Can the presence of specialized addiction staff in primary health care increase the number of alcohol-related medical consultations - A controlled intervention study.

Background: Few individuals with alcohol use disorders receive treatment. Primary care has been suggested as an arena for early treatment for these disorders. Aim: To evaluate whether the presence of a specialized addiction nurse can increase alcohol-related physician consultations in a primary care setting. Method: This controlled intervention study included one intervention and one control primary care unit in Malmö, Sweden. At the intervention unit, an addiction nurse experienced in alcohol use disorder treatment was present 20 h weekly for 12 months. At both units, an educational lecture on alcohol use disorders was given at study start. The outcome was physicians' monthly number of alcohol-related diagnostic codes. Data were compared between intervention and control units using Poisson Regression. Eight statistical models were analyzed and Akaike information criterion was used to select the final model. Results: The intervention was significantly associated with an increased number of registered alcohol-related diagnostic codes (risk ratio 1.33, 95 confidence interval 1.08-1.62). However, in sensitivity analyses, such a slope effect was more uncertain and no step effect was seen. A significant association was seen between the educational lecture and an increase in the number of registered alcohol-related codes at the sites (risk ratio 2.47, 1.37-4.46). Conclusion: The presence of specialized addiction staff in a primary healthcare setting might increase the number of alcohol-related physician consultations in primary care, although more research is needed. An educational lecture about alcohol use disorders could be a simple but effective intervention to increase alcohol-related physician consultations in primary care.

No obvious effect on mortality from a patient choice reform expanding access to opioid disorder treatment - results from a natural experiment of policy change in Sweden.

BACKGROUND: Opioid-related overdose deaths remain a common cause of death in many settings, and opioid maintenance treatment is evidence-based for the treatment of opioid use disorders. However, access to such treatment varies and is limited in many settings. METHODS: The present study examines the longitudinal effects of a regional patient choice reform which substantially increased availability to opioid maintenance treatment in one Swedish county, starting from 2014. A previous follow-up, limited in time, indicated a possible effect on mortality from this intervention, demonstrating a lower increase in overdose deaths than in counties without this reform. The present study follows overdose deaths through 2021, and compares the intervention county to the remaining parts in the country, using death certificate statistics from the national causes of death register. RESULTS: The present study does not demonstrate any significant difference in the development of overdose mortality in the county where this reform substantially expanded treatment access, compared to other counties in the country. CONCLUSIONS: The study underlines the importance to maintain extensive efforts against overdose deaths over and above the treatment of opioid use disorders, such as low-threshold provision of opioid antidotes or other interventions specifically addressing overdose risk behaviors.

Are Self-disorders in Schizophrenia Expressive of a Unifying Disturbance of Subjectivity: A Factor Analytic Approach.

BACKGROUND AND HYPOTHESIS: The idea that a disorder of the basic self is a central feature in schizophrenia has recently been corroborated in a meta-analysis and a systematic review. Manifestations of the self-disorder can be systematically explored with the Examination of Anomalous Self-Experience (EASE). In this study, we examined the factorial structure of EASE, and diagnostic efficacy of EASE. We hypothesized that EASE will have a monofactorial structure as an instability of the basic self will result in multiple deformations of self-experience which would be meaningfully interrelated as aspects of a unifying Gestalt. DESIGN: EASE data for 226 patients suffering from various mental disorders were analyzed under a confirmatory factor analysis framework (CFA). Area under the receiver operating characteristic curve (AUC) was calculated for the total EASE sums, and sensitivity and specificity values for prediction of schizophrenia spectrum disorders based on different cut-offs were obtained. RESULTS: Fit indices for the CFA model: RMSEA = 0.036, SRMR = 0.100, CFI = 0.983, TLI = 0.981. The AUC value was 0.946 (95% confidence interval: 0.919-0.974). Sensitivity as well as specificity for schizophrenia spectrum disorders were high. CONCLUSION: Our results lend support for EASE exhibiting a monofactorial structure and the notion of self-disorders as a central phenotypic feature of schizophrenia spectrum disorders.

The prognosis of schizophrenia: A systematic review and meta-analysis with meta-regression of 20-year follow-up studies.

OBJECTIVE: The aim was to examine the general outcome of schizophrenia after 20 years or more. METHODS: Using the PRISMA guidelines, we conducted a systematic review and meta-analysis with meta-regression on long-term follow-up studies of schizophrenia up until April 21, 2021. We included prospective studies with at least 20 years of follow-up on patients with a diagnosis of schizophrenia, and the studies had to include face-to-face clinical evaluation. We examined outcome in three nested groups: 'recovery', 'good or better' (including also 'recovery'), and 'moderate or better' (including also 'recovery' and 'good or better'). We used random-effects meta-analysis and meta-regression to examine mean estimates and possible moderators. RESULTS: We identified 1089 records, which were screened by two independent researchers. 14 prospective studies (1991 patients) published between 1978 and 2020 were found eligible. The studies used a range of different scales and definitions for outcome, and some used the same definitions for different outcomes. To compare outcome across studies, we designed and applied a unified template for outcome definitions and cutoffs, based on earlier studies' recommendations. Our meta-analysis found that 24.2 % had 'recovered' (n = 246, CI: 20.3-28.0 %), 35.5 % had a 'good or better' outcome (n = 766, CI: 26.0-45.0%), and 59.7% had 'moderate or better' outcome (n = 1139, CI: 49.3-70.1 %). CONCLUSIONS: The results contribute to debunk the myth that schizophrenia inevitably has a deteriorating course. Recovery is certainly possible. Schizophrenia remains, however, a severe and complex mental disorder, exhibiting a limited change in prognosis despite >100 years of research and efforts to improve treatment.

Excess mortality by suicide in high-risk subgroups of suicide attempters: a prospective study of standardised mortality rates in suicide attempters examined at a medical emergency inpatient unit.

OBJECTIVES: The primary aim of the present study was to investigate the putative excess mortality by suicide in suicide attempters. As a secondary aim, we investigate excess mortality in specific, clinically relevant subgroups: individuals with repeated suicide attempts (RA); individuals who used violent method at the attempt (VA); and those who scored high on the Suicide Intent Scale (HS) at the time of the baseline attempt. Finally, we investigate excess mortality in men and women separately and within 5 years and over 5 years after hospital admission for attempted suicide. DESIGN: Prospective register-based follow-up for 21-32 years. Standardised mortality ratio (SMR) was calculated for suicide using national census data. Clinically relevant subgroups were investigated separately. SETTING: Medical emergency inpatient unit in the south of Sweden. PARTICIPANTS: 1039 individuals who were psychiatrically assessed at admission to medical inpatient care for attempted suicide between 1987 and 1998. OUTCOME MEASURE: Suicide. RESULTS: The overall SMR for suicide was 23.50 (95% CI 18.68 to 29.56); significantly higher (p<0.001) among women (30.49 (95% CI 22.27 to 41.72)) than men (18.61 (95% CI 13.30 to 26.05)). Mortality was highest within the first 5 years after the index suicide attempt (48.79 (95% CI 35.64 to 66.77)) compared with those who died after 5 years (p<0.001) (14.74 (10.53 to 20.63)). The highest independent SMR was found for VA (70.22 (95% CI 38.89 to 126.80)). In a regression model including RA, VA and HS all contributed significantly to excess suicide mortality. CONCLUSIONS: An elevated risk of premature death by suicide was found in suicide attempters compared with the general population. Assessment of previous suicide attempts is important, even though the attempt/s may have occurred decades ago. When assessing suicide risk, clinicians should consider repeated attempts and whether the attempts involved high suicidal intent and violent method. Healthcare interventions may benefit from targeting identified subgroups of attempters.

A Normative Feedback Intervention on Gambling Behavior-A Longitudinal Study of Post-Intervention Gambling Practices in At-Risk Gamblers.

Background: In problem gambling, normative personalized feedback interventions have demonstrated promising effects. Given the widespread increase in online gambling in recent years, internet-delivered normative feedback may serve as a promising intervention. This study aimed to examine whether such an intervention, delivered by a gambling operator and aiming to help problem gamblers decrease their gambling, may in fact be associated with lower gambling practices post-intervention. Methods: Online questions on norms and beliefs about one's own and peers' gambling habits, derived from the Gambling Quantity and Perceived Norms Scale, were followed by personalized feedback, delivered online by the Swedish state-owned gambling operator. A total of 1,453 gamblers consented to participate in a pre-post measure of wagering levels. Results: Wagering decreased significantly post-intervention (28 days) compared to pre-intervention (28 days prior). The decrease was significantly more pronounced in younger and online casino gamblers. In an 84-day follow-up, the decrease remained significant, although less pronounced. Conclusions: An online normative intervention delivered by a state-owned gambling operator, addressing norms and beliefs about gambling levels, may lower risky gambling in the short term. Implications and further research needs are discussed.

Associations between off-label low-dose olanzapine or quetiapine and cardiometabolic mortality.

Olanzapine and quetiapine are routinely used off-label at lower doses, though it remains unclear whether treatment is associated with mortality. Here, we examined the associations between low-dose olanzapine/quetiapine, defined as 5 mg/day of olanzapine equivalents (OE) with cardiometabolic mortality in a population-based, longitudinal cohort of individuals who sought specialized psychiatric services. Through cross-linked Swedish registries, 428,525 individuals without psychotic, bipolar, or cardiometabolic disorders, or previous treatment with antipsychotics or cardiometabolic-related drugs were followed for up to 10.5 years. Extended stratified Cox proportional hazards regressions were employed to estimate the hazard ratios (HR) of cardiometabolic mortality as a function of cumulative OE exposures, adjusted for age, sex, inpatient care, and time-dependent psychiatric diagnoses and treatments. Individuals were followed for a total of 2.1 million person-years. Treatment with olanzapine/quetiapine occurred in 18,317 of the cohort. In total, 2606 cardiometabolic-related deaths occurred. Treatment status (treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted HR 0.86, 95% CI 0.64-1.15, P = 0.307). However, compared to no treatment, treatment for <6 months was significantly associated with a reduced risk (adjusted HR 0.56, 95% CI 0.37-0.87, P = 0.010) whereas treatment for 6-12 months was significantly associated with an increased risk (adjusted HR 1.89, 95% CI 1.22-2.92, P = 0.004), but not significantly beyond 12 months. Among those treated, each year exposed to an average 5 mg/day was significantly associated with increased cardiometabolic mortality (adjusted HR 1.45, 95% CI 1.06-1.99, P = 0.019). Overall, low-dose olanzapine/quetiapine treatment was weakly associated with cardiometabolic mortality. Clinicians should consider potential cardiometabolic sequelae at lower doses.

Self-Exclusion from Gambling-A Measure of COVID-19 Impact on Gambling in a Highly Online-Based Gambling Market?

The COVID-19 pandemic, and related changes of the gambling market, have been suspected to affect the risk of problem gambling. Despite media attention and political concern with this risk, study findings hitherto have been mixed. Voluntary self-exclusion from gambling was introduced on a national level in Sweden as a harm reduction tool in 2019, and this self-exclusion service in Sweden is a rare example of such an official, nationwide, multi-operator system. The present study aimed to evaluate whether short-term self-exclusion patterns were affected by different phases of COVID-19-related impacts on gambling markets in 2020. During the lock-down of sports in the spring months of 2020, three-month self-exclusion was unaffected, and one-month self-exclusion appeared to increase, though not more than in a recent period prior to COVID-19. Despite large differences in sports betting practices between women and men, self-exclusion patterns during COVID-19 were not apparently gender-specific. Altogether, self-exclusion from gambling, to date, does not appear to be affected by COVID-19-related changes in society, in contrast with beliefs about such changes producing greater help-seeking behavior in gamblers. Limitations are discussed, including the fact that in a recently introduced system, seasonality aspects and the autocorrelated nature of the data made substantial statistical measures unfeasible.

Changes in opioid-related deaths following increased access to opioid substitution treatment.

BACKGROUND: Opioid-related mortality is high and increasing in the Western world, and interventions aimed at reducing opioid-related deaths represent an important area of study. In Skåne County, Sweden, a patient choice reform resulted in increased access to opioid substitution treatment (OST). In addition, a gradual shift towards less restrictive terms for exclusion from OST has been implemented. The aim of this study was to assess the impact of these policy changes on opioid-related deaths. METHODS: Detailed data on opioid-related deaths in Skåne during the 2 years prior to and following the policy change were obtained from forensic records and from health care services. Data on overdose deaths for Skåne and the rest of Sweden were obtained using publicly available national register data. Time periods were used as the predictor for opioid-related deaths in the forensic data. The national level data were used in a natural experiment design in which rates of overdose deaths were compared between Skåne and the rest of Sweden before and after the intervention. RESULTS: There was no significant difference in the number of deaths in Skåne between the data collection periods (RR: 1.18 95% CI:0.89-1.57, p= 0.251). The proportion of deaths among patients enrolled in OST increased between the two periods (2.61, 1.12-6.10, p= 0.026). There was no change in deaths related to methadone or buprenorphine in relation to deaths due to the other opioids included in the study (0.92, 0.51-1.63, p= 0.764). An analysis of national mortality data showed an annual relative decrease in unintentional drug deaths in Skåne compared to the rest of Sweden following the onset of the reform (0.90, 0.84-0,97, p= 0.004). CONCLUSIONS: Opioid-related deaths, as assessed using forensic data, has not changed significantly in Skåne following a change to lower-threshold OST. By contrast, national level data indicate that the policy change has been associated with decreased overdose deaths. The discrepancy between these results highlights the need for more research to elucidate this issue. The result that more patients die during ongoing OST following an increase in access to treatment underlines the need for further preventive interventions within the OST treatment setting.

Sex-Specific Associations Between Bipolar Disorder Pharmacological Maintenance Therapies and Inpatient Rehospitalizations: A 9-Year Swedish National Registry Study.

Background: Long-term pharmacological maintenance therapy is often essential among people with bipolar disorder to reduce the need for inpatient care. Sex-specific responses to maintenance therapies are expected but remain largely unknown. Here, we examined for sex-specific associations between common maintenance therapies for bipolar disorder with inpatient rehospitalizations following patients' index discharges during 2006-2014. Methods: Population-based data on maintenance therapies and rehospitalizations were extracted from Swedish national registries. We adopted the within-individual design to compare the time on- vs. off- maintenance therapy for males and females, respectively. Extended stratified Cox proportional hazards regression models were employed to quantify the rate of rehospitalization as a function of common maintenance drugs and other important time-varying control variables. Results: Our primary analysis included 22,681 bipolar disorder rehospitalizations by 6,400 males and 9,588 (60.0%) females over an observation time of 62,813 person-years. The time spent on- vs. off- maintenance lithium, lamotrigine, quetiapine, or olanzapine was statistically significant upon adjustment among either sex for reducing the rate of bipolar rehospitalizations. Adjusted sex-specific statistically significant associations were also observed. Among females, the time on- (vs. off-) long-acting injectable risperidone reduced the rate of bipolar rehospitalizations by 73% (56-84%), carbamazepine by 44% (18-62%), aripiprazole by 29% (13-42%), and valproate by 23% (11-33%); whereas among males, ziprasidone by 65% (41-79%). Conclusion: The effectiveness of most maintenance therapies is generally comparable and uniform among both males and females. Despite some statistically significant sex-specific associations, estimates for each drug were fairly consistent between sexes.

Long-term risk factors for suicide in suicide attempters examined at a medical emergency in patient unit: results from a 32-year follow-up study.

OBJECTIVES: The overall aim of this study is to gain greater knowledge about the risk of suicide among suicide attempters in a very long-term perspective. Specifically, to investigate possible differences in clinical risk factors at short (≤5 years) versus long term (>5 years), with the hypothesis that risk factors differ in the shorter and longer perspective. DESIGN: Prospective study with register-based follow-up for 21-32 years. SETTING: Medical emergency inpatient unit in the south of Sweden. PARTICIPANTS: 1044 individuals assessed by psychiatric consultation when admitted to medical inpatient care for attempted suicide during 1987-1998. OUTCOME MEASURES: Suicide and all-cause mortality. RESULTS: At follow-up, 37.6% of the participants had died, 7.2% by suicide and 53% of these within 5 years of the suicide attempt. A diagnosis of psychosis at baseline represented the risk factor with the highest HR at long-term follow-up, that is, >5 years, followed by major depression and a history of attempted suicide before the index attempt. The severity of a suicide attempt as measured by SIS (Suicide Intent Scale) showed a non-proportional association with the hazard for suicide over time and was a relevant risk factor for suicide only within the first 5 years after an attempted suicide. CONCLUSIONS: The risk of suicide after a suicide attempt persists for up to 32 years after the index attempt. A baseline diagnosis of psychosis or major depression or earlier suicide attempts continued to be relevant risk factors in the very long term. The SIS score is a better predictor of suicide risk at short term, that is, within 5 years than at long term. This should be considered in the assessment of suicide risk and the implementation of care for these individuals.

Associations between Self-Disorders and First-Rank Symptoms: An Empirical Study.

BACKGROUND: The diagnostic weight of the first-rank symptoms was deemphasized in DSM-5 and a similar change is expected in ICD-11. This change was motivated by a lack of solid, empirical evidence of the diagnostic significance of first-rank symptoms for schizophrenia. Yet, it seems that Schneider's original concept of first-rank symptoms was overly simplified when it was introduced in DSM-III. Specifically, it was overlooked that first-rank symptoms, in Schneider's understanding, fundamentally involve a disorder of the self. The aim here is to empirically test Schneider's claim that first-rank symptoms involve self-disorders. METHODS: In a modified, cross-sectional study of 98 first-admission patients, the relation between lifetime presence of first-rank symptoms and self-disorders was examined. Self-disorders were examined with the EASE (Examination of Anomalous Self-Experiences). RESULTS: We found an odds ratio of 1.56 (95% CI 1.10-2.21) for having first-rank symptoms for each 5-point increase in the EASE (measuring self-disorder) using a generalized linear mixed model regression. We did not find first-rank symptoms in the absence of self-disorders. CONCLUSION: The close relation between first-rank symptoms and self-disorders seems to support Schneider's original concept of first-rank symptoms. We suggest that first-rank symptoms occurring without the pervasively altered self-experiences might not be different from other psychotic phenomena in terms of their diagnostic significance. Awareness of self-disorders can help clinicians in assessing and detecting first-rank symptoms.

Suicide mortality after discharge from inpatient care for bipolar disorder: A 14-year Swedish national registry study.

Bipolar disorder has long been associated with increased risks for suicidality; though factors associated with dying by suicide remain obscure. Here, we retrospectively examine the associations between the different phases of bipolar illness and other common comorbidities with death by suicide in the 120 days following each discharge for Swedes first admitted as inpatients for bipolar disorder during the years 2000-2014. Data on admissions and suicide deaths were extracted from the Swedish National Patient Register and the Cause of Death Register, respectively. ICD-10 diagnostic codes were used to define the phases: depressive, manic, mixed, and other; and the comorbidities: specific substance use disorders, attention deficit hyperactivity disorder, and personality disorders. Extended Cox regressions were employed to model the time to death by suicide as a function of the bipolar phases, comorbidities, and other important control variables. Our analysis included 60,643 admissions by 22,402 patients over an observation time of 15,187 person-years. Overall, 213 (35.7%) of all suicides occurred within 120 days of discharge. Upon adjustment and compared to the depressive phases, manic phases were significantly associated with a far lower hazard of dying by suicide (HR 0.34, 95% CI: 0.21-0.56, p < 0.001), though mixed phases were not (HR 0.92, 95% CI: 0.48-1.73, p = 0.957). With regard to comorbidity, only sedative use disorder remained significantly associated with dying by suicide upon adjustment (HR 2.08, 95% CI: 1.41-3.06, p = 0.001). Vigilant monitoring of patients post discharge and of prescription practices are recommended.

Gender influence on the bipolar disorder inpatient length of stay in Sweden, 2005-2014: A register-based study.

BACKGROUND: The influence of gender on bipolar disorder is controversial and it is unclear if inpatient care differs between men and women. Here, we investigate for gender differences in the inpatient length of stay for Swedes admitted for bipolar disorder and explore other factors that could explain any observed association. METHODS: Admission data were extracted from the Swedish National Patient Register and included all patients first admitted to a psychiatric inpatient unit with a bipolar disorder diagnosis, circa 2005-2014. Patients were then retrospectively followed for subsequent hospitalizations. Diagnostic subtypes were categorized by ICD-10 clusters: depressive, depressive with psychotic features, manic, manic with psychotic features, mixed, and other. Psychotropic therapies preceding the corresponding admissions were attained from the Prescribed Drug Register. Mixed-effects zero-truncated negative binomial regressions were employed to model the length of stay per admission. RESULTS: Analysis included 39,653 admissions by 16,271 inpatients (60.0% women). Overall, when compared to men, women spent 7.5% (95% CI: 4.2-11.0%, p < 0.001) extra days hospitalized per admission. However, upon adjusting for candidate confounders, including the bipolar subtype, and selected comorbidities and psychotropics, the association weakened wherein women then spent 3.7% (95% CI: 0.1-6.9%, p = 0.028) extra days hospitalized per admission. LIMITATIONS: The integrity of register data can be variable and the adherence to outpatient dispensed psychotropics could not be validated. CONCLUSION: Although the influence of gender on the bipolar disorder inpatient length of stay is evident, other factors attenuate and better explain this crude observation.

Gambling Disorder in Male Violent Offenders in the Prison System: Psychiatric and Substance-Related Comorbidity.

Gambling disorder is an addiction that can cause major suffering, and some populations seem to be more vulnerable than others. Offender populations have a remarkably high prevalence of gambling problems and they are also over-represented in a number of diagnoses related to gambling disorder, like substance use disorders and antisocial personality disorder. Yet, there are few studies investigating gambling disorder prevalence and related psychiatric comorbidity in this group. This study aims to investigate the prevalence of, and association between, gambling disorder and other psychiatric diagnoses in a sample of young, male violent offenders. Two hundred and sixty-four male offenders, all serving sentences for violent crimes (recruited between 2010 and 2012) participated in this study and went through comprehensive psychiatric evaluation, including assessment for Diagnostic and Statistical Manual of Mental Disorders 4th Edition criteria. Sixteen percent of the participants met criteria for gambling disorder. Antisocial personality disorder, cannabis, cocaine and anabolic steroids abuse were significantly more common among participants with gambling disorder. The gambling disorder group also showed significantly lower educational attainment. Cocaine abuse and failure to graduate elementary and middle school in expected time were independently associated with gambling disorder in a regression analysis. This study confirms the previously described high prevalence of gambling disorder in offenders. The psychiatric comorbidity was high and the problems had started early, with lower educational attainment in the gambling disorder group. The findings stress the importance of increased awareness of gambling problems among convicted offenders and of gambling research on young people with delinquent behavior. There is a need of more research to investigate this further, in order to develop preventive strategies and treatment.

Structured physical exercise and recovery from first episode psychosis in young adults, the FitForLife study.

Optimising autonomy is increasingly important in recovery from psychosis. To date, physical exercise has shown promise in the treatment of severe, enduring mental illnesses including psychosis - when used as an adjunct treatment. To assess the association between physical exercise and autonomy in young adults, a simple pre-post experimental design was utilised. Individuals aged 18-35 years, treated at one of three specialist outpatient units for first-episode psychosis in Stockholm, Sweden were invited to participate in a 12-week programme of structured group exercise. Autonomy was measured using four questions from the Camberwell Assessment of Needs questionnaire (physical health, social and close relationship and daily tasks). Comparisons were made between: 'no attendance' and 'any attendance'. The latter group was bisected into higher and lower categories. Ninety-four participants enrolled with a post-intervention response rate of 61%. Significant reductions were seen in self-rated needs for care, though there was no significant change in total scores or evidence of a dose response association. The results suggest a plausible association between physical exercise and autonomy which may represent the recovery process following the first episode of psychosis. Further randomised control trials are needed to explore the potential causality and robustness of this change.

Both localized and systemic bacterial infections are predicted by injection drug use: A prospective follow-up study in Swedish criminal justice clients.

BACKGROUND: Both skin and soft tissue infections (SSTI) and systemic bacterial infections are common in people who inject drugs (PWID), but data on incidence and risk factors are lacking. We compared registered diagnoses for such infections in Swedish criminal justice clients with regard to injecting drug use. METHODS: Baseline interview data from the Swedish Prison and Probation Service on drug use in PWID and non-PWID with problematic alcohol use were linked to follow-up data from national Swedish registers on hospital diagnoses and/or death. Associations between drug use and later diagnosis of SSTI and systemic bacterial infection (septicemia or bacterial infection of the heart, bone/joints or central nervous system) were analyzed by Cox regression. RESULTS: Incidence rates of SSTI was 28.3 per 1,000 person-years for PWID (n = 2,444) and 10.0 for non-PWID with problematic alcohol use (n = 735). Incidence rates of systemic bacterial infection was 9.1 per 1,000 person-years for PWID and 2.7 per 1,000 person-years for non-PWID. Injection drug use was associated with a significantly increased risk of bacterial infections, for main drugs heroin (SSTI: Hazard ratio [HR] 2.45; systemic infection: HR 2.75), amphetamine (SSTI: HR 1.60; systemic infection: HR 2.19), and polysubstance use (SSTI: HR 1.92; systemic infection: HR 2.01). In relation to injection use of amphetamine and polysubstance use, PWID mainly using heroin had higher risk of SSTI. CONCLUSIONS: Injection drug use predicted both SSTI and systemic bacterial infection, with a particularly high risk of SSTI in PWID mainly using heroin. The results imply the need for increased attention to bacterial infections among PWID, in terms of clinical management, prevention and research.

Benzodiazepine, z-drug and pregabalin prescriptions and mortality among patients in opioid maintenance treatment-A nation-wide register-based open cohort study.

BACKGROUND: Use of sedatives may increase risk of death in opioid users. The aim of the study was to assess whether prescription of sedatives may be associated with mortality in patients in opioid maintenance treatment. METHODS: This retrospective register-based open cohort study included nation-wide register data including all individuals who were dispensed methadone or buprenorphine as opioid maintenance treatment for opioid dependence between July, 2005 and December, 2012 (N=4501). Outcome variables were overdose mortality and non-overdose mortality, respectively. Extended Cox regression analyses examined associations between type of sedative prescriptions and death, controlling for sex, age, previous overdoses and suicide attempts, psychiatric in-patient treatment and opioid maintenance treatment status. Opioid maintenance was assumed to last for 90days (or 30days in a sensitivity analysis) after the last methadone or buprenorphine prescription. RESULTS: Benzodiazepine prescriptions were associated with non-overdose death (HR: 2.02, 95% CI: 1.29-3.18) but not significantly associated with overdose death (1.49, 0.97-2.29). Z-drug (1.60, 1.07-2.39) and pregabalin prescriptions (2.82, 1.79-4.43) were associated with overdose death. In the sensitivity analysis, all categories of sedatives, including benzodiazepines, were significantly associated with overdose death. CONCLUSIONS: Caution is advised when prescribing sedative drugs, including benzodiazepines, z-drugs and pregabalin, to patients in opioid maintenance treatment.