Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec

A systematic review of autism spectrum disorder and substance use and abuse was conducted based on the Preferred Reporting Items for Systematic Review and Meta-Analysis protocol guidelines (an internationally recognized standardized methodological framework for conducting systematic review). The objectives of the review were to update and extend findings reported by Arnevik and Helverschou’s review of the autism spectrum disorder and substance use literature by (1) evaluating study quality via the Mixed-Methods Appraisal Tool; (2) examining autism spectrum disorder and substance abuse diagnostic measures; (3) reporting on the prevalence of co-occurring autism spectrum disorder and substance abuse; and (4) identifying risk, protective, and positive treatment factors. Twenty-six studies on substance use and abuse in autism spectrum disorder were identified through a search of MEDLINE, PsycINFO and Google Scholar. Average study quality score was 75.4%. Prevalence rates of substance abuse among samples with autism spectrum disorder ranged from 1.3% to 36%, but due to variability in sample characteristics and diagnostic measures, a general prevalence rate could not be established. Risk and protective factors, recognized in the general population, such as familial substance abuse and comorbid externalizing disorders, and factors, which may be more likely to occur in individuals with autism spectrum disorder compared to the general population, such as few social resources (i.e. sense of social belonging, breadth of social support networks, and level of social capital) and low sensation-seeking, were identified. One intervention study was identified; however, methodological limitations preclude any conclusion regarding positive treatment factors at this time. More research, using standardized measures and comparable samples, is needed to understand risk and protective factors and to determine the prevalence of co-occurring substance abuse and autism spectrum disorder. Lay Abstract Symptoms characteristic of autism spectrum disorder were initially believed to protect individuals with autism spectrum disorder from developing substance abuse. However, recent studies suggest that up to 36% of individuals with autism spectrum disorder may have a co-occurring issue with substance abuse. In addition, substance abuse may worsen the difficulties with daily functioning some individuals with autism spectrum disorder experience. It is important to understand occurrence rates, and risk, protective and positive treatment factors of co-occurring autism spectrum disorder and substance abuse in order to promote the best possible support for this special population. This review aimed to find and synthesize evidence regarding risk, protective and treatment factors, and determine a general prevalence rate of co-occurring autism spectrum disorder and substance abuse from all studies on substance use and abuse in individuals with autism spectrum disorder. The review also aimed to assess study quality and identify a diagnostic measure for substance abuse in individuals with autism spectrum disorder. Twenty-six studies on substance use and abuse in autism spectrum disorder were included in the review. The rates of substance abuse among those with autism spectrum disorder identified by included studies ranged from 1.3% to 36%, but due to large differences in study methods, a general prevalence rate could not be determined. Risk and protective factors, recognized in the general population, such as familial substance abuse and co-occurring mental health issues, and factors which may be more likely to occur in individuals with autism spectrum disorder, such as limited social resources and low sensation-seeking, were identified. No diagnostic measures specific to individuals with autism spectrum disorder and substance abuse were identified. This review identified only one exploratory study on an adapted intervention for co-occurring autism spectrum disorder and substance abuse. However, there were many methodological challenges in this study that limit the conclusions that can be drawn from the data. More research, using consistent methods, is needed to understand risk and protective factors and to determine the prevalence of substance abuse among individuals with autism spectrum disorder. The potential for co-occurring autism spectrum disorder and substance abuse should be considered by professional working in both autism spectrum disorder and substance abuse services, as finding suggests substance abuse is possible among individuals with autism spectrum disorder and may occur more frequently than previously believed. In addition, autism spectrum disorder and substance abuse service providers should be sensitive to specific risk and protective factors identified by the review that may impact substance abuse course and outcomes.

Background People with social anxiety disorder (SAD) fear social interactions and may be reluctant to seek treatments involving exposure to social situations. Social exposure conducted in virtual reality (VR), embedded in individual cognitive–behavioural therapy (CBT), could be an answer. Aims To show that conducting VR exposure in CBT for SAD is effective and is more practical for therapists than conducting exposure in vivo. Method Participants were randomly assigned to either VR exposure ( n = 17), in vivo exposure ( n = 22) or waiting list ( n = 20). Participants in the active arms received individual CBT for 14 weekly sessions and outcome was assessed with questionnaires and a behaviour avoidance test. (Trial registration number ISRCTN99747069.) Results Improvements were found on the primary (Liebowitz Social Anxiety Scale) and all five secondary outcome measures in both CBT groups compared with the waiting list. Conducting exposure in VR was more effective at post-treatment than in vivo on the primary outcome measure and on one secondary measure. Improvements were maintained at the 6-month follow-up. VR was significantly more practical for therapists than in vivo exposure. Conclusions Using VR can be advantageous over standard CBT as a potential solution for treatment avoidance and as an efficient, cost-effective and practical medium of exposure.

IMPORTANCE: Clostridium difficile is the most common cause of health care-associated infection in US hospitals. Recurrence occurs in 25% to 30% of patients. OBJECTIVE: To determine the safety, fecal colonization, recurrence rate, and optimal dosing schedule of nontoxigenic C. difficile strain M3 (VP20621; NTCD-M3) for prevention of recurrent C. difficile infection (CDI). DESIGN, SETTING, AND PARTICIPANTS: Phase 2, randomized, double-blind, placebo-controlled, dose-ranging study conducted from June 2011 to June 2013 among 173 patients aged 18 years or older who were diagnosed as having CDI (first episode or first recurrence) and had successfully completed treatment with metronidazole, oral vancomycin, or both at 44 study centers in the United States, Canada, and Europe. INTERVENTIONS: Patients were randomly assigned to receive 1 of 4 treatments: oral liquid formulation of NTCD-M3, 10(4) spores/d for 7 days (n = 43), 10(7) spores/d for 7 days (n = 44), or 10(7) spores/d for 14 days (n = 42), or placebo for 14 days (n = 44). MAIN OUTCOMES AND MEASURES: The primary outcome was safety and tolerability of NTCD-M3 within 7 days of treatment. Exploratory secondary outcomes included fecal colonization with NTCD-M3 from end of study drug through week 6 and CDI recurrence from day 1 through week 6. RESULTS: Among 168 patients who started treatment, 157 completed treatment. One or more treatment-emergent adverse events were reported in 78% of patients receiving NTCD-M3 and 86% of patients receiving placebo. Diarrhea and abdominal pain were reported in 46% and 17% of patients receiving NTCD-M3 and 60% and 33% of placebo patients, respectively. Serious treatment-emergent adverse events were reported in 7% of patients receiving placebo and 3% of all patients who received NTCD-M3. Headache was reported in 10% of patients receiving NTCD-M3 and 2% of placebo patients. Fecal colonization occurred in 69% of NTCD-M3 patients: 71% with 10(7) spores/d and 63% with 10(4) spores/d. Recurrence of CDI occurred in 13 (30%) of 43 placebo patients and 14 (11%) of 125 NTCD-M3 patients (odds ratio [OR], 0.28; 95% CI, 0.11-0.69; P = .006); the lowest recurrence was in 2 (5%) of 43 patients receiving 10(7) spores/d for 7 days (OR, 0.1; 95% CI, 0.0-0.6; P = .01 vs placebo]). Recurrence occurred in 2 (2%) of 86 patients who were colonized vs 12 (31%) of 39 patients who received NTCD-M3 and were not colonized (OR, 0.01; 95% CI, 0.00-0.05; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with CDI who clinically recovered following treatment with metronidazole or vancomycin, oral administration of spores of NTCD-M3 was well tolerated and appeared to be safe. Nontoxigenic C. difficile strain M3 colonized the gastrointestinal tract and significantly reduced CDI recurrence. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01259726.

SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoproteins of SARS-CoV-2 mediate viral entry and are the main targets for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic, and public health interventions. Here, we perform a cross-sectional study on 106 SARS-CoV-2-infected individuals to evaluate humoral responses against SARS-CoV-2 Spike. Most infected individuals elicit anti-Spike antibodies within 2 weeks of the onset of symptoms. The levels of receptor binding domain (RBD)-specific immunoglobulin G (IgG) persist over time, and the levels of anti-RBD IgM decrease after symptom resolution. Although most individuals develop neutralizing antibodies within 2 weeks of infection, the level of neutralizing activity is significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.

Recent data from several studies and surveys confirm that our society has entered the digital and information age. Some authors mention that information and communication technologies (ICT) have the potential to enhance people’s power to act and promote equal citizen participation. These elements are particularly important for people living with intellectual disability (ID). However, it seems that the use of ICT is challenging for these people and that a digital divide has gradually formed between them and the connected citizen. The general objective of this theoretical article is to identify and illustrate the dimensions that must be taken into account to promote the digital participation of people with ID. The model is based on a qualitative analysis of scientific publications using a conceptual-style matrix (Miles &amp; Huberman, 2003). The coding categories were derived from two main sources: the accessibility pyramid and the Human Development Model - Disability Creation Process. Five challenges or conditions associated with digital inclusion were identified: access to digital devices, sensorimotor, cognitive and technical requierements and the comprehension of codes and conventions. For each one, the obstacles and facilitators identified in the literature are described. These reflections and principles led us to propose a model in the shape of a gear. The proper operation of the gear system depends on the fit between individual resources and environmental support. The model is a first step to understand the digital inclusion of people with ID.

Background: Whether an initial invasive strategy in patients with stable ischemic heart disease and at least moderate ischemia improves outcomes in the setting of a history of heart failure (HF) or left ventricular dysfunction (LVD) when ejection fraction is ≥35% but &lt;45% is unknown. Methods: Among 5179 participants randomized into ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), all of whom had left ventricular ejection fraction (LVEF) ≥35%, we compared cardiovascular outcomes by treatment strategy in participants with a history of HF/LVD at baseline versus those without HF/LVD. Median follow-up was 3.2 years. Results: There were 398 (7.7%) participants with HF/LVD at baseline, of whom 177 had HF/LVEF &gt;45%, 28 HF/LVEF 35% to 45%, and 193 LVEF 35% to 45% but no history of HF. HF/LVD was associated with more comorbidities at baseline, particularly previous myocardial infarction, stroke, and hypertension. Compared with patients without HF/LVD, participants with HF/LVD were more likely to experience a primary outcome composite of cardiovascular death, nonfatal myocardial infarction, or hospitalization for unstable angina, HF, or resuscitated cardiac arrest (4-year cumulative incidence rate, 22.7% versus 13.8%; cardiovascular death or myocardial infarction, 19.7% versus 12.3%; and all-cause death or HF, 15.0% versus 6.9%). Participants with HF/LVD randomized to the invasive versus conservative strategy had a lower rate of the primary outcome (17.2% versus 29.3%; difference in 4-year event rate, −12.1% [95% CI, −22.6 to −1.6%]), whereas those without HF/LVD did not (13.0% versus 14.6%; difference in 4-year event rate, −1.6% [95% CI, −3.8% to 0.7%]; P interaction = 0.055). A similar differential effect was seen for the primary outcome, all-cause mortality, and cardiovascular mortality when invasive versus conservative strategy–associated outcomes were analyzed with LVEF as a continuous variable for patients with and without previous HF. Conclusions: ISCHEMIA participants with stable ischemic heart disease and at least moderate ischemia with a history of HF or LVD were at increased risk for the primary outcome. In the small, high-risk subgroup with HF and LVEF 35% to 45%, an initial invasive approach was associated with better event-free survival. This result should be considered hypothesis-generating. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522.

Rapid and reliable screening of SARS-CoV-2 is fundamental to assess viral spread and limit the pandemic we are facing. In this study, we compared direct rRT-PCR method (without RNA extraction) using SeeGene AllplexTM 2019-nCoV rRT-PCR with the RealStar® SARS-CoV-2 rRT-PCR kit (Altona Diagnostics). Furthermore, we assessed the impact of swab storage media composition on PCR efficiency. We show that SeeGene and Altona's assays provide similar efficiency. Importantly, we provide evidence that RNA extraction can be successfully bypassed when samples are stored in UTM medium or in molecular water but not when samples are stored in saline solution and in Hanks medium.

OBJECTIVE: Since the first recovery college (RC) opened in England in 2009, many more have begun operating around the world. The body of knowledge regarding the effects of RCs is growing, suggesting their benefit to recovery, well-being, goal achievement, knowledge, self-management, social support, reduced stigma, and service use. The objective of this review was to establish the state of knowledge about RCs from current empirical literature and to document the methods used to evaluate them. METHODS: In consultation with an international expert panel, two independent evaluators performed a literature review with no date limits on publications in the Medline and Scopus electronic databases. RESULTS: A total of 460 articles were found, and 31 publications were retained. RC attendance was associated with high satisfaction among students, attainment of recovery goals, changes in service providers' practice, and reductions in service use and cost. CONCLUSIONS: To our knowledge, this is the first literature review of peer-reviewed publications about original studies evaluating the impacts of RCs, including studies pertaining to students, health service providers' practices, education and management practitioners, and citizens. Quantitative studies with a high level of evidence were underrepresented and should be considered as a future evaluation design. Furthermore, outcomes such as empowerment and reduced stigma should be assessed with standardized tools. The impact of RCs on attendees, family, friends, and caregivers and on the everyday practice of health service providers who attend RCs for continuing education or as tutors should also be assessed.

BACKGROUND: No primary practice care model has been shown to be superior in achieving high-quality primary care. We aimed to identify the organizational characteristics of primary care practices that provide high-quality primary care. METHODS: We performed a cross-sectional observational study involving a stratified random sample of 37 primary care practices from 3 regions of Quebec. We recruited 1457 patients who had 1 of 2 chronic care conditions or 1 of 6 episodic care conditions. The main outcome was the overall technical quality score. We measured organizational characteristics by use of a validated questionnaire and the Team Climate Inventory. Statistical analyses were based on multilevel regression modelling. RESULTS: The following characteristics were strongly associated with overall technical quality of care score: physician remuneration method (27.0; 95% confidence interval [CI] 19.0-35.0), extent of sharing of administrative resources (7.6; 95% CI 0.8-14.4), presence of allied health professionals (15.3; 95% CI 5.4-25.2) and/or specialist physicians (19.6; 95% CI 8.3-30.9), the presence of mechanisms for maintaining or evaluating competence (7.7; 95% CI 3.0-12.4) and average organizational access to the practice (4.9; 95% CI 2.6-7.2). The number of physicians (1.2; 95% CI 0.6-1.8) and the average Team Climate Inventory score (1.3; 95% CI 0.1-2.5) were modestly associated with high-quality care. INTERPRETATION: We identified a common set of organizational characteristics associated with high-quality primary care. Many of these characteristics are amenable to change through practice-level organizational changes.

INTRODUCTION: Intravascular large B-cell lymphoma (IVL) is an extremely rare malignancy, mainly studied through European and Asian series. Due to the low incidence of this condition, our understanding of the clinical presentation as well as the management of IVL relies on a limited number of patients.We report the largest North American study to date on IVL with 29 cases from Quebec hospital diagnosed between 1990 and 2016. The aim of our study is to describe the clinical presentations, diagnostic and staging procedures, therapeutic management and clinical outcomes of IVL patients in our population and compare the disease phenotype to European and Asian series reported.In our cohort, all patients had stage IV IVL at diagnosis, with a median age of 66.7 years (range 47.2-90.8). Clinical presentation was characterized by constitutional symptoms (100%), poor ECOG-PS (100% ≥ 2), cytopenias (93% anemia), and elevated lactate dehydrogenase (97%) and C-reactive protein (96%). Our cohort presented with mainly cutaneous and neurological symptoms. However, neurological involvement (75.9%) was predominant and no "cutaneous variant" was observed; this differs from European literature, where "classical" IVL is reported with mainly cutaneous involvement. Two of our Caucasian patients presented "Asian variant" IVL; this observation is not unusual, as cases of "classical" IVL have been reported in Asians and "Asian variant" IVL has been reported in Europeans. All patients were classified according to their immunophenotypic features in 3 different subgroups (CD5 or CD5CD10, CD5CD10, CD5CD10) with no difference in outcome. Finally, 62% of our cohort received anthracycline-based chemotherapy and 53% of them achieved a complete response. After a median follow-up of 328 days, OS at 3 years was 42.7% for the entire cohort and 47.4% for the cases with in vivo diagnosis. CONCLUSION: Unlike European studies on "classical" IVL, our study showed that the French Canadian presentation of this subtype of IVL is more frequently observed with neurological rather than cutaneous involvement. Finally, an early diagnosis is of primary importance since almost a quarter of patients receive a post-mortem diagnosis. A prompt diagnosis allows the introduction of an early treatment, associated with a CR in 53% of patients.

BACKGROUND: In 2011, >750 cases of measles were reported in Quebec, Canada, where a routine 2-dose measles immunization schedule, in which measles vaccine is given at 12 and 18 months of age, had been in effect since 1996. Effectiveness of this schedule was assessed during a high school outbreak. METHODS: Cases were identified by passive followed by active surveillance. Classical cases met the national surveillance definition; attenuated cases showed clinical signs and high measles-specific immunoglobulin G but did not fulfill all classical criteria. Immunization status was ascertained from written records, and vaccine effectiveness (VE) was calculated as 1 - [(risk of measles in vaccinated individuals)/(risk in unvaccinated individuals)] × 100%. RESULTS: Among 1306 students, 110 measles cases were identified; 98 were classical cases, and 12 were attenuated cases. The attack rates among unvaccinated and fully vaccinated students were 82% and 4.8%, respectively. The VE among 2-dose recipients was 95.5% against classical and 94.2% against all (classical + attenuated) measles. Among 2-dose recipients, attack rates with first immunization at 12 and ≥15 months of age were 5.8% and 2.0%, respectively, with corresponding VE values of 93.0% and 97.5%. The risk of measles in 2-dose recipients was significantly (3-4-fold) higher when vaccine was first administered at 12 months of age, compared with ≥15 months of age (P = .04). CONCLUSIONS: Despite compliance with the recommended 2-dose measles immunization schedule, 6% of high school students were susceptible during this outbreak. Residual susceptibility was 2-4-fold higher among 2-dose recipients who had received the first dose of vaccine prior to 15 months of age. If confirmed in other settings, these results suggest that administration of the first dose of measles vaccine before 15 months of age may not be optimal for measles elimination efforts.

BACKGROUND: Long-term oxygen therapy improves survival in patients with chronic obstructive pulmonary disease (COPD) and chronic severe daytime hypoxemia. However, the efficacy of oxygen therapy for the management of isolated nocturnal hypoxemia is uncertain. METHODS: We designed this double-blind, placebo-controlled, randomized trial to determine, in patients with COPD who have nocturnal arterial oxygen desaturation without qualifying for long-term oxygen therapy, whether nocturnal oxygen provided for a period of 3 to 4 years would decrease mortality or the worsening of disease such that patients meet current specifications for long-term oxygen therapy. Patients with an oxygen saturation of less than 90% for at least 30% of the recording time on nocturnal oximetry were assigned, in a 1:1 ratio, to receive either nocturnal oxygen or ambient air from a sham concentrator (placebo). The primary outcome was a composite of death from any cause or a requirement for long-term oxygen therapy as defined by the Nocturnal Oxygen Therapy Trial (NOTT) criteria in the intention-to-treat population. RESULTS: Recruitment was stopped prematurely because of recruitment and retention difficulties after 243 patients, of a projected 600, had undergone randomization at 28 centers. At 3 years of follow-up, 39.0% of the patients assigned to nocturnal oxygen (48 of 123) and 42.0% of those assigned to placebo (50 of 119) met the NOTT-defined criteria for long-term oxygen therapy or had died (difference, -3.0 percentage points; 95% confidence interval, -15.1 to 9.1). CONCLUSIONS: Our underpowered trial provides no indication that nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with COPD. (Funded by the Canadian Institutes of Health Research; INOX ClinicalTrials.gov number, NCT01044628.).

Abstract Multidisciplinary team (MDT) approach has been shown to reduce diabetic foot ulcerations (DFUs) and lower extremity amputations (LEAs), but there is heterogeneity between team members and interventions. Podiatrists have been suggested as “gatekeepers” for the prevention and management of DFUs. The purpose of our study is to review the effect of podiatric interventions in MDTs on DFUs and LEAs. We conducted a systematic review of available literature. Data's heterogeneity about DFU outcomes made it impossible for us to include it in a meta‐analysis, but we identified 12 studies fulfilling inclusion criteria that allowed for them to be included for LEA outcomes. With the exception of one study, all reported favourable outcomes for MDTs that include podiatry. We found statistical significance in favour of an MDT approach including podiatrists for our primary outcome (total LEAs (RR: 0.69, 95% CI 0.54–0.89, I 2 = 64%, P = 0.002)) and major LEAs (RR: 0.45, 95% CI 0.23–0.90, I 2 = 67%, P &lt; 0.02). Our systematic review, with a standard search strategy, is the first to specifically address the relevant role of podiatrists and their interventions in an MDT approach for DFU management. Our observations support the literature that MDTs including podiatrists have a positive effect on patient outcomes but there is insufficient evidence that MDTs with podiatry management can reduce the risk of LEAs. Our study highlights the necessity for intervention descriptions and role definition in team approach in daily practice and in published literature.

Abstract Rationale End-tidal CO2 (EtCO2) is used to monitor cardiopulmonary resuscitation (CPR), but it can be affected by intrathoracic airway closure. Chest compressions induce oscillations in expired CO2, and this could reflect variable degrees of airway patency. Objectives To understand the impact of airway closure during CPR, and the relationship between the capnogram shape, airway closure, and delivered ventilation. Methods This study had three parts: 1) a clinical study analyzing capnograms after intubation in patients with out-of-hospital cardiac arrest receiving continuous chest compressions, 2) a bench model, and 3) experiments with human cadavers. For 2 and 3, a constant CO2 flow was added in the lung to simulate CO2 production. Capnograms similar to clinical recordings were obtained and different ventilator settings tested. EtCO2 was compared with alveolar CO2 (bench). An airway opening index was used to quantify chest compression–induced expired CO2 oscillations in all three clinical and experimental settings. Measurements and Main Results A total of 89 patients were analyzed (mean age, 69 ± 15 yr; 23% female; 12% of hospital admission survival): capnograms exhibited various degrees of oscillations, quantified by the opening index. CO2 value varied considerably across oscillations related to consecutive chest compressions. In bench and cadavers, similar capnograms were reproduced with different degrees of airway closure. Differences in airway patency were associated with huge changes in delivered ventilation. The opening index and delivered ventilation increased with positive end-expiratory pressure, without affecting intrathoracic pressure. Maximal EtCO2 recorded between ventilator breaths reflected alveolar CO2 (bench). Conclusions During chest compressions, intrathoracic airway patency greatly affects the delivered ventilation. The expired CO2 signal can reflect CPR effectiveness but is also dependent on airway patency. The maximal EtCO2 recorded between consecutive ventilator breaths best reflects alveolar CO2.

OBJECTIVE: Hot flashes are frequent and bothersome in menopausal women and breast cancer survivors. Most pharmacological interventions or herbal therapies for hot flashes have limitations because of contraindications in breast cancer survivors, side effects, or lack of proven efficacy. The aim of this study was to assess the effects of psychoeducational interventions, including relaxation, on hot flashes in menopausal women and women previously diagnosed with breast cancer. DESIGN: MEDLINE, CINAHL, PsycInfo, the Cochrane Library, and reference lists of articles were searched for relevant articles published between January 1980 and December 2006. Data extraction and quality assessment were carried out by two of the authors. RESULTS: Fourteen studies involving 475 patients were included. Five studies evaluated psychoeducational interventions, including education, counseling, cognitive-behavioral strategies, and mindfulness-based stress reduction. All showed an improvement in vasomotor symptoms, although the experimental group in the two studies containing the largest numbers of participants also received pharmacological therapies. Nine trials evaluated the efficacy of relaxation techniques to improve hot flashes. Five of these studies showed a significant improvement in hot flashes. Only three of the 14 studies evaluated a psychoeducational intervention in breast cancer survivors. Two of these showed a significant improvement in hot flashes. CONCLUSIONS: Psychoeducational interventions, including relaxation, seem to alleviate hot flashes in menopausal women and breast cancer survivors; however, the methodological quality of published research is either fair or poor. More studies are required, especially in the breast cancer population where only a few studies are available, before psychoeducational interventions are offered as a treatment option.

OBJECTIVE: We aim to determine the incidence of delirium and describe its impacts on hospital length of stay (LOS) among non-delirious community-dwelling older adults with an 8-hour exposure to the emergency department (ED) environment. DESIGN: This is a prospective observational multicentre cohort study (March-July 2015). Patients were assessed two times per day during their entire ED stay and up to 24 hours on hospital ward. SETTING: The study took place in four Canadian EDs. PARTICIPANTS: 338 included patients: (1) aged ≥65 years; (2) who had an ED stay ≥8 hours; (3) were admitted to hospital ward and (4) were independent/semi-independent. MAIN OUTCOMES AND MEASURES: The primary outcomes of this study were incident delirium in the ED or within 24 hours of ward admission and ED and hospital LOS. Functional and cognitive status were assessed using validated Older Americans Resources and Services and the modified Telephone Interview for Cognitive Status tools. The Confusion Assessment Method was used to detect incident delirium. Univariate and multivariate analyses were conducted to evaluate outcomes. RESULTS: Mean age was 76.8 (±8.1), 17.7% were aged >85 years old and 48.8% were men. The mean incidence of delirium was 12.1% (n=41). Median IQR ED LOS was 32.4 (24.5-47.9) hours and hospital LOS was 146.6 (75.2-267.8) hours. Adjusted mean hospital LOS was increased by 105.4 hours (4.4 days) (95% CI 25.1 to 162.0, P<0.001) for patients who developed an episode of delirium compared with non-delirious patient. CONCLUSIONS: An incident delirium was observed in one of eight independent/semi-independent older adults after an 8-hour ED exposure. An episode of delirium increases hospital LOS by 4 days and therefore has important implications for patients and could contribute to ED overcrowding through a deleterious feedback loop.

BACKGROUND: CheckMate 817, a phase 3B study, evaluated flat-dose nivolumab plus weight-based ipilimumab in patients with metastatic non-small cell lung cancer (NSCLC). Here, in this research, we report on first-line treatment in patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (cohort A) and special populations (cohort A1: ECOG PS 2; or ECOG PS 0-1 with untreated brain metastases, renal impairment, hepatic impairment, or controlled HIV infection). METHODS: Cohorts A and A1 received nivolumab 240 mg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. The primary endpoint was the incidence of grade 3-4 and grade 5 immune-mediated adverse events (IMAEs; adverse events (AEs) deemed potentially immune-related, occurring <100 days of last dose, and treated with immune-modulating medication (except endocrine events)) and treatment-related select AEs (treatment-related AEs with potential immunological etiology requiring frequent monitoring/intervention, reported between first dose and 30 days after the last dose) in cohort A; efficacy endpoints were secondary/exploratory. In cohort A1, safety/efficacy assessment was exploratory. RESULTS: The most common grade 3-4 IMAEs were pneumonitis (5.1%), diarrhea/colitis (4.9%), and hepatitis (4.6%) in cohort A (N=391) and diarrhea/colitis (3.5%), hepatitis (3.5%), and rash (3.0%) in cohort A1 (N=198). The most common grade 3-4 treatment-related select AEs were hepatic (5.9%), gastrointestinal (4.9%), and pulmonary (4.6%) events in cohort A and gastrointestinal (4.0%), skin (3.5%), and endocrine (3.0%) events in cohort A1. No grade 5 IMAEs or treatment-related select AEs occurred. Treatment-related deaths occurred in 4 (1.0%) and 3 (1.5%) patients in cohorts A and A1, respectively. Three-year overall survival (OS) rates were 33.7% and 20.5%, respectively. CONCLUSIONS: Flat-dose nivolumab plus weight-based ipilimumab was associated with manageable safety and durable efficacy in cohort A, consistent with data from phase 3 metastatic NSCLC studies. Special populations of cohort A1 including patients with ECOG PS 2 or ECOG PS 0-1 with untreated brain metastases had manageable treatment-related toxicity and clinically meaningful 3-year OS rate. TRIAL REGISTRATION NUMBER: NCT02869789.

BACKGROUND: Ischemia with nonobstructive coronary arteries (INOCA) is common clinically, particularly among women, but its prevalence among patients with at least moderate ischemia and the relationship between ischemia severity and non-obstructive atherosclerosis severity are unknown. OBJECTIVES: The authors investigated predictors of INOCA in enrolled, nonrandomized participants in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), sex differences, and the relationship between ischemia and atherosclerosis in patients with INOCA. METHODS: Core laboratories independently reviewed screening noninvasive stress test results (nuclear imaging, echocardiography, magnetic resonance imaging or nonimaging exercise tolerance testing), and coronary computed tomography angiography (CCTA), blinded to results of the screening test. INOCA was defined as all stenoses <50% on CCTA in a patient with moderate or severe ischemia on stress testing. INOCA patients, who were excluded from randomization, were compared with randomized participants with ≥50% stenosis in ≥1 vessel and moderate or severe ischemia. RESULTS: Among 3,612 participants with core laboratory-confirmed moderate or severe ischemia and interpretable CCTA, 476 (13%) had INOCA. Patients with INOCA were younger, were predominantly female, and had fewer atherosclerosis risk factors. For each stress testing modality, the extent of ischemia tended to be less among patients with INOCA, particularly with nuclear imaging. There was no significant relationship between severity of ischemia and extent or severity of nonobstructive atherosclerosis on CCTA. On multivariable analysis, female sex was independently associated with INOCA (odds ratio: 4.2 [95% CI: 3.4-5.2]). CONCLUSIONS: Among participants enrolled in ISCHEMIA with core laboratory-confirmed moderate or severe ischemia, the prevalence of INOCA was 13%. Severity of ischemia was not associated with severity of nonobstructive atherosclerosis. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.

<h3>BACKGROUND AND PURPOSE:</h3> Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial. <h3>MATERIALS AND METHODS:</h3> Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of &gt;5 days, and overall morbidity and mortality (mRS &gt; 2) at 1 year. There was no blinding. <h3>RESULTS:</h3> Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%–15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%–26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12–3.83; <i>P</i> = .021). Morbidity and mortality (mRS &gt;2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%–6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%–30% versus 19/148, 12%; 95% CI, 8%–19%; relative risk: 1.74; 95% CI, 1.04–2.92; <i>P</i> = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%–56% versus 12/148, 8%; 95% CI, 5%–14%; relative risk: 0.18; 95% CI, 0.11–0.31; <i>P </i>&lt; .001) were more frequent after surgery. <h3>CONCLUSIONS:</h3> Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.