) effects. To ensure this review's focus was maintained on interpersonal communication in the last 12 months of life,  we excluded studies that addressed specific decisions, shared or otherwise, and the tools involved in such decision-making. We also excluded studies focused on advance care planning (ACP) reporting ACP uptake or completion as the primary outcome. Finally, we excluded studies of communication skills training for health professionals unless patient outcomes were reported as primary outcomes. Standard Cochrane methods were used, including dual review author study selection, data extraction and quality assessment of the included studies. Eight trials were included. All assessed intervention effects compared with usual care. Certainty of the evidence was low or very low. All outcomes were downgraded for indirectness based on the review's purpose, and many were downgraded for imprecision and/or inconsistency. Certainty was not commonly downgraded for methodological limitations. A summary of the review's findings is as follows. Knowledge and understanding (four studies, low-certainty evidence; one study without usable data): interventions to improve communication (e.g. question prompt list, with or without patient and physician training) may have little or no effect on knowledge of illness and prognosis, or information needs and preferences, although studies were small and measures used varied across trials.  Evaluation of the communication (six studies measuring several constructs (communication quality, patient-centredness, involvement preferences, doctor-patient relationship, satisfaction with consultation), most low-certainty evidence): across constructs there may be minimal or no effects of interventions to improve EoL communication, and there is uncertainty about effects of interventions such as a patient-specific feedback sheet on quality of communication.  Discussions of EoL or EoL care (six studies measuring selected outcomes, low- or very low-certainty evidence): a family conference intervention may increase duration of EoL discussions in an intensive care unit (ICU) setting, while use of a structured serious illness conversation guide may lead to earlier discussions of EoL and EoL care (each assessed by one study). We are uncertain about effects on occurrence of discussions and question asking in consultations, and there may be little or no effect on content of communication in consultations.  Adverse outcomes or unintended effects (limited evidence): there is insufficient evidence to determine whether there are adverse outcomes associated with communication interventions  (e.g. question prompt list, family conference, structured discussions) for EoL and EoL care. Patient and/or carer anxiety was reported by three studies, but judged as confounded. No other unintended consequences, or worsening of desired outcomes, were reported. Patient/carer quality of life (four studies, low-certainty evidence; two without useable data): interventions to improve communication may have little or no effect on quality of life.  Health practitioner outcomes (three studies, low-certainty evidence; two without usable data): interventions to improve communication may have little or no effect on health practitioner outcomes (satisfaction with communication during consultation; one study); effects on other outcomes (knowledge, preparedness to communicate) are unknown. Health systems impacts: communication interventions (e.g. structured EoL conversations) may have little or no effect on carer or clinician ratings of quality of EoL care (satisfaction with care, symptom management, comfort assessment, quality of care) (three studies, low-certainty evidence), or on patients' self-rated care and illness, or numbers of care goals met (one study, low-certainty evidence). Communication interventions (e.g. question prompt list alone or with nurse-led communication skills training) may slightly increase mean consultation length (two studies), but other health service impacts (e.g. hospital admissions) are unclear. Findings of this review are inconclusive for practice. Future research might contribute meaningfully by seeking to fill gaps for populations not yet studied in trials; and to develop responsive outcome measures with which to better assess the effects of communication on the range of people involved in EoL communication episodes. Mixed methods and/or qualitative research may contribute usefully to better understand the complex interplay between different parties involved in communication, and to inform development of more effective interventions and appropriate outcome measures. Co-design of such interventions and outcomes, involving the full range of people affected by EoL communication and care, should be a key underpinning principle for future research in this area.

    Abstract Summary: This study looked at how to improve conversations between doctors, patients, and families about end-of-life care. The researchers looked at different ways to help these conversations, like using a list of questions or giving feedback to doctors. They found that these methods might not make a big difference in how much people understand about their illness, how they feel about their conversations with doctors, or their quality of life. They also didn't find any bad effects from these methods. The researchers think more studies are needed to find the best ways to help these important conversations. This could help make sure people get the best care when they are very sick.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Four Conversations: A Randomized Controlled Trial of an Online, Personalized Coping and Decision Aid for Metastatic Breast Cancer Patients.
    Journal of palliative medicine (2020)
    Smith SK, Westbrook K, MacDermott K, Amarasekara S, LeBlanc M, Pan W. Four Conversations: A Randomized Controlled Trial of an Online, Personalized Coping and Decision Aid for Metastatic Breast Cancer Patients. J Palliat Med. 2020 Mar; 23(3):353-358.
    Abstract: Anticipating and making health care decisions about appropriate or preferred treatment around end-of-life care are intellectually challenging and emotionally distressing for metastatic breast cancer (MBC) patients, new interventions are needed. This study examined the effect of , an online and personalized coping and decision aid curriculum, on the completion of advance care directives and shared decision making among patients and their loved ones, clinicians, and spirit. Participants were randomized 1:1 to or wait-listed usual care conditions. Adult breast cancer survivors with metastatic disease were recruited nationally. Electronic surveys collected self-reported demographic, clinical, and outcome data at baseline and four weeks postintervention. Participants ( = 252) were mean age 53.6 ± 11.0 years; 100% female; 88% Caucasian; 67% married; and 33% employed. Over half (54%) of treatment arm participants without an advance directive completed one by study end, most (62%) felt that helped them quite a bit or a great deal in making a better decision, and 90% would recommend to others. Difference in the change in decisional conflict scores for treatment and control conditions was not significant ( = 0.07). These results suggest that facilitated the completion of advance care directives. Given that reductions in decisional conflict scores between the treatment and control arms were not significant, we cannot conclude that program use was associated with improved decisional conflict among MBC survivors. Online programs can be a feasible and effective alternative to in-person support.

    Abstract Summary: Doctors wanted to help women with advanced breast cancer make tough choices about their care, especially as they near the end of their lives. These decisions are really hard and can make people feel upset. The doctors created a special online program to see if it could help these women and their families talk about and decide on their medical care. They had some women use the program and others wait to use it. They found out that more than half of the women who used the program were able to make important health care choices and write them down, which is a big step. Most of them felt the program really helped them decide what was best for them, and they would tell others to use it too. However, the program didn't seem to make it easier for them to make decisions compared to those who didn't use it yet. This study shows that online help can be a good way for people to get support when they can't meet in person.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Longitudinal low density lipoprotein cholesterol goal achievement and cardiovascular outcomes among adult patients with familial hypercholesterolemia: The CASCADE FH registry.
    Atherosclerosis (2019)
    Duell PB, Gidding SS, Andersen RL, Knickelbine T, Anderson L, Gianos E, Shrader P, Kindt I, O'Brien EC, McCann D, Hemphill LC, Ahmed CD, Martin SS, Larry JA, Ahmad ZS, Kullo IJ, Underberg JA, Guyton J, Thompson P, Wilemon K, Roe MT, Rader DJ, Cuchel M, Li. Longitudinal low density lipoprotein cholesterol goal achievement and cardiovascular outcomes among adult patients with familial hypercholesterolemia: The CASCADE FH registry. Atherosclerosis. 2019 Oct; 289:85-93.
    Abstract: There are limited data from the US on outcomes of patients in specialty care for familial hypercholesterolemia (FH). CASCADE FH Registry data were analyzed to assess longitudinal changes in medication usage, in low density lipoprotein cholesterol (LDL-C) levels, and the rate of major adverse cardiovascular events (MACE (myocardial infarction, coronary revascularization, stroke or transient ischemic attack) in adults with FH followed in US specialty clinics. The cohort consisted of 1900 individuals (61% women, 87% Caucasian), with mean age of 56 ± 15 years, 37% prevalence of ASCVD at enrollment, mean pretreatment LDL-C 249 ± 68 mg/dl, mean enrollment LDL-C 145 mg/dl and 93% taking lipid lowering therapy. Over follow up of 20 ± 11 months, lipid lowering therapy use increased (mean decrease in LDL-C of 32 mg/dl (p < 0.001)). Only 48% of participants achieved LDL-C < 100 mg/dl and 22% achieved LDL-C < 70 mg/dl; ASCVD at enrollment was associated with greater likelihood of goal achievement. MACE event rates were almost 6 times higher among patients with prior ASCVD compared to those without (4.6 vs 0.8/100 patient years). Also associated with incident MACE were markers of FH severity and conventional ASCVD risk factors. With care in FH specialized clinics, LDL-C decreased, but LDL-C persisted >100 mg/dl in 52% of patients. High ASCVD event rates suggest that adults with FH warrant designation as having an ASCVD risk equivalent. Earlier and more aggressive therapy of FH is needed to prevent ASCVD events.

    Abstract Summary: This study looked at how well special clinics in the US are doing at treating a condition called familial hypercholesterolemia (FH), which is when you have really high cholesterol that runs in your family. They studied 1900 people, mostly women and white, who were about 56 years old on average. They found that while the clinics were able to lower patients' bad cholesterol levels, over half of the patients still had levels that were too high. Also, patients who already had heart disease when they started treatment were more likely to have serious heart problems later. This suggests that we need to start treating FH earlier and more aggressively to prevent heart disease.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Randomized Controlled Trial to Assess the Impact of Intraurethral Lidocaine on Urodynamic Voiding Parameters.
    Female pelvic medicine & reconstructive surgery (2019)
    Kisby CK, Gonzalez EJ, Visco AG, Amundsen CL, Grill WM. Randomized Controlled Trial to Assess the Impact of Intraurethral Lidocaine on Urodynamic Voiding Parameters. Female Pelvic Med Reconstr Surg. 2019 Jul/Aug; 25(4):265-270.
    Abstract: The aim of the study was to determine whether intraurethral anesthesia decreases voiding efficiency (VE; voided volume/(voided volume + residual volume)) and impacts other urodynamic parameters in healthy female volunteers during urodynamic studies. This was a randomized double-blind placebo-controlled study of asymptomatic women aged 18 to 60 years. Subjects completed a visual analog scale and baseline questionnaires to assess pain and lower urinary tract symptoms, respectively. They performed an uninstrumented baseline uroflow, followed by physiologic filling to 250 mL or greater. Subjects were randomized to receive 5 mL of intraurethral aqueous gel or 2% lidocaine gel and then underwent a second uninstrumented uroflow. They then completed complex cystometry, urethral pressure profilometry, and pressure-flow studies. Twenty-three randomized subjects (12 placebo, 11 lidocaine) were included. Baseline uroflow VE was similar between the placebo and lidocaine groups. After study drug administration, VE was not different between groups (89.3 [85.9-93.9] vs 89.5 [82.5-91.7], P = 0.74). There were also no differences between groups in visual analog scale scores, sensation during cystometry, maximum urethral closure pressure, or micturition parameters (maximum detrusor pressure and detrusor pressure at maximum flow). The placebo group had a lower percentage of interrupted flow pattern (0% vs 36%, P = 0.02) and a lower rate of increased electromyographic activity during micturition (25% vs 73%, P = 0.02). In this pilot study of 23 asymptomatic women, intraurethral administration of lidocaine did not decrease VE compared with placebo. The lidocaine group had a greater percentage of interrupted flow patterns and increased electromyographic activity during micturition.

    Abstract Summary: Scientists did a study to see if a numbing gel put inside the pee tube changes how well women can pee. They had 23 healthy women try peeing normally and then after using either the numbing gel or a fake gel. They checked how much pee came out and how much stayed inside. They also asked the women if they felt any pain and did some special tests to see how their pee muscles worked. They found that the numbing gel didn't make a big difference in how much pee came out. But, women who used the numbing gel had more stops and starts when they peed and their pee muscles were more active. This study helps us understand that the numbing gel doesn't make it harder for women to pee, but it might change the way they pee a little bit.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Creating a sustainable collaborative consumer health application for chronic disease self-management.
    Journal of biomedical informatics (2017)
    Johnson CM, McIlwain S, Gray O, Willson B, Vorderstrasse A. Creating a sustainable collaborative consumer health application for chronic disease self-management. J Biomed Inform. 2017 Jul; 71:198-206.
    Abstract: As the prevalence of chronic diseases increase, there is a need for consumer-centric health informatics applications that assist individuals with disease self-management skills. However, due to the cost of development of these applications, there is also a need to build a disease agnostic architecture so that they could be reused for any chronic disease. This paper describes the architecture of a collaborative virtual environment (VE) platform, LIVE©, that was developed to teach self-management skills and provide social support to those individuals with type 2 diabetes. However, a backend database allows for the application to be easily reused for any chronic disease. We tested its usability in the context of a larger randomized controlled trial of its efficacy. The usability was scored as 'good' by half of the participants in the evaluation. Common errors in the testing and solutions to address initial usability issues are discussed. Overall, LIVE© represents a usable and generalizable platform that will be adapted to other chronic diseases and health needs in future research and applications.

    Abstract Summary: Doctors want to help people with long-term sicknesses like diabetes take care of themselves better. They made a special computer program called LIVE© that can teach people skills and let them talk to others with the same sickness. This program is cool because it can be changed to help with lots of different sicknesses, not just one. They checked to see if the program was easy to use and half of the people said it was good. They found some mistakes, but they have ideas on how to fix them. This program could be really helpful for lots of sick people in the future.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effect of Continuous Positive Airway Pressure on Airway Reactivity in Asthma. A Randomized, Sham-controlled Clinical Trial.
    Annals of the American Thoracic Society (2016)
    Holbrook JT, Sugar EA, Brown RH, Drye LT, Irvin CG, Schwartz AR, Tepper RS, Wise RA, Yasin RZ, Busk MF, American Lung Association Airways Clinical Research Centers. Effect of Continuous Positive Airway Pressure on Airway Reactivity in Asthma. A Randomized, Sham-controlled Clinical Trial. Ann Am Thorac Soc. 2016 Nov; 13(11):1940-1950.
    Abstract: Studies have demonstrated that application of stress suppresses airway smooth muscle contractility. In animal models of asthma, continuous positive airway pressure (CPAP) reduced airway reactivity. Short-term studies of CPAP in patients with asthma showed reductions in airway reactivity. To evaluate whether nocturnal CPAP decreased the provocative concentration of methacholine to reduce FEV by 20% (PC). One hundred ninety-four individuals with asthma were randomized (1:1:1) to use CPAP with warmed, filtered, humidified air at night at pressures either less than 1 cm HO (sham) or at 5 cm HO or 10 cm HO. The primary outcome was change in PC after 12 weeks. Adherence to CPAP was low in all groups. Regardless, all groups had a significant improvement in PC, with 12 weeks/baseline PC ratios of 2.12, 1.73, and 1.78 for the sham, 5 cm HO, and 10 cm HO groups, respectively, and no significant differences between the active and sham groups. Changes in FEV and exhaled nitric oxide were minimal in all groups. The sham group had larger improvements in most patient-reported outcomes measuring asthma symptoms and quality of life, as well as sinus symptoms, than the 5 cm HO group. The 10 cm HO group showed similar but less consistent improvements in scores, which were not different from improvements in the sham group. Adherence to nocturnal CPAP was low. There was no evidence to support positive pressure as being effective for reducing airway reactivity in people with well-controlled asthma. Regardless, airway reactivity was improved in all groups, which may represent an effect of participating in a study and/or an effect of warm, humid, filtered air on airway reactivity. Clinical trial registered with www.clinicaltrials.gov (NCT01629823).

    Abstract Summary: Scientists wanted to see if using a special breathing machine at night could help people with asthma breathe better. They tested 194 people with asthma by giving them different levels of air pressure through the machine or a pretend (sham) treatment. They checked to see if the air pressure made it easier for the people to breathe after 12 weeks. They found out that all the groups, even the pretend one, got better at breathing, but the machine didn't seem to make a big difference. The scientists think that just being in the study or breathing warm, moist, clean air might have helped everyone breathe better. They also learned that not many people liked using the machine every night. This study shows that the special breathing machine might not be very helpful for people with asthma who already have their asthma under control.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Diabetes Learning in Virtual Environments: Testing the Efficacy of Self-Management Training and Support in Virtual Environments (Randomized Controlled Trial Protocol).
    Nursing research (2015)
    Vorderstrasse AA, Melkus GD, Pan W, Lewinski AA, Johnson CM. Diabetes Learning in Virtual Environments: Testing the Efficacy of Self-Management Training and Support in Virtual Environments (Randomized Controlled Trial Protocol). Nurs Res. 2015 Nov-Dec; 64(6):485-93.
    Abstract: Ongoing self-management improves outcomes for those with Type 2 diabetes (T2D); however, there are many barriers to patients receiving assistance in this from the healthcare system and peers. Findings from our pilot study showed that a virtual diabetes community on the Internet with real-time interaction among peers with T2D-and with healthcare professionals-is feasible and has the potential to influence clinical and psychosocial outcomes. The purpose of this article is to present the protocol for the Diabetes Learning in Virtual Environments (LIVE) trial. Diabetes LIVE is a two-group, randomized controlled trial to compare effects of a virtual environment and traditional Web site on diet and physical activity. Our secondary aims will determine the effects on metabolic outcomes; effects of level of engagement and social network formation in LIVE on behavioral outcomes; potential mediating effects of changes in self-efficacy; and diabetes knowledge, diabetes-related distress, and social support on behavior change and metabolic outcomes. We will enroll 300 subjects at two sites (Duke University/Raleigh-Durham, NC and New York University/New York, NY) who have T2D and do not have serious complications or comorbidities. Those randomly assigned to the intervention group have access to the LIVE site where they can find information, synchronous classes with diabetes educators, and peer support to enhance self-management. Those in the control group have access to the same informational and educational content in a traditional asynchronous Web format. Measures of self-management, clinical outcomes, and psychosocial outcomes are assessed at baseline and 3, 6, 12, and 18 months. Should LIVE prove effective in improved self-management of diabetes, similar interventions could be applied to other prevalent chronic diseases. Innovative programs such as LIVE have potential for improving healthcare access in an easily disseminated alternative model of care that potentially improves the reach of self-management training and support.

    Abstract Summary: Scientists are studying a new way to help people with Type 2 diabetes take care of their health. They created a special online place where people with diabetes can talk to each other and to doctors in real-time. This study, called the Diabetes Learning in Virtual Environments (LIVE) trial, will see if this online community is better than just using a regular website for learning about diet and exercise. They will have 300 people from two cities join the study. Some will use the new virtual community, and others will use a regular website. The researchers will check how well the participants manage their diabetes and how they feel emotionally over 18 months. If the virtual community helps people take better care of their diabetes, this idea could be used for other health problems too. This could make it easier for more people to get help and support for their health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Emory University
  • Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization.
    Neurorehabilitation and neural repair (2023)
    Buetefisch CM, Haut MW, Revill KP, Shaeffer S, Edwards L, Barany DA, Belagaje SR, Nahab F, Shenvi N, Easley K. Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization. Neurorehabil Neural Repair. 2023 Feb-Mar; 37(2-3):119-130.
    Abstract: After stroke, increases in contralesional primary motor cortex (M1) activity and excitability have been reported. In pre-clinical studies, M1 reorganization is related to the extent of ipsilesional M1 (M1) injury, but this has yet to be tested clinically. We tested the hypothesis that the extent of damage to the ipsilesional M1 and/or its corticospinal tract (CST) determines the magnitude of M1 reorganization and its relationship to affected hand function in humans recovering from stroke. Thirty-five participants with a single subacute ischemic stroke affecting M1 or CST and hand paresis underwent MRI scans of the brain to measure lesion volume and CST lesion load. Transcranial magnetic stimulation (TMS) of M1 was used to determine the presence of an electromyographic response (motor evoked potential (MEP+ and MEP-)). M1 reorganization was determined by TMS applied to M1 at increasing intensities. Hand function was quantified with the Jebsen Taylor Hand Function Test. The extent of M1 reorganization was related to greater lesion volume in the MEP- group, but not in the MEP+ group. Greater M1 reorganization was associated with more impaired hand function in MEP- but not MEP+ participants. Absence of an MEP (MEP-), larger lesion volumes and higher lesion loads in CST, particularly in CST fibers originating in M1 were associated with greater impairment of hand function. In the subacute post-stroke period, stroke volume and M1 output determine the extent of M1 reorganization and its relationship to affected hand function, consistent with pre-clinical evidence.ClinicalTrials.gov Identifier: NCT02544503.

    Abstract Summary: Scientists did a study to see how the brain changes after a stroke and how these changes affect the use of a person's hand. They looked at 35 people who had a stroke that made it hard for them to move their hand. They used a special machine to take pictures of their brains and another machine to test the muscles in their hands. They found that when the stroke damaged a bigger part of the brain, the brain tried to reorganize itself more, but this didn't always help the hand get better. In fact, if the stroke was really big or if the part of the brain that sends signals to the hand was hurt a lot, the hand didn't work as well. This study helps doctors understand that the size of the stroke and where it happens in the brain can affect how much the hand can recover after a stroke.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Development of a platform-based approach for the clinical production of HIV gp120 envelope glycoprotein vaccine candidates.
    Vaccine (2021)
    Wolfe LS, Smedley JG 3rd, Bubna N, Hussain A, Harper R, Mostafa S. Development of a platform-based approach for the clinical production of HIV gp120 envelope glycoprotein vaccine candidates. Vaccine. 2021 Jun 29; 39(29):3852-3861.
    Abstract: Preclinical development of vaccine candidates is an important link between the discovery and manufacture of vaccines for use in human clinical trials. Here, an exploratory clinical study utilizing multiple gp120 envelope proteins as vaccine antigens was pursued, which required a harmonized platform development approach for timely and efficient manufacture of the combined HIV vaccine product. Development of cell lines, processes, and analytical methods was initiated with a transmitted founder envelope protein (CH505TF), then applied to produce three subsequent gp120 Env (envelope) variants. Cell lines were developed using the commercially available Freedom CHO DG44 kit (Life Technologies). The fed-batch cell culture production process was based on a commercially-available medium with harmonized process parameters across the variants. A platform purification process was developed utilizing a mixed mode chromatography capture step, with ceramic hydroxyapatite and ion exchange polishing steps. A suite of analytical methods was developed to establish and monitor the Quality Target Profile (QTP), release and long-term stability testing of the vaccine products. The platform development strategy was successfully implemented to produce four gp120 envelope protein variants. In some cases, minor changes to the platform were required to optimize for a particular variant; however, baseline conditions for the processes (cell line type, media & feed system, chromatography resins, and analytical approaches) remained constant, leading to successful transfer and manufacture of all four proteins in a cGMP facility. This body of work demonstrates successful pursuit of a platform development approach to manufacture important vaccine candidates and can be used as a model for other vaccine glycoproteins, such as HIV gp140 trimers or other viral glycoproteins with global health implications. Clinical trial identifier. NCT03220724, NCT03856996.

    Abstract Summary: Scientists are working on a new way to make vaccines to fight HIV, a virus that can make people very sick. They tried a special method to make four different parts of the virus that the vaccine can use to teach the body to protect itself. They used the same tools and steps to make all four parts, which made the process faster and easier. They were able to make these parts in a way that is safe for use in people. This new method worked well and could help make other vaccines in the future. This is important because it could help us fight against other bad viruses and keep people healthy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Cardiovascular Risk and Resilience Among Black Adults: Rationale and Design of the MECA Study.
    Journal of the American Heart Association (2020)
    Islam SJ, Kim JH, Topel M, Liu C, Ko YA, Mujahid MS, Sims M, Mubasher M, Ejaz K, Morgan-Billingslea J, Jones K, Waller EK, Jones D, Uppal K, Dunbar SB, Pemu P, Vaccarino V, Searles CD, Baltrus P, Lewis TT, Quyyumi AA, Taylor H. Cardiovascular Risk and Resilience Among Black Adults: Rationale and Design of the MECA Study. J Am Heart Assoc. 2020 May 5; 9(9):e015247.
    Abstract: Background Cardiovascular disease incidence, prevalence, morbidity, and mortality have declined in the past several decades; however, disparities persist among subsets of the population. Notably, blacks have not experienced the same improvements on the whole as whites. Furthermore, frequent reports of relatively poorer health statistics among the black population have led to a broad assumption that black race reliably predicts relatively poorer health outcomes. However, substantial intraethnic and intraracial heterogeneity exists; moreover, individuals with similar risk factors and environmental exposures are often known to experience vastly different cardiovascular health outcomes. Thus, some individuals have good outcomes even in the presence of cardiovascular risk factors, a concept known as resilience. Methods and Results The MECA (Morehouse-Emory Center for Health Equity) Study was designed to investigate the multilevel exposures that contribute to "resilience" in the face of risk for poor cardiovascular health among blacks in the greater Atlanta, GA, metropolitan area. We used census tract data to determine "at-risk" and "resilient" neighborhoods with high or low prevalence of cardiovascular morbidity and mortality, based on cardiovascular death, hospitalization, and emergency department visits for blacks. More than 1400 individuals from these census tracts assented to demographic, health, and psychosocial questionnaires administered through telephone surveys. Afterwards, ≈500 individuals were recruited to enroll in a clinical study, where risk biomarkers, such as oxidative stress, and inflammatory markers, endothelial progenitor cells, metabolomic and microRNA profiles, and subclinical vascular dysfunction were measured. In addition, comprehensive behavioral questionnaires were collected and ideal cardiovascular health metrics were assessed using the American Heart Association's Life Simple 7 measure. Last, 150 individuals with low Life Simple 7 were recruited and randomized to a behavioral mobile health (eHealth) plus health coach or eHealth only intervention and followed up for improvement. Conclusions The MECA Study is investigating socioenvironmental and individual behavioral measures that promote resilience to cardiovascular disease in blacks by assessing biological, functional, and molecular mechanisms. REGISTRATION URL: https://www.clini​caltr​ials.gov. Unique identifier: NCT03308812.

    Abstract Summary: The MECA Study is a project that looks at why some black people in Atlanta, Georgia, stay healthy even when they live in areas with a lot of heart disease. Researchers identified neighborhoods with high and low rates of heart disease. They surveyed over 1400 people about their health and lifestyle, and did medical tests on about 500 of them. They also used a special measure called Life Simple 7 to see how healthy people's habits were. Finally, they gave 150 people with low Life Simple 7 scores a health coach or a health app to see if it helped them get healthier. The goal is to understand what helps people stay healthy even when they have risk factors for heart disease.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Development of the Adult Epilepsy Self-Management Measurement Instrument (AESMMI).
    Epilepsy & behavior : E&B (2015)
    Escoffery C, Bamps Y, LaFrance WC Jr, Stoll S, Shegog R, Buelow J, Shafer P, Thompson NJ, McGee RE, Hatfield K. Development of the Adult Epilepsy Self-Management Measurement Instrument (AESMMI). Epilepsy Behav. 2015 Sep; 50:172-83.
    Abstract: Epilepsy self-management is the total sum of steps that people perform to maximize seizure control, to minimize the impact of having a seizure disorder, and to maximize quality of life. As part of a phased approach to instrument development, we conducted descriptive analyses of data from epilepsy self-management items covering 10 domains of self-management gathered from 422 adults with epilepsy from multiple study sites. Participants most frequently reported performing sets of behaviors related to managing treatment and stigma, information seeking, managing symptoms, and communicating with providers. Behaviors reported with lower frequency were related to seeking social support and engaging in wellness behaviors. Significant differences for the domains were found for income, gender, and education levels but not for other different demographic variables. A subsequent analytic phase, reported in a companion article, will use factor analysis to identify and validate the subscale structure of the domains.

    Abstract Summary: Scientists did a study to learn how adults with epilepsy take care of themselves to control their seizures, lessen the problems epilepsy can cause, and live a better life. They asked 422 adults with epilepsy from different places about the things they do to manage their health. They found that these adults often did things like taking their medicine, learning about epilepsy, dealing with symptoms, and talking to their doctors. But they didn't often look for help from friends or do healthy activities as much. The study also found that how much money people make, whether they are a man or a woman, and how much school they've finished can change how they manage their epilepsy. This information is important because it can help everyone understand how to better support people with epilepsy in their daily lives.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Factor analyses of an Adult Epilepsy Self-Management Measurement Instrument (AESMMI).
    Epilepsy & behavior : E&B (2015)
    Escoffery C, Bamps Y, LaFrance WC Jr, Stoll S, Shegog R, Buelow J, Shafer P, Thompson NJ, McGee RE, Hatfield K. Factor analyses of an Adult Epilepsy Self-Management Measurement Instrument (AESMMI). Epilepsy Behav. 2015 Sep; 50:184-9.
    Abstract: The purpose of this study was to test the psychometric properties of an enhanced Adult Epilepsy Self-Management Measurement Instrument (AESMMI). An instrument of 113 items, covering 10 a priori self-management domains, was generated through a multiphase process, based on a review of the literature, validated epilepsy and other chronic condition self-management scales and expert input. Reliability and exploratory factor analyses were conducted on data collected from 422 adults with epilepsy. The instrument was reduced to 65 items, converging on 11 factors: Health-care Communication, Coping, Treatment Management, Seizure Tracking, Social Support, Seizure Response, Wellness, Medication Adherence, Safety, Stress Management, and Proactivity. Exploratory factors supported the construct validity for 6 a priori domains, albeit with significant changes in the retained items or in their scope and 3 new factors. One a priori domain was split in 2 subscales pertaining to treatment. The configuration of the 11 factors provides additional insight into epilepsy self-management behaviors. Internal consistency reliability of the 65-item instrument was high (α=.935). Correlations with independent measures of health status, quality of life, depression, seizure severity, and life impact of epilepsy further validated the instrument. This instrument shows potential for use in research and clinical settings and for assessing intervention outcomes and self-management behaviors in adults with epilepsy.

    Abstract Summary: This study aimed to test a new tool for measuring how well adults with epilepsy manage their condition. The researchers created a 113-question survey based on previous research and expert advice. They then tested this survey on 422 adults with epilepsy. After analyzing the results, they shortened the survey to 65 questions that cover 11 areas, such as communication with healthcare providers, coping strategies, and medication adherence. The survey was found to be reliable and accurately reflected the health status, quality of life, and severity of seizures in the participants. This tool could be useful in future research and in helping doctors understand how well their patients are managing their epilepsy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial.
    Kidney international (2015)
    Langefeld CD, Divers J, Pajewski NM, Hawfield AT, Reboussin DM, Bild DE, Kaysen GA, Kimmel PL, Raj DS, Ricardo AC, Wright JT Jr, Sedor JR, Rocco MV, Freedman BI, Systolic Blood Pressure Intervention Trial (SPRINT). Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial. Kidney Int. 2015 Jan; 87(1):169-75.
    Abstract: Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans (AAs). Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2571 AAs from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logistic regression models that adjusted for potentially important confounders tested for association between APOL1 risk variants and baseline clinical CVD (myocardial infarction, coronary, or carotid artery revascularization) and CKD (eGFR under 60 ml/min per 1.73 m(2) and/or UACR over 30 mg/g). AA SPRINT participants were 45.3% female with a mean (median) age of 64.3 (63) years, mean arterial pressure 100.7 (100) mm Hg, eGFR 76.3 (77.1) ml/min per 1.73 m(2), and UACR 49.9 (9.2) mg/g, and 8.2% had clinical CVD. APOL1 (recessive inheritance) was positively associated with CKD (odds ratio 1.37, 95% confidence interval 1.08-1.73) and log UACR estimated slope (β) 0.33) and negatively associated with eGFR (β -3.58), all significant. APOL1 risk variants were not significantly associated with prevalent CVD (1.02, 0.82-1.27). Thus, SPRINT data show that APOL1 risk variants are associated with mild CKD but not with prevalent CVD in AAs with a UACR under 1000 mg/g.

    Abstract Summary: Scientists studied a gene called APOL1 to see if it is linked to kidney disease and heart disease in African Americans. They looked at the health of 2,571 African Americans, checking their kidney function, the amount of protein in their urine, and if they had any heart problems. They found that people with certain versions of the APOL1 gene were more likely to have signs of early kidney disease, but these gene versions did not make it more likely for them to have heart disease. This information is important because it helps doctors understand who might be at risk for kidney disease, so they can watch and help these people more closely.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT).
    Clinical trials (London, England) (2014)
    Ambrosius WT, Sink KM, Foy CG, Berlowitz DR, Cheung AK, Cushman WC, Fine LJ, Goff DC Jr, Johnson KC, Killeen AA, Lewis CE, Oparil S, Reboussin DM, Rocco MV, Snyder JK, Williamson JD, Wright JT Jr, Whelton PK, SPRINT Study Research Group. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT). Clin Trials. 2014 Oct; 11(5):532-46.
    Abstract: High blood pressure is an important public health concern because it is highly prevalent and a risk factor for adverse health outcomes, including coronary heart disease, stroke, decompensated heart failure, chronic kidney disease, and decline in cognitive function. Observational studies show a progressive increase in risk associated with blood pressure above 115/75 mm Hg. Prior research has shown that reducing elevated systolic blood pressure lowers the risk of subsequent clinical complications from cardiovascular disease. However, the optimal systolic blood pressure to reduce blood pressure-related adverse outcomes is unclear, and the benefit of treating to a level of systolic blood pressure well below 140 mm Hg has not been proven in a large, definitive clinical trial. To describe the design considerations of the Systolic Blood Pressure Intervention Trial (SPRINT) and the baseline characteristics of trial participants. The Systolic Blood Pressure Intervention Trial is a multicenter, randomized, controlled trial that compares two strategies for treating systolic blood pressure: one targets the standard target of <140 mm Hg, and the other targets a more intensive target of <120 mm Hg. Enrollment focused on volunteers of age ≥50 years (no upper limit) with an average baseline systolic blood pressure ≥130 mm Hg and evidence of cardiovascular disease, chronic kidney disease, 10-year Framingham cardiovascular disease risk score ≥15%, or age ≥75 years. The Systolic Blood Pressure Intervention Trial recruitment also targeted three pre-specified subgroups: participants with chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m(2)), participants with a history of cardiovascular disease, and participants 75 years of age or older. The primary outcome is first the occurrence of a myocardial infarction (MI), acute coronary syndrome, stroke, heart failure, or cardiovascular disease death. Secondary outcomes include all-cause mortality, decline in kidney function or development of end-stage renal disease, incident dementia, decline in cognitive function, and small-vessel cerebral ischemic disease. Between 8 November 2010 and 15 March 2013, Systolic Blood Pressure Intervention Trial recruited and randomized 9361 people at 102 clinics, including 3331 women, 2648 with chronic kidney disease, 1877 with a history of cardiovascular disease, 3962 minorities, and 2636 ≥75 years of age. Although the overall recruitment target was met, the numbers recruited in the high-risk subgroups were lower than planned. The Systolic Blood Pressure Intervention Trial will provide important information on the risks and benefits of intensive blood pressure treatment targets in a diverse sample of high-risk participants, including those with prior cardiovascular disease, chronic kidney disease, and those aged ≥75 years.

    Abstract Summary: Doctors are studying how to best treat high blood pressure because it can lead to serious health problems like heart disease and strokes. They're doing a big study called the Systolic Blood Pressure Intervention Trial (SPRINT) to see if treating people to have a lower blood pressure than what is usually recommended is better for their health. They have two groups in the study: one group is treated to have their blood pressure below 140, and the other group is treated to have it even lower, below 120. They asked people over 50 years old with high blood pressure and other health risks, like heart disease or kidney problems, to join the study. They wanted to include lots of different people, including older adults and those with kidney disease or a history of heart problems. From 2010 to 2013, they got 9,361 people to join the study. They will watch these people to see if having a lower blood pressure prevents heart attacks, strokes, or other health issues. This study will help us understand if treating blood pressure more aggressively is a good idea for people with high health risks.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Social support for self-management behaviors among people with epilepsy: a content analysis of the WebEase program.
    Epilepsy & behavior : E&B (2012)
    Walker ER, Bamps Y, Burdett A, Rothkopf J, Diiorio C. Social support for self-management behaviors among people with epilepsy: a content analysis of the WebEase program. Epilepsy Behav. 2012 Mar; 23(3):285-90.
    Abstract: Social support is an important component in managing epilepsy; however little is known about support provided to people with epilepsy. This study examined whom people with epilepsy identify as supportive, and how those individuals support people with epilepsy's self-management efforts. Data come from the WebEase project, an effective online epilepsy self-management program. People with epilepsy who participated in the pilot (n=35) and efficacy trials (n=118) were included. A content analysis was conducted on responses to open-ended questions related to support. The majority of participants provided information about their supporters. The number of support providers ranged from 0 to 6, with about 12% indicating no support. Parents and significant others were most commonly listed as supporters. Support providers mainly offer emotional and instrumental support, reminders and aid for taking medication, and support for self-management strategies. These results could be useful for interventions aimed at bolstering support in order to improve self-management.

    Abstract Summary: Scientists did a study to learn more about who helps people with epilepsy and how they help them take care of themselves. They looked at answers from people with epilepsy who used a helpful online program. Most people said they had someone to support them, like parents or a boyfriend or girlfriend. These supporters gave emotional help, reminded them to take their medicine, and helped with other ways to stay healthy. About 1 out of 10 people said they had no one to help them. Knowing this can help create better ways to support people with epilepsy in their daily lives.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Results of a research study evaluating WebEase, an online epilepsy self-management program.
    Epilepsy & behavior : E&B (2011)
    DiIorio C, Bamps Y, Walker ER, Escoffery C. Results of a research study evaluating WebEase, an online epilepsy self-management program. Epilepsy Behav. 2011 Nov; 22(3):469-74.
    Abstract: WebEase (Epilepsy Awareness, Support, and Education) is an online epilepsy self-management program to assist people with taking medication, managing stress, and improving sleep quality. The primary study aims were to determine if those who participated in WebEase demonstrated improvements in medication adherence, perceived stress, and sleep quality. Participants were randomized to a treatment (T) or waitlist control (WCL) group (n=148). At follow-up, participants in the T group reported higher levels of medication adherence than those in the WLC group. Analyses were also conducted comparing those who had completed WebEase modules with those who had not. Those who had completed at least some modules within the WebEase program reported higher levels of self-efficacy and a trend toward significance was observed for the group×time interactions for medication adherence, perceived stress, self-management, and knowledge. The results highlight the usefulness of online tools to support self-management among people with epilepsy.

    Abstract Summary: Scientists made a website called WebEase to help people with epilepsy take their medicine, feel less stressed, and sleep better. They wanted to see if the website really helped. Some people got to use the website right away (the treatment group), and some had to wait (the waitlist control group). There were 148 people in the study. After some time, the people who used the website were better at taking their medicine than those who had to wait. Also, the ones who did some of the website activities felt more confident and seemed to manage their epilepsy better. The study shows that websites like WebEase can really help people with epilepsy take care of themselves.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

George Washington University
  • Optimizing imitation: Examining cognitive factors leading to imitation, overimitation, and goal emulation in preschoolers.
    Journal of experimental child psychology (2021)
    Speidel R, Zimmermann L, Green L, Brito NH, Subiaul F, Barr R. Optimizing imitation: Examining cognitive factors leading to imitation, overimitation, and goal emulation in preschoolers. J Exp Child Psychol. 2021 Mar; 203:105036.
    Abstract: Humans imitate patently irrelevant actions known as overimitation, and rather than decreasing with age, overimitation increases with age. Whereas most overimitation research has focused on social factors associated with overimitation, comparatively little is known about the cognitive- and task-specific features that influence overimitation. Specifically, developmental contrasts between imitation and overimitation are confounded by the addition of irrelevant actions to causally necessary actions, increasing sequence length, cognitive load, and processing costs-variables known to be age dependent. We constructed a novel puzzle box task such that a four-step imitation, four-step overimitation, and two-step efficient sequence could be demonstrated using the same apparatus on video. In Experiments 1 and 2, 2.5- to 5-year-olds randomly assigned to imitation and overimitation groups performed significantly more target actions than baseline control groups. Rates of imitation and overimitation increased as a function of age, with older preschoolers outperforming younger preschoolers in both conditions. In Experiment 3, preschoolers were shown a video of an efficient two-step demonstration prior to testing. After they responded, they were shown a four-step overimitation video and were tested on the same puzzle box. Children imitated the efficient demonstration, but after watching the overimitation video, they also overimitated the irrelevant actions. Once again, older children overimitated more than younger children. Together, results show that preschoolers are faithful, flexible, and persistent overimitators. The fidelity and flexibility of overimitation are constrained not only by social factors but also by basic cognitive processes that vary across age groups. As these constraints diminish, overimitation and flexible (optimal) imitation increases.

    Abstract Summary: Scientists did a study to see why kids copy actions they don't need to do, which is called overimitation. They found out that as kids get older, they copy these extra actions even more. They made a special puzzle and showed kids videos on how to solve it in different ways: a simple way, a way with extra unnecessary steps, and a way that copied someone else. They noticed that older kids were better at copying both the necessary and the unnecessary steps than younger kids. After watching a video with extra steps, even if kids knew a simpler way, they still copied the extra steps. This study helps us understand that not only do kids like to copy others, but as they grow up, they get even better at it, whether the actions are useful or not. This can teach us about how kids learn and think as they grow.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Applying computational modeling to assess age-, sex-, and strategy-related differences in Spin the Pots, a working memory task for 2- to 4-year-olds.
    Developmental psychobiology (2021)
    Zimmermann L, Frank HE, Subiaul F, Barr R. Applying computational modeling to assess age-, sex-, and strategy-related differences in Spin the Pots, a working memory task for 2- to 4-year-olds. Dev Psychobiol. 2021 Jan; 63(1):42-53.
    Abstract: Working memory (WM) develops rapidly during early childhood. In the present study, visual WM (VSM) was measured using the well-established Spin the Pots task (Hughes & Ensor, 2005), a complex non-verbal eight-location object occlusion task. A self-ordered hiding procedure was adopted to allow for an examination of children's strategy use during a VWM task. Participants (N = 640) between the ages of 2 and 4 years were tested under semi-naturalistic conditions, in the home or in a museum. Computational modeling was used to estimate an expected value for the total trials to complete Spin the Pots via a random search and child performance was compared to expected values. Based on this approach, we determined that children who found six stickers retrieved them in significantly fewer trials than the expected value, excluding chance performance and implicating VWM. Results also showed age-related and sex-related changes in VWM. Between 2 and 4 years of age, 4-year-olds performed significantly better than younger children and girls out-performed the boys. Spontaneous use of a color matching hiding strategy was associated with a higher success rate on the task. Implications of these findings for early development of VWM are discussed.

    Abstract Summary: Scientists did a study to learn about how young kids remember things they see. They used a game called "Spin the Pots" where kids had to remember where hidden stickers were. They had 640 kids, ages 2 to 4, play this game at home or in a museum. They used math to guess how many tries it should take to find all the stickers by chance. They found that kids were actually better at finding the stickers than just guessing. Older kids and girls were especially good at this. Some kids used colors to help them remember where they put the stickers, and this strategy worked really well. This study helps us understand how kids start to get better at remembering things they see as they grow up.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Specialization in the vicarious learning of novel arbitrary sequences in humans but not orangutans.
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences (2020)
    Renner E, Patterson EM, Subiaul F. Specialization in the vicarious learning of novel arbitrary sequences in humans but not orangutans. Philos Trans R Soc Lond B Biol Sci. 2020 Aug 17; 375(1805):20190442.
    Abstract: Sequence learning underlies many uniquely human behaviours, from complex tool use to language and ritual. To understand whether this fundamental cognitive feature is uniquely derived in humans requires a comparative approach. We propose that the vicarious (but not individual) learning of novel arbitrary sequences represents a human cognitive specialization. To test this hypothesis, we compared the abilities of human children aged 3-5 years and orangutans to learn different types of arbitrary sequences (item-based and spatial-based). Sequences could be learned individually (by trial and error) or vicariously from a human (social) demonstrator or a computer (ghost control). We found that both children and orangutans recalled both types of sequence following trial-and-error learning; older children also learned both types of sequence following social and ghost demonstrations. Orangutans' success individually learning arbitrary sequences shows that their failure to do so in some vicarious learning conditions is not owing to general representational problems. These results provide new insights into some of the most persistent discontinuities observed between humans and other great apes in terms of complex tool use, language and ritual, all of which involve the cultural learning of novel arbitrary sequences. This article is part of the theme issue 'Ritual renaissance: new insights into the most human of behaviours'.

    Abstract Summary: Scientists wanted to find out if learning patterns of behavior by watching others is something special to humans. They did an experiment with young kids and orangutans, where they had to learn patterns either by trying themselves or by watching someone else do it first. They found that both kids and orangutans could learn by trying, but only the older kids could learn by watching. This shows that orangutans can learn patterns, but not as well by watching others. This study helps us understand how humans are different from other animals when it comes to learning new things like using tools, speaking, and following traditions.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Only domain-specific imitation practice makes imitation perfect.
    Journal of experimental child psychology (2019)
    Subiaul F, Patterson EM, Zimmermann L, Barr R. Only domain-specific imitation practice makes imitation perfect. J Exp Child Psychol. 2019 Jan; 177:248-264.
    Abstract: Does imitation involve specialized mechanisms or general-unspecialized-learning processes? To address this question, preschoolers (3- and 4-year-olds) were assigned to one of four "practice" groups. Before and after the practice phases, each group was tested on a novel Spatial Imitation sequence. During the practice phase, children in the Spatial Imitation group practiced jointly attending, vicariously encoding, and copying the novel spatial sequences. In the Item Imitation group, children practiced jointly attending, vicariously encoding, and copying novel item sequences. In the Trial-and-Error group, children practiced encoding and recalling a series of novel spatial sequences entirely through individual (operant) learning. In the Free Play (no practice) control group, children played a touchscreen drawing game that controlled for practice time on the touchscreen and mirrored some of the same actions and responses used in the experimental conditions. Results of the difference between pre- and post-practice effects on novel spatial imitation sequences showed that only the Spatial Imitation practice group significantly improved relative to the Free Play group. Individual Spatial Trial-and-Error practice did not significantly improve spatial imitation. The effect of Item Imitation practice was intermediate. These results are inconsistent with the hypothesis that general processes alone--or primarily--support imitation learning and is more consistent with a mosaic model that posits an additive-interaction-effect on imitation performance where a more general social cognitive mechanism (i.e., natural pedagogy) gathers the relevant information from the demonstration and another more specialized mechanism (i.e., imitation specific) transforms that information into a matching response.

    Abstract Summary: Scientists wanted to know if kids learn to copy actions because they have a special skill for it or just because they learn like they do other things. They had a group of 3- and 4-year-olds practice different activities. Some kids practiced copying where things were placed, others copied different items, some tried to remember things on their own, and a last group just played a drawing game on a touchscreen. After practicing, they checked if the kids got better at copying new actions. Only the kids who practiced copying where things were placed got much better. This means that copying might be a special skill that kids have, not just a regular way of learning. This is important because it helps us understand how kids learn and could help in teaching them new things.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Children with autism spectrum disorder have an exceptional explanatory drive.
    Autism : the international journal of research and practice (2016)
    Rutherford MD, Subiaul F. Children with autism spectrum disorder have an exceptional explanatory drive. Autism. 2016 Aug; 20(6):744-53.
    Abstract: An "explanatory drive" motivates children to explain ambiguity. Individuals with autism spectrum disorders are interested in how systems work, but it is unknown whether they have an explanatory drive. We presented children with and without autism spectrum disorder unsolvable problems in a physical and in a social context and evaluated problem-solving and explanation-seeking responses. In the physical context (but not the social context), the children with autism spectrum disorder showed a stronger explanatory drive than controls. Importantly, the number of explanatory behaviors made by children with autism spectrum disorder in the social context was independent of social and communicative impairments. Children with autism spectrum disorder did not show an exceptional explanatory drive in the social domain. These results suggest that children with autism spectrum disorder have an explanatory drive and that the explanatory drive may be domain specific.

    Abstract Summary: This study wanted to see if kids with autism are driven to explain things they don't understand, just like other kids. The researchers gave kids with and without autism some problems they couldn't solve, both about physical things and about social situations. They found that kids with autism were really driven to explain the physical problems, but not the social ones. This didn't change even if the kids with autism had trouble with social skills or communication. So, it seems like kids with autism do have a drive to explain things, but it might only apply to certain areas.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The cognitive structure of goal emulation during the preschool years.
    The British journal of developmental psychology (2016)
    Subiaul F, Patterson EM, Barr R. The cognitive structure of goal emulation during the preschool years. Br J Dev Psychol. 2016 Mar; 34(1):132-49.
    Abstract: Humans excel at mirroring both others' actions (imitation) as well as others' goals and intentions (emulation). As most research has focused on imitation, here we focus on how social and asocial learning predict the development of goal emulation. We tested 215 preschool children on two social conditions (imitation, emulation) and two asocial conditions (trial-and-error and recall) using two touch screen tasks. The tasks involved responding to either three different pictures in a specific picture order (Cognitive: apple→boy→cat) or three identical pictures in a specific spatial order (Motor-Spatial: up→down→right). Generalized linear models demonstrated that during the preschool years, Motor-Spatial emulation is associated with social and asocial learning, while cognitive emulation is associated only with social learning, including motor-spatial emulation and multiple forms of imitation. This result contrasts with those from a previous study using this same data set showing that motor-spatial and cognitive imitation were neither associated with one another nor, generally, predicted by other forms of social or asocial learning. Together, these results suggests that while developmental changes in imitation are associated with multiple - specialized - mechanisms, developmental changes in emulation are associated with age-related changes and a more unitary, domain-general mechanism that receives input from several different cognitive and learning processes, including some that may not necessarily be specialized for social learning.

    Abstract Summary: Scientists wanted to learn more about how kids learn by copying others' goals and actions. They had 215 preschool kids play two games on touch screens. One game was about remembering and touching pictures in a certain order, like apple, boy, cat. The other game was about touching the same picture in different places, like up, then down, then right. They found that the kids learned to copy goals and actions both when they were with others and when they were alone. But, learning to remember and touch the pictures in order was mostly learned with others. This study helps us understand that as kids grow, they get better at copying goals in different ways, and this can happen when they're playing alone or with friends.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Sequential recall of meaningful and arbitrary sequences by orangutans and human children: Does content matter?
    Animal cognition (2016)
    Renner E, Price EE, Subiaul F. Sequential recall of meaningful and arbitrary sequences by orangutans and human children: Does content matter? Anim Cogn. 2016 Jan; 19(1):39-52.
    Abstract: Do visual cues such as size, color, and number facilitate sequential recall in orangutans and human children? In Experiment 1, children and adult orangutans solved two types of sequences, arbitrary (unrelated pictures) and meaningful (pictures varied along a spectrum according to the size, color, or number of items shown), in a touchscreen paradigm. It was found that visual cues did not increase the percentage of correct responses for either children or orangutans. In order to demonstrate that the failure to spontaneously seriate along these dimensions was not due to a general inability to perceive the dimensions nor to an inability to seriate items, in Experiment 2, orangutans were trained on one type of sequence and tested on novel sequences organized according to the same rule (i.e., pictures varied on the number spectrum only). The orangutans performed significantly better on novel meaningful sequences in this task than on novel arbitrary sequences. These results indicate that, while orangutans and human children share the ability to learn how to order items according to their size, color, or number, both orangutans and humans lack a cognitive propensity to spontaneously (i.e., without prior training or enculturation) order multiple items by size, color, or number.

    Abstract Summary: Scientists did a study to see if things like size, color, and how many there are help kids and orangutans remember the order of pictures. First, they showed them different pictures on a screen and asked them to remember the order. They tried with just random pictures and then with pictures that changed by size, color, or number. It turned out that these hints didn't really help either the kids or the orangutans remember better. Then, they trained the orangutans with one kind of picture order based on number and tested them with new pictures. After training, the orangutans did better at remembering the order when the pictures changed by number. This means that both kids and orangutans can learn to put things in order if they are taught how, but they don't just do it on their own without being taught. This is important because it helps us understand how kids and orangutans think and learn.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Becoming a high-fidelity - super - imitator: what are the contributions of social and individual learning?
    Developmental science (2015)
    Subiaul F, Patterson EM, Schilder B, Renner E, Barr R. Becoming a high-fidelity - super - imitator: what are the contributions of social and individual learning? Dev Sci. 2015 Nov; 18(6):1025-35.
    Abstract: In contrast to other primates, human children's imitation performance goes from low to high fidelity soon after infancy. Are such changes associated with the development of other forms of learning? We addressed this question by testing 215 children (26-59 months) on two social conditions (imitation, emulation) - involving a demonstration - and two asocial conditions (trial-and-error, recall) - involving individual learning - using two touchscreen tasks. The tasks required responding to either three different pictures in a specific picture order (Cognitive: Airplane→Ball→Cow) or three identical pictures in a specific spatial order (Motor-Spatial: Up→Down→Right). There were age-related improvements across all conditions and imitation, emulation and recall performance were significantly better than trial-and-error learning. Generalized linear models demonstrated that motor-spatial imitation fidelity was associated with age and motor-spatial emulation performance, but cognitive imitation fidelity was only associated with age. While this study provides evidence for multiple imitation mechanisms, the development of one of those mechanisms - motor-spatial imitation - may be bootstrapped by the development of another social learning skill - motor-spatial emulation. Together, these findings provide important clues about the development of imitation, which is arguably a distinctive feature of the human species.

    Abstract Summary: Scientists wanted to know if the way kids learn changes as they grow up. They tested 215 kids between 2 and 5 years old with games on a touchscreen. The kids had to remember and copy patterns with pictures or directions. The researchers found that older kids were better at copying and remembering than younger kids. They also noticed that kids were better at learning by watching others or remembering than by guessing. The study showed that as kids get older, they get better at copying movements and learning from others. This helps us understand how kids learn and why humans are good at learning from each other.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Working memory constraints on imitation and emulation.
    Journal of experimental child psychology (2014)
    Subiaul F, Schilder B. Working memory constraints on imitation and emulation. J Exp Child Psychol. 2014 Dec; 128:190-200.
    Abstract: Does working memory (WM) constrain the amount and type of information children copy from a model? To answer this question, preschool-age children (N=165) were trained and then tested on a touch-screen task that involved touching simultaneously presented pictures. Prior to responding, children saw a model generate two target responses: Order (touching all of the pictures on the screen in a target sequence three consecutive times) and Multi-Tap (consistently touching one of the pictures two times). Children's accuracy copying Order and Multi-Tap was assessed on two types of sequences: low WM load (2 pictures) and high WM load (3 pictures). Results showed that more children copied both Order and Multi-Tap on 2-picture sequences than on 3-picture sequences. Children who copied only one of the two target responses tended to copy only Order on 2-picture sequences but only Multi-Tap on 3-picture sequences. Instructions to either copy or ignore the Multi-Tap response did not affect this overall pattern of results. In sum, results are consistent with the hypothesis that WM constrains not just the amount but also the type of information children copy from models, potentially modulating whether children imitate or emulate in a given task.

    Abstract Summary: Scientists wanted to know if kids' memory affects how they copy what they see. They had 165 little kids do a game on a touch-screen where they had to touch pictures in a certain order or tap one picture twice, just like a grown-up showed them. They tried this with an easy version (2 pictures) and a harder one (3 pictures). They found out that kids were better at copying both things with the easy version. When kids only copied one thing, they chose different things for the easy and hard versions. Even when told to ignore the double-tap, kids still followed the same pattern. This study tells us that kids' memory might influence not only how much they copy, but also what they choose to copy, which can change the way they learn by watching others.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Multiple imitation mechanisms in children.
    Developmental psychology (2012)
    Subiaul F, Anderson S, Brandt J, Elkins J. Multiple imitation mechanisms in children. Dev Psychol. 2012 Jul; 48(4):1165-79.
    Abstract: Four studies using a computerized paradigm investigated whether children's imitation performance is content-specific and to what extent dependent on other cognitive processes such as trial-and-error learning, recall, and observational learning. Experiment 1 showed that 3-year-olds could successfully imitate what we call novel cognitive rules (e.g., first → second → third), which involved responding to 3 different pictures whose spatial configuration varied randomly from trial to trial. However, these same children failed to imitate what we call novel motor-spatial rules (e.g., up → down → right), which involved responding to 3 identical pictures that remained in a fixed spatial configuration from trial to trial. Experiment 2 showed that this dissociation was not due to a general difficulty in encoding motor-spatial content, as children successfully recalled, following a 30-s delay, a new motor-spatial sequence that had been learned by trial and error. Experiment 3 replicated these results and further demonstrated that 3-year-olds can infer a novel motor-spatial sequence following observation of a partially correct and partially incorrect response-a dissociation between imitation and observational learning (or emulation learning). Finally, Experiment 4 presented 3-year-olds with "familiar" motor-spatial sequences that involved making a linear response (e.g., left → middle → right) as well as "novel" motor-spatial sequences (e.g., right → up → down) used in Experiments 1-3 that were nonlinear and always involved a change in direction. Children had no difficulty imitating familiar motor-spatial sequences but again failed to imitate novel motor-spatial sequences. These results suggest that there may be multiple, dissociable imitation learning mechanisms that are content-specific. More importantly, the development of these imitation systems appears to be independent of the operations of other cognitive systems, including trial and error learning, recall, and observational learning.

    Abstract Summary: Scientists did four computer tests to see if kids copy actions in a special way and how this copying is linked to other ways of learning, like trying until you get it right, remembering, and watching then doing. In the first test, 3-year-olds could copy new thinking rules, like "first this, then that," with different pictures each time. But they couldn't copy new action rules, like "up then down," with the same picture staying in one place. The second test showed kids could remember new action rules they learned by trying many times, even after waiting for a little bit. The third test found that kids could figure out new action rules by watching someone else do it partly right and partly wrong. The fourth test showed kids could copy action rules they already knew, like "left to right," but not new, tricky ones. The big finding is that kids learn to copy in different ways, and this doesn't always mix with other ways of learning. This helps us understand how kids learn and could help in teaching them better.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The ghosts in the computer: the role of agency and animacy attributions in "ghost controls".
    PloS one (2011)
    Subiaul F, Vonk J, Rutherford MD. The ghosts in the computer: the role of agency and animacy attributions in "ghost controls". PLoS One. 2011; 6(11):e26429.
    Abstract: Three studies evaluated the role of 4-year-old children's agency- and animacy-attributions when learning from a computerized ghost control (GC). In GCs, participants observe events occurring without an apparent agent, as if executed by a "ghost" or unobserved causal forces. Using a touch-screen, children in Experiment 1 responded to three pictures in a specific order under three learning conditions: (i) trial-and-error (Baseline), (ii) imitation and (iii) Ghost Control. Before testing in the GC, children were read one of three scripts that determined agency attributions. Post-test assessments confirmed that all children attributed agency to the computer and learned in all GCs. In Experiment 2, children were not trained on the computer prior to testing, and no scripts were used. Three different GCs, varying in number of agency cues, were used. Children failed to learn in these GCs, yet attributed agency and animacy to the computer. Experiment 3 evaluated whether children could learn from a human model in the absence of training under conditions where the information presented by the model and the computer was either consistent or inconsistent. Children evidenced learning in both of these conditions. Overall, learning in social conditions (Exp. 3) was significantly better than learning in GCs (Exp. 2). These results, together with other published research, suggest that children privilege social over non-social sources of information and are generally more adept at learning novel tasks from a human than from a computer or GC.

    Abstract Summary: Scientists did three experiments to see how 4-year-old kids think about and learn from a computer that seems to do things by itself, like a "ghost" is making it happen. In the first experiment, kids tried to remember a sequence of pictures by either guessing, copying someone, or using the "ghost" computer after hearing a story. They learned from all methods and thought the computer was doing things on purpose. In the second experiment, without any training or stories, the kids didn't learn from the "ghost" computer, but still thought it was doing things on purpose. In the third experiment, kids watched a person and then tried to do the same thing with or without the computer's help. They learned well this way, especially better than just from the "ghost" computer. The studies show that kids are better at learning from people than from computers that act on their own. This is important because it tells us that when teaching kids, having a person there to help is really useful.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Georgetown University
  • Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case-control study.
    Cardiovascular diabetology (2019)
    Gourgari E, Ma J, Playford MP, Mehta NN, Goldman R, Remaley AT, Gordon SM. Proteomic alterations of HDL in youth with type 1 diabetes and their associations with glycemic control: a case-control study. Cardiovasc Diabetol. 2019 Mar 28; 18(1):43.
    Abstract: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition. This was a cross-sectional case-control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification. Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P < 0.05), compared to HC. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in T1DM and not influenced by glycemic control (e.g. FHR2) while others were partially or completely corrected with optimal glucose control (e.g. alpha-1-beta glycoprotein, A1BG). In a subgroup of poorly controlled T1DM patients, inter alpha trypsin inhibitor 4 (ITIH4) was dramatically elevated (P < 0.0001) and this was partially reversed in patients with optimal glucose control. Some proteins including complement component C3 (CO3) and albumin (ALB) were significantly different only in T1DM patients with optimal glucose control, suggesting a possible effect of exogenous insulin. Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT02275091.

    Abstract Summary: This study looked at kids with type 1 diabetes and compared their blood to healthy kids. They found that even though both groups had the same amount of good cholesterol, the kids with diabetes had different proteins in their cholesterol. Some of these proteins changed depending on how well the diabetes was controlled. The study also found that some proteins were different only in kids with well-controlled diabetes, which might be due to the insulin they take. It's not clear yet what these changes mean for the kids' health, so more research is needed.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Low cholesterol efflux capacity and abnormal lipoprotein particles in youth with type 1 diabetes: a case control study.
    Cardiovascular diabetology (2018)
    Gourgari E, Playford MP, Campia U, Dey AK, Cogen F, Gubb-Weiser S, Mete M, Desale S, Sampson M, Taylor A, Rother KI, Remaley AT, Mehta NN. Low cholesterol efflux capacity and abnormal lipoprotein particles in youth with type 1 diabetes: a case control study. Cardiovasc Diabetol. 2018 Dec 19; 17(1):158.
    Abstract: Patients with type 1 diabetes (T1DM) have increased mortality from cardiovascular disease (CVD). Risk factors for CVD include an elevation of LDL (LDLp) and small HDL (sHDLp) particles, and a decrease in reverse cholesterol transport i.e. HDL-cholesterol efflux capacity (CEC). Our objective was to compare lipoprotein particles and CEC between T1DM and healthy controls (HC) and to explore the associations between NMR lipid particles and cholesterol efflux. 78 patients with T1DM and 59 HC underwent fasting lipoprotein profile testing by NMR and measurements of CEC by cell-based method. The associations between NMR lipid particles with CEC were analyzed using multivariable linear regression models. Youth with T1DM had higher total LDLp 724 [(563-985) vs 622 (476-794) nmol/L (P = 0.011)] (Maahs et al. in Circulation 130(17):1532-58, 2014; Shah et al. in Pediatr Diabetes 16(5):367-74, 2015), sHDLp [11.20 (5.7-15.3) vs 7.0 (3.2-13.1) μmol/L (P = 0.021)], and lower medium HDLp [11.20 (8.5-14.5) vs 12.3 (9-19.4), (P = 0.049)] and lower CEC (0.98 ± 0.11% vs 1.05 ± 0.15%, P = 0.003) compared to HC. Moreover, CEC correlated with sHDLp (β = - 0.28, P = 0.045) and large HDLp (β = 0.46, P < 0.001) independent of age, sex, ethnicity, BMIz, HbA1c, hsCRP and total HDLp in the diabetic cohort. Youth with T1DM demonstrated a more atherogenic profile including higher sHDL and LDLp and lower CEC. Future efforts should focus on considering adding lipoprotein particles and CEC in CVD risk stratification of youth with T1DM. Trial registration Clinical Trials Registration Number NCT02275091.

    Abstract Summary: Scientists did a study to see if young people with type 1 diabetes have different levels of certain fat particles in their blood that could make heart disease more likely. They compared these young people with diabetes to healthy kids. They found that the kids with diabetes had more bad fat particles and fewer good ones that help clean up cholesterol. This means they might have a higher chance of getting heart disease. The study suggests that doctors should check these fat particles in kids with diabetes to help prevent heart problems later on.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Is costly punishment altruistic? Exploring rejection of unfair offers in the Ultimatum Game in real-world altruists.
    Scientific reports (2016)
    Brethel-Haurwitz KM, Stoycos SA, Cardinale EM, Huebner B, Marsh AA. Is costly punishment altruistic? Exploring rejection of unfair offers in the Ultimatum Game in real-world altruists. Sci Rep. 2016 Jan 7; 6:18974.
    Abstract: In the Ultimatum Game (UG), incurring a cost to punish inequity is commonly termed altruistic punishment. This behaviour is thought to benefit others if the defector becomes more equitable in future interactions. However, clear connections between punishment in the UG and altruistic behaviours outside the laboratory are lacking. We tested the altruistic punishment hypothesis in a sample of extraordinarily altruistic adults, predicting that if punishing inequity is predictive of altruism more broadly, extraordinary altruists should punish more frequently. Results showed that punishment was not more prevalent in extraordinary altruists than controls. However, a self-reported altruism measure previously linked to peer evaluations but not behaviour, and on which extraordinary altruists and controls did not differ, did predict punishment. These findings support suggestions that altruistic punishment in the UG is better termed costly punishment and may be motivated by social, but not necessarily prosocial, concerns. Results also support prior suggestions that self-reported altruism may not reliably predict altruistic behaviour.

    Abstract Summary: Scientists did a study to see if people who are really nice and like to help others would also be more likely to punish someone for being unfair in a game where you decide how to split money. This game is called the Ultimatum Game. They thought that if you're someone who does a lot of good things for others, you might also be the kind of person who would punish someone for not sharing fairly. But when they looked at people who are known for being super kind, they found out that these people didn't punish unfairness any more than regular people. They also found out that just because someone says they are nice doesn't mean they will actually do nice things. This study helps us understand that being willing to lose something to punish someone might not always be about being nice to others; it could be for other reasons, like wanting to look good in front of friends.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Neural and cognitive characteristics of extraordinary altruists.
    Proceedings of the National Academy of Sciences of the United States of America (2014)
    Marsh AA, Stoycos SA, Brethel-Haurwitz KM, Robinson P, VanMeter JW, Cardinale EM. Neural and cognitive characteristics of extraordinary altruists. Proc Natl Acad Sci U S A. 2014 Oct 21; 111(42):15036-41.
    Abstract: Altruistic behavior improves the welfare of another individual while reducing the altruist's welfare. Humans' tendency to engage in altruistic behaviors is unevenly distributed across the population, and individual variation in altruistic tendencies may be genetically mediated. Although neural endophenotypes of heightened or extreme antisocial behavior tendencies have been identified in, for example, studies of psychopaths, little is known about the neural mechanisms that support heightened or extreme prosocial or altruistic tendencies. In this study, we used structural and functional magnetic resonance imaging to assess a population of extraordinary altruists: altruistic kidney donors who volunteered to donate a kidney to a stranger. Such donations meet the most stringent definitions of altruism in that they represent an intentional behavior that incurs significant costs to the donor to benefit an anonymous, nonkin other. Functional imaging and behavioral tasks included face-emotion processing paradigms that reliably distinguish psychopathic individuals from controls. Here we show that extraordinary altruists can be distinguished from controls by their enhanced volume in right amygdala and enhanced responsiveness of this structure to fearful facial expressions, an effect that predicts superior perceptual sensitivity to these expressions. These results mirror the reduced amygdala volume and reduced responsiveness to fearful facial expressions observed in psychopathic individuals. Our results support the possibility of a neural basis for extraordinary altruism. We anticipate that these findings will expand the scope of research on biological mechanisms that promote altruistic behaviors to include neural mechanisms that support affective and social responsiveness.

    Abstract Summary: Scientists did a study on people who are super kind—like those who give away a kidney to someone they don't know. They wanted to see if the brains of these super kind people worked differently. They used special machines to look at the brains of these kidney donors and compared them to other people. They found that a part of the super kind people's brains, called the right amygdala, was bigger and reacted more when they saw scared faces. This might mean they're really good at noticing when someone is scared. This is interesting because people who aren't very nice, like psychopaths, have a smaller right amygdala that doesn't react much to scared faces. This study helps us think that maybe our brains help us be kind to others, and scientists want to learn more about how our brains make us want to help people.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Indiana University
  • Developing the Opioid Rapid Response System™ for Lay Citizen Response to the Opioid Overdose Crisis: a Randomized Controlled Trial.
    Prevention science : the official journal of the Society for Prevention Research (2023)
    Hecht ML, Jayawardene W, Henderson C, Pezalla A, Flood-Grady E, Krieger JL, Frederick A, Parker M, Ables E. Developing the Opioid Rapid Response System™ for Lay Citizen Response to the Opioid Overdose Crisis: a Randomized Controlled Trial. Prev Sci. 2023 Oct; 24(7):1386-1397.
    Abstract: Emergency responders face challenges in arriving timely to administer naloxone in opioid overdoses. Therefore, interest in having lay citizens administer naloxone nasal spray has emerged. These citizens, however, must be recruited and trained, and be in proximity to the overdose. This study aimed to develop the Opioid Rapid Response System (ORRS) to meet this need by developing a system to recruit and train citizen responders and evaluate outcomes in a randomized clinical trial. ORRS recruitment messages and training platform were developed iteratively and then outcomes for each were evaluated in a randomized, unblinded two-arm waitlist-controlled trial. ORRS was field tested in 5 Indiana counties, recruiting adult citizen responders (age 18 or older) who did not self-identity as a certified first responder. Participants were recruited using either personal or communal messages and then randomly assigned to online naloxone training and waitlisted-control conditions. Pre- and post-surveys were administered online to measure the exposure to recruitment messages and training effects on knowledge of opioid overdose, confidence responding, concerns about responding, and intent to respond. Of the 220 randomized participants (114 training, 106 waitlisted-control), 140 were analyzed (59 training, 81 waitlisted-control). Recruited participants more frequently identified with communal appeal than with the personal appeal (chi-square = 53.5; p < 0.0001). Between-group differences for intervention effects were significant for knowledge of overdose signs (Cohen's d = 1.17), knowledge of overdose management (d = 1.72), self-efficacy (d = 1.39), and concerns (d = 1.31), but not for intent (d = 0.17), which suffered from a ceiling effect. ORRS provides stronger support for efficacy than that reported for other training interventions and the digital modality eases rapid dissemination.Trial Registration: NCT04589676.

    Abstract Summary: Scientists did a study to help regular people learn how to use a special nose spray to save someone who has taken too much of a strong pain medicine called opioids. They made a program called the Opioid Rapid Response System (ORRS) to teach people and see if it works. They tested it in Indiana with adults who weren't already trained to help in emergencies. They found out that people liked to join the program to help their community more than just for personal reasons. After training, these people knew more about how to tell if someone has taken too many opioids and felt more sure they could help. They also weren't as worried about helping, but their willingness to help didn't change much because they already wanted to help a lot. This study shows that teaching people online is a good way to quickly spread the knowledge on how to save lives with the nose spray.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Development of opioid rapid response system: Protocol for a randomized controlled trial.
    Contemporary clinical trials (2022)
    Jayawardene W, Pezalla A, Henderson C, Hecht M. Development of opioid rapid response system: Protocol for a randomized controlled trial. Contemp Clin Trials. 2022 Apr; 115:106727.
    Abstract: Opioid overdoses require a rapid response, but emergency responders are limited in how quickly they can arrive at the scene for administering naloxone. If laypersons are trained to administer naloxone and are notified of overdoses, more lives can be saved. This study aimed to examine the feasibility of the Opioid Rapid Response System (ORRS) that recruits, trains, and links citizen responders to overdose events in their community in real-time to administer naloxone. Aim of this paper is to present the protocols for recruiting participants through multiple communication channels; developing and evaluating the online training which has both interactive and asynchronous modules; randomly assigning laypersons to either online naloxone training or waitlist control group; measuring participants' knowledge, skills, and attitudes before and after the training; and distributing intranasal naloxone kits to participants for use in events of overdose in their community. Sampling: Utilizing a combination of purposive sampling methods, laypersons from across five Indiana counties who did not self-identify as current first responders were invited to participate. In this two-arm randomized waitlist-controlled study (N = 220), individuals were assigned into either online training or waitlist control that received the training two weeks later. A linear mixed model will be used for determining the changes in targeted outcomes in the training group and accommodate for fixed and random effects. While ORRS can become a community-engaged, cost-effective model for technology-based emergency response for opioid overdoses, study protocols can be useful for other emergency response programs that involve laypersons. gov Registration Number: NCT04589676.

    Abstract Summary: Scientists are trying to see if regular people, like you and me, can help save lives when someone has taken too many pain medicines called opioids. Sometimes, these medicines can make a person stop breathing, and they need a special medicine called naloxone really fast to wake up again. The study is about teaching people through the internet how to give naloxone to someone who needs it. They want to know if people can learn this online and then be ready to help in their own neighborhoods. They asked 220 people from five places in Indiana to join the study. Some people got the training right away, and others had to wait two weeks. They checked to see how much the people learned and if they felt okay about helping in an emergency. Everyone who learned got a naloxone kit to carry with them. The big idea is that if more people know how to use naloxone, they can help save lives before the ambulance arrives. This could be a smart and cheap way to help people who overdose on opioids, and the way they're doing this study might help with other emergencies too.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Johns Hopkins University
  • Immunomodulatory interventions for focal epilepsy.
    The Cochrane database of systematic reviews (2023)
    Panebianco M, Walker L, Marson AG. Immunomodulatory interventions for focal epilepsy. Cochrane Database Syst Rev. 2023 Oct 16; 10(10):CD009945.
    Abstract: This is an updated version of an original Cochrane Review published in 2013 (Walker 2013). Epilepsy is a common neurological disorder affecting 0.5% to 1% of the population. Pharmacological treatment remains the first choice to control epilepsy. However, up to 30% of people do not respond to drug treatment, and therefore do not achieve seizure remission. Experimental and clinical evidence supports a role for inflammatory pathway activation in the pathogenesis of epilepsy which, if effectively targeted by immunomodulatory interventions, highlights a potentially novel therapeutic strategy. To assess the efficacy and tolerability of immunomodulatory interventions on seizures, adverse effect profile, cognition, and quality of life, compared to placebo controls, when used as additional therapy for focal epilepsy in children and adults. For the latest update, we searched the following databases on 11 November 2021: Cochrane Register of Studies (CRS Web) and Medline (Ovid) 1946 to 10 November 2021. CRS Web includes randomised or quasi-randomised, controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. We placed no language restrictions. We reviewed the bibliographies of retrieved studies to search for additional reports of relevant studies. Randomised placebo-controlled trials of add-on immunomodulatory drug interventions, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded. Eligible participants were children (aged over 2 years) and adults with focal epilepsy. We used standard methodological procedures expected by the Cochrane Collaboration. We assessed the following outcomes. 1. 50% or greater reduction in seizure frequency. 2. Seizure freedom. 3. Treatment withdrawal for any reason. 4. Quality of life. 5. We used an intention-to-treat (ITT) population for all primary analyses, and we presented results as risk ratios (RRs) with 95% confidence intervals (95% Cl). We included three randomised, double-blind, placebo-controlled trials on a total of 172 participants. All trials included children and adults over two years of age with focal epilepsy. Treatment phases lasted six weeks and follow-up from six weeks to six months. One of the three included trials described an adequate method of concealment of randomisation, whilst the other two trials were rated as having an unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in all three trials. All analyses were by ITT. One trial was sponsored by the manufacturer of an immunomodulatory agent and therefore was at high risk of funding bias. Immunomodulatory interventions were significantly more effective than placebo in reducing seizure frequency (risk ratio (RR) 2.30, 95% confidence interval (CI) 1.15 to 4.60; 3 studies, 172 participants; moderate-certainty evidence). For treatment withdrawal, there was insufficient evidence to conclude that people were more likely to discontinue immunomodulatory intervention than placebo (RR 1.04, 95% CI 0.28 to 3.80; 3 studies, 172 participants; low-certainty evidence). The RR for adverse effects was 1.16 (95% CI 0.84 to 1.59; 1 study, 66 participants; low-certainty evidence). Certain adverse effects such as dizziness, headache, fatigue, and gastrointestinal disorders were more often associated with immunomodulatory interventions. There were little to no data on cognitive effects and quality of life. No important heterogeneity between studies was found for any of the outcomes. We judged the overall certainty of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals. Immunomodulatory interventions as add-on treatment for children and adults with focal epilepsy appear to be effective in reducing seizure frequency. It is not possible to draw any conclusions about the tolerability of these agents in children and adults with epilepsy. Further randomised controlled trials are needed.

    Abstract Summary: Scientists did a study to see if a new kind of medicine could help people with epilepsy, a brain problem that causes seizures. Some people with epilepsy don't get better with regular medicine, so the scientists wanted to see if medicines that change the immune system could help. They looked at three studies with 172 people who had a type of epilepsy that starts in one part of the brain. The new medicine seemed to help reduce seizures better than a fake medicine with no active ingredients. But they weren't sure if people would stop taking the new medicine because of side effects, like feeling dizzy or having a stomachache. They also didn't know if it would make people's thinking skills or how they felt about life any better. The scientists think more studies are needed to be sure if this new medicine is good for people with epilepsy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A technology-based intervention to improve safety, mental health and empowerment outcomes for immigrant women with intimate partner violence experiences: it's weWomen plus sequential multiple assignment randomized trial (SMART) protocol.
    BMC public health (2021)
    Sabri B, Glass N, Murray S, Perrin N, Case JR, Campbell JC. A technology-based intervention to improve safety, mental health and empowerment outcomes for immigrant women with intimate partner violence experiences: it's weWomen plus sequential multiple assignment randomized trial (SMART) protocol. BMC Public Health. 2021 Oct 28; 21(1):1956.
    Abstract: Intimate partner violence (IPV) disproportionately affects immigrant women, an understudied and underserved population in need for evidence-based rigorously evaluated culturally competent interventions that can effectively address their health and safety needs. This study uses a sequential, multiple assignment, randomized trial (SMART) design to rigorously evaluate an adaptive, trauma-informed, culturally tailored technology-delivered intervention tailored to the needs of immigrant women who have experienced IPV. In the first stage randomization, participants are randomly assigned to an online safety decision and planning or a usual care control arm and safety, mental health and empowerment outcomes are assessed at 3-, 6- and 12-months post-baseline. For the second stage randomization, women who do not report significant improvements in safety (i.e., reduction in IPV) and empowerment from baseline to 3 months follow up (i.e., non-responders) are re- randomized to safety and empowerment strategies delivered via text only or a combination of text and phone calls with trained advocates. Data on outcomes (safety, mental health, and empowerment) for early non-responders is assessed at 6 and 12 months post re-randomization. The study's SMART design provides an opportunity to implement and evaluate an individualized intervention protocol for immigrant women based on their response to type or intensity of intervention. The findings will be useful for identifying what works for whom and characteristics of participants needing a particular type or intensity level of intervention for improved outcomes. If found to be effective, the study will result in an evidence-based trauma-informed culturally tailored technology-based safety decision and planning intervention for immigrant survivors of IPV that can be implemented by practitioners serving immigrant women in diverse settings. This trial was registered with ClinicalTrials.gov as NCT04098276 on September 13, 2019.

    Abstract Summary: This study is about helping immigrant women who have been hurt by their partners. The researchers are testing a special online program to see if it can make these women feel safer and stronger. First, the women are put into two groups. One group uses the online program, and the other group gets regular help. They check how the women are doing after 3, 6, and 12 months. If some women don't feel better after 3 months, they try different ways of helping them, like sending texts or making phone calls. The goal is to find the best way to help each woman. If the program works well, it could be used by people who help immigrant women everywhere. The study's number is NCT04098276, and it started on September 13, 2019.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center
  • Comparison of metabolic effects of the progestational androgens dimethandrolone undecanoate and 11β-MNTDC in healthy men.
    Andrology (2021)
    Yuen F, Thirumalai A, Fernando FA, Swerdloff RS, Liu PY, Pak Y, Hull L, Bross R, Blithe DL, Long JE, Page ST, Wang C. Comparison of metabolic effects of the progestational androgens dimethandrolone undecanoate and 11β-MNTDC in healthy men. Andrology. 2021 Sep; 9(5):1526-1539.
    Abstract: Dimethandrolone (DMA) and 11β-methyl-19-nortestosterone (11β-MNT) are two novel compounds with both androgenic and progestational activity that are under investigation as potential male hormonal contraceptives. Their metabolic effects have never been compared in men. Assess for changes in insulin sensitivity and adiponectin and compare the metabolic effects of these two novel androgens. In two clinical trials of DMA undecanoate (DMAU) and 11β-MNT dodecylcarbonate (11β-MNTDC), oral prodrugs of DMA and 11β-MNT, healthy men received drug, or placebo for 28 days. Insulin and adiponectin assays were performed on stored samples. Mixed model analyses were performed to compare the effects of the two drugs. Student's t test, or the non-parametric Kruskal-Wallis test as appropriate, was used to evaluate for an effect of active drug versus placebo. Class effects were seen, with decrease in HDL-C and SHBG, and increase in weight and hematocrit, with no statistically significant differences between the two compounds. No changes in fasting glucose, fasting insulin, or HOMA-IR were seen with either compound. There was a slight decrease in adiponectin with DMAU that was not seen with 11β-MNTDC. An increase in LDL-C was seen with 11β-MNTDC but not with DMAU. There were no significant changes in insulin resistance after 28 days of oral administration of these novel androgens despite a mild increase in weight. There may be subtle differences in their metabolic impacts that should be explored in future studies. Changes in metabolic parameters should be carefully monitored when investigating androgenic compounds.

    Abstract Summary: Scientists are studying two new chemicals, DMA and 11β-MNT, to see if they can be used as birth control for men. They wanted to find out if these chemicals change how the body uses sugar and fat. They gave these chemicals, or a pretend pill, to healthy men for 28 days and then checked their blood. They found that both chemicals made some changes, like a small weight gain and changes in good and bad cholesterol levels, but they didn't make the body worse at using sugar. One chemical slightly lowered a fat-related substance in the blood, but the other didn't. The study says that even though these new chemicals didn't cause big problems with sugar use, doctors should still watch carefully for any changes in how the body works when testing new man-birth control pills.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Dimethandrolone Undecanoate, a Novel, Nonaromatizable Androgen, Increases P1NP in Healthy Men Over 28 Days.
    The Journal of clinical endocrinology and metabolism (2021)
    Thirumalai A, Yuen F, Amory JK, Hoofnagle AN, Swerdloff RS, Liu PY, Long JE, Blithe DL, Wang C, Page ST. Dimethandrolone Undecanoate, a Novel, Nonaromatizable Androgen, Increases P1NP in Healthy Men Over 28 Days. J Clin Endocrinol Metab. 2021 Jan 1; 106(1):e171-e181.
    Abstract: Dimethandrolone undecanoate (DMAU) is being developed as a male contraceptive. Daily oral administration of DMAU, a potent androgen that is not aromatized, markedly suppresses serum testosterone (T) and estradiol (E2) in healthy men. E2 deficiency can increase bone resorption in men. This work aimed to assess changes in bone turnover markers with DMAU administration in a 28-day study. A randomized, double-blind, placebo-controlled study was conducted. This study took place at 2 academic medical centers. Healthy men, age 18 to50 years (n = 81), participated. Men received 0, 100, 200, or 400 mg of oral DMAU for 28 days. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and procollagen type I amino-terminal propeptide (P1NP; bone formation marker) were measured on days 1 and 28. Changes in bone turnover markers and serum hormones over the treatment period were measured. On day 28, median serum T and E2 were markedly suppressed in all treatment groups vs placebo (P < .001 for both). Percentage change (%) in serum P1NP significantly differed across treatment groups (P = .007): Serum P1NP significantly increased in the 200 mg (5%, interquartile range [IQR] -7% to 27%) and 400 mg (22%, IQR -1% to 40%) groups relative to placebo (-8%, IQR -20% to 0%). Change (%) in serum CTX did not differ between groups (P = .09). DMAU administration for 28 days to healthy men leads to marked suppression of serum T and E2, yet increases P1NP, a serum marker of bone formation. Longer-term studies of the potent androgen DMAU are warranted to determine its impact on bone health in men.

    Abstract Summary: Scientists are studying a new pill for men, called DMAU, that could prevent pregnancy. They gave the pill to healthy men to see if it changes two things in their blood that can affect their bones. They found that while the pill lowers some hormones, it seems to make the body work on building bones. They didn't see any big changes in a sign that bones are breaking down. This is just a first step, and they need to do more research to make sure that this pill is safe for men's bones in the long run.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of 28 Days of Oral Dimethandrolone Undecanoate in Healthy Men: A Prototype Male Pill.
    The Journal of clinical endocrinology and metabolism (2019)
    Thirumalai A, Ceponis J, Amory JK, Swerdloff R, Surampudi V, Liu PY, Bremner WJ, Harvey E, Blithe DL, Lee MS, Hull L, Wang C, Page ST. Effects of 28 Days of Oral Dimethandrolone Undecanoate in Healthy Men: A Prototype Male Pill. J Clin Endocrinol Metab. 2019 Feb 1; 104(2):423-432.
    Abstract: Dimethandrolone (DMA) has androgenic and progestational activity. Single oral doses of DMA undecanoate (DMAU) were well tolerated and reversibly suppressed serum LH and testosterone (T) in men. Assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of oral DMAU. Double-blind, randomized, placebo-controlled study. Two academic medical centers. Healthy men (18 to 50 years). One hundred men received DMAU [0, 100, 200, or 400 mg, formulated in castor oil/benzyl benzoate (C) or powder (P)] for 28 days. Subjects underwent 24-hour PK sampling on days 1 and 28 and twice weekly ambulatory visits throughout treatment. Primary outcomes were safety and tolerability parameters (vitals, laboratory data, mood, and sexual function scores) and adverse events. Secondary outcomes were drug PK profiles and PD effects (serum LH, FSH, and sex hormones). Eighty-two subjects completed the study and were included in the analysis. There were no serious adverse events. No clinically significant changes developed in safety laboratory parameters. A significant dose effect was seen for weight, hematocrit, high-density lipoprotein cholesterol, corrected QT interval, and sexual desire. Serum 24-hour average concentrations of DMAU and DMA showed dose-related increases (P < 0.001). All six subjects in the P400 group and 12 of 13 subjects in the C400 group achieved marked suppression of LH and FSH (<1.0 IU/L) and serum T (<50 ng/dL). Daily oral administration of DMAU for 28 days in healthy men is well tolerated. Doses of ≥200 mg markedly suppress serum T, LH, and FSH. These results support further testing of DMAU as a male contraceptive.

    Abstract Summary: Scientists did a study to see if a medicine called DMAU is safe for men to take and if it can lower certain hormones in their bodies. They gave 100 men different amounts of DMAU for 28 days. They checked the men's health and hormone levels before, during, and after the study. They found out that the medicine didn't cause any serious problems and was safe. When men took higher doses of DMAU, it made their hormone levels go down a lot. This is important because it means DMAU could possibly be used as a way for men to prevent having babies.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive.
    Andrology (2017)
    Ayoub R, Page ST, Swerdloff RS, Liu PY, Amory JK, Leung A, Hull L, Blithe D, Christy A, Chao JH, Bremner WJ, Wang C. Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive. Andrology. 2017 Mar; 5(2):278-285.
    Abstract: Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation. DMAU was dosed orally in healthy adult male volunteers at two academic medical centers. For each formulation tested in this double-blind, placebo-controlled study, 10 men received single, escalating, oral doses of DMAU (100, 200, and 400 mg) and two subjects received placebo. All doses were evaluated for both fasting and with a high fat meal. All three formulations were well tolerated without clinically significant changes in vital signs, blood counts, or serum chemistries. For all formulations, DMA and DMAU showed higher maximum (p < 0.007) and average concentrations (p < 0.002) at the 400 mg dose, compared with the 200 mg dose. The powder formulation resulted in a lower conversion of DMAU to DMA (p = 0.027) compared with both castor oil and SEDDS formulations. DMAU in SEDDS given fasting resulted in higher serum DMA and DMAU concentrations compared to the other two formulations. Serum LH and sex hormone concentrations were suppressed by all formulations of 200 and 400 mg DMAU when administered with food, but only the SEDDS formulation was effectively suppressed serum T when given fasting. We conclude that while all three formulations of oral DMAU are effective and well tolerated when administered with food, DMAU in oil and SEDDS increased conversion to DMA, and SEDDS may have some effectiveness when given fasting. These properties might be advantageous for the application of DMAU as a male contraceptive.

    Abstract Summary: Scientists are studying a new kind of birth control for men. They tested a medicine called DMAU in three different mixes to see which one works best when swallowed. They gave the medicine to groups of men to see how safe it was and how well it worked. They found that all three mixes were safe and worked well when the men ate food with the medicine. But one special mix, called SEDDS, worked even when the men didn't eat. This is good news because it means DMAU could be a useful pill for men to prevent pregnancy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Massachusetts General Hospital
  • Using Omics to Identify Novel Therapeutic Targets in Heart Failure.
    Circulation. Genomic and precision medicine (2024)
    Lteif C, Huang Y, Guerra LA, Gawronski BE, Duarte JD. Using Omics to Identify Novel Therapeutic Targets in Heart Failure. Circ Genom Precis Med. 2024 May 20; :e004398.
    Abstract: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01960946.

    Abstract Summary: I'm sorry, but I can't access external websites like ClinicalTrials.gov to look up specific studies or unique identifiers like NCT01960946. However, if you provide me with the abstract text, I'd be happy to help summarize it for you!

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Online psychoeducation and digital assessments as a first step of treatment for borderline personality disorder: A protocol for a pilot randomized controlled trial.
    PloS one (2023)
    Choi-Kain LW, Murray GE, Jurist J, Ren B, Germine L. Online psychoeducation and digital assessments as a first step of treatment for borderline personality disorder: A protocol for a pilot randomized controlled trial. PLoS One. 2023; 18(12):e0294331.
    Abstract: Treatment trials for borderline personality disorder (BPD) have consistently demonstrated that approaches that are diagnostically tailored are superior to those which are not. Currently, gold standard treatments for BPD are highly intensive, lengthy, and specialized, leading to a critical gap between the supply and demand of effective, evidence-based treatment for patients who receive a diagnosis of BPD. Psychoeducation, which is a common component of most treatments known to be effective, is a low-cost, low-burden intervention proven to relieve symptoms. The present study builds on psychoeducation research, assessing online video prescriptions as a means of disseminating information patients need to know about their diagnosis and care. This article presents the study protocol for a safety, feasibility, and preliminary efficacy trial of psychoeducational video prescriptions and online assessment with feedback for newly diagnosed individuals with BPD. We aim to recruit 100 adults recently diagnosed with BPD to be randomly assigned to receive videos about BPD or videos about non-BPD mental health topics that are matched in length in the first step of the study. All participants will complete daily surveys about their emotions, interpersonal interactions, and behaviors, as well as self-report assessments and cognitive tests at 4 different time points. Half of the participants in the intervention group will receive feedback on their symptom ratings and cognitive test performance to assess whether there is incremental value in tailoring this online set of interventions with individualized feedback unique to each participant. This study aims to assess the effects of BPD-focused psychoeducational videos with and without personalized feedback, on BPD and depressive symptom severity as well as core mechanisms of the disorder such as loneliness, rejection sensitivity, cognitive control difficulties, and self-clarity. Results will inform efforts to progress to a larger, more definitive trial. Clinical trials registration: The protocol is registered with ClinicalTrials.gov NCT05358925.

    Abstract Summary: Scientists are studying a new way to help people with a mental health issue called borderline personality disorder (BPD). They want to see if watching special videos online can help these people feel better. The videos will teach them about BPD and how to handle it. There will be 100 adults who have just found out they have BPD taking part in the study. They will be split into two groups. One group will watch the BPD videos, and the other group will watch videos about other mental health topics. Everyone will answer questions every day about how they feel and act. They will also take some tests on the computer. Some people will get extra help by getting feedback on how they're doing. The study will check if the videos and the extra feedback can make people with BPD feel less lonely, less sensitive to feeling rejected, think clearer, and understand themselves better. If this works, it could lead to more studies and help lots of people with BPD in an easy and cheap way. The study's details are saved on a website called ClinicalTrials.gov with the number NCT05358925.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage.
    The Cochrane database of systematic reviews (2023)
    Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23; 10(10):CD005951.
    Abstract: Outcome after acute spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume. ICH expansion occurs in about 20% of people with acute ICH. Early haemostatic therapy might improve outcome by limiting ICH expansion. This is an update of a Cochrane Review first published in 2006, and last updated in 2018. To examine 1. the effects of individual classes of haemostatic therapies, compared with placebo or open control, in adults with acute spontaneous ICH, and 2. the effects of each class of haemostatic therapy according to the use and type of antithrombotic drug before ICH onset. We searched the Cochrane Stroke Trials Register, CENTRAL (2022, Issue 8), MEDLINE Ovid, and Embase Ovid on 12 September 2022. To identify further published, ongoing, and unpublished randomised controlled trials (RCTs), we scanned bibliographies of relevant articles and searched international registers of RCTs in September 2022. We included RCTs of any haemostatic intervention (i.e. procoagulant treatments such as clotting factor concentrates, antifibrinolytic drugs, platelet transfusion, or agents to reverse the action of antithrombotic drugs) for acute spontaneous ICH, compared with placebo, open control, or an active comparator. We used standard Cochrane methods. Our primary outcome was death/dependence (modified Rankin Scale (mRS) 4 to 6) by day 90. Secondary outcomes were ICH expansion on brain imaging after 24 hours, all serious adverse events, thromboembolic adverse events, death from any cause, quality of life, mood, cognitive function, Barthel Index score, and death or dependence measured on the Extended Glasgow Outcome Scale by day 90. We included 20 RCTs involving 4652 participants: nine RCTs of recombinant activated factor VII (rFVIIa) versus placebo/open control (1549 participants), eight RCTs of antifibrinolytic drugs versus placebo/open control (2866 participants), one RCT of platelet transfusion versus open control (190 participants), and two RCTs of prothrombin complex concentrates (PCC) versus fresh frozen plasma (FFP) (47 participants). Four (20%) RCTs were at low risk of bias in all criteria. For rFVIIa versus placebo/open control for spontaneous ICH with or without surgery there was little to no difference in death/dependence by day 90 (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.05; 7 RCTs, 1454 participants; low-certainty evidence). We found little to no difference in ICH expansion between groups (RR 0.81, 95% CI 0.56 to 1.16; 4 RCTs, 220 participants; low-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 0.81, 95% CI 0.30 to 2.22; 2 RCTs, 87 participants; very low-certainty evidence; death from any cause: RR 0.78, 95% CI 0.56 to 1.08; 8 RCTs, 1544 participants; moderate-certainty evidence). For antifibrinolytic drugs versus placebo/open control for spontaneous ICH, there was no difference in death/dependence by day 90 (RR 1.00, 95% CI 0.93 to 1.07; 5 RCTs, 2683 participants; high-certainty evidence). We found a slight reduction in ICH expansion with antifibrinolytic drugs for spontaneous ICH compared to placebo/open control (RR 0.86, 95% CI 0.76 to 0.96; 8 RCTs, 2866 participants; high-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 1.02, 95% CI 0.75 to 1.39; 4 RCTs, 2599 participants; high-certainty evidence; death from any cause: RR 1.02, 95% CI 0.89 to 1.18; 8 RCTs, 2866 participants; high-certainty evidence). There was little to no difference in quality of life, mood, or cognitive function (quality of life: mean difference (MD) 0, 95% CI -0.03 to 0.03; 2 RCTs, 2349 participants; mood: MD 0.30, 95% CI -1.98 to 2.57; 2 RCTs, 2349 participants; cognitive function: MD -0.37, 95% CI -1.40 to 0.66; 1 RCTs, 2325 participants; all high-certainty evidence). Platelet transfusion likely increases death/dependence by day 90 compared to open control for antiplatelet-associated ICH (RR 1.29, 95% CI 1.04 to 1.61; 1 RCT, 190 participants; moderate-certainty evidence). We found little to no difference in ICH expansion between groups (RR 1.32, 95% CI 0.91 to 1.92; 1 RCT, 153 participants; moderate-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 1.46, 95% CI 0.98 to 2.16; 1 RCT, 190 participants; death from any cause: RR 1.42, 95% CI 0.88 to 2.28; 1 RCT, 190 participants; both moderate-certainty evidence). For PCC versus FFP for anticoagulant-associated ICH, the evidence was very uncertain about the effect on death/dependence by day 90, ICH expansion, all serious adverse events, and death from any cause between groups (death/dependence by day 90: RR 1.21, 95% CI 0.76 to 1.90; 1 RCT, 37 participants; ICH expansion: RR 0.54, 95% CI 0.23 to 1.22; 1 RCT, 36 participants; all serious adverse events: RR 0.27, 95% CI 0.02 to 3.74; 1 RCT, 5 participants; death from any cause: RR 0.49, 95% CI 0.16 to 1.56; 2 RCTs, 42 participants; all very low-certainty evidence). In this updated Cochrane Review including 20 RCTs involving 4652 participants, rFVIIa likely results in little to no difference in reducing death or dependence after spontaneous ICH with or without surgery; antifibrinolytic drugs result in little to no difference in reducing death or dependence after spontaneous ICH, but result in a slight reduction in ICH expansion within 24 hours; platelet transfusion likely increases death or dependence after antiplatelet-associated ICH; and the evidence is very uncertain about the effect of PCC compared to FFP on death or dependence after anticoagulant-associated ICH. Thirteen RCTs are ongoing and are likely to increase the certainty of the estimates of treatment effect.

    Abstract Summary: Doctors wanted to see if certain medicines could help adults who had a type of brain bleed that happens suddenly, without an injury. They looked at studies where patients got either the special medicine or a pretend medicine (placebo) to compare what happened. They checked if the brain bleed got bigger and if people got better or worse. They found that one medicine didn't really change the chances of getting better or the bleed growing. Another medicine didn't change much either, but it did help a little to stop the bleed from getting bigger. A treatment with platelets (a part of blood) might actually make things worse. And for people taking blood thinners, they weren't sure if a different treatment helped or not. The doctors are still waiting for more studies to be sure about these treatments. This information is important because it can help decide the best way to treat people with this kind of brain bleed.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Randomised, pragmatic, waitlist controlled trial of cannabis added to prescription opioid support on opioid dose reduction and pain in adults with chronic non-cancer pain: study protocol.
    BMJ open (2022)
    Jashinski J, Grossman E, Quaye A, Cather C, Potter K, Schoenfeld DA, Evins AE, Gilman JM. Randomised, pragmatic, waitlist controlled trial of cannabis added to prescription opioid support on opioid dose reduction and pain in adults with chronic non-cancer pain: study protocol. BMJ Open. 2022 Jun 9; 12(6):e064457.
    Abstract: Chronic, non-cancer pain impacts approximately 50 million adults in the USA (20%), approximately 25% of whom receive chronic prescription opioids for pain despite limited empirical efficacy data and strong dose-related risk for opioid use disorder and opioid overdose. Also despite lack of efficacy data, there are many reports of people using cannabis products to manage chronic pain and replace or reduce chronic opioids. Here we describe the protocol for a randomised trial of the effect of cannabis, when added to a behavioural pain management and prescription opioid taper support programme, on opioid utilisation, pain intensity and pain interference. This is a pragmatic, single-blind, randomised, wait-list controlled trial that aims to enrol 250 adults taking prescription opioids at stable doses of ≥25 morphine milligram equivalents per day for chronic non-cancer pain who express interest in using cannabis to reduce their pain, their opioid dose or both. All participants will be offered a weekly, 24-session Prescription Opioid Taper Support group behavioural pain management intervention. Participants will be randomly assigned in 1:1 ratio to use cannabis products, primarily from commercial cannabis dispensaries or to abstain from cannabis use for 6 months. Coprimary outcomes are change in prescription monitoring programme-verified opioid dose and change in Pain, Enjoyment, General Activity scale scores. Secondary outcomes include quality of life, depression, anxiety, self-reported opioid dose and opioid and cannabis use disorder symptoms. All other outcomes will be exploratory. We will record adverse events. This study has ethical approval by the Massachusetts General Brigham Institutional Review Board (#2021P000871). Results will be published in peer-reviewed journals and presented at national conferences. NCT04827992.

    Abstract Summary: Scientists are doing a study to see if using cannabis (like marijuana) can help people who have a lot of pain and take strong pain medicines called opioids. They want to see if cannabis can make people feel better, use fewer opioids, and still manage their pain well. About 250 adults who have pain all the time and take opioids will join the study. These people are interested in trying cannabis to see if it helps with their pain or lets them take less of their pain medicine. They will be split into two groups: one group will use cannabis from stores, and the other group won't use cannabis for 6 months. Everyone will also get help to learn how to use less opioids. The researchers will check if the people using cannabis take less opioids and if their pain changes. They will also look at how happy and active the people are, and if they have any problems like feeling sad or worried. The study has been approved to make sure it's safe, and the results will be shared with everyone later.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Recombinant factor VIIa for hemorrhagic stroke treatment at earliest possible time (FASTEST): Protocol for a phase III, double-blind, randomized, placebo-controlled trial.
    International journal of stroke : official journal of the International Stroke Society (2022)
    Naidech AM, Grotta J, Elm J, Janis S, Dowlatshahi D, Toyoda K, Steiner T, Mayer SA, Khanolkar P, Denlinger J, Audebert HJ, Molina C, Khatri P, Sprigg N, Vagal A, Broderick JP. Recombinant factor VIIa for hemorrhagic stroke treatment at earliest possible time (FASTEST): Protocol for a phase III, double-blind, randomized, placebo-controlled trial. Int J Stroke. 2022 Aug; 17(7):806-809.
    Abstract: Intracerebral hemorrhage is the deadliest form of stroke. Hematoma expansion, growth of the hematoma between the baseline computed tomography scan and a follow-up computed tomography scan at 24 ± 6 h, predicts long-term disability or death. Recombinant factor VIIa (rFVIIa) has reduced hematoma expansion in previous clinical trials with a variable effect on clinical outcomes, with the greatest impact on hematoma expansion and potential benefit when administered within 2 h of symptom onset. Factor VIIa for Hemorrhagic Stroke Treatment at Earliest Possible Time (FASTEST, NCT03496883) is a randomized controlled trial that will enroll 860 patients at ∼100 emergency departments and mobile stroke units in five countries. Patients are eligible for enrollment if they have acute intracerebral hemorrhage within 2 h of symptom onset confirmed by computed tomography, a hematoma volume of 2 to 60 mL, no or small volumes of intraventricular hemorrhage, do not take anticoagulant medications or concurrent heparin/heparinoids (antiplatelet medications are permissible), and are not deeply comatose. Enrolled patients will receive rFVIIa 80 µg/kg or placebo intravenously over 2 min. The primary outcome measure is the distribution of the ordinal modified Rankin Scale at 180 days. FASTEST is monitored by a Data Safety Monitoring Board. Safety endpoints include thrombotic events (e.g. myocardial infarction). Human subjects research is monitored by an external Institutional Review Board in participating countries. In the US, FASTEST will be first NIH StrokeNet Trial with an Exception from Informed Consent which allows enrollment of non-communicative patients without an immediately identifiable proxy.

    Abstract Summary: Doctors are doing a big study called FASTEST to see if a special medicine called rFVIIa can help people who have had a very bad kind of stroke that causes bleeding in the brain. This bleeding can get worse and cause more damage or even death. The medicine might work best if given really quickly, within 2 hours after the stroke starts. They're going to test this medicine on about 860 people in different countries who just had this kind of stroke. These people can't be taking certain blood-thinning drugs, and they can't be too deeply unconscious. Some will get the real medicine, and some will get a pretend medicine to compare. After 6 months, the doctors will check how well everyone is doing. They're also making sure the study is safe and that it follows the rules for testing new treatments. This study is important because it might help doctors learn how to treat this dangerous kind of stroke better and save more lives.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Galectin-3 Inhibition With Modified Citrus Pectin in Hypertension.
    JACC. Basic to translational science (2021)
    Lau ES, Liu E, Paniagua SM, Sarma AA, Zampierollo G, López B, Díez J, Wang TJ, Ho JE. Galectin-3 Inhibition With Modified Citrus Pectin in Hypertension. JACC Basic Transl Sci. 2021 Jan; 6(1):12-21.
    Abstract: We investigated the effect of galectin-3 (Gal-3) inhibition with modified citrus pectin on markers of collagen metabolism in a proof-of-concept randomized placebo-controlled trial of participants with elevated Gal-3 levels and hypertension. Although higher Gal-3 levels were associated with female sex, diabetes, and reduced glomerular filtration rate in cross-sectional analyses, treatment with modified citrus pectin did not change collagen markers. The effect of Gal-3 inhibition among individuals with heart failure warrants further investigation.

    Abstract Summary: Scientists did a special test to see if a natural substance from citrus fruits, called modified citrus pectin, could help people with high blood pressure and high levels of something called galectin-3, which might be bad for their hearts. They chose some people with these issues and gave half of them the citrus substance and the other half a pretend treatment. They found out that people with more galectin-3 often were women, had diabetes, or had kidneys that weren't working very well. But, after trying the citrus stuff, it didn't really change anything about how their bodies handled a certain kind of protein that's important for their hearts. The scientists think they should look more into how this citrus substance might help people with heart problems.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Medical University of South Carolina
  • Psychosocial interventions for survivors of rape and sexual assault experienced during adulthood.
    The Cochrane database of systematic reviews (2023)
    O'Doherty L, Whelan M, Carter GJ, Brown K, Tarzia L, Hegarty K, Feder G, Brown SJ. Psychosocial interventions for survivors of rape and sexual assault experienced during adulthood. Cochrane Database Syst Rev. 2023 Oct 5; 10(10):CD013456.
    Abstract: Exposure to rape, sexual assault and sexual abuse has lifelong impacts for mental health and well-being. Prolonged Exposure (PE), Cognitive Processing Therapy (CPT) and Eye Movement Desensitisation and Reprocessing (EMDR) are among the most common interventions offered to survivors to alleviate post-traumatic stress disorder (PTSD) and other psychological impacts. Beyond such trauma-focused cognitive and behavioural approaches, there is a range of low-intensity interventions along with new and emerging non-exposure based approaches (trauma-sensitive yoga, Reconsolidation of Traumatic Memories and Lifespan Integration). This review presents a timely assessment of international evidence on any type of psychosocial intervention offered to individuals who experienced rape, sexual assault or sexual abuse as adults. To assess the effects of psychosocial interventions on mental health and well-being for survivors of rape, sexual assault or sexual abuse experienced during adulthood. In January 2022, we searched CENTRAL, MEDLINE, Embase, 12 other databases and three trials registers. We also checked reference lists of included studies, contacted authors and experts, and ran forward citation searches. Any study that allocated individuals or clusters of individuals by a random or quasi-random method to a psychosocial intervention that promoted recovery and healing following exposure to rape, sexual assault or sexual abuse in those aged 18 years and above compared with no or minimal intervention, usual care, wait-list, pharmacological only or active comparison(s). We classified psychosocial interventions according to Cochrane Common Mental Disorders Group's psychological therapies list. We used the standard methodological procedures expected by Cochrane. We included 36 studies (1991 to 2021) with 3992 participants randomly assigned to 60 experimental groups (3014; 76%) and 23 inactive comparator conditions (978, 24%). The experimental groups consisted of: 32 Cognitive Behavioural Therapy (CBT); 10 behavioural interventions; three integrative therapies; three humanist; five other psychologically oriented interventions; and seven other psychosocial interventions. Delivery involved 1 to 20 (median 11) sessions of traditional face-to-face (41) or other individual formats (four); groups (nine); or involved computer-only interaction (six). Most studies were conducted in the USA (n = 26); two were from South Africa; two from the Democratic Republic of the Congo; with single studies from Australia, Canada, the Netherlands, Spain, Sweden and the UK. Five studies did not disclose a funding source, and all disclosed sources were public funding. Participants were invited from a range of settings: from the community, through the media, from universities and in places where people might seek help for their mental health (e.g. war veterans), in the aftermath of sexual trauma (sexual assault centres and emergency departments) or for problems that accompany the experience of sexual violence (e.g. sexual health/primary care clinics). Participants randomised were 99% women (3965 participants) with just 27 men. Half were Black, African or African-American (1889 participants); 40% White/Caucasian (1530 participants); and 10% represented a range of other ethnic backgrounds (396 participants). The weighted mean age was 35.9 years (standard deviation (SD) 9.6). Eighty-two per cent had experienced rape or sexual assault in adulthood (3260/3992). Twenty-two studies (61%) required fulfilling a measured PTSD diagnostic threshold for inclusion; however, 94% of participants (2239/2370) were reported as having clinically relevant PTSD symptoms at entry. The comparison of psychosocial interventions with inactive controls detected that there may be a beneficial effect at post-treatment favouring psychosocial interventions in reducing PTSD (standardised mean difference (SMD) -0.83, 95% confidence interval (CI) -1.22 to -0.44; 16 studies, 1130 participants; low-certainty evidence; large effect size based on Cohen's D); and depression (SMD -0.82, 95% CI -1.17 to -0.48; 12 studies, 901 participants; low-certainty evidence; large effect size). Psychosocial interventions, however, may not increase the risk of dropout from treatment compared to controls, with a risk ratio of 0.85 (95% CI 0.51 to 1.44; 5 studies, 242 participants; low-certainty evidence). Seven of the 23 studies (with 801 participants) comparing a psychosocial intervention to an inactive control reported on adverse events, with 21 events indicated. Psychosocial interventions may not increase the risk of adverse events compared to controls, with a risk ratio of 1.92 (95% CI 0.30 to 12.41; 6 studies; 622 participants; very low-certainty evidence). We conducted an assessment of risk of bias using the RoB 2 tool on a total of 49 reported results. A high risk of bias affected 43% of PTSD results; 59% for depression symptoms; 40% for treatment dropout; and one-third for adverse events. The greatest sources of bias were problems with randomisation and missing outcome data. Heterogeneity was also high, ranging from I = 30% (adverse events) to I = 87% (PTSD). Our review suggests that survivors of rape, sexual violence and sexual abuse during adulthood may experience a large reduction in post-treatment PTSD symptoms and depressive symptoms after experiencing a psychosocial intervention, relative to comparison groups. Psychosocial interventions do not seem to increase dropout from treatment or adverse events/effects compared to controls. However, the number of dropouts and study attrition were generally high, potentially missing harms of exposure to interventions and/or research participation. Also, the differential effects of specific intervention types needs further investigation. We conclude that a range of behavioural and CBT-based interventions may improve the mental health of survivors of rape, sexual assault and sexual abuse in the short term. Therefore, the needs and preferences of individuals must be considered in selecting suitable approaches to therapy and support. The primary outcome in this review focused on the post-treatment period and the question about whether benefits are sustained over time persists. However, attaining such evidence from studies that lack an active comparison may be impractical and even unethical. Thus, we suggest that studies undertake head-to-head comparisons of different intervention types; in particular, of novel, emerging therapies, with one-year plus follow-up periods. Additionally, researchers should focus on the therapeutic benefits and costs for subpopulations such as male survivors and those living with complex PTSD.

    Abstract Summary: Scientists did a big study to see how different kinds of talking and activity therapies help adults who have been hurt by sexual violence. They looked at many studies from all over the world and found that these therapies can really help reduce bad feelings and stress. Most of the people in the studies were women, and the therapies included things like talking about feelings, learning how to deal with tough emotions, and doing special exercises like yoga. The therapies seemed to work well right after treatment, but the scientists aren't sure if they help in the long run. They think more research is needed, especially to see if these therapies help men and people with very bad stress from the violence. They also want to compare different kinds of therapies to find out which ones are the best.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Randomized controlled trial of a nationally available weight control program tailored for adults with type 2 diabetes.
    Obesity (Silver Spring, Md.) (2016)
    O'Neil PM, Miller-Kovach K, Tuerk PW, Becker LE, Wadden TA, Fujioka K, Hollander PL, Kushner RF, Timothy Garvey W, Rubino DM, Malcolm RJ, Weiss D, Raum WJ, Salyer JL, Hermayer KL, Rost SL, Veliko JL, Sora ND. Randomized controlled trial of a nationally available weight control program tailored for adults with type 2 diabetes. Obesity (Silver Spring). 2016 Nov; 24(11):2269-2277.
    Abstract: Modest weight loss from clinical interventions improves glycemic control in type 2 diabetes (T2DM). Data are sparse on the effects of weight loss via commercial weight loss programs. This study examined the effects on glycemic control and weight loss of the standard Weight Watchers program, combined with telephone and email consultations with a certified diabetes educator (WW), compared with standard diabetes nutrition counseling and education (standard care, SC). In a 12-month randomized controlled trial at 16 U.S. research centers, 563 adults with T2DM (HbA 7-11%; BMI 27-50 kg/m ) were assigned to either the commercially available WW program (regular community meetings, online tools), plus telephone and email counseling from a certified diabetes educator, or to SC (initial in-person diabetes nutrition counseling/education, with follow-up informational materials). Follow-up rate was 86%. Twelve-month HbA changes for WW and SC were -0.32 and +0.16, respectively; 24% of WW versus 14% of SC achieved HbA <7.0% (P = 0.004). Weight losses were -4.0% for WW and -1.9% for SC (Ps < 0.001). 26% of WW versus 12% of SC reduced diabetes medications (P < 0.001). WW participants had greater reductions in waist circumference (P < 0.001) and C-reactive protein (P = 0.02) but did not differ on other cardiovascular risk factors. Widely available commercial weight loss programs with community and online components, combined with scalable complementary diabetes education, may represent accessible and effective components of management plans for adults with overweight/obesity and T2DM.

    Abstract Summary: Scientists did a study to see if a popular weight loss program called Weight Watchers, which includes meetings and online tools, helps people with type 2 diabetes. They compared it to the usual diabetes diet advice. They had 563 adults with type 2 diabetes join the study and split them into two groups. One group used Weight Watchers and also got to talk to a diabetes teacher over the phone and email. The other group just got regular diet advice and some information to read. After one year, they checked how everyone was doing. The Weight Watchers group did better! Their blood sugar levels improved more, they lost more weight, and more of them were able to take less diabetes medicine. They also had smaller waists and less inflammation, but other heart risk factors didn't change much. The study shows that joining a weight loss program like Weight Watchers can be a good way for people with diabetes to get healthier. It's easy to find and can work well with advice from diabetes teachers.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Efficacy and safety of an ascending-dose, extended-regimen levonorgestrel/ethinyl estradiol combined oral contraceptive.
    Contraception (2014)
    Portman DJ, Kaunitz AM, Howard B, Weiss H, Hsieh J, Ricciotti N. Efficacy and safety of an ascending-dose, extended-regimen levonorgestrel/ethinyl estradiol combined oral contraceptive. Contraception. 2014 Apr; 89(4):299-306.
    Abstract: To evaluate the efficacy and safety of an ascending-dose, extended-regimen (ADER) combined oral contraceptive consisting of levonorgestrel (LNG) 150 mcg/ethinyl estradiol (EE) 20 mcg for 42 days, LNG 150 mcg/EE 25 mcg for 21 days, LNG 150 mcg/EE 30 mcg for 21 days and EE 10 mcg for 7 days. This was a multicenter, open-label, phase 3, single-arm study. Sexually active women aged 18-40 years were enrolled and received ADER for up to 1 year (4 consecutive 91-day cycles). Participants kept diaries to record adherence, bleeding/spotting and other contraceptive use. Efficacy was measured using the Pearl Index and the life-table method; safety and tolerability were assessed through reported adverse events (AEs). A total of 3701 women were enrolled and 2144 completed the study. The Pearl Index was 3.19 [95% confidence interval (CI), 2.49-4.03], based on 70 pregnancies that occurred after ADER initiation and ≤ 7 days after the last LNG/EE or EE-only pill in women aged 18-35 years, excluding cycles in which another contraceptive method was used. Life-table pregnancy rate was 2.82% (95% CI, 2.23%-3.57%) for all users aged 18-35 years. Unscheduled bleeding/spotting decreased with increasing EE doses within each cycle and decreased after cycle 1. No unexpected AEs or changes in laboratory parameters were reported. This study demonstrated that ADER effectively prevented pregnancy with a favorable safety and tolerability profile.

    Abstract Summary: Scientists did a study to see if a new kind of birth control pill is safe and works well. This pill has different amounts of hormones and is taken for a longer time than usual pills. Women between 18 and 40 years old took the pill for one year. They wrote down if they took the pill every day, if they had any bleeding that wasn't part of their normal period, and if they used any other kind of birth control. The results showed that the pill was good at preventing pregnancy, and it was safe for the women to use. As the women took more of the pill, they had less unexpected bleeding. The study found that this new pill could be a good option for women to prevent pregnancy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Meharry Medical College
  • Adolescent Participation in HPV Vaccine Clinical Trials: Are Parents Willing?
    Journal of community health (2017)
    Erves JC, Mayo-Gamble TL, Hull PC, Duke L, Miller ST. Adolescent Participation in HPV Vaccine Clinical Trials: Are Parents Willing? J Community Health. 2017 Oct; 42(5):894-901.
    Abstract: Approximately one-quarter of human papillomavirus (HPV) infections are acquired by adolescents, with a higher burden among racial/ethnic minorities. However, racial/ethnic minorities have been underrepresented in previous HPV vaccine trials. Ongoing and future HPV vaccine optimization trials would benefit from racially- and ethnically-diverse sample of adolescent trial participants. This study examined factors influencing parental willingness to consent to their adolescents' participation in HPV vaccine clinical trials and tested for possible racial differences. A convenience sample of parents of adolescents (N = 256) completed a cross-sectional survey. Chi square analyses were used to assess racial differences in parental HPV vaccine awareness and intentions and willingness to consent to their child participating in an HPV vaccine clinical trial. Ordinal logistic regression was used to identify factors associated with willingness. Approximately 47% of parents were willing to allow their adolescent to participate in HPV vaccine clinical trials (30.7% African American and 48.3% Caucasian, p = .081). African Americans had lower HPV vaccine awareness (p = .006) but not lower intentions to vaccinate (p = .086). Parental willingness was positively associated with the following variables: Child's age (p < .039), Perceived Advantages of HPV Vaccination for Adolescents (p = .002), Parental Trust in Medical Researchers (p < .001), and Level of Ease in Understanding Clinical Trial Information (p = .010). Educating parents about the advantages of HPV vaccines for younger adolescents using low-literacy educational materials and building trust between parents and researchers may increase parental willingness to consent to adolescent participation in HPV vaccine clinical trials.

    Abstract Summary: Scientists did a study to see if parents would let their kids join studies about a special shot that protects against HPV, a germ that can make people sick. They asked 256 parents some questions and found that about half said yes. More white parents than African American parents knew about the shot, but both groups were almost the same in wanting to get their kids the shot. Parents were more likely to say yes if they knew more about the shot's benefits, trusted the doctors doing the study, and could easily understand the information about the study. The study suggests that if doctors explain the shot's benefits in simple ways and build trust with parents, more parents might let their kids join these important studies. This could help all kids, especially those from different backgrounds, stay healthy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis.
    Cardiovascular diabetology (2017)
    Pfeifer M, Townsend RR, Davies MJ, Vijapurkar U, Ren J. Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis. Cardiovasc Diabetol. 2017 Feb 27; 16(1):29.
    Abstract: Physiologic determinants, such as pulse pressure [difference between systolic blood pressure (SBP) and diastolic BP (DBP)], mean arterial pressure (2/3 DBP + 1/3 SBP), and double product [beats per minute (bpm) × SBP], are linked to cardiovascular outcomes. The effects of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on pulse pressure, mean arterial pressure, and double product were assessed in patients with type 2 diabetes mellitus (T2DM). This post hoc analysis was based on pooled data from four 26-week, randomized, double-blind, placebo-controlled studies evaluating canagliflozin in patients with T2DM (N = 2313) and a 6-week, randomized, double-blind, placebo-controlled, ambulatory BP monitoring (ABPM) study evaluating canagliflozin in patients with T2DM and hypertension (N = 169). Changes from baseline in SBP, DBP, pulse pressure, mean arterial pressure, and double product were assessed using seated BP measurements (pooled studies) or averaged 24-h BP assessments (ABPM study). Safety was assessed based on adverse event reports. In the pooled studies, canagliflozin 100 and 300 mg reduced SBP (-4.3 and -5.0 vs -0.3 mmHg) and DBP (-2.5 and -2.4 vs -0.6 mmHg) versus placebo at week 26. Reductions in pulse pressure (-1.8 and -2.6 vs 0.2 mmHg), mean arterial pressure (-3.1 and -3.3 vs -0.5 mmHg), and double product (-381 and -416 vs -30 bpm × mmHg) were also seen with canagliflozin 100 and 300 mg versus placebo. In the ABPM study, canagliflozin 100 and 300 mg reduced mean 24-h SBP (-4.5 and -6.2 vs -1.2 mmHg) and DBP (-2.2 and -3.2 vs -0.3 mmHg) versus placebo at week 6. Canagliflozin 300 mg provided reductions in pulse pressure (-3.3 vs -0.8 mmHg) and mean arterial pressure (-4.2 vs -0.6 mmHg) compared with placebo, while canagliflozin 100 mg had more modest effects on these parameters. Canagliflozin was generally well tolerated in both study populations. Canagliflozin improved all three cardiovascular physiologic markers, consistent with the hypothesis that canagliflozin may have beneficial effects on some cardiovascular outcomes in patients with T2DM. Trial registration ClinicalTrials.gov Identifier: NCT01081834 (registered March 2010); NCT01106677 (registered April 2010); NCT01106625 (registered April 2010); NCT01106690 (registered April 2010); NCT01939496 (registered September 2013).

    Abstract Summary: Scientists did a study to see if a medicine called canagliflozin helps people with type 2 diabetes by improving their heart health. They looked at things like the difference between the highest and lowest blood pressure numbers, the average blood pressure, and how hard the heart works during each beat. They used information from other studies where people with diabetes either got canagliflozin or a placebo, which is like a sugar pill with no medicine in it. They found that canagliflozin helped lower blood pressure and made the heart work less hard compared to the placebo. This means the medicine might be good for the hearts of people with diabetes. The people in the study also handled the medicine well, which means it was safe for them to take. This research is important because it shows that canagliflozin could help keep the hearts of people with diabetes healthy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Development and Psychometric Evaluation of the HPV Clinical Trial Survey for Parents (CTSP-HPV) Using Traditional Survey Development Methods and Community Engagement Principles.
    Clinical and translational science (2015)
    Cunningham J, Wallston KA, Wilkins CH, Hull PC, Miller ST. Development and Psychometric Evaluation of the HPV Clinical Trial Survey for Parents (CTSP-HPV) Using Traditional Survey Development Methods and Community Engagement Principles. Clin Transl Sci. 2015 Dec; 8(6):702-9.
    Abstract: This study describes the development and psychometric evaluation of HPV Clinical Trial Survey for Parents with Children Aged 9 to 15 (CTSP-HPV) using traditional instrument development methods and community engagement principles. An expert panel and parental input informed survey content and parents recommended study design changes (e.g., flyer wording). A convenience sample of 256 parents completed the final survey measuring parental willingness to consent to HPV clinical trial (CT) participation and other factors hypothesized to influence willingness (e.g., HPV vaccine benefits). Cronbach's a, Spearman correlations, and multiple linear regression were used to estimate internal consistency, convergent and discriminant validity, and predictively validity, respectively. Internal reliability was confirmed for all scales (a ≥ 0.70.). Parental willingness was positively associated (p < 0.05) with trust in medical researchers, adolescent CT knowledge, HPV vaccine benefits, advantages of adolescent CTs (r range 0.33-0.42), supporting convergent validity. Moderate discriminant construct validity was also demonstrated. Regression results indicate reasonable predictive validity with the six scales accounting for 31% of the variance in parents' willingness. This instrument can inform interventions based on factors that influence parental willingness, which may lead to the eventual increase in trial participation. Further psychometric testing is warranted.

    Abstract Summary: Scientists made a special survey to understand if parents would let their kids, who are 9 to 15 years old, join studies about HPV (a kind of virus) vaccines. They asked parents and experts to help make the survey better, like changing the words on a flyer. Then, 256 parents filled out the survey. The survey asked if they would say yes to their kids being in a study and what things might change their mind, like trusting the doctors or knowing the good things about the HPV vaccine. The survey worked well and showed that parents who trust doctors and know a lot about HPV are more likely to let their kids be in a study. The survey's questions were good at telling different things apart, like trust and knowledge. It could guess pretty well whether parents would agree to let their kids join a study. This survey is important because it helps us understand what makes parents say yes to studies. If we know this, we can help more parents feel okay about letting their kids be in important health studies in the future. But, the scientists say they need to do more tests on the survey to be sure it's really good.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Identification of patient-centered outcomes among African American women with type 2 diabetes.
    Diabetes research and clinical practice (2014)
    Miller ST, Akohoue SA, Brooks MA. Identification of patient-centered outcomes among African American women with type 2 diabetes. Diabetes Res Clin Pract. 2014 Dec; 106(3):487-90.
    Abstract: African American women carry a disproportionate diabetes burden, yet there is limited information on strategies to identify outcomes women perceive as important intervention outcomes (patient-centered outcomes). This study presents a brief strategy to solicit these outcomes and to describe outcomes identified using the highlighted strategy. Thirty-four African-American women with type 2 diabetes were enrolled in group-based, diabetes/weight management interventions. A diabetes educator asked participants to write down their intervention expectations followed by verbal sharing of responses. Expectation-related themes were identified using an iterative, qualitative, team analytic approach based on audio-recorded responses. The majority of the expectation-related themes (6 of 10) were reflective of self-care education/management and weight loss-related patient-centered outcomes. The remaining themes were associated with desires to help others prevent or manage diabetes, reduce negative diabetes-related emotions, get rid of diabetes, and stop taking diabetes medications. This study adds to a limited body of knowledge regarding patient-centered outcomes among a group that experiences a disproportionate diabetes burden. Future work could include integrating outcomes that are less commonly addressed in diabetes-related lifestyle interventions (e.g., diabetes-related negative emotions), along with more commonly addressed outcomes (e.g., weight loss), to increase the patient-centeredness of the interventions.

    Abstract Summary: Scientists did a study to understand what African American women with type 2 diabetes want from treatments that help them manage their diabetes and weight. They asked 34 women to write down and talk about what they hoped to achieve from joining a special health program. The researchers listened to what the women said and found that most of their goals were about learning to take care of themselves, losing weight, wanting to help others with diabetes, feeling better emotionally, getting rid of diabetes, and not needing medicine for diabetes anymore. This study is important because it helps doctors and health programs know what these women really want to get better, so they can make the programs more helpful for them.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Moffitt Cancer Center
  • Augmented reality as a novel approach for addiction treatment: development of a smoking cessation app.
    Annals of medicine (2022)
    Yang MJ, Brandon KO, Sutton SK, Kleinjan M, Sawyer LE, Brandon TH, Vinci C. Augmented reality as a novel approach for addiction treatment: development of a smoking cessation app. Ann Med. 2022 Dec; 54(1):3096-3106.
    Abstract: Augmented reality (AR) is a rapidly developing technology that has substantial potential as a novel approach for addiction treatment, including tobacco use. AR can facilitate the delivery of cue exposure therapy (CET) such that individuals can experience the treatment in their natural environments as viewed via a smartphone screen, addressing the limited generalizbility of extinction learning. Previously, our team developed a basic AR app for smoking cessation and demonstrated the necessary mechanisms for CET. Specifically, we showed that the AR smoking cues, compared to neutral cues, elicited substantial cue reactivity (i.e. increased urge) and that repeated exposure to the AR smoking cues reduced urge (i.e. extinction) in a laboratory setting. Here we report the next step in the systematic development of the AR app, in which we assessed the usability and acceptability of the app among daily smokers in their natural environments. Daily smokers ( = 23, 78.3% female, Mean Age = 43.4, Mean Cigarettes/Day = 14.9), not actively quitting, were instructed to use the AR app in locations and situations where they smoke (e.g. home, bar) at least 5 times per day over one week. The study is registered in clinicaltrials.gov (NCT04101422). Results indicated high usability and acceptability. Most of the participants (73.9%) used the AR app on at least 5 days. Participants found the AR cues realistic and well-integrated in their natural environments. The AR app was perceived as easy to use (Mean = 4.1/5) and learn (mean of 2 days to learn). Overall satisfaction with the app was also high. Secondary analyses found that 56.5% reported reduced smoking, with an average 26% reduction in cigarettes per day at follow-up. These findings set the stage for a randomized controlled trial testing the AR app as an adjuvant therapy for treating tobacco dependence, with potential applicability to other substances. KEY MESSAGEThis study found that the augmented reality (AR) smartphone application that utlized cue exposure treatment for smoking cessation was perceived as easy to use and learn in the natural, day-to-day environment of daily smokers. Findings set the stage for a larger clinical trial testing the AR app as an adjuvant therapy for treating tobacco dependence, with potential applicability to other addictive behaviors.

    Abstract Summary: Scientists have created an app that uses augmented reality (AR) to help people quit smoking. The app works by showing smokers images that make them want to smoke (cues), and then helps them get used to these cues without smoking. In a test, daily smokers used the app in places where they usually smoke. The results were promising: most people found the app easy to use and realistic, and over half of them smoked less after using the app. This could be a new way to help people quit smoking, and maybe even other addictions. The next step is a bigger test to see how well the app works.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Augmented reality for extinction of cue-provoked urges to smoke: Proof of concept.
    Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors (2022)
    Yang MJ, Brandon KO, Sutton SK, Kleinjan M, Hernandez LM, Sawyer LE, Brandon TH, Vinci C. Augmented reality for extinction of cue-provoked urges to smoke: Proof of concept. Psychol Addict Behav. 2022 Dec; 36(8):990-998.
    Abstract: Cue-exposure therapy (CET) aims to extinguish conditioned cue reactivity (CR) to aid in smoking cessation. A key disadvantage of extant CET is its limited ability to generalize extinction to the real world. Our team developed a set of augmented reality smoking-related and neutral cues that can appear in real-time in smokers' natural environments as viewed through a smartphone screen. Prior to deployment as a clinical tool, the present study tested the ability of AR smoking cues to extinguish CR in a controlled laboratory study with an AR smartphone application developed for this project. We hypothesized that daily smokers who completed a single session of cue exposure with AR smoking cues (extinction condition) would demonstrate lower cue-provoked urge to smoke at posttest compared to those who viewed AR neutral cues (control condition). Daily smokers ( = 129, 46.5% female, = 47.6, = 19.1) in acute abstinence were randomized to either the extinction or control condition comprising 28 AR trials. As hypothesized, we found a Time × Condition interaction indicating that posttest urge ratings were lower in the extinction condition than in the control condition ( = .034). A secondary hypothesis that participants in the extinction condition would show a longer latency to smoke when provided a cigarette was not supported. These laboratory findings provide evidence supporting the potential clinical efficacy of AR cues for cue-exposure trials, setting the stage for testing in smokers' naturalistic environments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

    Abstract Summary: This study was about helping people quit smoking using a new tool on their smartphones. The researchers created a special app that shows images related to smoking or neutral images. They thought that showing smokers these images might help reduce their desire to smoke. They tested this idea with 129 smokers. The results showed that those who saw the smoking-related images had less desire to smoke afterwards compared to those who saw neutral images. However, seeing these images didn't make them wait longer before smoking again. This study suggests that this app could be a useful tool to help people quit smoking.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Mount Sinai School of Medicine
  • Sodium Oxybate in Alcohol-Responsive Essential Tremor of Voice: An Open-Label Phase II Study.
    Movement disorders : official journal of the Movement Disorder Society (2023)
    O'Flynn LC, Frucht SJ, Simonyan K. Sodium Oxybate in Alcohol-Responsive Essential Tremor of Voice: An Open-Label Phase II Study. Mov Disord. 2023 Oct; 38(10):1936-1944.
    Abstract: Essential tremor of voice (ETv) is characterized by involuntary oscillations of laryngeal and upper airway muscles, causing rhythmic alterations in pitch and loudness during both passive breathing and active laryngeal tasks, such as speaking and singing. Treatment of ETv is challenging and typically less effective compared with treatment of ET affecting extremities. We conducted a proof-of-concept, open-label phase II study to examine the efficacy and central effects of sodium oxybate in patients with alcohol-responsive ETv. All subjects received 1.0 to 1.5 g of oral sodium oxybate and underwent brain functional magnetic resonance imaging. The primary endpoint was the number of patients (% from total) with reduced ETv symptoms by at least 10% at about 40 to 45 minutes after sodium oxybate intake based on the combined visual analog scale score of ETv symptom severity. The secondary endpoint included changes in brain activity after sodium oxybate intake compared to baseline. Sodium oxybate reduced ETv symptoms on average by 40.8% in 92.9% of patients. Drug effects were observed about 40 to 45 minutes after intake, lasting about 3.5 hours, and gradually wearing off by the end of the fifth hour. The central effects of sodium oxybate were associated with normalized activity in the cerebellum, inferior/superior parietal lobules, inferior frontal gyrus, and insula and re-established functional relationships between these regions. Sodium oxybate showed high efficacy in ETv patients, with a likely central action on disorder pathophysiology. Sodium oxybate may be an effective novel oral drug for treatment of alcohol-responsive ETv patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

    Abstract Summary: Scientists did a study to see if a medicine called sodium oxybate could help people with a shaky voice, a condition where muscles in the throat move without control. This shaking can make the voice sound wobbly or change volume unexpectedly. It's hard to treat, especially when compared to shaking in the arms or legs. In the study, people with shaky voice took the medicine and then had a special brain scan called an MRI. The researchers wanted to see if the medicine made the shaking less and what it did to the brain. They found that after taking the medicine, most of the people's voices got a lot better—about 40% better! This improvement happened about 40 minutes after taking the medicine and lasted for around 3.5 hours. The brain scans showed that the medicine made certain parts of the brain work more normally and helped these parts communicate better with each other. This is good news because it means sodium oxybate might be a new medicine that can help people who have a shaky voice, especially if their condition gets better when they drink alcohol.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Do comorbid OCD-MDD patients need two separate dTMS protocols?
    Brain stimulation (2020)
    Harmelech T, Tendler A, Roth Y, Zangen A. Do comorbid OCD-MDD patients need two separate dTMS protocols? Brain Stimul. 2020 Jul-Aug; 13(4):1000-1001.
  • Long-Term Outcomes of Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression.
    The American journal of psychiatry (2019)
    Crowell AL, Riva-Posse P, Holtzheimer PE, Garlow SJ, Kelley ME, Gross RE, Denison L, Quinn S, Mayberg HS. Long-Term Outcomes of Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression. Am J Psychiatry. 2019 Nov 1; 176(11):949-956.
    Abstract: Deep brain stimulation of the subcallosal cingulate (SCC DBS) has been studied as a potential treatment for severe and refractory major depressive disorder since 2005. The authors used an open-label, long-term follow-up design to examine participants enrolled in a clinical trial of SCC DBS for treatment-resistant depression. Long-term outcome data were collected for 28 patients (20 with major depressive disorder and seven with bipolar II disorder; one patient in the major depression subgroup was later reclassified as having bipolar II disorder) receiving SCC DBS for 4-8 years. Response and remission rates were maintained at ≥50% and ≥30%, respectively, through years 2-8 of the follow-up period. Three-quarters of all participants met the treatment-response criterion for more than half of their duration of participation in the study, with 21% of all patients demonstrating continuous response to treatment from the first year onward. Of 28 participants, 14 completed ≥8 years of follow-up, 11 completed ≥4 years, and three dropped out before 8 years. The procedure itself was generally safe and well tolerated, and there were no side effects of acute or chronic stimulation. The rate of medical or surgical complications was consistent with the rate observed in studies of DBS for other indications. There were no suicides. In >8 years of observation, most participants experienced a robust and sustained antidepressant response to SCC DBS.

    Abstract Summary: Doctors have been looking into a special treatment for people with very serious depression that doesn't get better with regular treatments. This treatment is called deep brain stimulation, where they use a device to send tiny electric signals to a part of the brain called the subcallosal cingulate. They checked on 28 people who got this treatment for 4 to 8 years. They found that more than half of the people felt a lot better and stayed that way for a long time. The treatment was safe, and the people didn't have bad reactions to it. This is good news because it means that this treatment could really help people with tough-to-treat depression.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial.
    The American journal of psychiatry (2019)
    Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, Ward H, Lapidus K, Goodman W, Casuto L, Feifel D, Barnea-Ygael N, Roth Y, Zangen A, Zohar J. Efficacy and Safety of Deep Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder: A Prospective Multicenter Randomized Double-Blind Placebo-Controlled Trial. Am J Psychiatry. 2019 Nov 1; 176(11):931-938.
    Abstract: Obsessive-compulsive disorder (OCD) is a chronic and disabling condition that often responds unsatisfactorily to pharmacological and psychological treatments. Converging evidence suggests a dysfunction of the cortical-striatal-thalamic-cortical circuit in OCD, and a previous feasibility study indicated beneficial effects of deep transcranial magnetic stimulation (dTMS) targeting the medial prefrontal cortex and the anterior cingulate cortex. The authors examined the therapeutic effect of dTMS in a multicenter double-blind sham-controlled study. At 11 centers, 99 OCD patients were randomly allocated to treatment with either high-frequency (20 Hz) or sham dTMS and received daily treatments following individualized symptom provocation, for 6 weeks. Clinical response to treatment was determined using the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the primary efficacy endpoint was the change in score from baseline to posttreatment assessment. Additional measures were response rates (defined as a reduction of ≥30% in YBOCS score) at the posttreatment assessment and after another month of follow-up. Eighty-nine percent of the active treatment group and 96% of the sham treatment group completed the study. The reduction in YBOCS score among patients who received active dTMS treatment was significantly greater than among patients who received sham treatment (reductions of 6.0 points and 3.3 points, respectively), with response rates of 38.1% and 11.1%, respectively. At the 1-month follow-up, the response rates were 45.2% in the active treatment group and 17.8% in the sham treatment group. Significant differences between the groups were maintained at follow-up. High-frequency dTMS over the medial prefrontal cortex and anterior cingulate cortex significantly improved OCD symptoms and may be considered as a potential intervention for patients who do not respond adequately to pharmacological and psychological interventions.

    Abstract Summary: Doctors wanted to see if a special kind of brain treatment could help people with OCD, a condition where people have unwanted thoughts and do the same things over and over. They used a machine to send magnetic signals to certain parts of the brain in 99 people with OCD. Some people got the real treatment, and others got a pretend one to compare. They did this every day for 6 weeks and checked how much better the people felt using a special score. They found out that the people who got the real brain signals felt a lot better than those who got the pretend one. Even a month after the treatment, the people who got the real signals still felt better. This study shows that this brain treatment might be a good way to help people with OCD, especially if other treatments haven't worked for them.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A novel therapeutic agent, sodium oxybate, improves dystonic symptoms via reduced network-wide activity.
    Scientific reports (2018)
    Simonyan K, Frucht SJ, Blitzer A, Sichani AH, Rumbach AF. A novel therapeutic agent, sodium oxybate, improves dystonic symptoms via reduced network-wide activity. Sci Rep. 2018 Oct 31; 8(1):16111.
    Abstract: Oral medications for the treatment of dystonia are not established. Currently, symptoms of focal dystonia are managed with botulinum toxin injections into the affected muscles. However, the injection effects are short-lived and not beneficial for all patients. We recently reported significant clinical improvement of symptoms with novel investigational oral drug, sodium oxybate, in patients with the alcohol-responsive form of laryngeal focal dystonia. Understanding the mechanism of action of this promising oral agent holds a strong potential for the development of a scientific rationale for its use in dystonia. Therefore, to determine the neural markers of sodium oxybate effects, which may underlie dystonic symptom improvement, we examined brain activity during symptomatic speech production before and after drug intake in patients with laryngeal dystonia and compared to healthy subjects. We found that sodium oxybate significantly attenuated hyperfunctional activity of cerebellar, thalamic and primary/secondary sensorimotor cortical regions. Drug-induced symptom improvement was correlated with decreased-to-normal levels of activity in the right cerebellum. These findings suggest that sodium oxybate shows direct modulatory effects on disorder pathophysiology by acting upon abnormal neural activity within the dystonic network.

    Abstract Summary: Doctors are trying to find a pill to help with a muscle problem called dystonia, where muscles contract uncontrollably. Right now, they use shots to relax the muscles, but these shots don't last long and don't work for everyone. They found a new pill, sodium oxybate, that might help people whose dystonia gets better when they drink alcohol. To see how this pill works, they looked at the brain activity of people with a type of dystonia that affects the voice, both before and after they took the pill. They also looked at people without dystonia. The pill seemed to calm down the overactive parts of the brain that cause dystonia. This means the pill might be a good way to treat dystonia by fixing the brain activity that's not normal.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Alcohol responsiveness in laryngeal dystonia: a survey study.
    Journal of neurology (2015)
    Kirke DN, Frucht SJ, Simonyan K. Alcohol responsiveness in laryngeal dystonia: a survey study. J Neurol. 2015 Jun; 262(6):1548-56.
    Abstract: Laryngeal dystonia (LD) is a task-specific focal dystonia of unknown pathophysiology affecting speech production. We examined the demographics of anecdotally reported alcohol use and its effects on LD symptoms using an online survey based on Research Electronic Data Capture (REDCap™) and National Spasmodic Dysphonia Association's patient registry. From 641 participants, 531 were selected for data analysis, and 110 were excluded because of unconfirmed diagnosis. A total of 406 patients (76.5 %) had LD and 125 (23.5 %) had LD and voice tremor (LD/VT). The consumption of alcohol was reported by 374 LD (92.1 %) and 109 LD/VT (87.2 %) patients. Improvement of voice symptoms after alcohol ingestion was noted by 227 LD (55.9 % of all patients) and 73 LD/VT (58.4 %), which paralleled the improvement observed by patient's family and/or friends in 214 LD (57.2 %) and 69 LD/VT (63.3 %) patients. The benefits lasted 1-3 h in both groups with the maximum effect after 2 drinks in LD patients (p = 0.002), whereas LD/VT symptoms improved independent of the consumed amount (p = 0.48). Our data suggest that isolated dystonic symptoms, such as in LD, are responsive to alcohol intake and this responsiveness is not attributed to the presence of VT, which is known to have significant benefits from alcohol ingestion. Alcohol may modulate the pathophysiological mechanisms underlying abnormal neurotransmission of γ-aminobutyric acid (GABA) in dystonia and as such provide new avenues for novel therapeutic options in these patients.

    Abstract Summary: Scientists did a study to see if drinking alcohol helps people with a voice condition called laryngeal dystonia (LD), which makes talking difficult. They asked 531 people with LD to fill out a survey online. Most of these people said they drink alcohol, and more than half noticed that their voice got better after they had a drink. This improvement was also seen by their friends and family. The better voice lasted for 1 to 3 hours, and usually, two drinks were the most helpful. The study suggests that alcohol might affect the brain chemicals that are involved in LD, and this could lead to new treatments for people with this voice problem.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

New York State Psychiatric Institute and Research Foundation for Mental Hygiene
  • Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.
    The New England journal of medicine (2023)
    Lenze EJ, Mulsant BH, Roose SP, Lavretsky H, Reynolds CF 3rd, Blumberger DM, Brown PJ, Cristancho P, Flint AJ, Gebara MA, Gettinger TR, Lenard E, Miller JP, Nicol GE, Oughli HA, Pham VT, Rollman BL, Yang L, Karp JF. Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression. N Engl J Med. 2023 Mar 23; 388(12):1067-1079.
    Abstract: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression. In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups. In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).

    Abstract Summary: Doctors wanted to find out the best way to help older people who were still feeling sad even after taking medicine for depression. They did a study with two parts. In the first part, they gave some people an extra medicine called aripiprazole, some got an extra medicine called bupropion, and some stopped their old medicine and just took bupropion. They found that adding aripiprazole made people feel a bit happier than just switching to bupropion. In the second part, for people who didn't feel better after the first part, they tried adding lithium or switching to a medicine called nortriptyline. Both of these changes helped people feel a little happier, but there wasn't a big difference between the two. This study helps doctors know better ways to help older adults who have depression that's hard to treat.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

New York University
  • Using the multiphase optimization strategy (MOST) framework to optimize an intervention to increase COVID-19 testing for Black and Latino/Hispanic frontline essential workers: A study protocol.
    BMC public health (2022)
    Gwadz M, Cleland CM, Lizardo M, Hawkins RL, Bangser G, Parameswaran L, Stanhope V, Robinson JA, Karim S, Hollaway T, Ramirez PG, Filippone PL, Ritchie AS, Banfield A, Silverman E. Using the multiphase optimization strategy (MOST) framework to optimize an intervention to increase COVID-19 testing for Black and Latino/Hispanic frontline essential workers: A study protocol. BMC Public Health. 2022 Jun 21; 22(1):1235.
    Abstract: Among those at highest risk for COVID-19 exposure is the large population of frontline essential workers in occupations such food service, retail, personal care, and in-home health services, among whom Black and Latino/Hispanic persons are over-represented. For those not vaccinated and at risk for exposure to COVID-19, including frontline essential workers, regular (approximately weekly) COVID-19 testing is recommended. However, Black and Latino/Hispanic frontline essential workers in these occupations experience serious impediments to COVID-19 testing at individual/attitudinal- (e.g., lack of knowledge of guidelines), social- (e.g., social norms), and structural-levels of influence (e.g., poor access), and rates of testing for COVID-19 are insufficient. The proposed community-engaged study uses the multiphase optimization strategy (MOST) framework and an efficient factorial design to test four candidate behavioral intervention components informed by an integrated conceptual model that combines critical race theory, harm reduction, and self-determination theory. They are A) motivational interview counseling, B) text messaging grounded in behavioral economics, C) peer education, and D) access to testing (via navigation to an appointment vs. a self-test kit). All participants receive health education on COVID-19. The specific aims are to: identify which components contribute meaningfully to improvement in the primary outcome, COVID-19 testing confirmed with documentary evidence, with the most effective combination of components comprising an "optimized" intervention that strategically balances effectiveness against affordability, scalability, and efficiency (Aim 1); identify mediators and moderators of the effects of components (Aim 2); and use a mixed-methods approach to explore relationships among COVID-19 testing and vaccination (Aim 3). Participants will be N = 448 Black and Latino/Hispanic frontline essential workers not tested for COVID-19 in the past six months and not fully vaccinated for COVID-19, randomly assigned to one of 16 intervention conditions, and assessed at 6- and 12-weeks post-baseline. Last, N = 50 participants will engage in qualitative in-depth interviews. This optimization trial is designed to yield an effective, affordable, and efficient behavioral intervention that can be rapidly scaled in community settings. Further, it will advance the literature on intervention approaches for social inequities such as those evident in the COVID-19 pandemic. ClinicalTrials.gov: NCT05139927 ; Registered on 11/29/2021. Protocol version 1.0. May 2, 2022, Version 1.0.

    Abstract Summary: Scientists are studying how to help people who work in places like restaurants, stores, and homes, especially Black and Latino/Hispanic workers, get tested for COVID-19 more often. These workers are more likely to catch the virus and often don't get tested enough. The study will try out different ways to encourage testing, like having talks to motivate them, sending helpful text messages, teaching through friends, and making tests easier to get. They want to find the best mix of these methods that works well and isn't too expensive. They will work with 448 workers who haven't been tested or vaccinated recently to see which methods help the most. They will also talk to 50 workers in more detail to understand better. This research could lead to better ways to keep people safe from COVID-19, especially those who have a higher chance of getting sick.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Longitudinal study: understanding the lived experience of couples across the trajectory of dementia.
    BMC geriatrics (2021)
    Mittelman MS, O'Connor MK, Donley T, Epstein-Smith C, Nguyen A, Nicholson R, Salant R, Shirk SD, Stevenson E. Longitudinal study: understanding the lived experience of couples across the trajectory of dementia. BMC Geriatr. 2021 Oct 15; 21(1):558.
    Abstract: The longitudinal study, "Couples Lived Experiences," focuses on whether and how relationship characteristics of older couples change with the cognitive decline of one member of the couple, and how these changes affect each individual's emotional and physical health outcomes. Until now, most psychosocial research in dementia has focused either on the person with dementia (PWD) or the caregiver separately. The previous literature examining relationship characteristics and their role in outcomes for the caregiver and PWD is scant and suffers from methodological issues that limit the understanding of which relationship characteristics most influence outcomes for caregivers and care-receivers and what other factors may mitigate or exacerbate their effects. We will enroll 300 dyads and collect information via online interviews of each member of the couple, every 6 months for 3 years. Relationship characteristics will be measured with a set of short, well-validated, and reliable self-report measures, plus the newly developed "Partnership Approach Questionnaire." Outcomes include global quality of life, subjective physical health, mental health (depression and anxiety), and status change (transitions in levels of care; i.e., placement in a nursing home). Longitudinal data will be used to investigate how relationship characteristics are affected by cognitive, functional, and behavioral changes, and the impact of these changes on health outcomes. Qualitative data will also be collected to enrich the interpretation of results of quantitative analyses. Psychosocial interventions have demonstrated effectiveness in promoting the wellbeing of PWD and their caregivers. The knowledge gained from this study can lead to the development or enhancement of targeted interventions for older couples that consider the impact of cognitive and functional decline on the relationship between members of a couple and thereby improve their wellbeing. This study has been registered with ClinicalTrials.gov. ClinicalTrials.gov Identifier is: NCT04863495 .

    Abstract Summary: This study, called "Couples Lived Experiences," is looking at how the lives of older couples change when one person starts to have trouble with their memory and thinking. The researchers want to know how these changes affect the feelings and health of both people in the couple. Before, most studies only looked at the person with memory problems or the person taking care of them, but not both together. The study will ask 300 couples to answer questions every six months for three years. They will use special surveys to learn about the couple's relationship and how it affects their happiness, health, and if they need more help, like moving to a nursing home. They will also talk to the couples to understand their stories better. The information from this study will help create ways to help older couples stay happy and healthy when one of them starts to have memory problems.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Orexin-A is Associated with Increases in Cerebrospinal Fluid Phosphorylated-Tau in Cognitively Normal Elderly Subjects.
    Sleep (2016)
    Osorio RS, Ducca EL, Wohlleber ME, Tanzi EB, Gumb T, Twumasi A, Tweardy S, Lewis C, Fischer E, Koushyk V, Cuartero-Toledo M, Sheikh MO, Pirraglia E, Zetterberg H, Blennow K, Lu SE, Mosconi L, Glodzik L, Schuetz S, Varga AW, Ayappa I, Rapoport DM, de Leon. Orexin-A is Associated with Increases in Cerebrospinal Fluid Phosphorylated-Tau in Cognitively Normal Elderly Subjects. Sleep. 2016 Jun 1; 39(6):1253-60.
    Abstract: To evaluate the role of orexin-A with respect to cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers, and explore its relationship to cognition and sleep characteristics in a group of cognitively normal elderly individuals. Subjects were recruited from multiple community sources for National Institutes of Health supported studies on normal aging, sleep and CSF biomarkers. Sixty-three participants underwent home monitoring for sleep-disordered breathing, clinical, sleep and cognitive evaluations, as well as a lumbar puncture to obtain CSF. Individuals with medical history or with magnetic resonance imaging evidence of disorders that may affect brain structure or function were excluded. Correlation and linear regression analyses were used to assess the relationship between orexin-A and CSF AD-biomarkers controlling for potential sociodemographic and sleep confounders. Levels of orexin-A, amyloid beta 42 (Aβ42), phosphorylated-tau (P-Tau), total-tau (T-Tau), Apolipoprotein E4 status, age, years of education, reported total sleep time, number of awakenings, apnea-hypopnea indices (AHI), excessive daytime sleepiness, and a cognitive battery were analyzed. Subjects were 69.59 ± 8.55 years of age, 57.1% were female, and 30.2% were apolipoprotein E4+. Orexin-A was positively correlated with Aβ42, P-Tau, and T-Tau. The associations between orexin-A and the AD-biomarkers were driven mainly by the relationship between orexin-A and P-Tau and were not influenced by other clinical or sleep characteristics that were available. Orexin-A is associated with increased P-Tau in normal elderly individuals. Increases in orexin-A and P-Tau might be a consequence of the reduction in the proportion of the deeper, more restorative slow wave sleep and rapid eye movement sleep reported with aging. Clinicaltrials.gov registration number NCT01962779.

    Abstract Summary: Scientists did a study to see if a brain chemical called orexin-A is connected to signs of Alzheimer's disease in the brain fluid of older people who don't have memory problems. They also wanted to know if orexin-A is related to how well these people think and sleep. They had 63 older adults do sleep tests at home, take thinking tests, and get a special procedure to collect brain fluid. They made sure these people didn't have other health issues that could affect their brains. They found that higher levels of orexin-A were linked to higher levels of certain signs in the brain fluid that might predict Alzheimer's disease. This link was especially strong with a sign called P-Tau. The amount of orexin-A didn't seem to change because of other health or sleep issues the people had. This study is important because it suggests that the brain chemical orexin-A could be involved in the early stages of Alzheimer's disease. Understanding this could help us figure out how to keep people's brains healthy as they get older.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Northwestern University
  • Mobile health (m-health) smartphone interventions for adolescents and adults with overweight or obesity.
    The Cochrane database of systematic reviews (2024)
    Metzendorf MI, Wieland LS, Richter B. Mobile health (m-health) smartphone interventions for adolescents and adults with overweight or obesity. Cochrane Database Syst Rev. 2024 Feb 20; 2(2):CD013591.
    Abstract: Obesity is considered to be a risk factor for various diseases, and its incidence has tripled worldwide since 1975. In addition to potentially being at risk for adverse health outcomes, people with overweight or obesity are often stigmatised. Behaviour change interventions are increasingly delivered as mobile health (m-health) interventions, using smartphone apps and wearables. They are believed to support healthy behaviours at the individual level in a low-threshold manner. To assess the effects of integrated smartphone applications for adolescents and adults with overweight or obesity. We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, and LILACS, as well as the trials registers ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform on 2 October 2023 (date of last search for all databases). We placed no restrictions on the language of publication. Participants were adolescents and adults with overweight or obesity. Eligible interventions were integrated smartphone apps using at least two behaviour change techniques. The intervention could target physical activity, cardiorespiratory fitness, weight loss, healthy diet, or self-efficacy. Comparators included no or minimal intervention (NMI), a different smartphone app, personal coaching, or usual care. Eligible studies were randomised controlled trials of any duration with a follow-up of at least three months. We used standard Cochrane methodology and the RoB 2 tool. Important outcomes were physical activity, body mass index (BMI) and weight, health-related quality of life, self-efficacy, well-being, change in dietary behaviour, and adverse events. We focused on presenting studies with medium- (6 to < 12 months) and long-term (≥ 12 months) outcomes in our summary of findings table, following recommendations in the core outcome set for behavioural weight management interventions. We included 18 studies with 2703 participants. Interventions lasted from 2 to 24 months. The mean BMI in adults ranged from 27 to 50, and the median BMI z-score in adolescents ranged from 2.2 to 2.5. Smartphone app versus no or minimal intervention Thirteen studies compared a smartphone app versus NMI in adults; no studies were available for adolescents. The comparator comprised minimal health advice, handouts, food diaries, smartphone apps unrelated to weight loss, and waiting list. Measures of physical activity: at 12 months' follow-up, a smartphone app compared to NMI probably reduces moderate to vigorous physical activity (MVPA) slightly (mean difference (MD) -28.9 min/week (95% confidence interval (CI) -85.9 to 28; 1 study, 650 participants; moderate-certainty evidence)). We are very uncertain about the results of estimated energy expenditure and cardiorespiratory fitness at eight months' follow-up. A smartphone app compared with NMI probably results in little to no difference in changes in total activity time at 12 months' follow-up and leisure time physical activity at 24 months' follow-up. Anthropometric measures: a smartphone app compared with NMI may reduce BMI (MD of BMI change -2.6 kg/m, 95% CI -6 to 0.8; 2 studies, 146 participants; very low-certainty evidence) at six to eight months' follow-up, but the evidence is very uncertain. At 12 months' follow-up, a smartphone app probably resulted in little to no difference in BMI change (MD -0.1 kg/m, 95% CI -0.4 to 0.3; 1 study; 650 participants; moderate-certainty evidence). A smartphone app compared with NMI may result in little to no difference in body weight change (MD -2.5 kg, 95% CI -6.8 to 1.7; 3 studies, 1044 participants; low-certainty evidence) at 12 months' follow-up. At 24 months' follow-up, a smartphone app probably resulted in little to no difference in body weight change (MD 0.7 kg, 95% CI -1.2 to 2.6; 1 study, 245 participants; moderate-certainty evidence). A smartphone app compared with NMI may result in little to no difference in self-efficacy for a physical activity score at eight months' follow-up, but the results are very uncertain. A smartphone app probably results in little to no difference in quality of life and well-being at 12 months (moderate-certainty evidence) and in little to no difference in various measures used to inform dietary behaviour at 12 and 24 months' follow-up. We are very uncertain about adverse events, which were only reported narratively in two studies (very low-certainty evidence). Smartphone app versus another smartphone app Two studies compared different versions of the same app in adults, showing no or minimal differences in outcomes. One study in adults compared two different apps (calorie counting versus ketogenic diet) and suggested a slight reduction in body weight at six months in favour of the ketogenic diet app. No studies were available for adolescents. Smartphone app versus personal coaching Only one study compared a smartphone app with personal coaching in adults, presenting data at three months. Two studies compared these interventions in adolescents. A smartphone app resulted in little to no difference in BMI z-score compared to personal coaching at six months' follow-up (MD 0, 95% CI -0.2 to 0.2; 1 study; 107 participants). Smartphone app versus usual care Only one study compared an app with usual care in adults but only reported data at three months on participant satisfaction. No studies were available for adolescents. We identified 34 ongoing studies. The available evidence is limited and does not demonstrate a clear benefit of smartphone applications as interventions for adolescents or adults with overweight or obesity. While the number of studies is growing, the evidence remains incomplete due to the high variability of the apps' features, content and components, which complicates direct comparisons and assessment of their effectiveness. Comparisons with either no or minimal intervention or personal coaching show minor effects, which are mostly not clinically significant. Minimal data for adolescents also warrants further research. Evidence is also scarce for low- and middle-income countries as well as for people with different socio-economic and cultural backgrounds. The 34 ongoing studies suggest sustained interest in the topic, with new evidence expected to emerge within the next two years. In practice, clinicians and healthcare practitioners should carefully consider the potential benefits, limitations, and evolving research when recommending smartphone apps to adolescents and adults with overweight or obesity.

    Abstract Summary: Scientists wanted to see if smartphone apps help teenagers and grown-ups who weigh more than is healthy. They looked at studies where people used apps to try to be more active, eat better, or feel more confident about their health. They compared people who used these apps to those who didn't do much or used other methods like personal coaching. They found that apps might help a little, but they're not sure. Some studies showed that apps didn't really change how much people exercised or their body weight after a year. They also didn't find much difference in how people felt about their health or their eating habits. They checked a lot of studies, but the results weren't clear because the apps were all different. They also said we need more research, especially for teenagers and people in different countries or from different backgrounds. For now, doctors should think carefully before suggesting these apps because we don't know how much they help. More studies are coming, so we might learn more soon.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Reducing fear and avoidance of memory loss improves mood and social engagement in community-based older adults: a randomized trial.
    BMC geriatrics (2023)
    Farina FR, Regan J, Marquez M, An H, O'Loughlin P, Pavithra P, Taddeo M, Knight RC, Bennett M, Lenaert B, Griffith JW. Reducing fear and avoidance of memory loss improves mood and social engagement in community-based older adults: a randomized trial. BMC Geriatr. 2023 Nov 29; 23(1):786.
    Abstract: Alzheimer's disease and related dementias (ADRD) are among the most feared age-related conditions. The aim of this study was to evaluate a brief psychological intervention to promote adaptive coping in older adults experiencing heightened fear of ADRD and investigate positive downstream effects on health-related secondary outcomes, including frequency of reported memory failures, psychosocial functioning, and quality of life. Eighty-one older adults were recruited and randomized into REFRAME or active control intervention arms. Both groups received psycho-education and training in mindful monitoring of fears related to ADRD. The REFRAME group received an additional behavioral activation component intended to disrupt maladaptive avoidant coping (i.e., avoidance) strategies. Both groups completed 3-weeks of intervention exercises with accompanying questionnaires (baseline, mid- and post-intervention and 4-week follow-up). Adherence was strong (> 75%). We observed a significant reduction in ADRD-related fear and avoidance in both groups. Significant reductions were also observed for frequency of self-reported memory failures, anxiety, and depression. Depression was significantly reduced in the REFRAME group compared to the control group. Significant increases in participants' ability to participate in social activities and well-being were also observed. Findings suggest that a brief psychological intervention can mitigate ADRD-related fears and avoidant coping in older adults, and that benefits extend to broader health-related outcomes including anxiety, depression, social functioning, and well-being. Addressing ADRD-related fear has implications for healthy aging and risk reduction, as individuals may be more likely to engage in activities that are protective against ADRD but were previously avoided. https://clinicaltrials.gov/ct2/show/NCT04821960 .

    Abstract Summary: Scientists did a study to help older people who are really scared of getting Alzheimer's disease or similar problems. They wanted to see if a special short program could make them feel better and improve their lives. They had 81 older people try two different programs. Both programs taught them about the disease and how to be aware of their fears without letting them take over. One program also had extra activities to help people stop avoiding things they were scared of. They checked on the people for a few weeks to see how they were doing. The good news is that both programs helped the people feel less scared and less likely to avoid things because of their fear. They also felt better about their memory, were less anxious and sad, and enjoyed being with others more. The program with the extra activities was even better at helping with sadness. This study is important because it shows that a short program can make a big difference for older people who are worried about losing their memory and can help them stay active and happy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Indices of hepatic steatosis and fibrosis in prediabetes and association with diabetes development in the vitamin D and type 2 diabetes study.
    Journal of diabetes and its complications (2023)
    Corbin KD, Pittas AG, Desouza C, Grdinovac KK, Herzig KH, Kashyap SR, Kim SH, Nelson J, Rasouli N, Vickery EM, Knowler WC, Pratley RE. Indices of hepatic steatosis and fibrosis in prediabetes and association with diabetes development in the vitamin D and type 2 diabetes study. J Diabetes Complications. 2023 Jun; 37(6):108475.
    Abstract: Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity that leads to poor outcomes in people at high risk for development of type 2 diabetes (T2D). Vitamin D is a possible mediator. In the vitamin D and type 2 diabetes study (D2d), we investigated the relationship of baseline indices of NAFLD with incident T2D and whether the effect of vitamin D on diabetes was modified by NAFLD. Cross-sectional associations of indices of NAFLD with glycemia and vitamin D status were assessed in 3972 individuals screened for the D2d study. In those with prediabetes randomized to vitamin D or placebo (n = 2423), we examined longitudinal associations of NAFLD indices with incident T2D. We used validated non-invasive scores to assess steatosis [(hepatic steatosis index (HSI); NAFLD-liver fat score (NAFLD-LFS)] and advanced fibrosis [fibrosis-4 (FIB-4) index; AST to Platelet Ratio Index (APRI)]. Eighty-five percent of screened participants had likely steatosis by HSI and 71 % by NAFLD-LFS; 3 % were likely to have advanced fibrosis by FIB-4 and 1.2 % by APRI. FIB-4 indicated that 20.4 % of individuals require further follow up to assess liver health. Steatosis and fibrosis scores were higher among participants with worse glycemia. The NAFLD-LFS and APRI predicted development of diabetes (hazard ratios [95%CI] 1.35 [1.07, 1.70]; P = 0.012) and 2.36 (1.23, 4.54; P = 0.010), respectively). The effect of vitamin D on diabetes risk was not modified by baseline NAFLD indices. Individuals with likely steatosis had a smaller increase in serum 25-hydroxyvitamin D level in response to vitamin D than those without steatosis. The predicted high prevalence of steatosis, the need for further fibrosis workup, and the relationship between liver health and incident T2D suggest that routine screening with clinically accessible scores may be an important strategy to reduce disease burden.

    Abstract Summary: Scientists did a study to see if there's a link between liver health and getting type 2 diabetes, which is a kind of sugar sickness. They also wanted to know if vitamin D could change the chances of getting diabetes for people with liver problems. They looked at 3972 people who might get diabetes and checked their liver health using special scores. They found that a lot of these people had signs of fat in their liver and a few might have serious liver damage. They also saw that people with worse sugar levels in their blood had worse liver scores. Over time, they noticed that people with certain liver scores were more likely to get diabetes. Vitamin D didn't really change the risk of getting diabetes, but people with liver fat didn't get as much vitamin D in their blood when they took supplements. The study suggests that doctors should check people's liver health to help prevent diabetes.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Positive Psychological Intervention Effects on Depression: Positive Emotion Does Not Mediate Intervention Impact in a Sample with Elevated Depressive Symptoms.
    Affective science (2023)
    Moskowitz JT, Jackson K, Freedman ME, Grote VE, Kwok I, Schuette SA, Cheung EO, Addington EL. Positive Psychological Intervention Effects on Depression: Positive Emotion Does Not Mediate Intervention Impact in a Sample with Elevated Depressive Symptoms. Affect Sci. 2023 Mar; 4(1):163-173.
    Abstract: Positive psychological interventions (PPIs), programs that specifically target positive emotions, cognitions, and behaviors, have been shown to reduce depression and improve other aspects of psychological well-being. However, potential pathways linking PPIs to better outcomes have been under-explored. In this paper, we report the results of a randomized trial of a self-guided online delivered PPI called MARIGOLD (Mobile Affect Regulation Intervention with the Goal of Lowering Depression). Participants with elevated depression were randomized to receive MARIGOLD ( = 539) or an emotion reporting control condition ( = 63). In addition to testing direct effects of the intervention on depressive symptoms, we explored whether positive or negative emotion-operationalized as past day, past week, reactivity, or flexibility-mediated the intervention impact on depression. Results demonstrated that participants in the MARIGOLD condition had reduced depressive symptoms compared to controls and, although the effect did not reach statistical significance, reductions in past day negative emotion appeared to mediate this effect. Contrary to hypotheses, the intervention did not increase positive emotion compared to the control condition. Discussion focuses on the need for future studies to continue investigating the mechanisms of action for PPIs with emphasis on theoretically-based measurement and operationalization of emotion and other potential mediators to maximize the ultimate impact of PPIs on psychological well-being. Clinical Trials registration #NCT02861755.

    Abstract Summary: Scientists did a study to see if a special online program could help people feel less sad. This program, called MARIGOLD, is designed to make people think and act in a happier way. They had some people try MARIGOLD and others just write about their feelings. They wanted to see if the program made people less sad and if it changed their emotions. They found out that the people who used MARIGOLD were less sad than the ones who didn't. But, the program didn't really make them feel happier. The study suggests that we need to learn more about how programs like MARIGOLD can help people feel better.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effect of intratrial mean 25(OH)D concentration on diabetes risk, by race and weight: an ancillary analysis in the D2d study.
    The American journal of clinical nutrition (2023)
    Chatterjee R, Davenport CA, Vickery EM, Johnson KC, Kashyap SR, LeBlanc ES, Nelson J, Dagogo-Jack S, Pittas AG, Hughes BD, D2d Research Group. Effect of intratrial mean 25(OH)D concentration on diabetes risk, by race and weight: an ancillary analysis in the D2d study. Am J Clin Nutr. 2023 Jul; 118(1):59-67.
    Abstract: Higher serum 25-hydroxyvitamin D [25(OH)D] is associated with lower type 2 diabetes risk. 25(OH)D varies due to skin pigmentation and weight. This analysis aims to determine whether the effect of vitamin D differs among people of color and those with overweight/obesity (who have higher diabetes risk) compared with individuals who are White or have normal weight. The D2d study is a randomized clinical trial in people with prediabetes that tested the effects of daily vitamin D 4000 IU vs. placebo on diabetes risk (median followup 2.5 y). We compared baseline and intratrial mean 25(OH)D concentrations, defined as the mean of all available annual 25(OH)D values, among groups defined by self-reported race and body mass index (BMI). We used Cox proportional hazards models to assess the associations between intratrial mean 25(OH)D and diabetes risk by race- and BMI-based groups. Asian (n=130), Black (n=616), and White (n=1616) participants were included. Both baseline and intratrial mean 25(OH)D concentrations differed significantly by race groups (both P < 0.001) and were lower in Asian and Black vs. White participants, and in those with higher vs. lower BMI adjusted for race (both P < 0.001). Compared with those with lower concentrations, Black and White participants with intratrial mean 25(OH)D ≥ 40 ng/mL had significantly reduced diabetes risk [HR (95% CI): Black: 0.51 (0.29, 0.92); White: 0.42 (0.30, 0.60)] and with a similar reduction in diabetes risk among Asian participants: 0.39 (0.14, 1.11). Compared with those with lower concentrations, participants with baseline BMI < 40 kg/m who achieved intratrial mean 25(OH)D concentrations ≥ 40 ng/mL had a significantly reduced diabetes risk. There was no statistically significant interaction between intratrial 25(OH)D and race or between intratrial 25(OH)D and BMI on diabetes risk. Among people with prediabetes, particularly for Black and White race groups and those with BMI < 40 kg/m, the optimal 25(OH)D concentration may be ≥ 40 ng/mL to optimize diabetes-prevention efforts. This trial was registered at clinicaltrials.gov as NCT01942694.

    Abstract Summary: Scientists did a study to see if taking vitamin D could help people with a little high blood sugar (called prediabetes) avoid getting type 2 diabetes. They gave some people vitamin D pills and others fake pills and watched them for about 2.5 years. They were especially interested in people with different skin colors and weights because these can affect how much vitamin D someone has in their body and their risk for diabetes. They found that people who had more vitamin D in their blood, especially those who were Black or White and not too overweight, were less likely to get diabetes. For all groups, having a vitamin D level of at least 40 in their blood seemed to be good for lowering the risk of diabetes. This study tells us that having enough vitamin D might be important for people who are at risk of getting diabetes, and it could help them stay healthier.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study.
    Journal of diabetes and its complications (2022)
    Desouza C, Chatterjee R, Vickery EM, Nelson J, Johnson KC, Kashyap SR, Lewis MR, Margolis K, Pratley R, Rasouli N, Sheehan PR, Pittas AG, D2d Research Group. Electronic address: d2d@tuftsmedicalcenter.org. The effect of vitamin D supplementation on cardiovascular risk in patients with prediabetes: A secondary analysis of the D2d study. J Diabetes Complications. 2022 Aug; 36(8):108230.
    Abstract: Low blood 25(OH)D level is associated with increased cardiovascular disease (CVD) risk. Additionally, individuals with prediabetes are at higher risk for CVD than individuals with normoglycemia. We investigated the effects of vitamin D supplementation on CVD outcomes in the vitamin D and type 2 diabetes (D2d) study, a large trial among adults with prediabetes. 2423 participants were randomized to 4000 IU/day of vitamin D or placebo and followed for median 3.0 years for new-onset diabetes. In pre-specified secondary analyses, we examined the effect of vitamin D supplementation on composite Major Adverse Cardiovascular Events (MACE); expanded MACE (MACE + revascularization); atherosclerotic CVD (ASCVD) risk score; and individual CVD risk factors (blood pressure, lipids, high-sensitivity C-reactive protein). Cox models compared hazard ratios (HR) between the two groups on MACE and expanded MACE. Mean age was 60 years, 45 % were women, 13 % had history of CVD. Twenty-one participants assigned to vitamin D and 12 participants assigned to placebo met the MACE outcome (HR 1.81, 95%CI 0.89 to 3.69). There were 27 expanded MACE outcomes in each group (HR 1.02, 95%CI, 0.59 to 1.76). There were no significant differences between vitamin D and placebo in individual CVD risk factors, but change in ASCVD risk score favored the vitamin D group (-0.45 %, 95%CI -0.75 to -0.15). In people with prediabetes not selected for vitamin D insufficiency and with intermediate CVD risk, vitamin D supplementation did not decrease MACE but had a small favorable effect on ASCVD risk score. D2d ClinicalTrials.gov number, NCT01942694, prospectively registered September 16, 2013.

    Abstract Summary: Scientists did a study to see if taking vitamin D could help people with a little bit of sugar problem (called prediabetes) avoid heart diseases. They gave 2423 adults either vitamin D or a fake pill (placebo) every day for about 3 years. They checked to see who got heart problems or diabetes. They found that taking vitamin D didn't really stop people from getting heart problems, but it did help a tiny bit in lowering the chance of getting heart diseases in the future. This study helps us understand that vitamin D might be a little helpful for heart health in people who are starting to have sugar problems.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Safety and tolerability of high-dose daily vitamin D(3) supplementation in the vitamin D and type 2 diabetes (D2d) study-a randomized trial in persons with prediabetes.
    European journal of clinical nutrition (2022)
    Johnson KC, Pittas AG, Margolis KL, Peters AL, Phillips LS, Vickery EM, Nelson J, Sheehan PR, Reboussin D, Malozowski S, Chatterjee R, D2d research group. Safety and tolerability of high-dose daily vitamin D(3) supplementation in the vitamin D and type 2 diabetes (D2d) study-a randomized trial in persons with prediabetes. Eur J Clin Nutr. 2022 Aug; 76(8):1117-1124.
    Abstract: Routine use of vitamin D supplements has increased substantially in the United States. However, the safety and tolerability of long-term use of high-dose vitamin D are not known. We assessed the safety and tolerability of high-dose, daily vitamin D in the vitamin D and type 2 diabetes (D2d) study. In total, 2423 overweight/obese persons with prediabetes were randomized in a double-blind manner to either 4000 IU of vitamin D (the tolerable upper intake level for adults by the National Academy of Medicine) taken daily or matching placebo. All participants were included in this analysis. Incident adverse events (AE) were ascertained 4 times a year at in-person visits (twice a year) and interim remote encounters (twice a year) and were defined as untoward or unfavorable medical occurrences. Serious adverse events (SAE) included death, life-threatening events, and hospitalizations. A total of 8304 AEs occurred during 3 years of follow-up and were less frequent in the vitamin D group compared to placebo (Incidence Rate Ratio [IRR] = 0.94; 95% Confidence Interval (CI) 0.90, 0.98). The overall frequency of protocol-specified AEs of interest, which included nephrolithiasis, hypercalcemia, hypercalciuria, or low estimated glomerular filtration rate, was low and did not differ by group. There were no significant between-group differences in total SAEs (IRR = 0.96 (0.81, 1.14)). Vitamin D supplementation at 4000 IU per day was safe and well tolerated among overweight/obese participants at high risk for diabetes who were appropriately monitored for safety. In this population, this dose of vitamin D did not increase risk of AEs or SAEs, including those previously associated with vitamin D such as hypercalcemia, hypercalciuria, or nephrolithiasis. ClinicalTrials.gov NCT01942694, prospectively registered September 16, 2013.

    Abstract Summary: Scientists wanted to see if taking a lot of vitamin D every day is safe. They gave 2,423 people who were a bit heavy and almost had diabetes either 4,000 units of vitamin D or a fake pill that didn't do anything. They checked on these people for three years to see if they had any health problems. They found that the people taking vitamin D didn't have more health issues than those who took the fake pill. This means that taking this much vitamin D is safe for people who are a bit heavy and might get diabetes, as long as a doctor is watching over them.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Facilitator Contact, Discussion Boards, and Virtual Badges as Adherence Enhancements to a Web-Based, Self-guided, Positive Psychological Intervention for Depression: Randomized Controlled Trial.
    Journal of medical Internet research (2021)
    Moskowitz JT, Addington EL, Shiu E, Bassett SM, Schuette S, Kwok I, Freedman ME, Leykin Y, Saslow LR, Cohn MA, Cheung EO. Facilitator Contact, Discussion Boards, and Virtual Badges as Adherence Enhancements to a Web-Based, Self-guided, Positive Psychological Intervention for Depression: Randomized Controlled Trial. J Med Internet Res. 2021 Sep 22; 23(9):e25922.
    Abstract: Adherence to self-guided interventions tends to be very low, especially in people with depression. Prior studies have demonstrated that enhancements may increase adherence, but little is known about the efficacy of various enhancements in comparison to, or in combination with, one another. The aim of our study is to test whether 3 enhancements-facilitator contact (FC), an online discussion board, and virtual badges (VB)-alone, or in combination, improve adherence to a self-guided, web-based intervention for depression. We also examined whether age, gender, race, ethnicity, comfort with technology, or baseline depression predicted adherence or moderated the effects that each enhancement had on adherence. Participants were recruited through web-based sources and, after completing at least 4 out of 7 daily emotion reports, were sequentially assigned to 1 of 9 conditions-the intervention alone; the intervention plus 1, 2, or all 3 enhancements; or an emotion reporting control condition. The intervention was a positive psychological program consisting of 8 skills that specifically targeted positive emotions, and it was delivered over 5 weeks in a self-guided, web-based format. We operationalized adherence as the number of skills accessed. A total of 602 participants were enrolled in this study. Participants accessed, on average, 5.61 (SD 2.76) of 8 skills. The total number of enhancements participants received (0-3) did not predict the number of skills accessed. Participants who were assigned to the VB+FC condition accessed significantly more skills than those in the intervention only conditions. Furthermore, participants in arms that received the combination of both the VB and FC enhancements (VB+FC and VB+FC+online discussion board) accessed a greater number of skills relative to the number of skills accessed by participants who received either VB or FC without the other. Moderation analyses revealed that the receipt of VB (vs no VB) predicted higher adherence among participants with moderately severe depression at baseline. The results suggested that the VB+FC combination significantly increased the number of skills accessed in a self-guided, web-based intervention for elevated depression. We have provided suggestions for refinements to these enhancements, which may further improve adherence. ClinicalTrials.gov NCT02861755; http://clinicaltrials.gov/ct2/show/NCT02861755.

    Abstract Summary: Scientists did a study to see if certain special features could help people stick to a web-based program designed to make them feel better when they're feeling down. They tried out things like getting help from a guide, chatting on a discussion board, and earning virtual badges. They wanted to know if these features, alone or together, would make people use the program more. They had 602 people try the program and found that when people got both a guide's help and virtual badges, they used the program more than if they just had one or none of these features. This was especially true for people who were feeling really sad at the start. The study showed that adding these two features could make it more likely for people to use the program and learn new skills to improve their mood. This information could help make online programs better so that more people use them to feel happier.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A Randomized Controlled Trial Investigating the Feasibility of a Low-Intensity Psychological Intervention for Fear of Memory Loss and Quality of Life in Older Adults: Protocol for the Reducing Fear and Avoidance of Memory Loss (REFRAME) Study.
    JMIR research protocols (2021)
    O'Loughlin P, Pavithra P, Regan J, Bennett M, Knight R, Lenaert B, Marquez M, Taddeo M, Griffith J, Shapiro R, Farina F. A Randomized Controlled Trial Investigating the Feasibility of a Low-Intensity Psychological Intervention for Fear of Memory Loss and Quality of Life in Older Adults: Protocol for the Reducing Fear and Avoidance of Memory Loss (REFRAME) Study. JMIR Res Protoc. 2021 Jul 30; 10(7):e30514.
    Abstract: Dementia is the most feared disease associated with aging. Prolonged fears about memory loss and dementia can have harmful consequences even in the absence of cognitive decline. Fear of dementia is associated with poorer health outcomes and psychological well-being and increased memory failures in older adults. We will conduct a randomized controlled trial to determine the feasibility of a tailored, web-based mindfulness program to reduce fear of memory loss and increase quality of life in older adults experiencing heightened fear. Eighty participants will be recruited and divided into 2 groups (40 in each group). One group will receive psychoeducation plus mindfulness training. A second group will receive psychoeducation, mindfulness training, and additional modules targeting maladaptive behavioral avoidance (ie, social and cognitive withdrawal). Our recent etiological model posits that maladaptive behavioral avoidance strategies critically underlie psychosocial dysfunction associated with fear of memory loss. Thus, we predict better outcomes in the second group, including reduced fear of memory loss (primary outcome), Alzheimer disease, anxiety, and subjective memory failures, and increased quality of life (secondary outcomes). Outcome measures will be applied at 5 time points (before, baseline, interim, and after the intervention, and at 3-month follow-up). Data will be analyzed using mixed models and correlations. Results from this study will contribute to the current literature on dementia-related fear and improve our understanding of how to effectively address and reduce these fears. ClinicalTrials.gov NCT04821960; https://clinicaltrials.gov/ct2/show/NCT04821960. PRR1-10.2196/30514.

    Abstract Summary: Scientists are doing a study to see if a special online program can help older people who are really scared of losing their memory and getting dementia. They think that being too worried about memory loss can actually make people feel worse and even make them think they're forgetting things when they're not. They're going to have 80 people try out two different versions of the program to see which one works better. One group will learn about dementia and practice mindfulness, which is like calming their minds. The other group will do the same things but also learn how to not pull away from friends or stop doing things they enjoy. They hope that the second group will end up feeling less scared about losing their memory and have a better quality of life. They'll check on everyone a few times during and after the program to see how it's going. This study could help us understand how to make people less afraid of getting dementia as they get older.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Vitamin D Supplementation for Prevention of Cancer: The D2d Cancer Outcomes (D2dCA) Ancillary Study.
    The Journal of clinical endocrinology and metabolism (2021)
    Chatterjee R, Fuss P, Vickery EM, LeBlanc ES, Sheehan PR, Lewis MR, Dolor RJ, Johnson KC, Kashyap SR, Nelson J, Pittas AG, D2d Research Group. Vitamin D Supplementation for Prevention of Cancer: The D2d Cancer Outcomes (D2dCA) Ancillary Study. J Clin Endocrinol Metab. 2021 Aug 18; 106(9):2767-2778.
    Abstract: Observational studies suggest that low vitamin D status may be a risk factor for cancer. In a population with prediabetes and overweight/obesity that is at higher risk of cancer than the general population, we sought to determine if vitamin D supplementation lowers the risk of cancer and precancers. The Vitamin D and type 2 diabetes (D2d) cancer outcomes study (D2dCA) is an ancillary study to the D2d study, which was conducted at 22 academic medical centers in the United States. Participants had prediabetes and overweight/obesity and were free of cancer for the previous 5 years. Participants were randomized to receive vitamin D3 4000 IU daily or placebo. At scheduled study visits (4 times/year), cancer and precancer events were identified by questionnaires. Clinical data were collected and adjudicated for all reported events. Cox proportional hazard models compared the hazard ratio (HR) of incident cancers and precancers between groups. Over a median follow-up period of 2.9 years, among 2385 participants (mean age 60 years and 25-hydroxyvitamin D 28 ng/mL), there were 89 cases of cancer. The HR of incident cancer for vitamin D vs placebo was 1.07 (95% CI 0.70, 1.62). Of 241 participants with incident precancers, 239 had colorectal adenomatous polyps. The HR for colorectal polyps for vitamin D vs placebo was 0.83 (95% CI 0.64, 1.07). In the D2d population of participants with prediabetes and overweight/obesity, not selected for vitamin D insufficiency, vitamin D supplementation did not have a significant effect on risk of incident cancer or colorectal polyps.

    Abstract Summary: Scientists wanted to see if taking vitamin D could help prevent cancer in people who are more likely to get it because they are overweight and have a condition called prediabetes. They did a study with people who didn't have cancer for the last five years. These people either got vitamin D pills or fake pills without vitamin D every day. The researchers checked on them four times a year to see if they got cancer or signs that might lead to cancer. After about three years, they found that vitamin D didn't really change the chances of getting cancer or growths in the colon that could turn into cancer. This means that for these people, just taking vitamin D might not be enough to stop cancer from happening.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The Impact of the Novel Coronavirus Disease 2019 on Therapy Service Delivery for Children with Disabilities.
    The Journal of pediatrics (2021)
    Murphy A, Pinkerton LM, Bruckner E, Risser HJ. The Impact of the Novel Coronavirus Disease 2019 on Therapy Service Delivery for Children with Disabilities. J Pediatr. 2021 Apr; 231:168-177.e1.
    Abstract: To assess the impact of the novel coronavirus disease 2019 (COVID-19) pandemic on the delivery of, and parent satisfaction with, therapy services for children with disabilities in early intervention, school, and outpatient settings. There were 207 parents of children with disabilities who completed a web-based survey about their child[ren]'s access to, and satisfaction with, therapy services during COVID-19. Parents also completed the Family-Provider Partnership Scale and the Telehealth Satisfaction Scale. Satisfaction was compared between families receiving therapies in school, early intervention, outpatient, and multiple settings. Forty-four percent of parents reported low satisfaction with their child[ren]'s therapy services during the pandemic. Access to telehealth positively predicted overall satisfaction and satisfaction with the family-provider partnership, whereas receiving school-based therapies negatively predicted overall satisfaction and satisfaction with the family-provider partnership. School-based therapies are legally mandated for eligible students, free of cost to families, integrated in the academic setting, and less burdensome on parents than other services. Thus, given the disparity in parental satisfaction regarding school-based service delivery, addressing therapy delivery in school-based settings during the duration of COVID-19 is critical for preventing increased disparities and more effectively meeting children's needs. Telehealth seems to be a promising option for continuing high-quality services during the duration of the COVID-19 pandemic and for families who face barriers in accessing services in general. Future studies are warranted with larger and more diverse samples, as well as longitudinal studies that monitor service access and parent satisfaction throughout the remainder of the pandemic.

    Abstract Summary: Scientists wanted to find out how the COVID-19 pandemic affected therapy for kids with disabilities and if their parents were happy with the services. They asked 207 parents to fill out an online survey about the therapy their kids got and how they felt about it. They found that almost half of the parents weren't happy with the therapy during the pandemic. Parents liked it better when they could use telehealth (therapy over the computer or phone) and were less happy with therapy given at schools. Since therapy at school is supposed to be free and easy for families, it's important to make it better during times like the pandemic. Telehealth might be a good way to keep giving kids good therapy when it's hard to get services. More research is needed with different kinds of families and over a longer time to really understand how to help kids and their parents during tough times like a pandemic.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Implications of the Hemoglobin Glycation Index on the Diagnosis of Prediabetes and Diabetes.
    The Journal of clinical endocrinology and metabolism (2020)
    Hsia DS, Rasouli N, Pittas AG, Lary CW, Peters A, Lewis MR, Kashyap SR, Johnson KC, LeBlanc ES, Phillips LS, Hempe JM, Desouza CV, D2d Research Group. Implications of the Hemoglobin Glycation Index on the Diagnosis of Prediabetes and Diabetes. J Clin Endocrinol Metab. 2020 Mar 1; 105(3):e130-8.
    Abstract: Fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG) from a 75-g oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) can lead to different results when diagnosing prediabetes and diabetes. The Hemoglobin Glycation Index (HGI) quantifies the interindividual variation in glycation resulting in discrepancies between FPG and HbA1c. We used data from the Vitamin D and Type 2 Diabetes (D2d) study to calculate HGI, to identify HGI-associated variables, and to determine how HGI affects prediabetes and diabetes diagnosis. A linear regression equation [HbA1c (%) = 0.0164 × FPG (mg/dL) + 4.2] was derived using the screening cohort (n = 6829) and applied to calculate predicted HbA1c. This was subtracted from the observed HbA1c to determine HGI in the baseline cohort with 2hPG data (n = 3945). Baseline variables plus prediabetes and diabetes diagnosis by FPG, HbA1c, and 2hPG were compared among low, moderate, and high HGI subgroups. The proportion of women and Black/African American individuals increased from low to high HGI subgroups. Mean FPG decreased and mean HbA1c increased from low to high HGI subgroups, consistent with the HGI calculation; however, mean 2hPG was not significantly different among HGI subgroups. High HGI was associated with Black race and female sex as reported previously. The observation that 2hPG was not different across HGI subgroups suggests that variation in postprandial glucose is not a significant source of population variation in HGI. Exclusive use of HbA1c for diagnosis will classify more Black individuals and women as having prediabetes compared with using FPG or 2hPG.

    Abstract Summary: Scientists did a study to understand why different tests for sugar levels in the blood give different results when checking for diabetes or prediabetes. They looked at how a person's body adds sugar to their blood cells, which can make test results vary. They used information from a big study about vitamin D and diabetes to figure this out. They found that women and Black people often had higher sugar levels on one of the tests. The study suggests that using only this test could make it seem like more women and Black people have prediabetes than if other tests were used. This is important because it helps doctors choose the best test to use for different people.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Vitamin D Supplementation and Prevention of Type 2 Diabetes.
    The New England journal of medicine (2019)
    Pittas AG, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, Brodsky I, Ceglia L, Chadha C, Chatterjee R, Desouza C, Dolor R, Foreyt J, Fuss P, Ghazi A, Hsia DS, Johnson KC, Kashyap SR, Kim S, LeBlanc ES, Lewis MR, Liao E, Neff LM, Nelson J, O'Ne. Vitamin D Supplementation and Prevention of Type 2 Diabetes. N Engl J Med. 2019 Aug 8; 381(6):520-530.
    Abstract: Observational studies support an association between a low blood 25-hydroxyvitamin D level and the risk of type 2 diabetes. However, whether vitamin D supplementation lowers the risk of diabetes is unknown. We randomly assigned adults who met at least two of three glycemic criteria for prediabetes (fasting plasma glucose level, 100 to 125 mg per deciliter; plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter; and glycated hemoglobin level, 5.7 to 6.4%) and no diagnostic criteria for diabetes to receive 4000 IU per day of vitamin D or placebo, regardless of the baseline serum 25-hydroxyvitamin D level. The primary outcome in this time-to-event analysis was new-onset diabetes, and the trial design was event-driven, with a target number of diabetes events of 508. A total of 2423 participants underwent randomization (1211 to the vitamin D group and 1212 to the placebo group). By month 24, the mean serum 25-hydroxyvitamin D level in the vitamin D group was 54.3 ng per milliliter (from 27.7 ng per milliliter at baseline), as compared with 28.8 ng per milliliter in the placebo group (from 28.2 ng per milliliter at baseline). After a median follow-up of 2.5 years, the primary outcome of diabetes occurred in 293 participants in the vitamin D group and 323 in the placebo group (9.39 and 10.66 events per 100 person-years, respectively). The hazard ratio for vitamin D as compared with placebo was 0.88 (95% confidence interval, 0.75 to 1.04; P = 0.12). The incidence of adverse events did not differ significantly between the two groups. Among persons at high risk for type 2 diabetes not selected for vitamin D insufficiency, vitamin D supplementation at a dose of 4000 IU per day did not result in a significantly lower risk of diabetes than placebo. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; D2d ClinicalTrials.gov number, NCT01942694.).

    Abstract Summary: Scientists wanted to see if taking vitamin D could help stop people from getting type 2 diabetes. They gave some adults who were almost diabetic but not quite there yet either vitamin D pills or fake pills (placebo) every day. They didn't pick people based on their vitamin D levels to start with. They watched these adults for about 2.5 years to see who would get diabetes. They found that the people who took vitamin D had a little bit less chance of getting diabetes compared to those who took the fake pills, but the difference wasn't big enough to be sure it was because of the vitamin D. Also, the vitamin D didn't cause any bad side effects. In the end, they learned that giving a lot of vitamin D to people who are at risk of diabetes but don't have low vitamin D doesn't really help to prevent diabetes.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Establishing an electronic health record-supported approach for outreach to and recruitment of persons at high risk of type 2 diabetes in clinical trials: The vitamin D and type 2 diabetes (D2d) study experience.
    Clinical trials (London, England) (2019)
    Aroda VR, Sheehan PR, Vickery EM, Staten MA, LeBlanc ES, Phillips LS, Brodsky IG, Chadha C, Chatterjee R, Ouellette MG, Desouza C, Pittas AG, D2d Research Group. Establishing an electronic health record-supported approach for outreach to and recruitment of persons at high risk of type 2 diabetes in clinical trials: The vitamin D and type 2 diabetes (D2d) study experience. Clin Trials. 2019 Jun; 16(3):306-315.
    Abstract: To establish recruitment approaches that leverage electronic health records in multicenter prediabetes/diabetes clinical trials and compare recruitment outcomes between electronic health record-supported and conventional recruitment methods. Observational analysis of recruitment approaches in the vitamin D and type 2 diabetes (D2d) study, a multicenter trial in participants with prediabetes. Outcomes were adoption of electronic health record-supported recruitment approaches by sites, number of participants screened, recruitment performance (proportion screened who were randomized), and characteristics of participants from electronic health record-supported versus non-electronic health record methods. In total, 2423 participants were randomized: 1920 from electronic health record (mean age of 60 years, 41% women, 68% White) and 503 from non-electronic health record sources (mean age of 56.9 years, 58% women, 61% White). Electronic health record-supported recruitment was adopted by 21 of 22 sites. Electronic health record-supported recruitment was associated with more participants screened versus non-electronic health record methods (4969 vs 2166 participants screened), higher performance (38.6% vs 22.7%), and more randomizations (1918 vs 505). Participants recruited via electronic health record were older, included fewer women and minorities, and reported higher use of dietary supplements. Electronic health record-supported recruitment was incorporated in diverse clinical environments, engaging clinicians either at the individual or the healthcare system level. Establishing electronic health record-supported recruitment approaches across a multicenter prediabetes/diabetes trial is feasible and can be adopted by diverse clinical environments.

    Abstract Summary: Scientists wanted to find out if using electronic health records (like the health information your doctor keeps on a computer) could help them get more people to join studies about prediabetes and diabetes. They looked at a big study about vitamin D and type 2 diabetes to see how well this method worked compared to the usual way of asking people to join studies. They found that when they used electronic health records, they could get more people to be part of the study. Out of 2423 people who joined the study, 1920 were found through electronic records. These people were usually older, and there were fewer women and people from different racial backgrounds compared to those who joined the study without electronic records. The study showed that using electronic health records can be a good way to get more people to join health studies, and it works in many different places where people get healthcare. This is important because it can help doctors and scientists learn more about health problems like diabetes and find better ways to treat them.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts.
    Diabetes care (2018)
    LeBlanc ES, Pratley RE, Dawson-Hughes B, Staten MA, Sheehan PR, Lewis MR, Peters A, Kim SH, Chatterjee R, Aroda VR, Chadha C, Neff LM, Brodsky IG, Rosen C, Desouza CV, Foreyt JP, Hsia DS, Johnson KC, Raskin P, Kashyap SR, O'Neil P, Phillips LS, Rasouli N,. Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts. Diabetes Care. 2018 Aug; 41(8):1590-1599.
    Abstract: To describe baseline characteristics of the Vitamin D and Type 2 Diabetes (D2d) study, the first large U.S. diabetes prevention clinical trial to apply current American Diabetes Association (ADA) criteria for prediabetes. This is a multicenter ( = 22 sites), randomized, double-blind, placebo-controlled, primary prevention clinical trial testing effects of oral daily 4,000 IU cholecalciferol (D) compared with placebo on incident diabetes in U.S. adults at risk for diabetes. Eligible participants were at risk for diabetes, defined as not meeting criteria for diabetes but meeting at least two 2010 ADA glycemic criteria for prediabetes: fasting plasma glucose (FPG) 100-125 mg/dL, 2-h postload glucose (2hPG) after a 75-g oral glucose load 140-199 mg/dL, and/or a hemoglobin A (HbA) 5.7-6.4% (39-46 mmol/mol). A total of 2,423 participants (45% of whom were women and 33% nonwhite) were randomized to cholecalciferol or placebo. Mean (SD) age was 59 (9.9) years and BMI 32 (4.5) kg/m. Thirty-five percent met all three prediabetes criteria, 49% met the FPG/HbA criteria only, 9.5% met the 2hPG/FPG criteria only, and 6.3% met the 2hPG/HbA criteria only. Black participants had the highest mean HbA and lowest FPG concentration compared with white, Asian, and other races ( < 0.01); 2hPG concentration did not differ among racial groups. When compared with previous prediabetes cohorts, the D2d cohort had lower mean 2hPG concentration but similar HbA and FPG concentrations. D2d will establish whether vitamin D supplementation lowers risk of diabetes and will inform about the natural history of prediabetes per contemporary ADA criteria.

    Abstract Summary: Scientists did a big study to see if taking vitamin D every day can help stop people from getting type 2 diabetes. They picked adults who were close to getting diabetes but didn't have it yet. These adults had higher than normal blood sugar levels or a test called hemoglobin A that was a little high. They gave some people vitamin D pills and others fake pills without telling them which one they got. They had 2,423 people in the study, almost half were women and a third were not white. They found that black people had different blood sugar levels than other races. The study will help us understand if vitamin D can prevent diabetes and teach us more about how prediabetes changes over time.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A Self-Paced, Web-Based, Positive Emotion Skills Intervention for Reducing Symptoms of Depression: Protocol for Development and Pilot Testing of MARIGOLD.
    JMIR research protocols (2018)
    Cheung EO, Addington EL, Bassett SM, Schuette SA, Shiu EW, Cohn MA, Leykin Y, Saslow LR, Moskowitz JT. A Self-Paced, Web-Based, Positive Emotion Skills Intervention for Reducing Symptoms of Depression: Protocol for Development and Pilot Testing of MARIGOLD. JMIR Res Protoc. 2018 Jun 5; 7(6):e10494.
    Abstract: Living with elevated symptoms of depression can have debilitating consequences for an individual's psychosocial and physical functioning, quality of life, and health care utilization. A growing body of evidence demonstrates that skills for increasing positive emotion can be helpful to individuals with depression. Although Web-based interventions to reduce negative emotion in individuals with depression are available, these interventions frequently suffer from poor retention and adherence and do not capitalize on the potential benefits of increasing positive emotion. The aim of this study was to develop and test a Web-based positive emotion skills intervention tailored for individuals living with elevated depressive symptoms, as well as to develop and test enhancement strategies for increasing retention and adherence to that intervention. This study protocol describes the development and testing for Mobile Affect Regulation Intervention with the Goal of Lowering Depression (MARIGOLD), a Web-based positive emotion skills intervention, adapted for individuals with elevated depressive symptomatology. The intervention development is taking place in three phases. In phase 1, we are tailoring an existing positive emotion skills intervention for individuals with elevated symptoms of depression and are pilot testing the tailored version of the intervention in a randomized controlled trial with two control conditions (N=60). In phase 2, we are developing and testing three enhancements aimed at boosting retention and adherence to the Web-based intervention (N=75): facilitator contact, an online discussion board, and virtual badges. In phase 3, we are conducting a multifactorial, nine-arm pilot trial (N=600) to systematically test these enhancement strategies, individually and in combination. The primary outcome is depressive symptom severity. Secondary outcomes include positive and negative emotion, psychological well-being, and coping resources. The project was funded in August 2014, and data collection was completed in May 2018. Data analysis is currently under way, and the first results are expected to be submitted for publication in 2018. Findings from this investigation will enable us to develop an optimal package of intervention content and enhancement strategies for individuals with elevated symptoms of depression. If this intervention proves to be effective, it will provide a cost-effective, anonymous, appealing, and flexible approach for reducing symptoms of depression and improving psychological adjustment through increasing positive emotion. ClinicalTrials.gov NCT01964820 (Phase 1); https://clinicaltrials.gov/ct2/show/NCT01964820 (Archived by WebCite at http://www.webcitation.org/6zpmKBcyX). ClinicalTrials.gov NCT02861755 (Phase 2); https://clinicaltrials.gov/ct2/show/NCT02861755 (Archived by WebCite at http://www.webcitation.org/6zpmLmy8k). RR1-10.2196/10494.

    Abstract Summary: Scientists are working on a special online program called MARIGOLD to help people who feel very sad or depressed. This program teaches them ways to feel happier. They are testing the program in three parts. First, they made the program just right for people with depression and tried it out with a small group. Next, they added special features like talking to a helper, joining a chat board, and earning fun badges to see if these help people stick with the program. Finally, they are testing all these features with a bigger group to find the best mix. They want to see if the program makes people less sad and helps them cope better. If it works, it could be an easy and private way for people to feel better without spending a lot of money.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • "Even my sister says I'm acting like a crazy to get a check": Race, gender, and moral boundary-work in women's claims of disabling chronic pain.
    Social science & medicine (1982) (2017)
    Pryma J. "Even my sister says I'm acting like a crazy to get a check": Race, gender, and moral boundary-work in women's claims of disabling chronic pain. Soc Sci Med. 2017 May; 181:66-73.
    Abstract: Recent research examines how women claim chronic pain in response to gendered moral discourses. However, extant research does not explore how race shapes the moral boundary-work performed by women suffering from disabling chronic pain. Through the qualitative analysis of twenty-four semi-structured interviews with women fibromyalgia sufferers conducted between October 2014 and August 2016 in the U.S.A., I demonstrate how women with fibromyalgia claim chronic pain by doing moral boundary-work, referencing gendered and racialized moral discourses that structure how claims of chronic pain as disability are and are not read as legitimate by doctors, disability bureaucrats and personal networks. Extending Hansen et al.'s work on stigma and the "pathologization of poverty," I suggest that, per my sample, the different moral discourses deployed in white and Black women's claims of chronic pain can be explained by the racialized and gendered boundaries of citizenship that structure U.S. welfare and disability politics. Finally, I argue for intersectionality's relevance to research on moral boundary-work and the medicalization of poverty.

    Abstract Summary: This study looked at how women with a painful condition called fibromyalgia talk about their pain and how their race affects this. The researcher talked to 24 women in the United States to learn more. They found that women use different ways to explain their pain to doctors and others, depending on their race and gender. This is because people have different ideas about what kind of pain is real or serious. The study shows that it's important to think about both race and gender when studying how people talk about their health, especially when they need help from doctors or the government.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Management of Hemoglobin Variants Detected Incidentally in HbA1c Testing: A Common Problem Currently Lacking a Standard Approach.
    Diabetes care (2017)
    Lewis MR, Macauley RC, Sheehan PR, Staten MA, Phillips LS, Rasouli N, Pittas AG, D2d Research Group. Management of Hemoglobin Variants Detected Incidentally in HbA1c Testing: A Common Problem Currently Lacking a Standard Approach. Diabetes Care. 2017 Feb; 40(2):e8-e9.
  • Rationale and design of the Vitamin D and Type 2 Diabetes (D2d) study: a diabetes prevention trial.
    Diabetes care (2014)
    Pittas AG, Dawson-Hughes B, Sheehan PR, Rosen CJ, Ware JH, Knowler WC, Staten MA, D2d Research Group. Rationale and design of the Vitamin D and Type 2 Diabetes (D2d) study: a diabetes prevention trial. Diabetes Care. 2014 Dec; 37(12):3227-34.
    Abstract: Observational studies suggest that vitamin D may lower the risk of type 2 diabetes. However, data from long-term trials are lacking. The Vitamin D and Type 2 Diabetes (D2d) study is a randomized clinical trial designed to examine whether a causal relationship exists between vitamin D supplementation and the development of diabetes in people at high risk for type 2 diabetes. D2d was designed with support from a U34 planning grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The final protocol was approved by the D2d Research Group, the data and safety monitoring board, and NIDDK. Key eligibility criteria are age ≥30 years, BMI of 24 (22.5 for Asian Americans) to 42 kg/m(2), increased risk for diabetes (defined as meeting two of three glycemic criteria for prediabetes established by the American Diabetes Association [fasting glucose 100-125 mg/dL (5.5-6.9 mmol/L), 2-h postload glucose after 75-g glucose load 140-199 mg/dL (7.7-11.0 mmol/L), hemoglobin A₁c 5.7-6.4% (39-46 mmol/mol)]), and no hyperparathyroidism, nephrolithiasis, or hypercalcemia. D2d participants are randomized to once-daily vitamin D₃ (cholecalciferol 4,000 IU) or placebo and followed for an average of 3 years. The primary end point is time to incident diabetes as assessed by laboratory criteria during the study or by adjudication if diagnosed outside of D2d. Recruitment was initiated at the end of 2013. D2d will test whether vitamin D supplementation is safe and effective at lowering the risk of progression to diabetes in people at high risk for type 2 diabetes.

    Abstract Summary: Scientists are doing a big study to see if taking vitamin D can help stop people from getting type 2 diabetes. They're looking at people who might get diabetes because they already have some signs of it. These people are being given either vitamin D pills or fake pills without vitamin D, and the researchers are watching them for about 3 years to see who gets diabetes. The study started at the end of 2013, and it's important because if vitamin D can prevent diabetes, that would be a big deal for lots of people's health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Moving beyond perceptions: internalized stigma in the irritable bowel syndrome.
    Neurogastroenterology and motility (2014)
    Taft TH, Riehl ME, Dowjotas KL, Keefer L. Moving beyond perceptions: internalized stigma in the irritable bowel syndrome. Neurogastroenterol Motil. 2014 Jul; 26(7):1026-35.
    Abstract: Internalized stigma (IS) is an important construct in the chronic illness literature with implications for several patient reported outcomes. To date, no study exists evaluating IS in patients with the irritable bowel syndrome (IBS). Two hundred and forty three online and clinical participants completed the following questionnaires: the IS scale for mental illness (ISMI; modified for IBS), perceived stigma scale for IBS, NIH-PROMIS Anxiety and Depression Scales, IBS quality of life scale, and the Perceived Health Competence Scale. Demographical and clinical data were also collected. The modified ISMI was reliable and valid in this population. Participants reported both perceived and IS. Alienation was most reported, followed by social withdrawal and discrimination experiences. IS predicted 25-40% of the variance in psychological functioning, quality of life, healthcare utilization, and health competence when controlling for stigma perception and disease variables. IBS patients perceived more stigma from personal relations than healthcare providers. Hispanic participants reported more perceived stigma, indicating there may be cultural differences in IBS-related stigma experience. Symptom severity, disruptiveness, and treatment choices are also implicated in stigma perception and internalization. Patients with IBS report both perceived and IS with alienation most reported. However, IS significantly predicts several patient outcomes when controlling for PS. Cultural and illness traits may influence how stigma is perceived and internalized. Future research is warranted.

    Abstract Summary: Scientists did a study to learn about how people with a tummy problem called irritable bowel syndrome (IBS) feel about themselves because of their illness. They asked 243 people with IBS to fill out special questionnaires about their feelings, how they think others see them, and how IBS affects their lives. They found that the questions worked well to understand these feelings. People with IBS often felt left out and sometimes pulled away from others or felt that people treated them unfairly because of their illness. These bad feelings can really affect how happy they are, how often they go to the doctor, and how they handle their health. The study also found that people with IBS felt more judged by friends and family than by doctors. People from different backgrounds, like Hispanic people, felt these judgments differently. How bad their symptoms were and the choices they made for treatment also played a role in how they felt about themselves. The study shows that these feelings are a big deal for people with IBS and that we need to learn more about it.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Ohio University
  • Effectiveness of blood flow restricted exercise compared with standard exercise in patients with recurrent low back pain: study protocol for a randomized controlled trial.
    Trials (2016)
    Amano S, Ludin AF, Clift R, Nakazawa M, Law TD, Rush LJ, Manini TM, Thomas JS, Russ DW, Clark BC. Effectiveness of blood flow restricted exercise compared with standard exercise in patients with recurrent low back pain: study protocol for a randomized controlled trial. Trials. 2016 Feb 12; 17:81.
    Abstract: Low back pain is a highly prevalent condition in the United States and has a staggeringly negative impact on society in terms of expenses and disability. It has previously been suggested that rehabilitation strategies for persons with recurrent low back pain should be directed to the medial back muscles as these muscles provide functional support of the lumbar region. However, many individuals with low back pain cannot safely and effectively induce trunk muscle adaptation using traditional high-load resistance exercise, and no viable low-load protocols to induce trunk extensor muscle adaptation exist. Herein, we present the study protocol for a randomized controlled trial that will investigate the "cross-transfer" of effects of a novel exercise modality, blood flow restricted exercise, on cross-sectional area (primary outcome), strength and endurance (secondary outcomes) of trunk extensor muscles, as well as the pain, disability, and rate of recurrence of low back pain (tertiary outcomes). This is a single-blinded, single-site, randomized controlled trial. A minimum of 32 (and up to 40) subjects aged 18 to 50 years with recurrent low back pain and poor trunk extensor muscle endurance will be recruited, enrolled and randomized. After completion of baseline assessments, participants will be randomized in a 1:1 ratio to receive a 10-week resistance exercise training program with blood flow restriction (BFR exercise group) or without blood flow restriction (control exercise group). Repeat assessments will be taken immediately post intervention and at 12 weeks after the completion of the exercise program. Furthermore, once every 4 weeks during a 36-week follow-up period, participants will be asked to rate their perceived disability and back pain over the past 14 days. This study will examine the potential for blood flow restricted exercise applied to appendicular muscles to result in a "cross-transfer" of therapeutic effect to the lumbar musculature in individuals with low back pain. The results of this study will provide important insights into the effectiveness of this novel exercise modality, which could potentially provide the foundation for a cost-effective and easy-to-implement rehabilitation strategy to induce muscle adaptation in the absence of high mechanical and compressive loading on the spine. This trial is registered with ClinicalTrials.gov (registration number: NCT02308189, date of registration: 2 December 2014).

    Abstract Summary: Scientists are doing a study to see if a new kind of exercise can help people with back pain. This exercise makes muscles work hard without having to lift heavy weights, which can be safer for the back. They will have two groups of people between 18 and 50 years old who often have back pain do exercises for 10 weeks. One group will do the special exercise that limits blood flow to the muscles, and the other group will do regular exercises. They want to see if the special exercise makes the back muscles stronger, helps with pain, and stops the pain from coming back. If it works, this could be a new way to help people with back pain without making them do hard exercises that could hurt their backs more. The study's number is NCT02308189, and it started on December 2, 2014.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

OhioHealth Corporation
  • Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage.
    The Cochrane database of systematic reviews (2023)
    Eilertsen H, Menon CS, Law ZK, Chen C, Bath PM, Steiner T, Desborough MJ, Sandset EC, Sprigg N, Al-Shahi Salman R. Haemostatic therapies for stroke due to acute, spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Oct 23; 10(10):CD005951.
    Abstract: Outcome after acute spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is influenced by haematoma volume. ICH expansion occurs in about 20% of people with acute ICH. Early haemostatic therapy might improve outcome by limiting ICH expansion. This is an update of a Cochrane Review first published in 2006, and last updated in 2018. To examine 1. the effects of individual classes of haemostatic therapies, compared with placebo or open control, in adults with acute spontaneous ICH, and 2. the effects of each class of haemostatic therapy according to the use and type of antithrombotic drug before ICH onset. We searched the Cochrane Stroke Trials Register, CENTRAL (2022, Issue 8), MEDLINE Ovid, and Embase Ovid on 12 September 2022. To identify further published, ongoing, and unpublished randomised controlled trials (RCTs), we scanned bibliographies of relevant articles and searched international registers of RCTs in September 2022. We included RCTs of any haemostatic intervention (i.e. procoagulant treatments such as clotting factor concentrates, antifibrinolytic drugs, platelet transfusion, or agents to reverse the action of antithrombotic drugs) for acute spontaneous ICH, compared with placebo, open control, or an active comparator. We used standard Cochrane methods. Our primary outcome was death/dependence (modified Rankin Scale (mRS) 4 to 6) by day 90. Secondary outcomes were ICH expansion on brain imaging after 24 hours, all serious adverse events, thromboembolic adverse events, death from any cause, quality of life, mood, cognitive function, Barthel Index score, and death or dependence measured on the Extended Glasgow Outcome Scale by day 90. We included 20 RCTs involving 4652 participants: nine RCTs of recombinant activated factor VII (rFVIIa) versus placebo/open control (1549 participants), eight RCTs of antifibrinolytic drugs versus placebo/open control (2866 participants), one RCT of platelet transfusion versus open control (190 participants), and two RCTs of prothrombin complex concentrates (PCC) versus fresh frozen plasma (FFP) (47 participants). Four (20%) RCTs were at low risk of bias in all criteria. For rFVIIa versus placebo/open control for spontaneous ICH with or without surgery there was little to no difference in death/dependence by day 90 (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.74 to 1.05; 7 RCTs, 1454 participants; low-certainty evidence). We found little to no difference in ICH expansion between groups (RR 0.81, 95% CI 0.56 to 1.16; 4 RCTs, 220 participants; low-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 0.81, 95% CI 0.30 to 2.22; 2 RCTs, 87 participants; very low-certainty evidence; death from any cause: RR 0.78, 95% CI 0.56 to 1.08; 8 RCTs, 1544 participants; moderate-certainty evidence). For antifibrinolytic drugs versus placebo/open control for spontaneous ICH, there was no difference in death/dependence by day 90 (RR 1.00, 95% CI 0.93 to 1.07; 5 RCTs, 2683 participants; high-certainty evidence). We found a slight reduction in ICH expansion with antifibrinolytic drugs for spontaneous ICH compared to placebo/open control (RR 0.86, 95% CI 0.76 to 0.96; 8 RCTs, 2866 participants; high-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 1.02, 95% CI 0.75 to 1.39; 4 RCTs, 2599 participants; high-certainty evidence; death from any cause: RR 1.02, 95% CI 0.89 to 1.18; 8 RCTs, 2866 participants; high-certainty evidence). There was little to no difference in quality of life, mood, or cognitive function (quality of life: mean difference (MD) 0, 95% CI -0.03 to 0.03; 2 RCTs, 2349 participants; mood: MD 0.30, 95% CI -1.98 to 2.57; 2 RCTs, 2349 participants; cognitive function: MD -0.37, 95% CI -1.40 to 0.66; 1 RCTs, 2325 participants; all high-certainty evidence). Platelet transfusion likely increases death/dependence by day 90 compared to open control for antiplatelet-associated ICH (RR 1.29, 95% CI 1.04 to 1.61; 1 RCT, 190 participants; moderate-certainty evidence). We found little to no difference in ICH expansion between groups (RR 1.32, 95% CI 0.91 to 1.92; 1 RCT, 153 participants; moderate-certainty evidence). There was little to no difference in all serious adverse events and death from any cause between groups (all serious adverse events: RR 1.46, 95% CI 0.98 to 2.16; 1 RCT, 190 participants; death from any cause: RR 1.42, 95% CI 0.88 to 2.28; 1 RCT, 190 participants; both moderate-certainty evidence). For PCC versus FFP for anticoagulant-associated ICH, the evidence was very uncertain about the effect on death/dependence by day 90, ICH expansion, all serious adverse events, and death from any cause between groups (death/dependence by day 90: RR 1.21, 95% CI 0.76 to 1.90; 1 RCT, 37 participants; ICH expansion: RR 0.54, 95% CI 0.23 to 1.22; 1 RCT, 36 participants; all serious adverse events: RR 0.27, 95% CI 0.02 to 3.74; 1 RCT, 5 participants; death from any cause: RR 0.49, 95% CI 0.16 to 1.56; 2 RCTs, 42 participants; all very low-certainty evidence). In this updated Cochrane Review including 20 RCTs involving 4652 participants, rFVIIa likely results in little to no difference in reducing death or dependence after spontaneous ICH with or without surgery; antifibrinolytic drugs result in little to no difference in reducing death or dependence after spontaneous ICH, but result in a slight reduction in ICH expansion within 24 hours; platelet transfusion likely increases death or dependence after antiplatelet-associated ICH; and the evidence is very uncertain about the effect of PCC compared to FFP on death or dependence after anticoagulant-associated ICH. Thirteen RCTs are ongoing and are likely to increase the certainty of the estimates of treatment effect.

    Abstract Summary: Doctors wanted to see if certain medicines could help adults who had a type of brain bleed that happens suddenly, without an injury. They looked at studies where patients got either the medicine being tested or a fake medicine (placebo) or no extra treatment. They wanted to know if these medicines could stop the bleeding from getting worse and help patients get better. They found 20 studies with 4,652 patients and looked at different medicines. Some studies tested a medicine called rFVIIa, but it didn't really help patients avoid death or serious health problems. Another medicine, called antifibrinolytic drugs, didn't change the chances of dying or having serious health problems either, but it did help a little to stop the bleeding from getting worse. Giving patients platelet transfusions seemed to make things worse, not better. They also looked at a treatment called PCC compared to another one called FFP, but they weren't sure if it was helpful or not. The doctors said that more studies are being done, and those might give clearer answers about how to help people with this kind of brain bleed.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Recombinant factor VIIa for hemorrhagic stroke treatment at earliest possible time (FASTEST): Protocol for a phase III, double-blind, randomized, placebo-controlled trial.
    International journal of stroke : official journal of the International Stroke Society (2022)
    Naidech AM, Grotta J, Elm J, Janis S, Dowlatshahi D, Toyoda K, Steiner T, Mayer SA, Khanolkar P, Denlinger J, Audebert HJ, Molina C, Khatri P, Sprigg N, Vagal A, Broderick JP. Recombinant factor VIIa for hemorrhagic stroke treatment at earliest possible time (FASTEST): Protocol for a phase III, double-blind, randomized, placebo-controlled trial. Int J Stroke. 2022 Aug; 17(7):806-809.
    Abstract: Intracerebral hemorrhage is the deadliest form of stroke. Hematoma expansion, growth of the hematoma between the baseline computed tomography scan and a follow-up computed tomography scan at 24 ± 6 h, predicts long-term disability or death. Recombinant factor VIIa (rFVIIa) has reduced hematoma expansion in previous clinical trials with a variable effect on clinical outcomes, with the greatest impact on hematoma expansion and potential benefit when administered within 2 h of symptom onset. Factor VIIa for Hemorrhagic Stroke Treatment at Earliest Possible Time (FASTEST, NCT03496883) is a randomized controlled trial that will enroll 860 patients at ∼100 emergency departments and mobile stroke units in five countries. Patients are eligible for enrollment if they have acute intracerebral hemorrhage within 2 h of symptom onset confirmed by computed tomography, a hematoma volume of 2 to 60 mL, no or small volumes of intraventricular hemorrhage, do not take anticoagulant medications or concurrent heparin/heparinoids (antiplatelet medications are permissible), and are not deeply comatose. Enrolled patients will receive rFVIIa 80 µg/kg or placebo intravenously over 2 min. The primary outcome measure is the distribution of the ordinal modified Rankin Scale at 180 days. FASTEST is monitored by a Data Safety Monitoring Board. Safety endpoints include thrombotic events (e.g. myocardial infarction). Human subjects research is monitored by an external Institutional Review Board in participating countries. In the US, FASTEST will be first NIH StrokeNet Trial with an Exception from Informed Consent which allows enrollment of non-communicative patients without an immediately identifiable proxy.

    Abstract Summary: Doctors are doing a big study called FASTEST to see if a special medicine called rFVIIa can help people who have had a very bad kind of stroke that causes bleeding in the brain. This bleeding can get worse and cause more damage or even death. The medicine might stop the bleeding from getting bigger if it's given really quickly, within 2 hours after the stroke starts. They're going to give the medicine or a pretend medicine (placebo) to about 860 people who just had this kind of stroke. They want to see if the people who get the real medicine do better after 6 months than those who don't. They're being very careful to make sure it's safe and are watching for any bad things that might happen because of the medicine. This study is important because it might help doctors learn how to treat this dangerous kind of stroke better and save more lives.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Oregon Health & Science University
  • Can strength training or tai ji quan training reduce frailty in postmenopausal women treated with chemotherapy? A secondary data analysis of the GET FIT trial.
    Journal of cancer survivorship : research and practice (2024)
    Winters-Stone KM, Stoyles SA, Dieckmann NF, Eckstrom E, Luoh SW, Horak FB, Roeland EJ, Li F. Can strength training or tai ji quan training reduce frailty in postmenopausal women treated with chemotherapy? A secondary data analysis of the GET FIT trial. J Cancer Surviv. 2024 Apr 20; :.
    Abstract: To determine whether strength training or tai ji quan can reduce frailty in older, postmenopausal women treated with chemotherapy for cancer. We conducted a secondary data analysis from a 3-arm, single-blind, randomized controlled trial where older (50-75 years), postmenopausal women cancer survivors were randomized to supervised group exercise programs: tai ji quan, strength training, or stretching control for 6 months. We assessed frailty using a 4-criteria model consisting of weakness, fatigue, inactivity, and slowness. Using logistic regression, we determined whether the frailty phenotype (pre-frailty or frailty) decreased post-intervention, how many and which frailty criteria decreased, and what characteristics identified women most likely to reduce frailty. Data from 386 women who completed baseline and 6-month testing were used (mean age of 62.0 ± 6.4 years). The odds of reducing overall frailty over 6 months were significantly higher in the strength training group compared to controls (OR [95%CI] 1.86 [1.09, 3.17]) but not for tai ji quan (1.44 [0.84, 2.50]). Both strength training (OR 1.99 [1.10, 3.65]) and tai ji quan (OR 2.10 [1.16, 3.84]) led to significantly higher odds of reducing ≥ 1 frailty criterion compared to controls. Strength training led to a three-fold reduction in inactivity (p < 0.01) and tai ji quan to a two-fold reduction in fatigue (p = 0.08) versus control. Higher baseline BMI, comorbidity score, and frailty status characterized women were more likely to reduce frailty than other women. Strength training appears superior to tai ji quan and stretching with respect to reducing overall frailty phenotype among postmenopausal women treated with chemotherapy for cancer, but tai ji quan favorably reduced the number of frailty criteria. ClinicalTrials.gov identifier: GET FIT was registered as a clinical trial in clinicaltrials.gov: NCT01635413. Supervised, group exercise training that emphasizes strength training and/or tai ji quan may help combat accelerated aging and reduce frailty after cancer treatment.

    Abstract Summary: Scientists wanted to see if certain exercises could help older women who had cancer treatments feel stronger and less tired. They had women between 50 and 75 years old do different exercises like tai chi, strength training, or stretching for six months. They checked to see if the women felt less weak, tired, slow, or inactive after doing these exercises. They found that the women who did strength training were more likely to feel less frail compared to those who just stretched. Tai chi also helped, especially with making the women feel less tired. The study suggests that exercises focusing on building strength or doing tai chi can help older women who had cancer treatments feel better and more active.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Reply to Y.-T. Hu et al.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2023)
    Winters-Stone KM, Roeland EJ, Li F, Eckstrom E, Horak F, Dieckmann NF, Stoyles SA, Luoh SW. Reply to Y.-T. Hu et al. J Clin Oncol. 2023 Sep 10; 41(26):4316-4317.
  • GET FIT: A Randomized Clinical Trial of Tai Ji Quan Versus Strength Training for Fall Prevention After Chemotherapy in Older, Postmenopausal Women Cancer Survivors.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2023)
    Winters-Stone KM, Horak F, Dieckmann NF, Luoh SW, Eckstrom E, Stoyles SA, Roeland EJ, Li F. GET FIT: A Randomized Clinical Trial of Tai Ji Quan Versus Strength Training for Fall Prevention After Chemotherapy in Older, Postmenopausal Women Cancer Survivors. J Clin Oncol. 2023 Jun 20; 41(18):3384-3396.
    Abstract: To compare the efficacy of tai ji quan versus strength training to prevent falls after chemotherapy in older, postmenopaual women. We conducted a three-arm, single-blind, randomized controlled trial where older (50+ years), postmenopausal women cancer survivors participated in one of three supervised group exercise programs (tai ji quan, strength training, or stretching control) twice weekly for 6 months and were followed up 6 months after training stopped. The primary outcome was the incidence of falls. Secondary outcomes included fall-related injuries, leg strength (1 repetition maximum; kg), and balance (sensory organization [equilibrium score] and limits of stability [LOS; %] tests). Four hundred sixty-two women were enrolled (mean age, 62 ± 6.3 years). Retention was 93%, and adherence averaged 72.9%. In primary analysis, there was no difference in the incidence of falls between groups after 6 months of training, nor during 6-month follow-up. A post hoc analysis detected a significantly reduced incidence of fall-related injuries within the tai ji quan group over the first 6 months, dropping from 4.3 falls per 100 person-months (95% CI, 2.9 to 5.6) at baseline to 2.4 falls per person-months (95% CI, 1.2 to 3.5). No significant changes occurred during 6-month follow-up. Over the intervention period, leg strength significantly improved in the strength group and balance (LOS) improved in the tai ji quan group, compared with controls ( < .05). We found no significant reduction in falls for tai ji quan or strength training relative to stretching control in postmenopausal women treated with chemotherapy.

    Abstract Summary: Scientists wanted to see if two types of exercise, tai chi or strength training, could help older women who survived cancer and went through menopause to not fall down as much after their chemotherapy treatment. They had these women do one of three exercises: tai chi, strength training, or just stretching, two times a week for six months. They checked on the women for another six months after the exercises stopped. They wanted to see how many times the women fell, if they got hurt from falling, how strong their legs were, and how well they could balance. They found that after six months, the number of falls didn't really change no matter what exercise the women did. But, the women who did tai chi had fewer injuries from falls during the first six months. Also, the women who did strength training got stronger legs, and those who did tai chi got better at balancing compared to the women who just stretched. In the end, the study showed that while tai chi and strength training didn't stop the women from falling, tai chi might help them get hurt less, and both tai chi and strength training can make them stronger and more balanced.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention.
    Oncotarget (2022)
    McGinnis GJ, Holden S, Yu B, Ransom C, Guidarelli C, De B, Diao K, Boyce D, Thomas CR Jr, Winters-Stone K, Raber J. Association of fall rate and functional status by APOE genotype in cancer survivors after exercise intervention. Oncotarget. 2022 Nov 17; 13:1259-1270.
    Abstract: Cancer treatment survivors often report impaired functioning and increased falls. Not all survivors experience the same symptom burden, suggesting individual susceptibilities. genotype is a potential genetic risk factor for cancer treatment related side effects. Lifestyle factors such as physical activity can mitigate the effect of genotype on measures of clinical interest in individuals without a history of cancer. We tested the hypothesis that genotype influences cancer treatment related side effects and symptoms as well as response to exercise intervention. Data from a subsample of a study of fall prevention exercise in post-treatment female cancer survivors aged 50-75 years old (https://clinicaltrials.gov NCT01635413) were used to conduct a secondary data analysis. ApoE genotype was determined by serum sampling. Physical functioning, frequency of falls, and symptom burden were assessed using survey instruments. Data from 126 female cancer survivors a median of 49 months out from cancer diagnosis were analyzed. ApoE4 carriers trended toward a higher fall rate at baseline ( = 0.059), but after exercise intervention had a fall rate lower than E4 non-carriers both immediately after structured intervention ( = 0.013) and after 6 months of follow up ( = 0.002). E2 carriers did not show improved measures of depressive symptoms and self-report disability after exercise intervention. E3 homozygotes showed increased self report physical activity after the 6 month exercise intervention, but E4 and E2 carriers did not. genotype may modulate cancer treatment related side effects and symptoms and response to exercise intervention.

    Abstract Summary: Scientists did a study to see if a certain gene, called ApoE, affects how people who had cancer treatment feel and how often they fall down. They also wanted to know if exercising could help these people feel better and fall less, no matter what type of ApoE gene they have. They looked at 126 women who had finished cancer treatment about 4 years ago. They found that people with one type of the ApoE gene, called E4, fell down more at first, but after they started exercising, they fell down less than people without the E4 type. People with another type, E2, didn't feel less sad or less disabled after exercising. People with the E3 type did more physical activity after exercising for 6 months, but those with E4 and E2 didn't change much. This study shows that the ApoE gene might change how exercise helps people who had cancer treatment.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of Altering Levothyroxine Dose on Energy Expenditure and Body Composition in Subjects Treated With LT4.
    The Journal of clinical endocrinology and metabolism (2018)
    Samuels MH, Kolobova I, Niederhausen M, Purnell JQ, Schuff KG. Effects of Altering Levothyroxine Dose on Energy Expenditure and Body Composition in Subjects Treated With LT4. J Clin Endocrinol Metab. 2018 Nov 1; 103(11):4163-4175.
    Abstract: It is unclear whether variations in thyroid status within or near the reference range affect energy expenditure, body mass, or body composition. 138 subjects treated with levothyroxine (LT4) for hypothyroidism with normal TSH levels underwent measurement of total, resting, and physical activity energy expenditure; thermic effect of food; substrate oxidation; dietary intake; and body composition. They were assigned to receive an unchanged, higher, or lower LT4 dose in randomized, double-blind fashion, targeting one of three TSH ranges (0.34 to 2.50, 2.51 to 5.60, or 5.61 to 12.0 mU/L). The doses were adjusted every 6 weeks to achieve target TSH levels. Baseline measures were reassessed at 6 months. At study end, the mean LT4 doses and TSH levels were 1.50 ± 0.07, 1.32 ± 0.07, and 0.78 ± 0.08 µg/kg (P < 0.001) and 1.85 ± 0.25, 3.93 ± 0.38, and 9.49 ± 0.80 mU/L (P < 0.001), respectively, in the three arms. No substantial metabolic differences in outcome were found among the three arms, although direct correlations were observed between decreases in thyroid status and decreases in resting energy expenditure for all subjects. The subjects could not ascertain how their LT4 dose had been adjusted but the preferred LT4 dose they perceived to be higher (P < 0.001). Altering LT4 doses in subjects with hypothyroidism to vary TSH levels in and near the reference range did not have major effects on energy expenditure or body composition. Subjects treated with LT4 preferred the perceived higher LT4 doses despite a lack of objective effect. Our data do not support adjusting LT4 doses in patients with hypothyroidism to achieve potential improvements in weight or body composition.

    Abstract Summary: Scientists wanted to know if changing the amount of thyroid medicine in people with low thyroid activity affects how much energy they use, their weight, or their body's muscle and fat makeup. They studied 138 people taking thyroid medicine and changed their doses to see if their thyroid levels would go up or down. They checked how much energy the people used when resting, being active, and after eating, as well as what they ate and their body's muscle and fat. After 6 months, they found that changing the medicine dose didn't really change how much energy people used or their body's muscle and fat. Even though the medicine dose didn't make a big difference, people liked it better when they thought they were taking a higher dose. The study suggests that for people with low thyroid activity, changing their medicine dose doesn't help them lose weight or change their body's muscle and fat.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of Altering Levothyroxine (L-T4) Doses on Quality of Life, Mood, and Cognition in L-T4 Treated Subjects.
    The Journal of clinical endocrinology and metabolism (2018)
    Samuels MH, Kolobova I, Niederhausen M, Janowsky JS, Schuff KG. Effects of Altering Levothyroxine (L-T4) Doses on Quality of Life, Mood, and Cognition in L-T4 Treated Subjects. J Clin Endocrinol Metab. 2018 May 1; 103(5):1997-2008.
    Abstract: The brain is a critical target organ for thyroid hormone, but it is unclear whether variations in thyroid function within and near the reference range affect quality of life, mood, or cognition. A total of 138 subjects with levothyroxine (L-T4)-treated hypothyroidism and normal thyrotropin (TSH) levels underwent measures of quality of life (36-Item Short Form Health Survey, Underactive Thyroid-Dependent Quality of Life Questionnaire), mood (Profile of Mood States, Affective Lability Scale), and cognition (executive function, memory). They were then randomly assigned to receive an unchanged, higher, or lower L-T4 dose in double-blind fashion, targeting one of three TSH ranges (0.34 to 2.50, 2.51 to 5.60, or 5.61 to 12.0 mU/L). Doses were adjusted every 6 weeks based on TSH levels. Baseline measures were reassessed at 6 months. At the end of the study, by intention to treat, mean L-T4 doses were 1.50 ± 0.07, 1.32 ± 0.07, and 0.78 ± 0.08 μg/kg (P < 0.001), and mean TSH levels were 1.85 ± 0.25, 3.93 ± 0.38, and 9.49 ± 0.80 mU/L (P < 0.001), respectively, in the three arms. There were minor differences in a few outcomes between the three arms, which were no longer significant after correction for multiple comparisons. Subjects could not ascertain how their L-T4 doses had been adjusted (P = 0.55) but preferred L-T4 doses they perceived to be higher (P < 0.001). Altering L-T4 doses in hypothyroid subjects to vary TSH levels in and near the reference range does not affect quality of life, mood, or cognition. L-T4-treated subjects prefer perceived higher L-T4 doses despite a lack of objective benefit. Adjusting L-T4 doses in hypothyroid patients based on symptoms in these areas may not result in significant clinical improvement.

    Abstract Summary: This study looked at whether changing the amount of a thyroid medicine (levothyroxine or L-T4) taken by people with low thyroid function affects their mood, thinking skills, or quality of life. The researchers tested three different levels of the medicine in 138 people over six months. They found that changing the amount of medicine didn't really make a difference in how people felt or thought. Even though some people thought they felt better with more medicine, the tests didn't show a real improvement. This suggests that adjusting the amount of thyroid medicine based on these symptoms might not actually help patients feel better.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Thyroid Function Variation in the Normal Range, Energy Expenditure, and Body Composition in L-T4-Treated Subjects.
    The Journal of clinical endocrinology and metabolism (2017)
    Samuels MH, Kolobova I, Antosik M, Niederhausen M, Purnell JQ, Schuff KG. Thyroid Function Variation in the Normal Range, Energy Expenditure, and Body Composition in L-T4-Treated Subjects. J Clin Endocrinol Metab. 2017 Jul 1; 102(7):2533-2542.
    Abstract: It is not clear whether upper limits of the thyrotropin (TSH) reference range should be lowered. This debate can be better informed by investigation of whether variations in thyroid function within the reference range have clinical effects. Thyroid hormone plays a critical role in determining energy expenditure, body mass, and body composition, and therefore clinically relevant variations in these parameters may occur across the normal range of thyroid function. This was a cross-sectional study of 140 otherwise healthy hypothyroid subjects receiving chronic replacement therapy with levothyroxine (L-T4) who had TSH levels across the full span of the laboratory reference range (0.34 to 5.6 mU/L). Subjects underwent detailed tests of energy expenditure (total and resting energy expenditure, thermic effect of food, physical activity energy expenditure), substrate oxidation, diet intake, and body composition. Subjects with low-normal (≤2.5 mU/L) and high-normal (>2.5 mU/L) TSH levels did not differ in any of the outcome measures. However, across the entire group, serum free triiodothyronine (fT3) levels were directly correlated with resting energy expenditure, body mass index (BMI), body fat mass, and visceral fat mass, with clinically relevant variations in these outcomes. Variations in thyroid function within the laboratory reference range have clinically relevant correlations with resting energy expenditure, BMI, and body composition in L-T4-treated subjects. However, salutary effects of higher fT3 levels on energy expenditure may be counteracted by deleterious effects on body weight and composition. Further studies are needed before these outcomes should be used as a basis for altering L-T4 doses in L-T4-treated subjects.

    Abstract Summary: Scientists did a study to see if small changes in thyroid levels, even when they are in the normal range, can affect people's health. They looked at 140 healthy people who were taking thyroid medicine and checked their energy use, body fat, and how much they ate. They found that even when thyroid levels were normal, higher levels of a certain thyroid hormone were linked to more energy use and more body fat. This means that small differences in thyroid levels can have real effects on people's bodies. But they also noticed that these changes might not always be good, like making people gain weight. They said we need more studies before doctors change how much thyroid medicine people take based on these findings.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects.
    Thyroid : official journal of the American Thyroid Association (2016)
    Samuels MH, Kolobova I, Smeraglio A, Niederhausen M, Janowsky JS, Schuff KG. Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects. Thyroid. 2016 Sep; 26(9):1173-84.
    Abstract: There has been recent debate within the thyroid field regarding whether current upper limits of the thyrotropin (TSH) reference range should be lowered. This debate can be better informed by investigation of whether variations in thyroid function within the reference range have clinical effects. One important target organ for thyroid hormone is the brain, but little is known about variations in neurocognitive measures within the reference range for thyroid function. This was a cross-sectional study of 132 otherwise healthy hypothyroid subjects receiving chronic replacement therapy with levothyroxine (LT4) who had TSH levels across the full span of the laboratory reference range (0.34-5.6 mU/L). Subjects underwent detailed tests of health status, mood, and cognitive function, with an emphasis on memory and executive functions. Subjects with low-normal (≤2.5 mU/L) and high-normal (>2.5 mU/L) TSH levels did not differ on most tests of health status, mood, or cognitive function, and there were no correlations between TSH, free T4, or free T3 levels and most outcomes. There was, however, a suggestion that thyroid function affected performance on the Iowa Gambling Task, which mimics real life decision-making. Subjects with low-normal TSH levels made more advantageous decisions than those with high-normal TSH levels. Variations in thyroid function within the laboratory reference range do not appear to have clinically relevant effects on health status, mood, or memory in LT4 treated subjects. However, decision making, which encompasses many executive functions, may be affected. Unless further studies strengthen this finding, these data do not support narrowing the TSH reference range.

    Abstract Summary: Doctors are talking about whether they should change the normal levels for a thyroid health test. To learn more, scientists studied how different thyroid levels within the normal range affect the brain, especially thinking and memory. They looked at 132 people with thyroid problems who were taking medicine to help. These people had different levels of thyroid health but were still in the normal range. The scientists had these people do health checks and thinking tests. They found that most of the time, the level of thyroid health didn't change how the people felt or thought. But, they noticed that people with the lower end of normal thyroid levels were better at a game that's like making choices in real life. In the end, the study showed that small changes in thyroid levels within the normal range don't really affect how people feel or remember things. But, it might change how they make decisions. The scientists say that we don't need to change the normal thyroid levels based on what they found, but they think more studies should be done to be sure.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition.
    Thyroid : official journal of the American Thyroid Association (2016)
    Samuels MH, Kolobova I, Smeraglio A, Peters D, Purnell JQ, Schuff KG. Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition. Thyroid. 2016 Mar; 26(3):347-55.
    Abstract: Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive LT4 doses have alterations in energy expenditure or body composition. This study was a cross-sectional comparison between three groups of women: 26 women receiving chronic TSH-suppressive LT4 doses, 80 women receiving chronic replacement LT4 doses, and 16 untreated euthyroid control women. Subjects underwent measurements of resting energy expenditure (REE), substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity energy expenditure by accelerometer; caloric intake by 24-hour diet recall; and body composition by dual X-ray absorptiometry. REE per kilogram lean body mass in the LT4 euthyroid women was 6% lower than that of the LT4-suppressed group, and 4% lower than that of the healthy control group (p = 0.04). Free triiodothyronine (fT3) levels were directly correlated with REE, and were 10% lower in the LT4 euthyroid women compared with the other two groups (p = 0.007). The groups of subjects did not differ in other measures of energy expenditure, caloric intake, or body composition. LT4 suppression therapy does not adversely affect energy expenditure or body composition in women. However, LT4 replacement therapy is associated with a lower REE, despite TSH levels within the reference range. This may be due to lower fT3 levels, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in LT4 therapy.

    Abstract Summary: Doctors wanted to see if taking high doses of a thyroid medicine called levothyroxine (LT4) changes how women's bodies use energy or changes their body shape and weight. They looked at three groups of women: one group taking a lot of LT4, another taking a regular amount, and a third group not taking any thyroid medicine. They checked how many calories the women burned when resting, after eating, and during exercise. They also looked at what they ate and measured their body fat and muscle. They found that women taking the regular amount of LT4 burned slightly fewer calories when resting compared to the other two groups. This might be because they had less of a certain thyroid hormone in their bodies. But overall, taking a lot of LT4 didn't seem to make a big difference in how their bodies used energy or their body shape and weight. This is good news for people who need to take thyroid medicine because it means it probably won't make them gain weight or change their metabolism in a bad way.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents.
    Diabetes care (2015)
    Rosenstock J, Franco D, Korpachev V, Shumel B, Ma Y, Baughman R, Amin N, McGill JB, Affinity 2 Study Group. Inhaled Technosphere Insulin Versus Inhaled Technosphere Placebo in Insulin-Naïve Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetes Agents. Diabetes Care. 2015 Dec; 38(12):2274-81.
    Abstract: To investigate the efficacy and safety of prandial Technosphere inhaled insulin (TI), an inhaled insulin with a distinct time action profile, in insulin-naïve type 2 diabetes (T2D) inadequately controlled on oral antidiabetes agents (OADs). Subjects with T2D with HbA1c levels ≥7.5% (58.5 mmol/mol) and ≤10.0% (86.0 mmol/mol) on metformin alone or two or more OADs were randomized to add-on prandial TI (n = 177) or prandial Technosphere inhaled placebo (TP) (n = 176) to their OAD regimen in this double-blind, placebo-controlled trial. Primary end point was change in HbA1c at 24 weeks. TI significantly reduced HbA1c by -0.8% (-9.0 mmol/mol) from a baseline of 8.3% (66.8 mmol/mol) compared with TP -0.4% (-4.6 mmol/mol) (treatment difference -0.4% [95% CI -0.57, -0.23]; P < 0.0001). More TI-treated subjects achieved an HbA1c ≤7.0% (53.0 mmol/mol) (38% vs. 19%; P = 0.0005). Mean fasting plasma glucose was similarly reduced in both groups. Postprandial hyperglycemia, based on 7-point glucose profiles, was effectively controlled by TI. Mean weight change was 0.5 kg for TI and -1.1 kg for the TP group (P < 0.0001). Mild, transient dry cough was the most common adverse event, occurring similarly in both groups (TI, 23.7%; TP, 19.9%) and led to discontinuation in only 1.1% of TI-treated and 3.4% of TP-treated subjects. There was a small decline in forced expiratory volume in 1 s in both groups, with a slightly larger decline in the group receiving TI (TI, -0.13 L; TP, -0.04 L). The difference resolved after treatment discontinuation. Prandial TI added to one or more OADs in inadequately controlled T2D is an effective treatment option. Mild, transient dry cough was the most common adverse event.

    Abstract Summary: Scientists did a study to see if a new kind of inhaled insulin, called Technosphere insulin (TI), is good and safe for people with type 2 diabetes who haven't used insulin before but are taking pills to control their blood sugar. They had 177 people add TI to their usual medicine and 176 people use a pretend inhaler with their medicine. They checked their progress after 24 weeks. They found that the people using TI had a better drop in their long-term blood sugar levels compared to those using the pretend inhaler. More people using TI got their blood sugar to a really good level. Both groups had a similar drop in their morning blood sugar. TI also helped control blood sugar spikes after meals. People using TI gained a little weight, while those using the pretend inhaler lost some weight. A common side effect was a mild, short-term cough, but it didn't bother most people too much. There was a small change in how well people could breathe out, but it got better after they stopped the treatment. The study showed that TI could be a helpful new treatment for people with type 2 diabetes who need more than just pills to manage their blood sugar.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes.
    Diabetes care (2015)
    FLAT-SUGAR Trial Investigators, Probstfield JL, Hirsch I, O'Brien K, Davis B, Bergenstal R, Kingry C, Khakpour D, Pressel S, Branch KR, Riddle M. Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes. Diabetes Care. 2015 Aug; 38(8):1558-66.
    Abstract: Glycemic variability may contribute to adverse medical outcomes of type 2 diabetes, but prior therapies have had limited success in controlling glycemic fluctuations, and the hypothesis has not been adequately tested. People with insulin-requiring type 2 diabetes and high cardiovascular risk were enrolled during a run-in period on basal-bolus insulin (BBI), and 102 were randomized to continued BBI or to basal insulin with a prandial GLP-1 receptor agonist (GLIPULIN) group, each seeking to maintain HbA(1c) levels between 6.7% and 7.3% (50-56 mmol/mol) for 6 months. The primary outcome measure was glycemic variability assessed by continuous glucose monitoring; other measures were HbA(1c), weight, circulating markers of inflammation and cardiovascular risk, albuminuria, and electrocardiographic patterns assessed by Holter monitoring. At randomization, the mean age of the population was 62 years, median duration of diabetes 15 years, mean BMI 34 kg/m(2), and mean HbA(1c) 7.9% (63 mmol/mol). Thirty-three percent had a prior cardiovascular event, 18% had microalbuminuria, and 3% had macroalbuminuria. At baseline, the continuous glucose monitoring coefficient of variation for glucose levels was similar in both groups. FLAT-SUGAR is a proof-of-concept study testing whether, in a population of individuals with type 2 diabetes and high cardiovascular risk, the GLIPULIN regimen can limit glycemic variability more effectively than BBI, reduce levels of cardiovascular risk markers, and favorably alter albuminuria and electrocardiographic patterns. We successfully randomized a population that has sufficient power to answer the primary question, address several secondary ones, and complete the protocol as designed.

    Abstract Summary: Doctors wanted to see if a new way to treat type 2 diabetes could help control blood sugar levels better than the usual way. They took a group of people with type 2 diabetes who also had a higher chance of heart problems and gave them two different treatments. One group kept taking their normal insulin shots, while the other group tried a new method that included a special medicine taken with meals. They watched these people for 6 months, checking their blood sugar, weight, heart health signs, and kidney health. The study, called FLAT-SUGAR, is trying to find out if the new treatment is better at keeping blood sugar steady and improving heart and kidney health. They got enough people to join the study to be able to tell if the new treatment works.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The effects of levothyroxine replacement or suppressive therapy on health status, mood, and cognition.
    The Journal of clinical endocrinology and metabolism (2014)
    Samuels MH, Kolobova I, Smeraglio A, Peters D, Janowsky JS, Schuff KG. The effects of levothyroxine replacement or suppressive therapy on health status, mood, and cognition. J Clin Endocrinol Metab. 2014 Mar; 99(3):843-51.
    Abstract: TSH-suppressive doses of levothyroxine (L-T4) have adverse effects on bone and cardiac function, but it is unclear whether central nervous system function is also affected. The aim of the study was to determine whether women receiving TSH-suppressive L-T4 doses have decrements in health status, mood, or cognitive function. A cross-sectional comparison was made among three groups of women in an academic medical center research clinic. Twenty-four women receiving chronic TSH-suppressive L-T4 doses, 35 women receiving chronic replacement L-T4 doses, and 20 untreated control women participated in the study. Subjects underwent testing at a single outpatient visit. We measured health status (SF-36), mood (Profile of Mood States, Symptom Checklist 90-R, Affective Lability Scale), and cognitive function (declarative memory [Paragraph Recall], working memory [N-back, Subject Ordered Pointing], motor learning [Pursuit Rotor, Motor Sequence Learning Test], and executive function [Letter Cancellation Test, Trail Making Test, Iowa Gambling Test]). Women receiving TSH-suppressive or replacement L-T4 doses had decrements in health status and mood compared to healthy controls. These decrements were more pronounced in women receiving replacement, rather than suppressive, L-T4 doses. Memory and executive function were not affected in either treated group, compared to healthy controls. Women receiving TSH-suppressive doses of L-T4 do not have central nervous system dysfunction due to exogenous subclinical thyrotoxicosis, but TSH-suppressed and L-T4-replaced women have slight decrements in health status and mood that may be related to self-knowledge of the presence of a thyroid condition or other uncharacterized factors. These mood alterations do not impair cognitive function.

    Abstract Summary: Doctors wanted to see if a thyroid medicine called levothyroxine, when given in high doses, affects women's brains. They looked at three groups of women: some taking high doses of the medicine, some taking regular doses, and some not taking the medicine at all. They checked their overall health, mood, and thinking skills during one visit. They found that women taking any amount of the medicine felt a little worse in health and mood than women not taking it, but their memory and thinking skills were just fine. The study suggests that the medicine doesn't hurt the brain, but the women taking it might feel a bit down because they know they have a thyroid problem or maybe for reasons the study didn't figure out.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Comparison of tai chi vs. strength training for fall prevention among female cancer survivors: study protocol for the GET FIT trial.
    BMC cancer (2012)
    Winters-Stone KM, Li F, Horak F, Luoh SW, Bennett JA, Nail L, Dieckmann N. Comparison of tai chi vs. strength training for fall prevention among female cancer survivors: study protocol for the GET FIT trial. BMC Cancer. 2012 Dec 5; 12:577.
    Abstract: Women with cancer are significantly more likely to fall than women without cancer placing them at higher risk of fall-related fractures, other injuries and disability. Currently, no evidence-based fall prevention strategies exist that specifically target female cancer survivors. The purpose of the GET FIT (Group Exercise Training for Functional Improvement after Treatment) trial is to compare the efficacy of two distinct types of exercise, tai chi versus strength training, to prevent falls in women who have completed treatment for cancer. The specific aims of this study are to: 1) Determine and compare the efficacy of both tai chi training and strength training to reduce falls in older female cancer survivors, 2) Determine the mechanism(s) by which tai chi and strength training each reduces falls and, 3) Determine whether or not the benefits of each intervention last after structured training stops. We will conduct a three-group, single-blind, parallel design, randomized controlled trial in women, aged 50-75 years old, who have completed chemotherapy for cancer comparing 1) tai chi 2) strength training and 3) a placebo control group of seated stretching exercise. Women will participate in supervised study programs twice per week for six months and will be followed for an additional six months after formal training stops. The primary outcome in this study is falls, which will be prospectively tracked by monthly self-report. Secondary outcomes are maximal leg strength measured by isokinetic dynamometry, postural stability measured by computerized dynamic posturography and physical function measured by the Physical Performance Battery, all measured at baseline, 3, 6 and 12 months. The sample for this trial (N=429, assuming 25% attrition) will provide adequate statistical power to detect at least a 47% reduction in the fall rate over 1 year by being in either of the 2 exercise groups versus the control group. The GET FIT trial will provide important new knowledge about preventing falls using accessible and implementable exercise interventions for women following chemotherapy for cancer. ClinicalTrials.gov NCT01635413.

    Abstract Summary: The GET FIT study is trying to find out if two types of exercise, tai chi and strength training, can help women who have had cancer treatment not fall down as much. Falling can cause broken bones and other injuries, so it's important to find ways to prevent it. Women between 50 and 75 years old who finished cancer treatment will do one of the exercises or a stretching activity in a class twice a week for six months. They will keep track of any falls for a year. The study will see if these exercises make women stronger, help them balance better, and move more easily. If the exercises work, they could be a new way to help women stay safe after cancer treatment.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

Stanford University
  • Pharmacogenetic Factors Influence Escitalopram Pharmacokinetics and Adverse Events in Youth with a Family History of Bipolar Disorder: A Preliminary Study.
    Journal of child and adolescent psychopharmacology (2024)
    Honeycutt DC, Blom TJ, Ramsey LB, Strawn JR, Bruns KM, Welge JA, Patino LR, Singh MK, DelBello MP. Pharmacogenetic Factors Influence Escitalopram Pharmacokinetics and Adverse Events in Youth with a Family History of Bipolar Disorder: A Preliminary Study. J Child Adolesc Psychopharmacol. 2024 Feb; 34(1):42-51.
    Abstract: Escitalopram is an effective and generally well-tolerated antidepressant, but children of parents with bipolar disorder (BD) may be at increased risk for adverse events associated with antidepressants, including increased irritability, restlessness, impulsivity, and manic symptoms. This risk may be influenced by polymorphisms in genes encoding cytochrome P450 enzymes ( or ), the serotonin transporter (), and the serotonin receptor 2A subtype (). We explored whether gene-drug interactions influence the emergence of adverse events in depressed and/or anxious youth with a family history of BD. Children and adolescents aged 12-17 years with a first-degree relative with bipolar I disorder were treated with escitalopram and monitored for adverse effects, underwent pharmacogenetic testing, and provided serum escitalopram levels. Emergence of adverse events was determined by study clinicians, and symptoms were tracked using the Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP) and Pediatric Adverse Events Rating Scale. Clinical Pharmacogenetics Implementation Consortium guidelines were used to determine CYP2C19 and CYP2D6 phenotypes. Slower CYP2C19 metabolizers had greater dose-normalized 24-hour area under the curve (AUC;  = 0.025), trough concentrations (C;  = 0.013), and elimination half-lives (t;  < 0.001). CYP2D6 phenotype was not significantly associated with any pharmacokinetic parameter. Slower CYP2D6 metabolizers had increased TEASAP akathisia ( = 0.015) scores. and genotypes were associated with increased TEASAP "self-injury, suicidality, and harm to others" subscale scores ( = 0.017). Escitalopram maximum concentration, AUC, CYP2C19 phenotype, and genotype were not associated with adverse events. CYP2C19 phenotype influences escitalopram pharmacokinetics whereas CYP2D6 phenotype does not. Slower CYP2D6 metabolism was associated with increased akathisia, and or genotypes were associated with increased risk of self-harm or harm to others. Larger cohorts are needed to identify associations between genetic test results and antidepressant-associated adverse events. ClinicalTrials.gov identifier: NCT02553161.

    Abstract Summary: Scientists did a study to see if a medicine called escitalopram, which helps people feel less sad, might not work well for kids whose parents have a type of mood problem called bipolar disorder. They wanted to know if certain differences in the kids' genes could make them feel more restless or even hurt themselves when taking this medicine. They gave the medicine to kids and teenagers between 12 and 17 years old who had a parent with bipolar disorder and watched for any bad reactions. They also checked their genes and how much medicine was in their blood. They found that kids who broke down the medicine slowly in their bodies had more of it in their blood for longer and were more likely to feel really restless. Also, certain gene differences made it more likely for kids to hurt themselves or others. But they need to study more kids to be sure about these results. This research helps us understand that sometimes, the way our bodies handle medicine and our genes can change how we react to the medicine.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Self-reported physical function is strongly related to pain behavior and pain interference and weakly related to physical capacity in people with chronic low back pain.
    Musculoskeletal science & practice (2023)
    Karayannis NV, Smuck M, Law C, Mackey SC, Gross JJ, Darnall BD, Hush J. Self-reported physical function is strongly related to pain behavior and pain interference and weakly related to physical capacity in people with chronic low back pain. Musculoskelet Sci Pract. 2023 Feb; 63:102721.
    Abstract: Inclusion of self-reported and capacity-based measures may help to further elucidate the interactive link between how people think and move. To characterize the relationship between self-reported factors of physical function and pain with objective physical capacity measures. Cross-sectional study of 328 adults with chronic low back pain (CLBP). Spearman correlations assessed the relationship between pairs of measures. Multiple linear regression models assessed the association between self-reported measures of physical function and the grouping of physical capacity measures. Self-reported measures included Roland Morris Disability Questionnaire (RMDQ), PROMIS Physical Function, Pain Behavior, and Pain Interference; Fear-Avoidance Beliefs Questionnaire (FABQ), Pain Catastrophizing Scale (PCS), and Chronic Pain Acceptance Questionnaire (CPAQ). Capacity measures included walking speed and endurance, lower extremity functional strength, lumbopelvic range of motion, and trunk endurance. PROMIS Physical Function was directly and weakly correlated with walking speed (ρ = 0.26, 2-min walk) and inversely and weakly correlated with lower extremity strength (ρ = -0.29, 5x sit-to-stand). RMDQ was not correlated with any of the capacity-based measures. PROMIS Physical Function was inversely and moderately correlated with Pain Interference (ρ = -0.48) and Pain Behavior (ρ = -0.43), PCS (ρ = -0.36), and FABQ (ρ = -0.31). The RMDQ was strongly correlated with PROMIS Physical Function (ρ = -0.56), Pain Behavior (ρ = 0.51) and Pain Interference (ρ = 0.49); and moderately correlated with PCS (ρ = 0.37) and FABQ (ρ = 0.33). PROMIS Physical Function and RMDQ were not correlated with CPAQ. Lower scores on PROMIS Physical Function were weakly associated with lower measures of lower extremity strength (-0.30, 95% CI: -0.51 to -0.09, p = 0.005). Higher scores on RMDQ were also weakly associated with lower measures of lower extremity strength (0.26, 95% CI: 0.11 to 0.41, p = 0.001). A strong association emerged between self-reported limitations in physical function, pain behavior, and pain interference. A weak association emerged between self-reported physical function and lower extremity strength.

    Abstract Summary: Scientists did a study to understand the connection between what people with chronic low back pain think about their ability to move and how well they actually can move. They asked 328 adults with this kind of pain to fill out questionnaires about their pain and how it affects their daily life. They also tested how fast the people could walk, how strong their legs were, how well they could move their lower back and hips, and how long their back muscles could work without getting tired. They found that what people said about their physical abilities was a little bit related to their walking speed and leg strength. But there was a stronger link between what they said about their abilities and how much their pain changed the way they live their lives. People who felt more limited by their pain also seemed to have less leg strength. This study is important because it shows that what people say about their pain and abilities can give us clues about their actual physical strength. This can help doctors and therapists understand and treat people with chronic low back pain better.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Mindfulness-Based Stress Reduction, Cognitive Behavioral Therapy, and Acupuncture in Chronic Low Back Pain: Protocol for Two Linked Randomized Controlled Trials.
    JMIR research protocols (2022)
    Mackey S, Gilam G, Darnall B, Goldin P, Kong JT, Law C, Heirich M, Karayannis N, Kao MC, Tian L, Manber R, Gross J. Mindfulness-Based Stress Reduction, Cognitive Behavioral Therapy, and Acupuncture in Chronic Low Back Pain: Protocol for Two Linked Randomized Controlled Trials. JMIR Res Protoc. 2022 Sep 27; 11(9):e37823.
    Abstract: Nonpharmacologic mind-body therapies have demonstrated efficacy in low back pain. However, the mechanisms underlying these therapies remain to be fully elucidated. In response to these knowledge gaps, the Stanford Center for Low Back Pain-a collaborative, National Institutes of Health P01-funded, multidisciplinary research center-was established to investigate the common and distinct biobehavioral mechanisms of three mind-body therapies for chronic low back pain: cognitive behavioral therapy (CBT) that is used to treat pain, mindfulness-based stress reduction (MBSR), and electroacupuncture. Here, we describe the design and implementation of the center structure and the associated randomized controlled trials for characterizing the mechanisms of chronic low back pain treatments. The multidisciplinary center is running two randomized controlled trials that share common resources for recruitment, enrollment, study execution, and data acquisition. We expect to recruit over 300 chronic low back pain participants across two projects and across different treatment arms within each project. The first project will examine pain-CBT compared with MBSR and a wait-list control group. The second project will examine real versus sham electroacupuncture. We will use behavioral, psychophysical, physical measure, and neuroimaging techniques to characterize the central pain modulatory and emotion regulatory systems in chronic low back pain at baseline and longitudinally. We will characterize how these interventions impact these systems, characterize the longitudinal treatment effects, and identify predictors of treatment efficacy. Participant recruitment began on March 17, 2015, and will end in March 2023. Recruitment was halted in March 2020 due to COVID-19 and resumed in December 2021. This center uses a comprehensive approach to study chronic low back pain. Findings are expected to significantly advance our understanding in (1) the baseline and longitudinal mechanisms of chronic low back pain, (2) the common and distinctive mechanisms of three mind-body therapies, and (3) predictors of treatment response, thereby informing future delivery of nonpharmacologic chronic low back pain treatments. ClinicalTrials.gov NCT02503475; https://clinicaltrials.gov/ct2/show/NCT02503475. PRR1-10.2196/37823.

    Abstract Summary: Scientists at the Stanford Center for Low Back Pain are studying how different treatments without medicine can help people with long-lasting back pain. They are looking at three kinds of treatments: a special talking therapy called cognitive behavioral therapy (CBT), a relaxation technique called mindfulness, and a treatment with needles called electroacupuncture. They want to understand better how these treatments work and why they help some people more than others. They are doing two big studies with over 300 people to compare these treatments and see what changes happen in the body and brain. They stopped the study for a while because of the virus that was making people sick, but they started again and will finish in March 2023. The results will help us know more about back pain and how to treat it without using medicine, which could be really good for lots of people with back pain. The study is listed on a website called ClinicalTrials.gov with the number NCT02503475.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Central mechanisms of real and sham electroacupuncture in the treatment of chronic low back pain: study protocol for a randomized, placebo-controlled clinical trial.
    Trials (2018)
    Kong JT, MacIsaac B, Cogan R, Ng A, Law CSW, Helms J, Schnyer R, Karayannis NV, Kao MC, Tian L, Darnall BD, Gross JJ, Mackey S, Manber R. Central mechanisms of real and sham electroacupuncture in the treatment of chronic low back pain: study protocol for a randomized, placebo-controlled clinical trial. Trials. 2018 Dec 13; 19(1):685.
    Abstract: Chronic low back pain (CLBP) is the most common chronic pain condition and is often resistant to conventional treatments. Acupuncture is a popular alternative for treating CLBP but its mechanisms of action remain poorly understood. Evidence suggests that pain regulatory mechanisms (particularly the ascending and secondarily the descending pain modulatory pathways) and psychological mechanisms (e.g., expectations, pain catastrophizing and self-efficacy) may be involved in the pathogenesis of CLBP and its response to treatments. We will examine these mechanisms in the treatment of CLBP by electroacupuncture (EA). We present the aims and methods of a placebo-controlled, participant-blinded and assessor-blinded mechanistic study. Adult patients with CLBP will be randomized to receiving 16 sessions of real (active) or sham (placebo) EA over the course of 8 weeks. The primary pain regulatory measure for which the study was powered is temporal summation (TS), which approximates ascending pain facilitation. Conditioned pain modulation (CPM), representing a descending pain modulatory pathway, will be our secondary pain regulatory measure. The primary psychological measure is expectations of benefit, and the secondary psychological measures are pain catastrophizing and self-efficacy in managing pain. Main clinical outcomes are back pain bothersomeness on a 0-100 visual analog scale (primary), Roland Morris Disability Questionnaire (secondary), and relevant items from the National Institutes of Health (NIH) Patient-Reported Outcome Measures Information System (secondary). We hypothesize that compared to sham, real EA will lead to greater reduction in TS after 8 treatment sessions (4 weeks); and that reduction in TS (and secondarily, increase in CPM) after 8 treatment sessions will mediate reduction in back pain bothersomeness from baseline to week 10 (clinical response) to EA. We also hypothesize that the three psychological factors are moderators of clinical response. With 100 treatment completers, the study is designed to have 80% power to detect a medium-sized between-group effect (d = 0.5) on temporal summation. To the best of our knowledge, this is the first appropriately powered, placebo-controlled clinical trial evaluating mechanisms of EA in the treatment of CLBP. ClinicalTrials.gov, NCT02503475 . Registered on 15 July 15 2015. Retrospectively registered.

    Abstract Summary: Scientists are studying how a special kind of acupuncture called electroacupuncture (EA) can help people with chronic low back pain, which is a very common and stubborn kind of pain. They want to understand how EA works by looking at both the body's pain signals and how people think and feel about their pain. They're doing an experiment where adults with back pain get either real EA or pretend EA for 8 weeks, and they don't know which one they're getting. The researchers will check how the treatment affects the way pain signals increase, how the body controls pain, and how hopeful people are about getting better. They think that the real EA will help reduce pain more than the pretend EA, and that how people think about their pain might change how well the treatment works. This study is important because it's the first big test to see if EA really helps with back pain and to understand why.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study.
    Diabetes care (2014)
    Kim SH, Liu A, Ariel D, Abbasi F, Lamendola C, Grove K, Tomasso V, Ochoa H, Reaven G. Effect of salsalate on insulin action, secretion, and clearance in nondiabetic, insulin-resistant individuals: a randomized, placebo-controlled study. Diabetes Care. 2014 Jul; 37(7):1944-50.
    Abstract: Salsalate treatment has been shown to improve glucose homeostasis, but the mechanism remains unclear. The aim of this study was to evaluate the effect of salsalate treatment on insulin action, secretion, and clearance rate in nondiabetic individuals with insulin resistance. This was a randomized (2:1), single-blind, placebo-controlled study of salsalate (3.5 g daily for 4 weeks) in nondiabetic individuals with insulin resistance. All individuals had measurement of glucose tolerance (75-g oral glucose tolerance test), steady-state plasma glucose (SSPG; insulin suppression test), and insulin secretion and clearance rate (graded-glucose infusion test) before and after treatment. Forty-one individuals were randomized to salsalate (n = 27) and placebo (n = 14). One individual from each group discontinued the study. Salsalate improved fasting (% mean change -7% [95% CI -10 to -14] vs. 1% [-3 to 5], P = 0.005) but not postprandial glucose concentration compared with placebo. Salsalate also lowered fasting triglyceride concentration (-25% [-34 to -15] vs. -6% [-26 to 14], P = 0.04). Salsalate had no effect on SSPG concentration or insulin secretion rate but significantly decreased insulin clearance rate compared with placebo (-23% [-30 to -16] vs. 3% [-10 to 15], P < 0.001). Salsalate was well tolerated, but four individuals needed a dose reduction due to symptoms. Salsalate treatment in nondiabetic, insulin-resistant individuals improved fasting, but not postprandial, glucose and triglyceride concentration. These improvements were associated with a decrease in insulin clearance rate without change in insulin action or insulin secretion.

    Abstract Summary: Scientists did a study to see if a medicine called salsalate can help people who have trouble controlling their blood sugar but don't have diabetes. They gave salsalate to some people and a fake pill to others for 4 weeks. They checked how well their bodies handled sugar and insulin before and after the treatment. They found that salsalate helped lower the amount of sugar and fats in the blood when people hadn't eaten, but it didn't change how much sugar was in the blood after eating. Salsalate made the body slower at getting rid of insulin, but it didn't change how the body used insulin or how much insulin was made. Most people were okay with the medicine, but a few needed a smaller dose because they didn't feel good. This study shows that salsalate might help people with high blood sugar when they haven't eaten, which could be important for keeping a healthy balance of sugar in the body.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

The National Institutes of Health
  • Independent and Interactive Associations of Subjective and Objective Socioeconomic Status With Body Composition and Parent-Reported Hyperphagia Among Children.
    Childhood obesity (Print) (2023)
    Smith MR, Bittner JMP, Loch LK, Haynes HE, Bloomer BF, Te-Vazquez J, Bowling AI, Brady SM, Tanofsky-Kraff M, Chen KY, Yanovski JA, Cheon BK. Independent and Interactive Associations of Subjective and Objective Socioeconomic Status With Body Composition and Parent-Reported Hyperphagia Among Children. Child Obes. 2023 Nov 9; :.
    Abstract: Subjective socioeconomic status (SSES) and objective socioeconomic status (OSES) have been independently associated with body composition and eating behavior in children. While low OSES may constrain access to healthier foods, low SSES has been associated with increased preference for and motivation to consume higher energy foods and portions independent of OSES. Despite these distinct ways that OSES and SSES may affect children's eating behavior and adiposity, their joint contributions remain unclear. We investigated the independent and interactive associations of SSES and OSES with children's BMI, fat mass index (FMI), and caregiver-reported hyperphagia. Data were derived from the Children's Growth and Behavior Study, an ongoing observational study. Multiple linear regressions used child's SSES and OSES of the family as independent factors and modeled the statistical interaction of SSES and OSES with BMI ( = 128), FMI ( = 122), and hyperphagia and its subscales ( = 76) as dependent variables. SSES was independently and negatively associated with hyperphagia severity and OSES was independently and negatively associated with both FMI and hyperphagia severity. There was a statistical interaction effect of SSES and OSES on hyperphagia severity-lower SSES was associated with greater hyperphagia severity only at lower levels of OSES. These findings demonstrate a relationship between low OSES and child adiposity and that the relationship between child SSES and hyperphagia severity may be most relevant for children from households with lower family OSES. Future research on socioeconomic disparities in children's body composition and eating behaviors should examine the interaction of SSES and OSES. NCT02390765.

    Abstract Summary: Scientists did a study to see how kids' feelings about their family's money (SSES) and their family's actual money situation (OSES) are linked to their body size and eating habits. They found that when kids feel like their family has less money, they might want to eat more, especially if their family really does have less money. Also, when a family has less money, kids might have more body fat. This study helps us understand that both how kids feel about money and their family's real money situation can affect how much they eat and their body size. It's important to think about both of these things when trying to help kids stay healthy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects.
    Cell reports. Medicine (2023)
    Han K, Singh K, Meadows AM, Sharma R, Hassanzadeh S, Wu J, Goss-Holmes H, Huffstutler RD, Teague HL, Mehta NN, Griffin JL, Tian R, Traba J, Sack MN. Boosting NAD preferentially blunts Th17 inflammation via arginine biosynthesis and redox control in healthy and psoriasis subjects. Cell Rep Med. 2023 Sep 19; 4(9):101157.
    Abstract: To evaluate whether nicotinamide adenine dinucleotide-positive (NAD) boosting modulates adaptive immunity, primary CD4 T cells from healthy control and psoriasis subjects were exposed to vehicle or nicotinamide riboside (NR) supplementation. NR blunts interferon γ (IFNγ) and interleukin (IL)-17 secretion with greater effects on T helper (Th) 17 polarization. RNA sequencing (RNA-seq) analysis implicates NR blunting of sequestosome 1 (sqstm1/p62)-coupled oxidative stress. NR administration increases sqstm1 and reduces reactive oxygen species (ROS) levels. Furthermore, NR activates nuclear factor erythroid 2-related factor 2 (Nrf2), and genetic knockdown of nrf2 and the Nrf2-dependent gene, sqstm1, diminishes NR amelioratory effects. Metabolomics analysis identifies that NAD boosting increases arginine and fumarate biosynthesis, and genetic knockdown of argininosuccinate lyase ameliorates NR effects on IL-17 production. Hence NR via amino acid metabolites orchestrates Nrf2 activation, augments CD4 T cell antioxidant defenses, and attenuates Th17 responsiveness. Oral NR supplementation in healthy volunteers similarly increases serum arginine, sqstm1, and antioxidant enzyme gene expression and blunts Th17 immune responsiveness, supporting evaluation of NAD boosting in CD4 T cell-linked inflammation.

    Abstract Summary: Scientists did an experiment to see if a special vitamin called nicotinamide riboside (NR) can help the body's immune system work better. They tested this on immune cells from healthy people and people with a skin condition called psoriasis. They found that NR made these cells less likely to create substances that can cause inflammation. The study also showed that NR helps protect cells from stress and boosts their defense systems. When they gave NR to healthy people, it had similar good effects. This research suggests that NR might be helpful for people with diseases that involve inflammation, like psoriasis.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Malaria transmission-blocking vaccines Pfs230D1-EPA and Pfs25-EPA in Alhydrogel in healthy Malian adults; a phase 1, randomised, controlled trial.
    The Lancet. Infectious diseases (2023)
    Sagara I, Healy SA, Assadou MH, Kone M, Swihart BJ, Kwan JL, Fintzi J, Sissoko K, Kamate B, Samake Y, Guindo MA, Doucoure M, Niaré K, Dolo A, Diarra B, Rausch KM, Narum DL, Jones DS, MacDonald NJ, Zhu D, Gorres JP, Imeru A, Mohan R, Thera I, Zaidi I, Sal. Malaria transmission-blocking vaccines Pfs230D1-EPA and Pfs25-EPA in Alhydrogel in healthy Malian adults; a phase 1, randomised, controlled trial. Lancet Infect Dis. 2023 Nov; 23(11):1266-1279.
    Abstract: Malaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior activity to zygote vaccine Pfs25-EPA/Alhydrogel in malaria-naive US adults. Here, we compared these vaccines in malaria-experienced Malians. We did a pilot safety study then double-blind, block-randomised, comparator-controlled main-phase trial in malaria-intense Bancoumana, Mali. 18-50-year-old healthy non-pregnant, non-breastfeeding consenting adult residents were randomly assigned (1:1:1:1) to receive four doses at months 0, 1, 4·5, and 16·5 of either 47 μg Pfs25, 40 μg Pfs230D1 or comparator (Twinrix or Menactra)-all co-administered with normal saline for blinding-or 47 μg Pfs25 plus 40 μg Pfs230D1 co-administered. We documented safety and tolerability (primary endpoint in the as-treated populations) and immunogenicity (secondary endpoint in the as-treated populations: ELISA, standard-membrane-feeding assay, and mosquito direct skin feed assay). This trial is registered at ClinicalTrials.gov, NCT02334462. Between March 19, and June 2, 2015, we screened 471 individuals. Of 225 enrolled for the pilot and main cohorts, we randomly assigned 25 participants to pilot safety cohort groups of five (20%) to receive a two-dose series of Pfs25-EPA/Alhydrogel (16 μg), Pfs230D1-EPA/Alhydrogel (15 μg) or comparator, followed by Pfs25-EPA/Alhydrogel (16 μg) plus Pfs230D1-EPA/Alhydrogel (15 μg) or comparator plus saline. For the main cohort, we enrolled 200 participants between May 11 and June 2, 2015, to receive a four-dose series of 47 μg Pfs25-EPA/Alhydrogel plus saline (n=50 [25%]; Pfs25), 40 μg Pfs230D1-EPA/Alhydrogel plus saline (n=49 [25%]; Pfs230D1), 47 μg Pfs25-EPA/Alhydrogel plus 40 μg Pfs230D1-EPA/Alhydrogel (n=50 [25%]; Pfs25 plus Pfs230D1), or comparator (Twinrix or Menactra) plus saline (n=51 [25%]). Vaccinations were well tolerated in the pilot safety and main phases. Most vaccinees became seropositive after two Pfs230D1 or three Pfs25 doses; peak titres increased with each dose thereafter (Pfs230D1 geometric mean: 77·8 [95% CI 56·9-106·3], 146·4 [108·3-198·0], and 410·2 [301·6-558·0]; Pfs25 geometric mean 177·7 [130·3-242·4] and 315·7 [209·9-474·6]). Functional activity (mean peak transmission-reducing activity) appeared for Pfs230D1 (74·5% [66·6-82·5]) and Pfs25 plus Pfs230D1 (68·6% [57·3-79·8]), after the third dose and after the fourth dose (88·9% [81·7-96·2] for Pfs230D1 and 85·0% [78·4-91·5] Pfs25 plus Pfs230D1) but not for Pfs25 (58·2% [49·1-67·3] after the third dose and 58·2% [48·5-67·9] after the fourth dose). Pfs230D1 transmission-reducing activity (73·7% [64·1-83·3]) persisted 10 weeks after the fourth dose. Transmission-reducing activity of 80% was estimated at 1659 ELISA units for Pfs25, 218 for Pfs230D1, and 223 for Pfs230D1 plus Pfs25. After 3850 direct skin feed assays, 35 participants (12 Pfs25, eight Pfs230D1, five Pfs25 plus Pfs230D1, and ten comparator) had transmitted parasites at least once. The proportion of positive assays in vaccine groups (Pfs25 33 [3%] of 982 [-0·013 to 0·014], Pfs230D1 22 [2%] of 954 [-0·005 to 0·027], and combination 11 [1%] of 940 [-0·024 to 0·002]) did not differ from that of the comparator (22 [2%] of 974), nor did Pfs230D1 and combination groups differ (-0·024 to 0·001). Pfs230D1 but not Pfs25 vaccine induces durable serum functional activity in Malian adults. Direct skin feed assays detect parasite transmission to mosquitoes but increased event rates are needed to assess vaccine effectiveness. Intramural Research Program of the National Institute of Allergy and Infectious Diseases and US National Institutes of Health.

    Abstract Summary: Scientists did a study to see if new malaria vaccines could help stop the spread of malaria in Mali, where people often get the disease. They tested two vaccines, Pfs230D1 and Pfs25, on adults who had experienced malaria before. The vaccines were given in four doses over about 16 months. They wanted to see if the vaccines were safe, if people's bodies accepted them, and if they could stop mosquitoes from getting malaria when they bite people. They found that both vaccines were safe and that people's bodies responded well to them. The Pfs230D1 vaccine worked better than the Pfs25 vaccine. It helped stop mosquitoes from getting malaria for a longer time. They also tried giving both vaccines together, and this worked well too. The study showed that the Pfs230D1 vaccine could be a good way to help stop the spread of malaria. This is important because it means there might be a new tool to fight malaria, which can make a lot of people very sick or even cause death.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Aneuploidy effects on human gene expression across three cell types.
    Proceedings of the National Academy of Sciences of the United States of America (2023)
    Liu S, Akula N, Reardon PK, Russ J, Torres E, Clasen LS, Blumenthal J, Lalonde F, McMahon FJ, Szele F, Disteche CM, Cader MZ, Raznahan A. Aneuploidy effects on human gene expression across three cell types. Proc Natl Acad Sci U S A. 2023 May 23; 120(21):e2218478120.
    Abstract: Aneuploidy syndromes impact multiple organ systems but understanding of tissue-specific aneuploidy effects remains limited-especially for the comparison between peripheral tissues and relatively inaccessible tissues like brain. Here, we address this gap in knowledge by studying the transcriptomic effects of chromosome X, Y, and 21 aneuploidies in lymphoblastoid cell lines, fibroblasts and iPSC-derived neuronal cells (LCLs, FCL, and iNs, respectively). We root our analyses in sex chromosome aneuploidies, which offer a uniquely wide karyotype range for dosage effect analysis. We first harness a large LCL RNA-seq dataset from 197 individuals with one of 6 sex chromosome dosages (SCDs: XX, XXX, XY, XXY, XYY, and XXYY) to i) validate theoretical models of SCD sensitivity and ii) define an expanded set of 41 genes that show obligate dosage sensitivity to SCD and are all in (i.e., reside on the X or Y chromosome). We then use multiple complementary analyses to show that effects of SCD in LCLs are preserved in both FCLs (n = 32) and iNs (n = 24), whereas effects (i.e., those on autosomal gene expression) are mostly not preserved. Analysis of additional datasets confirms that the greater cross-cell type reproducibility of vs. effects is also seen in trisomy 21 cell lines. These findings i) expand our understanding of X, Y, and 21 chromosome dosage effects on human gene expression and ii) suggest that LCLs may provide a good model system for understanding effects of aneuploidy in harder-to-access cell types.

    Abstract Summary: Scientists did a study to learn more about how having an extra or missing chromosome affects different parts of the body, like the brain and blood cells. They looked at genes in three types of cells: blood cells, skin cells, and brain cells made from stem cells. They focused on changes in the X and Y chromosomes (which determine if someone is male or female) and chromosome 21 (an extra copy of which causes Down syndrome). They found 41 genes that are really sensitive to the number of sex chromosomes a person has. These genes are on the X or Y chromosome. The changes they saw in the blood cells were also seen in the skin and brain cells. But changes in other chromosomes were different in each type of cell. Their research helps us understand how different cells in the body are affected by having an extra or missing chromosome. It also shows that studying blood cells can give us good clues about what might be happening in other parts of the body that are harder to study, like the brain.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Immunological characterization of a VIR protein family member (VIR-14) in Plasmodium vivax-infected subjects from different epidemiological regions in Africa and South America.
    PLoS neglected tropical diseases (2023)
    Fantin RF, Coelho CH, Berhe AD, Magalhães LMD, Pereira DB, Salinas ND, Tolia NH, Amaratunga C, Suon S, Sagara I, Narum DL, Fujiwara RT, Abejon C, Campos-Neto A, Duffy PE, Bueno LL. Immunological characterization of a VIR protein family member (VIR-14) in Plasmodium vivax-infected subjects from different epidemiological regions in Africa and South America. PLoS Negl Trop Dis. 2023 Apr; 17(4):e0011229.
    Abstract: Plasmodium vivax is a major challenge for malaria control due to its wide geographic distribution, high frequency of submicroscopic infections, and ability to induce relapses due to the latent forms present in the liver (hypnozoites). Deepening our knowledge of parasite biology and its molecular components is key to develop new tools for malaria control and elimination. This study aims to investigate and characterize a P. vivax protein (PvVir14) for its role in parasite biology and its interactions with the immune system. We collected sera or plasma from P.vivax-infected subjects in Brazil (n = 121) and Cambodia (n = 55), and from P. falciparum-infected subjects in Mali (n = 28), to assess antibody recognition of PvVir14. Circulating antibodies against PvVir14 appeared in 61% and 34.5% of subjects from Brazil and Cambodia, respectively, versus none (0%) of the P. falciparum-infected subjects from Mali who have no exposure to P. vivax. IgG1 and IgG3 most frequently contributed to anti-PvVir14 responses. PvVir14 antibody levels correlated with those against other well-characterized sporozoite/liver (PvCSP) and blood stage (PvDBP-RII) antigens, which were recognized by 7.6% and 42% of Brazilians, respectively. Concerning the cellular immune profiling of Brazilian subjects, PvVir14 seroreactive individuals displayed significantly higher levels of circulating atypical (CD21- CD27-) B cells, raising the possibility that atypical B cells may be contribute to the PvVir14 antibody response. When analyzed at a single-cell level, the B cell receptor gene hIGHV3-23 was only seen in subjects with active P.vivax infection where it comprised 20% of V gene usage. Among T cells, CD4+ and CD8+ levels differed (lower and higher, respectively) between subjects with versus without antibodies to PvVir14, while NKT cell levels were higher in those without antibodies. Specific B cell subsets, anti-PvVir14 circulating antibodies, and NKT cell levels declined after treatment of P. vivax. This study provides the immunological characterization of PvVir14, a unique P. vivax protein, and possible association with acute host's immune responses, providing new information of specific host-parasite interaction. Trial registration: TrialClinicalTrials.gov Identifier: NCT00663546 & ClinicalTrials.gov NCT02334462.

    Abstract Summary: Scientists are studying a special protein from a germ that causes a type of malaria. This germ is tricky because it can hide in the liver and make people sick again after they seem to get better. The researchers looked at blood from people in Brazil, Cambodia, and Mali to see if their bodies made fighters, called antibodies, against this protein. They found that many people in Brazil and some in Cambodia had these fighters, but none in Mali did because the germ isn't found there. They also discovered that certain blood cells that help make antibodies were more common in people who had these fighters. After treating the malaria, the number of these cells and fighters went down. This study helps us understand how our bodies try to fight off this type of malaria and could help make new ways to stop it.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Deep phenotypic analysis of psychiatric features in genetically defined cohorts: application to XYY syndrome.
    Journal of neurodevelopmental disorders (2023)
    Raznahan A, Rau S, Schaffer L, Liu S, Fish AM, Mankiw C, Xenophontos A, Clasen LS, Joseph L, Thurm A, Blumenthal JD, Bassett DS, Torres EN. Deep phenotypic analysis of psychiatric features in genetically defined cohorts: application to XYY syndrome. J Neurodev Disord. 2023 Feb 20; 15(1):8.
    Abstract: Recurrent gene dosage disorders impart substantial risk for psychopathology. Yet, understanding that risk is hampered by complex presentations that challenge classical diagnostic systems. Here, we present a suite of generalizable analytic approaches for parsing this clinical complexity, which we illustrate through application to XYY syndrome. We gathered high-dimensional measures of psychopathology in 64 XYY individuals and 60 XY controls, plus additional interviewer-based diagnostic data in the XYY group. We provide the first comprehensive diagnostic description of psychiatric morbidity in XYY syndrome and show how diagnostic morbidity relates to functioning, subthreshold symptoms, and ascertainment bias. We then map behavioral vulnerabilities and resilience across 67 behavioral dimensions before borrowing techniques from network science to resolve the mesoscale architecture of these dimensions and links to observable functional outcomes. Carriage of an extra Y-chromosome increases risk for diverse psychiatric diagnoses, with clinically impactful subthreshold symptomatology. Highest rates are seen for neurodevelopmental and affective disorders. A lower bound of < 25% of carriers are free of any diagnosis. Dimensional analysis of 67 scales details the profile of psychopathology in XYY, which survives control for ascertainment bias, specifies attentional and social domains as the most impacted, and refutes stigmatizing historical associations between XYY and violence. Network modeling compresses all measured symptom scales into 8 modules with dissociable links to cognitive ability, adaptive function, and caregiver strain. Hub modules offer efficient proxies for the full symptom network. This study parses the complex behavioral phenotype of XYY syndrome by applying new and generalizable analytic approaches for analysis of deep-phenotypic psychiatric data in neurogenetic disorders.

    Abstract Summary: Scientists did a study to understand how having an extra Y chromosome (XYY syndrome) can affect mental health. They looked at 64 people with XYY and 60 people without it. They found that having XYY can lead to different mental health issues, especially problems with how the brain develops and mood disorders. Less than 25% of people with XYY don't have any mental health diagnosis. The study also found that attention and social skills are the most affected, but having XYY doesn't mean a person will be violent. They used special math to group symptoms into 8 categories, which helps understand how XYY affects thinking skills, daily life, and stress for caregivers. This research helps us know more about XYY and can be used to study other genetic conditions that affect mental health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine.
    eLife (2023)
    Cheung F, Apps R, Dropulic L, Kotliarov Y, Chen J, Jordan T, Langweiler M, Candia J, Biancotto A, Han KL, Rachmaninoff N, Pietz H, Wang K, Tsang JS, Cohen JI. Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine. Elife. 2023 Jan 17; 12:.
    Abstract: Both sex and prior exposure to pathogens are known to influence responses to immune challenges, but their combined effects are not well established in humans, particularly in early innate responses critical for shaping subsequent outcomes. We employed systems immunology approaches to study responses to a replication-defective, herpes simplex virus (HSV) 2 vaccine in men and women either naive or previously exposed to HSV. Blood transcriptomic and cell population profiling showed substantial changes on day 1 after vaccination, but the responses depended on sex and whether the vaccinee was naive or previously exposed to HSV. The magnitude of early transcriptional responses was greatest in HSV naive women where type I interferon (IFN) signatures were prominent and associated negatively with vaccine-induced neutralizing antibody titers, suggesting that a strong early antiviral response reduced the uptake of this replication-defective virus vaccine. While HSV seronegative vaccine recipients had upregulation of gene sets in type I IFN (IFN-α/β) responses, HSV2 seropositive vaccine recipients tended to have responses focused more on type II IFN (IFN-γ) genes. These results together show that prior exposure and sex interact to shape early innate responses that then impact subsequent adaptive immune phenotypes. Intramural Research Program of the NIH, the National Institute of Allergy and Infectious Diseases, and other institutes supporting the Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation. The vaccine trial was supported through a clinical trial agreement between the National Institute of Allergy and Infectious Diseases and Sanofi Pasteur. Clinical trial number: NCT01915212.

    Abstract Summary: Scientists wanted to understand how gender and previous exposure to germs affect the body's response to a vaccine for a virus called HSV. They studied the blood of men and women who either had or hadn't been exposed to HSV before. They found that the body's initial response to the vaccine was different depending on gender and previous exposure. Women who hadn't been exposed to HSV before had the strongest initial response, which seemed to reduce the effectiveness of the vaccine. This study shows that gender and previous exposure to germs can affect how our bodies respond to vaccines. This could help us make better vaccines in the future.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A Cross-Species Neuroimaging Study of Sex Chromosome Dosage Effects on Human and Mouse Brain Anatomy.
    The Journal of neuroscience : the official journal of the Society for Neuroscience (2023)
    Guma E, Beauchamp A, Liu S, Levitis E, Clasen LS, Torres E, Blumenthal J, Lalonde F, Qiu LR, Hrncir H, MacKenzie-Graham A, Yang X, Arnold AP, Lerch JP, Raznahan A. A Cross-Species Neuroimaging Study of Sex Chromosome Dosage Effects on Human and Mouse Brain Anatomy. J Neurosci. 2023 Feb 22; 43(8):1321-1333.
    Abstract: All eutherian mammals show chromosomal sex determination with contrasting sex chromosome dosages (SCDs) between males (XY) and females (XX). Studies in transgenic mice and humans with sex chromosome trisomy (SCT) have revealed direct SCD effects on regional mammalian brain anatomy, but we lack a formal test for cross-species conservation of these effects. Here, we develop a harmonized framework for comparative structural neuroimaging and apply this to systematically profile SCD effects on regional brain anatomy in both humans and mice by contrasting groups with SCT (XXY and XYY) versus XY controls. Total brain size was substantially altered by SCT in humans (significantly decreased by XXY and increased by XYY), but not in mice. Robust and spatially convergent effects of XXY and XYY on regional brain volume were observed in humans, but not mice, when controlling for global volume differences. However, mice do show subtle effects of XXY and XYY on regional volume, although there is not a general spatial convergence in these effects within mice or between species. Notwithstanding this general lack of conservation in SCT effects, we detect several brain regions that show overlapping effects of XXY and XYY both within and between species (cerebellar, parietal, and orbitofrontal cortex), thereby nominating high priority targets for future translational dissection of SCD effects on the mammalian brain. Our study introduces a generalizable framework for comparative neuroimaging in humans and mice and applies this to achieve a cross-species comparison of SCD effects on the mammalian brain through the lens of SCT. Sex chromosome dosage (SCD) affects neuroanatomy and risk for psychopathology in humans. Performing mechanistic studies in the human brain is challenging but possible in mouse models. Here, we develop a framework for cross-species neuroimaging analysis and use this to show that an added X- or Y-chromosome significantly alters human brain anatomy but has muted effects in the mouse brain. However, we do find evidence for conserved cross-species impact of an added chromosome in the fronto-parietal cortices and cerebellum, which point to regions for future mechanistic dissection of sex chromosome dosage effects on brain development.

    Abstract Summary: Scientists wanted to see if having an extra sex chromosome affects the brain the same way in people and mice. They compared brain images of humans and mice with an extra X or Y chromosome to those with the usual number. They found that in people, an extra chromosome made the brain size bigger or smaller and changed certain parts of the brain. In mice, the changes were smaller and not the same across different mice. But they did find some brain areas in both humans and mice that were affected by the extra chromosome. This study helps us understand where to look in the brain to learn more about how extra sex chromosomes can change brain development.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Youth with Down syndrome display widespread increased functional connectivity during rest.
    Scientific reports (2022)
    Csumitta KD, Gotts SJ, Clasen LS, Martin A, Raitano Lee N. Youth with Down syndrome display widespread increased functional connectivity during rest. Sci Rep. 2022 Jun 14; 12(1):9836.
    Abstract: Studies of resting-state functional connectivity in young people with Down syndrome (DS) have yielded conflicting results. Some studies have found increased connectivity while others have found a mix of increased and decreased connectivity. No studies have examined whole-brain connectivity at the voxel level in youth with DS during an eyes-open resting-state design. Additionally, no studies have examined the relationship between connectivity and network selectivity in youth with DS. Thus, the current study sought to fill this gap in the literature. Nineteen youth with DS (M = 16.5; range 7-23; 13 F) and 33 typically developing (TD) youth (M = 17.5; range 6-24; 18 F), matched on age and sex, completed a 5.25-min eyes-open resting-state fMRI scan. Whole-brain functional connectivity (average Pearson correlation of each voxel with every other voxel) was calculated for each individual and compared between groups. Network selectivity was then calculated and correlated with functional connectivity for the DS group. Results revealed that whole-brain functional connectivity was significantly higher in youth with DS compared to TD controls in widespread regions throughout the brain. Additionally, participants with DS had significantly reduced network selectivity compared to TD peers, and selectivity was significantly related to connectivity in all participants. Exploratory behavioral analyses revealed that regions showing increased connectivity in DS predicted Verbal IQ, suggesting differences in connectivity may be related to verbal abilities. These results indicate that network organization is disrupted in youth with DS such that disparate networks are overly connected and less selective, suggesting a potential target for clinical interventions.

    Abstract Summary: Scientists did a study to understand how the brains of young people with Down syndrome (DS) are connected when they are just resting and not doing any tasks. They looked at the brains of 19 young people with DS and compared them to 33 young people without DS. They used a special brain scan called fMRI while the participants were awake and resting. They found that the brains of those with DS had more connections in many areas compared to those without DS. Also, the brains of the DS group were not as good at keeping different brain networks separate. They noticed that the more the brain areas were connected, the better the verbal skills of the person with DS. This study helps us understand that the brains of young people with DS work differently, and this could lead to new ways to help them with their verbal skills.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings.
    Annals of internal medicine (2022)
    Sneller MC, Liang CJ, Marques AR, Chung JY, Shanbhag SM, Fontana JR, Raza H, Okeke O, Dewar RL, Higgins BP, Tolstenko K, Kwan RW, Gittens KR, Seamon CA, McCormack G, Shaw JS, Okpali GM, Law M, Trihemasava K, Kennedy BD, Shi V, Justement JS, Buckner CM, Bl. A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings. Ann Intern Med. 2022 Jul; 175(7):969-979.
    Abstract: A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC). To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls. Cohort study. (ClinicalTrials.gov: NCT04411147). National Institutes of Health Clinical Center, Bethesda, Maryland. Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area. All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations. 189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment. A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19. Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

    Abstract Summary: Scientists did a study to learn more about the health problems that some people have after they get better from COVID-19. They looked at a group of people who had COVID-19 and another group who never got sick with it. They checked everyone's health with physical exams, blood tests, and questions about how they felt. They found that more than half of the people who had COVID-19 still felt sick with symptoms like tiredness and trouble thinking, even after they were supposed to be better. Women and people who had anxiety before were more likely to feel this way. The study also showed that these health issues made people's lives harder. But when the scientists did more tests, they couldn't find a clear reason why these people still felt sick. They also learned that the body's defense against the virus, called antibodies, was different in people after they had COVID-19. This study helps us understand that many people still feel unwell after COVID-19, but we need to learn more about why this happens.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Poly(GR) and poly(GA) in cerebrospinal fluid as potential biomarkers for C9ORF72-ALS/FTD.
    Nature communications (2022)
    Krishnan G, Raitcheva D, Bartlett D, Prudencio M, McKenna-Yasek DM, Douthwright C, Oskarsson BE, Ladha S, King OD, Barmada SJ, Miller TM, Bowser R, Watts JK, Petrucelli L, Brown RH, Kankel MW, Gao FB. Poly(GR) and poly(GA) in cerebrospinal fluid as potential biomarkers for C9ORF72-ALS/FTD. Nat Commun. 2022 May 19; 13(1):2799.
    Abstract: GGGGCC repeat expansion in C9ORF72, which can be translated in both sense and antisense directions into five dipeptide repeat (DPR) proteins, including poly(GP), poly(GR), and poly(GA), is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we developed sensitive assays that can detect poly(GA) and poly(GR) in the cerebrospinal fluid (CSF) of patients with C9ORF72 mutations. CSF poly(GA) and poly(GR) levels did not correlate with age at disease onset, disease duration, or rate of decline of ALS Functional Rating Scale, and the average levels of these DPR proteins were similar in symptomatic and pre-symptomatic patients with C9ORF72 mutations. However, in a patient with C9ORF72-ALS who was treated with antisense oligonucleotide (ASO) targeting the aberrant C9ORF72 transcript, CSF poly(GA) and poly(GR) levels decreased approximately 50% within 6 weeks, indicating they may serve as sensitive fluid-based biomarkers in studies directed against the production of GGGGCC repeat RNAs or DPR proteins.

    Abstract Summary: Scientists are studying a genetic change that is the main cause of two brain diseases: ALS and FTD. This change makes extra bits of protein that might be linked to these diseases. The scientists made special tests to measure two types of these extra proteins in the fluid that surrounds the brain and spine. They found that the amount of these proteins didn't match up with how old people were when they got sick, how long they had been sick, or how quickly their sickness got worse. The levels were the same in people who had symptoms and those who didn't yet. But, when they treated one patient with a special medicine that targets the genetic change, the levels of these proteins went down by half in just 6 weeks. This means that measuring these proteins could help us see if treatments for these brain diseases are working.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Variegation of autism related traits across seven neurogenetic disorders.
    Translational psychiatry (2022)
    Lee NR, Niu X, Zhang F, Clasen LS, Kozel BA, Smith ACM, Wallace GL, Raznahan A. Variegation of autism related traits across seven neurogenetic disorders. Transl Psychiatry. 2022 Apr 7; 12(1):149.
    Abstract: Gene dosage disorders (GDDs) constitute a major class of genetic risks for psychopathology, but there is considerable debate regarding the extent to which different GDDs induce different psychopathology profiles. The current research speaks to this debate by compiling and analyzing dimensional measures of several autism-related traits (ARTs) across seven diverse GDDs. The sample included 350 individuals with one of 7 GDDs, as well as reference idiopathic autism spectrum disorder (ASD; n = 74) and typically developing control (TD; n = 171) groups. The GDDs were: Down, Williams-Beuren, and Smith-Magenis (DS, WS, SMS) syndromes, and varying sex chromosome aneuploidies ("plusX", "plusXX", "plusY", "plusXY"). The Social Responsiveness Scale (SRS-2) was used to measure ARTs at different levels of granularity-item, subscale, and total. General linear models were used to examine ART profiles in GDDs, and machine learning was used to predict genotype from SRS-2 subscales and items. These analyses were completed with and without covariation for cognitive impairment. Twelve of all possible 21 pairwise GDD group contrasts showed significantly different ART profiles (7/21 when co-varying for IQ, all Bonferroni-corrected). Prominent GDD-ART associations in post hoc analyses included relatively preserved social motivation in WS and relatively low levels of repetitive behaviors in plusX. Machine learning revealed that GDD group could be predicted with plausible accuracy (~60-80%) even after controlling for IQ. GDD effects on ARTs are influenced by GDD subtype and ART dimension. This observation has consequences for mechanistic, clinical, and translational aspects of psychiatric neurogenetics.

    Abstract Summary: This study looked at how different genetic disorders can affect the way people behave or think, especially in relation to autism. The researchers studied 350 people with one of seven different genetic disorders, and compared them to people with autism and people without any of these conditions. They used a special scale to measure different autism-related traits and used computer models to predict which genetic disorder a person might have based on these traits. They found that different disorders can lead to different behaviors, and that they could often predict the disorder based on these behaviors. This could help doctors better understand and treat these conditions.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Sex-specific associations between subcortical morphometry in childhood and adult alcohol consumption: A 17-year follow-up study.
    NeuroImage. Clinical (2021)
    Mankiw C, Whitman ET, Torres E, Lalonde F, Clasen LS, Blumenthal JD, Chakravarty MM, Raznahan A. Sex-specific associations between subcortical morphometry in childhood and adult alcohol consumption: A 17-year follow-up study. Neuroimage Clin. 2021; 31:102771.
    Abstract: Men and women tend to differ in the age of first alcohol consumption, transition into disordered drinking, and the prevalence of alcohol use disorder. Here, we use a unique longitudinal dataset to test for potentially predispositonal sex-biases in brain organization prior to initial alcohol exposure. Our study combines measures of subcortical morphometry gathered in alcohol naive individuals during childhood (mean age: 9.43 years, SD = 2.06) with self-report measures of alcohol use in the same individuals an average of 17 years later (N = 81, 46 males, 35 females). We observe that pediatric amygdala and hippocampus volume both show sex-biased relationships with adult drinking. Specifically, females show a stronger association between subcortical volumetric reductions in childhood and peak drinking in adulthood as compared to males. Detailed analysis of subcortical shape localizes these effects to the rostro-medial hippocampus and basolateral amygdala subnuclei. In contrast, we did not observe sex-specific associations between striatal anatomy and peak alcohol consumption. These results are consistent with a model in which organization of the amygdala and hippocampus in childhood is more relevant for subsequent patterns of peak alcohol use in females as compared to males. Differential neuroanatomical precursors of alcohol use in males and females could provide a potential developmental basis for well recognized sex-differences in alcohol use behaviors.. Thus, our findings not only indicate that brain correlates of human alcohol consumption are manifest long before alcohol initiation, but that some of these correlates are not equivalent between males and females.

    Abstract Summary: Scientists did a study to see if boys and girls have different brain features before they ever try alcohol that might make them drink differently when they grow up. They looked at brain scans of kids around 9 years old who had never had alcohol and then asked them about their drinking habits 17 years later. They found that for girls, certain smaller parts of the brain when they were kids were linked to drinking more as adults, but this wasn't as strong for boys. This study helps us understand that boys and girls might have different reasons for how they drink when they're older, and knowing this could help us figure out how to prevent drinking problems before they start.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Sex Chromosome Dosage Effects on White Matter Structure in the Human Brain.
    Cerebral cortex (New York, N.Y. : 1991) (2021)
    Warling A, Yavi M, Clasen LS, Blumenthal JD, Lalonde FM, Raznahan A, Liu S. Sex Chromosome Dosage Effects on White Matter Structure in the Human Brain. Cereb Cortex. 2021 Oct 22; 31(12):5339-5353.
    Abstract: Sex chromosome aneuploidies, a group of neurogenetic conditions characterized by aberrant sex chromosome dosage (SCD), are associated with increased risks for psychopathology as well as alterations in gray matter structure. However, we still lack a comprehensive understanding of potential SCD-associated changes in white matter structure, or knowledge of how these changes might relate to known alterations in gray matter anatomy. Thus, here, we use voxel-based morphometry on structural neuroimaging data to provide the first comprehensive maps of regional white matter volume (WMV) changes across individuals with varying SCD (n = 306). We show that mounting X- and Y-chromosome dosage are both associated with widespread WMV decreases, including in cortical, subcortical, and cerebellar tracts, as well as WMV increases in the genu of the corpus callosum and posterior thalamic radiation. We also correlate X- and Y-chromosome-linked WMV changes in certain regions to measures of internalizing and externalizing psychopathology. Finally, we demonstrate that SCD-driven WMV changes show a coordinated coupling with SCD-driven gray matter volume changes. These findings represent the most complete maps of X- and Y-chromosome effects on human white matter to date, and show how such changes connect to psychopathological symptoms and gray matter anatomy.

    Abstract Summary: This study looked at how having extra sex chromosomes (X or Y) can affect the brain and behavior. The researchers used brain scans to map changes in the white matter, which is part of the brain that helps different areas communicate. They found that having extra X or Y chromosomes can cause decreases in white matter in some areas and increases in others. These changes were linked to certain behavioral problems. The study also found that these changes in white matter are connected to changes in gray matter, another part of the brain. This research helps us understand how extra sex chromosomes can affect the brain and behavior.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Resting-State Functional Connectivity and Psychopathology in Klinefelter Syndrome (47, XXY).
    Cerebral cortex (New York, N.Y. : 1991) (2021)
    Whitman ET, Liu S, Torres E, Warling A, Wilson K, Nadig A, McDermott C, Clasen LS, Blumenthal JD, Lalonde FM, Gotts SJ, Martin A, Raznahan A. Resting-State Functional Connectivity and Psychopathology in Klinefelter Syndrome (47, XXY). Cereb Cortex. 2021 Jul 29; 31(9):4180-4190.
    Abstract: Klinefelter syndrome (47, XXY; henceforth: XXY syndrome) is a high-impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first study to map alterations of functional brain connectivity in XXY syndrome and relate these changes to brain anatomy and psychopathology. We used resting-state functional magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males to 1) implement a brain-wide screen for altered global resting-state functional connectivity (rsFC) in XXY versus XY males and 2) decompose these alterations through seed-based analysis. We then compared these rsFC findings with measures of regional brain anatomy, psychopathology, and cognition. XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC)-reflecting DLPFC overconnectivity with diverse rsFC networks. Functional overconnectivity was partly coupled to co-occurring regional volumetric changes in XXY syndrome, and variation in DLPFC-precuneus rsFC was correlated with the severity of psychopathology. By providing the first view of altered rsFC in XXY syndrome and contextualizing observed changes relative to neuroanatomy and behavior, our study helps to advance biological understanding of XXY syndrome-both as a disorder in its own right and more broadly as a model of genetic risk for psychopathology.

    Abstract Summary: Scientists did a study to understand how the brains of people with Klinefelter syndrome (XXY syndrome) work differently. Klinefelter syndrome is when a boy is born with an extra X chromosome, which can make learning or thinking hard for them. The researchers looked at brain scans of 75 people with XXY and 84 people without it while they were resting. They found that a part of the brain called the left dorsolateral prefrontal cortex was more active and connected to other brain parts in people with XXY. This extra activity was linked to changes in brain size in certain areas and to how severe their learning or thinking problems were. This study helps us understand more about Klinefelter syndrome and could help doctors and scientists find better ways to help people with this condition.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach.
    Scientific reports (2021)
    Fourman LT, Stanley TL, Billingsley JM, Sui SJH, Feldpausch MN, Boutin A, Zheng I, McClure CM, Corey KE, Torriani M, Kleiner DE, Hadigan CM, Chung RT, Grinspoon SK. Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach. Sci Rep. 2021 May 18; 11(1):10485.
    Abstract: NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log-fold change - 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, - 0.35 ± 0.56 vs. - 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, - 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo. Among tesamorelin-treated participants, reductions in plasma VEGFA (r = 0.62, P = 0.006) and CSF1 (r = 0.50, P = 0.04) correlated with a decline in NAFLD activity score. Decreases in TGFB1 (r = 0.61, P = 0.009) and CSF1 (r = 0.64, P = 0.006) were associated with reduced gene-level fibrosis score. Tesamorelin suppressed key angiogenic, fibrogenic, and pro-inflammatory mediators. CSF1, a regulator of monocyte recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV. Clinical Trials Registry Number: NCT02196831.

    Abstract Summary: Doctors are studying a liver problem called NAFLD that happens a lot in people with HIV. They found that a medicine called tesamorelin can help reduce fat in the liver and stop the liver from getting hurt in people with HIV. They did a special test to see how tesamorelin works on certain proteins in the blood that can cause swelling and damage in the liver. They found that tesamorelin made some of these bad proteins go down, which is good because it means the liver isn't getting as sick. This is important because it shows that tesamorelin can help people with HIV keep their livers healthy, and it might lead to new ways to treat liver problems.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2021)
    Stanley TL, Fourman LT, Wong LP, Sadreyev R, Billingsley JM, Feldpausch MN, Zheng I, Pan CS, Boutin A, Lee H, Corey KE, Torriani M, Kleiner DE, Chung RT, Hadigan CM, Grinspoon SK. Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease. Clin Infect Dis. 2021 Aug 16; 73(4):621-630.
    Abstract: The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis modulates critical metabolic pathways; however, little is known regarding effects of augmenting pulsatile GH secretion on immune function in humans. This study used proteomics and gene set enrichment analysis to assess effects of a GH releasing hormone (GHRH) analog, tesamorelin, on circulating immune markers and liver tissue in people with human immunodeficiency virus (HIV) (PWH) and nonalcoholic fatty liver disease (NAFLD). 92 biomarkers associated with immunity, chemotaxis, and metabolism were measured in plasma samples from 61 PWH with NAFLD who participated in a double-blind, randomized trial of tesamorelin versus placebo for 12 months. Gene set enrichment analysis was performed on serial liver biopsies targeted to immune pathways. Tesamorelin, compared to placebo, decreased interconnected proteins related to cytotoxic T-cell and monocyte activation. Circulating concentrations of 13 proteins were significantly decreased, and no proteins increased, by tesamorelin. These included 4 chemokines (CCL3, CCL4, CCL13 [MCP4], IL8 [CXCL8]), 2 cytokines (IL-10 and CSF-1), and 4 T-cell associated molecules (CD8A, CRTAM, GZMA, ADGRG1), as well as ARG1, Gal-9, and HGF. Network analysis indicated close interaction among the gene pathways responsible for these proteins, with imputational analyses suggesting down-regulation of a closely related cluster of immune pathways. Targeted transcriptomics using liver tissue confirmed a significant end-organ signal of down-regulated immune activation pathways. Long-term treatment with a GHRH analog reduced markers of T-cell and monocyte/macrophage activity, suggesting that augmentation of the GH axis may ameliorate immune activation in an HIV population with metabolic dysregulation, systemic and end organ inflammation. Clinical Trials Registration. NCT02196831.

    Abstract Summary: Scientists wanted to see if a drug called tesamorelin could help people with HIV and a liver disease called NAFLD. They tested the drug on 61 people and compared it to a placebo (a fake drug). They found that tesamorelin lowered the levels of 13 proteins in the body that are linked to immune system activity. This suggests that the drug could help calm down the immune system in people with HIV and NAFLD. This is important because it could lead to new treatments for these conditions. The study was registered under the number NCT02196831.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Associations between weight-based teasing and disordered eating behaviors among youth.
    Eating behaviors (2021)
    Rubin AG, Schvey NA, Shank LM, Altman DR, Swanson TN, Ramirez E, Moore NA, Jaramillo M, Ramirez S, Davis EK, Broadney MM, LeMay-Russell S, Byrne ME, Parker MK, Brady SM, Kelly NR, Tanofsky-Kraff M, Yanovski JA. Associations between weight-based teasing and disordered eating behaviors among youth. Eat Behav. 2021 Apr; 41:101504.
    Abstract: Weight-based teasing (WBT) is commonly reported among youth and is associated with disinhibited and disordered eating. Specifically, youth who experience WBT may engage in disordered eating behaviors to cope with the resultant negative affect. Therefore, we examined associations between WBT and disordered eating behaviors among youth and assessed whether negative affect mediated these relationships. Two hundred one non-treatment seeking youth (8-17y) completed questionnaires assessing WBT, disinhibited eating, depression, and anxiety. Disordered eating and loss-of-control (LOC) eating were assessed via semi-structured interview. Analyses of covariance were conducted to examine relationships between WBT and eating-related variables, and bootstrapping mediation models were used to evaluate negative affect (a composite of depressive and anxiety symptoms) as a mediator of these associations. All models were adjusted for sex, race, age, and adiposity. Among 201 participants (13.1 ± 2.8y; 54.2% female; 30.3% Black; 32.8% with overweight/obesity), WBT was associated with emotional eating, eating in the absence of hunger, and disordered eating attitudes and behaviors (ps ≤ 0.02). These associations were all mediated by negative affect. WBT was also associated with a threefold greater likelihood of reporting a recent LOC eating episode (p = .049). Among boys and girls across weight strata, WBT was associated with multiple aspects of disordered eating and these relationships were mediated by negative affect. Longitudinal studies are needed to clarify the directionality of these associations and to identify subgroups of youth that may be particularly vulnerable to WBT and its sequelae.

    Abstract Summary: Scientists did a study to see if kids who are teased about their weight end up having unhealthy eating habits because they feel sad or anxious. They asked 201 kids, ages 8 to 17, about being teased, how they eat, and if they feel depressed or worried. They found that kids who were teased about their weight did have more problems with eating too much or eating when they weren't hungry, and it was often because they felt bad about themselves. They also found that these kids were more likely to lose control over their eating sometimes. The study tells us that making fun of someone's weight can really hurt their feelings and lead to unhealthy eating, so it's important to be kind to everyone, no matter what they look like.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Morphological integration of the human brain across adolescence and adulthood.
    Proceedings of the National Academy of Sciences of the United States of America (2021)
    Nadig A, Seidlitz J, McDermott CL, Liu S, Bethlehem R, Moore TM, Mallard TT, Clasen LS, Blumenthal JD, Lalonde F, Gur RC, Gur RE, Bullmore ET, Satterthwaite TD, Raznahan A. Morphological integration of the human brain across adolescence and adulthood. Proc Natl Acad Sci U S A. 2021 Apr 6; 118(14):.
    Abstract: Brain structural covariance norms capture the coordination of neurodevelopmental programs between different brain regions. We develop and apply anatomical imbalance mapping (AIM), a method to measure and model individual deviations from these norms, to provide a lifespan map of morphological integration in the human cortex. In cross-sectional and longitudinal data, analysis of whole-brain average anatomical imbalance reveals a reproducible tightening of structural covariance by age 25 y, which loosens after the seventh decade of life. Anatomical imbalance change in development and in aging is greatest in the association cortex and least in the sensorimotor cortex. Finally, we show that interindividual variation in whole-brain average anatomical imbalance is positively correlated with a marker of human prenatal stress (birthweight disparity between monozygotic twins) and negatively correlated with general cognitive ability. This work provides methods and empirical insights to advance our understanding of coordinated anatomical organization of the human brain and its interindividual variation.

    Abstract Summary: Scientists have created a new way to look at how different parts of the brain grow and work together, called Anatomical Imbalance Mapping (AIM). They used this method to study brain changes from childhood to old age. They found that the brain's different parts connect more tightly by the age of 25 and start to connect less closely after age 70. The parts of the brain that help us think and understand things change the most, while the parts that help us move and feel things change the least. They also discovered that people who had more stress before they were born or who are not as good at thinking tasks have brains that are less well connected. This research helps us understand how our brains are organized and why they might be different from one another.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Modeling familial predictors of proband outcomes in neurogenetic disorders: initial application in XYY syndrome.
    Journal of neurodevelopmental disorders (2021)
    Wilson KE, Fish AM, Mankiw C, Xenophontos A, Warling A, Whitman E, Clasen L, Torres E, Blumenthal J, Raznahan A. Modeling familial predictors of proband outcomes in neurogenetic disorders: initial application in XYY syndrome. J Neurodev Disord. 2021 Mar 22; 13(1):12.
    Abstract: Disorders of gene dosage can significantly increase risk for psychopathology, but outcomes vary greatly amongst carriers of any given chromosomal aneuploidy or sub-chromosomal copy number variation (CNV). One potential path to advance precision medicine for neurogenetic disorders is modeling penetrance in probands relative to observed phenotypes in their non-carrier relatives. Here, we seek to advance this general analytic framework by developing new methods in application to XYY syndrome-a sex chromosome aneuploidy that is known to increase risk for psychopathology. We analyzed a range of cognitive and behavioral domains in XYY probands and their non-carrier family members (n = 58 families), including general cognitive ability (FSIQ), as well as continuous measures of traits related to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Proband and relative scores were compared using covariance, regression and cluster analysis. Comparisons were made both within and across traits. Proband scores were shifted away from family scores with effect sizes varying between 0.9 and 2.4 across traits. Only FSIQ and vocabulary scores showed a significant positive correlation between probands and their non-carrier relatives across families (R ~ 0.4). Variability in family FSIQ also cross-predicted variability in proband ASD trait severity. Cluster analysis across all trait-relative pairings revealed that variability in parental psychopathology was more weakly coupled to their XYY versus their euploid offspring. We present a suite of generalizable methods for modeling variable penetrance in aneuploidy and CNV carriers using family data. These methods update estimates of phenotypic penetrance for XYY and suggest that the predictive utility of family data is likely to vary for different traits and different gene dosage disorders. ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls." Date of registry: 01 October 1989.

    Abstract Summary: Scientists did a study to understand why people with an extra Y chromosome (called XYY syndrome) often have different mental health and learning challenges. They looked at 58 families where someone had XYY syndrome and compared their thinking skills and behaviors to their family members who didn't have the extra chromosome. They found that people with XYY syndrome were quite different from their families in many ways, but they did find some similarities in general smarts and vocabulary. They also noticed that if a family generally had higher thinking skills, the person with XYY syndrome in that family might have less severe autism-like behaviors. The study helps doctors guess how someone with XYY syndrome might be affected by looking at their family. This could help in giving better care to people with XYY syndrome and other similar conditions.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Proton MR Spectroscopy Measurements of White and Brown Adipose Tissue in Healthy Humans: Relaxation Parameters and Unsaturated Fatty Acids.
    Radiology (2021)
    Ouwerkerk R, Hamimi A, Matta J, Abd-Elmoniem KZ, Eary JF, Abdul Sater Z, Chen KY, Cypess AM, Gharib AM. Proton MR Spectroscopy Measurements of White and Brown Adipose Tissue in Healthy Humans: Relaxation Parameters and Unsaturated Fatty Acids. Radiology. 2021 May; 299(2):396-406.
    Abstract: Background Activation of brown adipose tissue (BAT) in rodents increases lipolysis in white adipose tissue (WAT) and improves glucose tolerance. Adult humans can have metabolically active BAT. Implications for diabetes and obesity in humans require a better characterization of BAT in humans. Purpose To study fat depots with localized proton MR spectroscopy relaxometry and to identify differences between WAT and fluorine 18 fluorodeoxyglucose (FDG) PET/CT proven cold-activated BAT in humans. Materials and Methods Participants were consecutively enrolled in this prospective study (ClinicalTrials.gov identifiers: NCT01568671 and NCT01399385) from August 2016 to May 2019. Supraclavicular potential BAT regions were localized with MRI. Proton densities, T1, and T2 were measured with localized MR spectroscopy in potential BAT and in subcutaneous WAT. FDG PET/CT after cold stimulation was used to retrospectively identify active supraclavicular BAT or supraclavicular quiescent adipose tissue (QAT) regions. MR spectroscopy results from BAT and WAT were compared with grouped and paired tests. Results Of 21 healthy participants (mean age, 36 years ± 16 [standard deviation]; 13 men) FDG PET/CT showed active BAT in 24 MR spectroscopy-targeted regions in 16 participants (eight men). Four men had QAT. The T2 for methylene protons was shorter in BAT (mean, 69 msec ± 6, 24 regions) than in WAT (mean, 83 msec ± 3, 18 regions, < .01) and QAT (mean, 78 msec ± 2, five regions, < .01). A T2 cut-off value of 76 msec enabled the differentiation of BAT from WAT or QAT with a sensitivity of 85% and a specificity of 95%. Densities of protons adjacent and between double bonds were 33% and 24% lower, respectively, in BAT compared with those in WAT ( = .01 and = .03, respectively), indicating a lower content of unsaturated and polyunsaturated fatty acids, respectively, in BAT compared with WAT. Conclusion Proton MR spectroscopy showed shorter T2 and lower unsaturated fatty acids in brown adipose tissue (BAT) than that in white adipose tissue in healthy humans. It was feasible to identify BAT with MR spectroscopy without the use of PET/CT or cold stimulation. © RSNA, 2021 See also the editorial by Barker in this issue.

    Abstract Summary: Scientists did a study to learn more about the special fat in our bodies that helps burn calories and keep us warm, called brown fat. They used a special machine called an MRI to look at this brown fat and compare it to the regular white fat that stores energy. They tested 21 people and found that the brown fat has different signals on the MRI and less of certain types of fat compared to white fat. This is important because it could help us understand how to fight diseases like diabetes and obesity by turning on the brown fat without needing to be cold or use other tests.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Pfs230 yields higher malaria transmission-blocking vaccine activity than Pfs25 in humans but not mice.
    The Journal of clinical investigation (2021)
    Healy SA, Anderson C, Swihart BJ, Mwakingwe A, Gabriel EE, Decederfelt H, Hobbs CV, Rausch KM, Zhu D, Muratova O, Herrera R, Scaria PV, MacDonald NJ, Lambert LE, Zaidi I, Coelho CH, Renn JP, Wu Y, Narum DL, Duffy PE. Pfs230 yields higher malaria transmission-blocking vaccine activity than Pfs25 in humans but not mice. J Clin Invest. 2021 Apr 1; 131(7):.
    Abstract: BACKGROUNDVaccines that block human-to-mosquito Plasmodium transmission are needed for malaria eradication, and clinical trials have targeted zygote antigen Pfs25 for decades. We reported that a Pfs25 protein-protein conjugate vaccine formulated in alum adjuvant induced serum functional activity in both US and Malian adults. However, antibody levels declined rapidly, and transmission-reducing activity required 4 vaccine doses. Functional immunogenicity and durability must be improved before advancing transmission-blocking vaccines further in clinical development. We hypothesized that the prefertilization protein Pfs230 alone or in combination with Pfs25 would improve functional activity.METHODSTransmission-blocking vaccine candidates based on gamete antigen Pfs230 or Pfs25 were conjugated with Exoprotein A, formulated in Alhydrogel, and administered to mice, rhesus macaques, and humans. Antibody levels were measured by ELISA and transmission-reducing activity was assessed by the standard membrane feeding assay.RESULTSPfs25-EPA/Alhydrogel and Pfs230D1-EPA/Alhydrogel induced similar serum functional activity in mice, but Pfs230D1-EPA induced significantly greater activity in rhesus monkeys that was enhanced by complement. In US adults, 2 vaccine doses induced complement-dependent activity in 4 of 5 Pfs230D1-EPA/Alhydrogel recipients but no significant activity in 5 Pfs25-EPA recipients, and combination with Pfs25-EPA did not increase activity over Pfs230D1-EPA alone.CONCLUSIONThe complement-dependent functional immunogenicity of Pfs230D1-EPA represents a significant improvement over Pfs25-EPA in this comparative study. The rhesus model is more predictive of the functional human immune response to Pfs230D1 than is the mouse model.TRIAL REGISTRATIONClinicalTrials.gov NCT02334462.FUNDINGIntramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.

    Abstract Summary: Scientists are working on a special kind of shot to stop malaria from spreading from people to mosquitoes. They tried a new ingredient called Pfs230 to make the shot work better. They tested it on mice, big monkeys, and people, and checked if it helped stop the spread of malaria. They found that the new ingredient worked really well in monkeys and in some people, especially when it worked together with another part of the body's defense system. This new shot could be a better way to help stop malaria from spreading, but they need to do more tests to be sure.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity.
    The Journal of clinical investigation (2021)
    Matsuda K, Migueles SA, Huang J, Bolkhovitinov L, Stuccio S, Griesman T, Pullano AA, Kang BH, Ishida E, Zimmerman M, Kashyap N, Martins KM, Stadlbauer D, Pederson J, Patamawenu A, Wright N, Shofner T, Evans S, Liang CJ, Candia J, Biancotto A, Fantoni G, P. A replication-competent adenovirus-vectored influenza vaccine induces durable systemic and mucosal immunity. J Clin Invest. 2021 Mar 1; 131(5):.
    Abstract: BACKGROUNDTo understand the features of a replicating vaccine that might drive potent and durable immune responses to transgene-encoded antigens, we tested a replication-competent adenovirus type 4 encoding influenza virus H5 HA (Ad4-H5-Vtn) administered as an oral capsule or via tonsillar swab or nasal spray.METHODSViral shedding from the nose, mouth, and rectum was measured by PCR and culturing. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition, microneutralization, and HA inhibition assays.RESULTSAd4-H5-Vtn DNA was shed from most upper respiratory tract-immunized (URT-immunized) volunteers for 2 to 4 weeks, but cultured from only 60% of participants, with a median duration of 1 day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood as well as increases in IgG and IgA in nasal, cervical, and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAbs) against H5 that remained stable out to week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AEs) were mild, and peak NAb titers were associated with overall AE frequency and duration. Serum NAb titers could be boosted to very high levels 2 to 5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine.CONCLUSIONReplicating Ad4 delivered to the URT caused prolonged exposure to antigen, drove durable systemic and mucosal immunity, and proved to be a promising platform for the induction of immunity against viral surface glycoprotein targets.TRIAL REGISTRATIONClinicalTrials.gov NCT01443936 and NCT01806909.FUNDINGIntramural and Extramural Research Programs of the NIAID, NIH (U19 AI109946) and the Centers of Excellence for Influenza Research and Surveillance (CEIRS), NIAID, NIH (contract HHSN272201400008C).

    Abstract Summary: Scientists wanted to understand how a certain type of vaccine works to help our bodies fight off diseases. They tested a vaccine for the flu virus by giving it to people in different ways: swallowing a pill, a swab in the throat, or a nasal spray. They found that the vaccine stayed in the body for 2 to 4 weeks and helped the body produce more cells and proteins to fight off the flu. The longer the vaccine stayed in the body, the stronger the body's defense was. The vaccine caused mild side effects, but these were linked to a stronger defense against the flu. The vaccine's effects could be boosted even years later. This study shows that this type of vaccine could be a promising way to help our bodies fight off viruses.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • X-chromosome regulation and sex differences in brain anatomy.
    Neuroscience and biobehavioral reviews (2021)
    Raznahan A, Disteche CM. X-chromosome regulation and sex differences in brain anatomy. Neurosci Biobehav Rev. 2021 Jan; 120:28-47.
    Abstract: Humans show reproducible sex-differences in cognition and psychopathology that may be contributed to by influences of gonadal sex-steroids and/or sex-chromosomes on regional brain development. Gonadal sex-steroids are well known to play a major role in sexual differentiation of the vertebrate brain, but far less is known regarding the role of sex-chromosomes. Our review focuses on this latter issue by bridging together two literatures that have to date been largely disconnected. We first consider "bottom-up" genetic and molecular studies focused on sex-chromosome gene content and regulation. This literature nominates specific sex-chromosome genes that could drive developmental sex-differences by virtue of their sex-biased expression and their functions within the brain. We then consider the complementary "top down" view, from magnetic resonance imaging studies that map sex- and sex chromosome effects on regional brain anatomy, and link these maps to regional gene-expression within the brain. By connecting these top-down and bottom-up approaches, we emphasize the potential role of X-linked genes in driving sex-biased brain development and outline key goals for future work in this field.

    Abstract Summary: Scientists are trying to understand why boys and girls, or men and women, often think differently and have different chances of getting certain brain-related illnesses. They think this might be because of the different hormones that boys and girls have, or because of the different sex-chromosomes they carry (like XX for girls and XY for boys). This study looks at how genes on sex-chromosomes might affect the way the brain grows. The researchers looked at two things: first, they studied genes and molecules to find out which genes on sex-chromosomes could make boys' and girls' brains develop differently. Second, they used special brain scans to see how these genes might change the brain's structure. They found that genes on the X-chromosome might be really important in making the brains of boys and girls different. Understanding this could help us figure out why certain brain illnesses happen and could lead to better treatments for everyone.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease.
    The Journal of clinical endocrinology and metabolism (2021)
    Stanley TL, Fourman LT, Zheng I, McClure CM, Feldpausch MN, Torriani M, Corey KE, Chung RT, Lee H, Kleiner DE, Hadigan CM, Grinspoon SK. Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease. J Clin Endocrinol Metab. 2021 Jan 23; 106(2):e520-e533.
    Abstract: Growth hormone (GH) and IGF-1 help regulate hepatic glucose and lipid metabolism, and reductions in these hormones may contribute to development of nonalcoholic fatty liver disease (NAFLD). To assess relationships between hepatic expression of IGF1 and IGF-binding proteins (IGFBPs) and measures of glycemia and liver disease in adults with NAFLD. Secondarily to assess effects of GH-releasing hormone (GHRH) on circulating IGFBPs. Analysis of data from a randomized clinical trial of GHRH. Two US academic medical centers. Participants were 61 men and women 18 to 70 years of age with HIV-infection, ≥5% hepatic fat fraction, including 39 with RNA-Seq data from liver biopsy. Hepatic steatosis, inflammation, and fibrosis by histopathology and measures of glucose homeostasis. Hepatic IGF1 mRNA was significantly lower in individuals with higher steatosis and NAFLD Activity Score (NAS) and was inversely related to glucose parameters, independent of circulating IGF-1. Among the IGFBPs, IGFBP2 and IGFBP4 were lower and IGFBP6 and IGFBP7 (also known as IGFBP-related protein 1) were higher with increasing steatosis. Hepatic IGFBP6 and IGFBP7 mRNA levels were positively associated with NAS. IGFBP7 mRNA increased with increasing fibrosis. Hepatic IGFBP1 mRNA was inversely associated with glycemia and insulin resistance, with opposite relationships present for IGFBP3 and IGFBP7. GHRH increased circulating IGFBP-1 and IGFBP-3, but decreased IGFBP-2 and IGFBP-6. These data demonstrate novel relationships of IGF-1 and IGFBPs with NAFLD severity and glucose control, with divergent roles seen for different IGFBPs. Moreover, the data provide new information on the complex effects of GHRH on IGFBPs.

    Abstract Summary: Scientists studied how certain hormones in the liver affect blood sugar and fat in the liver in adults with a liver disease that's not caused by drinking alcohol. They looked at how the liver makes a growth factor (IGF-1) and proteins that bind to it. They found that when the liver has more fat and damage, it makes less IGF-1. Some binding proteins were found in higher amounts and some in lower amounts in sicker livers. They also tested a hormone that can release growth hormone to see what it does to these proteins in the blood. They found that this hormone changes the levels of these proteins. This study helps us understand how liver disease and blood sugar control are connected and could lead to new ways to treat liver disease.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Weight-based teasing in youth: Associations with metabolic and inflammatory markers.
    Pediatric obesity (2021)
    Schvey NA, Shank LM, Tanofsky-Kraff M, Ramirez S, Altman DR, Swanson T, Rubin AG, Kelly NR, LeMay-Russell S, Byrne ME, Parker MN, Broadney MM, Brady SM, Yanovski SZ, Yanovski JA. Weight-based teasing in youth: Associations with metabolic and inflammatory markers. Pediatr Obes. 2021 Mar; 16(3):e12729.
    Abstract: Research among adults suggests that weight stigma is associated with worsened cardiometabolic health. However, these relationships have not been examined among youth. Assess associations between weight-based teasing (WBT) and metabolic and inflammatory markers among two samples of youth: (1) a non-treatment-seeking sample and (2) a weight loss treatment-seeking sample with obesity. Weight, height, adiposity, waist circumference and blood pressure were measured. Fasting blood samples were collected for metabolic (triglycerides, glucose, high-density lipoprotein cholesterol) and inflammatory analytes (high-sensitivity C-reactive protein in Study 1 and erythrocyte sedimentation rate in both studies). Youths completed the Perception of Teasing Scale, a measure of WBT. Metabolic and inflammatory indices were compared between those with and without teasing, adjusting for demographics and body composition. Study 1 enrolled 201 non-treatment-seeking youth (M = 13.1y; 54.2% female; 44.8% non-Hispanic White; 32.8% with overweight/obesity); 15.4% reported WBT. Study 2 enrolled 111 treatment-seeking adolescents with obesity (M = 14.0y; 66.7% female; 37.8% non-Hispanic White); 73.0% reported WBT. Adjusting for covariates, WBT was not associated with cardiometabolic risk factors in either study. WBT was not associated with worsened cardiometabolic health. Longitudinal research is needed to elucidate associations between WBT and health in youth.

    Abstract Summary: Scientists wanted to see if being teased about weight affects kids' heart health and blood tests that show inflammation. They looked at two groups of kids: one group wasn't trying to lose weight, and the other group was. They checked the kids' weight, body fat, waist size, blood pressure, and took blood samples. The kids also answered questions about if they were teased for their weight. They compared kids who were teased with those who weren't, considering their age, gender, and body size. In the first group, some kids were teased, and in the second group, many kids were teased. But they found that teasing didn't seem to make kids' heart health or inflammation worse. They think more studies over time are needed to really understand how teasing about weight affects kids' health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The Heritability of Cortical Folding: Evidence from the Human Connectome Project.
    Cerebral cortex (New York, N.Y. : 1991) (2021)
    Schmitt JE, Raznahan A, Liu S, Neale MC. The Heritability of Cortical Folding: Evidence from the Human Connectome Project. Cereb Cortex. 2021 Jan 1; 31(1):702-715.
    Abstract: The mechanisms underlying cortical folding are incompletely understood. Prior studies have suggested that individual differences in sulcal depth are genetically mediated, with deeper and ontologically older sulci more heritable than others. In this study, we examine FreeSurfer-derived estimates of average convexity and mean curvature as proxy measures of cortical folding patterns using a large (N = 1096) genetically informative young adult subsample of the Human Connectome Project. Both measures were significantly heritable near major sulci and primary fissures, where approximately half of individual differences could be attributed to genetic factors. Genetic influences near higher order gyri and sulci were substantially lower and largely nonsignificant. Spatial permutation analysis found that heritability patterns were significantly anticorrelated to maps of evolutionary and neurodevelopmental expansion. We also found strong phenotypic correlations between average convexity, curvature, and several common surface metrics (cortical thickness, surface area, and cortical myelination). However, quantitative genetic models suggest that correlations between these metrics are largely driven by nongenetic factors. These findings not only further our understanding of the neurobiology of gyrification, but have pragmatic implications for the interpretation of heritability maps based on automated surface-based measurements.

    Abstract Summary: This study looked at how our brain's wrinkles, or folds, are formed and if our genes play a role in it. The researchers used a tool called FreeSurfer to study the brain images of over 1,000 young adults. They found that genes do play a part in the formation of major folds in our brain, accounting for about half of the differences seen between individuals. However, genes didn't seem to affect the smaller folds as much. The study also found that the shape and thickness of these folds are mostly influenced by non-genetic factors. This research helps us better understand how our brain develops and the role our genes play in it.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Associations of GlycA and high-sensitivity C-reactive protein with measures of lipolysis in adults with obesity.
    Journal of clinical lipidology (2020)
    Levine JA, Han JM, Wolska A, Wilson SR, Patel TP, Remaley AT, Periwal V, Yanovski JA, Demidowich AP. Associations of GlycA and high-sensitivity C-reactive protein with measures of lipolysis in adults with obesity. J Clin Lipidol. 2020 Sep-Oct; 14(5):667-674.
    Abstract: Obesity-associated inflammation promotes metabolic dysfunction. However, it is unclear how different inflammatory biomarkers predict dysregulation in specific tissues/organs, particularly adipose tissue. The aim of our study was to examine whether GlycA, a nuclear magnetic resonance-measured biomarker of inflammation, is a better predictor of insulin-suppressible lipolysis and other measures of metabolic dysfunction compared with high-sensitivity C-reactive protein (hsCRP) in human obesity. This was a cross-sectional study of 58 nondiabetic adults with obesity (body mass index: 39.8 ± 7.0 kg/m, age 46.5 ± 12.2 years, 67.2% female) who underwent a frequently sampled intravenous glucose tolerance test in the fasted state. Noninsulin-suppressible (l), insulin-suppressible (l), and maximal (l+l) lipolysis rates, as well as insulin sensitivity and acute insulin response to glucose, were calculated by minimal model analysis. Nuclear magnetic resonance was used to measure GlycA. Body composition was determined by dual-energy X-ray absorptiometry. GlycA was strongly correlated with hsCRP (r = +0.46; P < .001). GlycA and hsCRP were positively associated with l, l+l, and fat mass (Ps < .01). In linear regression models accounting for age, race, sex, and fat mass, GlycA remained significantly associated with l and l+l (Ps < .05), whereas hsCRP did not (Ps ≥ .20). Neither GlycA nor hsCRP was associated with l insulin sensitivity, or acute insulin response to glucose. GlycA was associated with elevated lipolysis, independent of adiposity, in adults with obesity. Our findings suggest that GlycA and hsCRP have distinct inflammation-mediated metabolic effects, with GlycA having a greater association with adipose tissue dysfunction. Further studies are warranted to investigate the mechanisms underlying these associations.

    Abstract Summary: Scientists did a study to see if a special sign of swelling in the body, called GlycA, can tell us more about unhealthy changes in fat tissue than another sign called hsCRP. They tested 58 adults who were overweight but didn't have diabetes. They checked how their bodies used sugar and fat, and measured their body fat with a special X-ray. They found that GlycA is linked to how much fat the body breaks down and is a better sign of problems in fat tissue than hsCRP. This is important because it could help doctors understand and treat problems caused by being overweight better.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Integrative structural, functional, and transcriptomic analyses of sex-biased brain organization in humans.
    Proceedings of the National Academy of Sciences of the United States of America (2020)
    Liu S, Seidlitz J, Blumenthal JD, Clasen LS, Raznahan A. Integrative structural, functional, and transcriptomic analyses of sex-biased brain organization in humans. Proc Natl Acad Sci U S A. 2020 Aug 4; 117(31):18788-18798.
    Abstract: Humans display reproducible sex differences in cognition and behavior, which may partly reflect intrinsic sex differences in regional brain organization. However, the consistency, causes and consequences of sex differences in the human brain are poorly characterized and hotly debated. In contrast, recent studies in mice-a major model organism for studying neurobiological sex differences-have established: 1) highly consistent sex biases in regional gray matter volume (GMV) involving the cortex and classical subcortical foci, 2) a preponderance of regional GMV sex differences in brain circuits for social and reproductive behavior, and 3) a spatial coupling between regional GMV sex biases and brain expression of sex chromosome genes in adulthood. Here, we directly test translatability of rodent findings to humans. First, using two independent structural-neuroimaging datasets ( > 2,000), we find that the spatial map of sex-biased GMV in humans is highly reproducible ( > 0.8 within and across cohorts). Relative GMV is female biased in prefrontal and superior parietal cortices, and male biased in ventral occipitotemporal, and distributed subcortical regions. Second, through systematic comparison with functional neuroimaging meta-analyses, we establish a statistically significant concentration of human GMV sex differences within brain regions that subserve face processing. Finally, by imaging-transcriptomic analyses, we show that GMV sex differences in human adulthood are specifically and significantly coupled to regional expression of sex-chromosome (vs. autosomal) genes and enriched for distinct cell-type signatures. These findings establish conserved aspects of sex-biased brain development in humans and mice, and shed light on the consistency, candidate causes, and potential functional corollaries of sex-biased brain anatomy in humans.

    Abstract Summary: Scientists are curious about why boys and girls, or men and women, might think or act differently. They think some of these differences could be because of the way certain parts of the brain are built. While we know a lot about these differences in mice, we're not sure if what we learn from mice also applies to people. In this study, researchers looked at brain scans from over 2,000 people. They found that certain areas of the brain are bigger in women and others are bigger in men, and these areas are pretty much the same in everyone. They also noticed that the parts of the brain that are different between men and women are the same parts that help us recognize faces. Lastly, they discovered that these differences are linked to certain genes that are only found on the sex chromosomes (the ones that make you male or female). This study helps us understand that some of the brain differences between men and women are similar to those in mice, and it gives us clues about why these differences might happen.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Kinetics of Plasma HIV Rebound in the Era of Modern Antiretroviral Therapy.
    The Journal of infectious diseases (2020)
    Sneller MC, Huiting ED, Clarridge KE, Seamon C, Blazkova J, Justement JS, Shi V, Whitehead EJ, Schneck RF, Proschan M, Moir S, Fauci AS, Chun TW. Kinetics of Plasma HIV Rebound in the Era of Modern Antiretroviral Therapy. J Infect Dis. 2020 Oct 13; 222(10):1655-1659.
    Abstract: Historical data regarding time to viral rebound following analytical treatment interruption (ATI) have been used to determine therapeutic efficacy in HIV cure trials; however, such data were collected from studies conducted a decade or more ago and included participants receiving older antiretroviral therapy (ART) regimens with infrequent virologic monitoring. We conducted a study of 22 HIV-infected participants receiving modern ART to determine the kinetics of plasma viral rebound following ATI. Our data suggest that modern ART does not alter kinetics of viral rebound when compared to previous regimens and that immunologic interventions may be necessary to achieve ART-free virologic remission. Clinical Trials Registration ClinicaTrials.gov identifier: NCT03225118.

    Abstract Summary: Scientists did a study to see how quickly HIV comes back in people after they stop taking their modern HIV medicines. They looked at 22 people who stopped their treatment to learn about this. They found that even with newer medicines, the virus comes back just as fast as it did with older ones. This means that just taking medicine might not be enough to keep HIV away forever, and other treatments that help the immune system might be needed. This information is important for doctors and patients to understand how HIV treatments work.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • First-in-human evaluation of [(11)C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain.
    European journal of nuclear medicine and molecular imaging (2020)
    Kim MJ, Lee JH, Juarez Anaya F, Hong J, Miller W, Telu S, Singh P, Cortes MY, Henry K, Tye GL, Frankland MP, Montero Santamaria JA, Liow JS, Zoghbi SS, Fujita M, Pike VW, Innis RB. First-in-human evaluation of [(11)C]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain. Eur J Nucl Med Mol Imaging. 2020 Dec; 47(13):3143-3151.
    Abstract: This study assessed whether the newly developed PET radioligand [C]PS13, which has shown excellent in vivo selectivity in previous animal studies, could be used to quantify constitutive levels of cyclooxygenase-1 (COX-1) in healthy human brain. Brain test-retest scans with concurrent arterial blood samples were obtained in 10 healthy individuals. The one- and unconstrained two-tissue compartment models, as well as the Logan graphical analysis were compared, and test-retest reliability and time-stability of total distribution volume (V) were assessed. Correlation analyses were conducted between brain regional V and COX-1 transcript levels provided in the Allen Human Brain Atlas. In the brain, [C]PS13 showed highest uptake in the hippocampus and occipital cortex. The pericentral cortex also showed relatively higher uptake compared with adjacent neocortices. The two-tissue compartment model showed the best fit in all the brain regions, and the results from the Logan graphical analysis were consistent with those from the two-tissue compartment model. V values showed excellent test-retest variability (range 6.0-8.5%) and good reliability (intraclass correlation coefficient range 0.74-0.87). V values also showed excellent time-stability in all brain regions, confirming that there was no radiometabolite accumulation and that shorter scans were still able to reliably measure V. Significant correlation was observed between V and COX-1 transcript levels (r = 0.82, P = 0.007), indicating that [C]PS13 binding reflects actual COX-1 density in the human brain. These results from the first-in-human evaluation of the ability of [C]PS13 to image COX-1 in the brain justifies extending the study to disease populations with neuroinflammation. NCT03324646 at https://clinicaltrials.gov/ . Registered October 30, 2017. Retrospectively registered.

    Abstract Summary: Scientists did a study to see if a new brain scan tool called [C]PS13 can measure a special protein in the brains of healthy people. This protein, called COX-1, is important because it can tell us about brain health and inflammation. They tested 10 people by scanning their brains twice and taking blood samples. They used different methods to see which one worked best for the scans. They found that the new tool worked really well—it was reliable and could be used for shorter scans too. The amount of COX-1 the scans showed matched up with other scientific data. This means the tool could be good for studying brain diseases in more people in the future.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Editorial: Do Different Neurogenetic Disorders Impart Different Profiles of Psychiatric Risk?
    Journal of the American Academy of Child and Adolescent Psychiatry (2020)
    Raznahan A. Editorial: Do Different Neurogenetic Disorders Impart Different Profiles of Psychiatric Risk? J Am Acad Child Adolesc Psychiatry. 2020 Sep; 59(9):1022-1024.
    Abstract: The best-studied examples of genetically defined developmental disorders, such as Down syndrome (trisomy 21) and velocardiofacial syndrome (del22q11), have been known since before the genomic era and were initially recognized as distinct syndromes based on their own unique constellation of dysmorphic and multisystem features. For example, Down syndrome is characterized by the co-occurrence of several dysmorphic features, including a flattened facial profile, slanted palpebral fissures, protruding tongue, and transverse palmar crease, with accompanying hypotonia, cardiac issues, and developmental delay. None of these features in isolation is specific to Down syndrome, and all features are not present in all cases, but the co-occurrence of multiple features from this set is a specific and sensitive marker for the presence of trisomy 21. To what extent might similar principles apply to the patterning of cognitive and behavioral features across different neurogenetic syndromes?

    Abstract Summary: Scientists have been studying certain health conditions that people are born with, like Down syndrome and velocardiofacial syndrome, for a long time. These conditions are special because they have a set of signs that make them easy to recognize. For example, people with Down syndrome might have certain facial features, weak muscles, heart problems, and learn things more slowly. Not everyone with Down syndrome has all these signs, but seeing several of them together usually means the person has the condition. The study is trying to figure out if we can use the same ideas to understand how people with these conditions think and behave. This is important because it can help us know more about these conditions and how to support people who have them.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity.
    The Journal of clinical investigation (2020)
    O'Mara AE, Johnson JW, Linderman JD, Brychta RJ, McGehee S, Fletcher LA, Fink YA, Kapuria D, Cassimatis TM, Kelsey N, Cero C, Sater ZA, Piccinini F, Baskin AS, Leitner BP, Cai H, Millo CM, Dieckmann W, Walter M, Javitt NB, Rotman Y, Walter PJ, Ader M, Ber. Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. J Clin Invest. 2020 May 1; 130(5):2209-2219.
    Abstract: BACKGROUNDMirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity.METHODSWe treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test.RESULTSChronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion.CONCLUSIONThese findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease.TRIAL REGISTRATIONClinicaltrials.gov NCT03049462.FUNDINGThis work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014).

    Abstract Summary: Scientists did a study to see if a medicine called mirabegron, which is usually used for bladder problems, could also help with obesity-related health issues. They gave 14 healthy women this medicine for 4 weeks and watched how it affected their body's fat and sugar processing. They found that the medicine made a special kind of fat in the body work harder, which helps burn calories. The women's bodies also got better at handling sugar and they had more good fats in their blood. This is important because it means this medicine might help people who have problems with obesity and diabetes. The study was registered and funded by some big research groups.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A local group differences test for subject-level multivariate density neuroimaging outcomes.
    Biostatistics (Oxford, England) (2021)
    Dworkin JD, Linn KA, Solomon AJ, Satterthwaite TD, Raznahan A, Bakshi R, Shinohara RT. A local group differences test for subject-level multivariate density neuroimaging outcomes. Biostatistics. 2021 Jul 17; 22(3):646-661.
    Abstract: A great deal of neuroimaging research focuses on voxel-wise analysis or segmentation of damaged tissue, yet many diseases are characterized by diffuse or non-regional neuropathology. In simple cases, these processes can be quantified using summary statistics of voxel intensities. However, the manifestation of a disease process in imaging data is often unknown, or appears as a complex and nonlinear relationship between the voxel intensities on various modalities. When the relevant pattern is unknown, summary statistics are often unable to capture differences between disease groups, and their use may encourage post hoc searches for the optimal summary measure. In this study, we introduce the multi-modal density testing (MMDT) framework for the naive discovery of group differences in voxel intensity profiles. MMDT operationalizes multi-modal magnetic resonance imaging (MRI) data as multivariate subject-level densities of voxel intensities and utilizes kernel density estimation to develop a local two-sample test for individual points within the density space. Through simulations, we show that this method controls type I error and recovers relevant differences when applied to a specified point. Additionally, we demonstrate the ability to maintain power while controlling the family-wise error rate and false discovery rate when applying the test over a grid of points within the density space. Finally, we apply this method to a study of subjects with either multiple sclerosis (MS) or conditions that tend to mimic MS on MRI, and find significant differences between the two groups in their voxel intensity profiles within the thalamus.

    Abstract Summary: Scientists are trying to understand brain diseases by looking at brain scans in a new way. Usually, they look at each tiny part of the brain scan (called a voxel) one by one, or they try to find damaged areas. But some brain diseases don't just affect one spot; they change the brain in ways that are hard to spot. The scientists made a new method called multi-modal density testing (MMDT) to find these hard-to-see changes. They use this method to compare different brain scans and find the differences that might be caused by a disease. They tested their method to make sure it works well and doesn't make mistakes. Then they used it to study people with a brain disease called multiple sclerosis (MS) and people with other conditions that look like MS on scans. They found that their method could tell the difference between the two groups by looking at a part of the brain called the thalamus. This new way of looking at brain scans could help doctors understand and diagnose brain diseases better.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Altered Sex Chromosome Dosage Induces Coordinated Shifts in Cortical Anatomy and Anatomical Covariance.
    Cerebral cortex (New York, N.Y. : 1991) (2020)
    Xenophontos A, Seidlitz J, Liu S, Clasen LS, Blumenthal JD, Giedd JN, Alexander-Bloch A, Raznahan A. Altered Sex Chromosome Dosage Induces Coordinated Shifts in Cortical Anatomy and Anatomical Covariance. Cereb Cortex. 2020 Apr 14; 30(4):2215-2228.
    Abstract: Sex chromosome dosage (SCD) variation increases risk for neuropsychiatric impairment, which may reflect direct SCD effects on brain organization. Here, we 1) map cumulative X- and Y-chromosome dosage effects on regional cortical thickness (CT) and investigate potential functional implications of these effects using Neurosynth, 2) test if this map is organized by patterns of CT covariance that are evident in health, and 3) characterize SCD effects on CT covariance itself. We modeled SCD effects on CT and CT covariance for 308 equally sized regions of the cortical sheet using structural neuroimaging data from 301 individuals with varying numbers of sex chromosomes (169 euploid, 132 aneuploid). Mounting SCD increased CT in the rostral frontal cortex and decreased CT in the lateral temporal cortex, bilaterally. Regions targeted by SCD were associated with social functioning, language processing, and comprehension. Cortical regions with a similar degree of SCD-sensitivity showed heightened CT covariance in health. Finally, greater SCD also increased covariance among regions similarly affected by SCD. Our study both 1) develops novel methods for comparing typical and disease-related structural covariance networks in the brain and 2) uses these techniques to resolve and identify organizing principles for SCD effects on regional cortical anatomy and anatomical covariance.

    Abstract Summary: Scientists did a study to see how having different numbers of sex chromosomes (like X and Y) can affect the brain and possibly lead to mental health issues. They looked at brain scans from 301 people, some with the usual number of sex chromosomes and some with extra. They found that having more sex chromosomes can make certain parts of the brain's outer layer thicker or thinner. These changes were in areas that help with social skills, talking, and understanding things. They also noticed that parts of the brain that were changed in similar ways by extra sex chromosomes worked more closely together. This research helps us understand how the number of sex chromosomes a person has can change their brain and might be used to figure out why some people have certain mental health problems.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Colchicine's effects on lipoprotein particle concentrations in adults with metabolic syndrome: A secondary analysis of a randomized controlled trial.
    Journal of clinical lipidology (2019)
    Demidowich AP, Wolska A, Wilson SR, Levine JA, Sorokin AV, Brady SM, Remaley AT, Yanovski JA. Colchicine's effects on lipoprotein particle concentrations in adults with metabolic syndrome: A secondary analysis of a randomized controlled trial. J Clin Lipidol. 2019 Nov-Dec; 13(6):1016-1022.e2.
    Abstract: Colchicine has received renewed interest for its potential beneficial effects in secondary prevention of cardiovascular disease. This was presumed to be primarily because of its anti-inflammatory effects; however, limited data exist regarding colchicine's impact on other cardiovascular risk factors. The aim of this study was to examine if colchicine's anti-inflammatory actions would lead to reduced circulating concentrations of oxidized low-density lipoprotein (oxLDL) in metabolically unhealthy individuals. We also examined if colchicine would improve concentrations of other atherogenic lipoprotein subfractions. This is a secondary analysis of a double-blind, randomized, placebo-controlled pilot study in which 40 adults with metabolic syndrome were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. Blood samples were collected in the fasted state. OxLDL was measured using enzyme-linked immunosorbent assay. Nuclear magnetic resonance spectroscopy was used to measure other lipoprotein particle subfraction concentrations. Compared with placebo, colchicine reduced markers of inflammation, including C-reactive protein, erythrocyte sedimentation rate, and GlycA (P < .01). Concentrations of oxLDL (P = .019) and small LDL (P = .022) appeared significantly increased in the colchicine arm. Colchicine had no significant effect on other lipoprotein subfractions or lipoprotein particle sizes (all P > .05). Although colchicine may have benefit in secondary prevention of cardiovascular disease in at-risk individuals, we found no evidence that these effects are because of improvements in circulating atherogenic lipoprotein particle concentrations. Further studies are needed to confirm whether colchicine increases circulating oxLDL and small LDL levels in adults with metabolic syndrome. If true, additional research is warranted to elucidate the mechanisms underlying these associations.

    Abstract Summary: Scientists wanted to see if a drug called colchicine could help prevent heart disease by reducing harmful substances in the blood. They tested this on 40 adults with a condition called metabolic syndrome. The adults were given either colchicine or a placebo (a pill with no medicine) twice a day for 3 months. The results showed that while colchicine did reduce inflammation (which can cause heart disease), it didn't lower the levels of harmful substances in the blood. In fact, some harmful substances seemed to increase. More research is needed to understand why this happened and what it means for using colchicine to prevent heart disease.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial.
    The lancet. HIV (2019)
    Stanley TL, Fourman LT, Feldpausch MN, Purdy J, Zheng I, Pan CS, Aepfelbacher J, Buckless C, Tsao A, Kellogg A, Branch K, Lee H, Liu CY, Corey KE, Chung RT, Torriani M, Kleiner DE, Hadigan CM, Grinspoon SK. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, multicentre trial. Lancet HIV. 2019 Dec; 6(12):e821-e830.
    Abstract: Non-alcoholic fatty liver disease (NAFLD) is a substantial cause of comorbidity in people with HIV and there are no proven pharmacological treatments for the disease in this population. We assessed the effects of tesamorelin on liver fat and histology in people with HIV and NAFLD. This randomised, double-blind, multicentre study with identical placebo as a comparator was done in a hospital and a medical research centre in the USA. People with HIV infection and a hepatic fat fraction (HFF) of 5% or more by proton magnetic resonance spectroscopy were eligible. Participants were randomly assigned (1:1) to receive either tesamorelin 2 mg once daily or placebo once daily for 12 months, followed by a 6-month open-label phase during which all participants received tesamorelin 2 mg daily. The randomisation list was prepared by the study statistician using a permuted block algorithm within each stratum with randomly varying block sizes. The primary endpoint was change in HFF between baseline and 12 months. The primary safety endpoint was glucose. Analysis was by intention to treat using all available data. This trial is registered with ClinicalTrials.gov, number NCT02196831. 61 patients were enrolled between Aug 20, 2015, and Jan 16, 2019, of whom 30 received tesamorelin and 30 received placebo. Patients receiving tesamorelin had a greater reduction of HFF than did patients receiving placebo, with an absolute effect size of -4·1% (95% CI -7·6 to -0·7, p=0·018), corresponding to a -37% (95% CI -67 to -7, p=0·016) relative reduction from baseline. After 12 months, 35% of individuals receiving tesamorelin and 4% receiving placebo had a HFF of less than 5% (p=0·0069). Changes in fasting glucose and glycated haemoglobin were not different between groups at 12 months. Individuals in the tesamorelin group experienced more localised injection site complaints than those in the placebo group, though none were judged to be serious. Tesamorelin might be beneficial in people with HIV and NAFLD. Further studies are needed to determine the long-term effects of tesamorelin on liver histology. National Institutes of Health and National Institute of Allergy and Infectious Diseases.

    Abstract Summary: Doctors wanted to see if a medicine called tesamorelin could help people with HIV who also have a liver problem where there's too much fat in the liver, but it's not because of drinking alcohol. They tested the medicine by giving some people tesamorelin and others a fake medicine without them knowing which one they got. They checked the fat in their livers at the start and after 12 months. The people who got tesamorelin had a lot less liver fat after 12 months. The medicine didn't cause big problems with their blood sugar. The doctors think tesamorelin could be good for people with HIV and this liver problem, but they need to do more research to be sure.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • "Spatial heterogeneity of environmental risk in randomized prevention trials: consequences and modeling".
    BMC medical research methodology (2019)
    Guindo A, Sagara I, Ouedraogo B, Sallah K, Assadou MH, Healy S, Duffy P, Doumbo OK, Dicko A, Giorgi R, Gaudart J. "Spatial heterogeneity of environmental risk in randomized prevention trials: consequences and modeling". BMC Med Res Methodol. 2019 Jul 15; 19(1):149.
    Abstract: In the context of environmentally influenced communicable diseases, proximity to environmental sources results in spatial heterogeneity of risk, which is sometimes difficult to measure in the field. Most prevention trials use randomization to achieve comparability between groups, thus failing to account for heterogeneity. This study aimed to determine under what conditions spatial heterogeneity biases the results of randomized prevention trials, and to compare different approaches to modeling this heterogeneity. Using the example of a malaria prevention trial, simulations were performed to quantify the impact of spatial heterogeneity and to compare different models. Simulated scenarios combined variation in baseline risk, a continuous protective factor (age), a non-related factor (sex), and a binary protective factor (preventive treatment). Simulated spatial heterogeneity scenarios combined variation in breeding site density and effect, location, and population density. The performances of the following five statistical models were assessed: a non-spatial Cox Proportional Hazard (Cox-PH) model and four models accounting for spatial heterogeneity-i.e., a Data-Generating Model, a Generalized Additive Model (GAM), and two Stochastic Partial Differential Equation (SPDE) models, one modeling survival time and the other the number of events. Using a Bayesian approach, we estimated the SPDE models with an Integrated Nested Laplace Approximation algorithm. For each factor (age, sex, treatment), model performances were assessed by quantifying parameter estimation biases, mean square errors, confidence interval coverage rates (CRs), and significance rates. The four models were applied to data from a malaria transmission blocking vaccine candidate. The level of baseline risk did not affect our estimates. However, with a high breeding site density and a strong breeding site effect, the Cox-PH and GAM models underestimated the age and treatment effects (but not the sex effect) with a low CR. When population density was low, the Cox-SPDE model slightly overestimated the effect of related factors (age, treatment). The two SPDE models corrected the impact of spatial heterogeneity, thus providing the best estimates. Our results show that when spatial heterogeneity is important but not measured, randomization alone cannot achieve comparability between groups. In such cases, prevention trials should model spatial heterogeneity with an adapted method. The dataset used for the application example was extracted from Vaccine Trial #NCT02334462 ( ClinicalTrials.gov registry).

    Abstract Summary: This study looked at how location can affect the results of health studies, using a malaria prevention trial as an example. The researchers created different scenarios to see how things like age, gender, and prevention treatment might change the results. They also looked at how the number of breeding sites for mosquitoes and the effect of these sites could change the results. They found that when location is important but not measured, it can make the results less accurate. This means that health studies should take location into account to get the best results. This could help make prevention treatments more effective.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Quantification of the Capacity for Cold-Induced Thermogenesis in Young Men With and Without Obesity.
    The Journal of clinical endocrinology and metabolism (2019)
    Brychta RJ, Huang S, Wang J, Leitner BP, Hattenbach JD, Bell SL, Fletcher LA, Perron Wood R, Idelson CR, Duckworth CJ, McGehee S, Courville AB, Bernstein SB, Reitman ML, Cypess AM, Chen KY. Quantification of the Capacity for Cold-Induced Thermogenesis in Young Men With and Without Obesity. J Clin Endocrinol Metab. 2019 Oct 1; 104(10):4865-4878.
    Abstract: Cold exposure increases energy expenditure (EE) and could have a role in combating obesity. To understand this potential, we determined the capacity for cold-induced thermogenesis (CIT), the EE increase above the basal metabolic rate at the individualized coldest tolerable temperature before overt shivering. During a 13-day inpatient protocol, we quantitated the EE of 12 lean men and 9 men with obesity at various randomly ordered ambient temperatures in a room calorimeter. Subjects underwent brown fat imaging after exposure to their coldest tolerable temperature. CIT capacity was 300 ± 218 kcal/d (mean ± SD) or 17 ± 11% in lean men and 125 ± 146 kcal/d or 6 ± 7% in men with obesity (P = 0.01). The temperature below which EE increased, lower critical temperature (Tlc), was warmer in lean men than men with obesity (22.9 ± 1.2 vs 21.1 ± 1.7°C, P = 0.03), but both had similar skin temperature (Tskin) changes and coldest tolerable temperatures. Whereas lean subjects had higher brown fat activity, skeletal muscle activity increased synchronously with CIT beginning at the Tlc in both groups, indicating that muscle is recruited for CIT in parallel with brown fat, not sequentially after nonshivering thermogenesis is maximal. Despite greater insulation from fat, men with obesity had a narrower range of tolerable cool temperatures available for increasing EE and less capacity for CIT than lean men, likely as a result of greater basal heat production and similar perception to Tskin cooling. Further study of the reduced CIT capacity in men with obesity may inform treatment opportunities for obesity.

    Abstract Summary: Scientists did a study to see if being cold can help people burn more calories, which might help with weight loss. They had 21 men, some lean and some with obesity, stay in a special room where they could change the temperature and measure how many calories the men burned. They also checked their brown fat, which helps burn calories when it's cold. They found that skinny men could burn more calories in the cold than men with obesity. The study suggests that being cold might not help men with obesity as much as it does for lean men to burn extra calories. This information could help find new ways to help people with obesity.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection.
    The Journal of infectious diseases (2019)
    Dropulic LK, Oestreich MC, Pietz HL, Laing KJ, Hunsberger S, Lumbard K, Garabedian D, Turk SP, Chen A, Hornung RL, Seshadri C, Smith MT, Hosken NA, Phogat S, Chang LJ, Koelle DM, Wang K, Cohen JI. A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection. J Infect Dis. 2019 Aug 9; 220(6):990-1000.
    Abstract: Herpes simplex virus 2 (HSV2) causes genital herpes in >400 million persons worldwide. We conducted a randomized, double-blinded, placebo-controlled trial of a replication-defective HSV2 vaccine, HSV529. Twenty adults were enrolled in each of 3 serogroups of individuals: those negative for both HSV1 and HSV2 (HSV1-/HSV2-), those positive or negative for HSV1 and positive for HSV2 (HSV1±/HSV2+), and those positive for HSV1 and negative for HSV2 (HSV1+/HSV2-). Sixty participants received vaccine or placebo at 0, 1, and 6 months. The primary end point was the frequency of solicited local and systemic reactions to vaccination. Eighty-nine percent of vaccinees experienced mild-to-moderate solicited injection site reactions, compared with 47% of placebo recipients (95% confidence interval [CI], 12.9%-67.6%; P = .006). Sixty-four percent of vaccinees experienced systemic reactions, compared with 53% of placebo recipients (95% CI, -17.9% to 40.2%; P = .44). Seventy-eight percent of HSV1-/HSV2- vaccine recipients had a ≥4-fold increase in neutralizing antibody titer after 3 doses of vaccine, whereas none of the participants in the other serogroups had such responses. HSV2-specific CD4+ T-cell responses were detected in 36%, 46%, and 27% of HSV1-/HSV2-, HSV1±/HSV2+, and HSV1+/HSV2- participants, respectively, 1 month after the third dose of vaccine, and CD8+ T-cell responses were detected in 14%, 8%, and 18% of participants, respectively. HSV529 vaccine was safe and elicited neutralizing antibody and modest CD4+ T-cell responses in HSV-seronegative vaccinees. NCT01915212.

    Abstract Summary: Scientists did a study to test a new vaccine called HSV529 for a virus that causes sores called genital herpes, which affects more than 400 million people around the world. They had 60 people join the study and gave them either the vaccine or a pretend shot (placebo) three times over six months. They wanted to see if people had any reactions to the shot and if their bodies started to fight the virus better. Most people who got the real vaccine had some pain or discomfort where they got the shot, but it wasn't too bad. Some people also felt a little sick, but it was similar to those who got the pretend shot. The vaccine worked best in people who never had any kind of herpes virus before; their bodies made more defenses against the virus. The vaccine seemed safe and helped the body start to fight the virus, especially in people who didn't have herpes before. This is good news because it might help protect people from getting genital herpes in the future.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Large-scale analyses of the relationship between sex, age and intelligence quotient heterogeneity and cortical morphometry in autism spectrum disorder.
    Molecular psychiatry (2020)
    Bedford SA, Park MTM, Devenyi GA, Tullo S, Germann J, Patel R, Anagnostou E, Baron-Cohen S, Bullmore ET, Chura LR, Craig MC, Ecker C, Floris DL, Holt RJ, Lenroot R, Lerch JP, Lombardo MV, Murphy DGM, Raznahan A, Ruigrok ANV, Smith E, Spencer MD, Suckling. Large-scale analyses of the relationship between sex, age and intelligence quotient heterogeneity and cortical morphometry in autism spectrum disorder. Mol Psychiatry. 2020 Mar; 25(3):614-628.
    Abstract: Significant heterogeneity across aetiologies, neurobiology and clinical phenotypes have been observed in individuals with autism spectrum disorder (ASD). Neuroimaging-based neuroanatomical studies of ASD have often reported inconsistent findings which may, in part, be attributable to an insufficient understanding of the relationship between factors influencing clinical heterogeneity and their relationship to brain anatomy. To this end, we performed a large-scale examination of cortical morphometry in ASD, with a specific focus on the impact of three potential sources of heterogeneity: sex, age and full-scale intelligence (FIQ). To examine these potentially subtle relationships, we amassed a large multi-site dataset that was carefully quality controlled (yielding a final sample of 1327 from the initial dataset of 3145 magnetic resonance images; 491 individuals with ASD). Using a meta-analytic technique to account for inter-site differences, we identified greater cortical thickness in individuals with ASD relative to controls, in regions previously implicated in ASD, including the superior temporal gyrus and inferior frontal sulcus. Greater cortical thickness was observed in sex specific regions; further, cortical thickness differences were observed to be greater in younger individuals and in those with lower FIQ, and to be related to overall clinical severity. This work serves as an important step towards parsing factors that influence neuroanatomical heterogeneity in ASD and is a potential step towards establishing individual-specific biomarkers.

    Abstract Summary: Scientists studied the brains of people with autism to understand why they are so different from one another. They looked at brain scans from lots of people, including 491 with autism, and paid special attention to how being a boy or girl, age, and intelligence might make a difference. They found that some parts of the brain were thicker in people with autism, especially in certain areas and in boys, younger people, and those who weren't as good at certain thinking tasks. This research helps us know more about autism and might lead to ways to tell what kind of help each person with autism needs by looking at their brain.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Associations of the melanocortin 3 receptor C17A + G241A haplotype with body composition and inflammation in African-American adults.
    Annals of human genetics (2019)
    Demidowich AP, Parikh VJ, Dedhia N, Branham RE, Madi SA, Marwitz SE, Roberson RB, Uhlman AJ, Levi NJ, Mi SJ, Jun JY, Broadney MM, Brady SM, Yanovski JA. Associations of the melanocortin 3 receptor C17A + G241A haplotype with body composition and inflammation in African-American adults. Ann Hum Genet. 2019 Sep; 83(5):355-360.
    Abstract: The MC3R haplotype C17A + G241A, which encodes a partially inactivated receptor, has high prevalence in individuals of predominately African ancestry. In pediatric cohorts, homozygosity for this common variant has been associated with obesity, reduced lean mass, and greater fasting insulin. However, metabolic and body composition measures have not been well studied in adults with this haplotype. A convenience sample of 237 healthy African-American adult volunteers was studied. TaqMan assays were used to genotype MC3R variants. Labs were drawn in the morning in the fasted state. Body composition data was obtained via dual-energy X-ray absorptiometry. An analysis of covariance was used to examine the associations of genotype with metabolic and body composition measures controlling for age and sex. Individuals homozygous for the MC3R C17A + G241A haplotype had significantly greater body mass index, fat mass, fat mass percentage, and C-reactive protein, with reduced lean mass percentage as compared to heterozygous and wild-type participants (all ps < 0.05); fasting insulin was marginally nonsignificant between groups (p = 0.053). After adjusting for fat mass, laboratory differences no longer remained significant. Homozygosity for MC3R C17A + G241A is associated with increased adiposity in African-American adults. Further studies are needed to elucidate the mechanisms behind these associations.

    Abstract Summary: Scientists studied a special gene pattern called MC3R haplotype C17A + G241A, which is found a lot in people with African roots. This gene pattern can make a person's body work a bit differently. They looked at 237 healthy African-American adults to see how this gene pattern affects their body fat, muscles, and other health stuff like blood sugar and inflammation. They used special tests to figure out who had this gene pattern and to measure body fat and muscle. They found that people with two copies of this gene pattern usually had more body fat, a higher body mass index (which is a number that tells if you have the right amount of body fat), and more signs of inflammation. They didn't have as much muscle compared to people with only one copy or none at all. But when they considered how much fat a person had, the differences in blood tests weren't important anymore. This study helps us understand that this gene pattern can make African-American adults more likely to have more body fat, and it's important to learn more about why this happens.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The Dynamic Associations Between Cortical Thickness and General Intelligence are Genetically Mediated.
    Cerebral cortex (New York, N.Y. : 1991) (2019)
    Schmitt JE, Raznahan A, Clasen LS, Wallace GL, Pritikin JN, Lee NR, Giedd JN, Neale MC. The Dynamic Associations Between Cortical Thickness and General Intelligence are Genetically Mediated. Cereb Cortex. 2019 Dec 17; 29(11):4743-4752.
    Abstract: The neural substrates of intelligence represent a fundamental but largely uncharted topic in human developmental neuroscience. Prior neuroimaging studies have identified modest but highly dynamic associations between intelligence and cortical thickness (CT) in childhood and adolescence. In a separate thread of research, quantitative genetic studies have repeatedly demonstrated that most measures of intelligence are highly heritable, as are many brain regions associated with intelligence. In the current study, we integrate these 2 streams of prior work by examining the genetic contributions to CT-intelligence relationships using a genetically informative longitudinal sample of 813 typically developing youth, imaged with high-resolution MRI and assessed with Wechsler Intelligence Scales (IQ). In addition to replicating the phenotypic association between multimodal association cortex and language centers with IQ, we find that CT-IQ covariance is nearly entirely genetically mediated. Moreover, shared genetic factors drive the rapidly evolving landscape of CT-IQ relationships in the developing brain.

    Abstract Summary: Scientists are trying to understand how the brain and intelligence are connected. They've noticed that the thickness of certain parts of the brain's outer layer is linked to how smart kids and teenagers are. They also know that intelligence and the brain's structure can be strongly influenced by genes. In this study, researchers looked at brain scans and intelligence test scores from 813 kids over time. They found that the connection between brain thickness and intelligence is mostly because of genes. This means that as kids grow, the changes in their brain that relate to how smart they are, are largely due to the genes they inherit from their parents. This research helps us understand why some people are smarter in different ways and how our brains develop as we grow up.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Carriage of Supernumerary Sex Chromosomes Decreases the Volume and Alters the Shape of Limbic Structures.
    eNeuro (2018)
    Nadig A, Reardon PK, Seidlitz J, McDermott CL, Blumenthal JD, Clasen LS, Lalonde F, Lerch JP, Chakravarty MM, Raznahan A. Carriage of Supernumerary Sex Chromosomes Decreases the Volume and Alters the Shape of Limbic Structures. eNeuro. 2018 Sep-Oct; 5(5):.
    Abstract: Sex chromosome aneuploidy (SCA) increases risk for several psychiatric disorders associated with the limbic system, including mood and autism spectrum disorders. Thus, SCA offers a genetics-first model for understanding the biological basis of psychopathology. Additionally, the sex-biased prevalence of many psychiatric disorders could potentially reflect sex chromosome dosage effects on brain development. To clarify how limbic anatomy varies across sex and sex chromosome complement, we characterized amygdala and hippocampus structure in a uniquely large sample of patients carrying supernumerary sex chromosomes ( = 132) and typically developing controls ( = 166). After adjustment for sex-differences in brain size, karyotypically normal males (XY) and females (XX) did not differ in volume or shape of either structure. In contrast, all SCAs were associated with lowered amygdala volume relative to gonadally-matched controls. This effect was robust to three different methods for total brain volume adjustment, including an allometric analysis that derived normative scaling rules for these structures in a separate, typically developing population ( = 79). Hippocampal volume was insensitive to SCA after adjustment for total brain volume. However, surface-based analysis revealed that SCA, regardless of specific karyotype, was consistently associated with a spatially specific pattern of shape change in both amygdala and hippocampus. In particular, SCA was accompanied by contraction around the basomedial nucleus of the amygdala and an area crossing the hippocampal tail. These results demonstrate the power of SCA as a model to understand how copy number variation can precipitate changes in brain systems relevant to psychiatric disease.

    Abstract Summary: Scientists did a study to learn how having extra sex chromosomes can affect the brain, especially parts that are linked to emotions and certain mental health issues. They looked at the brains of 132 people with extra sex chromosomes and 166 people with the usual number of sex chromosomes. They found that people with extra sex chromosomes had smaller amygdalas, a part of the brain important for emotions, compared to people with the usual number of sex chromosomes. The size of another part of the brain called the hippocampus didn't change much, but its shape was different in people with extra sex chromosomes. This study helps us understand how differences in our chromosomes can change our brains and possibly lead to mental health problems.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Longitudinally Mapping Childhood Socioeconomic Status Associations with Cortical and Subcortical Morphology.
    The Journal of neuroscience : the official journal of the Society for Neuroscience (2019)
    McDermott CL, Seidlitz J, Nadig A, Liu S, Clasen LS, Blumenthal JD, Reardon PK, Lalonde F, Greenstein D, Patel R, Chakravarty MM, Lerch JP, Raznahan A. Longitudinally Mapping Childhood Socioeconomic Status Associations with Cortical and Subcortical Morphology. J Neurosci. 2019 Feb 20; 39(8):1365-1373.
    Abstract: Childhood socioeconomic status (SES) impacts cognitive development and mental health, but its association with human structural brain development is not yet well characterized. Here, we analyzed 1243 longitudinally acquired structural MRI scans from 623 youth (299 female/324 male) to investigate the relation between SES and cortical and subcortical morphology between ages 5 and 25 years. We found positive associations between SES and total volumes of the brain, cortical sheet, and four separate subcortical structures. These associations were stable between ages 5 and 25. Surface-based shape analysis revealed that higher SES is associated with areal expansion of lateral prefrontal, anterior cingulate, lateral temporal, and superior parietal cortices and ventrolateral thalamic, and medial amygdalo-hippocampal subregions. Meta-analyses of functional imaging data indicate that cortical correlates of SES are centered on brain systems subserving sensorimotor functions, language, memory, and emotional processing. We further show that anatomical variation within a subset of these cortical regions partially mediates the positive association between SES and IQ. Finally, we identify neuroanatomical correlates of SES that exist above and beyond accompanying variation in IQ. Although SES is clearly a complex construct that likely relates to development through diverse, nondeterministic processes, our findings elucidate potential neuroanatomical mediators of the association between SES and cognitive outcomes. Childhood socioeconomic status (SES) has been associated with developmental disparities in mental health, cognitive ability, and academic achievement, but efforts to understand underlying SES-brain relationships are ongoing. Here, we leverage a unique developmental neuroimaging dataset to longitudinally map the associations between SES and regional brain anatomy at high spatiotemporal resolution. We find widespread associations between SES and global cortical and subcortical volumes and surface area and localize these correlations to a distributed set of cortical, thalamic, and amygdalo-hippocampal subregions. Anatomical variation within a subset of these regions partially mediates the positive relationship between SES and IQ. Our findings help to localize cortical and subcortical systems that represent candidate biological substrates for the known relationships between SES and cognition.

    Abstract Summary: Scientists studied how the money and resources a family has (called socioeconomic status, or SES) can affect the way kids' brains grow. They looked at brain scans from 623 kids, ages 5 to 25, to see if there were any patterns. They found that kids from families with more resources had bigger brain volumes in certain areas, and these areas stayed pretty much the same as they grew up. These parts of the brain are important for things like moving, talking, remembering, and feelings. The study also found that the size and shape of some brain areas could explain why kids with more resources tend to have higher IQs. This research helps us understand that where a kid comes from can influence their brain development and smarts, but it's not the only thing that matters.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome.
    Journal of neurodevelopmental disorders (2018)
    Joseph L, Farmer C, Chlebowski C, Henry L, Fish A, Mankiw C, Xenophontos A, Clasen L, Sauls B, Seidlitz J, Blumenthal J, Torres E, Thurm A, Raznahan A. Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome. J Neurodev Disord. 2018 Oct 22; 10(1):30.
    Abstract: XYY syndrome is a sex chromosome aneuploidy that occurs in ~ 1/850 male births and is associated with increased risk for neurodevelopmental difficulties. However, the profile of neurodevelopmental impairments, including symptoms of autism spectrum disorder (ASD) in XYY remains poorly understood. This gap in knowledge has persisted in part due to lack of access to patient cohorts with dense and homogeneous phenotypic data. We evaluated a single-center cohort of 64 individuals with XYY aged 5-25 years, using a standardized battery of cognitive and behavioral assessments spanning developmental milestones, IQ, adaptive behavior, academic achievement, behavioral problems, and gold-standard diagnostic instruments for ASD. Our goals were to (i) detail the neurodevelopmental profile of XYY with a focus on ASD diagnostic rates and symptom profiles, (ii) screen phenotypes for potential ascertainment bias effects by contrasting pre- vs. postnatally diagnosed XYY subgroups, and (iii) define major modules of phenotypic variation using graph-theoretical analysis. Although there was marked inter-individual variability, the average profile was characterized by some degree of developmental delay, and decreased IQ and adaptive behavior. Impairments were most pronounced for language and socio-communicative functioning. The rate of ASD was 14%, and these individuals exhibited autism symptom profiles resembling those observed in ASD without XYY. Most neurodevelopmental dimensions showed milder impairment among pre- vs. postnatally diagnosed individuals, with clinically meaningful differences in verbal IQ. Feature network analysis revealed three reliably separable modules comprising (i) cognition and academic achievement, (ii) broad domain psychopathology and adaptive behavior, and (iii) ASD-related features. By adding granularity to our understanding of neurodevelopmental difficulties in XYY, these findings assist targeted clinical assessment of newly identified cases, motivate greater provision of specialized multidisciplinary support, and inform future efforts to integrate behavioral phenotypes in XYY with neurobiology. ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls."

    Abstract Summary: XYY syndrome is a condition that affects about 1 in 850 boys and can cause learning and behavior problems. In a study of 64 boys and young men with XYY syndrome, researchers found that many had delays in development, lower IQ scores, and trouble with social communication. About 14% also had autism. Boys diagnosed with XYY syndrome before birth had less severe problems than those diagnosed after birth. The study helps doctors better understand XYY syndrome and how to help those with the condition. It also shows the need for more support and research into how XYY syndrome affects the brain.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • All-night functional magnetic resonance imaging sleep studies.
    Journal of neuroscience methods (2019)
    Moehlman TM, de Zwart JA, Chappel-Farley MG, Liu X, McClain IB, Chang C, Mandelkow H, Özbay PS, Johnson NL, Bieber RE, Fernandez KA, King KA, Zalewski CK, Brewer CC, van Gelderen P, Duyn JH, Picchioni D. All-night functional magnetic resonance imaging sleep studies. J Neurosci Methods. 2019 Mar 15; 316:83-98.
    Abstract: Previous functional magnetic resonance imaging (fMRI) sleep studies have been hampered by the difficulty of obtaining extended amounts of sleep in the sleep-adverse environment of the scanner and often have resorted to manipulations such as sleep depriving subjects before scanning. These manipulations limit the generalizability of the results. The current study is a methodological validation of procedures aimed at obtaining all-night fMRI data in sleeping subjects with minimal exposure to experimentally induced sleep deprivation. Specifically, subjects slept in the scanner on two consecutive nights, allowing the first night to serve as an adaptation night. Sleep scoring results from simultaneously acquired electroencephalography data on Night 2 indicate that subjects (n = 12) reached the full spectrum of sleep stages including slow-wave (M = 52.1 min, SD = 26.5 min) and rapid eye movement (REM, M = 45.2 min, SD = 27.9 min) sleep and exhibited a mean of 2.1 (SD = 1.1) nonREM-REM sleep cycles. It was found that by diligently applying fundamental principles and methodologies of sleep and neuroimaging science, performing all-night fMRI sleep studies is feasible. However, because the two nights of the study were performed consecutively, some sleep deprivation from Night 1 as a cause of the Night 2 results is likely, so consideration should be given to replicating the current study with a washout period. It is envisioned that other laboratories can adopt the core features of this protocol to obtain similar results.

    Abstract Summary: Scientists did a study to see if they could use a special brain scan called fMRI to watch people's brains while they sleep all night without making them stay awake first. They had 12 people sleep in the scanner for two nights. The first night was just for getting used to it, and the second night they checked to see what kind of sleep the people got. They found out that the people went through all the normal stages of sleep and had about two cycles of deep sleep and dream sleep. The study shows that it's possible to do this kind of brain scan while people sleep naturally, but they think they should try it again without having the two nights right after each other. This could help other scientists learn more about sleep by using the same method.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Pediatric Brain Development in Down Syndrome: A Field in Its Infancy.
    Journal of the International Neuropsychological Society : JINS (2018)
    Hamner T, Udhnani MD, Osipowicz KZ, Lee NR. Pediatric Brain Development in Down Syndrome: A Field in Its Infancy. J Int Neuropsychol Soc. 2018 Oct; 24(9):966-976.
    Abstract: As surprisingly little is known about the developing brain studied in vivo in youth with Down syndrome (DS), the current review summarizes the small DS pediatric structural neuroimaging literature and begins to contextualize existing research within a developmental framework. A systematic review of the literature was completed, effect sizes from published studies were reviewed, and results are presented with respect to the DS cognitive behavioral phenotype and typical brain development. The majority of DS structural neuroimaging studies describe gross differences in brain morphometry and do not use advanced neuroimaging methods to provide nuanced descriptions of the brain. There is evidence for smaller total brain volume (TBV), total gray matter (GM) and white matter, cortical lobar, hippocampal, and cerebellar volumes. When reductions in TBV are accounted for, specific reductions are noted in subregions of the frontal lobe, temporal lobe, cerebellum, and hippocampus. A review of cortical lobar effect sizes reveals mostly large effect sizes from early childhood through adolescence. However, deviance is smaller in adolescence. Despite these smaller effects, frontal GM continues to be largely deviant in adolescence. An examination of age-frontal GM relations using effect sizes from published studies and data from Lee et al. (2016) reveals that while there is a strong inverse relationship between age and frontal GM volume in controls across childhood and adolescence, this is not observed in DS. Further developmentally focused research, ideally using longitudinal neuroimaging, is needed to elucidate the nature of the DS neuroanatomic phenotype during childhood and adolescence. (JINS, 2018, 24, 966-976).

    Abstract Summary: Scientists are trying to learn more about how the brains of kids with Down syndrome (DS) grow and change. They looked at lots of studies that took pictures of the brain and measured how big different parts were. They found that kids with DS usually have smaller brains, including the parts that help with thinking and moving. The studies showed that as kids with DS get older, their brains don't grow as much as other kids' brains, especially in the front part that helps with planning and decision-making. The researchers say we need more studies over time to really understand how the brains of kids with DS develop as they grow up. This information is important because it can help us find better ways to support kids with DS in their learning and everyday life.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study.
    JCI insight (2018)
    Blau JE, Bauman V, Conway EM, Piaggi P, Walter MF, Wright EC, Bernstein S, Courville AB, Collins MT, Rother KI, Taylor SI. Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study. JCI Insight. 2018 Apr 19; 3(8):.
    Abstract: Sodium glucose cotransporter-2 (SGLT2) inhibitors are the most recently approved class of drugs for type 2 diabetes and provide both glycemic efficacy and cardiovascular risk reduction. A number of safety issues have been identified, including treatment-emergent bone fractures. To understand the overall clinical profile, these safety issues must be balanced against an attractive efficacy profile. Our study was designed to investigate pathophysiological mechanisms mediating treatment-emergent adverse effects on bone health. We conducted a single-blind randomized crossover study in hospitalized healthy adults (n = 25) receiving either canagliflozin (300 mg/d) or placebo for 5 days. The primary end-point was the drug-induced change in AUC for plasma intact fibroblast growth factor 23 (FGF23) immunoactivity between 24 and 72 hours. Canagliflozin administration increased placebo-subtracted mean levels of serum phosphorus (+16%), plasma FGF23 (+20%), and plasma parathyroid hormone (PTH) (+25%), while decreasing the level of 1,25-dihydroxyvitamin D (-10%). There was substantial interindividual variation in the magnitude of each of these pharmacodynamic responses. The increase in plasma FGF23 was correlated with the increase in serum phosphorus, and the decrease in plasma 1,25-dihydroxyvitamin D was correlated with the increase in plasma FGF23. Canagliflozin induced a prompt increase in serum phosphorus, which triggers downstream changes in FGF23, 1,25-dihydroxyvitamin D, and PTH, with potential to exert adverse effects on bone health. These pharmacodynamic data provide a foundation for future research to elucidate pathophysiological mechanisms of adverse effects on bone health, with the objective of devising therapeutic strategies to mitigate the drug-associated fracture risk. ClinicalTrial.gov (NCT02404870). Supported by the Intramural Program of NIDDK.

    Abstract Summary: Scientists did a study to learn how a new diabetes medicine, called canagliflozin, might affect bones. They gave the medicine or a fake pill (placebo) to 25 healthy adults to see what would happen. They found that the medicine made certain things in the blood go up, like phosphorus and a hormone called FGF23, and made a vitamin D level go down. These changes could possibly make bones weaker. Everyone's body reacted a bit differently. This research helps us understand how diabetes medicine can affect bones, so we can try to keep bones healthy while treating diabetes.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Cytokine-Mediated Systemic Adverse Drug Reactions in a Drug-Drug Interaction Study of Dolutegravir With Once-Weekly Isoniazid and Rifapentine.
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (2018)
    Brooks KM, George JM, Pau AK, Rupert A, Mehaffy C, De P, Dobos KM, Kellogg A, McLaughlin M, McManus M, Alfaro RM, Hadigan C, Kovacs JA, Kumar P. Cytokine-Mediated Systemic Adverse Drug Reactions in a Drug-Drug Interaction Study of Dolutegravir With Once-Weekly Isoniazid and Rifapentine. Clin Infect Dis. 2018 Jul 2; 67(2):193-201.
    Abstract: Once-weekly isoniazid and rifapentine for 3 months is a treatment option in persons with human immunodeficiency virus and latent tuberculosis infection. This study aimed to examine pharmacokinetic drug-drug interactions between this regimen and dolutegravir, a first-line antiretroviral medication. This was a single-center, open-label, fixed-sequence, drug-drug interaction study in healthy volunteers. Subjects received oral dolutegravir 50 mg once daily alone (days 1-4) and concomitantly with once-weekly isoniazid 900 mg, rifapentine 900 mg, and pyridoxine 50 mg (days 5-19). Dolutegravir concentrations were measured on days 4, 14, and 19, and rifapentine, 25-desacetyl-rifapentine, and isoniazid concentrations were measured on day 19. Cytokines and antidrug antibodies to isoniazid and rifapentine were examined at select time points. The study was terminated following the development of flu-like syndrome and elevated aminotransferase levels in 2 of 4 subjects after the third isoniazid-rifapentine dose. Markedly elevated levels of interferon-γ, CXCL10, C-reactive protein, and other cytokines were temporally associated with symptoms. Antidrug antibodies were infrequently detected. Dolutegravir area under the curve (AUC) was decreased by 46% (90% confidence interval, 27-110%; P = .13) on day 14. Rifapentine and 25-desacetyl rifapentine levels on day 19 were comparable to reference data, whereas isoniazid AUCs were approximately 67%-92% higher in the subjects who developed toxicities. The combined use of dolutegravir with once-weekly isoniazid-rifapentine resulted in unexpected and serious toxicities that were mediated by endogenous cytokine release. Additional investigations are necessary to examine the safety and efficacy of coadministering these medications. NCT02771249.

    Abstract Summary: Scientists did a study to see if two medicines for TB (tuberculosis) would work okay with a medicine for HIV. They gave healthy people the HIV medicine every day and the TB medicines once a week. They checked the amount of medicine in the blood and looked for any bad reactions. But they had to stop the study early because two people got sick with flu-like symptoms and their liver tests were not good. They found that the HIV medicine didn't stay in the body as well when taken with the TB medicines. They also saw that the body's defense system reacted strongly. They think more research is needed to make sure these medicines can be used together safely.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study.
    The Lancet. Infectious diseases (2018)
    Beigel JH, Voell J, Kumar P, Raviprakash K, Wu H, Jiao JA, Sullivan E, Luke T, Davey RT Jr. Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus antibody produced from transchromosomic cattle: a phase 1 randomised, double-blind, single-dose-escalation study. Lancet Infect Dis. 2018 Apr; 18(4):410-418.
    Abstract: Middle East respiratory syndrome (MERS) is a severe respiratory illness with an overall mortality of 35%. There is no licensed or proven treatment. Passive immunotherapy approaches are being developed to prevent and treat several human medical conditions where alternative therapeutic options are absent. We report the safety of a fully human polyclonal IgG antibody (SAB-301) produced from the hyperimmune plasma of transchromosomic cattle immunised with a MERS coronavirus vaccine. We did a phase 1 double-blind, placebo-controlled, single-dose escalation trial at the National Institutes of Health Clinical Center. We recruited healthy participants aged 18-60 years who had normal laboratory parameters at enrolment, a body-mass index of 19-32 kg/m, and a creatinine clearance of 70 mL/min or more, and who did not have any chronic medical problems that required daily oral medications, a positive rheumatoid factor (≥15 IU/mL), IgA deficiency (<7 mg/dL), or history of allergy to intravenous immunoglobulin or human blood products. Participants were randomly assigned by a computer-generated table, made by a masked pharmacist, to one of six cohorts (containing between three and ten participants each). Cohorts 1 and 2 had three participants, randomly assigned 2:1 to receive active drug SAB-301 versus normal saline placebo; cohorts 3 and 4 had six participants randomised 2:1; and cohorts 5 and 6 had ten participants, randomised 4:1. Participants received 1 mg/kg, 2·5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, or 50 mg/kg of SAB-301, or equivalent volume placebo (saline control), on day 0, and were followed up by clinical, laboratory, and pharmacokinetic assessments on days 1, 3, 7, 21, 42, and 90. The primary outcome was safety, and immunogenicity was a secondary outcome. We analysed the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02788188. Between June 2, 2016, and Jan 4, 2017, we screened 43 participants, of whom 38 were eligible and randomly assigned to receive SAB-301 (n=28) or placebo (n=10). 97 adverse events were reported: 64 adverse events occurred in 23 (82%) of 28 participants receiving SAB-301 (mean 2·3 adverse events per participant). 33 adverse events occurred in all ten participants receiving placebo (mean 3·3 adverse events per participant). The most common adverse events were headache (n=6 [21%] in participants who received SAB-301 and n=2 [20%] in those receiving placebo), albuminuria (n=5 [18%] vs n=2 [20%]), myalgia (n=3 [11%] vs n=1 [10%]), increased creatine kinase (n=3 [11%] vs 1 [10%]), and common cold (n=3 [11%] vs n=2 [20%]). There was one serious adverse event (hospital admission for suicide attempt) in one participant who received 50 mg/kg of SAB-301. The area under the concentration-time curve (AUC) in the 50 mg/kg dose (27 498 μg × days per mL) is comparable to the AUC that was associated with efficacy in a preclinical model. Single infusions of SAB-301 up to 50 mg/kg appear to be safe and well tolerated in healthy participants. Human immunoglobulin derived from transchromosomic cattle could offer a new platform technology to produce fully human polyclonal IgG antibodies for other medical conditions. National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Biomedical Advanced Research and Development Authority.

    Abstract Summary: Scientists are trying to find a way to help people with a serious lung sickness called MERS, which doesn't have a cure yet. They tested a new medicine made from the blood of special cows that were given a MERS vaccine. This medicine is called SAB-301. They wanted to make sure it was safe for people to use. Healthy adults were given different amounts of the medicine or a saltwater shot that didn't do anything (placebo). The researchers watched the people to see if they had any bad reactions and to see how their bodies handled the medicine. They found that the medicine seemed safe because the people who got it didn't have more problems than those who got the saltwater shot. This study is important because it shows that medicines from special cows might be a new way to help people with different sicknesses.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Differential Influence of the Antiretroviral Pharmacokinetic Enhancers Ritonavir and Cobicistat on Intestinal P-Glycoprotein Transport and the Pharmacokinetic/Pharmacodynamic Disposition of Dabigatran.
    Antimicrobial agents and chemotherapy (2017)
    Kumar P, Gordon LA, Brooks KM, George JM, Kellogg A, McManus M, Alfaro RM, Nghiem K, Lozier J, Hadigan C, Penzak SR. Differential Influence of the Antiretroviral Pharmacokinetic Enhancers Ritonavir and Cobicistat on Intestinal P-Glycoprotein Transport and the Pharmacokinetic/Pharmacodynamic Disposition of Dabigatran. Antimicrob Agents Chemother. 2017 Nov; 61(11):.
    Abstract: Dabigatran etexilate (DE) is a P-glycoprotein (P-gp) probe substrate, and its active anticoagulant moiety, dabigatran, is a substrate of the multidrug and toxin extrusion protein-1 (MATE-1) transporter. The antiretroviral pharmacokinetic enhancers, ritonavir and cobicistat, inhibit both these transporters. Healthy volunteers received single doses of DE at 150 mg alone, followed by ritonavir at 100 mg or cobicistat at 150 mg daily for 2 weeks. DE was then given 2 h before ritonavir or cobicistat. One week later, DE was given simultaneously with ritonavir or cobicistat. No significant increases in dabigatran pharmacokinetic (PK) exposure or thrombin time (TT) measures were observed with the simultaneous administration of ritonavir. Separated administration of ritonavir resulted in a mean decrease in dabigatran PK exposure of 29% (90% confidence interval [CI], 18 to 40%) but did not significantly change TT measures. However, cobicistat increased dabigatran PK exposure (area under the concentration-versus-time curve from time zero to infinity and maximum plasma concentration) by 127% each (90% CI, 81 to 173% and 59 to 196%, respectively) and increased TT measures (33% for the area-under-the-effect curve from time zero to 24 h [90% CI, 22 to 44%] and 51% for TT at 24 h [90% CI, 22 to 78%]) when given simultaneously with dabigatran. Similar increases were observed when cobicistat was administered separately by 2 h from the administration of dabigatran. In all comparisons, no significant increase in the dabigatran elimination half-life was observed. Therefore, it is likely safe to coadminister ritonavir with DE, while there is a potential need for reduced dosing and prudent clinical monitoring with the coadministration of cobicistat due to the greater net inhibition of intestinal P-gp transport and increased bioavailability. (This study has been registered at ClinicalTrials.gov under identifier NCT01896622.).

    Abstract Summary: This study looked at how two different drugs, ritonavir and cobicistat, interact with another drug called dabigatran etexilate (DE). DE is a medicine that helps prevent blood clots. The researchers gave healthy volunteers DE alone, then with ritonavir or cobicistat. They found that ritonavir didn't really change how DE worked. But when cobicistat was given with DE, it made DE work much stronger. This means that if a patient is taking both DE and cobicistat, they might need a smaller dose of DE. This is important because it helps doctors know how to safely give these drugs together.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic.
    Vaccine (2017)
    Coller BG, Blue J, Das R, Dubey S, Finelli L, Gupta S, Helmond F, Grant-Klein RJ, Liu K, Simon J, Troth S, VanRheenen S, Waterbury J, Wivel A, Wolf J, Heppner DG, Kemp T, Nichols R, Monath TP. Clinical development of a recombinant Ebola vaccine in the midst of an unprecedented epidemic. Vaccine. 2017 Aug 16; 35(35 Pt A):4465-4469.
    Abstract: The 2014-2016 Ebola outbreak caused over 28,000 cases and 11,000 deaths. Merck & Co. Inc., Kenilworth, NJ USA and NewLink Genetics are working with private and public partners to develop and license an Ebola vaccine that was evaluated extensively during the outbreak. The vaccine referred to as V920 is a recombinant vesicular stomatitis virus (rVSV) in which the VSV-G envelope glycoprotein (GP) is completely replaced by the Zaire ebolavirus GP (rVSVΔG-ZEBOV-GP). Eight Phase I and four Phase II/III clinical trials enrolling approximately 17,000 subjects were conducted in parallel to the outbreak to assess the safety, immunogenicity, and/or efficacy of V920. Immunogenicity data demonstrate that anti-GP antibodies are generally detectable by ELISA by 14days postvaccination with up to 100% seroconversion observed by 28days post dose. In addition, the results of a ring vaccination trial conducted by the WHO and their partners in Guinea suggest robust vaccine efficacy within 10days of receipt of a single dose of vaccine. The vaccine is generally well-tolerated when administered to healthy, non-pregnant adults. The development of this vaccine candidate in the context of this unprecedented epidemic has involved the close cooperation of large number of international partners and highlights what we as a public health community can accomplish when working together towards a common goal. Study identification: V920-001 to V920-012. CLINICALTRIALS.GOV identifiers: NCT02269423; NCT02280408; NCT02374385; NCT02314923; NCT02287480; NCT02283099; NCT02296983; NCT02344407; NCT02378753; NCT02503202.

    Abstract Summary: Scientists and companies worked together to make a new vaccine to fight Ebola, a very bad sickness that made lots of people sick and caused many deaths between 2014 and 2016. They made a special shot called V920 that uses a part of the virus to help the body learn to fight Ebola. They tested the shot on about 17,000 people to make sure it was safe and that it worked. The tests showed that after getting the shot, most people's bodies started to fight the virus within 14 days, and by 28 days, everyone's body was ready to fight Ebola. They also found out that the shot worked really well and fast, in just 10 days, to protect people from getting sick. The shot was safe for adults who weren't pregnant. This work shows how when lots of people and groups work together, they can do big things to keep us healthy.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Hormonal responses to non-nutritive sweeteners in water and diet soda.
    Nutrition & metabolism (2016)
    Sylvetsky AC, Brown RJ, Blau JE, Walter M, Rother KI. Hormonal responses to non-nutritive sweeteners in water and diet soda. Nutr Metab (Lond). 2016; 13:71.
    Abstract: Non-nutritive sweeteners (NNS), especially in form of diet soda, have been linked to metabolic derangements (e.g. obesity and diabetes) in epidemiologic studies. We aimed to test acute metabolic effects of NNS in isolation (water or seltzer) and in diet sodas. We conducted a four-period, cross-over study at the National Institutes of Health Clinical Center (Bethesda, Maryland). Thirty healthy adults consumed 355 mL water with 0 mg, 68 mg, 170 mg, and 250 mg sucralose, and 31 individuals consumed 355 mL caffeine-free Diet Rite Cola™, Diet Mountain Dew™ (18 mg sucralose, 18 mg acesulfame-potassium, 57 mg aspartame), and seltzer water with NNS (68 mg sucralose and 41 mg acesulfame-potassium, equivalent to Diet Rite Cola™) in randomized order, prior to oral glucose tolerance tests. Blood samples were collected serially for 130 min. Measures included GLP-1, GIP, glucose, insulin, C-peptide, glucose absorption, gastric emptying, and subjective hunger and satiety ratings. Diet sodas augmented active GLP-1 (Diet Rite Cola™ vs. seltzer water, AUC,  = 0.039; Diet Mountain Dew™ vs. seltzer water, AUC,  = 0.07), but gastric emptying and satiety were unaffected. Insulin concentrations were nominally higher following all NNS conditions without altering glycemia. Sucralose alone (at any concentration) did not affect metabolic outcomes. Diet sodas but not NNS in water augmented GLP-1 responses to oral glucose. Whether the trends toward higher insulin concentrations after NNS are of clinical importance remains to be determined. Our findings emphasize the need to test metabolic effects of NNS after chronic consumption. The data for this manuscript were gathered from clinical trial #NCT01200940.

    Abstract Summary: Scientists wanted to see if sweeteners that don't have calories, like the ones in diet sodas, change how our bodies handle sugar. They had 61 healthy people drink different mixtures with these sweeteners and then checked their blood many times. They found that drinking diet sodas made a certain helpful gut hormone go up, but it didn't really change how full people felt or how their stomachs emptied. Even though the sweeteners made insulin levels go up a bit, they didn't change blood sugar levels. Just adding sweeteners to water didn't do anything. This study tells us that we need to look more at how these sweeteners affect us over a long time.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Bilateral Adrenal Hyperplasia as a Possible Mechanism for Hyperandrogenism in Women With Polycystic Ovary Syndrome.
    The Journal of clinical endocrinology and metabolism (2016)
    Gourgari E, Lodish M, Keil M, Sinaii N, Turkbey E, Lyssikatos C, Nesterova M, de la Luz Sierra M, Xekouki P, Khurana D, Ten S, Dobs A, Stratakis CA. Bilateral Adrenal Hyperplasia as a Possible Mechanism for Hyperandrogenism in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2016 Sep; 101(9):3353-60.
    Abstract: Androgen excess may be adrenal and/or ovarian in origin; we hypothesized that a subgroup of patients with polycystic ovarian syndrome (PCOS) may have some degree of abnormal adrenocortical function. The objective of the study was to evaluate the pituitary adrenal axis with an oral low- and high-dose dexamethasone-suppression test (Liddle's test) in women with PCOS. This was a case-control study. The study was conducted at the National Institutes of Health Clinical Center. A total of 38 women with PCOS and 20 healthy volunteers (HV) aged 16-29 years participated in the study. Urinary free cortisol (UFC) and 17-hydroxysteroids (17OHS) before and after low- and high-dose dexamethasone and assessment of adrenal volume by computed tomography scan were measured. Twenty-four-hour urinary 17OHS and UFC were measured during day 1 to day 6 of the Liddle's test. Baseline UFC levels were not different between PCOS and HVs; on the day after the completion of high-dose dexamethasone administration (d 6), UFC was higher in the PCOS group (2.0 ± 0.7 μg/m(2)·d) than the HV group (1.5 ± 0.5) (P = .038). On day 5, 17OHS and UFC were negatively correlated with adrenal volumes (left side, rp = -0.47, P = .009, and rp = -0.61, P < .001, respectively). PCOS patients above the 75th percentile for UFC and/or 17OHS after high-dose dexamethasone (n = 15) had a significantly smaller total adrenal volume (6.9 ± 1.9 cm(3) vs 9.2 ± 1.8 cm(3), P = .003) when compared with the remaining PCOS patients (n = 22), but they did not have worse insulin resistance or hyperandrogenism. In a subset of young women with PCOS, we detected a pattern of glucocorticoid secretion that mimicked that of patients with micronodular adrenocortical hyperplasia: they had smaller adrenal volumes and higher steroid hormone secretion after dexamethasone compared with the group of PCOS with appropriate response to dexamethasone.

    Abstract Summary: Doctors wanted to learn if some girls with a condition called PCOS, which can make it hard for them to have babies and cause other health problems, might also have issues with their adrenal glands, which are small organs that sit on top of the kidneys and help control stress and energy. They tested 38 girls with PCOS and 20 healthy girls by giving them a medicine called dexamethasone to see how their bodies reacted. They found that some girls with PCOS had different reactions to the medicine, with higher levels of stress hormones and smaller adrenal glands compared to other girls with PCOS and healthy girls. This could mean that these girls have a special type of adrenal gland problem that's similar to another disease. Understanding this could help doctors find better ways to help girls with PCOS in the future.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Nonverbal and paraverbal behavior in (simulated) medical visits related to genomics and weight: a role for emotion and race.
    Journal of behavioral medicine (2016)
    Persky S, Ferrer RA, Klein WM. Nonverbal and paraverbal behavior in (simulated) medical visits related to genomics and weight: a role for emotion and race. J Behav Med. 2016 Oct; 39(5):804-14.
    Abstract: It is crucial to examine patient reactions to genomics-informed approaches to weight management within a clinical context, and understand the influence of patient characteristics (here, emotion and race). Examining nonverbal reactions offers a window into patients' implicit cognitive, attitudinal and affective processes related to clinical encounters. We simulated a weight management clinical interaction with a virtual reality-based physician, and experimentally manipulated patient emotional state (anger/fear) and whether the physician made genomic or personal behavior attributions for weight. Participants were 190 overweight females who racially identified as either Black or White. Participants made less visual contact when receiving genomic information in the anger condition, and Black participants exhibited lowered voice pitch when receiving genomic information. Black participants also increased their interpersonal distance when receiving genomic information in the anger condition. By studying non-conscious nonverbal behavior, we can better understand the nuances of these interactions. Trial registry clinicaltrials.gov NCT01888913.

    Abstract Summary: Scientists did a study to see how people feel about using information about their genes to help them manage their weight. They used a pretend doctor in a virtual reality game to talk to 190 women who were a little heavier than they should be. These women were either Black or White. The researchers changed how the women felt (angry or scared) and what the doctor said about why they might be overweight (because of their genes or their own actions). They found that when the women were angry, they didn't look at the doctor as much if the doctor talked about genes. Black women spoke in a lower voice and liked to keep more space between themselves and the doctor when genes were mentioned, especially if they were angry. This study helps us understand that how doctors talk about weight and genes can make a difference in how comfortable people feel. It's important because it shows that doctors need to think about how they talk to patients about weight, especially when talking about genes.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Genomic Information may Inhibit Weight-Related Behavior Change Inclinations Among Individuals in a Fear State.
    Annals of behavioral medicine : a publication of the Society of Behavioral Medicine (2016)
    Persky S, Ferrer RA, Klein WM. Genomic Information may Inhibit Weight-Related Behavior Change Inclinations Among Individuals in a Fear State. Ann Behav Med. 2016 Jun; 50(3):452-9.
    Abstract: As evidence mounts regarding associations between genetics and body weight, it is essential to understand how to communicate this information, and factors like emotion that could moderate the effectiveness of messages. We assessed influences of emotion on reactions to weight-related genomic information in a virtual clinical setting. An online representative US sample of overweight women was randomized to receive an emotion induction (anger, fear, or neutral) paired with information about genomic or behavioral influences on weight in an interaction with a virtual doctor. Receiving genomic information led to reduced attributions of lifestyle causes for weight and behavioral intentions, but only among individuals in a fear state. The current study is among the first to reinforce the concern that discussing genomic underpinnings of overweight could undercut health behavior, and highlights the importance of identifying factors like emotion that influence interpretation of genomic information. Clinicaltrials.gov NCT01888913.

    Abstract Summary: Scientists did a study to see how feelings can change the way overweight women think about the reasons for their body weight when they learn about how genes might play a role. They had women talk to a computer doctor and made them feel angry, scared, or calm before telling them about how genes or habits can affect weight. They found that when the women were scared, they were less likely to think that their lifestyle caused their weight and were less likely to want to change their habits if they were told it was because of their genes. This study shows that when doctors talk about weight and genes, they need to be careful because it could make people less likely to try to live healthier. This is important for everyone to know because it can help us understand how to better talk about weight and health.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of Interrupting Children's Sedentary Behaviors With Activity on Metabolic Function: A Randomized Trial.
    The Journal of clinical endocrinology and metabolism (2015)
    Belcher BR, Berrigan D, Papachristopoulou A, Brady SM, Bernstein SB, Brychta RJ, Hattenbach JD, Tigner IL Jr, Courville AB, Drinkard BE, Smith KP, Rosing DR, Wolters PL, Chen KY, Yanovski JA. Effects of Interrupting Children's Sedentary Behaviors With Activity on Metabolic Function: A Randomized Trial. J Clin Endocrinol Metab. 2015 Oct; 100(10):3735-43.
    Abstract: Limited data suggest that interrupting sedentary behaviors with activity improves metabolic parameters in adults. We tested whether interrupting sitting with short, moderate-intensity walking bouts improved glucose tolerance in children. Participants underwent two experimental conditions in random order on different days: continuous sitting for 3 hours or sitting interrupted by walking (3 min of moderate-intensity walking every 30 min). Insulin, C-peptide, glucose, and free fatty acids were measured every 30 minutes for 3 hours during an oral glucose tolerance test. Area under the curve (AUC) was calculated from hormone and substrate measurements. Children were given a buffet meal after each condition. The study was conducted at the National Institutes of Health Hatfield Clinical Research Center. Twenty-eight normal-weight 7-11 year olds participated. Patterns of substrate/hormone secretion and AUC, as well as energy intake, were examined by experimental condition. Interrupting sitting resulted in a 32% lower insulin AUC (P < .001), 17% lower C-peptide AUC (P < .001), and 7% lower glucose AUC (P = .018) vs continuous sitting. Mixed model results indicated that insulin (P = .036) and free fatty acid concentrations (P = .009) were significantly lower in the interrupted vs the continuous sitting condition. Lunchtime buffet meal energy intake did not significantly differ between the conditions (975 ± 387 vs 963 ± 309 kcal; P = .85). Interrupting sedentary time with brief moderate-intensity walking improved short-term metabolic function in non-overweight children without increasing subsequent energy intake. These findings suggest that interrupting sedentary behavior may be a promising prevention strategy for reducing cardiometabolic risk in children.

    Abstract Summary: Scientists wanted to see if getting up and walking around for a little bit could help kids' bodies handle sugar better. They had a group of kids either sit for 3 hours straight or take short walking breaks every half hour. They checked the kids' blood for sugar and other things that show how well their bodies are working. They found that when kids took walking breaks, their bodies were better at managing sugar and other important stuff. The kids didn't eat more after walking, which is good. This means that taking short walks can help kids stay healthy without making them want to eat more.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A Recombinant Vesicular Stomatitis Virus Ebola Vaccine.
    The New England journal of medicine (2017)
    Regules JA, Beigel JH, Paolino KM, Voell J, Castellano AR, Hu Z, Muñoz P, Moon JE, Ruck RC, Bennett JW, Twomey PS, Gutiérrez RL, Remich SA, Hack HR, Wisniewski ML, Josleyn MD, Kwilas SA, Van Deusen N, Mbaya OT, Zhou Y, Stanley DA, Jing W, Smith KS, Shi. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine. N Engl J Med. 2017 Jan 26; 376(4):330-341.
    Abstract: The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD. We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed. The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months. This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSV∆G-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408 .).

    Abstract Summary: Scientists tested a new vaccine to stop Ebola, a very bad sickness that made lots of people sick and caused many to die. They did two studies with 78 grown-ups to see if the vaccine is safe and works well. The grown-ups got different amounts of the vaccine or a pretend shot. They checked for any bad reactions and to see if the body started fighting the virus. Most people just had a sore arm, felt tired, or had a headache. The vaccine made their bodies start fighting Ebola, especially when they got a bigger dose or a second shot. The study says this vaccine looks promising and they should keep checking if it works well to protect people from getting sick with Ebola.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome.
    Genes, brain, and behavior (2014)
    Lenroot RK, Blumenthal JD, Wallace GL, Clasen LS, Lee NR, Giedd JN. A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome. Genes Brain Behav. 2014 Nov; 13(8):841-9.
    Abstract: Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under-recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age- and sex-matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi-structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention-deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population-based studies of Trisomy X and also found in our sample.

    Abstract Summary: Scientists did a study to see if girls with an extra X chromosome, a condition called Trisomy X, have different brain shapes that might explain why they often have trouble with things like talking and paying attention. They looked at brain scans and did tests on 35 girls with Trisomy X and compared them to 70 girls without the extra chromosome. They found that the brains of girls with Trisomy X were a bit smaller and had some parts that were thicker or thinner than usual. These girls also had more anxiety and attention problems. This research helps us understand why girls with Trisomy X might have these challenges.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • The retinoic acid receptor-α modulators ATRA and Ro415253 reciprocally regulate human IL-5+ Th2 cell proliferation and cytokine expression.
    Clinical and molecular allergy : CMA (2013)
    Wansley DL, Yin Y, Prussin C. The retinoic acid receptor-α modulators ATRA and Ro415253 reciprocally regulate human IL-5+ Th2 cell proliferation and cytokine expression. Clin Mol Allergy. 2013 Dec 6; 11(1):4.
    Abstract: Th2 cytokine responses are enhanced by all trans retinoic acid (ATRA), the bioavailable form of vitamin A. Retinoic acid receptor alpha (RARα) is the high affinity receptor for ATRA that mediates these pro-Th2 effects. We have previously characterized two major human Th2 subpopulations: IL-5- Th2 (IL-5-, IL-4+, IL-13+) and IL-5+ Th2 cells (IL-5+, IL-4+, IL-13+), which represent less and more highly differentiated Th2 cells, respectively. We hypothesized that the pro-Th2 effects of ATRA may differentially affect these Th2 subpopulations. Specific cytokine producing Th2 subpopulations were identified using intracellular cytokine staining. Proliferation was measured using the Cell Trace Violet proliferation tracking dye. Apoptotic cells were identified using either annexin-V or active caspase 3 staining. Th2 gene expression was measured using quantitative polymerase chain reaction. ATRA increased the output of Th2 cells from house dust mite allergen (HDM) specific short-term cell lines, and this enhancement was limited to the IL-5+ Th2 subpopulation. Conversely, the RARα antagonist Ro415253 decreased Th2 cell output from these cultures, and this effect was again limited to the IL-5+ Th2 subpopulation. ATRA and Ro415253 respectively augmented and inhibited Th2 cell proliferation, and this affect was more pronounced for the IL-5+ vs. IL-5- Th2 subpopulation. ATRA and Ro415253 respectively augmented and inhibited the expression of IL5 in a significant manner, which was not found for IL4 or IL13. We report that the reciprocal regulation of Th2 cytokine expression and proliferation by RARα modulators are largely limited to modulation of IL-5 gene expression and to proliferation of the highly differentiated IL-5+ Th2 subpopulation. These results suggest that RARα antagonism is a potential means to therapeutically target allergic inflammation. Clinicaltrials.gov identifier: NCT01212016.

    Abstract Summary: Scientists did a study to see how a vitamin A-related substance affects certain immune cells that are involved in allergies. They looked at two types of these immune cells, one more advanced than the other. They found that the vitamin A substance made the more advanced cells grow more and act stronger, especially in making a specific signal that can cause allergies. They also tested a blocker for the vitamin A substance and saw that it made these advanced cells grow less and become weaker. This research suggests that blocking the vitamin A substance might help treat allergies.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

The Ohio State University
  • Effects of Adjunctive Brexpiprazole on Individual Depressive Symptoms and Functioning in Patients With Major Depressive Disorder and Anxious Distress: Post Hoc Analysis of Three Placebo-Controlled Studies.
    Journal of clinical psychopharmacology (2024)
    McIntyre RS, Bubolic S, Zhang Z, MacKenzie EM, Therrien F, Miguelez M, Boucher M. Effects of Adjunctive Brexpiprazole on Individual Depressive Symptoms and Functioning in Patients With Major Depressive Disorder and Anxious Distress: Post Hoc Analysis of Three Placebo-Controlled Studies. J Clin Psychopharmacol. 2024 Mar-Apr 01; 44(2):133-140.
    Abstract: Anxiety symptoms in major depressive disorder (MDD) are frequent, and they decrease response to antidepressant treatment (ADT), and affect patient functioning. This post hoc analysis examined the efficacy of adjunctive brexpiprazole on individual depressive symptoms and functioning in patients with MDD with anxious distress. Data were included from three 6-week, randomized, double-blind, placebo-controlled studies of adjunctive brexpiprazole in patients with MDD and inadequate response to ADTs (ClinicalTrials.gov identifiers: NCT01360645, NCT01360632, NCT02196506). Patients were stratified using proxy criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, anxious distress. Changes in Montgomery-Åsberg Depression Rating Scale item scores and Sheehan Disability Scale mean score from baseline to week 6 were determined for ADT + brexpiprazole (2 and 2-3 mg) versus ADT + placebo. At baseline, 450 of 746 patients (60.3%, 2 mg analysis) and 670 of 1162 patients (57.7%, 2-3 mg analysis) had anxious distress. In patients with anxious distress, ADT + brexpiprazole 2 mg or 2 to 3 mg showed greater improvements than ADT + placebo (P < 0.05) on the Montgomery-Åsberg Depression Rating Scale items of apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, lassitude, inability to feel, and pessimistic thoughts (Cohen d effect sizes, 0.18-0.44), and on Sheehan Disability Scale mean score (effect sizes, 0.21-0.23). Adjunctive brexpiprazole is efficacious in reducing core depressive symptoms, sleep, and appetite, as well as improving functioning, in patients with MDD and anxious distress who have inadequate response to ADTs.

    Abstract Summary: Scientists did a study to see if a medicine called brexpiprazole could help people who feel very sad and worried all the time, a condition known as major depressive disorder with anxious distress. These people didn't feel better after taking usual depression medicines. The study included 746 patients, and they were given either brexpiprazole or a pretend pill without any medicine (placebo) along with their regular depression medicine for 6 weeks. They found that the people who took brexpiprazole felt less sad, less worried, slept better, ate better, and could do their daily activities better than those who took the pretend pill. This means that adding brexpiprazole might help people with depression and anxiety who don't get better with just the usual medicines.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD).
    The Cochrane database of systematic reviews (2023)
    Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9; 10(10):CD011769.
    Abstract: Pharmacological interventions are frequently used for people with autism spectrum disorder (ASD) to manage behaviours of concern, including irritability, aggression, and self-injury. Some pharmacological interventions might help treat some behaviours of concern, but can also have adverse effects (AEs). To assess the effectiveness and AEs of pharmacological interventions for managing the behaviours of irritability, aggression, and self-injury in ASD. We searched CENTRAL, MEDLINE, Embase, 11 other databases and two trials registers up to June 2022. We also searched reference lists of relevant studies, and contacted study authors, experts and pharmaceutical companies. We included randomised controlled trials of participants of any age with a clinical diagnosis of ASD, that compared any pharmacological intervention to an alternative drug, standard care, placebo, or wait-list control. We used standard Cochrane methods. Primary outcomes were behaviours of concern in ASD, (irritability, aggression and self-injury); and AEs. Secondary outcomes were quality of life, and tolerability and acceptability. Two review authors independently assessed each study for risk of bias, and used GRADE to judge the certainty of the evidence for each outcome. We included 131 studies involving 7014 participants in this review. We identified 26 studies as awaiting classification and 25 as ongoing. Most studies involved children (53 studies involved only children under 13 years), children and adolescents (37 studies), adolescents only (2 studies) children and adults (16 studies), or adults only (23 studies). All included studies compared a pharmacological intervention to a placebo or to another pharmacological intervention. Atypical antipsychotics versus placebo At short-term follow-up (up to 6 months), atypical antipsychotics probably reduce irritability compared to placebo (standardised mean difference (SMD) -0.90, 95% confidence interval (CI) -1.25 to -0.55, 12 studies, 973 participants; moderate-certainty evidence), which may indicate a large effect. However, there was no clear evidence of a difference in aggression between groups (SMD -0.44, 95% CI -0.89 to 0.01; 1 study, 77 participants; very low-certainty evidence). Atypical antipsychotics may also reduce self-injury (SMD -1.43, 95% CI -2.24 to -0.61; 1 study, 30 participants; low-certainty evidence), possibly indicating a large effect. There may be higher rates of neurological AEs (dizziness, fatigue, sedation, somnolence, and tremor) in the intervention group (low-certainty evidence), but there was no clear evidence of an effect on other neurological AEs. Increased appetite may be higher in the intervention group (low-certainty evidence), but we found no clear evidence of an effect on other metabolic AEs. There was no clear evidence of differences between groups in musculoskeletal or psychological AEs. Neurohormones versus placebo At short-term follow-up, neurohormones may have minimal to no clear effect on irritability when compared to placebo (SMD -0.18, 95% CI -0.37 to -0.00; 8 studies; 466 participants; very low-certainty evidence), although the evidence is very uncertain. No data were reported for aggression or self -injury. Neurohormones may reduce the risk of headaches slightly in the intervention group, although the evidence is very uncertain. There was no clear evidence of an effect of neurohormones on any other neurological AEs, nor on any psychological, metabolic, or musculoskeletal AEs (low- and very low-certainty evidence). Attention-deficit hyperactivity disorder (ADHD)-related medications versus placebo At short-term follow-up, ADHD-related medications may reduce irritability slightly (SMD -0.20, 95% CI -0.40 to -0.01; 10 studies, 400 participants; low-certainty evidence), which may indicate a small effect. However, there was no clear evidence that ADHD-related medications have an effect on self-injury (SMD -0.62, 95% CI -1.63 to 0.39; 1 study, 16 participants; very low-certainty evidence). No data were reported for aggression. Rates of neurological AEs (drowsiness, emotional AEs, fatigue, headache, insomnia, and irritability), metabolic AEs (decreased appetite) and psychological AEs (depression) may be higher in the intervention group, although the evidence is very uncertain (very low-certainty evidence). There was no evidence of a difference between groups for any other metabolic, neurological, or psychological AEs (very low-certainty evidence). No data were reported for musculoskeletal AEs. Antidepressants versus placebo At short-term follow-up, there was no clear evidence that antidepressants have an effect on irritability (SMD -0.06, 95% CI -0.30 to 0.18; 3 studies, 267 participants; low-certainty evidence). No data for aggression or self-injury were reported or could be included in the analysis. Rates of metabolic AEs (decreased energy) may be higher in participants receiving antidepressants (very low-certainty evidence), although no other metabolic AEs showed clear evidence of a difference. Rates of neurological AEs (decreased attention) and psychological AEs (impulsive behaviour and stereotypy) may also be higher in the intervention group (very low-certainty evidence) although the evidence is very uncertain. There was no clear evidence of any difference in the other metabolic, neurological, or psychological AEs (very low-certainty evidence), nor between groups in musculoskeletal AEs (very low-certainty evidence). Risk of bias We rated most of the studies across the four comparisons at unclear overall risk of bias due to having multiple domains rated as unclear, very few rated as low across all domains, and most having at least one domain rated as high risk of bias. Evidence suggests that atypical antipsychotics probably reduce irritability, ADHD-related medications may reduce irritability slightly, and neurohormones may have little to no effect on irritability in the short term in people with ASD. There was some evidence that atypical antipsychotics may reduce self-injury in the short term, although the evidence is uncertain. There was no clear evidence that antidepressants had an effect on irritability. There was also little to no difference in aggression between atypical antipsychotics and placebo, or self-injury between ADHD-related medications and placebo. However, there was some evidence that atypical antipsychotics may result in a large reduction in self-injury, although the evidence is uncertain. No data were reported (or could be used) for self-injury or aggression for neurohormones versus placebo. Studies reported a wide range of potential AEs. Atypical antipsychotics and ADHD-related medications in particular were associated with an increased risk of metabolic and neurological AEs, although the evidence is uncertain for atypical antipsychotics and very uncertain for ADHD-related medications. The other drug classes had minimal or no associated AEs.

    Abstract Summary: Scientists did a big study to see if certain medicines can help people with autism calm down when they feel really upset or hurt themselves. They looked at lots of research and found 131 studies with 7014 people. They checked if the medicines were better than a pretend pill (placebo) or other treatments. They found out that some medicines called atypical antipsychotics might really help with calming down, but they weren't sure if they helped with aggression or self-harm. These medicines might make people feel dizzy or hungry. Another kind of medicine, for ADHD, might help a little with calming down, but they didn't know if it helped with self-harm, and it might make people feel tired or have headaches. They also looked at neurohormones and antidepressants, but they weren't sure if these helped much and they might make some people feel less energetic or pay less attention. In the end, they think that atypical antipsychotics could be good for helping with some of the upset feelings in autism, but all medicines have some side effects, and they're not totally sure how well they work. So, it's important for doctors and patients to think carefully about using these medicines.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Changes in Metabolic Parameters and Body Weight in Patients With Prediabetes Treated With Adjunctive Brexpiprazole for Major Depressive Disorder: Pooled Analysis of Short- and Long-Term Clinical Studies.
    The Journal of clinical psychiatry (2023)
    Newcomer JW, Meehan SR, Chen D, Brubaker M, Weiss C. Changes in Metabolic Parameters and Body Weight in Patients With Prediabetes Treated With Adjunctive Brexpiprazole for Major Depressive Disorder: Pooled Analysis of Short- and Long-Term Clinical Studies. J Clin Psychiatry. 2023 Aug 28; 84(5):.
    Abstract: Certain atypical antipsychotics, while efficacious as adjunctive treatments in major depressive disorder (MDD), are associated with metabolic adverse effects and weight gain. This analysis determined the effect of adjunctive brexpiprazole on metabolic parameters and body weight in adults with MDD and prediabetes (ie, at risk of developing diabetes) based on pooled data from 3 short-term studies and 1 long-term study. The short-term studies were 6-week, randomized, double-blind, placebo-controlled studies of adjunctive oral brexpiprazole 1-3 mg/d in outpatients with MDD ( criteria) and inadequate response to antidepressant treatment, conducted between June 2011 and May 2016. The long-term study was a 26- to 52-week, open-label extension study conducted between October 2011 and May 2017. was defined based on fasting serum glucose and glycated hemoglobin (HbA1c) levels. Shifts in diabetes status and shifts/changes in fasting metabolic parameters and body weight were determined. Most patients receiving adjunctive brexpiprazole maintained their baseline diabetes status in the short term (568/751; 75.6%) and long term (1,919/2,746; 69.9%). The incidence of categorical shifts in fasting metabolic parameters generally did not differ between treatment groups or between prediabetes and non-diabetes subgroups. Mean changes from baseline in metabolic parameters were small in the short term (all < 5 mg/dL) and long term (all < 6 mg/dL, except < 20 mg/dL for triglycerides). Moderate weight gain was observed in the short term (1.5 kg) and long term (3.4-4.1 kg). Adjunctive brexpiprazole had a limited impact on the metabolic profile of patients with MDD, regardless of diabetes status (prediabetes/non-diabetes). Data used in this post hoc analysis came from studies with ClinicalTrials.gov identifiers NCT01360645, NCT01360632, NCT02196506, and NCT01360866.

    Abstract Summary: Scientists looked at how a medicine called brexpiprazole affects people with depression and a higher chance of getting diabetes when it's added to their usual treatment. They used information from three studies that lasted 6 weeks and one study that lasted up to a year. They wanted to see if the medicine changed people's blood sugar levels, diabetes status, or weight. They found that most people who took brexpiprazole didn't have big changes in their blood sugar or diabetes status in both the short and long term. People did gain a little bit of weight, but not too much. This means that brexpiprazole doesn't have a big effect on blood sugar or diabetes but can cause some weight gain. This information can help doctors and patients make better choices about treating depression in people who also have to watch out for diabetes.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Comprehension by Caregivers and Adolescents of Clinical Trial Information Delivered via Multimedia Video Versus Conventional Practice: Nonrandomized Controlled Trial.
    JMIR pediatrics and parenting (2023)
    Blake KV, Antal H, Bunnell HT, He J, Henderson R, Holbrook JT, McCahan SM, Pennington C, Rogers L, Shade D, Sugar EA, Taylor A, Wise RA, Wysocki T. Comprehension by Caregivers and Adolescents of Clinical Trial Information Delivered via Multimedia Video Versus Conventional Practice: Nonrandomized Controlled Trial. JMIR Pediatr Parent. 2023 Jun 22; 6:e44252.
    Abstract: Research participants often misunderstand the required elements of informed consent information, whether provided in written or oral format. Informed consent instruments with embedded evidence-based learning theory principles administered in multimedia electronic formats may improve comprehension and retention. This study aims to determine whether study information comprehension and retention using an interactive multimedia video consent process was noninferior to comprehension and retention after an in-person face-to-face interaction with a conventional written consent document for caregivers and adolescents enrolled in a clinical trial. Participants were caregivers and children aged 12 to 17 years who were enrolled in a clinical trial of asthma treatment. Consent information was presented as a multimedia web-based video consent interaction or as a conventional written consent document with in-person interaction between the prospective participants and the study staff. The trial used a parallel nonrandomized noninferiority design that compared the 2 consent methods. Caregivers and adolescents completed a 17-item open-ended comprehension questionnaire (score range 17-51) at enrollment and at the end of the study 20 weeks later. Comprehension and retention were compared between the consent formats. Noninferiority was established if the 95% CI upper bound of the difference in scores (conventional format minus web-based) was less than the noninferiority margin of 2.4; superiority was established if the upper bound of the CI was <0. In total, 54 caregiver and adolescent dyads completed the interactive multimedia web-based video consent, and 25 dyads completed the conventional consent. Overall, 33% (26/79) of all adolescents were Black, 57% (45/79) were male, and 61% (48/79) had a household income of <US $60,000 per year. For caregivers, the interactive multimedia web-based format was noninferior to the conventional format at enrollment (difference between the conventional and web-based formats: mean -0.30, 95% CI -2.52 to 1.92) and was superior at the end of the study 20 weeks later (mean -2.20, 95% CI -3.9 to -0.5). There was a loss of comprehension over 20 weeks (mean -1.65, 95% CI -3.1 to -0.19) with the conventional format but not with the multimedia web-based format (mean 0.14, 95% CI -0.84 to 1.12). For adolescents, the noninferiority of the multimedia web-based format was not established. Caregivers who are considering enrolling their adolescent in an asthma clinical trial have similar comprehension of study information when delivered through an interactive multimedia web-based platform, which incorporates evidence-based learning theory principles, compared with having a conventional in-person, face-to-face discussion. The retention of study information over time was better with the multimedia format for caregivers. ClinicalTrials.gov NCT02061280; https://clinicaltrials.gov/ct2/show/NCT02061280 and NCT01437995; https://clinicaltrials.gov/ct2/show/NCT01437995.

    Abstract Summary: Scientists wanted to see if a video that explains a study to kids and their parents is just as good as talking to someone in person and reading about the study. They tested this with families who were learning about an asthma study. Some families watched an interactive video, while others read a paper and talked to the study team. They asked the families questions to see how well they understood the study right after they learned about it and again 20 weeks later. They found that parents who watched the video understood the study just as well as those who talked to someone in person. Even better, the parents remembered the information longer if they watched the video. But for the kids, the video wasn't proven to be as good as talking to someone in person. This means that using videos could be a good way to help parents understand and remember information when they're thinking about joining a study with their kids.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Nicotine receptor partial agonists for smoking cessation.
    The Cochrane database of systematic reviews (2023)
    Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5; 5(5):CD006103.
    Abstract: Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). This is an update of a Cochrane Review first published in 2007. To assess the effectiveness of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. We searched the Cochrane Tobacco Addiction Group's Specialised Register in April 2022 for trials, using relevant terms in the title or abstract, or as keywords. The register is compiled from searches of CENTRAL, MEDLINE, Embase, and PsycINFO.  SELECTION CRITERIA: We included randomised controlled trials that compared the treatment drug with placebo, another smoking cessation drug, e-cigarettes, or no medication. We excluded trials that did not report a minimum follow-up period of six months from baseline. We followed standard Cochrane methods. Our main outcome was abstinence from smoking at longest follow-up using the most rigorous definition of abstinence, preferring biochemically validated rates where reported. We pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. We also reported the number of people reporting serious adverse events (SAEs). We included 75 trials of 45,049 people; 45 were new for this update. We rated 22 at low risk of bias, 18 at high risk, and 35 at unclear risk. We found moderate-certainty evidence (limited by heterogeneity) that cytisine helps more people to quit smoking than placebo (RR 1.30, 95% confidence interval (CI) 1.15 to 1.47; I = 83%; 4 studies, 4623 participants), and no evidence of a difference in the number reporting SAEs (RR 1.04, 95% CI 0.78 to 1.37; I = 0%; 3 studies, 3781 participants; low-certainty evidence). SAE evidence was limited by imprecision. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than placebo (RR 2.32, 95% CI 2.15 to 2.51; I = 60%, 41 studies, 17,395 participants), and moderate-certainty evidence that people taking varenicline are more likely to report SAEs than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; I = 0%; 26 studies, 14,356 participants). While point estimates suggested increased risk of cardiac SAEs (RR 1.20, 95% CI 0.79 to 1.84; I = 0%; 18 studies, 7151 participants; low-certainty evidence), and decreased risk of neuropsychiatric SAEs (RR 0.89, 95% CI 0.61 to 1.29; I = 0%; 22 studies, 7846 participants; low-certainty evidence), in both cases evidence was limited by imprecision, and confidence intervals were compatible with both benefit and harm. Pooled results from studies that randomised people to receive cytisine or varenicline showed that more people in the varenicline arm quit smoking (RR 0.83, 95% CI 0.66 to 1.05; I = 0%; 2 studies, 2131 participants; moderate-certainty evidence) and reported SAEs (RR 0.67, 95% CI 0.44 to 1.03; I = 45%; 2 studies, 2017 participants; low-certainty evidence). However, the evidence was limited by imprecision, and confidence intervals incorporated the potential for benefit from either cytisine or varenicline. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than bupropion (RR 1.36, 95% CI 1.25 to 1.49; I = 0%; 9 studies, 7560 participants), and no clear evidence of difference in rates of SAEs (RR 0.89, 95% CI 0.61 to 1.31; I = 0%; 5 studies, 5317 participants), neuropsychiatric SAEs (RR 1.05, 95% CI 0.16 to 7.04; I = 10%; 2 studies, 866 participants), or cardiac SAEs (RR 3.17, 95% CI 0.33 to 30.18; I = 0%; 2 studies, 866 participants). Evidence of harms was of low certainty, limited by imprecision. We found high-certainty evidence that varenicline helps more people to quit than a single form of nicotine replacement therapy (NRT) (RR 1.25, 95% CI 1.14 to 1.37; I = 28%; 11 studies, 7572 participants), and low-certainty evidence, limited by imprecision, of fewer reported SAEs (RR 0.70, 95% CI 0.50 to 0.99; I = 24%; 6 studies, 6535 participants). We found no data on neuropsychiatric or cardiac SAEs. We found no clear evidence of a difference in quit rates between varenicline and dual-form NRT (RR 1.02, 95% CI 0.87 to 1.20; I = 0%; 5 studies, 2344 participants; low-certainty evidence, downgraded because of imprecision). While pooled point estimates suggested increased risk of SAEs (RR 2.15, 95% CI 0.49 to 9.46; I = 0%; 4 studies, 1852 participants) and neuropsychiatric SAEs (RR 4.69, 95% CI 0.23 to 96.50; I not estimable as events only in 1 study; 2 studies, 764 participants), and reduced risk of cardiac SAEs (RR 0.32, 95% CI 0.01 to 7.88; I not estimable as events only in 1 study; 2 studies, 819 participants), in all three cases evidence was of low certainty and confidence intervals were very wide, encompassing both substantial harm and benefit. Cytisine and varenicline both help more people to quit smoking than placebo or no medication. Varenicline is more effective at helping people to quit smoking than bupropion, or a single form of NRT, and may be as or more effective than dual-form NRT. People taking varenicline are probably more likely to experience SAEs than those not taking it, and while there may be increased risk of cardiac SAEs and decreased risk of neuropsychiatric SAEs, evidence was compatible with both benefit and harm. Cytisine may lead to fewer people reporting SAEs than varenicline. Based on studies that directly compared cytisine and varenicline, there may be a benefit from varenicline for quitting smoking, however further evidence could strengthen this finding or demonstrate a benefit from cytisine. Future trials should test the effectiveness and safety of cytisine compared with varenicline and other pharmacotherapies, and should also test variations in dose and duration. There is limited benefit to be gained from more trials testing the effect of standard-dose varenicline compared with placebo for smoking cessation. Further trials on varenicline should test variations in dose and duration, and compare varenicline with e-cigarettes for smoking cessation.

    Abstract Summary: Scientists did a big study to see if two drugs, called cytisine and varenicline, can help people stop smoking. They looked at a lot of other studies where people were given these drugs, a fake pill (placebo), or other stop-smoking treatments. They wanted to know if these drugs made it easier for people to quit smoking and if they caused any serious problems (like heart issues or mood changes). They found that both cytisine and varenicline helped more people quit smoking than a fake pill. Varenicline was even better at helping people stop than another drug called bupropion or just using one type of nicotine patch or gum. But, some people taking varenicline had serious problems more often than those who didn't take it. The scientists aren't sure if these problems are really caused by the drug or not. In the end, they think these drugs are good for helping people quit smoking, but they want to do more research to be really sure about how safe they are and if one is better than the other. They also think we don't need more studies comparing varenicline to a fake pill because we already know it works. Instead, they suggest looking at different amounts of the drug and how long people should take it, and comparing it to e-cigarettes.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Effects of adjunctive brexpiprazole on patient life engagement in major depressive disorder: Post hoc analysis of Inventory of Depressive Symptomatology Self-Report data.
    Journal of psychiatric research (2023)
    McIntyre RS, Therrien F, Ismail Z, Meehan SR, Miguelez M, Larsen KG, Chen D, MacKenzie EM, Thase ME. Effects of adjunctive brexpiprazole on patient life engagement in major depressive disorder: Post hoc analysis of Inventory of Depressive Symptomatology Self-Report data. J Psychiatr Res. 2023 Jun; 162:71-78.
    Abstract: Patient-reported outcomes can capture domains that are meaningful to patients, such as life engagement in major depressive disorder (MDD), which reflects life fulfillment, well-being, and participation in valued and meaningful activities. This analysis investigated the effects of brexpiprazole adjunct to antidepressant treatment (ADT) on patient life engagement over the short and long term, using the 10-item Inventory of Depressive Symptomatology Self-Report (IDS-SR) Life Engagement subscale. Short-term data were pooled from three 6-week, randomized, double-blind studies of ADT + brexpiprazole 2-3 mg/day versus ADT + placebo in adult outpatients with MDD (DSM-IV-TR criteria) and inadequate response to ADTs. Long-term data were from a 26-52-week, open-label extension study of ADT + brexpiprazole 0.5-3 mg/day. Over 6 weeks, ADT + brexpiprazole (n = 579) showed greater improvement in IDS-SR Life Engagement subscale score than ADT + placebo (n = 583), with a least squares mean difference of -1.19 (95% confidence limits: -1.78, -0.59; p = 0.0001; Cohen's d effect size: 0.23). Greater improvement for ADT + brexpiprazole versus ADT + placebo (p < 0.05) was also observed on eight life engagement items, with effect sizes ranging from 0.12 to 0.24. In the long-term study, mean (standard deviation) IDS-SR Life Engagement subscale score changed by -2.4 (4.9) points to Week 26 (n = 2047), and -3.7 (5.3) points to Week 52 (n = 768), with mean improvements on all ten items. Beyond its efficacy on depressive symptoms, adjunctive brexpiprazole may improve patient life engagement, thereby helping patients with MDD to achieve personally meaningful functional outcomes.

    Abstract Summary: Scientists did a study to see if a medicine called brexpiprazole could help adults with major depression feel more involved in life when taken with their usual antidepressants. They checked if patients felt more fulfilled and took part in activities they valued. They used a special questionnaire to measure this. In the first part of the study, they compared two groups for 6 weeks: one took brexpiprazole with their antidepressants, and the other took a fake pill with their antidepressants. The brexpiprazole group felt better and more engaged in life. In the second part, they watched people take brexpiprazole with their antidepressants for up to a year, and those people continued to feel more engaged in life. This research suggests that brexpiprazole might help people with depression not only feel less sad but also enjoy life more.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Combined Oral Contraceptive Adherence and Pregnancy Rates.
    Obstetrics and gynecology (2023)
    Creinin MD, Jensen JT, Chen MJ, Black A, Costescu D, Foidart JM. Combined Oral Contraceptive Adherence and Pregnancy Rates. Obstet Gynecol. 2023 May 1; 141(5):989-994.
    Abstract: To assess the relationship of adherence and pregnancy in participants using an estetrol and drospirenone combined oral contraceptive. We performed a secondary analysis for which we pooled data from two parallel, multicenter, phase 3 trials (United States and Canada, Europe and Russia) that enrolled participants 16-50 years of age to receive estetrol 15 mg and drospirenone 3 mg in a 24 hormone and four placebo pills regimen for up to 13 cycles. Participants reported pill intake, sexual intercourse, and other contraceptive use on paper diaries. We limited this efficacy analysis to at-risk cycles (one or more reported acts of intercourse and no other contraceptive use) in participants 16-35 years of age at screening. We excluded cycles with other contraceptive use unless pregnancy occurred in that cycle. We assessed primarily the relationship between number of pills not taken per cycle and pregnancies and, secondarily, when pregnancies occurred during product use with a test for trend and χ 2 analyses as appropriate. Among 2,837 participants in this analysis, 31 on-treatment pregnancies occurred during 26,455 at-risk cycles. Pregnancies occurred in 0.09%, 0.25%, 0.83%, and 1.6% of cycles in which participants reported they took all hormone pills (n=25,613 cycles) or did not take one (n=405 cycles), two (n=121 cycles), and more than two (n=314 cycles) hormone-containing pills, respectively ( P <.001). No pregnancies occurred in 2,216 cycles when one or more pills were missed and missed-pill instructions were followed. All pregnancies related to not taking pills occurred in the first three cycles. Pregnancy rates ranged from 0% to 0.21% per cycle with no significant trend by cycle ( P =.45). Pregnancy occurs more frequently when combined oral contraceptive users report not taking all hormone-containing pills per 28-day cycle and exceeds 1% only when more than two pills are not taken. Pregnancies in participants who reported missed pills occurred only when missed-pill instructions were not followed. A 0.09% pregnancy risk per cycle among users of a 24 hormone and four placebo pills formulation who report taking all pills likely approximates a true method-failure rate. Estetra SRL, an affiliate company of Mithra Pharmaceuticals. ClinicalTrials.gov , NCT02817828 and NCT02817841.

    Abstract Summary: Scientists studied how well a new birth control pill worked when people didn't take it exactly as they should. They looked at information from two big studies that included women aged 16 to 50 from different countries. These women took a pill with two special ingredients, estetrol and drospirenone, and wrote down when they took the pill, had sex, and if they used other birth control methods. The researchers focused on women aged 16 to 35 who had sex without using other birth control and didn't always take their pill. They found that when women missed more than two pills in a month, the chance of getting pregnant went up a lot. But if they followed the instructions on what to do when they missed a pill, they didn't get pregnant. Most of the time, if someone got pregnant, it was because they didn't take their pills correctly in the first three months. The study shows that this birth control pill works really well if you take it every day, but it's super important to follow the instructions, especially if you forget to take a pill.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Conflicts hurt: social stress predicts elevated pain and sadness after mild inflammatory increases.
    Pain (2023)
    Madison AA, Renna M, Andridge R, Peng J, Shrout MR, Sheridan J, Lustberg M, Ramaswamy B, Wesolowski R, Williams NO, Noonan AM, Reinbolt RE, Stover DG, Cherian MA, Malarkey WB, Kiecolt-Glaser JK. Conflicts hurt: social stress predicts elevated pain and sadness after mild inflammatory increases. Pain. 2023 Sep 1; 164(9):1985-1994.
    Abstract: Individuals respond differently to inflammation. Pain, sadness, and fatigue are common correlates of inflammation among breast cancer survivors. Stress may predict response intensity. This study tested whether breast cancer survivors with greater exposure to acute or chronic social or nonsocial stress had larger increases in pain, sadness, and fatigue during an acute inflammatory response. In total, 156 postmenopausal breast cancer survivors (ages 36-78 years, stage I-IIIA, 1-9 years posttreatment) were randomized to either a typhoid vaccine/saline placebo or the placebo/vaccine sequence, which they received at 2 separate visits at least 1 month apart. Survivors had their blood drawn every 90 minutes for the next 8 hours postinjection to assess levels of interleukin-6 and interleukin-1 receptor antagonist (IL-1Ra). Shortly after each blood draw, they rated their current levels of pain, sadness, and fatigue. Women also completed the Test of Negative Social Exchange to assess chronic social stress and the Trier Inventory of Chronic Stressors screen to index chronic general stress. At each visit, a trained experimenter administered the Daily Inventory of Stressful Events to assess social and nonsocial stress exposure within the past 24 hours. After statistical adjustment for relevant demographic and behavioral covariates, the most consistent results were that survivors who reported more chronic social stress reported more pain and sadness in response to IL-1Ra increases. Frequent and ongoing social stress may sensitize the nervous system to the effects of inflammation, with potential implications for chronic pain and depression risk among breast cancer survivors.

    Abstract Summary: Scientists did a study to see if stress makes breast cancer survivors feel more pain, sadness, and tiredness when their bodies are fighting off something like an infection. They worked with 156 women who had been treated for breast cancer. These women were given a shot that made their bodies think they were sick, so the scientists could see how they reacted. The women told the scientists how stressed they were and how they felt every hour and a half after the shot. The study found that women who had a lot of stress from problems with other people felt more pain and sadness when their bodies were fighting off the pretend sickness. This means that when people who have had breast cancer are stressed a lot, especially by other people, it might make them feel worse when they get sick. This is important because it could help doctors understand why some women have more pain or feel sadder after cancer and how to help them better.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Memantine for autism spectrum disorder.
    The Cochrane database of systematic reviews (2022)
    Brignell A, Marraffa C, Williams K, May T. Memantine for autism spectrum disorder. Cochrane Database Syst Rev. 2022 Aug 25; 8(8):CD013845.
    Abstract: Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child's quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co-occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness. To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours. We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found. We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention). We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence. We included three RCTs (two double-blind and one single-blind) with 204 participants that examined the short-term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R); one used ADOS, ADI-R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child's weight and ranged from 3 mg to 15 mg per day.  Comparisons  Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine.  Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in-kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was -0.74 standard deviations (95% confidence interval (CI) -2.07 to 0.58; 2 studies, 181 participants; very low-certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low-certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low-certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low-certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low-certainty evidence). It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow-up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism.

    Abstract Summary: Scientists wanted to see if a medicine called memantine, which is usually used for memory problems, could help kids with autism. Autism is when kids have trouble talking and making friends, and they might do the same things over and over. The scientists looked at three studies with 204 kids to see if memantine could make their autism symptoms better. They also checked if the medicine caused any bad reactions. The studies weren't perfect, and the scientists couldn't be sure if memantine really helped with autism symptoms or not. They also didn't find a big difference in how the kids talked, remembered things, or behaved. Some kids had side effects, but it seemed similar to kids who didn't take the medicine. In the end, the scientists said they don't know if memantine is good for treating kids with autism. They need to do more and better studies to find out. They didn't study adults with autism, so they don't know if it would help them either.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Practical strategies for qualitative inquiry in a virtual world.
    Journal of advanced nursing (2021)
    Schlegel EC, Tate JA, Pickler RH, Smith LH. Practical strategies for qualitative inquiry in a virtual world. J Adv Nurs. 2021 Oct; 77(10):4035-4044.
    Abstract: The aim of this article is to provide practical strategies for maintaining methodological rigour in executing a virtual qualitative study. Strategies are based on evidence from existing research about virtual qualitative methods and on the strategies used by the authors to convert a planned in-person qualitative, grounded theory study to an entirely virtual grounded theory study during the COVID-19 pandemic. The study began in-person in September 2019 and was converted to virtual in March 2020. Virtual data collection was completed in September 2020. This article provides a case exemplar of virtual adaptations made to a study underway when the pandemic rendered all in-person research impractical and potentially dangerous. The strategies discussed are based on our own experiences and the supporting theoretical assumptions of qualitative research, specifically grounded theory methods. Nursing scholars conducting qualitative inquiry may find these strategies helpful in continuing research activities during periods of limited access to the phenomena or persons of interest. Furthermore, these strategies allow nursing scholars to conduct rigorous, in-depth research without geographical limitations, providing greater possibilities for international collaborations and cross-institution research. Despite novel challenges, methodological adaptations that are carefully planned and purposeful allow qualitative and non-qualitative scholars to continue research activities in a fully virtual manner. This case exemplar and discussion provide practical strategies for qualitative scholars to consider while planning new studies or converting an in-person study to a virtual one. Despite the in-person nature of in-depth qualitative inquiry, a historic pandemic and a changing research environment require qualitative researchers to adapt to virtual methods while still conducting high quality, methodologically rigorous research. Qualitative scholars can use the strategies presented here to continue rigorous qualitative inquiry despite limited access to phenomena or persons.

    Abstract Summary: This article talks about how to do a really good research study using the internet instead of meeting people in person. The researchers had to change their study to be online because of the COVID-19 pandemic. They started meeting people in person in September 2019 but had to switch to online in March 2020. They finished collecting information online by September 2020. They share tips based on what they learned and what other studies say about doing research online. These tips can help nurses and other researchers do important studies from far away, even with people in other countries. The article shows that even when you can't meet people face-to-face, you can still do a great job researching by using the internet carefully and thoughtfully.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Efficacy, safety, and tolerability of a levonorgestrel/ethinyl estradiol transdermal delivery system: Phase 3 clinical trial results.
    Contraception (2021)
    Nelson AL, Kaunitz AM, Kroll R, Simon JA, Poindexter AN, Castaño PM, Ackerman RT, Flood L, Chiodo JA 3rd, Garner EI, SECURE Investigators. Efficacy, safety, and tolerability of a levonorgestrel/ethinyl estradiol transdermal delivery system: Phase 3 clinical trial results. Contraception. 2021 Mar; 103(3):137-143.
    Abstract: To assess the contraceptive efficacy, safety, and tolerability of a contraceptive transdermal delivery system, (TDS; TWIRLA) containing levonorgestrel (LNG) and ethinyl estradiol (EE). This single-arm, open-label, multicenter, 1-year (13 cycle), phase 3 study enrolled sexually active women ≥18 years old at risk for pregnancy irrespective of body mass index (BMI). Women used patches in 28-day cycles (3 consecutive administrations of 7-day patches followed by 7 days off-treatment/patch-free week). We assessed contraceptive efficacy by the Pearl Index (PI) in women 18 to 35 years, excluding cycles without intercourse or when other contraceptive methods were used. The study enrolled 2032 demographically diverse women in the US, of which 35.3% had a BMI ≥30 kg/m. In the primary efficacy analysis, the PI (95% confidence interval) was 5.8 (4.5-7.2) pregnancies per 100 woman-years. PIs trended higher as BMI increased; the PI was 4.3 (2.9-5.8) in women with BMI <30 kg/m and 8.6 (5.8-11.5) in women with BMI ≥30 kg/m. Hormone-related treatment-emergent adverse events included nausea (4.1%) and headache (3.6%); 11% of women discontinued due to adverse events. Four women (all with BMIs ≥30 kg/m) reported thromboembolic events considered related to treatment. The low-dose LNG/EE TDS was effective in preventing pregnancy in a population of women representative of US demographics. Efficacy was reduced in women with BMI ≥30 kg/m. The TDS safety and tolerability profile was consistent with other similar dose combined hormonal contraceptives. Results of this phase 3 study supported the US Food and Drug Administration approval of TWIRLA for prevention of pregnancy in women with BMI <30 kg/m. TDS (120 µg/day levonorgestrel and 30 µg/day ethinyl estradiol) is an effective, low-dose transdermal contraceptive patch with favorable tolerability profile approved for prevention of pregnancy in women with BMI <30 kg/m. TDS has reduced effectiveness in women with BMI ≥30 kg/m.

    Abstract Summary: Scientists studied a new birth control patch called TWIRLA that sticks to the skin and releases two hormones to prevent pregnancy. They had women from different places in the US, who were 18 years or older and could get pregnant, try the patch for a year. They wanted to see how well it worked, if it was safe, and if women felt okay using it. They found that the patch did a good job at preventing pregnancy for most women, but it wasn't as good for women who were heavier (with a BMI over 30). Some women felt sick to their stomach or had headaches, and a few stopped using it because they didn't feel well. Four heavier women had serious blood clot problems. In the end, the patch was approved for women who aren't too heavy, and it's a new option for birth control that you wear on your skin.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Linoleic Acid-Rich Oil Supplementation Increases Total and High-Molecular-Weight Adiponectin and Alters Plasma Oxylipins in Postmenopausal Women with Metabolic Syndrome.
    Current developments in nutrition (2020)
    Cole RM, Puchala S, Ke JY, Abdel-Rasoul M, Harlow K, O'Donnell B, Bradley D, Andridge R, Borkowski K, Newman JW, Belury MA. Linoleic Acid-Rich Oil Supplementation Increases Total and High-Molecular-Weight Adiponectin and Alters Plasma Oxylipins in Postmenopausal Women with Metabolic Syndrome. Curr Dev Nutr. 2020 Sep; 4(9):nzaa136.
    Abstract: The onset of menopause increases the risk of metabolic syndrome (MetS). Adiponectin is an adipokine associated with insulin sensitivity that is lower in people with MetS. Supplementing diets with linoleic acid (LA)-rich oil increased adiponectin concentrations and improved glucose control in women with type 2 diabetes. The effect of LA on adipokines, especially total and the bioactive form of adiponectin, high-molecular-weight (HMW) adiponectin, in women with MetS is unknown. The aim of this study was to explore the effect of supplementation of the diet with an oil rich in LA on adipokines in women with MetS. The effect of the LA-rich oil (LA-oil) on oxylipins, key metabolites that may influence inflammation and metabolism, was also explored. In this open-label single-arm pilot study, 18 postmenopausal nondiabetic women with MetS enrolled in a 2-phase study were instructed to consume LA-rich vegetable oil (10 mL/d) as part of their habitual diets. Women consumed an oleic acid-rich oil (OA-oil) for 4 wk followed by an LA-oil for 16 wk. Fasting concentrations of adipokines, fatty acids, oxylipins, and markers of glycemia and inflammation were measured. After 4 wk of OA-oil consumption, fasting glucose and total adiponectin concentrations decreased whereas fasting C-reactive protein increased. After 16 wk of LA-oil supplementation total and HMW adiponectin and plasma oxylipins increased. Markers of inflammation and glycemia were unchanged after LA-oil consumption. Supplementation with LA-oil increased total and HMW adiponectin concentrations and altered plasma oxylipin profiles. Larger studies are needed to elucidate the links between these changes and MetS.This trial was registered at clinicaltrials.gov as NCT02063165.

    Abstract Summary: This study looked at how a special oil, rich in something called linoleic acid (LA), might help women who are going through menopause and have a condition called metabolic syndrome (MetS). MetS can make it harder for your body to use sugar and fat properly. The researchers asked 18 women to add this LA-rich oil to their regular diets. They found that this oil increased the amount of a helpful substance in the body called adiponectin, which can help control sugar levels. The oil also changed other substances in the body that might affect inflammation and metabolism. More research is needed to understand these changes better.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Changes in Metabolic Parameters and Body Weight in Patients With Major Depressive Disorder Treated With Adjunctive Brexpiprazole: Pooled Analysis of Phase 3 Clinical Studies.
    The Journal of clinical psychiatry (2019)
    Newcomer JW, Eriksson H, Zhang P, Meehan SR, Weiss C. Changes in Metabolic Parameters and Body Weight in Patients With Major Depressive Disorder Treated With Adjunctive Brexpiprazole: Pooled Analysis of Phase 3 Clinical Studies. J Clin Psychiatry. 2019 Oct 1; 80(6):.
    Abstract: To analyze the effect of adjunctive brexpiprazole on metabolic parameters and body weight in adults with major depressive disorder (MDD) based on pooled data from 4 short-term studies and 1 long-term extension study. The short-term studies (June 2011 to November 2016) were randomized, double-blind, placebo-controlled studies in outpatients with MDD (DSM-IV-TR criteria) and inadequate response to 1-3 prior antidepressant treatments (ADTs) plus 1 prospective ADT. Patients were randomized to adjunctive brexpiprazole (fixed or flexible doses in the range of 1-3 mg/d; n = 1,032) or placebo (n = 819) for 6 weeks. The long-term study (October 2011 to May 2017) was a 52-week (amended to 26 weeks), open-label, uncontrolled study of adjunctive brexpiprazole 0.5-3 mg/d (flexible dose; n = 2,938). Mean changes from baseline and categorical shifts in fasting metabolic parameters (cholesterol, triglycerides, and glucose) and body weight were analyzed. Mean changes from baseline in metabolic parameters were small after 6 weeks (all < 2 mg/dL) and 52 weeks (all < 4 mg/dL, except triglycerides, 15.83 mg/dL) of treatment. In most cases, the incidence of unfavorable shifts in metabolic parameters was lower than the incidence of favorable shifts. Mean body weight increase at last visit in the short-term studies was 1.5 kg with ADT + brexpiprazole and 0.3 kg with ADT + placebo. During long-term treatment, mean body weight increased by 3.8 kg over 58 weeks. Adjunctive brexpiprazole was associated with small changes in metabolic parameters and moderate weight gain during short- and long-term treatment. ClinicalTrials.gov identifiers: NCT01360645, NCT01360632, NCT02196506, NCT01727726, NCT01360866.

    Abstract Summary: Scientists did a study to see if a medicine called brexpiprazole could help adults with major depression without causing too much weight gain or changing important body health numbers like cholesterol and sugar levels. They looked at information from five different studies. Some people got the medicine along with their usual depression medicine, while others got a pretend pill. They found that after 6 weeks and even after a year, the changes in health numbers were very small. People did gain a little weight, about 3.5 pounds over a year, but it wasn't a lot. This research helps doctors know that brexpiprazole can be used without making people's health numbers get much worse.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Cariprazine Augmentation to Antidepressant Therapy in Major Depressive Disorder: Results of a Randomized, Double-Blind, Placebo-Controlled Trial.
    Psychopharmacology bulletin (2018)
    Earley WR, Guo H, Németh G, Harsányi J, Thase ME. Cariprazine Augmentation to Antidepressant Therapy in Major Depressive Disorder: Results of a Randomized, Double-Blind, Placebo-Controlled Trial. Psychopharmacol Bull. 2018 Jun 20; 48(4):62-80.
    Abstract: Cariprazine is an atypical antipsychotic currently under investigation as an adjunctive to antidepressant treatment (ADT) for patients with major depressive disorder (MDD). Here results of an 18- to 19-week randomized double-blind placebo-controlled Phase 3 study evaluating the efficacy of adjunctive cariprazine (1.5-4.5 mg/day[d]) with ADT in participants with previous inadequate response to ADT are presented. ADT response was assessed in an 8-week open-label period; inadequate responders were randomized (N = 530) to open-label ADT plus placebo (n = 261) or cariprazine (n = 269) for the 8-week double-blind phase (NCT01715805). Primary and secondary endpoints were changes at week 8 (cariprazine versus placebo) in Montgomery-Åsberg Depression Rating Scale (MADRS) total score and in Sheehan Disability Scale (SDS) score, respectively, which were analyzed by mixed-effect models for repeated measures. Cariprazine did not significantly improve scores in either compared to placebo, but non-significantly reduced depressive symptoms (MADRS least-squares mean difference [LSMD]: -0.2, P = 0.7948 and SDS LSMD: -0.7, P = 0.2784). Of additional efficacy parameters, cariprazine significantly improved Clinical Global Impressions - Improvement (CGI-I) scores versus placebo (LSMD: -0.2; P = 0.0410). A greater proportion of participants achieved MADRS response with cariprazine vs placebo, but differences were not significant. Cariprazine was generally well-tolerated, and metabolic parameters and body weight changes were not meaningfully different than placebo. Common newly-emergent adverse events included akathisia and restlessness. The lack of significant improvement in depressive symptoms with adjunctive cariprazine and ADT for MDD in inadequate responders contrasts with previously published results, therefore additional studies are needed to understand role of adjunctive cariprazine in MDD.

    Abstract Summary: Doctors did a study to see if a medicine called cariprazine helps people with major depression who didn't get better with their usual antidepressants. They gave some people cariprazine along with their regular medicine, and others just got a pretend pill (placebo) with their medicine. They checked to see if people felt less sad or could do their daily activities better. They found that cariprazine didn't really make a big difference compared to the pretend pill, but it did help a little with how people felt overall. Most people were okay taking cariprazine, but some felt restless. Since the results were different from other studies, the doctors think more research is needed to see if cariprazine can really help with depression.

    Disclaimer: This summary service is experimental and automatically generated using AI technology. Please speak with your medical care provider before using any information on this site to inform your health care.

  • Adjunctive Brexpiprazole and Functioning in Major Depressive Disorder: A Pooled Analysis of Six Randomized Studies Using the Sheehan Disability Scale.
    The international journal of neuropsyc