Faculty Bibliography

BACKGROUND:Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS:In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS/RESULTS:Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION/CONCLUSIONS:In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING/BACKGROUND:National Institute of Allergy and Infectious Diseases.

Background/UNASSIGNED:Young people who inject drugs (PWID) have high hepatitis C virus (HCV) incidence and low treatment initiation rates. Novel, simplified care models need to be developed to engage, treat, and cure hard-to-reach patient populations, such as young PWID. We present final data from the randomized pilot clinical trial "HCV-Seek Test and Rapid Treatment" for curing HCV in young PWID. Methods/UNASSIGNED:participant. Results/UNASSIGNED: = .01). Conclusions/UNASSIGNED:PWID, significantly higher rates of cure were achieved using the Rapid Treatment model compared with facilitated referral. Providing easy access to HCV treatment for young PWID in low-threshold settings and initiating HCV treatment quickly appears to be a promising strategy for treating this hard-to-reach population.

BACKGROUND:In the context of the current U.S. injection drug use epidemic, targeted public health harm reduction strategies have traditionally focused on overdose prevention and reducing transmission of blood-borne viral infections. Severe bacterial infections (SBI) associated with intravenous drug use have been increasing in frequency in the U.S. over the last decade. This qualitative study aims to identify the risk factors associated with SBI in hospitalized individuals with recent injection drug use. METHODS:Qualitative analysis (n = 15) was performed using an in-depth, semi-structured interview of participants admitted to Bellevue Hospital, NYC, with SBI and recent history of injection drug use. Participants were identified through a referral from either the Infectious Diseases or Addition Medicine consultative services. Interviews were transcribed, descriptively coded, and analyzed for key themes. RESULTS:Participants reported a basic understanding of prevention of blood-borne viral transmission but limited understanding of SBI risk. Participants described engagement in high risk injection behaviors prior to hospitalization with SBI. These practices included polysubstance use, repetitive tissue damage, nonsterile drug diluting water and multipurpose use of water container, lack of hand and skin hygiene, re-use of injection equipment, network sharing, and structural factors leading to an unstable drug injection environment. Qualitative analysis led to the proposal of an Ecosocial understanding of SBI risk, detailing the multi-level interplay between individuals and their social and physical environments in producing risk for negative health outcomes. CONCLUSIONS:Structural factors and injection drug use networks directly impact drug use, injection drug use practices, and harm reduction knowledge, ultimately resulting in tissue damage and inoculation of bacteria into the host and subsequent development of SBI. Effective healthcare and community prevention efforts targeted toward reducing risk of bacterial infections could prevent long-term hospitalizations, decrease health care expenditures, and reduce morbidity and mortality.

Importance/UNASSIGNED:To achieve hepatitis C elimination, treatment programs need to engage, treat, and cure people who inject drugs. Objective/UNASSIGNED:To compare a low-threshold, nonstigmatizing hepatitis C treatment program that was colocated at a syringe service program (accessible care) with facilitated referral to local clinicians through a patient navigation program (usual care). Design, Setting, and Participants/UNASSIGNED:This single-site randomized clinical trial was conducted at the Lower East Side Harm Reduction Center, a syringe service program in New York, New York, and included 167 participants who were hepatitis C virus RNA-positive and had injected drugs during the prior 90 days. Participants enrolled between July 2017 and March 2020. Data were analyzed after all patients completed 1 year of follow-up (after March 2021). Interventions/UNASSIGNED:Participants were randomized 1:1 to the accessible care or usual care arm. Main Outcomes and Measures/UNASSIGNED:The primary end point was achieving sustained virologic response within 12 months of enrollment. Results/UNASSIGNED:Among the 572 participants screened, 167 (mean [SD] age, 42.0 [10.6] years; 128 (77.6%) male, 36 (21.8%) female, and 1 (0.6) transgender individuals; 8 (4.8%) Black, 97 (58.5%) Hispanic, and 53 (32.1%) White individuals) met eligibility criteria and were enrolled, with 2 excluded postrandomization (n = 165). Baseline characteristics were similar between the 2 arms. In the intention-to-treat analysis, 55 of 82 participants (67.1%) in the accessible care arm and 19 of 83 participants (22.9%) in the usual care arm achieved a sustained virologic response (P < .001). Loss to follow-up (12.2% [accessible care] and 16.9% [usual care]; P = .51) was similar in the 2 arms. Of the participants who received therapy, 55 of 64 (85.9%) and 19 of 22 (86.3%) achieved a sustained virologic response in the accessible care and usual care arms, respectively (P = .96). Significantly more participants in the accessible care arm achieved all steps in the care cascade, with the greatest attrition in the usual care arm seen in referral to hepatitis C virus clinician and attending clinical visit. Conclusions and Relevance/UNASSIGNED:In this randomized clinical trial, among people who inject drugs with hepatitis C infection, significantly higher rates of cure were achieved using the accessible care model that focused on low-threshold, colocated, destigmatized, and flexible hepatitis C care compared with facilitated referral. To achieve hepatitis C elimination, expansion of treatment programs that are specifically geared toward engaging people who inject drugs is paramount. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03214679.

Background:Injection drug use (IDU) is the leading risk factor for hepatitis C virus (HCV) transmission in the U.S. While the general risk factors for HCV transmission are known, there is limited work on how these factors interact and impact young people who inject drugs (YPWID). Methods:rapid antibody testing. Integrating the observed statistical associations with extant literature on HCV risk, we also developed a qualitative system dynamics (SD) model to use as a supplemental data visualization tool to explore plausible pathways and interactions among key risk and protective factors for HCV. Results:Results showed a 31% HCV antibody prevalence with an overall incidence of 10 per 100 person-years. HCV status was independently correlated with having shared cookers with two or more people (AOR = 2.17); injected drugs 4-6 years (AOR = 2.49) and 7 or more years (AOR = 4.95); lifetime homelessness (AOR = 2.52); and having been incarcerated two or more times (AOR = 1.99). These outcomes along with the extant literature on HCV risk were used to develop the qualitative SD model, which describes a causal hypothesis around non-linearities and feedback loop structures underlying the spread of HCV among YPWID. Conclusions:Despite ongoing harm reduction efforts, close to a third of YPWID in the community sample have been exposed to HCV, have risks for injection drug use, and face challenges with structural factors that may be preventing adequate intervention. The qualitative SD model explores these issues and contributes to a better understanding of how these various risk factors interact and what policies could potentially be effective in reducing HCV infections.

BACKGROUND:While people who inject drugs (PWID) are vulnerable to the adverse outcomes of events like COVID-19, little is known regarding the impact of the current pandemic on PWID. We examine how COVID-19 has affected PWID in New York City across four domains: substance use, risk behaviors, mental health, and service utilization. METHODS:As part of a randomized trial to improve access to HCV treatment for PWID, we recruited 165 participants. Eligibility criteria included detectable HCV RNA and recent drug injection. The present cross-sectional analysis is based on a subsample of 106 participants. We compared responses between two separate samples: 60 participants interviewed prior to the pandemic (pre-COVID-19 sample) and 46 participants interviewed during the pandemic (COVID-19 sample). We also assessed differences by study group [accessible care (AC) and usual care (UC)]. RESULTS:Compared to the pre-COVID-19 sample, those interviewed during COVID-19 reported higher levels of mental health issues, syringe reuse, and alcohol consumption and greater reductions in syringe-service programs and buprenorphine utilization. In the analysis conducted by study group, the UC group reported significantly higher injection risk behaviors and lower access to buprenorphine treatment during COVID-19, while during the same period, the AC group reported lower levels of substance use and injection risk behaviors. CONCLUSION:The current study provides insight on how COVID-19 has negatively affected PWID. Placing dispensing machines of harm-reduction supplies in communities where PWID live and increasing secondary exchange, mobile services, and mail delivery of supplies may help maintain access to lifesaving supplies during big events, such as COVID-19. Trial registration ClinicalTrials.gov NCT03214679. Registered July 11 2017. https://clinicaltrials.gov/ct2/show/NCT03214679 .

BACKGROUND:Stigmatizing attitudes towards people who use drugs (PWUD) impact their access and retention in health care. Current measures of PWUD stigma in medical settings are limited. Therefore, we developed and validated theMedical Provider Stigma Experienced by PWUD (MPS-PWUD) scale. METHODS:As part of an ongoing clinical trial, we recruited HCV RNA positive people who inject drugs in New York City. Based on 164 participants, principal component analysis (PCA) was conducted on fifteen stigma items answered on a 5-point Likert scale. We evaluated internal consistency using Cronbach's alpha coefficient and assessed construct validity by comparing stigma levels with willingness to communicate health concerns with medical providers and likelihood to seek HCV treatment. RESULTS:PCA identified a 9-item scale with two components of stigmatization that explained 60.8 % of the total variance and overall high internal consistency (alpha = 0.90). Theenacted stigma (alpha = 0.90) consisted of 6 scale items related to the medical providers' stigmatizing actions or perceptions. The internalized stigma component (alpha = 0.84) included 3 scale items related to PWUD's shame or drug use disclosure. As hypothesized, higher levels of either stigma were associated with less likelihood to openly communicate with medical providers (p < 0.005). Participants with a higher level of enacted stigma were less likely to seek HCV treatment (p = 0.011). CONCLUSIONS:The validated MPS-PWUD scale could help healthcare providers, harm reduction services and researchers measure stigma experienced by PWUD in medical settings in efforts to minimize the impact of stigma on limiting access to and retention of care for PWUD.

Young people who use drugs have a rising hepatitis C (HCV) incidence in the United States, but they may face barriers to testing and treatment adoption due to stigma.We conducted a cross-sectional study of New York City residents aged 18-29 years who reported non-medical prescription opioid and/or heroin use in the past 30 days. Participants were recruited from the community between 2014-2016 via respondent-driven sampling. Participants completed an in-person structured survey that included questions about HCV-testing and treatment and received HCV antibody testing. There were 539 respondents: 353 people who inject drugs (PWID) and 186 non-PWID. For PWID, median age was 25 years, 65% were male, and 73% non-Hispanic White. For non-PWID, median age was 23 years, 73% were male, and 39% non-Hispanic White. 20% of PWID and 54% of non-PWID had never been tested for HCV (p<0.001). Years since first injection (aOR 1.16, CI: 1.02-1.32, p=0.02) and history of substance use treatment (aOR 3.17, CI: 1.53-6.61, p=0.02) were associated with prior testing among PWID. The seroprevalence of HCV among PWID was 25%, adjusted for sampling weights. Of the 75 who were aware of their HCV-positive status, 53% had received HCV-related medical care, and 28% had initiated treatment.HCV prevalence among young PWID is high and many have never been tested. Injection experience and treatment engagement is associated with testing. Interventions to increase testing earlier in injection careers, and to improve linkage to HCV treatment, will be critical for young PWID.