Faculty Bibliography

BACKGROUND/UNASSIGNED:People who inject drugs (PWID) in Puerto Rico are disproportionately affected by the hepatitis C virus (HCV) epidemic. However, there is a scarcity of data on the HCV care cascade among PWID in Puerto Rico. This study aims to describe the HCV cascade of care among PWID in Puerto Rico, identify gaps, and explore barriers to HCV care. METHODS/UNASSIGNED:Participants were recruited using respondent-driven sampling and tested for both HCV antibodies (Ab) and RNA (ribonucleic acid) using rapid testing and dried blood spot samples (DBS). The cascade of care was estimated based on the DBS HCV Ab and RNA results, as well as self-reported data on HCV screening, linkage to care, treatment uptake and sustained virologic response collected through a questionnaire. The cascade was constructed sequentially, with each step using the number of people from the preceding step as the base denominator. The survey also assessed participants' perceived barriers to HCV care. RESULTS/UNASSIGNED:Out of 150 participants, 126 (84%) had previously been HCV screened, 87% (109/126) were HCV Ab positive, 72% (79/109) were RNA positive,48% (38/79) were linked to care, 32% (12/38) initiated treatment, 58% (7/12) finished treatment, and 71% (5/7) achieved SVR. Barriers to HCV care included concerns about drug abstinence requirements, access to transportation, stigma in healthcare settings, and lack of knowledge about HCV treatment sites. CONCLUSION/UNASSIGNED:This study provides insights into the HCV cascade of care among PWID in Puerto Rico for the first time and highlights limited diagnosis, treatment uptake, and barriers to care.

Hepatitis C virus (HCV) elimination is an important global public health goal. However, the United States (US) is not on track to meet the World Health Organization's 2030 targets for HCV elimination. Recently, the White House proposed an HCV elimination plan that includes point-of-care (POC) HCV RNA testing, which is currently in use in many countries, but is not approved in the US. POC HCV RNA testing is crucial for implementing community-based testing, and for enabling test-and-treat programs, assessing cure, and monitoring for reinfection.. In this commentary, we review the status of POC HCV RNA testing in the US, discuss factors that are needed for successful implementation, and issue specific public health and policy recommendations that would allow for the use of POC HCV RNA testing to support HCV elimination.

BACKGROUND:Hepatitis C virus (HCV) treatment can effectively cure HCV among people who inject drugs (PWID). Perspectives of PWID treated in innovative models can reveal program features that address barriers to treatment, and guide implementation of similar models. METHODS:We interviewed 29 participants in the intervention arm of a randomized trial. The trial enrolled PWID with HCV in New York City from 2017 to 2020 and tested the effectiveness of a low-threshold HCV treatment model at a syringe services program. Participants were purposively sampled and interviewed in English or Spanish. The interview guide focused on prior experiences with HCV testing and treatment, and experiences during the trial. Interviews were inductively coded and analyzed using thematic analysis. RESULTS:Before enrollment, participants reported being tested for HCV in settings such as prison, drug treatment, and emergency rooms. Treatment was delayed because of not being seen as urgent by providers. Participants reported low self-efficacy, competing priorities, and systemic barriers to treatment such as insurance, waiting lists, and criminal-legal interactions. Stigma was a major factor. Treatment during the trial was facilitated through respect from staff, which overcame stigma. The flexible care model (allowing walk-ins and missed appointments) helped mitigate logistical barriers. The willingness of the staff to address social determinants of health was highly valued. CONCLUSION:Our findings highlight the need for low-threshold programs with nonjudgmental behavior from program staff, and flexibility to adapt to participants' needs. Social determinants of health remain a significant barrier, but programs' efforts to address these factors can engender trust and facilitate treatment. Trial registration NCT03214679.

BACKGROUND:People who inject drugs are at increased risk for several bacterial infections such as bacteremia, endocarditis, and osteomyelitis resulting in severe morbidity and high care costs. Limited data exist surrounding the injection drug use practices and behaviors that may increase the risk of these infections. METHODS:Individuals admitted to a single hospital in New York City with severe bacterial infection, between August 2020 and June 2021, were recruited to partake in an in-depth survey examining potential factors, both demographic and injection drug use behavioral, associated with severe bacterial infections. RESULTS:Thirty-four participants were recruited with injection drug use-associated severe bacterial infection. The mean age was 36.5 years; 21 (62%) were currently homeless, with 19 (56%) patients admitted for infective endocarditis. The mean length of hospital stay of all participants was 32.2 days; 94% received medication for opioid use disorder while admitted, whereas 35% left before treatment completion with a patient-directed discharge or elopement. Eight-two percent of participants were injected daily in the prior 30 days, with an average of 276 injections per participant. Fifty percent of participants reported requiring multiple sticks per injection event "always" or "very often," with 94% reporting reuse of syringes in the prior month. CONCLUSIONS:Severe bacterial infections in people who inject drugs resulted in prolonged and complex hospitalization that culminate in suboptimal outcomes despite aggressive measures to engage patients in medication for opioid use disorder. Numerous nonsterile injection drug use practices were identified, indicating a gap in current infection prevention harm reduction messaging.

Background. Though reinfection with SARS-CoV-2 is well documented, there remains uncertainty about the potential for more severe symptoms with reinfections compared to index infections. Methods. Patients who received SARS-CoV-2 PCR testing between March 1, 2020 and March 1, 2021 at New York City Health and Hospitals (NYC H+H) facilities and had two positive tests>=90 days apart were included in the analysis. Clinical and demographic data were extracted from the electronic medical record. Manual chart review was done to confirm symptomatology, assess COVID-19 related hospital admissions, and determine WHO disease severity. Patients were then classified as unlikely reinfection, possible reinfection, or probable reinfection based on symptomatology, PCR and antibody testing, and lack of alternative diagnoses. Patients were classified as 'unable to be assessed' if symptomatology could not be assessed for both episodes of PCR positivity. Results. During our study timeframe, 1,255,584 unique patients received at least one SARS-CoV-2 PCR test, 265 of whom had two positive tests>=90 days apart. We categorized 20 patients as unable to be assessed, 28 as unlikely reinfection (1 persistent PCR positivity, 27 unlikely true infection at index or second PCR-positive episode), and 217 as possible or probable reinfection. Of the 217, at their index episode 79 had an asymptomatic infection (36.4%) and 17 were severe or critical (7.8%). At their second episode, 162 patients had an asymptomatic infection (74.7%), and 5 were severe or critical (2.3%). Only 24 patients with possible/probable reinfection had a more severe COVID reinfection than index infection, and 20 of the 24 had asymptomatic index infections. Three patients were hospitalized at both episodes, and two deaths possibly attributable to COVID-19 reinfection were noted in this cohort. Figure 3: Change in WHO disease severity classification from index to second infection among probable/possible reinfection cases (n=217) Red indicates increase in disease severity from index to reinfection (n=24), blue indicates decrease in disease severity from index to reinfection (n=100), white indicates no change (n=74) and gray indicates unable to assess disease severity at index or second infection (n=19). Conclusion. COVID-19 reinfection was rare in a high incidence setting among patients tested at NYC H+H facilities. Disease severity was generally milder in reinfection, although severe and critical disease occurred in a small number of patients.These findings from earlier in the pandemic (presumably wild-type and alpha variant) provide data for comparison in understanding how reinfection is evolving with newer variants

Background. Injection drug use is a significant and growing public health concern in New York State (NYS). Infectious endocarditis (IE) is a serious complication of injection drug use, and is associated with significant morbidity and mortality, prolonged hospitalizations, and high healthcare costs. Methods. Data was extracted from the Agency for Healthcare Research and Quality's (AHRQ) Healthcare Cost and Utilization Project (HCUP)'s New York State Inpatient Database (SID) to determine incidence of IE in New York between 2000-2014. The HCUP-SID database includes inpatient discharge records from hospitals across the state regardless of payer and contains information on inpatient healthcare utilization. Regional incidence was then calculated using population values from the 2010 regional census. Cost of hospitalization was derived from the HCUP using the cost to charge ratio (CCR) file to estimate the cost of inpatient hospital stays. Results. During the study interval the number of statewide substance use-associated IE cases fluctuated between a low of 262 cases in 2000, and a high of 362 cases in 2007. Approximately 70-80% of the patients with substance use-associated IE in NYS in this study were insured through public programs (Medicare or Medicaid). In-hospital mortality from substance use-associated IE appears to be decreasing slightly, however, there is an accompanying increase in hospital costs, in part due to long average length of hospital stays between 13 and 18 days. The mean cost of hospitalization rose notably from $51,934 to $134,325 over the course of our study. Over 10% of hospitalizations culminated in patient directed discharges. Over the study period New York City's incidence rates appeared to decrease while other region's incidence rates appeared to increase, specifically in the Capital District, Central New York, and Southern Tier regions. Trends in substance use associated infectious endocarditis in NYS This figure shows trends in endocarditis in the study period. It shows a rise in cases in substance use associated endocarditis in NYS in less urban areas. Conclusion. Between 2000 and 2014 the rates of substance use-associated infective endocarditis in NYS fluctuated but remained fairly constant. Despite the relatively constant statewide rates, there was important regional variation, including decreasing incidence rates of SUIE in New York City and rising incidence rates in non-New York City counties

The science for rapid treatment initiation for hepatitis C virus infection is in place. Easy and quick diagnostic tools can provide results within an hour. Necessary assessment before treatment initiation is now minimal and manageable. Treatment has a low dose burden and high tolerability. Although the critical components for rapid treatment are accessible, certain barriers prevent wider utilization, including insurance restrictions and delays in the health care system. Rapid treatment initiation can improve linkage to care by addressing many barriers to care at once, which is essential for achieving a care plateau. Young people with low health care engagement, finitely engaged people (eg, those who are incarcerated), or people with high-risk injection drug behavior, and thereby high risk for transmission of hepatitis C virus, can benefit the most from rapid treatment. Several innovative care models have demonstrated the potential for rapid treatment initiation by overcoming barriers to care with rapid diagnostic testing, decentralization, and simplification. Expanding these models is likely to be an important component for the elimination of hepatitis C virus infection. This article reviews the current motivation for rapid treatment initiation for hepatitis C virus infection and published literature describing rapid treatment initiation models.

BACKGROUND:People who inject drugs are at increased risk for several bacterial infections such as bacteremia, endocarditis, and osteomyelitis resulting in severe morbidity and high care costs. Limited data exist surrounding the injection drug use practices and behaviors that may increase the risk of these infections. METHODS:Individuals admitted to a single hospital in New York City with severe bacterial infection, between August 2020 and June 2021, were recruited to partake in an in-depth survey examining potential factors, both demographic and injection drug use behavioral, associated with severe bacterial infections. RESULTS:Thirty-four participants were recruited with injection drug use-associated severe bacterial infection. The mean age was 36.5 years; 21 (62%) were currently homeless, with 19 (56%) patients admitted for infective endocarditis. The mean length of hospital stay of all participants was 32.2 days; 94% received medication for opioid use disorder while admitted, whereas 35% left before treatment completion with a patient-directed discharge or elopement. Eight-two percent of participants were injected daily in the prior 30 days, with an average of 276 injections per participant. Fifty percent of participants reported requiring multiple sticks per injection event "always" or "very often," with 94% reporting reuse of syringes in the prior month. CONCLUSIONS:Severe bacterial infections in people who inject drugs resulted in prolonged and complex hospitalization that culminate in suboptimal outcomes despite aggressive measures to engage patients in medication for opioid use disorder. Numerous nonsterile injection drug use practices were identified, indicating a gap in current infection prevention harm reduction messaging.

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.