Prenatal exposure to particulate matter and infant birth outcomes: Evidence from a population-wide database.

There are growing concerns about the impact of pollution on maternal and infant health. Despite an extensive correlational literature, observational studies which adopt methods that seek to address potential biases due to unmeasured confounders draw mixed conclusions. Using a population database of births in Northern Ireland (NI) linked to localized geographic information on pollution in mothers' postcodes (zipcodes) of residence during pregnancy, we examine whether prenatal exposure to PM2.5 is associated with a comprehensive range of birth outcomes, including placental health. Overall, we find little evidence that particulate matter is related to infant outcomes at the pollution levels experienced in NI, once we implement a mother fixed effects approach that accounts for time-invariant factors. This contrasts with strong associations in models that adjust for observed confounders but without fixed effects. While reducing ambient air pollution remains an urgent public health priority globally, our results imply that further improvements in short-run levels of prenatal PM2.5 exposure in a relatively low-pollution, higher-income country context, are unlikely to impact on birth outcomes at the population level.

Testosterone concentrations and risk of cardiovascular events in androgen-deficient men with atherosclerotic cardiovascular disease.

BACKGROUND: Whether androgen deficiency among men increases the risk of cardiovascular (CV) events or is merely a disease marker remains a subject of intense scientific interest. OBJECTIVES: Among male subjects in the AIM-HIGH Trial with metabolic syndrome and low baseline levels of high-density lipoprotein (HDL)-cholesterol who were randomized to niacin or placebo plus simvastatin, we examined the relationship between low baseline testosterone (T) concentrations and subsequent CV outcomes during a mean 3-year follow-up. METHODS: In this post hoc analysis of men with available baseline plasma T concentrations, we examined the relationship between clinical/demographic characteristics and T concentrations both as a continuous and dichotomous variable (<300 ng/dL ["low T"] vs. ≥300 ng/dL ["normal T"]) on rates of pre-specified CV outcomes, using Cox proportional hazards models. RESULTS: Among 2118 male participants in whom T concentrations were measured, 643 (30%) had low T and 1475 had normal T concentrations at baseline. The low T group had higher rates of diabetes mellitus, hypertension, elevated body mass index, metabolic syndrome, higher blood glucose, hemoglobin A1c, and triglyceride levels, but lower levels of both low-density lipoprotein and HDL-cholesterol, and a lower rate of prior myocardial infarction (MI). Men with low T had a higher risk of the primary composite outcome of coronary heart disease (CHD) death, MI, stroke, hospitalization for acute coronary syndrome, or coronary or cerebral revascularization (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07, and a higher risk of the CHD death, MI, and stroke composite endpoint (11.8% vs. 8.2%; final adjusted HR 1.37, P = .04), respectively. CONCLUSIONS: In this post hoc analysis, there was an association between low baseline testosterone concentrations and increased risk of subsequent CV events in androgen-deficient men with established CV disease and metabolic syndrome, particularly for the composite secondary endpoint of CHD death, MI, and stroke. CONDENSED ABSTRACT: In this AIM-HIGH Trial post hoc analysis of 2118 men with metabolic syndrome and low HDL-cholesterol with available baseline plasma testosterone (T) samples, 643 males (30%) had low T (mean: 229 ng/dL) and 1475 (70%) had normal T (mean: 444 ng/dL) concentrations. The "low T" group had a 24% higher risk of the primary 5-component endpoint (20.1%) compared with the normal T group (15.2%); final adjusted HR 1.23, P = .07). There was also a 31% higher risk of the secondary composite endpoint: coronary heart disease death, myocardial infarction, and stroke (11.8% vs. 8.2%, final adjusted HR 1.37, P = .04) in the low vs. normal T group, respectively.

Mixed binary-continuous copula regression models with application to adverse birth outcomes.

Bivariate copula regression allows for the flexible combination of two arbitrary, continuous marginal distributions with regression effects being placed on potentially all parameters of the resulting bivariate joint response distribution. Motivated by the risk factors for adverse birth outcomes, many of which are dichotomous, we consider mixed binary-continuous responses that extend the bivariate continuous framework to the situation where one response variable is discrete (more precisely, binary) whereas the other response remains continuous. Utilizing the latent continuous representation of binary regression models, we implement a penalized likelihood-based approach for the resulting class of copula regression models and employ it in the context of modeling gestational age and the presence/absence of low birth weight. The analysis demonstrates the advantage of the flexible specification of regression impacts including nonlinear effects of continuous covariates and spatial effects. Our results imply that racial and spatial inequalities in the risk factors for infant mortality are even greater than previously suggested.

How much does birth weight matter for child health in developing countries? Estimates from siblings and twins.

About 200 million children globally are not meeting their growth potential, and as a result will suffer the consequences in terms of future outcomes. I examine the effects of birth weight on child health and growth using information from 66 countries. I account for missing data and measurement error using instrumental variables and adopt an identification strategy based on siblings and twins. I find a consistent effect of birth weight on mortality risk, stunting, wasting, and coughing, with some evidence for fever, diarrhoea, and anaemia. Bounds analysis indicates that coefficients may be substantially underestimated due to mortality selection. Improving the pre-natal environment is likely to be important for helping children reach their full potential.

The economic burden of noncommunicable diseases and mental health conditions: results for Costa Rica, Jamaica, and Peru.

OBJECTIVE: We extend the EPIC model of the World Health Organization (WHO) and apply it to analyze the macroeconomic impact of noncommunicable diseases (NCDs) and mental health conditions in Costa Rica, Jamaica, and Peru. METHODS: The EPIC model quantifies the impact of NCDs and mental health conditions on aggregate output solely through the effect of chronic conditions on labor supply due to mortality. In contrast, the expanded EPIC-H Plus framework also incorporates reductions in effective labor supply due to morbidity and negative effects of health expenditure on output via the diversion of productive savings and reduced capital accumulation. We apply this methodology to Costa Rica, Jamaica, and Peru and estimate gross domestic product (GDP) output lost due to four leading NCDs (cardiovascular disease, cancer, chronic respiratory disease, and diabetes) and mental health conditions in these countries from 2015 to 2030. We also estimate losses from all NCDs and mental health conditions combined. RESULTS: Overall, our results show total losses associated with all NCDs and mental health conditions over the period 2015-2030 of US$ 81.96 billion (2015 US$) for Costa Rica, US$ 18.45 billion for Jamaica, and US$ 477.33 billion for Peru. Moderate variation exists in the magnitude of the burdens of diseases for the three countries. In Costa Rica and Peru, respiratory disease and mental health conditions are two leading contributors to lost output, while in Jamaica, cardiovascular disease alone accounts for 20.8% of the total loss, followed by cancer. CONCLUSIONS: These results indicate that the economic impact of NCDs and mental health conditions is substantial and that interventions to reduce the prevalence of chronic conditions in countries of Latin America and the Caribbean are likely to be highly cost-beneficial.

Accounting for non-response bias using participation incentives and survey design: An application using gift vouchers.

Standard corrections for missing data rely on the strong and generally untestable assumption of missing at random. Heckman-type selection models relax this assumption, but have been criticized because they typically require a selection variable which predicts non-response but not the outcome of interest, and can impose bivariate normality. In this paper we illustrate an application using a copula methodology which does not rely on bivariate normality. We implement this approach in data on HIV testing at a demographic surveillance site in rural South Africa which are affected by non-response. Randomized incentives are the ideal selection variable, particularly when implemented ex ante to deal with potential missing data. However, elements of survey design may also provide a credible method of correcting for non-response bias ex post. For example, although not explicitly randomized, allocation of food gift vouchers during our survey was plausibly exogenous and substantially raised participation, as did effective survey interviewers. Based on models with receipt of a voucher and interviewer identity as selection variables, our results imply that 37% of women in the population under study are HIV positive, compared to imputation-based estimates of 28%. For men, confidence intervals are too wide to reject the absence of non-response bias. Consistent results obtained when comparing different selection variables and error structures strengthen these conclusions. Our application illustrates the feasibility of the selection model approach when combined with survey metadata.

Vaccination and all-cause child mortality from 1985 to 2011: global evidence from the Demographic and Health Surveys.

Based on models with calibrated parameters for infection, case fatality rates, and vaccine efficacy, basic childhood vaccinations have been estimated to be highly cost effective. We estimated the association of vaccination with mortality directly from survey data. Using 149 cross-sectional Demographic and Health Surveys, we determined the relationship between vaccination coverage and the probability of dying between birth and 5 years of age at the survey cluster level. Our data included approximately 1 million children in 68,490 clusters from 62 countries. We considered the childhood measles, bacillus Calmette-Guérin, diphtheria-pertussis-tetanus, polio, and maternal tetanus vaccinations. Using modified Poisson regression to estimate the relative risk of child mortality in each cluster, we also adjusted for selection bias that resulted from the vaccination status of dead children not being reported. Childhood vaccination, and in particular measles and tetanus vaccination, is associated with substantial reductions in childhood mortality. We estimated that children in clusters with complete vaccination coverage have a relative risk of mortality that is 0.73 (95% confidence interval: 0.68, 0.77) times that of children in a cluster with no vaccinations. Although widely used, basic vaccines still have coverage rates well below 100% in many countries, and our results emphasize the effectiveness of increasing coverage rates in order to reduce child mortality.

On the assumption of bivariate normality in selection models: a Copula approach applied to estimating HIV prevalence.

BACKGROUND: Heckman-type selection models have been used to control HIV prevalence estimates for selection bias when participation in HIV testing and HIV status are associated after controlling for observed variables. These models typically rely on the strong assumption that the error terms in the participation and the outcome equations that comprise the model are distributed as bivariate normal. METHODS: We introduce a novel approach for relaxing the bivariate normality assumption in selection models using copula functions. We apply this method to estimating HIV prevalence and new confidence intervals (CI) in the 2007 Zambia Demographic and Health Survey (DHS) by using interviewer identity as the selection variable that predicts participation (consent to test) but not the outcome (HIV status). RESULTS: We show in a simulation study that selection models can generate biased results when the bivariate normality assumption is violated. In the 2007 Zambia DHS, HIV prevalence estimates are similar irrespective of the structure of the association assumed between participation and outcome. For men, we estimate a population HIV prevalence of 21% (95% CI = 16%-25%) compared with 12% (11%-13%) among those who consented to be tested; for women, the corresponding figures are 19% (13%-24%) and 16% (15%-17%). CONCLUSIONS: Copula approaches to Heckman-type selection models are a useful addition to the methodological toolkit of HIV epidemiology and of epidemiology in general. We develop the use of this approach to systematically evaluate the robustness of HIV prevalence estimates based on selection models, both empirically and in a simulation study.

Using interviewer random effects to remove selection bias from HIV prevalence estimates.

BACKGROUND: Selection bias in HIV prevalence estimates occurs if non-participation in testing is correlated with HIV status. Longitudinal data suggests that individuals who know or suspect they are HIV positive are less likely to participate in testing in HIV surveys, in which case methods to correct for missing data which are based on imputation and observed characteristics will produce biased results. METHODS: The identity of the HIV survey interviewer is typically associated with HIV testing participation, but is unlikely to be correlated with HIV status. Interviewer identity can thus be used as a selection variable allowing estimation of Heckman-type selection models. These models produce asymptotically unbiased HIV prevalence estimates, even when non-participation is correlated with unobserved characteristics, such as knowledge of HIV status. We introduce a new random effects method to these selection models which overcomes non-convergence caused by collinearity, small sample bias, and incorrect inference in existing approaches. Our method is easy to implement in standard statistical software, and allows the construction of bootstrapped standard errors which adjust for the fact that the relationship between testing and HIV status is uncertain and needs to be estimated. RESULTS: Using nationally representative data from the Demographic and Health Surveys, we illustrate our approach with new point estimates and confidence intervals (CI) for HIV prevalence among men in Ghana (2003) and Zambia (2007). In Ghana, we find little evidence of selection bias as our selection model gives an HIV prevalence estimate of 1.4% (95% CI 1.2% - 1.6%), compared to 1.6% among those with a valid HIV test. In Zambia, our selection model gives an HIV prevalence estimate of 16.3% (95% CI 11.0% - 18.4%), compared to 12.1% among those with a valid HIV test. Therefore, those who decline to test in Zambia are found to be more likely to be HIV positive. CONCLUSIONS: Our approach corrects for selection bias in HIV prevalence estimates, is possible to implement even when HIV prevalence or non-participation is very high or very low, and provides a practical solution to account for both sampling and parameter uncertainty in the estimation of confidence intervals. The wide confidence intervals estimated in an example with high HIV prevalence indicate that it is difficult to correct statistically for the bias that may occur when a large proportion of people refuse to test.

Long-term exposure to ambient PM2.5 and population health: evidence from linked census data.

Particulate matter suspended in the air that is comprised of microscopic particles with a diameter of 2.5µm or less (PM2.5) is among the most impactful pollutants globally. Extensive evidence shows exposure to ambient PM2.5 is associated with a wide range of poor health outcomes. However, few studies examine long-run pollution exposures in nationally representative data. This study exploits Census data for Northern Ireland, linked to average PM2.5 concentrations at the 1x1km grid-square level during the period 2002-2010. We combine outcome measures in 2011 with data on complete residential histories. Before adjusting for other covariates, we show strong relationships between PM2.5 exposure, self-rated general health, disability, and all available (eleven) domain-specific health measures in the data. Associations with poor general health, chronic illness, breathing difficulties, mobility difficulties, and deafness are robust to extensive conditioning and to further analysis designed to examine sensitivity to unobserved confounders.

Association of Increasing the Minimum Wage in the US With Experiences of Maternal Stressful Life Events.

Importance: Exposure to stressful life events (SLEs) before and during pregnancy is associated with adverse health for pregnant people and their children. Minimum wage policies have the potential to reduce exposure to SLEs among socioeconomically disadvantaged pregnant people. Objective: To examine the association of increasing the minimum wage with experience of maternal SLEs. Design, Setting, and Participants: This repeated cross-sectional study included 199 308 individuals who gave birth between January 1, 2004, and December 31, 2015, in 39 states that participated in at least 2 years of the Pregnancy Risk Assessment Monitoring Survey between 2004 and 2015. Statistical analysis was performed from September 1, 2022, to January 6, 2023. Exposure: The mean minimum wage in the 2 years prior to the month and year of delivery in an individual's state of residence. Main Outcomes and Measures: The main outcomes were number of financial, partner-related, traumatic, and total SLEs in the 12 months before delivery. Individual-level covariates included age, race and ethnicity, marital status, parity, educational level, and birth month. State-level covariates included unemployment, gross state product, uninsurance, poverty, state income supports, political affiliation of governor, and Medicaid eligibility levels. A 2-way fixed-effects analysis was conducted, adjusting for individual and state-level covariates and state-specific time trends. Results: Of the 199 308 women (mean [SD] age at delivery, 25.7 [6.1] years) in the study, 1.4% were American Indian or Alaska Native, 2.5% were Asian or Pacific Islander, 27.2% were Hispanic, 17.6% were non-Hispanic Black, and 48.8% were non-Hispanic White. A $1 increase in the minimum wage was associated with a reduction in total SLEs (-0.060; 95% CI, -0.095 to -0.024), financial SLEs (-0.032; 95% CI, -0.056 to -0.007), and partner-related SLEs (-0.019; 95% CI, -0.036 to -0.003). When stratifying by race and ethnicity, minimum wage increases were associated with larger reductions in total SLEs for Hispanic women (-0.125; 95% CI, -0.242 to -0.009). Conclusions and Relevance: In this repeated cross-sectional study of women with a high school education or less across 39 states, an increase in the state-level minimum wage was associated with reductions in experiences of maternal SLEs. Findings support the potential of increasing the minimum wage as a policy for improving maternal well-being among socioeconomically disadvantaged pregnant people. These findings have relevance for current policy debates regarding the minimum wage as a tool for improving population health.

Maternal depression and economic well-being: A quasi-experimental approach.

Maternal depression is associated with adverse impacts on the health of women and their children. However, further evidence is needed on the extent to which maternal depression influences women's economic well-being and how unmeasured confounders affect estimates of this relationship. In this study, we aimed to measure the association between maternal depression and economic outcomes (income, employment, and material hardship) over a 15-year time horizon. We conducted longitudinal analyses using the Fragile Families and Child Wellbeing Study, an urban birth cohort study in the United States. We assessed the potential contribution of time-invariant unmeasured confounders using a quasi-experimental approach and also investigated the role of persistent versus transient depressive symptoms on economic outcomes up to 15 years after childbirth. In models that adjusted for time-invariant unmeasured confounders, maternal depression was associated with not being employed (an adjusted risk difference of 3 percentage points (95% CI 0.01 to 0.05)) and experiencing any material hardship (an adjusted risk difference of 14 percentage points (95% CI 0.12 to 0.16)), as well as with reductions in the ratio of household income to poverty by 0.10 units (95% CI -0.16 to -0.04) and annual household income by $2114 (95% CI -$3379 to -$850). Impacts at year 15 were strongest for those who experienced persistent depression. Results of our study strengthen the case for viewing mental health support services as interventions that may also foster economic well-being, and highlight the importance of including economic impacts in assessments of the cost-effectiveness of mental health interventions.

Levels of depression, anxiety, and psychological distress among Ugandan adults during the first wave of the COVID-19 pandemic: cross-sectional evidence from a mobile phone-based population survey.

Objectives: Policy measures to slow the spread of coronavirus disease 2019 (COVID-19), such as curfews and business closures, may have negative effects on mental health. Populations in low- and middle-income countries (LMICs) may be particularly affected due to high rates of poverty and less comprehensive welfare systems, but the evidence is scarce. We evaluated predictors of depression, anxiety, and psychological distress in Uganda, which implemented one of the world's most stringent lockdowns. Methods: We conducted a mobile phone-based cross-sectional survey from December 2020 through April 2021 among individuals aged 18 years or over in Uganda. We measured depression, anxiety, and psychological distress using the Patient Health Questionnaire (PHQ)-2, the Generalized Anxiety Disorder (GAD)-2, and the PHQ-4. We applied linear regression to assess associations between experiences of COVID-19 (including fear of infection, social isolation, income loss, difficulty accessing medical care, school closings, and interactions with police) and PHQ-4 score, adjusted for sociodemographic characteristics. Results: 29.2% of 4066 total participants reported scores indicating moderate psychological distress, and 12.1% reported scores indicating severe distress. Distress was most common among individuals who were female, had lower levels of education, and lived in households with children. Related to COVID-19, PHQ-4 score was significantly associated with difficulty accessing medical care, worries about COVID-19, worries about interactions with police over lockdown measures, and days spent at home. Conclusions: There is an urgent need to address the significant burden of psychological distress associated with COVID-19 and policy responses in LMICs. Pandemic mitigation strategies must consider mental health consequences.

Childhood Stunting and Wasting Following Independence in South Sudan.

BACKGROUND: South Sudan has experienced ongoing civil and environmental problems since gaining independence in 2011 that may influence childhood nutritional status. OBJECTIVE: To estimate the prevalence of undernutrition among children in South Sudan in 2018 and 2019 compared to the prevalence in 2010. METHODS: Data on height and weight were collected using a 2-stage stratified sample framework in which households were randomly selected at the county level and nutritional status was calculated for all children under 5 years of age to determine height-for-age, weight-for-height, and weight-for-age Z-scores (HAZ, WHZ, and WAZ) and the prevalence of stunting, wasting, and underweight. Linear and logistic regression analyses were used to determine factors associated with nutritional status and the odds ratio for nutritional outcomes. RESULTS: In 2010, the mean HAZ, WHZ, and WAZ was -0.78, -0.82, and -1.15, respectively, and the prevalence of stunting, wasting, and underweight was 30%, 23%, and 32%, respectively. In 2018 and 2019, the mean HAZ, WHZ, and WAZ was -0.50, -0.70, -0.77 and -0.53, -0.77, -0.76, respectively. The prevalence of stunting, wasting, and underweight in 2018 and 2019 was 17%, 14%, 15% and 16%, 16%, 17%, respectively. Age was negatively associated with all nutritional indices and girls had higher HAZ, WHZ, and WAZ and a lower mid upper arm circumference (P < .01) compared to boys. The risk of poor nutritional outcomes was associated with vaccine status and varied by state of residence. CONCLUSIONS: Following independence in 2010, the prevalence of undernutrition in South Sudan decreased, but the risk for undernutrition varied by state and efforts to address food security and health need to ensure equitable access for all children in South Sudan.

Optimal pharmacotherapy to combat the atherogenic lipid triad.

PURPOSE OF REVIEW: A lipid triad involving an atherogenic dyslipidemia characterized by moderate/high LDL-C, low HDL-C, and elevated triglyceride (TG) occurs in numerous clinical settings associated with high cardiovascular risk. This article focuses on optimizing treatment of atherogenic dyslipidemias involving this lipid triad, emphasizing niacin-based or fibrate-based therapies. RECENT FINDINGS: Niacin-based therapies comprehensively improve the atherogenic lipid profile, lead to atherosclerosis regression, and exert benefits across a spectrum of cardiovascular endpoints in studies based on limited patient numbers. Fibrates impact TG, HDL-C, and LDL-C according to lipid phenotype and underlying metabolic abnormality. In a recent meta-analysis, fibrates significantly reduced major cardiovascular events (-10%) and coronary events (-13%) across a wide range of lipid phenotypes, but had no impact on stroke, sudden death, or mortality. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial in type 2 diabetic patients similarly showed no significant effect of fenofibrate + simvastatin (vs. simvastatin) on nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death; a subgroup (17%) with marked atherogenic dyslipidemia trended toward benefit. Both niacin and fibrates attenuate vascular inflammation but the potential clinical relevance is indeterminate. SUMMARY: Optimal cardiovascular risk reduction in patients exhibiting the lipid triad requires integrated pharmacotherapy to normalize LDL-C, HDL-C, TGs, and potentially lipoprotein(a). Ongoing studies may provide definitive evidence of the impact of niacin plus statins on cardiovascular outcomes.

Characterization of HCV-infected people who inject drugs (PWID) in the setting of clinical care in Canada (CAPICA): A retrospective study.

Background: People who use drugs (PWUD) are among the highest risk category for becoming infected with the hepatitis C virus (HCV) in Canada. There is a need for more information on the demographics of HCV-infected PWUD/PWID who have recently injected drugs or who are actively injecting drugs. Methods: CAPICA was a multicentre, retrospective database/chart review conducted from October 2015 to February 2016 that was designed to characterize HCV-infected people who inject drugs (PWID) and are enrolled in clinical care in Canada. The aim was to identify factors of health care engagement essential in the design systems of HCV care and treatment in this population. The study enrolled 420 patients with a history of injection drug use within the last 12 months who had been diagnosed with chronic viremic HCV infection and had been participants in an outpatient clinical care setting in the past 12 months. Patients who were co-infected with HIV/HCV were excluded. Results: Harm reduction programs were in place at 92% (11/12) of the sites, and 75% (9) of these sites offered opioid agonist therapy (OAT), with 48% of the patients currently taking OAT. HCV genotype 1a was most prevalent (56%), followed by G3 (34%), and the most common fibrosis score was F1 (34%). The average reinfection rate was about 5%. Seventeen percent of the patients were undergoing HCV treatment or had recently failed therapy, while 83% were not being treated. Conclusions: In a multivariate analysis, the following factors were significantly associated with treatment: increasing age (OR 1.10), a fibrosis score of F4 (OR 4.91), moderate alcohol consumption (OR 3.70), and not using a needle exchange program (OR 6.95).

Effects of Extended-Release Niacin on Quartile Lp-PLA2 Levels and Clinical Outcomes in Statin-treated Patients with Established Cardiovascular Disease and Low Baseline Levels of HDL-Cholesterol: Post Hoc Analysis of the AIM HIGH Trial.

BACKGROUND: Lipoprotein-associated phospholipase A2 (LpPLA2) is an inflammatory marker that has been associated with the presence of vulnerable plaque and increased risk of cardiovascular (CV) events. OBJECTIVE: To assess the effect of extended-release niacin (ERN) on Lp-PLA2 activity and clinical outcomes. METHODS: We performed a post hoc analysis in 3196 AIM-HIGH patients with established CV disease and low baseline levels of high-density lipoprotein cholesterol (HDL-C) who were randomized to ERN versus placebo on a background of simvastatin therapy (with or without ezetimibe) to assess the association between baseline Lp-PLA2 activity and the rate of the composite primary end point (CV death, myocardial infarction, stroke, hospitalization for unstable angina, and symptom-driven revascularization). RESULTS: Participants randomized to ERN, but not those randomized to placebo, experienced a significant 8.9% decrease in LpPLA2. In univariate analysis, the highest quartile of LpPLA2 activity (>208 nmol/min/mL, Q4) was associated with higher event rates compared to the lower quartiles in the placebo group (log rank P = .032), but not in the ERN treated participants (log rank P = .718). However, in multivariate analysis, adjusting for sex, diabetes, baseline LDL-C, HDL-C, and triglycerides, there was no significant difference in outcomes between the highest Lp-PLA2 activity quartile versus the lower quartiles in both the placebo and the ERN groups. CONCLUSION: Among participants with stable CV disease on optimal medical therapy, elevated Lp-PLA2 was associated with higher CV events; however, addition of ERN mitigates this effect. This association in the placebo group was attenuated after multivariable adjustment, which suggests that Lp-PLA2 does not improve risk assessment beyond traditional risk factors.

Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study).

International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides for patients at moderately high to high coronary heart disease (CHD) risk. Combination therapy is often required to achieve multiple lipid treatment goals, and > or =50% reduction in low-density lipoprotein cholesterol (LDL-C) is needed in some patients to achieve aggressive LDL-C targets. In this context, we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin (niacin ER), a statin plus ezetimibe, and a highly potent statin alone. This was an open-label, multicenter, 12-week study in 292 patients (50% women) who qualified for drug therapy based on number of CHD risk factors. Patients were randomized to four parallel arms, titrated from low to moderate or high doses: atorvastatin/niacin ER, rosuvastatin/niacin ER, simvastatin/ezetimibe, or rosuvastatin alone. Baseline mean values were, for LDL-C 197 mg/dL (5.1 mmol/L), HDL-C 49 mg/dL (1.3 mmol/L), triglycerides 168 mg/dL (1.9 mmol/L). There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment. All groups lowered LDL-C by approximately 50% or more (range -49 to -57%), achieving mean levels of 82-98 mg/dL (2.1-2.5 mmol/L). Changes in non-HDL-C (range -46 to -55%) mirrored those for LDL-C and did not differ among treatment groups. Statin/niacin ER combination regimens also increased HDL-C and large HDL (HDL2) and lowered triglycerides and lipoprotein (a) significantly more than other regimens. No drug-related myopathy or hepatotoxicity was observed. In this study, low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD.

A review of the evidence linking child stunting to economic outcomes.

Background: To understand the full impact of stunting in childhood it is important to consider the long-run effects of undernutrition on the outcomes of adults who were affected in early life. Focusing on the costs of stunting provides a means of evaluating the economic case for investing in childhood nutrition. Methods: We review the literature on the association between stunting and undernutrition in childhood and economic outcomes in adulthood. At the national level, we also evaluate the evidence linking stunting to economic growth. Throughout, we consider randomized controlled trials (RCTs), quasi-experimental approaches and observational studies. Results: Long-run evaluations of two randomized nutrition interventions indicate substantial returns to the programmes (a 25% and 46% increase in wages for those affected as children, respectively). Cost-benefit analyses of nutrition interventions using calibrated return estimates report a median return of 17.9:1 per child. Assessing the wage premium associated with adult height, we find that a 1-cm increase in stature is associated with a 4% increase in wages for men and a 6% increase in wages for women in our preferred set of studies which attempt to address unobserved confounding and measurement error. In contrast, the evidence on the association between economic growth and stunting is mixed. Conclusions: Countries with high rates of stunting, such as those in South Asia and sub-Saharan Africa, should scale up policies and programmes aiming to reduce child undernutrition as cost-beneficial investments that expand the economic opportunities of their children, better allowing them and their countries to reach their full potential. However, economic growth as a policy will only be effective at reducing the prevalence of stunting when increases in national income are directed at improving the diets of children, addressing gender inequalities and strengthening the status of women, improving sanitation and reducing poverty and inequities.

National South African HIV prevalence estimates robust despite substantial test non-participation.

BACKGROUND: South African (SA) national HIV seroprevalence estimates are of crucial policy relevance in the country, and for the worldwide HIV response. However, the most recent nationally representative HIV test survey in 2012 had 22% test non-participation, leaving the potential for substantial bias in current seroprevalence estimates, even after controlling for selection on observed factors. OBJECTIVE: To re-estimate national HIV prevalence in SA, controlling for bias due to selection on both observed and unobserved factors in the 2012 SA National HIV Prevalence, Incidence and Behaviour Survey. METHODS: We jointly estimated regression models for consent to test and HIV status in a Heckman-type bivariate probit framework. As selection variable, we used assigned interviewer identity, a variable known to predict consent but highly unlikely to be associated with interviewees' HIV status. From these models, we estimated the HIV status of interviewed participants who did not test. RESULTS: Of 26 710 interviewed participants who were invited to test for HIV, 21.3% of females and 24.3% of males declined. Interviewer identity was strongly correlated with consent to test for HIV; declining a test was weakly associated with HIV serostatus. Our HIV prevalence estimates were not significantly different from those using standard methods to control for bias due to selection on observed factors: 15.1% (95% confidence interval (CI) 12.1 - 18.6) v. 14.5% (95% CI 12.8 - 16.3) for 15 - 49-year-old males; 23.3% (95% CI 21.7 - 25.8) v. 23.2% (95% CI 21.3 - 25.1) for 15 - 49-year-old females. CONCLUSION: The most recent SA HIV prevalence estimates are robust under the strongest available test for selection bias due to missing data. Our findings support the reliability of inferences drawn from such data.