Population-Based Repeated Cross-Sectional Study of Hospitalizations for Comorbid Physical and Psychiatric Disorders in Young Adults in Ontario, Canada.

PURPOSE: To measure trends in the rates and costs of hospitalizations over a 15-year period among young adults with physical and/or psychiatric disorders. METHODS: This population-based, repeated cross-sectional study identified all 18- to 26- year-olds hospitalized in Ontario, Canada from April 1, 2003 and March 31, 2018 (fiscal years 2003-2017). Using discharge diagnoses, we assigned hospitalizations to one of four categories: 1) psychiatric disorder only; 2) primary psychiatric disorder with comorbid physical illness; 3) primary physical with comorbid psychiatric disorder; and 4) physical illness only. We compared health service utilization and changes in rates of hospitalizations over time using restricted cubic spline regression. Secondary outcome measures included change in hospital costs for each hospitalization category over the study period. RESULTS: Of 1,076,951 hospitalizations in young adults (73.7% female), 195,726 (18.2%) had a psychiatric disorder (either primary or comorbid). There were 129,676 hospitalizations (12.0%) with psychiatric disorders only, 36,287 (3.4%) with primary psychiatric and comorbid physical disorders, 29,763 (2.8%) with primary physical and comorbid psychiatric disorders, and 881,225 (81.8%) with physical disorders only. Rates of hospitalization for psychiatric disorders only increased 81% from 4.32 to 7.84/1,000 population, and those with physical health disorders with comorbid psychiatric disorders increased 172% from 0.47 to 1.28/1,000 population. Substance-related disorders were the most common comorbid psychiatric disorders among youth hospitalized for physical illness and increased 260% from 0.9 to 3.3/1,000 population. DISCUSSION: Hospitalizations among young adults with primary and comorbid psychiatric disorders have increased significantly over the past 15 years. Health system resources should be adequately directed to meet the shifting and complex needs of hospitalized young adults.

Analysis of Extreme Length of Stay Hospitalizations for Children and Youth in a Quaternary Care Hospital.

Length of stay (LOS) is an important issue for many healthcare organizations. In-patients with extreme LOS account for a disproportionately large percentage of hospital costs. Our analysis of over 15,000 pediatric hospital discharges at The Hospital for Sick Children (Toronto, Canada) between 2015 and 2016 revealed that the vast majority of patients with extreme LOS were discharged directly home, with only a minority receiving home-based services. Patients with the greatest LOS were accounted for by primarily four subspecialty services. Although this report outlines an analysis of pediatric in-patients, our findings and implications are relevant for all jurisdictions and populations as many acute care hospitals often "hold" patients with complex, chronic illness as in-patients for extended periods because alternate appropriate services may not exist or be available. Our case study highlights three key areas to improve quality of care for patients with extreme LOS: alternate levels of care, system resources and transitions to home.

Universal access to no-cost contraception for youth in Canada.

Timely access to effective contraception reduces the incidence of unintended pregnancy. Cost is a significant barrier to using contraception for youth in Canada. Many must pay out-of-pocket because they have no pharmaceutical insurance, their insurance does not cover the contraceptives they desire, or they wish to obtain contraceptives without their parents' knowledge. To address these barriers and reduce rates of unintended pregnancy, this statement recommends that all youth should have confidential access to contraception, at no cost, until the age of 25. The statement also recommends measures to help achieve this goal across Canada.

Social Determinants of Health among Youth Seeking Substance Use and Mental Health Treatment.

OBJECTIVE: The extent to which social determinants of health problems occur among youth with mental health and addiction concerns and the impact of social determinants on their treatment is unknown. This study examined the prevalence of social determinants of health problems among treatment-seeking youth, their perceptions of interference with treatment, and the association between social determinants of health and mental health/addiction difficulties. METHOD: Youth ages 15-24 seeking out-patient treatment for substance use concerns, with or without concurrent mental health concerns, reported on substance use, mental health and social determinants of health. Descriptive statistics and logistic regression analyses were used to determine the extent of social determinant of health problems and their relationship with mental health, substance use, and crime or violence problems. RESULTS: In all, 80% of youth endorsed social determinants of health concerns in at least one domain; nearly 70% identified financial concerns, and many identified substantial problems in each domain and anticipated treatment impacts. Youth most frequently identified financial problems as likely to impact treatment. Cumulative number of social determinants of health problems and individual domains of social determinants of health problems were related to overall mental health and addiction concerns. CONCLUSIONS: Given their prevalence and association with mental health and addiction concerns, social determinants of health problems should be routinely assessed among treatment-seeking youth and integrative services that address these concerns in addition to symptomatology should be considered.

OBJECTIF: La mesure dans laquelle les déterminants sociaux des problèmes de santé sont présents chez les jeunes ayant des problèmes de santé mentale et de dépendance ainsi que l'impact des déterminants sociaux sur leur traitement sont inconnus. Cette étude a examiné la prévalence des déterminants sociaux des problèmes de santé chez les jeunes recherchant un traitement, leurs perceptions de l'interférence avec le traitement, et l'association entre les déterminants sociaux de la santé et les difficultés de santé mentale/dépendance. MÉTHODE: Des jeunes de 15 à 24 ans cherchant un traitement ambulatoire pour des problèmes d'utilisation de substances, avec ou sans problèmes de santé mentale co-occurrents, ont rapporté leur utilisation de substances, leur santé mentale et les déterminants sociaux de la santé. Des statistiques descriptives et des analyses de régression logistique ont servi à déterminer la portée des déterminants sociaux des problèmes de santé et leur relation avec les problèmes de santé mentale, d'utilisation de substances, et de criminalité ou de violence. RÉSULTATS: En tout, 80 % des jeunes ont reconnu l'action des déterminants sociaux des problèmes de santé dans au moins un domaine; près de 70 % ont identifié les ennuis financiers, et beaucoup ont identifié des problèmes substantiels dans chaque domaine et anticipé les impacts sur le traitement. Les jeunes estimaient très fréquemment que les problèmes financiers étaient susceptibles d'avoir un impact sur le traitement. Le nombre cumulatif de déterminants sociaux des problèmes de santé et les domaines individuels des déterminants sociaux des problèmes de santé étaient liés aux problèmes généraux de santé mentale et de dépendance. CONCLUSIONS: Étant donné leur prévalence et leur association aux problèmes de santé mentale et de dépendance, les déterminants sociaux des problèmes de santé devraient être régulièrement évalués chez les jeunes recherchant un traitement et des services intégratifs qui s'attaquent à ces problèmes en plus de la symptomatologie devaient être envisagés.

Identification of effective subdominant anti-HIV-1 CD8+ T cells within entire post-infection and post-vaccination immune responses.

Defining the components of an HIV immunogen that could induce effective CD8+ T cell responses is critical to vaccine development. We addressed this question by investigating the viral targets of CD8+ T cells that potently inhibit HIV replication in vitro, as this is highly predictive of virus control in vivo. We observed broad and potent ex vivo CD8+ T cell-mediated viral inhibitory activity against a panel of HIV isolates among viremic controllers (VC, viral loads <5000 copies/ml), in contrast to unselected HIV-infected HIV Vaccine trials Network (HVTN) participants. Viral inhibition of clade-matched HIV isolates was strongly correlated with the frequency of CD8+ T cells targeting vulnerable regions within Gag, Pol, Nef and Vif that had been identified in an independent study of nearly 1000 chronically infected individuals. These vulnerable and so-called "beneficial" regions were of low entropy overall, yet several were not predicted by stringent conservation algorithms. Consistent with this, stronger inhibition of clade-matched than mismatched viruses was observed in the majority of subjects, indicating better targeting of clade-specific than conserved epitopes. The magnitude of CD8+ T cell responses to beneficial regions, together with viral entropy and HLA class I genotype, explained up to 59% of the variation in viral inhibitory activity, with magnitude of the T cell response making the strongest unique contribution. However, beneficial regions were infrequently targeted by CD8+ T cells elicited by vaccines encoding full-length HIV proteins, when the latter were administered to healthy volunteers and HIV-positive ART-treated subjects, suggesting that immunodominance hierarchies undermine effective anti-HIV CD8+ T cell responses. Taken together, our data support HIV immunogen design that is based on systematic selection of empirically defined vulnerable regions within the viral proteome, with exclusion of immunodominant decoy epitopes that are irrelevant for HIV control.

Improved quantification of HIV-1-infected CD4+ T cells using an optimised method of intracellular HIV-1 gag p24 antigen detection.

The capacity of CD8+ T cells to inhibit HIV-1 replication in vitro strongly correlates with virus control in vivo. Post-hoc evaluations of HIV-1 vaccine candidates suggest that this immunological parameter is a promising benchmark of vaccine efficacy. Large-scale analysis of CD8+ T cell antiviral activity requires a rapid, robust and economical assay for accurate quantification of HIV-1 infection in primary CD4+ T cells. Detection of intracellular HIV-1 p24 antigen (p24 Ag) by flow cytometry is one such method but it is thought to be less sensitive and quantitative than p24 Ag ELISA. We report that fixation and permeabilisation of HIV-infected cells using paraformaldehyde/50% methanol/Nonidet P-40 instead of a conventional paraformaldehyde/saponin-based protocol improved their detection across multiplicities of infection (MOI) ranging from 10(-2) to 8×10(-5), and by nearly two-fold (p<0.001) at the optimal MOI tested (10(-2)). The frequency of infected cells was strongly correlated with p24 Ag release during culture, thus validating its use as a measure of productive infection. We were also able to quantify infection with a panel of HIV-1 isolates representing the major clades. The protocol described here is rapid and cost-effective compared with ELISA and thus could be a useful component of immune monitoring of HIV-1 vaccines and interventions to reduce viral reservoirs.