Perturbations in growth trajectory due to early diet affect age-related deterioration in performance

Fluctuations in early developmental conditions can cause changes in growth trajectories that subsequently affect the adult phenotype. Here, we investigated whether compensatory growth has long-term consequences for patterns of senescence. Using three-spined sticklebacks (Gasterosteus aculeatus), we show that a brief period of dietary manipulation in early life affected skeletal growth rate not only during the manipulation itself, but also during a subsequent compensatory phase when fish caught up in size with controls. However, this growth acceleration influenced swimming endurance and its decline over the course of the breeding season, with a faster decline in fish that had undergone faster growth compensation. Similarly, accelerated growth led to a more pronounced reduction in the breeding period (as indicated by the duration of sexual ornamentation) over the following two breeding seasons, suggesting faster reproductive senescence. Parallel experiments showed a heightened effect of accelerated growth on these age-related declines in performance if the fish were under greater time stress to complete their compensation prior to the breeding season. Compensatory growth led to a reduction in median life span of 12% compared to steadily growing controls. While life span was independent of the eventual adult size attained, it was negatively correlated with the age-related decline in swimming endurance and sexual ornamentation. These results, complementary to those found when growth trajectories were altered by temperature rather than dietary manipulations, show that the costs of accelerated growth can last well beyond the time over which growth rates differ and are affected by the time available until an approaching life-history event such as reproduction

The US President’s Malaria Initiative and under-five child mortality in Sub-Saharan Africa: A difference-in-differences analysis

Background Despite substantial financial contributions by the United States President’s Malaria Initiative (PMI) since 2006, no studies have carefully assessed how this program may have affected important population-level health outcomes. We utilized multiple publicly available data sources to evaluate the association between introduction of PMI and child mortality rates in sub-Saharan Africa (SSA). Methods and findings We used difference-in-differences analyses to compare trends in the primary outcome of under-5 mortality rates and secondary outcomes reflecting population coverage of malaria interventions in 19 PMI-recipient and 13 non-recipient countries between 1995 and 2014. The analyses controlled for presence and intensity of other large funding sources, individual and household characteristics, and country and year fixed effects. PMI program implementation was associated with a significant reduction in the annual risk of under-5 child mortality (adjusted risk ratio [RR] 0.84, 95% CI 0.74–0.96). Each dollar of per-capita PMI expenditures in a country, a measure of PMI intensity, was also associated with a reduction in child mortality (RR 0.86, 95% CI 0.78–0.93). We estimated that the under-5 mortality rate in PMI countries was reduced from 28.9 to 24.3 per 1,000 personyears. Population coverage of insecticide-treated nets increased by 8.34 percentage points (95% CI 0.86–15.83) and coverage of indoor residual spraying increased by 6.63 percentage points (95% CI 0.79–12.47) after PMI implementation. Per-capita PMI spending was also associated with a modest increase in artemisinin-based combination therapy coverage (3.56 percentage point increase, 95% CI −0.07–7.19), though this association was only marginally significant (p = 0.054). Our results were robust to several sensitivity analyses. Because our study design leaves open the possibility of unmeasured confounding, we cannot definitively interpret these results as causal. Conclusions PMI may have significantly contributed to reducing the burden of malaria in SSA and reducing the number of child deaths in the region. Introduction of PMI was associated with increased coverage of malaria prevention technologies, which are important mechanisms through which child mortality can be reduced. To our knowledge, this study is the first to assess the association between PMI and all-cause child mortality in SSA with the use of appropriate comparison groups and adjustments for regional trends in child mortality

Cost-benefit analysis of alternative tax policies on sugar-sweetened beverages in Mexico

In 2014, Mexico implemented a tax on sugar-sweetened beverages (SSB) equivalent to one Mexican peso (MP) per liter to address the high obesity prevalence. This tax has effectively reduced SSB purchases and yielded healthcare savings; however, it remains unknown whether SSB taxes lead to net benefits at the societal level in Mexico. Moreover, public health experts recommend increasing the tax. The objective of this study is to estimate the net benefits of SSB taxes compared to a scenario of no tax in urban Mexico. Taxes include the one-MP tax and alternative higher taxes (two and three MP per SSB liter). Thus, we conducted a cost-benefit analysis from the perspective of the government, producers, and consumers for a simulated closed cohort of adults in a life-table model. We defined net benefits as the difference between economic benefits (the value of statistical life, healthcare savings, and tax revenue) and costs (consumer surplus and profit losses). We found that, at the societal level, all simulated taxes will eventually generate benefits that surpass costs within ten years. Overall net benefits can reach USD 7.1 billion and 15.3 billion for the one-MP and the three-MP tax, respectively. Hence, these benefits increased at a declining rate compared to taxes. The government and consumers will experience overall positive net benefits among society's members. Policymakers should consider time horizons and tradeoffs between health gains and economic outcomes across different society members

Oxidative status and fitness components in the Seychelles warbler

1. Oxidative damage, caused by reactive oxygen species during aerobic respiration, is thought to be an important mediator of life-history trade-offs. To mitigate oxidative damage, antioxidant defence mechanisms are deployed, often at the cost of resource allocation to other body functions. Both reduced resource allocation to body functions and direct oxidative damage may decrease individual fitness, through reducing survival and/or reproductive output. 2. The oxidative costs of reproduction have gained much attention recently, but few studies have investigated the long-term consequences of oxidative damage on survival and (future) reproductive output under natural conditions. 3. Using a wild population of the cooperatively breeding Seychelles warbler (Acrocephalus sechellensis), we tested the prediction that high levels of reactive oxygen species, or high antioxidant investments to avoid oxidative damage, have fitness consequences because they reduce survival and/or reproductive output. 4. We found that individuals with higher circulating non-enzymatic antioxidant capacity had a lower probability of surviving until the next year. However, neither current reproductive output, nor future reproductive output in the surviving individuals, was associated with circulating non-enzymatic antioxidant capacity or oxidative damage. 5. The negative relationship between antioxidant capacity and survival that we observed concurs with the findings of an extensive comparative study on birds, however the mechanisms underlying this association remain to be resolved

Recurrent Acute Decompensated Heart Failure Admissions for Patients With Reduced Versus Preserved Ejection Fraction (from the Atherosclerosis Risk in Communities Study)

Hospitals are required to report all-cause 30-day readmissions for patients discharged with heart failure. Same-cause readmissions have received less attention but may differ for heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF). The ARIC study began abstracting medical records for cohort members hospitalized with acute decompensated heart failure (ADHF) in 2005. ADHF was validated by physician review, with HFrEF defined by ejection fraction <50%. Recurrent admissions for ADHF were analyzed within 30 days, 90 days, 6 months, and 1 year of the index hospitalization using repeat-measures Cox regression models. All recurrent ADHF admissions per patient were counted rather than the more typical analysis of only the first occurring readmission. From 2005 to 2014, 1,133 cohort members survived at least 1 hospitalization for ADHF and had ejection fraction recorded. Half were classified as HFpEF. Patients with HFpEF were more often women and had more co-morbidities. The overall ADHF readmission rate was greatest within 30 days of discharge but was higher for patients with HFrEF (115 vs 88 readmissions per 100 person-years). After adjustments for demographics, year of admission, and co-morbidities, there was a trend for higher ADHF readmissions with HFrEF, relative to HFpEF, at 30 days (hazard ratio [HR] 1.41, 95% confidence interval [CI] 0.92 to 2.18), 90 days (HR 1.39, 95% CI 1.05 to 1.85), 6 months (HR 1.47, 95% CI, 1.18 to 1.84), and 1 year (HR 1.42, 95% CI 1.18 to 1.70) of follow-up. In conclusion, patients with HFrEF have a greater burden of short- and long-term readmissions for recurrent ADHF

Evolution of the Corticotropin-releasing Hormone Signaling System and Its Role in Stress-induced Phenotypic Plasticity

Developing animals respond in variation in their habitats by altering their rules of development and/or their morphologies (i.e., they exhibit phenotypic plasticity). In vertebrates, one mechanism by which plasticity is expressed is through activation of the neuroendocrine system, which transduces environmental information into a physiological response. Recent findings of ours with amphibians and of others with mammals show that the primary vertebrate stress neuropeptide, corticotropin-releasing hormone (CRH), is essential for adaptive developmental responses to environmental stress. For instance, CRH-dependent mechanisms cause accelerated metamorphosis in response to pond-drying in some amphibian species, and intrauterine fetal stress syndromes in humans precipitate preterm birth. CRH may be a phylogenetically ancient developmental signaling molecule that allows developing organisms to escape deleterious changes in their larval/fetal habitat. The response to CRH is mediated by at least two different receptor subtypes and may also be modulated by a secreted binding protein.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73287/1/j.1749-6632.1999.tb07877.x.pd

Mind the Gap: Hospitalizations from Multiple Sources in a Longitudinal Study

Background Medicare claims and prospective studies with self-reported utilization are important sources of hospitalization data for epidemiologic and outcomes research. Objectives To assess the concordance of Medicare claims merged with interview-based surveillance data to determine factors associated with source completeness. Methods The Atherosclerosis Risk in Communities (ARIC) study recruited 15,792 cohort participants aged 45 to 64 years in the period 1987 to 1989 from four communities. Hospitalization records obtained through cohort report and hospital record abstraction were matched to Medicare inpatient records (MedPAR) from 2006 to 2011. Factors associated with concordance were assessed graphically and using multinomial logit regression. Results Among fee-for-service enrollees, MedPAR and ARIC hospitalizations matched approximately 67% of the time. For Medicare Advantage enrollees, completeness increased after initiation of hospital financial incentives in 2008 to submit shadow bills for Medicare Advantage enrollees. Concordance varied by geographic site, age, veteran status, proximity to death, study attrition, and whether hospitalizations were within ARIC catchment areas. Conclusions ARIC and MedPAR records had good concordance among fee-for-service enrollees, but many hospitalizations were available from only one source. MedPAR hospital records may be missing for veterans or observation stays. Maintaining study participation increases stay completeness, but new sources such as electronic health records may be more efficient than surveillance for mobile elderly populations

Predictors of Medication Adherence in the Elderly: The Role of Mental Health

The aging population routinely has comorbid conditions requiring complicated medication regimens, yet nonadherence can preclude optimal outcomes. This study explored the association of adherence in the elderly with demographic, socioeconomic, and disease burden measures. Data were from the fifth visit (2011-2013) for 6,538 participants in the Atherosclerosis Risk in Communities Study, conducted in four communities. The Morisky–Green–Levine Scale measured self-reported adherence. Forty percent of respondents indicated some nonadherence, primarily due to poor memory. Logit regression showed, surprisingly, that persons with low reading ability were more likely to report being adherent. Better self-reported physical or mental health both predicted better adherence, but the magnitude of the association was greater for mental than for physical health. Compared with persons with normal or severely impaired cognition, mild cognitive impairment was associated with lower adherence. Attention to mental health measures in clinical settings could provide opportunities for improving medication adherence

Antihypertensive adherence and outcomes among community-dwelling Medicare beneficiaries: the Atherosclerosis Risk in Communities Study

Rationale, aims, and objectives: Despite proven benefits for reducing incidence of major cardiac events, antihypertensive drug therapy remains underutilized in the United States. This analysis assesses antihypertensive drug adherence, utilization predictors, and associations between adherence and outcomes (a composite of cardiovascular events, Medicare inpatient payments, and inpatient days). Methods: The sample consisted of Atherosclerosis Risk in Communities Study cohort participants reporting hypertension without prevalent cardiovascular disease during 2006 to 2007 annual follow-up calls. Atherosclerosis Risk in Communities records were linked to Medicare claims through 2012. Antihypertensive medication adherence was measured as more than 80% proportion days covered by using Medicare Part D claims. Standard and hierarchical regression models were used to evaluate adjusted associations between person characteristics and adherence and between adherence and outcomes. Results: Among 1826 hypertensive participants with Part D coverage, 31.5% had no antihypertensive class with more than 80% proportion days covered in the 3 months preceding the report of hypertension in 2006 to 2007. After adjustment for confounders, positive predictors of use included female gender and diabetes; negative predictors were African-American race and current smoking. Adjusted association between receiving no therapy and a composite endpoint of cardiovascular outcomes through 2012 was not statistically significant (hazard ratio: 0.93; 95% confidence interval: 0.72, 1.22) nor was the adjusted association with Medicare inpatient days or payments (incremental difference at 48 months in payments: $1217; 95$2030, $4463). Conclusions: Despite having medical and prescription coverage, nearly a third of hypertensive participants were not adherent to antihypertensive drug therapy. Differences in clinical outcomes associated with nonadherence, though not statistically significant, were consistent with results from randomized trials. The approach provides a model framework for rigorous assessment of detailed data that are increasingly available through emerging sources