Distribution of intranasal naloxone to potential opioid overdose bystanders in Sweden: effects on overdose mortality in a full region-wide study.

OBJECTIVES: Distribution of take-home naloxone is suggested to reduce opioid-related fatalities, but few studies have examined the effects on overdose deaths in the general population of an entire community. This study aimed to assess the effects on overdose deaths of a large-scale take-home naloxone programme starting in June 2018, using an observational design with a historic control period. DESIGN: From the national causes of death register, deaths diagnosed as X42 or Y12 (International Classification of Diseases, 10th revision, ICD-10) were registered as overdoses. Numbers of overdoses were calculated per 100 000 inhabitants in the general population, and controlled for data including only individuals with a prior substance use disorder in national patient registers, to focus on effects within the primary target population of the programme. The full intervention period (2019-2021) was compared with a historic control period (2013-2017). SETTING: Skåne county, Sweden. PARTICIPANTS: General population. INTERVENTIONS: Large-scale take-home naloxone distribution to individuals at risk of overdose. PRIMARY AND SECONDARY OUTCOME MEASURES: Decrease in overdose deaths per 100 000 inhabitants, in total and within the population with substance use disorder diagnosis. RESULTS: Annual average number of overdose deaths decreased significantly from 3.9 to 2.8 per 100 000 inhabitants from the control period to the intervention period (a significant decrease in men, from 6.7 to 4.3, but not in women, from 1.2 to 1.3). Significant changes remained when examining only prior substance use disorder patients, and decreases in overdose deaths could not be attributed to a change in treatment needs for opioid use disorders in healthcare and social services. CONCLUSIONS: The present study, involving 3 years of take-home naloxone distribution, demonstrated a decreased overdose mortality in the population, however, only in men. The findings call for further implementation of naloxone programmes, and for further studies of potential effects and barriers in women. TRIAL REGISTRATION NUMBER: NCT03570099.

Malmö Treatment Referral and Intervention Study (MATRIS)-36-month follow-up on retention and substance use among patients referred from needle exchange to opioid agonist treatment-The role of stimulant use at baseline.

INTRODUCTION: Opioid use disorder (OUD) is the leading cause of overdose morbidity and mortality globally. Retention in opioid agonist treatment (OAT) is crucial as it effectively reduces overdose mortality among individuals suffering from OUD. Previous research on treatment retention among heroin-dependent individuals referred from needle exchange programs (NEP) to OAT is scarce, and with predictors for retention in OAT being somewhat inconclusive, further investigations into this subject is of great interest. The aim of our study was to assess 36-month treatment outcomes-defined as retention and illicit drug abstinence-and predictors of OAT discontinuation. METHODS: This is a longitudinal cohort study of 71 study subjects successfully referred from a NEP to OAT. Participants were included between October 2011 and April 2013 and followed for 36 months. The study collected data from a structured baseline interview and from patient records, including laboratory data. RESULTS: At the 36-month follow-up, retention was 51 % (n = 36), with mean days in treatment of 422 for those who discontinued treatment. Amphetamine use during the 30 days before inclusion was positively correlated with treatment discontinuation (AOR 1.22 [95 % CI 1.02-1.46]). No statistically significant association with retention was seen for gender, age, suicide attempt prior to treatment, or benzodiazepine use during 30 days prior to treatment. Opiate use and use of other substances were reduced over time, with major reductions occurring during the first 6 months. CONCLUSIONS: Hitherto, baseline factors predicting retention in OAT have been insufficiently demonstrated. Active referral from NEP to OAT is effective when it comes to long-term retention and reduction of substance use while in treatment. Except from use of amphetamine, the use of other substances prior to OAT was not associated with treatment discontinuation. Further and in-depth analyses of baseline predictors are of importance for OAT retention.

Characteristics of and Experience Among People Who Use Take-Home Naloxone in Skåne County, Sweden.

Background: Opioid overdose related injury or death can be prevented by bystander naloxone administration. For naloxone to be present when and where overdoses occur, opioid prevention education and naloxone distribution (OPEND) must be established on a broad level. This is the 30-month follow-up of the first multi-site naloxone project in Sweden, implemented at 31 sites in the County of Skåne 2018. Aim: To address participant characteristics and factors associated with returning for naloxone refill and with having used naloxone for overdose reversal. An additional aim was to describe self-reported reasons for naloxone refill and overdose experiences. Methods: Data were collected during June 2018-December 2020 through questionnaires at baseline and upon naloxone refill of the initial and subsequent naloxone kit. Descriptive statistics was used to address participant characteristics, those returning for naloxone refill and reporting overdose reversal. Chi-2 test was used for variable comparison between groups. Factors associated with overdose reversals were examined by logistic regression analysis. Reasons for naloxone refill, overdose situation and management were presented descriptively. Results: Among 1,079 study participants, 22% (n = 235) returned for naloxone refill, of which 60% (n = 140) reported a total of 229 overdose reversals. Reversals were more likely to be reported by participants trained at needle exchange programs (NEPs) [adjusted odds ratio (AOR) = 5.18, 95% Confidence interval (CI) = 3.38-7.95)], with previous experience of own (AOR = 1.63, 95% CI = 1.03-2.58) or witnessed (AOR = 2.12, 95% CI = 1.05-4.29) overdose, or who had used sedatives during the last 30 days before initial training (AOR = 1.56, 95% CI = 1.04-2.33). A majority of overdoses reportedly occurred in private settings (62%), where the victim was a friend (35%) or acquaintance (31%) of the rescuer. Conclusion: Participants with own risk factors associated with overdose (e.g., injection use, concomitant use of benzodiazepines and previous experience of own overdose) were more likely to report administering naloxone for overdose reversal. Overdose management knowledge was high. The findings indicate that implementation of multi-site OPEND reaches individuals at particularly high risk of own overdose in settings with limited previous harm reduction strategies and favors a further scaling up of naloxone programs in similar settings.

Substance Use, Hospitalizations, and Co-Occurring Disorders among Patients Transferred from a Needle Exchange Program to Opioid Maintenance Treatment.

Opioid use disorders (OUD) is a relapsing condition with high mortality. Opioid maintenance treatment (OMT) reduces heroin use, and overall morbidity and mortality. The prevalence of psychiatric and substance use disorders, potential baseline predictors for psychiatric hospitalization, and psychiatric diagnoses at follow-up were investigated and may give hints about possible preventative strategies. The medical records for 71 patients were reviewed 36 months following referral to OMT from a needle exchange program (NEP). Their psychiatric diagnoses and hospitalizations were identified. Their baseline characteristics were assessed for potential differences between hospitalized versus non-hospitalized patients and between patients with and without psychiatric diagnoses in a longitudinal observational study without controls. A regression analysis was performed to identify predictors for hospitalization when controlling for OMT status. Sixty-five percent of the patients were hospitalized at least once with a psychiatric diagnosis. Substance-related reasons were prevalent, and detoxification occurred among 59% of patients, with sedative- hypnotics (benzodiazepines, zopiclone, zolpidem, and pregabalin) being the substance used by 52% of patients. Baseline use of these drugs and/or buprenorphine predicted for hospitalization when controlling for OMT status. During the follow-up period, 72% of patients met the criteria for a psychiatric diagnosis other than OUD. The prevalence of non-substance use disorders overlapping with SUD was 41%, and that overlapping with anxiety disorder was 27% of all participants. Increased attention to psychiatric co-occurring disorders in the treatment of OUD is required and the importance of addressing sedative-hypnotics use when initiating OMT is highlighted.

Protocol for a multi-site study of the effects of overdose prevention education with naloxone distribution program in Skåne County, Sweden.

BACKGROUND: Continuously high rates of overdose deaths in Sweden led to the decision by the Skåne County to initiate the first regional take-home naloxone program in Sweden. The project aims to study the effect of overdose prevention education and naloxone distribution on overdose mortality in Skåne County. Secondary outcome measures include non-fatal overdoses and overdose-related harm in the general population, as well as cohort-specific effects in study participants regarding overdoses, mortality and retention in naloxone program. METHODS: Implementation of a multi-site train-the-trainer cascade model was launched in June 2018. Twenty four facilities, including opioid substitution treatment units, needle exchange programs and in-patient addiction units were included for the first line of start-up, aspiring to reach a majority of individuals at-risk within the first 6 months. Serving as self-sufficient naloxone hubs, these units provide training, naloxone distribution and study recruitment. During 3 years, questionnaires are obtained from initial training, follow up, every sixth month, and upon refill. Estimated sample size is 2000 subjects. Naloxone distribution rates are reported, by each unit, every 6 months. Medical diagnoses, toxicological raw data and data on mortality and cause of death will be collected from national and regional registers, both for included naloxone recipients and for the general population. Data on vital status and treatment needs will be collected from registers of emergency and prehospital care. DISCUSSION: Despite a growing body of literature on naloxone distribution, studies on population effect on mortality are scarce. Most previous studies and reports have been uncontrolled, thus not being able to link naloxone distribution to survival, in relation to a comparison period. As Swedish registers present the opportunity to monitor individuals and entire populations over time, conditions for conducting systematic follow-ups in the Swedish population are good, serving the opportunity to study the impact of large scale overdose prevention education and naloxone distribution and thus fill the knowledge gap. TRIAL REGISTRATION: Naloxone Treatment in Skåne County - Effect on Drug-related Mortality and Overdose-related Complications, NCT03570099, registered on 26 June 2018.

Health Related Quality of Life in Individuals Transferred from a Needle Exchange Program and Starting Opioid Agonist Treatment.

BACKGROUND: Opioid agonist treatment (OAT), for the treatment of heroin dependence, has been reported to improve overall health and lower mortality. Drug use and retention in treatment have often been used as measures of treatment success. More recently, however, researchers have suggested that measurements of quality of life should be an outcome in substance use treatment evaluations. In a recent randomized controlled trial we demonstrated high rates of successful rapid referral from a needle exchange program (NEP) to OAT. The aim of this study was to see whether an improvement in health related quality of life (HRQoL) could be seen at 3-month follow-up after starting OAT and whether it was associated with any baseline characteristics. We also wanted to compare our sample to a sample from the general population with regard to HRQoL. METHODS: This was a 3-month follow-up of 71 patients who started OAT. Measurements of HRQoL with EQ-5D (an instrument developed by the EuroQol group) were made at baseline and at three months. RESULTS: Mean EQ-5D VAS (visual analogue scale) for the study sample at baseline was 47.3, which was lower than a Swedish reference population reporting 83.3. Individuals reporting being prescribed a drug for a psychiatric condition had significantly lower EQ-5D index values. Improvement in EQ-5D index score was significantly less for individuals reporting previous overdoses (-0.10, p=0.025). Individuals reporting previous suicide attempts had significantly lower EQ-5D VAS score at baseline. A significant increase of the EQ-5D VAS difference over time was found with a mean difference of 10.94 (p=0.008) for the total sample. CONCLUSION: To our knowledge this is the first time HRQoL as an outcome is reported in a population transferred from a NEP to OAT. Our results indicate that OAT can result in increased HRQoL, even with this type of rapid low-threshold referral.

Malmö Treatment Referral and Intervention Study-High 12-Month Retention Rates in Patients Referred from Syringe Exchange to Methadone or Buprenorphine/Naloxone Treatment.

BACKGROUND: Heroin dependence is associated with high mortality. Opioid agonist treatment (OAT) with methadone or buprenorphine has strong evidence for treatment of this relapsing condition. In our setting, OAT has been associated with strict and demanding intake procedures, often with requirements of social stability, but also high, approximately 80 percent 12-month retention rates. In a recent randomized controlled trial, we demonstrated high rates of successful rapid referral from a syringe exchange programme (SEP) to treatment with methadone or buprenorphine, including actual treatment initiation. The objectives of this study were to assess 12-month retention rates, in order to assess whether a novel referral program of current drug users at a SEP would achieve retention rates comparable to more traditional intake procedures. METHODS: The present report is a 12-month follow-up of 71 patients who successfully started treatment with methadone or buprenorphine/naloxone. Patient data from baseline and at 12 months were collected. RESULTS: Out of the 71 patients who started treatment, 58 (82%) were still in treatment after 12 months. CONCLUSION: This was a population, referred from a SEP, with a high drug use severity on admission and no pretreatment requirement for social stability, but there were still high retention rates at 12 months comparable to regular opioid agonist clinics in our setting.

Malmö Treatment Referral and Intervention Study (MATRIS)­effective referral from syringe exchange to treatment for heroin dependence: a pilot randomized controlled trial.

AIMS: Syringe exchange has been suggested as a potential conduit to treatment for drug dependence, but this has never been documented in Europe. The primary aim was to compare the effectiveness of strength-based case management intervention (CMI) against referral only to facilitate treatment attendance in a syringe exchange programme. We also assessed the effectiveness of a syringe exchange programme for referral of heroin-dependent patients to evidence-based treatment with methadone or buprenorphine (buprenorphine-naloxone). DESIGN: Single-site, two-group randomized controlled trial. SETTING: The syringe exchange programme in Malmö, Sweden and an out-patient clinic (research treatment facility) for maintenance treatment, situated outside the hospital area and run by Malmö Addiction Centre. PARTICIPANTS: Heroin-dependent patients willing to participate (n = 75) were referred to maintenance treatment and randomized to either a strength-based case management intervention aiming to facilitate referral (n = 36) or to referral-only (n = 39). INTERVENTION: The intervention group received an appointment for maintenance treatment and a CMI adjusted to individual patient needs. The CMI was semi-structured, assessing the patients' strengths and needs and identifying what practical help they might need to get to the appointment for maintenance treatment. The control group received an appointment for maintenance treatment. MEASURES: The primary outcome was treatment entry. FINDINGS: Among patients who turned up for recruitment interview and randomization, the percentage of patients who started treatment was 95% in the intervention group and 94% in the control group. Treatment entry was unrelated to intervention status [unadjusted odds ratio (OR) = 0.92 (0.12­6.89), P = 1.00 and adjusted OR = 0.96 (0.12­7.83)]. CONCLUSIONS: A randomized controlled trial in a syringe exchange programme showed no evidence that a strength-based case management intervention improved attendance for treatment over referral alone. Attendance rates were high in both groups.

Respondent-driven sampling in a syringe exchange setting.

AIMS: Respondent-driven sampling is a research technique, new to the Scandinavian setting, used in hard-to-reach populations, such as subjects at risk for HIV, including drug users. This study aimed to evaluate the use of respondent-driven sampling originating from syringe exchange clients, as a method to identify 'hidden' drug users without treatment or social service contact. METHODS: Nine heroin and amphetamine injectors were recruited as 'seeds' and instructed to recruit up to three heavy drug users in a chain-referral process. Recruited clients were interviewed about drug use, social conditions and contacts with treatment, syringe exchange and other authorities. In order to estimate whether the recruitment managed to evolve into groups of 'hidden' drug users, clients included beyond the fourth wave of chain-referral were compared with seeds (wave 0) and clients recruited in waves 1-3. RESULTS: Five seeds were generative, and in total, 66 clients were assessed. Except for one of the 35 variables studied, clients in waves 4-9 did not differ from clients in waves 0-3, and were no less likely to have contacts with authorities. All clients except one were injectors and syringe exchangers, and clients recruited later in the chain-referral even tended to attend the syringe exchange more frequently. CONCLUSIONS: Respondent-driven sampling originating from syringe exchange clients may have difficulty reaching beyond the population of injectors and syringe exchangers. The technique, new to this geographical setting, has potential for future studies, but particular efforts may be necessary to study out-of-treatment heavy drug users unknown to the syringe exchange program.