Long-term functional outcome in adult prison inmates with ADHD receiving OROS-methylphenidate.

In a recent randomized, double-blind, placebo-controlled trial, we established a robust efficacy (Cohen's d = 2.17) of osmotic release oral system-methylphenidate (OROS-methylphenidate) delivered 72 mg daily for 5 weeks versus placebo on attention deficit hyperactivity disorder (ADHD) symptoms, global severity and global functioning in 30 adult male prison inmates with ADHD and coexisting disorders. Outcomes continued to improve during the subsequent 47-week open-label extension with OROS-methylphenidate delivered at a flexible daily dosage of up to 1.3 mg/kg body weight. In the present study, we evaluated long-term effectiveness and maintenance of improvement over the cumulated 52-week trial on cognition, motor activity, institutional behaviour and quality of life. Post hoc, we explored the associations between investigators' and self-ratings of ADHD symptoms and between ratings of symptoms and functioning, respectively. Outcomes, calculated by repeated measures ANOVA, improved from baseline until week 16, with maintenance or further improvement until week 52. Both verbal and visuospatial working memory, and abstract verbal reasoning improved significantly over time, as well as several cognition-related measures and motor activity. No substance abuse was detected and a majority of participants took part in psychosocial treatment programmes. The quality of life domains of Learning, and Goals and values improved over time; the latter domain was at open-label endpoint significantly related to improvements in attention. Investigators' and self-ratings of ADHD symptoms, as well as global symptom severity related most significantly to global functioning at week 52. Finally, investigators' and self-ratings of ADHD symptoms associated significantly at baseline with increasing convergence over time.

Risk of violent crime in individuals with epilepsy and traumatic brain injury: a 35-year Swedish population study.

BACKGROUND: Epilepsy and traumatic brain injury are common neurological conditions, with general population prevalence estimates around 0.5% and 0.3%, respectively. Although both illnesses are associated with various adverse outcomes, and expert opinion has suggested increased criminality, links with violent behaviour remain uncertain. METHODS AND FINDINGS: We combined Swedish population registers from 1973 to 2009, and examined associations of epilepsy (n = 22,947) and traumatic brain injury (n = 22,914) with subsequent violent crime (defined as convictions for homicide, assault, robbery, arson, any sexual offense, or illegal threats or intimidation). Each case was age and gender matched with ten general population controls, and analysed using conditional logistic regression with adjustment for socio-demographic factors. In addition, we compared cases with unaffected siblings. Among the traumatic brain injury cases, 2,011 individuals (8.8%) committed violent crime after diagnosis, which, compared with population controls (n = 229,118), corresponded to a substantially increased risk (adjusted odds ratio [aOR] = 3.3, 95% CI: 3.1-3.5); this risk was attenuated when cases were compared with unaffected siblings (aOR = 2.0, 1.8-2.3). Among individuals with epilepsy, 973 (4.2%) committed a violent offense after diagnosis, corresponding to a significantly increased odds of violent crime compared with 224,006 population controls (aOR = 1.5, 1.4-1.7). However, this association disappeared when individuals with epilepsy were compared with their unaffected siblings (aOR = 1.1, 0.9-1.2). We found heterogeneity in violence risk by age of disease onset, severity, comorbidity with substance abuse, and clinical subgroups. Case ascertainment was restricted to patient registers. CONCLUSIONS: In this longitudinal population-based study, we found that, after adjustment for familial confounding, epilepsy was not associated with increased risk of violent crime, questioning expert opinion that has suggested a causal relationship. In contrast, although there was some attenuation in risk estimates after adjustment for familial factors and substance abuse in individuals with traumatic brain injury, we found a significantly increased risk of violent crime. The implications of these findings will vary for clinical services, the criminal justice system, and patient charities.

The genetic and environmental etiology of antisocial behavior from childhood to emerging adulthood.

Previous research suggests that both genetic and environmental influences are important for antisocial behavior across the life span, even though the prevalence and incidence of antisocial behavior varies considerably across ages. However, little is known of how genetic and environmental effects influence the development of antisocial behavior. A total of 2,600 male and female twins from the population-based Swedish Twin Registry were included in the present study. Antisocial behavior was measured on four occasions, when twins were 8-9, 13-14, 16-17, and 19-20 years old. Longitudinal analyses of the data were conducted using structural equation modeling. The stability of antisocial behavior over time was explained by a common latent persistent antisocial behavior factor. A common genetic influence accounted for 67% of the total variance in this latent factor, the shared environment explained 26%, and the remaining 7% was due to the non-shared environment. Significant age-specific shared environmental factors were found at ages 13-14 years, suggesting that common experiences (e.g., peers) are important for antisocial behavior at this age. Results from this study show that genetic as well as shared environmental influences are important in antisocial behavior that persists from childhood to emerging adulthood.

Prison suicide in 12 countries: an ecological study of 861 suicides during 2003-2007.

BACKGROUND: Although suicide rates among prisoners are high and vary between countries, it is uncertain whether this reflects the importation of risk from the general population or is associated with incarceration rates. METHODS: We collected data on suicides and undetermined deaths in 12 countries (Australia, Belgium, Canada, Denmark, England and Wales, Finland, Ireland, Netherlands, New Zealand, Norway, Scotland, and Sweden) directly from their prison administrations for 2003-2007. These were compared with rates of suicides in the general population separately by gender using Pearson's correlations. In addition, they were compared with rates of incarceration. Linear regression was used to examine any association after adjustment for rates of incarceration. RESULTS: Data were collected on 861 suicides in prison, of which 810 were in men. In the men, crude relative rates of suicide were at least three times higher than the general population. Western European countries had similar rates of prisoner suicide which were mostly higher than those in Australia, Canada, and New Zealand. There was no association between rates of suicide in prisoners and general population rates or rates of incarceration. In the women, inmate suicide rates varied widely and were mostly raised compared with rates in the general population. In addition, these rates did not appear to be associated with general population rates of suicide. CONCLUSIONS: Rates of prison suicide do not reflect general population suicide rates, suggesting that variations in prison suicide rates reflect differences in criminal justice systems including, possibly, the provision of psychiatric care in prison.

Sexual offending in women and psychiatric disorder: a national case-control study.

Women commit 4-5% of all sexual crimes, but there is considerable uncertainty about associations with psychosis and substance abuse. We examined the prevalence of psychiatric hospitalization, psychotic disorders, and substance abuse in a nationwide sample of female sexual offenders. We obtained data from Swedish national registers for criminal convictions, hospital discharge diagnoses, and demographic and socioeconomic factors between 1988 and 2000, and merged them using unique identifiers. Convicted female sexual offenders (n = 93) were compared with all females convicted of non-sexual violent offences (n = 13,452) and a random sample of general population women (n = 20,597). Over 13 years, 36.6% of female sexual offenders had been admitted to psychiatric hospital and 7.5% been discharged with a diagnosis of a psychotic disorder. Compared to non-sexual violent offenders, there were no significant differences in the proportion diagnosed with psychosis or substance abuse. Compared to women in the general population, however, there was a significantly increased risk in sex offenders of psychiatric hospitalization (age-adjusted odds ratio [AOR] = 15.4; 95% CI: 10.0-23.7), being diagnosed with a psychotic disorder (AOR = 16.2; 95% CI: 7.2-36.4), and with substance use disorders (AOR = 22.6; 95% CI: 13.0-39.1). We conclude that the prevalence of psychotic and substance use disorders was not different between sexual offenders and other violent offenders, suggesting non-specificity of sexual offending in women. Nevertheless, substantially increased prevalences of psychiatric disorder, underline the importance of screening and assessment of female sexual and other violent offenders.

Schizophrenia and violence: systematic review and meta-analysis.

BACKGROUND: Although expert opinion has asserted that there is an increased risk of violence in individuals with schizophrenia and other psychoses, there is substantial heterogeneity between studies reporting risk of violence, and uncertainty over the causes of this heterogeneity. We undertook a systematic review of studies that report on associations between violence and schizophrenia and other psychoses. In addition, we conducted a systematic review of investigations that reported on risk of homicide in individuals with schizophrenia and other psychoses. METHODS AND FINDINGS: Bibliographic databases and reference lists were searched from 1970 to February 2009 for studies that reported on risks of interpersonal violence and/or violent criminality in individuals with schizophrenia and other psychoses compared with general population samples. These data were meta-analysed and odds ratios (ORs) were pooled using random-effects models. Ten demographic and clinical variables were extracted from each study to test for any observed heterogeneity in the risk estimates. We identified 20 individual studies reporting data from 18,423 individuals with schizophrenia and other psychoses. In men, ORs for the comparison of violence in those with schizophrenia and other psychoses with those without mental disorders varied from 1 to 7 with substantial heterogeneity (I(2) = 86%). In women, ORs ranged from 4 to 29 with substantial heterogeneity (I(2) = 85%). The effect of comorbid substance abuse was marked with the random-effects ORs of 2.1 (95% confidence interval [CI] 1.7-2.7) without comorbidity, and an OR of 8.9 (95% CI 5.4-14.7) with comorbidity (p<0.001 on metaregression). Risk estimates of violence in individuals with substance abuse (but without psychosis) were similar to those in individuals with psychosis with substance abuse comorbidity, and higher than all studies with psychosis irrespective of comorbidity. Choice of outcome measure, whether the sample was diagnosed with schizophrenia or with nonschizophrenic psychoses, study location, or study period were not significantly associated with risk estimates on subgroup or metaregression analysis. Further research is necessary to establish whether longitudinal designs were associated with lower risk estimates. The risk for homicide was increased in individuals with psychosis (with and without comorbid substance abuse) compared with general population controls (random-effects OR = 19.5, 95% CI 14.7-25.8). CONCLUSIONS: Schizophrenia and other psychoses are associated with violence and violent offending, particularly homicide. However, most of the excess risk appears to be mediated by substance abuse comorbidity. The risk in these patients with comorbidity is similar to that for substance abuse without psychosis. Public health strategies for violence reduction could consider focusing on the primary and secondary prevention of substance abuse. Please see later in the article for Editors' Summary.

Schizophrenia, substance abuse, and violent crime.

CONTEXT: Persons with schizophrenia are thought to be at increased risk of committing violent crime 4 to 6 times the level of general population individuals without this disorder. However, risk estimates vary substantially across studies, and considerable uncertainty exists as to what mediates this elevated risk. Despite this uncertainty, current guidelines recommend that violence risk assessment should be conducted for all patients with schizophrenia. OBJECTIVE: To determine the risk of violent crime among patients diagnosed as having schizophrenia and the role of substance abuse in mediating this risk. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal designs were used to link data from nationwide Swedish registers of hospital admissions and criminal convictions in 1973-2006. Risk of violent crime in patients after diagnosis of schizophrenia (n = 8003) was compared with that among general population controls (n = 80 025). Potential confounders (age, sex, income, and marital and immigrant status) and mediators (substance abuse comorbidity) were measured at baseline. To study familial confounding, we also investigated risk of violence among unaffected siblings (n = 8123) of patients with schizophrenia. Information on treatment was not available. MAIN OUTCOME MEASURE: Violent crime (any criminal conviction for homicide, assault, robbery, arson, any sexual offense, illegal threats, or intimidation). RESULTS: In patients with schizophrenia, 1054 (13.2%) had at least 1 violent offense compared with 4276 (5.3%) of general population controls (adjusted odds ratio [OR], 2.0; 95% confidence interval [CI], 1.8-2.2). The risk was mostly confined to patients with substance abuse comorbidity (of whom 27.6% committed an offense), yielding an increased risk of violent crime among such patients (adjusted OR, 4.4; 95% CI, 3.9-5.0), whereas the risk increase was small in schizophrenia patients without substance abuse comorbidity (8.5% of whom had at least 1 violent offense; adjusted OR, 1.2; 95% CI, 1.1-1.4; P<.001 for interaction). The risk increase among those with substance abuse comorbidity was significantly less pronounced when unaffected siblings were used as controls (28.3% of those with schizophrenia had a violent offense compared with 17.9% of their unaffected siblings; adjusted OR, 1.8; 95% CI, 1.4-2.4; P<.001 for interaction), suggesting significant familial (genetic or early environmental) confounding of the association between schizophrenia and violence. CONCLUSIONS: Schizophrenia was associated with an increased risk of violent crime in this longitudinal study. This association was attenuated by adjustment for substance abuse, suggesting a mediating effect. The role of risk assessment, management, and treatment in individuals with comorbidity needs further examination.

Incremental validity of the Psychopathy Checklist facet scores: predicting release outcome in six samples.

The incremental validity of the 4 facet scores (Interpersonal, Affective, Lifestyle, Antisocial) of the Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991, 2003) and the Psychopathy Checklist: Screening Version (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995) was evaluated in 6 forensic/correctional samples with average follow-ups ranging from 20 weeks to 10 years. Results indicated that whereas Facet 4 (Antisocial) achieved incremental validity relative to the first 3 facets (Interpersonal, Affective, and Lifestyle) in predicting recidivism in all 6 samples, a block of the first 3 facets achieved incremental validity relative to the 4th facet in only 1 sample. Thus, although there was consistent support for the incremental validity of Facet 4 above and beyond the first 3 facets, there was minimal support for the incremental validity of Facets 1, 2, and 3 above and beyond Facet 4. The implications of these findings for the psychopathy construct in general and the PCL-R/SV in particular are discussed.

The association between psychiatric diagnosis and violent re-offending in adult offenders in the community.

BACKGROUND: High rates of repeat offending are common across nations that are socially and culturally different. Although psychiatric disorders are believed to be risk factors for violent reoffending, the available evidence is sparse and liable to bias. METHOD: We conducted a historical cohort study in Sweden of a selected sample of 4828 offenders given community sentences who were assessed by a psychiatrist during 1988-2001, and followed up for an average of 5 years for first violent offence, death, or emigration, using information from national registers. Hazard ratios for violent offending were calculated by Cox regression models. RESULTS: Nearly a third of the sample (n = 1506 or 31.3%) offended violently during follow-up (mean duration: 4.8 years). After adjustment for socio-demographic and criminal history variables, substance use disorders (hazard ratio 1.97, 95% CI, 1.40-2.77) and personality disorders (hazard ratio 1.71, 1.20-2.44) were significantly associated with an increased risk of violent offending. No other diagnoses were related to recidivism risk. Adding information on diagnoses of substance use and personality disorders to data recorded on age, sex, and criminal history improved only minimally the prediction of violent offending. CONCLUSION: Diagnoses of substance use and personality disorders are associated with the risk of subsequent violent offending in community offenders about as strongly as are its better documented demographic and criminal history risk factors. Despite this, assessment of such disorders in addition to demographic and criminal history factors enhances only minimally the prediction of violent offending in the community.

Evidence of gender bias in legal insanity evaluations: a case vignette study of clinicians, judges and students.

Forensic psychiatric decision-making plays a key role in the legal process of homicide cases. Research show that women defendants have a higher likelihood of being declared legally insane and being diverted to hospital. This study attempted to explore if this gender difference is explained by biases in the forensic psychiatric assessments. Participants were 45 practicing forensic psychiatric clinicians, 46 chief judges and 80 psychology students. Participants received a written vignette describing a homicide case, with either a female or a male perpetrator. The results suggested strong gender effects on legal insanity judgements. Forensic psychiatric clinicians and psychology students assessed the case information as more indicative of legal insanity if the perpetrator was a woman than a man. Judges assessed offenders of their own gender, as they were more likely to be declared legally insane than a perpetrator of the opposite gender. Implications of and possible ways to minimize such gender biases in forensic psychiatric evaluations need to be thoroughly considered by the legal system.

The population impact of severe mental illness on violent crime.

OBJECTIVE: This study aimed to determine the population impact of patients with severe mental illness on violent crime. METHOD: Sweden possesses high-quality national registers for all hospital admissions and criminal convictions. All individuals discharged from the hospital with ICD diagnoses of schizophrenia and other psychoses (N=98,082) were linked to the crime register to determine the population-attributable risk of patients with severe mental illness to violent crime. The attributable risk was calculated by gender, three age bands (15-24, 25-39, and 40 years and over), and offense type. RESULTS: Over a 13-year period, there were 45 violent crimes committed per 1,000 inhabitants. Of these, 2.4 were attributable to patients with severe mental illness. This corresponds to a population-attributable risk fraction of 5.2%. This attributable risk fraction was higher in women than men across all age bands. In women ages 25-39, it was 14.0%, and in women over 40, it was 19.0%. The attributable risk fractions were lowest in those ages 15-24 (2.3% for male patients and 2.9% for female patients). CONCLUSIONS: The population impact of patients with severe mental illness on violent crime, estimated by calculating the population-attributable risk, varies by gender and age. Overall, the population-attributable risk fraction of patients was 5%, suggesting that patients with severe mental illness commit one in 20 violent crimes.

Suicide trends in discharged patients with mood disorders: associations with selective serotonin uptake inhibitors and comorbid substance misuse.

We determined the rates of suicide in two consecutive time intervals of low and high selective serotonin reuptake inhibitor (SSRI) prescribing for men and women with mood disorders, who were at relatively high risk of suicide, in a discharged hospitalized sample. High quality Swedish national registers were cross-linked to estimate rates of suicide. The results were stratified by three age-bands, and rates of comorbid substance misuse were explored. These were compared with general population suicide rates. There were 1606 suicides in discharged patients with mood disorders. Suicide rates decreased for all women during 1989-94 and 1995-2000 [odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.64-0.85] and a trend was found towards lower rates in men (OR = 0.89, 95% CI = 0.78-1.02). Approximately 90% of suicides occurred in those aged over 40 years; thus, the inpatient sample lacked the power to discriminate clear effects in the younger age groups. There was no increase or decrease in the rates of substance use disorders in patients who committed suicide. There were 20 851 suicides in the general population during 1989-2000. Suicide rates were lower at all ages for men and women in the general population in the interval of high SSRI prescribing. We conclude that there is no evidence from this study of an increase in suicide rates following the introduction of SSRIs in the general population or in a high-risk inpatient sample.

Mechanisms Involved in Thromboxane A2 -induced Vasoconstriction of Rat Intracavernous Small Penile Arteries.

Diabetes is associated with erectile dysfunction and with hypercontractility in erectile tissue and this is in part ascribed to increased formation of thromboxane. Rho kinase (ROCK) is a key regulator of calcium sensitization and contraction in vascular smooth muscle. This study investigated the role of calcium and ROCK in contraction evoked by activation of the thromboxane receptors. Rat intracavernous penile arteries were mounted for isometric tension and intracellular calcium ([Ca2+ ]i ) recording and corpus cavernosum for measurements of MYPT1 phosphorylation. In penile arteries, U46619 by activation of thromboxane receptors concentration dependently increased calcium and contraction. U46619-induced calcium influx was blocked by nifedipine, a blocker of L-type calcium channels, and by 2-aminoethoxydiphenyl borate, a blocker of transient receptor potential (TRP) channels. Inhibitors of ROCK, Y27632 and glycyl-H1152P, concentration dependently reduced U46619-induced contraction, but only Y27632 reduced [Ca2+ ]i levels in the penile arteries activated with either high extracellular potassium or U46619. MYPT-Thr850 phosphorylation in corpus cavernous strips was increased in response to U46619 through activation of TP receptors and was found to be a direct result of phosphorylation by ROCK. Y27632 induced less relaxation in mesenteric arteries, H1152P induced equipotent relaxations, and a protein kinase C inhibitor, Ro-318220, failed to relax intracavernous penile arteries, but induced full relaxation in rat mesenteric arteries. Our findings suggest that U46619 contraction depends on Ca2+ influx through L-type and TRP channels, and ROCK-dependent mechanisms in penile arteries. Inhibition of the ROCK pathway is a potential approach for the treatment of erectile dysfunction associated with hypertension and diabetes.

Methodological development: structured outcome assessment and community risk monitoring (SORM).

This paper describes an effort to develop a clinical tool for the continuous monitoring of risk for violence in forensic mental health clients who have left their institutions and who are dwelling in the community on a conditional release basis. The model is called Structured Outcome Assessment and Community Risk Monitoring (SORM). The SORM consists of 30 dynamic factors and each factor in SORM is assessed in two ways: The current absence, presence or partial och intermittent presence of the factors, which is an actuarial (systematized and 'objective') assessment. Secondly, the risk effect, i.e. whether the presence/absence of factors currently increases, decreases or is perceived as unrelated to violence risk, is a clinical (or impressionistic) assessment. Thus, the factors considered via the SORM can be coded as risk factors or protective factors (or as factors unimportant to risk of violence) depending on circumstances that apply in the individual case. Further, the SORM has a built-in module for gathering idiographical information about risk-affecting contextual factors. The use of the SORM and its potential as a risk monitoring instrument is illustrated via preliminary data and case vignettes from an ongoing multicenter project. In this research project, patients leaving any of the 9 participating forensic hospitals in Sweden is assessed at release on a variety of static background factors, and the SORM is then administered every 30 days for 2 years.

Psychiatric morbidity among homicide offenders: a Swedish population study.

OBJECTIVE: The authors examined psychiatric diagnoses of all individuals convicted of homicide and attempted homicide in Sweden from 1988 to 2001 (N=2,005). METHOD: High-quality national crime and hospital registers were linked to investigate standardized psychiatric diagnoses of homicide offenders. RESULTS: The presence or absence of psychiatric diagnoses was ascertained for 1,625 (81%) of the homicide offenders; 1,464 (90%) of these offenders had a psychiatric diagnosis. Twenty percent (N=409) of all 2,005 offenders had a psychotic illness, and 54% (N=589) of a subgroup of 1,091 offenders with information on secondary diagnoses had a personality disorder as a principal or secondary diagnosis. Only 10% of the offenders for whom psychiatric diagnostic information was available had no diagnosis. CONCLUSIONS: Using a comprehensive method for identifying psychiatric illness in homicide offenders, the authors found higher rates of psychiatric morbidity than previous studies. Their findings underline the importance of psychiatric assessment in homicide offenders and suggest that treatment might have a preventive role.

Cross-system concordance of personality disorder diagnoses of DSM-IV and diagnostic criteria for research of ICD-10.

The aim in this study was to examine the cross-system concordance between the personality disorders (PDs) of DSM-IV and Diagnostic Criteria for Research of ICD-10 Classification of Mental and Behavioral Disorders, 10th rev. (ICD-10) PD diagnoses were made by a structured interview in a clinical psychiatric sample of 138 individuals. Both categorical and dimensional scores for each PD were established. The frequency of patients with a PD diagnosis on either classification who were also positive on the other varied from 26% for the schizoid PDs to 88% for the histrionic PDs. The chance-corrected agreement (Cohen's kappa) ranged from .37 to .94. The dimensional correlation (Pearson's r) between pairs of PD criteria sets was in the range of .79 to .98. In conclusion, when analyzed categorically, some of the PDs of DSM-IV and ICD-10-DCR were only moderately concordant. The reasons appear to be different criteria formulations and arbitrary thresholds for diagnoses. In contrast to categorical diagnoses, dimensional agreement was high, implicating similar trait-concept definitions. The least concordant pair of PD was antisocial (DSM-IV)-dissocial (ICD-10).

Self-reported personality traits and disorders (DSM-IV) and risk of criminal recidivism: a prospective study.

Assessment and management of criminal offenders require valid methods to recognize personality psychopathology and other risk and protective factors for recidivism. We prospectively explored the association between dimensional and categorical measures of personality disorder (PD) measured with the DSM-IV and ICD-10 Personality Questionnaire (DIP-Q, Ottosson et al., 1995) and registered reconvictions in adult offenders. One hundred and sixty-eight offenders consecutively referred for pre-sentencing forensic psychiatric evaluation in Sweden during 1995-1996 completed DIP-Q self-reports. The subjects received different types of sanctions and were followed for an average of 36 months after release from prison, discharge from a forensic psychiatric hospital, or onset of nondetaining sentences. Age-adjusted odds ratios revealed a 4.8 times higher risk for any recidivism and a 3.7 times higher risk for violent recidivism among subjects whose self-reports suggested a categorical diagnosis of antisocial PD as compared to offenders without antisocial PD. The remaining nine categorical DSM-IV PD diagnoses were not significantly related to recidivism. In dimensional analyses, each additional antisocial and schizoid PD symptom endorsed by participants at baseline increased the risk for violent reoffending. Our results suggest a relationship between self-reported behavioral instability and interpersonal dysfunction captured primarily by DSM-IV antisocial and schizoid PD constructs, and criminal re-offending also in a multi-problem sample of identified offenders.

Cardiovascular effects of current and future anti-obesity drugs.

The prevalence of obesity increases and is associated with increases in co-morbidities e.g. type 2 diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, heart disease, stroke, asthma, several forms of cancer, depression, and may result in reduction of expected remaining lifespan. We have reviewed the adverse effects on the cardiovascular system of anti-obesity drugs now retracted from the market as well as the cardiovascular profile of current drugs and potential pathways which are considered for treatment of obesity. Fenfluramine, and sibutramine were withdrawn due to increased cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine alone or in combination with topiramate and lorcaserin, although cardiovascular side effects need to be clarified regarding phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential of nebivolol remains unexplored. Pathways with anti-obesity potential include sirtuin activation, blockade of transient receptor potential (TRPV1) channels, acetyl-CoA carboxylase 1 and 2 inhibitors, uncoupling protein activators, bile acids, crotonins, CB1 antagonists, but the cardiovascular profile remains to be investigated. For type 2 diabetes, new drug classes with possible advantageous cardiovascular profiles, e.g. GLP-1 analogues and sodium-glucose co-transport type 2 inhibitors, are associated with weight loss and are currently being evaluated as anti-obesity drugs.

Authorship bias in violence risk assessment? A systematic review and meta-analysis.

Various financial and non-financial conflicts of interests have been shown to influence the reporting of research findings, particularly in clinical medicine. In this study, we examine whether this extends to prognostic instruments designed to assess violence risk. Such instruments have increasingly become a routine part of clinical practice in mental health and criminal justice settings. The present meta-analysis investigated whether an authorship effect exists in the violence risk assessment literature by comparing predictive accuracy outcomes in studies where the individuals who designed these instruments were study authors with independent investigations. A systematic search from 1966 to 2011 was conducted using PsycINFO, EMBASE, MEDLINE, and US National Criminal Justice Reference Service Abstracts to identify predictive validity studies for the nine most commonly used risk assessment tools. Tabular data from 83 studies comprising 104 samples was collected, information on two-thirds of which was received directly from study authors for the review. Random effects subgroup analysis and metaregression were used to explore evidence of an authorship effect. We found a substantial and statistically significant authorship effect. Overall, studies authored by tool designers reported predictive validity findings around two times higher those of investigations reported by independent authors (DOR=6.22 [95% CI=4.68-8.26] in designers' studies vs. DOR=3.08 [95% CI=2.45-3.88] in independent studies). As there was evidence of an authorship effect, we also examined disclosure rates. None of the 25 studies where tool designers or translators were also study authors published a conflict of interest statement to that effect, despite a number of journals requiring that potential conflicts be disclosed. The field of risk assessment would benefit from routine disclosure and registration of research studies. The extent to which similar conflict of interests exists in those developing risk assessment guidelines and providing expert testimony needs clarification.