Faculty Bibliography

BACKGROUND: Synthetic cannabinoids use has been a public health concern given association with hospitalization and death among users. While national reports estimate that reported use is declining among adolescents, differences by birth cohort may indicate subgroups who remain at higher risk, both in the overall adolescent population and among demographic subgroups. METHODS: We estimated age, period, and cohort models of self-reported past-year synthetic cannabinoid use (queried as "synthetic marijuana" ["K2," "Spice"]) among 54,865 adolescents aged 13-19 attending high school from 2011 to 2015. RESULTS: Past-year use decreased from 11.86% in 2011 to 4.75% in 2015. This decrease was best represented as a linear downward trend. When stratified by key covariates, however, results indicated evidence of a positive cohort effect for students of higher socioeconomic status (SES). For those students, use did not decrease at the same rate as the overall population; younger cohorts of high SES students remain at higher risk for synthetic cannabinoid use than older cohorts as well as lower SES peers. A similar and stronger association was found for frequent marijuana users (>/=20 occasions of past-year use). Multi-level models indicated that groups at highest risk included older adolescents, Hispanics and other/mixed race students, cigarette users, and frequent marijuana users. CONCLUSION: Synthetic cannabinoid use is associated with morbidity as well as mortality; continued attention to reducing synthetic cannabinoid use remains an important public health priority to maximizing student health.

BACKGROUND: Type 2 myocardial infarction (MI) is defined as myocardial necrosis (myonecrosis) due to an imbalance in supply and demand with clinical evidence of ischemia. Some clinical scenarios of supply-demand mismatch predispose to myonecrosis but limit the identification of symptoms and ECG changes referable to ischemia; therefore, the MI definition may not be met. Factors that predispose to type 2 MI and myonecrosis without definite MI, approaches to treatment, and outcomes remain poorly characterized. METHODS: Patients admitted to an academic medical center with an ICD-9 diagnosis of secondary myocardial ischemia or non-primary diagnosis of non-ST-elevation MI were retrospectively reviewed. Cases were classified as either MI (n=255) or myonecrosis without definite MI (n=220) based on reported symptoms, ischemic ECG changes, and new wall motion abnormalities. RESULTS: Conditions associated with type 2 MI or myonecrosis included non-cardiac surgery (38%), anemia or bleeding requiring transfusion (32%), sepsis (31%), tachyarrhythmia (23%), hypotension (22%), respiratory failure (23%), and severe hypertension (8%). Inpatient mortality was 5%, with no difference between patients with MI and those with myonecrosis (6% vs. 5%, p=0.41). At discharge, only 43% of patients received aspirin and statin therapy. CONCLUSIONS: Type 2 MI and myonecrosis occur frequently in the setting of supply-demand mismatch due to non-cardiac surgery, sepsis, or anemia. Myonecrosis without definite MI is associated with similar in-hospital mortality as type 2 MI; both groups warrant further workup for cardiovascular disease. Antiplatelet and statin prescriptions were infrequent at discharge, reflecting physician uncertainty about the role of secondary prevention in these patients.

Background. Only half of the 3.5 million individuals with chronic hepatitis C (HCV) in the US are aware of their infection. Emergency departments (ED) provide a primary point of entry to the healthcare system for marginalized populations who are traditionally at elevated risk for HCV and are becoming an important venue for screening and linkage efforts. Optimal methods for HCV screening (universal versus targeted) in ED remain undefined. We aim to ascertain the relative prevalence of HCV infection by age and other risk factors through non-targeted screening for HCV in our high-volume urban ED. Methods. In this ongoing prospective observational cohort study, consenting adult ED patients participate in a researcher-administered structured interview and are offered a rapid HCV antibody (HCV Ab) screening test. If reactive, confirmatory serologic HCV Ab and HCV RNA are sent immediately and a clinic appointment is scheduled within 4 weeks. Participants are contacted with HCV RNA PCR results; those with detectable viral load are encouraged to attend follow-up appointment and receive a reminder call one week prior to appointment. Successful linkage to care is defined as appointment attendance. Results. A total of 2018 eligible patients were approached July 2015-April 2016. Seven hundred thirty-two participated in a structured interview. Seven hundred seven accepted an HCVAb rapid test. HCV antibody prevalence in the ED was 3.8% (0.43% in non-baby boomers without injection drug use (IDU), 7.6% in baby boomers, 34% in persons endorsing IDU). Twenty-three HCVAb-reactive participants submitted blood for confirmatory testing. A total of 12 of 23 (52%) had detectable HCV RNA, corresponding to 1.7% prevalence of chronic infection. Targeted screening of the birth cohort and those with IDU would have missed 7.4% (2 of 27) of HCVAb positive patients and 8.3% (1 of 12) with chronic infection. A total of 4 of 12 (33.3%) with chronic infection were linked to care, 2 have upcoming appointments, 1 died before appointment. Conclusion. Prevalence of HCV in our ED was higher than the national estimate of 3.4% among baby boomers used to justify national birth cohort screening. Optimal ED HCV screening methods should target baby boomers and those endorsing IDU, but a modest proportion of infections will be missed without universal screening

Background: Optical coherence tomography (OCT) derived measures of retinal layer thicknesses have been shown to correlate with visual function, grey matter volume and Expanded Disability Status Scale (EDSS) scores in multiple sclerosis (MS). However, the prognostic value of retinal measurements for predicting long term disability in MS patients is still being evaluated. Goal: To determine whether retinal thicknesses as assessed by OCT predict disability in MS 10 years later. Methods: A total of 89 MS patients who were scanned on Stratus OCT between 2006 and 2007 underwent formal, blinded EDSS determination during 2015-2016. Average peripapillary retinal nerve fibre layer (RNFL) thickness and total macular volume (TMV) were assessed by calculating the mean value of these measures for both eyes in each subject. Patients were categorised by baseline diagnosis as relapsing remitting (RRMS), secondary progressive (SPMS), or primary progressive MS (PPMS). Mixed effects linear regression models were used to investigate whether average TMV and RNFL thicknesses at baseline predict EDSS scores after 10 years. Results: The final analysis included 75 RRMS, 9 SPMS, and 5 PPMS patients. 14 of the 75 patients with a baseline diagnosis of RRMS transitioned to SPMS during follow-up period. Baseline analyses revealed that the RRMS cohort was significantly younger than the SPMS and PPMS cohorts (mean differences= 21.5 years and 11.7 years respectively; p< 0.001 for both) and that SPMS patients had a longer disease duration than RRMS and PPMS patients (mean differences=14.2 years and 13.2 years respectively; p< 0.001 for both). A history of optic neuritis (ON) was observed in the RRMS and SPMS cohorts (41% and 44%, respectively), but not in the PPMS cohorts (0%; p=0.253). Adjusting for age, sex, and a history of ON, the mean TMV values at baseline predicted EDSS scores after a median follow-up of 9.3 years. On average, a 1mm3 lower TMV value at baseline predicts a mean decrease of 2 in EDSS at follow-up (adjusted R²=0.20; p=0.012). Mean baseline RNFL values did not significantly predict EDSS scores (adjusted R²=0.18; p=0.069). Conclusions: As has been previously shown with brain atrophy and lesion volume, retinal measures can have predictive value for medium-term disability in MS. Our preliminary findings support the utility of OCT as a tool to predict neurodegeneration and disease progression over time in MS patients

AKI, a frequently transient condition, is not accepted by the US Food and Drug Association as an end point for drug registration trials. We assessed whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative end point in trials of AKI prevention and/or treatment. Among 161,185 United States veterans undergoing major surgery between 2004 and 2011, we characterized in-hospital AKI by Kidney Disease Improving Global Outcomes creatinine criteria and decline in eGFR from prehospitalization to postdischarge time points and quantified associations of these values with ESRD and mortality over a median of 3.8 years. An eGFR decline of ≥30% at 30, 60, and 90 days after discharge occurred in 3.1%, 2.5%, and 2.6%, of survivors without AKI and 15.9%, 12.2%, and 11.7%, of survivors with AKI. For patients with in-hospital AKI compared with those with no AKI and stable eGFR, a 30% decline in eGFR at 30, 60, and 90 days after discharge demonstrated adjusted hazard ratios (95% confidence intervals) of ESRD of 5.60 (4.06 to 7.71), 6.42 (4.76 to 8.65), and 7.27 (5.14 to 10.27), with corresponding estimates for 40% decline in eGFR of 6.98 (5.21 to 9.35), 8.03 (6.11 to 10.56), and 10.95 (8.10 to 14.82). Risks for mortality were smaller but consistent in direction. A 30%-40% decline in eGFR after AKI could be a surrogate end point for ESRD in trials of AKI prevention and/or treatment, but additional trial evidence is needed.

Surgical sterilization is the primary method of contraception among low-income women in India. This article, using qualitative analysis of key informant, in-depth interviews, and quantitative analyses, examines the antecedents, process, and outcomes of sterilization for women in a low-income area in Mumbai, India. Family planning policies, socioeconomic factors, and gender roles constrain women's reproductive choices. Procedures for sterilization rarely follow protocol, particularly during pre-procedure counseling and consent. Women who choose sterilization often marry early, begin conceiving soon after marriage, and reach or exceed ideal family size early due to problems in accessing reversible contraceptives. Despite these constraints, this study indicates that from the perspective of women, the decision to undergo sterilization is empowering, as they have fulfilled their reproductive duties and can effectively exercise control over their fertility and sexuality. This empowerment results in little post-sterilization regret, improved emotional health, and improved sexual relationships following sterilization.

PURPOSE OF THE STUDY: Cognitive impairment (CI) is one of several factors known to influence hospitalization, hospital length of stay, and rehospitalization among older adults. Redesigning care delivery systems sensitive to the influence of CI may reduce acute care utilization while improving care quality. To develop a foundation of fundamental needs for health care redesign, we conducted focus groups with inpatient and outpatient providers to identify barriers, facilitators, and suggestions for improvements in care delivery for patients with CI. DESIGN AND METHODS: Focus group sessions were conducted with providers to identify their approach to caring for cognitively impaired hospitalized adults; obstacles and facilitators to providing this care; and suggestions for improving the care process. Using a thematic analysis, two reviewers analyzed these transcripts to develop codes and themes. RESULTS: Seven themes emerged from the focus group transcripts. These were: (1) reflections on serving the cognitively impaired population; (2) descriptions of perceived barriers to care; (3) strategies that improve or facilitate caring for hospitalized older adults; (4) the importance of fostering a hospital friendly to the needs of older adults; (5) the need for educating staff, patients, and caregivers; (6) the central role of good communication; and (7) steps needed to provide more effective care. IMPLICATIONS: Providing effective acute care services to older adults with CI is an important challenge in health care reform. An understanding derived from the perspective of multiple professional disciplines is an important first step. Future research will build on this preliminary study in developing new acute care models for patients with CI.

The APOL1 high-risk genotype, present in approximately 13% of blacks in the United States, is a risk factor for kidney function decline in populations with CKD. It is unknown whether genetic screening is indicated in the general population. We evaluated the prognosis of APOL1 high-risk status in participants in the population-based Atherosclerosis Risk in Communities (ARIC) study, including associations with eGFR decline, variability in eGFR decline, and related adverse health events (AKI, ESRD, hypertension, diabetes, cardiovascular disease, pre-ESRD and total hospitalization rate, and mortality). Among 15,140 ARIC participants followed from 1987-1989 (baseline) to 2011-2013, 75.3% were white, 21.5% were black/APOL1 low-risk, and 3.2% were black/APOL1 high-risk. In a demographic-adjusted analysis, blacks had a higher risk for all assessed adverse health events; however, in analyses adjusted for comorbid conditions and socioeconomic status, blacks had a higher risk for hypertension, diabetes, and ESRD only. Among blacks, the APOL1 high-risk genotype associated only with higher risk of ESRD in a fully adjusted analysis. Black race and APOL1 high-risk status were associated with faster eGFR decline (P<0.001 for each). However, we detected substantial overlap among the groups: median (10th-90th percentile) unadjusted eGFR decline was 1.5 (1.0-2.2) ml/min per 1.73 m(2) per year for whites, 2.1 (1.4-3.1) ml/min per 1.73 m(2) per year for blacks with APOL1 low-risk status, and 2.3 (1.5-3.5) ml/min per 1.73 m(2) per year for blacks with APOL1 high-risk status. The high variability in eGFR decline among blacks with and without the APOL1 high-risk genotype suggests that population-based screening is not yet justified.

BACKGROUND:The primary biomarkers used to define CKD are serum creatinine and albuminuria. These biomarkers have directed focus on the filtration and barrier functions of the kidney glomerulus even though albuminuria results from tubule dysfunction as well. Given that proximal tubules make up ∼90% of kidney cortical mass, we evaluated whether a sensitive and specific marker of proximal tubule injury, urinary kidney injury molecule-1 (KIM-1), is elevated in individuals with CKD or with risk factors for CKD. METHODS:We measured urinary KIM-1 in participants of five cohort studies from the USA and Sweden. Participants had a wide range of kidney function and were racially and ethnically diverse. Multivariable linear regression models were used to test the association of urinary KIM-1 with demographic, clinical and laboratory values. RESULTS:In pooled, multivariable-adjusted analyses, log-transformed, creatinine-normalized urinary KIM-1 levels were higher in those with lower eGFR {β = -0.03 per 10 mL/min/1.73 m(2) [95% confidence interval (CI) -0.05 to -0.02]} and greater albuminuria [β = 0.16 per unit of log albumin:creatinine ratio (95% CI 0.15-0.17)]. Urinary KIM-1 levels were higher in current smokers, lower in blacks than nonblacks and lower in users versus nonusers of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. CONCLUSION:Proximal tubule injury appears to be an integral and measurable element of multiple stages of CKD.