Effects of a laboratory-based aerobic exercise intervention on brain volume and cardiovascular health markers: protocol for a randomised clinical trial.

INTRODUCTION: Physical activity (PA) has beneficial effects on brain health and cardiovascular disease (CVD) risk. Yet, we know little about whether PA-induced changes to physiological mediators of CVD risk influence brain health and whether benefits to brain health may also explain PA-induced improvements to CVD risk. This study combines neurobiological and peripheral physiological methods in the context of a randomised clinical trial to better understand the links between exercise, brain health and CVD risk. METHODS AND ANALYSIS: In this 12-month trial, 130 healthy individuals between the ages of 26 and 58 will be randomly assigned to either: (1) moderate-intensity aerobic PA for 150 min/week or (2) a health information control group. Cardiovascular, neuroimaging and PA measurements will occur for both groups before and after the intervention. Primary outcomes include changes in (1) brain structural areas (ie, hippocampal volume); (2) systolic blood pressure (SBP) responses to functional MRI cognitive stressor tasks and (3) heart rate variability. The main secondary outcomes include changes in (1) brain activity, resting state connectivity, cortical thickness and cortical volume; (2) daily life SBP stress reactivity; (3) negative and positive affect; (4) baroreflex sensitivity; (5) pulse wave velocity; (6) endothelial function and (7) daily life positive and negative affect. Our results are expected to have both mechanistic and public health implications regarding brain-body interactions in the context of cardiovascular health. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of Pittsburgh Institutional Review Board (IRB ID: 19020218). This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. TRIAL REGISTRATION NUMBER: NCT03841669.

Bias-corrected and doubly robust inference for the three-level longitudinal cluster-randomized trials with missing continuous outcomes and small number of clusters: Simulation study and application to a study for adults with serious mental illnesses.

Longitudinal cluster-randomized designs have been popular tools for comparative effective research in clinical trials. The methodologies for the three-level hierarchical design with longitudinal outcomes need to be better understood under more pragmatic settings; that is, with a small number of clusters, heterogeneous cluster sizes, and missing outcomes. Generalized estimating equations (GEEs) have been frequently used when the distribution of data and the correlation model are unknown. Standard GEEs lead to bias and an inflated type I error rate due to the small number of available clinics and non-completely random missing data in longitudinal outcomes. We evaluate the performance of inverse probability weighted (IPW) estimating equations, with and without augmentation, for two types of missing data in continuous outcomes and individual-level treatment allocation mechanisms combined with two bias-corrected variance estimators. Our intensive simulation results suggest that the proposed augmented IPW method with bias-corrected variance estimation successfully prevents the inflation of false positive findings and improves efficiency when the number of clinics is small, with moderate to severe missing outcomes. Our findings are expected to aid researchers in choosing appropriate analysis methods for three-level longitudinal cluster-randomized designs. The proposed approaches were applied to analyze data from a longitudinal cluster-randomized clinical trial involving adults with serious mental illnesses.

IDENTIFICATION OF IMMUNE RESPONSE COMBINATIONS ASSOCIATED WITH HETEROGENEOUS INFECTION RISK IN THE IMMUNE CORRELATES ANALYSIS OF HIV VACCINE STUDIES.

In HIV vaccine/prevention research, probing into the vaccine-induced immune responses that can help predict the risk of HIV infection provides valuable information for the development of vaccine regimens. Previous correlate analysis of the Thai vaccine trial aided the discovery of interesting immune correlates related to the risk of developing an HIV infection. The present study aimed to identify the combinations of immune responses associated with the heterogeneous infection risk. We explored a "change-plane" via combination of a subset of immune responses that could help separate vaccine recipients into two heterogeneous subgroups in terms of the association between immune responses and the risk of developing infection. Additionally, we developed a new variable selection algorithm through a penalized likelihood approach to investigate a parsimonious marker combination for the change-plane. The resulting marker combinations can serve as candidate correlates of protection and can be used for predicting the protective effect of the vaccine against HIV infection. The application of the proposed statistical approach to the Thai trial has been presented, wherein the marker combinations were explored among several immune responses and antigens.

The relationship between fat mass and obesity associated gene polymorphism rs9939609 and resting cerebral blood flow in a midlife sample with overweight and obesity.

Background: The single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity associated fat mass and obesity associated gene (FTO) gene has been linked with increased BMI in adults. Higher BMI has been associated with poor brain health and may exert deleterious effects on neurocognitive health through cerebral hypoperfusion. However, it is unclear if there is a relationship between the FTO genotype and cerebral perfusion, or whether FTO genotype moderates the effects of weight loss on cerebral perfusion. Using data from a randomized controlled behavioral weight loss trial in adults with overweight and obesity, we tested (1) whether carriers of the A allele for FTO rs9939609 demonstrate different patterns of resting cerebral blood flow (rCBF) compared to T carriers, and (2) whether the FTO genotype moderates the effects of weight loss on rCBF. We hypothesized that carriers of the A allele would exhibit lower resting CBF in frontal brain areas compared to T/T homozygotes at baseline, and that intervention-induced weight loss may partially remediate these differences. Methods and results: One hundred and five adults (75.2% female, mean age 44.9 years) with overweight or obesity were included in the analyses. These participants represent a subsample of participants in a larger randomized controlled trial (NCT01500356). A resting pseudo-continuous arterial spin labeling (pCASL) scan was acquired to examine rCBF. Age, sex, and BMI were included as covariates. At baseline, A carriers had greater rCBF in a diffuse cluster extending into the brainstem, motor cortex, and occipital lobe, but lower perfusion in the temporal lobe. We found no evidence that FTO moderated the effect of the intervention group assignment on rCBF changes. Conclusion: Overall, these results indicate that (a) individual variation in rCBF within a sample with overweight and obesity may be attributed to a common FTO variant, but (b) a weight loss intervention is effective at increasing rCBF, regardless of FTO genotype.

Aerobic exercise improves episodic memory in late adulthood: a systematic review and meta-analysis.

Background: Aerobic exercise remains one of the most promising approaches for enhancing cognitive function in late adulthood, yet its potential positive effects on episodic memory remain poorly understood and a matter of intense debate. Prior meta-analyses have reported minimal improvements in episodic memory following aerobic exercise but have been limited by restrictive inclusion criteria and infrequent examination of exercise parameters. Methods: We conducted a meta-analysis of randomized controlled trials to determine if aerobic exercise influences episodic memory in late adulthood (M = 70.82 years) and examine possible moderators. Thirty-six studies met inclusion criteria, representing data from 2750 participants. Results: Here we show that aerobic exercise interventions are effective at improving episodic memory (Hedges'g = 0.28; p = 0.002). Subgroup analyses revealed a moderating effect of age (p = 0.027), with a significant effect for studies with a mean age between 55-68 but not 69-85. Mixed-effects analyses demonstrated a positive effect on episodic memory among studies with a high percentage of females (65-100%), participants with normal cognition, studies reporting intensity, studies with a no-contact or nonaerobic physical activity control group, and studies prescribing >3900 total minutes of activity (range 540-8190 min). Conclusions: Aerobic exercise positively influences episodic memory among adults ≥55 years without dementia, with larger effects observed among various sample and intervention characteristics-the clearest moderator being age. These results could have far-reaching clinical and public health relevance, highlighting aerobic exercise as an accessible, non-pharmaceutical intervention to improve episodic memory in late adulthood.

Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity.

PURPOSE: Increased prevalence of cytotoxic T lymphocytes (CTL) in the tumor microenvironment (TME) predicts positive outcomes in patients with epithelial ovarian cancer (EOC), whereas the regulatory T cells (Treg) predict poor outcomes. Guided by the synergistic activity of TLR3 ligands, IFNα, and COX-2 blockers in selectively enhancing CTL-attractants but suppressing Treg-attractants, we tested a novel intraperitoneal chemoimmunotherapy combination (CITC), to assess its tolerability and TME-modulatory impact in patients with recurrent EOC. PATIENTS AND METHODS: Twelve patients were enrolled in phase I portion of the trial NCT02432378, and treated with intraperitoneal cisplatin, intraperitoneal rintatolimod (dsRNA, TLR3 ligand), and oral celecoxib (COX-2 blocker). Patients in cohorts 2, 3, and 4 also received intraperitoneal IFNα at 2, 6, and 18 million units (MU), respectively. Primary objectives were to evaluate safety, identify phase 2 recommended dose (P2RD), and characterize changes in the immune TME. Peritoneal resident cells and intraperitoneal wash fluid were profiled via NanoString and Meso Scale Discovery (MSD) multiplex assay, respectively. RESULTS: The P2RD of IFNα was 6 MU. Median progression-free survival and overall survival were 8.4 and 30 months, respectively. Longitudinal sampling of the peritoneal cavity via intraperitoneal washes demonstrated local upregulation of IFN-stimulated genes (ISG), including CTL-attracting chemokines (CXCL-9, -10, -11), MHC I/II, perforin, and granzymes. These changes were present 2 days after chemokine modulation and subsided within 1 week. CONCLUSIONS: The chemokine-modulating intraperitoneal-CITC is safe, tolerable, and associated with ISG changes that favor CTL chemoattraction and function. This combination (plus DC vaccine) will be tested in a phase II trial. See related commentary by Aranda et al., p. 1993.

Cardiorespiratory fitness levels and body mass index of pre-adolescent children and older adults during the COVID-19 pandemic.

Introduction: The social and behavioral effects of the COVID-19 pandemic have impacted the health and physiology of most people, including those never diagnosed with COVID-19. While the impact of the pandemic has been felt across the lifespan, its effects on cardiorespiratory fitness (commonly considered a reflection of total body health) of older adults and children may be particularly profound due to social distancing and stay-at-home advisories, as well as the closure of sport facilities and non-essential businesses. The objective of this investigation was to leverage baseline data from two ongoing clinical trials to determine if cardiorespiratory fitness and body mass index were different during COVID-19 relative to before COVID-19 in older adults and children. Methods: Healthy older individuals (N = 593; 65-80 years) and 200 typically developing children (8-10 years) completed a graded maximal exercise test and had their height and weight measured. Results: Results revealed that older adults and children tested during COVID-19 had significantly lower cardiorespiratory fitness levels than those tested before COVID-19 shutdowns (older adults: 30% lower; children: 53% lower; p's ≤ 0.001). In addition, older adults and children tested during COVID-19 had significantly higher BMI (older adults: 31.34 ± 0.57 kg/m2, p = 0.004; children: 19.27 ± 0.44 kg/m2, p = 0.05) than those tested before COVID-19 shutdowns (older adults: 29.51 ± 0.26 kg/m2, children: 18.13 ± 0.35 kg/m2). However, these differences in BMI did not remain significant when controlling for cardiorespiratory fitness. Discussion: Results from this investigation indicate that the COVID-19 pandemic, and behavior changes taken to reduce potential exposure, may have led to lower cardiorespiratory fitness levels in older adults and children, as well as higher body mass index. These findings provide relevant public health information as lower cardiorespiratory fitness levels and higher body mass indexes recorded during the pandemic could have far-reaching and protracted health consequences. Public health guidance is needed to encourage physical activity to maintain cardiorespiratory fitness and healthy body composition. Clinical trial registration: Older adults: https://clinicaltrials.gov/ct2/show/NCT02875301, identifier: NCT02875301; Children: https://clinicaltrials.gov/ct2/show/NCT03592238, identifier: NCT03592238.

Estimating the financial costs associated with a phase III, multi-site exercise intervention trial: Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE).

INTRODUCTION: Supervised exercise interventions are expensive and time intensive. However, there are financial costs to consider in addition to the intervention itself, namely: advertising and recruitment, outcome assessments, and other trial-related costs. OBJECTIVES: In this analysis, we examine the financial costs associated with the administration of Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) to quantify the costs associated with large exercise intervention trials and to provide future investigators with financial estimates if they wish to pursue studies of a similar design. METHODS: Cost per randomized participant were calculated in four areas: (1) advertising and recruitment, (2) outcome assessments, (3) delivery of the intervention, and (4) other trial-related expenses. Overall trial costs associated with data analysis, faculty salaries, and indirect costs were estimated as well. RESULTS: The total cost per randomized participant was estimated to be $16,494. Outcome assessments accounted for the highest proportion of per-participant (75%) and total trial (38%) costs. Neuroimaging assessments (MRI & PET) cost $8247 per randomized participant, accounting for two-thirds (67%) of outcome assessment costs and half (50%) of per-participant costs. CONCLUSION: Large clinical trials of exercise are expensive (~$21 million), particularly when administering several visits to assess study aims. Outcome assessments, specifically those involving neuroimaging, accounted for a significant proportion of total costs in this analysis. Future investigators must budget accordingly if they wish to conduct a comprehensive, multi-site exercise intervention trial that examines numerous physiological and psychological outcomes.

Stakeholder impact on the implementation of integrated care: Opportunities to consider for patient-centered outcomes research.

Nearly half of Americans live with chronic disease. Many have multiple chronic conditions that often present as a combination of physical and mental health conditions. Aligning stakeholder-driven, patient-centered outcomes research with population health strategies such as innovative ways to deliver care management can reduce the burden of multiple chronic conditions. In addition, successfully creating meaningful, inclusive research requires actively engaging stakeholders throughout the lifecycle of a study. This study integrates stakeholder engagement, using a large health plan in western Pennsylvania, to conduct a randomized controlled trial. Three care management strategies, High-Touch, High-Tech, and Usual Care, are compared for effectiveness among members with multiple chronic conditions. Care strategies are delivered via the Community Team, a multidisciplinary community-based team, offering in-person (High-Touch) and digital (High-Tech) care management in 14 counties across Pennsylvania. Participants are followed for 12months, with repeated measurements of self-reported health status and activation in care, while tracking administrative measurements of primary and specialty health service utilization. Quality of life, care satisfaction, engagement in care, and service utilization will be compared using generalized mixed models. Additionally, semi-structured interviews are conducted for both participants and care managers over the course of the study to evaluate feasibility. This manuscript presents implementation strategies, while noting that the implementation of patient-centered outcomes research in a real-world setting requires rapid evaluation, redesign of workflow, and tailored approaches for success.

Exercise interventions preserve hippocampal volume: A meta-analysis.

Hippocampal volume is a marker of brain health and is reduced with aging and neurological disease. Exercise may be effective at increasing and preserving hippocampal volume, potentially serving as a treatment for conditions associated with hippocampal atrophy (e.g., dementia). This meta-analysis aimed to identify whether exercise training has a positive effect on hippocampal volume and how population characteristics and exercise parameters moderate this effect. Studies met the following criteria: (a) controlled trials; (b) interventions of physical exercise; (c) included at least one time-point of hippocampal volume data before the intervention and one after; (d) assessed hippocampal volume using either manual or automated segmentation algorithms. Animal studies, voxel-based morphometry analyses, and multi-modal interventions (e.g., cognitive training or meditation) were excluded. The primary analysis in n = 23 interventions from 22 published studies revealed a significant positive effect of exercise on total hippocampal volume. The overall effect was significant in older samples (65 years of age or older) and in interventions that lasted over 24 weeks and had less than 150 min per week of exercise. These findings suggest that moderate amounts of exercise for interventions greater than 6 months have a positive effect on hippocampal volume including in older populations vulnerable to hippocampal atrophy.

Changes in cerebral perfusion following a 12-month exercise and diet intervention.

Overweight and obesity may damage the cerebrovascular architecture, resulting in a significant reduction in cerebral blood flow. To date, there have been few randomized clinical trials (RCT) examining whether obesity-related reductions in cerebral blood flow could be modified by weight loss. Further, it is unknown whether the behavioral intervention strategy for weight loss (i.e., diet alone or diet combined with exercise) differentially influences cerebral blood flow in adults with overweight or obesity. The primary aim of this study was to determine whether a 12-month RCT of exercise and diet increases cerebral blood flow in 125 midlife (Mean age ± SD = 44.63 ± 8.36 years) adults with overweight and obesity. Further, we evaluated whether weight loss via diet combined with aerobic exercise has an added effect on changes in cerebral blood flow compared to weight loss via diet alone and whether there were regionally specific effects of the type of behavioral intervention on cerebral blood flow patterns. Consistent with our predictions, a 12-month diet and exercise program resulting in 10% weight loss increased cerebral blood flow. These effects were widespread and extended throughout frontal, parietal, and subcortical regions. Further, there was some regional specificity of effects for both diet-only and diet combined with exercise. Our results demonstrate that weight-related reductions in cerebral blood flow can be modified by 10% weight loss over the course of 12 months and that interventions involving exercise exposure may provide unique effects on cerebral blood flow compared to interventions involving only diet.

Promoting collaborative psychiatric care decision-making in community mental health centers: Insights from a patient-centered comparative effectiveness trial.

OBJECTIVE: Mental health service-users face important medication decisions; yet not all are active participants in the decision-making process. Little is known about which technology-supported interventions might effectively promote collaborative decision-making in psychiatric care. We compared the effectiveness of two technology-supported collaborative care decision-making approaches. METHOD: We used a cluster-randomized design with a mixed-methods approach. Participants were Medicaid-enrolled adults receiving psychiatric care in participating community mental health centers. Measurement-based care used computerized systematic symptom and medication screenings to inform provider decision-making. Person-centered care supported participants in completing computerized Health Reports and preparing to work with providers on collaborative decision-making about psychiatric care. Primary study outcomes included the patient experience of medication management and shared decision-making during psychiatric care. Analyses examined the impact of both approaches and explored moderating variables. We used qualitative methods to understand participation and implementation experiences. RESULTS: Across 14 sites 2,363 participants enrolled (1,162 in measurement-based care, 1,201 in person-centered care). We observed statistically significant improvements in patient experience of medication management scores for both study arms; however, the clinical significance of this change was minor. We found no significant changes for shared decision-making. Qualitative interviews revealed a range of factors associated usefulness of intervention assessment, provider-service-user communication, and site-level logistics. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: We observed modest positive findings related to our patient-centered outcomes. We identified important implementation facilitators and barriers that can inform the implementation of future comparative effectiveness patient-centered research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The IGNITE trial: Participant recruitment lessons prior to SARS-CoV-2.

Full and diverse participant enrollment is critical to the success and generalizability of all large-scale Phase III trials. Recruitment of sufficient participants is among the most significant challenges for many studies. The novel SARS-CoV-2 coronavirus pandemic has further changed and challenged the landscape for clinical trial execution, including screening and randomization. The Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) study has been designed as the most comprehensive test of aerobic exercise effects on cognition and brain health. Here we assess recruitment into IGNITE prior to the increased infection rates in the United States, and examine new challenges and opportunities for recruitment with a goal of informing the remaining required recruitment as infection containment procedures are lifted. The results may assist the design and implementation of recruitment for future exercise studies, and outline opportunities for study design that are flexible in the face of emerging threats.

The Effects of a 12-Month Weight Loss Intervention on Cognitive Outcomes in Adults with Overweight and Obesity.

Obesity is associated with poorer executive functioning and reward sensitivity. Yet, we know very little about whether weight loss through diet and/or increased exercise engagement improves cognitive function. This study evaluated whether weight loss following a dietary and exercise intervention was associated with improved cognitive performance. We enrolled 125 middle-aged adults with overweight and obesity (98 female) into a 12-month behavioral weight loss intervention. Participants were assigned to one of three groups: energy-restricted diet alone, an energy-restricted diet plus 150 min of moderate intensity exercise per week or an energy restricted diet plus 250 min of exercise per week. All participants completed tests measuring executive functioning and/or reward sensitivity, including the Iowa Gambling Task (IGT). Following the intervention, weight significantly decreased in all groups. A MANCOVA controlling for age, sex and race revealed a significant multivariate effect of group on cognitive changes. Post-hoc ANCOVAs revealed a Group x Time interaction only on IGT reward sensitivity, such that the high exercise group improved their performance relative to the other two intervention groups. Post-hoc ANCOVAs also revealed a main effect of Time, independent of intervention group, on IGT net payoff score. Changes in weight were not associated with other changes in cognitive performance. Engaging in a high amount of exercise improved reward sensitivity above and beyond weight loss alone. This suggests that there is additional benefit to adding exercise into behavioral weight loss regimens on executive functioning, even without additional benefit to weight loss.

Feasibility of implementing mobile technology-delivered mental health treatment in routine adult sickle cell disease care.

Sickle cell disease (SCD) is a severe hemoglobinopathy characterized by acute and chronic pain. Sufferers of the disease, most of whom are underrepresented minorities, are at increased risk for mental health disorders. The purpose of this study is to test the acceptability and implementation of a computerized cognitive behavioral therapy (cCBT) intervention, Beating the Blues, to improve depression, anxiety, and pain in patients with SCD. Adults with SCD and significant symptoms of depression (Patient Health Questionnaire [PHQ-9] score ≥ 10) or anxiety (Generalized Anxiety Disorder Scale [GAD-7] score ≥ 10) were eligible to participate and be randomized to either receive eight sessions of cCBT with care coach support or treatment as usual. Participants reported daily pain and mood symptoms using a mobile diary app. Depression, anxiety, and pain symptoms were assessed at 1, 3, and 6 months. Thirty patients were enrolled: 18 to cCBT, and 12 to control. The cCBT intervention was feasible to implement in clinical settings and acceptable to participants. Patients in the cCBT arm reported a marginally greater decrease in depression at 6 months (-3.82, SE = 1.30) than those in the control group (-0.50, SE = 1.60; p = .06). There were no significant effects of treatment on anxiety; however, cCBT was associated with improved daily pain reported via a mobile diary app (p = .014). cCBT, delivered via mobile device, is a feasible strategy to provide mental health care to adults living with SCD. cCBT was acceptable to the target population; was able to be implemented in real-world, nonideal conditions; and has the potential to improve patient-reported outcomes.

Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE): Protocol.

Despite the ubiquity of normal age-related cognitive decline there is an absence of effective approaches for improving neurocognitive health. Fortunately, moderate intensity exercise is a promising method for improving brain and cognitive health in late life, but its effectiveness remains a matter of skepticism and debate because of the absence of large, comprehensive, Phase III clinical trials. Here we describe the protocol for such a randomized clinical trial called IGNITE (Investigating Gains in Neurocognition in an Intervention Trial of Exercise), a study capable of more definitively addressing whether exercise influences cognitive and brain health in cognitively normal older adults. We are conducting a 12-month, multi-site, randomized dose-response exercise trial in 639 cognitively normal adults between 65 and 80 years of age. Participants are randomized to (1) a moderate intensity aerobic exercise condition of 150 min/week (N = 213), (2) a moderate intensity aerobic exercise condition at 225 min/week (N = 213), or (3) a light intensity stretching-and-toning control condition for 150 min/week (N = 213). Participants are engaging in 3 days/week of supervised exercise and two more days per week of unsupervised exercise for 12 months. A comprehensive cognitive battery, blood biomarkers and battery of psychosocial questionnaires is assessed at baseline, 6 and 12-months. In addition, brain magnetic resonance imaging, physiological biomarkers, cardiorespiratory fitness, physical function, and positron emission tomography of amyloid deposition are assessed at baseline and at the 12-month follow-up. The results from this trial could transform scientific-based policy and health care recommendations for approaches to improve cognitive function in cognitively normal older adults.

Weight-Loss Outcomes from a Pilot Study of African Dance in Older African Americans.

OBJECTIVE: Obesity is a risk factor for both cognitive and physical impairment in late adulthood. Though the rates of obesity are high in many groups, older African Americans are disproportionately affected. A randomized pilot intervention of African Dance was conducted with 28 African American older adults with obesity (mean age = 68.4 ± 5.1 years; mean BMI = 33.4 ± 6.2). The goal of the study was to evaluate the physiological outcomes of a culturally sensitive exercise intervention and specifically changes in weight. METHODS: Participants were randomly assigned to an African Dance (experimental) or Culture Education (control) group. They attended their assigned class for 1 hour per session, 3 days per week, for 6 months. RESULTS: There was a significant group × time interaction on weight (P  = 0.005) such that the African Dance group lost weight (mean = 4.0 ± 6.0 lb) while the Culture Education group gained weight (mean = 2.6 ± 3.9 lb). CONCLUSIONS: These results suggest that a culturally sensitive form of physical activity, African Dance, may be effective for promoting weight loss in a population at increased risk for obesity and cognitive decline.

Evaluation of biomarkers for treatment selection using individual participant data from multiple clinical trials.

Biomarkers that predict treatment effects may be used to guide treatment decisions, thus improving patient outcomes. A meta-analysis of individual participant data (IPD) is potentially more powerful than a single-study data analysis in evaluating markers for treatment selection. Our study was motivated by the IPD that were collected from 2 randomized controlled trials of hypertension and preeclampsia among pregnant women to evaluate the effect of labor induction over expectant management of the pregnancy in preventing progression to severe maternal disease. The existing literature on statistical methods for biomarker evaluation in IPD meta-analysis have evaluated a marker's performance in terms of its ability to predict risk of disease outcome, which do not directly apply to the treatment selection problem. In this study, we propose a statistical framework for evaluating a marker for treatment selection given IPD from a small number of individual clinical trials. We derive marker-based treatment rules by minimizing the average expected outcome across studies. The application of the proposed methods to the IPD from 2 studies in women with hypertension in pregnancy is presented.

A Payer-Guided Approach To Widespread Diffusion Of Behavioral Health Homes In Real-World Settings.

People with serious mental illness experience decreased life expectancy related to co-occurring medical conditions. A nonprofit behavioral health managed care organization implemented an innovative behavioral health home, in partnership with community mental health providers, to build a culture of wellness among all staff members, with a focus on prevention and holistic (that is, behavioral, social, and physical) health. The behavioral health home added one of two distinct care approaches, one patient driven and the other provider driven. The innovative approaches were implemented at eleven community mental health providers: Six delivered patient-driven care, and five delivered provider-driven care. We studied outcomes in the period October 2013-January 2016. Multiple diffusion strategies were utilized to encourage uptake. Our results revealed that both approaches significantly increased patient activation in care (more quickly in provider-supported care), engagement in primary and specialty care, and perceived mental health status. The success of this behavioral health home in improving important outcomes and the use of novel diffusion strategies led to its dissemination to forty-three additional providers across Pennsylvania.