A Causal Mediation Analysis for Investigating the Effect of a Randomized Cash-Transfer Program in Nicaragua.

Mediation analysis can be applied to data from randomized trials of health and social interventions to draw causal inference concerning their mechanisms. We used data from a cluster-randomized trial in Nicaragua, fielded between 2000 and 2002, to investigate whether the impact of providing access to a conditional cash-transfer program on child nutritional outcomes was mediated by child health check-ups and household dietary diversity. In a sample of 443 children 6-35 months old, we estimated the controlled direct (CDE) effect of random assignment on measured height-for-age z scores had we intervened so that all children received a health check-up and had the same level of household dietary diversity, using inverse-probability weighted marginal structural models to account for mediator-outcome confounding. Sensitivity analyses corrected the CDE for potential nondifferential error in the measurement of dietary diversity. Treatment assignment increased height-for-age z score by 0.37 (95% CI: 0.05, 0.69) standard deviations. The CDE was 0.20 (95% CI: -0.17, 0.57) standard deviations, suggesting nearly one-half of the program's impact on child nutrition would be eliminated had we intervened on these factors, although estimates were relatively imprecise. This study provides an illustration of how causal mediation analysis can be applied to examine the mechanisms of multifaceted interventions.

Health care services use, stillbirth, and neonatal and infant survival following implementation of the Maternal Health Voucher Scheme in Bangladesh: A difference-in-differences analysis of Bangladesh Demographic and Health Survey data, 2000 to 2016.

BACKGROUND: Starting in 2006 to 2007, the Government of Bangladesh implemented the Maternal Health Voucher Scheme (MHVS). This program provides pregnant women with vouchers that can be exchanged for health services from eligible public and private sector providers. In this study, we examined whether access to the MHVS was associated with maternal health services utilization, stillbirth, and neonatal and infant mortality. METHODS AND FINDINGS: We used information on pregnancies and live births between 2000 to 2016 reported by women 15 to 49 years of age surveyed as part of the Bangladesh Demographic and Health Surveys. Our analytic sample included 23,275 pregnancies lasting at least 7 months for analyses of stillbirth and between 15,125 and 21,668 live births for analyses of health services use, neonatal, and infant mortality. With respect to live births occurring prior to the introduction of the MHVS, 31.3%, 14.1%, and 18.0% of women, respectively, reported receiving at least 3 antenatal care visits, delivering in a health institution, and having a skilled birth attendant at delivery. Rates of neonatal and infant mortality during this period were 40 and 63 per 1,000 live births, respectively, and there were 32 stillbirths per 1,000 pregnancies lasting at least 7 months. We applied a difference-in-differences design to estimate the effect of providing subdistrict-level access to the MHVS program, with inverse probability of treatment weights to address selection into the program. The introduction of the MHVS program was associated with a lagged improvement in the probability of delivering in a health facility, one of the primary targets of the program, although associations with other health services were less evident. After 6 years of access to the MHVS, the probabilities of reporting at least 3 antenatal care visits, delivering in a health facility, and having a skilled birth attendant present increased by 3.0 [95% confidence interval (95% CI) = -4.8, 10.7], 6.5 (95% CI = -0.6, 13.6), and 5.8 (95% CI = -1.8, 13.3) percentage points, respectively. We did not observe evidence consistent with the program improving health outcomes, with probabilities of stillbirth, neonatal mortality, and infant mortality decreasing by 0.7 (95% CI = -1.3, 2.6), 0.8 (95% CI = -1.7, 3.4), and 1.3 (95% CI = -2.5, 5.1) percentage points, respectively, after 6 years of access to the MHVS. The sample size was insufficient to detect smaller associations with adequate precision. Additionally, we cannot rule out the possibility of measurement error, although it was likely nondifferential by treatment group, or unmeasured confounding by concomitant interventions that were implemented differentially in treated and control areas. CONCLUSIONS: In this study, we found that the introduction of the MHVS was positively associated with the probability of delivering in a health facility, but despite a longer period of follow-up than most extant evaluations, we did not observe attendant reductions in stillbirth, neonatal mortality, or infant mortality. Further work and engagement with stakeholders is needed to assess if the MHVS has affected the quality of care and health inequalities and whether the design and eligibility of the program should be modified to improve maternal and neonatal health outcomes.

Impacts of universal childcare on early behavioral development: evidence from a birth cohort in Québec, Canada.

PURPOSE: To examine associations between universal pre-school childcare use and later behaviors among children at age 6 years. METHODS: Using annual follow-up data of a birth cohort (N=1450), we estimated differences in behavioral scores by primary childcare arrangement between ages 2-5 years - universal subsidized childcare program (CPE care), non-CPE childcare, and parental or family care (no regular care) - using propensity score inverse probability weights. RESULTS: Teachers reported slightly higher levels of hyperactivity (0.73, 95% CI: 0.32, 1.1) and indirect aggression (0.58, 95%CI: 0.24, 0.91) among children who attended a CPE than children in non-CPE care. However, these patterns were not observed from either maternal or paternal reports. Similarly, teachers' assessments of slightly higher physical aggression (0.50, 95% CI: 0.11, 0.88) and opposition (0.63, 95% CI: 0.21, 1.05) scores among children in CPE care than children who did not have a regular childcare were not observed in parental assessments. Behavioral scores by childcare arrangement were similar between girls and boys and across family socioeconomic position. CONCLUSIONS: Universal pre-school childcare does not appear to have substantial impacts on child behaviors at early school age, however teachers rated externalizing behaviors to be slightly higher among children who attended universal childcare.

Did the Great Recession affect mortality rates in the metropolitan United States? Effects on mortality by age, gender and cause of death.

OBJECTIVES: Mortality rates generally decline during economic recessions in high-income countries, however gaps remain in our understanding of the underlying mechanisms. This study estimates the impacts of increases in unemployment rates on both all-cause and cause-specific mortality across U.S. metropolitan regions during the Great Recession. METHODS: We estimate the effects of economic conditions during the recent and severe recessionary period on mortality, including differences by age and gender subgroups, using fixed effects regression models. We identify a plausibly causal effect by isolating the impacts of within-metropolitan area changes in unemployment rates and controlling for common temporal trends. We aggregated vital statistics, population, and unemployment data at the area-month-year-age-gender-race level, yielding 527,040 observations across 366 metropolitan areas, 2005-2010. RESULTS: We estimate that a one percentage point increase in the metropolitan area unemployment rate was associated with a decrease in all-cause mortality of 3.95 deaths per 100,000 person years (95%CI -6.80 to -1.10), or 0.5%. Estimated reductions in cardiovascular disease mortality contributed 60% of the overall effect and were more pronounced among women. Motor vehicle accident mortality declined with unemployment increases, especially for men and those under age 65, as did legal intervention and homicide mortality, particularly for men and adults ages 25-64. We find suggestive evidence that increases in metropolitan area unemployment increased accidental drug poisoning deaths for both men and women ages 25-64. CONCLUSIONS: Our finding that all-cause mortality decreased during the Great Recession is consistent with previous studies. Some categories of cause-specific mortality, notably cardiovascular disease, also follow this pattern, and are more pronounced for certain gender and age groups. Our study also suggests that the recent recession contributed to the growth in deaths from overdoses of prescription drugs in working-age adults in metropolitan areas. Additional research investigating the mechanisms underlying the health consequences of macroeconomic conditions is warranted.

The effect of metropolitan-area mortgage delinquency on health behaviors, access to health services, and self-rated health in the United States, 2003-2010.

The recent housing crisis offers the opportunity to understand the effects of unique indicators of macroeconomic conditions on health. We linked data on the proportion of mortgage borrowers per US metropolitan-area who were at least 90 days delinquent on their payments with individual-level outcomes from a representative sample of 1,021,341 adults surveyed through the Behavioral Risk Factor Surveillance System (BRFSS) between 2003 and 2010. We estimated the effects of metropolitan-area mortgage delinquency on individual health behaviors, medical coverage, and health status, as well as whether effects varied by race/ethnicity. Results showed that increases in the metropolitan-area delinquency rate resulted in decreases in heavy alcohol consumption and increases in exercise and health insurance coverage. However, the delinquency rate was also associated with increases in smoking and obesity in some population groups, suggesting the housing crisis may have induced stress-related behavioral change. Overall, the effects of metropolitan-area mortgage delinquency on population health were relatively modest.

Trends in Socioeconomic Inequalities in Motor Vehicle Accident Deaths in the United States, 1995-2010.

Motor vehicle accident (MVA) mortality has been declining overall, but little is known about trends by socioeconomic position. We examined trends in education-related inequalities in US MVA death rates from 1995 to 2010. We used mortality data from the National Center for Health Statistics and population estimates from the Current Population Survey, and we calculated vehicle- and person-miles traveled using data from the National Household Travel Survey. We used negative binomial regression to estimate crude and age-, sex-, and race-adjusted mortality rates among adults aged 25 years or more. We found larger mortality decreases among the more highly educated and some evidence of mortality increases among the least educated. Adjusted death rates were 15.3 per 100,000 population (95% confidence interval (CI): 10.7, 19.9) higher at the bottom of the education distribution than at the top of the education distribution in 1995, increasing to 17.9 per 100,000 population (95% CI: 14.8, 21.0) by 2010. In relative terms, adjusted death rates were 2.4 (95% CI: 1.7, 3.0) times higher at the bottom of the education distribution than at the top in 1995, increasing to 4.3 times higher (95% CI: 3.4, 5.3) by 2010. Inequality increases were larger in terms of vehicle-miles traveled. Although overall MVA death rates declined during this period, socioeconomic differences in MVA mortality have persisted or worsened over time.

Trends in Educational Inequalities in Drug Poisoning Mortality: United States, 1994-2010.

OBJECTIVES: We estimated trends in drug poisoning death rates by educational attainment and investigated educational inequalities in drug poisoning mortality by race, gender, and region. METHODS: We linked drug poisoning death counts from the National Vital Statistics System to population denominators from the Current Population Survey to estimate drug poisoning rates by gender, race, region, and educational attainment (less than high school degree, high school degree, some college, college degree) from 1994 to 2010. RESULTS: There were 372,485 drug poisoning deaths. Education-related inequalities increased during the study among all demographic groups and varied by region. Absolute increases in educational inequalities were higher among Whites than Blacks and men than women. The age-adjusted rate difference between White men with less than a high school degree increased from 8.7 per 100,000 in 1994 to 27.4 in 2010 (change = 18.7). Among Black men, the corresponding increases were 11.7 and 18.3, respectively (change = 6.6). CONCLUSIONS: We found strong educational patterning in drug poisoning rates, chiefly by region and race. Rates are highest and increasing the fastest among groups with less education.

Economic downturns and suicide mortality in the USA, 1980-2010: observational study.

BACKGROUND: Several studies have suggested strong associations between economic downturns and suicide mortality, but are at risk of bias due to unmeasured confounding. The rationale for our study was to provide more robust evidence by using a quasi-experimental design. METHODS: We analysed 955,561 suicides occurring in the USA from 1980 to 2010 and used a broad index of economic activity in each US state to measure economic conditions. We used a quasi-experimental, fixed-effects design and we also assessed whether the effects were heterogeneous by demographic group and during periods of official recession. RESULTS: After accounting for secular trends, seasonality and unmeasured fixed characteristics of states, we found that an economic downturn similar in magnitude to the 2007 Great Recession increased suicide mortality by 0.14 deaths per 100,000 population [95% confidence interval (CI) 0.00, 0.28] or around 350 deaths. Effects were stronger for men (0.28, 95% CI 0.07, 0.49) than women and for those with less than 12 years of education (1.22 95% CI 0.83, 1.60) compared with more than 12 years of education. The overall effect did not differ for recessionary (0.11, 95% CI -0.02, 0.25) vs non-recessionary periods (0.15, 95% CI 0.01, 0.29). The main study limitation is the potential for misclassified death certificates and we cannot definitively rule out unmeasured confounding. CONCLUSIONS: We found limited evidence of a strong, population-wide detrimental effect of economic downturns on suicide mortality. The overall effect hides considerable heterogeneity by gender, socioeconomic position and time period.

Effectiveness of an organized colorectal cancer screening program on increasing adherence in asymptomatic average-risk Canadians.

BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and second highest cause of cancer-related mortality in Canada. Despite the availability of screening services and establishment of guidelines, utilization of colorectal cancer screening in Canada remains low. In 2008, the province of Ontario launched ColonCancerCheck, an organized colorectal cancer screening program aimed at increasing CRC screening adherence. In this study, we adopt a quasi-experimental approach to estimate and describe the impact of ColonCancerCheck on screening behavior in the asymptomatic average risk population. METHODS: Annual screening rates from the target population were estimated using five cycles of the Canadian Community Health Survey, a cross-sectional nationally representative survey of health status, healthcare use, and determinants of health in the Canadian population. We used a difference-in-differences design to measure the overall impact of ColonCancerCheck on past-year fecal occult blood testing (FOBT) and endoscopy in Ontario relative to the rest of Canada. Several verification tests validated the suitability of our model specification. RESULTS: The difference-in-differences analysis shows that ColonCancerCheck increased FOBT screening in the average risk population by 5.2 percentage points (95% CI [3.2, 7.2]), an increase of 33% relative to pre-program screening rates. The program had no observed effect on endoscopy screening and we found no evidence that ColonCancerCheck differentially altered the screening practices of population sub-groups. CONCLUSIONS: Our findings suggest ColonCancerCheck has been successful at increasing use of FOBT in the asymptomatic average risk population.

Economic conditions and health behaviours during the 'Great Recession'.

BACKGROUND: The adoption of healthier behaviours has been hypothesised as a mechanism to explain empirical findings of population health improvements during some economic downturns. METHODS: We estimated the effect of the local unemployment rate on health behaviours using pooled annual surveys from the 2003-2010 Behavioral Risk Factor Surveillance Surveys, as well as population-based telephone surveys of the US adult general population. Analyses were based on approximately 1 million respondents aged 25 years or older living in 90 Metropolitan Statistical Areas and Metropolitan Divisions (MMSAs). The primary exposure was the quarterly MMSA-specific unemployment rate. Outcomes included alcohol consumption, smoking status, attempts to quit smoking, body mass index, overweight/obesity and past-month physical activity or exercise. RESULTS: The average unemployment rate across MMSAs increased from a low of 4.5% in 2007 to a high of 9.3% in 2010. In multivariable models accounting for individual-level sociodemographic characteristics and MMSA and quarter fixed effects, a one percentage-point increase in the unemployment rate was associated with 0.15 (95% CI -0.31 to 0.01) fewer drinks consumed in the past month and a 0.14 (95% CI -0.28 to 0.00) percentage-point decrease in the prevalence of past-month heavy drinking; these effects were driven primarily by men. Changes in the unemployment rate were not consistently associated with other health behaviours. Although individual-level unemployment status was associated with higher levels of alcohol consumption, smoking and obesity, the MMSA-level effects of the recession were largely invariant across employment groups. CONCLUSIONS: Our results do not support the hypothesis that health behaviours mediate the effects of local-area economic conditions on mortality.

Heterologous boost vaccines for bacillus Calmette-Guérin prime immunization against tuberculosis.

The current tuberculosis (TB) epidemic continues to call for the development of effective vaccination strategies. The initial TB vaccine research effort mostly focused on the search for a vaccine that might be better than, and thus could replace, the current bacillus Calmette-Guérin (BCG) vaccine. It has increasingly been realized that BCG or an improved BCG will continue to be used as a prime TB vaccine and there is a need to develop effective boost vaccines that could enhance and prolong the protective immunity of BCG prime immunization. Mounting experimental evidence suggests that recombinant vaccines, including both recombinant protein and genetic vector vaccines, are effective in boosting immune activation and protection by BCG vaccination. This review will discuss recent advances and the authors' views in the development of there boost vaccines.