Risk of repeat self-harm among individuals presenting to healthcare services: development and validation of a clinical risk assessment model (OxSET).

BACKGROUND: A self-harm episode is a major risk factor for repeat self-harm. Existing tools to assess and predict repeat self-harm have major methodological limitations, and few are externally validated. OBJECTIVE: To develop and validate a risk assessment model of repeat self-harm up to 6 months after an episode of non-fatal self-harm that resulted in an emergency visit to hospital or specialised care. METHODS: Using Swedish national registers, we identified 53 172 people aged≥10 years who self-harmed during 2008-2012. We allocated 37 523 individuals to development (2820 or 7.5% repeat self-harm incidents within 6 months) and 15 649 to geographic validation (1373 repeat episodes) samples, based on region of residence. In a temporal validation of people who self-harmed during 2018-2019, we identified 25 036 individuals (2886 repeat episodes). We fitted a multivariable accelerated failure time model to predict risk of repeat self-harm. FINDINGS: In the external validations (n=40 685), rates of repeat self-harm were 8.8%-11.5% over 6 months. The final model retained 17 factors. Calibration and discrimination were similar in both validation samples, with observed-to-expected ratio=1.15 (95% CI=1.09 to 1.21) and c-statistic=0.72 (95% CI=0.70 to 0.73) in the geographical validation. At 6 months and a 10% risk cut-off, sensitivity was 51.5% (95% CI=48.8% to 54.2%) and specificity was 80.7% (95% CI=80.1% to 81.4%) in geographic validation; corresponding values were 56.9% (95% CI=55.1% to 58.7%) and 76.0% (95% CI=75.5% to 76.6%) in temporal validation. Discrimination was slightly worse at the 1-month prediction horizon (c-statistics of 0.66-0.68). CONCLUSIONS: Using mostly routinely collected data, simple risk assessment models and tools can provide acceptable levels of accuracy for repeat of self-harm. CLINICAL IMPLICATIONS: This risk model (OXford SElf-harm repeat tool) may assist clinical decision-making.

Genomic Validation in the UK Biobank Cohort Suggests a Role of C8B and MFG-E8 in the Pathogenesis of Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a severe facial pain disease of uncertain pathophysiology and unclear genetic background. Although recent research has reported a more important role of genetic factors in TN pathogenesis, few candidate genes have been proposed to date. The present study aimed to identify independent genetic variants in the protein-coding genes associated with TN. We focused on genes previously linked to TN based on the results of four proteomic studies conducted by our research team. The goal was to validate these findings on the genetic level to enhance our understanding of the role of genetics in TN. The study is based on the participants from UK Biobank cohort. Following quality control, 175 independent single nucleotide polymorphisms (SNPs) in 17 genes were selected. The study sample comprised of diagnosed TN cases (N = 555) and randomly matched controls (N = 6245) based on specific criteria. Two SNPs corresponding to C8B rs706484 [odds ratio (OR) (95% confidence interval (CI)): 1.357 (1.158-1.590); p: 0.00016] and MFG-E8 rs2015495 [OR (95% CI): 1.313 (1.134-1.521); p: 0.00028] showed significant positive association with TN, indicating a positive effect of the SNP alleles on gene expression and disease risk. Interestingly, both SNPs are Expression Quantitative Trait Loci (eQTLs), and are associated with changes in the expression activity of their corresponding gene. Our findings suggest novel genetic associations between C8B, a key component of the complement system, and MFG-E8, which plays a role in regulating neuroinflammation, in relation to TN. The identified genetic variations may help explain why some individuals develop TN while others do not, indicating a potential genetic predisposition to the condition.

Impact of traumatic brain injury on risk for schizophrenia and bipolar disorder.

The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental confounding effects have also been understudied. Therefore, we aim to investigate the impact of TBI on the risk of SCZ and BD and whether the effect varies by injury severity, age at injury, and sex. We identified 4,184 SCZ and 18,681 BD cases born between 1973 and 1998 in the Swedish National Registers. Case-control samples matched (1:5) on birth year, sex, and birthplace were created along with a family design study, with cases matched to non-case full siblings. TBI was associated with higher risk of SCZ and BD (IRR=1.33 for SCZ, IRR=1.78 for BD). The association remained significant in the sibling comparison study. Moderate or severe TBI was associated with higher risk for both SCZ and BD compared to mild TBI. Older age at injury was associated with higher risk of SCZ and BD, and the effect of TBI was stronger in women than men. Findings indicate that TBI is a risk factor for both SCZ and BD with differential impact by age, severity and sex and that this association cannot be explained by familial confounding alone.

Medication utilization in traumatic brain injury patients-insights from a population-based matched cohort study.

Introduction: Traumatic brain injury (TBI) is associated with health problems across multiple domains and TBI patients are reported to have high rates of medication use. However, prior evidence is thin due to methodological limitations. Our aim was thus to examine the use of a wide spectrum of medications prescribed to address pain and somatic conditions in a population-based cohort of TBI patients, and to compare this to a sex- and age-matched cohort. We also examined how patient factors such as sex, age, and TBI severity were associated with medication use. Methods: We assessed Swedish nationwide registers to include all individuals treated for TBI in hospitals or specialist outpatient care between 2006 and 2012. We examined dispensed prescriptions for eight different non-psychotropic medication classes for the 12 months before, and 12 months after, the TBI. We applied a fixed-effects model to compare TBI patients with the matched population cohort. We also stratified TBI patients by sex, age, TBI severity and carried out comparisons using a generalized linear model. Results: We identified 239,425 individuals with an incident TBI and 239,425 matched individuals. TBI patients were more likely to use any medication [Odds ratio (OR) = 2.03, 95% Confidence Interval (CI) = 2.00-2.05], to present with polypharmacy (OR = 1.96, 95% CI = 1.90-2.02), and to use each of the eight medication classes before their TBI, as compared to the matched population cohort. Following the TBI, TBI patients were more likely to use any medication (OR = 1.83, 95% CI = 1.80-1.86), to present with polypharmacy (OR = 1.74, 95% CI = 1.67-1.80), and to use all medication classes, although differences were attenuated. However, differences increased for antibiotics/antivirals (OR = 2.02, 95% CI = 1.99-2.05) and NSAIDs/antirheumatics (OR = 1.62, 95% CI = 1.59-1.65) post-TBI. We also found that females and older patients were more likely to use medications after their TBI than males and younger patients, respectively. Patients with more severe TBIs demonstrated increased use of antibiotics/ antivirals and NSAIDs/antirheumatics than those with less severe TBIs. Discussion: Taken together, our results point to poor overall health in TBI patients, suggesting that medical follow-up should be routine, particularly in females with TBI, and include a review of medication use to address potential polypharmacy.

The risk and development of work disability among individuals with gambling disorder: a longitudinal case-cohort study in Sweden.

BACKGROUND: This longitudinal register study aimed to investigate the association between gambling disorder (GD) and work disability and to map work disability in subgroups of individuals with GD, three years before and three years after diagnosis. METHODS: We included individuals aged 19-62 with GD between 2005 and 2018 (n = 2830; 71.1% men, mean age: 35.1) and a matched comparison cohort (n = 28 300). Work disability was operationalized as the aggregated net days of sickness absence and disability pension. Generalized estimating equation models were used to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for the risk of long-term work disability (>90 days of work disability/year). Secondly, we conducted Group-based Trajectory Models on days of work disability. RESULTS: Individuals with GD showed a four-year increased risk of long-term work disability compared to the matched cohort, peaking at the time of diagnosis (AOR = 1.89; CI 1.67-2.13). Four trajectory groups of work disability days were identified: constant low (60.3%, 5.6-11.2 days), low and increasing (11.4%, 11.8-152.5 days), medium-high and decreasing (11.1%, 65.1-110 days), and constant high (17.1%, 264-331 days). Individuals who were females, older, with prior psychiatric diagnosis, and had been dispensed a psychotropic medication, particularly antidepressants, were more likely to be assigned to groups other than the constant low. CONCLUSION: Individuals with GD have an increased risk of work disability which may add financial and social pressure and is an additional incentive for earlier detection and prevention of GD.

The genetics of gaming: A longitudinal twin study.

Background: Gaming is a popular past-time activity among children and adolescents, but it there is also a possible link to negative consequences such as psychological distress and lowered academic achievement. However, there are fundamental knowledge gaps remaining regarding central characteristics of gaming such as heritability, stability over time, and sex differences. We examined the genetic and environmental contribution to gaming behavior, including sex differences, continuity and change, in a longitudinal cohort of twins. Methods: This is the first longitudinal twin study on gaming, involving 32,006 twins in Sweden. Parents were asked about the twins' gaming at ages 9, 15 and 18. We used univariate and multivariate twin analyses to estimate the relative contribution of genetic and environmental influences at each time-point as well as across time. Sex-differences were also explored. Results: The results showed large sex differences, where genetics explained more of the variance for boys (31.3%-62.5% depending on age) than for girls (19.4%-23.4%). Genetic factors explained an increasing amount of the variance for boys (31.3% at age 9, 62.5% at age 15 and 53.9% at age 18). Shared environmental factors explained a larger proportion of the variance among girls, which remained relatively stable over time (70.5% at age 9, 61.8% at age 15 and 60.5% at age 18). The results also indicated that most of the variance came from genetic and environmental sources specific to each age. Conclusions: Compared to many other behavioral phenotypes, such as gambling, gaming was relatively unstable with a large degree of genetic innovation. There were large sex differences in the contribution of genetic and environmental factors. This suggests that excessive gaming could be the result of age- and sex-specific genetic and environmental factors, and should be taken into account when mapping gaming behaviors, since these behaviors might be under continual etiological transformation.

Access to Rehabilitation After Hospitalization for Traumatic Brain Injury: A National Longitudinal Cohort Study in Sweden.

BACKGROUND: Rehabilitation is suggested to improve outcomes following traumatic brain injury (TBI), however, the extent of access to rehabilitation among TBI patients remains unclear. OBJECTIVE: To examine the level of access to rehabilitation after TBI, and its association with health and sociodemographic factors. METHOD: We conducted a longitudinal cohort study using Swedish nationwide healthcare and sociodemographic registers. We identified 15 880 TBI patients ≥18 years hospitalized ≥3 days from 2008 to 2012 who were stratified into 3 severity groups; grade I (n = 1366; most severe), grade II (n = 5228), and grade III (n = 9268; least severe). We examined registered contacts with specialized rehabilitation or geriatric care (for patients ≥65 years) during the hospital stay, and/or within 1 year post-discharge. We performed a generalized linear model analysis to estimate the risk ratio (RR) for receiving specialized rehabilitation or geriatric care after a TBI based on sociodemographic and health factors. RESULTS: Among TBI patients, 46/35% (grade I), 14/40% (grade II), and 5/18% (grade III) received specialized rehabilitation or geriatric care, respectively. Being currently employed or studying was positively associated (RR 1.7, 2.3), while living outside of a city area was negatively associated (RR 0.36, 0.79) with receiving specialized rehabilitation or geriatric care. Older age and a prior substance use disorder were negatively associated with receiving specialized rehabilitation (RR 0.51 and 0.81). CONCLUSION: Our results suggest insufficient and unequal access to rehabilitation for TBI patients, highlighting the importance of organizing and standardizing post-TBI rehabilitation to meet the needs of patients, regardless of their age, socioeconomic status, or living area.

Development and Validation of a Prediction Tool for Reoffending Risk in Domestic Violence.

Importance: Current risk assessment tools for domestic violence against family members were developed with small and selected samples, have low accuracy with few external validations, and do not report key performance measures. Objective: To develop new tools to assess risk of reoffending among individuals who have perpetrated domestic violence. Design, Setting, and Participants: This prognostic study investigated a national cohort of all individuals arrested for domestic violence between 1998 and 2013 in Sweden using information from multiple national registers, including National Crime Register, National Patient Register, Longitudinal Integrated Database for Health Insurance and Labour Market Studies Register, and Multi-Generation Register. Data were analyzed from August 2022 to June 2023. Exposure: Arrest for domestic violence. Main Outcomes and Measures: Prediction models were developed for 3 reoffending outcomes after arrest for domestic violence: conviction of a new violent crime (including domestic violence), conviction of any new crime, and rearrest for domestic violence at 1 year, 3 years, and 5 years. The prediction models were created using sociodemographic factors, criminological factors, and mental health status-related factors, linking data from multiple population-based longitudinal registers. Cox proportional hazard multivariable regression was used to develop prediction models and validate them in external samples. Key performance measures, including discrimination at prespecified cutoffs and calibration statistics, were investigated. Results: The cohort included 27 456 individuals (mean [SD] age, 39.4 [11.6] years; 24 804 men [90.3%]) arrested for domestic violence, of whom 4222 (15.4%) reoffended and were convicted for a new violent crime during a mean (SD) follow-up of 26.5 (27.0) months, 9010 (32.8%) reoffended and were convicted for a new crime (mean [SD] follow-up, 22.4 [25.1] months), and 2080 (7.6%) were rearrested for domestic violence (mean [SD] follow-up, 25.7 [30.6] months). Prediction models were developed with sociodemographic, criminological, and mental health factors and showed good measures of discrimination and calibration for violent reoffending and any reoffending. The area under the receiver operating characteristic curve (AUC) for risk of violent reoffending was 0.75 (95% CI, 0.74-0.76) at 1 year, 0.76 (95% CI, 0.75-0.77) at 3 years, and 0.76 (95% CI, 0.75-0.77) 5 years. The AUC for risk of any reoffending was 0.76 (95% CI, 0.75-0.77) at 1 year and at 3 years and 0.76 (95% CI, 0.75-0.76) at 5 years. The model for domestic violence reoffending showed modest discrimination (C index, 0.63; 95% CI, 0.61-0.65) and good calibration. The validation models showed discrimination and calibration performance similar to those of derivation models for all 3 reoffending outcomes. The prediction models have been translated into 3 simple online risk calculators that are freely available to use. Conclusions and Relevance: This prognostic study developed scalable, evidence-based prediction tools that could support decision-making in criminal justice systems, particularly at the arrest stage when identifying those at higher risk of reoffending and screening out individuals at low risk of reoffending. Furthermore, these tools can enhance treatment allocation by enabling criminal justice services to focus on modifiable risk factors identified in the tools for individuals at high risk of reoffending.

Risk of death by suicide following self-harm presentations to healthcare: development and validation of a multivariable clinical prediction rule (OxSATS).

BACKGROUND: Assessment of suicide risk in individuals who have self-harmed is common in emergency departments, but is often based on tools developed for other purposes. OBJECTIVE: We developed and validated a predictive model for suicide following self-harm. METHODS: We used data from Swedish population-based registers. A cohort of 53 172 individuals aged 10+ years, with healthcare episodes of self-harm, was split into development (37 523 individuals, of whom 391 died from suicide within 12 months) and validation (15 649 individuals, 178 suicides within 12 months) samples. We fitted a multivariable accelerated failure time model for the association between risk factors and time to suicide. The final model contains 11 factors: age, sex, and variables related to substance misuse, mental health and treatment, and history of self-harm. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis guidelines were followed for the design and reporting of this work. FINDINGS: An 11-item risk model to predict suicide was developed using sociodemographic and clinical risk factors, and showed good discrimination (c-index 0.77, 95% CI 0.75 to 0.78) and calibration in external validation. For risk of suicide within 12 months, using a 1% cut-off, sensitivity was 82% (75% to 87%) and specificity was 54% (53% to 55%). A web-based risk calculator is available (Oxford Suicide Assessment Tool for Self-harm or OxSATS). CONCLUSIONS: OxSATS accurately predicts 12-month risk of suicide. Further validations and linkage to effective interventions are required to examine clinical utility. CLINICAL IMPLICATIONS: Using a clinical prediction score may assist clinical decision-making and resource allocation.

Associations between ß-blockers and psychiatric and behavioural outcomes: A population-based cohort study of 1.4 million individuals in Sweden.

BACKGROUND: ß-blockers are widely used for treating cardiac conditions and are suggested for the treatment of anxiety and aggression, although research is conflicting and limited by methodological problems. In addition, ß-blockers have been associated with precipitating other psychiatric disorders and suicidal behaviour, but findings are mixed. We aimed to examine associations between ß-blockers and psychiatric and behavioural outcomes in a large population-based cohort in Sweden. METHODS AND FINDINGS: We conducted a population-based longitudinal cohort study using Swedish nationwide high-quality healthcare, mortality, and crime registers. We included 1,400,766 individuals aged 15 years or older who had collected ß-blocker prescriptions and followed them for 8 years between 2006 and 2013. We linked register data on dispensed ß-blocker prescriptions with main outcomes, hospitalisations for psychiatric disorders (not including self-injurious behaviour or suicide attempts), suicidal behaviour (including deaths from suicide), and charges of violent crime. We applied within-individual Cox proportional hazards regression to compare periods on treatment with periods off treatment within each individual in order to reduce possible confounding by indication, as this model inherently adjusts for all stable confounders (e.g., genetics and health history). We also adjusted for age as a time-varying covariate. In further analyses, we adjusted by stated indications, prevalent users, cardiac severity, psychiatric and crime history, individual ß-blockers, ß-blocker selectivity and solubility, and use of other medications. In the cohort, 86.8% (n = 1,215,247) were 50 years and over, and 52.2% (n = 731,322) were women. During the study period, 6.9% (n = 96,801) of the ß-blocker users were hospitalised for a psychiatric disorder, 0.7% (n = 9,960) presented with suicidal behaviour, and 0.7% (n = 9,405) were charged with a violent crime. There was heterogeneity in the direction of results; within-individual analyses showed that periods of ß-blocker treatment were associated with reduced hazards of psychiatric hospitalisations (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.91 to 0.93, p < 0.001), charges of violent crime (HR: 0.87, 95% CI: 0.81 to 0.93, p < 0.001), and increased hazards of suicidal behaviour (HR: 1.08, 95% CI: 1.02 to 1.15, p = 0.012). After stratifying by diagnosis, reduced associations with psychiatric hospitalisations during ß-blocker treatment were mainly driven by lower hospitalisation rates due to depressive (HR: 0.92, 95% CI: 0.89 to 0.96, p < 0.001) and psychotic disorders (HR: 0.89, 95% CI: 0.85 to 0.93, p < 0.001). Reduced associations with violent charges remained in most sensitivity analyses, while associations with psychiatric hospitalisations and suicidal behaviour were inconsistent. Limitations include that the within-individual model does not account for confounders that could change during treatment, unless measured and adjusted for in the model. CONCLUSIONS: In this population-wide study, we found no consistent links between ß-blockers and psychiatric outcomes. However, ß-blockers were associated with reductions in violence, which remained in sensitivity analyses. The use of ß-blockers to manage aggression and violence could be investigated further.

Prediction of reoffending risk in men convicted of sexual offences: development and validation of novel and scalable risk assessment tools (OxRIS).

Background: Current risk assessment tools have a limited evidence base with few validations, poor reporting of outcomes, and rarely include modifiable factors. Methods: We examined a national cohort of men convicted of sexual crimes in Sweden. We developed prediction models for three outcomes: violent (including sexual), any, and sexual reoffending. We used Cox proportional hazard regression to develop multivariable prediction models and validated these in an external sample. We reported discrimination and calibration statistics at prespecified cut-offs. Findings: We identified 16,231 men convicted of sexual offences, of whom 14.8% violently reoffended during a mean follow up of 38 months, 31.4% for any crime (34 months), and 3.6% for sexual crimes (42 months). Models for violent and any reoffending showed good discrimination and calibration. At 1, 3, and 5 years, the area under the curve (AUC) was 0.75-0.76 for violent reoffending and 0.74-0.75 for any reoffending. The prediction model for sexual reoffending showed modest discrimination (AUC = 0.67) and good calibration. We have generated three simple and web-based risk calculators, which are freely available. Interpretation: Scalable evidence-based risk assessment tools for sexual offenders in the criminal justice system and forensic mental health could assist decision-making and treatment allocation by identifying those at higher risk, and screening out low risk persons.

Comparative effect of metformin versus sulfonylureas with dementia and Parkinson's disease risk in US patients over 50 with type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes is a risk factor for dementia and Parkinson's disease (PD). Drug treatments for diabetes, such as metformin, could be used as novel treatments for these neurological conditions. Using electronic health records from the USA (OPTUM EHR) we aimed to assess the association of metformin with all-cause dementia, dementia subtypes and PD compared with sulfonylureas. RESEARCH DESIGN AND METHODS: A new user comparator study design was conducted in patients ≥50 years old with diabetes who were new users of metformin or sulfonylureas between 2006 and 2018. Primary outcomes were all-cause dementia and PD. Secondary outcomes were Alzheimer's disease (AD), vascular dementia (VD) and mild cognitive impairment (MCI). Cox proportional hazards models with inverse probability of treatment weighting (IPTW) were used to estimate the HRs. Subanalyses included stratification by age, race, renal function, and glycemic control. RESULTS: We identified 96 140 and 16 451 new users of metformin and sulfonylureas, respectively. Mean age was 66.4±8.2 years (48% male, 83% Caucasian). Over the 5-year follow-up, 3207 patients developed all-cause dementia (2256 (2.3%) metformin, 951 (5.8%) sulfonylurea users) and 760 patients developed PD (625 (0.7%) metformin, 135 (0.8%) sulfonylurea users). After IPTW, HRs for all-cause dementia and PD were 0.80 (95% CI 0.73 to 0.88) and 1.00 (95% CI 0.79 to 1.28). HRs for AD, VD and MCI were 0.81 (0.70-0.94), 0.79 (0.63-1.00) and 0.91 (0.79-1.04). Stronger associations were observed in patients who were younger (<75 years old), Caucasian, and with moderate renal function. CONCLUSIONS: Metformin users compared with sulfonylurea users were associated with a lower risk of all-cause dementia, AD and VD but not with PD or MCI. Age and renal function modified risk reduction. Our findings support the hypothesis that metformin provides more neuroprotection for dementia than sulfonylureas but not for PD, but further work is required to assess causality.

Associations between prisons and recidivism: A nationwide longitudinal study.

OBJECTIVES: To examine differences in recidivism rates between different prisons using two designs-between-individual and within-individual-to account for confounding factors. METHODS: We examined recidivism rates among 37,891 individuals released from 44 Swedish prisons in three security levels, and who were followed from 2006 to 2013. We used longitudinal data from nationwide registers, including all convictions from district courts. First, we applied a between-individual design (Cox proportional hazards regression), comparing reconviction rates between individuals released from prisons within the same security level, while adjusting for a range of individual-level covariates. Second, we applied a within-individual design (stratified Cox proportional hazards regression), comparing rates of reconviction within the same individuals, i.e., we compared rates after release from one prison to the rates in the same individual after release from another prison, thus adjusting for all time-invariant confounders within each individual (e.g. genetics and early environment). We also adjusted for a range of time-varying individual-level covariates. RESULTS: Results showed differences in the hazard of recidivism between different prisons in between-individual analyses, with hazards ranging from 1.22 (1.05-1.43) to 4.99 (2.44-10.21). Results from within-individual analyses, which further adjusted for all time-invariant confounders, showed minimal differences between prisons, with hazards ranging from 0.95 (0.87-1.05) to 1.05 (0.95-1.16). Only small differences were found when violent and non-violent crimes were analyzed separately. CONCLUSIONS: The study highlights the importance of research designs that more fully adjust for individual-level confounding factors to avoid over-interpretation of the variability in comparisons across prisons.

Psychotropic and pain medication use in individuals with traumatic brain injury-a Swedish total population cohort study of 240 000 persons.

OBJECTIVE: To examine psychotropic and pain medication use in a population-based cohort of individuals with traumatic brain injury (TBI), and compare them with controls from similar backgrounds. METHODS: We assessed Swedish nationwide registers to include all individuals diagnosed with incident TBI between 2006 and 2012 in hospitals or specialist outpatient care. Full siblings never diagnosed with TBI acted as controls. We examined dispensed prescriptions for psychotropic and pain medications for the 12 months before and after the TBI. RESULTS: We identified 239 425 individuals with incident TBI, and 199 658 unaffected sibling controls. In the TBI cohort, 36.6% had collected at least one prescription for a psychotropic or pain medication in the 12 months before the TBI. In the 12 months after, medication use increased to 45.0%, an absolute rate increase of 8.4% (p<0.001). The largest post-TBI increases were found for opioids (from 16.3% to 21.6%, p<0.001), and non-opioid pain medications (from 20.3% to 26.6%, p<0.001). The majority of prescriptions were short-term; 20.6% of those prescribed opioids and 37.3% of those with benzodiazepines collected prescriptions for more than 6 months. Increased odds of any psychotropic or pain medication were associated with individuals before (OR: 1.62, 95% CI: 1.59 to 1.65), and after the TBI (OR: 2.30, 95% CI: 2.26 to 2.34) as compared with sibling controls, and ORs were consistently increased for all medication classes. CONCLUSION: High rates of psychotropic and pain medications after a TBI suggest that medical follow-up should be routine and review medication use.

Associations between statin use and suicidality, depression, anxiety, and seizures: a Swedish total-population cohort study.

BACKGROUND: Statins have shown both protective and adverse associations with neuropsychiatric outcomes. We aimed to examine the possible associations between statins and suicidality, depression, anxiety, and seizures. METHODS: Using Swedish national registers, we linked data on dispensed statin prescriptions with data on unplanned (emergency) hospital visits or specialised outpatient care for four neuropsychiatric outcomes: suicidal behaviour (including deaths from suicide), depressive disorders, anxiety disorders, and seizures. We included all individuals in the registries who were dispensed statins and who were aged 15 years or older between Jan 1, 2006, and Dec 31, 2013. We applied a within-individual design using stratified Cox proportional hazards regression to compare the incidence of the defined outcomes during periods on statins and periods off statins within each individual, thus adjusting for time-invariant confounders. Non-specific effects of treatment were tested by investigating these outcomes in relation to thiazide diuretic use and antihistamine use in the same cohort. FINDINGS: The statin-users cohort comprised 1 149 384 individuals, of whom 1 015 949 (88·4%) were aged 50 years or older, 625 616 (54·4%) were male, and 523 768 (45·6%) were female. The study period consisted of 2 053 310 non-treatment periods and 2 997 545 treatment periods, and 957 216 (83·3%) individuals had a medication status change (from on statins to off statins, or vice versa). Suicide outcomes were found in 6372 (0·6%) individuals, depressive disorders in 23 745 (2·1%), anxiety disorders in 30 100 (2·6%), and seizures in 28 844 (2·5%). There were no clear associations between periods of statin treatment and suicidal behaviour or deaths from suicide (hazard ratio 0·99 [95% CI 0·90-1·08]), anxiety disorders (0·99 [0·95-1·02]), or seizures (1·00 [0·97-1·04]). Statins were associated with reduced hazards of depressive disorders (0·91 [0·87-0·94]), which remained after adjustment for concurrent antidepressant use (0·91 [0·88-0·94]). Hazard ratios for depressive disorders were 0·61 (0·38-1·00; n=14 718) with thiazide diuretic use and 0·84 (0·67-1·06; n=23 715) with antihistamine use. INTERPRETATION: Statin use is not associated with suicidality, anxiety disorders, or seizures. Whether the observed association between statin use and reduced diagnoses of clinical depression is confounded by non-specific benefits related to being prescribed medication needs further research. FUNDING: Wellcome Trust, Swedish Research Council, National Institute for Health Research (NIHR) Research Professorship, NIHR Oxford Health Biomedical Research Centre, American Foundation for Suicide Prevention, Karolinska Institutet.

Associations between selective serotonin reuptake inhibitors and violent crime in adolescents, young, and older adults - a Swedish register-based study.

This study identified individuals ever dispensed a selective serotonin reuptake inhibitor (SSRI) aged 15-60 years during 2006-2013, using Swedish national registers. The outcome was violent crime conviction. The main statistical analyses assessed risks of violent crime during periods on compared to off SSRI treatment within individuals. Further analyses investigated risk over time in relation to treatment initiation and discontinuation. The study identified 785,337 individuals (64.2% female), experiencing 32,203 violent crimes in 5,707,293 person-years. Between-individual analyses found statistically significantly elevated Hazard Ratios (HRs) overall (HR = 1.10), and in 15-24 and 25-34 year-olds (HR = 1.19 and 1.16), but non-significant HRs in 35-44 and 45-60-year-olds (HR = 1.02 and 1.04). In within-individual analyses, where 2.6% of SSRI users were informative, hazards were elevated overall (HR = 1.26, 95% CI = 1.19, 1.34), and across age groups (HR of 1.35 [95% CI = 1.19, 1.54] in 25-34-year-olds to 1.15 [95% CI = 0.99, 1.33] in 35-44-year-olds). In the overall cohort, the within-individual HRs were significantly elevated throughout treatment (HRs of 1.24 to 1.35) and for up to 12 weeks post-discontinuation (HRs of 1.37 and 1.20). While questions on causality remain, these results indicate that there may be an increased risk of violent crime during SSRI treatment in a small group of individuals. It may persist throughout medicated periods, across age groups, and after treatment discontinuation. Further confirmation is needed from studies with different designs, and clinical focus should be on high-risk individuals, as a majority of SSRI-users (around 97% in our cohort) will not commit violent crimes.

Mental disorders and intimate partner violence perpetrated by men towards women: A Swedish population-based longitudinal study.

BACKGROUND: Intimate partner violence (IPV) against women is associated with a wide range of adverse outcomes. Although mental disorders have been linked to an increased risk of perpetrating IPV against women, the direction and magnitude of the association remain uncertain. In a longitudinal design, we examined the association between mental disorders and IPV perpetrated by men towards women in a population-based sample and used sibling comparisons to control for factors shared by siblings, such as genetic and early family environmental factors. METHODS AND FINDINGS: Using Swedish nationwide registries, we identified men from 9 diagnostic groups over 1998-2013, with sample sizes ranging from 9,529 with autism to 88,182 with depressive disorder. We matched individuals by age and sex to general population controls (ranging from 186,017 to 1,719,318 controls), and calculated the hazard ratios of IPV against women. We also estimated the hazard ratios of IPV against women in unaffected full siblings (ranging from 4,818 to 37,885 individuals) compared with the population controls. Afterwards, we compared the hazard ratios for individuals with psychiatric diagnoses with those for siblings using the ratio of hazard ratios (RHR). In sensitivity analyses, we examined the contribution of previous IPV against women and common psychiatric comorbidities, substance use disorders and personality disorders. The average follow-up time across diagnoses ranged from 3.4 to 4.8 years. In comparison to general population controls, all psychiatric diagnoses studied except autism were associated with an increased risk of IPV against women in men, with hazard ratios ranging from 1.5 (95% CI 1.3-1.7) to 7.7 (7.2-8.3) (p-values < 0.001). In sibling analyses, we found that men with depressive disorder, anxiety disorder, alcohol use disorder, drug use disorder, attention deficit hyperactivity disorder, and personality disorders had a higher risk of IPV against women than their unaffected siblings, with RHR values ranging from 1.7 (1.3-2.1) to 4.4 (3.7-5.2) (p-values < 0.001). Sensitivity analyses showed higher risk of IPV against women in men when comorbid substance use disorders and personality disorders were present, compared to risk when these comorbidities were absent. In addition, increased IPV risk was also found in those without previous IPV against women. The absolute rates of IPV against women ranged from 0.1% to 2.1% across diagnoses over 3.4 to 4.8 years. Individuals with alcohol use disorders (1.7%, 1,406/82,731) and drug use disorders (2.1%, 1,216/57,901) had the highest rates. Our analyses were restricted to IPV leading to arrest, suggesting that the applicability of our results may be limited to more severe forms of IPV perpetration. CONCLUSIONS: Our results indicate that most of the studied mental disorders are associated with an increased risk of perpetrating IPV towards women, and that substance use disorders, as principal or comorbid diagnoses, have the highest absolute and relative risks. The findings support the development of IPV risk identification and prevention services among men with substance use disorders as an approach to reduce the prevalence of IPV.

Associations between gabapentinoids and suicidal behaviour, unintentional overdoses, injuries, road traffic incidents, and violent crime: population based cohort study in Sweden.

OBJECTIVE: To examine associations between gabapentinoids and adverse outcomes related to coordination disturbances (head or body injuries, or both and road traffic incidents or offences), mental health (suicidal behaviour, unintentional overdoses), and criminality. DESIGN: Population based cohort study. SETTING: High quality prescription, patient, death, and crime registers, Sweden. PARTICIPANTS: 191 973 people from the Swedish Prescribed Drug Register who collected prescriptions for gabapentinoids (pregabalin or gabapentin) during 2006 to 2013. MAIN OUTCOME MEASURES: Primary outcomes were suicidal behaviour, unintentional overdoses, head/body injuries, road traffic incidents and offences, and arrests for violent crime. Stratified Cox proportional hazards regression was conducted comparing treatment periods with non-treatment periods within an individual. Participants served as their own control, thus accounting for time invariant factors (eg, genetic and historical factors), and reducing confounding by indication. Additional adjustments were made by age, sex, comorbidities, substance use, and use of other antiepileptics. RESULTS: During the study period, 10 026 (5.2%) participants were treated for suicidal behaviour or died from suicide, 17 144 (8.9%) experienced an unintentional overdose, 12 070 (6.3%) had a road traffic incident or offence, 70 522 (36.7%) presented with head/body injuries, and 7984 (4.1%) were arrested for a violent crime. In within-individual analyses, gabapentinoid treatment was associated with increased hazards of suicidal behaviour and deaths from suicide (age adjusted hazard ratio 1.26, 95% confidence interval 1.20 to 1.32), unintentional overdoses (1.24, 1.19 to 1.28), head/body injuries (1.22, 1.19 to 1.25), and road traffic incidents and offences (1.13, 1.06 to 1.20). Associations with arrests for violent crime were less clear (1.04, 0.98 to 1.11). When the drugs were examined separately, pregabalin was associated with increased hazards of all outcomes, whereas gabapentin was associated with decreased or no statistically significant hazards. When stratifying on age, increased hazards of all outcomes were associated with participants aged 15 to 24 years. CONCLUSIONS: This study suggests that gabapentinoids are associated with an increased risk of suicidal behaviour, unintentional overdoses, head/body injuries, and road traffic incidents and offences. Pregabalin was associated with higher hazards of these outcomes than gabapentin.

Parental nicotine replacement therapy and offspring bronchitis/bronchiolitis and asthma - a nationwide population-based cohort study.

BACKGROUND: Prior evidence shows that environmental tobacco smoke is a risk factor for respiratory tract infections, wheeze, and asthma. Nicotine replacement therapy has been shown to increase smoking cessation. However, no prior studies have explored if parental use decreases the risk of bronchitis/bronchiolitis and asthma in the offspring. OBJECTIVE: To examine whether nicotine replacement therapy varenicline, given to parents, was associated with a reduction in bronchitis/bronchiolitis and/or asthma in their children. METHODS: This study is a population-based cohort study, linking data from nationwide registers, and using a within-individual design that minimizes selection effects and controls for time-invariant confounding factors. Participants included 37,420 parents with a collected prescription of varenicline with 72,392 offspring <18 years of age. Exposure was defined as collected prescriptions of varenicline among the parents. Primary outcomes were offspring hospital visits for bronchitis/bronchiolitis (ICD10: J20 or J21) and offspring hospital visits for asthma (ICD10: J45). RESULTS: Parental varenicline treatment was associated with a lower rate of visits for bronchitis/bronchiolitis in their children (incidence rate ratio [IRR]=0.67; 95% CI=0.50-0.91), but no association was found for asthma (IRR=1.08; 95% CI=0.97-1.19). The rate reduction of bronchitis/bronchiolitis was similar when we restricted data to children aged 0-3 years (IRR=0.71; 95% CI=0.52-0.97) and to maternal varenicline treatment (IRR=0.64; 95% CI=0.43-0.96). When restricting the outcomes to unplanned visits only (ie, excluding booked appointments, followups, and referrals), no associations were found (IRR=0.72, 95% CI=0.51-1.02). CONCLUSION: In this cohort study, nicotine replacement treatment in parents was associated with reduced hospital visits for bronchitis/bronchiolitis in their children.

Medications for Alcohol and Opioid Use Disorders and Risk of Suicidal Behavior, Accidental Overdoses, and Crime.

OBJECTIVE: The authors examined associations between medications for alcohol and opioid use disorders (acamprosate, naltrexone, methadone, and buprenorphine) and suicidal behavior, accidental overdoses, and crime. METHOD: In this total population cohort study, 21,281 individuals who received treatment with at least one of the four medications between 2005 and 2013 were identified. Data on medication use and outcomes were collected from Swedish population-based registers. A within-individual design (using stratified Cox proportional hazards regression models) was used to compare rates of suicidal behavior, accidental overdoses, and crime for the same individuals during the period when they were receiving the medication compared with the period when they were not. RESULTS: No significant associations with any of the primary outcomes were found for acamprosate. For naltrexone, there was a reduction in the hazard ratio for accidental overdoses during periods when individuals received treatment compared with periods when they did not (hazard ratio=0.82, 95% CI=0.70, 0.96). Buprenorphine was associated with reduced arrest rates for all crime categories (i.e., violent, nonviolent, and substance-related) as well as reduction in accidental overdoses (hazard ratio=0.75, 95% CI=0.60, 0.93). For methadone, there were significant reductions in the rate of suicidal behaviors (hazard ratio=0.60, 95% CI=0.40-0.88) as well as reductions in all crime categories. However, there was an increased risk for accidental overdoses among individuals taking methadone (hazard ratio=1.25, 95% CI=1.13, 1.38). CONCLUSIONS: Medications currently used to treat alcohol and opioid use disorders also appear to reduce suicidality and crime during treatment.