Faculty Bibliography

OBJECTIVE:In sub Saharan Africa one of the key challenges in assessment using neuropsychological tools has been the lack of adequately validated and easily implementable measures. This study will translate into English, adapt and standardize the Computerized Battery for Neuropsychological Evaluation of Children (BENCI). The BENCI battery will be adapted using back-translation design, comprehensive cultural adaptation and standardized in a case-control study involving two groups of children: HIV infected and HIV unexposed, uninfected children. The content adaptation will be iteratively carried out using knowledge of English and feedback from pilot testing with children. The proposed study will first involve the cultural adaptation of the BENCI. It will then recruit 544 children aged 8-11 years with half of them being HIV+, while the other half will be HIV unexposed-uninfected. Test-retest reliability will be analyzed using Pearson's correlation while ANOVA and correlational analyses will be used to calculate discriminant, convergent and construct validity. RESULTS:This study will result in an open access adequately adapted and standardized measure of neuropsychological functioning for use with children in East Africa. The protocol paper provides an opportunity to share the planned methods and approaches.

Large-scale functional connectome formation and re-organization is apparent in the second trimester of pregnancy, making it a crucial and vulnerable time window in connectome development. Here we identified which architectural principles of functional connectome organization are initiated prior to birth, and contrast those with topological characteristics observed in the mature adult brain. A sample of 105 pregnant women participated in human fetal resting-state fMRI studies (fetal gestational age between 20 and 40 weeks). Connectome analysis was used to analyze weighted network characteristics of fetal macroscale brain wiring. We identified efficient network attributes, common functional modules and high overlap between the fetal and adult brain network. Our results indicate that key features of the functional connectome are present in the second and third trimesters of pregnancy. Understanding the organizational principles of fetal connectome organization may bring opportunities to develop markers for early detection of alterations of brain function.SIGNIFICANCE STATEMENTThe fetal to neonatal period is well known as a critical stage in brain development. Rapid neurodevelopmental processes establish key functional neural circuits of the human brain. Prenatal risk factors may interfere with early trajectories of connectome formation and thereby shape future health outcomes. Recent advances in MRI have made it possible to examine fetal brain functional connectivity. In this study, we evaluate the network topography of normative functional network development during connectome genesis in utero Understanding the developmental trajectory of brain connectivity provides a basis for understanding how the prenatal period shapes future brain function and disease dysfunction.

Importance:Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions. Objective:To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR). Design, Setting, and Participants:Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540). Exposures:Demographic and clinical factors. Main Outcomes and Measures:Incident eGFR of less than 60 mL/min/1.73 m2. Results:Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A1c, and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25. Conclusions and Relevance:Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Importance/UNASSIGNED:The prevalence of the use of electronic cigarettes (e-cigarettes) in the United States has grown rapidly since their introduction to the market more than a decade ago. While several studies have demonstrated an association between combustible cigarette smoking and depression, the association between e-cigarette use and depression has not been thoroughly studied. Objective/UNASSIGNED:To examine the association between e-cigarette use and depression in a nationally representative sample of the adult population in the United States. Design, Setting, and Participants/UNASSIGNED:Cross-sectional study of the Behavioral Risk Factor Surveillance System database, 2016 to 2017. The Behavioral Risk Factor Surveillance System is the largest national telephone-based survey of randomly sampled adults in the United States. A total of 892 394 participants with information on e-cigarette use and depression were included. Data analysis was conducted in May 2019. Exposures/UNASSIGNED:Electronic cigarette use status defined by self-report as never, former, or current use. Main Outcomes and Measures/UNASSIGNED:Self-reported history of a clinical diagnosis of depression. Results/UNASSIGNED:Of the 892 394 participants (414 326 [29.0%] aged ≥60 years; 502 448 [51.3%] women), there were 28 736 (4.4%) current e-cigarette users, of whom 13 071 (62.1%) were aged between 18 and 39 years. Compared with never e-cigarette users, current e-cigarette users were more likely to be single, male, younger than 40 years, and current combustible cigarette smokers (single, 120 797 [24.3%] vs 10 517 [48.4%]; men, 318 970 [46.6%] vs 14 962 [60.1%]; aged 18-39 years, 129 085 [32.2%] vs 13 071 [62.1%]; current combustible cigarette use, 217 895 [7.9%] vs 8823 [51.8%]). In multivariable adjusted models, former e-cigarette users had 1.60-fold (95% CI, 1.54-1.67) higher odds of reporting a history of clinical diagnosis of depression than never users, whereas current e-cigarette users had 2.10 (95% CI, 1.98-2.23) times higher odds. Additionally, higher odds of reporting depression were observed with increased frequency of use among current e-cigarette users compared with never users (daily use: odds ratio, 2.39; 95% CI, 2.19-2.61; occasional use: odds ratio, 1.96; 95% CI, 1.82-2.10). Similar results were seen in subgroup analyses by sex, race/ethnicity, smoking status, and student status. Conclusions and Relevance/UNASSIGNED:This study found a significant cross-sectional association between e-cigarette use and depression, which highlights the need for prospective studies analyzing the longitudinal risk of depression with e-cigarette use. If confirmed by other study designs, the potential mental health consequences may have regulatory implications for novel tobacco products.

Importance/UNASSIGNED:Cardiovascular disease, cancer, and other noncommunicable diseases (NCDs) are the leading causes of mortality in low- and middle-income countries. Previous studies show that nonphysician health workers (NPHWs), including nurses and volunteers, can provide effective diagnosis and treatment of NCDs. However, the factors that facilitate and impair these programs are incompletely understood. Objective/UNASSIGNED:To identify health system barriers to and facilitators of NPHW-led care for NCDs in low- and middle-income countries. Data Sources/UNASSIGNED:All systematic reviews in PubMed published by May 1, 2018. Study Selection/UNASSIGNED:The search terms used for this analysis included "task shifting" and "non-physician clinician." Only reviews of NPHW care that occurred entirely or mostly in low- and middle-income countries and focused entirely or mostly on NCDs were included. All studies cited within each systematic review that cited health system barriers to and facilitators of NPHW care were reviewed. Data Extraction and Synthesis/UNASSIGNED:Assessment of study eligibility was performed by 1 reviewer and rechecked by another. The 2 reviewers extracted all data. Reviews were performed from November 2017 to July 2018. All analyses were descriptive. Main Outcomes and Measures/UNASSIGNED:All barriers and facilitators mentioned in all studies were tallied and sorted according to the World Health Organization's 6 building blocks for health systems. Results/UNASSIGNED:This systematic review and qualitative analysis identified 15 review articles, which cited 156 studies, of which 71 referenced barriers to and facilitators of care. The results suggest 6 key lessons: (1) select qualified NPHWs embedded within the community they serve; (2) provide detailed, ongoing training and supervision; (3) authorize NPHWs to prescribe medication and render autonomous care; (4) equip NPHWs with reliable systems to track patient data; (5) furnish NPHWs consistently with medications and supplies; and (6) compensate NPHWs adequately commensurate with their roles. Conclusions and Relevance/UNASSIGNED:Although the health system barriers to NPHW screening, treatment, and control of NCDs and their risk factors are numerous and complex, a diverse set of care models has demonstrated strategies to address nearly all of these challenges. These facilitating approaches-which relate chiefly to strong, consistent NPHW training, guidance, and logistical support-generate a blueprint for the creation and scale-up of such programs adaptable across multiple chronic diseases, including in high-income countries.

Importance/UNASSIGNED:To control spending, the Centers for Medicare & Medicaid Services reduced Medicare fee-for-service (FFS) payments for noninvasive cardiac tests (NCTs) performed in provider-based office settings (ambulatory offices not administratively affiliated with hospitals) starting in 2005. Contemporaneously, payments for hospital-based outpatient testing increased. The association between differential payments by site and test location is unknown. Objectives/UNASSIGNED:To quantify trends in differential Medicare FFS payments for NCTs performed in hospital-based and provider-based settings, determine the association between the hospital-based outpatient testing to provider-based office testing payment ratio and the proportion of hospital-based NCTs, and to examine trends in test location between Medicare FFS and 3 Medicare Advantage health maintenance organizations for which Centers for Medicare & Medicaid Services payments do not depend on testing location. Design, Setting, and Participants/UNASSIGNED:This observational claims-based study used Medicare FFS claims from 1999 to 2015 (5% random sample) and Medicare Advantage claims from 3 large health maintenance organizations (2005-2015) among Medicare FFS beneficiaries aged 65 years or older and a health maintenance organization control group. Statistical analysis was performed from May 1, 2017, to July 15, 2019. Exposures/UNASSIGNED:The weighted mean payment ratio of Medicare FFS hospital-based outpatient testing to provider-based office testing for outpatient NCTs. Main Outcomes and Measures/UNASSIGNED:Proportion of outpatient NCTs performed in the hospital-based setting and Medicare FFS costs. Results/UNASSIGNED:The data included a mean of 1.72 million patient-years annually in Medicare FFS (mean age, 75.2 years; 57.3% female in 2015) and a mean of 142 230 patient-years annually in the managed care control group (mean age, 74.8 years; 56.2% female in 2015). The Medicare payment ratio of FFS hospital-based outpatient testing to provider-based office testing increased from 1.05 in 2005 to 2.32 in 2015. The FFS hospital-based outpatient testing proportion increased from 21.1% in 2008 to 43.2% in 2015 and was correlated with the payment ratio (correlation coefficient with a 1-year lag, 0.767; P < .001). In contrast, the hospital-based outpatient testing proportion for the control group declined from 16.6% in 2008 to 15.2% in 2015 (correlation coefficient, -0.024, P = .95). The estimated extra costs owing to tests shifting to the hospital-based outpatient setting in the Medicare FFS group was $661 million in 2015, including $161 million in patient out-of-pocket costs. Conclusions and Relevance/UNASSIGNED:In settings in which reimbursement depends on test location, increasing hospital-based payments correlated with greater proportions of outpatient NCTs performed in the hospital-based outpatient setting. Site-neutral payments may offer an incentive for testing to be performed in the more efficient location.

BACKGROUND:Four of the largest HIV prevention trials have been conducted in sub-Saharan Africa, enrolling hundreds of thousands of participants in catchment areas of millions of people. The trials have focused on community-level interventions to increase diagnosis and initiation of antiretroviral therapy (ART) to improve health and reduce HIV transmission. Universal test-and-treat strategies are deployed to achieve viral suppression thereby reducing risk to uninfected persons, known as treatment as prevention (TasP). PURPOSE:We review the work that found HIV plasma load to correlate with transmission risk, demonstrated that ART could reduce genital tract viral expression, and showed early treatment to be beneficial for persons living with HIV, and that HIV-uninfected sexual partners were protected from infection. We review the seemingly inconsistent findings of the major TasP trials: the TasP [National Agency for AIDS Research (ANRS) 12249] study in South Africa, the SEARCH trial in Kenya and Uganda, the Botswana Combination Prevention Project Ya Tsie study, and the HIV Prevention Trials Network 071 (PopART) trial in Zambia and South Africa. FINDINGS:All the trials reinforce the critical need to identify approaches to optimize programs and incentivize uptake and engagement in HIV testing and ART-based care in ways that consistently reduce HIV transmission. That other chronic conditions can be screened for and treated in the same infrastructures suggests added value of HIV investments. CONCLUSIONS:Implementation challenges are a principal frontier in the global struggle to reduce HIV transmission and mortality using TasP, complementing efforts to find a cure for HIV and an effective, deployable vaccine.

Hundreds of gene therapies are currently in various stages of research and development. A subset of these involve gene editing technologies such as CRISPR. In this hypothetical case, a patient with chronic pain has initiated a CRISPR-based intervention obtained from a clinic in the Cayman Islands. His physician doubts it is approved by the US Food and Drug Administration and worries about its safety. The case presents ethical questions about potential violations of US regulations regarding the sale of products intended to affect human health, patients' lack of understanding about risks of unproven drugs, and suboptimal support for and management of patients with chronic pain. We discuss how physicians should address these questions.

In New York City, over 90% of women newly diagnosed with human immunodeficiency virus (HIV) are Black and Latina; a quarter of these infections occur among 30-39 year-olds. A survey was administered to 343 Black and Puerto Rican women (2014-2016) to examine two HIV infection risk factors: relationship exclusivity and having experienced childhood sexual abuse (CSA). A majority of male partners (69.7%) had at least one risk for HIV transmission. Women in non-exclusive sexual relationships (nESRs) had higher-risk partners, but engaged in safer sex practices than those in ESRs. Two-thirds of women in ESRs (64.8%) reported unprotected vaginal intercourse, although 33.5% had partners with a history of concurrent relationships. Among women in nESRs, having experienced CSA was a strong risk factor for HIV infection. Black and Latina women's vulnerability to HIV infection is significant, even when in exclusive relationships. Safer sex counseling should be integrated in primary care.

We sought to qualitatively explore how those at highest risk for lung cancer, current smokers, experienced, understood, and made decisions about participation in lung cancer screening (LCS) after being offered in the target setting for implementation, routine primary care visits. Thirty-seven current smokers were identified within 4 weeks of being offered LCS at seven sites participating in the Veterans Health Administration Clinical Demonstration Project and interviewed via telephone using semi-structured qualitative interviews. Transcripts were coded by two raters and analyzed thematically using iterative inductive content analysis. Five challenges to smokers' decision-making lead to overestimated benefits and minimized risks of LCS: fear of lung cancer fixated focus on inflated screening benefits; shame, regret, and low self-esteem stemming from continued smoking situated screening as less averse and more beneficial; screening was mistakenly believed to provide general evaluation of lungs and reassurance was sought about potential damage caused by smoking; decision-making was deferred to providers; and indifference about numerical educational information that was poorly understood. Biased understanding of risks and benefits was complicated by emotion-driven, uninformed decision-making. Emotional and cognitive biases may interfere with educating and supporting smokers' decision-making and may require interventions tailored for their unique needs.