Faculty Bibliography

Importance: Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective: To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design: A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures: Mean SBP level, cause-specific deaths, and health burden related to SBP (>/=110-115 mm Hg and also >/=140 mm Hg) by age, sex, country, and year. Results: Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73119 (95% uncertainty interval [UI], 67949-78241) to 81373 (95% UI, 76814-85770) per 100000, and SBP of 140 mm Hg or higher increased from 17307 (95% UI, 17117-17492) to 20526 (95% UI, 20283-20746) per 100000. The estimated annual death rate per 100000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance: In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (>/=110-115 and >/=140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

It has been suggested that neurological problems more frequent in those born preterm are expressed prior to birth, but owing to technical limitations, this has been difficult to test in humans. We applied novel fetal resting-state functional MRI to measure brain function in 32 human fetuses in utero and found that systems-level neural functional connectivity was diminished in fetuses that would subsequently be born preterm. Neural connectivity was reduced in a left-hemisphere pre-language region, and the degree to which connectivity of this left language region extended to right-hemisphere homologs was positively associated with the time elapsed between fMRI assessment and delivery. These results provide the first evidence that altered functional connectivity in the preterm brain is identifiable before birth. They suggest that neurodevelopmental disorders associated with preterm birth may result from neurological insults that begin in utero.

BACKGROUND AND OBJECTIVES:Diet soda consumption is common in the United States and is associated with impaired glucose metabolism, diabetes, and metabolic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We prospectively analyzed diet soda consumption, assessed by food frequency questionnaire at baseline (1987-1989) and a follow-up examination (1993-1995), and incident ESRD through December 31, 2012 in the Atherosclerosis Risk in Communities study (n=15,368). RESULTS:Baseline mean age of participants was 54 years, 55% were female, and 27% were black. The majority of participants (43.5%) consumed <1 glass/wk of diet soda; 17.8% consumed 1-4 glasses/wk; 25.3% consumed 5-7 glasses/wk; and 13.5% consumed >7 glasses/wk. Over a median follow-up of 23 years, 357 incident ESRD cases were observed. Relative to <1 glass/wk of diet soda, consuming 1-4 glasses/wk, 5-7 glasses/wk, and >7 glasses/wk, respectively, was associated with 1.08-times (95% confidence interval [95% CI], 0.75 to 1.55), 1.33-times (95% CI, 1.01 to 1.75), and 1.83-times (95% CI, 1.01 to 2.52) higher risk of ESRD after adjusting for age, sex, race-center, education level, smoking status, physical activity, total caloric intake, eGFR, body mass index category, diabetes, systolic BP, and serum uric acid (P value for trend <0.001). Results were similar after additional adjustment for dietary acid load, diet quality, dietary sodium, dietary fructose, sugar-sweetened beverages, and dietary phosphorus. Risk estimates were similar by body mass index category (P value for interaction = 0.82), but the association between diet soda and ESRD was only significant for those who were overweight or obese at baseline. Sugar-sweetened beverage consumption was not significantly associated with ESRD in the fully adjusted model. CONCLUSIONS:Diet soda consumption was associated with higher ESRD risk in this general population sample. Further research is necessary to validate these findings in other study populations and to examine potential mechanisms through which diet soda could impact kidney disease.

BACKGROUND AND OBJECTIVES:Serum β-trace protein (BTP) and β-2 microglobulin (B2M) are associated with risk of ESRD and death in the general population and in populations at high risk for these outcomes (GP/HR) and those with CKD, but results differ among studies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:) for ESRD (2075 events) and death (7275 events). RESULTS:provided the most consistent improvement in associations and prediction across both outcomes and populations. Assessment of heterogeneity did not yield clinically relevant differences. For ESRD, addition of albuminuria substantially attenuated the improvement in risk prediction and risk classification with novel filtration markers. For mortality, addition of albuminuria did not affect the improvement in risk prediction with the use of novel markers, but lessened improvement in risk classification, especially for the CKD cohort. CONCLUSIONS:is not accurate or albuminuria is not available. Educational efforts to increase measurement of albuminuria in clinical practice may be more cost-effective than measurement of BTP and B2M for improving prognostic information.

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.

Importance: The increasing use of cesarean delivery is an emerging global health issue. Prior estimates of China's cesarean rate have been based on surveys with limited geographic coverage. Objective: To provide updated information about cesarean rates and geographic variation in cesarean use in China. Design, Setting, and Data Sources: Descriptive study, covering every county (n = 2865) in mainland China's 31 provinces, using county-level aggregated information on the number of live births, cesarean deliveries, maternal deaths, and perinatal deaths, collected by the Office for National Maternal & Child Health Statistics of China, from 2008 through 2014. Exposures: Live births. Main Outcomes and Measures: Annual rate of cesarean deliveries. Results: Over the study period, there were 100873051 live births, of which 32947229 (32.7%) were by cesarean delivery. In 2008, there were 13160634 live births, of which 3788029 (28.8%) were by cesarean delivery and in 2014 there were 15123276 live births, of which 5280124 (34.9%) were by cesarean delivery. Rates varied markedly by province, from 4.0% to 62.5% in 2014. Despite the overall increase, by 2014 rates of cesarean delieries in 14 of the nation's 17 "super cities" had declined by 4.1 to 17.5 percentage points from their earlier peak values (median, 11.4; interquartile range, 6.3-15.4). In 4 super cities with the largest decreases, there was no increase in maternal or perinatal mortality. Conclusions and Relevance: Between 2008 and 2014, the overall annual rate of cesarean deliveries increased in China, reaching 34.9%. There was major geographic variation in rates and trends over time, with rates declining in some of the largest urban areas.

BACKGROUND: Ecstasy (MDMA) use has regained popularity in the United States, particularly in the form of "Molly," which is often marketed as pure MDMA. Surveys have generally not included "Molly" in the definition of ecstasy, so rates of use may be underestimated. As popularity of ecstasy increases, research is needed to examine use among those at highest risk for use-nightlife attendees. METHODS: We surveyed 679 young adults (age 18-25) entering nightclubs and festivals holding electronic dance music (EDM) parties in New York City in 2015. A variation of time-space sampling was utilized. We examined prevalence and correlates of self-reported lifetime ecstasy use. RESULTS: Self-reported lifetime ecstasy use was common (42.8%, 95% CI: 32.8, 52.7). Use was most common among older participants, frequent party attendees, and those reporting higher levels of exposure to users. Those surveyed outside of festivals were less likely to report use compared to those surveyed outside of nightclubs (AOR = 0.37, p = .015). Over a third of ecstasy users (36.8%)reported use in pill, powder, and crystal form. Ecstasy users were also more likely to report use of other drugs, including novel psychoactive substances (e.g., 2C series drugs, synthetic cathinones ["bath salts"]). Half (50.4%) reported suspecting (21.9%) or finding out (28.5%) that their ecstasy had ever contained a drug other than MDMA. CONCLUSION: A large percentage of nightlife attendees in NYC report lifetime ecstasy use. Findings should inform prevention and harm reduction programming. Further research is needed as ecstasy continues to change (e.g., in form, purity, and name).

SETTING:Four regions in Kazakhstan where participants were recruited from June 2012 to May 2014. OBJECTIVE:To examine associations between incarceration history and tobacco, alcohol, and drug consumption, and human immunodeficiency virus (HIV) infection and diabetes mellitus (DM) with TB. DESIGN:This matched case-control study included 1600 participants who completed a survey on sociodemographics, history of incarceration, tobacco, alcohol and drug use, and HIV and DM diagnosis. Conditional logistic regression analysis was used to examine associations between a TB diagnosis and risk factors. RESULTS:Participants who had ever smoked tobacco (aOR 1.73, 95%CI 1.23-2.43, P  0.01), ever drank alcohol (aOR 1.41, 95%CI 1.03-1.93, P  0.05), were HIV-positive (aOR 36.37, 95%CI 2.05-646.13, P  0.05) or had DM (aOR 13.96, 95%CI 6.37-30.56, P  0.01) were more likely to have TB. CONCLUSIONS:The association between TB and tobacco use, alcohol use, HIV and DM in Kazakhstan suggests a need for comprehensive intervention and prevention approaches that also address tobacco and alcohol use, DM and HIV.

BACKGROUND: Alcohol use is common among older adults, and this population has unique risks with alcohol consumption in even lower amounts than younger persons. No recent studies have estimated trends in alcohol use including binge alcohol use and alcohol use disorders (AUD) among older adults. METHODS: We examined alcohol use among adults age >/=50 in the National Survey on Drug Use and Health (NSDUH) from 2005 to 2014. Trends of self-reported past-month binge alcohol use and AUD were estimated. Logistic regression models were used to examine correlates of binge alcohol use and AUD. RESULTS: The prevalence of both past-month binge alcohol use and AUD increased significantly among adults age >/=50 from 2005/2006 to 2013/2014, with a relative increase of 19.2% for binge drinking (linear trend p<0.001) and a 23.3% relative increase for AUD (linear trend p=0.035). While males had a higher prevalence of binge alcohol use and AUD compared to females, there were significant increases in both among females. In adjusted models of aggregated data, being Hispanic, male, and a smoker or illicit drug user were associated with binge alcohol use, while being male, a smoker, an illicit drug user, or reporting past-year depression or mental health treatment were associated with AUD. CONCLUSIONS: Alcohol use among older adults is increasing in the US, including past-month binge alcohol use and AUD with increasing trends among females. Providers and policymakers need to be aware of these changes to address the increase of older adults with unhealthy drinking.