Faculty Bibliography

Importance:Predialysis nephrology care is associated with better survival among patients with end-stage kidney disease. Objective:To examine national trends in racial/ethnic disparities in receipt of predialysis nephrology care at least 1 year before dialysis initiation in the United States from 2005 to 2015. Design, Setting, and Participants:This national registry study assessed US registry data of 1 000 390 adults in the US Renal Data System who initiated maintenance dialysis treatment from January 1, 2005, to December 31, 2015, in multiple cross-sectional analyses. Multivariable logistic regression models were used to examine national trends in racial/ethnic disparities in receipt of predialysis nephrology care with adjustments for potential confounders. Data were analyzed April 17, 2020. Exposure:Race/ethnicity of the patients. Main Outcomes and Measures:Receipt of at least 12 months of predialysis nephrology care as determined by clinician-based documentation on the End Stage Renal Disease Medical Evidence Report Form CMS 2728. Results:Among 1 000 390 adults (57.2% male; 54.6% White, 27.8% Black, 14.0% Hispanic, and 3.6% Asian; mean [SD] age, 62.4 [15.6] years) who initiated maintenance dialysis in the United States from 2005 to 2015, 310 743 (31.1%) received at least 12 months of predialysis nephrology care. In 2005 to 2007, compared with White adults, the adjusted odds ratio for receipt of at least 12 months of predialysis nephrology care was 0.82 (95% CI, 0.80-0.84) among Black adults, 0.67 (95% CI, 0.65-0.69) among Hispanic adults, and 0.84 (95% CI, 0.80-0.89) among Asian adults; in 2014 to 2015, the adjusted odds ratio was 0.76 (95% CI, 0.74-0.78) among Black adults, 0.61 (95% CI, 0.60-0.63) among Hispanic adults, and 0.90 (95% CI: 0.86-0.95) among Asian adults. Conclusions and Relevance:In this cross-sectional study of more than 1 million US adults with end-stage kidney disease, racial and ethnic disparities in predialysis nephrology care did not substantially improve from 2005 to 2015. Study findings suggest that national strategies to address racial/ethnic disparities in predialysis nephrology care are needed.

Importance/UNASSIGNED:Bisphenol A (BPA) is a major public health concern because of its high-volume industrial production, ubiquitous exposure to humans, and potential toxic effects on multiple organs and systems in humans. However, prospective studies regarding the association of BPA exposure with long-term health outcomes are sparse. Objective/UNASSIGNED:To examine the association of BPA exposure with all-cause mortality and cause-specific mortality among adults in the United States. Design, Setting, and Participants/UNASSIGNED:This nationally representative cohort study included 3883 adults aged 20 years or older who participated in the US National Health and Nutrition Examination Survey 2003-2008 and provided urine samples for BPA level measurements. Participants were linked to mortality data from survey date through December 31, 2015. Data analyses were conducted in July 2019. Exposures/UNASSIGNED:Urinary BPA levels were quantified using online solid-phase extraction coupled to high-performance liquid chromatography-isotope dilution tandem mass spectrometry. Main Outcomes and Measures/UNASSIGNED:Mortality from all causes, cardiovascular disease, and cancer. Results/UNASSIGNED:This cohort study included 3883 adults aged 20 years or older (weighted mean [SE] age, 43.6 [0.3] years; 2032 women [weighted, 51.4%]). During 36 514 person-years of follow-up (median, 9.6 years; maximum, 13.1 years), 344 deaths occurred, including 71 deaths from cardiovascular disease and 75 deaths from cancer. Participants with higher urinary BPA levels were at higher risk for death. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and urinary creatinine levels, the hazard ratio comparing the highest vs lowest tertile of urinary BPA levels was 1.49 (95% CI, 1.01-2.19) for all-cause mortality, 1.46 (95% CI, 0.67-3.15) for cardiovascular disease mortality, and 0.98 (95% CI, 0.40-2.39) for cancer mortality. Conclusions and Relevance/UNASSIGNED:In this nationally representative cohort of US adults, higher BPA exposure was significantly associated with an increased risk of all-cause mortality. Further studies are needed to replicate these findings in other populations and determine the underlying mechanisms.

Many healthcare providers screen high-risk individuals exclusively with an HbA1c despite its insensitivity for detecting dysglycemia. The two cases presented describe the inherent caveats of interpreting HbA1c without performing an oral glucose tolerance test (OGTT). The first case reflects the risk of over-diagnosing type 2 diabetes (T2D) in an older African American male in whom HbA1c levels, although variable, were primarily in the mid- prediabetes range (5.7-6.4% [39-46 mmol/mol]) for many years although the initial OGTT demonstrated borderline impaired fasting glucose (IFG) with a fasting plasma glucose (FPG) of 102 mg/dl [5.7 mmol/L]) without evidence for impaired glucose tolerance (IGT) (2-hour glucose >140-199 mg/dl ([7.8 -11.1 mmol/L]). As subsequent HbA1c levels were diagnostic of T2D (6.5-6.6% [48-49 mmol/mol]), a second OGTT performed was normal. The second case illustrates the risk of under-diagnosing T2D in a male with HIV having normal HbA1c levels over many years who underwent an OGTT when mild prediabetes [HbA1c = 5.7% (39 mmol/mol)] developed which was diagnostic of T2D. To avoid inadvertent mistreatment, it is therefore essential to perform an OGTT, despite its limitations, in high-risk individuals particularly when glucose or fructosamine and HbA1c values are discordant. Innate differences in the relationship between fructosamine or fasting glucose to HbA1c are demonstrated by the glycation gap or hemoglobin glycation index.

Importance/UNASSIGNED:An important consequence of cannabis legalization is the potential increase in the number of cannabis-impaired drivers on roads, which may result in higher rates of traffic-related injuries and fatalities. To date, limited information about the effects of recreational cannabis laws (RCLs) on traffic fatalities is available. Objective/UNASSIGNED:To estimate the extent to which the implementation of RCLs is associated with traffic fatalities in Colorado and Washington State. Design, Setting, and Participants/UNASSIGNED:This ecological study used a synthetic control approach to examine the association between RCLs and changes in traffic fatalities in Colorado and Washington State in the post-RCL period (2014-2017). Traffic fatalities data were obtained from the Fatality Analysis Reporting System from January 1, 2005, to December 31, 2017. Data from Colorado and Washington State were compared with synthetic controls. Data were analyzed from January 1, 2005, to December 31, 2017. Main Outcome(s) and Measures/UNASSIGNED:The primary outcome was the rate of traffic fatalities. Sensitivity analyses were performed (1) excluding neighboring states, (2) excluding states without medical cannabis laws (MCLs), and (3) using the enactment date of RCLs to define pre-RCL and post-RCL periods instead of the effective date. Results/UNASSIGNED:Implementation of RCLs was associated with increases in traffic fatalities in Colorado but not in Washington State. The difference between Colorado and its synthetic control in the post-RCL period was 1.46 deaths per 1 billion vehicle miles traveled (VMT) per year (an estimated equivalent of 75 excess fatalities per year; probability = 0.047). The difference between Washington State and its synthetic control was 0.08 deaths per 1 billion VMT per year (probability = 0.674). Results were robust in most sensitivity analyses. The difference between Colorado and synthetic Colorado was 1.84 fatalities per 1 billion VMT per year (94 excess deaths per year; probability = 0.055) after excluding neighboring states and 2.16 fatalities per 1 billion VMT per year (111 excess deaths per year; probability = 0.063) after excluding states without MCLs. The effect was smaller when using the enactment date (24 excess deaths per year; probability = 0.116). Conclusions and Relevance/UNASSIGNED:This study found evidence of an increase in traffic fatalities after the implementation of RCLs in Colorado but not in Washington State. Differences in how RCLs were implemented (eg, density of recreational cannabis stores), out-of-state cannabis tourism, and local factors may explain the different results. These findings highlight the importance of RCLs as a factor that may increase traffic fatalities and call for the identification of policies and enforcement strategies that can help prevent unintended consequences of cannabis legalization.

Pulmonary disease after World Trade Center particulate matter(WTC-PM) exposure is associated with dyslipidemia and the receptor for advanced glycation end products (RAGE); however, the mechanisms are not well understood. We utilized a murine model and a multiOMIC assessment to understand the role of RAGE in the pulmonary long-term effects of a single high intensity exposure to WTC-PM. After 1-month(1-M), WTC-PM exposed wild-type(WT) mice had airway hyperreactivity(AHR) while RAGE-deficient(Ager-/-) were protected. PM-exposed WT mice also had histologic evidence of airspace disease while Ager-/- remained unchanged. Inflammatory mediators such as G-CSF, IP-10, and KC were differentially expressed after WTC-PM exposure. WTC-PM induced α-SMA, DIAPH1, RAGE and significant lung collagen deposition in WT compared to Ager-/-. Compared to WT with PM exposure, relative expression of phosphorylated to total CREB and JNK were significantly increased in the lung of PM-exposed Ager-/-, whereas Akt was decreased. Random forests of the refined lung metabolomic profile classified subjects with 92% accuracy; principal components analysis captured 86.7% of the variance in 3 components and demonstrated prominent sub-pathway involvement including known mediators of lung disease such as vitamin B6 metabolites, sphingolipids, fatty acids, and phosphatidylcholines. Treatment with a partial RAGE antagonist, pioglitazone, yielded similar fold-change expression of metabolites(N6-carboxymethyllysine, 1-methylnicotinamide, (N(1)+N(8))-acetylspermidine and Succinylcarnitine(C4-DC)) between WT and Ager-/- exposed to WTC-PM. RAGE can mediate WTC-PM-induced AHR, and warrants further investigation.

OBJECTIVE:s rates of childhood obesity and pediatric type 2 diabetes (T2D) increase, a better understanding is needed of how these two conditions relate, and which subgroups of children are more likely to develop diabetes with and without obesity. METHODS:To compare hotspots of childhood obesity and pediatric T2D in New York City, we performed geospatial clustering analyses on obesity estimates obtained from surveys of school-aged children and diabetes estimates obtained from healthcare claims data, from 2009-2013. Analyses were performed at the Census tract level. We then used multivariable regression analysis to identify sociodemographic and environmental factors associated with these hotspots. RESULTS:We identified obesity hotspots in Census tracts with a higher proportion of Black or Hispanic residents, with low median household income, or located in a food swamp. 51.1% of pediatric T2D hotspots overlapped with obesity hotspots. For pediatric T2D, hotspots were identified in Census tracts with a higher proportion of Black residents and a lower proportion of Hispanic residents. CONCLUSIONS:Non-Hispanic Black neighborhoods had a higher probability of being hotspots of both childhood obesity and pediatric type 2 diabetes. However, we identified a discordance between hotspots of childhood obesity and pediatric diabetes in Hispanic neighborhoods, suggesting either under-detection or under-diagnosis of diabetes, or that obesity may influence diabetes risk differently in these two populations. These findings warrant further investigation of the relationship between childhood obesity and pediatric diabetes among different racial and ethnic groups, and may help guide pediatric public health interventions to specific neighborhoods.

Background/UNASSIGNED:The COVID-19 pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non COVID-19) demonstrated improvement in pulmonary function in ARDS patients using fibrinolytic therapy. A follow-up trial using the widely available tissue-plasminogen activator (alteplase) is now needed to assess optimal dosing and safety in this critically ill patient population. Objective/UNASSIGNED:To describe the design and rationale of a Phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID-19-induced ARDS. Patients/Methods/UNASSIGNED:A rapidly adaptive, pragmatic, open label, randomized, controlled, phase IIa clinical trial will be conducted with three groups: intravenous(IV) alteplase 50mg, IV alteplase 100mg, and control (standard-of-care). Inclusion criteria are known/suspected COVID-19 infection with PaO2/FiO2 ratio<150mmHg for >4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50mg or 100mg followed by heparin infusion for systemic anticoagulation, with alteplase re-dosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. Results/UNASSIGNED:The primary outcome is improvement in PaO2/FiO2 at 48 hours post-randomization. Other outcomes include: ventilator- and ICU-free-days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifity eligible patients will be enrolled in a rapidly adaptive, modified stepped-wedge design with four looks at the data. Conclusion/UNASSIGNED:Findings will provide timely information on the safety, efficacy and optimal dosing of tPA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial. (NCT04357730; FDA IND 149634).

The rapid growth of the coronavirus disease 2019 (COVID-19) pandemic, limited availability of personal protective equipment, and uncertainties regarding transmission modes of the novel severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2) have heightened concerns for safety of healthcare workers (HCWs). Systematic studies of occupational risks for COVID-19 in the context of community risks are difficult and are only recently starting to be reported. Ongoing quality improvement studies in various locales and within many affected healthcare institutions are needed. We propose a template design for small-scale quality improvement surveys. Such surveys have the potential for rapid implementation and completion, are cost-effective, impose little administrative or workforce burden, can reveal occupational risks while taking into account community risks, and can be easily repeated with short intervals of time between repetitions. We describe a template design and propose a survey instrument that is easily modifiable to fit the particular needs of various healthcare institutions in the hope of beginning a collaborative effort to refine the design and instrument. These methods, along with data management and analytic techniques, can be widely useful and shared globally. Our goal is to facilitate quality improvement surveys aimed at reducing the risk of occupational infection of healthcare workers during the COVID-19 pandemic.

Human papillomavirus (HPV) is the most common sexually transmitted infection among adults in the United States, and can cause several types of cancer. This is of particular concern for sexual minority men, as their increased risk of HIV acquisition increases risk for HPV and HPV-associated cancers, particularly when coupled with low rates of HPV vaccination. As part of a larger study of the syndemic of HIV, substance use, and mental health among young sexual minority men in New York City, we sought to explore what sexual minority men know about HPV and the HPV vaccine, along with their experiences have been communicating about the virus and vaccine. We interviewed 38 young sexual minority men with diverse sociodemographic characteristics and identified three main themes: low knowledge about HPV infection and vaccination, highly gendered misconceptions about HPV only affecting women, and lack of communication from healthcare providers about HPV. The prevalence of incorrect HPV knowledge, coupled with inadequate education and vaccination in healthcare settings, indicates a missed opportunity for HPV prevention in a high-risk and high-need population.