Quality-adjusted life years among people who inject drugs in a needle syringe program in Sweden.

PURPOSE: Needle syringe programs (NSP) significantly reduce risk behavior and HIV and hepatitis transmission in people who inject drugs (PWID). However, PWID are underrepresented in studies on health-related quality of life (HRQoL), representing a barrier to evaluate effects of public health and preventive measures related to injecting drug use. In this study, we investigate how well the two questionnaires EQ-5D-3L and SF-6D measure health in PWID. We also estimate HRQoL in the PWID population. METHOD: Data on demographics, injection drug use, HIV, hepatitis status, and self-reported HRQoL were collected from 550 PWID enrolled in the Stockholm NSP at enrollment and at 6-, 12-, and 24-month follow-up. Self-rated HRQoL was measured as QALY, using EQ-5D-3L and the SF-6D. Item response theory (IRT) was used to evaluate which of the two instruments that measure health most accurately in this population. Regression analysis was used to estimate population-specific QALYs. RESULTS: The IRT analysis showed that SF-6D was better suited to measure health in PWID. More specifically, SF-6D to a larger extent discriminated between persons regardless of their health status, while EQ-5D was more suitable to detect persons with poorer health. Self-rated HRQoL showed that average QALY was lower among PWID compared to the general Swedish population. However, a general increase in self-reported health was noted over time among participants. CONCLUSION: This study increase knowledge of what instruments are most suitable to measure health among PWID. This is of great importance when evaluating effects of public health and preventive measures in the PWID population.

A study protocol for a European, mixed methods, prospective, cohort study of the effectiveness of naloxone administration by community members, in reversing opioid overdose: NalPORS.

BACKGROUND: Worldwide, opioid use causes more than 100,000 overdose deaths annually. Naloxone has proven efficacy in reversing opioid overdoses and is approved as an emergency antidote to opioid overdose. Take home naloxone (THN) programmes have been introduced to provide 'community members', who are likely to observe opioid overdoses, with naloxone kits and train them to recognise an overdose and administer naloxone. The acceptability and feasibility of THN programmes has been demonstrated, but the real-life effectiveness of naloxone administration by community members is not known. In recent years, the approval of several concentrated naloxone nasal-spray formulations (in addition to injectable formulations, eg.prenoxad) potentially increases acceptability and scope for wider provision. This study aims to determine the effectiveness of THN (all formulations) in real-world conditions. METHODS: A European, multi-country, prospective cohort study, to assess the use of THN by community members to reverse opioid overdoses in a six-month, follow-up period. Participants provided with THN from participating harm reduction and drug treatment sites will be recruited to the study and followed-up for six months. We are particularly interested in the experiences of community members who have been provided with THN and have witnessed an opioid overdose. All participants who witness an opioid overdose during the six-month period (target approx. 600) will be asked to take part in a structured interview about this event. Of these, 60 will be invited to participate in a qualitative interview. A Post Authorisation Efficacy Study (PAES) for the concentrated nasal naloxone, Nyxoid, has been integrated into the study design. DISCUSSION: There are many challenges involved in evaluating the real-life effectiveness of THN. It is not possible to use a randomised trial design, recruitment of community members provided with THN will depend upon recruitment sites distributing THN kits, and the type of THN received by participants will depend on regulations and on local clinical and policy decision-makers. Following up this population, some of whom may be itinerant, over the 6-month study period will be challenging, but we plan to maintain contact with participants through regular text message reminders and staff contact. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05072249. Date of Registration: 8.10.2021.

Patterns of mortality risk among patients with substance use disorder: an opportunity for proactive patient safety?

BACKGROUND: Patients with substance use disorder (SUD) suffer from excess mortality compared to the overall population. This study aims to identify patterns in death rates among patients with SUD visiting a SUD emergency ward and to explore whether this knowledge can be used as input to identify patients at risk and increase patient safety. METHODS: Hospital visit data to a SUD emergency ward were collected between 2010 and 2020 through medical records. Data included gender, age, SUD diagnosis, and the time of death. The Kruskal-Wallis rank sum test was used to test between ordinal variables, and risk ratio was used to quantify the difference in mortality risk. All statistical tests were two-sided, with a 95% confidence interval and a minimum significance level of 0.05. RESULTS: The male patients in the study group had 1.41-1.59 higher mortality risk than the female patients. The study revealed an average death rate of 0.14 among all patients during the study period. Although patients with a diagnosed alcohol use disorder constituted 73.7% of the cohort, having an opioid use disorder or sedative hypnotics use disorder was associated with the highest death rates; 1.29-1.52 and 1.47-1.74 higher mortality risk than those without such diagnoses. CONCLUSION: This study demonstrates that data from visits to SUD emergency wards can be used to identify mortality risk factors, such as gender, type of diagnosis, number of diagnoses, and number of visits to the SUD emergency ward. Knowledge about patterns of patient visits and mortality risk could be used to increase patient safety through a decision support tool integrated with the electronic medical records. An improved system for early detection of increased mortality risk offers an opportunity for an adaptive patient safety system.

Hepatitis C elimination in Sweden: Progress, challenges and opportunities for growth in the time of COVID-19.

BACKGROUND & AIMS: In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated, to establish a baseline and inform public health interventions. Considering the changing landscape of HCV treatment, prevention, and care, and in light of the COVID-19 pandemic, this analysis seeks to evaluate Sweden's progress towards the World Health Organization (WHO) elimination targets and identify remaining barriers. METHODS: The data used for modelling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources and expert input. A dynamic Markov model was employed to forecast population sizes and incidence of HCV through 2030. Two scenarios ('2019 Base' and 'WHO Targets') were developed to evaluate Sweden's progress towards HCV elimination. RESULTS: At the beginning of 2019, there were 29 700 (95% uncertainty interval: 19 300-33 700) viremic infections in Sweden. Under the base scenario, Sweden would achieve and exceed the WHO targets for diagnosis, treatment and liver-related death. However, new infections would decrease by less than 10%, relative to 2015. Achieving all WHO targets by 2030 would require (i) expanding harm reduction programmes to reach more than 90% of people who inject drugs (PWID) and (ii) treating 90% of HCV + PWID engaged in harm reduction programmes and ≥7% of PWID not involved in harm reduction programmes, annually by 2025. CONCLUSIONS: It is of utmost importance that Sweden, and all countries, find sustainability in HCV programmes by broadening the setting and base of providers to provide stability and continuity of care during turbulent times.

Absence of interferon-λ 4 enhances spontaneous clearance of acute hepatitis C virus genotypes 1-3 infection.

OBJECTIVES: Absence of a functional interferon-λ 4 (IFN-λ4) gene (IFNL4) predicts spontaneous resolution of acute hepatitis C virus (HCV) infections in regions with a predominance of genotype 1, whereas variants of the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) entailing reduced activity associate with increased sustained virologic response rates following some therapeutic regimens. This study aimed at investigating the impact of IFNL4 on acute HCV genotype 2 or 3 infections, and whether ITPase activity influenced outcome. MATERIALS AND METHODS: Two hundred and seven people who injected drugs (PWID) with documented anti-HCV seroconversion, and 57 PWID with reinfection with HCV were analyzed regarding IFNL4 (rs368234815 and rs12979860) and ITPA (rs1127354 and rs7270101), and longitudinally followed regarding HCV RNA. RESULTS: The spontaneous clearance of HCV infection in anti-HCV seronegative PWID was enhanced when IFN-λ4 was absent (44% vs. 20% for IFNL4 TT/TTrs1368234815 and ΔGrs1368234815 respectively, p < .001; OR 3.2) across genotypes 1-3. The proportion lacking IFN-λ4 was further increased following resolution of repeated re-exposure to HCV (74% among re-infected participants who had cleared at least two documented HCV infections). ITPA genetic variants did not independently impact on the outcome, but among males lacking IFN-λ4, reduced ITPase activity markedly augmented the likelihood of resolution (65% vs. 29% for <100% and 100% ITPase activity, p = .006). CONCLUSIONS: Absence of IFN-λ4 entails an enhanced likelihood of spontaneous resolution both following primary acute infection and repeated re-exposure to HCV across genotypes 1-3. Among men lacking IFN-λ4, reduced ITPase activity improved outcome.

Univariable associations between a history of incarceration and HIV and HCV prevalence among people who inject drugs across 17 countries in Europe 2006 to 2020 - is the precautionary principle applicable?

BackgroundPeople who inject drugs (PWID) are frequently incarcerated, which is associated with multiple negative health outcomes.AimWe aimed to estimate the associations between a history of incarceration and prevalence of HIV and HCV infection among PWID in Europe.MethodsAggregate data from PWID recruited in drug services (excluding prison services) or elsewhere in the community were reported by 17 of 30 countries (16 per virus) collaborating in a European drug monitoring system (2006-2020; n = 52,368 HIV+/-; n = 47,268 HCV+/-). Country-specific odds ratios (OR) and prevalence ratios (PR) were calculated from country totals of HIV and HCV antibody status and self-reported life-time incarceration history, and pooled using meta-analyses. Country-specific and overall population attributable risk (PAR) were estimated using pooled PR.ResultsUnivariable HIV OR ranged between 0.73 and 6.37 (median: 2.1; pooled OR: 1.92; 95% CI: 1.52-2.42). Pooled PR was 1.66 (95% CI 1.38-1.98), giving a PAR of 25.8% (95% CI 16.7-34.0). Univariable anti-HCV OR ranged between 1.06 and 5.04 (median: 2.70; pooled OR: 2.51; 95% CI: 2.17-2.91). Pooled PR was 1.42 (95% CI: 1.28-1.58) and PAR 16.7% (95% CI: 11.8-21.7). Subgroup analyses showed differences in the OR for HCV by geographical region, with lower estimates in southern Europe.ConclusionIn univariable analysis, a history of incarceration was associated with positive HIV and HCV serostatus among PWID in Europe. Applying the precautionary principle would suggest finding alternatives to incarceration of PWID and strengthening health and social services in prison and after release ('throughcare').

Hepatitis C elimination - Macro-elimination.

In 2016 the WHO set a goal to obtain an 80% reduction in new chronic HCV cases, requiring a level of diagnosis of 90%, treatment coverage of 80% and resulting in a 65% reduction in HCV-related deaths by 2030. This goal is easier to reach in specific populations such as people who inject drugs (PWID), men who have sex with men (MSM) or blood-transfusion recipients before screening for HCV became mandatory and in high-income regions. It is much more difficult to achieve macro-elimination throughout the population especially in low-income areas with underdeveloped infrastructures, a high prevalence of HCV and limited economic resources. To achieve the WHO goals by 2030, awareness of HCV must increase and the cascade of care must be improved and implemented. Diagnostic procedures and treatment should be affordable and universally available. At the end of 2017 fewer than 15 countries were on track to reach these goals by 2030.

High risk of non-alcoholic liver disease mortality in patients with chronic hepatitis C with illicit substance use disorder.

Aims: Hepatitis C virus (HCV) is a slowly progressive disease, often transmitted among people who inject drugs (PWID). Mortality in PWID is high, with an overrepresentation of drug-related causes. This study investigated the risk of death in patients with chronic hepatitis C virus (HCV) infection with or without illicit substance use disorder (ISUD).Methods: Patients with HCV were identified using the Swedish National Patient Registry according to the International Classification of Diseases-10 (ICD-10) code B18.2, with ≤5 matched comparators from the general population. Patients with ≥2 physician visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have ISUD. The underlying cause of death was analyzed for alcoholic liver disease, non-alcoholic liver disease, liver cancer, drug-related and external causes, non-liver cancers, or other causes. Mortality risks were assessed using the standardized mortality ratio (SMR) with 95% CIs and Cox regression analyses for cause-specific hazard ratios.Results: In total, 38,186 patients with HCV were included, with 31% meeting the ISUD definition. Non-alcoholic liver disease SMRs in patients with and without ISUD were 123.2 (95% CI, 103.7-145.2) and 69.4 (95% CI, 63.8-75.3), respectively. The significant independent factors associated with non-alcoholic liver disease mortality were older age, being unmarried, male sex, and having ISUD.Conclusions: The relative risks for non-alcoholic liver disease mortality were elevated for patients with ISUD. Having ISUD was a significant independent factor for non-alcoholic liver disease. Thus, patients with HCV with ISUD should be given HCV treatment to reduce the risk for liver disease.

A qualitative study of facilitators and barriers to participate in a needle exchange program for women who inject drugs.

BACKGROUND: Women who inject drugs (WWID) show higher levels of injecting risk behaviour compared to men, putting them at risk of contracting HIV and hepatitis C (HCV). Compared to men, WWID are also less present in harm reduction programs such as needle exchange programs (NEP). The aim of this study is to investigate reasons for, and barriers to, participation in NEP among WWID in Sweden, and to identify measures that could be taken to strengthen the program and increase participation among WWID. METHOD: In-depth interviews (IDIs) were conducted with 20 WWID who had participated in the Stockholm NEP for at least six months and was over 18 years old. IDIs were audio recorded and transcribed et verbatim. Qualitative content analysis was used to identify themes. RESULTS: The need for sterile injection equipment was identified as the main driver to join and remain in the NEP program. Continuous participation in the NEP was further driven by easy access to a multitude of health-related services. The most valued service was the sexual and reproductive health services (SRHR), allowing participants to access contraceptives, cervical cancer screening and sexually transmitted infections testing (STI-testing). NEP staffs' respectful treatment of participants further contributed to program participation. However, participants also expressed a number of concerns around NEP participation, which created barriers to joining. These included losing custody or visitation rights to children, male partner jealousy and violence, unwillingness to spend time in the waiting area and fear of receiving positive HIV/HCV test results. Practical barriers included limited opening hours and travel distance to the NEP. To strengthen the program, most participants requested additional SRHR services. Most participants also proposed some form of "women only" access to the NEP, to strengthen the feeling of the NEP as a safe space. CONCLUSION: This study identified factors that may increase uptake of NEP among WWID. Additional SRHR services and "women only" access are recommended to be implemented and evaluated as part of NEP. These findings may inform and improve the current scale-up of NEPs in Sweden to ensure equal access to services.

Hepatitis C virus (HCV) related liver fibrosis in people who inject drugs (PWID) at the Stockholm Needle Exchange - evaluated with liver elasticity.

Background and aims: Sharing of unsterile injection equipment among people who inject drugs (PWID) is the major transmission-route for hepatitis C (HCV). HCV is highly prevalent in PWID in the Stockholm needle exchange programme (NEP). The frequency of advanced liver fibrosis among the participants is, however, unknown. Methods: From December 2016 to April 2018, all participants with chronic hepatitis C infection (CHC) were offered liver fibrosis evaluation at the Stockholm NEP, including liver stiffness measurement (LSM), a medical history and expanded blood tests to evaluate APRI and FIB-4 scores. Results: A total of 2037 individuals were enrolled of whom 964 (47.3%) had CHC. LSM was performed in 203 (21.1%) of eligible participants of whom 85% had mild fibrosis (LSM ≤9.4 kPa) and 15% advanced fibrosis (LSM ≥9.5 kPa). APRI >1 and FIB-4 > 3.25 only identified 30% of participants with advanced fibrosis. However, all 31(100%) participants with advanced fibrosis were detected when APRI >1 was combined with an age of ≥40 years and an injection drug use (IDU) duration of ≥15 years. Conclusions: We found that the diagnostic work-up for advanced fibrosis can be simplified with this combination of easily available factors. This allows identification of PWID in need of immediate HCV treatment to prevent further disease progression. Furthermore, LSM can be avoided among PWID with mild fibrosis, identified by age <40 years combined with IDU duration of <15 years and APRI score <1. This strategy enhances the HCV care cascade where LSM is not easily available, and will thus facilitate HCV treatment initiation.

Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe.

BACKGROUND & AIMS: Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. METHODS: We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. RESULTS: At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. CONCLUSIONS: The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. LAY SUMMARY: Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).

Incidence and spontaneous clearance of hepatitis C virus (HCV) in people who inject drugs at the Stockholm Needle Exchange-Importance for HCV elimination.

The major transmission route for hepatitis C virus (HCV) is through sharing of unsterile injection equipment among people who inject drugs (PWID). The WHO strategy for HCV elimination by 2030 proposes increased efforts to treat PWID populations that drive the HCV epidemic. Among participants in the Stockholm needle exchange programme (NEP), the HCV prevalence is 60%. We aimed to study HCV incidence, spontaneous HCV clearance rate, and predictors associated with new HCV infections and reinfections in NEP participants. All 2320 patients enrolled in the programme between 8 April 2013 and 23 September 2016 were tested for HCV at baseline, and responded to a questionnaire regarding sociodemographic data and injection risk behaviour. Tests for HCV were repeated at an interval of 3-6 months. The anti-HCV prevalence in the NEP participants at baseline was 77%, and the prevalence of HCV RNA was 57%. 24% of the anti-HCV positive were HCV RNA negative with a spontaneously cleared HCV infection. The overall HCV incidence rate was 22/100 PY. The HCV incidence rate in the HCV naive group was 26/100 PY, and in the spontaneously cleared group 19/100. Although there were no significant differences in becoming HCV infected between the two groups (31% vs 29%), the rate of spontaneous HCV clearance was significantly lower in the HCV naive group, 20% vs 44%, (P < 0.05). A high HCV incidence rate was noted among the PWID indicating that treatment needs to be scaled up in conjunction with harm reduction measures to achieve HCV elimination goals set by WHO. This includes high coverage needle exchange programmes and effective addiction treatment for substance users, including opiate substitution treatment.

The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies.

UNLABELLED: OBJECTIVE. Recently, new highly effective direct-acting antivirals (DAAs) against hepatitis C virus (HCV) were introduced. Whether these will alleviate the anticipated increase of liver disease burden in Sweden is unknown, partly because high costs may restrict the use. The objectives were to model the HCV epidemic in Sweden, the burden of disease, and the potential impact of different treatment strategies. MATERIAL AND METHODS: HCV disease progression was modeled to 2030. Scenarios were simulated using new DAAs with sustained annual treatment rate (n = 1130), reduced treatment rate (n = 380) to maintain budget, and increased treatment rates (n = 1430 or 2260) to reduce HCV infections. RESULTS: With today's triple therapies, the estimated number of serious liver complications and death are expected to peak in 2021. Using new DAAs among F0-F4 patients, an unchanged annual treatment rate can reduce the number of HCV infections by 10% by 2030; however, hepatocellular carcinoma (HCC) and mortality will remain unchanged. By reducing to 380 treatments annually and focusing on patients with advanced fibrosis (F3-F4), serious complications will remain constant but the total number of HCV infections will increase. By doubling the number of DAA treatments, HCC-incidence and liver-related deaths would decrease by 65-70% by 2030. CONCLUSION: Mortality and HCC can be reduced with new DAAs and sustained treatment uptake when restricted to F2-F4 patients, or with increased uptake in F0-F4 patients. Treatment restrictions to limit cost may reduce the positive effects and increase the burden of HCV infection. These results may be important for the future strategies of HCV management.

Changes in hepatitis C virus prevalence and incidence among people who inject drugs in the direct acting antiviral era.

BACKGROUND: The World Health Organization (WHO) has set a goal to eliminate hepatitis C virus (HCV) infection by 2030, including a 90% reduction of HCV incidence. With the introduction of a needle syringe program (NSP) in Stockholm, Sweden, and unrestricted availability of direct acting antiviral (DAA) treatment, we investigate the change of prevalence and incidence of HCV infection among people who inject drugs (PWID) over time. METHODS: All persons attending the Stockholm NSP 2013-2021 (n=4,138) were included. The prevalence of viremic HCV infection was investigated yearly. For incidence analysis, PWID at risk with at least one follow-up test were included. Participants were divided into naive defined as anti-HCV negative (n=791), and exposed, defined as anti-HCV positive with a negative HCV RNA (n=1,030). Risk factors for HCV infection were analyzed using parametric exponential proportional hazards regression models. RESULTS: The prevalence of viremic HCV infection decreased from 62% to 30% year 2013-2021 while the prevalence of cured after treatment increased from 0 to 22%, corresponding to 42% cured after treatment out of eligible in 2021. The overall incidence rate in naive was 16.9 (95% CI 15.0-19.0) and in exposed 12.8 (95% CI 11.6-14.2) per 100 person years (PY) and was not significantly reduced years 2013-2015 to 2020-2021 in either group. Risk factors for incident HCV infection in multivariable analysis were sharing needles/syringes, younger age, custody/prison past year, and homelessness, whereas opioid agonist treatment was protective. CONCLUSION: The prevalence of HCV was halved in PWID as unrestricted DAA treatment became available and NSP was established in Stockholm. However, overall incidence was not reduced. To meet the WHO incidence goal, targeting PWID with high injection risk behaviors for testing and treatment is essential, along with engagement in harm reduction services.

Sweden's first Take-Home Naloxone program: participant characteristics, dose endpoints and predictors for overdose reversals.

BACKGROUND: Opioid overdoses are a growing concern, particularly among people who inject drugs. Sweden, with a comparatively high proportion of drug-related mortality, introduced its first Take-Home Naloxone (THN) program in 2018, at the Stockholm needle and syringe program (NSP). In this study we compare THN participant characteristics regarding refills and overdose reversals as well as investigate predictors associated with number of reversals. We also investigate interventions performed in overdose situations and endpoints for naloxone doses. METHODS: This was a prospective open inclusion cohort study conducted between January 24th 2018 and March 31st 2022 at the Stockholm NSP. Participants received THN, free of charge, after a training session and provided data regarding drug use and overdose experiences. During refill visits, participants reported if the naloxone was used for overdose reversal and, if so, responded to a ten-item questionnaire which included stating whether the naloxone recipient was the participant themselves or somebody else. Questionnaire data was combined with NSP database demographic data. Zero-inflated Poisson regression was applied to analyse predictors for number of reported overdose reversals. RESULTS: Among study participants (n = 1,295), 66.5% stated opioids as their primary drug, and 61.4% and 81.0% had previous experience of a personal or witnessed overdose, respectively. Overall, 44.0% of participants reported a total of 1,625 overdose reversals and the victim was known to have survived in 95.6% of cases. Stimulant use (aIRR 1.26; 95% CI 1.01, 1.58), benzodiazepine use (aIRR 1.75; 95% CI 1.1, 2.78) and homelessness (aIRR 1.35; 95% CI 1.06, 1.73) were predictors associated with an increased number of reported overdose reversals. Mortality was higher among those who reported at least one overdose reversal (HR 3.4; 95% CI 2.2, 5.2). CONCLUSIONS: An NSP's existent framework can be utilised to effectively implement a THN program, provide basic training and reach numerous high-risk individuals. During the four-year study, THN participants reversed a sizeable number of potentially fatal overdoses, of which many were reported by participants whose primary drug was not opioids. Naloxone refill rate was high, indicating that participants were motivated to maintain a supply of naloxone in case of future overdose events.

A rapid assessment of take-home naloxone provision during COVID-19 in Europe.

BACKGROUND: In March 2020, the World Health Organization declared COVID-19 a global pandemic. In the following weeks, most European countries implemented national lockdowns to mitigate viral spread. Services for people who use drugs had to quickly revise their operating procedures to rearrange service provision while adhering to lockdown requirements. Given the scarcity of literature published on overdose prevention during COVID-19 in Europe, we aimed to examine how these changes to service provision affected take-home naloxone (THN) programmes and naloxone availability across Europe. METHODS: Between November 2020 and January 2021, we conducted a rapid assessment with country experts from European countries that provide THN. We sent country experts a template to report monthly THN distribution data (January 1, 2019-October 31, 2020) and a structured 6-item survey for completion. RESULTS: Responses were received from 14 of the 15 European countries with THN provision of which 11 participated in the rapid assessment: Austria, Denmark, England, Estonia, Lithuania, Northern Ireland, Norway, Scotland, Spain (Catalonia only), Sweden, and Wales. All reported reduced organisational capacity during COVID-19, and some put into place a range of novel approaches to manage the restrictions on face-to-face service provision. In six countries, the introduction of programme innovation occurred alongside the publication of government guidelines recommending increased THN provision during COVID-19. Eight of the eleven participating countries managed to maintain 2019-level monthly THN distribution rates or even increase provision during the pandemic. CONCLUSION: Through programme innovation supported by public guidelines, many European THN programmes managed to ensure stable or even increased THN provision during the pandemic, despite social distancing and stay-at-home orders affecting client mobility.

A prospective cohort study of risk behaviours, retention and loss to follow-up over 5 years among women and men in a needle exchange program in Stockholm, Sweden.

BACKGROUND: Needle exchange programs (NEP) are important in reducing risk behaviours among people who inject drugs (PWID), also exposed to HIV and hepatitis C (HCV) through injecting drug use (IDU). Women (WWID) compared to men who inject drugs (MWID), are particularly vulnerable with complex needs, however less is known about their risk determinants and NEP outcomes. METHODS: In an open prospective NEP cohort, 697 WWID and 2122 MWID were followed, 2013-2018. Self-reported socio/drug-related determinants for receptive injection (needle/syringe and paraphernalia) and sexual risk behaviours at enrolment, lost to follow-up (LTFU) and probability of retention, were assessed for both groups. Multivariable logistic regression (adjusted odds ratios, aOR) for enrolment and Poisson regression (adjusted incidence rate ratios, aIRR) for LTFU, were used. Cumulative NEP-retention probability was analysed using a six- and 12-month scenario. RESULTS: At NEP enrolment, injection risk behaviours among WWID were associated with: younger age; homelessness; amphetamine-IDU; non-participation in opioid substitution therapy (OST); history of custody and among MWID: lower education level; cohabitation; homelessness, being a tenant; amphetamine-IDU; non-participation in OST; history of being sectioned, HIV-negative and HCV-positive. Condomless sex among WWID was associated with: younger age; lower education-level; cohabitation; having a partner; amphetamine-IDU; non-participation in OST; being HIV-negative and HCV-positive and among MWID: younger age; married; cohabitation; having a partner; amphetamine-IDU; non-participation in OST; history of custody, prison and being HIV-negative. WWID had higher NEP-retention levels compared to MWID over time. Being LTFU among WWID was associated with being HIV-negative and reporting injection risk behaviours and among MWID, younger age, non-participation in OST, being HIV-negative and having protected sex. CONCLUSIONS: Despite better NEP compliance among WWID, high injection and sexual risk behaviours in both gender-subgroups, especially in intimate relationships, suggests ongoing HCV and HIV-infection risks. Subgroup-variation in the NEP continuum of care warrants more gender-disaggregated research and tailoring gender-sensitive services may improve prevention, health and retention outcomes.

Mortality among amphetamine users with hepatitis C virus infection: A nationwide study.

AIMS: To investigate liver-related and all-cause mortality among amphetamine users with hepatitis C virus (HCV) infection and compare this with opioid users with HCV infection and the uninfected general population. METHODS: In this national register study of mortality in persons notified with HCV infection 1990-2015 and a substance-related diagnosis in Sweden, amphetamine users (n = 6,509) were compared with opioid users (n = 5,739) and a matched comparison group without HCV infection/substance use (n = 152,086). RESULTS: Amphetamine users were observed for 91,000 years and 30.1% deceased. Crude liver-related mortality was 1.8 times higher in amphetamine users than opioid users (crude mortality rate ratio 1.78, 95% CI 1.45-2.19), but there was no significant difference when adjusting for age and other defined risk factors. An alcohol-related diagnosis was associated with liver-related death and was more common among amphetamine users. Crude and adjusted liver-related mortality was 39.4 and 5.8 times higher, respectively, compared with the uninfected group. All-cause mortality was lower than in opioid users (adjusted mortality rate ratio 0.78, 95% CI 0.73-0.84), but high compared with the uninfected group. External causes of death dominated in younger ages whereas liver-related death was more common among older individuals. CONCLUSIONS: This national register study presents a higher crude risk of liver-related death among HCV-infected amphetamine users compared with opioid users or the uninfected general population. The higher risk of liver-related death compared with opioid users may be explained by lower competing death risk and higher alcohol consumption. Treatment of HCV infection and alcohol use disorders are needed to reduce the high liver-related mortality.

Significant decrease in injection risk behaviours among participants in a needle exchange programme.

Background and aims: Sharing of unsterile injection equipment contributes to transmission of hepatitis C virus (HCV), HIV and hepatitis B virus (HBV) among people who inject drugs (PWID) but is largely preventable through needle exchange programmes (NEP). Sweden has been one of the last countries in Europe to scale up access to NEP for PWID, who consequently have high prevalence rates of HCV and HIV. The aim of the study was to investigate demographic and drug-related determinants of injection risk behaviours, sharing of needle/syringe and paraphernalia, and patterns of change over time in subgroups of PWID participating in the Stockholm NEP.Methods: The Stockholm NEP started in 2013 as the first formal NEP in the region. A total of 2860 PWID were included in this prospective open cohort study. The association between demographic and drug-related determinants and injection risk behaviours were analysed at baseline and followed up at 6, 12, 24, 36 and 48 months post-enrolment.Results: The following factors were associated with high levels of injection risk behaviours at inclusion: female gender, homelessness, low education level, younger age, amphetamine use, not in opioid substitution therapy (OST), being HIV negative and being HCV positive. We found an overall significant decrease in injection risk behaviours over time among participants. Not previously investigated in depth, we found that subgroups of participants varied in degrees of injection risk behaviour reduction over time and that women decreased injection risk behaviours faster than men. Enrolment in OST, HIV positive and age <25 years at inclusion were not associated with a decrease in injection risk behaviours over time.Conclusions: In this prospective cohort study over 4 years, we found that NEP participation was associated with a significant decrease in injection risk behaviours.

Hepatitis C infection among injection drug users in Stockholm Sweden: prevalence and gender.

Hepatitis C virus (HCV) infection is widespread among injection drug users. Young women seem to be at higher risk of acquiring HCV. To optimize future intervention and prevention measures, we studied the epidemiology of human immunodeficiency virus (HIV), hepatitis B (HBV), and HCV infection among men and women. Inclusion criteria for this cross-sectional multicentre study were: history of ever injecting drugs, age > 18 y, and no previous HIV diagnosis. In 310 participants, plasma/serum samples were analysed for HBV, HIV and HCV (anti-HCV, HCV-RNA, and HCV genotype). HCV antibodies were noted in 268 (86.5%) participants, of whom 207 (77.0%) also had detectable HCV-RNA. Genotypes 1 and 3 dominated, at 35.9% and 33.0%, respectively. Women acquired HCV (but not HBV) to a significantly higher degree (RR 2.97, 95% confidence interval 1.11-7.93) during the first y of injecting drugs. They also recovered spontaneously from HCV infection more frequently (RR 2.49, 95% CI 1.28-4.53). The HCV prevalence of about 50% within 2 y after initiation of injection drug use underlines the need for early intervention efforts. Possible causes for higher HCV prevalence and the implications of favourable spontaneous recovery rates among women should be considered when designing intervention and prevention measures.