Public health detailing to increase naloxone access in NYC pharmacies.

BACKGROUND: Drug overdose is a public health crisis in the United States. Opioid overdose deaths are preventable using naloxone, an opioid antagonist that reverses the effect of an opioid and prevents fatal overdose. OBJECTIVES: This study aimed to evaluate changes in naloxone standing order status, attitudes, and practice behavior after an 8-week public health detailing campaign on increasing naloxone access conducted among pharmacists in independent pharmacies in New York City (NYC). METHODS: Campaign recommendations were to (1) enroll in the NYC pharmacy naloxone standing order program, (2) offer naloxone to at-risk patients, and (3) educate patients on how to use naloxone. Evaluation was performed using initial and follow-up surveys administered to pharmacists during detailing visits and Department of Health and Mental Hygiene data on pharmacies in the standing order program. RESULTS: Detailing visits were completed with 1153 pharmacists; follow-up visits were completed with 457 (40%). Self-reported attitudes and practice behavior related to the 3 campaign recommendations improved (P < 0.01). After the campaign, 519 new pharmacies enrolled in the standing order program. CONCLUSIONS: The detailing campaign substantially increased the number of pharmacies enrolled in the standing order program and was associated with improved attitudes and practice behavior related to naloxone provision to varying degrees. Other jurisdictions could consider detailing pharmacists as a strategy to increase naloxone access.

Costs of opioid overdose education and naloxone distribution in New York City.

Background: Naloxone is an opioid antagonist medication that can be administered by lay people or medical professionals to reverse opioid overdoses and reduce overdose mortality. Cost was identified as a potential barrier to providing expanded overdose education and naloxone distribution (OEND) in New York City (NYC) in 2017. We estimated the cost of delivering OEND for different types of opioid overdose prevention programs (OOPPs) in NYC. Methods: We interviewed naloxone coordinators at 11 syringe service programs (SSPs) and 10 purposively sampled non-SSPs in NYC from December 2017 to September 2019. The samples included diverse non-SSP program types, program sizes, and OEND funding sources. We calculated one-time start up costs and ongoing operating costs using micro-costing methods to estimate the cost of personnel time and materials for OEND activities from the program perspective, but excluding naloxone kit costs. Results: Implementing an OEND program required a one-time median startup cost of $874 for SSPs and $2,548 for other programs excluding overhead, with 80% of those costs attributed to time and travel for training staff. SSPs spent a median of $90 per staff member trained and non-SSPs spent $150 per staff member. The median monthly cost of OEND program activities excluding overhead was $1,579 for SSPs and $2,529 for non-SSPs. The costs for non-SSPs varied by size, with larger, multi-site programs having higher median costs compared to single-site programs. The estimated median cost per kit dispensed excluding and including overhead was $19 versus $25 per kit for SSPs, and $36 versus $43 per kit for non-SSPs, respectively. Conclusions: OEND operating costs vary by program type and number of sites. Funders should consider that providing free naloxone to OEND programs does not cover full operating costs. Further exploration of cost-effectiveness and program efficiency should be considered across different types of OEND settings.

Hepatitis C Treatment Outcomes for People Who Inject Drugs Treated in an Accessible Care Program Located at a Syringe Service Program.

Hepatitis C virus (HCV) is a significant public health problem that disproportionately afflicts people who inject drugs. We describe outcomes of HCV treatment co-located within a syringe services program (SSP). Fifty-three participants started therapy, and 91% achieved sustained virologic response. SSPs provide an effective venue for HCV treatment.

Witnessed overdoses and naloxone use among visitors to Rikers Island jails trained in overdose rescue.

With the opioid overdose mortality rates rising nationally, The New York City Department of Health and Mental Hygiene (NYC DOHMH) has worked to expand overdose rescue training (ORT) and naloxone distribution. This study sought to determine rates of overdose witnessing and naloxone use among overdose rescue-trained visitors to the NYC jails on Rikers Island. We conducted a six-month prospective study of visitors to NYC jails on Rikers Island who received ORT. We collected baseline characteristics of study participants, characteristics of overdose events, and responses to witnessed overdose events, including whether the victim was the incarcerated individual the participant was visiting on the day of training. Bivariate analyses compared baseline characteristics of participants who witnessed overdoses to those who did not, and of participants who used naloxone to those who did not. Overall, we enrolled 283 participants visiting NYC's Rikers Island jails into the study. Six months after enrollment, we reached 226 participants for follow-up by phone. 40 participants witnessed 70 overdose events, and 28 participants reported using naloxone. Of the 70 overdose events, three victims were the incarcerated individuals visited on the day of training; nine additional victims were recently released from jail and/or prison. Visitors to persons incarcerated at Rikers Island witness overdose events and are able to perform overdose rescues with naloxone. This intervention reaches a population that includes not only those recently released, but also other people who experienced overdose.

Risk factors for hepatitis C seropositivity among young people who inject drugs in New York City: Implications for prevention.

BACKGROUND: Hepatitis C virus (HCV) infection remains a significant problem in the United States, with people who inject drugs (PWID) disproportionately afflicted. Over the last decade rates of heroin use have more than doubled, with young persons (18-25 years) demonstrating the largest increase. METHODS: We conducted a cross-sectional study in New York City from 2005 to 2012 among young people who injected illicit drugs, and were age 18 to 35 or had injected drugs for ≤5 years, to examine potentially modifiable factors associated with HCV among young adults who began injecting during the era of syringe services. RESULTS: Among 714 participants, the median age was 24 years; the median duration of drug injection was 5 years; 31% were women; 75% identified as white; 69% reported being homeless; and 48% [95% CI 44-52] had HCV antibodies. Factors associated with HCV included older age (adjusted odds ratio [AOR], 1.99 [1.52-2.63]; p<0.001), longer duration of injection drug use (AOR, 1.68 [1.39-2.02]; p<0.001),more frequent injection (AOR, 1.26 [1.09-1.45]; p = 0.001), using a used syringe with more individuals (AOR, 1.26 [1.10-1.46]; p = 0.001), less confidence in remaining uninfected (AOR, 1.32 [1.07-1.63]; p<0.001), injecting primarily in public or outdoors spaces (AOR, 1.90 [1.33-2.72]; p<0.001), and arrest for carrying syringes (AOR, 3.17 [1.95-5.17]; p<0.001). CONCLUSIONS: Despite the availability of harm reduction services, the seroprevalence of HCV in young PWID in New York City remained high and constant during 2005-2012. Age and several injection behaviors conferred independent risk. Individuals were somewhat aware of their own risk. Public and outdoor injection and arrest for possession of a syringe are risk factors for HCV that can be modified through structural interventions.

Can hepatitis C be eradicated in the United States?

The advent of highly effective antiviral regimens will make the eradication of hepatitis C in high-income countries such as the United States technically feasible. But eradicating hepatitis C will require escalating our response to the epidemic in key domains, including surveillance and epidemiology, prevention, screening, care and treatment, policy, research, and advocacy. Surveillance must be nimble enough to quickly assess the magnitude of new transmission patterns as they emerge. Basic prevention strategies - community-based outreach and education, testing and counseling, and access to sterile injection equipment and opioid substitution therapies - must be scaled up and adapted to target groups in which new epidemics are emerging. All adults should be screened for hepatitis C, but special efforts must focus on groups with increased prevalence through community outreach and rapid testing. Government, industry, and payers must work together to assure full access to health services and antiviral drugs for everyone who is infected. Access to the new regimens must not be compromised by excessively high prices or arbitrary payer restrictions. Partnerships must be forged between hepatitis providers and programs that serve people who inject illicit drugs. Healthcare providers and systems, especially primary care practitioners, need education and training in treating hepatitis C and caring for substance-using populations. Services must be provided to the disadvantaged and stigmatized members of society who bear a disproportionate burden of the epidemic. Environments must be created where people who use drugs can receive prevention and treatment services without shame or stigma. Action is needed to end the policy of mass incarceration of people who use drugs, reduce the stigma associated with substance use, support the human rights of people who use drugs, expand social safety net services for the poor and the homeless, remove the legal barriers to hepatitis C prevention, and build public health infrastructure to reach, engage, and serve marginalized populations. Governments must take action to bring about these changes. Public health agencies must work with penal institutions to provide prevention and treatment services, including antiviral therapy, to those in need in jails and prisons or on probation or parole. Research is needed to guide efforts in each of these domains. Strong and sustained political advocacy will be needed to build and sustain support for these measures. Leadership must be provided by physicians, scientists, and the public health community in partnership with community advocates and people living with or at risk for hepatitis C. Eliminating hepatitis C from the United States is possible, but will require a sustained national commitment to reach, test, treat, cure, and prevent every case. With strong political leadership, societal commitment, and community support, hepatitis C can be eradicated in the United States. If this is to happen in our lifetimes, the time for action is now. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication."

Spontaneous clearance of chronic hepatitis C virus infection is associated with appearance of neutralizing antibodies and reversal of T-cell exhaustion.

BACKGROUND: Hepatitis C virus (HCV) readily establishes chronic infection with exhaustion of HCV-specific T cells and escape from neutralizing antibodies. Spontaneous recovery from chronic infection is rare and has never to our knowledge been studied immunologically. METHODS: We prospectively studied, from prior to infection through >2 years of follow-up, cytokines, HCV-specific T cells, and antibodies, as well as viral sequence evolution in a white male who spontaneously cleared HCV genotype 1a after 65 weeks. RESULTS: Significant alanine aminotransferase and plasma cytokine elevation and broad HCV-specific T-cell responses did not result in HCV clearance in the acute phase. Frequency and effector function of HCV-specific T cells decreased thereafter, and HCV titers stabilized as is typical for the chronic phase. HCV clearance after 65 weeks followed the appearance of neutralizing antibodies at week 48 and was associated with reversal of HCV-specific T-cell exhaustion, as evidenced by reduced programmed death-1 (PD-1) expression and improved T-cell function. Clearance occurred without inflammation or superinfection with hepatitis B virus, human cytomegalovirus virus, influenza, and Epstein-Barr virus. CONCLUSIONS: T-cell exhaustion is reversible at least in the first 2 years of chronic HCV infection, and this reversion in conjunction with neutralizing antibodies may clear HCV. These findings are relevant for immunotherapy of chronic infections.

Induction of CXCR3- and CCR5-associated chemokines during acute hepatitis C virus infection.

BACKGROUND & AIMS: Characterization of inflammatory mediators, such as chemokines, during acute hepatitis C virus (HCV) infection might shed some light on viral clearance mechanisms. METHODS: Plasma levels of CXCR3 (CXCL9-11)- and CCR5 (CCL3-4)-associated chemokines, ALT, and HCV RNA were measured in nine injection drug users (median 26 samples/patient) before and during 10 acute (eight primary and two secondary) HCV infections. Using functional data analysis, we estimated smooth long-term trends in chemokine expression levels to obtain the magnitude and timing of overall changes. Residuals were analyzed to characterize short-term fluctuations. RESULTS: CXCL9-11 induction began 38-53days and peaked 72-83days after virus acquisition. Increases in ALT levels followed a similar pattern. Substantial negative auto-correlations of chemokine levels at 1 week lags suggested substantial week-to-week oscillations. Significant correlations were observed between CXCL10 and HCV RNA as well as ALT and CXCR3-associated chemokines measured in the preceding week, CCL3-4 expression levels did not change appreciably during acute HCV infection. CONCLUSIONS: Elevation of CXCR3-associated chemokines late during acute HCV infection suggests a role for cellular immune responses in chemokine induction. Week-to-week oscillations of HCV RNA, chemokines, and ALT suggest frequent, repeated cycles of gain and loss of immune control during acute hepatitis C.