Canadian Institute Research Articles

"I don't have the energy": Racial stress, young Black motherhood, and Canadian social policies.

Significant socio-economic, health, and mental health disparities due to highly entrenched and systemic anti-Black racism in Canadian institutions, policies, and practices are now well documented in research and policy reports. Yet, few in-depth studies have addressed the mental health impacts of anti-Black racism on Canadian populations. This article is rooted in a community-based, qualitative research project with young first and second-generation Black Caribbean-Canadian mothers and is informed by Black Feminist epistemologies and intersectional theories and methodologies. Our research demonstrates how participants' childhood experiences with xenophobic and racist immigration policies and educational, child welfare, and childcare systems caused their future mental health challenges as young Black mothers, and how these struggles were exacerbated by their encounters with the racist, ageist, xenophobic medical, social, and mental health services they had to access as young mothers. Based on these findings, we recommend enhancements to current social policies to minimize the differential mental health impacts on young Black Canadian mothers.

Profiling medical specialties and informing aspiring physicians: a data-driven approach.

A detailed, unbiased perspective of the inter-relations among medical fields could help students make informed decisions on their future career plans. Using a data-driven approach, the inter-relations among different medical fields were decomposed and clustered based on the similarity of their working environments.Publicly available, aggregate databases were merged into a single rich dataset containing demographic, working environment and remuneration information for physicians across Canada. These data were collected from the Canadian Institute for Health Information, the Canadian Medical Association, and the Institute for Clinical Evaluative Sciences, primarily from 2018 to 2019. The merged dataset includes 25 unique medical specialties, each with 36 indicator variables. Latent Profile Analysis (LPA) was used to group specialties into distinct clusters based on relatedness.The 25 medical specialties were decomposed into seven clusters (latent variables) that were chosen based on the Bayesian Information Criterion. The Kruskal-Wallis test identified eight indicator variables that significantly differed between the seven profiles. These variables included income, work settings and payment styles. Variables that did not significantly vary between profiles included demographics, professional satisfaction, and work-life balance satisfaction.The 25 analyzed medical specialties were grouped in an unsupervised manner into seven profiles via LPA. These profiles correspond to expected and meaningful groups of specialties that share a common theme and set of indicator variables (e.g. procedurally-focused, clinic-based practice). These profiles can help aspiring physicians narrow down and guide specialty choice.

Improved Resnet Model Based on Positive Traffic Flow for IoT Anomalous Traffic Detection

The Internet of Things (IoT) has been highly appreciated by several nations and societies as a worldwide strategic developing sector. However, IoT security is seriously threatened by anomalous traffic in the IoT. Therefore, creating a detection model that can recognize such aberrant traffic is essential to ensuring the overall security of the IoT. We outline the main approaches that are used today to detect anomalous network traffic and suggest a Resnet detection model based on fused one-dimensional convolution (Conv1D) for this purpose. Our method combines one-dimensional convolution and a Resnet network to create a new network model. This network model improves the residual block by including Conv1D and Conv2D layers for two-dimensional convolution. This change enhances the model’s ability to identify aberrant traffic by enabling the network to extract feature information from one-dimensional linearity and two-dimensional space. The CIC IoT Dataset from the Canadian Institute for Cybersecurity Research was used to assess the effectiveness of the proposed enhanced residual network technique. The outcomes demonstrate that the algorithm performs better at identifying aberrant traffic in the IoT than the original residual neural network. The accuracy achieved can be as high as 99.9%.

PL02.1.A DELINEATING AND TARGETING A NOVEL METABOLISM-BASED POST-TRANSLATIONAL MECHANISM REGULATING THE ABUNDANCE OF THE ‘UNDRUGGABLE’ ONCOPROTEIN C-MYC IN MEDULLOBLASTOMA

Abstract BACKGROUND Brain tumors are the leading cause of cancer death in children, and medulloblastoma (MB) is one of the most common pediatric central nervous system malignancies. Amplification of the c-MYC oncogene is frequently observed in the most aggressive and lethal subgroup of this disease, group 3 (G3), but not in other subgroups. Patients that have G3 MB tumors with high c-MYC abundance are more likely to present as metastatic and are prone to develop fatal recurrent tumors. Unfortunately, the functional ubiquity and disordered structure of c-MYC makes it difficult to target for cancer treatment. Therefore, it is critical to identify novel, out-of-the-box strategies to suppress oncogenic c-MYC in highly aggressive G3 MB brain tumors. Recently, metabolism has emerged as a major regulator of overall cellular signaling processes through post-translational and epigenetic mechanisms. While c-MYC is known to regulate cellular metabolism, whether metabolism plays a role in reciprocally supporting enhanced c-MYC abundance in cancer is unknown. We hypothesize that an intrinsic feedback mechanism may exist where metabolic activity modulates c-MYC abundance that could be exploited as a therapeutic strategy to improve outcomes for G3 MB patients. MATERIAL AND METHODS Using various well-characterized G3 MB cells, patient-derived G3 MB cells, orthotopic intracerebellar xenograft models, patient tumor bioinformatics, detailed biochemical characterization, and point-mutation analyses, we have identified a novel metabolism-dependent post-translational modification that regulates c-MYC stability in G3 MB. RESULTS In-depth molecular analyses unveiled that c-MYC is susceptible to oxidation and proteasomal degradation under conditions of metabolic stress. Targeting mitochondrial respiration via inhibition of complex-I promotes the accumulation of reactive oxygen species (ROS) and leads to rapid cysteine oxidation and proteasomal degradation of c-MYC in G3 MB cells, but not normal human brain astrocytes or neural stem cells (NSCs). Point mutation analysis combined with biochemical oxidation assays identified the specific cysteine residues of c-MYC that are susceptible to oxidation and ultimately responsible for enhanced c-MYC degradation following complex-I inhibition. Importantly, oral administration of a blood-brain barrier permeable complex-I inhibitor impaired the growth of intracerebellar MB xenograft tumors in mice, significantly prolonging animal survival. CONCLUSION Altogether, these findings unveil a novel mechanism through which metabolism regulates the post-translational stability of c-MYC and provides insights for designing rationale therapeutic strategies for the treatment of MB patients. SUPPORT This work is supported by a project grant from the Canadian Institutes of Health Research (CIHR).

Toward capabilities for adult working learners in Canada and the United States

AbstractThis article focuses on adult working learners who attend postsecondary institutions in Canada and the United States. We identify how these institutions deliver curriculum and instruction in the form of career‐technical education (CTE) and vocational education offering occupational credentials. In British Columbia and the U.S., most vocational programming culminates in the associate degree whereas the rest of Canada commonly confers diplomas as well as associate degrees. Other postsecondary credentials, including certifications and licensure, are integrated within programs in both countries. This chapter analyzes policies, programs, and practices for adult working learners in the two countries and provides perspectives on how a focus on the capabilities of adult working learners is beneficial to the needs of the individual, communities, and society as a whole.

Breast Cancer After Reduction Mammoplasty: A Population-Based Analysis of Incidence, Treatment and Screening Patterns.

The risk of breast cancer may be decreased in women who undergo reduction mammoplasty. The purpose of this study was to describe the incidence and treatment of breast cancer after reduction mammoplasty and to better understand the use of breast cancer screening modalities in these patients. This population-based retrospective analysis utilized the Discharge Abstract Database held by the Canadian Institute for Health Information and the National Ambulatory Care Reporting System to identify all women aged 20 years or older who underwent reduction mammoplasty in Alberta, Canada. The incidence and treatment of breast cancer were compared among patients who underwent reduction mammoplasty and age-sex-matched controls. Imaging utilization, including the use of mammography, ultrasound, and breast biopsy, was also compared. Between 2003 and 2007, 8021 patients over 20 years old underwent reduction mammoplasty in Alberta. Patients were followed for an average of 12.6 years. Eighty-nine (1.1%) patients who underwent reduction mammoplasty developed breast cancer after surgery, compared to 453 (1.9%) controls (P < 0.0001). Among patients diagnosed with breast cancer, there was no difference in patient and tumor characteristics. Women who underwent reduction mammoplasty were more likely to undergo mastectomy for cancer (41.6% vs 1.5%; P < 0.0001) and were more likely to undergo mammography (66.7% vs 58.7%; P < 0.0001), ultrasound (29.2% vs 26.2%; P < 0.0001) and biopsy for benign disease (7.2% vs 6%, P < 0.0001) compared to controls. Despite an increased frequency of breast cancer screening, the incidence of breast cancer is lower after reduction mammoplasty compared with women who did not undergo breast reduction. After a diagnosis of breast cancer, surgical treatment patterns differ between groups, whereby mastectomy is more common after reduction mammoplasty.

Measuring Potentially Avoidable Acute Care Transfers From Long-Term Care Homes in Quebec: a Cross Sectional Study.

Potentially avoidable emergency department transfers (PAEDTs) and hospitalizations (PAHs) from long-term care (LTC) homes are two key quality improvement metrics. We aimed to: 1) Measure proportions of PAEDTs and PAHs in a Quebec sample; and 2) Compare them with those reported for the rest of Canada. We conducted a repeated cross-sectional study of residents who were received at one tertiary hospital between April 2017 and March 2019 from seven LTC homes in Quebec, Canada. The MedUrge emergency department database was used to extract transfers and resident characteristics. Using published definitions, PAEDTs and PAHs were identified from principal emergency department and hospitalization diagnoses, respectively. PAEDT and PAH proportions were compared to those reported by the Canadian Institute for Health Information. A total of 1,233 transfers by 692 residents were recorded, among which 36.3% were classified as being potentially avoidable: 22.8% 'PAEDT only', 11.6% 'both PAEDT & PAH', and 1.9% 'PAH only'. Shortness of breath was the most common reason for transfer. Pneumonia was the most common diagnosis from the 'both PAEDT & PAH' category. PAEDTs and PAHs accounted for 95% and 37% of potentially avoidable transfers, respectively. Among 533 hospitalizations, 31.3% were PAHs. These proportions were comparable to the rest of Canada, with some differences in proportions of transfers due to congestive heart failure, urinary tract infection, and implanted device management. PAEDTs far outweigh PAHs in terms of frequency, and their monitoring is important for quality assurance as they may inform LTC-level interventions aimed at their reduction.

Immunological effects and safety of live rotavirus vaccination after antenatal exposure to immunomodulatory biologic agents: a prospective cohort study from the Canadian Immunization Research Network.

People with inflammatory or autoimmune diseases are recommended to continue immunomodulatory biologic agents throughout pregnancy. However, concerns regarding potential immunosuppression in infants exposed to biologic agents have led to recommendations to avoid live vaccines in the first 6-12 months of life. We aimed to examine whether live rotavirus vaccine could be administered safely to infants exposed to biologic agents, assessed in the Canadian Special Immunization Clinic (SIC) Network. In this prospective cohort study, infants exposed to biologic agents in utero were referred to one of six SIC sites in Canada for rotavirus vaccination recommendations. Children with other contraindications to rotavirus vaccination or older than 15 weeks were excluded. Clinical and laboratory evaluations were conducted according to a standard clinical pathway. Data were collected for relevant medical history, pregnancy outcomes, biologic agent exposure history, physical examination, laboratory results of the child, SIC recommendations for rotavirus vaccination, rotavirus vaccine series completion, and adverse events after immunisation. After parental consent, deidentified data were transferred to a central database for analysis. Children recommended for rotavirus vaccination were followed up for 8 months after series initiation to ascertain severe and serious adverse events, including severe diarrhoea, vomiting, and intussusception. Between May 1, 2017, and Dec 31, 2021, 202 infants were assessed and 191 eligible infants were enrolled (97 [51%] were female and 94 [49%] were male). When including those exposed to multiple agents, the most common biologic agents to which infants were exposed were infliximab (67 [35%] of 191), adalimumab (49 [26%]), ustekinumab (18 [9%]), and vedolizumab (17 [9%]). Biologic agent exposure continued into the third trimester for 178 (93%) infants. No clinically significant abnormalities in lymphocyte subsets, quantitative immunoglobulins, or mitogen responses were detected. After SIC assessment, rotavirus vaccination was recommended for 187 (98%) of 191 infants, all of whom were followed up. By end of follow-up on Aug 19, 2022, 168 (90%) infants had initiated rotavirus vaccination; 150 (80%) completed the series. No serious adverse events after immunisation were reported, but three (2%) infants required medical attention, one for vomiting and change in stools who was subsequently diagnosed with gastroesophageal reflux disease, one for rash on labia unrelated to vaccination, and one for vomiting and diarrhoea associated with a milk allergy. Findings from this study suggest that lymphocyte subsets and the safety of live rotavirus vaccination are generally not affected by in-utero exposure to biologic agents. Rotavirus vaccination can be offered to infants exposed to anti-TNF agents in utero. Public Health Agency of Canada and Canadian Institutes of Health Research through the Canadian Immunization Research Network.

Students’ attitudes, beliefs and perceptions surrounding 2SLGBTQIA + health education and inclusiveness in Canadian physiotherapy programs

BackgroundPatients who identify as 2SLGBTQIA + report negative experiences with physiotherapy. The objectives were to evaluate student attitudes, beliefs and perceptions related to 2SLGBTQIA + health education and working with individuals who identify as 2SLGBTQIA + in entry-level physiotherapy programs in Canada and to evaluate physiotherapy program inclusiveness towards 2SLGBTQIA + persons.MethodsWe completed a nationwide, cross-sectional survey of physiotherapy students from Canadian institutions. We recruited students via email and social media from August-December 2021. Frequency results are presented with percentages. Logistic regression models (odds ratios [OR], 95%CI) were used to evaluate associations between demographics and training hours with feelings of preparedness and perceived program 2SLGBTQIA + inclusiveness.ResultsWe obtained 150 survey responses (mean age = 25 years [range = 20 to 37]) from students where 35 (23%) self-identified as 2SLGBTQIA + . While most students (≥ 95%) showed positive attitudes towards working with 2SLGBTQIA + patients, only 20 students (13%) believed their physiotherapy program provided sufficient knowledge about 2SLGBTQIA + health and inclusiveness. Students believed more 2SLGBTQIA + training is needed (n = 137; 92%), believed training should be mandatory (n = 141; 94%) and were willing to engage in more training (n = 138; 92%). Around half believed their physiotherapy program (n = 80, 54%) and clinical placements (n = 75, 50%) were 2SLGBTQIA + -inclusive and their program instructors (n = 69, 46%) and clinical instructors (n = 47, 31%) used sex/gender-inclusive language. Discrimination towards 2SLGBTQIA + persons was witnessed 56 times by students and most (n = 136; 91%) reported at least one barrier to confronting these behaviours. Older students (OR = 0.89 [0.79 to 0.99]), individuals assigned female at birth (OR = 0.34 [0.15 to 0.77]), and students self-identifying as 2SLGBTQIA + (OR = 0.38 [0.15 to 0.94]) were less likely to believe their program was 2SLGBTQIA + inclusive. Older students (OR = 0.85 [0.76 to 0.94]) and 2SLGBTQIA + students (OR = 0.42 [0.23 to 0.76]) felt the same about their placements. Students who reported > 10 h of 2SLGBTQIA + training were more likely to believe their program was inclusive (OR = 3.18 [1.66 to 6.09]).ConclusionsEntry-level physiotherapy students in Canada show positive attitudes towards working with 2SLGBTQIA + persons but believe exposure to 2SLGBTQIA + health and inclusiveness is insufficient in their physiotherapy programs. This suggests greater attention dedicated to 2SLGBTQIA + health would be valued.

Ensemble Model Based on Hybrid Deep Learning for Intrusion Detection in Smart Grid Networks.

The Smart Grid aims to enhance the electric grid's reliability, safety, and efficiency by utilizing digital information and control technologies. Real-time analysis and state estimation methods are crucial for ensuring proper control implementation. However, the reliance of Smart Grid systems on communication networks makes them vulnerable to cyberattacks, posing a significant risk to grid reliability. To mitigate such threats, efficient intrusion detection and prevention systems are essential. This paper proposes a hybrid deep-learning approach to detect distributed denial-of-service attacks on the Smart Grid's communication infrastructure. Our method combines the convolutional neural network and recurrent gated unit algorithms. Two datasets were employed: The Intrusion Detection System dataset from the Canadian Institute for Cybersecurity and a custom dataset generated using the Omnet++ simulator. We also developed a real-time monitoring Kafka-based dashboard to facilitate attack surveillance and resilience. Experimental and simulation results demonstrate that our proposed approach achieves a high accuracy rate of 99.86%.

Guidance on take-home naloxone distribution and use by community overdose responders in Canada.

The increasing toxicity of opioids in the unregulated drug market has led to escalating numbers of overdoses in Canada and worldwide; takehome naloxone (THN) is an evidence-based intervention that distributes kits containing naloxone to people in the community who may witness an overdose. The purpose of this guidance is to provide policy recommendations for territorial, provincial and federal THN programs, using evidence from scientific and grey literature and community evidence that reflects 11 years of THN distribution in Canada. The Naloxone Guidance Development Group - a multidisciplinary team including people with lived and living experience and expertise of drug use - used the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument to inform development of this guidance. We considered published evidence identified through systematic reviews of all literature types, along with community evidence and expertise, to generate recommendations between December 2021 and September 2022. We solicited feedback on preliminary recommendations through an External Review Committee and a public input process. The project was funded by the Canadian Institutes of Health Research through the Canadian Research Initiative in Substance Misuse. We used the Guideline International Network principles for managing competing interests. Existing evidence from the literature on THN was of low quality. We incorporated evidence from scientific and grey literature, and community expertise to develop our recommendations. These were in 3 areas: routes of naloxone administration, THN kit contents and overdose response. Take-home naloxone programs should offer the choice of both intramuscular and intranasal formulations of naloxone in THN kits. Recommended kit contents include naloxone, a naloxone delivery device, personal protective equipment, instructions and a carrying case. Trained community overdose responders should prioritize rescue breathing in the case of respiratory depression, and conventional cardiopulmonary resuscitation in the case of cardiac arrest, among other interventions. This guidance development project provides direction for THN programs in Canada in the context of limited published evidence, with recommendations developed in collaboration with diverse stakeholders.

Truth and Reconciliation in Medical Schools: Forging a Critical Reflective Framework to Advance Indigenous Health Equity.

In 2015, the Truth and Reconciliation Commission (TRC) of Canada outlined 94 Calls to Action, which formalized a responsibility for all people and institutions in Canada to confront and craft paths to remedy the legacy of the country's colonial past. Among other things, these Calls to Action challenge medical schools to examine and improve existing strategies and capacities for improving Indigenous health outcomes within the areas of education, research, and clinical service. This article outlines efforts by stakeholders at one medical school to mobilize their institution to address the TRC's Calls to Action via the Indigenous Health Dialogue (IHD). The IHD used a critical collaborative consensus-building process, which employed decolonizing, antiracist, and Indigenous methodologies, offering insights for academic and nonacademic entities alike on how they might begin to address the TRC's Calls to Action. Through this process, a critical reflective framework of domains, reconciliatory themes, truths, and action themes was developed, which highlights key areas in which to develop Indigenous health within the medical school to address health inequities faced by Indigenous peoples in Canada. Education, research, and health service innovation were identified as domains of responsibility, while recognizing Indigenous health as a distinct discipline and promoting and supporting Indigenous inclusion were identified as domains within leadership in transformation. Insights are provided for the medical school, including that dispossession from land lays at the heart of Indigenous health inequities, requiring decolonizing approaches to population health, and that Indigenous health is a discipline of its own, requiring a specific knowledge base, skills, and resources for overcoming inequities.

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial

Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

Association Between Hematoma Expansion Severity and Outcome and Its Interaction With Baseline Intracerebral Hemorrhage Volume.

Hematoma expansion (HE) is a major determinant of neurologic deterioration and poor outcome in intracerebral hemorrhage (ICH) and represents an appealing therapeutic target. We analyzed the prognostic effect of different degrees of HE. This was a retrospective analysis of patients with ICH admitted at 8 academic institutions in Italy, Germany, Canada, China, and the United States. All patients underwent baseline and follow-up imaging for HE assessment. Relative HE (rHE) was classified as follows: none (<0%), mild (0%-33%), moderate (33.1%-66%), and severe (>66%). Absolute HE (aHE) was classified as none (<0 mL), mild (0-6.0 mL), moderate (6.1-12.5 mL), and severe (>12.5 mL). Predictors of poor functional outcome (90 days modified Rankin Scale 4-6) were explored with logistic regression. We included 2,163 patients, of whom 1,211 (56.0%) had poor outcome. The occurrence of severe aHE or rHE was more common in patients with unfavorable outcome (13.9% vs 6.5%, p < 0.001 and 18.3% vs 7.2%, p < 0.001 respectively). This association was confirmed in logistic regression (rHE odds ratio [OR] 1.98, 95% CI 1.38-2.82, p < 0.001; aHE OR 1.73, 95% CI 1.23-2.45, p = 0.002) while there was no association between mild or moderate HE and poor outcome. The association between severe HE and poor outcome was significant only in patients with baseline ICH volume below 30 mL. The strongest association between HE and outcome was observed in patients with smaller initial volume experiencing severe HE. These findings may inform clinical trial design and guide clinicians in selecting patients for antiexpansion therapies.

Evaluation of the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in infantile epilepsy (Gene-STEPS): an international, multicentre, pilot cohort study

Most neonatal and infantile-onset epilepsies have presumed genetic aetiologies, and early genetic diagnoses have the potential to inform clinical management and improve outcomes. We therefore aimed to determine the feasibility, diagnostic yield, and clinical utility of rapid genome sequencing in this population. We conducted an international, multicentre, cohort study (Gene-STEPS), which is a pilot study of the International Precision Child Health Partnership (IPCHiP). IPCHiP is a consortium of four paediatric centres with tertiary-level subspecialty services in Australia, Canada, the UK, and the USA. We recruited infants with new-onset epilepsy or complex febrile seizures from IPCHiP centres, who were younger than 12 months at seizure onset. We excluded infants with simple febrile seizures, acute provoked seizures, known acquired cause, or known genetic cause. Blood samples were collected from probands and available biological parents. Clinical data were collected from medical records, treating clinicians, and parents. Trio genome sequencing was done when both parents were available, and duo or singleton genome sequencing was done when one or neither parent was available. Site-specific protocols were used for DNA extraction and library preparation. Rapid genome sequencing and analysis was done at clinically accredited laboratories, and results were returned to families. We analysed summary statistics for cohort demographic and clinical characteristics and the timing, diagnostic yield, and clinical impact of rapid genome sequencing. Between Sept 1, 2021, and Aug 31, 2022, we enrolled 100 infants with new-onset epilepsy, of whom 41 (41%) were girls and 59 (59%) were boys. Median age of seizure onset was 128 days (IQR 46-192). For 43 (43% [binomial distribution 95% CI 33-53]) of 100 infants, we identified genetic diagnoses, with a median time from seizure onset to rapid genome sequencing result of 37 days (IQR 25-59). Genetic diagnosis was associated with neonatal seizure onset versus infantile seizure onset (14 [74%] of 19 vs 29 [36%] of 81; p=0·0027), referral setting (12 [71%] of 17 for intensive care, 19 [44%] of 43 non-intensive care inpatient, and 12 [28%] of 40 outpatient; p=0·0178), and epilepsy syndrome (13 [87%] of 15 for self-limited epilepsies, 18 [35%] of 51 for developmental and epileptic encephalopathies, 12 [35%] of 34 for other syndromes; p=0·001). Rapid genome sequencing revealed genetic heterogeneity, with 34 unique genes or genomic regions implicated. Genetic diagnoses had immediate clinical utility, informing treatment (24 [56%] of 43), additional evaluation (28 [65%]), prognosis (37 [86%]), and recurrence risk counselling (all cases). Our findings support the feasibility of implementation of rapid genome sequencing in the clinical care of infants with new-onset epilepsy. Longitudinal follow-up is needed to further assess the role of rapid genetic diagnosis in improving clinical, quality-of-life, and economic outcomes. American Academy of Pediatrics, Boston Children's Hospital Children's Rare Disease Cohorts Initiative, Canadian Institutes of Health Research, Epilepsy Canada, Feiga Bresver Academic Foundation, Great Ormond Street Hospital Charity, Medical Research Council, Murdoch Children's Research Institute, National Institute of Child Health and Human Development, National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre, One8 Foundation, Ontario Brain Institute, Robinson Family Initiative for Transformational Research, The Royal Children's Hospital Foundation, University of Toronto McLaughlin Centre.

An audit of the dissemination strategies and plan included in international food-based dietary guidelines.

Food-based dietary guidelines (FBDGs) are an important resource to improve population health, however little is known about the types of strategies to disseminate them. This study sought to describe dissemination strategies and content of dissemination plans that were available for FBDGs. A cross-sectional audit of FBDGs with a published English-language version sourced from the United Nations Food and Agriculture Organization repository. We searched for publicly available dissemination strategies and any corresponding plans available in English language. Two authors extracted data on strategies, which were grouped according to the Model for Dissemination Research Framework (including source, audience, channel, and message). For guidelines with a dissemination plan, we described goals, audience, strategies, and expertise and resources according to the Canadian Institute for Health Research guidance. FBDGs from 53 countries mostly from high-income (n=28, 52.8%), upper-middle income (n=18, 34%) areas were included. n/a. The source of guidelines were most frequently health departments (79.2%). The message included quantities and types of foods, and physical activity recommendations, and 88.7% included summarised versions of main messages. The most common channel were infographics and information booklets, and the main end-users were the public. For 12 countries (22.6%), we were able to source an English-language dissemination plan, where none met all recommendations outlined by the CIHR. The public was the most frequently identified end-user and thus most dissemination strategies and plans focused on this group. Few FBDGs had formal dissemination plans and of those, there was limited detailed provided.

Ten-year follow-up of endoscopic mucosal resection versus esophagectomy for esophageal intramucosal adenocarcinoma in the setting of Barrett's esophagus: a Canadian experience.

Endoscopic mucosal resection (EMR) is an effective treatment for esophageal intramucosal adenocarcinoma (IMC), with similar recurrence and mortality rates versus esophagectomy in up to 5years of follow-up. Long-term outcomes to 10years have not been studied. This retrospective study investigates IMC eradication, recurrence, morbidity and mortality at 10years following EMR versus esophagectomy in a single Canadian institution. Patients with IMC treated via esophagectomy or EMR from 2006 to 2015 were included. Post-EMR endoscopic follow-up occurred every 3months for 1year, every 6months for 2years and every 12months thereafter. Categorical variables were expressed as percentages and continuous variables as mean with standard deviation or median and interquartile range. The student's t-test and Fischer's exact test were used for comparisons. Survival analysis utilized the Kaplan-Meier estimator and log-rank test. Twenty-four patients were included. Patient and tumor characteristics were similar between groups. Median follow-up for EMR and esophagectomy were 85.2months [IQR 64.8] and 126months [IQR 54] respectively. A mean of 1.3 EMR (SD 1.1) were required for eradication, which was seen in 12 patients (12/14, 86%). No EMR-related complications occurred. Disease progression was seen in two patients (2/14, 14%); local recurrence was seen in 1 patient (1/14, 7%). Esophagectomy eradicated IMC in 10 patients (10/10, 100%); recurrence was seen in 2 (2/10, 20%, metastatic). Major, early esophagectomy-related morbidity affected 3 patients (3/10, 30%), and late morbidity was documented for 9 (9/10, 90%). Esophagectomy and EMR had similar recurrence rates (p = 0.554). Esophagectomy was associated with significantly more procedure-related morbidity (p < 0.001). There was no difference in mortality (p = 0.442) or disease-free survival (p = 0.512) between treatment groups. EMR and esophagectomy for the treatment of IMC are associated with comparable recurrence rates and disease-free survival in 10-year follow-up. EMR is associated with significantly lower procedure-associated morbidity. EMR can be used to treat T1a distal esophageal adenocarcinoma with minimal procedure-related morbidity, and acceptable oncologic outcomes in long-term follow-up.

Tracking emergency response actions during COVID-19 leads to development of an innovative public health evaluation tool

SettingEarly in the pandemic, KFL&A Public Health needed a way to capture, organize, and display COVID-19-related events to be accountable for and evaluate our actions.InterventionWe used accessible software (Microsoft Office 365 suite, Microsoft PowerBI) to develop a data collection and visualization system. The Canadian Institute for Health Information (CIHI) developed a timeline and categorization approach for provincial and national COVID-related interventions, which was used to develop a regional version for local events using similar categories. We collected and displayed qualitative data alongside epidemiological data that allowed users to display different timelines of actions and outcomes and evaluate our response.OutcomesIn developing the timeline, we took stock of the information and data we wanted to collect, sort, and display locally. Next, we collected information on response actions, case and contact tracing, and staffing changes in a database that we displayed on a timeline. We included CIHI’s data set to provide insight into pandemic response across all jurisdictions.ImplicationsOur timeline tool has many advantages for public health authorities beyond responding to a rapidly evolving emergency. By collecting information on events as they occur, decisions and actions are documented that may otherwise be overlooked. This enables decision-makers to visualize the impact of public health actions on health outcomes over time. The tool is completely customizable and scalable depending on the project scope and we plan to apply this method to other public health programming. Finally, we include lessons learned from quickly developing these tools in a real-time pandemic setting, both locally at KFL&A Public Health and nationally at CIHI.

Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial)

Endoscopic ultrasound-guided choledochoduodenostomy with a lumen-apposing metal stent (EUS-CDS) is a promising modality for management of malignant distal biliary obstruction (MDBO) with potential for better stent patency. We compared its outcomes with endoscopic retrograde cholangiopancreatography with metal stenting (ERCP-M). In this multicenter randomized controlled trial, we recruited patients with MDBO secondary to borderline resectable, locally advanced, or unresectable peri-ampullary cancers across 10 Canadian institutions and 1 French institution. This was a superiority trial with a noninferiority assessment of technical success. Patients were randomized to EUS-CDS or ERCP-M. The primary end point was the rate of stent dysfunction at 1 year, considering competing risks of death, clinical failure, and surgical resection. Analyses were performed according to intention-to-treat principles. From February 2019 to February 2022, 144 patients were recruited; 73 were randomized to EUS-CDS and 71 were randomized to ERCP-M. The mean (SD) procedure time was 14.0 (11.4) minutes for EUS-CDS and 23.1 (15.6) minutes for ERCP-M (P < .01); 40% of the former was performed without fluoroscopy. Technical success was achieved in 90.4% (95% CI, 81.5% to 95.3%) of EUS-CDS and 83.1% (95% CI, 72.7% to 90.1%) of ERCP-M with a risk difference of 7.3% (95% CI, -4.0% to 18.8%) indicating noninferiority. Stent dysfunction occurred in 9.6% vs 9.9% of EUS-CDS and ERCP-M cases, respectively (P= .96). No differences in adverse events, pancreaticoduodenectomy and oncologic outcomes, or quality of life were noted. Although not superior in stent function, EUS-CDS is an efficient and safe alternative to ERCP-M in patients with MDBO. These findings provide evidence for greater adoption of EUS-CDS in clinical practice as a complementary and exchangeable first-line modality to ERCP in patients with MDBO. gov, Number: NCT03870386.

Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression

BackgroundAntidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied.MethodsWe conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression.ResultsOf 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P=0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups.ConclusionsIn a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.)