ACTRIIA-Fc rebalances activin/GDF versus BMP signaling in pulmonary hypertension.

Human genetics, biomarker, and animal studies implicate loss of function in bone morphogenetic protein (BMP) signaling and maladaptive transforming growth factor-ß (TGFß) signaling as drivers of pulmonary arterial hypertension (PAH). Although sharing common receptors and effectors with BMP/TGFß, the function of activin and growth and differentiation factor (GDF) ligands in PAH are less well defined. Increased expression of GDF8, GDF11, and activin A was detected in lung lesions from humans with PAH and experimental rodent models of pulmonary hypertension (PH). ACTRIIA-Fc, a potent GDF8/11 and activin ligand trap, was used to test the roles of these ligands in animal and cellular models of PH. By blocking GDF8/11- and activin-mediated SMAD2/3 activation in vascular cells, ACTRIIA-Fc attenuated proliferation of pulmonary arterial smooth muscle cells and pulmonary microvascular endothelial cells. In several experimental models of PH, prophylactic administration of ACTRIIA-Fc markedly improved hemodynamics, right ventricular (RV) hypertrophy, RV function, and arteriolar remodeling. When administered after the establishment of hemodynamically severe PH in a vasculoproliferative model, ACTRIIA-Fc was more effective than vasodilator in attenuating PH and arteriolar remodeling. Potent antiremodeling effects of ACTRIIA-Fc were associated with inhibition of SMAD2/3 activation and downstream transcriptional activity, inhibition of proliferation, and enhancement of apoptosis in the vascular wall. ACTRIIA-Fc reveals an unexpectedly prominent role of GDF8, GDF11, and activin as drivers of pulmonary vascular disease and represents a therapeutic strategy for restoring the balance between SMAD1/5/9 and SMAD2/3 signaling in PAH.

School-Based Health Centers to Advance Health Equity: A Community Guide Systematic Review.

CONTEXT: Children from low-income and racial or ethnic minority populations in the U.S. are less likely to have a conventional source of medical care and more likely to develop chronic health problems than are more-affluent and non-Hispanic white children. They are more often chronically stressed, tired, and hungry, and more likely to have impaired vision and hearing-obstacles to lifetime educational achievement and predictors of adult morbidity and premature mortality. If school-based health centers (SBHCs) can overcome educational obstacles and increase receipt of needed medical services in disadvantaged populations, they can advance health equity. EVIDENCE ACQUISITION: A systematic literature search was conducted for papers published through July 2014. Using Community Guide systematic review methods, reviewers identified, abstracted, and summarized available evidence of the effectiveness of SBHCs on educational and health-related outcomes. Analyses were conducted in 2014-2015. EVIDENCE SYNTHESIS: Most of the 46 studies included in the review evaluated onsite clinics serving urban, low-income, and racial or ethnic minority high school students. The presence and use of SBHCs were associated with improved educational (i.e., grade point average, grade promotion, suspension, and non-completion rates) and health-related outcomes (i.e., vaccination and other preventive services, asthma morbidity, emergency department use and hospital admissions, contraceptive use among females, prenatal care, birth weight, illegal substance use, and alcohol consumption). More services and more hours of availability were associated with greater reductions in emergency department overuse. CONCLUSIONS: Because SBHCs improve educational and health-related outcomes in disadvantaged students, they can be effective in advancing health equity.

Early Childhood Education to Promote Health Equity: A Community Guide Systematic Review.

CONTEXT: Children in low-income and racial and ethnic minority families often experience delays in development by 3 years of age and may benefit from center-based early childhood education. DESIGN: A meta-analysis on the effects of early childhood education by Kay and Pennucci best met Community Guide criteria and forms the basis of this review. RESULTS: There were increases in intervention compared with control children in standardized test scores (median = 0.29 SD) and high school graduation (median = 0.20 SD) and decreases in grade retention (median = 0.23 SD) and special education assignment (median = 0.28 SD). There were decreases in crime (median = 0.23 SD) and teen births (median = 0.46 SD) and increases in emotional self-regulation (median = 0.21 SD) and emotional development (median = 0.04 SD). All effects were favorable, but not all were statistically significant. Effects were also long-lasting. CONCLUSIONS: Because many programs are designed to increase enrollment for high-risk students and communities, they are likely to advance health equity.

Out-of-School-Time Academic Programs to Improve School Achievement: A Community Guide Health Equity Systematic Review.

CONTEXT: Low-income and minority status in the United States are associated with poor educational outcomes, which, in turn, reduce the long-term health benefits of education. OBJECTIVE: This systematic review assessed the extent to which out-of-school-time academic (OSTA) programs for at-risk students, most of whom are from low-income and racial/ethnic minority families, can improve academic achievement. Because most OSTA programs serve low-income and ethnic/racial minority students, programs may improve health equity. DESIGN: Methods of the Guide to Community Preventive Services were used. An existing systematic review assessing the effects of OSTA programs on academic outcomes (Lauer et al 2006; search period 1985-2003) was supplemented with a Community Guide update (search period 2003-2011). MAIN OUTCOME MEASURE: Standardized mean difference. RESULTS: Thirty-two studies from the existing review and 25 studies from the update were combined and stratified by program focus (ie, reading-focused, math-focused, general academic programs, and programs with minimal academic focus). Focused programs were more effective than general or minimal academic programs. Reading-focused programs were effective only for students in grades K-3. There was insufficient evidence to determine effectiveness on behavioral outcomes and longer-term academic outcomes. CONCLUSIONS: OSTA programs, particularly focused programs, are effective in increasing academic achievement for at-risk students. Ongoing school and social environments that support learning and development may be essential to ensure the longer-term benefits of OSTA programs.

Effects of mental health benefits legislation: a community guide systematic review.

CONTEXT: Health insurance benefits for mental health services typically have paid less than benefits for physical health services, resulting in potential underutilization or financial burden for people with mental health conditions. Mental health benefits legislation was introduced to improve financial protection (i.e., decrease financial burden) and to increase access to, and use of, mental health services. This systematic review was conducted to determine the effectiveness of mental health benefits legislation, including executive orders, in improving mental health. EVIDENCE ACQUISITION: Methods developed for the Guide to Community Preventive Services were used to identify, evaluate, and analyze available evidence. The evidence included studies published or reported from 1965 to March 2011 with at least one of the following outcomes: access to care, financial protection, appropriate utilization, quality of care, diagnosis of mental illness, morbidity and mortality, and quality of life. Analyses were conducted in 2012. EVIDENCE SYNTHESIS: Thirty eligible studies were identified in 37 papers. Implementation of mental health benefits legislation was associated with financial protection (decreased out-of-pocket costs) and appropriate utilization of services. Among studies examining the impact of legislation strength, most found larger positive effects for comprehensive parity legislation or policies than for less-comprehensive ones. Few studies assessed other mental health outcomes. CONCLUSIONS: Evidence indicates that mental health benefits legislation, particularly comprehensive parity legislation, is effective in improving financial protection and increasing appropriate utilization of mental health services for people with mental health conditions. Evidence was limited for other mental health outcomes.

Legislations and policies to expand mental health and substance abuse benefits in health insurance plans: a community guide systematic economic review.

BACKGROUND: Health insurance plans have historically limited the benefits for mental health and substance abuse (MH/SA) services compared to benefits for physical health services. In recent years, legislative and policy initiatives in the U.S. have been taken to expand MH/SA health insurance benefits and achieve parity with physical health benefits. The relevance of these legislations for international audiences is also explored, particularly for the European context. AIMS OF THE STUDY: This paper reviews the evidence of costs and economic benefits of legislative or policy interventions to expand MH/SA health insurance benefits in the U.S. The objectives are to assess the economic value of the interventions by comparing societal cost to societal benefits, and to determine impact on costs to insurance plans resulting from expansion of these benefits. METHODS: The search for economic evidence covered literature published from January 1950 to March 2011 and included evaluations of federal and state laws or rules that expanded MH/SA benefits as well as voluntary actions by large employers. Two economists screened and abstracted the economic evidence of MH/SA benefits legislation based on standard economic and actuarial concepts and methods. RESULTS: The economic review included 12 studies: eleven provided evidence on cost impact to health plans, and one estimated the effect on suicides. There was insufficient evidence to determine if the intervention was cost-effective or cost-saving. However, the evidence indicates that MH/SA benefits expansion did not lead to any substantial increase in costs to insurance plans, measured as a percentage of insurance premiums. DISCUSSION AND LIMITATIONS: This review is unable to determine the overall economic value of policies that expanded MH/SA insurance benefits due to lack of cost-effectiveness and cost-benefit studies, predominantly due to the lack of evaluations of morbidity and mortality outcomes. This may be remedied in time when long-term MH/SA patient-level data becomes available to researchers. A limitation of this review is that legislations considered here have been superseded by recent legislations that have stronger and broader impacts on MH/SA benefits within private and public insurance: Mental Health Parity and Addiction Equity Act of 2008 (MHPAEA) and the Patient Protection and Affordable Care Act of 2010 (ACA). IMPLICATIONS FOR FUTURE RESEARCH: Economic assessments over the long term such as cost per QALY saved and cost-benefit will be feasible as more data becomes available from plans that implemented recent expansions of MH/SA benefits. Results from these evaluations will allow a better estimate of the economic impact of the interventions from a societal perspective. Future research should also evaluate the more downstream effects on business decisions about labor, such as effects on hiring, retention, and the offer of health benefits as part of an employee compensation package. Finally, the economic effect of the far reaching ACA of 2010 on mental health and substance abuse prevalence and care is also a subject for future research.

Programs to increase high school completion: a community guide systematic health equity review.

CONTEXT: High school completion (HSC) is an established predictor of long-term morbidity and mortality. U.S. rates of HSC are substantially lower among students from low-income families and most racial/ethnic minority populations than students from high-income families and the non-Hispanic white population. This systematic review assesses the effectiveness of programs to increase HSC and the potential of these programs to improve lifelong health among at-risk students. EVIDENCE ACQUISITION: A search located a meta-analysis (search period 1985-2010/2011) on the effects of programs to increase HSC or General Educational Development (GED) diploma receipt; the meta-analysis was concordant with Community Guide definitions and methodologic standards. Programs were assessed separately for the general student population (152 studies) and students who were parents or pregnant (15 studies). A search for studies published between 2010 and August 2012 located ten more recent studies, which were assessed for consistency with the meta-analysis. Analyses were conducted in 2013. EVIDENCE SYNTHESIS: The review focused on the meta-analysis. Program effectiveness was measured as the increased rate of HSC (or GED receipt) by the intervention group compared with controls. All assessed program types were effective in increasing HSC in the general student population: vocational training, alternative schooling, social-emotional skills training, college-oriented programming, mentoring and counseling, supplemental academic services, school and class restructuring, multiservice packages, attendance monitoring and contingencies, community service, and case management. For students who had children or were pregnant, attendance monitoring and multiservice packages were effective. Ten studies published after the search period for the meta-analysis were consistent with its findings. CONCLUSIONS: There is strong evidence that a variety of HSC programs can improve high school or GED completion rates. Because many programs are targeted to high-risk students and communities, they are likely to advance health equity.