Faculty Bibliography

BACKGROUND AND AIMS/OBJECTIVE:In a US randomized-effectiveness trial comparing extended-release naltrexone (XR-NTX) with buprenorphine-naloxone (BUP-NX) for the prevention of opioid relapse among participants recruited during inpatient detoxification (CTN-0051), the requirement to complete opioid detoxification prior to initiating XR-NTX resulted in lower rates of initiation of XR-NTX (72% XR-NTX versus 94% BUP-NX). DESIGN/METHODS:This was a retrospective secondary analysis of CTN-0051 trial data, including follow-up data over 24-36 weeks. SETTING/METHODS:Eight community-based, inpatient-detoxification and follow-up outpatient treatment facilities in the United States. PARTICIPANTS/METHODS:A total of 283 participants randomized to receive XR-NTX. MEASUREMENTS/METHODS:Efficiency was estimated using a multivariable generalized structural equation model to explore simultaneous determinants of XR-NTX induction and induction duration (detoxification + residential days). Cost-effectiveness was estimated from the health-care sector perspective and included expected costs and quality-adjusted life-years (QALYs). FINDINGS/RESULTS:Treatment site was the only modifiable factor that simultaneously increased the likelihood of XR-NTX induction and decreased induction duration. Incorporating the higher predicted probability of XR-NTX induction, and fewer predicted days of detoxification and subsequent residential treatment into the cost-effectiveness framework, reduced the incremental average 24-week total cost of XR-NTX treatment from $5317 more than that of BUP-NX (P = 0.01) to a non-statistically-significant difference of $1016 (P = 0.63). QALYs gained remained similar across arms. CONCLUSION/CONCLUSIONS:Adopting an efficient model of extended-release naltrexone initiation could result in extended-release naltrexone and buprenorphine-naloxone being of comparable economic value from the health-care sector perspective over 24-36 weeks for patients seeking treatment for opioid use disorder at an inpatient detoxification facility.

BACKGROUND:Inhibition of the renin angiotensin aldosterone system (RAAS) improves survival and reduces adverse cardiac events in heart failure with reduced ejection fraction, but the benefit is not well-defined following left ventricular assist device (LVAD). METHODS:We analyzed the ISHLT IMACS registry for adults with a primary, continuous-flow LVAD from January 2013 to September 2017 who were alive at postoperative month 3 without a major adverse event, and categorized patients according to treatment an angiotensin converting enzyme inhibitor (ACEI/ARB) or mineralocorticoid receptor antagonist (MRA). Propensity score matching was performed separately for ACEI/ARB vs none (n = 4,118 each) and MRA vs none (n = 3,892 each). RESULTS:Of 11,494 patients included, 50% were treated with ACEI/ARB and 38% with MRA. Kaplan-Meier survival was significantly better for patients receiving ACEI/ARB (p < 0.001) but not MRA (p = 0.31). In Cox proportional hazards analyses adjusted for known predictors of mortality following LVAD, ACEI/ARB use (hazard ratio 0.81 [95% confidence interval 0.71-0.93], p < 0.0001) but not MRA use (hazard ratio 1.03 [95% confidence interval 0.88-1.21], p = 0.69) was independently associated with lower mortality. Among patients treated with an ACEI/ARB, there was a significantly lower unadjusted risk of cardiovascular death (p < 0.001), risk of gastrointestinal bleeding (p = 0.01), and creatinine level (p < 0.001). MRA therapy was associated with lower risk of gastrointestinal bleeding (p = 0.01) but higher risk of hemolysis (p < 0.01). Potential limitations include residual confounding and therapy crossover. CONCLUSION:These findings suggest a benefit for ACEI/ARB therapy in patients with heart failure after LVAD implantation.

In eSwatini and across sub-Saharan Africa, adolescent girls and young women (AGYW) are at significantly higher risk of HIV infection and poorer sexual and reproductive health (SRH) than their male counterparts. AGYW demonstrate low demand for SRH services, further contributing to poor outcomes. Strategic marketing approaches, including those used by multinational corporations, have potential to support demand creation for SRH services among AGYW, but there is limited empirical evidence on the direct application of private-sector strategic marketing approaches in this context. Therefore, we examined how Project Last Mile worked with eSwatini's Ministry of Heath to translate strategic marketing approaches from the Coca-Cola system to attract AGYW to SRH services. We present qualitative market research using the ZMET® methodology with 12 young Swazi women (ages 15-24), which informed development of a highly branded communication strategy consistent with other successful gain-framing approaches. Qualitative in-depth interviews with 19 stakeholders revealed receptivity to the market research findings, and highlighted local ownership over the strategic marketing process and brand. These results can inform similar efforts to translate strategic marketing to support demand generation in pursuit of public health goals to reduce HIV risk and improve SRH.

Although cancer screening has greatly reduced colorectal cancer, breast cancer, and cervical cancer morbidity and mortality over the last few decades, adherence to cancer screening guidelines remains inconsistent, particularly among certain demographic groups. This study aims to validate a rule-based algorithm to determine adherence to cancer screening. A novel screening algorithm was applied to electronic health record (EHR) from an urban healthcare system in New York City to automatically determine adherence to national cancer screening guidelines for patients deemed eligible for screening. First, a subset of patients was randomly selected from the EHR and their data were exported in a de-identified manner for manual review of screening adherence by two teams of human reviewers. Interrater reliability for manual review was calculated using Cohen's Kappa and found to be high in all instances. The sensitivity and specificity of the algorithm was calculated by comparing the algorithm to the final manual dataset. When assessing cancer screening adherence, the algorithm performed with a high sensitivity (79%, 70%, 80%) and specificity (92%, 99%, 97%) for colorectal cancer, breast cancer, and cervical cancer screenings, respectively. This study validates an algorithm that can effectively determine patient adherence to colorectal cancer, breast cancer, and cervical cancer screening guidelines. This design improves upon previous methods of algorithm validation by using computerized extraction of essential components of patients' EHRs and by using de-identified data for manual review. Use of the described algorithm could allow for more precise and efficient allocation of public health resources to improve cancer screening rates.

BACKGROUND AND AIMS/OBJECTIVE:Obesity is an independent risk factor for atherosclerotic cardiovascular disease (CVD), and platelet hyperactivation in obesity may contribute to this association. Olive oil consumption is associated with lower cardiovascular disease (CVD) risk in the general population. However, little is known for individuals with obesity. We investigated whether olive oil intake is associated with platelet activation in obesity. METHODS AND RESULTS/RESULTS:. Olive oil intake was stratified into <1 time/week (n = 21), 1-3 times/week (n = 18), ≥4 times/week (n = 24). Strata did not differ by age, BMI or platelet count. Unstimulated P-selectin expression did not differ by olive oil consumption. Subjects with more frequent olive oil intake exhibited lower P-selectin expression on submaximal thrombin exposure. CONCLUSIONS:More frequent olive oil intake is associated with reduced thrombin-induced platelet activation in obesity.

In 2018, the U.S. Department of Housing and Urban Development required public housing authorities to implement a smoke-free housing (SFH) policy that included individual apartments. We analyzed the policy implementation process in the New York City Public Housing Authority (NYCHA). From June-November 2019, we conducted 9 focus groups with 64 NYCHA residents (smokers and nonsmokers), 8 key informant interviews with NYCHA staff and resident association leaders, and repeated surveys with a cohort of 130 nonsmoking households pre- and 12-month post policy. One year post policy implementation, participants reported widespread smoking violations and multi-level factors impeding policy implementation. These included the shared belief among residents and staff that the policy overreached by "telling people what to do in their own apartments". This hindered compliance and enforcement efforts. Inconsistent enforcement of illegal marijuana use, staff smoking violations, and a lack of accountability for other pressing housing issues created the perception that smokers were being unfairly targeted, as did the lack of smoking cessation resources. Resident support for the policy remained unchanged but satisfaction with enforcement declined (60.1% vs. 48.8%, p = 0.047). We identified multilevel contextual factors that are influencing SFH policy implementation. Findings can inform the design of strategies to optimize policy implementation.

INTRODUCTION/BACKGROUND:Similar to other non-communicable diseases (NCDs), people who develop cardiovascular disease (CVD) typically have more than one risk factor. The clustering of cardiovascular risk factors begins in youth, early adulthood, and middle age. The presence of multiple risk factors simultaneously has been shown to increase the risk for atherosclerosis development in young and middle-aged adults and risk of CVD in middle age. OBJECTIVE:This study aimed to address the interrelationship of CVD risk factors and their accumulation in a large sample of young adults in the United Arab Emirates (UAE). METHODS:Baseline data was drawn from the UAE Healthy Future Study (UAEHFS), a volunteer-based multicenter study that recruits Emirati nationals. Data of participants aged 18 to 40 years was used for cross-sectional analysis. Demographic and health information was collected through self-reported questionnaires. Anthropometric data and blood pressure were measured, and blood samples were collected. RESULTS:A total of 5126 participants were included in the analysis. Comorbidity analyses showed that dyslipidemia and obesity co-existed with other cardiometabolic risk factors (CRFs) more than 70% and 50% of the time, respectively. Multivariate logistic regression analysis of the risk factors with age and gender showed that all risk factors were highly associated with each other. The strongest relationship was found with obesity; it was associated with four-fold increase in the odds of having central obesity [adjusted OR 4.70 (95% CI (4.04-5.46)], and almost three-fold increase odds of having abnormal glycemic status [AOR 2.98 (95% (CI 2.49-3.55))], hypertension (AOR 3.03 (95% CI (2.61-3.52))] and dyslipidemia [AOR 2.71 (95% CI (2.32-3.15)]. Forty percent of the population accumulated more than 2 risk factors, and the burden increased with age. CONCLUSION/CONCLUSIONS:In this young population, cardiometabolic risk factors are highly prevalent and are associated with each other, therefore creating a heavy burden of risk factors. This forecasts an increase in the burden of CVD in the UAE. The robust longitudinal design of the UAEHFS will enable researchers to understand how risk factors cluster before disease develops. This knowledge will offer a novel approach to design group-specific preventive measures for CVD development.

(1) Background: The King-Devick (KD) rapid number naming test is sensitive for concussion diagnosis, with increased test time from baseline as the outcome measure. Eye tracking during KD performance in concussed individuals shows an association between inter-saccadic interval (ISI) (the time between saccades) prolongation and prolonged testing time. This pilot study retrospectively assesses the relation between ISI prolongation during KD testing and cognitive performance in persistently-symptomatic individuals post-concussion. (2) Results: Fourteen participants (median age 34 years; 6 women) with prior neuropsychological assessment and KD testing with eye tracking were included. KD test times (72.6 ± 20.7 s) and median ISI (379.1 ± 199.1 msec) were prolonged compared to published normative values. Greater ISI prolongation was associated with lower scores for processing speed (WAIS-IV Coding, r = 0.72, p = 0.0017), attention/working memory (Trails Making A, r = -0.65, p = 0.006) (Digit Span Forward, r = 0.57, p = -0.017) (Digit Span Backward, r= -0.55, p = 0.021) (Digit Span Total, r = -0.74, p = 0.001), and executive function (Stroop Color Word Interference, r = -0.8, p = 0.0003). (3) Conclusions: This pilot study provides preliminary evidence suggesting that cognitive dysfunction may be associated with prolonged ISI and KD test times in concussion.

OBJECTIVE:Deep significance clustering (DICE) is a self-supervised learning framework. DICE identifies clinically similar and risk-stratified subgroups that neither unsupervised clustering algorithms nor supervised risk prediction algorithms alone are guaranteed to generate. MATERIALS AND METHODS:Enabled by an optimization process that enforces statistical significance between the outcome and subgroup membership, DICE jointly trains 3 components, representation learning, clustering, and outcome prediction while providing interpretability to the deep representations. DICE also allows unseen patients to be predicted into trained subgroups for population-level risk stratification. We evaluated DICE using electronic health record datasets derived from 2 urban hospitals. Outcomes and patient cohorts used include discharge disposition to home among heart failure (HF) patients and acute kidney injury among COVID-19 (Cov-AKI) patients, respectively. RESULTS:Compared to baseline approaches including principal component analysis, DICE demonstrated superior performance in the cluster purity metrics: Silhouette score (0.48 for HF, 0.51 for Cov-AKI), Calinski-Harabasz index (212 for HF, 254 for Cov-AKI), and Davies-Bouldin index (0.86 for HF, 0.66 for Cov-AKI), and prediction metric: area under the Receiver operating characteristic (ROC) curve (0.83 for HF, 0.78 for Cov-AKI). Clinical evaluation of DICE-generated subgroups revealed more meaningful distributions of member characteristics across subgroups, and higher risk ratios between subgroups. Furthermore, DICE-generated subgroup membership alone was moderately predictive of outcomes. DISCUSSION:DICE addresses a gap in current machine learning approaches where predicted risk may not lead directly to actionable clinical steps. CONCLUSION:DICE demonstrated the potential to apply in heterogeneous populations, where having the same quantitative risk does not equate with having a similar clinical profile.

BACKGROUND:Primary care practices have remained on the frontline of health care service delivery throughout the COVID-19 pandemic. The purpose of our study was to understand the early pandemic experience of primary care practices, how they adapted care processes for chronic disease management and preventive care, and the future potential of these practices' service delivery adaptations. METHODS:We interviewed 44 providers and staff at 22 high-performing primary care practices located throughout the United States between March and May 2020. Interviews were transcribed and coded using a modified rapid assessment process due to the time-sensitive nature of the study. RESULTS:Practices reported employing a variety of adaptations to care during the COVID-19 pandemic including maintaining safe and socially distanced access through increased use of telehealth visits, using disease registries to identify and proactively outreach to patients, providing remote patient education, and incorporating more home-based monitoring into care. Routine screening and testing slowed considerably, resulting in concerns about delayed detection. Patients with fewer resources, lower health literacy, and older adults were the most difficult to reach and manage during this time. CONCLUSION:Our findings indicate that primary care structures and processes developed for remote chronic disease management and preventive care are evolving rapidly. Emerging adapted care processes, most notably remote provision of care, are promising and may endure beyond the pandemic, but issues of equity must be addressed (e.g., through payment reform) to ensure vulnerable populations receive the same benefit.