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Obstructive sleep apnea (OSA) is a common treatable condition with important health and societal consequences.We aimed to assess annual incidence and prevalence of clinically recognized and geographic clustering of OSA in Alberta, Canada using administrative health data case definitions.We used two administrative health databases in Alberta to identify ICD-9 and ICD-10 diagnostic codes for adults and children ≥ two years old diagnosed with OSA from 2003-2020. We defined OSA using an algorithm that was developed and validated in Alberta: at least three claims or one hospitalization within two years. We mapped residential postal code to 70 sub-regional health authorities (SRHAs). Crude, age group- and sex-specific incidence and prevalence, and age group- and sex-standardized rates were calculated for Alberta and for SRHAs. Spatial scan statistics identified clusters of SRHAs in which OSA cases were higher ("hot spots") or lower ("cold spots") than expected.Between 2003 and 2020, OSA prevalence increased from 0.14% to 4.59%. Annual incidence of OSA increased after 2013. Incidence and prevalence were higher in older adults, and higher in children aged 2-11 compared to 12-17 years. Cluster analysis revealed regional variation in OSA incidence and prevalence over time with no consistent pattern except for cold spots in one large metropolitan centre (Calgary).From 2003-2020 the incidence and prevalence of clinically recognized OSA increased but varied by geography. Administrative health data can be used to guide interventions aimed at improving health service delivery and quality of OSA care.

Mastitis, the most frequent disease in dairy cattle. Resistance to mastitis is a complex, polygenic trait controlled by several genes, each with small effects. Genome-wide association studies have been widely used to identify genomic variants associated with complex traits, including resistance to mastitis, to elucidate the underlying genetic architecture of the trait. However, no systematic review and gene prioritization analysis have been conducted to date on GWAS results for resistance to mastitis in dairy cattle. Hence, the objective was to perform a systematic review and gene prioritization analysis of GWAS studies to identify potential functional candidate genes associated with resistance to mastitis-related traits in dairy cattle. Four electronic databases were searched from inception to December 2020, supplemented with multiple sources of gray literature, to identify eligible articles. Annotation for genes and quantitative trait loci (QTL), and QTL enrichment analysis were conducted using GALLO. Gene prioritization analysis was performed by a guilty-by-association approach using GUILDify and ToppGene. From 52 articles included within this systematic review, 30 articles were used for further functional analyses. Gene and QTL annotation resulted in 9,125 and 43,646 unique genes and QTL, respectively, from 39 studies. In general, overlapping of genes across studies was very low (mean ± SD = 0.02% ± 0.07%). Most annotated genes were associated with somatic cell count-related traits and the Holstein breed. Within all annotated genes, 74 genes were shared among Holstein, Jersey, and Ayrshire breeds. Approximately 7.5% of annotated QTL were related to QTL class "health." Within the health QTL class, 2.6 and 2.2% of QTL were associated with clinical mastitis and somatic cell count-related traits. Enrichment analysis of QTL demonstrated that many enriched QTL were associated with somatic cell score located in Bos taurus autosomes 5, 6, 16, and 20. The prioritization analysis resulted in 427 significant genes after multiple test correction (false discovery rate of 5%) from 26 studies. Most prioritized genes were located in Bos taurus autosomes 19 and 7, and most top-ranked genes were from the cytokine superfamily (e.g., chemokines, interleukins, transforming growth factors, and tumor necrosis factor genes). Although most prioritized genes (397) were associated with somatic cell count-related traits, only 54 genes were associated with clinical mastitis-related traits. Twenty-four genes (ABCC9, ACHE, ADCYAP1, ARC, BCL2L1, CDKN1A, EPO, GABBR2, GDNF, GNRHR, IKBKE, JAG1, KCNJ8, KCNQ1, LIFR, MC3R, MYOZ3, NFKB1, OSMR, PPP3CA, PRLR, SHARPIN, SLC1A3, and TNFRSF25) were reported for both somatic cell count and clinical mastitis-related traits. Prioritized genes were mainly associated with immune response, regulation of secretion, locomotion, cell proliferation, and development. In conclusion, this study provided a fine-mapping of previously identified genomic regions associated with resistance to mastitis and identified key functional candidate genes for resistance to mastitis, which can be used to develop enhanced genomic strategies to combat mastitis by increasing mastitis resistance through genetic selection.

In 2019, two Canadian provinces became the first jurisdictions in North America to pass deemed consent legislation to increase deceased organ donation and transplantation rates. We sought to explore the perspectives of the deemed consent legislation for organ donation in Canada from the viewpoint of individuals commenting on press articles.In this qualitative descriptive study, we extracted public comments regarding deemed consent from online articles published by four major Canadian news outlets between January 2019 and July 2020. A total of 4357 comments were extracted from 35 eligible news articles. Comments were independently analyzed by two research team members using a conventional content analysis approach.Commenters' perceptions of the deemed consent legislation for organ donation in Canada predominantly fit within three organizational groups: perceived positive implications of the bills, perceived negative implications of the bills, and key considerations. Three themes emerged within each group that summarized perspectives of the proposed legislation. Themes regarding the perceived positive implications of the bills included majority rules, societal effect, and prioritizing donation. Themes regarding the perceived negative implications of the bills were a right to choose, the potential for abuse and errors, and a possible slippery slope. Improving government transparency and communication, clarifying questions and addressing concerns, and providing evidence for the bills were identified as key considerations.If deemed consent legislation is meant to increase organ donation and transplantation, addressing public concerns will be important to ensure successful implementation.

Introduction La compréhension des motifs de la grande variation des dépenses en soins de santé chez les patients atteints de schizophrénie est susceptible de contribuer à l’élaboration d’interventions visant à améliorer les résultats pour les patients et l’efficience des dépenses en soins de santé. Notre étude visait à déterminer les facteurs associés aux dépenses élevées en soins de santé chez les patients atteints de schizophrénie. Méthodologie Cette étude transversale en série a utilisé les dossiers de santé administratifs de résidents de l’Alberta (Canada) entre le 1er janvier 2008 et le 31 décembre 2017 ainsi que les méthodes provinciales d’établissement des coûts afin de calculer les dépenses totales en soins de santé et les coûts par secteur. Les facteurs modifiant la probabilité d’être un patient à coût élevé (dans le 95e percentile ou plus) atteint de schizophrénie ont été estimés au moyen d’équations d’estimation généralisées. Résultats Cette étude a recueilli 242 818 années‑personnes d’observations chez 38 177 patients atteints de schizophrénie. Une probabilité accrue d’être un patient à coût élevé a été associée à un âge plus jeune (18 à 29 ans), le fait d’être de sexe masculin, un état de logement instable et des besoins de soins dans de multiples spécialités médicales. Les associations estimées les plus fortes entre l’état d’un patient à coût élevé et la comorbidité concernaient le cancer métastatique (RC = 2,26) et la cirrhose (RC = 2,07). À l’opposé, la polypharmacie a été associée à une diminution de la probabilité de coûts élevés comparativement aux patients non traités. Conclusion Les facteurs associés au fait d’être un patient à coût élevé résultent d’interactions complexes entre facteurs individuels, facteurs structurels et facteurs liés au traitement. Les efforts visant à améliorer les résultats des patients et à faire face à la hausse des coûts des soins de santé doivent tenir compte de la valeur de l’affectation des ressources au dépistage précoce et au soutien des patients atteints de schizophrénie ainsi qu’à la prévention et à la gestion de la comorbidité

Background: Confirmatory tests are recommended for diagnosing primary aldosteronism, but the supporting evidence is unclear. Methods: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials. Studies evaluating any guideline-recommended confirmatory test (ie, saline infusion test, salt loading test, fludrocortisone suppression test, and captopril challenge test), compared with a reference standard were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. Meta-analyses were conducted using hierarchical summary receiver operating characteristic models. Results: Fifty-five studies were included, comprising 26 studies (3654 participants) for the recumbent saline infusion test, 4 studies (633 participants) for the seated saline infusion test, 2 studies (99 participants) for the salt loading test, 7 studies (386 participants) for the fludrocortisone suppression test, and 25 studies (2585 participants) for the captopril challenge test. Risk of bias was high, affecting more than half of studies, and across all domains. Studies with case-control sampling overestimated accuracy by 7-fold (relative diagnostic odds ratio, 7.26 [95% CI, 2.46–21.43]) and partial verification or use of inconsistent reference standards overestimated accuracy by 5-fold (5.12 [95% CI, 1.48–17.77]). There were large variations in how confirmatory tests were conducted, interpreted, and verified. Under most scenarios, confirmatory testing resulted in an excess of missed cases. The certainty of evidence underlying each test (Grading of Recommendations, Assessment, Development, and Evaluations) was very low. Conclusions: Recommendations for confirmatory testing in patients with abnormal screening tests and high probability features of primary aldosteronism are based on very low-quality evidence and their routine use should be reconsidered.

OBJECTIVE Endoscopic third ventriculostomy and choroid plexus cauterization (ETV+CPC) is a novel procedure for infant hydrocephalus that was developed in sub-Saharan Africa to mitigate the risks associated with permanent implanted shunt hardware. This study summarizes the hydrocephalus literature surrounding the ETV+CPC intraoperative abandonment rate, perioperative mortality rate, cerebrospinal fluid infection rate, and failure rate. METHODS This systematic review and meta-analysis followed a prespecified protocol and abides by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy using MEDLINE, EMBASE, PsychInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from database inception to October 2019. Studies included controlled trials, cohort studies, and case-control studies of patients with hydrocephalus younger than 18 years of age treated with ETV+CPC. Pooled estimates were calculated using DerSimonian and Laird random-effects modeling, and the significance of subgroup analyses was tested using meta-regression. The quality of the pooled outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS After screening and reviewing 12,321 citations, the authors found 16 articles that met the inclusion criteria. The pooled estimate for the ETV+CPC failure rate was 0.44 (95% CI 0.37–0.51). Subgroup analysis by geographic income level showed statistical significance (p < 0.01), with lower-middle-income countries having a lower failure rate (0.32, 95% CI 0.28–0.36) than high-income countries (0.53, 95% CI 0.47–0.60). No difference in failure rate was found between hydrocephalus etiology (p = 0.09) or definition of failure (p = 0.24). The pooled estimate for perioperative mortality rate (n = 7 studies) was 0.001 (95% CI 0.00–0.004), the intraoperative abandonment rate (n = 5 studies) was 0.04 (95% CI 0.01–0.08), and the postoperative CSF infection rate (n = 5 studies) was 0.0004 (95% CI 0.00–0.003). All pooled outcomes were found to be low-quality evidence. CONCLUSIONS This systematic review and meta-analysis provides the most comprehensive pooled estimate for the ETV+CPC failure rate to date and demonstrates, for the first time, a statistically significant difference in failure rate by geographic income level. It also provides the first reported pooled estimates for the risk of ETV+CPC perioperative mortality, intraoperative abandonment, and CSF infection. The low quality of this evidence highlights the need for further research to improve the understanding of these critical clinical outcomes and their relevant explanatory variables and thus to appreciate which patients may benefit most from an ETV+CPC. Systematic review registration no.: CRD42020160149 (https://www.crd.york.ac.uk/prospero/)

Migrant populations in high-income countries have faced myriad health and social inequities during the COVID-19 pandemic. Migrants often work in frontline essential services that expose them to COVID-19. Migrant workers in meat processing plants have endured large COVID-19 outbreaks across multiple countries.We examine current scientific evidence around COVID-19 transmission, outcomes, and prevention for migrant workers and highlight meat processing plants as an example.We performed a series of PubMed searches between January 1, 2020 and January 12, 2022.Migrant workers in high-income countries often work in occupations at high risk for COVID-19 transmission, contract COVID-19 at higher rates, and experience worse outcomes than native-born counterparts. For example, meat processing plants represent almost ideal environments for rapid and large-scale SARS-CoV-2 viral transmission; often, large migrant workforces confined to small workspaces perform physically demanding work in noisy environments that require shouting to communicate, increasing workers' respiratory rates and the quantity of aerosolized droplets expelled and thus increasing viral transmission risk. Although enhanced vaccination outreach programs remain an important equity approach for migrant worker safety, they alone are insufficient. The emergence and rapid spread of multiple increasingly transmissible SARS-CoV-2 variants of concern with variable vaccine escape properties, including Omicron in November 2021, highlight the importance of improved infection prevention and control strategies to protect migrant workers. Across countries, strategies such as improving ventilation and mask quality in many high-risk occupational settings are already required by employment law. Universal mandatory vaccination program should also be considered.COVID-19 transmission prevention for migrant workers requires an aggressive multicomponent plan that includes (a) improved on-site ventilation and infection prevention and control strategies; (b) improved social supports such as paid sick leave; (c) mobile vaccination clinics and community engagement to overcome vaccine hesitancy and barriers; and (d) consideration of universal mandatory vaccination programs.

There is substantial variability in the reported incidence and outcomes of acute kidney injury (AKI). The extent to which this is attributable to differences in source populations versus methodological differences between studies is uncertain. We used 4 population-based datasets from Canada, Denmark, and the United Kingdom to measure the annual incidence and prognosis of AKI and acute kidney disease (AKD), using a homogenous analytical approach that incorporated KDIGO creatinine-based definitions and subsets of the AKI/AKD criteria. The cohorts included 7 million adults ≥18 years of age between 2011 and 2014; median age 59-68 years, 51.9-54.4% female sex. Age- and sex-standardised incidence rates for AKI or AKD were similar between regions and years; range 134.3-162.4 events/10,000 person years. Among patients who met either KDIGO 48-hour or 7-day AKI creatinine criteria, the standardised 1-year mortality was similar (30.4%-38.5%) across the cohorts, which was comparable to standardised 1-year mortality among patients who met AKI/AKD criteria using a baseline creatinine within 8-90 days prior (32.0%-37.4%). Standardised 1-year mortality was lower (21.0%-25.5% across cohorts) among patients with AKI/AKD ascertained using a baseline creatinine >90 days prior. These findings illustrate that the incidence and prognosis of AKI and AKD based on KDIGO criteria are consistent across 3 high-income countries when capture of laboratory tests is complete, creatinine-based definitions are implemented consistently within but not beyond a 90-day period, and adjustment is made for population age and sex. These approaches should be consistently applied to improve the generalizability and comparability of AKI research and clinical reporting.

Albumin-to-creatinine ratio (ACR), the preferred method to quantify proteinuria, can be calculated from urine dipstick protein or protein-to-creatinine ratio (PCR). The performance of calculated vs. measured ACR in predicting kidney failure and death without kidney failure in people with chronic kidney disease (CKD) is unknown. Here, we used population-based data from Alberta, Canada, to identify adults with incident moderate-severe CKD (sustained for more than 90 days) from 2008-04-01 to 2017-03-31, who had same-day measures of ACR and urine dipstick (ACR-dipstick cohort) or PCR (ACR-PCR cohort) in the two years before cohort entry. We followed participants until 2019-03-31 and trained competing risk models of kidney failure and death without kidney failure including age, sex, estimated glomerular filtration rate, diabetes, cardiovascular disease, and either measured or calculated ACR. Model performance was tested in cohorts created using the same algorithm in Manitoba, Canada. The ACR-dipstick and ACR-PCR cohorts included 18,731 and 4,542 people (training cohorts) and 821 and 1,831 people (testing cohorts), respectively. In internal and external testing, there was closer agreement between predictions based on measured vs. PCR-calculated ACR than between those based on measured vs. dipstick-calculated ACR. The dipstick-calculated ACR had higher Brier scores than measured ACR from year three for both outcomes, indicating worsening calibration. Models including measured or calculated ACR had similar discrimination: year one-to-five area under the receiver operating characteristic curve of 83-89% for kidney failure and 69-75% for mortality. Thus, if confirmed in different ethnic groups, calculated ACR can be used for risk predictions when the measured ACR is not available. PCR-calculated ACR may have superior performance to dipstick-calculated ACR.

Objectives Schizophrenia is characterized by high levels of disability often resulting in increased healthcare utilization and spending. With expanding healthcare costs across all healthcare sectors, there is a need to understand how healthcare spending has changed over time. We conducted a population-based study using administrative health data from Alberta, Canada, to describe changes in medical complexity and direct healthcare spending among patients with schizophrenia over a 10-year period. Methods A serial cross-sectional study from January 1, 2008, to December 31, 2017, was conducted to determine changes in demographic characteristics, medical complexity, and costs among all adults (18 years or older) with schizophrenia. Total healthcare spending and sector-specific costs attributable to hospitalizations, emergency department visits, practitioner billings, and prescriptions were calculated and compared over time. Results Over the 10-year period the contact prevalence of patients with schizophrenia increased from 0.6% ( n = 16,183) to 1.0% ( n = 33,176) within the province. There was a marked change in medical complexity with the number of patients living with 3 or more comorbidities increasing from 33.0% to 47.3%. Direct annual healthcare costs increased 2-fold from 321 to 639 million CAD (493 million USD) with a 7-fold increase in medication expenditures over the 10-year time frame. As of 2017, spending on pharmaceutical treatment surpassed hospitalizations as the leading spending category in this population. Conclusions Healthcare spending among patients with schizophrenia continues to increase and may be partially attributable to growing rates of multimorbidity within this population. Although promising second-generation antipsychotic medications have entered the market, this has resulted in considerable changes in the distribution of healthcare spending over time. These findings will inform policy discussions around resource allocation and efforts to curb health spending while also improving care for patients with schizophrenia.

Background People with kidney failure have a high incidence of major surgery, though the risk of perioperative outcomes at a population-level is unknown. Our objective was to estimate the proportion of people with kidney failure that experience acute myocardial infarction (AMI) or death within 30 days of major non-cardiac surgery, based on surgery type. Methods In this retrospective population-based cohort study, we used administrative health data to identify adults from Alberta, Canada with major surgery between April 1, 2005 and February 28, 2017 that had preoperative estimated glomerular filtration rates (eGFRs) 2 or received chronic dialysis. The index surgical procedure for each participant was categorized within one of fourteen surgical groupings based on Canadian Classification of Health Interventions (CCI) codes applied to hospitalization administrative datasets. We estimated the proportion of people that had AMI or died within 30 days of the index surgical procedure (with 95% confidence intervals [CIs]) following logistic regression, stratified by surgery type. Results Overall, 3398 people had a major surgery (1905 hemodialysis; 590 peritoneal dialysis; 903 non-dialysis). Participants were more likely male (61.0%) with a median age of 61.5 years (IQR 50.0–72.7). Within 30 days of surgery, 272 people (8.0%) had an AMI or died. The probability was lowest following ophthalmologic surgery at 1.9% (95%CI: 0.5, 7.3) and kidney transplantation at 2.1% (95%CI: 1.3, 3.2). Several types of surgery were associated with greater than one in ten risk of AMI or death, including retroperitoneal (10.0% [95%CI: 2.5, 32.4]), intra-abdominal (11.7% [8.7, 15.5]), skin and soft tissue (12.1% [7.4, 19.1]), musculoskeletal (MSK) (12.3% [9.9, 15.5]), vascular (12.6% [10.2, 15.4]), anorectal (14.7% [6.3, 30.8]), and neurosurgical procedures (38.1% [20.3, 59.8]). Urgent or emergent procedures had the highest risk, with 12.1% experiencing AMI or death (95%CI: 10.7, 13.6) compared with 2.6% (1.9, 3.5) following elective surgery. Conclusions After major non-cardiac surgery, the risk of death or AMI for people with kidney failure varies significantly based on surgery type. This study informs our understanding of surgery type and risk for people with kidney failure. Future research should focus on identifying high risk patients and strategies to reduce these risks.

IntroductionThe use of gender-affirming oestrogen therapy (GAOT) is an integral part of the gender-affirming transition process for transgender women (assigned male at birth who identify as women) and gender-diverse individuals. However, its use may present significant cardiovascular implications, which may be influenced by systemic oestradiol levels. Therefore, we aim to establish the association between serum oestradiol levels and incidence of adverse cardiovascular events in individuals using GAOT.Methods and analysisWe will conduct a systematic review addressing the association between serum oestradiol levels and risk of adverse cardiovascular events in individuals using GAOT. Our primary outcome is the incidence of adverse cardiovascular events, our secondary outcome is the incidence of cardiovascular-related mortality and our tertiary outcome is cardiovascular-related risk factors. Electronic databases (Cochrane Central Register of Controlled Trials, Embase, MEDLINE and Web of Science) will be searched from inception until September 2022. Two investigators will independently complete screening to determine appropriateness of inclusion. Extracted data will include information on serum sex hormone levels (oestradiol and testosterone), participants, GAOT (route of administration, formulations, dosages and duration of exposure), incidence of cardiovascular outcomes, study quality and risk of bias. Inter-reviewer reliability will be calculated at both phases. Data will be presented both descriptively and meta-analysed using a random effects model, if appropriate. Heterogeneity will be explored and meta-regressed if noted.Ethics and disseminationEthics approval is not needed. We will disseminate findings through international conferences, distributions to transgender and gender-diverse support organisations, decision-makers and key stakeholders. The final systematic review will be published in a peer-reviewed journal.Trial registration numberCRD42021247717.

Understanding the reasons for the wide variation in health care spending among patients with schizophrenia may benefit the development of interventions aimed at improving patient outcomes and health care spending efficiency. The aim of our study was to determine factors associated with high health care spending in the patient population.A serial cross-sectional study used the administrative health records of residents of Alberta, Canada between 1 January 2008 and 31 December 2017 and provincial costing methodologies to calculate total health care spending and sector-specific costs. Factors that modified the odds of being a high cost (i.e. 95th percentile or higher) patient with schizophrenia were estimated using generalized estimating equations.This study captured 242 818 person-years of observations among 38 177 unique patients with schizophrenia. Increased odds of being a high-cost patient were associated with younger age (18-29 years), male sex, unstable housing status and requiring care from multiple medical specialties. The strongest estimated associations between high cost status and comorbidity were for metastatic cancer (OR = 2.26) and cirrhosis (OR = 2.07). In contrast, polypharmacy was associated with a decreased odds of being high cost compared with untreated patients.Factors associated with being a high-cost patient are the result of complex interactions between individual, structural and treatment-related factors. Efforts to improve patient outcomes and address rising health care costs must consider the value of allocating resources towards early detection and support of patients with schizophrenia along with the prevention/management of comorbidity.La compréhension des motifs de la grande variation des dépenses en soins de santé chez les patients atteints de schizophrénie est susceptible de contribuer à l’élaboration d’interventions visant à améliorer les résultats pour les patients et l’efficience des dépenses en soins de santé. Notre étude visait à déterminer les facteurs associés aux dépenses élevées en soins de santé chez les patients atteints de schizophrénie.Cette étude transversale en série a utilisé les dossiers de santé administratifs de résidents de l’Alberta (Canada) entre le 1er janvier 2008 et le 31 décembre 2017 ainsi que les méthodes provinciales d’établissement des coûts afin de calculer les dépenses totales en soins de santé et les coûts par secteur. Les facteurs modifiant la probabilité d’être un patient à coût élevé (dans le 95e percentile ou plus) atteint de schizophrénie ont été estimés au moyen d’équations d’estimation généralisées.Cette étude a recueilli 242 818 années-personnes d’observations chez 38 177 patients atteints de schizophrénie. Une probabilité accrue d’être un patient à coût élevé a été associée à un âge plus jeune (18 à 29 ans), le fait d’être de sexe masculin, un état de logement instable et des besoins de soins dans de multiples spécialités médicales. Les associations estimées les plus fortes entre l’état d’un patient à coût élevé et la comorbidité concernaient le cancer métastatique (RC = 2,26) et la cirrhose (RC = 2,07). À l’opposé, la polypharmacie a été associée à une diminution de la probabilité de coûts élevés comparativement aux patients non traités.Les facteurs associés au fait d’être un patient à coût élevé résultent d’interactions complexes entre facteurs individuels, facteurs structurels et facteurs liés au traitement. Les efforts visant à améliorer les résultats des patients et à faire face à la hausse des coûts des soins de santé doivent tenir compte de la valeur de l’affectation des ressources au dépistage précoce et au soutien des patients atteints de schizophrénie ainsi qu’à la prévention et à la gestion de la comorbidité.Younger patients with schizophrenia (18–29 years old) were more likely than older patients to be high cost. Of the 29 comorbidities assessed, 17 were associated with an increased odds of being a high­cost patient. Increasing involvement of medical specialties increases the odds of being a high­cost patient. The odds of being a high­cost patient if unstably housed are 2.49 times greater than if stably housed. This suggests that the risk factors driving cost extend beyond clinical or demographic domains.Les patients plus jeunes atteints de schizophrénie (18 à 29 ans) étaient plus susceptibles que les patients plus âgés d’être des patients à coûts élevés. Sur les 29 comorbidités évaluées, 17 ont été associées à une probabilité accrue d’être un patient à coût élevé. Une contribution plus importante de spécialités médicales augmente la probabilité d’être un patient à coût élevé. La probabilité pour un patient d’être un patient à coût élevé est 2,49 fois plus forte s’il est mal logé que s’il est logé de façon stable. Cela laisse penser que les facteurs de risque à l’origine des coûts transcendent les domaines cliniques et les caractéristiques individuelles.

Background Treatment of endoscopically resected T1 colorectal cancers is based on the risk of lymph node metastasis. Risk is based on histopathologic features, although there is lack of consensus as to what constitutes high-risk features. Objective The purpose of this study was to conduct a systematic review and meta-analysis of histopathologic risk factors for lymph node metastasis. Data sources A search of MEDLINE, Embase, Scopus, and Cochrane controlled register of trials for risk factors for lymph node metastasis was performed from inception until August 2018. Study selection Included patients must have had an oncologic resection to confirm lymph node status and reported at least 1 histopathologic risk factor. Intervention Rates of lymph node positivity were compared between patients with and without risk factors. Main outcome measures We report the results of the meta-analysis as ORs. Results Of 8592 citations, 60 met inclusion criteria. Pooled analyses found that lymphovascular invasion, vascular invasion, neural invasion, and poorly differentiated histology were significantly associated with lymph node metastasis, as were depths of 1000 µm (OR = 2.76), 1500 µm (OR = 4.37), 2000 µm (OR = 2.37), submucosal level 3 depth (OR = 3.08), and submucosal level 2/3 (OR = 3.08) depth. Depth of 3000 µm, Haggitt level 4, and widths of 3000 µm and 4000 µm were not significantly associated with lymph node metastasis. Tumor budding (OR = 4.99) and poorly differentiated clusters (OR = 14.61) were also significantly associated with lymph node metastasis. Limitations Included studies reported risk factors independently, making it impossible to examine the additive metastasis risk in patients with numerous risk factors. Conclusions We identified 1500 μm as the depth most significantly associated with lymph node metastasis. Novel factors tumor budding and poorly differentiated clusters were also significantly associated with lymph node metastasis. These findings should help inform guidelines regarding risk stratification of T1 tumors and prompt additional investigation into the exact contribution of poorly differentiated clusters to lymph node metastasis.

Rationale & Objective There is limited evidence to guide follow-up after acute kidney injury (AKI). Knowledge gaps include which patients to prioritize, at what time point, and for mitigation of which outcomes. In this study, we sought to compare the net benefit of risk model–based clinical decisions following AKI. Study Design External validation of 2 risk models of AKI outcomes: the Grampian -Aberdeen (United Kingdom) AKI readmissions model and the Alberta (Canada) kidney disease risk model of chronic kidney disease (CKD) glomerular (G) filtration rate categories 4 and 5 (CKD G4 and G5). Process mining to delineate existing care pathways. Setting & Participants Validation was based on data from adult hospital survivors of AKI from Grampian, 2011-2013. Predictors KDIGO-based measures of AKI severity and comorbidities specified in the original models. Outcomes Death or readmission within 90 days for all hospital survivors. Progression to new CKD G4-G5 for patients surviving at least 90 days after AKI. Analytical Approach Decision curve analysis to assess the “net benefit” of use of risk models to guide clinical care compared to alternative approaches (eg, prioritizing all AKI, severe AKI, or only those without kidney recovery). Results 26,575 of 105,461 hospital survivors in Grampian (mean age, 60.9 ± 19.8 [SD] years) were included for validation of the death or readmission model, and 9,382 patients (mean age, 60.9 ± 19.8 years) for the CKD G4-G5 model. Both models discriminated well (area under the curve [AUC], 0.77 and 0.86, respectively). Decision curve analysis showed greater net benefit for follow up of all AKI than only severe AKI in most cases. Both original and refitted models provided net benefit superior to any other decision strategy. In process mining of all hospital discharges, 41% of readmissions and deaths occurred among people recovering after AKI. 1,464 of 3,776 people (39%) readmitted after AKI had received no intervening monitoring. Limitations Both original models overstated risks, indicating a need for regular updating. Conclusions Follow up after AKI has potential net benefit for preempting readmissions, death, and subsequent CKD progression. Decisions could be improved by using risk models and by focusing on AKI across a full spectrum of severity. The current lack of monitoring among many with poor outcomes indicates possible opportunities for implementation of decision support.

Background Characteristics of patients using newer 2nd and 3rd line antidiabetic drugs in a real-world setting are poorly understood. We described the characteristics of new users of sodium-glucose co-transporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in Canada and the United Kingdom (UK) between 2016 and 2018. Methods We conducted a multi-database cohort study using administrative health databases from 7 Canadian provinces and the UK Clinical Practice Research Datalink. We assembled a base cohort of antidiabetic drug users between 2006 and 2018, from which we constructed 3 cohorts of new users of SGLT-2i, DPP-4i, and GLP-1 RA between 2016 and 2018. Results Our cohorts included 194,070 new users of DPP-4i, 166,722 new users of SGLT-2i, and 27,719 new users of GLP-1 RA. New users of GLP-1 RA were more likely to be younger (mean ± SD: 56.7 ± 12.2 years) than new users of DPP-4i (67.8 ± 12.3 years) or SGLT-2i (64.4 ± 11.1 years). In Canada, new users of DPP-4i were more likely to have a history of coronary artery disease (22%) than new users of SGLT-2i (20%) or GLP-1 RA (15%). Conclusion Although SGLT-2i, DPP-4i, and GLP-1 RAs are recommended as 2nd or 3rd line therapy for type 2 diabetes, important differences exist in the characteristics of users of these drugs. Contrary to existing guidelines, new users of DPP-4i had a higher prevalence of cardiovascular disease at baseline than new users of SGLT2i or GLP-1RA.

Background There is increasing evidence demonstrating the importance of the neighbourhood built environment in supporting physical activity. Physical activity provides numerous health benefits including improvements in health-related fitness (i.e., muscular, cardiorespiratory, motor, and morphological fitness). Emerging evidence also suggests that the neighbourhood built environment is associated with health-related fitness. Our aim was to summarize evidence on the associations between the neighbourhood built environment and components of health-related fitness in adults. Methods We undertook a systematic review following PRISMA guidelines. Our data sources included electronic searches in MEDLINE, Embase, CINAHL, Web of Science, SPORTDiscus, Environment Complete, ProQuest Dissertations and Theses, and Transport Research International Documentation from inception to March 2021. Our eligibility criteria consisted of observational and experimental studies estimating associations between the neighbourhood built environment and health-related fitness among healthy adults (age ≥ 18 years). Eligible studies included objective or self-reported measures of the neighbourhood built environment and included either objective or self-reported measures of health-related fitness. Data extraction included study design, sample characteristics, measured neighbourhood built environment characteristics, and measured components of health-related fitness. We used individual Joanna Briggs Institute study checklists based on identified study designs. Our primary outcome measure was components of health-related fitness (muscular; cardiorespiratory; motor, and morphological fitness). Results Twenty-seven studies (sample sizes = 28 to 419,562; 2002 to 2020) met the eligibility criteria. Neighbourhood destinations were the most consistent built environment correlate across all components of health-related fitness. The greatest number of significant associations was found between the neighbourhood built environment and morphological fitness while the lowest number of associations was found for motor fitness. The neighbourhood built environment was consistently associated with health-related fitness in studies that adjusted for physical activity. Conclusion The neighbourhood built environment is associated with health-related fitness in adults and these associations may be independent of physical activity. Longitudinal studies that adjust for physical activity (including resistance training) and sedentary behaviour, and residential self-selection are needed to obtain rigorous causal evidence for the link between the neighbourhood built environment and health-related fitness. Trial registration Protocol registration: PROSPERO number CRD42020179807.

IntroductionHomelessness poses unique barriers to diabetes management. Population-level data on the risks of diabetes outcomes among people experiencing homelessness are needed to inform resource investment. The aim of this study was to create a population cohort of people with diabetes with a history of homelessness to understand their unique demographic and clinical characteristics and improve long-term health outcomes.MethodsOntario residents with diabetes were identified in administrative hospital databases between 2006 and 2020. A history of homelessness was identified using a validated algorithm. Demographic and clinical characteristics were compared between people with and without a history of homelessness. Propensity score matching was used to create a cohort of people with diabetes experiencing homelessness matched to comparable non-homeless controls.ResultsOf the 1,455,567 patients with diabetes who used hospital services, 0.7% (n=8,599) had a history of homelessness. Patients with a history of homelessness were younger (mean: 54 vs 66 years), more likely to be male (66% vs 51%) and more likely to live in a large urban centre (25% vs 7%). Notably, they were also more likely to be diagnosed with mental illness (49% vs 2%) and be admitted to a designated inpatient mental health bed (37% versus 1%). A suitable match was found for 5219 (75%) people with documented homelessness. The derived matched cohort was balanced on important demographic and clinical characteristics.ConclusionPeople with diabetes experiencing homelessness have unique characteristics that may require additional supports. Population-level comparisons can inform the delivery of tailored diabetes care and self-management resources.

In this study on medication adherence among newly diagnosed patients with uncomplicated, incident hypertension, we conducted a retrospective cohort study using available administrative and laboratory data from April 1, 2012 to March 31, 2017 in Alberta, Canada to understand the extent to which baseline laboratory assessment and/or subsequent follow-up was associated with persistence with antihypertensive therapy. We determined the frequency of baseline and follow-up testing and compared the rates of medication persistence by patient-, neighbourhood-, and treatment-related factors. Of 103 232 patients with newly diagnosed, uncomplicated hypertension who filled their first prescription within our study timeframe, 52.5% were non-persistent within 6 months. Persistent patients were more often female and residing in neighbourhoods with higher social status (with exception to rurality). Aside from older age, the strongest predictor of persistence was performance of laboratory testing related to hypertension with an apparent effect in which higher levels of medication persistence were seen with more frequent laboratory testing. We concluded that medication persistence was far from optimal, dropping off considerably after 6 months for more than half of patients. Medication persistence is a substantial barrier to realizing the full societal benefits of antihypertensive treatment. Ongoing follow up with patients, including laboratory testing, may be a critical component of better long term treatment persistence.

A range of first-line similarly effective medications ranging in price are recommended for treating uncomplicated hypertension. Considering drug costs alone, thiazides and thiazide-like diuretics are the most cost-efficient option. We determined incident prescribing of thiazides for newly diagnosed hypertension as first-line treatment in Alberta, factors that predicted receiving thiazides vs more costly medications, and how much could be saved if more patients were prescribed thiazides.Using a retrospective cohort design, factors predicting receiving thiazides vs other agents were determined using mixed effects logistic regression. Cost savings were simulated by shifting patients from other antihypertensive medications to thiazides and calculating the difference.Within our cohort of 89,548 adults, only 12% received thiazides as first-line treatment whereas 44% received angiotensin converting enzyme inhibitors, 17% received angiotensin receptor blockers, 16% received calcium channel blockers, and 10% received β-blockers. Antihypertensive medications were typically prescribed by office-based, general practitioners (88%). Being male and receiving a prescription from a physician with ≥ 20 years of practice and a high clinical workload were associated with increased odds of receiving nonthiazides. In the extreme case that all patients received thiazides as their first prescription, spending would have been reduced by a maximum of 95% (CAD$1.8 million).Only 12% of Albertan adults with incident, uncomplicated hypertension were prescribed thiazides as first-line treatment. With the opportunity for drug cost savings, future research should evaluate the risk of adverse events and side effects across the drug classes and whether the costs associated with managing those risks could offset the savings achieved through increased thiazide use.De nombreux médicaments tous aussi efficaces les uns que les autres, mais de prix variable, sont recommandés pour le traitement de première intention de l’hypertension non compliquée. Si l’on tient compte du coût du médicament seulement, les thiazides et les diurétiques apparentés aux thiazides sont les options les plus économiques. Nous avons évalué le taux de prescription d’un thiazide pour le traitement de première intention de l’hypertension nouvellement diagnostiquée en Alberta, les facteurs de prédiction de la prescription d’un thiazide plutôt que d’un autre médicament plus coûteux, ainsi que les économies qui pourraient être réalisées si on prescrivait un thiazide à un plus grand nombre de patients.Dans le cadre de notre étude de cohorte rétrospective, nous avons déterminé les facteurs de prédiction de la prescription d’un thiazide plutôt que d’un autre agent à l’aide d’une régression logistique à effets mixtes. Nous avons simulé les économies qui pourraient être réalisées en faisant passer à un thiazide les patients à qui un autre médicament antihypertenseur a été prescrit et en calculant la différence.Dans notre cohorte de 89 548 adultes, seulement 12 % des patients ont reçu un thiazide en première intention; 44 % ont reçu un inhibiteur de l’enzyme de conversion de l’angiotensine; 17 %, un antagoniste des récepteurs de l’angiotensine; 16 %, un inhibiteur calcique; et 10 %, des bêtabloquants. Les agents antihypertenseurs sont généralement prescrits par des omnipraticiens en cabinet (88 %). Le fait d’être un homme et le fait d’obtenir une prescription auprès d’un médecin exerçant depuis au moins 20 ans et ayant une lourde charge de travail clinique étaient associés à une probabilité supérieure de recevoir un agent autre qu’un thiazide. Dans le cas extrême où tous les patients se verraient prescrire un thiazide en première intention, la réduction des dépenses pourrait atteindre 95 % (soit 1,8 million de dollars canadiens).En Alberta, un thiazide a été prescrit en première intention à seulement 12 % des adultes venant de recevoir un diagnostic d’hypertension non compliquée. Compte tenu des économies qui pourraient être réalisées si un thiazide était prescrit dans ce contexte, il conviendrait d’effectuer des recherches plus poussées pour évaluer le risque de manifestations indésirables et d’effets secondaires associé aux différentes classes de médicaments, et pour déterminer si les coûts liés à la prise en charge de ce risque annuleraient les économies réalisées en augmentant le recours aux thiazides.

Background Trends in off-label postpartum use of domperidone and the impact of safety advisories on its use remain unknown. Our objectives were to describe postpartum use of domperidone in Canada, to evaluate the impact of Health Canada advisories on prescribing patterns, and to describe the association between domperidone use and a composite end point of sudden cardiac death or ventricular tachycardia (VT) among postpartum patients. Methods We conducted a multidatabase cohort study involving pregnant patients with live births between 2004 and 2017 using administrative health databases from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario). We excluded patients with less than 1 year of prepregnancy database history and with approved indications for domperidone. We assessed domperidone use in the 6 months postpartum and the impact of the 2012 and 2015 Health Canada advisories on prescribing via interrupted time series analysis. We estimated crude rates of VT and sudden cardiac death. Results We included 1 190 987 live births. Mean maternal age was 28.6 (standard error 0.6) years. Domperidone use increased over time, from 7% in 2003-2005 to 12% in 2009-2011, when it plateaued. The 2012 advisory was followed by a drop in use and a reduction in slope, and the 2015 advisory had a more modest impact. Crude analysis suggests that domperidone may be associated with increased VT or sudden cardiac death (0.74 v. 0.37 per 10 000 person-years; difference per 10 000 person-years: 0.37, 95% confidence interval -0.67 to 1.41). Interpretation Postpartum domperidone use increased between 2004 and 2017, with prescribing attenuated after Health Canada advisories and a very low absolute rate of VT or sudden cardiac death. These findings suggest that Health Canada advisories affected prescribing; any potential increase in VT or sudden cardiac death with use of domperidone is small and could not be confirmed in this large study STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04024865.

INTRODUCTION: CF is a genetic disease that can lead to significant morbidity. As the CF population increases and treatment regimens escalate in complexity, CF care costs are expected to rise and co...

RATIONALE: Sleep disordered breathing (SDB) is associated with adverse health consequences that can be mitigated through timely and effective management. Guidelines provide wait time targets, but t...

Aims Current guidelines recommend surgery within 48 hours among patients presenting with hip fractures; however, optimal surgical timing for patients on oral anticoagulants (OACs) remains unclear. Individual studies are limited by small sample sizes and heterogeneous outcomes. The aim of this study was to conduct a systematic review and meta-analysis to summarize the effect of pre-injury OACs on time-to-surgery (TTS) and all-cause mortality among older adults with hip fracture treated surgically. Methods We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 14 October 2019 to identify studies directly comparing outcomes among hip fracture patients receiving direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) prior to hospital admission to hip fracture patients not on OACs. Random effects meta-analyses were used to pool all outcomes (TTS, in-hospital mortality, and 30-day mortality). Results A total of 34 studies (involving 39,446 patients) were included in our systematic review. TTS was 13.7 hours longer (95% confidence interval (CI) 9.8 to 17.5; p < 0.001) among hip fracture patients on OACs compared to those not on OACs. This translated to a three-fold higher odds of having surgery beyond the recommended 48 hours from admission (odds ratio (OR) 3.0 (95% CI 2.1 to 4.3); p = 0.001). In-hospital mortality was higher (OR 1.4 (95% CI 1.0 to 1.8); p < 0.03) among anticoagulated patients. Among studies comparing anticoagulants, there was no statistically significant difference in time-to-surgery between patients taking a DOAC compared to a VKA. Conclusion Patients presenting with a hip fracture who were taking OACs prior to injury experience a delay in time-to-surgery and higher mortality than non-anticoagulated patients. Patients on DOACs may be at risk of further delays. Evaluating expedited surgical protocols in hip fracture patients on OACs is an urgent priority, with the potential to decrease morbidity and mortality in this group of high-risk patients. Cite this article: Bone Joint J 2021;103-B(2):222–233.

Objective The aim of the study was to perform a systematic review assessing the research investigating the association between celiac disease (CD) and autism spectrum disorder (ASD). Methods A literature search of MEDLINE and EMBASE was performed without limits placed on year or language. Observational studies reporting on the occurrence of CD among patients with ASD and/or the occurrence of ASD among patients with CD were included. Study design, characteristics, diagnostic criteria for ASD and CD, and the frequency of positive cases in the studied sample were recorded. Study quality was assessed using an adapted Newcastle-Ottawa Quality Assessment Scale. Due to substantial heterogeneity between studies, a meta-analysis was not performed. Results Of the 298 unique citations identified within our search strategy, 17 articles evaluating the association between CD and ASD were included. Of those articles, 13 observed samples of patients with ASD, and 6 observed samples of patients with CD. Overall, most studies had small sample sizes and reported no evidence for an association between the 2 conditions. However, a limited number of population-based studies of higher quality suggested a potential association between CD and ASD. Conclusions Most studies assessing an association between CD and ASD are at risk for systematic and/or random error. A potential link has, however, been shown in a handful of high-quality studies, and, therefore, this comorbidity cannot be ruled out. Future studies should recruit larger sample sizes, include precise definitions of CD and ASD, and exclude patients with ASD on a gluten-free diet.