Faculty Bibliography

AIMS:To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers. METHODS:We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics. RESULTS:Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [β-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%). CONCLUSIONS:These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications.

Expression of plasminogen activator inhibitor (PAI)-1, the major physiological inhibitor of fibrinolysis, is increased in the lung following inhalation of ozone (O3), a gaseous air pollutant. PAI-1 regulates expression of interleukin (IL)-6, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-2, which are cytokines that promote lung injury, pulmonary inflammation, and/or airway hyperresponsiveness following acute exposure to O3 Given these observations, we hypothesized that PAI-1 contributes to the severity of the aforementioned sequelae by regulating expression of IL-6, KC, and MIP-2 following acute exposure to O3 To test our hypothesis, wild-type mice and mice genetically deficient in PAI-1 (PAI-1-deficient mice) were acutely exposed to either filtered room air or O3 (2 ppm) for 3 h. Four and/or twenty-four hours following cessation of exposure, indices of lung injury [bronchoalveolar lavage fluid (BALF) protein and epithelial cells], pulmonary inflammation (BALF IL-6, KC, MIP-2, macrophages, and neutrophils), and airway responsiveness to aerosolized acetyl-beta-methylcholine chloride (respiratory system resistance) were measured in wild-type and PAI-1-deficient mice. O3 significantly increased indices of lung injury, pulmonary inflammation, and airway responsiveness in wild-type and PAI-1-deficient mice. With the exception of MIP-2, which was significantly lower in PAI-1-deficient as compared to wild-type mice 24 h following cessation of exposure to O3, no other genotype-related differences occurred subsequent to O3 exposure. Thus, following acute exposure to O3, PAI-1 neither regulates pulmonary expression of IL-6 and KC nor functionally contributes to any of the pulmonary pathological sequelae that arise from the noxious effects of inhaled O3.

PURPOSE:The development of a sustainable pediatric diabetes surveillance system for the United States requires a better understanding of issues related to case ascertainment. METHODS:Using the SEARCH for Diabetes in Youth registry, we examined whether time from diabetes diagnosis to case registration differed by diabetes type, patient demographics, and the type of provider reporting the case to the study. Plots for time from diagnosis to registration were developed, and differences by key variables were examined using the log-rank test. RESULTS:Compared with time to registration for type 1 cases, it took 2.6 (95% confidence interval [CI], 2.5-2.6) times longer to register 50% of type 2 diabetes cases, and 2.3 (95% CI, 2.0-2.5) times longer to register 90% of type 2 cases. For type 1 diabetes cases, a longer time to registration was associated with older age, minority race/ethnicity, and cases, where the referring provider was not an endocrinologist. For type 2 diabetes cases, older age, non-Hispanic white race/ethnicity, and cases reported by providers other than an endocrinologist took longer to identify and register. CONCLUSIONS:These findings highlight the need for continued childhood diabetes surveillance to identify future trends and influences on changes in prevalence and incidence.

AIMS: To identify population characteristics associated with local variation in the prevalence of diabetic complications and compare the geographic distribution of different types of complications in New York City. METHODS: Using an all-payer database of emergency visits, we identified the proportion of unique adults with diabetes who also had cardiac, neurologic, renal and lower extremity complications. We performed multivariable regression to identify associations of demographic and socioeconomic factors, and diabetes-specific emergency department use with the prevalence of diabetic complications by Census tract. We also used geospatial analysis to compare local hotspots of diabetic complications. RESULTS: We identified 4.6million unique New York City adults, of which 10.5% had diabetes. Adjusting for demographic and socioeconomic factors, diabetes-specific emergency department use was associated with severe microvascular renal and lower extremity complications (p-values<0.001), but not with severe macrovascular cardiac or neurologic complications (p-values of 0.39 and 0.29). Our hotspot analysis demonstrated significant geographic heterogeneity in the prevalence of diabetic complications depending on the type of complication. Notably, the geographic distribution of hotspots of myocardial infarction were inversely correlated with hotspots of end-stage renal disease and lower extremity amputations (coefficients: -0.28 and -0.28). CONCLUSIONS: We found differences in the local geographic distribution of diabetic complications, which highlight the contrasting risk factors for developing macrovascular versus microvascular diabetic complications. Based on our analysis, we also found that high diabetes-specific emergency department use was correlated with poor diabetic outcomes. Emergency department utilization data can help identify the location of specific populations with poor glycemic control.

Clinical Practice Guidelines for Treating Tobacco Use and Dependence advocate for using counseling targeted at tobacco users' motivation to quit during each office visit. We evaluate tobacco use screening and counseling interventions delivered during routine periodic health examinations by 44 adult primary care physicians practicing in 22 clinics of a large health system in southeast Michigan. 484 office visits were audio-recorded and transcribed. For this study, current tobacco users (N = 91) were identified using pre-visit surveys and audio-recordings. Transcripts were coded for the delivery of tobacco-related counseling interventions. The extent to which counseling interventions were used and/or targeted to the patients' readiness to quit was the main outcome measure. The majority of tobacco users (n = 77) had their tobacco use status assessed, and most received some sort of tobacco-related counseling (n = 74). However, only 15% received the recommended counseling targeted to their readiness to quit. On the other hand, 19% received less counseling than recommended given their readiness to quit, 7% received only nonindicated counseling, and 59% received nonindicated counseling in addition to indicated counseling. Results illustrate physicians' commitment to cessation counseling and also identify potential opportunities to improve the efficiency of tobacco-related counseling in primary care.

Within a population-based study of 3356 children, we investigated whether infant neuromotor development was associated with cognition in early childhood. Neuromotor development was examined with an adapted version of Touwen's Neurodevelopmental Examination between 9 and 20 weeks. Parents rated their children's executive functioning at 4 years. At age 6 years, children performed intelligence and language comprehension tests, using Dutch test batteries. At age 6-9 years, neuropsychological functioning was assessed in 486 children using the validated NEPSY-II-NL test battery. We showed that less optimal neurodevelopment in infancy may predict poor mental rotation, immediate memory, shifting, and planning; but not nonverbal intelligence or language comprehension.

Given changing demographics, patients with cardiovascular (CV) disease in developed countries are now older and more complex than even a decade ago. This trend is expected to continue into the foreseeable future; accordingly, cardiologists are encountering patients with a greater number of comorbid illnesses as well as "geriatric conditions," such as cognitive impairment and frailty, which complicate management and influence outcomes. Simultaneously, technological advances have widened the therapeutic options available for patients, including those with the most advanced CV disease. In the setting of these changes, geriatric cardiology has recently emerged as a discipline that aims to adapt principles from geriatric medicine to everyday cardiology practice. Accordingly, the tasks of a "geriatric cardiologist" may include both traditional evidence-based CV management plus comprehensive geriatric assessment, medication reduction, team-based coordination of care, and explicit incorporation of patient goals into management. Given that the field is still in its relative infancy, the training pathways and structure of clinical programs in geriatric cardiology are still being delineated. In this review, we highlight the rationale behind geriatric cardiology as a discipline, several current approaches by geriatric cardiology programs, and future directions for the field.

INTRODUCTION: For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays.Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification.Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized.This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies. METHODS: The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients.Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX. RESULTS: The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase.Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms).Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness. CONCLUSIONS: XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance.Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed. CLINICAL TRIAL REGISTRATION: NCT02032433.

OBJECTIVE: Longitudinal assessment of lower respiratory symptoms (LRS) in community members with World Trade Center (WTC) exposures. METHODS: Adult members of a treatment program with complete standardized visits were evaluated (n = 798). Association of demographic characteristics, mental health symptoms and lung function with trajectory of LRS between initial and monitoring visit was evaluated. RESULTS: Severe LRS were present in 70% at initial and 63% at monitoring visit. Initial severe LRS were associated with WTC dust cloud exposure and mental health symptoms. Spirometry measures were not associated with LRS severity or trajectory; improvement in LRS was associated with improved lung function measured with forced oscillometry techniques. CONCLUSION: Many community patients in a WTC treatment program had severe LRS associated with exposures and mental health symptoms. Improvement in LRS was associated with improvement in measures of small airway function. Am. J. Ind. Med. 59:777-787, 2016. (c) 2016 Wiley Periodicals, Inc.