Faculty Bibliography

Arsenic (As) exposure has been associated with both urologic malignancy and renal dysfunction; however, its association with hematuria is unknown. We evaluated the association between drinking water As exposure and hematuria in 7843 men enrolled in the Health Effects of Arsenic Longitudinal Study (HEALS). Cross-sectional analysis of baseline data was conducted with As exposure assessed in both well water and urinary As measurements, while hematuria was measured using urine dipstick. Prospective analyses with Cox proportional regression models were based on urinary As and dipstick measurements obtained biannually since baseline up to six years. At baseline, urinary As was significantly related to prevalence of hematuria (P-trend<0.01), with increasing quintiles of exposure corresponding with respective prevalence odds ratios of 1.00 (reference), 1.29 (95% CI: 1.04-1.59), 1.41 (95% CI: 1.15-1.74), 1.46 (95% CI: 1.19-1.79), and 1.56 (95% CI: 1.27-1.91). Compared to those with relatively little absolute urinary As change during follow-up (-10.40 to 41.17mug/l), hazard ratios for hematuria were 0.99 (95% CI: 0.80-1.22) and 0.80 (95% CI: 0.65-0.99) for those whose urinary As decreased by >47.49mug/l and 10.87 to 47.49mug/l since last visit, respectively, and 1.17 (95% CI: 0.94-1.45) and 1.36 (95% CI: 1.10-1.66) for those with between-visit increases of 10.40 to 41.17mug/l and >41.17mug/l, respectively. These data indicate a positive association of As exposure with both prevalence and incidence of dipstick hematuria. This exposure effect appears modifiable by relatively short-term changes in drinking water As.

BACKGROUND: Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest. METHODS AND FINDINGS: We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged >/=45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan-accounting for approximately 71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37-1.51) and 1.48-fold (1.38-1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%-17.2%) and 3.3% (2.6%-4.0%) of deaths, respectively, in men and women aged >/=45 y in the seven countries/regions combined, with a total number of estimated deaths of approximately 1,575,500 (95% CI = 1,398,000-1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged >/=45 y. CONCLUSIONS: Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged >/=45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors' Summary.

BACKGROUND: Industrialization in the northwest provinces of the People's Republic of China is accelerating rapid increases in early life environmental exposures, yet no publications have assessed health care provider capacity to manage common hazards. METHODS: To assess provider attitudes and beliefs regarding the environment in children's health, determine self-efficacy in managing concerns, and identify common approaches to managing patients with significant exposures or environmentally-mediated conditions, a two-page survey was administered to pediatricians, child care specialists, and nurses in five provinces (Gansu, Shaanxi, Xinjiang, Qinghai, and Ningxia). Descriptive and multivariable analyses assessed predictors of strong self-efficacy, beliefs or attitudes. RESULTS: 960 surveys were completed with <5% refusal; 695 (72.3%) were valid for statistical analyses. The role of environment in health was rated highly (mean 4.35 on a 1-5 scale). Self-efficacy reported with managing lead, pesticide, air pollution, mercury, mold and polychlorinated biphenyl exposures were generally modest (2.22-2.52 mean). 95.4% reported patients affected with 11.9% reporting seeing >20 affected patients. Only 12.0% reported specific training in environmental history taking, and 12.0% reported owning a text on children's environmental health. Geographic disparities were most prominent in multivariable analyses, with stronger beliefs in environmental causation yet lower self-efficacy in managing exposures in the northwestern-most province. CONCLUSIONS: Health care providers in Northwest China have strong beliefs regarding the role of environment in children's health, and frequently identify affected children. Few are trained in environmental history taking or rate self-efficacy highly in managing common hazards. Enhancing provider capacity has promise for improving children's health in the region.

BACKGROUND: Anthropometric measures such as waist-hip-ratio (WHR), waist-height-ratio (WHtR), waist circumference, Mid-upper arm circumference (MUAC), and upper thigh circumference, have been linked to the risk of cardiovascular disease (CVD). However, their relationships with subclinical atherosclerosis are unclear. Studies in normal-weight populations, especially in Asian countries where leanness is prevalent, are lacking. METHODS: We conducted a cross-sectional study to assess the associations of WHR, WHtR, waist circumference, hip circumference, body mass index (BMI), MUAC and upper thigh circumference with carotid intima-media thickness (cIMT) among 562 middle-aged participants free of CVD in rural Bangladesh. RESULTS: After adjusting for age and sex, WHR and waist circumference but not BMI showed a positive significant association with cIMT. In multivariate analysis, each standard deviation (SD) increase of WHR (0.08) or WHtR (0.07) was associated with an 8.96 mum (95% CI, 1.12-16.81) or 11.45 mum (95%CI, 0.86-22.04) difference in cIMT, respectively, after controlling for age, sex, BMI, smoking status, education level, and systolic blood pressure (SBP). The associations of WHR and WHtR with cIMT were independent of the influence of other anthropometric measures. The associations of other anthropometric measures and cIMT were not apparent. CONCLUSIONS: In our relatively lean, healthy Asian population, WHR and WHtR appear to be better predictors of early atherosclerosis than other common surrogates of adiposity.

OBJECTIVES: To estimate global, regional (21 regions) and national (187 countries) sodium intakes in adults in 1990 and 2010. DESIGN: Bayesian hierarchical modelling using all identifiable primary sources. DATA SOURCES AND ELIGIBILITY: We searched and obtained published and unpublished data from 142 surveys of 24 h urinary sodium and 103 of dietary sodium conducted between 1980 and 2010 across 66 countries. Dietary estimates were converted to urine equivalents based on 79 pairs of dual measurements. MODELLING METHODS: Bayesian hierarchical modelling used survey data and their characteristics to estimate mean sodium intake, by sex, 5 years age group and associated uncertainty for persons aged 20+ in 187 countries in 1990 and 2010. Country-level covariates were national income/person and composition of food supplies. MAIN OUTCOME MEASURES: Mean sodium intake (g/day) as estimable by 24 h urine collections, without adjustment for non-urinary losses. RESULTS: In 2010, global mean sodium intake was 3.95 g/day (95% uncertainty interval: 3.89 to 4.01). This was nearly twice the WHO recommended limit of 2 g/day and equivalent to 10.06 (9.88-10.21) g/day of salt. Intake in men was approximately 10% higher than in women; differences by age were small. Intakes were highest in East Asia, Central Asia and Eastern Europe (mean >4.2 g/day) and in Central Europe and Middle East/North Africa (3.9-4.2 g/day). Regional mean intakes in North America, Western Europe and Australia/New Zealand ranged from 3.4 to 3.8 g/day. Intakes were lower (<3.3 g/day), but more uncertain, in sub-Saharan Africa and Latin America. Between 1990 and 2010, modest, but uncertain, increases in sodium intakes were identified. CONCLUSIONS: Sodium intakes exceed the recommended levels in almost all countries with small differences by age and sex. Virtually all populations would benefit from sodium reduction, supported by enhanced surveillance.

OBJECTIVE: Limited studies suggest that blood pressure variability over time is a risk factor of long-term cardiovascular outcomes. However, most of these were in populations with pre-existing cardiovascular diseases (CVD) and studies in general population are lacking. METHODS: The study included 11,153 participants in a population-based, prospective cohort study in Araihazar, Bangladesh. Resting blood pressure was measured at baseline and every two years thereafter. Participants were followed up for an average of 6.5years (2002-2009). RESULTS: Male gender, older age, baseline systolic blood pressure (SBP), and absence of betel leaf use were independently positively associated with greater SBP variability over time. There was a significant association between SBP variability and the risk of death from overall CVD, especially from major CVD events. The positive association with the risk of death from any cause and stroke in age- and sex-adjusted models was attenuated in fully-adjusted models. In addition, the hazard ratio (HR) of stroke mortality was greater for individuals with both high baseline and high SBP variability. Similar patterns of HRs were observed for all-cause and CVD mortalities. CONCLUSION: In this rural Bangladeshi population, variability in SBP contributes to the risk of death from CVD and may further potentiate the increased mortality risk associated with high SBP.

BACKGROUND: Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal. METHODS: Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls. RESULTS: Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62). CONCLUSIONS: We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.