Faculty Bibliography

BACKGROUND:Untreated, miliary tuberculosis (TB) has a mortality approaching 100%. As it is uncommon there is little specific data to guide its management. We report detailed data from a UK cohort of patients with miliary tuberculosis and the associations and predictive ability of admission blood tests with clinical outcomes. METHODS:Routinely collected demographic, clinical, blood, imaging, histopathological and microbiological data were assessed for all patients with miliary TB identified from the London TB register from 2008 to 2012 from Northwest London Hospitals NHS Trust. Multivariable logistic regression was used to assess factors independently associated with the need for critical care intervention. Receiver operator characteristics (ROC) were calculated to assess the discriminatory ability of admission blood tests to predict clinical outcomes. RESULTS:Fifty-two patients were identified with miliary tuberculosis, of whom 29% had confirmed central nervous system (CNS) involvement. Magnetic resonance imaging (MRI) was more sensitive than computed tomography (CT) or lumbar puncture for detecting CNS disease. Severe complications were frequent, with 15% requiring critical care intervention with mechanical ventilation. This was independently associated with admission hyponatraemia and elevated alanine aminotransferase (ALT). Having an admission sodium ≥125 mmol/L and an ALT <180 IU/L had 82% sensitivity and 100% specificity for predicting a favourable outcome with an area under the ROC curve (AUC) of 0.91. Despite the frequency of severe complications, one-year mortality was low at 2%. CONCLUSIONS:Although severe complications of miliary tuberculosis were frequent, mortality was low with timely access to critical care intervention, anti-tuberculous therapy and possibly corticosteroid use. Clinical outcomes could accurately be predicted using routinely collected biochemistry data.

Identifying undiagnosed HIV infection is necessary for the elimination of HIV transmission in the United States. The present study evaluated the efficacy of 3 community-based approaches for uncovering undiagnosed HIV among heterosexuals at high-risk (HHR), who are mainly African American/Black and Hispanic. Heterosexuals comprise 24% of newly reported HIV infections in the United States, but experience complex multilevel barriers to HIV testing. We recruited African American/Black and Hispanic HHR in a discrete urban area with both elevated HIV prevalence and poverty rates. Approaches tested were (1) respondent-driven sampling (RDS) and confidential HIV testing in 2 sessions (n = 3116); (2) RDS and anonymous HIV testing in one session (n = 498); and (3) venue-based sampling (VBS) and HIV testing in a single session (n = 403). The main outcome was newly diagnosed HIV infection. RDS with anonymous testing and one session reached HHR with less HIV testing experience and more risk factors than the other approaches. Furthermore, RDS with anonymous (4.0%) and confidential (1.0%) testing yielded significantly higher rates of newly diagnosed HIV than VBS (0.3%). Thus peer-referral approaches were more efficacious than VBS for uncovering HHR with undiagnosed HIV, particularly a single-session/anonymous strategy, and have a vital role to play in efforts to eliminate HIV transmission.

BACKGROUND: Nearly three decades into the epidemic, sub-Saharan Africa (SSA) remains the region most heavily affected by human immunodeficiency virus (HIV), with nearly 70% of the 34 million people living with HIV globally residing in the region. In SSA, female and male youth (15 to 24 years) are at a disproportionately high risk of HIV infection compared to adults. As such, there is a need to target HIV prevention strategies to youth and to tailor them to a gender-specific context. This protocol describes the process for the multi-staged approach in the design of the MP3 Youth pilot study, a gender-specific, combination, HIV prevention intervention for youth in Kenya. OBJECTIVE: The objective of this multi-method protocol is to outline a rigorous and replicable methodology for a gender-specific combination HIV prevention pilot study for youth in high-burden settings, illustrating the triangulated methods undertaken to ensure that age, sex, and context are integral in the design of the intervention. METHODS: The mixed-methods, cross-sectional, longitudinal cohort pilot study protocol was developed by first conducting a systematic review of the literature, which shaped focus group discussions around prevention package and delivery options, and that also informed age- and sex- stratified mathematical modeling. The review, qualitative data, and mathematical modeling created a triangulated evidence base of interventions to be included in the pilot study protocol. To design the pilot study protocol, we convened an expert panel to select HIV prevention interventions effective for youth in SSA, which will be offered in a mobile health setting. The goal of the pilot study implementation and evaluation is to apply lessons learned to more effective HIV prevention evidence and programming. RESULTS: The combination HIV prevention package in this protocol includes (1) offering HIV testing and counseling for all youth; (2) voluntary medical circumcision and condoms for males; (3) pre-exposure prophylaxis (PrEP), conditional cash transfer (CCT), and contraceptives for females; and (4) referrals for HIV care among those identified as HIV-positive. The combination package platform selected is mobile health teams in an integrated services delivery model. A cross-sectional analysis will be conducted to determine the uptake of the interventions. To determine long-term impact, the protocol outlines enrolling selected participants in mutually exclusive longitudinal cohorts (HIV-positive, PrEP, CCT, and HIV-negative) followed by using mobile phone text messages (short message service, SMS) and in-person surveys to prospectively assess prevention method uptake, adherence, and risk compensation behaviors. Cross-sectional and sub-cohort analyses will be conducted to determine intervention packages uptake. CONCLUSIONS: The literature review, focus groups, and modeling indicate that offering age- and gender- specific combination HIV prevention interventions that include biomedical, behavioral, and structural interventions can have an impact on HIV risk reduction. Implementing this protocol will show the feasibility of delivering these services at scale. The MP3 Youth study is one of the few combination HIV prevention intervention protocols incorporating youth- and gender-specific interventions in one delivery setting. Lessons learned from the design of the protocol can be incorporated into the national guidance for combination HIV prevention for youth in Kenya and other high-burden SSA settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT01571128; http://clinicaltrials.gov/ct2/show/NCT01571128?term=MP3+youth&rank=1 (Archived by WebCite at http://www.webcitation.org/6nmioPd54).

Runaway and homeless youth (RHY) are served by specialized settings (e.g., Drop-In Centers, Transitional Living Programs, and multi-program settings), but little is known about the characteristics of these organizations or their effects on RHY's behavioral and psychosocial outcomes. To address this gap we studied 29 randomly selected diverse settings across New York State, including those in rural, suburban, and urban areas. Within settings, we used the Youth Program Quality Assessment model to observe and rate programs for RHY (N=53), assess program administrators (N=30), and conduct anonymous structured assessment batteries with RHY aged 16-21 years (N =463). We found settings overall evidenced satisfactory-to-high quality on a multi perspective setting quality score. With respect to RHY's behavioral outcomes, engagement in school/job training/work was high (81%), substance use was moderate (mean use: 17 of the past 90 days), and 37% evidenced involvement in the street economy (e.g., drug dealing, burglary). RHY in Transitional Living Programs and multi-program settings had more engagement in school/job training/work and less involvement in the street economy than their peers in Drop-In Centers. The quality of settings was not associated with these three behavioral outcomes (school/training/work, substance use, street economy), likely due to issues of restricted range. However, higher setting quality was associated with four constructive psychosocial outcomes; namely, RHY's perceptions that settings foster positive outcomes in these three domains, and perceived resilience. Thus the present study highlights settings' overall good quality, with some variability, and provides guidance on strategies to assess setting quality. Consistent with the existing literature, RHY in Drop-In Centers are highly vulnerable and may require additional types of services/programs to achieve their potential. Further, while the present study suggests all settings benefit RHY, better quality settings may be able to move beyond meeting RHY's basic requirements and address higher order relational, psychosocial, and motivational needs. Importantly, fostering a sense of resilience among RHY, as well as young people's experiences of settings as helpful to them in achieving good behavioral outcomes, may have long-term beneficial effects on RHY's engagement in other settings, relationships, adaptation, and functioning. (C) 2017 Elsevier Ltd. All rights reserved.

BACKGROUND: Ecstasy (MDMA) use has regained popularity in the United States, particularly in the form of "Molly," which is often marketed as pure MDMA. Surveys have generally not included "Molly" in the definition of ecstasy, so rates of use may be underestimated. As popularity of ecstasy increases, research is needed to examine use among those at highest risk for use-nightlife attendees. METHODS: We surveyed 679 young adults (age 18-25) entering nightclubs and festivals holding electronic dance music (EDM) parties in New York City in 2015. A variation of time-space sampling was utilized. We examined prevalence and correlates of self-reported lifetime ecstasy use. RESULTS: Self-reported lifetime ecstasy use was common (42.8%, 95% CI: 32.8, 52.7). Use was most common among older participants, frequent party attendees, and those reporting higher levels of exposure to users. Those surveyed outside of festivals were less likely to report use compared to those surveyed outside of nightclubs (AOR = 0.37, p = .015). Over a third of ecstasy users (36.8%)reported use in pill, powder, and crystal form. Ecstasy users were also more likely to report use of other drugs, including novel psychoactive substances (e.g., 2C series drugs, synthetic cathinones ["bath salts"]). Half (50.4%) reported suspecting (21.9%) or finding out (28.5%) that their ecstasy had ever contained a drug other than MDMA. CONCLUSION: A large percentage of nightlife attendees in NYC report lifetime ecstasy use. Findings should inform prevention and harm reduction programming. Further research is needed as ecstasy continues to change (e.g., in form, purity, and name).

BACKGROUND: Almost half of adult men in Vietnam are current cigarette smokers. Recent surveys also suggest a high prevalence of water pipe use, particularly in rural areas. Yet services to treat tobacco dependence are not readily available. The purpose of this study was to characterize current tobacco use treatment patterns among Vietnamese health care providers and factors influencing adherence to recommended guidelines for tobacco use screening and cessation interventions for water pipe, cigarette and dual users. METHODS: We conducted cross sectional surveys of 929 male current tobacco users immediately after they completed a primary care visit at one of 18 community health centers. RESULTS: Thirty-four percent of smokers used cigarettes only, 24% water pipe only, and 42% were dual users. Overall 12% of patients reported that a provider asked them if they used tobacco products during the visit. Providers were significantly more likely to screen cigarette smokers compared with water pipe or dual users (16%, 9% and 11% respectively). Similarly, 9% of current cigarette smokers received advice to quit compared to 6% of water pipe and 5% of dual users. No patients reported that their health care provider offered them assistance to quit (e.g., self-help materials, referral). CONCLUSION: Despite ratifying the Framework Convention on Tobacco Control, Vietnam has not made progress in implementing policies and systems to ensure smokers are receiving evidence-based treatment. High rates of water pipe and dual use indicate a need for health care provider training and policy changes to facilitate treatment for both cigarette and water pipe use.

BACKGROUND: African American/Black and Hispanic persons living with HIV (AABH-PLWH) are under-represented in AIDS clinical trials (ACTs) in the United States. Barriers AABH-PLWH experience to ACTs are multi-faceted, including distrust of medical research, low levels of knowledge, unsupportive social norms, lack of referral, and challenges navigating ACT systems. In past research we found a multi-component peer-driven intervention was efficacious in boosting rates of screening for/enrollment into ACTs. The present qualitative study seeks to understand AABH-PLWH's perspectives on which specific intervention features or components had utility. Interventions features explored included structural elements (e.g., small group sessions, individual sessions on the ACT research unit); approaches (e.g., Motivational Interviewing); and specific components (e.g., small-group discussion of historical and cultural factors reducing participation among AABH-PLWH). METHODS: A total of 37 AABH-PLWH (mean age 50.6 years, SD=7.5 years; 48.6% female; 62.2% African American/Black, 27.0% Hispanic) were purposively selected from a larger study for in-depth interviews, which were audio-recorded, transcribed verbatim, and analyzed using systematic content analysis. RESULTS: We found the intervention improved knowledge and positive attitudes toward ACTs, and triggered social-level facilitators such as altruism and more positive social norms. Discussions of cultural/historical barriers to ACTs associated with race/ethnicity had utility. Holding a session on the ACT research unit reduced fear and increased motivation. Results highlighted the value of Motivational Interviewing, and several components were perceived as less useful (e.g., involving social network members in ACT decisions). CONCLUSION: Findings can inform future intervention designs to address racial/ethnic disparities in ACTs and have implications for trials of other conditions where racial/ethnic disparities persist.

After HIV diagnosis, heterosexuals in high-poverty urban areas evidence delays in linkage to care and antiretroviral therapy initiation compared to other groups. Yet barriers to/facilitators of HIV care among these high-risk heterosexuals are understudied. Under the theory of triadic influence, putative barriers to HIV care engagement include individual/attitudinal-level (e.g., fear, medical distrust), social-level (e.g., stigma), and structural-level influences (e.g., poor access). Participants were African-American/Black and Hispanic adults found newly diagnosed with HIV (N = 25) as part of a community-based HIV testing study with heterosexuals in a high-poverty, high-HIV-incidence urban area. A sequential explanatory mixed-methods design was used. We described linkage to HIV care and clinical outcomes [CD4 counts, viral load (VL) levels] over 1 year, and then addressed qualitative research questions about the experience of receiving a new HIV diagnosis, its effects on timely engagement in HIV care, and other barriers and facilitators. Participants were assessed five times, receiving a structured interview battery, laboratory tests, data extraction from the medical record, a post-test counseling session, and in-person/phone contacts to foster linkage to care. Participants were randomly selected for qualitative interviews (N = 15/25) that were recorded and transcribed, then analyzed using systematic content analysis. Participants were 50 years old, on average (SD = 7.2 years), mostly male (80%), primarily African-American/Black (88%), and low socioeconomic status. At the first follow-up, rates of engagement in care were high (78%), but viral suppression was modest (39%). Rates improved by the final follow-up (96% engaged, 62% virally suppressed). Two-thirds (69%) were adequately retained in care over 1 year. Qualitative results revealed multi-faceted responses to receiving an HIV diagnosis. Problems accepting and internalizing one's HIV status were common. Reaching acceptance of one's HIV-infected status was frequently a protracted and circuitous process, but acceptance is vital for engagement in HIV care. Fear of stigma and loss of important relationships were potent barriers to acceptance. Thus, partially as a result of difficulties accepting HIV status, delays in achieving an undetectable VL are common in this population, with serious potential negative consequences for individual and public health. Interventions to foster acceptance of HIV status are needed.