Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (TTP) results from severe hereditary deficiency of ADAMTS13. The efficacy and safety of recombinant ADAMTS13 and standard therapy (plasma-derived products) administered as routine prophylaxis or on-demand treatment in patients with congenital TTP is not known. METHODS: In this phase 3, open-label, crossover trial, we randomly assigned patients in a 1:1 ratio to two 6-month periods of prophylaxis with recombinant ADAMTS13 (40 IU per kilogram of body weight, administered intravenously) or standard therapy, followed by the alternate treatment; thereafter, all the patients received recombinant ADAMTS13 for an additional 6 months. The trigger for this interim analysis was trial completion by at least 30 patients. The primary outcome was acute TTP events. Manifestations of TTP, safety, and pharmacokinetics were assessed. Patients who had an acute TTP event could receive on-demand treatment. RESULTS: A total of 48 patients underwent randomization; 32 completed the trial. No acute TTP event occurred during prophylaxis with recombinant ADAMTS13, whereas 1 patient had an acute TTP event during prophylaxis with standard therapy (mean annualized event rate, 0.05). Thrombocytopenia was the most frequent TTP manifestation (annualized event rate, 0.74 with recombinant ADAMTS13 and 1.73 with standard therapy). Adverse events occurred in 71% of the patients with recombinant ADAMTS13 and in 84% with standard therapy. Adverse events that were considered by investigators to be related to the trial drug occurred in 9% of the patients with recombinant ADAMTS13 and in 48% with standard therapy. Trial-drug interruption or discontinuation due to adverse events occurred in no patients with recombinant ADAMTS13 and in 8 patients with standard therapy. No neutralizing antibodies developed during recombinant ADAMTS13 treatment. The mean maximum ADAMTS13 activity after recombinant ADAMTS13 treatment was 101%, as compared with 19% after standard therapy. CONCLUSIONS: During prophylaxis with recombinant ADAMTS13 in patients with congenital TTP, ADAMTS13 activity reached approximately 100% of normal levels, adverse events were generally mild or moderate in severity, and TTP events and manifestations were rare. (Funded by Takeda Development Center Americas and Baxalta Innovations; ClinicalTrials.gov number, NCT03393975.).

Effectiveness of Violence Prevention Interventions: Umbrella Review of Research in the General Population.

To address the societal harms of violence, many violence prevention interventions have been developed, tested, and implemented in the general population. These have been reported in systematic reviews and meta-analyses, which have typically focused on one type of intervention or outcome. We aimed to provide a comprehensive overview of the current evidence regarding the effectiveness of different psychosocial interventions in reducing all forms of violence toward others. We have conducted an umbrella review of previous meta-analyses using standard approaches and converted findings on effectiveness into odds ratios. We tested for the underlying quality of the meta-analytic evidence by examining heterogeneity, excess statistical significance, prediction intervals, and small study effects. We identified 16 meta-analyses, including nine investigating psychosocial interventions, and five legislative and policy changes. Most meta-analyses reported positive effects of tested interventions. The strongest effects were found for sports-based initiatives, and the weakest for general population programs aimed at early childhood, youth development, and reducing sexual assault perpetration by men. Legislative changes had varying effectiveness. We conclude that simple, scalable, and cost-efficient programs, such as sport-based initiatives, have the clearest empirical support as population-based approaches to violence prevention.

Modifiable risk factors for inpatient violence in psychiatric hospital: prospective study and prediction model.

BACKGROUND: Violence perpetrated by psychiatric inpatients is associated with modifiable factors. Current structured approaches to assess inpatient violence risk lack predictive validity and linkage to interventions. METHODS: Adult psychiatric inpatients on forensic and general wards in three psychiatric hospitals were recruited and followed up prospectively for 6 months. Information on modifiable (dynamic) risk factors were collected every 1-4 weeks, and baseline background factors. Data were transferred to a web-based monitoring system (FOxWeb) to calculate a total dynamic risk score. Outcomes were extracted from an incident-reporting system recording aggression and interpersonal violence. The association between total dynamic score and violent incidents was assessed by multilevel logistic regression and compared with dynamic score excluded. RESULTS: We recruited 89 patients and conducted 624 separate assessments (median 5/patient). Mean age was 39 (s.d. 12.5) years with 20% (n = 18) female. Common diagnoses were schizophrenia-spectrum disorders (70%, n = 62) and personality disorders (20%, n = 18). There were 93 violent incidents. Factors contributing to violence risk were a total dynamic score of ⩾1 (OR 3.39, 95% CI 1.25-9.20), 10-year increase in age (OR 0.67, 0.47-0.96), and female sex (OR 2.78, 1.04-7.40). Non-significant associations with schizophrenia-spectrum disorder were found (OR 0.50, 0.20-1.21). In a fixed-effect model using all covariates, AUC was 0.77 (0.72-0.82) and 0.75 (0.70-0.80) when the dynamic score was excluded. CONCLUSIONS: In predicting violence risk in individuals with psychiatric disorders, modifiable factors added little incremental value beyond static ones in a psychiatric inpatient setting. Future work should make a clear distinction between risk factors that assist in prediction and those linked to needs.

Psychiatric comorbidity and risk of premature mortality and suicide among those with chronic respiratory diseases, cardiovascular diseases, and diabetes in Sweden: A nationwide matched cohort study of over 1 million patients and their unaffected siblings.

BACKGROUND: Persons with noncommunicable diseases have elevated rates of premature mortality. The contribution of psychiatric comorbidity to this is uncertain. We aimed to determine the risks of premature mortality and suicide in people with common noncommunicable diseases, with and without psychiatric disorder comorbidity. METHODS AND FINDINGS: We used nationwide registries to study all individuals born in Sweden between 1932 and 1995 with inpatient and outpatient diagnoses of chronic respiratory diseases (n = 249,825), cardiovascular diseases (n = 568,818), and diabetes (n = 255,579) for risks of premature mortality (≤age 65 years) and suicide until 31 December 2013. Patients diagnosed with either chronic respiratory diseases, cardiovascular diseases, or diabetes were compared with age and sex-matched population controls (n = 10,345,758) and unaffected biological full siblings (n = 1,119,543). Comorbidity with any psychiatric disorder, and by major psychiatric categories, was examined using diagnoses from patient registers. Associations were quantified using stratified Cox regression models that accounted for time at risk, measured sociodemographic factors, and unmeasured familial confounders via sibling comparisons. Within 5 years of diagnosis, at least 7% (range 7.4% to 10.8%; P < 0.001) of patients with respiratory diseases, cardiovascular diseases, or diabetes (median age at diagnosis: 48 to 54 years) had died from any cause, and 0.3% (0.3% to 0.3%; P < 0.001) had died from suicide, 25% to 32% of people with these medical conditions had co-occurring lifetime diagnoses of any psychiatric disorder, most of which antedated the medical diagnosis. Comorbid psychiatric disorders were associated with higher all-cause mortality (15.4% to 21.1%) when compared to those without such conditions (5.5% to 9.1%). Suicide mortality was also elevated (1.2% to 1.6% in comorbid patients versus 0.1% to 0.1% without comorbidity). When we compared relative risks with siblings without noncommunicable diseases and psychiatric disorders, the comorbidity with any psychiatric disorder was associated with substantially increased mortality rates (adjusted HR range: aHRCR = 7.2 [95% CI: 6.8 to 7.7; P < 0.001] to aHRCV = 8.9 [95% CI: 8.5 to 9.4; P < 0.001]). Notably, comorbid substance use disorders were associated with a higher mortality rate (aHR range: aHRCR = 8.3 [95% CI: 7.6 to 9.1; P < 0.001] to aHRCV = 9.9 [95% CI: 9.3 to 10.6; P < 0.001]) than depression (aHR range: aHRCR = 5.3 [95% CI: 4.7 to 5.9; P < 0.001] to aHRCV = 7.4 [95% CI: 7.0 to 7.9; P < 0.001]), but risks of suicide were similar for these 2 psychiatric comorbidities. One limitation is that we relied on secondary care data to assess psychiatric comorbidities, which may have led to missing some patients with less severe comorbidities. Residual genetic confounding is another limitation, given that biological full siblings share an average of half of their cosegregating genes. However, the reported associations remained large even after adjustment for shared and unmeasured familial confounders. CONCLUSIONS: In this longitudinal study of over 1 million patients with chronic health diseases, we observed increased risks of all-cause and suicide mortality in individuals with psychiatric comorbidities. Improving assessment, treatment, and follow-up of people with comorbid psychiatric disorders may reduce the risk of mortality in people with chronic noncommunicable diseases.

Feasibility of using Clinical Practice Research Datalink data to identify patients with chronic obstructive pulmonary disease to enrol into real-world trials.

PURPOSE: To assess the feasibility of using Clinical Practice Research Datalink (CPRD) data for identifying populations of patients with chronic obstructive pulmonary disease (COPD) eligible for a hypothetical pragmatic trial. METHODS: A retrospective multidatabase cohort study using CPRD primary care and linked secondary care data to describe the characteristics of populations of patients with COPD. Patients' demographic and lifestyle factors, comorbidity profile, spirometry measurements and treatment changes were evaluated, as was the distribution of follow-up time and types of losses during follow-up. Characteristics were evaluated using descriptive statistics. RESULTS: A total of 322 991 patients from 1148 primary care practices in the United Kingdom across two CPRD primary care databases, CPRD GOLD and CPRD Aurum, were potentially eligible to participate in a hypothetical trial using CPRD, starting on 31 December 2017. Patients with COPD in CPRD GOLD and CPRD Aurum were comparable in terms of age (median age 70 vs. 68 years), gender (50% vs. 52% male), disease severity (e.g., 25% vs. 24% Medical Research Council [MRC] dyspnoea score grades 3-5) and history of respiratory conditions (e.g., 43% vs. 38% asthma). High proportions of patients with COPD in CPRD GOLD and CPRD Aurum were available on 31 December 2012 for follow-up at 1, 2, and 5 years (92%, 85% and 67%, respectively). CONCLUSIONS: Patients and data from CPRD GOLD and CPRD Aurum were comparable across key aspects relevant to COPD trials. A pragmatic trial using CPRD to recruit patients with COPD is scientifically feasible.

Recidivism rates in individuals receiving community sentences: A systematic review.

OBJECTIVE: We aimed to systematically review recidivism rates in individuals given community sentences internationally. We sought to explore sources of variation between these rates and how reporting practices may limit their comparability across jurisdictions. Finally, we aimed to adapt previously published guidelines on recidivism reporting to include community sentenced populations. METHODS: We searched MEDLINE, PsycINFO, SAGE and Google Scholar for reports and studies of recidivism rates using non-specific and targeted searches for the 20 countries with the largest prison populations worldwide. We identified 28 studies with data from 19 countries. Of the 20 countries with the largest prison populations, only 2 reported recidivism rates for individuals given community sentences. RESULTS: The most commonly reported recidivism information between countries was for 2-year reconviction, which ranged widely from 14% to 43% in men, and 9% to 35% in women. Explanations for recidivism rate variations between countries include when the follow-up period started and whether technical violations were taken into account. CONCLUSION: Recidivism rates in individuals receiving community sentences are typically lower in comparison to those reported in released prisoners, although these two populations differ in terms of their baseline characteristics. Direct comparisons of the recidivism rates in community sentenced cohorts across jurisdictions are currently not possible, but simple changes to existing reporting practices can facilitate these. We propose recommendations to improve reporting practices.

The prediction of suicide in severe mental illness: development and validation of a clinical prediction rule (OxMIS).

Assessment of suicide risk in individuals with severe mental illness is currently inconsistent, and based on clinical decision-making with or without tools developed for other purposes. We aimed to develop and validate a predictive model for suicide using data from linked population-based registers in individuals with severe mental illness. A national cohort of 75,158 Swedish individuals aged 15-65 with a diagnosis of severe mental illness (schizophrenia-spectrum disorders, and bipolar disorder) with 574,018 clinical patient episodes between 2001 and 2008, split into development (58,771 patients, 494 suicides) and external validation (16,387 patients, 139 suicides) samples. A multivariable derivation model was developed to determine the strength of pre-specified routinely collected socio-demographic and clinical risk factors, and then tested in external validation. We measured discrimination and calibration for prediction of suicide at 1 year using specified risk cut-offs. A 17-item clinical risk prediction model for suicide was developed and showed moderately good measures of discrimination (c-index 0.71) and calibration. For risk of suicide at 1 year, using a pre-specified 1% cut-off, sensitivity was 55% (95% confidence interval [CI] 47-63%) and specificity was 75% (95% CI 74-75%). Positive and negative predictive values were 2% and 99%, respectively. The model was used to generate a simple freely available web-based probability-based risk calculator (Oxford Mental Illness and Suicide tool or OxMIS) without categorical cut-offs. A scalable prediction score for suicide in individuals with severe mental illness is feasible. If validated in other samples and linked to effective interventions, using a probability score may assist clinical decision-making.

Prediction of violent reoffending in prisoners and individuals on probation: a Dutch validation study (OxRec).

Scalable and transparent methods for risk assessment are increasingly required in criminal justice to inform decisions about sentencing, release, parole, and probation. However, few such approaches exist and their validation in external settings is typically lacking. A total national sample of all offenders (9072 released from prisoners and 6329 individuals on probation) from 2011-2012 in the Netherlands were followed up for violent and any reoffending over 2 years. The sample was mostly male (n = 574 [6%] were female prisoners and n = 784 [12%] were female probationers), and median ages were 30 in the prison sample and 34 in those on probation. Predictors for a scalable risk assessment tool (OxRec) were extracted from a routinely collected dataset used by criminal justice agencies, and outcomes from official criminal registers. OxRec's predictive performance in terms of discrimination and calibration was tested. Reoffending rates in the Dutch prisoner cohort were 16% for 2-year violent reoffending and 44% for 2-year any reoffending, with lower rates in the probation sample. Discrimination as measured by the c-index was moderate, at 0.68 (95% CI: 0.66-0.70) for 2-year violent reoffending in prisoners and between 0.65 and 0.68 for other outcomes and the probation sample. The model required recalibration, after which calibration performance was adequate (e.g. calibration in the large was 1.0 for all scenarios). A recalibrated model for OxRec can be used in the Netherlands for individuals released from prison and individuals on probation to stratify their risk of future violent and any reoffending. The approach that we outline can be considered for external validations of criminal justice and clinical risk models.

High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro-E.W.I.N.G.99 and Ewing-2008.

Purpose For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. Methods Randomization between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if they were younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or had a tumor volume at diagnosis ≥ 200 mL if unresected, or initially resected, or resected after radiotherapy. A 15% improvement in 3-year event-free survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between 2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were randomly assigned to VAI (n = 118) or BuMel (n = 122). Seventy-eight percent entered the trial because of poor histologic response after chemotherapy alone. Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of event was significantly decreased by BuMel compared with VAI: HR, 0.64 (95% CI, 0.43 to 0.95; P = .026); 3- and 8-year EFS were, respectively, 69.0% (95% CI, 60.2% to 76.6%) versus 56.7% (95% CI, 47.6% to 65.4%) and 60.7% (95% CI, 51.1% to 69.6%) versus 47.1% (95% CI, 37.7% to 56.8%). Overall survival (OS) also favored BuMel: HR, 0.63 (95% CI, 0.41 to 0.95; P = .028); 3- and 8-year OS were, respectively, 78.0% (95% CI, 69.6% to 84.5%) versus 72.2% (95% CI, 63.3% to 79.6%) and 64.5% (95% CI, 54.4% to 73.5%) versus 55.6% (95% CI, 45.8% to 65.1%). Results were consistent in the sensitivity analysis. Two patients died as a result of BuMel-related toxicity, one after standard chemotherapy. Significantly more BuMel patients experienced severe acute toxicities from this course of chemotherapy compared with multiple VAI courses. Conclusion BuMel improved EFS and OS when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.

Genetic and Functional Characterization of ADAMTS13 Variants in a Patient Cohort with Upshaw-Schulman Syndrome Investigated in Germany.

Upshaw-Schulman syndrome (USS) is caused by severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency due to homozygous or compound heterozygous mutations in the ADAMTS13 gene. Previous studies suggest three possible disease mechanisms: (1) reduced secretion of ADAMTS13 variants, (2) impaired proteolytic activity, (3) defective biosynthesis due to nonsense-mediated decay. Expression studies have failed to establish a clear genotype/phenotype correlation that could explain the significant variability in the age of onset and patients' clinical courses. In this study, we investigated ADAMTS13 sequence variations in 30 USS patients and identified 31 disease-causing mutations; among them 10 novel variants. While none of the recombinant proteins exhibited significant retention in the endoplasmic reticulum, secretion and activity analysis revealed defective release for all but one missense mutant. The latter exhibited normal secretion but impaired activity due to inactivation of the catalytic domain. Truncated mutants showed secretion and residual activity even though the patients suffered from a severe phenotype. The expression systems which we used may not be appropriate here, as they do not assess nonsense-mediated decay causing degradation of mRNA. In some patients, phenotypic severity could be explained by the combined effects of two mutations. Genetic screening in combination with in vitro characterization of ADAMTS13 variants from both alleles is a valuable tool to predict the phenotypic severity of USS. When necessary, supplementary methods, such as kinetics under flow conditions and mRNA processing assays, can be included. Such data are helpful to identify patients who are at high risk for severe attacks and therefore might benefit from prophylactic treatment.

Selecting a risk assessment tool to use in practice:a 10-point guide.

With the increase in the number of risk assessment tools and clinical algorithms in many areas of science and medicine, this Perspective article provides an overview of research findings that can assist in informing the choice of an instrument for practical use. We take the example of violence risk assessment tools in criminal justice and forensic psychiatry, where there are more than 200 such instruments and their use is typically mandated. We outline 10 key questions that researchers, clinicians and other professionals should ask when deciding what tool to use, which are also relevant for public policy and commissioners of services. These questions are based on two elements: research underpinning the external validation, and derivation or development of a particular instrument. We also recommend some guidelines for reporting drawn from consensus guidelines for research in prognostic models.

Identification of low risk of violent crime in severe mental illness with a clinical prediction tool (Oxford Mental Illness and Violence tool [OxMIV]): a derivation and validation study.

BACKGROUND: Current approaches to stratify patients with psychiatric disorders into groups on the basis of violence risk are limited by inconsistency, variable accuracy, and unscalability. To address the need for a scalable and valid tool to assess violence risk in patients with schizophrenia spectrum or bipolar disorder, we describe the derivation of a score based on routinely collected factors and present findings from external validation. METHODS: On the basis of a national cohort of 75 158 Swedish individuals aged 15-65 years with a diagnosis of severe mental illness (schizophrenia spectrum or bipolar disorder) with 574 018 patient episodes between Jan 1, 2001, and Dec 31, 2008, we developed predictive models for violent offending (primary outcome) within 1 year of hospital discharge for inpatients or clinical contact with psychiatric services for outpatients (patient episode) through linkage of population-based registers. We developed a derivation model to determine the relative influence of prespecified criminal history and sociodemographic and clinical risk factors, which are mostly routinely collected, and then tested it in an external validation. We measured discrimination and calibration for prediction of violent offending at 1 year using specified risk cutoffs. FINDINGS: Of the cohort of 75 158 patients with schizophrenia spectrum or bipolar disorder, we assigned 58 771 (78%) to the derivation sample and 16 387 (22%) to the validation sample. In the derivation sample, 830 (1%) individuals committed a violent offence within 12 months of their patient episode. We developed a 16-item model. The strongest predictors of violent offending within 12 months were conviction for previous violent crime (adjusted odds ratio 5·03 [95% CI 4·23-5·98]; p<0·0001), male sex (2·32 [1·91-2·81]; p<0·0001), and age (0·63 per 10 years of age [0·58-0·67]; p<0·0001). In external validation, the model showed good measures of discrimination (c-index 0·89 [0·85-0·93]) and calibration. For risk of violent offending at 1 year, with a 5% cutoff, sensitivity was 62% (95% CI 55-68) and specificity was 94% (93-94). The positive predictive value was 11% and the negative predictive value was more than 99%. We used the model to generate a simple web-based risk calculator (Oxford Mental Illness and Violence tool [OxMIV]). INTERPRETATION: We have developed a prediction score in a national cohort of patients with schizophrenia spectrum or bipolar disorder, which can be used as an adjunct to decision making in clinical practice by identifying those who are at low risk of violent offending. The low positive predictive value suggests that further clinical assessment in individuals at high risk of violent offending is required to establish who might benefit from additional risk management. Further validation in other countries is needed. FUNDING: Wellcome Trust and Swedish Research Council.

What is the impact of a research publication?

An increasing number of metrics are used to measure the impact of research papers. Despite being the most commonly used, the 2-year impact factor is limited by a lack of generalisability and comparability, in part due to substantial variation within and between fields. Similar limitations apply to metrics such as citations per paper. New approaches compare a paper's citation count to others in the research area, while others measure social and traditional media impact. However, none of these measures take into account an individual author's contribution to the paper or the number of authors, which we argue are key limitations. The UK's 2014 Research Exercise Framework included a detailed bibliometric analysis comparing 15 selected metrics to a 'gold standard' evaluation of almost 150 000 papers by expert panels. We outline the main correlations between the most highly regarded papers by the expert panel in the Psychiatry, Clinical Psychology and Neurology unit and these metrics, most of which were weak to moderate. The strongest correlation was with the SCImago Journal Rank, a variant of the journal impact factor, while the amount of Twitter activity showed no correlation. We suggest that an aggregate measure combining journal metrics, field-standardised citation data and alternative metrics, including weighting or colour-coding of individual papers to account for author contribution, could provide more clarity.

Violence prevention in psychiatry: an umbrella review of interventions in general and forensic psychiatry.

Relative risks of violence in psychiatric patients are high compared to the general population and existing evidence in non-psychiatric populations may not translate to reductions in violence in psychiatric populations. We searched 10 databases including Medline, EMBASE, CINAHL and Scopus, from inception until August 2015 for systematic reviews and meta-analyses of violence prevention interventions in psychiatry. Reviews were included if they used a hard outcome measure (i.e. police or hospital recorded violence, or reincarceration) and contained randomized or non-randomized controlled studies. Five reviews met our inclusion criteria (n = 8876 patients in total), of which four received a GRADE rating of 'low' or 'very low'. Three randomized studies (n = 636) reported that therapeutic community interventions may reduce reincarceration in drug-using offenders with co-occurring mental illness ('moderate' GRADE rating). The lack of intervention research in violence prevention in general and forensic psychiatry suggests that interventions from non-psychiatric populations may need to be relied upon.

Correction: Mortality, Rehospitalisation and Violent Crime in Forensic Psychiatric Patients Discharged from Hospital: Rates and Risk Factors.

[This corrects the article DOI: 10.1371/journal.pone.0155906.].

Mortality, Rehospitalisation and Violent Crime in Forensic Psychiatric Patients Discharged from Hospital: Rates and Risk Factors.

OBJECTIVES: To determine rates and risk factors for adverse outcomes in patients discharged from forensic psychiatric services. METHOD: We conducted a historical cohort study of all 6,520 psychiatric patients discharged from forensic psychiatric hospitals between 1973 and 2009 in Sweden. We calculated hazard ratios for mortality, rehospitalisation, and violent crime using Cox regression to investigate the effect of different psychiatric diagnoses and two comorbidities (personality or substance use disorder) on outcomes. RESULTS: Over mean follow-up of 15.6 years, 30% of patients died (n = 1,949) after discharge with an average age at death of 52 years. Over two-thirds were rehospitalised (n = 4,472, 69%), and 40% violently offended after discharge (n = 2,613) with a mean time to violent crime of 4.2 years. The association between psychiatric diagnosis and outcome varied-substance use disorder as a primary diagnosis was associated with highest risk of mortality and rehospitalisation, and personality disorder was linked with the highest risk of violent offending. Furthermore comorbid substance use disorder typically increased risk of adverse outcomes. CONCLUSION: Violent offending, premature mortality and rehospitalisation are prevalent in patients discharged from forensic psychiatric hospitals. Individualised treatment plans for such patients should take into account primary and comorbid psychiatric diagnoses.