Faculty Bibliography

OBJECTIVE:We compared levels and associations of traditional (fasting glucose, HbA1c) and nontraditional (fructosamine, glycated albumin, and 1,5-anhydroglucitol [1,5-AG]) biomarkers of hyperglycemia with incident cardiovascular disease (CVD), incident end-stage renal disease (ESRD), and prevalent retinopathy in black and white adults. RESEARCH DESIGN AND METHODS:We included 10,373 participants without (8,096 white, 2,277 black) and 727 with diagnosed diabetes (425 white, 302 black) from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox proportional hazards models to compare hazards ratios of CVD and ESRD among blacks and whites from baseline (1990-1992) through 2012. We compared the odds ratios (from logistic regression) of retinopathy among blacks and whites. We tested for the interaction of each biomarker with race. RESULTS:Median values of biomarkers were higher among blacks versus whites (all P < 0.001). Relative risks for each biomarker with incident CVD and ESRD, and odds ratios for each biomarker with prevalent retinopathy, were similar by race (all P values for interaction by race >0.10). CONCLUSIONS:The prognostic value of HbA1c, fructosamine, glycated albumin, and 1,5-AG with incident CVD, incident ESRD, and prevalent retinopathy were similar by race. Our results support similar interpretation of HbA1c and nontraditional biomarkers of hyperglycemia among black and whites with respect to long-term complications.

BACKGROUND:It is unclear whether traditional and genetic risk factors in middle age predict the onset of gout in older age. METHODS:We studied the incidence of gout in older adults using the Atherosclerosis Risk in Communities study, a prospective U.S. population-based cohort of middle-aged adults enrolled between 1987 and 1989 with ongoing follow-up. A genetic urate score was formed from common urate-associated single nucleotide polymorphisms for eight genes. The adjusted hazard ratio and 95% confidence interval of incident gout by traditional and genetic risk factors in middle age were estimated using a Cox proportional hazards model. RESULTS:The cumulative incidence from middle age to age 65 was 8.6% in men and 2.5% in women; by age 75 the cumulative incidence was 11.8% and 5.0%. In middle age, increased adiposity, beer intake, protein intake, smoking status, hypertension, diuretic use, and kidney function (but not sex) were associated with an increased gout risk in older age. In addition, a 100 µmol/L increase in genetic urate score was associated with a 3.29-fold (95% confidence interval: 1.63-6.63) increased gout risk in older age. CONCLUSIONS:These findings suggest that traditional and genetic risk factors in middle age may be useful for identifying those at risk of gout in older age.

Small molecules are extensively metabolized and cleared by the kidney. Changes in serum metabolite concentrations may result from impaired kidney function and can be used to estimate filtration (e.g., the established marker creatinine) or may precede and potentially contribute to CKD development. Here, we applied a nontargeted metabolomics approach using gas and liquid chromatography coupled to mass spectrometry to quantify 493 small molecules in human serum. The associations of these molecules with GFR estimated on the basis of creatinine (eGFRcr) and cystatin C levels were assessed in ≤1735 participants in the KORA F4 study, followed by replication in 1164 individuals in the TwinsUK registry. After correction for multiple testing, 54 replicated metabolites significantly associated with eGFRcr, and six of these showed pairwise correlation (r≥0.50) with established kidney function measures: C-mannosyltryptophan, pseudouridine, N-acetylalanine, erythronate, myo-inositol, and N-acetylcarnosine. Higher C-mannosyltryptophan, pseudouridine, and O-sulfo-L-tyrosine concentrations associated with incident CKD (eGFRcr <60 ml/min per 1.73 m(2)) in the KORA F4 study. In contrast with serum creatinine, C-mannosyltryptophan and pseudouridine concentrations showed little dependence on sex. Furthermore, correlation with measured GFR in 200 participants in the AASK study was 0.78 for both C-mannosyltryptophan and pseudouridine concentration, and highly significant associations of both metabolites with incident ESRD disappeared upon adjustment for measured GFR. Thus, these molecules may be alternative or complementary markers of kidney function. In conclusion, our study provides a comprehensive list of kidney function-associated metabolites and highlights potential novel filtration markers that may help to improve the estimation of GFR.

BACKGROUND: Outdoor fine particulate matter (PM2.5) has been identified as a global health threat, but the number of large U.S. prospective cohort studies with individual participant data remains limited, especially at lower recent exposures. OBJECTIVES: To test the relationship between long-term exposure PM2.5 and death risk from all non-accidental causes, cardiovascular (CVD), and respiratory diseases in 517,041 men and women enrolled in the National Institutes of Health-AARP cohort. METHODS: Individual participant data were linked with residence PM2.5 exposure estimates across the continental U.S for a 2000-2009 follow up period when matching census-tract level PM2.5 exposure data were available. Participants enrolled ranged from 50-71 yrs. of age, residing in 6 U.S. States and 2 cities. Cox Proportional Hazard models yielded Hazard Ratio (HR) estimates per 10 microg/m3 of PM2.5 exposure. RESULTS: PM2.5 exposure was significantly associated with total mortality (HR= 1.03, 95% CI =1.00, 1.05) and CVD mortality (HR=1.10, 95% CI=1.05, 1.15), but the association with respiratory mortality was not statistically significant (HR=1.05, 95% CI=0.98,1.13). A significant association was found with respiratory mortality only among never smokers (HR=1.27; 95% CI: 1.03, 1.56). Associations with 10 microg/m3 PM2.5 exposures in yearly participant residential annual mean, or in metropolitan area-wide mean, were consistent with baseline exposure model results. Associations with PM2.5 were similar when adjusted for ozone exposures. Analyses of California residents alone also yielded statistically significant PM2.5 mortality HR's for total and CVD mortality. CONCLUSIONS: Long-term exposure to PM2.5 air pollution was associated with an increased risk of total and CVD mortality, providing an independent test of the PM2.5 - mortality relationship in a new large U.S. prospective cohort experiencing lower post-2000 PM2.5 exposure levels.

This review identifies 10 common errors and problems in the statistical analysis, design, interpretation, and reporting of obesity research and discuss how they can be avoided. The 10 topics are: 1) misinterpretation of statistical significance, 2) inappropriate testing against baseline values, 3) excessive and undisclosed multiple testing and "P-value hacking," 4) mishandling of clustering in cluster randomized trials, 5) misconceptions about nonparametric tests, 6) mishandling of missing data, 7) miscalculation of effect sizes, 8) ignoring regression to the mean, 9) ignoring confirmation bias, and 10) insufficient statistical reporting. It is hoped that discussion of these errors can improve the quality of obesity research by helping researchers to implement proper statistical practice and to know when to seek the help of a statistician.

Hurricane Sandy struck New York City on October 29, 2012, causing not only a large amount of physical damage, but also straining people's health and disrupting health care services throughout the city. In prior research, we determined that emergency department (ED) visits from the most vulnerable hurricane evacuation flood zones in New York City increased after Hurricane Sandy for several medical diagnoses, but also for the diagnosis of homelessness. In the current study, we aimed to further explore this increase in ED visits for homelessness after Hurricane Sandy's landfall. We performed an observational before-and-after study using an all-payer claims database of ED visits in New York City to compare the demographic characteristics, insurance status, geographic distribution, and health conditions of ED patients with a primary or secondary ICD-9 diagnosis of homelessness or inadequate housing in the first week after Hurricane Sandy's landfall versus the baseline weekly average in 2012 prior to Hurricane Sandy. We found statistically significant increases in ED visits for diagnosis codes of homelessness or inadequate housing in the week after Hurricane Sandy's landfall. Those accessing the ED for homelessness or inadequate housing were more often elderly and insured by Medicare after versus before the hurricane. Secondary diagnoses among those with a primary ED diagnosis of homelessness or inadequate housing also differed after versus before Hurricane Sandy. These observed differences in the demographic, insurance, and co-existing diagnosis profiles of those with an ED diagnosis of homelessness or inadequate housing before and after Hurricane Sandy suggest that a new population cohort-potentially including those who had lost their homes as a result of storm damage-was accessing the ED for homelessness or other housing issues after the hurricane. Emergency departments may serve important public health and disaster response roles after a hurricane, particularly for people who are homeless or lack adequate housing. Further, tracking ED visits for homelessness may represent a novel surveillance mechanism to assess post-disaster infrastructure impact and to prepare for future disasters.

INTRODUCTION: People with a mental health diagnosis have high rates of tobacco use and encounter limited availability of tobacco treatment targeted to their needs. This study compared the effectiveness of a specialized telephone smoking-cessation intervention developed for mental health patients with standard state quit-line counseling. DESIGN: RCT. SETTING/PARTICIPANTS: The study was conducted at six Veterans Health Administration facilities in the Northeast U.S. Participants were 577 mental health clinic patients referred by their providers for smoking-cessation treatment. INTERVENTION: From 2010 to 2012, the study implemented a telephone program that included patient referral from a mental health provider, mailed cessation medications, and telephone counseling. Participants were randomized to receive a specialized multisession telephone counseling protocol (n=270) or transfer to their state's quit-line for counseling (n=307). MAIN OUTCOME MEASURES: Participants completed telephone surveys at baseline, 2 months, and 6 months. The study's primary outcome was self-reported 30-day abstinence at 6 months. Secondary outcomes were self-reported 30-day abstinence, counseling satisfaction and counseling content at 2 months, and self-reported use of cessation treatment and quit attempts at 6 months. Logistic regression was used to compare treatment groups on outcomes, controlling for baseline cigarettes per day and site. Inverse probability weighting and multiple imputation were used to handle missing abstinence outcomes. Data were analyzed in 2014-2015. RESULTS: At 6 months, participants in the specialized counseling arm were more likely to report 30-day abstinence (26% vs 18%, OR=1.62, 95% CI=1.24, 2.11). There was no significant group difference in abstinence at 2 months (18% vs 14%, OR=1.31, 95% CI=0.49, 3.49). Participants in the specialized arm were more likely to be assisted with developing a quit plan; receive follow-up calls after quitting; and receive counseling on several domains, including motivation, confidence, smoking triggers, coping with urges, and mental health symptoms (all p<0.05). Specialized counseling participants were more satisfied with treatment and more likely to find the counseling useful (p<0.05). CONCLUSIONS: The specialized counseling intervention was more effective at helping patients quit than transfer to a state quit-line. Patients were more satisfied with the specialized counseling program. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT00724308.

OBJECTIVE: Characterize the onset and timing of cognitive decline in Parkinson disease (PD) from the first recognizable stage of cognitively symptomatic PD-mild cognitive impairment (PD-MCI) to PD dementia (PDD). Thirty-nine participants progressed from PD to PDD and 25 remained cognitively normal. METHODS: Bayesian-estimated disease-state models described the onset of an individual's cognitive decline across 12 subtests with a change point. RESULTS: Subtests measuring working memory, visuospatial processing ability, and crystalized memory changed significantly 3 to 5 years before their first nonzero Clinical Dementia Rating and progressively worsened from PD to PD-MCI to PDD. Crystalized memory deficits were the hallmark feature of imminent conversion of cognitive status. Episodic memory tasks were not sensitive to onset of PD-MCI. For cognitively intact PD, all 12 subtests showed modest linear decline without evidence of a change point. CONCLUSIONS: Longitudinal disease-state models support a prodromal dementia stage (PD-MCI) marked by early declines in working memory and visuospatial processing beginning 5 years before clinical diagnosis of PDD. Cognitive declines in PD affect motor ability (bradykinesia), working memory, and processing speed (bradyphrenia) resulting in PD-MCI where visuospatial imagery and memory retrieval deficits manifest before eventual development of overt dementia. Tests of episodic memory may not be sufficient to detect and quantify cognitive decline in PD.

Child poverty in the United States is widespread and has serious negative effects on the health and well-being of children throughout their life course. Child health providers are considering ways to redesign their practices in order to mitigate the negative effects of poverty on children and support the efforts of families to lift themselves out of poverty. To do so, practices need to adopt effective methods to identify poverty-related social determinants of health and provide effective interventions to address them. Identification of needs can be accomplished with a variety of established screening tools. Interventions may include resource directories, best maintained in collaboration with local/regional public health, community, and/or professional organizations; programs embedded in the practice (eg, Reach Out and Read, Healthy Steps for Young Children, Medical-Legal Partnership, Health Leads); and collaboration with home visiting programs. Changes to health care financing are needed to support the delivery of these enhanced services, and active advocacy by child health providers continues to be important in effecting change. We highlight the ongoing work of the Health Care Delivery Subcommittee of the Academic Pediatric Association Task Force on Child Poverty in defining the ways in which child health care practice can be adapted to improve the approach to addressing child poverty.