Dataset Information

Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials.

ABSTRACT:

Objective

The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected menopause-related quality of life (QOL) measures. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects on menopause-related QOL relative to control in women with VMS.

Methods

We pooled individual-level data from 1,005 peri- and postmenopausal women with 14 or more VMS/week across the four RCTs. Interventions included escitalopram 10 to 20 mg/d; yoga/aerobic exercise; 1.8 g/d omega-3-fatty acids; oral 17-beta-estradiol 0.5 mg/d; venlafaxine XR 75 mg/d; and cognitive behavioral therapy for insomnia (CBT-I). Outcomes measures were the Menopause-specific Quality of Life scale and its subscales.

Results

Significant improvements in total Menopause-specific Quality of Life from baseline were observed with estradiol, escitalopram, CBT-I, and yoga, with mean decreases of 0.3 to 0.5 points relative to control. The largest improvement in the vasomotor subscale was observed with estradiol (-1.2 points), with more modest but significant effects seen with escitalopram, yoga, and CBT-I. Significant improvements in the psychosocial subscale were observed for escitalopram, venlafaxine, and CBT-I. For the physical subscale, the greatest improvement was observed for CBT-I and exercise, whereas for the sexual subscale, the greatest improvement was observed for CBT-I, with yoga and estradiol demonstrating smaller effects.

Conclusions

These results suggest that for menopause-related QOL, women have a variety of treatment strategies to choose from and can select an approach based on most bothersome symptoms and individual preferences.

SUBMITTER: Diem SJ

PROVIDER: S-EPMC8034544 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Publications

Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials.

Diem Susan J SJ LaCroix Andrea Z AZ Reed Susan D SD Larson Joseph C JC Newton Katherine M KM Ensrud Kristine E KE Woods Nancy F NF Guthrie Katherine A KA

Menopause (New York, N.Y.) 20201001 10

<h4>Objective</h4>The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected menopause-related quality of life (QOL) measures. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects on menopause-related QOL relative to control in women with VMS.<h4>Methods</h4>We pooled in ...[more]

PMID: 32701665

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Project description:ObjectiveTo describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network tested these interventions in three randomized clinical trials.MethodsAn analysis of pooled individual-level data from three randomized clinical trials is presented. Participants were 899 perimenopausal and postmenopausal women with at least 14 bothersome vasomotor symptoms per week. Interventions included 10-20 mg escitalopram per day, nonaerobic yoga, aerobic exercise, 1.8 g per day omega-3 fatty acid supplementation, 0.5 mg low-dose oral 17-beta-estradiol (E2) per day, and 75 mg low-dose venlafaxine XR per day. The main outcome measures were changes from baseline in mean daily vasomotor symptom frequency and bother during 8-12 weeks of treatment. Linear regression models estimated differences in outcomes between each intervention and corresponding control group adjusted for baseline characteristics. Models included trial-specific intercepts, effects of the baseline outcome measure, and time.ResultsThe 8-week reduction in vasomotor symptom frequency from baseline relative to placebo was similar for escitalopram at -1.4 per day (95% confidence interval [CI] -2.7 to -0.2), low-dose E2 at -2.4 (95% CI -3.4 to -1.3), and venlafaxine at -1.8 (95% CI -2.8 to -0.8); vasomotor symptom bother reduction was minimal and did not vary across these three pharmacologic interventions (mean -0.2 to -0.3 relative to placebo). No effects on vasomotor symptom frequency or bother were seen with aerobic exercise, yoga, or omega-3 supplements.ConclusionThese analyses suggest that escitalopram, low-dose E2, and venlafaxine provide comparable, modest reductions in vasomotor symptom frequency and bother among women with moderate hot flushes.Clinical trial registrationClinicalTrials.gov, www.clinicaltrials.gov, NCT00894543 (MsFLASH 01), NCT01178892 (MsFLASH 02), and NCT01418209 (MsFLASH 03).

Project description:BackgroundFrailty is common in clinical practice, but trials rarely report on participant frailty. Consequently, clinicians and guideline-developers assume frailty is largely absent from trials and have questioned the relevance of trial findings to frail people. Therefore, we examined frailty in phase 3/4 industry-sponsored clinical trials of pharmacological interventions for three exemplar conditions: type 2 diabetes mellitus (T2DM), rheumatoid arthritis (RA), and chronic obstructive pulmonary disease (COPD).MethodsWe constructed a 40-item frailty index (FI) in 19 clinical trials (7 T2DM, 8 RA, 4 COPD, mean age 42-65 years) using individual-level participant data. Participants with a FI > 0.24 were considered 'frail'. Baseline disease severity was assessed using HbA1c for T2DM, Disease Activity Score-28 (DAS28) for RA, and % predicted FEV1 for COPD. Using generalised gamma regression, we modelled FI on age, sex, and disease severity. In negative binomial regression, we modelled serious adverse event rates on FI and combined results for each index condition in a random-effects meta-analysis.ResultsAll trials included frail participants: prevalence 7-21% in T2DM trials, 33-73% in RA trials, and 15-22% in COPD trials. The 99th centile of the FI ranged between 0.35 and 0.45. Female sex was associated with higher FI in all trials. Increased disease severity was associated with higher FI in RA and COPD, but not T2DM. Frailty was associated with age in T2DM and RA trials, but not in COPD. Across all trials, and after adjusting for age, sex, and disease severity, higher FI predicted increased risk of serious adverse events; the pooled incidence rate ratios (per 0.1-point increase in FI scale) were 1.46 (95% CI 1.21-1.75), 1.45 (1.13-1.87), and 1.99 (1.43-2.76) for T2DM, RA, and COPD, respectively.ConclusionThe upper limit of frailty in trials is lower than has been described in the general population. However, mild to moderate frailty was common, suggesting trial data may be harnessed to inform disease management in people living with frailty. Participants with higher FI experienced more serious adverse events, suggesting screening for frailty in trial participants would enable identification of those that merit closer monitoring. Frailty is identifiable and prevalent among middle-aged and older participants in phase 3/4 drug trials and has clinically important safety implications.

Project description:Background and aimsRisk stratification of sudden cardiac death after myocardial infarction and prevention by defibrillator rely on left ventricular ejection fraction (LVEF). Improved risk stratification across the whole LVEF range is required for decision-making on defibrillator implantation.MethodsThe analysis pooled 20 data sets with 140 204 post-myocardial infarction patients containing information on demographics, medical history, clinical characteristics, biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging. Separate analyses were performed in patients (i) carrying a primary prevention cardioverter-defibrillator with LVEF ≤ 35% [implantable cardioverter-defibrillator (ICD) patients], (ii) without cardioverter-defibrillator with LVEF ≤ 35% (non-ICD patients ≤ 35%), and (iii) without cardioverter-defibrillator with LVEF > 35% (non-ICD patients >35%). Primary outcome was sudden cardiac death or, in defibrillator carriers, appropriate defibrillator therapy. Using a competing risk framework and systematic internal-external cross-validation, a model using LVEF only, a multivariable flexible parametric survival model, and a multivariable random forest survival model were developed and externally validated. Predictive performance was assessed by random effect meta-analysis.ResultsThere were 1326 primary outcomes in 7543 ICD patients, 1193 in 25 058 non-ICD patients ≤35%, and 1567 in 107 603 non-ICD patients >35% during mean follow-up of 30.0, 46.5, and 57.6 months, respectively. In these three subgroups, LVEF poorly predicted sudden cardiac death (c-statistics between 0.50 and 0.56). Considering additional parameters did not improve calibration and discrimination, and model generalizability was poor.ConclusionsMore accurate risk stratification for sudden cardiac death and identification of low-risk individuals with severely reduced LVEF or of high-risk individuals with preserved LVEF was not feasible, neither using LVEF nor using other predictors.

Project description: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.

Project description:BackgroundIndividual patient data (IPD) meta-analysis of existing randomized controlled trials (RCTs) is a promising approach to achieving sufficient statistical power to identify sub-groups. We created a repository of IPD from multiple low back pain (LBP) RCTs to facilitate a study of treatment moderators. Due to sparse heterogeneous data, the repository needed to be robust and flexible to accommodate millions of data points prior to any subsequent analysis.MethodsWe systematically identified RCTs of therapist delivered intervention for inclusion to the repository. Some were obtained through project publicity. We requested both individual items and aggregate scores of all baseline characteristics and outcomes for all available time points. The repository is made up of a hybrid database: entity-attribute-value and relational database which is capable of storing sparse heterogeneous datasets. We developed a bespoke software program to extract, transform and upload the shared data.ResultsThere were 20 datasets with more than 3 million data points from 9328 participants. All trials collected covariates and outcomes data at baseline and follow-ups. The bespoke standardized repository is flexible to accommodate millions of data points without compromising data integrity. Data are easily retrieved for analysis using standard statistical programs.ConclusionsThe bespoke hybrid repository is complex to implement and to query but its flexibility in supporting datasets with varying sets of responses and outcomes with different data types is a worthy trade off. The large standardized LBP dataset is also an important resource useable by other LBP researchers.SignificanceA flexible adaptive database for pain studies that can easily be expanded for future researchers to map, transform and upload their data in a safe and secure environment. The data are standardized and harmonized which will facilitate future requests from other researchers for secondary analyses.

Project description:BackgroundMicrorandomized trials (MRTs) have emerged as the gold standard for the development and evaluation of multicomponent, adaptive mobile health (mHealth) interventions. However, not much is known about the state of participant engagement measurement in MRTs of mHealth interventions.ObjectiveIn this scoping review, we aimed to quantify the proportion of existing or planned MRTs of mHealth interventions to date that have assessed (or have planned to assess) engagement. In addition, for the trials that have explicitly assessed (or have planned to assess) engagement, we aimed to investigate how engagement has been operationalized and to identify the factors that have been studied as determinants of engagement in MRTs of mHealth interventions.MethodsWe conducted a broad search for MRTs of mHealth interventions in 5 databases and manually searched preprint servers and trial registries. Study characteristics of each included evidence source were extracted. We coded and categorized these data to identify how engagement has been operationalized and which determinants, moderators, and covariates have been assessed in existing MRTs.ResultsOur database and manual search yielded 22 eligible evidence sources. Most of these studies (14/22, 64%) were designed to evaluate the effects of intervention components. The median sample size of the included MRTs was 110.5. At least 1 explicit measure of engagement was included in 91% (20/22) of the included MRTs. We found that objective measures such as system usage data (16/20, 80%) and sensor data (7/20, 35%) are the most common methods of measuring engagement. All studies included at least 1 measure of the physical facet of engagement, but the affective and cognitive facets of engagement have largely been neglected (only measured by 1 study each). Most studies measured engagement with the mHealth intervention (Little e) and not with the health behavior of interest (Big E). Only 6 (30%) of the 20 studies that measured engagement assessed the determinants of engagement in MRTs of mHealth interventions; notification-related variables were the most common determinants of engagement assessed (4/6, 67% studies). Of the 6 studies, 3 (50%) examined the moderators of participant engagement-2 studies investigated time-related moderators exclusively, and 1 study planned to investigate a comprehensive set of physiological and psychosocial moderators in addition to time-related moderators.ConclusionsAlthough the measurement of participant engagement in MRTs of mHealth interventions is prevalent, there is a need for future trials to diversify the measurement of engagement. There is also a need for researchers to address the lack of attention to how engagement is determined and moderated. We hope that by mapping the state of engagement measurement in existing MRTs of mHealth interventions, this review will encourage researchers to pay more attention to these issues when planning for engagement measurement in future trials.

Dataset Information

Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials.

Objective

Methods

Results

Conclusions

Publications

Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials.

Similar Datasets

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