Faculty Bibliography

Background: In ED patients who present with acute drug overdose, severe QTc prolongation (>500 ms) has been shown to be a predictor of adverse cardiovascular events (ACVE). However, it is unclear what clinical factors are associated with delayed severe QTc prolongation (dsQTp), and it is unknown whether dsQTp can predict ACVE. This study aims to: (1) Define clinical factors associated with dsQTp, and (2) test whether dsQTp is an independent predictor for ACVE.
Method(s): This was a prospective cohort study at 2 urban tertiary care EDs. Data was collected by trained research assistants, and included demographics, drug exposure, medication administration, initial and repeat ECG data, lab data, and outcome measures. dsQTp was defined as presence of initial QTc 499. The primary study outcome was the composite of ACVE defined as in-hospital occurrence of any of the following: MI, shock, ventricular dysrhythmia, and cardiac arrest. Univariate statistics and multivariable logistic regression calculations were made using SPSS version 24. With a fixed sample size of 1670, we calculated that we would have 99% power to show a 3-fold increase in risk with 0.05 alpha.
Result(s): Out of 2311 patients screened, 641 were excluded (age 500) leaving 1670 patients for analysis. The dsQTp group (N = 27) was found to be older than the control group (N = 1643)(40.1 vs 51.6, P
Conclusion(s): This cohort study reveals a subset of ED patients who are at greater risk of overdose-related ACVE but not immediately apparent by the initial ECG. Further study is needed to identify which patients are at risk for dsQTp, as they may require prolonged observation and repeated ECGs. Limitations include missing repeat QTc measurements, and inability to control for overdose severity as a surrogate for repeat ECGs. Future study is warranted to further characterize patients at risk for dsQTp to evaluate other exposure-related factors as yet undiscovered

Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from pre-diagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10mg/L compared to <1mg/L (OR=1.67, 95% CI=1.12, 2.48). A CRP concentration >10mg/L was positively associated with risk of mucinous (OR=9.67, 95% CI=1.10, 84.80) and endometrioid carcinoma (OR=3.41, 95% CI=1.07, 10.92), and suggestively positive, though not statistically significant, for serous (OR=1.43, 95% CI=0.82, 2.49) and clear cell carcinoma (OR=2.05, 95% CI=0.36, 11.57; p-heterogeneity=0.20). Heterogeneity was observed with oral contraceptive use (p-interaction=0.03), where the increased risk was present only among ever users (OR=3.24, 95% CI=1.62, 6.47). The present study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis, and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma.

Background Little is known regarding use of cardiac therapies and clinical outcomes among older myocardial infarction (MI) patients with cognitive impairment. Methods and Results Patients ≥65 years old with MI in the NCDR (National Cardiovascular Data Registry) Chest Pain-MI Registry between January 2015 and December 2016 were categorized by presence and degree of chart-documented cognitive impairment. We evaluated whether cognitive impairment was associated with all-cause in-hospital mortality after adjusting for known prognosticators. Among 43 812 ST-segment-elevation myocardial infarction (STEMI) patients, 3.9% had mild and 2.0% had moderate/severe cognitive impairment; among 90 904 non-ST-segment-elevation myocardial infarction (NSTEMI patients, 5.7% had mild and 2.6% had moderate/severe cognitive impairment. A statistically significant but numerically small difference in the use of primary percutaneous coronary intervention was observed between patients with STEMI with and without cognitive impairment (none, 92.1% versus mild, 92.8% versus moderate/severe, 90.4%; P=0.03); use of fibrinolysis was lower among patients with cognitive impairment (none, 40.9% versus mild, 27.4% versus moderate/severe, 24.2%; P<0.001). Compared with NSTEMI patients without cognitive impairment, rates of angiography, percutaneous coronary intervention, and coronary artery bypass grafting were significantly lower among patients with NSTEMI with mild (41%, 45%, and 70% lower, respectively) and moderate/severe cognitive impairment (71%, 74%, and 93% lower, respectively). After adjustment, compared with no cognitive impairment, presence of moderate/severe (STEMI: odds ratio, 2.2, 95% CI, 1.8-2.7; NSTEMI: odds ratio, 1.7, 95% CI, 1.4-2.0) and mild cognitive impairment (STEMI: OR, 1.3, 95% CI, 1.1-1.5; NSTEMI: odds ratio, 1.3, 95% CI, 1.2-1.5) was associated with higher in-hospital mortality. Conclusions Patients with NSTEMI with cognitive impairment are substantially less likely to receive invasive cardiac care, while patients with STEMI with cognitive impairment receive similar primary percutaneous coronary intervention but less fibrinolysis. Presence and degree of cognitive impairment was independently associated with increased in-hospital mortality. Approaching clinical decision making for older patients with MI with cognitive impairment requires further study.

This study used repeated measures data to identify developmental profiles of elevated risk for ADHD (i.e., six or more inattentive and/or hyperactive-impulsive symptoms), with an interest in the age at which ADHD risk first emerged. Risk factors that were measured across the first 3 years of life were used to predict profile membership. Participants included 1,173 children who were drawn from the Family Life Project, an ongoing longitudinal study of children's development in low-income, nonmetropolitan communities. Four heuristic profiles of ADHD risk were identified. Approximately two thirds of children never exhibited elevated risk for ADHD. The remaining children were characterized by early childhood onset and persistent risk (5%), early childhood limited risk (10%), and middle childhood onset risk (19%). Pregnancy and delivery complications and harsh-intrusive caregiving behaviors operated as general risk for all ADHD profiles. Parental history of ADHD was uniquely predictive of early onset and persistent ADHD risk, and low primary caregiver education was uniquely predictive of early childhood limited ADHD risk. Results are discussed with respect to how changes to the age of onset criterion for ADHD in DSM5 may affect etiological research and the need for developmental models of ADHD that inform ADHD symptom persistence and desistance.

Background Canadian Cardiovascular Society (CCS) angina severity classification is associated with mortality, myocardial infarction, and coronary revascularization in clinical trial and registry data. The objective of this study was to determine associations between CCS class and all-cause mortality and healthcare utilization, using natural language processing to extract CCS classifications from clinical notes. Methods and Results In this retrospective cohort study of veterans in the United States with stable angina from January 1, 2006, to December 31, 2013, natural language processing extracted CCS classifications. Veterans with a prior diagnosis of coronary artery disease were excluded. Outcomes included all-cause mortality (primary), all-cause and cardiovascular-specific hospitalizations, coronary revascularization, and 1-year healthcare costs. Of 299 577 veterans identified, 14 216 (4.7%) had ≥1 CCS classification extracted by natural language processing. The mean age was 66.6±9.8 years, 99% of participants were male, and 81% were white. During a median follow-up of 3.4 years, all-cause mortality rates were 4.58, 4.60, 6.22, and 6.83 per 100 person-years for CCS classes I, II, III, and IV, respectively. Multivariable adjusted hazard ratios for all-cause mortality comparing CCS II, III, and IV with those in class I were 1.05 (95% CI, 0.95-1.15), 1.33 (95% CI, 1.20-1.47), and 1.48 (95% CI, 1.25-1.76), respectively. The multivariable hazard ratio comparing CCS IV with CCS I was 1.20 (95% CI, 1.09-1.33) for all-cause hospitalization, 1.25 (95% CI, 0.96-1.64) for acute coronary syndrome hospitalizations, 1.00 (95% CI, 0.80-1.26) for heart failure hospitalizations, 1.05 (95% CI, 0.88-1.25) for atrial fibrillation hospitalizations, 1.92 (95% CI, 1.40-2.64) for percutaneous coronary intervention, and 2.51 (95% CI, 1.99-3.16) for coronary artery bypass grafting surgery. Conclusions Natural language processing-extracted CCS classification was positively associated with all-cause mortality and healthcare utilization, demonstrating the prognostic importance of anginal symptom assessment and documentation.

BACKGROUND:Sub-Saharan Africa (SSA) has the highest number of people living with HIV/AIDS, with Nigeria, South Africa, and Uganda accounting for 48% of new infections. A systematic review of the HIV burden among women engaged in sex work (WESW) in 50 low- and middle-income countries found that they had increased odds of HIV infection relative to the general female population. Social structural factors, such as the sex work environment, violence, stigma, cultural issues, and criminalization of sex work are critical in shaping sexually transmitted infection (STI)/HIV risks among WESW and their clients in Uganda. Poverty is the most commonly cited reason for involvement in sex work in SSA. Against this backdrop, this study protocol describes a randomized controlled trial (RCT) that tests the impact of adding economic empowerment to traditional HIV risk reduction (HIVRR) to reduce new incidence of STIs and HIV among WESW in Rakai and the greater Masaka regions in Uganda. METHODS:This three-arm RCT will evaluate the efficacy of adding savings, financial literacy and vocational training/mentorship to traditional HIVRR on reducing new incidence of STI infections among 990 WESW across 33 hotspots. The three arms (n = 330 each) are: 1) Control group: only HIVRR versus 2) Treatment group 1: HIVRR plus Savings plus Financial Literacy (HIVRR + S + FL); and 3) Treatment group 2: HIVRR plus S plus FL plus Vocational Skills Training and Mentorship (V) (HIVRR + S + FL + V). Data will be collected at baseline (pre-test), 6, 12, 18 and 24-months post-intervention initiation. This study will use an embedded experimental mixed methods design where qualitative data will be collected post-intervention across all conditions to explore participant experiences. DISCUSSION:When WESW have access to more capital and/or alternative forms of employment and start earning formal income outside of sex work, they may be better able to improve their skills and employability for professional advancement, thereby reducing their STI/HIV risk. The study findings may advance our understanding of how best to implement gender-specific HIV prevention globally, engaging women across the HIV treatment cascade. Further, results will provide evidence for the intervention's efficacy to reduce STIs and inform implementation sustainability, including costs and cost-effectiveness. TRIAL REGISTRATION:ClinicalTrials.gov , ID: NCT03583541 .

Introduction: This study explored factors influencing patient access to medications for opioid use disorder (OUD), particularly for individuals eligible but historically suboptimal follow-up with in-house referrals to office-based opioid treatment (OBOT). Objectives: In-depth qualitative interviews among a mostly underserved sample of adults with OUD elicited: 1) knowledge and experiences across the OUD treatment cascade; and 2) more nuanced elements of patient-centered care, including shared decision making with providers, experiences in OBOT versus specialty addiction treatment, transitioning from methadone to buprenorphine or extended-release naltrexone (XR-NTX), and voluntary discontinuation of medications for OUD. Methods: We conducted semi-structured qualitative interviews between January and February of 2018 among adult inpatient detoxification program patients with OUD (n = 23). Preliminary analysis of interviews yielded key themes and ideas that were coded from a grounded theory approach. Results: Willingness to engage with OBOT was influenced by a complex array of practical considerations, including access to patient-centered care in OBOT settings, positive experiences with illicitly obtained buprenorphine, and differential experiences pertaining to OBOT versus specialty addiction treatment. Responses were generally favorable towards OBOT with buprenorphine, yet knowledge regarding extended-release naltrexone was limited. Respondents were often frustrated by clinicians when requesting to transition from methadone to buprenorphine or XR-NTX. Lastly, participants elucidated limited access to OBOT programs in underserved neighborhoods and suburban settings. Conclusion: Limited access to patient-centered care in OBOT with buprenorphine and extended-release naltrexone may exacerbate challenges to retention and/or reengagement with OUD care.