Use of illicit substances and violent behaviour in psychotic disorders: two nationwide case-control studies and meta-analyses

Background. Substance use disorder explains much of the excess risk of violent behaviour in psychotic disorders. However, it is unclear to what extent the pharmacological properties and subthreshold use of illicit substances are associated with violence. Methods. Individuals with psychotic disorders were recruited for two nationwide projects: GROUP (N = 871) in the Netherlands and NEDEN (N = 921) in the United Kingdom. Substance use and violent behaviour were assessed with standardized instruments and multiple sources of information. First, we used logistic regression models to estimate the associations of daily and nondaily use with violence for cannabis, stimulants, depressants and hallucinogens in the GROUP and NEDEN samples separately. Adjustments were made for age, sex and educational level. We then combined the results in random-effects meta-analyses. Results. Daily use, compared with nondaily or no use, and nondaily use, compared with no use, increased the pooled odds of violence in people with psychotic disorders for all substance categories. The increases were significant for daily use of cannabis [pooled odds ratio (pOR) 1.6, 95% confidence interval (CI) 1.2–2.0), stimulants (pOR 2.8, 95% CI 1.7–4.5) and depressants (pOR 2.2, 95% CI 1.1–4.5), and nondaily use of stimulants (pOR 1.6, 95% CI 1.2–2.0) and hallucinogens (pOR 1.5, 95% CI 1.1–2.1). Daily use of hallucinogens, which could only be analysed in the NEDEN sample, significantly increased the risk of violence (adjusted odds ratio 3.3, 95% CI 1.2–9.3). Conclusions. Strategies to prevent violent behaviour in psychotic disorders should target any substance use

Characterization of vitamin D supplementation and clinical outcomes in a large cohort of early Parkinson's disease.

BackgroundVitamin D (VitD) deficiency is common in Parkinson's disease (PD) and has been raised as a possible PD risk factor. In the past decade, VitD supplementation for potential prevention of age related conditions has become more common. In this study, we sought to characterize VitD supplementation in early PD and determine as an exploratory analysis whether baseline characteristics or disease progression differed according to reported VitD use.MethodsWe analyzed data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term study (LS-1), a longitudinal study of 1741 participants. Subjects were divided into following supplement groups according to subject exposure (6 months prior to baseline and during the study): no VitD supplement, multivitamin (MVI), VitD ≥400 IU/day, and VitD + multivitamin (VitD+MVI). Clinical status was followed using the Unified Parkinson's Disease Rating Scale, Symbol Digit Modalities Test, total daily levodopa equivalent dose, and Parkinson's Disease Questionnaire.ResultsAbout 5% of subjects took VitD alone, 7% took VitD+MVI, 34% took MVI alone, while 54% took no supplement. Clinical outcomes at 3 years were similar across all groups.ConclusionThis study shows VitD supplementation ≥400 IU/day was not common in early PD and that its use was similar to that seen in the US population. At 3 years, there was no difference in disease progression according to vitamin D supplement use

Impact of Modifiable Bleeding Risk Factors on Major Bleeding in Patients With Atrial Fibrillation Anticoagulated With Rivaroxaban.

Background Reducing major bleeding events is a challenge when managing anticoagulation in patients with atrial fibrillation. This study evaluated the impact of modifiable and nonmodifiable bleeding risk factors in patients with atrial fibrillation receiving rivaroxaban and estimated the impact of risk factor modification on major bleeding events. Methods and Results Modifiable and nonmodifiable risk factors associated with major bleeding events were identified from the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) prospective registry data set (6784 rivaroxaban-treated patients). Parameters showing univariate association with bleeding were used to construct a multivariable model identifying independent risk factors. Modeling was used to estimate attributed weights to risk factors. Heavy alcohol use (hazard ratio [HR]=2.37; 95% CI 1.24-4.53); uncontrolled hypertension (HR after parameter-wise shrinkage=1.79; 95% CI 1.05-3.05); and concomitant treatment with antiplatelets, nonsteroidal anti-inflammatory drugs, or paracetamol (HR=1.80; 95% CI 1.24-2.61) were identified as modifiable, independent bleeding risk factors. Increasing age (HR=1.25 [per 5-year increment]; 95% CI 1.12-1.38); heart failure (HR=1.97; 95% CI 1.36-2.86); and vascular disease (HR=1.91; 95% CI 1.32-2.77) were identified as nonmodifiable bleeding risk factors. Overall, 128 (1.9%) patients experienced major bleeding events; of these, 11% had no identified bleeding risk factors, 50% had nonmodifiable bleeding risk factors only, and 39% had modifiable bleeding risk factors (with or without nonmodifiable risk factors). The presence of 1 modifiable bleeding risk factor doubled the risk of major bleeding. Conclusions Elimination of modifiable bleeding risk factors is a potentially effective strategy to reduce bleeding risk in atrial fibrillation patients receiving rivaroxaban. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01606995

Potential role for clinical calibration to increase engagement with and application of home telemonitoring: a report from the HeartCycle programme

Aims: There is a need for alternative strategies that might avoid recurrent admissions in patients with heart failure. Home Telemonitoring (HTM) to monitor patient’s symptoms from a distance may be useful. This study attempts to assess changes in HTM vital signs in response to daily life activities (variations in medication, salt intake, exercise and stress) and to stablish which variations affect weight, blood pressure (BP) and heart rate (HR). Methods and results: We assessed 76 patients with heart failure (mean age 76 ± 10.8 years, 75% male, mainly in NYHA class II/III and from ischaemic etiology cause). Patients were given a calendar of interventions scheduling activities approximately twice-a-week before measuring their vital signs. Eating salty food or a large meal were the activities that had a significant impact on weight gain (+0.3 kg; p<0.001 and p=0.006, respectively). Exercise and skipping a dose of medication other than diuretics increased heart rate (+3 bpm, p=0.001 and almost +2 bpm, p=0.016, respectively). Conclusions: Our HTM system was able to detect small changes in vital signs related to these activities. Further studies should assess if providing such a schedule of activities might be useful for patient education and could improve long-term adherence to recommended lifestyle changes

Exploring the structural relationship between interviewer and self-rated affective symptoms in Huntington’s disease

This study explores the structural relationship between self-report and interview measures of affect in Huntington’s disease. The findings suggest continued use of both to recognize the multidimensionality within a single common consideration of distress

Incorporating Biomarker Stratification into STAMPEDE: an Adaptive Multi-arm, Multi-stage Trial Platform

The treatment and outcomes for advanced prostate cancer have experienced significant progress over recent years. Importantly, the additional benefits of 'up front' chemotherapy (docetaxel) and abiraterone, over and above conventional androgen deprivation, have been separately demonstrated in the multi-arm, multi-stage (MAMS) STAMPEDE protocol, which continues recruitment to other questions. Alongside this, insights into the underlying molecular biology and, inevitably, the molecular heterogeneity of prostate cancer are opening the door to new therapeutic approaches. Incorporating this understanding and testing these hypotheses within STAMPEDE brings new challenges to the MAMS approach, but has the potential to further improve the outlook for this disease

Improving chronic disease prevention and screening in primary care: results of the BETTER pragmatic cluster randomized controlled trial.

BackgroundPrimary care provides most of the evidence-based chronic disease prevention and screening services offered by the healthcare system. However, there remains a gap between recommended preventive services and actual practice. This trial (the BETTER Trial) aimed to improve preventive care of heart disease, diabetes, colorectal, breast and cervical cancers, and relevant lifestyle factors through a practice facilitation intervention set in primary care.MethodsPragmatic two-way factorial cluster RCT with Primary Care Physicians' practices as the unit of allocation and individual patients as the unit of analysis. The setting was urban Primary Care Team practices in two Canadian provinces. Eight Primary Care Team practices were randomly assigned to receive the practice-level intervention or wait-list control; 4 physicians in each team (32 physicians) were randomly assigned to receive the patient-level intervention or wait-list control. Patients randomly selected from physicians' rosters were stratified into two groups: 1) general and 2) moderate mental illness. The interventions involved a multifaceted, evidence-based, tailored practice-level intervention with a Practice Facilitator, and a patient-level intervention involving a one-hour visit with a Prevention Practitioner where patients received a tailored 'prevention prescription'. The primary outcome was a composite Summary Quality Index of 28 evidence-based chronic disease prevention and screening actions with pre-defined targets, expressed as the ratio of eligible actions at baseline that were met at follow-up. A cost-effectiveness analysis was conducted.Results789 of 1,260 (63%) eligible patients participated. On average, patients were eligible for 8.96 (SD 3.2) actions at baseline. In the adjusted analysis, control patients met 23.1% (95% CI: 19.2% to 27.1%) of target actions, compared to 28.5% (95% CI: 20.9% to 36.0%) receiving the practice-level intervention, 55.6% (95% CI: 49.0% to 62.1%) receiving the patient-level intervention, and 58.9% (95% CI: 54.7% to 63.1%) receiving both practice- and patient-level interventions (patient-level intervention versus control, P &lt; 0.001). The benefit of the patient-level intervention was seen in both strata. The extra cost of the intervention was $26.43CAN (95$16 to $44) per additional action met.ConclusionsA Prevention Practitioner can improve the implementation of clinically important prevention and screening for chronic diseases in a cost-effective manner

Perinatal insults and neurodevelopmental disorders may impact Huntington's disease age of diagnosis

Introduction: The age of diagnosis of Huntington's disease (HD) varies among individuals with the same HTT CAG-repeat expansion size. We investigated whether early-life events, like perinatal insults or neurodevelopmental disorders, influence the diagnosis age. Methods: We used data from 13,856 participants from REGISTRY and Enroll-HD, two large international multicenter observational studies. Disease-free survival analyses of mutation carriers with an HTT CAG repeat expansion size above and including 36 were computed through Kaplan-Meier estimates of median time until an HD diagnosis. Comparisons between groups were computed using a Cox proportional hazard survival model adjusted for CAG-repeat expansion length. We also assessed whether the group effect depended on gender and the affected parent. Results: Insults in the perinatal period were associated with an earlier median age of diagnosis of 45.00 years (95%CI: 42.07–47.92) compared to 51.00 years (95%CI: 50.68–51.31) in the reference group, with a CAG-adjusted hazard ratio of 1.61 (95%CI: 1.26–2.06). Neurodevelopmental disorders were also associated with an earlier median age of diagnosis than the reference group of 47.00 years (95% CI: 43.38–50.62) with a CAG-adjusted hazard ratio of 1.42 (95%CI: 1.16–1.75). These associations did not change significantly with gender or affected parent. Conclusions: These results, derived from large observational datasets, show that perinatal insults and neurodevelopmental disorders are associated with earlier ages of diagnosis of magnitudes similar to the effects of known genetic modifiers of HD. Given their clear temporal separation, these early events may be causative of earlier HD onset, but further research is needed to prove causation