McMaster University

Purpose: This study aimed to characterize contemporary management of Canadian patients with cardiovascular implantable electronic devices (CIEDs) undergoing radiation therapy (RT) in light of updated American Association of Physicists in Medicine guidelines. Methods and materials: A 22-question web-based survey was distributed to members of the Canadian Association of Radiation Oncology, Canadian Organization of Medical Physicists, and Canadian Association of Medical Radiation Technologists from January to February 2020. Respondent demographics, knowledge, and management practices were elicited. Statistical comparisons by respondent demographics were performed using χ2 and Fisher exact tests. Results: In total, 155 surveys were completed by 54 radiation oncologists, 26 medical physicists, and 75 radiation therapists in academic (51%) and community (49%) practices across all provinces. The majority of respondents (77%) had managed >10 patients with CIEDs in their career. Most respondents (70%) reported using risk-stratified institutional management protocols. Respondents used manufacturer recommendations, rather than American Association of Physicists in Medicine or institutionally recommended dose limits, when the manufacturer limit was 0 Gy (44%), 0 to 2 Gy (45%), or >2 Gy (34%). The majority of respondents (86%) reported institutional policies to refer to a cardiologist for CIED evaluation both before and after completion of RT. Cumulative dose to CIED, pacing dependence, and neutron production were considered during risk stratification by 86%, 74%, and 50% of participants, respectively. Dose and energy thresholds for high-risk management were not known by 45% and 52% of respondents, with radiation oncologists and radiation therapists significantly less likely to report thresholds than medical physicists (P < .001). Although 59% of respondents felt comfortable managing patients with CIEDs, community respondents were less likely to feel comfortable than academic respondents (P = .037). Conclusions: The management of Canadian patients with CIEDs undergoing RT is characterized by variability and uncertainty. National consensus guidelines may have a role in improving provider knowledge and confidence in caring for this growing population.

About two-thirds of Canadian COVID-19 related deaths occurred in long-term care homes (LTCHs). Multiple jobholding and excessive part-time work among staff have been discussed as vectors of transmission. Using an administrative census of registered nurses (RNs) and registered practical nurses (RPNs) in the Canadian province of Ontario, this paper contrasts the prevalence of multiple jobholding, part-time/casual work, and other job and worker characteristics across health sectors in 2019 and 2020 to establish whether the LTCH sector deviates from the norms in Ontario healthcare. Prior to COVID-19, about 19% of RNs and 21% of RPNs in LTCHs held multiple jobs. For RPNs, this was almost identical to the RPN provincial average, while for RNs this was 2.5 percentage points above the RN provincial average. In 2020, multiple jobholding fell significantly in LTCHs after the province passed a single site order to reduce COVD-19 transmission. Although there are many similarities across sectors, nurses, especially RNs, in LTCHs differ on some dimensions. They are more likely to be internationally educated and, together with nurses in hospitals, those who work part- time/casual are more likely to prefer full-time hours (involuntary part-time/casual). Overall, while multiple jobholding and part-time work among nurses are problematic for infection prevention and control, these employment practices in LTCHs did not substantially deviate from the norms in the rest of healthcare in Ontario.

Background Diabetic neuropathy is the most common microvascular complication of diabetes mellitus and a major risk factor for diabetes-related lower-extremity complications. Diffuse neuropathy is the most frequently encountered pattern of neurological dysfunction and presents clinically as distal symmetrical sensorimotor polyneuropathy. Due to the increasing public health significance of diabetes mellitus and its complications, screening for diabetic peripheral neuropathy is essential. Consequently, a review of the principles that guide screening practices, especially in resource-limited clinical settings, is urgently needed. Main body Numerous evidence-based assessments are used to detect diabetic peripheral neuropathy. In accordance with current guideline recommendations from the American Diabetes Association, International Diabetes Federation, International Working Group on the Diabetic Foot, and National Institute for Health and Care Excellence, a screening algorithm for diabetic peripheral neuropathy based on multiphasic clinical assessment, stratification according to risk of developing diabetic foot syndrome, individualized treatment, and scheduled follow-up is suggested for use in resource-limited settings. Conclusions Screening for diabetic peripheral neuropathy in resource-limited settings requires a practical and comprehensive approach in order to promptly identify affected individuals. The principles of screening for diabetic peripheral neuropathy are: multiphasic approach, risk stratification, individualized treatment, and scheduled follow-up. Regular screening for diabetes-related foot disease using simple clinical assessments may improve patient outcomes.

Introduction: Recent shifts in the patient, family and caregiver engagement field have focused greater attention on measurement and evaluation, including the impacts of engagement efforts. Current evaluation tools offer limited support to organizations seeking to reorient their efforts in this way. We addressed this gap through the development of an impact measurement framework and accompanying evaluation toolkit-the Engage with Impact Toolkit. Methods: The measurement framework and toolkit were co-designed with the Evaluating Patient Engagement Working Group, a multidisciplinary group of patient, family and caregiver partners, engagement specialists, researchers and government personnel. Project activities occurred over four phases: (1) project scoping and literature review; (2) modified concept mapping; (3) working group deliberations and (4) toolkit web design. Results: The project scope was to develop a measurement framework and an evaluation toolkit for patient engagement in health systems that were practical, accessible, menu-driven and aligned with current system priorities. Concept mapping yielded 237 impact statements that were sorted, discussed and combined into 81 unique items. A shorter list of 50 items (rated 8.0 or higher out of 10) was further consolidated to generate a final list of 35 items mapped across 8 conceptual domains of impact: (1) knowledge and skills; (2) confidence and trust; (3) equity and inclusivity; (4) priorities and decisions; (5) effectiveness and efficiency; (6) patient-centredness; (7) culture change and (8) patient outcomes and experience. Working Group members rated the final list for importance (1-5) and identified a core set of 33 items (one for each of the 8 domains and 25 supplementary items). Two domains (priorities and decisions; and culture change) yielded the highest overall importance ratings (4.8). A web-based toolkit (www.evaluateengagement.ca) hosts the measurement framework and related evaluation supports. Conclusion: The Engage with Impact Toolkit builds on existing engagement evaluation tools but brings a more explicit focus to supporting organizations to assess the impacts of their engagement work. Patient contribution: Patient, family and caregiver partners led the early conceptualization of this work and were involved at all stages and in all aspects of the work. As end-users of the toolkit, their perspectives, knowledge and opinions were critical.

Background Diagnosis of shockable rhythms leading to defibrillation remains integral to improving out‐of‐hospital cardiac arrest outcomes. New machine learning techniques have emerged to diagnose arrhythmias on ECGs. In out‐of‐hospital cardiac arrest, an algorithm within an automated external defibrillator is the major determinant to deliver defibrillation. This study developed and validated the performance of a convolution neural network (CNN) to diagnose shockable arrhythmias within a novel, miniaturized automated external defibrillator. Methods and Results There were 26 464 single‐lead ECGs that comprised the study data set. ECGs of 7‐s duration were retrospectively adjudicated by 3 physician readers (N=18 total readers). After exclusions (N=1582), ECGs were divided into training (N=23 156), validation (N=721), and test data sets (N=1005). CNN performance to diagnose shockable and nonshockable rhythms was reported with area under the receiver operating characteristic curve analysis, F1, and sensitivity and specificity calculations. The duration for the CNN to output was reported with the algorithm running within the automated external defibrillator. Internal and external validation analyses included CNN performance among arrhythmias, often mistaken for shockable rhythms, and performance among ECGs modified with noise to mimic artifacts. The CNN algorithm achieved an area under the receiver operating characteristic curve of 0.995 (95% CI, 0.990–1.0), sensitivity of 98%, and specificity of 100% to diagnose shockable rhythms. The F1 scores were 0.990 and 0.995 for shockable and nonshockable rhythms, respectively. After input of a 7‐s ECG, the CNN generated an output in 383±29 ms (total time of 7.383 s). The CNN outperformed adjudicators in classifying atrial arrhythmias as nonshockable (specificity of 99.3%–98.1%) and was robust against noise artifacts (area under the receiver operating characteristic curve range, 0.871–0.999). Conclusions We demonstrate high diagnostic performance of a CNN algorithm for shockable and nonshockable rhythm arrhythmia classifications within a digitally connected automated external defibrillator. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03662802 ; Unique identifier: NCT03662802

Background: Older adults are recommended to receive influenza vaccination annually and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk. Methods: Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and non-users aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio (OR) for influenza infection between statin users and non-users by vaccination status. Results: Among subjects tested for influenza across the 9 seasons, 54,243 had continuous statin exposure prior to testing and 48,469 were deemed unexposed. VE against laboratory-confirmed influenza was similar between statin users and non-users (17% [95%CI, 13-20%] and 17% [95%CI, 13-21%] respectively; test for interaction, p=0.87). In both vaccinated and unvaccinated subjects, statin users had higher odds of laboratory-confirmed influenza than non-users (OR for vaccinated =1.15; 95%CI, 1.10-1.21; OR for unvaccinated=1.15; 95%CI, 1.10-1.20). These findings were consistent by mean daily dose and statin type. VE did not differ between users and non-users of other cardiovascular drugs, except for beta-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated beta-blocker users. Conclusions: Influenza VE did not differ between statin users and non-users. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated subjects, but these associations might be impacted by residual confounding.

Background The importance of investigating sex- and gender-dependent differences has been recently emphasized by major funding agencies. Notably, the influence of biological sex on clinical outcomes in sepsis is unclear, and observational studies suffer from the effect of confounding factors. The controlled experimental environment afforded by preclinical studies allows for clarification and mechanistic evaluation of sex-dependent differences. We propose a systematic review to assess the impact of biological sex on baseline responses to disease induction as well as treatment responses in animal models of sepsis. Given the lack of guidance surrounding sex-based analyses in preclinical systematic reviews, careful consideration of various factors is needed to understand how best to conduct analyses and communicate findings. Methods MEDLINE and Embase will be searched (2011-present) to identify preclinical studies of sepsis in which any intervention was administered and sex-stratified data reported. The primary outcome will be mortality. Secondary outcomes will include organ dysfunction, bacterial load, and IL-6 levels. Study selection will be conducted independently and in duplicate by two reviewers. Data extraction will be conducted by one reviewer and audited by a second independent reviewer. Data extracted from included studies will be pooled, and meta-analysis will be conducted using random effects modeling. Primary analyses will be stratified by animal age and will assess the impact of sex at the following time points: pre-intervention, in response to treatment, and post-intervention. Risk of bias will be assessed using the SYRCLE’s risk-of-bias tool. Illustrative examples of potential methods to analyze sex-based differences are provided in this protocol. Discussion Our systematic review will summarize the current state of knowledge on sex-dependent differences in sepsis. This will identify current knowledge gaps that future studies can address. Finally, this review will provide a framework for sex-based analysis in future preclinical systematic reviews. Systematic review registration PROSPERO CRD42022367726.

This review focuses on vaccine distribution and allocation in the context of the current COVID-19 pandemic. The implications discussed are in the areas of equity in vaccine distribution and allocation (at a national level as well as worldwide), vaccine hesitancy, game-theoretic modeling to guide decision-making and policy-making at a governmental level, distribution and allocation barriers (in particular in low-income countries), and operations research (OR) mathematical models to plan and execute vaccine distribution and allocation. To conduct this review, we adopt a novel methodology that consists of three phases. The first phase deploys a bibliometric analysis; the second phase concentrates on a network analysis; and the last phase proposes a refined literature review based on the results obtained by the previous two phases. The quantitative techniques utilized to conduct the first two phases allow describing the evolution of the research in this area and its potential ramifications in future. In conclusion, we underscore the significance of operations research (OR)/management science (MS) research in addressing numerous challenges and trade-offs connected to the current pandemic and its strategic impact in future research.

Objectives: Engaging in mind-body exercises (MBEs: e.g., Tai Chi and yoga) can have physical and mental health benefits particularly for older adults. Many MBEs require precise timing and coordination of complex body postures posing challenges for online instruction. Such challenges include difficulty viewing instructors as they demonstrate different movements and lack of feedback to participants. With the shift of exercise programs to online platforms during the COVID-19 pandemic, we conducted a scoping review to examine the feasibility, usability, and acceptability of online MBE classes for older adults. Materials and Methods: We followed the scoping review methodology and adhered to the PRISMA reporting checklist. We searched five databases: Medline, Embase, CINHAL, Web of Science, and ACM digital library. Screening of articles and data extraction was conducted independently by two reviewers. Settings/Location: Online/virtual. Subjects: Older adults ≥55 years of age. Outcome Measures: Feasibility measures. Results: Of 6711 studies retrieved, 18 studies were included (715 participants, mean age 66.9 years). Studies reported moderate to high retention and adherence rates (mean >75%). Older adults reported online MBE classes were easy to use and reported high satisfaction with the online format. We also identified barriers (e.g., lack of space and privacy and unstable internet connection) and facilitators (e.g., convenience and technical support) to the online format. Opinions related to social connectedness were mixed. Conclusion: Online MBE programs for older adults appear to be a feasible and acceptable alternative to in-person programs. It is important to consider the type of exercise (e.g., MBE), diverse teaching styles, and learner needs when designing online exercise classes.

The actinobacterial species Cellulomonas fimi ATCC484 has long been known to secrete mannose-containing proteins, but a closer examination of glycoproteins associated with the cell has never been reported. Using ConA lectin chromatography and mass spectrometry we have surveyed the cell associated glycoproteome from C. fimi and collected detailed information on the glycosylation sites of 19 cell-associated glycoproteins. In addition, we have expressed a previously known C. fimi secreted cellulase, Celf_3184, (formerly CenA), a putative peptide prolyl-isomerase, Celf_2022, and a penicillin binding protein, Celf_0189, in the mannosylation capable host, Corynebacterium glutamicum. We found that the glycosylation machinery in C. glutamicum was able to use the recombinant C. fimi proteins as substrates and that the glycosylation matched closely that found in the native proteins when expressed in C. fimi. We are pursuing this observation as a prelude to dissecting the biosynthetic machinery and biological consequences of this protein mannosylation.

Objective: To systematically examine the content of opioid-related advertisements. Design: Content analysis and quantitative assessment. Setting: North America. Participants: Researchers examined advertisements in 2 issues per year from 1996 to 2016 of American Family Physician, Canadian Family Physician, the Canadian Medical Association Journal, JAMA, and the New England Journal of Medicine. Main outcome measures: Number of advertisements, nature of the claims made, and quality of cited evidence in the advertisements. Results: Opioid advertisements composed 89 of the 3173 pharmaceutical advertisements in 210 journal issues searched. Seventy-three advertisements were able to be obtained for analysis. Thirty-four (46.6%) did not mention the addictive potential of opioids, and 54 of 73 (74.0%) did not mention the possibility of death. All referenced studies in advertisements were funded by pharmaceutical organizations or had pharmaceutical company employees as authors. No advertisements cited high-quality evidence. Conclusion: Many claims of the effectiveness and safety of opioids were published in medical journals through advertisements. Advertisements did not usually mention key negative information about opioids. Although the extent to which these advertisements directly influenced the development of the opioid crisis in North America is unknown, the marked omission of important detrimental effects of opioids may have played a role. Further efforts to restrict opioid marketing may be warranted.

The emergence of narrative medicine has promoted reflective practices and story-telling as means of promoting compassion, building resiliency, and understanding the "patient" and "physician" as "persons." However, though some narrative medicine pieces describe patients' experiences, the narrative of the patient is usually told by physicians, producing a second-hand facsimile of the patient's lived experience. Stories written by physicians may have their roots in patient encounters, but are filtered through the physician's, rather than the patient's, understanding of the world. This focus on patient stories told by physicians replicates traditional gaps in legitimacy between the voices of physicians and patients and maintains the locus of power with physicians and the health care system. This paper explores the ways in which well-meaning physicians aiming to elevate patients' stories frequently fall short, and what we can do to better elevate patients' voices on the wards, in clinics, and in the medical literature. Stories about patients are important to help clinicians and trainees develop and practice compassionate person-centered care; stories written by patients on topics and with orientations of their choosing are currently lacking, and, we argue, even more important.

Abdominal pain is common in patients with gastrointestinal disorders, but its pathophysiology is unclear, in part due to poor understanding of basic mechanisms underlying visceral sensitivity. Accumulating evidence suggests that gut microbiota is an important determinant of visceral sensitivity. Clinical and basic research studies also show that sex plays a role in pain perception, although the precise pathways are not elucidated. We investigated pain responses in germ-free and conventionally raised mice of both sexes, and assessed visceral sensitivity to colorectal distension, neuronal excitability of dorsal root ganglia (DRG) neurons and the production of substance P and calcitonin gene-related peptide (CGRP) in response to capsaicin or a mixture of G-protein coupled receptor (GPCR) agonists. Germ-free mice displayed greater in vivo responses to colonic distention than conventional mice, with no differences between males and females. Pretreatment with intracolonic capsaicin or GPCR agonists increased responses in conventional, but not in germ-free mice. In DRG neurons, gut microbiota and sex had no effect on neuronal activation by capsaicin or GPCR agonists. While stimulated production of substance P by DRG neurons was similar in germ-free and conventional mice, with no additional effect of sex, the CGRP production was higher in germ-free mice, mainly in females. Absence of gut microbiota increases visceral sensitivity to colorectal distention in both male and female mice. This is, at least in part, due to increased production of CGRP by DRG neurons, which is mainly evident in female mice. However, central mechanisms are also likely involved in this process. ARTICLE HISTORY

Importance: Children with medical complexity (CMC) have chronic conditions and high health needs and may experience fragmented care. Objective: To compare the effectiveness of a structured complex care program, Complex Care for Kids Ontario (CCKO), with usual care. Design, setting, and participants: This randomized clinical trial used a waitlist variation for randomizing patients from 12 complex care clinics in Ontario, Canada, over 2 years. The study was conducted from December 2016 to June 2021. Participants were identified based on complex care clinic referral and randomly allocated into an intervention group, seen at the next available clinic appointment, or a control group that was placed on a waitlist to receive the intervention after 12 months. Intervention: Assignment of a nurse practitioner-pediatrician dyad partnering with families in a structured complex care clinic to provide intensive care coordination and comprehensive plans of care. Main outcomes and measures: Co-primary outcomes, assessed at baseline and at 6, 12, and 24 months postrandomization, were service delivery indicators from the Family Experiences With Coordination of Care that scored (1) coordination of care among health care professionals, (2) coordination of care between health care professionals and families, and (3) utility of care planning tools. Secondary outcomes included child and parent health outcomes and child health care system utilization and cost. Results: Of 144 participants randomized, 141 had complete health administrative data, and 139 had complete baseline surveys. The median (IQR) age of the participants was 29 months (9-102); 83 (60%) were male. At 12 months, scores for utility of care planning tools improved in the intervention group compared with the waitlist group (adjusted odds ratio, 9.3; 95% CI, 3.9-21.9; P < .001), with no difference between groups for the other 2 co-primary outcomes. There were no group differences for secondary outcomes of child outcomes, parent outcomes, and health care system utilization and cost. At 24 months, when both groups were receiving the intervention, no primary outcome differences were observed. Total health care costs in the second year were lower for the intervention group (median, CAD$17 891; IQR, 6098-61 346; vs CAD$37 524; IQR, 9338-119 547 [US $13 415; IQR, 4572-45 998; vs US $28 136; IQR, 7002-89 637]; P = .01). Conclusions and relevance: The CCKO program improved the perceived utility of care planning tools but not other outcomes at 1 year. Extended evaluation periods may be helpful in assessing pediatric complex care interventions. Trial registration: ClinicalTrials.gov Identifier: NCT02928757.

Objective: Little is known about the treatment of post-coronavirus disease 2019 (COVID-19) condition (PCC). This article examines the effectiveness of pharmacological interventions for treating people with PCC. Methods: We searched Medline, EMBASE, ClinicalTrials. gov, and the International Clinical Trials Registry Platform. Two independent review authors screened citations, extracted data, and assessed the quality of the included studies. Due to heterogeneity in participants, interventions, and outcomes, we synthesized data narratively. We assessed the certainty of evidence using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Participants: People with PCC. Interventions: Pharmacological interventions include corticosteroids, ivabradine, and inhaled hydrogen. Outcome Measures: Olfactory function, sinus tachycardia, respiratory function. Results: We identified 5 completed studies and 41 ongoing studies. Oral corticosteroids and olfactory training had higher olfactory scores after 10 weeks (MD: 5.60, 95% confidence interval [CI]: 1.41 to 9.79). Patients allocated oral corticosteroid, and nasal irrigation demonstrated improved recovery of olfactory function compared with the control group at 40 days (median 60, interquartile range [IQR]: 40 vs. median 30, IQR: 25, p = 0.024). Patients allocated to topical corticosteroid nasal spray and olfactory training had improved recovery of olfactory function after 2 weeks (median 7, IQR: 5−10 vs. median 5, IQR: 2−8, p = 0.08). Participants allocated to ivabradine had a greater mean reduction in heart rate compared with participants randomized to carvedilol (MD: −4.24, 95% CI: −10.09 to 1.61). Participants allocated to inhaled hydrogen therapy had an improved vital capacity (MD: 0.20, 95% CI: 0.07 to 0.33), forced expiratory volume (MD: 0.19, 95% CI: 0.04 to 0.34), 6-minute walk test (MD: 55.0, 95% CI: 36.04 to 73.96).

Background: This report describes the use of hyperbaric oxygen therapy for the acute management of an intraoperative air embolism encountered during a neurosurgical procedure. Furthermore, the authors highlight the concomitant diagnosis of tension pneumocephalus requiring evacuation prior to hyperbaric therapy. Observations: A 68-year-old male developed acute ST-segment elevation and hypotension during elective disconnection of a posterior fossa dural arteriovenous fistula. The semi-sitting position had been used to minimize cerebellar retraction, raising the concern for acute air embolism. Intraoperative transesophageal echocardiography was utilized to establish the diagnosis of air embolism. The patient was stabilized on vasopressor therapy, and immediate postoperative computed tomography revealed air bubbles in the left atrium along with tension pneumocephalus. He underwent urgent evacuation for the tension pneumocephalus followed by hyperbaric oxygen therapy to manage the hemodynamically significant air embolism. The patient was eventually extubated and went on to fully recover; a delayed angiogram revealed complete cure of the dural arteriovenous fistula. Lessons: Hyperbaric oxygen therapy should be considered for an intracardiac air embolism resulting in hemodynamic instability. In the postoperative neurosurgical setting, care should be taken to exclude pneumocephalus requiring operative intervention prior to hyperbaric therapy. A multidisciplinary management approach facilitated expeditious diagnosis and management for the patient.