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.
A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects With Type 2 Diabetes and Nephropathy SONAR: Study Of Diabetic Nephropathy With Atrasentan
University of Chicago Medical Center
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Sex differences in response to the endothelin receptor antagonist atrasentan in individuals with type 2 diabetes and chronic kidney disease: a post hoc analysis of the SONAR trial.
Diabetologia (2024)
Smeijer JD, de Vries ST, Kohan DE, Hou FF, Heerspink HJL.
Sex differences in response to the endothelin receptor antagonist atrasentan in individuals with type 2 diabetes and chronic kidney disease: a post hoc analysis of the SONAR trial.
Diabetologia.
2024 Dec 11;
:.
Abstract: In the Study Of diabetic Nephropathy with AtRasentan (SONAR), the endothelin receptor antagonist (ERA) atrasentan slowed progression of chronic kidney disease (CKD) in individuals with type 2 diabetes. Pre-clinical research suggests sex-based differences in the endothelin system might influence the efficacy and safety of atrasentan. We therefore assessed the effects of atrasentan in men and women participating in SONAR. SONAR was a double-blind, placebo-controlled trial that compared atrasentan 0.75 mg/day with placebo in individuals with type 2 diabetes and CKD (eGFR 25-75 ml/min per 1.73 m, urine albumin/creatinine ratio [UACR] 300-5000 mg/g). The primary endpoint was defined as the time from randomisation to the first occurrence of a doubling in serum creatinine or kidney failure (eGFR <15 ml/min per 1.73 m, chronic dialysis, kidney transplantation or death from kidney failure). Hospitalisation for heart failure was the secondary endpoint. We performed Cox proportional hazards regression analyses to compare the treatment effect of atrasentan between male and female participants on the risk of the composite kidney outcome as well as hospitalisation for heart failure. Additionally, differences between male and female participants in atrasentan plasma exposure and eGFR change were assessed using, respectively, a t test and linear mixed effect model. Among 3668 randomised participants, 946 (25.8%) were female. Atrasentan significantly reduced the risk of the composite kidney outcome in female participants (HR 0.46 [95% CI 0.28, 0.76]) but not in male participants (HR 0.83 [95% CI 0.65, 1.05]; p value for interaction 0.032). Atrasentan compared with placebo reduced eGFR decline to a greater extent in female than in male participants (treatment effect difference between male vs female participants -0.99 ml/min per 1.73 m, p value for interaction=0.020). The RR for hospitalisation for heart failure with atrasentan vs placebo was 1.14 (95% CI 0.74, 1.76) in male participants and 1.88 (95% CI 0.98, 3.63) in female participants (p value for interaction=0.217). Female participants also had significantly higher atrasentan plasma exposure than male participants (geometric mean AUC 54.5 vs 42.6 ng/ml×h; p<0.001). Atrasentan showed greater kidney protection in female than in male participants but also induced more heart failure events in the female participants. These data suggest that sex-specific dosing regimens may be considered to optimise ERA treatment. ClinicalTrials.gov NCT01858532.
Abstract Summary: Scientists did a study called SONAR to see if a medicine called atrasentan can help people with type 2 diabetes who also have a kidney problem that gets worse over time. They wanted to know if this medicine worked the same for men and women. They gave some people the medicine and others a fake pill (placebo) and watched what happened to their kidneys and if they had to go to the hospital for heart problems.
They found that the medicine helped women's kidneys more than men's and slowed down the damage. But, women taking the medicine had more heart problems than men. Women also had more of the medicine in their blood than men. This means that doctors might need to give different amounts of the medicine to men and women to make sure it's safe and works well. The study helps us understand that the same medicine can work differently for men and women.
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.
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Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression.
Journal of the American Society of Nephrology : JASN (2023)
Heerspink HJL, Jongs N, Schloemer P, Little DJ, Brinker M, Tasto C, Karpefors M, Wheeler DC, Bakris G, Perkovic V, Nkulikiyinka R, Rossert J, Gasparyan SB.
Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression.
J Am Soc Nephrol.
2023 Dec 1;
34(12):2025-2038.
Abstract: The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR but does not weigh the relative clinical importance of the end point components. By contrast, a hierarchical composite end point (HCE) accounts for the clinical importance of the end point components. The authors developed and validated a kidney HCE that combines clinical kidney outcomes with longitudinal GFR changes (GFR slope). They demonstrate that in seven major placebo-controlled kidney outcome trials with different medications, treatment effect estimates on the HCE were consistently in similar directions and of similar magnitudes compared with treatment effects on the established kidney end point. The HCE's prioritization of clinical outcomes and ability to combine dichotomous outcomes with GFR slope make it an attractive alternative to the established kidney end point. The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR. However, the statistical method does not weigh the relative clinical importance of the end point components. A HCE accounts for the clinical importance of the end point components and enables combining dichotomous outcomes with continuous measures. We developed and validated a new HCE for kidney disease progression, performing post hoc analyses of seven major Phase 3 placebo-controlled trials that assessed the effects of canagliflozin, dapagliflozin, finerenone, atrasentan, losartan, irbesartan, and aliskiren in patients with CKD. We calculated the win odds (WOs) for treatment effects on a kidney HCE, defined as a hierarchical composite of all-cause mortality; kidney failure; sustained 57%, 50%, and 40% GFR declines from baseline; and GFR slope. The WO describes the odds of a more favorable outcome for receiving the active compared with the control. We compared the WO with the hazard ratio (HR) of the primary kidney outcome of the original trials. In all trials, treatment effects calculated with the WO reflected a similar direction and magnitude of the treatment effect compared with the HR. Clinical trials incorporating the HCE would achieve increased statistical power compared with the established composite end point at equivalent sample sizes. In seven major kidney clinical trials, the WO and HR provided similar direction of treatment effect estimates with smaller HRs associated with larger WOs. The prioritization of clinical outcomes and inclusion of broader composite end points makes the HCE an attractive alternative to the established kidney end point.
Abstract Summary: Scientists did a study to find a better way to measure how well treatments work for kidney problems. They created a new system that puts the most important health issues first. They tested this new system by looking at past studies where people with kidney disease took different medicines. They found that their new system showed the same results as the old way of measuring, but it was better because it gave more information about how the treatments helped with different health issues. This new way of measuring could help doctors and scientists understand how well treatments work and could lead to better care for people with kidney 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.
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Insulin resistance, kidney outcomes and effects of the endothelin receptor antagonist atrasentan in patients with type 2 diabetes and chronic kidney disease.
Cardiovascular diabetology (2023)
Smeijer JD, Kohan DE, Rossing P, Correa-Rotter R, Liew A, Tang SCW, de Zeeuw D, Gansevoort RT, Ju W, Lambers Heerspink HJ.
Insulin resistance, kidney outcomes and effects of the endothelin receptor antagonist atrasentan in patients with type 2 diabetes and chronic kidney disease.
Cardiovasc Diabetol.
2023 Sep 16;
22(1):251.
Abstract: Insulin resistance (IR) is a pathophysiologic hallmark of type 2 diabetes and associated with the presence of chronic kidney disease (CKD). Experimental studies suggest that endothelin-1 increases IR. We assessed the association between IR and cardio-renal outcomes and the effect of the selective endothelin receptor antagonist atrasentan on IR in patients with type 2 diabetes and CKD. We used data from the RADAR and SONAR trials that recruited participants with type 2 diabetes and CKD [eGFR 25-75 mL/min/1.73 m², urine albumin-to-creatinine ratio of 300-5000 mg/g]. IR was calculated using the homeostatic model assessment (HOMA-IR). The association between HOMA-IR and the pre-specified cardio-renal outcomes was assessed using multivariable Cox proportional hazards regression, and effects of atrasentan on HOMA-IR by a linear mixed effect model. In the SONAR trial, each log-unit increase in HOMA-IR was associated with an increased risk of the composite cardio-renal outcome [hazard ratio 1.32 (95%CI 1.09,1.60; p = 0.004)], kidney outcome [hazard ratio 1.30 (95%CI 1.00,1.68; p-value = 0.048)], and the kidney or all-cause mortality outcome [hazard ratio 1.25 (95%CI 1.01,1.55; p-value = 0.037)]. After 12 weeks treatment in the RADAR trial (N = 123), atrasentan 0.75 mg/day and 1.25 mg/day compared to placebo reduced HOMA-IR by 19.1 (95%CI -17.4, 44.3) and 26.7% (95%CI -6.4, 49.5), respectively. In the SONAR trial (N = 1914), atrasentan 0.75 mg/day compared to placebo reduced HOMA-IR by 9.6% (95%CI 0.6, 17.9). More severe IR is associated with increased risk of cardio-renal outcomes. The endothelin receptor antagonist atrasentan reduced IR. RADAR trial (Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan): NCT01356849. SONAR trial (The Study Of Diabetic Nephropathy With AtRasentan) NCT01858532.
Abstract Summary: Scientists did a study to see if a medicine called atrasentan can help people with type 2 diabetes and kidney disease by lowering insulin resistance (IR), which is when the body doesn't use insulin well. Insulin is important because it helps sugar get into cells for energy. They looked at data from two big studies with people who have diabetes and kidney problems. They found that when IR was higher, people had more heart and kidney problems. They also discovered that taking atrasentan made IR lower. This is good news because it might mean that atrasentan can help protect the hearts and kidneys of people with 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.
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Post hoc analysis of the SONAR trial indicates that the endothelin receptor antagonist atrasentan is associated with less pain in patients with type 2 diabetes and chronic kidney disease.
Kidney international (2023)
Chan KW, Smeijer JD, Schechter M, Jongs N, Vart P, Kohan DE, Gansevoort RT, Liew A, Tang SCW, Wanner C, de Zeeuw D, Heerspink HJL.
Post hoc analysis of the SONAR trial indicates that the endothelin receptor antagonist atrasentan is associated with less pain in patients with type 2 diabetes and chronic kidney disease.
Kidney Int.
2023 Dec;
104(6):1219-1226.
Abstract: Pain is prevalent among patients with diabetes and chronic kidney disease (CKD). The management of chronic pain in these patients is limited by nephrotoxicity of commonly used drugs including non-steroidal anti-inflammatory drugs (NSAIDs) and opioids. Since previous studies implicated endothelin-1 in pain nociception, our post hoc analysis of the SONAR trial assessed the association between the endothelin receptor antagonist atrasentan and pain and prescription of analgesics. SONAR was a randomized, double-blind, placebo-controlled clinical trial that recruited participants with type 2 diabetes and CKD (estimated glomerular filtration rate 25-75 ml/min/1.73 m; urinary albumin-to-creatinine ratio 300-5000 mg/g). Participants were randomized to receive atrasentan or placebo (1834 each arm). The main outcome was pain-related adverse events (AEs) reported by investigators. We applied Cox regression to assess the effect of atrasentan compared to placebo on the risk of the first reported pain-related AE and, secondly, first prescription of analgesics. We used the Anderson-Gill method to assess effects on all (first and subsequent) pain-related AEs. During 2.2-year median follow-up, 1183 pain-related AEs occurred. Rates for the first pain-related event were 138.2 and 170.2 per 1000 person-years in the atrasentan and placebo group respectively (hazard ratio 0.82 [95% confidence interval 0.72-0.93]). Atrasentan also reduced the rate of all (first and subsequent) pain-related AEs (rate ratio 0.80 [0.70-0.91]). These findings were similar after accounting for competing risk of death (sub-hazard ratio 0.81 [0.71-0.92]). Patients treated with atrasentan initiated fewer analgesics including NSAIDs and opioids compared to placebo during follow-up (hazard ratio = 0.72 [0.60-0.88]). Thus, atrasentan was associated with reduced pain-related events and pain-related use of analgesics in carefully selected patients with type 2 diabetes and CKD.
Abstract Summary: Doctors did a study to see if a medicine called atrasentan could help with pain in people who have diabetes and kidney problems. They gave some people atrasentan and others a fake pill (placebo) to compare what happened. They found that the people who took atrasentan had less pain and didn't need as many painkillers, including common ones that can hurt their kidneys. This is good news because it means there might be a safer way for these patients to feel better without using medicines that can make their kidney problems 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.
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Increase in BNP in Response to Endothelin-Receptor Antagonist Atrasentan Is Associated With Incident Heart Failure.
JACC. Heart failure (2022)
Smeijer JD, Koomen J, Kohan DE, McMurray JJV, Bakris GL, Correa-Rotter R, Hou FF, Januzzi JL, Kitzman DW, Kolansky DM, Makino H, Perkovic V, Tobe S, Parving HH, de Zeeuw D, Heerspink HJL.
Increase in BNP in Response to Endothelin-Receptor Antagonist Atrasentan Is Associated With Incident Heart Failure.
JACC Heart Fail.
2022 Jul;
10(7):498-507.
Abstract: The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization. The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk. Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mg/day. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pg/mL), were randomized to atrasentan 0.75 mg/day or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations. Among 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR: 1.39; 95% CI: 0.97-1.99; P = 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR: 2.32; 95% CI: 1.81-2.97) and percent increase in BNP during response enrichment (HR: 1.46; 95% CI: 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR: 1.02; 95% CI: 0.66-1.56) while retaining nephroprotective effects (HR: 0.58; 95% CI: 0.44-0.78). In patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan [SONAR]; NCT01858532).
Abstract Summary: Doctors did a study to see if a medicine called atrasentan could help people with type 2 diabetes and kidney disease avoid kidney failure. They found out that while it did help the kidneys, some patients had to go to the hospital for heart problems more often. They wanted to know if they could tell early on who might have heart issues by checking a heart-related substance in the blood called BNP and how much a person's weight changed. They gave some people the medicine and others a placebo (a pill with no medicine) and watched what happened. They found out that if a person's BNP went up a lot at the beginning, they were more likely to have heart problems. But, if they didn't let people with a big increase in BNP take the medicine, fewer had heart problems, and it still helped their kidneys. This means checking BNP when starting atrasentan could help doctors keep patients safe.
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.
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The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function: A Post Hoc Analysis of the SONAR Randomized Trial.
Clinical journal of the American Society of Nephrology : CJASN (2021)
Waijer SW, Gansevoort RT, Bakris GL, Correa-Rotter R, Hou FF, Kohan DE, Kitzman DW, Makino H, McMurray JJV, Perkovic V, Tobe S, Parving HH, de Zeeuw D, Heerspink HJL.
The Effect of Atrasentan on Kidney and Heart Failure Outcomes by Baseline Albuminuria and Kidney Function: A Post Hoc Analysis of the SONAR Randomized Trial.
Clin J Am Soc Nephrol.
2021 Dec;
16(12):1824-1832.
Abstract: Atrasentan reduces the risk of kidney failure but increases the risk of edema and, possibly, heart failure. Patients with severe CKD may obtain greater absolute kidney benefits from atrasentan but may also be at higher risk of heart failure. We assessed relative and absolute effects of atrasentan on kidney and heart failure events according to baseline eGFR and urinary albumin-creatinine ratio (UACR) in a analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial. The effect of atrasentan versus placebo in 3668 patients with type 2 diabetes and CKD with elevated albuminuria was examined in the SONAR trial. We used Cox proportional hazards regression analysis to study effects on the primary kidney outcome (composite of doubling of serum creatinine, kidney failure, or kidney death) and heart failure hospitalization across subgroups of eGFR (<30, ≥30-45, and ≥45 ml/min per 1.73 m) and UACR (<1000, ≥1000-3000, and ≥3000 mg/g). Atrasentan reduced the relative risk of the primary kidney outcome (hazard ratio, 0.71; 95% confidence interval, 0.58 to 0.88) consistently across all subgroups of baseline eGFR and UACR (all interaction >0.21). Patients in the highest UACR and lowest eGFR subgroups, in whom rates of the primary kidney outcome were highest, showed the largest absolute benefit (all interaction <0.01). The risk of heart failure hospitalization was higher in the atrasentan group (hazard ratio, 1.39; 95% confidence interval, 0.97 to 1.99) and was consistent across subgroups, with no evidence that relative or absolute risks differed across eGFR or UACR subgroups (all interaction >0.09). Atrasentan reduced the relative risk of the primary kidney outcome consistently across baseline UACR and eGFR subgroups. The absolute risk reduction was greater among patients in the lowest eGFR and highest albuminuria category who were at highest baseline risk. Conversely, the relative and absolute risks of heart failure hospitalization were similar across baseline UACR and eGFR subgroups. Study of Diabetic Nephropathy with Atrasentan (SONAR), NCT01858532.
Abstract Summary: Scientists did a study to see if a medicine called atrasentan helps people with diabetes and kidney problems. They looked at 3668 patients and checked if the medicine could prevent their kidneys from getting worse or if it could cause heart problems. They found that atrasentan can help protect the kidneys, especially for those with more serious kidney issues. However, it might also increase the chance of having heart problems, like heart failure. The study showed that the medicine's ability to protect the kidneys was the same for everyone, no matter how bad their kidney problem was at the start. But the risk of heart problems didn't change either, no matter the person's kidney health when they began the study. This information is important for doctors and patients to think about when choosing treatments.
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.
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Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease.
Clinical pharmacology and therapeutics (2021)
Koomen JV, Stevens J, Bakris G, Correa-Rotter R, Hou FF, Kitzman DW, Kohan DE, Makino H, McMurray JJV, Parving HH, Perkovic V, Tobe SW, de Zeeuw D, Heerspink HJL.
Individual Atrasentan Exposure is Associated With Long-term Kidney and Heart Failure Outcomes in Patients With Type 2 Diabetes and Chronic Kidney Disease.
Clin Pharmacol Ther.
2021 Jun;
109(6):1631-1638.
Abstract: Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population.
Abstract Summary: Scientists studied a medicine called atrasentan to see if it helps protect the kidneys of people with type 2 diabetes and kidney disease. They looked at how much of the medicine was in the blood and if it was linked to good results for the kidneys and heart. They found that the right amount of atrasentan in the blood helped the kidneys a lot and didn't cause too much trouble for the heart. This means that taking atrasentan every day might be a good way to help people with diabetes keep their kidneys 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.
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Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial.
Lancet (London, England) (2019)
Heerspink HJL, Parving HH, Andress DL, Bakris G, Correa-Rotter R, Hou FF, Kitzman DW, Kohan D, Makino H, McMurray JJV, Melnick JZ, Miller MG, Pergola PE, Perkovic V, Tobe S, Yi T, Wigderson M, de Zeeuw D, SONAR Committees and Investigators.
Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial.
Lancet.
2019 May 11;
393(10184):1937-1947.
Abstract: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1·73 m of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days) or end-stage kidney disease (eGFR <15 mL/min per 1·73 m sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4-2·9). 79 (6·0%) of 1325 patients in the atrasentan group and 105 (7·9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0·65 [95% CI 0·49-0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%) of 1325 patients in the atrasentan group and 34 (2·6%) of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85-2·07]; p=0·208). 58 (4·4%) patients in the atrasentan group and 52 (3·9%) in the placebo group died (HR 1·09 [95% CI 0·75-1·59]; p=0·65). Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. AbbVie.
Abstract Summary: Doctors did a big study to see if a medicine called atrasentan helps people with type 2 diabetes who also have kidney problems. They tested adults from many countries who had diabetes and signs of kidney damage. The patients took a small dose of atrasentan every day. If the medicine helped them and didn't cause too much water to build up in their bodies, they kept taking it or got a fake pill without knowing which one they got. They checked to see if the medicine stopped their kidneys from getting worse.
After watching over 2,600 patients for about 2 years, they found that those who took atrasentan were less likely to have serious kidney problems than those who took the fake pill. However, the medicine did make some people hold on to water or have anemia, and a few more people went to the hospital for heart problems compared to the fake pill group.
The study showed that atrasentan might help protect the kidneys in people with diabetes, but doctors have to be careful about the water buildup and other side effects.
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.
Genetic Risks for Bicuspid Aortic Valve Disease&Role of Rare Copy Number Variants in Bicuspid Aortic Valve&Genetic Basis of Early Onset Bicuspid Aortic Valve Disease
University of Texas Health Science Center at Houston
National Institute of Health (NIH) - 03496883 (FASTEST), rFVIIa for Acute hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial (Pro00041014)
OhioHealth Corporation
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Spontaneous intracerebral hemorrhage: Recent advances and critical thinking on future clinical trial design.
Chinese medical journal (2024)
Yu W, Alexander MJ.
Spontaneous intracerebral hemorrhage: Recent advances and critical thinking on future clinical trial design.
Chin Med J (Engl).
2024 Dec 10;
:.
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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.
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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.
National Institute of Health (NIH) - 03496883 (FASTEST), rFVIIa for Acute hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial (Pro00041014)
Massachusetts General Hospital
-
Spontaneous intracerebral hemorrhage: Recent advances and critical thinking on future clinical trial design.
Chinese medical journal (2024)
Yu W, Alexander MJ.
Spontaneous intracerebral hemorrhage: Recent advances and critical thinking on future clinical trial design.
Chin Med J (Engl).
2024 Dec 10;
:.
-
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.
-
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.
Recombinant Factor VIIa (rFVIIa) for Acute Hemorrhagic Stroke Administered at Earliest Time (FASTEST) Trial
University of California San Francisco
-
Spontaneous intracerebral hemorrhage: Recent advances and critical thinking on future clinical trial design.
Chinese medical journal (2024)
Yu W, Alexander MJ.
Spontaneous intracerebral hemorrhage: Recent advances and critical thinking on future clinical trial design.
Chin Med J (Engl).
2024 Dec 10;
:.
-
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 different kinds of treatments to see if they could stop the bleeding from getting worse. They found information from 20 studies with 4,652 people.
They learned that one medicine didn't really change the chances of dying or needing a lot of help afterward. Another kind of medicine slightly stopped the bleeding from getting worse, but it didn't really change the chances of dying or needing help either. Giving platelets, a part of blood that helps with clotting, might actually make things worse for people who had a brain bleed while taking medicine to stop blood clots. For people who had a brain bleed while on blood thinners, they weren't sure if giving a different treatment instead of the usual frozen blood plasma made a difference.
This research is important because it helps doctors understand which treatments might or might not work for people with this kind of brain bleed. More studies are being done 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.
-
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 will give the medicine or a pretend medicine to 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 checking to make sure the medicine is safe and doesn't cause other problems like heart attacks.
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.
Communication App to Manage Symptoms and Improve Adjuvant Endocrine Therapy Adherence
University of Tennessee Health Science Center
-
Symptom Monitoring App Use Associated With Medication Adherence Among Woman Survivors of Breast Cancer on Adjuvant Endocrine Therapy.
JCO clinical cancer informatics (2024)
Krukowski RA, Hu X, Arshad S, Anderson JN, Stepanski E, Vidal GA, Schwartzberg LS, Graetz I.
Symptom Monitoring App Use Associated With Medication Adherence Among Woman Survivors of Breast Cancer on Adjuvant Endocrine Therapy.
JCO Clin Cancer Inform.
2024 Dec;
8:e2400179.
Abstract: Oral adjuvant endocrine therapy (AET) reduces the risk of cancer recurrence and death for women with hormone receptor-positive (HR+) breast cancer. Because of adverse symptoms and socioecologic barriers, AET adherence rates are low. We conducted post hoc analyses of a randomized trial of a remote symptom and adherence monitoring app to evaluate characteristics associated with higher app use, satisfaction, and how app use was associated with AET adherence. Patients prescribed AET were randomly assigned to receive one of three intervention conditions: app, app + feedback, or enhanced usual care. Baseline and 6-month follow-up surveys, app use, and pillbox-monitored AET adherence data for app and app + feedback participants were used. Logistic regression evaluated the association between sociodemographic/clinical characteristics and app utilization and satisfaction, and how app use was associated with AET adherence (>80%). Overall, 163 women with early-stage HR+ breast cancer were included; 35.0% had high app use (≥75% of weeks enrolled). No sociodemographic characteristics were associated with app use. Satisfaction with the app was higher among those who were younger (88.9% for age 31-49 years 54.9% for age 65+ years, < .001), identified as White (76.8% 60.1% for Black, = .045), had lower health literacy (85.4% 68.2% with higher health literacy, = .017), or were nonurban residents (85.7% 68.6% for urban, = .021). Most participants (90.3%) with high app use were AET-adherent compared with 66.8% for those with lower app use ( < .001). Use of a remote monitoring app was similar across sociodemographic characteristics, and more frequent app use was associated with a higher likelihood of 6-month AET adherence. Encouraging women to monitor medication adherence and communicate adverse symptoms could improve AET adherence.
Abstract Summary: Doctors give women with a certain type of breast cancer a special medicine to take by mouth to help stop the cancer from coming back. But sometimes, women have a hard time sticking to their medicine schedule because it can make them feel bad or other reasons. Researchers looked at how a special app on the phone that helps women keep track of their medicine and how they feel could make it easier for them to take their medicine regularly.
They had some women use the app, some use the app and get feedback, and some just get extra attention without the app. They checked to see who used the app a lot, who liked the app, and if using the app helped women take their medicine more than 80% of the time.
They found that 35% of the women used the app a lot. Younger women, White women, women who had a harder time understanding health information, and women who didn't live in big cities liked the app more. Women who used the app a lot were more likely to take their medicine regularly.
The study shows that using an app can help women with breast cancer take their medicine as they should, which can help them stay healthy. It's important for doctors to help women use tools like this app to keep track of their 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.
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Remote Monitoring App for Endocrine Therapy Adherence Among Patients With Early-Stage Breast Cancer: A Randomized Clinical Trial.
JAMA network open (2024)
Graetz I, Hu X, Kocak M, Krukowski RA, Anderson JN, Waters TM, Curry AN, Robles A, Paladino A, Stepanski E, Vidal GA, Schwartzberg LS.
Remote Monitoring App for Endocrine Therapy Adherence Among Patients With Early-Stage Breast Cancer: A Randomized Clinical Trial.
JAMA Netw Open.
2024 Jun 3;
7(6):e2417873.
Abstract: Adjuvant endocrine therapy (AET) use among women with early-stage, hormone receptor-positive breast cancer reduces the risk of cancer recurrence, but its adverse symptoms contribute to lower adherence. To test whether remote monitoring of symptoms and treatment adherence with or without tailored text messages improves outcomes among women with breast cancer who are prescribed AET. This nonblinded, randomized clinical trial (RCT) following intention-to-treat principles included English-speaking women with early-stage breast cancer prescribed AET at a large cancer center with 14 clinics across 3 states from November 15, 2018, to June 11, 2021. All participants had a mobile device with a data plan and an email address and were asked to use an electronic pillbox to monitor AET adherence and to complete surveys at enrollment and 1 year. Participants were randomized into 3 groups: (1) an app group, in which participants received instructions for and access to the study adherence and symptom monitoring app for 6 months; (2) an app plus feedback group, in which participants received additional weekly text messages about managing symptoms, adherence, and communication; or (3) an enhanced usual care (EUC) group. App-reported missed doses, increases in symptoms, and occurrence of severe symptoms triggered follow-ups from the oncology team. The primary outcome was 1-year, electronic pillbox-captured AET adherence. Secondary outcomes included symptom management abstracted from the medical record, as well as patient-reported health care utilization, symptom burden, quality of life, physician communication, and self-efficacy for managing symptoms. Among 304 female participants randomized (app group, 98; app plus feedback group, 102; EUC group, 104), the mean (SD) age was 58.6 (10.8) years (median, 60 years; range, 31-83 years), and 60 (19.7%) had an educational level of high school diploma or less. The study completion rate was 87.5% (266 participants). There were no statistically significant differences by treatment group in AET adherence (primary outcome): 76.6% for EUC, 73.4% for the app group (difference vs EUC, -3.3%; 95% CI, -11.4% to 4.9%; P = .43), and 70.9% for the app plus feedback group (difference vs EUC, -5.7%; 95% CI, -13.8% to 2.4%; P = .17). At the 1-year follow-up, app plus feedback participants had fewer total health care encounters (adjusted difference, -1.23; 95% CI, -2.03 to -0.43; P = .003), including high-cost encounters (adjusted difference, -0.40; 95% CI, -0.67 to -0.14; P = .003), and office visits (adjusted difference, -0.82; 95% CI, -1.54 to -0.09; P = .03) over the previous 6 months compared with EUC participants. This RCT found that a remote monitoring app with alerts to the patient's care team and tailored text messages to patients did not improve AET adherence among women with early-stage breast cancer; however, it reduced overall and high-cost health care encounters and office visits without affecting quality of life. ClinicalTrials.gov Identifier: NCT03592771.
Abstract Summary: Doctors want to help women with a certain kind of early breast cancer take their medicine regularly because it can stop the cancer from coming back. But sometimes, the medicine can make them feel bad, and they might not take it as they should. To see if they could help, doctors did a study with 304 women. They gave some women an app to track when they took their medicine and how they felt. Some also got special text messages with advice. Another group just got regular care. They found that the app and texts didn't help women take their medicine more, but those who got texts went to the doctor less and saved money on healthcare without feeling worse. This study shows that while the app and texts didn't help with taking medicine, they did help in other ways.
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.
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THRIVE study protocol: a randomized controlled trial evaluating a web-based app and tailored messages to improve adherence to adjuvant endocrine therapy among women with breast cancer.
BMC health services research (2019)
Paladino AJ, Anderson JN, Krukowski RA, Waters T, Kocak M, Graff C, Blue R, Jones TN, Buzaglo J, Vidal G, Schwartzberg L, Graetz I.
THRIVE study protocol: a randomized controlled trial evaluating a web-based app and tailored messages to improve adherence to adjuvant endocrine therapy among women with breast cancer.
BMC Health Serv Res.
2019 Dec 19;
19(1):977.
Abstract: Long-term use of adjuvant endocrine therapy (AET) among women with early-stage, hormone receptor-positive breast cancer significantly reduces the risk of hospitalizations, cancer recurrence, and mortality. AET is associated with adverse symptoms that often result in poor adherence. A web-enabled app offers a novel way to communicate and manage symptoms for women on AET. In a region with significant racial disparities in breast cancer outcomes, our study tests the impact of a web-enabled app that collects and transmits patient-reported symptoms to healthcare teams to facilitate timely and responsive symptom management on medication adherence. In this randomized controlled trial, we randomize 300 patients initiating AET to one of three arms: 1) an "App" group (n = 100) that receives weekly reminders to use the THRIVE study app; 2) an "App+Feedback" group (n = 100) that receives weekly reminders and tailored feedback based on their use of the app; or 3) a "Usual Care" group (n = 100) that receives usual care only. Participants are stratified by race: 50% White and 50% Black. The duration of the intervention is six months following enrollment, and outcomes are assessed at 12-months. The primary outcome is adherence, which is captured using an electronic monitoring pillbox. Secondary outcomes include symptom burden, quality of life, self-efficacy for managing symptoms, and healthcare costs. We also evaluate the impact of the intervention on racial disparities in adherence. Data are derived from three sources: electronic health record data to capture treatment changes, healthcare utilization, and health outcomes; self-report survey data related to adherence, symptom burden, and quality of life; and an electronic medication monitoring device that captures adherence. A successful web-enabled intervention could be disseminated across systems, conditions, and populations. By evaluating the impact of this intervention on a comprehensive set of measures, including AET adherence, patient outcomes, and costs, our study will provide valuable and actionable results for providers, policy makers, and insurers who strive to achieve the "Triple Aim" - reduce costs while improving health outcomes and the patient care experience. NCT03592771. Prospectively registered on July 19, 2018.
Abstract Summary: Doctors found that a special medicine helps women with a certain kind of breast cancer stay healthy and out of the hospital. But sometimes, the medicine can make them feel bad, and they stop taking it. The study is about a new app that helps these women tell their doctors about any bad feelings from the medicine. They are checking if the app helps women keep taking their medicine. They have 300 women in the study, and they are split into three groups. One group uses the app, another group gets messages from the app, and the last group doesn't use the app. They are looking at women of different races to see if the app helps everyone the same. They will use pill bottles that record when the medicine is taken, ask the women questions, and look at their health records to see if the app works. If the app helps, it could be used for more people and different health problems. This could make healthcare better and less expensive.
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.
Quantitative Evaluation of Visual and Auditory Dysfunction and Multi-Sensory Integration in Complex TBI Patients
Vanderbilt University Medical Center
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Primary Visual Pathway Changes in Individuals With Chronic Mild Traumatic Brain Injury.
JAMA ophthalmology (2024)
Rasdall MA, Cho C, Stahl AN, Tovar DA, Lavin P, Kerley CI, Chen Q, Ji X, Colyer MH, Groves L, Longmuir R, Chomsky A, Gallagher MJ, Anderson A, Landman BA, Rex TS.
Primary Visual Pathway Changes in Individuals With Chronic Mild Traumatic Brain Injury.
JAMA Ophthalmol.
2024 Nov 27;
:.
Abstract: Individuals with mild traumatic brain injury (TBI) often report vision problems despite having normal visual acuity and fundus examinations. Diagnostics are needed for these patients. To determine if a battery of assessments or machine-learning approaches can aid in diagnosing visual dysfunction in patients with mild TBI. This prospective, observational, case-control study was conducted between May 2018 and November 2021. The study setting was at a level 1 trauma research hospital. Participant eligibility included adult males and females with recorded best-corrected visual acuity and normal fundus examination. Individuals in the case group had a history of mild TBI; controls had no history of TBI. Exclusion criteria included a history of ocular, neurological, or psychiatric disease, moderate-severe TBI, recent TBI, metal implants, age younger than 18 years, and pregnancy. Cases and controls were sex- and age-matched. Data analysis was performed from July 2023 to March 2024. History of mild TBI in the case group. The single-session visit included the Neurobehavioral Symptom Inventory and measurements of oculomotor function, optical coherence tomography, contrast sensitivity, visual evoked potentials, visual field testing, and magnetic resonance imaging. A total of 28 participants (mean [SD] age, 35.0 [12.8] years; 15 male [53.6%]) with mild TBI and 28 controls (mean [SD] age, 35.8 [8.5] years; 19 female [67.9%]) were analyzed. Participants with mild TBI showed reduced prism convergence test breakpoint (-8.38; 95% CI, -14.14 to -2.62; P = .008) and recovery point (-8.44; 95% CI, -13.82 to -3.06; P = .004). Participants with mild TBI also had decreased contrast sensitivity (-0.07; 95% CI, -0.13 to -0.01; P = .04) and increased visual evoked potential binocular summation index (0.32; 95% CI, 0.02-0.63; P = .02). A subset of participants exhibited reduced peripapillary retinal nerve fiber layer thickness, increased optic nerve/sheath size, and brain cortical volumes. Machine learning identified subtle differences across the primary visual pathway, including the optic radiations and occipital lobe regions, independent of visual symptoms. Results of this case-control study suggest that the visual system was affected in individuals with mild TBI, even in those who did not self-report vision problems. These findings support the utility of a battery of assessments or machine-learning approaches to accurately diagnose this population.
Abstract Summary: Scientists did a study to see if special tests and computer programs could help find eye problems in people who had a small injury to their brain, even if they think they can see just fine. They looked at adults who had this kind of brain injury and compared them to people who didn't. They did a bunch of eye tests and also took pictures of their brains. They found that the people with the brain injury had some trouble with their eyes that the tests could see, even when the people didn't notice any problems themselves. This means that using these tests and computer programs could really help doctors figure out if someone's eyes are not working right after a small brain injury.
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.
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Joint analysis of structural connectivity and cortical surface features: correlates with mild traumatic brain injury.
Proceedings of SPIE--the International Society for Optical Engineering (2021)
Kerley CI, Cai LY, Yu C, Crawford LM, Elenberger JM, Singh ES, Schilling KG, Aboud KS, Landman BA, Rex TS.
Joint analysis of structural connectivity and cortical surface features: correlates with mild traumatic brain injury.
Proc SPIE Int Soc Opt Eng.
2021;
11596:.
Abstract: Mild traumatic brain injury (mTBI) is a complex syndrome that affects up to 600 per 100,000 individuals, with a particular concentration among military personnel. About half of all mTBI patients experience a diverse array of chronic symptoms which persist long after the acute injury. Hence, there is an urgent need for better understanding of the white matter and gray matter pathologies associated with mTBI to map which specific brain systems are impacted and identify courses of intervention. Previous works have linked mTBI to disruptions in white matter pathways and cortical surface abnormalities. Herein, we examine these hypothesized links in an exploratory study of joint structural connectivity and cortical surface changes associated with mTBI and its chronic symptoms. Briefly, we consider a cohort of 12 mTBI and 26 control subjects. A set of 588 cortical surface metrics and 4,753 structural connectivity metrics were extracted from cortical surface regions and diffusion weighted magnetic resonance imaging in each subject. Principal component analysis (PCA) was used to reduce the dimensionality of each metric set. We then applied independent component analysis (ICA) both to each PCA space individually and together in a joint ICA approach. We identified a stable independent component across the connectivity-only and joint ICAs which presented significant group differences in subject loadings (p<0.05, corrected). Additionally, we found that two mTBI symptoms, slowed thinking and forgetfulness, were significantly correlated (p<0.05, corrected) with mTBI subject loadings in a surface-only ICA. These surface-only loadings captured an increase in bilateral cortical thickness.
Abstract Summary: Scientists are studying how mild brain injuries, which happen a lot, especially in the military, can cause long-term problems like thinking slowly or forgetting things. They looked at the brains of 12 people with these injuries and 26 people without them, using special brain scans to measure the brain's connections and the surface of the brain. They used math to make sense of all the information they got from the scans. They found that people with brain injuries had different brain connections and thicker areas in some parts of their brain. Understanding these changes can help doctors figure out how to help people with these injuries 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.
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MRI correlates of chronic symptoms in mild traumatic brain injury.
Proceedings of SPIE--the International Society for Optical Engineering (2020)
Kerley CI, Schilling KG, Blaber J, Miller B, Newton A, Anderson AW, Landman BA, Rex TS.
MRI correlates of chronic symptoms in mild traumatic brain injury.
Proc SPIE Int Soc Opt Eng.
2020;
11313:.
Abstract: Some veterans with a history of mild traumatic brain injury (mTBI) have reported experiencing auditory and visual dysfunction that persist beyond the acute phase of the incident. The etiology behind these symptoms is difficult to characterize, since mTBI is defined by negative imaging findings on current clinical imaging. There are several competing hypotheses that could explain functional deficits; one example is shear injury, which may manifest in diffusion-weighted magnetic resonance (MR) imaging (DWI). Herein, we explore this alternative hypothesis in a pilot study of multi-parametric MR imaging. Briefly, we consider a cohort of 8 mTBI patients relative to 22 control subjects using structural T1-weighted imaging (T1w) and connectivity with DWI. 1,344 metrics were extracted per subject from whole brain regions and connectivity patterns in sensory networks. For each set of imaging-derived metrics, the control subject metrics were embedded in a low-dimensional manifold with principal component analysis, after which mTBI subject metrics were projected into the same space. These manifolds were employed to train support vector machines (SVM) to classify subjects as controls or mTBI. Two of the SVMs trained achieved near-perfect accuracy averaged across four-fold cross-validation. Additionally, we present correlations between manifold dimensions and 22 self-reported mTBI symptoms and find that five principal components from the manifolds (one component from the T1w manifold and four components from the DWI manifold) are significantly correlated with symptoms (p<0.05, uncorrected). The novelty of this work is that the DWI and T1w imaging metrics seem to contain information critical for distinguishing between mTBI and control subjects. This work presents an analysis of the pilot phase of data collection of the Quantitative Evaluation of Visual and Auditory Dysfunction and Multi-Sensory Integration in Complex TBI Patients study and defines specific hypotheses to be tested in the full sample.
Abstract Summary: Some soldiers who have hurt their heads in a mild way (mTBI) have problems with seeing and hearing that don't go away quickly. It's hard to figure out why this happens because the tools doctors use to look at the brain don't show anything wrong. In this small study, researchers used special brain scans on 8 soldiers with mTBI and compared them to 22 people without mTBI. They looked at lots of different brain measurements and used a computer program to see if they could tell the difference between the two groups. They found that their method worked really well and could also connect the brain scan results to the problems the soldiers said they were having. This study is important because it shows that these new brain scans might help us understand and maybe even help soldiers with these kinds of 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.
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Distortion correction of diffusion weighted MRI without reverse phase-encoding scans or field-maps.
PloS one (2020)
Schilling KG, Blaber J, Hansen C, Cai L, Rogers B, Anderson AW, Smith S, Kanakaraj P, Rex T, Resnick SM, Shafer AT, Cutting LE, Woodward N, Zald D, Landman BA.
Distortion correction of diffusion weighted MRI without reverse phase-encoding scans or field-maps.
PLoS One.
2020;
15(7):e0236418.
Abstract: Diffusion magnetic resonance images may suffer from geometric distortions due to susceptibility induced off resonance fields, which cause geometric mismatch with anatomical images and ultimately affect subsequent quantification of microstructural or connectivity indices. State-of-the art diffusion distortion correction methods typically require data acquired with reverse phase encoding directions, resulting in varying magnitudes and orientations of distortion, which allow estimation of an undistorted volume. Alternatively, additional field maps acquisitions can be used along with sequence information to determine warping fields. However, not all imaging protocols include these additional scans and cannot take advantage of state-of-the art distortion correction. To avoid additional acquisitions, structural MRI (undistorted scans) can be used as registration targets for intensity driven correction. In this study, we aim to (1) enable susceptibility distortion correction with historical and/or limited diffusion datasets that do not include specific sequences for distortion correction and (2) avoid the computationally intensive registration procedure typically required for distortion correction using structural scans. To achieve these aims, we use deep learning (3D U-nets) to synthesize an undistorted b0 image that matches geometry of structural T1w images and intensity contrasts from diffusion images. Importantly, the training dataset is heterogenous, consisting of varying acquisitions of both structural and diffusion. We apply our approach to a withheld test set and show that distortions are successfully corrected after processing. We quantitatively evaluate the proposed distortion correction and intensity-based registration against state-of-the-art distortion correction (FSL topup). The results illustrate that the proposed pipeline results in b0 images that are geometrically similar to non-distorted structural images, and more closely match state-of-the-art correction with additional acquisitions. In addition, we show generalizability of the proposed approach to datasets that were not in the original training / validation / testing datasets. These datasets included varying populations, contrasts, resolutions, and magnitudes and orientations of distortion and show efficacious distortion correction. The method is available as a Singularity container, source code, and an executable trained model to facilitate evaluation.
Abstract Summary: Scientists are trying to fix a problem with certain brain scans called diffusion MRI images. These images can sometimes get squished or stretched in the wrong way, which makes it hard to match them up with other types of brain scans. Usually, to fix this, they need extra scans that show how the images got messed up, but not all hospitals do these extra scans.
In this study, the scientists made a special computer program that can guess how to fix the squished images without needing the extra scans. They used something called deep learning, which is like teaching a computer to think like a human brain, to make the program. They tested it and found that it works really well, even on brain scans from different hospitals or different types of people.
This is great because it means doctors can get a better look at the brain without needing extra scans, which can save time and money. The scientists shared their computer program online so other people can use it to help fix their brain scans 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.
The Impact of Social Determinants of Health on Women with Incontinence Living in Rural Communities
Vanderbilt University Medical Center
Technology to Enhance Treatment for Early Conduct Problems in Low Income Families
University of North Carolina at Chapel Hill
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Helping the Noncompliant Child and Child Behavior Outcomes: An Exploratory Examination of Financial Strain.
Prevention science : the official journal of the Society for Prevention Research (2024)
Highlander A, Parent J, J Jones D.
Helping the Noncompliant Child and Child Behavior Outcomes: An Exploratory Examination of Financial Strain.
Prev Sci.
2024 Nov 8;
:.
Abstract: Theoretical models and empirical research have highlighted the impact of economic disadvantage on children's psychosocial development broadly and the onset, maintenance, and treatment of early-onset (3-8 years) behavior disorders (BDs) more specifically. In the context of intervention, evidence suggests that economic disadvantage may pose risk for diminished parent-mediated treatment efficacy (e.g., Behavioral Parent Training [BPT]) given its impact on salient factors in the family system. Though, studies have shown significant variability in BPT outcomes within families experiencing economic disadvantage, suggesting that additional influences may further contribute to disparities in the trajectory of treatment and maintenance of treatment gains for this population. To address this gap in existing knowledge, financial strain, or the inability to meet financial needs, was examined in families (N = 54) of young children (3-8 years old) with low-income and clinically elevated behavior problems participating in one BPT program, Helping the Noncompliant Child (HNC). Results demonstrated that families who experienced greater levels of financial strain prior to engaging in HNC exhibited diminished maintenance of parent reported child behavior gains following treatment. Financial strain did not significantly influence rate of change or maintenance of treatment gains for HNC clinician-coded child compliance. Clinical implications and directions for future research are discussed. ClinicalTrials.gov Identifier: NCT02191956, registered on 6/18/2014.
Abstract Summary: Scientists have been studying how not having enough money affects kids' behavior and emotions, especially when they have behavior problems between the ages of 3 and 8. They noticed that when parents don't have much money, it's harder for them to help their kids get better, even with special parent training programs. To learn more, researchers looked at 54 families with not a lot of money and kids who didn't listen well. These families tried a program called Helping the Noncompliant Child. They found that the families with the most money problems didn't see as much long-term improvement in their kids' behavior after the program. The study didn't find that money problems changed how quickly kids started to listen during the program, though. This research helps us understand that for families with less money, we might need to do more to help them keep their kids on track after they finish a behavior program.
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.
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A randomized controlled trial of technology-enhanced behavioral parent training: sustained parent skill use and child outcomes at follow-up.
Journal of child psychology and psychiatry, and allied disciplines (2022)
Parent J, Anton MT, Loiselle R, Highlander A, Breslend N, Forehand R, Hare M, Youngstrom JK, Jones DJ.
A randomized controlled trial of technology-enhanced behavioral parent training: sustained parent skill use and child outcomes at follow-up.
J Child Psychol Psychiatry.
2022 Sep;
63(9):992-1001.
Abstract: Early-onset (3-8 years old) disruptive behavior disorders (DBDs) have been linked to a range of psychosocial sequelae in adolescence and beyond, including delinquency, depression, and substance use. Given that low-income families are overrepresented in statistics on early-onset DBDs, prevention and early-intervention targeting this population is a public health imperative. The efficacy of Behavioral Parent Training (BPT) programs such as Helping the Noncompliant Child (HNC) has been called robust; however, given the additional societal and structural barriers faced by low-income families, family engagement and retention barriers can cause effects to wane with time. This study extends preliminary work by examining the potential for a Technology-Enhanced HNC (TE-HNC) program to improve and sustain parent skill proficiency and child outcomes among low-income families. A randomized controlled trial with two parallel arms was the design for this study. A total of 101 children (3-8-years-old) with clinically significant problem behaviors from low-income households were randomized to HNC (n = 54) or TE-HNC (n = 47). Participants were assessed at pre-treatment, post-treatment, 3-month, and 6-month follow-ups. Primary outcomes were parent-reported and observed child behavior problems. Secondary outcomes included observed parenting skills use (ClinicalTrials.gov Identifier: NCT02191956). Primary analyses used latent curve modeling to examine treatment differences in the trajectory of change during treatment, maintenance of treatment gains, and levels of outcomes at the 6-month follow-up. Both programs yielded improvements in parenting skills and child problems at post-treatment. However, TE-HNC families evidenced greater maintenance of parent-reported and observed child behavior and observed positive parenting skills at the 6-month follow-up. Our findings contribute to an ongoing line of work suggesting that technology-enhanced treatment models hold promise for increasing markers of engagement in BPT and sustaining long-term outcomes among low-income families.
Abstract Summary: Scientists studied how to help kids aged 3 to 8 who have trouble behaving, especially those from families with less money. They tested a special program that teaches parents how to deal with their kids' behavior. Some families used the regular program, while others used a version with extra technology help. They checked on the families before and after the program, and then again 3 and 6 months later. They found that both programs helped parents and kids, but the tech version was better at keeping the good results even after 6 months. This study shows that using technology can make it easier for families with less money to stick with the program and help their kids behave better for a longer 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.
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The relationships between religiosity and youth internalizing symptoms in African American parent-adolescent dyads.
Cultural diversity & ethnic minority psychology (2018)
Faro AL, McKee LG, Garcia RL, Jones DJ.
The relationships between religiosity and youth internalizing symptoms in African American parent-adolescent dyads.
Cultur Divers Ethnic Minor Psychol.
2018 Jan;
24(1):139-149.
Abstract: African American (AA) adolescents face a greater risk of internalizing symptoms, including symptoms of both depression and anxiety, compared with other racial groups; yet, relatively less is known about the variables that contribute to internalizing symptoms. With the aim of advancing this work, this study examined factors that may buffer against such symptoms (maternal warmth, religiosity), as well as those that may confer additional risk (maternal psychopathology). One hundred ninety-three AA single mothers and their adolescent youth reported on religiosity, maternal warmth and depressive symptoms, and youth internalizing symptoms. Dyadic structural equation modeling was used to examine the effects of mother and adolescent religiosity, maternal warmth, maternal depressive symptoms, and adolescent age on youth internalizing symptoms as reported by both the mother and the adolescent. Consistent with hypotheses, maternal depressive symptoms were significantly associated with youth internalizing symptoms (as reported by the adolescent). Further, the impact of maternal religiosity on self-reported youth internalizing symptoms and its subscales was moderated by adolescent age. Specifically, maternal religiosity was associated with fewer self-reported internalizing symptoms in young adolescents, whereas the effect waned in older youth. Possible predictive coprocesses such as maternal influence on adolescent religious choices and identity formation are explored in the context of adolescent internalizing symptomatology. (PsycINFO Database Record
Abstract Summary: This study looked at why some African American teenagers might feel more sad or worried than kids from other groups. The researchers wanted to see if a mom's love, her own mental health, and how religious the family is could make a difference in these feelings. They asked 193 African American moms and their kids about their beliefs, how much love the mom shows, and how the kids are feeling.
They found that if a mom was feeling depressed, her child was more likely to feel sad or worried too. Also, if the mom was religious, it helped younger kids not feel as bad, but it didn't really help the older teenagers as much. This research helps us understand that a mom's feelings and beliefs can really affect her kids, especially when they're younger. It's important for everyone to know this so we can help kids who are feeling down or anxious.
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.
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Socioeconomic status, parenting, and externalizing problems in African American single-mother homes: A person-oriented approach.
Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) (2015)
Anton MT, Jones DJ, Youngstrom EA.
Socioeconomic status, parenting, and externalizing problems in African American single-mother homes: A person-oriented approach.
J Fam Psychol.
2015 Jun;
29(3):405-415.
Abstract: African American youth, particularly those from single-mother homes, are overrepresented in statistics on externalizing problems. The family is a central context in which to understand externalizing problems; however, reliance on variable-oriented approaches to the study of parenting, which originate from work with intact, middle-income, European American families, may obscure important information regarding variability in parenting styles among African American single mothers, and in turn, variability in youth outcomes as well. The current study demonstrated that within African American single-mother families: (a) a person-, rather than variable-, oriented approach to measuring parenting style may further elucidate variability; (b) socioeconomic status may provide 1 context within which to understanding variability in parenting style; and (c) 1 marker of socioeconomic status, income, and parenting style may each explain variability in youth externalizing problems; however, the interaction between income and parenting style was not significant. Findings have potential implications for better understanding the specific contexts in which externalizing problems may be most likely to occur within this at-risk and underserved group.
Abstract Summary: This study looked at why some African American kids, especially those with just their mom at home, might act out more. Instead of just looking at things one by one, the researchers tried to see the whole picture of how moms raise their kids. They found that how much money a family has can change the way moms parent, and this can affect kids' behavior. But, the mix of money and parenting style didn't really make a big difference in how kids acted. This research helps us understand better why some kids might have trouble and how to help 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.
Customized Cortical Stimulation Therapy in the Rehabilitation of Stroke Patients
Emory University
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Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial.
Neurorehabilitation and neural repair (2024)
Wischnewski M, Edwards L, Revill KP, Drake D, Hobbs G, Buetefisch CM.
Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial.
Neurorehabil Neural Repair.
2024 Oct 27;
:15459683241292615.
Abstract: Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) protocols targeting primary motor cortex (M1) are used in rehabilitation of neurological diseases for their therapeutic potential, safety, and tolerability. Although lower intensity LF-rTMS can modulate M1 neurophysiology, results are variable, and a systematic assessment of its dose effect is lacking. To determine the dose-response of LF-rTMS on stimulated and non-stimulated M1. In a sham-controlled randomized double-blind crossover study the effect of LF-TMS protocols were determined in 20 right-handed older healthy participants. In 3 sessions, 1 Hz rTMS at 80% (rTMS), 90% (rTMS) of motor threshold or sham stimulation were applied to left upper extremity M1. Outcome measures were curve parameters of the stimulus-response curve (maximum motor evoked potential [MEP], slope and the intensity to evoke 50% MEP), short-interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI). Within LF-rTMS sessions, rTMS, increased MEP in the stimulated M1. Furthermore, rTMS, increased the slope in the non-stimulated M1. LF-rTMS effects on SICI were dependent on the participants' baseline SICI, hemisphere, and intensity of conditioning pulse. Finally, rTMS increased whereas rTMS decreased IHI, for both IHI directions. These changes were dependent on baseline IHI and hemisphere and were no longer significant when baseline IHI was accounted for. Intensity of subthreshold LF-rTMS has differential effects on excitation and inhibition of stimulated and non-stimulated M1. The effects were small and were only demonstrated within the LF-rTMS sessions but were not different when compared to sham. rTMS related changes in SICI and IHI were dependent on baseline level. NCT02544503, NCT01726218.
Abstract Summary: Scientists did a study to see how a special kind of low-strength brain stimulation affects the part of the brain that controls movement. They used a machine to send magnetic pulses to the brains of 20 older people who were right-handed. They did this three times with different strengths or a pretend (sham) treatment. They measured how the brain's movement area responded, both where they stimulated and on the other side of the brain.
They found that the brain's response changed a little bit when they used the magnetic pulses, but these changes were not very big and were only seen during the treatment. The changes depended on how the person's brain worked before the treatment. The results help us understand how this brain stimulation works, but more research is needed to see how it can help people with brain diseases.
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.
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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.
TREAT (Time Restricted EATing) to improve cardiometabolic health
Columbia University
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Late eating is associated with poor glucose tolerance, independent of body weight, fat mass, energy intake and diet composition in prediabetes or early onset type 2 diabetes.
Nutrition & diabetes (2024)
Díaz-Rizzolo DA, Santos Baez LS, Popp CJ, Borhan R, Sordi-Guth A, Manoogian ENC, Panda S, Cheng B, Laferrère B.
Late eating is associated with poor glucose tolerance, independent of body weight, fat mass, energy intake and diet composition in prediabetes or early onset type 2 diabetes.
Nutr Diabetes.
2024 Oct 25;
14(1):90.
Abstract: This study investigates the impact of habitual late calorie intake on glucose metabolism in adults with overweight or obesity and diet or metformin-controlled prediabetes or type 2 diabetes independently of body weight, fat mass, energy intake or diet composition. Participants (n = 26) were classified as Later Eaters (LE) if ≥45% daily calories were consumed after 5 pm and Early Eaters (EE) if not, based on daily caloric intake assessed over 2-wk. EE and LE did not differ in anthropometrics or daily energy intake, but LE consumed more carbohydrates (p = 0.038) and fats (p = 0.039) after 5 pm. Fasting glucose, insulin, and C-peptide did not differ between groups but LE exhibited higher glucose concentrations after an oral glucose tolerance test (p = 0.001), even after adjusting for body weight, fat mass, energy intake and diet composition (p < 0.05). Glucose results remained when participants with T2D were excluded (p = 0.031). After diabetes status adjustment, differences in glucose concentrations were higher in LE for time 30 (p = 0.028) and 60 min (p = 0.036). LE, compared to EE, had poorer glucose tolerance, independent of body weight, fat mass, daily energy intake and diet composition. ClinicalTrials.gov: NCT04465721.
Abstract Summary: Scientists did a study to see if eating late affects blood sugar levels in people who are a bit heavy and have early signs of diabetes or actual diabetes, but are keeping it under control with diet or medicine. They had 26 people join the study. Some ate most of their food after 5 pm (Later Eaters), and some did not (Early Eaters). They found that the Later Eaters and Early Eaters were similar in size and how much they ate every day, but Later Eaters had more carbs and fats after 5 pm. When they checked their blood sugar levels after drinking a sugary drink, the Later Eaters had higher blood sugar levels, even when the scientists considered their weight, body fat, how much they ate, and what they ate. This was true even for those who didn't have full-blown diabetes yet. The study shows that eating late might make it harder for the body to handle sugar, which is important for everyone to know, especially people who are trying to avoid diabetes or manage 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.
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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.
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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.
Text Message Safety Behavior Fading Intervention for Appearance Concerns
Florida State University
Whole Prediabetes: A Precision Nutrition Approach to Test the Feasibility of Delivering a Family-Centered Whole Foods Diet in Adults with Prediabetes and their Offspring
Vanderbilt University Medical Center
Supporting Our Caregivers In ADRD Learning (SOCIAL): Reducing Stress for Caregivers of Persons with Dementia
Massachusetts General Hospital
Recurrence Markers, Cognitive Burden and Neurobiological Homeostasis in Late-Life Depression (Rembrandt)
Vanderbilt University Medical Center
Alzheimer's Disease Neuroimaging Initiative 3
Vanderbilt University Medical Center
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Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort.
Alzheimer's & dementia : the journal of the Alzheimer's Association (2024)
Miller AA, Sharp ES, Wang S, Zhao Y, Mecca AP, van Dyck CH, O'Dell RS, Alzheimer's Disease Neuroimaging Initiative (ADNI).
Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort.
Alzheimers Dement.
2024 Nov;
20(11):7847-7858.
Abstract: Hearing loss is identified as one of the largest modifiable risk factors for cognitive impairment and dementia. Studies evaluating this relationship have yielded mixed results. We investigated the longitudinal relationship between self-reported hearing loss and cognitive/functional performance in 695 cognitively normal (CN) and 941 participants with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative. Within CN participants with hearing loss, there was a significantly greater rate of cognitive decline per modified preclinical Alzheimer's cognitive composite. Within both CN and MCI participants with hearing loss, there was a significantly greater rate of functional decline per the functional activities questionnaire (FAQ). In CN and MCI participants, hearing loss did not significantly contribute to the risk of progression to a more impaired diagnosis. These results confirm previous studies demonstrating a significant longitudinal association between self-reported hearing loss and cognition/function but do not demonstrate an increased risk of conversion to a more impaired diagnosis. NCT00106899 (ADNI: Alzheimer's Disease Neuroimaging Initiative, clinicaltrials.gov), NCT01078636 (ADNI-GO: Alzheimer's Disease Neuroimaging Initiative Grand Opportunity, clinicaltrials.gov), NCT01231971 (ADNI2: Alzheimer's Disease Neuroimaging Initiative 2, clinicaltrials.gov), NCT02854033 (ADNI3: Alzheimer's Disease Neuroimaging Initiative 3, clinicaltrials.gov). Hearing loss is a potential modifiable risk factor for dementia. We assessed the effect of self-reported hearing loss on cognition and function in the ADNI cohort. Hearing loss contributes to significantly faster cognitive and functional decline. Hearing loss was not associated with conversion to a more impaired diagnosis.
Abstract Summary: Scientists studied how hearing loss might affect people's thinking skills and daily activities over time. They looked at two groups of older adults: some with normal thinking skills and some with mild thinking problems. They found that people who said they had trouble hearing also seemed to have their thinking skills and ability to do daily tasks get worse faster than those who didn't report hearing problems. However, hearing loss didn't seem to make it more likely for someone to develop serious thinking problems. This study helps us understand that having trouble hearing might be linked to how well our brains work as we 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.
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Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis.
Alzheimer's & dementia : the journal of the Alzheimer's Association (2024)
Howe MD, Caruso MR, Manoochehri M, Kunicki ZJ, Emrani S, Rudolph JL, Huey ED, Salloway SP, Oh H, Alzheimer's Disease Neuroimaging Initiative.
Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis.
Alzheimers Dement.
2024 Oct;
20(10):7220-7231.
Abstract: The relationship between cerebrovascular disease (CVD) and amyloid beta (Aβ) in Alzheimer's disease (AD) is understudied. We hypothesized that magnetic resonance imaging (MRI)-based CVD biomarkers-including cerebral microbleeds (CMBs), lacunar infarction, and white matter hyperintensities (WMHs)-would correlate with Aβ positivity on positron emission tomography (Aβ-PET). We cross-sectionally analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 1352). Logistic regression was used to calculate odds ratios (ORs), with Aβ-PET positivity as the standard-of-truth. Following adjustment, WMHs (OR = 1.25) and superficial CMBs (OR = 1.45) remained positively associated with Aβ-PET positivity (p < 0.001). Deep CMBs and lacunes exhibited a varied relationship with Aβ-PET in cognitive subgroups. The combined diagnostic model, which included CVD biomarkers and other accessible measures, significantly predicted Aβ-PET (pseudo-R= 0.41). The study highlights the translational value of CVD biomarkers in diagnosing AD, and underscores the need for more research on their inclusion in diagnostic criteria. gov: ADNI-2 (NCT01231971), ADNI-3 (NCT02854033). Cerebrovascular biomarkers linked to amyloid beta (Aβ) in Alzheimer's disease (AD). White matter hyperintensities and cerebral microbleeds reliably predict Aβ-PET positivity. Relationships with Aβ-PET vary by cognitive stage. Novel accessible model predicts Aβ-PET status. Study supports multimodal diagnostic approaches.
Abstract Summary: Scientists wanted to see if certain signs of blood vessel problems in the brain could help us understand Alzheimer's disease better. They used special brain scans called MRI and PET scans to look at these signs, which include tiny brain bleeds, small strokes, and bright spots on the MRI that show damaged areas. They studied a lot of people's brain scans and found that the bright spots and the tiny bleeds on the surface of the brain were often seen in people who also had signs of Alzheimer's on their PET scans. However, the relationship between these signs and Alzheimer's changed depending on how bad a person's memory and thinking problems were. They created a new way to predict if someone might have Alzheimer's by looking at these brain scan signs and other simple tests. This study helps doctors think about using different kinds of tests to diagnose Alzheimer's 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.
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Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis.
medRxiv : the preprint server for health sciences (2024)
Howe MD, Caruso MR, Manoochehri M, Kunicki ZJ, Emrani S, Rudolph JL, Huey ED, Salloway SP, Oh H, Alzheimer’s Disease Neuroimaging Initiative.
Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis.
medRxiv.
2024 May 28;
:.
Abstract: The relationship between cerebrovascular disease (CVD) and amyloid-β (Aβ) in Alzheimer disease (AD) is understudied. We hypothesized that magnetic resonance imaging (MRI)-based CVD biomarkers, including cerebral microbleeds (CMBs), ischemic infarction, and white matter hyperintensities (WMH), would correlate with Aβ positivity on positron emission tomography (Aβ-PET). We cross-sectionally analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, N=1,352). Logistic regression was used to calculate odds ratios (ORs), with Aβ-PET positivity as the standard-of-truth. Following adjustment, WMH (OR=1.25) and superficial CMBs (OR=1.45) remained positively associated with Aβ-PET positivity (p<.001). Deep CMBs and infarcts exhibited a varied relationship with Aβ-PET in cognitive subgroups. The combined diagnostic model, which included CVD biomarkers and other accessible measures, significantly predicted Aβ-PET (pseudo-R =.41). The study highlights the translational value of CVD biomarkers in diagnosing AD, and underscores the need for more research on their inclusion in diagnostic criteria. ADNI-2 ( NCT01231971 ), ADNI-3 ( NCT02854033 ).
Abstract Summary: Scientists did a study to see if certain signs of blood vessel problems in the brain can help tell if someone has Alzheimer's disease. They used special brain scans called MRI and PET scans to look for these signs in 1,352 people. They found that two signs, called white matter hyperintensities and cerebral microbleeds, were often seen in people who had Alzheimer's. This means that checking for these signs could help doctors figure out if someone has Alzheimer's. The study shows that it's important to learn more about how these brain blood vessel signs can help in diagnosing Alzheimer's 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.
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Associations of longitudinal plasma p-tau181 and NfL with tau-PET, Aβ-PET and cognition.
Journal of neurology, neurosurgery, and psychiatry (2021)
Rauchmann BS, Schneider-Axmann T, Perneczky R, Alzheimer's Disease Neuroimaging Initiative (ADNI).
Associations of longitudinal plasma p-tau181 and NfL with tau-PET, Aβ-PET and cognition.
J Neurol Neurosurg Psychiatry.
2021 Dec;
92(12):1289-1295.
Abstract: To explore if changes over time of plasma phosphorylated tau (p-tau)181 and neurofilament light chain (NfL) predict future tau and amyloid β (Aβ) PET load and cognitive performance, we studied a subsample of the Alzheimer's disease (AD) neuroimaging cohort with longitudinal blood peptide assessments. Eight hundred and sixty-five AD Neuroimaging Initiative participants were included. Using established AD cut-points for the cerebrospinal fluid concentrations of Aβ42, total-tau and p-tau181, subjects were classified according to the National Institute on Aging-Alzheimer's Association research framework, grouping markers into those of Aβ deposition (A), tau pathology (T) and neurodegeneration (N). Analysis of variance was used to compare the plasma biomarker data between the ATN groups. The rate of change over time of p-tau181 and NfL was obtained from linear mixed effects models and compared between the ATN groups. Linear regression analysis was used to investigate the association of baseline plasma biomarker concentrations and rates of change with future PET tau and Aβ load and cognitive performance. P-tau181 and NfL plasma concentrations increased along the AD spectrum, but only NfL showed greater rates of change in AD patients versus controls. Cognitive performance was associated cross-sectionally with NfL in all subgroups, and with p-tau181 only in AD spectrum individuals. The baseline concentrations of both plasma markers predicted PET Aβ and tau load and cognitive performance. The rate of change of NfL predicted future PET tau and cognitive performance. P-tau and NfL behave differently within the same individuals over time and may therefore offer complementary diagnostic information. NCT02854033, NCT01231971.
Abstract Summary: Scientists did a study to see if measuring certain things in the blood could help predict Alzheimer's disease. They looked at two blood markers, called p-tau181 and NfL, in 865 people. They wanted to see if changes in these markers could tell us about future brain health and how well people could think and remember things. They found that as Alzheimer's disease gets worse, the levels of these markers in the blood go up. NfL was especially good at showing changes over time in people with Alzheimer's compared to healthy people. Both markers were useful in guessing how much of the bad stuff that builds up in the brain, like tau and amyloid, there would be later on. Also, NfL levels were linked to how well people could think at the time of the test. This study is important because it shows that these blood tests could help doctors figure out who might get Alzheimer's and how the disease might progress.
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.
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Early detection of amyloid load using (18)F-florbetaben PET.
Alzheimer's research & therapy (2021)
Bullich S, Roé-Vellvé N, Marquié M, Landau SM, Barthel H, Villemagne VL, Sanabria Á, Tartari JP, Sotolongo-Grau O, Doré V, Koglin N, Müller A, Perrotin A, Jovalekic A, De Santi S, Tárraga L, Stephens AW, Rowe CC, Sabri O, Seibyl JP, Boada M.
Early detection of amyloid load using (18)F-florbetaben PET.
Alzheimers Res Ther.
2021 Mar 27;
13(1):67.
Abstract: A low amount and extent of Aβ deposition at early stages of Alzheimer's disease (AD) may limit the use of previously developed pathology-proven composite SUVR cutoffs. This study aims to characterize the population with earliest abnormal Aβ accumulation using F-florbetaben PET. Quantitative thresholds for the early (SUVR) and established (SUVR) Aβ deposition were developed, and the topography of early Aβ deposition was assessed. Subsequently, Aβ accumulation over time, progression from mild cognitive impairment (MCI) to AD dementia, and tau deposition were assessed in subjects with early and established Aβ deposition. The study population consisted of 686 subjects (n = 287 (cognitively normal healthy controls), n = 166 (subjects with subjective cognitive decline (SCD)), n = 129 (subjects with MCI), and n = 101 (subjects with AD dementia)). Three categories in the Aβ-deposition continuum were defined based on the developed SUVR cutoffs: Aβ-negative subjects, subjects with early Aβ deposition ("gray zone"), and subjects with established Aβ pathology. SUVR using the whole cerebellum as the reference region and centiloid (CL) cutoffs for early and established amyloid pathology were 1.10 (13.5 CL) and 1.24 (35.7 CL), respectively. Cingulate cortices and precuneus, frontal, and inferior lateral temporal cortices were the regions showing the initial pathological tracer retention. Subjects in the "gray zone" or with established Aβ pathology accumulated more amyloid over time than Aβ-negative subjects. After a 4-year clinical follow-up, none of the Aβ-negative or the gray zone subjects progressed to AD dementia while 91% of the MCI subjects with established Aβ pathology progressed. Tau deposition was infrequent in those subjects without established Aβ pathology. This study supports the utility of using two cutoffs for amyloid PET abnormality defining a "gray zone": a lower cutoff of 13.5 CL indicating emerging Aβ pathology and a higher cutoff of 35.7 CL where amyloid burden levels correspond to established neuropathology findings. These cutoffs define a subset of subjects characterized by pre-AD dementia levels of amyloid burden that precede other biomarkers such as tau deposition or clinical symptoms and accelerated amyloid accumulation. The determination of different amyloid loads, particularly low amyloid levels, is useful in determining who will eventually progress to dementia. Quantitation of amyloid provides a sensitive measure in these low-load cases and may help to identify a group of subjects most likely to benefit from intervention. Data used in this manuscript belong to clinical trials registered in ClinicalTrials.gov ( NCT00928304 , NCT00750282 , NCT01138111 , NCT02854033 ) and EudraCT (2014-000798-38).
Abstract Summary: This study looked at how a protein called Aβ builds up in the brain at the start of Alzheimer's disease. Using a special brain scan, the researchers found two important levels of Aβ buildup. The first level shows the early buildup of Aβ, and the second level shows when there's a lot of Aβ, which is common in Alzheimer's. They found that people with a lot of Aβ were more likely to get Alzheimer's. Also, another protein called tau didn't build up unless there was a lot of Aβ. This study helps us understand who might get Alzheimer's and could help find ways to stop it 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.
Phase 4 Randomized double-blind, active and placebo-controlled multicenter study evaluating the neuropsychiatric safety and efficacy of 12 weeks varenicline tartrate 1 mg bid and bupropion hydrochloride 150 mg bid for smoking cessation in subjects with and without a history of psychiatric disorders
University of Minnesota
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Do tobacco regulatory and economic factors influence smoking cessation outcomes? A post-hoc analysis of the multinational EAGLES randomised controlled trial.
BMJ open (2024)
Daniel B, Lawrence DE, McKenna BS, Saccone P, McRae T, Evins AE, Anthenelli RM.
Do tobacco regulatory and economic factors influence smoking cessation outcomes? A post-hoc analysis of the multinational EAGLES randomised controlled trial.
BMJ Open.
2024 Sep 20;
14(9):e079092.
Abstract: We previously reported global regional differences in smoking cessation outcomes, with smokers of US origin having lower quit rates than smokers from some other countries. This post-hoc analysis examined global regional differences in individual-level and country-level epidemiological, economic and tobacco regulatory factors that may affect cessation outcomes. EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study) was a randomised controlled trial that evaluated first-line cessation medications and placebo in 8144 smokers with and without psychiatric disorders from 16 countries across seven regions. Generalised linear and stepwise logistic regression models that considered pharmacotherapy treatment, psychiatric diagnoses, traditional individual-level predictors (eg, demographic and smoking characteristics) and country-specific smoking prevalence rates, gross domestic product (GDP) per capita, relative cigarette cost and WHO-derived MPOWER scores were used to predict 7-day point prevalence abstinence at the end of treatment. In addition to several traditional predictors, three of four country-level variables predicted short-term abstinence: GDP (0.54 (95% CI 0.47, 0.63)), cigarette relative income price (0.62 (95% CI 0.53, 0.72)) and MPOWER score (1.03 (95% CI 1.01, 1.06)). Quit rates varied across regions (22.0% in Australasia to 55.9% in Mexico). With northern North America (USA and Canada) as the referent, the likelihood of achieving short-term abstinence was significantly higher in Western Europe (OR 1.4 (95% CI 1.14, 1.61)), but significantly lower in Eastern Europe (0.39 (95% CI 0.22, 0.69)) and South America (0.17 (95% CI 0.08, 0.35)). Increased tobacco regulation was associated with enhanced quitting among participants in the EAGLES trial. Paradoxically, lower GDP, and more affordable cigarette pricing relative to a country's GDP, were also associated with higher odds of quitting. Geographical region was also a significant independent predictor. ClinicalTrials.gov, NCT01456936.
Abstract Summary: Scientists did a study called EAGLES to see why people from different parts of the world quit smoking at different rates. They looked at 8,144 smokers from 16 countries and checked things like how much money people make, how much cigarettes cost, and the rules about smoking in each country. They found that people in places with stricter smoking rules and higher cigarette prices were more likely to stop smoking. Also, in richer countries, fewer people quit smoking. This study helps us understand that making cigarettes more expensive and having strong rules about smoking can help more 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.
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Medication-assisted quit rates in participants with smoking-related diseases in EAGLES: Post hoc analyses of a double-blind, randomized, placebo-controlled clinical trial.
Tobacco induced diseases (2022)
Tønnesen P, Lawrence D, Tonstad S.
Medication-assisted quit rates in participants with smoking-related diseases in EAGLES: Post hoc analyses of a double-blind, randomized, placebo-controlled clinical trial.
Tob Induc Dis.
2022;
20:46.
Abstract: Greater understanding is required of how smokers with smoking-related diseases respond to smoking cessation medications. This analysis of EAGLES data compared continuous abstinence rates (CARs) in smokers with/without smoking-related diseases and assessed participant demographic and baseline characteristics that may serve as predictors of continuous abstinence (CA). EAGLES was a 24-week (12-week treatment, 12-week follow-up), double-blind, active- (nicotine replacement therapy; patch) and placebo-controlled study in motivated-to-quit smokers with/without psychiatric disorders. This analysis assessed CARs at weeks 9-12 (CAR9-12) and 9-24 (CAR9-24) in participants with smoking-related diseases [asthma, chronic obstructive pulmonary disease (COPD), diabetes, and/or cardiovascular disease (n=1372)] versus controls without these comorbidities (n=6039). Participants received varenicline 1 mg twice daily, bupropion 150 mg twice daily, nicotine patches 21 mg/day with taper, or placebo for 12 weeks. Stepwise logistic modeling was also performed to analyze odds ratio (OR) for predictors of CA at weeks 9-12 (CA9-12) and 9-24 (CA9-24). Smokers with smoking-related diseases were older, had a longer smoking history, more quit attempts, and were more likely to have a psychiatric disorder and reside in the US versus smokers without comorbidities. Fagerström Test for Cigarette Dependence scores and treatment adherence were comparable between cohorts. Smokers with smoking-related diseases had lower CARs versus controls (CAR9-12: 20.8% vs 24.0%; CAR9-24: 13.0% vs 16.9%). Use of smoking cessation medication was the strongest predictor of CA after control for demographics, smoking characteristics, and psychiatric disorder. By treatment, OR and CI were: varenicline CA9-12 (OR=3.82; 95% CI: 3.21-4.54) and CA9-24 (OR=2.92; 95% CI: 2.40-3.54); bupropion CA9-12 (OR=2.17; 95% CI: 1.81-2.60) and CA9-24 (OR=1.99; 95% CI: 1.63-2.44); nicotine patches CA9-12 (OR=2.23; 95% CI: 1.87-2.67) and CA9-24 (OR=1.86; 95% CI: 1.52-2.28). Smokers with smoking-related diseases had lower quit rates than controls. Of the active treatments compared, varenicline was most effective in smokers with asthma, COPD, diabetes, or cardiovascular disease. NCT01456936 (https://clinicaltrials.gov/ct2/show/NCT01456936).
Abstract Summary: Scientists did a study to see how well different stop-smoking medicines work for people who smoke and have diseases caused by smoking, like asthma or heart problems. They looked at a big group of smokers, some with these health issues and some without, to see who could quit smoking and stay quit for 12 and 24 weeks. They gave them different medicines or a pretend medicine (placebo) and watched what happened.
They found that people with smoking-related diseases had a harder time staying quit compared to those without these diseases. The medicine called varenicline worked best for helping people quit, especially for those with health problems from smoking. This study helps us understand that even if quitting is tougher for these smokers, there are medicines that can really help them stop.
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.
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The effects of varenicline, bupropion, nicotine patch, and placebo on smoking cessation among smokers with major depression: A randomized clinical trial.
Depression and anxiety (2022)
Cinciripini PM, Kypriotakis G, Green C, Lawrence D, Anthenelli RM, Minnix J, Blalock JA, Beneventi D, Morris C, Karam-Hage M.
The effects of varenicline, bupropion, nicotine patch, and placebo on smoking cessation among smokers with major depression: A randomized clinical trial.
Depress Anxiety.
2022 May;
39(5):429-440.
Abstract: Improving treatment outcomes for smokers with major depressive disorder (MDD) can have significant public health implications. To evaluate the safety and efficacy of smoking cessation pharmacotherapy among smokers with MDD. Secondary analysis of a randomized, double-blind, active- (nicotine patch) and placebo-controlled trial of 12 weeks of either varenicline or bupropion with a 12-week follow-up. Community volunteers 18-75 years of age; smoke 10+ cigarettes/day; with clinically stable MDD (N = 2635) or no psychiatric disorder (N = 4028), from 140 sites in 16 countries. Twelve weeks of pharmacotherapy (placebo [PLA], nicotine replacement therapy [NRT], bupropion [BUP], varenicline [VAR]) plus brief cessation counseling. Primary safety outcome: the occurrence of ≥1 treatment-emergent, moderate to severe neuropsychiatric adverse event (NPSAE). Primary efficacy outcome: biochemically confirmed continuous abstinence (CA) during the final 4 weeks of treatment (Weeks 9-12). A total of 6653 participants (56% female; 39% MDD) ~47 years old. Risk of NPSAEs did not differ by medication for MDD. MDD had higher risk (p < .0001) for NPSAEs than the NPC. Efficacy (6653; intent-to-treat): CA rates for MDD versus NPC respectively were 31.2% versus 38.0% VAR; 23.0% versus 26.1% BUP; 22.6% versus 26.4% NRT; and 13.4% versus 13.7% PLA but no differential treatment effect was noted within the cohorts. All active treatments differed from PLA but VAR showed the largest effect. Results suggest that for MDD smokers, inclusive of those with recurrent episode, varenicline plus counseling may be the best pharmacological option for the treatment of smoking given its greater efficacy effect size and similar risk of NPSAEs. ClinicalTrials.gov Identifier: NCT01456936. https://clinicaltrials.gov/ct2/show/NCT01456936.
Abstract Summary: Scientists did a study to see if medicine helps people with major depression stop smoking safely. They had 6653 volunteers, some with depression and some without, try different stop-smoking medicines or a fake pill for 12 weeks. They also talked with a counselor. They checked who stopped smoking without having bad side effects. They found that the medicine varenicline worked best, especially for people with depression. It helped more people quit smoking than the other medicines or the fake pill, and it was just as safe. This means that varenicline could be a good choice for people with depression who want to stop 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.
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In Reply: Changing the Culture of Tobacco Dependence Treatment Among Not Only Patients, But Also Prescribers.
Mayo Clinic proceedings (2021)
Ebbert JO, Jimenez-Ruiz C, Dutro MP, Fisher M, Li J, Hays JT.
In Reply: Changing the Culture of Tobacco Dependence Treatment Among Not Only Patients, But Also Prescribers.
Mayo Clin Proc.
2021 Sep;
96(9):2495.
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Frequently Reported Adverse Events With Smoking Cessation Medications: Post Hoc Analysis of a Randomized Trial.
Mayo Clinic proceedings (2021)
Ebbert J, Jimenez-Ruiz C, Dutro MP, Fisher M, Li J, Hays JT.
Frequently Reported Adverse Events With Smoking Cessation Medications: Post Hoc Analysis of a Randomized Trial.
Mayo Clin Proc.
2021 Jul;
96(7):1801-1811.
Abstract: To compare the incidence, severity, and clinical course of frequently reported adverse events (AEs) after treatment with smoking cessation pharmacotherapies. This was a multinational, multicenter, post hoc analysis of frequently reported treatment-emergent AEs from a large, phase 4, double-blind, randomized, triple-dummy, placebo-controlled trial (EAGLES), conducted between November 30, 2011, and January 13, 2015, that included smokers with and without psychiatric disorders (N=8144). Treatments were varenicline 1 mg twice daily, bupropion sustained-release 150 mg twice daily, and nicotine patch 21 mg once daily with tapering (12-week treatment, 12-week nontreatment follow-up), with incidence, time to onset, and duration of frequently reported AEs (≥5% of participants in any treatment group) measured. Risk differences for AEs for varenicline and bupropion vs nicotine patch were compared. Across frequently reported AEs, nausea, insomnia, abnormal dreams, anxiety, irritability, dry mouth, fatigue, and application site pruritus differed significantly in active treatment vs placebo groups. Risk differences were as follows: for nausea with varenicline vs nicotine patch, 15.50% (95% CI, 13.20% to 17.80%); for insomnia with bupropion vs nicotine patch, 2.58% (CI, 0.65% to 4.51%); and for abnormal dreams with varenicline and bupropion vs nicotine patch, -2.49% (CI, -4.35% to -0.64%) and -5.60% (CI, -7.27% to -3.93%), respectively. Frequently reported AEs of severe intensity and treatment discontinuation were experienced by less than 1.5% and less than 3% of participants across all groups, respectively. Active treatments were well tolerated with comparable AE profiles. Most AEs are not clinically important, and prescribers can reassure patients that those experienced will be manageable. Clinicaltrials.gov Identifier: NCT01456936.
Abstract Summary: Scientists did a big study to see what side effects people might have when they use different medicines to help them stop smoking. They looked at a lot of people, some with and some without mental health issues, who were trying to quit smoking. The medicines they tested were called varenicline, bupropion, and a nicotine patch. They wanted to see how often and how bad the side effects were, like feeling sick, not being able to sleep, having weird dreams, feeling anxious or grumpy, having a dry mouth, feeling tired, or having itchy skin where the patch was.
They found that these side effects did happen more with the medicines than with a fake medicine (placebo), but they weren't too bad. Very few people had to stop taking the medicine because of the side effects. The researchers said that doctors can tell people that if they do get side effects, they won't be too hard to handle. This is good news for people who want to quit smoking because it means the medicines to help them quit are mostly okay to take.
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.
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Estimation of risk of neuropsychiatric adverse events from varenicline, bupropion and nicotine patch versus placebo: secondary analysis of results from the EAGLES trial using Bayes factors.
Addiction (Abingdon, England) (2021)
Beard E, Jackson SE, Anthenelli RM, Benowitz NL, Aubin LS, McRae T, Lawrence D, Russ C, Krishen A, Evins AE, West R.
Estimation of risk of neuropsychiatric adverse events from varenicline, bupropion and nicotine patch versus placebo: secondary analysis of results from the EAGLES trial using Bayes factors.
Addiction.
2021 Oct;
116(10):2816-2824.
Abstract: Analysed using classical frequentist hypothesis testing with alpha set to 0.05, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) did not find enough evidence to reject the hypothesis of no difference in neuropsychiatric adverse events (NPSAEs) attributable to varenicline, bupropion, or nicotine patch compared with placebo. This might be because the null hypothesis was true or because the data were insensitive. The present study aimed to test the hypothesis more directly using Bayes factors. EAGLES was a randomised, double-blind, triple-dummy, controlled trial. Global (16 countries across five continents), between November 2011 and January 2015. Participants were smokers with (n = 4116) and without (n = 4028) psychiatric disorders. Varenicline (1 mg twice daily), bupropion (150 mg twice daily), nicotine patch (21 mg once daily with taper) and matched placebos. The outcomes included: (i) a composite measure of moderate/severe NPSAEs; and (ii) a composite measure of severe NPSAEs. The relative evidence for there being no difference in NPSAEs versus data insensitivity for the medications was calculated in the full and sub-samples using Bayes factors and corresponding robustness regions. For all but two comparisons, Bayes factors were <1/3, indicating moderate to strong evidence for no difference in risk of NPSAEs between active medications and placebo (Bayes factor = 0.02-0.23). In the psychiatric cohort versus placebo, the data were suggestive, but not conclusive of no increase in NPSAEs with varenicline (Bayes factor = 0.52) and bupropion (Bayes factor = 0.71). Here, the robustness regions ruled out a ≥7% and ≥8% risk increase with varenicline and bupropion, respectively. Secondary analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study trial using Bayes factors provides moderate to strong evidence that use of varenicline, bupropion or nicotine patches for smoking cessation does not increase the risk of neuropsychiatric adverse events relative to use of placebo in smokers without a history of psychiatric disorder. For smokers with a history of psychiatric disorder the evidence also points to no increased risk but with less confidence.
Abstract Summary: Scientists did a big study called EAGLES to see if certain stop-smoking medicines (varenicline, bupropion, or nicotine patches) cause bad side effects in the brain, compared to a fake medicine (placebo). They tested lots of smokers, some with and some without mental health issues, from all over the world. They used a special math method called Bayes factors to be really sure about their results. They found that, for most people, these medicines didn't increase the risk of having brain side effects. For people with mental health problems, the results were pretty good too, but the scientists weren't as sure. This means that these stop-smoking medicines are probably safe for your brain, whether you've had mental health issues or not.
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.
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Psychiatric Comorbidity and Multimorbidity in the EAGLES Trial: Descriptive Correlates and Associations With Neuropsychiatric Adverse Events, Treatment Adherence, and Smoking Cessation.
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco (2021)
Correa JB, Lawrence D, McKenna BS, Gaznick N, Saccone PA, Dubrava S, Doran N, Anthenelli RM.
Psychiatric Comorbidity and Multimorbidity in the EAGLES Trial: Descriptive Correlates and Associations With Neuropsychiatric Adverse Events, Treatment Adherence, and Smoking Cessation.
Nicotine Tob Res.
2021 Aug 29;
23(10):1646-1655.
Abstract: Psychiatric and substance use disorders represent barriers to smoking cessation. We sought to identify correlates of psychiatric comorbidity (CM; 2 diagnoses) and multimorbidity (MM; 3+ diagnoses) among smokers attempting to quit and to evaluate whether these conditions predicted neuropsychiatric adverse events (NPSAEs), treatment adherence, or cessation efficacy (CE). Data were collected from November 2011 to January 2015 across sixteen countries and reflect the psychiatric cohort of the EAGLES trial. Participants were randomly assigned to receive varenicline, bupropion, nicotine replacement therapy, or placebo for 12 weeks and were followed for an additional 12 weeks posttreatment. NPSAE outcomes reflected 16 moderate-to-severe neuropsychiatric symptom categories, and CE outcomes included continuous abstinence at weeks 9-12 and 9-24. Of the 4103 participants included, 36.2% were diagnosed with multiple psychiatric conditions (20.9% CM, 15.3% MM). Psychiatric CM and MM were associated with several baseline factors, including male gender, nonwhite race or ethnicity, more previous quit attempts, and more severe mental health symptoms. The incidence of moderate-to-severe NPSAEs was significantly higher (p < .01) in participants with MM (11.9%) than those with CM (5.1%) or primary diagnosis only (4.6%). There were no significant (ps > .05) main effects or interactions with treatment condition for diagnostic grouping on treatment adherence or CE outcomes. While having multiple psychiatric diagnoses increased risk of developing moderate-to-severe NPSAEs during a quit attempt, neither CM nor MM were associated with treatment adherence or odds of quitting. These findings reassure providers to advise smokers with multiple stable psychiatric conditions to consider using Food and Drug Administration (FDA)-approved medications when trying to quit. Psychiatric MM may be associated with development of NPSAEs when smokers make a medication-assisted quit attempt, but it does not appear to be differentially associated with medication compliance or efficacy. Prescribing healthcare professionals are encouraged to not only promote use of FDA-approved pharmacotherapies by smokers with complex psychiatric presentations, but also to closely monitor such smokers for neuropsychiatric side effects that may be related to their mental health conditions. NCT01456936.
Abstract Summary: Scientists wanted to see if having mental health issues or using substances made it harder for people to stop smoking. They looked at smokers from 16 countries who were trying to quit. These smokers were given different treatments: a drug called varenicline, another drug called bupropion, a nicotine replacement, or a fake treatment (placebo) for 12 weeks. They checked on them for 12 more weeks after that.
They found that over a third of the smokers had more than one mental health problem. Smokers with more mental health issues had a higher chance of experiencing serious mood or behavior changes when they tried to quit. However, having these issues didn't make it harder for them to stick to their treatment or to successfully quit smoking.
The study tells doctors that it's okay to give medicines approved by the FDA to help smokers with mental health problems quit smoking. But, doctors should also watch these smokers carefully for any serious mood or behavior changes that might happen because of their mental health 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.
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Assessment of Racial Differences in Pharmacotherapy Efficacy for Smoking Cessation: Secondary Analysis of the EAGLES Randomized Clinical Trial.
JAMA network open (2021)
Nollen NL, Ahluwalia JS, Sanderson Cox L, Okuyemi K, Lawrence D, Samuels L, Benowitz NL.
Assessment of Racial Differences in Pharmacotherapy Efficacy for Smoking Cessation: Secondary Analysis of the EAGLES Randomized Clinical Trial.
JAMA Netw Open.
2021 Jan 4;
4(1):e2032053.
Abstract: Understanding Black vs White differences in pharmacotherapy efficacy and the underlying reasons is critically important to reducing tobacco-related health disparities. To compare pharmacotherapy efficacy and examine variables to explain Black vs White differences in smoking abstinence. This study is a secondary analysis of the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) double-blind, placebo-controlled, randomized clinical trial, which took place at clinical trial centers, academic centers, and outpatient clinics in 29 states in the US. US Black and White smokers who smoked 10 or more cigarettes per day with and without psychiatric comorbidity were enrolled between November 2011 and January 2015. Data analysis was performed from July 2019 to January 2020. Participants were randomized (1:1:1:1) in a double-blind, triple-dummy, placebo- and active-controlled (nicotine patch) trial of varenicline and bupropion for 12 weeks with follow-up through week 24. Biochemically verified continuous cigarette abstinence rate (CAR) from weeks 9 to 24. Baseline, postbaseline treatment, and safety characteristics were examined as variables to explain race differences in abstinence. Of the 1065 Black smokers enrolled, 255 were randomized to receive varenicline, 259 received bupropion, 286 received nicotine replacement therapy (NRT [ie, nicotine patch]), and 265 received placebo. Among the 3044 White smokers enrolled, 778 were randomized to receive varenicline, 769 received bupropion, 738 received NRT, and 759 received placebo. Participants were predominantly female (614 Black [57.7%] and 1786 White [58.7%] women) and heavy smokers (mean [SD] cigarettes per day, 18.2 [7.9] for Black and 20.0 [7.5] for White smokers), with a mean (SD) age of 47.2 (11.2) years for Black and 46.5 (12.7) years for White participants. Treatment and race were associated with CAR for weeks 9 to 24. The CAR was 4.9% lower for Black vs White participants (odds ratio [OR], 0.53; 95% CI, 0.41-0.69; P < .001); differences were found across all treatments. Pooling psychiatric and nonpsychiatric cohorts, varenicline (OR, 2.63; 95% CI, 1.90-3.63; P < .001), bupropion (OR, 1.75; 95% CI, 1.25-2.46; P = .001), and NRT (OR, 1.52; 95% CI, 1.07-2.16; P = .02) had greater efficacy than placebo for White participants. Only varenicline (OR, 2.63; 95% CI, 1.26-5.48; P = .01) had greater efficacy than placebo for Black participants. Baseline, postbaseline, and safety characteristics differed by race, but these variables did not eliminate the association of race with CAR. Black participants had 49% reduced odds of CAR for weeks 9 to 24 compared with White participants in the adjusted model (OR, 0.51; 95% CI, 0.39-0.66; P < .001). Black and White smokers achieved the highest rate of abstinence while taking varenicline, suggesting that it is the best first-line therapy for these groups. However, Black smokers were less responsive to all therapies, including placebo. Understanding variables (eg, socioeconomic or biological) beyond those may lead to improved treatment outcomes for Black smokers. ClinicalTrials.gov Identifier: NCT01456936.
Abstract Summary: Scientists did a study to see if quitting smoking medicines work the same for Black and White people. They had 1065 Black smokers and 3044 White smokers try different medicines or a pretend medicine (placebo) to help them stop smoking. They checked who could stop smoking without cheating from week 9 to week 24. They found that the medicine called varenicline was the best for helping both Black and White people quit smoking. But, Black smokers had a harder time quitting with any treatment compared to White smokers. The study didn't find out why, but it might be because of things like money problems or body differences. Knowing more about these reasons could help Black smokers quit better 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.
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Efficacy and Safety of Pharmacotherapeutic Smoking Cessation Aids in Schizophrenia Spectrum Disorders: Subgroup Analysis of EAGLES.
Psychiatric services (Washington, D.C.) (2021)
Evins AE, West R, Benowitz NL, Russ C, Lawrence D, McRae T, Maravic MC, Heffner JL, Anthenelli RM.
Efficacy and Safety of Pharmacotherapeutic Smoking Cessation Aids in Schizophrenia Spectrum Disorders: Subgroup Analysis of EAGLES.
Psychiatr Serv.
2021 Jan 1;
72(1):7-15.
Abstract: This study aimed to evaluate the efficacy and safety of varenicline, bupropion, and nicotine replacement therapy (NRT) among smokers with schizophrenia spectrum disorders in post hoc analyses of Evaluating Adverse Events in a Global Smoking Cessation Study data. Smokers with schizophrenia spectrum disorder (N=390) and without a psychiatric illness (control group, N=4,028) were randomly assigned to receive varenicline, bupropion, NRT patch, or placebo for 12 weeks. Outcomes included abstinence rates during treatment and follow-up, number needed to treat (NNT) for abstinence, incidence of neuropsychiatric adverse events (NPSAEs), and temporal relationship between NPSAEs and abstinence status. Smokers with schizophrenia smoked more and had greater dependence and fewer prior trials of cessation pharmacotherapy at baseline. At each time point, smokers with schizophrenia assigned to varenicline had significantly greater odds of abstinence compared with their matched placebo group, with NNT comparable to the control group. Bupropion and NRT increased odds of abstinence; confidence intervals (CIs) included 1 for some comparisons, and NNT for smokers with schizophrenia was greater than for the control group. No treatment was associated with significantly more NPSAEs, compared with placebo, in either cohort. The estimated NPSAE rate was 5% (95% CI=3.0-7.7) for smokers with schizophrenia and 1% (95% CI=0.6-2.1) for the control group. Over one-third of NPSAEs occurred during partial or full abstinence, suggesting a multifactorial nature. For smokers with schizophrenia, varenicline led to significantly higher abstinence rates, and NNT was comparable to the control group. A significant proportion of NPSAEs occurred during early abstinence. No treatment significantly increased NPSAE prevalence.
Abstract Summary: Scientists did a study to see if three different stop-smoking aids—varenicline, bupropion, and nicotine patches—work well and are safe for people with a type of mental illness called schizophrenia. They compared 390 smokers with schizophrenia to 4,028 smokers without mental illness. Everyone was given one of the stop-smoking aids or a fake treatment for 12 weeks. They checked who could quit smoking during and after the treatment and if anyone had bad reactions, especially with their mood or thinking.
They found that the smokers with schizophrenia smoked more and had a harder time quitting before the study. The varenicline worked best for helping them quit, just like it did for the other group. Bupropion and nicotine patches also helped, but not as much. None of the treatments made people have more bad reactions than the fake treatment. About 5% of the people with schizophrenia had some mood or thinking issues, but these didn't just happen because they stopped smoking.
This study is important because it shows that varenicline can really help people with schizophrenia quit smoking without causing extra health problems. This could help lots of people with schizophrenia live healthier 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.
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Efficacy and safety of pharmacotherapies for smoking cessation in anxiety disorders: Subgroup analysis of the randomized, active- and placebo-controlled EAGLES trial.
Depression and anxiety (2020)
Ayers CR, Heffner JL, Russ C, Lawrence D, McRae T, Evins AE, Anthenelli RM.
Efficacy and safety of pharmacotherapies for smoking cessation in anxiety disorders: Subgroup analysis of the randomized, active- and placebo-controlled EAGLES trial.
Depress Anxiety.
2020 Mar;
37(3):247-260.
Abstract: Smoking rates are high in adults with anxiety disorders (ADs), yet little is known about the safety and efficacy of smoking-cessation pharmacotherapies in this group. Post hoc analyses in 712 smokers with AD (posttraumatic stress disorder [PTSD], n = 192; generalized anxiety disorder [GAD], n = 243; panic disorder [PD], n = 277) and in a nonpsychiatric cohort (NPC; n = 4,028). Participants were randomly assigned to varenicline, bupropion, nicotine-replacement therapy (NRT), or placebo plus weekly smoking-cessation counseling for 12 weeks, with 12 weeks follow-up. General linear models were used to test the effects of treatment group, cohort, and their interaction on neuropsychiatric adverse events (NPSAEs), and continuous abstinence weeks 9-12 (treatment) and 9-24 (follow-up). NPSAE incidence for PTSD (6.9%), GAD (5.4%), and PD (6.2%) was higher versus NPC (2.1%), regardless of treatment. Across all treatments, smokers with PTSD (odds ratio [OR] = 0.58), GAD (OR = 0.72), and PD (OR = 0.53) had lower continuous abstinence rates weeks 9-12 (CAR9-12) versus NPC. Varenicline demonstrated superior efficacy to placebo in smokers with GAD and PD, respectively (OR = 4.53; 95% confidence interval [CI] = 1.20-17.10; and OR = 8.49; 95% CI = 1.57-45.78); NRT was superior to placebo in smokers with PD (OR = 7.42; 95% CI = 1.37-40.35). While there was no statistically significant effect of any treatment on CAR9-12 for smokers with PTSD, varenicline improved 7-day point prevalence abstinence at end of treatment in this subcohort. Individuals with ADs were more likely than those without psychiatric illness to experience moderate to severe NPSAEs during smoking-cessation attempts, regardless of treatment. While the study was not powered to evaluate abstinence outcomes with these subgroups of smokers with ADs, varenicline provided significant benefit for cessation in those with GAD and PD, while NRT provided significant benefit for those with PD.
Abstract Summary: Scientists wanted to see if medicines that help people stop smoking also work well for adults who have anxiety problems. They looked at 712 smokers with different anxiety disorders and 4,028 smokers without mental health issues. The smokers got either a pretend pill (placebo) or one of three real stop-smoking medicines, plus they talked to a counselor every week for 12 weeks. They checked who stopped smoking and who had bad reactions to the medicines.
They found that people with anxiety disorders had more bad reactions than those without mental health issues, no matter which medicine they took. However, one medicine called varenicline helped people with two types of anxiety disorders stop smoking better than the pretend pill. Another treatment, nicotine replacement, also helped people with one type of anxiety disorder quit smoking.
This study is important because it shows that some stop-smoking medicines can really help people with certain anxiety disorders to quit smoking, even though they might have a harder time with side effects.
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.
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Safety and efficacy of first-line smoking cessation pharmacotherapies in bipolar disorders: Subgroup analysis of a randomized clinical trial.
Journal of affective disorders (2019)
Heffner JL, Evins AE, Russ C, Lawrence D, Ayers CR, McRae T, Aubin LS, Krishen A, West R, Anthenelli RM.
Safety and efficacy of first-line smoking cessation pharmacotherapies in bipolar disorders: Subgroup analysis of a randomized clinical trial.
J Affect Disord.
2019 Sep 1;
256:267-277.
Abstract: Post hoc analyses of EAGLES data to examine safety and efficacy of first-line smoking cessation pharmacotherapies in smokers with bipolar disorders (BD). Smokers with BD I/II (n = 285; 81.4% with BD I) and a comparison nonpsychiatric cohort (NPC; n = 2794) were randomly assigned to varenicline, bupropion, nicotine replacement therapy (NRT), or placebo for 12 weeks, plus weekly counseling. Primary outcomes were occurrence of moderate to severe neuropsychiatric adverse events (NPSAEs) and Weeks 9-12 biochemically-confirmed continuous abstinence (CA) rates. For BD smokers, NPSAE risk differences versus placebo were: varenicline, 6.17 (95% CI: -7.84 to 20.18); bupropion, 4.09 (-8.82 to 16.99); NRT, -0.56 (-12.34 to 11.22). ORs for Weeks 9-12 CA, comparing active medication to placebo among BD smokers were: varenicline, 2.61 (0.68-9.95); bupropion, 1.29 (0.31-5.37), NRT, 0.71 (0.14-3.74). Pooling across treatments, NPSAE occurrence was higher (10.7% versus 2.3%; P < 0.001) and CA rates were lower (22.8% versus 13.3%; P = 0.008) in BD than NPC. Study not powered to detect differences in safety and efficacy in the BD subcohort; generalizability limited to stably treated BD without current substance use disorders. Smokers with BD had higher risk of NPSAEs and were less likely to quit overall than NPC smokers. Among smokers with BD, NPSAE risk difference estimates for active treatments versus placebo ranged from 1% lower to 6% higher. Efficacy of varenicline in smokers with BD was similar to EAGLES main outcomes; bupropion and NRT effect sizes were descriptively lower. Varenicline may be a tolerable and effective cessation treatment for smokers with BD. ClinicalTrials.gov identifier (https://clinicaltrials.gov/): NCT01456936.
Abstract Summary: Scientists did a study to see if certain medicines help people with bipolar disorder (BD) stop smoking without causing bad side effects. They looked at 285 smokers with BD and 2,794 smokers without mental health issues. The smokers got either a pretend pill (placebo) or one of three real stop-smoking medicines for 12 weeks, and they also got counseling. They checked who had serious mood or behavior problems and who stopped smoking for good.
They found that smokers with BD had a slightly higher chance of mood or behavior problems with the real medicines compared to the pretend pill, but it wasn't a big difference. Also, the medicine called varenicline seemed to work as well for smokers with BD as it did for others in past studies. The other two medicines didn't seem to work as well. Overall, people with BD had more trouble quitting smoking and had more mood or behavior problems than people without BD.
The study suggests that varenicline might be a good choice to help people with BD quit smoking, but more research is needed 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.
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Predictors of Neuropsychiatric Adverse Events with Smoking Cessation Medications in the Randomized Controlled EAGLES Trial.
Journal of general internal medicine (2019)
Anthenelli RM, Gaffney M, Benowitz NL, West R, McRae T, Russ C, Lawrence D, St Aubin L, Krishen A, Evins AE.
Predictors of Neuropsychiatric Adverse Events with Smoking Cessation Medications in the Randomized Controlled EAGLES Trial.
J Gen Intern Med.
2019 Jun;
34(6):862-870.
Abstract: Pre-treatment factors that increase smokers' risk of experiencing neuropsychiatric adverse events (NPSAEs) when quitting smoking are unknown. To identify baseline smoker characteristics beyond the history of mental illness that predict which participants were more likely to experience moderate to severe NPSAEs in EAGLES. A prospective correlational cohort study in the context of a multinational, multicenter, double-blind, randomized trial. Smokers without (N = 3984; NPC)/with (N = 4050; PC) histories of, or current clinically stable, psychiatric disorders including mood (N = 2882; 71%), anxiety (N = 782; 19%), and psychotic (N = 386; 10%) disorders. Bupropion, 150 mg twice daily, or varenicline, 1 mg twice daily, versus active control (nicotine patch, 21 mg/day with taper) and placebo for 12 weeks with 12-week non-treatment follow-up. Primary safety outcome was the incidence of a composite measure of moderate/severe NPSAEs. Associations among baseline demographic/clinical characteristics and the primary safety endpoint were analyzed post hoc via generalized linear regression. The incidence of moderate to severe NPSAEs was higher among smokers in the PC (238/4050; 5.9%) than in the NPC (84/3984; 2.1%). Three baseline characteristics predicted increased risk for experiencing clinically significant NPSAEs when quitting regardless of carrying a psychiatric diagnosis: current symptoms of anxiety (for every ~ 4-unit increase in HADS anxiety score, the absolute risk of occurrence of the NPSAE endpoint increased by 1% in both PC and NPC); prior history of suicidal ideation and/or behavior (PC, 4.4% increase; P = 0.001; NPC, 4.1% increase; P = 0.02), and being of White race (versus Black: PC, 2.9% ± 0.9 [SE] increase; P = 0.002; and NPC, 3.4% ± 0.8 [SE] increase; P = 0.001). Among smokers with psychiatric disorders, younger age, female sex, history of substance use disorders, and proxy measures of nicotine dependence or psychiatric illness severity also predicted greater risk. There were no significant interactions between these characteristics and treatment. Smokers with unstable psychiatric disorders or with current, active substance abuse were excluded from the study. Irrespective of cessation pharmacotherapy use, smokers attempting to quit were more likely to experience moderate to severe NPSAEs if they reported current anxiety or prior suicidal ideation at baseline and were White. In smokers with a psychiatric history, female sex, younger age, and greater severity of nicotine dependence were also predictive. ClinicalTrials.gov Identifier: NCT01456936.
Abstract Summary: Scientists wanted to find out what makes some people feel really bad in their minds when they stop smoking. They looked at a lot of people who smoked—some with mental health problems and some without. These people were given different things to help them quit smoking, like special medicines or a nicotine patch, and the scientists watched them for 24 weeks.
They found that people who were already feeling anxious, had thought about hurting themselves before, or were White had a higher chance of feeling bad in their minds when they quit smoking. For people who had mental health problems, being younger, a girl, or really addicted to nicotine also made it more likely for them to feel bad when they stopped smoking.
This study helps us understand that when people try to quit smoking, doctors should pay extra attention to those who might have a harder time because of how they feel inside. This way, they can get the right support and have a better chance of quitting smoking without feeling too bad.
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.
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Factors associated with the efficacy of smoking cessation treatments and predictors of smoking abstinence in EAGLES.
Addiction (Abingdon, England) (2018)
West R, Evins AE, Benowitz NL, Russ C, McRae T, Lawrence D, St Aubin L, Krishen A, Maravic MC, Anthenelli RM.
Factors associated with the efficacy of smoking cessation treatments and predictors of smoking abstinence in EAGLES.
Addiction.
2018 Aug;
113(8):1507-1516.
Abstract: To assess (1) how far the efficacies of front-line smoking cessation pharmacotherapies vary as a function of smoker characteristics and (2) associations between these characteristics and success of smoking cessation attempts. Prospective correlational study in the context of a double-blind randomized trial. The outcome was regressed individually onto each covariate after adjusting for treatment, and then a forward stepwise model constructed. Treatment moderator effects of covariates were tested by treatment × covariate interactions. Health service facilities in multiple countries. Data came from 8120 smokers willing to make a quit attempt, randomized to varenicline, bupropion, nicotine replacement therapy (NRT) or placebo in Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) between 30 November 2011 and 13 January 2015. Smoker characteristics measured at baseline were country, psychiatric history, sex, age, body mass index (BMI), ethnic group, life-time suicidal ideation/behaviour, anxiety, depression, aggression, psychotropic medication, history of alcohol/substance use disorder, age of starting smoking, cigarette dependence [Fagerström Test for Cigarette Dependence (FTCD)] and prior use of study medicines. Outcome was biochemically confirmed continuous abstinence at weeks 9-24 from start of treatment. No statistically significant treatment × covariate interactions were found. Odds of success were associated independently positively with age [odds ratio (OR) = 1.01; 95% confidence interval (CI) = 1.00, 1.01], BMI (1.01; 95% CI = 1.00, 1.02) and age of starting smoking (1.03; 95% CI = 1.02, 1.04). Odds were associated independently negatively with US (versus non-US) study site (0.53; 95% CI = 0.46, 0.61), black (versus white) ethnic group (0.57; 95% CI = 0.45, 0.72), mood disorder (0.85; 95% CI = 0.73, 0.99), anxiety disorder (0.71; 95% CI = 0.55, 0.90) and psychotic disorder (0.73; 95% CI = 0.50, 1.07), taking psychotropic medication (0.81; 95% CI = 0.68, 0.95), FTCD (0.89; 95% CI = 0.87, 0.92) and previous use of NRT (0.78; 95% CI = 0.67, 0.91). While a range of smoker characteristics-including psychiatric history, cigarette dependence and prior use of nicotine replacement therapy (NRT)-are associated with lower cessation rates, they do not substantially influence the efficacy of varenicline, bupropion or NRT.
Abstract Summary: Scientists did a study to see if different types of medicine help people quit smoking better depending on who they are. They looked at a lot of smokers from different places who wanted to stop smoking and gave them different quitting medicines or a pretend medicine. They checked to see who was able to quit smoking for good. They found out that older people, those who started smoking later in life, and those with a higher body weight had a better chance of quitting. But, people in the US, those with certain mental health issues, and those who had used some quitting medicines before didn't do as well. The study showed that no matter who the person was, the medicines worked pretty much the same. This is important because it means that these medicines can help lots of different 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.
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Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial.
Lancet (London, England) (2016)
Anthenelli RM, Benowitz NL, West R, St Aubin L, McRae T, Lawrence D, Ascher J, Russ C, Krishen A, Evins AE.
Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial.
Lancet.
2016 Jun 18;
387(10037):2507-20.
Abstract: Substantial concerns have been raised about the neuropsychiatric safety of the smoking cessation medications varenicline and bupropion. Their efficacy relative to nicotine patch largely relies on indirect comparisons, and there is limited information on safety and efficacy in smokers with psychiatric disorders. We compared the relative neuropsychiatric safety risk and efficacy of varenicline and bupropion with nicotine patch and placebo in smokers with and without psychiatric disorders. We did a randomised, double-blind, triple-dummy, placebo-controlled and active-controlled (nicotine patch; 21 mg per day with taper) trial of varenicline (1 mg twice a day) and bupropion (150 mg twice a day) for 12 weeks with 12-week non-treatment follow-up done at 140 centres (clinical trial centres, academic centres, and outpatient clinics) in 16 countries between Nov 30, 2011, and Jan 13, 2015. Participants were motivated-to-quit smokers with and without psychiatric disorders who received brief cessation counselling at each visit. Randomisation was computer generated (1:1:1:1 ratio). Participants, investigators, and research personnel were masked to treatment assignments. The primary endpoint was the incidence of a composite measure of moderate and severe neuropsychiatric adverse events. The main efficacy endpoint was biochemically confirmed continuous abstinence for weeks 9-12. All participants randomly assigned were included in the efficacy analysis and those who received treatment were included in the safety analysis. The trial is registered at ClinicalTrials.gov (number NCT01456936) and is now closed. 8144 participants were randomly assigned, 4116 to the psychiatric cohort (4074 included in the safety analysis) and 4028 to the non-psychiatric cohort (3984 included in the safety analysis). In the non-psychiatric cohort, 13 (1·3%) of 990 participants reported moderate and severe neuropsychiatric adverse events in the varenicline group, 22 (2·2%) of 989 in the bupropion group, 25 (2·5%) of 1006 in the nicotine patch group, and 24 (2·4%) of 999 in the placebo group. The varenicline-placebo and bupropion-placebo risk differences (RDs) for moderate and severe neuropsychiatric adverse events were -1·28 (95% CI -2·40 to -0·15) and -0·08 (-1·37 to 1·21), respectively; the RDs for comparisons with nicotine patch were -1·07 (-2·21 to 0·08) and 0·13 (-1·19 to 1·45), respectively. In the psychiatric cohort, moderate and severe neuropsychiatric adverse events were reported in 67 (6·5%) of 1026 participants in the varenicline group, 68 (6·7%) of 1017 in the bupropion group, 53 (5·2%) of 1016 in the nicotine patch group, and 50 (4·9%) of 1015 in the placebo group. The varenicline-placebo and bupropion-placebo RDs were 1·59 (95% CI -0·42 to 3·59) and 1·78 (-0·24 to 3·81), respectively; the RDs versus nicotine patch were 1·22 (-0·81 to 3·25) and 1·42 (-0·63 to 3·46), respectively. Varenicline-treated participants achieved higher abstinence rates than those on placebo (odds ratio [OR] 3·61, 95% CI 3·07 to 4·24), nicotine patch (1·68, 1·46 to 1·93), and bupropion (1·75, 1·52 to 2·01). Those on bupropion and nicotine patch achieved higher abstinence rates than those on placebo (OR 2·07 [1·75 to 2·45] and 2·15 [1·82 to 2·54], respectively). Across cohorts, the most frequent adverse events by treatment group were nausea (varenicline, 25% [511 of 2016 participants]), insomnia (bupropion, 12% [245 of 2006 participants]), abnormal dreams (nicotine patch, 12% [251 of 2022 participants]), and headache (placebo, 10% [199 of 2014 participants]). Efficacy treatment comparison did not differ by cohort. The study did not show a significant increase in neuropsychiatric adverse events attributable to varenicline or bupropion relative to nicotine patch or placebo. Varenicline was more effective than placebo, nicotine patch, and bupropion in helping smokers achieve abstinence, whereas bupropion and nicotine patch were more effective than placebo. Pfizer and GlaxoSmithKline.
Abstract Summary: Scientists did a big study to see if two medicines, varenicline and bupropion, which help people stop smoking, are safe for the brain and if they work well. They tested these medicines against a nicotine patch and a fake pill (placebo) in people who wanted to quit smoking, some of whom had mental health issues. They had 8,144 people in the study from different places around the world.
They found that the medicines didn't cause a lot of bad side effects for the brain. Also, varenicline helped more people stop smoking than the nicotine patch, bupropion, or the fake pill. Bupropion and the nicotine patch also helped more people quit than the fake pill. The most common side effects were feeling sick from varenicline, not being able to sleep from bupropion, having weird dreams from the nicotine patch, and getting headaches from the fake pill.
This study is important because it shows that these medicines are safe for the brain and can really help people stop smoking, even for those with mental health issues.
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 determinants of health and urinary symptoms--ResearchMatch
Vanderbilt University Medical Center
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Coping With Interstitial Cystitis/Bladder Pain Syndrome.
Neurourology and urodynamics (2024)
Sutherland S, Grace Kelly A, McKernan LC, Dmochowski RR, Reynolds WS, Sebesta EM.
Coping With Interstitial Cystitis/Bladder Pain Syndrome.
Neurourol Urodyn.
2024 Nov;
43(8):1895-1902.
Abstract: Compensatory coping, or maladaptive alterations in behavior with the intention of preventing or managing symptoms, is increasingly being explored as a key factor in how people respond to bladder conditions. Preliminary investigations have identified relations between coping behaviors and psychological distress in urologic conditions, including interstitial cystitis/bladder pain syndrome (IC/BPS). However, previous explorations of coping have not accounted for heterogeneity in coping behaviors or addressed the likelihood that some coping behaviors may be more adaptive than others. This study sought to examine how two specific types of coping behaviors, primary control coping and disengaged coping, are related to distress and symptoms in IC/BPS, and to explore the potential role of pain phenotype in this relationship. A secondary data analysis was conducted with a large community data set (N = 677 women with IC/BPS) and employed descriptive and inferential statistics to characterize coping patterns and explore novel predictors of distress. Results indicated that almost all participants engaged in at least one compensatory coping behavior within the last week. Both types of coping behaviors correlated with psychological symptoms, and when controlling for relevant clinical variables (i.e., age and severity of urinary symptoms), disengaged coping behaviors were significantly associated with psychological distress. Further, the addition of pain phenotype to multiple regression models resulted in a more effective predictive model when considering the relation between coping behaviors and depression. By investigating more deeply the relationship between coping and distress, understanding of potential risk factors and mechanisms is increased, offering valuable insights for intervention strategies for IC/BPS patients.
Abstract Summary: Scientists did a study to learn about how people with a bladder condition called interstitial cystitis/bladder pain syndrome (IC/BPS) deal with their symptoms. They looked at two ways people cope: trying to control the situation or giving up on dealing with it. They used information from 677 women with IC/BPS to see how these coping ways are linked to feeling upset or having more symptoms. They found that almost everyone tried at least one way to cope in the last week. The way people coped was connected to how stressed or depressed they felt. When they also considered the type of pain the person had, they could better predict who would feel depressed. This study helps us understand that the way people try to handle their bladder condition can affect their feelings. Knowing this can help create better ways to support people with IC/BPS.
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.
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Household Toilet and Sanitation Insecurity is Associated With Urinary Symptoms, Psychosocial Burden, and Compensatory Bladder Behaviors.
Urology (2024)
Sebesta E, Furuyama W, Dmochowski R, Stuart Reynolds W.
Household Toilet and Sanitation Insecurity is Associated With Urinary Symptoms, Psychosocial Burden, and Compensatory Bladder Behaviors.
Urology.
2024 Sep;
191:72-78.
Abstract: To investigate whether being "at-risk" for toilet and sanitation insecurity in the United States is associated with urinary symptoms, voiding behaviors, and psychosocial burden. Based on census data, nearly 2 million people in the United States do not have access to adequate plumbing. More may have inconsistent access related to cost, inadequate facilities for the number of people in a home, or declining regional infrastructure. The effects of inadequate access in the United States are poorly characterized. This is a secondary analysis of a community-based sample of adults electronically recruited to complete questionnaires on clinical and sociodemographic information, living situations, home toilets and plumbing, urinary symptoms, compensatory bladder behaviors, and psychosocial burden. Multivariable logistic regression was used to assess for associations between being at-risk for toilet and sanitation insecurity and urinary and psychosocial symptoms. Linear regression was used to assess for association with adopting compensatory bladder behaviors. This sample included 4218 participants, of whom 17% were identified as being at-risk for toilet and sanitation insecurity. Being at-risk for toilet and sanitation insecurity was associated with worse overall urinary symptoms and greater bother from these symptoms, in addition to worse self-assessed mental and physical health, anxiety, stress, depression, and fewer social supports. Finally, those at-risk for toilet and sanitation insecurity were more likely to adopt burdensome and unhealthy compensatory bladder behaviors. As with other social determinants of health, toilet and sanitation insecurity may be an under-appreciated contributor to urinary symptoms, unhealthy toileting behaviors, and psychosocial distress.
Abstract Summary: Scientists did a study to see if people who might not have good toilets or plumbing at home in the United States have problems with going to the bathroom and feeling stressed or sad. They asked 4,218 adults to answer questions about their health, how they live, and their toilets at home. They found that 17% of these people didn't have good access to toilets or plumbing. These people had more trouble with bathroom issues, felt more bothered by these problems, and were not feeling as good mentally and physically. They also felt more anxious, stressed, and depressed, and didn't have as much support from friends or family. Plus, they had to do things that weren't good for them just to manage going to the bathroom. The study shows that not having a good toilet or plumbing can make people feel bad in many ways.
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.
Salt-Sensitivity and Immunity Cell Activation
Vanderbilt University Medical Center
Using mHealth to improve adherence and reduce blood pressure in individuals with hypertension and bipolar disorder
University Hospitals Cleveland Medical Center
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A 6-month, prospective, randomized controlled trial of customized adherence enhancement versus a bipolar-specific educational control in poorly adherent adolescents and young adults living with bipolar disorder.
Bipolar disorders (2024)
Levin JB, DelBello M, Modi AC, Briggs F, Forthun LF, McVoy M, Yala J, Cooley R, Black J, Conroy C, Sajatovic M.
A 6-month, prospective, randomized controlled trial of customized adherence enhancement versus a bipolar-specific educational control in poorly adherent adolescents and young adults living with bipolar disorder.
Bipolar Disord.
2024 Nov;
26(7):696-707.
Abstract: Few studies have addressed medication adherence in adolescents and young adults (AYAs) with bipolar disorder (BD). This 6-month prospective randomized-controlled trial (RCT) tested customized adherence enhancement for adolescents and young adults (CAE-AYA), a behavioral intervention for AYAs versus enhanced treatment as usual (ETAU). Inclusion criteria were AYAs age 13-21 with BD type I or II with suboptimal adherence defined as missing ≥20% of medications. Assessments were conducted at Screening, Baseline, and weeks 8, 12 and 24. Primary outcome was past 7 day self-reported Tablets Routine Questionnaire (TRQ) validated by electronic pillbox monitoring (SimpleMed). Symptom measures included the Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS). The mean sample age (N = 36) was 19.1 years (SD = 2.0); 66.7% (N = 24) female, BD Type I (81%). The mean missed medication on TRQ for the total sample was 35.4% (SD = 28.8) at screening and 30.4% (SD = 30.5) at baseline. Both CAE-AYA and ETAU improved on TRQ from screening to baseline. Baseline mean missed medication using SimpleMed was 51.6% (SD = 38.5). Baseline HAM-D and YMRS means were 7.1 (SD = 4.7) and 6.0 (SD = 7.3), respectively. Attrition rate at week 24 was 36%. Baseline to 24-week change on TRQ, adjusting for age, gender, educational level, living situation, family history, race, and ethnicity, showed improvement favoring CAE-AYA versus ETAU of 15%. SimpleMed interpretation was limited due to substantial missing data. There was a significant reduction in depression favoring CAE-AYA. CAE-AYA may improve adherence in AYAs with BD, although conclusions need to be made cautiously given study limitations. ClinicalTrials.gov identifier: NCT04348604.
Abstract Summary: Scientists did a study to help teenagers and young people who have bipolar disorder take their medicine regularly. They tried a special program called CAE-AYA and compared it to the usual way of helping. They checked if the young people took their medicine using a special pillbox that records when pills are taken and by asking them. They also looked at how the young people felt, checking their mood for signs of depression or mania. They found that the special program might be better at helping these young people take their medicine and feel less depressed. But they're not totally sure because there were some problems with the study, like missing information. They think this program could be helpful, but they need 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.
Development for a Novel Transdiagnostic Intervention for Anhedonia
Duke University
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A parallel-arm, randomized trial of Behavioral Activation Therapy for anhedonia versus mindfulness-based cognitive therapy for adults with anhedonia.
Behaviour research and therapy (2024)
Cernasov PM, Walsh EC, Nagy GA, Kinard JL, Kelley L, Phillips RD, Pisoni A, Diehl J, Haworth K, West J, Freeman L, Pfister C, Scott M, Daughters SB, Gaylord S, Dichter GS, Smoski MJ.
A parallel-arm, randomized trial of Behavioral Activation Therapy for anhedonia versus mindfulness-based cognitive therapy for adults with anhedonia.
Behav Res Ther.
2024 Nov;
182:104620.
Abstract: Anhedonia, deficits in motivation and pleasure, is a transdiagnostic symptom of psychopathology and negative prognostic marker. In this randomized, parallel-arm clinical trial, a novel intervention, Behavioral Activation Treatment for Anhedonia (BATA), was compared to an individually administered Mindfulness-Based Cognitive Therapy (MBCT) in a transdiagnostic cohort of adults with clinically significant anhedonia (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Participants received 8-15 individual psychotherapy sessions, once weekly, with either BATA (n = 61) or MBCT (n = 55) and completed repeated self-report assessment of anhedonia and other internalizing symptoms. Indicators of treatment feasibility were similar across conditions, though MBCT showed a trend towards greater attrition rates than BATA, with an adjusted odd's ratio of 2.04 [0.88, 4.73]. Treatment effects on the primary clinical endpoint of anhedonia symptoms did not significantly differ, with a 14-week estimated difference on the Snaith Hamilton Pleasure Scale (SHAPS) of -0.20 [-2.25, 1.84] points in BATA compared to MBCT (z = 0.19, p = 0.845, d = 0.05). The expected 14-week change in SHAPS scores across conditions was -7.18 [-8.22, -6.15] points (z = 13.6, p < 0.001, d = 1.69). There were no significant differences in the proportion of participants demonstrating reliable and clinically significant improvements in SHAPS scores, or in the magnitude of internalizing symptom reductions. Limitations included a modest sample size, lack of longer-term follow up data, and non-preregistered analytic plan. There was no evidence to support superior clinical efficacy of BATA over MBCT in a transdiagnostic cohort of adults with elevated anhedonia. Both interventions reduced anhedonia symptoms to a comparable magnitude of other existing treatments.
Abstract Summary: Scientists did a study to help people who have trouble feeling happy or motivated, which can be a sign of different mental health issues. They tested two ways to help: one called Behavioral Activation Treatment for Anhedonia (BATA) and another called Mindfulness-Based Cognitive Therapy (MBCT). Adults who were having these problems tried one of the two methods for a few weeks. They found that both ways helped people about the same amount, and there wasn't one that was better than the other. This is good news because it means there are different options that 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.
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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 MJ, Dichter GS.
The effects of psychotherapy for anhedonia on subcortical brain volumes measured with ultra-high field MRI.
J Affect Disord.
2024 Sep 15;
361:128-138.
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.
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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.
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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.
Randomized controlled trial of an internet-based prevention intervention for parents with irritable bowel syndrome (REACH)
University of Washington
HVTN 119, Version 1.0: A phase 1 clinical trial to evaluate the safety and immunogenicity of pDNA vaccines expressing HIV M Group p24Gag conserved elements and/or p55Gag, administered with IL-12 pDNA by intramuscular electroporation, in healthy, HIV-uninfected adult participants.
University of California San Francisco
Depressed Mood Improvement Through Nicotine Dosing 2
Vanderbilt University Medical Center
Using large language models to summarize scientific abstracts
Vanderbilt University Medical Center
Perspectives on Returning Value to Research Participants
Vanderbilt University Medical Center
Cognitive-Behavioral Therapy for Girls Who Experienced Weight-related Bullying
Yale University
Cardiovascular Effects of GLP-1 Receptor Activation
Vanderbilt University Medical Center
Advarra: AHEAD 3-45 Study: A Placebo-Controlled, Double-Blind, Parallel-Treatment Arm,
216 Week Study to Evaluate Efficacy and Safety of Treatment With BAN2401 in Subjects With Preclinical
Alzheimers Disease and Elevated Amyloid (A45 Trial) and in Subjects With Early Preclinical Alzheimers
Disease and Intermediate Amyloid (A3 Trial)
Vanderbilt University Medical Center
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Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease.
Alzheimer's & dementia : the journal of the Alzheimer's Association (2024)
Devanarayan V, Doherty T, Charil A, Sachdev P, Ye Y, Murali LK, Llano DA, Zhou J, Reyderman L, Hampel H, Kramer LD, Dhadda S, Irizarry MC.
Plasma pTau217 predicts continuous brain amyloid levels in preclinical and early Alzheimer's disease.
Alzheimers Dement.
2024 Aug;
20(8):5617-5628.
Abstract: This study investigated the potential of phosphorylated plasma Tau217 ratio (pTau217R) and plasma amyloid beta (Aβ) 42/Aβ40 in predicting brain amyloid levels measured by positron emission tomography (PET) Centiloid (CL) for Alzheimer's disease (AD) staging and screening. Quantification of plasma pTau217R and Aβ42/Aβ40 employed immunoprecipitation-mass spectrometry. CL prediction models were developed on a cohort of 904 cognitively unimpaired, preclinical and early AD subjects and validated on two independent cohorts. Models integrating pTau217R outperformed Aβ42/Aβ40 alone, predicting amyloid levels up to 89.1 CL. High area under the receiver operating characteristic curve (AUROC) values (89.3% to 94.7%) were observed across a broad CL range (15 to 90). Utilizing pTau217R-based models for low amyloid levels reduced PET scans by 70.5% to 78.6%. pTau217R effectively predicts brain amyloid levels, surpassing cerebrospinal fluid Aβ42/Aβ40's range. Combining it with plasma Aβ42/Aβ40 enhances sensitivity for low amyloid detection, reducing unnecessary PET scans and expanding clinical utility. NCT02956486 (MissionAD1), NCT03036280 (MissionAD2), NCT04468659 (AHEAD3-45), NCT03887455 (ClarityAD) HIGHLIGHTS: Phosphorylated plasma Tau217 ratio (pTau217R) effectively predicts amyloid-PET Centiloid (CL) across a broad spectrum. Integrating pTau217R with Aβ42/Aβ40 extends the CL prediction upper limit to 89.1 CL. Combined model predicts amyloid status with high accuracy, especially in cognitively unimpaired individuals. This model identifies subjects above or below various CL thresholds with high accuracy. pTau217R-based models significantly reduce PET scans by up to 78.6% for screening out individuals with no/low amyloid.
Abstract Summary: Scientists did a study to see if they could use blood tests to guess how much of a certain protein called amyloid is in the brain. This protein can show if someone might get Alzheimer's disease. They used a special machine to measure amyloid in the brain and then tried to predict these measurements using two things in the blood: pTau217R and Aβ42/Aβ40. They tested their ideas on over 900 people with different stages of memory health.
They found that using pTau217R in the blood was really good at guessing the amyloid levels in the brain, even better than using another method that checks the fluid from the spine. When they combined pTau217R with Aβ42/Aβ40, the predictions got even better. This is important because it means that a lot of people might not need to have a big machine scan their brain to check for Alzheimer's disease. Instead, they could just have a simple blood test. This could help doctors find out who needs more testing and who doesn't, making it easier and faster to look after people's brains.
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.
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Racial and ethnic differences in plasma biomarker eligibility for a preclinical Alzheimer's disease trial.
Alzheimer's & dementia : the journal of the Alzheimer's Association (2024)
Molina-Henry DP, Raman R, Liu A, Langford O, Johnson K, Shum LK, Glover CM, Dhadda S, Irizarry M, Jimenez-Maggiora G, Braunstein JB, Yarasheski K, Venkatesh V, West T, Verghese PB, Rissman RA, Aisen P, Grill JD, Sperling RA.
Racial and ethnic differences in plasma biomarker eligibility for a preclinical Alzheimer's disease trial.
Alzheimers Dement.
2024 Jun;
20(6):3827-3838.
Abstract: In trials of amyloid-lowering drugs for Alzheimer's disease (AD), differential eligibility may contribute to under-inclusion of racial and ethnic underrepresented groups. We examined plasma amyloid beta 42/40 and positron emission tomography (PET) amyloid eligibility for the ongoing AHEAD Study preclinical AD program (NCT04468659). Univariate logistic regression models were used to examine group differences in plasma and PET amyloid screening eligibility. Of 4905 participants screened at time of analysis, 1724 were plasma eligible to continue in screening: 13.3% Hispanic Black, 24.7% Hispanic White, 20.8% non-Hispanic (NH) Asian, 24.7% NH Black, and 38.9% NH White. Plasma eligibility differed across groups in models controlling for covariates (odds ratio from 1.9 to 4.0 compared to the NH White reference group, P < 0.001). Among plasma eligible participants, PET eligibility did not differ by group. These results suggest that prevalence of brain amyloid pathology differed, but that eligibility based on plasma was equally effective across racial and ethnic group members. Plasma amyloid eligibility is lower in underrepresented racial and ethnic groups. In plasma eligible adults, positron emission tomography eligibility rates are similar across race and ethnicity. Plasma biomarker tests may be similarly effective across racial and ethnic groups.
Abstract Summary: Scientists are studying new medicines that might help with Alzheimer's disease, a sickness that affects the brain. They want to make sure that people from all different backgrounds can join in these studies. They looked at two ways to test if someone can be in the study: a blood test and a special brain scan called PET. They tested 4,905 people and found that the number of people who could join the study after the blood test was different for different racial and ethnic groups. But, once people passed the blood test, the brain scan showed that everyone, no matter their background, had the same chance to join the study. This means that the blood test works well for everyone, but it seems like not as many people from certain groups have the signs of Alzheimer's that the study is looking for. This information can help make sure that everyone has a fair chance to be part of research on new Alzheimer's 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.
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Plasma Aβ42/Aβ40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease.
Alzheimer's & dementia : the journal of the Alzheimer's Association (2024)
Rissman RA, Langford O, Raman R, Donohue MC, Abdel-Latif S, Meyer MR, Wente-Roth T, Kirmess KM, Ngolab J, Winston CN, Jimenez-Maggiora G, Rafii MS, Sachdev P, West T, Yarasheski KE, Braunstein JB, Irizarry M, Johnson KA, Aisen PS, Sperling RA, AHEAD 3-45.
Plasma Aβ42/Aβ40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease.
Alzheimers Dement.
2024 Feb;
20(2):1214-1224.
Abstract: Incorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aβ) into screening algorithms may improve screening efficiency. Plasma Aβ, phosphorylated tau (p-tau)181, and p-tau217 concentration levels from AHEAD 3-45 study participants were measured using mass spectrometry. Tau concentration ratios for each proteoform were calculated to normalize for inter-individual differences. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by > 20 Centiloids. Mixture of experts analysis assessed the value of including tau concentration ratios into the existing predictive algorithm for amyloid positron emission tomography status. The area under the receiver operating curve (AUC) was 0.87 for Aβ42/Aβ40, 0.74 for phosphorylated variant p-tau181 ratio (p-tau181/np-tau181), and 0.92 for phosphorylated variant p-tau217 ratio (p-tau217/np-tau217). The Plasma Predicted Centiloid (PPC), a predictive model including p-tau217/np-tau217, Aβ42/Aβ40, age, and apolipoprotein E improved AUC to 0.95. Including plasma p-tau217/np-tau217 along with Aβ42/Aβ40 in predictive algorithms may streamline screening preclinical individuals into anti-amyloid clinical trials. gov Identifier: NCT04468659 HIGHLIGHTS: The addition of plasma phosphorylated variant p-tau217 ratio (p-tau217/np-tau217) significantly improved plasma biomarker algorithms for identifying preclinical amyloid positron emission tomography positivity. Prediction performance at higher NAV Centiloid levels was improved with p-tau217/np-tau217. All models generated for this study are incorporated into the Plasma Predicted Centiloid (PPC) app for public use.
Abstract Summary: Scientists are studying new ways to find out if someone might get Alzheimer's disease by looking at special signs in their blood. They checked levels of certain proteins in the blood of people who might get Alzheimer's. They found that by measuring these proteins, they could guess who might have signs of Alzheimer's in their brain scans. They made a special app that uses this information to help doctors guess better. This could help people get into studies for new Alzheimer's treatments earlier.
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.
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Centralizing prescreening data collection to inform data-driven approaches to clinical trial recruitment.
Alzheimer's research & therapy (2023)
Kirn DR, Grill JD, Aisen P, Ernstrom K, Gale S, Heidebrink J, Jicha G, Jimenez-Maggiora G, Johnson L, Peskind E, McCann K, Shaffer E, Sultzer D, Wang S, Sperling R, Raman R.
Centralizing prescreening data collection to inform data-driven approaches to clinical trial recruitment.
Alzheimers Res Ther.
2023 May 2;
15(1):88.
Abstract: Recruiting to multi-site trials is challenging, particularly when striving to ensure the randomized sample is demographically representative of the larger disease-suffering population. While previous studies have reported disparities by race and ethnicity in enrollment and randomization, they have not typically investigated whether disparities exist in the recruitment process prior to consent. To identify participants most likely to be eligible for a trial, study sites frequently include a prescreening process, generally conducted by telephone, to conserve resources. Collection and analysis of such prescreening data across sites could provide valuable information to improve understanding of recruitment intervention effectiveness, including whether traditionally underrepresented participants are lost prior to screening. We developed an infrastructure within the National Institute on Aging (NIA) Alzheimer's Clinical Trials Consortium (ACTC) to centrally collect a subset of prescreening variables. Prior to study-wide implementation in the AHEAD 3-45 study (NCT NCT04468659), an ongoing ACTC trial recruiting older cognitively unimpaired participants, we completed a vanguard phase with seven study sites. Variables collected included age, self-reported sex, self-reported race, self-reported ethnicity, self-reported education, self-reported occupation, zip code, recruitment source, prescreening eligibility status, reason for prescreen ineligibility, and the AHEAD 3-45 participant ID for those who continued to an in-person screening visit after study enrollment. Each of the sites was able to submit prescreening data. Vanguard sites provided prescreening data on a total of 1029 participants. The total number of prescreened participants varied widely among sites (range 3-611), with the differences driven mainly by the time to receive site approval for the main study. Key learnings instructed design/informatic/procedural changes prior to study-wide launch. Centralized capture of prescreening data in multi-site clinical trials is feasible. Identifying and quantifying the impact of central and site recruitment activities, prior to participants signing consent, has the potential to identify and address selection bias, instruct resource use, contribute to effective trial design, and accelerate trial enrollment timelines.
Abstract Summary: Scientists are trying to make sure that when they test new medicines, the group of people in the study looks like the group of people who have the sickness the medicine is for. Sometimes, not everyone has the same chance to be in these studies. The scientists did a special part of a big study to see who gets asked to join before they even say yes. They looked at things like how old people are, if they are a boy or a girl, what race they are, and where they live. They did this in seven places and learned from 1029 people. They found out that they can collect this information from many places and it helps them understand who might not be getting a fair chance to join the study. This can help them make the study better and faster, and make sure more kinds of people can be 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.
Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects with Type 2 Diabetes Mellitus and Diabetic Nephropathy
University of Chicago Medical Center
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Effects of canagliflozin on total heart failure events across the kidney function spectrum: Participant-level pooled analysis from the CANVAS Program and CREDENCE trial.
European journal of heart failure (2024)
Vaduganathan M, Cannon CP, Jardine MJ, Heerspink HJL, Arnott C, Neuen BL, Sarraju A, Gogate J, Seufert J, Neal B, Perkovic V, Mahaffey KW, Kosiborod MN.
Effects of canagliflozin on total heart failure events across the kidney function spectrum: Participant-level pooled analysis from the CANVAS Program and CREDENCE trial.
Eur J Heart Fail.
2024 Sep;
26(9):1967-1975.
Abstract: People with type 2 diabetes (T2D) face high risks of heart failure (HF) hospitalizations that are often recurrent, especially as kidney function declines. We examined the effects of canagliflozin on total HF events by baseline kidney function in patients with T2D at high cardiovascular risk and/or with chronic kidney disease. Leveraging pooled participant-level data from the CANVAS programme (n = 10 142) and CREDENCE trial (n = 4401), first and total HF hospitalizations were examined. Cox proportional hazards models were built for the time to first HF hospitalization, and proportional means models based on cumulative mean functions were used for recurrent HF hospitalizations. Treatment effects were evaluated overall as well as within baseline estimated glomerular filtration rate (eGFR) strata (<45, 45-60, and >60 ml/min/1.73 m). HF hospitalizations were independently and blindly adjudicated. Among 14 540 participants with available baseline eGFR values, 672 HF hospitalizations occurred over a median follow-up of 2.5 years. Among participants who experienced a HF hospitalization, 357 had a single event (201 in placebo-treated patients and 156 in canagliflozin-treated patients), 77 had 2 events, and 39 had >2 events. Canagliflozin reduced risk of first HF hospitalization (hazard ratio 0.58, 95% confidence interval [CI] 0.48-0.70) consistently across baseline eGFR strata (p = 0.84). Canagliflozin reduced total HF hospitalizations overall (mean event ratio 0.63, 95% CI 0.54-0.73) and across eGFR subgroups (p = 0.51). Canagliflozin also reduced cardiovascular death and total HF hospitalizations (mean event ratio 0.72, 95% CI 0.65-0.80) and across eGFR subgroups (p = 0.82). The absolute risk reductions were numerically larger, and numbers needed to treat were smaller when evaluating total events versus first events alone. These observed HF benefits were highly consistent across the range of eGFR, with larger absolute benefits in participants who had worse kidney function at baseline. In individuals with T2D at high cardiovascular risk and/or with chronic kidney disease, canagliflozin reduced the total burden of HF hospitalizations, with consistent benefits observed across the kidney function spectrum. ClinicalTrials.gov Identifier: CANVAS (NCT01032629), CANVAS-R (NCT01989754), CREDENCE (NCT02065791).
Abstract Summary: Doctors wanted to see if a medicine called canagliflozin could help people with type 2 diabetes who are at risk of heart problems or have kidney disease. They looked at over 14,000 people to see how often they had to go to the hospital for heart failure. They found that people who took canagliflozin didn't have to go to the hospital as much for heart problems. This was true for people with different levels of kidney health. The medicine helped prevent not just the first time someone went to the hospital, but also if they had to go back again. This is good news because it means that taking canagliflozin might help a lot of people with diabetes stay out of the hospital and have healthier 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.
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Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.
The Cochrane database of systematic reviews (2024)
Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF.
Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.
Cochrane Database Syst Rev.
2024 May 21;
5(5):CD015588.
Abstract: Diabetes is associated with high risks of premature chronic kidney disease (CKD), cardiovascular diseases, cardiovascular death and impaired quality of life. People with diabetes are more likely to develop kidney impairment, and approximately one in three adults with diabetes have CKD. People with CKD and diabetes experience a substantially higher risk of cardiovascular outcomes. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors have shown potential effects in preventing kidney and cardiovascular outcomes in people with CKD and diabetes. However, new trials are emerging rapidly, and evidence synthesis is essential to summarising cumulative evidence. This review aimed to assess the benefits and harms of SGLT2 inhibitors for people with CKD and diabetes. We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2023 using a search strategy designed by an Information Specialist. Studies in the Register are continually identified through regular searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. Randomised controlled studies were eligible if they evaluated SGLT2 inhibitors versus placebo, standard care or other glucose-lowering agents in people with CKD and diabetes. CKD includes all stages (from 1 to 5), including dialysis patients. Two authors independently extracted data and assessed the study risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The primary review outcomes were all-cause death, 3-point and 4-point major adverse cardiovascular events (MACE), fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and kidney failure. Fifty-three studies randomising 65,241 people with CKD and diabetes were included. SGLT2 inhibitors with or without other background treatments were compared to placebo, standard care, sulfonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, or insulin. In the majority of domains, the risks of bias in the included studies were low or unclear. No studies evaluated the treatment in children or in people treated with dialysis. No studies compared SGLT2 inhibitors with glucagon-like peptide-1 receptor agonists or tirzepatide. Compared to placebo, SGLT2 inhibitors decreased the risk of all-cause death (20 studies, 44,397 participants: RR 0.85, 95% CI 0.78 to 0.94; I = 0%; high certainty) and cardiovascular death (16 studies, 43,792 participants: RR 0.83, 95% CI 0.74 to 0.93; I = 29%; high certainty). Compared to placebo, SGLT2 inhibitors probably make little or no difference to the risk of fatal or nonfatal MI (2 studies, 13,726 participants: RR 0.95, 95% CI 0.80 to 1.14; I = 24%; moderate certainty), and fatal or nonfatal stroke (2 studies, 13,726 participants: RR 1.07, 95% CI 0.88 to 1.30; I = 0%; moderate certainty). Compared to placebo, SGLT2 inhibitors probably decrease 3-point MACE (7 studies, 38,320 participants: RR 0.89, 95% CI 0.81 to 0.98; I = 46%; moderate certainty), and 4-point MACE (4 studies, 23,539 participants: RR 0.82, 95% CI 0.70 to 0.96; I = 77%; moderate certainty), and decrease hospital admission due to heart failure (6 studies, 28,339 participants: RR 0.70, 95% CI 0.62 to 0.79; I = 17%; high certainty). Compared to placebo, SGLT2 inhibitors may decrease creatinine clearance (1 study, 132 participants: MD -2.63 mL/min, 95% CI -5.19 to -0.07; low certainty) and probably decrease the doubling of serum creatinine (2 studies, 12,647 participants: RR 0.70, 95% CI 0.56 to 0.89; I = 53%; moderate certainty). SGLT2 inhibitors decrease the risk of kidney failure (6 studies, 11,232 participants: RR 0.70, 95% CI 0.62 to 0.79; I = 0%; high certainty), and kidney composite outcomes (generally reported as kidney failure, kidney death with or without ≥ 40% decrease in estimated glomerular filtration rate (eGFR)) (7 studies, 36,380 participants: RR 0.68, 95% CI 0.59 to 0.78; I = 25%; high certainty) compared to placebo. Compared to placebo, SGLT2 inhibitors incur less hypoglycaemia (16 studies, 28,322 participants: RR 0.93, 95% CI 0.89 to 0.98; I = 0%; high certainty), and hypoglycaemia requiring third-party assistance (14 studies, 26,478 participants: RR 0.75, 95% CI 0.65 to 0.88; I = 0%; high certainty), and probably decrease the withdrawal from treatment due to adverse events (15 studies, 16,622 participants: RR 0.94, 95% CI 0.82 to 1.08; I = 16%; moderate certainty). The effects of SGLT2 inhibitors on eGFR, amputation and fracture were uncertain. No studies evaluated the effects of treatment on fatigue, life participation, or lactic acidosis. The effects of SGLT2 inhibitors compared to standard care alone, sulfonylurea, DPP-4 inhibitors, or insulin were uncertain. SGLT2 inhibitors alone or added to standard care decrease all-cause death, cardiovascular death, and kidney failure and probably decrease major cardiovascular events while incurring less hypoglycaemia compared to placebo in people with CKD and diabetes.
Abstract Summary: Scientists did a big study to see if a special medicine called SGLT2 inhibitors can help people with diabetes who also have kidney problems. Diabetes can make it more likely for someone to get sick with heart or kidney diseases. The researchers looked at information from many different studies that included over 65,000 people. They found that this medicine can lower the chance of dying from any cause or from heart problems. It also helps to prevent serious heart events and keeps people from going to the hospital for heart failure. Plus, it's good for the kidneys and doesn't cause low blood sugar as much as some other treatments. This is really important because it means this medicine could help lots of people with diabetes and kidney disease 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.
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Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cause-Specific Cardiovascular Death in Patients with CKD: A Meta-Analysis of CKD Progression Trials.
Clinical journal of the American Society of Nephrology : CJASN (2024)
Fletcher RA, Herrington WG, Agarwal R, Mayne KJ, Arnott C, Jardine MJ, Mahaffey KW, Perkovic V, Staplin N, Wheeler DC, Chertow GM, Heerspink HJL, Neuen BL.
Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Cause-Specific Cardiovascular Death in Patients with CKD: A Meta-Analysis of CKD Progression Trials.
Clin J Am Soc Nephrol.
2024 Apr 16;
19(9):1180-2.
Abstract: Clinical Trial registry name and registration number: ClinicalTrials.gov Identifiers: NCT02065791 (CREDENCE), NCT03036150 (DAPA-CKD), NCT03594110 (EMPA-KIDNEY).
Abstract Summary: Doctors did some big studies (CREDENCE, DAPA-CKD, and EMPA-KIDNEY) to see if certain medicines could help people with sick kidneys. They wrote down all the details on a website called ClinicalTrials.gov and gave each study a special number so people could find them easily. They tested the medicines on lots of people to make sure they were safe and worked well. They found out that these medicines can really help protect the kidneys and keep them working longer. This is great news for everyone because it means there are new ways to help people with kidney problems 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.
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Vascular endothelial growth factors and risk of cardio-renal events: Results from the CREDENCE trial.
American heart journal (2024)
Januzzi JL Jr, Liu Y, Sattar N, Yavin Y, Pollock CA, Butler J, Jardine M, Heerspink HJL, Masson S, Breyer M, Hansen MK.
Vascular endothelial growth factors and risk of cardio-renal events: Results from the CREDENCE trial.
Am Heart J.
2024 May;
271:38-47.
Abstract: Circulating concentrations of vascular endothelial growth factor (VEGF) family members may be abnormally elevated in type 2 diabetes (T2D). The roles of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFLT-1), and VEGF-A in cardio-renal complications of T2D are not established. The 2602 individuals with diabetic kidney disease (DKD) from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial were randomized to receive canagliflozin or placebo and followed for incident cardio-renal outcomes. PlGF, sFLT-1, and VEGF-A were measured at baseline, year 1, and year 3. Primary outcome was a composite of end-stage kidney disease, doubling of the serum creatinine, or renal/cardiovascular death. Cox proportional hazard regression was used to investigate the association between biomarkers with adverse clinical events. At baseline, individuals with higher PlGF levels had more prevalent cardiovascular disease compared to those with lower values. Treatment with canagliflozin did not meaningfully change PlGF, sFLT-1, and VEGF-A concentrations at years 1 and 3. In a multivariable model, 1 unit increases in baseline log PlGF (hazard ratio [HR]: 1.76, 95% confidence interval [CI]: 1.23, 2.54, P-value = .002), sFLT-1 (HR: 3.34, [95% CI: 1.71, 6.52], P-value < .001), and PlGF/sFLT-1 ratio (HR: 4.83, [95% CI: 0.86, 27.01], P-value = .07) were associated with primary composite outcome, while 1 unit increase in log VEGF-A did not increase the risk of primary outcome (HR: 0.96 [95% CI: 0.81, 1.07]). Change by 1 year of each biomarker was also assessed: HR (95% CI) of primary composite outcome was 2.45 (1.70, 3.54) for 1 unit increase in 1-year concentration of log PlGF, 4.19 (2.18, 8.03) for 1 unit increase in 1-year concentration of log sFLT-1, and 21.08 (3.79, 117.4) for 1 unit increase in 1-year concentration of log PlGF/sFLT-1. Increase in 1-year concentrations of log VEGF-A was not associated with primary composite outcome (HR: 1.08, [95% CI: 0.93, 1.24], P-value = .30). People with T2D and DKD with elevated levels of PlGF, sFLT-1, and PlGF/sFLT-1 ratio were at a higher risk for cardiorenal events. Canagliflozin did not meaningfully decrease concentrations of PlGF, sFLT-1, and VEGF-A. CREDENCE, https://clinicaltrials.gov/ct2/show/NCT02065791.
Abstract Summary: Scientists did a study to see if certain blood markers are linked to heart and kidney problems in people with type 2 diabetes and kidney disease. They checked the levels of these markers in 2602 people who were either given a diabetes medicine called canagliflozin or a placebo. They found that people with higher levels of certain markers had a greater chance of having heart and kidney issues. The medicine didn't really change the levels of these markers. This research helps us understand that testing for these markers could tell doctors who is at higher risk for serious 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.
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Primary and Secondary Cardiovascular and Kidney Prevention With Canagliflozin: Insights From the CANVAS Program and CREDENCE Trial.
Journal of the American Heart Association (2024)
Sharma A, Razaghizad A, Joury A, Levin A, Bajaj HS, Mancini GBJ, Wong NC, Slee A, Ang FG, Rapattoni W, Neuen BL, Arnott C, Perkovic V, Mahaffey KW.
Primary and Secondary Cardiovascular and Kidney Prevention With Canagliflozin: Insights From the CANVAS Program and CREDENCE Trial.
J Am Heart Assoc.
2024 Feb 6;
13(3):e031586.
Abstract: This study evaluated the effects of canagliflozin in patients with type 2 diabetes with and without prevalent cardiovascular disease (secondary and primary prevention). This was a pooled participant-level analysis of the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. The CANVAS Program included participants with type 2 diabetes at elevated cardiovascular risk, whereas the CREDENCE trial included participants with type 2 diabetes and albuminuric chronic kidney disease. Hazard ratios (HRs) with interaction terms were obtained from Cox regression models to estimate relative risk reduction with canagliflozin versus placebo across the primary and secondary prevention groups. We analyzed 5616 (38.9%) and 8804 (61.1%) individuals in the primary and secondary prevention subgroups, respectively. Primary versus secondary prevention participants were on average younger (62.2 versus 63.8 years of age) and more often women (42% versus 31%). Canagliflozin reduced the risk of major adverse cardiovascular events (HR, 0.84 [95% CI, 0.76-0.94]) consistently across primary and secondary prevention subgroups (=0.86). Similarly, no treatment effect heterogeneity was observed with canagliflozin for hospitalization for heart failure, cardiovascular death, end-stage kidney disease, or all-cause mortality (all >0.5). Canagliflozin reduced cardiovascular and kidney outcomes with no statistical evidence of heterogeneity for the treatment effect across the primary and secondary prevention subgroups in the CANVAS Program and CREDENCE trial. Although studies on the optimal implementation of canagliflozin within these populations are warranted, these results reinforce canagliflozin's role in cardiorenal prevention and treatment in individuals with type 2 diabetes. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01032629, NCT01989754, NCT02065791.
Abstract Summary: Scientists looked at how a medicine called canagliflozin helps people with type 2 diabetes, especially those who already have heart problems or are at risk of getting them. They used information from two big studies that included lots of people with diabetes, some with kidney disease too. They found that canagliflozin was good at lowering the chance of having heart issues or kidney problems, no matter if the person already had heart disease or not. This is important because it means that this medicine can help lots of people with diabetes stay healthier by protecting their hearts and kidneys.
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.
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Associations of Angiopoietin 2 and Vascular Endothelial Growth Factor-A Concentrations with Clinical End Points.
Clinical journal of the American Society of Nephrology : CJASN (2024)
Mohebi R, Liu Y, Hansen MK, Yavin Y, Sattar N, Pollock CA, Butler J, Jardine M, Masson S, Heerspink HJL, Januzzi JL Jr.
Associations of Angiopoietin 2 and Vascular Endothelial Growth Factor-A Concentrations with Clinical End Points.
Clin J Am Soc Nephrol.
2024 Apr 1;
19(4):429-437.
Abstract: Angiopoietin 2 regulates endothelial function partially mediated by vascular endothelial growth factor-A (VEGF-A) and may play a role in diabetic kidney disease (DKD). We assessed the association of angiopoietin 2 and VEGF-A with cardiorenal outcomes and investigated the effect of canagliflozin on angiopoietin 2 and VEGF-A concentrations. Two thousand five hundred sixty-five study participants with DKD and available plasma samples treated with canagliflozin or placebo in the Canagliflozin and Kidney Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial were included. Angiopoietin 2 and VEGF-A concentrations were measured at baseline, year 1, and year 3. The primary composite end point of the trial was a composite of kidney failure, doubling of the serum creatinine level, and kidney or cardiovascular death. Patients with the highest baseline quartile of angiopoietin 2, but not VEGF-A, concentration had the highest risk clinical profile. Treatment with canagliflozin significantly lowered concentrations of angiopoietin 2 (adjusted geometric mean ratio: 0.94; 95% confidence interval, 0.92 to 0.95; P < 0.001), but not VEGF-A. In multivariable-adjusted modeling, each 50% increment in log baseline angiopoietin 2 concentrations was associated with a higher risk of primary composite outcome (hazard ratio, 1.27; 95% confidence interval, 1.13 to 1.43). Angiopoietin 2 change at year 1 compared with baseline explained 10% of the effect of canagliflozin on the primary composite outcome. VEGF-A concentrations were not associated with outcomes, alone or in combination with angiopoietin 2. Higher angiopoietin 2 levels were associated with cardiorenal risk among individuals with DKD independent of VEGF-A. Canagliflozin lowered angiopoietin 2 concentrations. Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy, NCT02065791 .
Abstract Summary: Scientists did a study to see if a medicine called canagliflozin could help people with a kind of kidney disease that happens because of diabetes. They looked at two things in the blood, angiopoietin 2 and VEGF-A, to see if they were connected to heart and kidney problems. They tested the blood of 2,565 people with this kidney disease, both before and after giving them the medicine or a placebo.
They found that people with higher levels of angiopoietin 2 had more health risks, but this wasn't true for VEGF-A. The good news is that the medicine canagliflozin helped lower the levels of angiopoietin 2. This drop in angiopoietin 2 seemed to explain some of the good effects of the medicine on the heart and kidneys. VEGF-A levels didn't really change and didn't seem to affect people's health in this study.
So, the big takeaway is that canagliflozin might be a helpful medicine for people with kidney problems from diabetes because it lowers angiopoietin 2 in the blood.
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.
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Effect of SGLT2 Inhibitors on Discontinuation of Renin-angiotensin System Blockade: A Joint Analysis of the CREDENCE and DAPA-CKD Trials.
Journal of the American Society of Nephrology : JASN (2023)
Fletcher RA, Jongs N, Chertow GM, McMurray JJV, Arnott C, Jardine MJ, Mahaffey KW, Perkovic V, Rockenschaub P, Rossing P, Correa-Rotter R, Toto RD, Vaduganathan M, Wheeler DC, Heerspink HJL, Neuen BL.
Effect of SGLT2 Inhibitors on Discontinuation of Renin-angiotensin System Blockade: A Joint Analysis of the CREDENCE and DAPA-CKD Trials.
J Am Soc Nephrol.
2023 Dec 1;
34(12):1965-1975.
Abstract: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are foundational therapy for CKD but are underused, in part because they are frequently withheld and not restarted due to hyperkalemia, AKI, or hospitalization. Consequently, ensuring persistent use of ACE inhibitors and ARBs in CKD has long been a major clinical priority. In this joint analysis of the CREDENCE and DAPA-CKD trials, the relative risk of discontinuation of ACE inhibitors and ARBs was reduced by 15% in patients randomized to sodium-glucose cotransporter 2 (SGLT2) inhibitors. This effect was more pronounced in patients with urine albumin:creatinine ratio ≥1000 mg/g, for whom the absolute benefits of these medications are the greatest. These findings indicate that SGLT2 inhibitors may enable better use of ACE inhibitors and ARBs in patients with CKD. Strategies to enable persistent use of renin-angiotensin system (RAS) blockade to improve outcomes in CKD have long been sought. The effect of SGLT2 inhibitors on discontinuation of RAS blockade has yet to be evaluated. We conducted a joint analysis of canagliflozin and renal events in diabetes with established nephropathy clinical evaluation (CREDENCE) and dapagliflozin and prevention of adverse outcomes in CKD (DAPA-CKD), two randomized, double-blind, placebo-controlled, event-driven trials of SGLT2 inhibitors in patients with albuminuric CKD. The main outcome was time to incident temporary or permanent discontinuation of RAS blockade, defined as interruption of an ACE inhibitor or ARB for at least 4 weeks or complete cessation during the double-blind on-treatment period. Cox regression analyses were used to estimate the treatment effects from each trial. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were pooled with fixed effects meta-analysis to obtain summary treatment effects, overall and across key subgroups. During median follow-up of 2.2 years across both trials, 740 of 8483 (8.7%) patients discontinued RAS blockade. The relative risk for discontinuation of RAS blockade was 15% lower in patients randomized to receiving SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74 to 0.99), with consistent effects across trials ( P -heterogeneity = 0.92). The relative effect on RAS blockade discontinuation was more pronounced among patients with baseline urinary albumin:creatinine ratio ≥1000 mg/g (pooled HR, 0.77; 95% CI, 0.63 to 0.94; P -heterogeneity = 0.009). In patients with albuminuric CKD with and without type 2 diabetes, SGLT2 inhibitors facilitate the use of RAS blockade. ClinicalTrials.gov, NCT02065791 and NCT03036150 . This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_11_21_JASN0000000000000248.mp3.
Abstract Summary: Doctors often give people with kidney problems special medicines to help their kidneys work better. But sometimes, they have to stop these medicines because they can cause other issues. This study looked at whether a different kind of medicine, called SGLT2 inhibitors, can help people keep taking their kidney medicines without having to stop. They found that people who took SGLT2 inhibitors didn't have to stop their kidney medicines as much. This is really good news because it means that people with kidney problems might be able to take their medicines longer and 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.
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Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression.
Journal of the American Society of Nephrology : JASN (2023)
Heerspink HJL, Jongs N, Schloemer P, Little DJ, Brinker M, Tasto C, Karpefors M, Wheeler DC, Bakris G, Perkovic V, Nkulikiyinka R, Rossert J, Gasparyan SB.
Development and Validation of a New Hierarchical Composite End Point for Clinical Trials of Kidney Disease Progression.
J Am Soc Nephrol.
2023 Dec 1;
34(12):2025-2038.
Abstract: The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR but does not weigh the relative clinical importance of the end point components. By contrast, a hierarchical composite end point (HCE) accounts for the clinical importance of the end point components. The authors developed and validated a kidney HCE that combines clinical kidney outcomes with longitudinal GFR changes (GFR slope). They demonstrate that in seven major placebo-controlled kidney outcome trials with different medications, treatment effect estimates on the HCE were consistently in similar directions and of similar magnitudes compared with treatment effects on the established kidney end point. The HCE's prioritization of clinical outcomes and ability to combine dichotomous outcomes with GFR slope make it an attractive alternative to the established kidney end point. The established composite kidney end point in clinical trials combines clinical events with sustained large changes in GFR. However, the statistical method does not weigh the relative clinical importance of the end point components. A HCE accounts for the clinical importance of the end point components and enables combining dichotomous outcomes with continuous measures. We developed and validated a new HCE for kidney disease progression, performing post hoc analyses of seven major Phase 3 placebo-controlled trials that assessed the effects of canagliflozin, dapagliflozin, finerenone, atrasentan, losartan, irbesartan, and aliskiren in patients with CKD. We calculated the win odds (WOs) for treatment effects on a kidney HCE, defined as a hierarchical composite of all-cause mortality; kidney failure; sustained 57%, 50%, and 40% GFR declines from baseline; and GFR slope. The WO describes the odds of a more favorable outcome for receiving the active compared with the control. We compared the WO with the hazard ratio (HR) of the primary kidney outcome of the original trials. In all trials, treatment effects calculated with the WO reflected a similar direction and magnitude of the treatment effect compared with the HR. Clinical trials incorporating the HCE would achieve increased statistical power compared with the established composite end point at equivalent sample sizes. In seven major kidney clinical trials, the WO and HR provided similar direction of treatment effect estimates with smaller HRs associated with larger WOs. The prioritization of clinical outcomes and inclusion of broader composite end points makes the HCE an attractive alternative to the established kidney end point.
Abstract Summary: Scientists did a study to find a better way to measure how well treatments work for kidney problems. They created a new system called a "hierarchical composite end point" (HCE) that looks at different results from treatments and decides which ones are more important. They tested this new system by looking at past studies where people with kidney disease took different medicines. They found that this new system showed the same results as the old way of measuring, but it was better because it could tell which treatments were more important for people's health. This new system could help doctors and scientists understand how well treatments work for kidney 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.
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The effects of canagliflozin in type 2 diabetes in subgroups defined by population-specific body mass index: Insights from the CANVAS Program and CREDENCE trial.
Diabetes, obesity & metabolism (2023)
Yu J, Sweeting AN, Gianacas C, Houston L, Lee V, Fletcher RA, Perkovic V, Li Q, Neuen BL, Berwanger O, Heerspink HJL, de Zeeuw D, Arnott C.
The effects of canagliflozin in type 2 diabetes in subgroups defined by population-specific body mass index: Insights from the CANVAS Program and CREDENCE trial.
Diabetes Obes Metab.
2023 Dec;
25(12):3724-3735.
Abstract: To assess the effects of canagliflozin on clinical outcomes and intermediate markers across population-specific body mass index (BMI) categories in the CANVAS Program and CREDENCE trial. Individual participant data were pooled and analysed in subgroups according to population-specific BMI. The main outcomes of interest were: major adverse cardiovascular events (MACE, a composite of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death); composite renal outcome; and changes in systolic blood pressure (SBP), body weight, albuminuria and estimated glomerular filtration rate (eGFR) slope. Cox proportional hazards models and mixed-effect models were used. A total of 14 520 participants were included, of whom 9378 (65%) had obesity. Overall, canagliflozin reduced the risk of MACE (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.75 to 0.93) with no heterogeneity of treatment effect across BMI subgroups (P = 0.76). Similarly, canagliflozin reduced composite renal outcomes (HR 0.75, 95% CI 0.66 to 0.84) with no heterogeneity across subgroups observed (P = 0.72). The effects of canagliflozin on body weight and SBP differed across BMI subgroups (P <0.01 and 0.04, respectively) but were consistent for albuminuria (P = 0.60). Chronic eGFR slope with canagliflozin treatment was consistent across subgroups (P >0.95). The cardiovascular and renal benefits of canagliflozin and its safety profile were consistent across population-specific BMI subgroups for adults in the CANVAS Program and CREDENCE trial.
Abstract Summary: Scientists did a study to see if a medicine called canagliflozin helps adults with different body sizes stay healthy. They looked at over 14,000 people, many of whom were overweight, to see if the medicine could prevent heart problems, help kidneys work better, and control blood pressure and weight. They found that canagliflozin was good at reducing the risk of heart issues and helping kidneys, no matter the person's body size. It also helped people lose weight and lower their blood pressure, but the amount varied for different body sizes. This study shows that canagliflozin is safe and works well for adults with different body sizes to keep their hearts and kidneys 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.
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Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial.
Circulation (2023)
Januzzi JL, Mohebi R, Liu Y, Sattar N, Heerspink HJL, Tefera E, Vaduganathan M, Butler J, Yavin Y, Li J, Pollock CA, Perkovic V, Neal B, Hansen MK.
Cardiorenal Biomarkers, Canagliflozin, and Outcomes in Diabetic Kidney Disease: The CREDENCE Trial.
Circulation.
2023 Aug 22;
148(8):651-660.
Abstract: People with type 2 diabetes and albuminuria are at an elevated risk for cardiac and renal events. The optimal biomarkers to aid disease prediction and to understand the benefits of sodium-glucose cotransporter-2 inhibition remain unclear. Among 2627 study participants in the CREDENCE trial (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, growth differentiation factor-15, and IGFBP7 (insulin-like growth factor binding protein 7) were measured. The effect of canagliflozin on biomarker concentrations was evaluated. The prognostic potential of each biomarker on the primary outcome (a composite of end-stage kidney disease [dialysis, transplantation, or a sustained estimated glomerular filtration rate of <15 mL·min·1.73 m], doubling of the serum creatinine level, or renal death or cardiovascular death) was assessed. The median (quartiles 1 and 3) concentration of each biomarker was generally elevated: NT-proBNP, 180 ng/L (82, 442 ng/L); high-sensitivity cardiac troponin T, 19 ng/L (12, 29 ng/L); growth differentiation factor-15, 2595 ng/L (1852, 3775 ng/L); and IGFBP7, 121.8 ng/mL (105.4, 141.5 ng/mL). At 1 year, the biomarkers all rose by 6% to 29% in the placebo arm but only by 3% to 10% in the canagliflozin arm (all <0.01 in multivariable linear mixed-effect models). Baseline concentrations of each biomarker were strongly predictive of cardiac and renal outcomes. When the biomarkers were analyzed together in a multimarker panel, individuals with high risk scores (hazard ratio [HR], 4.01 [95% CI, 2.52-6.35]) and moderate risk scores (HR, 2.39 [95% CI, 1.48-3.87]) showed a higher risk for the primary outcome compared with those with low risk scores. By 1 year, a 50% increase in NT-proBNP (HR, 1.11 [95% CI, 1.08-1.15]), high-sensitivity cardiac troponin T (HR, 1.86 [95% CI, 1.64-2.10]), growth differentiation factor-15 (HR, 1.45 [95% CI, 1.24-1.70]), and IGFBP7 (HR, 3.76 [95% CI, 2.54-5.56]) was associated with risk of the primary outcome. Multiple cardiorenal stress biomarkers are strongly prognostic in people with type 2 diabetes and albuminuria. Canagliflozin modestly reduced the longitudinal trajectory of rise in each biomarker. Change in the biomarker level in addition to the baseline level augments the primary outcome prediction. URL: https://www. gov; Unique identifier: NCT02065791.
Abstract Summary: Scientists did a study to help people with type 2 diabetes who also have a kidney problem that can cause heart issues. They wanted to find the best way to predict who might get sicker and see if a medicine called canagliflozin could help. They tested 2,627 people and looked at four different things in their blood that might show signs of heart and kidney stress.
They found that the levels of these things in the blood were higher than normal for most people in the study. After one year, the people who didn't get the medicine had their levels go up a lot, but the levels didn't go up as much in the people who took canagliflozin. The scientists also found that if these blood levels were high to start with, the person was more likely to have heart or kidney problems.
In conclusion, checking these four blood levels can help predict health problems in people with type 2 diabetes and kidney issues, and taking canagliflozin might slow down the increase of these levels. This is important because it could help doctors take better care of their patients.
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.
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Insulin growth factor axis and cardio-renal risk in diabetic kidney disease: an analysis from the CREDENCE trial.
Cardiovascular diabetology (2023)
Mohebi R, Liu Y, Hansen MK, Yavin Y, Sattar N, Pollock CA, Butler J, Jardine M, Masson S, Heerspink HJL, Januzzi JL Jr.
Insulin growth factor axis and cardio-renal risk in diabetic kidney disease: an analysis from the CREDENCE trial.
Cardiovasc Diabetol.
2023 Jul 12;
22(1):176.
Abstract: The insulin-like growth factors (IGF) play a crucial role in regulating cellular proliferation, apoptosis, and key metabolic pathways. The ratio of IGF-1 to IGF binding protein-3 (IGFBP-3) is an important factor in determining IGF-1 bioactivity. We sought to investigate the association of IGF-1 and IGFBP-3 with cardio-renal outcomes among persons with type 2 diabetes. Samples were available from 2627 individuals with type 2 diabetes and chronic kidney disease that were randomized to receive canagliflozin or placebo and were followed up for incident cardio-renal events. Primary outcome was defined as a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal/cardiovascular death. IGF-1 and IGFBP-3 were measured at baseline, Year-1 and Year-3. Elevated IGF-1 level was defined according to age-specific cutoffs. Cox proportional hazard regression was used to investigate the association between IGF-1 level, IGFBP-3, and the ratio of IGF-1/IGFBP-3 with clinical outcomes. Elevated IGF-1 was associated with lower glomerular filtration rate at baseline. Treatment with canagliflozin did not significantly change IGF-1 and IGFBP-3 concentrations by 3 years (p-value > 0.05). In multivariable models, elevated IGF-1 (above vs below age-specific cutoffs) was associated with the primary composite outcome (incidence rate:17.8% vs. 12.7% with a hazard ratio [HR]: 1.52; 95% confidence interval CI 1.09-2.13;P: 0.01), renal composite outcome (HR: 1.65; 95% CI 1.14-2.41; P: 0.01), and all-cause mortality (HR: 1.52; 95% CI 1.00-2.32; P; 0.05). Elevations in log IGFBP-3 did not associate with any clinical outcomes. Increase in log IGF-1/IGFBP-3 ratio was also associated with a higher risk of the primary composite outcome (HR per unit increase: 1.57; 95% CI 1.09-2.26; P; 0.01). These results further suggest potential importance of IGF biology in the risk for cardio-renal outcomes in type 2 diabetes. SGLT2 inhibition has no impact on the biology of IGF despite its significant influence on outcomes. CREDENCE; ClinicalTrials.gov Identifier: NCT02065791.
Abstract Summary: Scientists did a study to see how certain growth factors in the body, which help cells grow and stay healthy, are linked to heart and kidney problems in people with type 2 diabetes. They looked at 2627 people with diabetes and kidney disease who were either given a diabetes medicine called canagliflozin or a placebo. They checked the levels of these growth factors when the study started, after one year, and after three years.
They found that people with higher levels of a growth factor called IGF-1 often had worse kidney function at the start. Also, those with higher IGF-1 levels were more likely to have serious kidney and heart problems or to die from these issues. The medicine didn't really change the levels of these growth factors.
This study is important because it shows that the amount of IGF-1 in the body could help doctors figure out who might have a higher risk of heart and kidney problems if they have type 2 diabetes. This could help in taking care of their health 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.
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Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials.
Journal of the American Heart Association (2023)
Fletcher RA, Arnott C, Rockenschaub P, Schutte AE, Carpenter L, Vaduganathan M, Agarwal R, Bakris G, Chang TI, Heerspink HJL, Jardine MJ, Mahaffey KW, Neal B, Pollock C, Jun M, Rodgers A, Perkovic V, Neuen BL.
Canagliflozin, Blood Pressure Variability, and Risk of Cardiovascular, Kidney, and Mortality Outcomes: Pooled Individual Participant Data From the CANVAS and CREDENCE Trials.
J Am Heart Assoc.
2023 Jul 4;
12(13):e028516.
Abstract: Background Sodium glucose cotransporter-2 inhibitors reduce systolic blood pressure (SBP), but whether they affect SBP variability is unknown. There also remains uncertainty regarding the prognostic value of SBP variability for different clinical outcomes. Methods and Results Using individual participant data from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program and CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial, we assessed the effect of canagliflozin on SBP variability in people with type 2 diabetes across 4 study visits over 1.5 years as measured by standard deviation, coefficient of variation, and variability independent of the mean. We used multivariable Cox regression models to estimate associations of SBP variability with cardiovascular, kidney, and mortality outcomes. In 11 551 trial participants, canagliflozin modestly lowered the standard deviation of SBP variability (-0.25 mm Hg [95% CI, -0.44 to -0.06]), but there was no effect on coefficient of variation (0.02% [95% CI, -0.12 to 0.16]) or variability independent of the mean (0.08 U [95% CI, -0.11 to 0.26]) when adjusting for correlation with mean SBP. Each 1 standard deviation increase in standard deviation of SBP variability was independently associated with higher risk of hospitalization for heart failure (hazard ratio [HR], 1.19 [95% CI, 1.02-1.38]) and all-cause mortality (HR, 1.12 [95% CI, 1.01-1.25]), with consistent results observed for coefficient of variation and variability independent of the mean. Increases in SBP variability were not associated with kidney outcomes. Conclusions In people with type 2 diabetes at high cardiovascular risk or with chronic kidney disease, higher visit-to-visit SBP variability is independently associated with risks of hospitalization for heart failure and all-cause mortality. Canagliflozin has little to no effect on SBP variability, independent of its established SBP-lowering effect. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01032629, NCT01989754, NCT02065791.
Abstract Summary: Doctors wanted to see if a diabetes medicine called canagliflozin could make blood pressure less up-and-down in people with type 2 diabetes. They checked the blood pressure of over 11,000 people many times for 1.5 years. They found that the medicine made blood pressure a tiny bit steadier, but not by much. They also learned that when blood pressure goes up and down a lot, it can lead to more hospital visits for heart problems and a higher chance of dying from any cause. However, these ups and downs didn't seem to affect kidney health. This study helps us understand that keeping blood pressure steady is important for staying healthy, but this medicine doesn't help much with that.
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.
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Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE.
Cardiovascular diabetology (2023)
Ferrannini G, Pollock C, Natali A, Yavin Y, Mahaffey KW, Ferrannini E.
Extremes of both weight gain and weight loss are associated with increased incidence of heart failure and cardiovascular death: evidence from the CANVAS Program and CREDENCE.
Cardiovasc Diabetol.
2023 Apr 29;
22(1):100.
Abstract: Obesity is an independent risk factor for cardiovascular disease (CVD) in patients with type 2 diabetes (T2D). However, it is not known to what extent weight fluctuations might be associated with adverse outcomes. We aimed at assessing the associations between extreme weight changes and cardiovascular outcomes in two large randomised controlled trials of canagliflozin in patients with T2D and high cardiovascular (CV) risk. In the study populations of the CANVAS Program and CREDENCE trials, weight change was evaluated between randomization and week 52-78, defining subjects in the top 10% of the entire distribution of weight changes as gainers, subjects in the bottom 10% as losers and the remainder as stable. Univariate and multivariate Cox proportional hazards models were used to test the associations between weight changes categories, randomised treatment and covariates with heart failure hospitalisation (hHF) and the composite of hHF and CV death. Median weight gain was 4.5 kg in gainers and median weight loss was 8.5 kg in losers. The clinical phenotype of gainers as well as that of losers were similar to that of stable subjects. Weight change within each category was only slightly larger with canagliflozin than placebo. In both trials, gainers and losers had a higher risk of hHF and of hHF/CV death compared with stable at univariate analysis. In CANVAS, this association was still significant by multivariate analysis for hHF/CV death in both gainers and losers vs. stable (hazard ratio - HR 1.61 [95% confidence interval - CI: 1.20-2.16] and 1.53 [95% CI 1.14-2.03] respectively). Results were similar in CREDENCE for gainers vs. stable (adjusted HR for hHF/CV death 1.62 [95% CI 1.19-2.16]) CONCLUSIONS: Extremes of weight gain or loss were independently associated with a higher risk of the composite of hHF and CV death. In patients with T2D and high CV risk, large changes in body weight should be carefully assessed in view of individualised management. CANVAS ClinicalTrials.gov number: NCT01032629. CREDENCE ClinicalTrials.gov number: NCT02065791.
Abstract Summary: Doctors wanted to see if gaining or losing a lot of weight quickly affects heart health in people with type 2 diabetes who are already at risk for heart problems. They looked at two big studies where people took a diabetes medicine called canagliflozin. They checked the weight of these people after about a year and put them into three groups: those who gained a lot of weight, those who lost a lot of weight, and those whose weight stayed the same.
They found that people who gained or lost a lot of weight had a higher chance of going to the hospital for heart failure or even dying from heart problems compared to those whose weight didn't change much. This means that for people with type 2 diabetes who might have heart issues, it's important to watch out for big weight changes and talk to a doctor about the best way to 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.
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Glycemic Control and Effects of Canagliflozin in Reducing Albuminuria and eGFR: A Post Hoc Analysis of the CREDENCE Trial.
Clinical journal of the American Society of Nephrology : CJASN (2023)
van der Hoek S, Jongs N, Oshima M, Neuen BL, Stevens J, Perkovic V, Levin A, Mahaffey KW, Pollock C, Greene T, Wheeler DC, Jardine MJ, Heerspink HJL.
Glycemic Control and Effects of Canagliflozin in Reducing Albuminuria and eGFR: A Post Hoc Analysis of the CREDENCE Trial.
Clin J Am Soc Nephrol.
2023 Jun 1;
18(6):748-758.
Abstract: In the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, the sodium-glucose cotransporter-2 (SGLT2) inhibitor canagliflozin improved kidney and cardiovascular outcomes and reduced the rate of estimated glomerular filtration decline (eGFR slope) in patients with type 2 diabetes and CKD. In other clinical trials of patients with CKD or heart failure, the protective effects of SGLT2 inhibitors on eGFR slope were greater in participants with versus participants without type 2 diabetes. This post hoc analysis of the CREDENCE trial assessed whether the effects of canagliflozin on eGFR slope varied according to patient subgroups by baseline glycated hemoglobin A1c (HbA1c). CREDENCE ( ClinicalTrials.gov [ NCT02065791 ]) was a randomized controlled trial in adults with type 2 diabetes with an HbA1c of 6.5%-12.0%, an eGFR of 30-90 ml/min per 1.73 m 2 , and a urinary albumin-to-creatinine ratio of 300-5000 mg/g. Participants were randomly assigned to canagliflozin 100 mg once daily or placebo. We studied the effect of canagliflozin on eGFR slope using linear mixed-effects models. The annual difference in total eGFR slope was 1.52 ml/min per 1.73 m 2 (95% confidence interval [CI], 1.11 to 1.93) slower in participants randomized to canagliflozin compared with placebo. The rate of eGFR decline was faster in those with poorer baseline glycemic control. The mean difference in total eGFR slope between canagliflozin and placebo was greater in participants with poorer baseline glycemic control (difference in eGFR slope of 0.39, 1.36, 2.60, 1.63 ml/min per 1.73 m 2 for HbA1c subgroups 6.5%-7.0%, 7.0%-8.0%, 8.0%-10.0%, 10.0%-12.0%, respectively; Pinteraction = 0.010). The mean difference in change from baseline in urinary albumin-to-creatinine ratio between participants randomized to canagliflozin and placebo was smaller in patients with baseline HbA1c 6.5%-7.0% (-17% [95% CI, -28 to -5]) compared with those with an HbA1c of 7.0%-12% (-32% [95% CI, -40 to -28]; Pinteraction = 0.03). The effect of canagliflozin on eGFR slope in patients with type 2 diabetes and CKD was more pronounced in patients with higher baseline HbA1c, partly because of the more rapid decline in kidney function in these individuals. Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE), NCT02065791.
Abstract Summary: Scientists did a study called CREDENCE to see if a medicine called canagliflozin helps people with type 2 diabetes and kidney problems. They gave some people the medicine and others a placebo, which is like a sugar pill with no medicine in it. They found that the medicine slowed down the worsening of kidney function, especially in people who had higher blood sugar levels to start with. This is important because it shows that this medicine can help protect the kidneys of people with diabetes, and it might work even better for those who have more trouble controlling 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.
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Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial.
American journal of kidney diseases : the official journal of the National Kidney Foundation (2023)
Yi TW, Smyth B, Di Tanna GL, Arnott C, Cardoza K, Kang A, Pollock C, Agarwal R, Bakris G, Charytan DM, de Zeeuw D, Heerspink HJL, Neal B, Wheeler DC, Cannon CP, Zhang H, Zinman B, Perkovic V, Levin A, Mahaffey KW, Jardine M, CREDENCE Trial Investigators.
Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial.
Am J Kidney Dis.
2023 Jul;
82(1):84-96.e1.
Abstract: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study. Secondary analysis of a randomized controlled trial. Participants in the CREDENCE trial. Participants were randomly assigned to receive canagliflozin 100mg/d or placebo. Primary composite outcome of kidney failure, doubling of serum creatinine concentration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (<60, 60-69, and≥70 years) and sex in the intention-to-treat population using Cox regression models. The mean age of the cohort was 63.0±9.2 years, and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.48-0.82], and 0.89 [0.61-1.29] for ages<60, 60-69, and≥70 years, respectively; P=0.3for interaction) or sexes (HRs, 0.71 [95% CI, 0.54-0.95] and 0.69 [0.56-0.84] in women and men, respectively; P=0.8for interaction). No differences in safety outcomes by age group or sex were observed. This was a post hoc analysis with multiple comparisons. Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants. This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical. The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791.
Abstract Summary: Scientists wanted to see if a medicine called canagliflozin helps adults with diabetes and kidney problems in the same way, no matter their age or if they are a boy or a girl. They looked at a big study where people took either canagliflozin or a pretend pill every day. They checked if the medicine stopped their kidneys from getting worse or if it kept them from dying because of kidney or heart problems. They found that the medicine worked well for everyone, both younger and older people, and for both boys and girls. It was especially good at helping younger people avoid kidney problems. This information is important because it shows that this medicine can help lots of different people with diabetes keep their kidneys 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.
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Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria.
Journal of the American College of Cardiology (2022)
Sarraju A, Bakris G, Cannon CP, Cherney D, Damaraju CV, Figtree GA, Gogate J, Greene T, Heerspink HJL, Januzzi JL Jr, Neal B, Jardine MJ, Blais J, Kosiborod M, Levin A, Lingvay I, Weir MR, Perkovic V, Mahaffey KW.
Cardiovascular Effects of Canagliflozin in Relation to Renal Function and Albuminuria.
J Am Coll Cardiol.
2022 Nov 1;
80(18):1721-1731.
Abstract: People with type 2 diabetes mellitus (T2DM) have elevated cardiovascular (CV) risk, including for hospitalization for heart failure (HHF). Canagliflozin reduced CV and kidney events in patients with T2DM and high CV risk or nephropathy in the CANVAS (CANagliflozin cardioVascular Assessment Study) Program and the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. The aim of this study was to assess the effects of canagliflozin on CV outcomes according to baseline estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (UACR) in pooled patient-level data from the CANVAS Program and CREDENCE trial. Canagliflozin effects on CV death or HHF were assessed by baseline eGFR (<45, 45-60, and >60 mL/min/1.73 m) and UACR (<30, 30-300, and >300 mg/g). HRs and 95% CIs were estimated by using Cox regression models overall and according to subgroups. A total of 14,543 participants from the CANVAS Program (N = 10,142) and the CREDENCE (N = 4,401) trial were included, with a mean age of 63 years, 35% female, 75% White, 13.2% with baseline eGFR <45 mL/min/1.73 m, and 31.9% with UACR >300 mg/g. Rates of CV death or HHF increased as eGFR declined and/or UACR increased. Canagliflozin significantly reduced CV death or HHF compared with placebo (19.4 vs 28.0 events per 1,000 patient-years; HR: 0.70; 95% CI: 0.62-0.79), with consistent results across eGFR and UACR categories (all P interaction >0.40). Risk of CV death or HHF was higher in those with lower baseline eGFR and/or higher UACR. Canagliflozin consistently reduced CV death or HHF in participants with T2DM and high CV risk or nephropathy regardless of baseline renal function or level of albuminuria. (Canagliflozin Cardiovascular Assessment Study [CANVAS], NCT01032629; A Study of the Effects of Canagliflozin [JNJ-24831754] on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus [CANVAS-R], NCT01989754; and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy [CREDENCE], NCT02065791).
Abstract Summary: Scientists did a study to see if a medicine called canagliflozin helps people with type 2 diabetes who are at risk for heart problems, including heart failure. They looked at two big studies with over 14,000 people to see if canagliflozin could help prevent death from heart issues or stop people from having to go to the hospital for heart failure. They checked how well the people's kidneys were working and how much of a certain protein was in their urine, because these can affect heart health. They found that canagliflozin helped reduce these heart problems for all different types of people with diabetes, no matter how well their kidneys were working or how much protein was in their urine. This is good news because it means this medicine can help lots of people with diabetes stay healthier and avoid serious 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.
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Canagliflozin, mental health adverse events and diabetes: Exploratory analysis of the CREDENCE trial and CANVAS Program.
Diabetes, obesity & metabolism (2022)
Nunes JC, Yu J, Arnott C, Jardine MJ, Perkovic V, Mahaffey KW.
Canagliflozin, mental health adverse events and diabetes: Exploratory analysis of the CREDENCE trial and CANVAS Program.
Diabetes Obes Metab.
2022 Dec;
24(12):2459-2464.
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Effect of Canagliflozin on Total Cardiovascular Burden in Patients With Diabetes and Chronic Kidney Disease: A Post Hoc Analysis From the CREDENCE Trial.
Journal of the American Heart Association (2022)
Li JW, Arnott C, Heerspink HJL, MBiostat QL, Cannon CP, Wheeler DC, Charytan DM, Barraclough J, Figtree GA, Agarwal R, Bakris G, de Zeeuw D, Greene T, Levin A, Pollock C, Zhang H, Zinman B, Mahaffey KW, Perkovic V, Neal B, Jardine MJ.
Effect of Canagliflozin on Total Cardiovascular Burden in Patients With Diabetes and Chronic Kidney Disease: A Post Hoc Analysis From the CREDENCE Trial.
J Am Heart Assoc.
2022 Aug 16;
11(16):e025045.
Abstract: Background The sodium-glucose cotransporter 2 inhibitor canagliflozin reduced the risk of first cardiovascular composite events in the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. In this post hoc analysis, we evaluated the effect of canagliflozin on total (first and recurrent) cardiovascular events. Methods and Results The CREDENCE trial compared canagliflozin or matching placebo in 4401 patients with type 2 diabetes, albuminuria, and estimated glomerular filtration rate of 30 to <90 mL/min per 1.73 m, over a median of 2.6 years. The primary outcome was analyzed as a composite of any cardiovascular event including myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, and cardiovascular death. Negative binomial regression models were used to assess the effect of canagliflozin on the net burden of cardiovascular events. During the trial, 634 patients had 883 cardiovascular events, of whom 472 (74%) had just 1 cardiovascular event and 162 (26%) had multiple cardiovascular events. Canagliflozin reduced first cardiovascular events by 26% (hazard ratio, 0.74 [95% CI, 0.63-0.86]; <0.001) and total cardiovascular events by 29% (incidence rate ratio, 0.71 [95% CI, 0.59-0.86]; <0.001). The absolute risk difference per 1000 patients treated over 2.5 years was -44 (95% CI, -67 to -21) first cardiovascular events and -73 (95% CI, -114 to -33) total events. Conclusions Canagliflozin reduced cardiovascular events, with a larger absolute benefit for total cardiovascular than first cardiovascular events. These findings provide further support for the benefit of continuing canagliflozin therapy after an initial event to prevent recurrent cardiovascular events. Registration Information URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02065791.
Abstract Summary: Scientists did a study to see if a medicine called canagliflozin could help people with type 2 diabetes who also have heart problems. They tested this medicine on over 4,000 patients for about 2.5 years. They found that this medicine reduced the number of heart problems by 26% for first-time issues and 29% for repeated issues. This means that for every 1,000 patients who took the medicine for 2.5 years, there were 44 fewer first-time heart problems and 73 fewer total heart problems. This shows that canagliflozin can help prevent heart problems in people with type 2 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.
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Potential Effects of Elimination of the Black Race Coefficient in eGFR Calculations in the CREDENCE Trial.
Clinical journal of the American Society of Nephrology : CJASN (2022)
Charytan DM, Yu J, Jardine MJ, Cannon CP, Agarwal R, Bakris G, Greene T, Levin A, Pollock C, Powe NR, Arnott C, Mahaffey KW, CREDENCE study investigators.
Potential Effects of Elimination of the Black Race Coefficient in eGFR Calculations in the CREDENCE Trial.
Clin J Am Soc Nephrol.
2022 Mar;
17(3):361-373.
Abstract: The effect of including race in the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation on screening, recruitment, and outcomes of clinical trials is unclear. The inclusion and outcomes of participants in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, which randomized individuals with type 2 diabetes and CKD to canagliflozin or placebo, were evaluated after calculating eGFR using the 2009 CKD-EPI creatinine equation with and without a race-specific coefficient or the 2021 CKD-EPI creatinine equation. Treatment effects were estimated using proportional hazards models and piecewise linear mixed effects models for eGFR slope. Of 4401 randomized participants, 2931 (67%) were White participants, 224 (5%) were Black participants, 877 (20%) were Asian participants, and 369 (8%) participants were other race. Among randomized participants, recalculation of screening eGFR using the 2009 equation without a race-specific coefficient had no effect on the likelihood of non-Black participants meeting inclusion criteria but would have excluded 22 (10%) randomized Black participants for eGFR<30 ml/min per 1.73 m. Recalculation with the 2021 equation would have excluded eight (4%) Black participants for low eGFR and one (0.4%) Black participant for eGFR≥90 ml/min per 1.73 m, whereas 30 (0.7%) and 300 (7%) non-Black participants would have been excluded for low and high eGFR, respectively. A high proportion (eight of 22; 36%) of end points in Black participants occurred in individuals who would have been excluded following recalculation using the race-free 2009 equation but not when recalculated with the 2021 equation (one of eight; 13%). Cardiovascular and kidney treatment effects remained consistent across eGFR categories following recalculation with either equation. Changes in estimated treatment effects on eGFR slope were modest but were qualitatively larger following recalculation using the 2021 equation. However, the effect of canagliflozin on chronic change in eGFR was attenuated by 7% among Black participants and increased 6% in non-Black participants. In the CREDENCE trial, eGFR recalculation without the race-specific coefficient had small but potentially important effects on event rates and the relative proportion of Black participants without substantially changing efficacy estimates. Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), NCT02065791.
Abstract Summary: Scientists did a study to see if including a person's race in a kidney health test changes who gets to join a diabetes and kidney disease study and what the results are. They looked at a medicine called canagliflozin in a big study with people who have type 2 diabetes and kidney problems. They used different ways to measure how well the kidneys work, with and without considering the person's race. They found that not using race in the test would have stopped some Black people from joining the study, and these people had important health events during the study. The medicine worked well for everyone, no matter how they measured kidney health. This research helps us understand that small changes in how we test kidney health can affect who gets into studies and what we learn from 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.
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Canagliflozin and Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial.
American journal of kidney diseases : the official journal of the National Kidney Foundation (2022)
Heerspink HJL, Oshima M, Zhang H, Li J, Agarwal R, Capuano G, Charytan DM, Craig J, de Zeeuw D, Di Tanna GL, Levin A, Neal B, Perkovic V, Wheeler DC, Yavin Y, Jardine MJ.
Canagliflozin and Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial.
Am J Kidney Dis.
2022 Feb;
79(2):244-256.e1.
Abstract: Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs). A randomized, double-blind, placebo-controlled, multicenter international trial. 4,401 trial participants with T2DM, CKD, and urinary albumin-creatinine ratio >300-5,000 mg/g. Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo. Rates of kidney-related AEs were analyzed using an on-treatment approach, overall and by screening estimated glomerular filtration rate (eGFR) strata (30-<45, 45-<60, and 60-<90 mL/min/1.73 m). Canagliflozin was associated with a reduction in the overall incidence rate of kidney-related AEs (60.2 vs 84.0 per 1,000 patient-years; hazard ratio [HR], 0.71 [95% CI, 0.61-0.82]; P < 0.001), with consistent results for serious kidney-related AEs (HR, 0.72 [95% CI, 0.51-1.00]; P = 0.05) and acute kidney injury (AKI; HR, 0.85 [95% CI, 0.64-1.13]; P = 0.3). The rates of kidney-related AEs were lower with canagliflozin relative to placebo across the 3 eGFR strata (HRs of 0.73, 0.60, and 0.81 for eGFR 30-<45, 45-<60, and 60-<90 mL/min/1.73 m, respectively; P = 0.3 for interaction), with similar results for AKI (P = 0.9 for interaction). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio, 2.2 [95% CI, 1.0-4.7]; P = 0.04). Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured, and creatinine data after an AKI event were not available for all participants. Compared with placebo, canagliflozin was associated with a reduced incidence of serious and nonserious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney-related AEs. The CREDENCE trial and this analysis were funded by Janssen Research & Development, LLC, and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical. The CREDENCE trial was registered at ClinicalTrials.gov with identifier number NCT02065791.
Abstract Summary: Scientists did a big study called CREDENCE to see if a medicine called canagliflozin helps people with type 2 diabetes and kidney problems. They gave the medicine to some people and a pretend pill (placebo) to others. They found that the people who took canagliflozin had fewer kidney problems. Even when some people got a sudden kidney injury, those who took canagliflozin were more likely to get better quickly. This study is important because it shows that canagliflozin can help keep kidneys safe in people with diabetes. The study was paid for by the company that makes canagliflozin, and they worked with doctors and researchers to do the research.
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.
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Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.
Stroke (2021)
Zhou Z, Jardine MJ, Li Q, Neuen BL, Cannon CP, de Zeeuw D, Edwards R, Levin A, Mahaffey KW, Perkovic V, Neal B, Lindley RI, CREDENCE Trial Investigators*.
Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.
Stroke.
2021 May;
52(5):1545-1556.
Abstract: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis. In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HR, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HR, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HR, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HR, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HR, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m]) subgroup (HR, 0.50 [95% CI, 0.31-0.79]). Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.
Abstract Summary: Doctors wanted to see if a medicine called SGLT2i could help people with type 2 diabetes and kidney problems avoid strokes and heart rhythm issues. They did a study with 4401 people, giving some the medicine and others a placebo. They found that the medicine might help prevent certain types of strokes and heart rhythm problems, especially in people with more serious kidney issues. They think more research is needed to be sure, but this could be good news for keeping people with diabetes and kidney disease 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.
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Effects of canagliflozin on myocardial infarction: a post hoc analysis of the CANVAS programme and CREDENCE trial.
Cardiovascular research (2022)
Yu J, Li J, Leaver PJ, Arnott C, Huffman MD, Udell JA, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Matthews DR, Shaw W, Rosenthal N, Neal B, Figtree GA.
Effects of canagliflozin on myocardial infarction: a post hoc analysis of the CANVAS programme and CREDENCE trial.
Cardiovasc Res.
2022 Mar 16;
118(4):1103-1114.
Abstract: Given the benefits of sodium glucose co-transporter 2 inhibition (SGLT2i) in protecting against heart failure in diabetic patients, we sought to explore the potential impact of SGLT2i on the clinical features of patients presenting with myocardial infarction (MI) through a post hoc analysis of CANVAS Programme and CREDENCE trial. Individuals with type 2 diabetes and history or high risk of cardiovascular disease (CANVAS Programme) or type 2 diabetes and chronic kidney disease (CREDENCE) were included. The intervention was canagliflozin 100 or 300 mg (combined in the analysis) or placebo. MI events were adjudicated as ST-elevation myocardial infarction (STEMI), non-STEMI, and type 1 MI or type 2 MI. A total of 421 first MI events in the CANVAS Programme and 178 first MI events in the CREDENCE trial were recorded (83 fatal, 128 STEMI, 431 non-STEMI, and 40 unknown). No benefit of canagliflozin compared with placebo on time to first MI event was observed [hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.75, 1.05]. Canagliflozin was associated with lower risk for non-STEMI (HR 0.78; 95% CI 0.65, 0.95) but suggested a possible increase in STEMI (HR 1.55; 95% CI 1.06, 2.27), with no difference in risk of type 1 or type 2 MI. There was no change in fatal MI (HR 1.22, 95% CI 0.78, 1.93). Canagliflozin was not associated with a reduction in overall MI in the pooled CANVAS Programme and CREDENCE trial population. The possible differential effect on STEMI and Non-STEMI observed in the CANVAS cohort warrants further investigation. ClinicalTrials.gov identifiers: NCT01032629, NCT01989754, and NCT02065791.
Abstract Summary: Doctors wanted to see if a medicine called canagliflozin could help people with diabetes avoid heart attacks. They looked at two big studies with people who had diabetes and either heart problems or kidney disease. Some people got canagliflozin, and some got a pretend pill. They found that canagliflozin didn't stop heart attacks in general. But it did seem to help with one kind of heart attack (non-STEMI) and maybe made another kind (STEMI) happen more. The medicine didn't change the number of people who died from heart attacks. The doctors think more research is needed to understand why the medicine helped with one kind of heart attack but not the 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.
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Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria: A CREDENCE Secondary Analysis.
Clinical journal of the American Society of Nephrology : CJASN (2021)
Jardine M, Zhou Z, Lambers Heerspink HJ, Hockham C, Li Q, Agarwal R, Bakris GL, Cannon CP, Charytan DM, Greene T, Levin A, Li JW, Neuen BL, Neal B, Oh R, Oshima M, Pollock C, Wheeler DC, de Zeeuw D, Zhang H, Zinman B, Mahaffey KW, Perkovic V.
Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria: A CREDENCE Secondary Analysis.
Clin J Am Soc Nephrol.
2021 Mar 8;
16(3):384-395.
Abstract: The kidney protective effects of renin-angiotensin system inhibitors are greater in people with higher levels of albuminuria at treatment initiation. Whether this applies to sodium-glucose cotransporter 2 (SGLT2) inhibitors is uncertain, particularly in patients with a very high urine albumin-to-creatinine ratio (UACR; ≥3000 mg/g). We examined the association between baseline UACR and the effects of the SGLT2 inhibitor, canagliflozin, on efficacy and safety outcomes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) randomized controlled trial. The study enrolled 4401 participants with type 2 diabetes, an eGFR of 30 to <90 ml/min per 1.73 m, and UACR of >300 to 5000 mg/g. Using Cox proportional hazards regression, we examined the relative and absolute effects of canagliflozin on kidney, cardiovascular, and safety outcomes according to a baseline UACR of ≤1000 mg/g (=2348), >1000 to <3000 mg/g (=1547), and ≥3000 mg/g (=506). In addition, we examined the effects of canagliflozin on UACR itself, eGFR slope, and the intermediate outcomes of glycated hemoglobin, body weight, and systolic BP. Overall, higher UACR was associated with higher rates of kidney and cardiovascular events. Canagliflozin reduced efficacy outcomes for all UACR levels, with no evidence that relative benefits varied between levels. For example, canagliflozin reduced the primary composite outcome by 24% (hazard ratio [HR], 0.76; 95% confidence interval [95% CI], 0.56 to 1.04) in the lowest UACR subgroup, 28% (HR, 0.72; 95% CI, 0.56 to 0.93) in the UACR subgroup >1000 to <3000 mg/g, and 37% (HR, 0.63; 95% CI, 0.47 to 0.84) in the highest subgroup (=0.55). Absolute risk reductions for kidney outcomes were greater in participants with higher baseline albuminuria; the number of primary composite events prevented across ascending UACR categories were 17 (95% CI, 3 to 38), 45 (95% CI, 9 to 81), and 119 (95% CI, 35 to 202) per 1000 treated participants over 2.6 years (=0.02). Rates of kidney-related adverse events were lower with canagliflozin, with a greater relative reduction in higher UACR categories. Canagliflozin safely reduces kidney and cardiovascular events in people with type 2 diabetes and severely increased albuminuria. In this population, the relative kidney benefits were consistent over a range of albuminuria levels, with greatest absolute kidney benefit in those with an UACR ≥3000 mg/g. ClinicalTrials.gov: CREDENCE, NCT02065791. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_02_22_CJN15260920_final.mp3.
Abstract Summary: This study looked at how a drug called canagliflozin helps people with type 2 diabetes who have a lot of a protein called albumin in their urine, a sign of kidney problems. The researchers studied over 4,000 people and found that the drug helped reduce kidney and heart problems in these patients. The drug was especially helpful for those with very high levels of albumin in their urine. This is good news because it means this drug can help protect the kidneys and hearts of people with type 2 diabetes, especially those with serious kidney issues.
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.
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Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial.
Circulation (2021)
Ye N, Jardine MJ, Oshima M, Hockham C, Heerspink HJL, Agarwal R, Bakris G, Schutte AE, Arnott C, Chang TI, Górriz JL, Cannon CP, Charytan DM, de Zeeuw D, Levin A, Mahaffey KW, Neal B, Pollock C, Wheeler DC, Luca Di Tanna G, Cheng H, Perkovic V, Neuen BL.
Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial.
Circulation.
2021 May 4;
143(18):1735-1749.
Abstract: People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown. The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP-lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups. The trial included 4401 participants, of whom 3361 (76.4%) had baseline systolic BP ≥130 mm Hg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50 mm Hg (95% CI, -4.27 to -2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP-lowering therapy subgroups (all interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP-lowering agents during the trial (hazard ratio, 0.68 [95% CI, 0.61-0.75]). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease (hazard ratio, 0.70 [95% CI, 0.59-0.82]) was consistent across BP and BP-lowering therapy subgroups (all interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes. In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.
Abstract Summary: Doctors wanted to see if a medicine called canagliflozin helps lower blood pressure in people who have type 2 diabetes and kidney disease. They did a study with 4401 people, giving some the medicine and others a placebo, which is like a sugar pill with no medicine in it. They found that canagliflozin did help lower blood pressure pretty quickly and kept it lower during the study. It worked for everyone, no matter how high their blood pressure was or what other medicines they were taking. Also, people who took canagliflozin didn't need to start taking more blood pressure medicines as often. This medicine also helped with kidney problems and heart disease without causing other issues. So, the study shows that canagliflozin can be good for people with diabetes and kidney disease to help protect their organs and control blood pressure.
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.
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Effects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure: Results from the CREDENCE trial.
American heart journal (2021)
Sarraju A, Li J, Cannon CP, Chang TI, Agarwal R, Bakris G, Charytan DM, de Zeeuw D, Greene T, Heerspink HJL, Levin A, Neal B, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Perkovic V, Jardine M, Mahaffey KW.
Effects of canagliflozin on cardiovascular, renal, and safety outcomes in participants with type 2 diabetes and chronic kidney disease according to history of heart failure: Results from the CREDENCE trial.
Am Heart J.
2021 Mar;
233:141-148.
Abstract: We aimed to assess the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy according to prior history of heart failure in the Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation (CREDENCE) trial. We found that participants with a prior history of heart failure at baseline (15%) were more likely to be older, female, white, have a history of atherosclerotic cardiovascular disease, and use diuretics and beta blockers (all P < .001), and that, compared with placebo, canagliflozin safely reduced renal and cardiovascular events with consistent effects in patients with and without a prior history of heart failure (all efficacy P interaction >.150). These results support the efficacy and safety of canagliflozin in patients with type 2 diabetes and nephropathy regardless of prior history of heart failure.
Abstract Summary: Doctors wanted to see if a medicine called canagliflozin is good and safe for people with type 2 diabetes who also have kidney problems, even if they've had heart problems before. They did a study with some people who had heart problems and some who didn't. They found out that canagliflozin helps both groups and doesn't cause bad side effects. This is important because it means that this medicine can help lots of people with diabetes and kidney issues stay healthier, even if they've had heart issues in the past.
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.
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Linear Projection of Estimated Glomerular Filtration Rate Decline with Canagliflozin and Implications for Dialysis Utilization and Cost in Diabetic Nephropathy.
Diabetes therapy : research, treatment and education of diabetes and related disorders (2021)
Durkin M, Blais J.
Linear Projection of Estimated Glomerular Filtration Rate Decline with Canagliflozin and Implications for Dialysis Utilization and Cost in Diabetic Nephropathy.
Diabetes Ther.
2021 Feb;
12(2):499-508.
Abstract: Diabetes is a common cause of end-stage kidney disease leading to dialysis or kidney transplantation. Estimated glomerular filtration rate (eGFR) measures kidney function, and differences in the rate (slope) of eGFR decline can be used to assess treatment effects on kidney function over time. In the CREDENCE trial, the sodium glucose co-transporter 2 inhibitor canagliflozin slowed the rate of eGFR decline by 60% compared to placebo in patients with diabetes and chronic kidney disease. This analysis utilized eGFR slopes from CREDENCE to estimate the difference in time to dialysis by treatment arm and estimated the economic value of that delay. A linear decline in eGFR and maintenance of stable therapy were assumed for the canagliflozin and placebo arms in CREDENCE. Mean eGFR over time was calculated using acute (baseline to week 3) and chronic (week 3 onward) slopes. Reaching eGFR of 10 ml/min/1.73 m was assumed to represent the need for chronic dialysis. The difference in time to dialysis between treatments was calculated. Based on the average duration of dialysis, annual dialysis costs were determined, discounting 2020 US dollars at an inflation rate of 4%. Following the acute and chronic eGFR slopes, the projected time to dialysis was 22.85 years for canagliflozin and 9.90 years for placebo. Based on 95% confidence intervals from CREDENCE, the model-estimated difference in time to dialysis was 9.27-17.48 years. With a mean baseline participant age of 63 years, the delay in dialysis with canagliflozin would be associated with a reduction in dialysis costs of approximately $170,000 per patient in 2020 dollars. Using clinical trial data, canagliflozin treatment was projected to delay dialysis by approximately 13 years, which could translate to a substantial cost savings. More precise estimates should be investigated with considerations for nonlinear eGFR slope trajectory, competing risks, and patient characteristics. ClinicalTrials.gov identifier, NCT02065791.
Abstract Summary: Doctors did a study to see if a medicine called canagliflozin could help people with diabetes and sick kidneys wait longer before needing dialysis (a treatment to clean their blood when kidneys can't). They found that this medicine can slow down the damage to kidneys. People taking canagliflozin might not need dialysis for about 13 more years compared to those who didn't take it. This could save a lot of money for each patient because dialysis is expensive. The study used numbers from a big test (called the CREDENCE trial) to guess how much longer people could wait for dialysis and how much money could be saved.
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.
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Cost-Effectiveness of Canagliflozin Added to Standard of Care for Treating Diabetic Kidney Disease (DKD) in Patients with Type 2 Diabetes Mellitus (T2DM) in England: Estimates Using the CREDEM-DKD Model.
Diabetes therapy : research, treatment and education of diabetes and related disorders (2021)
Willis M, Nilsson A, Kellerborg K, Ball P, Roe R, Traina S, Beale R, Newell I.
Cost-Effectiveness of Canagliflozin Added to Standard of Care for Treating Diabetic Kidney Disease (DKD) in Patients with Type 2 Diabetes Mellitus (T2DM) in England: Estimates Using the CREDEM-DKD Model.
Diabetes Ther.
2021 Jan;
12(1):313-328.
Abstract: On the basis of reductions in diabetic kidney disease (DKD) progression and major adverse cardiovascular events observed in the landmark CREDENCE trial, canagliflozin 100 mg received an extension to its EU marketing authorisation in July 2020 to include the treatment of DKD in people with type 2 diabetes mellitus (T2DM) making it the first pharmacological therapy to receive regulatory authorisation for treatment of DKD since the RENAAL and IDNT trials in nearly 20 years. Efficient allocation of limited healthcare resources requires evaluation not only of clinical safety and efficacy but also economic consequences. The study aim was to estimate the cost-effectiveness of canagliflozin when added to current standard of care (SoC) versus SoC alone from the perspective of the NHS in England. A microsimulation model was developed using patient-level data from CREDENCE, including risk equations for the key clinical outcomes of start of dialysis, hospitalisation for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. DKD progression was modelled using estimated glomerular filtration rate and urinary albumin-to-creatinine ratio evolution equations. Risk for kidney transplant was sourced from UK-specific sources given the near absence of events in CREDENCE. Patient characteristics and treatment effects were sourced from CREDENCE. Unit costs (£2019) and disutility weights were sourced from the literature and discounted at 3.5% annually. The time horizon was 10 years in the base case, and sensitivity analysis was performed. Canagliflozin was associated with sizable gains in life-years and quality-adjusted life-year (QALYs) over 10 years, with gains increasing with simulation duration. Cost offsets associated with reductions in cardiovascular and renal complications were sufficient to achieve overall net cost savings. The findings were generally confirmed in the sensitivity analyses. Model results suggest that adding canagliflozin 100 mg to SoC can improve patient outcomes while reducing overall net costs from the NHS perspective in England. ClinicalTrials.gov identifier, NCT02065791.
Abstract Summary: Scientists did a study to see if a medicine called canagliflozin is good for people with type 2 diabetes who also have a kidney problem called diabetic kidney disease. They wanted to know if it helps people stay healthier and if it's worth the money for the health service in England. They used a special computer program to look at what happened to people who took the medicine in a big test called the CREDENCE trial. They found out that the medicine can help people live longer and better lives, and it can also save money because it keeps them from having heart and kidney problems. This is good news because it means the medicine can help people with diabetes and kidney disease without costing too much.
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.
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Development and Internal Validation of a Discrete Event Simulation Model of Diabetic Kidney Disease Using CREDENCE Trial Data.
Diabetes therapy : research, treatment and education of diabetes and related disorders (2020)
Willis M, Asseburg C, Slee A, Nilsson A, Neslusan C.
Development and Internal Validation of a Discrete Event Simulation Model of Diabetic Kidney Disease Using CREDENCE Trial Data.
Diabetes Ther.
2020 Nov;
11(11):2657-2676.
Abstract: The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study showed that compared with placebo, canagliflozin 100 mg significantly reduced the risk of major cardiovascular events and adverse renal outcomes in patients with diabetic kidney disease (DKD). We developed a simulation model that can be used to estimate the long-term health and economic consequences of DKD treatment interventions for patients matching the CREDENCE study population. The CREDENCE Economic Model of DKD (CREDEM-DKD) was developed using patient-level data from CREDENCE (which recruited patients with estimated glomerular filtration rate 30 to < 90 mL/min/1.73 m, urinary albumin to creatinine ratio > 300-5000 mg/g, and taking the maximum tolerated dose of a renin-angiotensin-aldosterone system inhibitor). Risk prediction equations were fit for start of maintenance dialysis, doubling of serum creatinine, hospitalization for heart failure, nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality. A micro-simulation model was constructed using these risk equations combined with user-definable kidney transplant event risks. Internal validation was performed by loading the model to replicate the CREDENCE study and comparing predictions with trial Kaplan-Meier estimate curves. External validation was performed by loading the model to replicate a subgroup of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program with patient characteristics that would have qualified for inclusion in CREDENCE. Risk prediction equations generally fit well and exhibited good concordance, especially for the placebo arm. In the canagliflozin arm, modest underprediction was observed for myocardial infarction, along with overprediction of dialysis, doubling of serum creatinine, and all-cause mortality. Discrimination was strong (0.85) for the renal outcomes, but weaker for the macrovascular outcomes and all-cause mortality (0.60-0.68). The model performed well in internal and external validation exercises. CREDEM-DKD is an important new tool in the evaluation of treatment interventions in the DKD population. ClinicalTrials.gov identifier, NCT02065791.
Abstract Summary: Scientists did a study called CREDENCE to see if a medicine called canagliflozin helps people with diabetes who also have kidney problems. They found out that this medicine can lower the risk of heart problems and make the kidneys healthier. Then, they made a special computer program called CREDEM-DKD to guess what might happen to these patients in the future, like if they would need dialysis (a kidney treatment), have heart issues, or other health problems.
They used information from the CREDENCE study to make the computer program. They checked to make sure the program worked well by comparing its guesses to what really happened in the study and another study called CANVAS. The program did a good job of guessing kidney problems but wasn't as good at guessing heart problems or when someone might die.
This computer program is a helpful tool for doctors to understand and explain what might happen to patients with diabetes and kidney problems in the long run. It can also help figure out if treatments are worth the cost.
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.
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Renal, Cardiovascular, and Safety Outcomes of Canagliflozin by Baseline Kidney Function: A Secondary Analysis of the CREDENCE Randomized Trial.
Journal of the American Society of Nephrology : JASN (2020)
Jardine MJ, Zhou Z, Mahaffey KW, Oshima M, Agarwal R, Bakris G, Bajaj HS, Bull S, Cannon CP, Charytan DM, de Zeeuw D, Di Tanna GL, Greene T, Heerspink HJL, Levin A, Neal B, Pollock C, Qiu R, Sun T, Wheeler DC, Zhang H, Zinman B, Rosenthal N, Perkovic V, C.
Renal, Cardiovascular, and Safety Outcomes of Canagliflozin by Baseline Kidney Function: A Secondary Analysis of the CREDENCE Randomized Trial.
J Am Soc Nephrol.
2020 May;
31(5):1128-1139.
Abstract: Canagliflozin reduced renal and cardiovascular events in people with type 2 diabetes in the CREDENCE trial. We assessed efficacy and safety of canagliflozin by initial estimated glomerular filtration rate (eGFR). CREDENCE randomly assigned 4401 participants with an eGFR of 30 to <90 ml/min per 1.73 m and substantial albuminuria to canagliflozin 100 mg or placebo. We used Cox proportional hazards regression to analyze effects on renal and cardiovascular efficacy and safety outcomes within screening eGFR subgroups (30 to <45, 45 to <60, and 60 to <90 ml/min per 1.73 m) and linear mixed effects models to analyze the effects on eGFR slope. At screening, 1313 (30%), 1279 (29%), and 1809 (41%) participants had an eGFR of 30 to <45, 45 to <60, and 60 to <90 ml/min per 1.73 m, respectively. The relative benefits of canagliflozin for renal and cardiovascular outcomes appeared consistent among eGFR subgroups (all interaction >0.11). Subgroups with lower eGFRs, who were at greater risk, exhibited larger absolute benefits for renal outcomes. Canagliflozin's lack of effect on serious adverse events, amputations, and fractures appeared consistent among eGFR subgroups. In all subgroups, canagliflozin use led to an acute eGFR drop followed by relative stabilization of eGFR loss. Among those with an eGFR of 30 to <45 ml/min per 1.73 m, canagliflozin led to an initial drop of 2.03 ml/min per 1.73 m. Thereafter, decline in eGFR was slower in the canagliflozin versus placebo group (-1.72 versus -4.33 ml/min per 1.73 m; between-group difference 2.61 ml/min per 1.73 m). Canagliflozin safely reduced the risk of renal and cardiovascular events, with consistent results across eGFR subgroups, including the subgroup initiating treatment with an eGFR of 30 to <45 ml/min per 1.73 m. Absolute benefits for renal outcomes were greatest in subgroups with lower eGFR. Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE), NCT02065791.
Abstract Summary: Scientists did a study to see if a medicine called canagliflozin helps people with type 2 diabetes who also have kidney problems. They gave the medicine to some people and a pretend pill (placebo) to others. They checked to see if the medicine helped with kidney and heart health. They found that canagliflozin was good for both, no matter how well the person's kidneys were working at the start. People with worse kidney problems saw the biggest health improvements. The medicine didn't cause serious side effects, like more broken bones or the need for amputations. When people first took the medicine, their kidney numbers went down a little but then got stable, which is better than getting worse over time. This study shows that canagliflozin is safe and can help people with type 2 diabetes protect their kidneys and 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.
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Evaluating the Effects of Canagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease According to Baseline HbA1c, Including Those With HbA1c
Circulation (2020)
Cannon CP, Perkovic V, Agarwal R, Baldassarre J, Bakris G, Charytan DM, de Zeeuw D, Edwards R, Greene T, Heerspink HJL, Jardine MJ, Levin A, Li JW, Neal B, Pollock C, Wheeler DC, Zhang H, Zinman B, Mahaffey KW.
Evaluating the Effects of Canagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease According to Baseline HbA1c, Including Those With HbA1c
Circulation.
2020 Feb 4;
141(5):407-410.
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Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups.
Circulation (2019)
Mahaffey KW, Jardine MJ, Bompoint S, Cannon CP, Neal B, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Capuano G, de Zeeuw D, Greene T, Levin A, Pollock C, Sun T, Wheeler DC, Yavin Y, Zhang H, Zinman B, Rosenthal N, Brenner BM, Perkov.
Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups.
Circulation.
2019 Aug 27;
140(9):739-750.
Abstract: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02065791.
Abstract Summary: Scientists did a study to see if a medicine called canagliflozin helps people with type 2 diabetes and kidney problems. They wanted to know if it could prevent heart problems and make their kidneys work better. They had 4401 people take either canagliflozin or a fake pill (placebo) and checked to see how they did. They found that canagliflozin helped everyone by lowering the chance of having heart issues and kidney failure. This was true even for people who hadn't had heart problems before. This is good news because it means this medicine can help lots of people with diabetes and kidney disease 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.
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Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy.
The New England journal of medicine (2019)
Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, Edwards R, Agarwal R, Bakris G, Bull S, Cannon CP, Capuano G, Chu PL, de Zeeuw D, Greene T, Levin A, Pollock C, Wheeler DC, Yavin Y, Zhang H, Zinman B, Meininger G, Brenner BM, Mahaff.
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy.
N Engl J Med.
2019 Jun 13;
380(24):2295-2306.
Abstract: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P = 0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P = 0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P = 0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.).
Abstract Summary: Doctors wanted to see if a medicine called canagliflozin could help people with type 2 diabetes who also have a kidney problem where they lose protein in their pee. They gave some people this medicine and others a fake pill without any medicine in it. Everyone in the study was already taking medicine to help their kidneys. They checked to see if the people's kidneys got worse, if they needed dialysis or a kidney transplant, or if they died from kidney or heart problems.
They found out that the people who took canagliflozin were less likely to have these bad things happen to them. Their kidneys did better, and they also had fewer heart problems. The study was stopped early because the medicine was working so well. This is good news because it means this medicine can help people with type 2 diabetes protect their kidneys and 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.
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The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics.
American journal of nephrology (2017)
Jardine MJ, Mahaffey KW, Neal B, Agarwal R, Bakris GL, Brenner BM, Bull S, Cannon CP, Charytan DM, de Zeeuw D, Edwards R, Greene T, Heerspink HJL, Levin A, Pollock C, Wheeler DC, Xie J, Zhang H, Zinman B, Desai M, Perkovic V, CREDENCE study investigators.
The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics.
Am J Nephrol.
2017 Dec 13;
46(6):462-472.
Abstract: People with diabetes and kidney disease have a high risk of cardiovascular events and progression of kidney disease. Sodium glucose co-transporter 2 inhibitors lower plasma glucose by reducing the uptake of filtered glucose in the kidney tubule, leading to increased urinary glucose excretion. They have been repeatedly shown to induce modest natriuresis and reduce HbA1c, blood pressure, weight, and albuminuria in patients with type 2 diabetes. However, the effects of these agents on kidney and cardiovascular events have not been extensively studied in patients with type 2 diabetes and established kidney disease. The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial aims to compare the efficacy and safety of canagliflozin -versus placebo at preventing clinically important kidney and cardiovascular outcomes in patients with diabetes and established kidney disease. CREDENCE is a randomized, double-blind, event-driven, placebo-controlled trial set in in 34 countries with a projected duration of ∼5.5 years and enrolling 4,401 adults with type 2 diabetes, estimated glomerular filtration rate ≥30 to <90 mL/min/1.73 m2, and albuminuria (urinary albumin:creatinine ratio >300 to ≤5,000 mg/g). The study has 90% power to detect a 20% reduction in the risk of the primary outcome (α = 0.05), the composite of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. CREDENCE will provide definitive evidence about the effects of canagliflozin on renal (and cardiovascular) outcomes in patients with type 2 diabetes and established kidney disease. EudraCT number: 2013-004494-28; ClinicalTrials.gov identifier: NCT02065791.
Abstract Summary: Doctors are doing a big study called CREDENCE to see if a medicine named canagliflozin can help people with type 2 diabetes who also have kidney problems. This medicine might lower blood sugar and help with heart health. They are testing it against a placebo, which is like a sugar pill with no medicine in it. They want to find out if canagliflozin can stop kidney disease from getting worse and prevent heart problems. Over 4,000 adults from 34 different countries are in the study, which will last about 5 and a half years. If the study shows that canagliflozin works, it could be really important for people with diabetes and kidney disease to keep them 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.
Healthy Donor Controls for Immune Evaluation
Vanderbilt University Medical Center
Cannabinoid Control of Fear Extinction Neural Circuits
University of Illinois at Chicago
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Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms.
The Cochrane database of systematic reviews (2024)
Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C.
Early pharmacological interventions for prevention of post-traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms.
Cochrane Database Syst Rev.
2024 May 20;
5(5):CD013613.
Abstract: Acute traumatic stress symptoms may develop in people who have been exposed to a traumatic event. Although they are usually self-limiting in time, some people develop post-traumatic stress disorder (PTSD), a severe and debilitating condition. Pharmacological interventions have been proposed for acute symptoms to act as an indicated prevention measure for PTSD development. As many individuals will spontaneously remit, these interventions should balance efficacy and tolerability. To assess the efficacy and acceptability of early pharmacological interventions for prevention of PTSD in adults experiencing acute traumatic stress symptoms. We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase and two other databases. We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 23 January 2023. We included randomised controlled trials on adults exposed to any kind of traumatic event and presenting acute traumatic stress symptoms, without restriction on their severity. We considered comparisons of any medication with placebo, or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy. We used standard Cochrane methodological procedures. Using a random-effects model, we analysed dichotomous data as risk ratios (RR) and calculated the number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD). Our primary outcomes were PTSD severity and dropouts due to adverse events. Secondary outcomes included PTSD rate, functional disability and quality of life. We included eight studies that considered four interventions (escitalopram, hydrocortisone, intranasal oxytocin, temazepam) and involved a total of 779 participants. The largest trial contributed 353 participants and the next largest, 120 and 118 participants respectively. The trials enrolled participants admitted to trauma centres or emergency departments. The risk of bias in the included studies was generally low except for attrition rate, which we rated as high-risk. We could meta-analyse data for two comparisons: escitalopram versus placebo (but limited to secondary outcomes) and hydrocortisone versus placebo. One study compared escitalopram to placebo at our primary time point of three months after the traumatic event. There was inconclusive evidence of any difference in terms of PTSD severity (mean difference (MD) on the Clinician-Administered PTSD Scale (CAPS, score range 0 to 136) -11.35, 95% confidence interval (CI) -24.56 to 1.86; 1 study, 23 participants; very low-certainty evidence), dropouts due to adverse events (no participant left the study early due to adverse events; 1 study, 31 participants; very low-certainty evidence) and PTSD rates (RR 0.59, 95% CI 0.03 to 13.08; NNTB 37, 95% CI NNTB 15 to NNTH 1; 1 study, 23 participants; very low-certainty evidence). The study did not assess functional disability or quality of life. Three studies compared hydrocortisone to placebo at our primary time point of three months after the traumatic event. We found inconclusive evidence on whether hydrocortisone was more effective in reducing the severity of PTSD symptoms compared to placebo (MD on CAPS -7.53, 95% CI -25.20 to 10.13; I = 85%; 3 studies, 136 participants; very low-certainty evidence) and whether it reduced the risk of developing PTSD (RR 0.47, 95% CI 0.09 to 2.38; NNTB 14, 95% CI NNTB 8 to NNTH 5; I = 36%; 3 studies, 136 participants; very low-certainty evidence). Evidence on the risk of dropping out due to adverse events is inconclusive (RR 3.19, 95% CI 0.13 to 75.43; 2 studies, 182 participants; low-certainty evidence) and it is unclear whether hydrocortisone might improve quality of life (MD on the SF-36 (score range 0 to 136, higher is better) 19.70, 95% CI -1.10 to 40.50; 1 study, 43 participants; very low-certainty evidence). No study assessed functional disability. This review provides uncertain evidence regarding the use of escitalopram, hydrocortisone, intranasal oxytocin and temazepam for people with acute stress symptoms. It is therefore unclear whether these pharmacological interventions exert a positive or negative effect in this population. It is important to note that acute traumatic stress symptoms are often limited in time, and that the lack of data prevents the careful assessment of expected benefits against side effects that is therefore required. To yield stronger conclusions regarding both positive and negative outcomes, larger sample sizes are required. A common operational framework of criteria for inclusion and baseline assessment might help in better understanding who, if anyone, benefits from an intervention. As symptom severity alone does not provide the full picture of the impact of exposure to trauma, assessment of quality of life and functional impairment would provide a more comprehensive picture of the effects of the interventions. The assessment and reporting of side effects may facilitate a more comprehensive understanding of tolerability.
Abstract Summary: Scientists did a study to see if taking medicine right after a scary event can help stop a serious problem called PTSD. They looked at different medicines to see if they work and if they're safe. They checked a lot of information and studies with 779 people in them. Some people got a sugar pill (placebo) and some got real medicine. They wanted to know if the medicine could make people feel less scared or stressed later on, and if it could help them live their lives better without making them feel sick or worse.
They found out that they can't be sure if the medicines really help or not. The results weren't clear because there weren't enough people in the studies, and they didn't all measure things the same way. They also didn't look at how the medicines might affect how people live their day-to-day lives. The scientists say they need to do more research with more people and check on more things to really understand if these medicines are good for people who have been through something really scary.
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.
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Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD).
The Cochrane database of systematic reviews (2022)
Bertolini F, Robertson L, Bisson JI, Meader N, Churchill R, Ostuzzi G, Stein DJ, Williams T, Barbui C.
Early pharmacological interventions for universal prevention of post-traumatic stress disorder (PTSD).
Cochrane Database Syst Rev.
2022 Feb 10;
2(2):CD013443.
Abstract: Post-traumatic stress disorder (PTSD) is a severe and debilitating condition. Several pharmacological interventions have been proposed with the aim to prevent or mitigate it. These interventions should balance efficacy and tolerability, given that not all individuals exposed to a traumatic event will develop PTSD. There are different possible approaches to preventing PTSD; universal prevention is aimed at individuals at risk of developing PTSD on the basis of having been exposed to a traumatic event, irrespective of whether they are showing signs of psychological difficulties. To assess the efficacy and acceptability of pharmacological interventions for universal prevention of PTSD in adults exposed to a traumatic event. We searched the Cochrane Common Mental Disorders Controlled Trial Register (CCMDCTR), CENTRAL, MEDLINE, Embase, two other databases and two trials registers (November 2020). We checked the reference lists of all included studies and relevant systematic reviews. The search was last updated on 13 November 2020. We included randomised clinical trials on adults exposed to any kind of traumatic event. We considered comparisons of any medication with placebo or with another medication. We excluded trials that investigated medications as an augmentation to psychotherapy. We used standard Cochrane methodological procedures. In a random-effects model, we analysed dichotomous data as risk ratios (RR) and number needed to treat for an additional beneficial/harmful outcome (NNTB/NNTH). We analysed continuous data as mean differences (MD) or standardised mean differences (SMD). We included 13 studies which considered eight interventions (hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare enteral formula, Oxepa enteral formula and 5-hydroxytryptophan) and involved 2023 participants, with a single trial contributing 1244 participants. Eight studies enrolled participants from emergency departments or trauma centres or similar settings. Participants were exposed to a range of both intentional and unintentional traumatic events. Five studies considered participants in the context of intensive care units with traumatic events consisting of severe physical illness. Our concerns about risk of bias in the included studies were mostly due to high attrition and possible selective reporting. We could meta-analyse data for two comparisons: hydrocortisone versus placebo, but limited to secondary outcomes; and propranolol versus placebo. No study compared hydrocortisone to placebo at the primary endpoint of three months after the traumatic event. The evidence on whether propranolol was more effective in reducing the severity of PTSD symptoms compared to placebo at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, serious inconsistency amongst the studies' results, and very serious imprecision of the estimate of effect (SMD -0.51, 95% confidence interval (CI) -1.61 to 0.59; I = 83%; 3 studies, 86 participants; very low-certainty evidence). No study provided data on dropout rates due to side effects at three months post-traumatic event. The evidence on whether propranolol was more effective than placebo in reducing the probability of experiencing PTSD at three months after the traumatic event is inconclusive, because of serious risk of bias amongst the included studies, and very serious imprecision of the estimate of effect (RR 0.77, 95% CI 0.31 to 1.92; 3 studies, 88 participants; very low-certainty evidence). No study assessed functional disability or quality of life. Only one study compared gabapentin to placebo at the primary endpoint of three months after the traumatic event, with inconclusive evidence in terms of both PTSD severity and probability of experiencing PTSD, because of imprecision of the effect estimate, serious risk of bias and serious imprecision (very low-certainty evidence). We found no data on dropout rates due to side effects, functional disability or quality of life. For the remaining comparisons, the available data are inconclusive or missing in terms of PTSD severity reduction and dropout rates due to adverse events. No study assessed functional disability. This review provides uncertain evidence only regarding the use of hydrocortisone, propranolol, dexamethasone, omega-3 fatty acids, gabapentin, paroxetine, PulmoCare formula, Oxepa formula, or 5-hydroxytryptophan as universal PTSD prevention strategies. Future research might benefit from larger samples, better reporting of side effects and inclusion of quality of life and functioning measures.
Abstract Summary: Scientists did a big study to see if certain medicines can help stop people from getting PTSD after they go through something really scary. PTSD is when someone keeps feeling stressed and scared after the scary thing is over. The researchers looked at a lot of different medicines to see if they could help people not get PTSD. They checked out 13 studies with 2023 people in them. Some of the medicines they looked at were hydrocortisone and propranolol.
They found out that it's not clear if these medicines really help. The studies had some problems, like not enough people finished them, or the results weren't reported the right way. Also, the studies didn't agree with each other, and some didn't have enough information. They didn't even look at how these medicines might affect how people live their lives or how happy they are.
So, right now, we don't know for sure if these medicines can stop PTSD. The scientists say we need more and better studies to figure it out. They also say it's important to know if the medicines have bad side effects and if they make people's lives 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.
Galectin-3 Inhibition With Modified Citrus Pectin in Hypertension
Massachusetts General Hospital
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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 Jun;
17(3):e004398.
Abstract: Omics refers to the measurement and analysis of the totality of molecules or biological processes involved within an organism. Examples of omics data include genomics, transcriptomics, epigenomics, proteomics, metabolomics, and more. In this review, we present the available literature reporting omics data on heart failure that can inform the development of novel treatments or innovative treatment strategies for this disease. This includes polygenic risk scores to improve prediction of genomic data and the potential of multiomics to more efficiently identify potential treatment targets for further study. We also discuss the limitations of omic analyses and the barriers that must be overcome to maximize the utility of these types of studies. Finally, we address the current state of the field and future opportunities for using multiomics to better personalize heart failure treatment strategies.
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.
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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.
Chronic Heart Outcomes in Rheumatic Disease (CHORD) Study
Vanderbilt University Medical Center
RIC Financial Incentive Study
Vanderbilt University Medical Center
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Impact of financial compensation on enrollment and participation in a remote, mobile-app based research study.
Journal of clinical and translational science (2024)
Meier S, Cheng A, Tischbein M, Shyr C, Jerome RN, Edwards TL, Stroud M, Wilkins CH, Harris PA.
Impact of financial compensation on enrollment and participation in a remote, mobile-app based research study.
J Clin Transl Sci.
2024;
8(1):e75.
Abstract: There is no consensus on how to determine appropriate financial compensation for research recruitment. Selecting incentive amounts that are reasonable and respectful, without undue inducement, remains challenging. Previously, we demonstrated that incentive amount significantly impacts participants' willingness to complete various hypothetical research activities. Here we further explore this relationship in a mock decentralized study. Adult ResearchMatch volunteers were invited to join a prospective study where interested individuals were given an opportunity to view details for a study along with participation requirements, then offered a randomly generated compensation amount between $0 and $50 to enroll and participate. Individuals agreeing to participate were then asked to complete tasks using a remote mobile application (MyCap), for two weeks. Tasks included a weekly survey, a daily gratitude journal and daily phone tapping task. Willingness to participate was 85% across all incentive levels but not significantly impacted by amount. Task completion appeared to increase as a function of compensation until a plateau at $25. While participants described the study as low burden and reported that compensation was moderately important to their decision to join, only 31% completed all study tasks. While offering compensation in this study did not have a strong effect on enrollment rate, this work provides insight into participant motivation when joining and participating in studies employing mobile applications.
Abstract Summary: Scientists are trying to figure out the best way to pay people who join research studies. They want to pay enough to be fair, but not so much that people join just for the money. In a pretend study, grown-ups were asked to join a research project using their phones. They could get paid between $0 and $50. They had to answer questions, write about things they were thankful for every day, and do a tapping task on their phone for two weeks. Most people said yes to joining, no matter how much money was offered. But, people did more tasks when they were paid more, up to $25. After that, paying more didn't make a difference. Even though the study was easy and people said the money mattered a bit, only about 1 in 3 did all the tasks. This study helps us understand why people might join and stay in studies that use phone apps.
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.
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Development, implementation, and dissemination of operational innovations across the trial innovation network.
Journal of clinical and translational science (2023)
Palm ME, Edwards TL, Wieber C, Kay MT, Marion E, Boone L, Nanni A, Jones M, Pham E, Hildreth M, Lane K, McBee N, Benjamin DK Jr, Bernard GR, Dean JM, Dwyer JP, Ford DE, Hanley DF, Harris PA, Wilkins CH, Selker HP.
Development, implementation, and dissemination of operational innovations across the trial innovation network.
J Clin Transl Sci.
2023;
7(1):e251.
Abstract: Improving the quality and conduct of multi-center clinical trials is essential to the generation of generalizable knowledge about the safety and efficacy of healthcare treatments. Despite significant effort and expense, many clinical trials are unsuccessful. The National Center for Advancing Translational Science launched the Trial Innovation Network to address critical roadblocks in multi-center trials by leveraging existing infrastructure and developing operational innovations. We provide an overview of the roadblocks that led to opportunities for operational innovation, our work to develop, define, and map innovations across the network, and how we implemented and disseminated mature innovations.
Abstract Summary: Scientists do experiments called clinical trials to find out if medical treatments are safe and work well. Sometimes, these trials involve many hospitals and can be hard to do right, which can make the results not very helpful. To fix this, a group called the Trial Innovation Network was made. They use what hospitals already have and come up with new ways to do things better. This study talks about the problems they found and the new ideas they used to make clinical trials better. They also share how they put these ideas into action so that more people can use them. This helps make sure that when doctors treat patients, they are using the best and safest methods.
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.
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ResearchMatch on FHIR: Development and evaluation of a recruitment registry and electronic health record system interface for volunteer profile completion.
Journal of clinical and translational science (2023)
Cheng AC, Dunkel L, Byrne LM, Tischbein M, Burts D, Hamilton J, Phillips K, Embry B, Tan J, Olson E, Harris PA.
ResearchMatch on FHIR: Development and evaluation of a recruitment registry and electronic health record system interface for volunteer profile completion.
J Clin Transl Sci.
2023;
7(1):e222.
Abstract: Obtaining complete and accurate information in recruitment registries is essential for matching potential participants to research studies for which they qualify. Since electronic health record (EHR) systems are required to make patient data available to external systems, an interface between EHRs and recruitment registries may improve accuracy and completeness of volunteers' profiles. We tested this hypothesis on ResearchMatch (RM), a disease- and institution-neutral recruitment registry with 1357 studies across 255 institutions. We developed an interface where volunteers signing up for RM can authorize transfer of demographic data, medical conditions, and medications from the EHR into a registration form. We obtained feedback from a panel of community members to determine acceptability of the planned integration. We then developed the EHR interface and performed an evaluation study of 100 patients to determine whether RM profiles generated with EHR-assisted adjudication included more conditions and medications than those without the EHR connection. Community member feedback revealed that members of the public were willing to authenticate into the EHR from RM with proper messaging about choice and privacy. The evaluation study showed that out of 100 participants, 75 included more conditions and 69 included more medications in RM profiles completed with the EHR connection than those without. Participants also completed the EHR-connected profiles in 16 fewer seconds than non-EHR-connected profiles. The EHR to RM integration could lead to more complete profiles, less participant burden, and better study matches for many of the over 148,000 volunteers who participate in ResearchMatch.
Abstract Summary: Scientists wanted to see if they could get better information about volunteers who want to join research studies. They thought that using electronic health records (EHR) could help. They tried this idea on a big list called ResearchMatch that helps match volunteers with studies. They made a system where volunteers could let their health information be added to their ResearchMatch profile. They asked people what they thought about this and then tested it with 100 patients. They found that profiles with health record information had more details about health conditions and medicines. Also, these profiles were finished faster. This could help volunteers find the right studies more easily.
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.
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Leveraging the Expertise of the CTSA Program to Increase the Impact and Efficiency of Clinical Trials.
JAMA network open (2023)
Harris PA, Dunsmore SE, Atkinson JC, Benjamin DK Jr, Bernard GR, Dean JM, Dwyer JP, Ford DF, Selker HP, Waddy SP, Wiley KL, Wilkins CH, Cook SK, Burr JS, Edwards TL, Huvane J, Kennedy N, Lane K, Majkowski R, Nelson S, Palm ME, Stroud M, Thompson DD, Busac.
Leveraging the Expertise of the CTSA Program to Increase the Impact and Efficiency of Clinical Trials.
JAMA Netw Open.
2023 Oct 2;
6(10):e2336470.
Abstract: Multicenter clinical trials play a critical role in the translational processes that enable new treatments to reach all people and improve public health. However, conducting multicenter randomized clinical trials (mRCT) presents challenges. The Trial Innovation Network (TIN), established in 2016 to partner with the Clinical and Translational Science Award (CTSA) Consortium of academic medical institutions in the implementation of mRCTs, consists of 3 Trial Innovation Centers (TICs) and 1 Recruitment Innovation Center (RIC). This unique partnership has aimed to address critical roadblocks that impede the design and conduct of mRCTs, in expectation of accelerating the translation of novel interventions to clinical practice. The TIN's challenges and achievements are described in this article, along with examples of innovative resources and processes that may serve as useful models for other clinical trial networks providing operational and recruitment support. The TIN has successfully integrated more than 60 CTSA institution program hubs into a functional network for mRCT implementation and optimization. A unique support system for investigators has been created that includes the development and deployment of novel tools, operational and recruitment services, consultation models, and rapid communication pathways designed to reduce delays in trial start-up, enhance recruitment, improve engagement of diverse research participants and communities, and streamline processes that improve the quality, efficiency, and conduct of mRCTs. These resources and processes span the clinical trial spectrum and enable the TICs and RIC to serve as coordinating centers, data centers, and recruitment specialists to assist trials across the National Institutes of Health and other agencies. The TIN's impact has been demonstrated through its response to both historical operational challenges and emerging public health emergencies, including the national opioid public health crisis and the COVID-19 pandemic. The TIN has worked to reduce barriers to implementing mRCTs and to improve mRCT processes and operations by providing needed clinical trial infrastructure and resources to CTSA investigators. These resources have been instrumental in more quickly and efficiently translating research discoveries into beneficial patient treatments.
Abstract Summary: Scientists do big studies called multicenter clinical trials to test new treatments and help everyone's health. These studies can be hard to do, so in 2016, a group called the Trial Innovation Network (TIN) started helping by working with lots of medical schools. TIN helps solve problems that make these studies slow or difficult. They've made tools and ways to talk quickly so that studies can start faster, include people from different places, and work better.
TIN has connected over 60 places into a team that makes these big studies better and faster. They help with planning, finding people to join the studies, and sharing information. This has been really important for dealing with big health problems like the opioid crisis and COVID-19. Because of TIN, new treatments can get to patients quicker, which is great for everyone'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.
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Effects of financial incentives on volunteering for clinical trials: A randomized vignette experiment.
Contemporary clinical trials (2021)
Bickman L, Domenico HJ, Byrne DW, Jerome RN, Edwards TL, Stroud M, Lebo L, Mcguffin K, Wilkins CH, Harris PA.
Effects of financial incentives on volunteering for clinical trials: A randomized vignette experiment.
Contemp Clin Trials.
2021 Nov;
110:106584.
Abstract: Financial incentives may aid recruitment to clinical trials, but evidence regarding risk/burden-driven variability in participant preferences for incentives is limited. We developed and tested a framework to support real-world decisions on recruitment budget. We included two phases: an Anchoring Survey, to ensure we could capture perceived unpleasantness on a range of life events, and a Vignette Experiment, to explore relationships between financial incentives and participants' perceived risk/burden and willingness to participate in high- and low-risk/burden versions of five vignettes drawn from common research activities. We compared vignette ratings to identify similarly rated life events from the Anchoring Survey to contextualize ratings of study risk. In our Anchoring Survey (n = 643), mean ratings (scale 1 = lowest risk/burden to 5 = highest risk/burden) indicated that the questions made sense to participants, with highest risk assigned to losing house in a fire (4.72), and lowest risk assigned to having blood pressure taken (1.13). In the Vignette Experiment (n = 534), logistic regression indicated that amount of offered financial incentive and perceived risk/burden level were the top two drivers of willingness to participate in four of the five vignettes. Comparison of event ratings in the Anchoring Survey with the Vignette Experiment ratings suggested reasonable concordance on severity of risk/burden. We demonstrated feasibility of a framework for assessing participant perceptions of risk for study activities and discerned directionality of relationship between financial incentives and willingness to participate. Future work will explore use of this framework as an evidence-gathering approach for gauging appropriate incentives in real-world study contexts.
Abstract Summary: Scientists did a study to see if money helps get more people to join health studies. They made a plan to help decide how much money to offer. First, they asked 643 people to rate different life events by how bad they were, like losing a house in a fire being really bad. Then, they had 534 people look at made-up health study situations and decide if they would join, based on how risky or hard the study seemed and if they were offered money. They found that how much money was offered and how risky or hard the study seemed were the biggest reasons people would say yes to joining. The study showed that their plan could work to figure out how much money to offer people to join real health studies 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.
"Impact of Financial Incentives on Study Participation and Protocol Adherence
Vanderbilt University Medical Center
Novel Behavioral Intervention to Target Social Reward Sensitivity and Attachment.
University of California San Diego
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Amplification of positivity for depression and anxiety: Neural prediction of treatment response.
Behaviour research and therapy (2024)
Kryza-Lacombe M, Spaulding I, Ku CK, Pearson N, Stein MB, Taylor CT.
Amplification of positivity for depression and anxiety: Neural prediction of treatment response.
Behav Res Ther.
2024 Jul;
178:104545.
Abstract: Psychosocial treatments targeting the positive valence system (PVS) in depression and anxiety demonstrate efficacy in enhancing positive affect (PA), but response to treatment varies. We examined whether individual differences in neural activation to positive and negative valence incentive cues underlies differences in benefitting from a PVS-targeted treatment. Individuals with clinically elevated depression and/or anxiety (N = 88, ages 18 to 55) participated in one of two randomized, waitlist-controlled trials of Amplification of Positivity (AMP; NCT02330627, NCT03196544), a cognitive and behavioral intervention targeting the PVS. Participants completed a monetary incentive delay (MID) task during fMRI acquisition at baseline measuring neural activation to the possibility of gaining or losing money. Change in PA from before to after treatment was assessed using the Positive and Negative Affect Schedule. No significant associations were observed between baseline neural activation during gain anticipation and AMP-related changes in PA in regions of interest (striatum and insula) or whole-brain analyses. However, higher baseline striatal and insula activation during loss anticipation was associated with greater increases in PA post-AMP. This study provides preliminary evidence suggesting neural reactivity to negative valence cues may inform who stands to benefit most from treatments targeting the PVS.
Abstract Summary: Scientists did a study to see if a special kind of therapy that helps people focus on good feelings can make people with sadness or worry feel happier. They worked with 88 people between 18 and 55 years old who felt very sad or worried. These people tried a therapy called Amplification of Positivity (AMP) and played a game where they could win or lose money while their brain activity was watched with a special machine. The researchers wanted to see if the way people's brains reacted to the chance of winning or losing money before the therapy could tell us who would feel happier after the therapy. They found that people whose brains were more active when they might lose money felt happier after the therapy. This study helps us understand that how our brains react to possibly losing something might help us know who will feel better with this kind of therapy.
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.
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Changes in neural reward processing following Amplification of Positivity treatment for depression and anxiety: Preliminary findings from a randomized waitlist controlled trial.
Behaviour research and therapy (2021)
Kryza-Lacombe M, Pearson N, Lyubomirsky S, Stein MB, Wiggins JL, Taylor CT.
Changes in neural reward processing following Amplification of Positivity treatment for depression and anxiety: Preliminary findings from a randomized waitlist controlled trial.
Behav Res Ther.
2021 Jul;
142:103860.
Abstract: Positive valence system (PVS) deficits are increasingly recognized as important treatment targets for depression and anxiety. Emerging behavioral treatments designed to upregulate the PVS show initial promise; however, neural mechanisms underlying these approaches remain unknown. This study investigated neural reward-processing-related changes following Amplification of Positivity (AMP)-a treatment designed to enhance positive thinking, emotions and behaviors through positive activity interventions (Clinicaltrials.gov: NCT02330627). Individuals with depression and/or anxiety (N = 29) were randomized to 10 sessions of AMP (n = 16) or waitlist (WL; n = 13). Participants completed a monetary incentive delay task during fMRI at baseline and post-assessment. Hypothesis-driven region of interest (ventral striatum, insula, anterior cingulate) and exploratory whole-brain activation and connectivity analyses evaluated pre-to-post changes for AMP vs. WL when anticipating potential monetary gain or loss. No between-group brain activation changes emerged in regions of interest or whole-brain analyses. Increased neural connectivity from pre-to-post-treatment was observed in AMP vs. WL, including ventral striatum, anterior insula, and anterior cingulate connectivity with prefrontal, limbic, occipital and parietal regions-predominantly during loss anticipation. This preliminary study is the first to examine neural mechanisms of positive activity interventions in depression and anxiety and suggests that AMP may strengthen brain connectivity in reward processing, attention, and emotion regulation networks.
Abstract Summary: Scientists are studying a new way to help people who feel sad or worried all the time. This new method, called Amplification of Positivity (AMP), aims to make people think and feel more positively by doing certain activities. They wanted to see if AMP changes how the brain works when people think about winning or losing money. They had 29 people with sadness or worry problems try AMP or just wait (as a comparison group). They used a special brain scan called fMRI to look at their brains before and after the treatment while they thought about money.
They didn't find any big changes in the specific brain areas they were looking at, but they did see that the brains of the people who tried AMP were working together better, especially when they thought about losing money. This means that AMP might help the brain's different parts communicate better when dealing with loss, which could be good for people who are feeling down or anxious.
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.
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Enhancing Social Connectedness in Anxiety and Depression Through Amplification of Positivity: Preliminary Treatment Outcomes and Process of Change.
Cognitive therapy and research (2020)
Taylor CT, Pearlstein SL, Kakaria S, Lyubomirsky S, Stein MB.
Enhancing Social Connectedness in Anxiety and Depression Through Amplification of Positivity: Preliminary Treatment Outcomes and Process of Change.
Cognit Ther Res.
2020 Aug;
44(4):788-800.
Abstract: Anxiety and depressive disorders are often characterized by perceived social disconnection, yet evidence-based treatments produce only modest improvements in this domain. The well-established link between positive affect (PA) and social connectedness suggests that directly targeting PA in treatment may be valuable. A secondary analysis of a waitlist-controlled trial (N=29) was conducted to evaluate treatment response and process of change in social connectedness within a 10-session positive activity intervention protocol-Amplification of Positivity (AMP)-designed to increase PA in individuals seeking treatment for anxiety or depression (ClinicalTrials.gov Identifier: NCT02330627). Perceived social connectedness and PA/negative affect (NA) were assessed throughout treatment. Time-lagged multilevel mediation models examined the process of change in affect and connectedness throughout treatment. The AMP group displayed significantly larger improvements in social connectedness from pre- to post-treatment compared to waitlist; improvements were maintained through 6-month follow-up. Within the AMP group, increases in PA and decreases in NA both uniquely predicted subsequent increases in connectedness throughout treatment. However, experiencing heightened NA throughout treatment attenuated the effect of changes in PA on connectedness. Improvements in connectedness predicted subsequent increases in PA, but not changes in NA. These preliminary findings suggest that positive activity interventions may be valuable for enhancing social connectedness in individuals with clinically impairing anxiety or depression, possibly through both increasing positive emotions and decreasing negative emotions.
Abstract Summary: Scientists did a study to see if a special program could help people with anxiety or depression feel more connected to others. This program, called Amplification of Positivity (AMP), had 10 sessions focused on helping people feel more positive. They compared people who did the AMP program right away with people who had to wait for it. They found that the people who did the AMP program felt more connected to others, and this feeling lasted for at least 6 months. The study showed that feeling more positive and less negative helped people feel closer to others. This means that doing activities that make you feel good might help you make friends and feel less alone if you're feeling anxious or sad.
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.
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Upregulating the positive affect system in anxiety and depression: Outcomes of a positive activity intervention.
Depression and anxiety (2017)
Taylor CT, Lyubomirsky S, Stein MB.
Upregulating the positive affect system in anxiety and depression: Outcomes of a positive activity intervention.
Depress Anxiety.
2017 Mar;
34(3):267-280.
Abstract: Research suggests that the positive affect system may be an important yet underexplored treatment target in anxiety and depression. Existing interventions primarily target the negative affect system, yielding modest effects on measures of positive emotions and associated outcomes (e.g., psychological well-being). The objective of the present pilot study was to evaluate the efficacy of a new transdiagnostic positive activity intervention (PAI) for anxiety and depression. Twenty-nine treatment-seeking individuals presenting with clinically impairing symptoms of anxiety and/or depression were randomly allocated to a 10-session protocol comprised of PAIs previously shown in nonclinical samples to improve positive thinking, emotions, and behaviors (e.g., gratitude, acts of kindness, optimism; n = 16) or a waitlist (WL) condition (n = 13). Participants were assessed at pre- and posttreatment, as well as 3- and 6-month follow-up, on measures of positive and negative affect, symptoms, and psychological well-being. ClinicalTrials.gov Identifier: NCT02330627 RESULTS: The PAI group displayed significantly larger improvements in positive affect and psychological well-being from pre- to posttreatment compared to WL. Posttreatment and follow-up scores in the PAI group were comparable to general population norms. The PAI regimen also resulted in significantly larger reductions in negative affect, as well as anxiety and depression symptoms, compared to WL. Improvements across all outcomes were large in magnitude and maintained over a 6-month follow-up period. Targeting the positive affect system through a multicomponent PAI regimen may be beneficial for generating improvements in positive emotions and well-being, as well as reducing negative affect and symptoms, in individuals with clinically impairing anxiety or depression.
Abstract Summary: Scientists did a study to see if a new kind of activity could help people feel happier and less anxious or sad. They had 29 people who were feeling really anxious or sad try out these special activities, like being thankful or doing nice things for others, for 10 sessions. Another group of 13 people just waited without doing these activities. They checked how everyone felt before and after the sessions, and again 3 and 6 months later. The people who did the activities felt a lot better and less anxious or sad, even after 6 months. This study shows that doing positive activities might really help people who are feeling down or worried.
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 CBT Intervention to Reduce Fear of Hypoglycemia
University of Illinois at Chicago
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FREE: A randomized controlled feasibility trial of a cognitive behavioral therapy and technology-assisted intervention to reduce fear of hypoglycemia in young adults with type 1 diabetes.
Journal of psychosomatic research (2024)
Martyn-Nemeth P, Duffecy J, Quinn L, Park C, Reutrakul S, Mihailescu D, Park M, Penckofer S.
FREE: A randomized controlled feasibility trial of a cognitive behavioral therapy and technology-assisted intervention to reduce fear of hypoglycemia in young adults with type 1 diabetes.
J Psychosom Res.
2024 Jun;
181:111679.
Abstract: The purpose of this study was to test the preliminary effectiveness of a cognitive behavioral therapy intervention (Fear Reduction Efficacy Evaluation [FREE]) designed to reduce fear of hypoglycemia in young adults with type 1 diabetes. The primary outcome was fear of hypoglycemia, secondary outcomes were A1C, and glycemic variability. A randomized clinical trial was used to test an 8-week intervention (FREE) compared to an attention control (diabetes education) in 50 young adults with type 1 diabetes who experienced fear of hypoglycemia at baseline. All participants wore a continuous glucose monitor for the 8-week study period. Self-reported fear of hypoglycemia point-of-care A1C testing, continuous glucose monitor-derived glucose variability were measured at baseline, Week 8, and Week 12 (post-program). Compared to controls, those participating in the FREE intervention experienced a reduction in fear of hypoglycemia (SMD B = -8.52, p = 0.021), change in A1C (SMD B = 0.04, p = 0.841) and glycemic variability (glucose standard deviation SMD B = -2.5, p = 0.545) by the end of the intervention. This represented an 8.52% greater reduction in fear of hypoglycemia. A cognitive behavioral therapy intervention (FREE) resulted in improvements in fear of hypoglycemia. govNCT03549104.
Abstract Summary: Scientists did a study to see if a special program could help young people with type 1 diabetes feel less scared of their blood sugar dropping too low, which is called hypoglycemia. They had 50 young people try either this new program, called FREE, or a regular diabetes class for 8 weeks. They wore devices to check their blood sugar all the time. The researchers found that the kids who did the FREE program were less scared of low blood sugar than the ones who just learned about diabetes. Even though their blood sugar levels and how much these levels changed didn't improve a lot, feeling less scared is a good thing. This study shows that the FREE program might help young people with diabetes worry less about 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.
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A cognitive behavioral therapy intervention to reduce fear of hypoglycemia in young adults with type 1 diabetes (FREE): study protocol for a randomized controlled trial.
Trials (2019)
Martyn-Nemeth P, Duffecy J, Quinn L, Park C, Mihailescu D, Penckofer S.
A cognitive behavioral therapy intervention to reduce fear of hypoglycemia in young adults with type 1 diabetes (FREE): study protocol for a randomized controlled trial.
Trials.
2019 Dec 30;
20(1):796.
Abstract: In persons with type 1 diabetes (T1D), hypoglycemia is the major limiting factor in achieving optimal glycemic control. All persons with T1D are at risk for hypoglycemia (blood glucose level < 70 mg/dl), which is life-threatening and accompanied by serious physical and psychological symptoms, resulting in profound fear of hypoglycemia (FOH) and reduced quality of life. Young adults with T1D are at risk for FOH and have worse glycemic control and self-management behavior than other age groups with T1D. FOH also results in increased glycemic variability (GV). A major gap exists in how to manage FOH. Our overall objective is to reduce FOH and improve diabetes self-management, glycemic control, and GV in young adults with T1D to reduce or delay diabetes complications and improve quality of life. We aim to (1) determine the feasibility and acceptability of an eight-week cognitive behavioral therapy (CBT)-based Fear Reduction Efficacy Evaluation (FREE) intervention in young adults with T1D who experience FOH; and (2) determine the impact of the FREE intervention, compared to an attention control group, on the outcomes FOH, self-management, glycemic control (A1C), and glycemic variability (continuous glucose monitoring recordings). A randomized controlled trial in 50 young adults aged 18 to 35 years with T1D will be used. Eligible subjects will be randomized to the intervention program (Fear Reduction Efficacy Evaluation [FREE]) or attention control group. A one-week run-in phase is planned, with baseline measures of FOH, self-management behavior, A1C, and real-time continuous glucose monitoring recordings (RT-CGM) to calculate GV for both groups. The intervention group will participate in eight weekly individual one-hour sessions using CBT and exposure treatment for specific fears. RT-CGM and a daily FOH diary will be used as feedback cues as part of the FREE program. The attention control group will participate in eight weekly individual one-hour diabetes self-management education (DSME) sessions and wear a RT-CGM device (to measure GV only) over 8 weeks. At completion, FOH will be measured, and RT-CGM recordings will be analyzed to determine differences between the FREE and control groups. Findings from this proposed pilot study will serve as the foundation for a larger trial to reduce FOH and improve self-management, glycemic control, and GV. ClinicalTrials.gov: A cognitive behavioral therapy (CBT) intervention to reduce fear of hypoglycemia in type 1 diabetes, NCT03549104. Registered June 7, 2018.
Abstract Summary: Scientists are studying a new way to help young adults with type 1 diabetes who are scared of their blood sugar dropping too low, which can be dangerous. This fear can make it harder for them to take care of their diabetes. The researchers are testing a special program that uses something called cognitive behavioral therapy to see if it can make these young people less afraid and help them manage their diabetes better. They will compare two groups of people: one that gets the new therapy and one that learns about diabetes management in a different way. They will check to see if the new therapy helps by looking at how well the participants control their blood sugar and how they feel about their diabetes. This study could lead to better ways to help people with diabetes live healthier and happier 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.
Group Exercise Training for Functional Improvement after Treatment
Oregon Health & Science University
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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 Aug;
18(4):1179-1189.
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.
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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.
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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.
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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.
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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.
Optimizing Psychosocial Treatment of Interstitial Cystitis/Bladder Pain Syndrome
Vanderbilt University Medical Center
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A randomized-controlled pilot trial of telemedicine-delivered cognitive-behavioral therapy tailored for interstitial cystitis/bladder pain syndrome.
Pain (2024)
McKernan LC, McGonigle T, Vandekar SN, Crofford LJ, Williams DA, Clauw DJ, Bruehl S, Corbett BA, Dmochowski RR, Walsh EG, Kelly AG, Sutherland SL, Connors EL, Ryden A, Reynolds WS.
A randomized-controlled pilot trial of telemedicine-delivered cognitive-behavioral therapy tailored for interstitial cystitis/bladder pain syndrome.
Pain.
2024 Aug 1;
165(8):1748-1760.
A Phase 3, Multicenter, Randomized, Double-blind, Placebo controlled Trial of the Safety and Efficacy of Two Fixed Doses of OPC-34712 as Adjunctive Therapy in the Treatment of Adults with Major Depressive Disorder, the Polaris Trial
The Ohio State University
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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.
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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.
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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.
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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.
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Adjunctive Brexpiprazole and Functioning in Major Depressive Disorder: A Pooled Analysis of Six Randomized Studies Using the Sheehan Disability Scale.
The international journal of neuropsychopharmacology (2019)
Hobart M, Zhang P, Weiss C, Meehan SR, Eriksson H.
Adjunctive Brexpiprazole and Functioning in Major Depressive Disorder: A Pooled Analysis of Six Randomized Studies Using the Sheehan Disability Scale.
Int J Neuropsychopharmacol.
2019 Mar 1;
22(3):173-179.
Abstract: Patients with major depressive disorder and inadequate response to antidepressant treatments may experience a prolonged loss of functioning. This post hoc analysis aimed to determine the effect of adjunctive brexpiprazole on functioning in such patients. A pooled analysis of data from the 6-week, randomized, double-blind treatment phases of 6 studies of adjunctive brexpiprazole (2 and 3 mg/d in fixed-dose studies; 1-3 mg/d in flexible-dose studies) vs placebo in patients with major depressive disorder and inadequate response to antidepressant treatments (NCT01360645, NCT01360632, NCT02196506, NCT01727726, NCT00797966, NCT01052077). Functioning was measured by change in Sheehan Disability Scale score from baseline to week 6. Considering Sheehan Disability Scale mean score across all 6 studies (n = 2066 randomized), the least squares mean difference between antidepressant treatments + brexpiprazole and antidepressant treatments + placebo at week 6 was -0.40 (95% CI: -0.56, -0.23; P < .0001). Antidepressant treatments + brexpiprazole showed a greater benefit than antidepressant treatments + placebo on the social life (-0.45; -0.63, -0.27; P < .001) and family life (-0.50; -0.70, -0.31; P < .001) items but not on the work/studies item (-0.16; -0.38, 0.06; P = .16). Pooled analyses of just the (1) fixed-dose, (2) flexible-dose, and (3) Phase 3 studies showed the same pattern of benefits for antidepressant treatments + brexpiprazole. Brexpiprazole, as adjunct to antidepressant treatments, improved functioning in patients with major depressive disorder and inadequate response to antidepressant treatments.
Abstract Summary: Doctors wanted to see if a medicine called brexpiprazole could help people with major depression who weren't feeling better after taking other antidepressants. They looked at information from 6 different studies where people took brexpiprazole or a placebo (a pill with no medicine) along with their regular antidepressants for 6 weeks. They checked if people's daily lives got better, like being able to do better at work, at home, or with friends.
They found that people who took brexpiprazole with their antidepressants did better in their social and family lives compared to those who just took the placebo. However, there wasn't a big difference in how well they did at work or school. Overall, adding brexpiprazole seemed to help people with depression do better in their day-to-day activities.
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.
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Brexpiprazole as adjunctive treatment of major depressive disorder with anxious distress: Results from a post-hoc analysis of two randomised controlled trials.
Journal of affective disorders (2016)
McIntyre RS, Weiller E, Zhang P, Weiss C.
Brexpiprazole as adjunctive treatment of major depressive disorder with anxious distress: Results from a post-hoc analysis of two randomised controlled trials.
J Affect Disord.
2016 Sep 1;
201:116-23.
Abstract: Anxiety symptoms are prevalent in major depressive disorder (MDD) and are associated with greater illness severity, suicidality, impaired functioning and poor response to antidepressant treatment (ADT). The efficacy and safety of brexpiprazole - a serotonin-dopamine activity modulator - as adjunctive treatment in patients with MDD was recently evaluated in two phase 3 studies. We here present a post-hoc analysis of the efficacy of adjunctive brexpiprazole in patients with MDD and symptoms of anxious distress, defined using proxies for DSM-5 criteria. Eligible patients were randomized to 2mg brexpiprazole+ADT or placebo+ADT (NCT01360645); or 1mg brexpiprazole+ADT, 3mg brexpiprazole+ADT, or placebo+ADT (NCT01360632), respectively. Patients were defined as having anxious distress if they had ≥2 of the symptoms tension (MADRS item 3 score ≥3), restlessness (IDS item 24 score ≥2), concentration (MADRS item 6 score ≥3), or apprehension (HAM-D item 10 score ≥3). Primary efficacy endpoint was change in MADRS total score from baseline to Week 6. 55% of the patients had anxious distress at baseline. Adjunctive brexpiprazole showed greater improvement than adjunctive placebo on the primary efficacy endpoint in both patients with (least square mean difference to placebo+ADT: 2mg+ADT: -2.95, p=0.0023; 3mg+ADT: -2.81, p=0.0027); and without anxious distress (1mg+ADT: -2.37, p=0.0093; 3mg+ADT: -2.23, p=0.0131). Brexpiprazole in patients with anxious distress was not associated with an increased incidence of activating adverse events (e.g., akathisia). Adjunctive brexpiprazole 2-3mg may be efficacious in reducing depressive symptoms and is well tolerated, in patients with MDD and anxious distress.
Abstract Summary: Scientists studied a new medicine called brexpiprazole to see if it helps people with major depression who also feel very anxious. They gave some patients this new medicine along with their usual depression medicine, while others just got a pretend pill with their usual medicine. They checked if the patients felt less depressed and less anxious after six weeks. They found that the new medicine helped people feel better, both those who were very anxious and those who were not. The good news is that the new medicine didn't make people feel too restless or have other similar side effects. This means that brexpiprazole might be a good medicine to help people with depression and anxiety 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.
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Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study.
The Journal of clinical psychiatry (2015)
Thase ME, Youakim JM, Skuban A, Hobart M, Zhang P, McQuade RD, Nyilas M, Carson WH, Sanchez R, Eriksson H.
Adjunctive brexpiprazole 1 and 3 mg for patients with major depressive disorder following inadequate response to antidepressants: a phase 3, randomized, double-blind study.
J Clin Psychiatry.
2015 Sep;
76(9):1232-40.
Abstract: To evaluate efficacy, safety, and tolerability of brexpiprazole adjunctive to antidepressant treatments (ADTs) in patients with major depressive disorder (as defined by DSM-IV-TR criteria) with inadequate response to ADTs. Patients still depressed despite 1-3 prior ADTs followed by 8 weeks of prospective physician-determined, open-label ADT were randomized (1:1:1) to double-blind brexpiprazole 3 mg/d, brexpiprazole 1 mg/d, or placebo for 6 weeks. The primary efficacy end point was change in Montgomery-Asberg Depression Rating Scale (MADRS) total score from baseline to week 6. The key secondary efficacy end point was change in Sheehan Disability Scale mean score. The Hochberg procedure corrected for multiplicity. The efficacy population comprised all patients who had ≥ 1 dose of study drug with baseline and ≥ 1 postrandomization MADRS scores; the efficacy population per final protocol consisted of efficacy population patients meeting amended criteria for inadequate response throughout the 8-week prospective ADT. The study was conducted between June 2011 and September 2013. In the efficacy population per final protocol, brexpiprazole 3 mg (n = 213) showed a greater improvement in MADRS total score versus placebo (n = 203; -8.29 vs -6.33; P = .0079), whereas brexpiprazole 1 mg did not (n = 211; -7.64 vs -6.33; P = .0737). The brexpiprazole groups showed comparable improvement in SDS mean score versus placebo (least squares [LS] mean difference: [1 mg] -0.49, P = .0158; [3 mg] -0.48, P = .0191). The most frequent adverse events were akathisia (4.4%, 13.5%, 2.3%), headache (9.3%, 6.1%, 7.7%), and weight increase (6.6%, 5.7%, 0.9%) in brexpiprazole 1-mg, 3-mg, and placebo groups, respectively. Mean changes from baseline in Abnormal Involuntary Movement Scale (LS mean difference = 0.08, P = .0141) and Barnes Akathisia Rating Scale (LS mean difference = 0.17, P = .0001) total scores were significantly greater with brexpiprazole 3 mg versus placebo. Brexpiprazole 3 mg demonstrated efficacy versus placebo in the efficacy population per final protocol. Both doses of brexpiprazole were well tolerated. ClinicalTrials.gov identifier: NCT01360632.
Abstract Summary: Doctors wanted to see if a medicine called brexpiprazole could help people who were still feeling very sad even after trying other medicines for depression. They tested two different amounts of the medicine to see which one worked better. People in the study took the medicine or a pretend pill for 6 weeks. They checked to see if people felt less sad and if they could do their daily activities better.
They found that the higher amount of the medicine helped people feel less sad compared to the pretend pill, but the lower amount didn't make a big difference. Both amounts helped people do their daily stuff better. Some people felt a little restless or had headaches or gained weight, but these problems weren't too bad.
The study showed that the higher amount of brexpiprazole could be a good extra medicine for people who are still feeling sad even after trying other treatments. This could be important for people who need more help with their 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.
Mechanism of Antidepressant-Related Dysfunctional Arousal in High-Risk Youth
Stanford University
Evaluating the EVO treatment optimized for resource constraints: Elements Vital to treat Obesity
Northwestern University
SMART 2.0: Social Mobile Approaches to Reducing weighT in Young Adults
University of California San Diego
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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 apps 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 we might know more. For now, doctors should think carefully before suggesting these apps because we don't know how much they help.
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.
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Social Mobile Approaches to Reducing Weight (SMART) 2.0: protocol of a randomized controlled trial among young adults in university settings.
Trials (2022)
Mansour-Assi SJ, Golaszewski NM, Costello VL, Wing D, Persinger H, Coleman A, Lytle L, Larsen BA, Jain S, Weibel N, Rock CL, Patrick K, Hekler E, Godino JG.
Social Mobile Approaches to Reducing Weight (SMART) 2.0: protocol of a randomized controlled trial among young adults in university settings.
Trials.
2022 Jan 3;
23(1):7.
Abstract: Excess weight gain in young adulthood is associated with future weight gain and increased risk of chronic disease. Although multimodal, technology-based weight-loss interventions have the potential to promote weight loss among young adults, many interventions have limited personalization, and few have been deployed and evaluated for longer than a year. We aim to assess the effects of a highly personalized, 2-year intervention that uses popular mobile and social technologies to promote weight loss among young adults. The Social Mobile Approaches to Reducing Weight (SMART) 2.0 Study is a 24-month parallel-group randomized controlled trial that will include 642 overweight or obese participants, aged 18-35 years, from universities and community colleges in San Diego, CA. All participants receive a wearable activity tracker, connected scale, and corresponding app. Participants randomized to one intervention group receive evidence-based information about weight loss and behavior change techniques via personalized daily text messaging (i.e., SMS/MMS), posts on social media platforms, and online groups. Participants in a second intervention group receive the aforementioned elements in addition to brief, technology-mediated health coaching. Participants in the control group receive a wearable activity tracker, connected scale, and corresponding app alone. The primary outcome is objectively measured weight in kilograms over 24 months. Secondary outcomes include anthropometric measurements; physiological measures; physical activity, diet, sleep, and psychosocial measures; and engagement with intervention modalities. Outcomes are assessed at baseline and 6, 12, 18, and 24 months. Differences between the randomized groups will be analyzed using a mixed model of repeated measures and will be based on the intent-to-treat principle. We hypothesize that both SMART 2.0 intervention groups will significantly improve weight loss compared to the control group, and the group receiving health coaching will experience the greatest improvement. We further hypothesize that differences in secondary outcomes will favor the intervention groups. There is a critical need to advance understanding of the effectiveness of multimodal, technology-based weight-loss interventions that have the potential for long-term effects and widespread dissemination among young adults. Our findings should inform the implementation of low-cost and scalable interventions for weight loss and risk-reducing health behaviors. ClinicalTrials.gov NCT03907462 . Registered on April 9, 2019.
Abstract Summary: Scientists are studying a new way to help young people lose weight using technology like mobile apps and social media. They think gaining too much weight when you're young can lead to health problems later. In their study, called SMART 2.0, they have 642 young adults who are a bit heavier than they should be. These young people get special tools like a fitness tracker and an app to help them keep track of their weight.
There are three groups in the study. The first group gets daily text messages and social media posts with tips on how to lose weight. The second group gets all that plus help from a health coach through technology. The third group only gets the fitness tracker and app without the extra advice.
The researchers will check everyone's weight and health over two years to see which group does the best. They think the groups getting the extra help will lose more weight, especially the one with the health coach. This study is important because it could show a cheap and easy way for lots of young people to stay healthy by losing weight.
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.
Insulin Detemir in Obesity Management (IDIOM)
Vanderbilt University Medical Center
Assessing Brain Health in Adults
Vanderbilt University Medical Center
Nutrition, Inflammation and Insulin Resistance in End-Stage Renal Disease—Aim 1
Vanderbilt University Medical Center
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A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis.
Journal of cachexia, sarcopenia and muscle (2024)
Ertuglu LA, Deger SM, Alsouqi A, Hung A, Gamboa J, Mambungu C, Sha F, Siew E, Abumrad NN, Ikizler TA.
A randomized controlled pilot trial of anakinra and pioglitazone for protein metabolism in patients on maintenance haemodialysis.
J Cachexia Sarcopenia Muscle.
2024 Feb;
15(1):401-411.
Abstract: Chronic inflammation and insulin resistance are highly prevalent in patients on maintenance haemodialysis (MHD) and are strongly associated with protein energy wasting. We conducted a pilot, randomized, placebo-controlled trial of recombinant human interleukin-1 receptor antagonist (IL-1ra) and pioglitazone to explore the safety, feasibility and efficacy for insulin-mediated protein metabolism in patients undergoing MHD. Twenty-four patients were randomized to receive IL-1ra, pioglitazone or placebo for 12 weeks. Changes in serum inflammatory markers and insulin-mediated protein synthesis, breakdown and net balance in the whole-body and skeletal muscle compartments were assessed using hyperinsulinaemic-hyperaminoacidemic clamp technique at baseline and Week 12. Among 24 patients, median (interquartile range) age was 51 (40, 61), 79% were African American and 21% had diabetes mellitus. All patients initiated on intervention completed the study, and no serious adverse events were observed. There was a statistically significant decrease in serum high-sensitivity C-reactive protein in the pioglitazone group compared with placebo, but not in the IL-1ra group. No significant differences in the changes of whole-body or skeletal muscle protein synthesis, breakdown and net balance were found between the groups. In this pilot study, there were no statistically significant effects of 12 weeks of IL-1ra or pioglitazone on protein metabolism in patients on MHD. gov registration: NCT02278562.
Abstract Summary: Doctors wanted to see if two medicines could help people on dialysis with inflammation and trouble using insulin, which can make them lose muscle and energy. They tested 24 patients, giving some a medicine called IL-1ra, some another called pioglitazone, and some a fake pill for 12 weeks. They checked for inflammation and how the body made and broke down proteins. Most patients were African American, and a few had diabetes. Everyone finished the study safely. The pioglitazone group had less inflammation, but overall, the medicines didn't really change how the body handled proteins. This was just a first test 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.
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Insulin resistance is a significant determinant of sarcopenia in advanced kidney disease.
American journal of physiology. Endocrinology and metabolism (2018)
Deger SM, Hewlett JR, Gamboa J, Ellis CD, Hung AM, Siew ED, Mamnungu C, Sha F, Bian A, Stewart TG, Abumrad NN, Ikizler TA.
Insulin resistance is a significant determinant of sarcopenia in advanced kidney disease.
Am J Physiol Endocrinol Metab.
2018 Dec 1;
315(6):E1108-E1120.
Abstract: Maintenance hemodialysis (MHD) patients display significant nutritional abnormalities. Insulin is an anabolic hormone with direct effects on skeletal muscle (SM). We examined the anabolic actions of insulin, whole-body (WB), and SM protein turnover in 33 MHD patients and 17 participants without kidney disease using hyperinsulinemic-euglycemic-euaminoacidemic (dual) clamp. Gluteal muscle biopsies were obtained before and after the dual clamp. At baseline, WB protein synthesis and breakdown rates were similar in MHD patients. During dual clamp, controls had a higher increase in WB protein synthesis and a higher suppression of WB protein breakdown compared with MHD patients, resulting in statistically significantly more positive WB protein net balance [2.02 (interquartile range [IQR]: 1.79 and 2.36) vs. 1.68 (IQR: 1.46 and 1.91) mg·kg fat-free mass·min for controls vs. for MHD patients, respectively, P < 0.001]. At baseline, SM protein synthesis and breakdown rates were higher in MHD patients versus controls, but SM net protein balance was similar between groups. During dual clamp, SM protein synthesis increased statistically significantly more in controls compared with MHD patients ( P = 0.03), whereas SM protein breakdown decreased comparably between groups. SM net protein balance was statistically significantly more positive in controls compared with MHD patients [67.3 (IQR: 46.4 and 97.1) vs. 15.4 (IQR: -83.7 and 64.7) μg·100 ml·min for controls and MHD patients, respectively, P = 0.03]. Human SM biopsy showed a positive correlation between glucose and leucine disposal rates, phosphorylated AKT to AKT ratio, and muscle mitochondrial markers in controls but not in MHD patients. Diminished response to anabolic actions of insulin in the stimulated setting could lead to muscle wasting in MHD patients.
Abstract Summary: Doctors wanted to learn how insulin, a hormone that helps our bodies build muscle, works in people who have to get their blood cleaned by a machine because their kidneys don't work well (called maintenance hemodialysis patients). They compared these patients with people who don't have kidney problems. They used a special test that gives insulin and keeps blood sugar and amino acids (building blocks of protein) steady to see how the body makes and breaks down protein.
They found that in healthy people, the body made more protein and broke down less when given insulin. But for those on hemodialysis, their bodies didn't make as much protein, and they didn't stop breaking down protein as much as healthy people did. This means that the insulin wasn't helping them build muscle as well as it should, which could lead to muscle loss over time. This is important because it shows that patients on hemodialysis might need special help to keep their muscles strong.
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.
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Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients.
JCI insight (2017)
Deger SM, Hung AM, Gamboa JL, Siew ED, Ellis CD, Booker C, Sha F, Li H, Bian A, Stewart TG, Zent R, Mitch WE, Abumrad NN, Ikizler TA.
Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients.
JCI Insight.
2017 Nov 16;
2(22):.
Abstract: Systemic inflammation and muscle wasting are highly prevalent and coexist in patients on maintenance hemodialysis (MHD). We aimed to determine the effects of systemic inflammation on skeletal muscle protein metabolism in MHD patients. Whole body and skeletal muscle protein turnover were assessed by stable isotope kinetic studies. We incorporated expressions of E1, E214K, E3αI, E3αII, MuRF-1, and atrogin-1 in skeletal muscle tissue from integrin β1 gene KO CKD mice models. Among 129 patients with mean (± SD) age 47 ± 12 years, 74% were African American, 73% were male, and 22% had diabetes mellitus. Median high-sensitivity C-reactive protein (hs-CRP) concentration was 13 (interquartile range 0.8, 33) mg/l. There were statistically significant associations between hs-CRP and forearm skeletal muscle protein synthesis, degradation, and net forearm skeletal muscle protein balance (P < 0.001 for all). The associations remained statistically significant after adjustment for clinical and demographic confounders, as well as in sensitivity analysis, excluding patients with diabetes mellitus. In attempting to identify potential mechanisms involved in this correlation, we show increased expressions of E1, E214K, E3αI, E3αII, MuRF-1, and atrogin-1 in skeletal muscle tissue obtained from an animal model of chronic kidney disease. These data suggest that systemic inflammation is a strong and independent determinant of skeletal muscle protein homeostasis in MHD patients, providing rationale for further studies using anticytokine therapies in patients with underlying systemic inflammation. This study was in part supported by NIH grants R01 DK45604 and 1K24 DK62849, the Clinical Translational Science Award UL1-TR000445 from the National Center for Advancing Translational Sciences, the Veterans Administration Merit Award I01 CX000414, the SatelliteHealth Normon Coplon Extramural Grant Program, and the FDA grant 000943.
Abstract Summary: This study looked at how inflammation in the body affects muscle health in people who are on regular dialysis treatments. The researchers studied protein changes in the muscles of 129 patients, most of whom were African American men. They found that higher levels of a protein that indicates inflammation were linked to more muscle protein breakdown. This was true even when they considered other factors like age and diabetes. They also found similar results in mice with kidney disease. This suggests that reducing inflammation might help protect muscles in people on dialysis. This could be a new area for future research and 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.
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Leucine disposal rate for assessment of amino acid metabolism in maintenance hemodialysis patients.
BMC nutrition (2016)
Denny GB, Deger SM, Chen G, Bian A, Sha F, Booker C, Kesler JT, David S, Ellis CD, Ikizler TA.
Leucine disposal rate for assessment of amino acid metabolism in maintenance hemodialysis patients.
BMC Nutr.
2016;
2:.
Abstract: Protein energy wasting (PEW) is common in patients undergoing maintenance hemodialysis (MHD) and closely associated with poor outcomes. Insulin resistance and associated alterations in amino acid metabolism are potential pathways leading to PEW. We hypothesized that the measurement of leucine disposal during a hyperinsulinemic- euglycemic-euaminoacidemic clamp (HEAC) procedure would accurately measure the sensitivity to insulin for its actions on concomitant carbohydrate and protein metabolism in MHD patients. We examined 35 MHD patients and 17 control subjects with normal kidney function by hyperinsulinemic-euglycemic clamp (HEGC) followed by HEAC clamp procedure to obtain leucine disposal rate (LDR) along with isotope tracer methodology to assess whole body protein turnover. The glucose disposal rate (GDR) by HEGC was 5.1 ± 2.1 mg/kg/min for the MHD patients compared to 6.3 ± 3.9 mg/kg/min for the controls ( = 0.38). The LDR during HEAC was 0.09 ± 0.03 mg/kg/min for the MHD patients compared to 0.11 ± 0.05 mg/kg/min for the controls ( = 0.009). The LDR level was correlated with whole body protein synthesis ( = 0.25; = 0.08), with whole body protein breakdown ( = -0.38 = 0.01) and net protein balance ( = 0.85; < 0.001) in the overall study population. Correlations remained significant in subgroup analysis. The GDR derived by HEGC and LDR correlated well in the controls ( = 0.79, < 0.001), but less so in the MHD patients ( = 0.58, < 0.001). Leucine disposal rate reliably measures amino acid utilization in MHD patients and controls in response to high dose insulin.
Abstract Summary: Scientists did a study to understand a health problem called protein energy wasting (PEW), which happens a lot in people who need to clean their blood regularly with a machine (hemodialysis) because their kidneys don't work well. They thought that the way the body uses sugar and protein might be different in these people because of something called insulin resistance. To test this, they compared 35 people with kidney problems to 17 healthy people. They used a special test that measures how the body uses sugar and protein when given a lot of insulin.
They found that the people with kidney problems didn't use sugar and protein as well as the healthy people. The test also showed how the body makes and breaks down protein. This information is important because it can help doctors understand and maybe treat the health problem where people lose too much protein and energy, which is common in people with kidney problems who need hemodialysis.
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.
Diagnostics, Imaging And Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project
Boston University
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Flortaucipir tau PET findings from former professional and college American football players in the DIAGNOSE CTE research project.
Alzheimer's & dementia : the journal of the Alzheimer's Association (2024)
Su Y, Protas H, Luo J, Chen K, Alosco ML, Adler CH, Balcer LJ, Bernick C, Au R, Banks SJ, Barr WB, Coleman MJ, Dodick DW, Katz DI, Marek KL, McClean MD, McKee AC, Mez J, Daneshvar DH, Palmisano JN, Peskind ER, Turner RW 2nd, Wethe JV, Rabinovici G, Johnso.
Flortaucipir tau PET findings from former professional and college American football players in the DIAGNOSE CTE research project.
Alzheimers Dement.
2024 Mar;
20(3):1827-1838.
Abstract: Tau is a key pathology in chronic traumatic encephalopathy (CTE). Here, we report our findings in tau positron emission tomography (PET) measurements from the DIAGNOSE CTE Research Project. We compare flortaucipir PET measures from 104 former professional players (PRO), 58 former college football players (COL), and 56 same-age men without exposure to repetitive head impacts (RHI) or traumatic brain injury (unexposed [UE]); characterize their associations with RHI exposure; and compare players who did or did not meet diagnostic criteria for traumatic encephalopathy syndrome (TES). Significantly elevated flortaucipir uptake was observed in former football players (PRO+COL) in prespecified regions (p < 0.05). Association between regional flortaucipir uptake and estimated cumulative head impact exposure was only observed in the superior frontal region in former players over 60 years old. Flortaucipir PET was not able to differentiate TES groups. Additional studies are needed to further understand tau pathology in CTE and other individuals with a history of RHI.
Abstract Summary: Scientists did a study to learn more about a brain problem called chronic traumatic encephalopathy (CTE), which can happen to people who have had many head injuries. They used a special brain scan called PET to look at a substance called tau, which builds up in the brains of people with CTE. They compared the brain scans of 104 ex-professional football players, 58 ex-college football players, and 56 older men who never had lots of head injuries. They found that the football players had more tau in certain parts of their brains. Older players over 60 showed a link between tau and the number of times they hit their heads while playing. But the scans couldn't tell if someone had the symptoms of CTE. More research is needed to understand how tau affects the brain after many head injuries. This study is important because it helps us learn how playing football might change the brain and how to tell if someone has CTE.
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.
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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.
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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.
Enhancing Social Competence in Adults with Autism Spectrum Disorder: A Pilot RCT
Vanderbilt University Medical Center
Positive Affect as a Source of Resilience for Adults in Chronic Pain
Weill Cornell Medical College
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Feasibility, Acceptability, and Preliminary Efficacy of a Positive Affect Skills Intervention for Adults With Fibromyalgia.
Innovation in aging (2023)
Ong AD, Wilcox KT, Moskowitz JT, Wethington E, Addington EL, Sanni MO, Kim P, Reid MC.
Feasibility, Acceptability, and Preliminary Efficacy of a Positive Affect Skills Intervention for Adults With Fibromyalgia.
Innov Aging.
2023;
7(10):igad070.
Abstract: To examine the feasibility, acceptability, and preliminary efficacy of a positive affect skills intervention for middle-aged and older adults with fibromyalgia syndrome (FMS). Ninety-five participants with FMS aged 50 and older (94% female) were randomized to 1 of 2 conditions: (a) Lessons in Affect Regulation to Keep Stress and Pain UndeR control (LARKSPUR; = 49) or (b) emotion reporting/control ( = 46). LARKSPUR included 5 weeks of skill training that targeted 8 skills to help foster positive affect, including (a) noticing positive events, (b) savoring positive events, (c) identifying personal strengths, (d) behavioral activation to set and work toward attainable goals, (e) mindfulness, (f) positive reappraisal, (g) gratitude, and (h) acts of kindness. Outcome data were collected via online surveys at baseline, postintervention, and 1-month follow-up. Completion rates (88%) and satisfaction ratings (10-point scale) were high (LARKSPUR: = 9.14, standard deviation () = 1.49; control: = 8.59, = 1.97). Improvements were greater in LARKSPUR participants compared with control participants on measures of positive affect (Cohen's = 0.19 [0.15, 0.24]), negative affect (Cohen's = -0.07 [-0.11, -0.02]), and pain catastrophizing (Cohen's = -0.14 [-0.23, -0.05]). Improvements in positive affect (Cohen's = 0.17 [0.13, 0.22]) and negative affect (Cohen's = -0.11 [-0.15, -0.06]) were maintained at 1-month follow-up. Dose-response analyses indicated that intervention engagement significantly predicted pre-to-post and post-to-follow-up reductions in pain catastrophizing. The current preliminary findings add to existing literature and highlight the specific potential of internet-delivered positive affect skills programs for adults with FMS. NCT04869345.
Abstract Summary: Scientists did a study to see if teaching older people with fibromyalgia (a condition that causes pain all over the body) how to feel more positive could help them feel better. They had 95 people over 50 years old join the study. These people were split into two groups. One group learned special skills for five weeks to help them notice and enjoy good things, understand their strengths, set goals, be mindful, think positively, be thankful, and do kind things. The other group just reported on their feelings.
They checked how the people were doing before, right after, and one month after the study. Most people finished the study and liked it a lot. The group that learned the special skills felt more positive, less negative, and didn't think about their pain in a bad way as much as the other group. These good changes stayed even one month later. The more people practiced these skills, the less they felt bad about their pain.
This study shows that learning to feel more positive through the internet can really help adults with fibromyalgia 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.
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Lessons in Affect Regulation to Keep Stress and Pain UndeR control (LARKSPUR): Design of a randomized controlled trial to increase positive affect in middle-aged and older adults with fibromyalgia.
Contemporary clinical trials (2022)
Ong AD, Moskowitz JT, Wethington E, Addington EL, Sanni M, Goktas S, Sluys E, Swong S, Kim P, Reid MC.
Lessons in Affect Regulation to Keep Stress and Pain UndeR control (LARKSPUR): Design of a randomized controlled trial to increase positive affect in middle-aged and older adults with fibromyalgia.
Contemp Clin Trials.
2022 Sep;
120:106880.
Abstract: Fibromyalgia syndrome (FMS) is a leading cause of functional limitations and disability for which there is no cure. Positive psychological interventions for improving health have received increasing attention, but evidence of the feasibility, acceptability, and impact of such interventions in adult populations with FMS is limited. To describe the rationale and design of a 5-week, online positive affect skills intervention, LARKSPUR: Lessons in Affect Regulation to Keep Stress and Pain UndeR control. FMS participants (N = 90) will be randomized to one of two conditions: (1) LARKSPUR or (2) emotion reporting/attention control. LARKSPUR is an online multicomponent intervention that targets eight skills to help foster positive affect: (1) noticing positive events, (2) savoring positive events, (3) identifying personal strengths, (4) behavioral activation to set and work toward attainable goals, (5) mindfulness, (6) positive reappraisal, (7) gratitude, and (8) acts of kindness. The primary outcomes include feasibility (i.e., recruitment, retention, adherence) and acceptability (i.e., helpfulness, usability, satisfaction). Secondary outcomes include pain intensity and pain interference. If feasibility and acceptability metrics are met and reductions in pain outcomes are achieved, we will undertake future efficacy and effectiveness trials of LARKSPUR among older adults with FMS. NCT04869345.
Abstract Summary: This study is about a new online program called LARKSPUR that helps adults with fibromyalgia, a condition that causes pain and disability, to manage their stress and pain. The program teaches eight skills, like noticing good things, being grateful, and setting achievable goals. The study will have 90 participants who will either use LARKSPUR or another method. The researchers will see if people like using the program, if they stick with it, and if it helps reduce their pain. If it works well, they plan to test it with more people in the future. This could be a new way to help people with fibromyalgia.
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.
Psychoeducational Videos and Digital Assessments for BPD
Massachusetts General Hospital
Improving emotional well-being and quality of life in older adults experiencing dementia-related fear
Northwestern University
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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.
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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.
ASPirin in Reducing Events in the Elderly
University of Iowa
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Long-term blood pressure variability and frailty risk in older adults.
Journal of hypertension (2024)
Fravel MA, Ernst ME, Woods RL, Beilin L, Zhou Z, Orchard SG, Chowdhury E, Reid CM, Saifuddin Ekram A, Espinoza SE, Nelson MR, Stocks N, Polkinghorne KR, Wolfe R, Ryan J.
Long-term blood pressure variability and frailty risk in older adults.
J Hypertens.
2024 Feb 1;
42(2):244-251.
Abstract: In healthy older adults, the relationship between long-term, visit-to-visit variability in blood pressure (BP) and frailty is uncertain. Secondary analysis of blood pressure variability (BPV) and incident frailty in >13 000 participants ≥65-70 years enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial and its observational follow-up (ASPREE-XT). Participants were without dementia, physical disability, or cardiovascular disease at baseline. BPV was estimated using standard deviation of mean BP from three annual visits (baseline through the second annual follow-up). Frailty was defined using Fried phenotype and a frailty deficit accumulation index (FDAI). Participants with frailty during the BPV estimation period were excluded from the main analysis. Adjusted Cox proportional hazards regression evaluated the association between BPV and incident frailty, and linear mixed models for change in frailty scores, through a maximum of 9 years of follow-up. Participants in the highest systolic BPV tertile were at higher risk of frailty compared to those in the lowest (referent) tertile of systolic BPV [Fried hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04-1.31; FDAI HR 1.18, 95% CI 1.07-1.30]. Findings were consistent when adjusted for multiple covariates and when stratified by antihypertensive use. Linear mixed models showed that higher systolic BPV was associated with increasing frailty score over time. Diastolic BPV was not consistently associated. High systolic BPV, independent of mean BP, is associated with increased risk of frailty in healthy older adults. Variability of BP across visits, even in healthy older adults, can convey important risk information beyond mean BP. ClinicalTrials.gov NCT01038583 and ISRCTN83772183.
Abstract Summary: Scientists did a study to see if changes in blood pressure over time could make older people more likely to become frail. They looked at over 13,000 people who were 65-70 years old and healthy. These people didn't have memory problems, trouble moving around, or heart disease when the study started. The researchers checked their blood pressure several times over three years and then watched them for up to nine years. They found that older adults whose blood pressure went up and down a lot were more likely to become frail than those whose blood pressure stayed the same. This was true even when they considered other health factors and whether the person was taking medicine for high blood pressure. The study shows that for older adults, keeping blood pressure steady is important for staying strong and 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.
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Genome-Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the CETP Gene.
Journal of the American Heart Association (2023)
Yu C, Bakshi A, Watts GF, Renton AE, Fulton-Howard B, Goate AM, Natarajan P, Chasman DI, Robman L, Woods RL, Guymer R, Wolfe R, Thao LTP, McNeil JJ, Tonkin AM, Nicholls SJ, Lacaze P.
Genome-Wide Association Study of Cardiovascular Resilience Identifies Protective Variation in the CETP Gene.
J Am Heart Assoc.
2023 Nov 7;
12(21):e031459.
Abstract: Background The risk of atherosclerotic cardiovascular disease (ASCVD) increases sharply with age. Some older individuals, however, remain unaffected despite high predicted risk. These individuals may carry cardioprotective genetic variants that contribute to resilience. Our aim was to assess whether asymptomatic older individuals without prevalent ASCVD carry cardioprotective genetic variants that contribute to ASCVD resilience. Methods and Results We performed a genome-wide association study using a 10-year predicted ASCVD risk score as a quantitative trait, calculated only in asymptomatic older individuals aged ≥70 years without prevalent ASCVD. Our discovery genome-wide association study of N=12 031 ASCVD event-free individuals from the ASPREE (Aspirin in Reducing Events in the Elderly) trial identified 2 independent variants, rs9939224 (<5×10) and rs56156922 (<10), in the (cholesteryl ester transfer protein) gene. The gene is a regulator of plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) levels, and it is a therapeutic drug target. The associations were replicated in the UK Biobank (subpopulation of N=13 888 individuals aged ≥69 years without prevalent ASCVD). Carriers of the identified variants (versus noncarriers) had higher plasma high-density lipoprotein cholesterol levels, lower plasma low-density lipoprotein cholesterol levels, and reduced risk of incident ASCVD events during follow-up. Expression quantitative trait loci analysis predicted the identified variants reduce gene expression across various tissues. Previously reported associations between genetic inhibition and increased risk of age-related macular degeneration were not observed among the 3917 ASPREE trial participants with retinal imaging and genetic data available. Conclusions Common genetic variants in the gene region are associated with cardiovascular resilience during aging. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.
Abstract Summary: Scientists wanted to find out why some older people don't get heart diseases even when they have a high chance of getting them. They thought these people might have special genes that protect their hearts. To find out, they looked at the genes of over 12,000 older people who didn't have heart diseases. They found two special parts in a gene that seemed to help keep these people's hearts healthy. This gene helps control the levels of good and bad fats in the blood, which are important for heart health. They checked their findings with another big group of older people and found the same thing. People with these special gene parts had better fat levels in their blood and a lower chance of getting heart diseases. This discovery is important because it could help us understand how to protect more people's hearts 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.
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Genome-Wide Association Study of Pericardial Fat Area in 28 161 UK Biobank Participants.
Journal of the American Heart Association (2023)
Salih A, Ardissino M, Wagen AZ, Bard A, Szabo L, Ryten M, Petersen SE, Altmann A, Raisi-Estabragh Z.
Genome-Wide Association Study of Pericardial Fat Area in 28 161 UK Biobank Participants.
J Am Heart Assoc.
2023 Nov 7;
12(21):e030661.
Abstract: BACKGROUND Pericardial adipose tissue (PAT) is the visceral adipose tissue compartment surrounding the heart. Experimental and observational research has suggested that greater PAT deposition might mediate cardiovascular disease, independent of general or subcutaneous adiposity. We characterize the genetic architecture of adiposity-adjusted PAT and identify causal associations between PAT and adverse cardiac magnetic resonance imaging measures of cardiac structure and function in 28 161 UK Biobank participants. METHODS AND RESULTS The PAT phenotype was extracted from cardiac magnetic resonance images using an automated image analysis tool previously developed and validated in this cohort. A genome-wide association study was performed with PAT area set as the phenotype, adjusting for age, sex, and other measures of obesity. Functional mapping and Bayesian colocalization were used to understand the biologic role of identified variants. Mendelian randomization analysis was used to examine potential causal links between genetically determined PAT and cardiac magnetic resonance-derived measures of left ventricular structure and function. We discovered 12 genome-wide significant variants, with 2 independent sentinel variants (rs6428792, =4.20×10 and rs11992444, =1.30×10) at 2 distinct genomic loci, that were mapped to 3 potentially causal genes: T-box transcription factor 15 (), tryptophanyl tRNA synthetase 2, mitochondrial () and early B-cell factor-2 () through functional annotation. Bayesian colocalization additionally suggested a role of RP4-712E4.1. Genetically predicted differences in adiposity-adjusted PAT were causally associated with adverse left ventricular remodeling. CONCLUSIONS This study provides insights into the genetic architecture determining differential PAT deposition, identifies causal links with left structural and functional parameters, and provides novel data about the pathophysiological importance of adiposity distribution.
Abstract Summary: Scientists did a study to learn more about the fat that surrounds the heart, called pericardial adipose tissue (PAT). They wanted to see if having more PAT could cause heart problems, even if a person doesn't have too much fat elsewhere on their body. They looked at heart scans from over 28,000 people and used special computer tools to measure the PAT. They also checked the people's genes to find any that might be linked to having more PAT.
They found 12 spots in the genes that were important, and two of these spots were really special because they were connected to three genes that might explain why some people have more heart fat. They also used a special method to see if having more PAT could actually lead to changes in the heart that aren't good, like making it harder for the heart to pump blood.
The study showed that certain genes can make a person have more fat around their heart, and this can lead to heart problems. This information is important because it helps us understand that where fat is in the body can affect heart health, not just how much fat there is overall. This could help doctors find new ways to keep hearts healthy by focusing on PAT.
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.
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Associations between low sex hormone concentrations and depression in older women: An observational study.
Maturitas (2023)
Islam RM, Bell RJ, Berk M, Handelsman DJ, McNeil JJ, Wolfe R, Woods RL, Davis SR.
Associations between low sex hormone concentrations and depression in older women: An observational study.
Maturitas.
2023 Oct;
176:107822.
Abstract: We investigated whether low sex hormone concentrations are associated with depression in older women. This was a cross-sectional study of Australian women, aged at least 70 years, not taking medications modulating sex hormone levels. Associations between hormones, measured by liquid chromatography-tandem mass spectrometry, and depression were examined by logistic regression adjusted for potential confounders. The primary outcome was a Center for Epidemiologic Studies Depression score >10, designated as 'depression', with an expanded definition that included anti-depressant use as a secondary outcome. For the 5535 participants in the analysis, median age 74.0 years (interquartile range 71.7-77.7), depression prevalence was 5.8 % (95 % CI 5.2-6.4 %). In the adjusted models, a statistically significantly greater likelihood of depression was seen for women with testosterone and oestrone blood concentrations in quartile 1 compared with quartiles 2-4 (odds ratio 1.33, 95 % CI 1.04 to 1.70, p = 0.022; and 1.37, 95 % CI 1.06 to 1.78, p = 0.017, respectively). For the expanded definition, the odds ratios for the lowest testosterone and oestrone quartile compared with other quartiles were 1.47 (95 % CI 1.24 to 1.75, p < 0.001) and 1.31 (95 % CI 1.09 to 1.58, p < 0.001), respectively. A significant association for low DHEA was seen only for the expanded definition of depression (1.36, 95 % CI 1.13 to 1.64, p = 0.001). Receiver operating characteristic curves showed that the contribution of each sex hormone to the likelihood of depression was small. Amongst older women not taking medications that influence sex hormone concentrations, low testosterone and oestrone levels are associated with a greater likelihood of depression, but the effects are small. International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and clinicaltrials.gov (NCT01038583).
Abstract Summary: Scientists wanted to find out if having low levels of certain hormones could make older women feel depressed. They looked at Australian women who were 70 years or older and not taking any hormone medicines. They tested the women's blood to measure their hormone levels and asked questions to see if they were feeling depressed.
They found that women with very low levels of two hormones, testosterone and oestrone, were a little more likely to feel depressed compared to women with higher levels. But, the difference was not very big. They also noticed that another hormone, DHEA, was only linked to feeling depressed when they included women taking antidepressants in their study.
The study shows that for older women not on hormone medicines, having lower levels of certain hormones might be connected to feeling depressed, but it doesn't make a big difference. This information could help doctors understand why some older women feel depressed.
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.
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Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly : A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial.
Annals of internal medicine (2023)
McQuilten ZK, Thao LTP, Pasricha SR, Artz AS, Bailey M, Chan AT, Cohen HJ, Lockery JE, Murray AM, Nelson MR, Schneider HG, Wolfe R, Woods RL, Wood EM, McNeil JJ.
Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly : A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial.
Ann Intern Med.
2023 Jul;
176(7):913-921.
Abstract: Daily low-dose aspirin increases major bleeding; however, few studies have investigated its effect on iron deficiency and anemia. To investigate the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations. Post hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial. (ClinicalTrials.gov: NCT01038583). Primary/community care in Australia and the United States. Community-dwelling persons aged 70 years or older (≥65 years for Black persons and Hispanic persons). 100 mg of aspirin daily or placebo. Hemoglobin concentration was measured annually in all participants. Ferritin was measured at baseline and 3 years after random assignment in a large subset. 19 114 persons were randomly assigned. Anemia incidence in the aspirin and placebo groups was 51.2 events and 42.9 events per 1000 person-years, respectively (hazard ratio, 1.20 [95% CI, 1.12 to 1.29]). Hemoglobin concentrations declined by 3.6 g/L per 5 years in the placebo group and the aspirin group experienced a steeper decline by 0.6 g/L per 5 years (CI, 0.3 to 1.0 g/L). In 7139 participants with ferritin measures at baseline and year 3, the aspirin group had greater prevalence than placebo of ferritin levels less than 45 µg/L at year 3 (465 [13%] vs. 350 [9.8%]) and greater overall decline in ferritin by 11.5% (CI, 9.3% to 13.7%) compared with placebo. A sensitivity analysis quantifying the effect of aspirin in the absence of major bleeding produced similar results. Hemoglobin was measured annually. No data were available on causes of anemia. Low-dose aspirin increased incident anemia and decline in ferritin in otherwise healthy older adults, independent of major bleeding. Periodic monitoring of hemoglobin should be considered in older persons on aspirin. National Institutes of Health and Australian National Health and Medical Research Council.
Abstract Summary: Scientists did a study to see if taking a small amount of aspirin every day affects people's blood levels and iron. They looked at older people, some who took aspirin and some who took a pretend pill (placebo). They found that the group taking aspirin had more cases of anemia, which means not having enough healthy red blood cells, and they also had lower iron levels. This happened even when they didn't have any big bleeding problems. The study suggests that older people who take aspirin should have their blood checked regularly to make sure they're not getting anemia.
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.
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Potentially inappropriate medication use is associated with increased risk of incident disability in healthy older adults.
Journal of the American Geriatrics Society (2023)
Lockery JE, Collyer TA, Woods RL, Orchard SG, Murray A, Nelson MR, Stocks NP, Wolfe R, Moran C, Ernst ME, ASPREE Investigator Group.
Potentially inappropriate medication use is associated with increased risk of incident disability in healthy older adults.
J Am Geriatr Soc.
2023 Aug;
71(8):2495-2505.
Abstract: Efforts to minimize medication risks among older adults include avoidance of potentially inappropriate medications (PIMs). However, most PIMs research has focused on older people in aged or inpatient care, creating an evidence gap for community-dwelling older adults. To address this gap, we investigated the impact of PIMs use in the ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial cohort. Analysis included 19,114 community-dwelling ASPREE participants aged 70+ years (65+ if US minorities) without major cardiovascular disease, cognitive impairment, or significant physical disability. PIMs were defined according to a modified 2019 AGS Beers Criteria. Cox proportional-hazards regression models were used to estimate the association between baseline PIMs exposure and disability-free survival, death, incident dementia, disability, and hospitalization, with adjustment for sex, age, country, years of education, frailty, average gait speed, and comorbidities. At baseline, 7396 (39% of the total) participants were prescribed at least one PIM. Compared with those unexposed, participants on a PIM at baseline were at an increased risk of persistent physical disability (adjusted hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.21, 1.80) and hospitalization (adjusted HR 1.26, 95% CI 1.20, 1.32), but had similar rates of disability-free survival (adjusted HR 1.02; 95% CI 0.93, 1.13) and death (adjusted HR 0.92, 95% CI 0.81, 1.05). These effects did not vary by polypharmacy status in interaction analyses. PIMs exposure was associated with higher risk of disability followed by hospitalization (adjusted HR 1.92, 95% CI 1.25, 2.96) as well as vice versa (adjusted HR 1.54, 95% CI 1.15, 2.05). PPIs, anti-psychotics and benzodiazepines, were associated with increased risk of disability. PIMs exposure is associated with subsequent increased risk of both incident disability and hospitalization. Increased risk of disability prior to hospitalization suggests that PIMs use may start the disability cascade in healthy older adults. Our findings emphasize the importance of caution when prescribing PIMs to older adults in otherwise good health.
Abstract Summary: Scientists did a study to see if certain medicines might not be good for older people living at home. They looked at over 19,000 older adults who were pretty healthy and didn't have serious heart problems, trouble thinking, or trouble moving around. They checked what medicines these people were taking and followed them to see if they had any health problems like getting hurt and not being able to move well, having to go to the hospital, or getting dementia.
They found that about 39% of these older adults were taking at least one medicine that might not be good for them. These adults had a higher chance of getting hurt and not being able to move well, and they also went to the hospital more often. But these medicines didn't make them die sooner or live without health problems any less than other people.
The study showed that some medicines, like stomach acid pills, antipsychotics, and anxiety pills, could make it more likely for older people to get hurt and not be able to move well. So, the study tells us that doctors should be really careful when giving these kinds of medicines to older people who are otherwise 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.
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Associations of body size with all-cause and cause-specific mortality in healthy older adults.
Scientific reports (2023)
Carr PR, Webb KL, Neumann JT, Thao LTP, Beilin LJ, Ernst ME, Fitzgibbon B, Gasevic D, Nelson MR, Newman AB, Orchard SG, Owen A, Reid CM, Stocks NP, Tonkin AM, Woods RL, McNeil JJ.
Associations of body size with all-cause and cause-specific mortality in healthy older adults.
Sci Rep.
2023 Mar 7;
13(1):3799.
Abstract: In the general population, body mass index (BMI) and waist circumference are recognized risk factors for several chronic diseases and all-cause mortality. However, whether these associations are the same for older adults is less clear. The association of baseline BMI and waist circumference with all-cause and cause-specific mortality was investigated in 18,209 Australian and US participants (mean age: 75.1 ± 4.5 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) study, followed up for a median of 6.9 years (IQR: 5.7, 8.0). There were substantially different relationships observed in men and women. In men, the lowest risk of all-cause and cardiovascular mortality was observed with a BMI in the range 25.0-29.9 kg/m [HR: 0.85; 95% CI, 0.73-1.00] while the highest risk was in those who were underweight [HR: 1.82; 95% CI 1.30-2.55], leading to a clear U-shaped relationship. In women, all-cause mortality was highest in those with the lowest BMI leading to a J-shaped relationship (HR: 1.64; 95% CI 1.26-2.14). Waist circumference showed a weaker relationship with all-cause mortality in both men and women. There was little evidence of a relationship between either index of body size and subsequent cancer mortality in men or women, while non-cardiovascular non-cancer mortality was higher in underweight participants. For older men, being overweight was found to be associated with a lower risk of all-cause mortality, while among both men and women, a BMI in the underweight category was associated with a higher risk. Waist circumference alone had little association with all-cause or cause-specific mortality risk.Trial registration ASPREE https://ClinicalTrials.gov number NCT01038583.
Abstract Summary: Scientists wanted to find out if being heavier or having a bigger waist size affects the chances of getting sick or dying for older people, just like it does for others. They looked at over 18,000 older adults from Australia and the USA for about 7 years. They found that for older men, being a bit overweight was actually linked to a lower chance of dying from heart problems or other causes. But being too skinny was riskier for both men and women. Having a bigger waist didn't seem to make as much of a difference. This study helps us understand that for older people, being a little overweight might not be as bad as we thought, especially for men.
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.
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Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.
JNCI cancer spectrum (2023)
Orchard SG, Lockery JE, Broder JC, Ernst ME, Espinoza S, Gibbs P, Wolfe R, Polekhina G, Zoungas S, Loomans-Kropp HA, Woods RL, ASPREE Investigator Group.
Association of metformin, aspirin, and cancer incidence with mortality risk in adults with diabetes.
JNCI Cancer Spectr.
2023 Mar 1;
7(2):.
Abstract: Metformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin's impact on metformin users. Analysis included community-dwelling ASPREE participants (aged ≥70 years, or ≥65 years for members of US minority populations) with diabetes. Diabetes was defined as a fasting blood glucose level greater than 125 mg/dL, self-report of diabetes, or antidiabetic medication use. Cox proportional hazards regression models were used to analyze the association of metformin and a metformin-aspirin interaction with cancer incidence and mortality, with adjustment for confounders. Of 2045 participants with diabetes at enrollment, 965 were concurrently using metformin. Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19). Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64). The possible effect modification of aspirin on cancer mortality, however, was not statistically significant (interaction P = .11). In community-dwelling older adults with diabetes, metformin use was associated with reduced cancer incidence. Increased cancer mortality risk in metformin users randomized to aspirin warrants further investigation. ClinicalTrials.gov ID NCT01038583.
Abstract Summary: Doctors often give people with diabetes two medicines called metformin and aspirin. Metformin might help prevent cancer, but aspirin could make cancer more deadly for older people. This study looked at older adults with diabetes to see if metformin helps them live longer without getting cancer. They also checked if taking aspirin changes anything.
The study included older people, some who were taking metformin, and some who were also taking aspirin or a fake pill (placebo). They found that those taking metformin got cancer less often. However, for those taking both metformin and aspirin, there was a higher chance of dying from cancer, but this finding needs more research to be sure.
This study is important because it suggests that metformin might help older people with diabetes avoid getting cancer, but combining it with aspirin could be risky. More studies are needed to understand this 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.
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Sex hormones, SHBG and cognitive performance among older Australian women: an observational study.
Climacteric : the journal of the International Menopause Society (2023)
Sultana F, Davis SR, Murray AM, Woods RL, McNeil JJ, Islam RM.
Sex hormones, SHBG and cognitive performance among older Australian women: an observational study.
Climacteric.
2023 Apr;
26(2):121-128.
Abstract: This study aims to explore the associations between sex hormones and cognitive performance in older women. Associations between sex hormones, sex hormone binding globulin (SHBG) and cognitive performance were examined in women aged at least 70 years, without dementia and not using medications that influence sex hormones. Linear and generalized linear regression models included age, body mass index, education, smoking, alcohol, living circumstances, diabetes, hypertension, depression and impaired renal function. The included 5511 women had a median (interquartile range) age of 73.9 (71.6-77.6) years. No associations were found for estrone, estradiol, testosterone or dehydroepiandrosterone and cognitive performance. SHBG concentrations above quartile 1 (Q1) were significantly inversely associated with processing speed (Q2, = -0.94, 95% confidence interval [CI] - 1.64 to -0.24, = 0.009; Q3, = -0.82, 95% CI -1.53 to -0.10, = 0.025; and Q4, = -0.95, 95% CI -1.70 to -0.20, = 0.013). Sex hormones were not associated with cognitive performance. The finding that low SHBG is associated with better processing speed warrants further investigation. The null findings for the sex hormones establish a firm baseline to confidently explore the association between sex hormones and longitudinal cognitive performance in this population. International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and ClinicalTrials.gov (NCT01038583).
Abstract Summary: Scientists did a study to see if there's a link between certain hormones and how well older women can think and remember things. They looked at a bunch of women who were 70 or older, who didn't have memory problems and weren't taking hormone-related medicine. They checked things like age, weight, education, smoking, drinking, living situation, diabetes, high blood pressure, sadness, and kidney health. They had 5,511 women in the study.
They found that most hormones didn't affect the women's thinking or memory. But they did notice that women with lower levels of a hormone called SHBG were a bit quicker at processing information. This was interesting, so they think it should be looked into more. The study helps us know that these hormones don't usually change how well older women think, which is good to know for future research.
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.
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The Association between Metabolic Syndrome, Frailty and Disability-Free Survival in Healthy Community-dwelling Older Adults.
The journal of nutrition, health & aging (2023)
Saifuddin Ekram ARM, Espinoza SE, Ernst ME, Ryan J, Beilin L, Stocks NP, Ward SA, McNeil JJ, Shah RC, Woods RL.
The Association between Metabolic Syndrome, Frailty and Disability-Free Survival in Healthy Community-dwelling Older Adults.
J Nutr Health Aging.
2023;
27(1):1-9.
Abstract: To examine the association between metabolic syndrome (MetS) and frailty, and determine whether co-existent MetS and frailty affect disability-free survival (DFS), assessed through a composite of death, dementia or physical disability. Longitudinal study. Community-dwelling older adults from Australia and the United States (n=18,264) from "ASPirin in Reducing Events in the Elderly" (ASPREE) study. MetS was defined according to American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines (2018). A modified Fried phenotype and a deficit accumulation Frailty Index (FI) were used to assess frailty. Association between MetS and frailty was examined using multinomial logistic regression. Cox regression was used to analyze the association between MetS, frailty and DFS over a median follow-up of 4.7 years. Among 18,264 participants, 49.9% met the criteria for MetS at baseline. Participants with Mets were more likely to be pre-frail [Relative Risk Ratio (RRR): 1.22; 95%Confidence Interval (CI): 1.14, 1.30)] or frail (RRR: 1.66; 95%CI: 1.32, 2.08) than those without MetS. MetS alone did not shorten DFS while pre-frailty or frailty alone did [Hazard Ratio (HR): 1.68; 95%CI: 1.45, 1.94; HR: 2.65; 95%CI:1.92, 3.66, respectively]. Co-existent MetS with pre-frailty/frailty did not change the risk of shortened DFS. MetS was associated with pre-frailty or frailty in community-dwelling older individuals. Pre-frailty or frailty increased the risk of reduced DFS but presence of MetS did not change this risk. Assessment of frailty may be more important than MetS in predicting survival free of dementia or physical disability.
Abstract Summary: Scientists did a study to see if having a group of health problems called metabolic syndrome (MetS) makes older people more likely to become weak and less able to take care of themselves without getting sick, losing their memory, or dying. They looked at over 18,000 older adults from Australia and the USA. They found that people with MetS were more likely to start getting weak. However, just having MetS didn't make it more likely for someone to have problems with their memory or to have trouble moving around. But if someone was already getting weak, having MetS didn't make things worse. This study tells us that checking if an older person is getting weak might be more helpful than just looking for MetS to keep them healthy and able to do things on their own.
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.
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The Association between Frailty and Dementia-Free and Physical Disability-Free Survival in Community-Dwelling Older Adults.
Gerontology (2023)
Ekram ARMS, Ryan J, Espinoza SE, Newman AB, Murray AM, Orchard SG, Fitzgerald SM, McNeil JJ, Ernst ME, Woods RL.
The Association between Frailty and Dementia-Free and Physical Disability-Free Survival in Community-Dwelling Older Adults.
Gerontology.
2023;
69(5):549-560.
Abstract: Frailty is a common geriatric syndrome that adversely impacts health outcomes. This study examined correlates of physical frailty in healthy community-dwelling older adults and studied the effect of frailty on disability-free survival (DFS), defined as survival free of independence-limiting physical disability or dementia. This is a post hoc analysis of 19,114 community-dwelling older adults (median age: 74.0 years, interquartile range or IQR: 6.1 years) from Australia and the USA enrolled in the "ASPirin in Reducing Events in the Elderly (ASPREE)" clinical trial. Frailty was assessed using a modified Fried phenotype and a deficit accumulation frailty index (FI) utilizing a ratio score derived from 66 items. Multinomial logistic regression was used to examine the correlates of frailty and Cox regression to analyze the association between frailty and DFS (and its components). At study enrollment, 39.0% were prefrail, and 2.2% of participants were frail, according to Fried phenotype. Older age, higher waist circumference, lower education, ethnoracial origin, current smoking, depression, and polypharmacy were associated with prefrailty and frailty according to Fried phenotype and FI. Fried phenotype defined prefrailty and frailty predicted reduced DFS (prefrail: HR: 1.67; 95% CI: 1.50-1.86 and frail: HR: 2.80; 95% CI: 2.27-3.46), affecting each component of DFS including dementia, physical disability, and mortality. Effect sizes were larger, according to FI. Our study showed that prefrailty is common in community-dwelling older adults initially free of cardiovascular disease, dementia, or independence-limiting physical disability. Prefrailty and frailty significantly reduced disability-free survival. Addressing modifiable correlates, like depression and polypharmacy, might reduce the adverse impact of frailty on dementia-free and physical disability-free survival.
Abstract Summary: Scientists did a study to learn about frailty, which is when older people get weak and it can lead to health problems. They looked at 19,114 older adults who lived on their own in Australia and the USA. They wanted to see how frailty affected the chances of living without getting a disability or dementia. They found that being a little frail was common, and being very frail was less common. Older people, those with bigger waists, less education, certain ethnic backgrounds, smokers, people feeling sad, and those taking many medicines were more likely to be frail. Frail people had a higher chance of getting a disability, dementia, or dying earlier. The study suggests that helping older adults with these problems might let them live longer without disabilities or dementia.
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.
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Does Aspirin Prevent Incident Heart Failure in Healthy Older Adults? Examining the Evidence From the ASPREE Trial.
Circulation. Heart failure (2022)
Zhou Z, Nelson M, Ernst ME, Reid C, McNeil J, Tonkin A, ASPREE Investigator Group.
Does Aspirin Prevent Incident Heart Failure in Healthy Older Adults? Examining the Evidence From the ASPREE Trial.
Circ Heart Fail.
2022 Jun;
15(6):e009511.
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Association between hypertension and cutaneous melanoma, and the effect of aspirin: extended follow-up of a large randomised controlled trial.
Cancer epidemiology (2022)
Yan MK, Orchard SG, Adler NR, Wolfe R, McLean C, Rodríguez LM, Woods RL, Gibbs P, Chan AT, Haydon A, Mar VJ.
Association between hypertension and cutaneous melanoma, and the effect of aspirin: extended follow-up of a large randomised controlled trial.
Cancer Epidemiol.
2022 Aug;
79:102173.
Abstract: The association between hypertension and melanoma is unclear, and previous analyses of data from the ASPirin in Reducing Events in the Elderly (ASPREE) study demonstrated a reduced number of invasive melanoma events amongst aspirin-exposed hypertensive individuals. Data from the ASPREE study which included (1) the intervention period with a median follow-up of 4.7 years, and (2) the observational period with an additional 2 years follow-up, were combined for this analysis. Logistic regression analyses examined the association between baseline hypertension and treatment status and past melanoma history. Survival analyses examined the association between hypertension and melanoma risk, and the effect of aspirin across hypertension groups. Cox proportional hazards models were used to compare incidence across groups. 19,114 participants (median age of 74 years) were randomised to daily 100 mg aspirin or placebo. At baseline, hypertension and past melanoma history were recorded in 14,195 and 685 individuals, respectively. After adjustment for confounders, hypertension was significantly associated with past melanoma history (OR=1.34, 95%CI: 1.11-1.62). In a prospective analysis, baseline hypertension was not associated with melanoma risk. However, aspirin was associated with a reduced risk of incident melanoma amongst individuals with uncontrolled hypertension (blood pressure ≥140/90 mmHg; HR=0.63, 95%CI 0.44-0.89), but not in those with controlled hypertension (HR=1.04, 95%CI 0.74-1.46). Our results support a reduced melanoma incidence amongst individuals with uncontrolled hypertension exposed to aspirin. Additional studies are required to confirm these findings.
Abstract Summary: Scientists wanted to know if there's a link between high blood pressure and skin cancer called melanoma. They looked at a big study where older people either took aspirin or a fake pill every day for about 5 years, and then they kept checking on them for 2 more years. They found that people with high blood pressure were more likely to have had melanoma in the past. But high blood pressure didn't make it more likely for them to get melanoma later on. The cool part is that people with high blood pressure that wasn't under control seemed to get less melanoma if they took aspirin. This didn't happen for people whose high blood pressure was under control. The scientists think aspirin might help prevent skin cancer for some people, 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.
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Effect of Aspirin on CKD Progression in Older Adults: Secondary Analysis From the ASPREE Randomized Clinical Trial.
American journal of kidney diseases : the official journal of the National Kidney Foundation (2022)
Polkinghorne KR, Wetmore JB, Thao LTP, Wolfe R, Woods RL, Ernst ME, Nelson MR, Reid CM, Shah RC, McNeil JJ, Murray AM.
Effect of Aspirin on CKD Progression in Older Adults: Secondary Analysis From the ASPREE Randomized Clinical Trial.
Am J Kidney Dis.
2022 Dec;
80(6):810-813.
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Prediction of disability-free survival in healthy older people.
GeroScience (2022)
Neumann JT, Thao LTP, Murray AM, Callander E, Carr PR, Nelson MR, Wolfe R, Woods RL, Reid CM, Shah RC, Newman AB, Williamson JD, Tonkin AM, McNeil JJ, ASPREE investigators.
Prediction of disability-free survival in healthy older people.
Geroscience.
2022 Jun;
44(3):1641-1655.
Abstract: Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6-77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people.Trial registration Clinicaltrials.gov (NCT01038583).
Abstract Summary: Scientists wanted to find out what helps older people stay healthy and active without disabilities. They looked at information from a big study where older people took aspirin to see if it helped them stay healthy. These people were already healthy when they started and didn't have heart problems, dementia, or trouble moving around.
The researchers used a special computer program to pick out important health signs from 25 different things like mood, lifestyle, and body measurements. They made different health prediction models for men and women.
They found that for both men and women, being older, having a slower walking speed, a weaker hand grip, and not having a normal body weight could mean a higher chance of getting sick or disabled. For men, smoking and having kidney problems were extra risks. For women, having diabetes or feeling very sad were extra risks.
The models they made were pretty good at guessing who would stay healthy. This study helps us understand what to look out for to help older people stay healthy for as long as possible.
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.
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Associations between blood sex steroid concentrations and risk of major adverse cardiovascular events in healthy older women in Australia: a prospective cohort substudy of the ASPREE trial.
The lancet. Healthy longevity (2022)
Islam RM, Bell RJ, Handelsman DJ, McNeil JJ, Nelson MR, Reid CM, Tonkin AM, Wolfe RS, Woods RL, Davis SR.
Associations between blood sex steroid concentrations and risk of major adverse cardiovascular events in healthy older women in Australia: a prospective cohort substudy of the ASPREE trial.
Lancet Healthy Longev.
2022 Feb;
3(2):e109-e118.
Abstract: Blood testosterone concentrations in women decline during the reproductive years and reach a nadir in the seventh decade, after which concentrations increase and are restored to those of reproductive-aged women early in the eighth decade. We aimed to establish the association between the concentration of testosterone in the blood and risk of major adverse cardiovascular events (MACE) and all-cause mortality in healthy older women. SHOW was a prospective cohort substudy of the longitudinal randomised ASPREE trial. Eligible participants were women aged at least 70 years from Australia with unimpaired cognition, no previous MACE, and a life expectancy of at least 5 years. Participants who were receiving hormonal or steroid therapy were ineligible for inclusion. We measured serum concentrations of sex steroids with liquid chromatography-tandem mass spectrometry and of SHBG with immunoassay. We compared lower concentrations of sex hormones with higher concentrations using four quartiles. Primary endpoints were risk of MACE and all-cause mortality, the associations of which with sex steroid concentrations were assessed using Cox proportional hazards regression that included age, body-mass index, smoking status, alcohol consumption, diabetes, hypertension, dyslipidaemia, impaired renal function, and treatment allocation in the ASPREE trial (aspirin placebo). ASPREE is registered with ClinicalTrials.gov, NCT01038583. Of the 9180 women recruited to the ASPREE trial between March 10, 2010, and Dec 31 2014, 6358 participants provided sufficient biobank samples at baseline and 5535 were included in the final analysis. Median age at entry was 74·0 years (IQR 71·7-77·7). During a median 4·4 years of follow-up (24 553 person-years), 144 (2·6%) women had a first MACE (incidence 5·9 per 1000 person-years). During a median 4·6 years of follow-up (3·8-5·6), 200 women died (7·9 per 1000 person-years). In the fully adjusted models, higher concentrations of testosterone were associated with a lower incidence of MACE (quartile 4 quartile 1: hazard ratio 0·57 [95% CI 0·36-0·91]; p=0·02), as were higher concentrations of DHEA (quartile 4 quartile 1: 0·61 [0·38-0·97]; p=0·04). For oestrone, a lower risk of MACE was seen for concentrations in quartile 2 only, compared with quartile 1 (0·55 [0·33-0·92]; p=0·02). In fully adjusted models, no association was seen between SHBG and MACE, or between any hormone or SHBG and all-cause mortality. Blood concentrations of testosterone and DHEA above the lowest quartile in older women were associated with a reduced risk of a first-ever MACE. Given that the physiological effects of DHEA are mediated through its steroid metabolites, if the current findings were to be replicated, trials investigating testosterone therapy for the primary prevention of ischaemic cardiovascular disease events in older women would be warranted. The National Health and Medical Research Council of Australia, US National Institute on Aging, the Victorian Cancer Agency, the Commonwealth Scientific and Industrial Research Organisation, and Monash University.
Abstract Summary: Scientists wanted to find out if there's a link between the amount of testosterone in older women's blood and their risk of heart problems or dying from any cause. They studied women over 70 who were healthy and not on hormone treatments. They measured different hormones in the women's blood and watched them for about 4.5 years to see if they had heart issues or passed away.
They found that women with higher levels of testosterone and another hormone called DHEA had fewer heart problems. But these hormone levels didn't change the chances of dying from any cause. The study suggests that having more testosterone might help prevent heart problems in older women. If more research confirms this, doctors might consider giving testosterone to older women to keep their hearts 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.
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Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older.
Circulation. Genomic and precision medicine (2022)
Neumann JT, Riaz M, Bakshi A, Polekhina G, Thao LTP, Nelson MR, Woods RL, Abraham G, Inouye M, Reid CM, Tonkin AM, McNeil J, Lacaze P.
Prognostic Value of a Polygenic Risk Score for Coronary Heart Disease in Individuals Aged 70 Years and Older.
Circ Genom Precis Med.
2022 Feb;
15(1):e003429.
Abstract: The use of a polygenic risk score (PRS) to improve risk prediction of coronary heart disease (CHD) events has been demonstrated to have clinical utility in the general adult population. However, the prognostic value of a PRS for CHD has not been examined specifically in older populations of individuals aged ≥70 years, who comprise a distinct high-risk subgroup. The objective of this study was to evaluate the predictive value of a PRS for incident CHD events in a prospective cohort of older individuals without a history of cardiovascular events. We used data from 12 792 genotyped, healthy older individuals enrolled into the ASPREE trial (Aspirin in Reducing Events in the Elderly), a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. Participants had no previous history of diagnosed atherothrombotic cardiovascular events, dementia, or persistent physical disability at enrollment. We calculated a PRS (meta-genomic risk score) consisting of 1.7 million genetic variants. The primary outcome was a composite of incident myocardial infarction or CHD death over 5 years. At baseline, the median population age was 73.9 years, and 54.9% were female. In total, 254 incident CHD events occurred. When the PRS was added to conventional risk factors, it was independently associated with CHD (hazard ratio, 1.24 [95% CI, 1.08-1.42], =0.002). The area under the curve of the conventional model was 70.53 (95% CI, 67.00-74.06), and after inclusion of the PRS increased to 71.78 (95% CI, 68.32-75.24, =0.019), demonstrating improved prediction. Reclassification was also improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.15-0.28). A PRS for CHD performs well in older people and improves prediction over conventional cardiovascular risk factors. Our study provides evidence that genomic risk prediction for CHD has clinical utility in individuals aged 70 years and older. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.
Abstract Summary: Scientists wanted to see if a special score that looks at many different genes could help predict heart disease in older people. They studied over 12,000 healthy older adults who had never had heart problems before. These adults were part of a big study that also looked at whether taking aspirin every day could help them stay healthy longer. The researchers used the gene score, which includes information from 1.7 million genetic variants, to guess who might have heart problems like a heart attack or die from heart disease in the next five years.
They found that this gene score did a good job of predicting heart disease on top of other usual risk factors like high blood pressure or cholesterol. When they added the gene score to these risk factors, they could predict heart disease even better. This means that using this gene score could help doctors figure out which older people might need more help to prevent heart disease. This is important because it could help keep older adults healthy and free from 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.
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Effect of methotrexate on melanoma risk in older adults: Secondary analysis of a randomised controlled trial.
The Australasian journal of dermatology (2022)
Yan MK, Wolfe R, Orchard SG, Ernst ME, Mar VJ.
Effect of methotrexate on melanoma risk in older adults: Secondary analysis of a randomised controlled trial.
Australas J Dermatol.
2022 Feb;
63(1):114-115.
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Long-Term Blood Pressure Variability and Kidney Function in Participants of the ASPREE Trial.
American journal of hypertension (2022)
Ernst ME, Fravel MA, Webb KL, Wetmore JB, Wolfe R, Chowdhury E, Reid CM, Woods RL, Beilin L, Margolis KL, Murray AM, Polkinghorne KR.
Long-Term Blood Pressure Variability and Kidney Function in Participants of the ASPREE Trial.
Am J Hypertens.
2022 Feb 1;
35(2):173-181.
Abstract: Whether long-term blood pressure variability (BPV) predicts kidney function decline in generally healthy older adults is unknown. We investigated this association in ASPirin in Reducing Events in the Elderly (ASPREE) trial participants. Between 2010 and 2014, Australian and US individuals aged ≥70 years (≥65 if US minority) were recruited and followed with annual study visits for a median of 4.7 years. Time-to-event analyses and linear mixed effects models were used to examine associations between incident chronic kidney disease (CKD), and trajectories of estimated glomerular filtration rate (eGFR) and log albumin-creatinine ratio (log ACR) with systolic BPV as a continuous measure, and, by tertile of SD of systolic blood pressure (BP). BPV was estimated using systolic BP measures from baseline through the second annual visit, and kidney outcomes were assessed following this period. Incident CKD occurred in 1,829 of 6,759 participants (27.2%), and more commonly in BPV tertiles 2 (27.4%) and 3 (28.3%) than tertile 1 (25.5%); however, the risk was not significantly increased after covariate adjustment (tertile 3 hazard ratio = 1.02; 95% confidence interval: 0.91-1.14). Analysis of eGFR (n = 16,193) and log ACR trajectories (n = 15,213) showed individuals in the highest BPV tertile having the lowest eGFR and highest log ACR, cross-sectionally. However, the trajectories of eGFR and log ACR did not differ across BPV tertiles. CKD and markers of reduced kidney function occur more commonly in individuals with higher BPV; however, BPV does not influence trajectory of decline in kidney function over time in older adults who are in generally good health. Trial Number NCT01038583 and ISRCTN83772183.
Abstract Summary: Scientists wanted to find out if changes in blood pressure over time could predict worsening kidney health in older people who are usually healthy. They studied a group of older adults from Australia and the United States, checking their health every year for about 5 years. They looked at how much each person's blood pressure went up and down and whether they developed kidney problems.
They found that 27 out of 100 people got kidney disease, and it was a little more common in people whose blood pressure changed a lot. But when they considered other health factors, the link between blood pressure changes and kidney disease wasn't strong. Also, the way kidney health got worse over time was the same no matter how much a person's blood pressure changed.
In simple terms, while older adults with more ups and downs in blood pressure seemed to have more kidney problems, the changes in blood pressure didn't make their kidney health get worse faster. This information is important because it helps us understand that, for healthy older people, having blood pressure that changes a lot might not be as bad for their kidneys as we thought.
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.
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Protective lipid-lowering variants in healthy older individuals without coronary heart disease.
Open heart (2021)
Lacaze P, Riaz M, Sebra R, Hooper AJ, Pang J, Tiller J, Polekhina G, Tonkin A, Reid C, Zoungas S, Murray AM, Nicholls S, Watts G, Schadt E, McNeil JJ.
Protective lipid-lowering variants in healthy older individuals without coronary heart disease.
Open Heart.
2021 Jul;
8(2):.
Abstract: Genetic variants that disrupt the function of the (proprotein convertase subtilisin kexin type 9) and (apolipoprotein B)genes result in lower serum low-density lipoprotein cholesterol (LDL-C) levels and subsequently confer protection against coronary heart disease (CHD). The objective of this study was to measure the prevalence and selective advantage of such variants among healthy older individuals without a history of CHD. We performed targeted sequencing of the and genes in 13 131 healthy individuals without CHD aged 70 years or older enrolled into the ASPirin in Reducing Events in the Elderly trial. We detected variants in the and genes with predicted loss-of-function. We associated variant carrier status with serum LDL-C and total cholesterol (TC) levels at the time of study enrolment, adjusting for statin use. We detected 22 different rare candidate variants with putative lipid-lowering effect, carried by 104 participants (carrier rate 1 in 126). Serum LDL-C and TC concentrations for rare PCSK9/APOB variant carriers were consistently lower than non-carriers. Rare variant carrier status was associated with 19.4 mg/dL (14.6%) lower LDL-C, compared with non-carriers (p≤0.001, adjusted for statin use). Statin prescriptions were less prevalent in rare variant carriers (16%) than non-carriers (35%). The more common R46L variant (rs11591147-T) was associated with 15.5 mg/dL (11.8%) lower LDL-C in heterozygotes, and 25.2 mg/dL (19.2%) lower LDL-C in homozygotes (both p≤0.001). Lipid-lowering genetic variants are carried by healthy older individuals and contribute to CHD-free survival. NCT01038583.
Abstract Summary: Scientists did a study to see how certain rare changes in two genes, called PCSK9 and APOB, can lead to lower levels of bad cholesterol (LDL-C) in the blood and help protect against heart disease. They looked at these genes in over 13,000 older people who were healthy and didn't have heart disease. They found that some people had these special gene changes, which made their bad cholesterol levels lower than those who didn't have the changes. People with these gene changes also didn't need to take as many cholesterol-lowering drugs (like statins). This research helps us understand that some people have a natural protection against heart disease because of their 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.
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Long-Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults.
Journal of the American Heart Association (2021)
Ernst ME, Ryan J, Chowdhury EK, Margolis KL, Beilin LJ, Reid CM, Nelson MR, Woods RL, Shah RC, Orchard SG, Wolfe R, Storey E, Tonkin AM, Brodtmann A, McNeil JJ, Murray AM.
Long-Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults.
J Am Heart Assoc.
2021 Jul 6;
10(13):e019613.
Abstract: Background Blood pressure variability (BPV) in midlife increases risk of late-life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow-up visits. Time-to-event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction =0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19-2.39) but not women (HR, 1.01; 95% CI, 0.72-1.42). For cognitive decline, similar increased risks were observed for men and women (interaction =0.15; men: HR, 1.36; 95% CI, 1.16-1.59; women: HR, 1.14; 95% CI, 0.98-1.32). Conclusions High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583; isrctn.com. Identifier: ISRCTN83772183.
Abstract Summary: Scientists did a study to see if changes in blood pressure in older people who were still mentally sharp could make them more likely to get dementia or have their thinking skills get worse. They looked at over 19,000 older adults who didn't have dementia or big memory problems when the study started. These adults had their blood pressure checked and did thinking tests at the beginning and then again later on.
The study found that older men with bigger changes in their blood pressure over time were more likely to get dementia and have their thinking skills decline. This was true even when the scientists took into account their usual blood pressure and whether they were taking medicine for it. For women, the results weren't as clear.
In simple words, if an older person, especially a man, has blood pressure that goes up and down a lot, it might mean they have a higher chance of getting dementia or having trouble with tasks that require thinking and remembering.
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.
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Predictive Performance of a Polygenic Risk Score for Incident Ischemic Stroke in a Healthy Older Population.
Stroke (2021)
Neumann JT, Riaz M, Bakshi A, Polekhina G, Thao LTP, Nelson MR, Woods RL, Abraham G, Inouye M, Reid CM, Tonkin AM, Williamson JD, Donnan GA, Brodtmann A, Cloud GC, McNeil JJ, Lacaze P.
Predictive Performance of a Polygenic Risk Score for Incident Ischemic Stroke in a Healthy Older Population.
Stroke.
2021 Aug;
52(9):2882-2891.
Abstract: Polygenic risk scores (PRSs) can be used to predict ischemic stroke (IS). However, further validation of PRS performance is required in independent populations, particularly older adults in whom the majority of strokes occur. We predicted risk of incident IS events in a population of 12 792 healthy older individuals enrolled in the ASPREE trial (Aspirin in Reducing Events in the Elderly). The PRS was calculated using 3.6 million genetic variants. Participants had no previous history of cardiovascular events, dementia, or persistent physical disability at enrollment. The primary outcome was IS over 5 years, with stroke subtypes as secondary outcomes. A multivariable model including conventional risk factors was applied and reevaluated after adding PRS. Area under the curve and net reclassification were evaluated. At baseline, mean population age was 75 years. In total, 173 incident IS events occurred over a median follow-up of 4.7 years. When PRS was added to the multivariable model as a continuous variable, it was independently associated with IS (hazard ratio, 1.41 [95% CI, 1.20–1.65] per SD of the PRS; P<0.001). The PRS alone was a better discriminator for IS events than most conventional risk factors. PRS as a categorical variable was a significant predictor in the highest tertile (hazard ratio, 1.74; P=0.004) compared with the lowest. The area under the curve of the conventional model was 66.6% (95% CI, 62.2–71.1) and after inclusion of the PRS, improved to 68.5 ([95% CI, 64.0–73.0] P=0.095). In subgroup analysis, the continuous PRS remained an independent predictor for large vessel and cardioembolic stroke subtypes but not for small vessel stroke. Reclassification was improved, as the continuous net reclassification index after adding PRS to the conventional model was 0.25 (95% CI, 0.17–0.43). PRS predicts incident IS in a healthy older population but only moderately improves prediction over conventional risk factors. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.
Abstract Summary: Scientists did a study to see if a special score based on a person's genes can tell if older people might have a stroke. They looked at the health of 12,792 older people who had never had heart problems, dementia, or serious physical disabilities. They used a big list of 3.6 million gene changes to make a score for each person. Over about 5 years, they watched to see who had a stroke.
They found that the gene score could help predict strokes better than just looking at usual health risks. People with higher scores were more likely to have a stroke. When they added the gene score to the usual health checks, they got a little better at predicting strokes, especially certain types.
This study is important because it shows that looking at genes can help tell which older adults might have a stroke. This could help doctors keep an eye on people who might need more help to 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.
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A Cohort Study of Anticholinergic Medication Burden and Incident Dementia and Stroke in Older Adults.
Journal of general internal medicine (2021)
Lockery JE, Broder JC, Ryan J, Stewart AC, Woods RL, Chong TT, Cloud GC, Murray A, Rigby JD, Shah R, Storey E, Ward SA, Wolfe R, Reid CM, Collyer TA, Ernst ME, ASPREE Investigator Group, ASPREE Investigator Group listed on www.aspree.org.
A Cohort Study of Anticholinergic Medication Burden and Incident Dementia and Stroke in Older Adults.
J Gen Intern Med.
2021 Jun;
36(6):1629-1637.
Abstract: Anticholinergic medications may increase risk of dementia and stroke, but prospective studies in healthy older people are lacking. Compare risk of incident dementia and stroke by anticholinergic burden among initially healthy older people. Prospective cohort study. Primary care (Australia and USA). 19,114 community-dwelling participants recruited for the ASPREE trial, aged 70+ years (65+ if US minorities) without major cardiovascular disease, dementia diagnosis, or Modified Mini-Mental State Examination score below 78/100. Baseline anticholinergic exposure was calculated using the Anticholinergic Cognitive Burden (ACB) score. Dementia was adjudicated using Diagnostic and Statistical Manual of Mental Disorders volume IV criteria, and stroke using the World Health Organization definition. At baseline, 15,000 participants (79%) had an ACB score of zero, 2930 (15%) a score of 1-2, and 1184 (6%) a score of ≥ 3 (indicating higher burden). After a median follow-up of 4.7 years and adjusting for baseline covariates, a baseline ACB score of ≥ 3 was associated with increased risk of ischemic stroke (adjusted HR 1.58, 95% CI 1.06, 2.35), or dementia (adjusted HR 1.36, 95% CI 1.01, 1.82), especially of mixed etiology (adjusted HR 1.53, 95% CI 1.06, 2.21). Results were similar for those exposed to moderate/highly anticholinergic medications. Residual confounding and reverse causality are possible. Assessment of dose or duration was not possible. High anticholinergic burden in initially healthy older people was associated with increased risk of incident dementia and ischemic stroke. A vascular effect may underlie this association. These findings highlight the importance of minimizing anticholinergic exposure in healthy older people.
Abstract Summary: Scientists did a study to see if certain medicines that affect the nerves, called anticholinergic medications, could make older people more likely to get dementia or have a stroke. They looked at over 19,000 older adults who were healthy at the start and didn't have serious heart problems or dementia. They used a special score to see how much of these medicines people were taking.
After about 5 years, they found that people who took more of these medicines had a higher chance of getting dementia or having a stroke, especially a type of dementia caused by different problems in the brain. The study suggests that older people should try to take less of these medicines to 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.
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Longitudinal changes over three years in sex steroid hormone levels in women aged 70 years and over.
Clinical endocrinology (2021)
Islam RM, Bell RJ, Handelsman DJ, Robinson PJ, Wolfe R, Davis SR, ASPREE Investigator Group.
Longitudinal changes over three years in sex steroid hormone levels in women aged 70 years and over.
Clin Endocrinol (Oxf).
2021 Mar;
94(3):443-448.
Abstract: Sex steroid levels in women vary with increasing age from the age of 70 years (70+). Whether this reflects change within individuals with age or a survival advantage is not known. This study aimed to determine the stability of circulating sex steroids and SHBG over time in individual women aged 70+. A prospective cohort study. 400 women, aged 70+ not using any sex steroid, anti-androgen/oestrogen or glucocorticoid therapy. Sex steroid concentrations, measured by liquid chromatography-tandem mass spectrometry and sex hormone-binding globulin (SHBG) by immunoassay, in paired blood samples drawn 3 years apart and analysed together. 400 women, median (IQR) age 78.0 (8.6) years, were included in the analysis. Mean testosterone concentrations were statistically significantly higher in follow-up samples compared with baseline. The change was modest (mean change 31 pmol/L, 95% confidence interval (CI) 2.4-59.8; p = .034), and an increase was not observed in all women. There was a statistically significant decline in mean body mass index (mean change -0.4 kg/m , 95% CI 0.6 to -0.3; p < .001) and a significant increase in the mean serum SHBG concentration (mean change 4.0 nmol/L, 95% CI 2.7-5.4; p < .001). The change observed in testosterone was not explained by the observed change in SHBG. There was no significant change in the mean oestrone or dehydroepiandrosterone concentration. Testosterone concentrations in women aged 70+ were more likely to increase than decrease. Whether increasing testosterone concentrations in older women confer a survival advantage needs investigation.
Abstract Summary: Scientists wanted to learn if the levels of certain hormones in women's bodies change as they get older, especially after age 70. They studied 400 women who were not taking any hormone treatments. They checked the women's hormone levels twice, three years apart, to see if there were any changes. They found that, on average, a hormone called testosterone went up a little bit in these women, but not in everyone. Another hormone that carries testosterone in the blood also went up. They didn't see big changes in other hormones they checked. The study suggests that as women get older, their testosterone levels might go up, but it's not the same for everyone. The researchers think it's important to find out if this increase in testosterone helps older women live longer or healthier 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.
The role of endogenous opioids in mindfulness-based chronic pain relief.
University of California San Diego
Children's Growth and Behavior Study
The National Institutes of Health
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Independent and Interactive Associations of Subjective and Objective Socioeconomic Status With Body Composition and Parent-Reported Hyperphagia Among Children.
Childhood obesity (Print) (2024)
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.
2024 Sep;
20(6):394-402.
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.
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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.
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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.
Behavior and Neural Features in Early Life
Vanderbilt University Medical Center
Promoting Transportation Safety in Adolescence
University of Pennsylvania
Imaging Lymphatic Function for a Differential Diagnosis of Lipedema and Obesity
Vanderbilt University Medical Center
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National survey of patient symptoms and therapies among 707 women with a lipedema phenotype in the United States.
Vascular medicine (London, England) (2024)
Aday AW, Donahue PM, Garza M, Crain VN, Patel NJ, Beasley JA, Herbst KL, Beckman JA, Taylor SL, Pridmore M, Chen SC, Donahue MJ, Crescenzi R.
National survey of patient symptoms and therapies among 707 women with a lipedema phenotype in the United States.
Vasc Med.
2024 Feb;
29(1):36-41.
Abstract: National survey data exploring the patient experience with lipedema are lacking. We conducted national surveys from 2016 to 2022 of women with lipedema as well as female controls. Surveys collected information on symptomatology, pain, and therapies. We performed logistic regression comparing symptoms among those with lipedema versus controls adjusting for age and BMI. A total of 707 women with lipedema and 216 controls completed the surveys. Those with lipedema had a mean age of 48.6 years and mean BMI of 40.9 kg/m. Lipedema symptom onset occurred frequently at puberty (48.0%) or pregnancy (41.2%). Compared to controls, women with lipedema were more likely to report leg swelling in heat (odds ratio [OR], 66.82; 95% CI, 33.04-135.12; < 0.0001), easy bruising (OR, 26.23; 95% CI, 15.58-44.17; < 0.0001), altered gait (OR, 15.54; 95% CI, 7.58-31.96; < 0.0001), flu-like symptoms (OR, 12.99; 95% CI, 4.27-39.49; < 0.0001), joint hypermobility (OR, 12.88; 95% CI, 6.68-24.81; < 0.0001), cool skin (OR, 12.21; 95% CI, 5.20-28.69; < 0.0001), varicose veins (OR, 11.29; 95% CI, 6.71-18.99; < 0.0001), and fatigue (OR, 9.59; 95% CI, 6.10-15.09; < 0.0001). Additionally, 70.3% had upper arm involvement, 21.2% reported foot swelling, and 16.6% reported foot pain. Most (52.2%) reported no symptom improvement with diet or exercise. Common therapies used included compression therapy (45.0%), gastric bypass (15.7%), and lower-extremity liposuction (14.0%). In a large, national, symptom survey, women with lipedema reported excess pain, swelling, and fat in the legs along with numerous symptoms beyond those classically described. Symptom responses to common therapies remain understudied.
Abstract Summary: Scientists did a big study from 2016 to 2022 to learn about a condition called lipedema that affects women. Lipedema can make legs swell and feel painful. They asked 707 women with lipedema and 216 women without it about their symptoms, pain, and what treatments they tried. They found that women with lipedema often started having symptoms when they hit puberty or during pregnancy. These women had more leg swelling, especially in the heat, bruised easily, walked differently, felt like they had the flu, had stretchy joints, cool skin, big veins, and felt very tired. Many also had arm problems, and some had swollen or painful feet. Diet and exercise didn't really help over half of them. Some treatments they used were special tight clothes to help with swelling, weight loss surgery, and surgery to remove fat from their legs. The study showed that women with lipedema have a lot of pain and other problems that aren't well-known, and we need to learn more about how to help 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.
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Physical Therapy in Women with Early Stage Lipedema: Potential Impact of Multimodal Manual Therapy, Compression, Exercise, and Education Interventions.
Lymphatic research and biology (2022)
Donahue PMC, Crescenzi R, Petersen KJ, Garza M, Patel N, Lee C, Chen SC, Donahue MJ.
Physical Therapy in Women with Early Stage Lipedema: Potential Impact of Multimodal Manual Therapy, Compression, Exercise, and Education Interventions.
Lymphat Res Biol.
2022 Aug;
20(4):382-390.
Abstract: Lipedema is a distinct adipose disorder from obesity necessitating awareness as well as different management approaches to address pain and optimize quality of life (QoL). The purpose of this proof-of-principle study is to evaluate the therapeutic potential of physical therapy interventions in women with lipedema. Participants with Stage 1-2 lipedema and early Stage 0-1 lymphedema ( = 5, age = 38.4 ± 13.4 years, body mass index = 27.2 ± 4.3 kg/m) underwent nine visits of physical therapy in 6 weeks for management of symptoms impacting functional mobility and QoL. Pre- and post-therapy, participants were scanned with 3 Tesla sodium and water magnetic resonance imaging (MRI), underwent biophysical measurements, and completed questionnaires measuring function and QoL (patient-specific functional scale, PSFS, and RAND-36). Pain was measured at each visit using the 0-10 visual analog scale (VAS). Treatment effect was calculated for all study variables. The primary symptomatology measures of pain and function revealed clinically significant post-treatment improvements and large treatment effects (Cohen's for pain VAS = -2.5 and PSFS = 4.4). The primary sodium MRI measures, leg skin sodium, and subcutaneous adipose tissue (SAT) sodium, reduced following treatment and revealed large treatment effects (Cohen's for skin sodium = -1.2 and SAT sodium = -0.9). This proof-of-principle study provides support that persons with lipedema can benefit from physical therapy to manage characteristic symptoms of leg pain and improve QoL. Objective MRI measurement of reduced tissue sodium in the skin and SAT regions indicates reduced inflammation in the treated limbs. Further research is warranted to optimize the conservative therapy approach in lipedema, a condition for which curative and disease-modifying treatments are unavailable.
Abstract Summary: Scientists did a study to see if special exercises could help women with a condition called lipedema. This condition is different from being overweight and can cause pain and make life harder. They had five women do physical therapy for six weeks and checked their pain levels, how well they could move, and used a special MRI scan to look at the salt in their legs before and after the therapy.
After the therapy, the women felt less pain, could move better, and the MRI showed less salt in their legs, which means less swelling and inflammation. This study shows that exercises can really help people with lipedema feel better, even though there's no cure for the condition yet. More studies are needed to find the best way to help these people with exercises.
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.
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Elevated magnetic resonance imaging measures of adipose tissue deposition in women with breast cancer treatment-related lymphedema.
Breast cancer research and treatment (2022)
Crescenzi R, Donahue PMC, Garza M, Lee CA, Patel NJ, Gonzalez V, Jones RS, Donahue MJ.
Elevated magnetic resonance imaging measures of adipose tissue deposition in women with breast cancer treatment-related lymphedema.
Breast Cancer Res Treat.
2022 Jan;
191(1):115-124.
Abstract: Breast cancer treatment-related lymphedema (BCRL) is a common co-morbidity of breast cancer therapies, yet factors that contribute to BCRL progression remain incompletely characterized. We investigated whether magnetic resonance imaging (MRI) measures of subcutaneous adipose tissue were uniquely elevated in women with BCRL. MRI at 3.0 T of upper extremity and torso anatomy, fat and muscle tissue composition, and T relaxometry were applied in left and right axillae of healthy control (n = 24) and symptomatic BCRL (n = 22) participants to test the primary hypothesis that fat-to-muscle volume fraction is elevated in symptomatic BCRL relative to healthy participants, and the secondary hypothesis that fat-to-muscle volume fraction is correlated with MR relaxometry of affected tissues and BCRL stage (significance criterion: two-sided p < 0.05). Fat-to-muscle volume fraction in healthy participants was symmetric in the right and left sides (p = 0.51); in BCRL participants matched for age, sex, and BMI, fat-to-muscle volume fraction was elevated on the affected side (fraction = 0.732 ± 0.184) versus right and left side in controls (fraction = 0.545 ± 0.221, p < 0.001). Fat-to-muscle volume fraction directly correlated with muscle T (p = 0.046) and increased with increasing level of BCRL stage (p = 0.041). Adiposity quantified by MRI is elevated in the affected upper extremity of women with BCRL and may provide a surrogate marker of condition onset or severity. NCT02611557.
Abstract Summary: Doctors wanted to learn more about a common problem called lymphedema that can happen after breast cancer treatment. This problem causes swelling in the arms. They used a special machine called an MRI to look at the fat and muscle in the arms of women who had this swelling and women who didn't. They found that women with swelling had more fat compared to muscle in their swollen arm. They also noticed that the more severe the swelling, the more fat there was. This discovery could help doctors find out sooner if someone is getting lymphedema and how bad it is.
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