Faculty Bibliography

BACKGROUND:A common belief is that one quarter to one third of all diabetes cases remain undiagnosed. However, such prevalence estimates may be overstated by epidemiologic studies that do not use confirmatory testing, as recommended by clinical diagnostic criteria. OBJECTIVE:To provide national estimates of undiagnosed diabetes by using a confirmatory testing strategy, in line with clinical practice guidelines. DESIGN/METHODS:Cross-sectional study. SETTING/METHODS:National Health and Nutrition Examination Survey results from 1988 to 1994 and 1999 to 2014. PARTICIPANTS/METHODS:U.S. adults aged 20 years and older. MEASUREMENTS/METHODS:Confirmed undiagnosed diabetes was defined as elevated levels of fasting glucose (≥7.0 mmol/L [≥126 mg/dL]) and hemoglobin A1c (≥6.5%) in persons without diagnosed diabetes. RESULTS:The prevalence of total (diagnosed plus confirmed undiagnosed) diabetes increased from 5.5% (9.7 million adults) in 1988 to 1994 to 10.8% (25.5 million adults) in 2011 to 2014. Confirmed undiagnosed diabetes increased during the past 2 decades (from 0.89% in 1988 to 1994 to 1.2% in 2011 to 2014) but has decreased over time as a proportion of total diabetes cases. In 1988 to 1994, the percentage of total diabetes cases that were undiagnosed was 16.3%; by 2011 to 2014, this estimate had decreased to 10.9%. Undiagnosed diabetes was more common in overweight or obese adults, older adults, racial/ethnic minorities (including Asian Americans), and persons lacking health insurance or access to health care. LIMITATION/CONCLUSIONS:Cross-sectional design. CONCLUSION/CONCLUSIONS:Establishing the burden of undiagnosed diabetes is critical to monitoring public health efforts related to screening and diagnosis. When a confirmatory definition is used, undiagnosed diabetes is a relatively small fraction of the total diabetes population; most U.S. adults with diabetes (about 90%) have received a diagnosis of the condition. PRIMARY FUNDING SOURCE/BACKGROUND:National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and National Heart, Lung, and Blood Institute.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS/RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500.

Background: Consistent evidence at high levels of water arsenic (>/=100 microg/l), and growing evidence at low-moderate levels (<100 microg/l), support a link with cardiovascular disease (CVD). The shape of the dose-response across low-moderate and high levels of arsenic in drinking water is uncertain and critical for risk assessment. Methods: We conducted a systematic review of general population epidemiological studies of arsenic and incident clinical CVD (all CVD, coronary heart disease (CHD) and stroke) with three or more exposure categories. In a dose-response meta-analysis, we estimated the pooled association between log-transformed water arsenic (log-linear) and restricted cubic splines of log-transformed water arsenic (non-linear) and the relative risk of each CVD endpoint. Results: Twelve studies (pooled N = 408 945) conducted at high ( N = 7) and low-moderate ( N = 5) levels of water arsenic met inclusion criteria, and 11 studies were included in the meta-analysis. Compared with 10 microg/l, the estimated pooled relative risks [95% confidence interval (CI)] for 20 microg/l water arsenic, based on a log-linear model, were 1.09 (1.03, 1.14) ( N = 2) for CVD incidence, 1.07 (1.01, 1.14) ( N = 6) for CVD mortality, 1.11 (1.05, 1.17) ( N = 4) for CHD incidence, 1.16 (1.07, 1.26) ( N = 6) for CHD mortality, 1.08 (0.99, 1.17) ( N = 2) for stroke incidence and 1.06 (0.93, 1.20) ( N = 6) for stroke mortality. We found no evidence of non-linearity, although these tests had low statistical power. Conclusions: Although limited by the small number of studies, this analysis supports quantitatively including CVD in inorganic arsenic risk assessment, and strengthens the evidence for an association between arsenic and CVD across low-moderate to high levels.

OBJECTIVE:This study evaluated the impact of an integrated behavioral health home (BHH) pilot on adults with psychotic and bipolar disorders. METHODS:Quasi-experimental methods were used to compare outcomes before (September 2014-August 2015) and after the intervention (September 2015-August 2016) among ambulatory BHH patients and a control group. Electronic health records were compared between 424 BHH patients (N=369, psychotic disorder; N=55, bipolar disorder) and 1,521 individuals from the same urban, safety-net health system who were not enrolled in the BHH. Groups were weighted by propensity score on the basis of sex, age, race-ethnicity, language, 2010 U.S. Census block group characteristics, Medicare and Medicaid enrollment, and diabetes diagnosis. RESULTS:BHH patients had fewer total psychiatric hospitalizations and fewer total emergency visits compared with the control group, a difference that was predominantly driven by patients with at least one psychiatric hospitalization or ED visit. There were no differences in medical hospitalizations. Although BHH patients were more likely to receive HbA1c screening, there were no differences between the groups in lipid monitoring. Regarding secondary outcomes, there were no significant differences in changes in metabolic monitoring parameters among patients with diabetes. CONCLUSIONS:Participation in a pilot ambulatory BHH program among patients with psychotic and bipolar disorders was associated with significant reductions in ED visits and psychiatric hospitalizations and increased HbA1c monitoring. This evaluation builds on prior research by specifying intervention details and the clinical target population, strengthening the evidence base for care integration to support further program dissemination.

BACKGROUND: Ecstasy/MDMA has been one of the most prevalent party drugs for decades, and powder ecstasy recently increased in popularity. We examined trends in use to determine who to best target for prevention and harm reduction. METHODS: Secondary analysis of the 2007-2014 National Survey on Drug Use and Health, a repeated cross-sectional, nationally representative probability sample, was conducted. Linear trends in past-year ecstasy use and trends in demographic and other past-year substance use characteristics among ecstasy users were examined among participants ages 12-34 (N=332,560). RESULTS: Past-year prevalence of ecstasy use was stable across years at 2% (P=0.693). Over time, the proportion of ecstasy users with a college degree increased from 11.5% in 2007/08 to 24.5% in 2013/14 (P<0.001). The proportion of users who were age 12-17 decreased, as did proportions of users who are non-Hispanic black, and reported income <$20,000/year (Ps<0.001). Prevalence of past-year use of marijuana, LSD, ketamine, and DMT/AMT/Foxy increased among ecstasy users (Ps<0.05); DMT/AMT/Foxy use increased more than four-fold from 2.1% in 2007/08 to 8.7% in 2013/14. Perception of great risk associated with LSD use decreased among users and ease of obtaining LSD increased (Ps<0.05). Past-year use of 5 or more other substances also increased over time (P<0.05). CONCLUSIONS: Ecstasy use in the US appears to be increasing among those with college degrees and use of other substances among ecstasy users is growing-particularly use of otherwise rare substances such as tryptamines. Results inform prevention and harm reduction strategies in this increasingly shifting group of ecstasy users.

Context:Mineral and bone disorders (MBDs) might be relevant in the etiology of infection. Objective:To determine whether MBD biomarkers were associated with the incidence of hospitalization with infection. We also assessed the cross-sectional association between MBD biomarker levels and kidney function. Design, Setting, Participants:Community-based cohort study of 11,218 participants with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 in the Atherosclerosis Risk in Communities study. We assessed the cross-sectional associations of five MBD markers-fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), calcium corrected for hypoalbuminemia, and phosphorus-with eGFR from 1990 to 1992 and their longitudinal associations with incident hospitalization with infection in 1990 to 2013. Main Outcome:Incident hospitalization with infection. Results:In age-, sex-, and race-adjusted models, lower eGFRs were significantly associated with greater levels of FGF23, PTH, and corrected calcium but not 25(OH)D or phosphorus. During follow-up, 5078 hospitalizations with infection occurred. In fully adjusted Cox models, with the second quartile as the reference, the hazard ratio (HR) was significantly greater in the highest quartile of FGF23 [HR, 1.12; 95% confidence interval (CI), 1.03 to 1.21], PTH (HR, 1.09; 95% CI, 1.01 to 1.18), and corrected calcium (HR, 1.11; 95% CI, 1.03 to 1.20), and lowest quartile for 25(OH)D (HR, 1.11; 95% CI, 1.03 to 1.21). The association with phosphorus was significant only when the outcome was restricted to primary diagnosis of infection. These findings were consistent across subgroups of age, sex, race, and eGFR (<60 vs ≥60 mL/min/1.73 m2). Conclusions:MBD biomarkers were associated with eGFR and the subsequent risk of infection, supporting MBD involvement in the etiology of infection.

BACKGROUND: Amphetamine is the most prevalent prescription stimulant in the United States, both medically and nonmedically. Reliable data on nonmedical use is needed to continue to inform prevention. To determine whether adolescents accurately self-report nonmedical amphetamine use, we compared self-reports of nonmedical amphetamine use and nonmedical Adderall use in a national sample. METHODS: We examined self-reported nonmedical Adderall and amphetamine use in a nationally representative sample of 24,740 high school seniors in the Monitoring the Future study (2010-2015). We examined prevalence and correlates of discordant responses among past-year Adderall users, defined as reporting past-year nonmedical Adderall use, but not reporting past-year nonmedical amphetamine use. RESULTS: While 6.9% reported nonmedical Adderall use and 7.9% reported nonmedical amphetamine use, over a quarter (28.7%) of Adderall users reported no amphetamine use. Those at highest risk for Adderall use tended to be at lower odds of providing a discordant response. Older students (aged >/=18), black students, and those with parents of lower educational attainment were more likely to report no amphetamine use, despite reporting Adderall use. Lifetime use of various drugs was associated with decreased odds of providing a discordant response; however, only nonmedical opioid use was associated with significant decreased odds in multivariable models. Disapproval towards amphetamine use increased odds of providing a discordant response, while higher exposure to users decreased odds of providing a discordant response. CONCLUSION: Prevalence of nonmedical amphetamine use may be underreported on some surveys, particularly among specific subpopulations. Future surveys must ensure accurate and consistent responses.

BACKGROUND: Despite reductions in youth pedestrian and bicyclist deaths over the past two decades, these injuries remain a substantial cause of morbidity and mortality for children and adolescents. There is a need for additional information on non-fatal pediatric pedestrian injuries and the role of traumatic brain injury (TBI), a leading cause of acquired disability. METHODS: Using a multi-year national sample of emergency department (ED) records, we estimated annual motorized-vehicle related pediatric pedestrian and bicyclist (i.e. pedalcyclist) injury rates by age and region. We modeled in-hospital fatality risk controlling for age, gender, injury severity, TBI, and trauma center status. RESULTS: ED visits for pediatric pedestrian injuries declined 19.3% (95% CI 16.8, 21.8) from 2006 to 2012, with the largest decreases in 5-to-9 year olds and 10-to-14 year olds. Case fatality rates also declined 14.0%. There was no significant change in bicyclist injury rates. TBI was implicated in 6.7% (95% CI 6.3, 7.1) of all pedestrian and bicyclist injuries and 55.5% (95% CI 27.9, 83.1) of fatalities. Pedestrian ED visits were more likely to be fatal than bicyclist injuries (aOR = 2.4, 95% CI 2.3, 2.6), with significant additive interaction between pedestrian status and TBI. CONCLUSIONS: TBI in young pedestrian ED patients was associated with a higher risk of mortality compared to cyclists. There is a role for concurrent clinical focus on TBI recovery alongside ongoing efforts to mitigate and prevent motor vehicle crashes with pedestrians and bicyclists. Differences between youth pedestrian and cycling injury trends merit further exploration and localized analyses, with respect to behavior patterns and interventions. ED data captures a substantially larger number of pediatric pedestrian injuries compared to crash reports and can play a role in those analyses.

Creatinine-based glomerular filtration rate estimation (eGFR_cr) has been improved and refined since the 1970s through both the Modification of Diet in Renal Disease (MDRD) Study equation in 1999 and the CKD Epidemiology Collaboration (CKD-EPI) equation in 2009, with current clinical practice dependent primarily on eGFR for accurate assessment of GFR. However, researchers and clinicians have recognized limitations of relying on creatinine as the only filtration marker, which can lead to inaccurate GFR estimates in certain populations due to the influence of non-GFR determinants of serum or plasma creatinine. Therefore, recent literature has proposed incorporation of multiple serum or plasma filtration markers into GFR estimation to improve precision and accuracy and decrease the impact of non-GFR determinants for any individual biomarker. To this end, the CKD-EPI combined creatinine-cystatin C equation (eGFR_cr-cys) was developed in 2012 and demonstrated superior accuracy to equations relying on creatinine or cystatin C alone (eGFR_cr or eGFR_cys). Now, the focus has broadened to include additional novel filtration markers to further refine and improve GFR estimation. Beta-2-microglobulin (B2M) and beta-trace-protein (BTP) are two filtration markers with established assays that have been proposed as candidates for improving both GFR estimation and risk prediction. GFR estimating equations based on B2M and BTP have been developed and validated, with the CKD-EPI combined BTP-B2M equation (eGFR_BTP-B2M) demonstrating similar performance to eGFR and eGFR. Additionally, several studies have demonstrated that both B2M and BTP are associated with outcomes in CKD patients, including cardiovascular events, ESRD and mortality. This review will primarily focus on these two biomarkers, and will highlight efforts to identify additional candidate biomarkers through metabolomics-based approaches.