Evaluation of Hepatitis C Screening and Treatment Among Psychiatry Inpatients.

Objective: To evaluate uptake of hepatitis C virus (HCV) testing and treatment among psychiatry inpatients at Canada's largest mental health institution, the Centre for Addiction and Mental Health (CAMH).Methods: We reviewed medical records for all forensic and long-stay mental health patients from January 2017 to May 2021 to examine rates of HCV testing (antibody and RNA), treatment, and follow-up and completed a logistical regression to identify predictors associated with HCV antibody (Ab) screening among inpatients.Results: Of 1,031 patients, 73% (n = 753) were male, mean age was 44 years (range: 20-92), and mean length of stay was 7.1 months (range: 0 days-24 years). Most, 83% (n = 856), were diagnosed with schizophrenia spectrum disorders. In total, 652/1,031 (63%) of individuals in this cohort received HCV Ab screening. When broken down by admission rather than individual, 570/1,303 (44%) forensic admissions had an associated HCV Ab screening, and 318/1,450 (22%) non-forensic admissions had an associated HCV Ab screening. Individuals admitted to a forensic unit and those diagnosed with schizophrenia or substance use disorders were more likely to undergo HCV Ab screening, while individuals of Asian ethnicity were less likely (all P < .05). HCV Ab positivity was 4.9%, and most (84%, n = 27) HCV Ab-positive individuals had subsequent RNA testing, of whom 56% (n = 15) tested HCV RNA positive. Of 15 RNA-positive individuals, 10 initiated treatments, 7 on-site at CAMH and 3 at a local hepatology center. A total of 7 individuals (1 treated by specialists and 6 on-site) achieved sustained virological response or cure. The remaining 3 were lost to follow-up, 2 of whom were treated at the hepatology clinic.Conclusions: Based on the high prevalence of HCV, mental health inpatients should be included in groups for whom universal screening is recommended. Since on-site treatment was more successful than referral to external hepatology specialists, utilizing inpatient admission as an opportunity for HCV screening and treatment should receive more consideration.

Leveraging COVID-19 vaccination to promote hepatitis C screening.

Health care initiatives, such as hepatitis C virus (HCV) screening, have been greatly overshadowed by the corona virus disease 2019 (COVID-19) pandemic. However, COVID-19 vaccination programs also provide an opportunity to engage with a high volume of people in a health care setting. We collaborated with a large COVID vaccination center to offer HCV point-of-care testing followed by dried blood spot collection for HCV RNA. Additionally, this opportunity was used to evaluate the practical significance of a 5-minute version of the OraQuick HCV antibody test in lieu of the standard 20-minute test. We tested 2317 individuals; 31 were HCV antibody positive and six were RNA positive of which four were treated and reached sustained virological response. Over a third of those surveyed said they would not have participated had the test required 20 minutes. Conclusion : Colocalizing HCV testing and linkage to care at a COVID vaccination clinic was found to be highly feasible; furthermore, a shortened antibody test greatly improves the acceptance of testing.

Birth cohort hepatitis C antibody prevalence in real-world screening settings in Ontario.

Background: Widespread screening and treatment of hepatitis C virus (HCV) is required to decrease late-stage liver disease and liver cancer. Clinical practice guidelines and Canadian Task Force on Preventative Health Care recommendations differ on the value of one-time birth cohort (1945-75) HCV screening in Canada. To assess the utility of this approach, we conducted a real-world analysis of HCV antibody (Ab) prevalence among birth cohort individuals seen in different clinical contexts. Methods: Cross-sectional study of individuals born between 1945 and 1975 who completed HCV Ab testing at multiple participating centres in Ontario, Canada between January 2016 and December 2020. Differences in prevalence were compared by year of birth, gender, and setting. Results: Among 16,672 birth cohort individuals tested, HCV Ab prevalence was 3.2%. Prevalence was higher among younger individuals which increased from 0.9% among those born between 1945 and 1956 to 4.6% among those born between 1966 and 1975. Prevalence was higher among males (4.4%) compared with females (2.0%) and differed by test site. In primary care, the prevalence was 0.5%, whereas the prevalence was highest among those tested at drug treatment centres (28.7%) and through community outreach (14.0%). Conclusions: HCV Ab prevalence remains high in the 1945-1975 birth cohort. These data highlight the need to re-evaluate existing Canadian Preventative Task Force recommendations, to consider incorporating one-time birth cohort and/or other population-based approaches to HCV screening into the clinical workflow as a preventative health measure, and to increase training among community providers to screen for and treat HCV.

Diagnostic Accuracy of Assays Using Point-of-Care Testing or Dried Blood Spot Samples for the Determination of Hepatitis C Virus RNA: A Systematic Review.

BACKGROUND: Finger-stick point-of-care and dried blood spot (DBS) hepatitis C virus (HCV) RNA testing increases testing uptake and linkage to care. This systematic review evaluated the diagnostic accuracy of point-of-care testing and DBS to detect HCV RNA. METHODS: Bibliographic databases and conference presentations were searched for eligible studies. Meta-analysis was used to pool estimates. RESULTS: Of 359 articles identified, 43 studies were eligible and included. When comparing the Xpert HCV Viral Load Fingerstick assay to venous blood samples (7 studies with 987 samples), the sensitivity and specificity for HCV RNA detection was 99% (95% confidence interval [CI], 97%-99%) and 99% (95% CI, 94%-100%) and for HCV RNA quantification was 100% (95% CI, 93%-100%) and 100% (95% CI, 94%-100%). The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing was 6% (95% CI, 3%-11%). When comparing DBS to venous blood samples (28 studies with 3988 samples) the sensitivity and specificity for HCV RNA detection was 97% (95% CI, 95%-98%) and 100% (95% CI, 98%-100%) and for HCV RNA quantification was 98% (95% CI, 96%-99%) and 100% (95% CI, 95%-100%). CONCLUSIONS: Excellent diagnostic accuracy was observed across assays for detection of HCV RNA from finger-stick and DBS samples. The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing highlights the importance of operator training and quality assurance programs.

Between- and within-person associations between opioid overdose risk and depression, suicidal ideation, pain severity, and pain interference.

BACKGROUND: To better understand overdose (OD) risk and develop tailored overdose risk interventions, we surveyed 234 opioid-using veterans residing in New York City, 2014-2017. Our aim was to better understand how predictors of OD may be associated with physical and mental health challenges, including pain severity and interference, depression and suicidal ideation over time. METHODS: Veterans completed monthly assessments of the Overdose Risk Behavior Scale (ORBS), pain severity and interference, suicidal ideation, and depression for up to two years and were assessed an average of 14 times over 611 days. To estimate between-person and within-person associations between time-varying covariates and opioid risk behavior, mixed-effects regression was used on the 145-person subsample of veterans completing the baseline and at least three follow-up assessments. RESULTS: The level of each time-varying covariate at the average of study time (between-person effect) was positively related to ORBS for pain severity and interference, suicidal ideation, and depression. Deviations from individuals' personal trajectories (within-person effect) were positively related to ORBS for pain severity and interference, suicidal ideation, and depression. CONCLUSIONS: US military veterans endure physical and mental health challenges elevating risk for opioid-related overdose. When pain severity, pain interference, suicidal ideation and depression were higher than usual, opioid risk behavior was higher. Conversely, when these health issues were less of a problem than usual, opioid risk behavior was lower. Assessing the physical and mental health of opioid-using veterans over time may support the development and implementation of interventions to reduce behaviors that increase the likelihood of overdose.

Military veterans' overdose risk behavior: Demographic and biopsychosocial influences.

BACKGROUND: U.S. military veterans face many biopsychosocial (BPS) challenges post-service that may elevate risk for opioid-related overdose including physical pain, mental health concerns and social stressors. Some veterans use opioids to manage pain and cope with social readjustment. This study assessed associations between BPS factors and recent engagement in overdose risk behavior in a community sample of post-9/11 veterans who used opioids in New York City. METHODS: Participants (n = 218) were recruited through convenience sampling and completed a baseline assessment including a validated Opioid Risk Behavior Scale (ORBS) that measured past-30-day engagement in 22 opioid-related overdose risk behaviors. Analyses examined associations between ORBS scores and hypothesized demographic, biological/physical, psychological and social predictors. Incident rate ratios estimated the expected relative difference in ORBS score associated with each predictor. RESULTS: Participants reported an average of 4.72 overdose risk behaviors in the past 30 days. Significant independent predictors of higher ORBS score, after adjustment for demographics and current prescription medications, were past-30-day: depression symptoms; unsheltered or living in a homeless shelter (vs. private housing); history of mental health treatment; experiencing stressful life events; average pain severity; and pain interference. CONCLUSION: Veterans face myriad BPS challenges and, while drug-related overdose risks are well understood, findings suggest that other factors-including mental health, pain and stressful life events-may also be associated with overdose risk among opioid-using veterans. The larger challenges veterans face should be considered in the context of BPS forms of pain management when tailoring and delivering overdose prevention interventions.

Life after opioid-involved overdose: survivor narratives and their implications for ER/ED interventions.

BACKGROUND AND AIMS: Numerous states in the United States are working to stem opioid-involved overdose (OD) by engaging OD survivors before discharge from emergency departments (EDs). This analysis examines interactions between survivors and medical care providers that may influence opioid risk behaviors post-OD. DESIGN: Qualitative stakeholder analysis involving in-depth interviews with samples from three groups. SETTING: Two hospitals in high OD-mortality neighborhoods in New York City (NYC), USA. PARTICIPANTS: Total N = 35: emergency medical services personnel (EMS; n = 9) and ED medical staff (EDS; n = 6) both working in high OD-mortality neighborhoods in NYC; recent opioid-involved OD survivors who had been administered naloxone and transported to a hospital ED (n = 20). MEASUREMENTS: EMS and EDS interviews examined content of verbal interactions with survivors and attitudes related to people who use opioids. Survivor interviews addressed healthcare experiences, OD-related behavioral impacts and barriers to risk-reduction post-OD. FINDINGS: Both EMS and EDS stakeholders described frequent efforts to influence survivors' subsequent behavior, but some acknowledged a loss of empathy, and most described burnout related to perceived ingratitude or failure to influence patients. Survivors reported being motivated to reduce opioid risk following a non-fatal OD and many described successful risk-reduction efforts post-OD. Intentions to cease opioid use or reduce risk were complicated by unmanaged, naloxone-related withdrawal, lack of social support and perceived disrespect from EMS and/or EDS. CONCLUSIONS: Emergency department interventions with opioid-involved overdose (OD) survivors may benefit from training emergency medical staff to assure a continuity of non-judgmental, socially supportive remediation attempts throughout contacts with different care-givers. Brief interventions to educate emergency medical staff about current theories of addiction and evidence-based treatment may achieve this goal while reducing care-giver burnout and improving the uptake and efficacy of post-OD interventions delivered in emergency departments.

"Feeling confident and equipped": Evaluating the acceptability and efficacy of an overdose response and naloxone administration intervention to service industry employees in New York City.

BACKGROUND: The problem of injection drug use in public bathrooms has been documented from the perspectives of people who inject drugs and service industry employees (SIEs). Previous studies suggest that SIEs are unaware of how to respond to opioid overdoses, yet there are no behavioral interventions designed for SIEs to address their specific needs. In response to this gap in the field, we constructed, implemented, and evaluated a three-module behavioral intervention for SIEs grounded in the Information-Motivation-Behavioral skills model. This paper focuses on the evaluation of one module, namely, the intervention component addressing overdose response and naloxone administration (ORNA). METHODS: Participants were SIEs (N = 18 from two separate business establishments) recruited using convenience sampling. The study utilized a pre-/post-test concurrent nested mixed method design and collected quantitative and qualitative data including an evaluation of the intervention module. The primary outcomes were opioid overdose-related knowledge and attitudes. Acceptability was also assessed. RESULTS: SIEs demonstrated significant improvements (p < 0.01, Cohen's d = 1.45) in opioid overdose-related knowledge as well as more positive opioid overdose-related attitudes (p< 0.01, Cohen's d = 2.45) following the intervention. Participants also reported high levels of acceptability of the module and suggestions for improvement (i.e., more role-playing). CONCLUSIONS: This study highlights the acceptability and evidence of efficacy of the ORNA module, as well as the utility of training SIEs in ORNA. The expansion of this training to other SIEs and public employees (librarians, etc.) who manage public bathrooms warrants further investigation.

Perspectives on supervised injection facilities among service industry employees in New York City: A qualitative exploration.

BACKGROUND: Approximately 100 supervised injection facilities (SIFs) operate in 66 cities around the world to reduce overdose deaths, the spread of disease and public disorder, though none legally exist in the United States. Public bathrooms are among the most common public places for injection reported by people who inject drugs in New York City (NYC) and service industry employees (SIEs) inadvertently become first-responders when overdoses occur in business bathrooms. The goal of this study was to assess SIE acceptability of SIFs and the perceived effects that SIFs would have on them, their colleagues, their businesses and communities. METHODS: Semi-structured qualitative interviews were conducted with 15 SIEs recruited through convenience sampling throughout NYC. Participants were provided with peer-reviewed scientific evidence prior to discussing SIFs. Data were analysed using a hybrid deductive and inductive approach. RESULTS: Most SIEs had encountered drug use (93%, n = 14/15) and syringes (73%, n = 11/15) in their business bathrooms and three had encountered unresponsive individuals. Nearly all workers (93%, n = 14/15) were supportive of SIFs and believed SIFs would reduce injection drug use in their business bathrooms. Participants also believed that 'not in my backyard' arguments from community boards may impede SIF operation. CONCLUSIONS: Service industry employees are critical stakeholders due to their exposure to occupational health hazards related to public injection. Those interviewed were amenable to SIF operation as a form of occupational harm reduction and their experiences provide an important dimension to the political debate surrounding SIFs.

Opioid-Involved Overdose Among Male Afghanistan/Iraq-Era U.S. Military Veterans: A Multidimensional Perspective.

BACKGROUND: Mirroring nationwide trends in a broad range of U.S. populations, an alarming number of Afghanistan/Iraq-era U.S. Military veterans have experienced opioid-related overdoses. A growing body of research has examined the proximal behaviors that can precipitate an overdose; considerably less is known about more distal physiological, psychosocial and structural influences on these risk behaviors. OBJECTIVES: This study adopts a multidimensional approach to better understand opioid-related overdose among U.S. Military veterans, and seeks to explore not only the proximal behavioral precipitants of overdose events, but also the complex nexus of physiological, psychological, and sociological influences that undergird overdose events. METHODS: This qualitative examination is based on interview data from 36 male veterans who were discharged from the military after September 2001 and experienced at least one opioid-related overdose during or after military service. Participants were recruited in New York City during 2014 to share narrative accounts of their overdoses. RESULTS: Veterans' accounts indicate that background experiences, such as self-medication for social and psychological pain, trauma, social alienation and isolation, and histories of illicit drug use, precondition the more immediate factors and behaviors that precipitate overdose (including bingeing on drugs, mixing drugs, naiveté about dosage, and ambivalence about life/death). CONCLUSIONS: Findings suggest the need for comprehensive drug safety and overdose education that is sensitive to veterans' physiological, psychological, and sociological conditions. A multidimensional understanding of the distal and proximal overdose risks faced by veterans and other vulnerable groups may help lay a foundation for more inclusive/holistic approaches to overdose prevention and education.

Development of an opioid-related Overdose Risk Behavior Scale (ORBS).

BACKGROUND: Drug overdose has emerged as the leading cause of injury-related death in the United States, driven by prescription opioid (PO) misuse, polysubstance use, and use of heroin. To better understand opioid-related overdose risks that may change over time and across populations, there is a need for a more comprehensive assessment of related risk behaviors. Drawing on existing research, formative interviews, and discussions with community and scientific advisors an opioid-related Overdose Risk Behavior Scale (ORBS) was developed. METHODS: Military veterans reporting any use of heroin or POs in the past month were enrolled using venue-based and chain referral recruitment. The final scale consisted of 25 items grouped into 5 subscales eliciting the number of days in the past 30 during which the participant engaged in each behavior. Internal reliability, test-retest reliability and criterion validity were assessed using Cronbach's alpha, intraclass correlations (ICC) and Pearson's correlations with indicators of having overdosed during the past 30 days, respectivelyInternal reliability, test-retest reliability and criterion validity were assessed using Cronbach's alpha, intraclass correlations (ICC) and Pearson's correlations with indicators of having overdosed during the past 30 days, respectively. RESULTS: Data for 220 veterans were analyzed. The 5 subscales-(A) Adherence to Opioid Dosage and Therapeutic Purposes; (B) Alternative Methods of Opioid Administration; (C) Solitary Opioid Use; (D) Use of Nonprescribed Overdose-associated Drugs; and (E) Concurrent Use of POs, Other Psychoactive Drugs and Alcohol-generally showed good internal reliability (alpha range = 0.61 to 0.88), test-retest reliability (ICC range = 0.81 to 0.90), and criterion validity (r range = 0.22 to 0.66). The subscales were internally consistent with each other (alpha = 0.84). The scale mean had an ICC value of 0.99, and correlations with validators ranged from 0.44 to 0.56. CONCLUSIONS: These results constitute preliminary evidence for the reliability and validity of the new scale. If further validated, it could help improve overdose prevention and response research and could help improve the precision of overdose education and prevention efforts.

Drug use in business bathrooms: An exploratory study of manager encounters in New York City.

BACKGROUND: Though public bathroom drug injection has been documented from the perspective of people who inject drugs, no research has explored the experiences of the business managers who oversee their business bathrooms and respond to drug use. These managers, by default, are first-responders in the event of a drug overdose and thus of intrinsic interest during the current epidemic of opioid-related overdoses in the United States. This exploratory study assists in elucidating the experiences that New York City business managers have with people who inject drugs, their paraphernalia, and their overdoses. METHODS: A survey instrument was designed to collect data on manager encounters with drug use occurring in their business bathrooms. Recruitment was guided by convenience and purposive approaches. RESULTS: More than half of managers interviewed (58%, n=50/86) encountered drug use in their business bathrooms, more than a third (34%) of these managers also found syringes, and the vast majority (90%) of managers had received no overdose recognition or naloxone training. Seven managers encountered unresponsive individuals who required emergency assistance. CONCLUSION: The results from this study underscore the need for additional research on the experiences that community stakeholders have with public injection as well as educational outreach efforts among business managers. This research also suggests that there is need for a national dialogue about potential interventions, including expanded overdose recognition and naloxone training and supervised injection facilities (SIF)/drug consumption rooms (DCR), that could reduce public injection and its associated health risks.

The Portapotty Experiment: Neoliberal approaches to the intertwined epidemics of opioid-related overdose and HIV/HCV, and why we need cultural anthropologists in the South Bronx.

The following report from the field focuses on the authors' collective efforts to operate an ad hoc safer injection facility (SIF) out of portapotties (portable toilets) in an area of the South Bronx that has consistently experienced some of the highest overdose morbidity and mortality rates in New York City over the past decade (New York City Department of Health and Mental Hygiene, 2011, 2015, 2016). Safer injection facilities (also known as supervised injection facilities, drug consumption rooms, etc.) operating outside the US provide a legal, hygienic, and supervised environment for individuals to use drugs in order to minimize the likelihood of fatal overdose and the spread of blood-borne infections while reducing public injection. In the US, the operation of SIFs is federally prohibited by the federal "Crack House" statute though federal, state, and local elected officials can sanction their operation to various degrees (Beletsky, Davis, Anderson, & Burris, 2008). The activists, researchers, undergraduate students and peers from syringe exchange programs who came together to operate the portapotties discovered that they were, in many ways, emblematic of neoliberal solutions to disease prevention: primarily focused on auditing individual risk behaviors and virtually blind to the wider social context that shapes those lives. That social context - the culture of drug injection - was and is out in the open for all of us to see. Going forward, the cultural anthropologist's toolbox will be opened up and used by large groups of undergraduate students to better understand the culture of drug use and how it is changing.

Interaction of paroxetine with mitochondrial proteins mediates neuroprotection.

There are severe neurological complications that arise from HIV infection, ranging from peripheral sensory neuropathy to cognitive decline and dementia for which no specific treatments are available. The HIV proteins secreted from infected macrophages, gp120 and Tat, are neurotoxic. The goal of this study was to screen, identify and develop neuroprotective compounds relevant to HIV-associated neurocognitive disorders (HAND). We screened more than 2000 compounds that included FDA approved drugs for protective efficacy against oxidative stress-mediated neurodegeneration and identified selective serotonin reuptake inhibitors (SSRIs) as potential neuroprotectants. Numerous SSRIs were then extensively evaluated as protectants against neurotoxicity as measured by changes in neuronal cell death, mitochondrial potential, and axodendritic degeneration elicited by HIV Tat and gp120 and other mitochondrial toxins. While many SSRIs demonstrated neuroprotective actions, paroxetine was potently neuroprotective (100 nM potency) against these toxins in vitro and in vivo following systemic administration in a gp120 neurotoxicity model. Interestingly, the inhibition of serotonin reuptake by paroxetine was not required for neuroprotection, since depletion of the serotonin transporter had no effect on its neuroprotective properties. We determined that paroxetine interacts selectively and preferentially with brain mitochondrial proteins and blocks calcium-dependent swelling but had less effect on liver mitochondria. Additionally, paroxetine induced proliferation of neural progenitor cells in vitro and in vivo in gp120 transgenic animals. Therefore, SSRIs such as paroxetine may provide a novel adjunctive neuroprotective and neuroregenerative therapy to treat HIV-infected individuals.

Kinetic and mechanistic characterization of the glyceraldehyde 3-phosphate dehydrogenase from Mycobacterium tuberculosis.

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a glycolytic protein responsible for the conversion of glyceraldehyde 3-phosphate (G3P), inorganic phosphate and nicotinamide adenine dinucleotide (NAD(+)) to 1,3-bisphosphoglycerate (1,3-BPG) and the reduced form of nicotinamide adenine dinucleotide (NADH). Here we report the characterization of GAPDH from Mycobacterium tuberculosis (Mtb). This enzyme exhibits a kinetic mechanism in which first NAD(+), then G3P bind to the active site resulting in the formation of a covalently bound thiohemiacetal intermediate. After oxidation of the thiohemiacetal and subsequent nucleotide exchange (NADH off, NAD(+) on), the binding of inorganic phosphate and phosphorolysis yields the product 1,3-BPG. Mutagenesis and iodoacetamide (IAM) inactivation studies reveal the conserved C158 to be responsible for nucleophilic catalysis and that the conserved H185 to act as a catalytic base. Primary, solvent and multiple kinetic isotope effects revealed that the first half-reaction is rate limiting and utilizes a step-wise mechanism for thiohemiacetal oxidation via a transient alkoxide to promote hydride transfer and thioester formation.