Faculty Bibliography

Pregnancy is increasingly considered a period of vulnerability for extreme heat exposure. Multiple lines of evidence support that heat stress is associated with placental insufficiency, poor fetal growth and decreased birth weight. In this narrative review, we first summarize evidence linking ambient temperature or experimentally-induced heat stress with fetal and placental growth outcomes in humans, ruminants and murine species. We then synthesize the literature on putative underlying biological pathways with a focus on the placenta. Reviewed mechanisms include: reduced uterine-placental blood flow, impaired supply of metabolic substrates to the fetus, activation of the maternal stress-response system, and disruption of other endocrine and immune system endpoints. Taken together, this body of evidence supports that exposure to extreme ambient heat likely has adverse consequences for placental development and function. However, research investigating placenta-mediated pathophysiological mechanisms in humans remains extremely limited.

BACKGROUND:Public health experts have urged governments around the world to regulate newly legalized cannabis as they do alcohol to effectively and efficiently protect health. However, research evaluating the alignment of alcohol and cannabis policies is sparse. We assessed similarities and differences in local alcohol and cannabis control policies across California, and characterized localities adopting distinct policy approaches. METHODS:Using standard legal epidemiologic techniques, we collected and coded local alcohol and cannabis control policies relevant to public health for 12 California counties and all incorporated cities within them (N=241). We assessed whether localities were equally stringent on alcohol and cannabis policies by comparing overall restrictiveness (summed policy scores) and 9 specific provisions that applied to both substances. We captured distinct local alcohol-cannabis policy approaches using latent class analysis, and examined this classification in relation to local demographic, socioeconomic, political, and retail market characteristics. RESULTS:All 241 localities permitted alcohol sales, while 71% banned cannabis sales. Among those that did not ban cannabis sales, more stringent alcohol policy scores were associated with more stringent cannabis policy scores (linear regression coefficient: 0.16 [95% CI: 0.07, 0.25]). Local governments rarely adopted the same provisions for alcohol and cannabis (e.g., limits on hours of sale, advertising restrictions), and only two regulated the co-location of cannabis and alcohol outlets. Localities that were restrictive on alcohol yet permissive on cannabis (12%) were more urban, politically progressive, and had more low-income and racial/ethnic minority residents. Localities that were more permissive on alcohol and restrictive on cannabis (51%) were more socioeconomically advantaged. CONCLUSION/CONCLUSIONS:We found few similarities between local alcohol and cannabis control policies. California's experience suggests that, as governments around the world legalize cannabis, lessons learned from regulating alcohol are not routinely applied to cannabis, particularly in communities distinguished by high social and economic advantages.

BACKGROUND:Although studies to date have broadly shown that cardiovascular disease (CVD) increases cognitive and physical impairment risk, there is still limited understanding of the magnitude of this risk among relevant CVD subtypes or age cohorts. METHODS:We analyzed longitudinal data from 16 679 U.S. Health and Retirement Study participants who were aged ≥65 years at study entry. Primary endpoints were physical impairment (activities of daily living impairment) or cognitive impairment (Langa-Weir Classification of dementia). We compared these endpoints among participants who developed incident CVD versus those who were CVD free, both in the short term (<2-year postdiagnosis) and long term (>5 years), controlling for sociodemographic and health characteristics. We then analyzed the effects by CVD subtype (atrial fibrillation, congestive heart failure, ischemic heart disease, and stroke) and age-at-diagnosis (65-74, 75-84, and ≥85). RESULTS:Over a median follow-up of 10 years, 8 750 participants (52%) developed incident CVD. Incident CVD was associated with significantly higher adjusted odds (aOR) of short-term and long-term physical and cognitive impairment. The oldest (≥85) age-at-diagnosis subgroup had the highest risk of short-term physical (aOR 3.01, 95% confidence interval [CI]: 2.40-3.77) and cognitive impairment (aOR 1.96, 95% CI: 1.55-2.48), as well as long-term impairment. All CVD subtypes were associated with higher odds of physical and cognitive impairment, with the highest risk for patients with incident stroke. CONCLUSIONS:Incident CVD was associated with an increased risk of physical and cognitive impairment across CVD subtypes. Impairment risk after CVD was highest among the oldest patients (≥85 years) who should therefore remain a target for prevention efforts.

Relatively few studies on the adverse health impacts of outdoor air pollution have been conducted in Latin American cities, whose pollutant mixtures and baseline health risks are distinct from North America, Europe, and Asia. This study evaluates respiratory morbidity risk associated with ambient air pollution in Quito, Ecuador, and specifically evaluates if the local air quality index accurately reflects population-level health risks. Poisson generalized linear models using air pollution, meteorological, and hospital admission data from 2014 to 2015 were run to quantify the associations of air pollutants and index values with respiratory outcomes in single- and multi-pollutant models. Significant associations were observed for increased respiratory hospital admissions and ambient concentrations of fine particulate matter (PM_2.5), ozone (O₃), nitrogen dioxide (NO₂), and sulfur dioxide (SO₂), although some of these associations were attenuated in two-pollutant models. Significant associations were also observed for index values, but these values were driven almost entirely by daily O₃ concentrations. Modifications to index formulation to more fully incorporate the health risks of multiple pollutants, particularly for NO₂, have the potential to greatly improve risk communication in Quito. This work also increases the equity of the existing global epidemiological literature by adding new air pollution health risk values from a highly understudied region of the world.

BACKGROUND:Hearing loss is highly prevalent in older ages and has several health consequences. Some cardiovascular risk factors are associated with worse hearing at older ages. Still, the role of midlife leisure-time physical activity (PA) as a risk factor for hearing loss is yet to be investigated. METHODS:Among 3 198 participants of the Atherosclerosis Risk in Communities study, we investigated the associations of midlife and change from mid- to late-life PA (assessed via modified Baecke questionnaire) with hearing loss (audiometric battery [worse-ear pure-tone average, and speech-in-noise test]) at older ages. We used regression analyses, adjusted for demographics, medical conditions, and noise exposure, to estimate differences in hearing between those who met and did not meet PA recommendations at midlife and at late life. RESULTS:A total of 1 386 (43.3%) participants met PA recommendations at midlife. These participants, compared to those who did not meet recommendations, had lower (better) pure-tone average by 1.51 (0.46, 2.55) decibels, identified 0.37 (0.01, 0.74) more words (better score) in the speech-in-noise test, and had a lower relative risk of having hearing loss at older ages (eg, relative risk ratio for severe hearing loss vs normal hearing = 0.70 [0.52, 0.95]). Similarly, those who persistently met PA recommendations from mid- to late life had, compared with those who did not, a better hearing at older ages. CONCLUSIONS:Meeting PA public health recommendations in midlife and mid- to late life was associated with better hearing at older ages and reduced risk of hearing loss. Promoting adequate levels of PA may be an essential component of hearing care.

OBJECTIVES/OBJECTIVE:This study aimed to examine trends in cannabis-positive urine drug screens (UDSs) among emergency department (ED) patients from 2008 to 2019 using data from the Veterans Health Administration (VHA) health care system, and whether these trends differed by age group (18-34, 35-64, and 65-75 years), sex, and race, and ethnicity. METHOD/METHODS:VHA electronic health records from 2008 to 2019 were used to identify the percentage of unique VHA patients seen each year at an ED, received a UDS, and screened positive for cannabis. Trends in cannabis-positive UDS were examined by age, race and ethnicity, and sex within age groups. RESULTS:Of the VHA ED patients with a UDS, the annual prevalence positive for cannabis increased from 16.42% in 2008 to 27.2% in 2019. The largest increases in cannabis-positive UDS were observed in the younger age groups. Male and female ED patients tested positive for cannabis at similar levels. Although the prevalence of cannabis-positive UDS was consistently highest among non-Hispanic Black patients, cannabis-positive UDS increased in all race and ethnicity groups. DISCUSSION/CONCLUSIONS:The increasing prevalence of cannabis-positive UDS supports the validity of previously observed population-level increases in cannabis use and cannabis use disorder from survey and administrative records. Time trends via UDS results provide additional support that previously documented increases in self-reported cannabis use and disorder from surveys and claims data are not spuriously due to changes in patient willingness to report use as it becomes more legalized, or due to greater clinical attention over time.

BACKGROUND:N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a cardiac biomarker used in the clinical management of heart failure. We sought to create updated reference intervals for NT-proBNP for healthy US children, adolescents, and adults. METHODS:We identified a population of healthy individuals using the 1999 to 2004 cycles of the National Health and Nutrition Examination Survey (NHANES). We measured serum NT-proBNP in 12 346 adults and 15 752 children and adolescents with the Elecsys NT-proBNP assay on the Roche e601 autoanalyzer. We compared 4 methods for reference interval calculation, and presented the final reference intervals using the robust method partitioned by age and sex categories. RESULTS:NT-proBNP values were available for 1949 healthy adults and 5250 healthy children and adolescents. NT-proBNP concentrations in males and females varied according to age, being higher in early childhood, relatively lower in late adolescence, and highest through middle age and older age. Females tended to have higher NT-proBNP concentrations compared to men from late adolescence until middle age. The upper reference limit, or 97.5th percentile, for 50 to 59 year-old men was 225 ng/L (90% CI: 158 to 236), and for 50 to 59 year-old women, 292 ng/L (90% CI: 242 to 348). CONCLUSIONS:Among healthy individuals, NT-proBNP concentrations varied greatly according age and sex. The reference intervals presented here should inform future clinical decision limits and suggest that age- and sex-specific intervals may be necessary to more precisely characterize risk.

BACKGROUND:Myocardial injury is an important pediatric diagnosis. Establishing normative data from a representative pediatric sample is vital to provide accurate upper reference limits (URLs) for defining myocardial injury using high-sensitivity cardiac troponin. METHODS:Among participants 1 to 18 years of age in the 1999-2004 National Health and Nutrition Examination Survey, we measured high-sensitivity troponin T using one assay (Roche) and high-sensitivity troponin I using 3 assays (Abbott, Siemens, and Ortho). In a strictly defined healthy subgroup, we estimated 97.5th and 99th percentile URLs for each assay using the recommended nonparametric method. RESULTS:Of 5695 pediatric participants, 4029 met criteria for the healthy subgroup (50% males; mean age 12.6 years). Our 99th percentile URL estimates for all 4 high-sensitivity troponin assays among children and adolescents were lower than the manufacturer-reported URLs (derived from adults). The 99th percentile URLs (95% CI) were 15 ng/L (95% CI, 12-17) for high-sensitivity troponin T, 16 ng/L (95% CI, 12-19) for high-sensitivity troponin I with the Abbott assay, 38 ng/L (95% CI, 25-46) for high-sensitivity troponin I with the Siemens assay, and 7 ng/L (95% CI, 5, 12) for high-sensitivity troponin I with the Ortho assay. The 95% CIs for age-, sex-, and race and ethnicity-specific 99th percentile URLs overlapped. However, the 97.5th percentile URL for each assay was measured with superior statistical precision (ie, tighter 95% CIs) and demonstrated differences by sex. For male compared with female children and adolescents, 97.5th percentile URLs were 11 ng/L (95% CI, 10-12) versus 6 ng/L (95% CI, 6-7) for high-sensitivity troponin T, 9 ng/L (95% CI, 7-10) versus 5 ng/L (95% CI, 4-6) for high-sensitivity troponin I with the Abbott assay, 21 ng/L (95% CI, 18-25) versus 11 ng/L (95% CI, 9-13) for high-sensitivity troponin I with the Siemens assay, and 4 ng/L (95% CI, 3-5) versus 2 ng/L (95% CI, 1-3) for high-sensitivity troponin I with the Ortho assay. In contrast to the 99th percentiles, the point estimates of 97.5th percentile pediatric URLs for high-sensitivity troponin were also much more stable to differences in the analytic approaches taken to estimate URLs. CONCLUSIONS:Because myocardial infarction is rare in children and adolescents, the use of statistically more precise and reliable sex-specific 97.5th percentile high-sensitivity troponin URLs might be considered to define pediatric myocardial injury.