Early Psychosis Intervention and Primary Care: A Mixed Methods Study of Family Physician Knowledge, Attitudes, Preferences, and Needs.

Family physicians (FPs) play an important but underappreciated role in the pathways to care for people with early psychosis. We conducted a mixed-methods study to describe the knowledge, attitudes, preferences, and needs of FPs towards the recognition and management of early psychosis. We sent a cross-sectional postal survey to a random sample of FPs in Ontario, Canada, and conducted in-depth qualitative interviews with twenty. FPs were generally aware of important early psychosis symptoms, however, there were some knowledge gaps. Among surveyed FPs, 25% were unsure of the availability of early psychosis intervention services in their region, and most (80%) would prefer to co-manage with specialists. In the qualitative interviews, FPs expressed varied comfort levels in recognizing psychosis, and that timely access to psychiatry was a main concern. Our findings suggest that FPs require better support in recognizing and managing early psychosis and facilitating connections with specialized care.

Opioid-related overdose deaths among people experiencing homelessness, 2017 to 2021: A population-based analysis using coroner and health administrative data from Ontario, Canada.

AIMS: To measure the change in proportion of opioid-related overdose deaths attributed to people experiencing homelessness and to compare the opioid-related fatalities between individuals experiencing homelessness and not experiencing homelessness at time of death. DESIGN, SETTING AND PARTICIPANTS: Population-based, time-trend analysis using coroner and health administrative databases from Ontario, Canada from 1 July 2017 and 30 June 2021. MEASUREMENTS: Quarterly proportion of opioid-related overdose deaths attributed to people experiencing homelessness. We also obtained socio-demographic and health characteristics of decedents, health-care encounters preceding death, substances directly contributing to death and circumstances surrounding deaths. FINDINGS: A total of 6644 individuals (median age = 40 years, interquartile range = 31-51; 74.1% male) experienced an accidental opioid-related overdose death, among whom 884 (13.3%) were identified as experiencing homelessness at the time of death. The quarterly proportion of opioid-related overdose deaths attributed to people experiencing homelessness increased from 7.2% (26/359) in July-September 2017 to 16.8% (97/578) by April-June 2021 (trend test P < 0.01). Compared with housed decedents, those experiencing homelessness were younger (61.3 versus 53.1% aged 25-44), had higher prevalence of mental health or substance use disorders (77.1 versus 67.1%) and more often visited hospitals (32.1 versus 24.5%) and emergency departments (82.6 versus 68.5%) in the year prior to death. Fentanyl and its analogues more often directly contributed to death among people experiencing homelessness (94.0 versus 81.4%), as did stimulants (67.4 versus 51.6%); in contrast, methadone was less often present (7.8 versus 12.4%). Individuals experiencing homelessness were more often in the presence of a bystander during the acute toxicity event that led to death (55.8 versus 49.7%); and where another individual was present, more often had a resuscitation attempted (61.7 versus 55.1%) or naloxone administered (41.2 versus 28.9%). CONCLUSIONS: People experiencing homelessness account for an increasing proportion of fatal opioid-related overdoses in Ontario, Canada, reaching nearly one in six such deaths in 2021.

The effect of non-medical cannabis retailer proximity on use of mental health services for psychotic disorders in Ontario, Canada.

BACKGROUND: Cannabis is associated with the onset and persistence of psychotic disorders. Evidence suggests that accessibility of substances is associated with an increased risk of use-related harms. We sought to examine the effect of residing in proximity to non-medical cannabis retailers on the prevalence of health service use for psychosis. METHODS: We conducted a cross-sectional study using linked health administrative data, and used geospatial analyses to determine whether people in Ontario, Canada (aged 14-60 years) resided within walking (1.6 km) or driving (5.0 km) distance of non-medical cannabis retailers (open as of February-2020). We identified outpatient visits, emergency department (ED) visits, and hospitalizations for psychotic disorders between 01-April-2019 and 17-March-2020. We used zero-inflated Poisson regression models and gamma generalized linear models to estimate the association between cannabis retailer proximity and indicators of health service use. RESULTS: Non-medical cannabis retailers were differentially located in areas with high levels of marginalization and pre-existing health service use for psychosis. People residing within walking or driving distance of a cannabis retailer had a higher rate of psychosis-related outpatient visits, ED visits, and hospitalizations, compared to people living outside these areas. This effect was stronger among those with no prior service use for psychosis. CONCLUSIONS: Proximity to a non-medical cannabis retailer was associated with higher health service use for psychosis, even after adjustment for prior health service use. These findings suggest that opening of non-medical cannabis retailers could worsen the burden of psychosis on mental health services in areas with high-risk populations.

Sex differences in the clinical presentation of early psychosis in a primary care setting.

Primary care is an important part of the help-seeking pathway for young people experiencing early psychosis, but sex differences in clinical presentation in these settings are unexplored. We aimed to identify sex differences in clinical presentation to primary care services in the 1-year period prior to a first diagnosis of psychotic disorder. We identified first-onset cases of non-affective psychotic disorder over a 10-year period (2005-2015) using health administrative data linked with electronic medical records (EMRs) from primary care (n = 465). Detailed information on encounters in the year prior to first diagnosis was abstracted, including psychiatric symptoms, other relevant behaviours, and diagnoses recorded by the family physician (FP). We used modified Poisson regression models to examine sex differences in the signs, symptoms, and diagnoses recorded by the FP, adjusting for various clinical and sociodemographic factors. Positive symptoms (PR = 0.76, 95%CI: 0.58, 0.98) and substance use (PR = 0.54, 95%CI: 0.40, 0.72) were less prevalent in the medical records of women. Visits by women were more likely to be assigned a diagnosis of depression or anxiety (PR = 1.18, 95%CI: 1.00, 1.38), personality disorder (PR = 5.49, 95%CI: 1.22, 24.62), psychological distress (PR = 11.29, 95%CI: 1.23, 103.91), and other mental or behavioral disorders (PR = 3.49, 95%CI: 1.14, 10.66) and less likely to be assigned a diagnosis of addiction (PR = 0.33, 95%CI: 0.13, 0.87). We identified evidence of sex differences in the clinical presentation of early psychosis and recorded diagnoses in the primary care EMR. Further research is needed to better understand sex differences in clinical presentation in the primary care context, which can facilitate better understanding, detection, and intervention for first-episode psychotic disorders.

Sex and gender differences in symptoms of early psychosis: a systematic review and meta-analysis.

First-episode psychosis (FEP) can be quite variable in clinical presentation, and both sex and gender may account for some of this variability. Prior literature on sex or gender differences in symptoms of psychosis have been inconclusive, and a comprehensive summary of evidence on the early course of illness is lacking. The objective of this study was to conduct a systematic review and meta-analysis of the literature to summarize prior evidence on the sex and gender differences in the symptoms of early psychosis. We conducted an electronic database search (MEDLINE, Scopus, PsycINFO, and CINAHL) from 1990 to present to identify quantitative studies focused on sex or gender differences in the symptoms of early psychosis. We used random effects models to compute pooled standardized mean differences (SMD) and risk ratios (RR), with 95% confidence intervals (CI), for a range of symptoms. Thirty-five studies met the inclusion criteria for the systematic review, and 30 studies were included in the meta-analysis. All studies examined sex differences. Men experienced more severe negative symptoms (SMD = - 0.15, 95%CI = - 0.21, - 0.09), whereas women experienced more severe depressive symptoms (SMD = 0.21, 95%CI = 0.14, 0.27) and had higher functioning (SMD = 0.16, 95%CI = 0.10, 0.23). Women also had a lower prevalence of substance use issues (RR = 0.65, 95%CI = 0.61, 0.69). Symptoms of early psychosis varied between men and women; however, we were limited in our ability to differentiate between biological sex and gender factors. These findings may help to inform early detection and intervention efforts to better account for sex and gender differences in early psychosis presentation.

Clinical potential of canagliflozin in cardiovascular risk reduction in patients with type 2 diabetes.

Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes mellitus, as well as the leading diabetes-associated health care cost. The prevalence and associated impact of cardiovascular disease among those with diabetes engenders the need to identify cardiovascular effects of antihyperglycemic agents. This review seeks to evaluate the impact of canagliflozin, a SGLT2 inhibitor, on cardiovascular risk factors and outcomes. The 14 published trials to-date exploring various cardiovascular risk factors and outcomes among patients receiving canagliflozin were identified and included within the review. Overall these studies demonstrate that among patients with type 2 diabetes mellitus, canagliflozin results in decreased systolic and diastolic blood pressure, lower body weight, and also exhibits renoprotective effects. These findings were similar when canagliflozin was compared to placebo or other antihyperglycemic agents and explored among subsets such as those with chronic kidney disease. In addition, findings from the three trials exploring cardiovascular outcomes of canagliflozin included reduction in cardiovascular mortality and lower incidence of heart failure-associated hospitalizations. Results from studies including other SGLT2 inhibitors suggest that cardiovascular benefits are likely a class-effect found among current SGLT2 inhibitors. Continued research specific to canagliflozin is needed to clarify risks of adverse effects and determine optimal dosing requirements for canagliflozin in regard to cardiovascular risk reduction.

University-Affiliated Alcohol Marketing Enhances the Incentive Salience of Alcohol Cues.

We tested whether affiliating beer brands with universities enhances the incentive salience of those brands for underage drinkers. In Study 1, 128 undergraduates viewed beer cues while event-related potentials (ERPs) were recorded. Results showed that beer cues paired with in-group backgrounds (logos for students' universities) evoked an enhanced P3 ERP component, a neural index of incentive salience. This effect varied according to students' levels of identification with their university, and the amplitude of the P3 response prospectively predicted alcohol use over 1 month. In Study 2 ( N = 104), we used a naturalistic advertisement exposure to experimentally create in-group brand associations and found that this manipulation caused an increase in the incentive salience of the beer brand. These data provide the first evidence that marketing beer via affiliating it with students' universities enhances the incentive salience of the brand for underage students and that this effect has implications for their alcohol involvement.

Marked differences in the structures and protein associations of lymphocyte and monocyte CD4: resolution of a novel CD4 isoform.

The structures, molecular interactions and functions of CD4 in a subset of T lymphocytes have been well characterized. The CD4 receptors of other cell types have, however, been poorly documented. We have previously shown that lymphocytes and monocytes/macrophages differ in their expression of CD4 monomers and dimers. In the present study, we have shown further significant differences. Variability in the blocking of CD4 mAb binding by sulfated polyanions indicated differences in exofacial CD4 structures. In contrast to the well-documented 55 kDa monomers in lymphocytic cells, monocytic cells were found to coexpress two monomer isoforms: the 55 kDa form and a novel 59 kDa species. Experimental uncoupling of CD4 disulfides indicated that the oxidized 55 kDa monomer could be converted to the 59 kDa form. This was achieved by chemical reduction of purified native or recombinant CD4, or in cell transfection experiments by mutation of cysteine to alanine in domain 1 (D1) (Cys16 or Cys84) and in domain 4 (D4) (Cys303 or Cys345). All of these modifications promote CD4 distension on SDS-PAGE analysis and indicate that, when CD4 inter-beta-sheet disulfides in the D1 and D4 Ig folds are disrupted, there is an unravelling of the oxidized form to an extended 59 kDa unfolded state. We hypothesize that this may be a transition-state, structural-intermediate in the formation of disulfide-linked homodimers. Also identified were CD4-tyrosine kinase dissimilarities in which lymphocyte CD4 associated with Lck, but monocyte CD4 associated with HcK. These findings show that there is complex heterogeneity in structures and interactions in the CD4 of T lymphocytes and monocytes.