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The literature on psychosis-relevant outcomes in cannabis users does not adequately address the confounding effects of other substance use/misuse and psychiatric disorders.
We studied a unique population for whom cannabis use is central and necessary to their way of life. They are forbidden from using other substances, including tobacco and alcohol. Their use of cannabis is heavy, chronic, and begins early. The cases were compared with matched controls who did not use cannabis, alcohol, or drugs. The controls were from the same location and shared similar beliefs and lifestyle, except for cannabis use. Attenuated psychosis-relevant phenomena were assessed with the Schizotypal Personality Questionnaire (SPQ) and cognitive functioning with a culture-neutral computerized cognitive battery.
Fifteen cases and 12 matched controls were studied. The cases averaged >30 000 lifetime cannabis exposures. Relative to controls, the cases had significantly higher mean (s.d.) SPQ scores 24 (14.32) v. 13 (8.92), p = 0.031; and poorer cognitive performance, reflected by a lower mean (s.d.) composite cognitive score −0.23 (0.32) v. +0.28 (0.52), p = 0.03. Moderate to large effect sizes were noted for differences in tests of attention, psychomotor speed, working memory, cognitive flexibility, visuo-spatial processing, and verbal memory. A subsample of cases had higher SPQ scores and worse cognitive performance than their siblings not using cannabis.
Heavy, chronic, and early cannabis use that is not confounded by other drug use is associated with psychosis-relevant phenomena and cognitive deficits. The findings are relevant to the evolving attitudes and laws about cannabis.
Choosing Wisely Canada (CWC) is a national initiative designed to encourage patient-clinician discussions about the appropriate, evidence-based use of medical tests, procedures and treatments. The Canadian Association of Emergency Physicians’ (CAEP) Choosing Wisely Canada (CWC) working group developed and released ten recommendations relevant to Emergency Medicine in June 2015 (items 1–5) and October 2016 (items 6–10). In November 2016, the CAEP CWC working group developed a process for updating the recommendations. This process involves: 1) Using GRADE to evaluate the quality of evidence, 2) reviewing relevant recommendations on an ad hoc basis as new evidence emerges, and 3) reviewing all recommendations every five years. While the full review of the CWC recommendations will be performed in 2020, a number of high-impact studies were published after our initial launch that prompted an ad hoc review of the relevant three of our ten recommendations prior to the full review in 2020. This paper describes the results of the CAEP CWC working group's ad hoc review of three of our ten recommendations in light of recent publications.
Members of online bipolar disorder forums often report experiences of mood-stabilisation on the ketogenic diet, which has traditionally been used in the treatment of epilepsy. We examined the nature and extent of such reports.
To investigate associations between a ketogenic diet and mood stabilisation among individuals with bipolar disorder.
We undertook an observational analytic study of free-text comments in online forums about mood effects of dietary interventions (ketogenic, omega-3 enriched or vegetarian) classified by a priori categories of change in mood stabilisation in 274 people with bipolar disorder.
There were 141 (85.5%) free-text comments on ketogenic diets that reported a positive impact on mood stabilisation. Reports of significant mood stabilisation or remission of symptoms over a period were substantially higher for a ketogenic diet than for other diets (93/165, 56.4%, 95% CI 48.4–64.1) v. 14/94, 14.9%, 95% CI 8.4–23.7), odds ratio 7.4, 95% CI 3.8–14.1, P < 0.0001), many with detailed reports of the improvements experienced and several lasting for extended periods (months to years). Other reported associations included fewer episodes of depression (in 41.2%, 95% CI 30.6–52.4 of individuals); improved clarity of thought and speech (28.2%, 95% CI 19.0–39.0); increased energy (25.9, 95% CI 17.0–36.5); and weight loss (25.9%, 95% CI 17.0–36.5).
Despite the inherent limitations of the observational data based on self-reports posted online, the association strength and reports of sustained benefit support a hypothesis of a ketogenic diet being associated with beneficial effects on mood stabilisation. Caution should be exercised in interpreting this data until a controlled trial can be carried out to examine this hypothesis. These preliminary observations are generally consistent with a mitochondrial dysfunction component to bipolar disorder aetiology with ketones bypassing a block between glycolysis and the tricarboxylic acid cycle.
Andrew Harding, in his excursus on ‘legal transplantation’, observed: ‘[W]e do live in a world of legal connectivity in which we share common problems which can only be addressed by a limited range of solutions which are unlikely not to have been tried before’. This prescient remark is apt in the context of the growing importance of the proportionality concept in the Australian public law arena. The proportionality concept attained particular prominence when the High Court of Australia found a freedom of political communication impliedly embedded in the Constitution. It was inevitable that with the establishment of such an implied fundamental constitutional guarantee, the High Court had to craft a principle to enable the saving or invalidation of legislation claimed to be in violation of the implied freedom.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Introduction: Patients with advanced or end-stage illness frequently present to emergency departments (EDs), many of whom are in need of palliative care (PC). Emergency physicians have struggled in providing high quality care to these patients and there is a need to identify cost-effective PC interventions delivered in the ED to improve patient outcomes. The objective of this systematic review was to examine the effectiveness of ED-based PC interventions. Methods: A comprehensive search of nine electronic databases and grey literature sources was conducted to identify any comparative studies assessing the effectiveness of ED-based PC interventions to improve health outcomes of patients with advanced or end-stage illness. Two independent reviewers completed study selection, quality assessment, and data extraction. Differences were mediated via third-party adjudication. Relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random effects model and heterogeneity (I2) was reported. Results: From 5882 potentially eligible citations, 12 studies were included. Two studies are currently on-going clinical trials, and as such, 10 studies were included in this analysis. The studies consisted of before-after studies (n = 5), RCTs (n = 4), and an observational cohort (n = 1). Interventions assessed among the included studies consisted primarily of ED-directed PC consultations (n = 6), while other studies assessed screening of patients with advanced or end-stage illness and PC needs (n = 2), education on PC for ED-staff (n = 1), and an ED-based critical care unit (n = 1). Infrequent reporting of important outcomes (e.g., Mortality, ED relapse) limited the ability of this review to conduct meaningful meta-analysis. There was no difference in patient mortality between two studies assessing ED-directed PC consultations (RR = 0.89; 95% CI: 0.71, 1.13; I2 = 0%). One before-after study (RR = 0.73; 95% CI: 0.47, 1.13) and two RCTs (RR = 2.19; 95% CI: 0.40, 11.92; I2 = 96%) did not identify significant differences in PC consultations intervention (implementation of ED-directed PC consultations) and control (usual care) patients. Conclusion: This review found limited evidence to support the recommendation of any particular ED-based intervention for patients presenting to the ED with advanced or end-stage illness. High quality studies and standardized outcome reporting are needed to better understand the impact of PC interventions in the ED setting.
Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.
Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk.
Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.
Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
A number of procedures for fluorescent X-ray analysis have been introduced to accommodate the samples that are produced from research on the recovery of values from secondary metal sources. For some applications, standards are conveniently available such as those that can be purchased from the National Bureau of Standards. For other applications, secondary standards must be prepared and analyzed by independent methods. The sample preparation procedures vary considerably. For monitoring process efficiency, sample preparation is often kept at a minimum such as simply pouring loose powders into disposable cups. For the most accurate analyses, sample preparatton requires casting the alloys and finishing the surfaces. Matrix correction procedures are employed where concentrations of major constituents vary over wide ranges.
X-ray fluorescence induced by charged particles has been employed in trace element analysis of both animal and human blood, tissue and bone samples. Preparation techniques included microtome slicing and wet digestion in nitric acid, internal chemical standards being used in the latter case.
Most of the specimens arose from a study of interactions between the toxic elements lead and zinc in growing foals; this was motivated by reports of sickness and death in foals raised near lead-zinc smelters. The cause of toxicity in animals from environmental pollution is often attributed to Single factors, whereas in reality interactions among many factors, including a variety of toxic and nutrient trace elements, should be considered.
A variety of spectra are presented and elemental concentrations derived. Agreement between the X-ray data and atomic absorption spectrophotometry is encouraging. The results demonstrate the potential of particle-excited X-ray fluorescenee as a broad-range analytical technique for the study of trace element interactions.