Patterns of filled prescriptions and the association with risk of drug-induced death. A population-based nested case-control register study.

PURPOSE: Opioid analgesics (OA) and other pharmaceuticals have been associated with drug-induced deaths. However, there is a lack of knowledge regarding patterns of use of these pharmaceuticals in the population and regarding such associations. We identify and describe subgroups of people with different patterns of filled prescriptions of OA and other relevant pharmaceuticals and examine associations with drug-induced deaths. In addition, we estimate the proportion of drug-induced deaths with a filled OA prescription and OA as cause of death. METHODS: A Norwegian population-based nested case-control register study with cases (drug-induced deaths 2010-2018, N = 2388) and population controls matched for age, gender and year of inclusion (N = 21 465). Patterns of filled prescriptions for opioid analgesics (OA), benzodiazepines and benzodiazepine-related drugs, gabapentinoids, ADHD medication and antidepressants/antipsychotics were explored by k-means cluster analysis. Associations with drug-induced deaths were estimated by conditional logistic regression adjusted for sociodemographic characteristics. Overlap of filled OA prescriptions and OA as cause of death was estimated. RESULTS: Five clusters were identified: 'few prescriptions', 'weak OA', 'ADHD medication', 'sedative/psychiatric morbidity' and 'strong OA'. The 'strong OA' cluster had higher socioeconomic status compared to the other groupings. The risk of drug-induced death was also highest in this cluster (OR = 35.5; CI 25.6-49.3) and, for 68% (CI 64-73) of cases, filled prescriptions for OA was indicated as the underlying cause of death. CONCLUSIONS: The cluster analysis identified a subgroup with filled prescriptions of OA and other pharmaceuticals and a higher socioeconomic status than other subgroups. This subgroup had a high risk of drug-induced death that needs to be addressed.

Attitudes Toward Cannabis Use Legalization and Openness to Legal Use Among Young Partygoers in Norway.

OBJECTIVE: The purpose of this study was to examine attitudes toward legalization of cannabis use and openness to legal use among Norwegian partygoers. METHOD: We examined a combined sample (N = 4,790; 46.2% female) of young partygoers (M age = 23.7, SD = 7.3) from three Norwegian studies on substance use in various settings: music festivals (n = 1,312), nightlife (n = 2,005), and high school graduation (n = 1,473). Through onsite surveys, the participants were asked if they thought cannabis use should be legal in Norway and whether they themselves would use the drug if legalized. These responses (yes/no/don't know) were examined in relation to participants' characteristics and cannabis use history using summary statistics and multinomial regression models. RESULTS: Although 46.1% of participants reported having used cannabis at least once, only 1/3 (32.6%) favored legalization and 1/4 (25.6%) stated they would themselves use cannabis if legalized. Yet, even among never-users, we observed non-opposition to legalization (16.4% in favor; 14.9% don't know) and openness to legal use (8.2% would use; 12.4% don't know). Histories of cannabis, tobacco, or any other drug use, sex (male), and age younger than 21 years (vs. 30 or older) were consistently associated with affirmative responses to both questions. Openness to legal use was strongly associated with favorable legalization attitudes and age younger than 21, even after accounting for lifetime cannabis use history. CONCLUSIONS: Favoring cannabis legalization and openness to legal use were relatively low in this sample of young Norwegian partygoers. Yet, prevalence of cannabis use may increase after legalization among its supporters and among those younger than 21, especially if "don't know" responses are considered.

Increases in drug overdose deaths in Norway and the United States during the COVID-19 pandemic.

INTRODUCTION: Little international comparative work exists describing pandemic-related spikes in overdose and related implications for drug and public health policy. We compared increases in overdose deaths during the pandemic in Norway and the United States, two countries in the top 10 for per-capita overdose mortality, yet with very different approaches to the pandemic, healthcare and drug policy. METHODS: We examined monthly overdoses in 2020 versus baseline rates (the monthly average across 2017-2019). We compared excess overdose mortality to shifts in human mobility and social interaction, measured using cellphone-based mobility data, an indicator of the societal response to the pandemic. RESULTS: Both the US and Norway saw large magnitude exacerbations in overdose mortality during the pandemic-related lockdowns, reaching 46.8% and 57.0% above baseline, respectively. Maximum increases occurred 2-3 months after peak reductions in mobility, suggesting lagged mechanisms. While overdose mortality returned to baseline relatively quickly in Norway, rates remained elevated in the US to the end of 2020. CONCLUSIONS: Spikes in overdose mortality in both contexts may relate to disruptions in healthcare access and the drug supply becoming more potent. Norway's quicker return to baseline may reflect more robust access to harm reduction and addiction-related healthcare services. Nevertheless, it is notable that even in Norway - with universal access to high-quality services, low COVID-19 rates, and a highly effective public health infrastructure - a greater than 50% spike in overdose deaths was still seen at the onset of lockdown measures. This may have important implications for future pandemic and disaster planning.

Individuals Dying of Overdoses Related to Pharmaceutical Opioids Differ from Individuals Dying of Overdoses Related to Other Substances: A Population-Based Register Study.

BACKGROUND: Pharmaceutical opioid (PO) overdose deaths have increased in many Western countries. There are indications that those dying from a PO overdose differ from those dying from other types of overdoses. These differences might pose a challenge as the majority of current preventive measures are tailored toward those with the characteristics of "conventional" overdose deaths. OBJECTIVE: We investigated differences in the characteristics of persons who died from PO overdoses compared to all other overdoses. MATERIAL AND METHODS: Using the Norwegian Cause of Death Registry, we retrieved information on overdoses classified according to ICD-10 and identified PO overdoses (T40.2; T40.4) and all other overdoses (T40.X; T43.6) in 2010-2019. By linking data from nationwide registers, we analyzed data on opioid dispensations and the history of mental and behavioral disorders. 1,224 persons were registered with PO overdoses and 1,432 persons with other overdoses. RESULTS: Persons in the PO overdose group were older and were more frequently women (35.0% vs. 20.5%) than persons with other overdoses. They had a higher prevalence of chronic pain (35.8% vs. 13.2%), history of cancer (8.1% vs. 1.8%), filled prescriptions of analgetic opioids more frequently the month before death (38.8% vs. 12.0%), and used threefold higher doses of prescribed opioids compared to individuals in all other overdose group (66 vs. 26 oral morphine equivalents/day). In the PO overdose group, oxycodone and fentanyl were more frequently dispensed, while codeine was more frequently dispensed in the other overdose groups. A lower proportion of those in the PO overdose group had recorded diagnoses of substance use disorders, schizophrenia, and hyperkinetic disorder compared to the other overdose groups. CONCLUSION: Persons dying from overdoses on POs often differ from the population targeted by existing prevention strategies, as they are more frequently older women with chronic pain and using high doses of prescription opioids.

Increasing trend in accidental pharmaceutical opioid overdose deaths and diverging overdose death correlates following the opioid prescription policy liberalization in Norway 2010-2018.

BACKGROUND: During the last decade, opioid prescription policies in Norway have been liberalised and pharmaceutical opioid (PO) dispensing has increased. Against this backdrop, we examined the trends in and the correlates of accidental overdose deaths attributable to PO in the period 2010-2018 in comparison with traditional heroin overdose deaths. METHODS: Accidental overdose deaths attributable to PO or heroin were identified through the Norwegian Cause of Death Registry (n = 1267) and cross-linked with population and patient registries. Overdose death correlates were examined using multivariable logistic regression. FINDINGS: The trend in accidental overdose deaths attributable to PO increased significantly from 2010 to 2018. Females, people aged 50 years or older, disability pension recipients and/or those with the highest net wealth had a greater risk of a PO vs. heroin overdose death, while those dying in public spaces, living in urban areas, having recent specialized drug treatment encounters, and/or criminal charge(s) had a lower risk. Among those with primary health care encounters, those with back problems and accidents and injuries had a greater risk of a PO vs. heroin overdose death, while those with a substance use disorder had a lower risk. CONCLUSION: The increase in accidental overdose deaths attributable to PO coincides with the period of opioid prescription policy liberalization and an increase in PO consumption in Norway. The PO and heroin overdose deaths differed in terms of the associated sociodemographic characteristics, primary and secondary health care encounters, diagnoses, and criminal charges, indicating a need for additional interventions aimed at preventing PO overdose deaths specifically.

A COVID-19 Survey among People Who Use Drugs in Norway.

BACKGROUND: to combat the COVID-19 pandemic, adherence to COVID-19 recommendations and vaccination against COVID-19 have been important. Among people who use drugs (PWUD), little is known regarding compliance towards COVID-19 recommendations, COVID-19 testing, or attitudes towards COVID-19 vaccination. We aimed to examine these issues in a sample of PWUD. METHODS: a cross-sectional study was conducted between January and March 2021. Through users' organizations and different low-threshold services for substance users, we recruited former drug users and professionals to include participants and perform the interviews. Participants completed an interviewer-administered questionnaire. Any person above 16 years of age who used substances were recruited. RESULTS: 477 Norwegian PWUD participated in the study. The mean age was 43.8 (SD 12.8) years and 77% were males. Thirty-four percent had injected drugs the past four weeks. Alcohol (41%) and cannabis (41%) were the most common drugs used the past four weeks, followed by tranquilizers (37%), central stimulants (35%) and opioids (30%). The majority (90%) had washed their hands frequently, used alcohol sanitizer during the past two weeks, had used face masks, kept one-meter distance to other people and stayed at home if feeling unwell. Fifty-four percent had been COVID-19 tested. More than half the sample (58%) had positive attitudes to COVID-19 vaccination, while 26% were fairly or very unlikely to accept vaccination. Those older (OR = 0.96, 95% CI 0.94; 0.98) and using face masks (OR = 0.49, 95% CI 0.30; 0.79) were more likely to have positive attitudes towards vaccination, while those reporting low life-satisfaction (OR = 3.86, 95% CI 1.43; 10.40), using opioids (OR = 2.97, 95% CI 1.43; 6.18) or almost never staying at home when feeling unwell (OR = 2.76, 95% 1.39; 5.45) expressed more negative attitudes towards vaccination. CONCLUSION: there was generally a high compliance towards COVID-19 recommendations, but one quarter of the sample was sceptical towards COVID-19 vaccination. This indicates a need for targeted and tailored information and well-designed vaccination roll-out programs to reach all PWUD.

Injecting Alone is More Common among Men, Frequent Injectors and Polysubstance Users in a Sample of People Who Inject Drugs.

Injecting alone increases the risk of a fatal overdose. We examined the extent of such behavior in a sample of people who inject drugs (PWID) and the typical characteristics of those injecting alone at least once during the past four weeks.A cross-sectional study. PWID recruited from the street and from low-threshold services in seven Norwegian cities in September 2017 (n = 359). Associations between characteristics and injecting alone were examined using logistic regression analysis. The independent variables were gender (female/male), age, having received overdose-prevention education (no/yes), and, in the past four weeks; homelessness/shelter use (no/yes), in opioid substitution treatment (no/yes), injecting ≥ four days a week (no/yes), and substances injected (opioids only/opioids and other/other only/central stimulants (CS) only/CS and other/CS and opioids/CS, opioids and other). The adjusted odds ratios (aOR) and 95% Confidence Intervals (CI) were reported.Of the 359 PWID, 84.4% reported having injected alone. Males were more likely than females to inject alone (aOR = 1.88 95% CI 1.00-3.54). Furthermore, those injecting frequently (aOR = 1.99 95% CI 1.02-3.86) and those injecting multiple substances (CS, opioids and other) (aOR = 2.94 95% CI 1.01-8.58) were more likely to inject alone compared to those injecting less frequently and opioids only. Although not statistically significant, the effect sizes in the logistic regression models suggest that polysubstance use may be driven by CS use.Injecting alone was common in our sample of PWID, and male gender, frequent injecting and polysubstance injecting were associated with this behavior.

Characteristics and risk of incarceration among "hard-to-reach" people who use drugs: A five-year prospective cohort study combining self-reports and registry data.

BACKGROUND: Incarcerations are associated with an increased risk of morbidity and mortality among people who use drugs (PWUD). In a sample of 884 PWUD, we examine and estimate the risk of incarcerations (i.e., number, duration, and most serious offense). METHODS: In this prospective cohort study, PWUD were recruited from street- and low-threshold services in seven Norwegian cities in 2013 (Sept-Nov), and followed through the Correctional Service Registry until 20.12.2018. The risk of incarceration during follow-up was examined with multivariable logistic (no incarceration vs. at least one) and multinomial regression models ("no incarcerations", vs. "1″, "≥2″), while accounting for gender, age, homelessness/shelter use, opioid substitution treatment, illegal income sources, injecting behaviours, previous incarcerations, and recruitment city. RESULTS: During follow-up, there were in total 662 incarceration episodes, and 44.7% of the participants were incarcerated at least once. Overall, 37.5% of those incarcerated had at least one episode due to a drug offense. The average incarceration duration was 65.2 days with 3.5% of the episodes lasting ≥one year. Gender (male), homelessness/shelter use, illegal income sources, injecting stimulants, and previous incarcerations increased the odds of incarceration, while older age decreased the odds. Gender (male), younger age, self-reported theft or theft and dealing, injecting stimulants or heroin and stimulants and previous incarcerations increased the risk of multiple incarcerations. CONCLUSION: In a five-year prospective study of PWUD, incarcerations were common, and short-term sentences and recidivism were the norm. This is of concern as incarcerations add to an already elevated morbidity and mortality risk in this population.

COVID-19 survey among people who use drugs in three cities in Norway.

BACKGROUND: Little is known regarding what people who use drugs (PWUD) know about COVID-19 related issues and changes in the drug market due to COVID-19. We therefore conducted a survey to explore these issues. METHODS: In a cross-sectional study, we interviewed 226 PWUD from three Norwegian cities in May/June 2020. Participants completed an interview-administrated questionnaire. Three separate multiple binary logistic regression models were estimated with the outcomes (no/yes): 1. Familiarity with COVID-19 symptoms, 2. Awareness of COVID-19 services tailored towards PWUD and, 3. Willingness to take a COVID-19 test. RESULTS: The mean age was 44.1 years and 73 % were males. Fifty-four percent were injectors, and heroin/other opioids (35.8 %) and cocaine/amphetamine (25.2 %) were the most common main drugs used. Overall, 54.9 % were in opioid maintenance treatment (OMT). The majority (65.9 %) stated they knew the COVID-19 symptoms. Almost all the participants (91.2 %) reported they would take a COVID-19 test if experiencing relevant symptoms. The majority (63.7 %) were not aware of COVID-19 services available to PWUD. OMT patients were more likely to be familiar with COVID-19 symptoms (aOR = 3.4, 95 % CI 1.7; 6.8), and to be aware of COVID-19 services (aOR = 2.7, 95 % CI 1.1; 6.3). Overall, 35.4 % reported reduced drug availability, mainly for tranquilizers, while 61.5 % reported increased drug prices, mainly for cannabis. CONCLUSION: Drug treatment may play an important role in COVID-19 prevention, as those in OMT were more likely to be aware of symptoms and of availability of services.

Prehospital naloxone administration - what influences choice of dose and route of administration?

BACKGROUND: Amidst the ongoing opioid crisis there are debates regarding the optimal route of administration and dosages of naloxone. This applies both for lay people administration and emergency medical services, and in the development of new naloxone products. We examined the characteristics of naloxone administration, including predictors of dosages and multiple doses during patient treatment by emergency medical service staff in order to enlighten this debate. METHODS: This was a prospective observational study of patients administered naloxone by the Oslo City Center emergency medical service, Norway (2014-2018). Cases were linked to The National Cause of Death Registry. We investigated the route of administration and dosage of naloxone, clinical and demographic variables relating to initial naloxone dose and use of multiple naloxone doses and one-week mortality. RESULTS: Overall, 2215 cases were included, and the majority (91.9%) were administered intramuscular naloxone. Initial doses were 0.4 or 0.8 mg, and 15% of patients received multiple dosages. Unconscious patients or those in respiratory arrest were more likely to be treated with 0.8 mg naloxone and to receive multiple doses. The one-week mortality from drug-related deaths was 4.1 per 1000 episodes, with no deaths due to rebound opioid toxicity. CONCLUSIONS: Intramuscular naloxone doses of 0.4 and 0.8 mg were effective and safe in the treatment of opioid overdose in the prehospital setting. Emergency medical staff appear to titrate naloxone based on clinical presentation.

How may alternative drug policy settings influence criminal charges? A longitudinal study of cannabis patients and a general population sample.

BACKGROUND: This study examines criminal charges amongst cannabis use disorder (CUD) patients and a matched sample in a setting of drug criminalization, and simulates the effect of policy changes on the proportion obtaining a criminal record and on the number of charges for those being charged. METHODS: All CUD patients entering specialist treatment in Norway in 2009-2010 (n=3,951) were included from the Norwegian Patient Registry and a random sample matched on age and gender drawn from the general population by Statistics Norway (n=7,902). Data were linked to the Norwegian Crime Registry (2009-2014). The nature and extent of all charges were examined. A static simulation exercise assessed the hypothetical effect on charges if a) all charges for use and possession of illicit drugs were eliminated ("decriminalization") and b) in addition, all charges for cultivation, manufacturing, and sales were eliminated ("legalization"). RESULTS: Two thirds (66%) of patients and 12% of matched sample were charged during the observation period. While the most common offence for patients was drug law violations (52%), relatively few (14%) had no other charges. Road traffic violations was the most common offence for the matched sample and 1.2% were charged with drug offences only. The mean number of charges were 9 for the patients and 3 for the matched sample. Simulations suggest that decriminalization may decrease the proportion being charged by 8% for patients and 4% for the matched sample under "decriminalization", compared to 24% and 11%, respectively if all drugs were legalized. The number of charges for patients and non-patients would drop by 23% and 13% respectively, while legalization may decrease the number of charges by 46% and 25%, respectively. CONCLUSION: The simulations suggest that the impacts of decriminalisation and legalisation on the proportion being charged are relatively modest, while the policy changes are likely to lead to substantial reductions in the number of charges for both the patient and non-patient groups.

Drug Use by Music Festival Attendees: A Novel Triangulation Approach Using Self-Reported Data and Test Results of Oral Fluid and Pooled Urine Samples.

Background: Self-reported data are commonly used when investigating illicit substance use. However, self-reports have well-known limitations such as limited recall and socially desirable responding. Mislabeling or adulteration of drugs on the illicit market may also cause incorrect reporting. Objectives: We aimed to examine what could be gained in terms of illicit drug use findings among music festival attendees when including biological sample test results in the assessment. Methods: We included 651 attendees at three music festivals in Norway from June to August 2016. Self-reported drug use was recorded using questionnaires, and samples of oral fluid were analyzed to detect use of illicit drugs. In addition, we analyzed samples of pooled urine from portable toilets at each festival. Results: All methods identified cannabis, MDMA, and cocaine as the most commonly used drugs. Overall, 6.6% of respondents reported use of illicit substances during the previous 48 hours. Oral fluid testing identified a larger number of drug users as 12.6% tested positive for illicit drugs. In oral fluid testing, we identified ketamine and three new psychoactive substances (NPS) that had not been reported on the questionnaire. In pooled urine testing, we identified amphetamine and three additional NPS that were neither reported used nor found in oral fluid samples. Conclusions/Importance: Drug testing of biological samples proved to be an important supplement to self-reports as a larger number of illicit substances could be detected.

Correspondence between Oral Fluid Drug Test Results and Self-Reported Illicit Drug Use among Music Festival Attendees.

BACKGROUND: Use of illicit substances is often under-reported. Testing positive in oral fluid provides an objective confirmation of recent intake. OBJECTIVES: To examine the agreement between oral fluid test results and self-reported substance use among music festival attendees, and factors associated with reporting past 48 h drug use among users identified by drug testing. METHODS: One thousand three hundred nine participants were recruited from six music festivals in Norway (June-August 2016). They completed a questionnaire and provided oral fluid samples analyzed for amphetamines, MDMA, tetrahydrocannabinol (cannabis), and cocaine. Additionally, their blood alcohol levels were measured. RESULTS: Overall, 5.5% reported use of amphetamines, cannabis, cocaine, and/or MDMA during past 48 h in the questionnaire, whereas 10.8% tested positive in oral fluid. Only 16.7% of identified cocaine users and 31.1% of identified MDMA users reported past 48 h cocaine or MDMA use, respectively. Higher proportions of identified cannabis and amphetamine users reported past 48 h use (53.8% and 55.6%, respectively). Multivariable logistic regression analysis showed that among participants who tested positive, those reporting weekly illicit substance use (Adjusted Odds Ratio [AOR] 30.6; 95% Confidence Interval [CI] 6.3-147.9), and using such substances when younger than 18 years (AOR 5.0; 95% CI 1.9-13.4) were more likely to report past 48 h use. Conclusions/Importance: Oral fluid testing appears to be an important tool when studying illicit substance use among music festival attendees, as significant under-reporting was observed. Among those testing positive, regular, and experienced users were more likely to report recent use, compared to less regular and experienced users.

Identification and Assessment of Drug-User Groups Among Nightlife Attendees: Self-Reports, Breathalyzer-Tests and Oral Fluid Drug Tests.

BACKGROUND AND OBJECTIVES: Even though nightlife studies with potentially intoxicated participants provide the much needed information on drug use, they face additional methodological challenges. This study aimed to explore the utility of such studies by (i) classifying nightlife attendees based on their self-reported drug use and by (ii) examining whether these classifications were meaningful when assessed against other sources of data, including oral fluid drug tests. METHODS: Self-reported questionnaires, oral fluid samples and blood alcohol concentration readings were collected in a sample of 1,085 nightlife patrons recruited outside 12 popular nightclubs in Oslo, Norway, in 2014. Patrons were classified using multiple approaches, including latent class analysis. Group differences were examined by logistic regression models. RESULTS: Participants were classified into 5 mutually exclusive groups: 2 among current non-users ("Never-users"; "Previous users"), 2 among current users ("Multiple drugs"; "Cannabis mainly") and one "Incomplete information" group. Meaningful differences across these groups were observed. For instance, positive tests for any illicit drug were more common in "Multiple drugs" group than in "Cannabis mainly" (62.7 vs. 29.1%, adjusted OR [aOR] 3.77 [2.42-5.84]) or "Incomplete information" groups (62.7 vs. 34.4%, aOR 2.46 [1.26-4.79]). Despite their self-declared non-use, illicit substances were detected in oral fluids of "Never-users" (13.1%; 95% CI 9.9-17.2) and "Previous users" (7.9%; 95% CI 5.1-12.1). CONCLUSIONS: Despite some discrepancies between self-reports and biological tests, self-reports proved both suitable and useful in identification of substantively different drug-user typologies, potentially informing targeted policy responses. Still, methodological challenges associated with onsite studies of illicit drug use should be further explored.

Illegal substance use among 1,309 music festival attendees: An investigation using oral fluid sample drug tests, breathalysers and questionnaires.

AIMS: Illegal substance use at music festivals is less documented than it is in nightlife and electronic dance music settings. This study investigated such use through questionnaires, breathalysers and oral fluid drug testing. We also examined the associations between testing positive for illegal substances and demographics, self-reported substance use and measured blood alcohol concentration levels. METHODS: A cross-sectional study of 1,309 festival attendees from six Norwegian music festivals taking place between July and August 2016. Logistic regression models estimated the likelihood of a positive oral fluid drug test. Covariates were male, age, education, employment, smoking status, early age for alcohol intoxication, alcohol intoxication ⩾2 times a week, past-month and past-year illegal substance use, blood alcohol concentration levels and festivals. RESULTS: Overall, 12% reported illegal substance use in the past 30 days and 11% tested positive for illegal substances. Cannabis (6%), cocaine (3%) and MDMA/ecstasy (2%) were most commonly detected. One-third had a blood alcohol concentration ⩾0.10%. Of those with a positive test result ( n=146), 95% had detectable alcohol levels and 41% had a blood alcohol concentration above 0.10%. Those studying or working part-time were less likely to test positive compared to those who were not employed. Furthermore, those reporting daily smoking and past-year cannabis or MDMA/ecstasy use were more likely to test positive, compared to those not reporting such use. CONCLUSIONS: Illegal substance use was less prevalent than in previous nightlife and electronic dance music studies. Almost all those testing positive for illegal substances had detectable alcohol levels and 41% had a blood alcohol concentration greater than 0.10%, possibly indicating combined use.

Naloxone distribution and possession following a large-scale naloxone programme.

AIMS: To examine uptake following a large-scale naloxone programme by estimating distribution rates since programme initiation and the proportion among a sample of high-risk individuals who had attended naloxone training, currently possessed or had used naloxone. We also estimated the likelihood of naloxone possession and use as a function of programme duration, individual descriptive and substance use indicators. DESIGN: (1) Distribution data (June 2014-August 2017) and date of implementation for each city and (2) a cross-sectional study among a sample of illicit substance users interviewed September 2017. SETTING: Seven Norwegian cities. PARTICIPANTS: A total of 497 recruited users of illegal opioids and/or central stimulants. MEASUREMENTS: Primary outcomes: naloxone possession and use. Random-intercepts logistic regression models (covariates: male, age, homelessness/shelter use, overdose, incarceration, opioid maintenance treatment, income sources, substance use indicators, programme duration). FINDINGS: Overall, 4631 naloxone nasal sprays were distributed in the two pilot cities, with a cumulative rate of 495 per 100 000 population. In the same two cities, among high-risk individuals, 44% and 62% reported current naloxone possession. The possession rates of naloxone corresponded well to the duration of each participating city's distribution programme. Overall, in the six distributing cities, 58% reported naloxone training, 43% current possession and 15% naloxone use. The significant indicators for possession were programme duration [adjusted odds ratios (aOR) = 1.44, 95% confidence interval (CI = 0.82-2.37], female gender (aOR = 1.97, 95% CI = 1.20-3.24) and drug-dealing (aOR = 2.36, 95% CI = 1.42-3.93). The significant indicators for naloxone use were programme duration (aOR = 1.49 95%, CI = 1.15-1.92), homelessness/shelter use (aOR = 2.06, 95% CI = 1.02-4.17), opioid maintenance treatment (OMT) (aOR = 2.07, 95% CI = 1.13-3.78), drug-dealing (aOR = 2.40, 95% CI = 1.27-4.54) and heroin injecting (aOR = 2.13, 95% CI = 1.04-4.38). CONCLUSIONS: A large-scale naloxone programme in seven Norwegian cities with a cumulative distribution rate of 495 per 100 000 population indicated good saturation in a sample of high-risk individuals, with programme duration in each city as an important indicator for naloxone possession and use.

Patterns of substance use and mortality risk in a cohort of 'hard-to-reach' polysubstance users.

AIMS: To examine the mortality risk in a cohort of 'hard-to-reach' polysubstance users and its putative associations with substance use. Specifically, we estimated all-cause mortality risk as a function of individual substance use indicators, and then as a function of their complex, 'real-life' patterns as identified through latent class analysis (LCA). DESIGN: Prospective cohort study among street- and low-threshold service-recruited polysubstance users included between September and November 2013 and followed through the National Cause of Death Registry until 31 October 2015. SETTING: Seven Norwegian cities. PARTICIPANTS: A total of 884 users of illegal opioids and/or stimulants. Of these, 357 were in opioid substitution treatment (OST) at the time of inclusion. Forty-four participants died during follow-up. MEASUREMENTS: Primary outcome: all-cause mortality risk. Unadjusted and adjusted Cox proportional hazard (PH) regression models (covariates: male, age, homelessness/shelter use, overdose experience, OST status, years of injecting, individual substance use indicators, city, use patterns). LCA models estimated separately for those in and those not in OST due to measurement invariance. FINDINGS: The crude mortality rate was 2.52 per 100 person-years. Standardized mortality ratio was 26.11 [95% confidence interval (CI) = 10.06-54.87] for women and 10.71 (95% CI = 6.39-16.81) for men. No single drug use indicator, such as 'heroin injection' or 'number of drugs used', was associated with the mortality risk. However, meaningful use patterns were identified; three OST and non-OST patterns each. The non-OST patterns 'polysubstance injectors' [hazard ratio (HR) = 3.45, 95% CI = 0.98-12.14] and 'low frequent injectors' (HR = 3.17, CI = 1.05-9.56) were associated significantly with the mortality risk even when adjusted for other known risk factors. CONCLUSIONS: In a Norwegian prospective cohort study, 'hard-to-reach' polysubstance users had a more than 10 times higher mortality risk than the general population. Mortality risk was not a function of any single drug use indicator, but two distinct combinations of substances, frequencies and routes of administration were associated with the mortality risk.

Are overdoses treated by ambulance services an opportunity for additional interventions? A prospective cohort study.

AIMS: To assess whether people who inject drugs (PWID) and who are treated for overdose by ambulance services have a greater mortality risk compared with other PWID, and to compare mortality risk within potentially critical time-periods (1 week, 1 month, 3 months, 6 months, 1 year, 5 years) after an overdose attendance with the mortality risk within potentially non-critical time-periods (time before and/or after critical periods). DESIGN: A prospective cohort study. SETTING: Oslo, Norway. PARTICIPANTS: A total of 172 PWID street-recruited in 1997 and followed-up until the end of 2004. MEASUREMENTS: Interview data linked to data from ambulance records, Norwegian Correctional Services, Opioid Substitution Treatment records and National Cause of Death Registry. Separate Cox regression models (one for each critical time-period) were estimated. FINDINGS: Ambulance services treated 54% of the participants for an overdose during follow-up. The mortality rate was 2.8 per 100 person-years for those with an overdose and 3.3 for those without; the adjusted hazard ratio (HR) was 1.3 (95% CI = 0.6, 2.6, P = 0.482). Mortality risk was greater in all but the shortest critical time-period following ambulance attendance than in the non-critical periods. The mortality risk remained significantly elevated during critical periods, even when adjusted for total time spent in prison and substitution treatment. The HR ranged from 9.4 (95% CI = 3.5, 25.4) in the month after an overdose to 13.9 (95% CI = 6.4, 30.2) in the 5-year period. CONCLUSIONS: Mortality risk among people who inject drugs is significantly greater in time-periods after an overdose attendance than outside these time-periods.

Illicit use of opioid substitution drugs: prevalence, user characteristics, and the association with non-fatal overdoses.

BACKGROUND AND AIMS: Diversion of opioid substitution drugs (OSD) is of public concern. This study examined the prevalence, frequency, and predictors of illicit OSD use in a group of injecting drug users (IDUs) and assessed if such use was associated with non-fatal overdoses. METHODS: Semi-annual cross-sectional interviews conducted in Oslo, Norway (2006-2013), from 1355 street-recruited IDUs. Hurdle, logistic, and multinomial regression models were employed. RESULTS: Overall, 27% reported illicit OSD use in the past four weeks; 16.8% methadone, 12.5% buprenorphine, and 2.9% both drugs. Almost 1/10 reported at least one non-fatal overdose in the past four weeks, and roughly 1/3 reported such experience in the past year. Use of additional drugs tended to be equally, or more prevalent among illicit OSD users than other IDUs. In terms of illicit OSD use being a risk factor for non-lethal overdoses, our results showed significant associations only for infrequent buprenorphine use (using once or less than once per week). Other factors associated with non-fatal overdoses included age, education, homelessness, as well as the benzodiazepines, stimulants, and heroin use. CONCLUSIONS: Users of diverted OSD may represent a high-risk population, as they used more additional drugs and used them more frequently than other IDUs. However, illicit OSD use may be less harmful than previously assumed. After accounting for an extensive set of covariates, only infrequent illicit buprenorphine use, but not methadone use, was associated with non-fatal overdoses.