Faculty Bibliography

IMPORTANCE:Vascular risk factors have been associated with cognitive decline. Midlife exposure to these factors may be most important in conferring late-life risk of cognitive impairment. OBJECTIVES:To examine Atherosclerosis Risk in Communities (ARIC) participants in midlife and to explore associations between midlife vascular risk factors and 25-year dementia incidence. DESIGN, SETTING, AND PARTICIPANTS:This prospective cohort investigation of the Atherosclerosis Risk in Communities (ARIC) Study was conducted from 1987-1989 through 2011-2013. The dates of this analysis were April 2015 through August 2016. The setting was ARIC field centers (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). The study comprised 15 744 participants (of whom 27.1% were black and 72.9% white) who were aged 44 to 66 years at baseline. MAIN OUTCOMES AND MEASURES:Demographic and vascular risk factors were measured at baseline (obesity, smoking, diabetes, prehypertension, hypertension, and hypercholesterolemia) as well as presence of the APOE ε4 genotype. After the baseline visit, participants had 4 additional in-person visits, for a total of 5 in-person visits, hospitalization surveillance, telephone calls, and repeated cognitive evaluations. Most recently, in 2011-2013, through the ARIC Neurocognitive Study (ARIC-NCS), participants underwent a detailed neurocognitive battery, informant interviews, and adjudicated review to define dementia cases. Additional cases were identified through the Telephone Interview for Cognitive Status-Modified or informant interview, for participants not attending the ARIC-NCS visit, or by an International Classification of Diseases, Ninth Revision dementia code during a hospitalization. Fully adjusted Cox proportional hazards regression was used to evaluate associations of baseline vascular and demographic risk factors with dementia. RESULTS:In total, 1516 cases of dementia (57.0% female and 34.9% black, with a mean [SD] age at visit 1 of 57.4 [5.2] years) were identified among 15 744 participants. Black race (hazard ratio [HR], 1.36; 95% CI, 1.21-1.54), older age (HR, 8.06; 95% CI, 6.69-9.72 for participants aged 60-66 years), lower educational attainment (HR, 1.61; 95% CI, 1.28-2.03 for less than a high school education), and APOE ε4 genotype (HR, 1.98; 95% CI, 1.78-2.21) were associated with increased risk of dementia, as were midlife smoking (HR, 1.41; 95% CI, 1.23-1.61), diabetes (HR, 1.77; 95% CI, 1.53-2.04), prehypertension (HR, 1.31; 95% CI, 1.14-1.51), and hypertension (HR, 1.39; 95% CI, 1.22-1.59). The HR for dementia for diabetes was almost as high as that for APOE ε4 genotype. CONCLUSIONS AND RELEVANCE:Midlife vascular risk factors are associated with increased risk of dementia in black and white ARIC Study participants. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.

BACKGROUND: There are limited data about the extent of DSM-5 substance use disorders (SUDs) among primary care patients. METHODS: This study analyzed data from a multisite validation study of a substance use screening instrument conducted in a diverse sample of 2000 adults aged >/=18 years recruited from five primary care practices in four states. Prevalence and correlates of 12-month DSM-5 SUDs were examined. RESULTS: Overall, 75.5% of the sample used any substance, including alcohol (62.0%), tobacco (44.1%), or illicit drugs/nonmedical medications (27.9%) in the past 12 months (marijuana 20.8%, cocaine 7.3%, opioids 4.8%, sedatives 4.1%, heroin 3.9%). The prevalence of any 12-month SUD was 36.0% (mild disorder 14.2%, moderate/severe disorder 21.8%): tobacco 25.3% (mild 11.5%, moderate/severe 13.8%); alcohol 13.9% (mild 6.9%, moderate/severe 7.0%); and any illicit/nonmedical drug 14.0% (mild 4.0%, moderate/severe 10.0%). Among past 12-month users, a high proportion of tobacco or drug users met criteria for a disorder: tobacco use disorder 57.4% (26.1% mild, 31.3% moderate/severe) and any drug use disorder 50.2% (14.3% mild, 35.8% moderate/severe); a lower proportion of alcohol users (22.4%) met criteria for alcohol use disorder (11.1% mild, 11.3% moderate/severe). Over 80% of adults with opioid/heroin use disorder met criteria for a moderate/severe disorder. Younger ages, male sex, and low education were associated with increased odds of having SUD. CONCLUSION: These findings reveal the high prevalence of SUDs in primary care and underscore the need to identify and address them.

The health of people ever incarcerated in New York City (NYC) jails during 2001 to 2005 was characterized by matching jail, shelter, mortality, sexually transmitted infection, HIV, and tuberculosis (TB) data from the NYC Departments of Health and Mental Hygiene, Correction, and Homeless Services. Compared with nonincarcerated people and those living in the lowest income NYC neighborhoods, those ever incarcerated had higher HIV prevalence and HIV case rates. Ever-incarcerated females also had higher rates of gonorrhea and syphilis than nonincarcerated females. Ever-incarcerated people who used the single adult homeless shelter system had higher HIV, gonorrhea, and TB case rates and all-cause mortality rates than ever-incarcerated people without shelter use, when adjusting for other variables. People ever incarcerated in NYC jails are at risk for conditions of public health importance. Sex-specific jail- and community-based interventions are needed.

Background: The United Arab Emirates (UAE) is experiencing increasing rates of obesity, type 2 diabetes (T2D) and its complications. We tested if soluble levels of cell surface-cleaved RAGE (sRAGE) or endogenous secretory RAGE (esRAGE), the product of alternative mRNA splicing of AGER, are associated with T2D and obesity in the UAE.
Method(s): A case-control study was performed in the Diabetes, Endocrinology and General Medical Clinics of the Sheikh Khalifa Medical City in Abu Dhabi. 216 T2D subjects and 215 controls (mean age 57.4+/-12.1 vs. 50.7+/-15.4 years, respectively) were enrolled. Plasma sRAGE and esRAGE levels, anthropomorphic characteristics and routine chemistries were measured. The relationship between sRAGE and esRAGE with obesity and T2D status was tested using a linear regression model.
Result(s): Univariate analyses comparing T2D case and control subjects revealed differences in sRAGE (1,033+/-545.3 vs. 1,169+/-664.1 pg/ml, respectively; p=0.02) but not esRAGE. Covariate adjustment revealed that differences in sRAGE were significant after correction for age and sex and additionally for waist-hip ratio (WHR); total cholesterol (TC), HDL; hsCRP; Vit D; or triglyceride (TG) levels separately. In cases or controls, we tested associations of body mass index (BMI) or WHR with sRAGE and esRAGE. In controls but not T2D cases, sRAGE and esRAGE were significantly associated with BMI, after correction for age and sex and additionally for eGFR; blood pressure; TC, HDL; hsCRP; Vit D; creatinine; TG and HbA1c in a combined model. In the case of WHR, in controls and T2D cases, there were no associations with sRAGE, but only in T2D cases, WHR was associated with esRAGE after correction for age and sex and blood pressure; TC, HDL; hsCRP, HbA1c, creatinine; TG, eGFR, Vit D and TG in a combined model.
Conclusion(s): Levels of sRAGE but not esRAGE distinguish T2D case vs. controls in the UAE population. Genetic and unique obesity-dependent factors may underlie lack of association between esRAGE in cases vs. controls, which may affect vulnerability to T2D and its complications in the UAE

Chronic kidney disease (CKD) is a major global public health problem with significant gaps in research, care, and policy. In order to mitigate the risks and adverse effects of CKD, the International Society of Nephrology has created a cohesive set of activities to improve the global outcomes of people living with CKD. Improving monitoring of renal disease progression can be done by screening and monitoring albuminuria and estimated glomerular filtration rate in primary care. Consensus on how many times and how often albuminuria and estimated glomerular filtration rate are measured should be defined. Meaningful changes in both renal biomarkers should be determined in order to ascertain what is clinically relevant. Increasing social awareness of CKD and partnering with the technological community may be ways to engage patients. Furthermore, improving the prediction of cardiovascular events in patients with CKD can be achieved by including the renal risk markers albuminuria and estimated glomerular filtration rate in cardiovascular risk algorithms and by encouraging uptake of assessing cardiovascular risk by general practitioners and nephrologists. Finally, examining ways to further validate and implement novel biomarkers for CKD will help mitigate the global problem of CKD. The more frequent use of renal biopsy will facilitate further knowledge into the underlying etiologies of CKD and help put new biomarkers into biological context. Real-world assessments of these biomarkers in existing cohorts is important, as well as obtaining regulatory approval to use these biomarkers in clinical practice. Collaborations among academia, physician and patient groups, industry, payer organizations, and regulatory authorities will help improve the global outcomes of people living with CKD.

Concerns persist that individuals with substance use disorders who are under community criminal justice supervision experience circumstances that might compromise their provision of valid, informed consent for research participation. These concerns include the possibilities that desire to obtain access to treatment might lead individuals to ignore important information about research participation, including information about risks, or that cognitive impairment associated with substance use might interfere with attending to important information. We report results from a consent quiz (CQ) administered in a multisite randomized clinical trial of long-acting naltrexone to prevent relapse to opioid use disorder among adults under community criminal justice supervision-a treatment option difficult to access by this population of individuals. Participants were required to answer all 11 items correctly before randomization. On average, participants answered 9.8 items correctly (89%) at baseline first attempt (n=306). At week 21 (n=212), participants scored 87% (9.5 items correct) without review. Performance was equivalent to, or better than, published results from other populations on a basic consent quiz instrument across multiple content domains. The consent quiz is an efficient method to screen for adequate knowledge of consent information as part of the informed consent process. Clinical researchers who are concerned about these issues should consider using a consent quiz with corrected feedback to enhance the informed consent process. Overall, while primarily useful as an educational tool, employing a CQ as part of the gateway to participation in research may be particularly important as the field continues to advance and tests novel experimental treatments with significant risks and uncertain potential for benefit.