No decline in drug overdose deaths in Norway: An ecological approach to understanding at-risk groups and the impact of interventions.

Aim: This Norwegian case study examines groups at risk of drug overdose deaths, evidence-based harm reduction interventions, low-threshold services and treatment implemented, as well as trends in drug overdose deaths between 2010 and 2021. We aimed to explore the relevance of interventions for at-risk groups and discuss their potential impact on drug overdose trends. Method/data: Using an ecological approach, we analysed the following: (1) groups identified through latent profile analysis (LPA) among a sample of 413 high-risk drug users collected in 2010-2012, supplemented with other relevant studies up to 2021; (2) published information on harm-reduction interventions, low-threshold services and treatment in Norway; and (3) nationwide drug overdose mortality figures supplemented with published articles on the topic. Results: High-risk drug users in 2010-2012 commonly engaged in frequent illegal drug use, injecting and poly-drug use (including pharmaceutical opioids), which continued into following decade. The interventions implemented between 2010 and 2021 were relevant for at-risk groups identified in the surveys. However, there was no decrease in the trend of drug overdose deaths up to 2021. While relevant interventions may have mitigated a theoretical increase in mortality, new at-risk groups may have contributed to fatal outcomes associated with pharmaceutical opioids. Conclusion: The interventions were relevant to the risk groups identified among high-risk drug users and potentially effective in preventing an increase in drug overdose trends. However, tailored interventions are needed for individuals at risk of death from prescribed opioids. Comprehensive studies encompassing all at-risk populations, including both legal and non-medical users of prescription opioids, are needed.

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.

Key Interpretation Challenges for Wastewater-Based Epidemiology of Illicit Drugs: A Norwegian Three-City Case Study.

INTRODUCTION: Wastewater-based epidemiology (WBE) has emerged as a timely, non-invasive, and cost-effective indicator of illicit drug consumption. It is increasingly used by international organizations as a proxy measure for estimates of drug prevalence and related trends. Nevertheless, the literature exploring the limitations of WBE remains limited. This paper aims to shed further light on important shortcomings of WBE with recommendations on moving forward. METHOD: Utilizing case study and statistical analysis, the paper critically reviews methodological challenges associated with WBE results related to (i) levels, (ii) trends, and (iii) between-city comparisons of drug use. Data from raw influent wastewater samples from wastewater plants in the cities of Oslo, Bergen and Stavanger/Sandnes were analysed for amphetamine, methamphetamine, MDMA, and cocaine (benzoylecgonine) over a 3-year period. Normalized population loads were calculated and variation in daily loads analysed with plots and estimation of means, confidence intervals, and coefficient of variation. Linear regression models examined trends and between-city differences. RESULTS: Plots and statistical analyses revealed extensive variation in daily loads, with min/max values of 6.1/453.9 mg/day per 1,000 inhabitants 15-64 years for amphetamine and correspondingly 9.4/675.9 mg for methamphetamine. Substantial differences in load levels and patterns across time and plants were also observed. A carefully designed sampling procedure and a relatively large number of daily samples are required to obtain estimates of sufficient precision for determining trends in space or time. Cross-referencing with alternative trend variables can improve the interpretation of WBE trend indicators. Finally, when using mean load levels for different wastewater-treatment plants to assess spatial variation in drug use, the representativeness of the catchment area should be evaluated before interpreting observed changes as city differences. CONCLUSION: Although WBE is a useful supplementary indicator of illicit drug consumption, important methodological issues and potential shortcomings should be taken into account when designing sampling procedures and interpreting the analytical results.

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.

Patients admitted to treatment for substance use disorder in Norway: a population-based case-control study of socio-demographic correlates and comparative analyses across substance use disorders.

BACKGROUND: Improved knowledge regarding socio-demographic correlates of people with substance use disorders (SUDs) is essential to better plan and provide adequate services for SUD patients and their families, and to improve our understanding of the complex mechanisms underlying progression into and development of various SUDs. This study aimed to: i) describe demographic, economic, and social correlates of people with SUDs in comparison with those of the general population and ii) compare these correlates across SUDs from licit versus illicit substances, as well as across specific SUDs. METHODS: A national population-based case-control study included all SUD patients enrolled in specialized drug treatment in Norway in 2009-2010 (N = 31 245) and a population control sample, frequency-matched on age and gender (N = 31 275). Data on education level, labour market participation, income level and sources, and family/living arrangement were obtained by linkages to national registers. RESULTS: Demographic, economic, and social correlates of SUD patients differed substantially from those of the general population, and across specific SUDs. Among SUD patients, those with illicit - as compared to licit - SUDs were younger (mean quotient = 0.72 [0.71-0.72]), more often had low education level (RR = 1.68 [1.63-1.73]), were less often in paid work (RR = 0.74 [0.72-0.76]) and had lower income (mean quotient = 0.61 [0.60-0.62]). Comparison of patients with different SUD diagnoses revealed substantial demographic differences, including the relatively low mean age among cannabis patients and the high share of females among sedatives/hypnotics patients. Opioid patients stood out by being older, and more often out of work, receiving social security benefits, and living alone. Cocaine and alcohol patients were more often better educated, included in the work force, and had a better financial situation. CONCLUSION: Findings revealed substantial and important differences in socio-demographic correlates between SUD patients and the general population, between SUD patients with illicit and with licit substance use, and across specific SUD patient groups.

Socio-economic differences in all-cause mortality in people with alcohol use disorder: a prospective cohort study.

BACKGROUND AND AIMS: While alcohol-attributable mortality rates are higher in low socio-economic status (SES) groups, less is known about SES differences in all-cause mortality in alcohol use disorder (AUD). The aim of this study was to explore whether there are SES differences in people with AUD, regarding (i) treatment admission, (ii) all-cause mortality risk and (iii) relative mortality risk. DESIGN AND SETTING: A prospective cohort study in Norway, follow-up period from 2009-10 to 2013. Data on SES and mortality were obtained through linkages to national registries, using national unique ID numbers. PARTICIPANTS: AUD patients (age 20+) admitted to treatment in 2009-10 (n = 11 726) and age and gender frequency-matched controls from the general population (n = 12 055). MEASUREMENTS: The SES indicator was education level (low, intermediate and high). Mortality was calculated as deaths per 1000 person-years during the 4-year observation period. FINDINGS: Admission to AUD treatment was elevated in the low compared with the high SES categories (OR = 3.31, 95% CI = 3.09, 3.55). Among AUD patients, mortality risk was elevated in the low SES category (HR = 1.23, 95% CI = 1.04, 1.45). Relative mortality risk from AUD was significantly higher in the high SES (HR = 8.65, 95% CI = 6.16, 12.14) compared with the low SES categories (HR = 3.29, 95% CI = 2.61, 4.15). CONCLUSION: Admission to treatment for alcohol use disorders in Norway appears to decrease with increasing socio-economic status, and relative mortality risk from alcohol use disorder appears to increase with increasing socio-economic status.

A comparison of trends in wastewater-based data and traditional epidemiological indicators of stimulant consumption in three locations.

AIMS: To compare long-term trends in wastewater data with other indicators of stimulant use in three locations and to test the reliability of estimates based on 1 week of sampling. DESIGN: Comparison of trends in quantities ('loads') of stimulants or their metabolites in wastewater with trends in other indicators of stimulant use (e.g. treatment, police, population survey data). SETTING AND PARTICIPANTS: Populations in Oslo (Norway), South-East Queensland (Australia) and Eindhoven (the Netherlands). MEASUREMENTS: Wastewater data were modelled for MDMA (3,4-methyl​enedioxy​methamphetamine), benzoylecgonine (a metabolite of cocaine), amphetamine and methamphetamine in Oslo; benzoylecgonine in Eindhoven; and methamphetamine in South-East Queensland. Choice of stimulants modelled in each region was primarily determined by availability of useable data. FINDINGS: In Oslo, wastewater data, driving under the influence of drugs statistics and seizure data all suggested increasing MDMA use between 2009 and 2017. In South-East Queensland, there was an estimated 31.1% [95% confidence interval (CI) = 29.4-32.9%] annual increase in daily loads of methamphetamine in wastewater between 2009 and 2016, compared with a 14.1% (95% CI = 10.9-17.3%) annual increase in seizures. Some of the increase in wastewater can be explained by increased purity. In Eindhoven, there was no evidence of a change in cocaine consumption from wastewater, but a reduction was observed in numbers in treatment for cocaine use from 2012 to 2017. In approximately half the cases examined in Oslo, credible intervals around estimates of annual average loads from a regression model versus estimates based on a single week of sampling did not overlap. CONCLUSIONS: Long-term trends in loads of stimulants in wastewater appear to be broadly consistent with trends in other indicators of stimulant use in three locations. Wastewater data should be interpreted alongside epidemiological indicators and purity data. One week of wastewater sampling may not be sufficient for valid inference about drug consumption.

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.

Economic Evaluation of Direct-Acting Antivirals for Hepatitis C in Norway.

PURPOSE: New direct-acting antiviral (DAA) drugs have revolutionized the treatment of hepatitis C in recent years. OBJECTIVE: Our objective was to analyse the cost effectiveness of combinations of different DAAs compared with ribavirin and peginterferon-α-2a, taking into account rebates from tender negotiations. METHODS: We used a compartmental model specifically developed for Norway to simulate hepatitis C and complications with and without different DAAs. All costs were based on Norwegian fees and estimates, estimating healthcare sector costs for the year 2016. We performed Monte Carlo simulations on uncertain input parameters to facilitate probabilistic sensitivity analyses. RESULTS: For patients diagnosed with genotype 1, the combination of paritaprevir, ritonavir, ombitasvir and dasabuvir was cost effective compared with eight other available alternatives, given a cost-effectiveness threshold of €70,000 per quality-adjusted life-year. For genotype 2, the combination of sofosbuvir and ribavirin was the most effective and cost-effective alternative for all patients. Among available alternatives for patients with genotype 3, sofosbuvir in combination with peginterferon and ribavirin was the most cost-effective alternative, although the combination of daclatasvir and sofosbuvir was somewhat more effective. CONCLUSIONS: For each of the hepatitis C genotypes 1, 2 and 3, there were combinations of DAAs that were cost effective in a Norwegian setting. As a result of recent tender negotiations in Norway, treating all diagnosed patients with hepatitis C with the most cost-effective DAAs will result in lower total expenditure on these medications compared with 2015.

Modelling the burden of hepatitis C infection among people who inject drugs in Norway, 1973-2030.

BACKGROUND: Lack of Hepatitis C virus (HCV) incidence data in (Norwegian) high-risk groups impedes the ability to make informed decisions on prevention measures. Thus we rely on modelling to estimate the incidence and burden of HCV infections. METHODS: We constructed a compartmental model for HCV infections in Norway among active and former people who inject drugs (PWIDs). We based yearly transition rates on literature. The model was fitted to absolute numbers of hepatitis C associated cirrhosis, hepatocellular carcinoma (HCC) and death from national data sources (2000-2013). We estimated the number (95%CI) of HCV infections, cirrhosis, HCC and death and disability adjusted life years (DALYs) due to HCV infections in Norway, 1973-2030. We assumed treatment rates in the projected period were similar to those in 2013. RESULTS: The estimated proportion of chronic HCV (including those with cirrhosis and HCC) among PWIDs was stable from 2000 (49%; 4441/9108) to 2013 (43%; 3667/8587). We estimated that the incidence of HCV among PWIDs was 381 new infections in 2015. The estimated number of people with cirrhosis, HCC, and liver transplant was predicted to increase until 2022 (1537 people). DALYs among active PWIDs estimated to peak in 2006 (3480 DALYs) and decrease to 1870 DALYs in 2030. Chronic HCV infection contributes most to the total burden of HCV infection, and peaks at 1917 DALYs (52%) in 2007. The burden of HCV related to PWID increased until 2006 with 81/100,000 DALYs inhabitants and decreased to 68/100,000 DALYs in 2015. CONCLUSION: The burden of HCV associated with injecting drug use is considerable, with chronic HCV infection contributing most to the total burden. This model can be used to estimate the impact of different interventions on the HCV burden in Norway and to perform cost-benefit analyses of various public health measures.

Lack of overlap and large discrepancies in the characteristics of the deceased in two sources of drug death. A linkage study of the Cause of Death and the Police Registries in Norway 2007-2009.

BACKGROUND: Registries for drug deaths may include different persons and provide different characteristics of the deceased. The aim of this study was to establish whether a database of drug-induced deaths (Cause of Death Registry (CDR) using the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) definition and the Police registry of drug deaths) included the same persons and provided the same characteristics of the deceased and thus yielded the same information for establishing targeted prevention measures. METHODS: Notifications from 2007 to 2009 were drawn from the CDR and the police registry of drug deaths and the unique Norwegian personal identification number was used to match the registrations. RESULTS: The two sources of drug deaths yielded 1384 registrations, encompassing 929 individuals of whom only 49% were included in both registries. A large proportion of the deceased (40%) were not listed in the police registry. This group was older (mean age 43 years vs. 35 years); dependence and suicide were listed more often as cause of death (33% vs. 8%); and heroin was listed less often as the type of drug causing death (24% vs. 67%) than those included in both registries. In particular, among women not included in the police registry, the cause of death was identified with much greater frequency as pharmaceuticals with morphine or codeine (47% vs. 16%). CONCLUSION: The large discrepancies in size, overlap, and characteristics of the deceased included in two sources of drug death imply that prevention measures based on the two sources will differ.

Estimating incidence of problem drug use using the Horwitz-Thompson estimator - A new approach applied to people who inject drugs in Oslo 1985-2008.

BACKGROUND: The trend in the number of new problem drug users per year (incidence) is the most important measure for studying the diffusion of problem drug use. Due to sparse data sources and complicated statistical models, estimation of incidence of problem drug use is challenging. The aim of this study is to widen the palette of available methods and data types for estimating incidence of problem drug use over time, and for identifying the trends. METHODS: This study presents a new method of incidence estimation, applied to people who inject drugs (PWID) in Oslo. The method took into account the transition between different phases of drug use progression - active use, temporary cessation, and permanent cessation. The Horwitz-Thompson estimator was applied. Data included 16 cross-sectional samples of problem drug users who reported their onset of injecting drug use. We explored variation in results for selected probable scenarios of parameter variation for disease progression, as well as the stability of the results based on fewer years of cross-sectional samples. RESULTS: The method yielded incidence estimates of problem drug use, over time. When applied to people in Oslo who inject drugs, we found a significant reduction of incidence of 63% from 1985 to 2008. This downward trend was also present when the estimates were based on fewer surveys (five) and in the results of sensitivity analysis for likely scenarios of disease progression. CONCLUSION: This new method, which incorporates temporarily inactive problem drug users, may become a useful tool for estimating the incidence of problem drug use over time. The method may be less data intensive than other methods based on first entry to treatment and may be generalized to other groups of substance users. Further studies on drug use progression would improve the validity of the results.

Changes in mortality due to major alcohol-related diseases in four Nordic countries, France and Germany between 1980 and 2009: a comparative age-period-cohort analysis.

AIMS: To investigate age, period and cohort effects on time trends of alcohol-related mortality in countries with different drinking habits and alcohol policies. DESIGN AND SETTING: Age-period-cohort (APC) analyses on alcohol-related mortality were conducted in Denmark, Finland, Norway, Sweden, France and Germany. PARTICIPANTS: Cases included alcohol-related deaths in the age range 20-84 years between 1980 and 2009. MEASUREMENTS: Mortality data were taken from national causes of death registries and covered the ICD codes alcoholic psychosis, alcohol use disorders, alcoholic liver disease and toxic effect of alcohol. FINDINGS: In all countries changes across age, period and cohort were found to be significant for both genders [effect value with confidence interval (CI) shown in Supporting information, Table S1]. Period effects pointed to an increase in alcohol-related mortality in Denmark, Finland and Germany and a slightly decreasing trend in Sweden, while in Norway an inverse U-shaped curve and in France a U-shaped curve was found. Compared with the cohorts born before 1960, the risk of alcohol-related mortality declined substantially in cohorts born in the 1960s and later. Pairwise between-country comparisons revealed more statistically significant differences for period (P < 0.001 for all 15 comparisons by gender) than for age [P < 0.001 in seven (men) and four (women) of 15 comparisons] or cohort [P < 0.01 in two (men) and three (women) of 15 comparisons]. CONCLUSIONS: Strong period effects suggest that temporal changes in alcohol-related mortality in Denmark, Finland, Norway, Sweden, France and Germany between 1980 and 2009 were related to secular differences affecting the whole population and that these effects differed across countries.

Drug-related causes of death: Socioeconomic and demographic characteristics of the deceased.

AIM: The aim of this study was to describe subgroups of those who died from a drug-related cause of death employing demographic and socioeconomic data. METHODS: A total of 1,628 persons with registered drug-related deaths in the Norwegian Cause of Death Registry between 2003 and 2009 were matched with research registers of data on demographic and socioeconomic factors during the five years prior to their deaths. RESULTS: Three equal-sized clusters were identified: persons with very low socioeconomic status, disability pensioners and people on the edge of the workforce. CONCLUSIONS: Socioeconomic situation prior to drug-related deaths was more heterogeneous than expected. Greater knowledge about the members of the disability pensioner and the edge of the workforce clusters must be established in order to make prevention efforts towards these groups more precise and goal oriented.

HCV treatment uptake in people who have injected drugs - observations in a large cohort that received addiction treatment 1970-1984.

OBJECTIVES: The aim of this study was to document antiviral treatment uptake among former or current people who inject drugs (PWID) with chronic hepatitis C and to explore a possible association between treatment and mortality. MATERIAL AND METHODS: This is a longitudinal cohort study of PWID admitted for drug abuse treatment 1970-1984. The 245 hepatitis C virus (HCV) RNA-positive patients alive by the end of 1996 were followed 1997-2012 through linkage to several health registers. Treatment uptake was mainly documented by information on prescription of antiviral medication registered in the Norwegian Prescription Database from 2004. Cox regression, with a time-dependent covariate measuring end-of-treatment, was employed to evaluate mortality after treatment. RESULTS: At the end of the follow-up, median time since HCV exposure was 36 years, and 19.2% (47/245) had been prescribed antiviral treatment for chronic HCV infection. No gender difference was observed. Among those alive at the end of the study period, 27.8% (44/158) had been treated. Relative hazard of death was 0.21 (95% confidence interval [CI] 0.07-0.68), comparing periods for patients after versus before or without treatment. Mortality rate after treatment was 0.8 per 100 person years (95% CI 0.3-2.4) compared to 2.8 (95% CI 2.2-3.5) in untreated patients and before treatment. The most important causes of death among the untreated were drug-related. CONCLUSIONS: Among PWID infected with HCV, approximately one-fourth of those still alive at a median of 36 years after exposure had received HCV treatment. Treatment was associated with increased survival, probably mainly due to selection bias.

Self-reports of consumption of amphetamines, cocaine and heroin in a survey among marginalized drug users.

BACKGROUND AND AIM: Scientific literature offers few measurements of the quantities consumed by individual drug users. Such measurements are used for calculating the total drug consumption by the quantity-frequency method, and are extremely important for the comparison with waste water derived consumption estimates. The aim of this study was to measure quantities of amphetamines, cocaine and heroin consumed by marginalized drug users, using a multi-city questionnaire survey design. Variation by gender, age, frequency of use, main drug used and city was explored. RESULTS: The self-reported quantity used on the last day of use was for amphetamines on average 800 mg, for cocaine 1,014 mg and for heroin 682 mg. The self-reported usual dose was on average 297 mg, 487 mg and 297 mg respectively, while the median value was 250 mg for all three drugs. Overall, gender and age group were less important than frequency of use and the main drug used for establishing differences regarding the outcome variables. There were some differences regarding cities. No measure of purity was carried out at the interview sites, so the calculation of pure quantities was based on aggregate results from analyses of seizures by police and customs. CONCLUSIONS: The self-reported quantities of drugs consumed in three cities in Norway was equal to or somewhat higher among marginalized users than earlier assumed, where assumptions were based on limited literature and anecdotal information.

Liver fibrosis progression at autopsy in injecting drug users infected by hepatitis C: a longitudinal long-term cohort study.

BACKGROUND & AIMS: There is a paucity of unbiased data on the natural history of hepatitis C virus (HCV) infection in injecting drug users (IDUs). The purpose of this study was to assess the risk of developing advanced fibrosis associated with chronic hepatitis C (CHC) infection among injecting drug users (IDUs) who underwent an autopsy. METHODS: A longitudinal cohort design was applied, in which the stage of liver fibrosis in anti-HCV positive IDUs with or without chronic HCV infection was assessed in liver tissue from autopsies performed up to 35 years after HCV exposure. The cohort originated from 864 IDUs consecutively admitted for drug abuse treatment 1970-1984. Stored sera, mostly drawn at the time of admission for drug treatment, were available in 635 subjects. 220 out of 523 anti-HCV positive subjects had died before 2009. Liver tissue from autopsies was available from 102/220 subjects, of which 61 were HCV RNA positive. Liver sections were classified according to METAVIR scores for fibrosis. Two pathologists, both blinded for serologic results, scored sections of liver tissue. RESULTS: Among HCV RNA positive subjects 16.4% (10/61) had septal fibrosis (F3) or cirrhosis (F4) compared to 2.4% (1/41) among anti HCV positive/HCV RNA negative subjects (p=0.026). Of 18 HCV RNA positive subjects autopsied <15 years after HCV exposure none had F3 or F4. Among subjects autopsied >25 years after exposure 35% (6/17) had F3-F4. CONCLUSIONS: Among IDUs chronically infected by HCV, 1/3 developed septal fibrosis or cirrhosis 25 years or more after exposure.

A multi-state model to estimate incidence of heroin use.

BACKGROUND: Existing incidence estimates of heroin use are usually based on one information source. This study aims to incorporate more sources to estimate heroin use incidence trends in Spain between 1971 and 2005. METHODS: A multi-state model was constructed, whereby the initial state "heroin consumer" is followed by transition to either "admitted to first treatment" or to "left heroin use" (i.e. permanent cessation or death). Heroin use incidence and probabilities of entering first treatment ever were estimated following a back-calculation approach. RESULTS: The highest heroin use incidence rates in Spain, around 1.5 per 1,000 inhabitants aged 10-44, occurred between 1985 and 1990; subdividing by route of administration reveals higher incidences of injection between 1980 and 1985 (a mean of 0.62 per 1.000) and a peak for non-injectors in 1990 (0.867 per 1,000). CONCLUSIONS: A simple conceptual model for heroin users' trajectories related to treatment admission, provided a broader view of the historical trend of heroin use incidence in Spain.

All-cause and liver-related mortality in hepatitis C infected drug users followed for 33 years: a controlled study.

BACKGROUND & AIMS: The course of chronic hepatitis C virus (HCV) in injecting drug users (IDUs) has not been well described. The aim of this study was to compare long-term all-cause and liver-related mortality among anti-HCV positive IDUs with and without persisting HCV infection. METHODS: A retrospective-prospective controlled cohort design was applied. All IDUs admitted to resident drug treatment (1970-1984) and with available stored sera were screened for anti-HCV antibody. Anti-HCV positive individuals were further tested for the presence of HCV RNA. All-cause and liver-related mortality was compared between HCV RNA positive (n=328) and HCV RNA negative individuals (n=195). The observation was accomplished through register linkage to national registers. Mean observation time was 33 years. RESULTS: All-cause mortality rate was 1.85 (95% CI 1.62-2.11) per 100 person-years, male 2.11 (95% CI 1.84-2.46), female 1.39 (95% CI 1.07-1.79). Mortality rates were not influenced by persisting HCV infection. Main causes of death were intoxications (45.0%), suicide (9.1%), and accidents (8.2%). Liver disease was the cause of death in 7.5% of deaths among HCV RNA positive subjects. Five of 13 deaths among male IDUs with persisting HCV infection occurring after the age of 50 years were caused by liver disease. CONCLUSIONS: The all-cause mortality in IDUs is high and with no difference between HCV RNA positive and HCV RNA negative individuals, the first three decades after HCV transmission. However, among IDUs with chronic HCV infection who have survived until 50years of age, HCV infection emerges as the main cause of death.

Estimation of cocaine consumption in the community: a critical comparison of the results from three complimentary techniques.

OBJECTIVES: A range of approaches are now available to estimate the level of drug use in the community so it is desirable to critically compare results from the differing techniques. This paper presents a comparison of the results from three methods for estimating the level of cocaine use in the general population. DESIGN: The comparison applies to; a set of regional-scale sample survey questionnaires, a representative sample survey on drug use among drivers and an analysis of the quantity of cocaine-related metabolites in sewage. SETTING: 14 438 participants provided data for the set of regional-scale sample survey questionnaires; 2341 drivers provided oral-fluid samples and untreated sewage from 570 000 people was analysed for biomarkers of cocaine use. All data were collected in Oslo, Norway. RESULTS: 0.70 (0.36-1.03) % of drivers tested positive for cocaine use which suggest a prevalence that is higher than the 0.22 (0.13-0.30) % (per day) figure derived from regional-scale survey questionnaires, but the degree to which cocaine consumption in the driver population follows the general population is an unanswered question. Despite the comparatively low-prevalence figure the survey questionnaires did provide estimates of the volume of consumption that are comparable with the amount of cocaine-related metabolites in sewage. Per-user consumption estimates are however highlighted as a significant source of uncertainty as little or no data on the quantities consumed by individuals are available, and much of the existing data are contradictory. CONCLUSIONS: The comparison carried out in the present study can provide an excellent means of checking the quality and accuracy of the three measurement techniques because they each approach the problem from a different viewpoint. Together the three complimentary techniques provide a well-balanced assessment of the drug-use situation in a given community and identify areas where more research is needed.