Faculty Bibliography

BACKGROUND:Due to practical challenges associated with genetic sequencing in low-resource environments, the burden of hepatitis C virus (HCV) in forcibly displaced people is understudied. We examined the use of field applicable HCV sequencing methods and phylogenetic analysis to determine HCV transmission dynamics in internally displaced people who inject drugs (IDPWID) in Ukraine. METHODS:In this cross-sectional study, we used modified respondent-driven sampling to recruit IDPWID who were displaced to Odesa, Ukraine, before 2020. We generated partial and near full length genome (NFLG) HCV sequences using Oxford Nanopore Technology (ONT) MinION in a simulated field environment. Maximum likelihood and Bayesian methods were used to establish phylodynamic relationships. RESULTS:Between June and September 2020, we collected epidemiological data and whole blood samples from 164 IDPWID (PNAS Nexus.2023;2(3):pgad008). Rapid testing (Wondfo® One Step HCV; Wondfo® One Step HIV1/2) identified an anti-HCV seroprevalence of 67.7%, and 31.1% of participants tested positive for both anti-HCV and HIV. We generated 57 partial or NFLG HCV sequences and identified eight transmission clusters, of which at least two originated within a year and a half post-displacement. CONCLUSIONS:Locally generated genomic data and phylogenetic analysis in rapidly changing low-resource environments, such as those faced by forcibly displaced people, can help inform effective public health strategies. For example, evidence of HCV transmission clusters originating soon after displacement highlights the importance of implementing urgent preventive interventions in ongoing situations of forced displacement.

BACKGROUND:Cannabis legalization for medical and recreational purposes has been suggested as an effective strategy to reduce opioid and benzodiazepine use and deaths. We examined the county-level association between medical and recreational cannabis laws and poisoning deaths involving opioids and benzodiazepines in the US from 2002 to 2020. METHODS:Our ecologic county-level, spatiotemporal study comprised 49 states. Exposures were state-level implementation of medical and recreational cannabis laws and state-level initiation of cannabis dispensary sales. Our main outcomes were poisoning deaths involving any opioid, any benzodiazepine, and opioids with benzodiazepines. Secondary analyses included overdoses involving natural and semi-synthetic opioids, synthetic opioids, and heroin. RESULTS:Implementation of medical cannabis laws was associated with increased deaths involving opioids (rate ratio [RR] = 1.14; 95% credible interval [CrI] = 1.11, 1.18), benzodiazepines (RR = 1.19; 95% CrI = 1.12, 1.26), and opioids+benzodiazepines (RR = 1.22; 95% CrI = 1.15, 1.30). Medical cannabis legalizations allowing dispensaries was associated with fewer deaths involving opioids (RR = 0.88; 95% CrI = 0.85, 0.91) but not benzodiazepine deaths; results for recreational cannabis implementation and opioid deaths were similar (RR = 0.81; 95% CrI = 0.75, 0.88). Recreational cannabis laws allowing dispensary sales was associated with consistent reductions in opioid- (RR = 0.83; 95% CrI = 0.76, 0.91), benzodiazepine- (RR = 0.79; 95% CrI = 0.68, 0.92), and opioid+benzodiazepine-related poisonings (RR = 0.83; 95% CrI = 0.70, 0.98). CONCLUSIONS:Implementation of medical cannabis laws was associated with higher rates of opioid- and benzodiazepine-related deaths, whereas laws permitting broader cannabis access, including implementation of recreational cannabis laws and medical and recreational dispensaries, were associated with lower rates. The estimated effects of the expanded availability of cannabis seem dependent on the type of law implemented and its provisions.

For 5 decades, US federal regulations have segregated methadone treatment for opioid use disorder from the rest of the health care system, confining its availability to specialty treatment programs that are highly regulated. These regulations have led to severe shortages in the availability of methadone and grave underutilization of this lifesaving medication despite a worsening overdose crisis. In this commentary, we discuss current barriers to methadone in the US opioid treatment system and how recent changes to federal regulations fall short of the reforms needed to significantly expand access to this treatment. Instead, we propose the urgent need to expand methadone to mainstream health care settings by allowing for office-based prescribing and pharmacy dispensing of methadone, the norm in many other developed countries.

Buprenorphine is a highly effective treatment for opioid use disorder (OUD) and a critical tool for addressing the worsening US overdose crisis. However, multiple barriers to treatment-including stringent federal regulations-have historically made this medication hard to reach for many who need it. In 2020, under the COVID-19 public health emergency, federal regulators substantially changed access to buprenorphine by allowing prescribers to initiate patients on buprenorphine via telehealth without first evaluating them in person. As the public health emergency has been set to expire in May of 2023, Congress and federal agencies can leverage extensive evidence from studies conducted during the wake of the pandemic to make evidence-based decisions on the regulation of buprenorphine going forward. To aid policy makers, this narrative review synthesizes and interprets peer-reviewed research on the effect of buprenorphine flexibilities on the uptake and implementation of telehealth, and its impact on OUD patient and prescriber experiences, access to treatment, and health outcomes. Overall, our review finds that many prescribers and patients took advantage of telehealth, including the audio-only option, with a wide range of benefits and few downsides. As a result, federal regulators-including agencies and Congress-should continue nonrestricted use of telehealth for buprenorphine initiation.

BACKGROUND/UNASSIGNED:Acute-care interventions that identify patients with substance use disorders (SUDs), initiate treatment, and link patients to community-based services, have proliferated in recent years. Yet, much is unknown about the specific strategies being used to support continuity of care from emergency department (ED) or inpatient hospital settings to community-based SUD treatment. In this scoping review, we synthesize the existing literature on patient transition interventions, and form an initial typology of reported strategies. METHODS/UNASSIGNED:We searched Pubmed, Embase, CINAHL and PsychINFO for peer-reviewed articles published between 2000-2021 that studied interventions linking SUD patients from ED or inpatient hospital settings to community-based SUD services. Eligible articles measured at least one post-discharge treatment outcome and included a description of the strategy used to promote linkage to community care. Detailed information was extracted on the components of the transition strategies and a thematic coding process was used to categorize strategies into a typology based on shared characteristics. Facilitators and barriers to transitions of care were synthesized using the Consolidated Framework for Implementation Research. RESULTS/UNASSIGNED:Forty-five articles met inclusion criteria. 62% included ED interventions and 44% inpatient interventions. The majority focused on patients with opioid (71%) followed by alcohol (31%) use disorder. The transition strategies reported across studies were heterogeneous and often not well described. An initial typology of ten transition strategies, including five pre- and five post-discharge transition strategies is proposed. The most common strategy was scheduling an appointment with a community-based treatment provider prior to discharge. A range of facilitators and barriers were described, which can inform efforts to improve hospital-to-community transitions of care. CONCLUSIONS/UNASSIGNED:Strategies to support transitions from acute-care to community-based SUD services, although critical for ensuring continuity of care, vary greatly across interventions and are inconsistently measured and described. More research is needed to classify SUD care transition strategies, understand their components, and explore which lead to the best patient outcomes.

BACKGROUND AND AIMS:Low outcome prevalence, often observed with opioid-related outcomes, poses an underappreciated challenge to accurate predictive modeling. Outcome class imbalance, where non-events (i.e. negative class observations) outnumber events (i.e. positive class observations) by a moderate to extreme degree, can distort measures of predictive accuracy in misleading ways, and make the overall predictive accuracy and the discriminatory ability of a predictive model appear spuriously high. We conducted a simulation study to measure the impact of outcome class imbalance on predictive performance of a simple SuperLearner ensemble model and suggest strategies for reducing that impact. DESIGN, SETTING, PARTICIPANTS:Using a Monte Carlo design with 250 repetitions, we trained and evaluated these models on four simulated data sets with 100 000 observations each: one with perfect balance between events and non-events, and three where non-events outnumbered events by an approximate factor of 10:1, 100:1, and 1000:1, respectively. MEASUREMENTS:We evaluated the performance of these models using a comprehensive suite of measures, including measures that are more appropriate for imbalanced data. FINDINGS:Increasing imbalance tended to spuriously improve overall accuracy (using a high threshold to classify events vs non-events, overall accuracy improved from 0.45 with perfect balance to 0.99 with the most severe outcome class imbalance), but diminished predictive performance was evident using other metrics (corresponding positive predictive value decreased from 0.99 to 0.14). CONCLUSION:Increasing reliance on algorithmic risk scores in consequential decision-making processes raises critical fairness and ethical concerns. This paper provides broad guidance for analytic strategies that clinical investigators can use to remedy the impacts of outcome class imbalance on risk prediction tools.

BACKGROUND AND AIMS:Both local socio-economic conditions and prescription opioid supply are associated with drug overdose deaths, which exhibit substantial geographical heterogeneity across the United States. We measured whether the associations of prescription opioid supply with drug overdose deaths vary by local socio-economic conditions. DESIGN:Ecological county-level study, including 3109 US counties between 2006 and 2019 (n = 43 526 county-years) using annual mortality data. SETTING:United States. CASES:A total of 711 447 drug overdose deaths. MEASUREMENTS:We modeled overdose counts using Bayesian hierarchical Poisson models, estimating associations between four types of drug overdose deaths (deaths involving any drugs, any opioid, prescription opioids only and heroin), prescription opioid supply and five socio-economic indicators: unemployment, poverty rate, income inequality, Rey index (components include mean household income, % high school graduates, % blue-collar workers and unemployment rate), and American human development index (HDI; an indicator of community wellbeing). FINDINGS:Drug overdose deaths and all substance-specific overdose deaths were higher in counties with higher income inequality [adjusted odds ratios (aORs) = 1.09-1.13], Rey index (aORs = 1.15-1.21) and prescription opioid supply (aORs = 1.14-1.21), and lower in counties with higher HDI scores (aORs = 0.75-0.92). Poverty rate, income inequality and HDI scores were found to modify the effect of prescription opioid supply on heroin overdose deaths. The plot of the interactions showed that when disadvantage is high, increasing prescription opioid supply does not increase heroin overdose deaths. The less disadvantage there is, indicated by lower poverty rates, higher HDI scores and lower income inequality, the greater the effect of increasing prescription opioid supply relative to population size on heroin overdose deaths in US counties. CONCLUSIONS:In the United States, prescription opioid supply is associated with higher drug overdose deaths; associations are stronger in counties with less disadvantage and less income inequality, but only for heroin overdose deaths.

PURPOSE/UNASSIGNED:We aimed to synthesize insights from systems science approaches applied to domestic and gender-based violence. METHODS/UNASSIGNED:We conducted a systematic review of systems science studies (systems thinking, group model-building, agent-based modeling [ABM], system dynamics [SD] modeling, social network analysis [SNA], and network analysis [NA]) applied to domestic or gender-based violence, including victimization, perpetration, prevention, and community responses. We used blinded review to identify papers meeting our inclusion criteria (i.e., peer-reviewed journal article or published book chapter that described a systems science approach to domestic or gender-based violence, broadly defined) and assessed the quality and transparency of each study. RESULTS/UNASSIGNED:Our search yielded 1,841 studies, and 74 studies met our inclusion criteria (45 SNA, 12 NA, 8 ABM, and 3 SD). Although research aims varied across study types, the included studies highlighted social network influences on risks for domestic violence, clustering of risk factors and violence experiences, and potential targets for intervention. We assessed the quality of the included studies as moderate, though only a minority adhered to best practices in model development and dissemination, including stakeholder engagement and sharing of model code. CONCLUSIONS/UNASSIGNED:Systems science approaches for the study of domestic and gender-based violence have shed light on the complex processes that characterize domestic violence and its broader context. Future research in this area should include greater dialogue between different types of systems science approaches, consideration of peer and family influences in the same models, and expanded use of best practices, including continued engagement of community stakeholders. SUPPLEMENTARY INFORMATION/UNASSIGNED:The online version contains supplementary material available at 10.1007/s10896-023-00578-8.

BACKGROUND:Common adolescent psychiatric symptoms cluster into two dominant domains: internalizing and externalizing. Both domains are linked to self-esteem, which serves as a protective factor against a wide range of internalizing and externalizing problems. This study examined trends in US adolescents' self-esteem and externalizing symptoms, and their correlation, by sex and patterns of time use. METHODS:= 338 896 adolescents, grades:8/10/12, years:1991-2020), we generated six patterns of time use using latent profile analysis with 17 behavior items (e.g. sports participation, parties, paid work). Groups were differentiated by high/low engagement in sports and either paid work or high/low peer socialization. Within each group, we mapped annual, sex-stratified means of (and correlation between) self-esteem and externalizing factors. We also examined past-decade rates of change for factor means using linear regression and mapped proportions with top-quartile levels of poor self-esteem, externalizing symptoms, or both. RESULTS:We found consistent increases in poor self-esteem, decreases in externalizing symptoms, and a positive correlation between the two across nearly all activity groups. We also identified a relatively constant proportion of those with high levels of both in every group. Increases in poor self-esteem were most pronounced for female adolescents with low levels of socializing, among whom externalizing symptoms also increased. CONCLUSIONS:Rising trends in poor self-esteem are consistent across time use groups, as is the existence of a group facing poor self-esteem and externalizing symptoms. Effective interventions for adolescents' poor self-esteem/co-occurring symptoms are needed broadly, but especially among female adolescents with low peer socialization.