Leveraging a clinical emergency department dataset to estimate two-dose COVID-19 vaccine effectiveness and duration of protection in Canada.

BACKGROUND: During the COVID-19 pandemic, clinical care shifted toward virtual and Emergency Department care. We explored the feasibility of mRNA vaccine effectiveness (VE) estimation against SARS-CoV-2-related Emergency Department visits and hospitalizations using prospectively collected Emergency Department data. METHODS: We estimated two-dose VE using a test-negative design and data from 10 participating sites of the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN). We included Emergency Department patients presenting with COVID-19 symptoms and nucleic acid amplification testing for SARS-CoV-2 between July 19 and December 31, 2021. We excluded patients with unclear vaccination and one or more than 2 vaccine doses by their Emergency Department visit. RESULTS: Among 3,405 eligible patients, adjusted two-dose mRNA VE against SARS-CoV-2-related Emergency Department visits was 93.3 % (95 % CI 87.9-96.3 %) between 7-55 days, sustained over 80 % through 139 days post-vaccination. In stratified analyses, VE was similar among patients with select immune-compromising conditions, chronic kidney disease, lung disease, unstable housing, and reported illicit substance use. CONCLUSIONS: Two-dose mRNA VE against SARS-CoV-2-related Emergency Department visit was high and sustained, including among vulnerable subgroups. Compared to administrative datasets, active Emergency Department enrolment enables standardization for testing access and indication and supports separate VE assessment among special population subgroups. Compared to other active enrolment settings, Emergency Departments more consistently function during crises when alternate healthcare sectors become variably closed. TRIAL REGISTRATION: Clinicaltrials.gov, NCT0470294.

Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome.

A substantial number of patients recovering from acute SARS-CoV-2 infection present serious lingering symptoms, often referred to as long COVID (LC). However, a subset of these patients exhibits the most debilitating symptoms characterized by ongoing myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). We specifically identified and studied ME/CFS patients from two independent LC cohorts, at least 12 months post the onset of acute disease, and compared them to the recovered group (R). ME/CFS patients had relatively increased neutrophils and monocytes but reduced lymphocytes. Selective T cell exhaustion with reduced naïve but increased terminal effector T cells was observed in these patients. LC was associated with elevated levels of plasma pro-inflammatory cytokines, chemokines, Galectin-9 (Gal-9), and artemin (ARTN). A defined threshold of Gal-9 and ARTN concentrations had a strong association with LC. The expansion of immunosuppressive CD71+ erythroid cells (CECs) was noted. These cells may modulate the immune response and contribute to increased ARTN concentration, which correlated with pain and cognitive impairment. Serology revealed an elevation in a variety of autoantibodies in LC. Intriguingly, we found that the frequency of 2B4+CD160+ and TIM3+CD160+ CD8+ T cells completely separated LC patients from the R group. Our further analyses using a multiple regression model revealed that the elevated frequency/levels of CD4 terminal effector, ARTN, CEC, Gal-9, CD8 terminal effector, and MCP1 but lower frequency/levels of TGF-ß and MAIT cells can distinguish LC from the R group. Our findings provide a new paradigm in the pathogenesis of ME/CFS to identify strategies for its prevention and treatment.

Leaving emergency departments without completing treatment among First Nations and non-First Nations patients in Alberta: a mixed-methods study.

BACKGROUND: Our previous research showed that, in Alberta, Canada, a higher proportion of visits to emergency departments and urgent care centres by First Nations patients ended in the patient leaving without being seen or against medical advice, compared with visits by non-First Nations patients. We sought to analyze whether these differences persisted after controlling for patient demographic and visit characteristics, and to explore reasons for leaving care. METHODS: We conducted a mixed-methods study, including a population-based retrospective cohort study for the period of April 2012 to March 2017 using provincial administrative data. We used multivariable logistic regression models to control for demographics, visit characteristics, and facility types. We evaluated models for subgroups of visits with pre-selected illnesses. We also conducted qualitative, in-person sharing circles, a focus group, and 1-on-1 telephone interviews with health directors, emergency care providers, and First Nations patients from 2019 to 2022, during which we reviewed the quantitative results of the cohort study and asked participants to comment on them. We descriptively categorized qualitative data related to reasons that First Nations patients leave care. RESULTS: Our quantitative analysis included 11 686 287 emergency department visits, of which 1 099 424 (9.4%) were by First Nations patients. Visits by First Nations patients were more likely to end with them leaving without being seen or against medical advice than those by non-First Nations patients (odds ratio 1.96, 95% confidence interval 1.94-1.98). Factors such as diagnosis, visit acuity, geography, or patient demographics other than First Nations status did not explain this finding. First Nations status was associated with greater odds of leaving without being seen or against medical advice in 9 of 10 disease categories or specific diagnoses. In our qualitative analysis, 64 participants discussed First Nations patients' experiences of racism, stereotyping, communication issues, transportation barriers, long waits, and being made to wait longer than others as reasons for leaving. INTERPRETATION: Emergency department visits by First Nations patients were more likely to end with them leaving without being seen or against medical advice than those by non-First Nations patients. As leaving early may delay needed care or interfere with continuity of care, providers and departments should work with local First Nations to develop and adopt strategies to retain First Nations patients in care.

Geographic variation in breast reconstruction surgery after mastectomy for females with breast cancer in Alberta, Canada.

BACKGROUND: Breast cancer is the most common cancer affecting females in Canada, and about half of females with breast cancer are treated with mastectomy. We sought to evaluate geographic variation in breast reconstruction surgery in Alberta, Canada. METHODS: Using linked population-based administrative databases, we extracted data on all Alberta females aged 18 years and older who were diagnosed with breast cancer and treated with mastectomy during 2004-2017. Analyses included regression modelling of odds of reconstruction at 1 year and a spatial scan to identify geographic clusters of lower numbers of reconstruction. RESULTS: A total of 16 198 females diagnosed with breast cancer were treated with a mastectomy, and 1932 (11.9%) had reconstruction within 1 year postmastectomy. Those with reconstruction were more likely to be younger (adjusted odds ratio [OR] 16.7, 95% confidence interval [CI] 13.7-20.3; aged 21-44 yr v. ≥ 65 yr) and were less likely to be from lower-income neighbourhoods. They were more likely to have at least 1 comorbidity and were more likely to have advanced stages of cancer and to require chemotherapy (adjusted OR 0.55, 95% CI 0.47-0.65) or radiotherapy after mastectomy (adjusted OR 0.59, 95% CI 0.39-0.87) than females without reconstruction. We identified rural northern and southeastern clusters with frequencies of reconstruction that were 69.6% and 41.6% of what was expected, respectively. CONCLUSION: We found an overall postmastectomy rate of breast reconstruction of 11.9%, and we identified geographic variation. Predictors of reconstruction in Alberta were similar to those previously described in the literature, specifically with patients in rural communities having lower rates of reconstruction than their urban counterparts. These results suggest that further interventions are required to identify the specific barriers to reconstruction within rural communities and to create strategies to ensure equitable access to all residents.

Characteristics and outcomes of patients with COVID-19 who return to the emergency department: a multicentre observational study by the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN).

OBJECTIVE: Unplanned return emergency department (ED) visits can reflect clinical deterioration or unmet need from the original visit. We determined the characteristics and outcomes of patients with COVID-19 who return to the ED for COVID-19-related revisits. METHODS: This retrospective observational study used data for all adult patients visiting 47 Canadian EDs with COVID-19 between 1 March 2020 and 31 March 2022. Multivariable logistic regression assessed the characteristics associated with having a no return visit (SV=single visit group) versus at least one return visit (MV=return visit group) after being discharged alive at the first ED visit. RESULTS: 39 809 patients with COVID-19 had 44 862 COVID-19-related ED visits: 35 468 patients (89%) had one visit (SV group) and 4341 (11%) returned to the ED (MV group) within 30 days (mean 2.2, SD=0.5 ED visit). 40% of SV patients and 16% of MV patients were admitted at their first visit, and 41% of MV patients not admitted at their first ED visit were admitted on their second visit. In the MV group, the median time to return was 4 days, 49% returned within 72 hours. In multivariable modelling, a repeat visit was associated with a variety of factors including older age (OR=1.25 per 10 years, 95% CI (1.22 to 1.28)), pregnancy (1.86 (1.46 to 2.36)) and presence of comorbidities (eg, 1.72 (1.40 to 2.10) for cancer, 2.01 (1.52 to 2.66) for obesity, 2.18 (1.42 to 3.36) for organ transplant), current/prior substance use, higher temperature or WHO severe disease (1.41 (1.29 to 1.54)). Return was less likely for females (0.82 (0.77 to 0.88)) and those boosted or fully vaccinated (0.48 (0.34 to 0.70)). CONCLUSIONS: Return ED visits by patients with COVID-19 within 30 days were common during the first two pandemic years and were associated with multiple factors, many of which reflect known risk for worse outcomes. Future studies should assess reasons for revisit and opportunities to improve ED care and reduce resource use. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04702945.

Heatstroke presentations to urban hospitals during BC's extreme heat event: lessons for the future.

BACKGROUND: Climate change is leading to more extreme heat events in temperate climates that typically have low levels of preparedness. Our objective was to describe the characteristics, treatments, and outcomes of adults presenting to hospitals with heatstroke during BC's 2021 heat dome. METHODS: We conducted a review of consecutive adults presenting to 7 hospitals in BC's Lower Mainland. We screened the triage records of all patients presenting between June 25th and 30th, 2021 for complaints related to heat, and reviewed the full records of those who met heatstroke criteria. Our primary outcome was in-hospital mortality. We used Mann-Whitney U tests and logistic regression to investigate associations between patient and treatment factors and mortality. RESULTS: Among 10,247 consecutive presentations to urban hospitals during the extreme heat event, 1.3% (139; 95% confidence intervals [CI] 1.1-1.6%) met criteria for heatstroke. Of heatstroke patients, 129 (90.6%) were triaged into the two highest acuity levels. Patients with heatstroke had a median age of 84.4 years, with 122 (87.8%) living alone, and 101 (84.2%) unable to activate 911 themselves. A minority (< 5, < 3.6%) of patients presented within 48 h of the onset of extreme heat. Most patients (107, 77.0%) required admission, and 11.5% (16) died in hospital. Hypotension on presentation was associated with mortality (odds ratio [OR] 5.3). INTERPRETATION: Heatstroke patients were unable to activate 911 themselves, and most presented with a 48-h delay. This delay may represent a critical window of opportunity for pre-hospital and hospital systems to prepare for the influx of high-acuity resource-intensive patients.

RéSUMé: CONTEXTE: Les changements climatiques entraînent une augmentation des épisodes de chaleur extrême dans les climats tempérés qui ont généralement de faibles niveaux de préparation. Notre objectif était de décrire les caractéristiques, les traitements et les résultats des adultes présentant un coup de chaleur à l'hôpital pendant le dôme de chaleur de 2021 en Colombie-Britannique. MéTHODES: Nous avons effectué un examen des adultes consécutifs qui se sont présentés dans sept hôpitaux du Lower Mainland de la Colombie-Britannique. Nous avons examiné les dossiers de triage de tous les patients qui se sont présentés entre le 25 et le 30 juin 2021 pour les plaintes liées à la chaleur et examiné les dossiers complets de ceux qui répondaient aux critères de coup de chaleur. Notre principal résultat était la mortalité à l'hôpital. Nous avons utilisé les tests de Mann-Whitney U et la régression logistique pour étudier les associations entre le patient et les facteurs de traitement et la mortalité. RéSULTATS: Parmi les 10247 présentations consécutives aux hôpitaux urbains pendant l'événement de chaleur extrême, 1,3 % (139; intervalles de confiance [IC] à 95 %) répondaient aux critères de coup de chaleur. Parmi les patients ayant subi un coup de chaleur, 129 (90,6 %) ont été classés dans les deux niveaux d'acuité les plus élevés. Les patients atteints d'un coup de chaleur avaient un âge médian de 84,4 ans, 122 (87,8 %) vivant seuls et 101 (84,2 %) incapables d'activer le 911 eux-mêmes. Une minorité (< 5, < 3,6 %) de patients se sont présentés dans les 48 heures suivant l'apparition de la chaleur extrême. La plupart des patients (107, 77,0 %) ont dû être admis et 11,5 % (16) sont décédés à l'hôpital. L'hypotension au moment de la présentation était associée à la mortalité (rapport de cotes [RC] 5.3). INTERPRéTATION: Les patients atteints d'un coup de chaleur n'ont pas pu activer le 911 eux-mêmes, et la plupart se sont présentés avec un délai de 48 heures. Ce délai peut représenter une fenêtre critique d'opportunité pour les systèmes préhospitaliers et hospitaliers de se préparer à l'afflux de patients à forte intensité de ressources.

Effects of pharmacogenetic profiles on pediatric pain relief and adverse events with ibuprofen and oxycodone.

Introduction: Individual genetic variation may influence clinical effects for pain medications. Effects of CYP2C9, CYP3A4, and CYP2D6 polymorphisms on clinical effectiveness and safety for ibuprofen and oxycodone were studied. Objective: Primary objectives were to AU2 evaluate if allelic variations would affect clinical effectiveness and adverse events (AEs) occurrence. Methods: This pragmatic prospective, observational cohort included children aged 4 to 16 years who were seen in a pediatric emergency department with an acute fracture and prescribed ibuprofen or oxycodone for at-home pain management. Saliva samples were obtained for genotyping of allelic variants, and daily telephone follow-up was conducted for 3 days. Pain was measured using the Faces Pain Scale-Revised. Results: We included 210 children (n = 140 ibuprofen and n = 70 oxycodone); mean age was 11.1 (±SD 3.5) years, 33.8% were female. Median pain reduction on day 1 was similar between groups [ibuprofen 4 (IQR 2,4) and oxycodone 4 (IQR 2,6), P = 0.69]. Over the 3 days, the oxycodone group experienced more AE than the ibuprofen group (78.3% vs 53.2%, P < 0.001). Those with a CYP2C9*2 reduced function allele experienced less adverse events with ibuprofen compared with those with a normal functioning allele CYP2C9*1 (P = 0.003). Neither CYP3A4 variants nor CYP2D6 phenotype classification affected clinical effect or AE. Conclusion: Although pain relief was similar, children receiving oxycodone experienced more AE, overall, than those receiving ibuprofen. For children receiving ibuprofen or oxycodone, pain relief was not affected by genetic variations in CYP2C9 or CYP3A4/CYP2D6, respectively. For children receiving ibuprofen, the presence of CYP2C9*2 was associated with less adverse events.

Characterizing intubation practices in response to the COVID-19 pandemic: a survey of the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) sites.

OBJECTIVE: The risk of occupational exposure during endotracheal intubation has required the global Emergency Medicine (EM), Anesthesia, and Critical Care communities to institute new COVID- protected intubation guidelines, checklists, and protocols. This survey aimed to deepen the understanding of the changes in intubation practices across Canada by evaluating the pre-COVID-19, early-COVID-19, and present-day periods, elucidating facilitators and barriers to implementation, and understanding provider impressions of the effectiveness and safety of the changes made. METHODS: We conducted an electronic, self-administered, cross-sectional survey of EM physician site leads within the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) to characterize and compare airway management practices in the pre-COVID-19, early-COVID-19, and present-day periods. Ethics approval for this study was obtained from the University of Manitoba Health Research Ethics Board. The electronic platform SurveyMonkey ( www.surveymonkey.com ) was used to collect and store survey tool responses. Categorical item responses, including the primary outcome, are reported as numbers and proportions. Variations in intubation practices over time were evaluated through mixed-effects logistic regression models. RESULTS: Invitations were sent to 33 emergency department (ED) physician site leads in the CCEDRRN. We collected 27 survey responses, 4 were excluded, and 23 analysed. Responses were collected in English (87%) and French (13%), from across Canada and included mainly physicians practicing in mainly Academic and tertiary sites (83%). All respondents reported that the intubation protocols used in their EDs changed in response to the COVID-19 pandemic (100%, n = 23, 95% CI 0.86-1.00). CONCLUSIONS: This study provides a novel summary of changes to airway management practices in response to the evolving COVID-19 pandemic in Canada. Information from this study could help inform a consensus on safe and effective emergent intubation of persons with communicable respiratory infections in the future.

Transitions in health care settings for frequent and infrequent users of emergency departments: a population-based retrospective cohort study.

BACKGROUND: Efforts to reduce emergency department (ED) volumes often target frequent users. We examined transitions in care across ED, hospital, and community settings, and in-hospital death, for high system users (HSUs) compared to controls. METHODS: Population-based databases provided ED visits and hospitalizations in Alberta and Ontario, Canada. The retrospective cohort included the top 10% of all the ED users during 2015/2016 (termed HSUs) and a random sample of controls (4 per each HSU) from the bottom 90% per province. Rates of transitions among ED, hospitalization, community settings, and in-hospital mortality were adjusted for sociodemographic and ED variables in a multistate statistical model. RESULTS: There were 2,684,924 patients and 579,230 (21.6%) were HSUs. Patient characteristics associated with shorter community to ED transition times for HSUs included Alberta residence (ratio of hazard ratio [RHR] = 1.11, 95% confidence interval [CI] 1.11,1.12), living in areas in the lower income quintile (RHR = 1.06, 95%CI 1.06,1.06), and Ontario residents without a primary health care provider (RHR = 1.13, 95%CI 1.13,1.14). Once at the ED, characteristics associated with shorter ED to hospital transition times for HSUs included higher acuity (e.g., RHR = 1.70, 95% CI 1.61, 1.81 for emergent), and for many diagnoses including chest pain (RHR = 1.71, 95%CI 1.65,1.76) and gastrointestinal (RHR = 1.66, 95%CI 1.62,1.71). Once admitted to hospital, HSUs did not necessarily have longer stays except for conditions such as chest pain (RHR = 0.90, 95% CI 0.86, 0.95). HSUs had shorter times to death in the ED if they presented for cancer (RHR = 2.51), congestive heart failure (RHR = 1.93), myocardial infarction (RHR = 1.53), and stroke (RHR = 1.84), and shorter times to death in-hospital if they presented with cancer (RHR = 1.29). CONCLUSIONS: Differences between HSUs and controls in predictors of transitions among care settings were identified. Co-morbidities and limitations in access to primary care are associated with more rapid transitions from community to ED and hospital among HSUs. Interventions targeting these challenges may better serve patients across health systems.. TRIAL REGISTRATION: Not applicable.

Comparing methods to classify admitted patients with SARS-CoV-2 as admitted for COVID-19 versus with incidental SARS-CoV-2: A cohort study.

INTRODUCTION: Not all patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection develop symptomatic coronavirus disease 2019 (COVID-19), making it challenging to assess the burden of COVID-19-related hospitalizations and mortality. We aimed to determine the proportion, resource utilization, and outcomes of SARS-CoV-2 positive patients admitted for COVID-19, and assess the impact of using the Center for Disease Control's (CDC) discharge diagnosis-based algorithm and the Massachusetts state department's drug administration-based classification system on identifying admissions for COVID-19. METHODS: In this retrospective cohort study, we enrolled consecutive SARS-CoV-2 positive patients admitted to one of five hospitals in British Columbia between December 19, 2021 and May 31,2022. We completed medical record reviews, and classified hospitalizations as being primarily for COVID-19 or with incidental SARS-CoV-2 infection. We applied the CDC algorithm and the Massachusetts classification to estimate the difference in hospital days, intensive care unit (ICU) days and in-hospital mortality and calculated sensitivity and specificity. RESULTS: Of 42,505 Emergency Department patients, 1,651 were admitted and tested positive for SARS-CoV-2, with 858 (52.0%, 95% CI 49.6-54.4) admitted for COVID-19. Patients hospitalized for COVID-19 required ICU admission (14.0% versus 8.2%, p<0.001) and died (12.6% versus 6.4%, p<0.001) more frequently compared with patients with incidental SARS-CoV-2. Compared to case classification by clinicians, the CDC algorithm had a sensitivity of 82.9% (711/858, 95% CI 80.3%, 85.4%) and specificity of 98.1% (778/793, 95% CI 97.2%, 99.1%) for COVID-19-related admissions and underestimated COVID-19 attributable hospital days. The Massachusetts classification had a sensitivity of 60.5% (519/858, 95% CI 57.2%, 63.8%) and specificity of 78.6% (623/793, 95% CI 75.7%, 81.4%) for COVID-19-related admissions, underestimating total number of hospital and ICU bed days while overestimating COVID-19-related intubations, ICU admissions, and deaths. CONCLUSION: Half of SARS-CoV-2 hospitalizations were for COVID-19 during the Omicron wave. The CDC algorithm was more specific and sensitive than the Massachusetts classification, but underestimated the burden of COVID-19 admissions. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04702945.

Perinatal and early life factors and asthma control among preschoolers: a population-based retrospective cohort study.

BACKGROUND: Preventing poor childhood asthma control is crucial for short-term and long-term respiratory health. This study evaluated associations between perinatal and early-life factors and early childhood asthma control. METHODS: This retrospective study used administrative health data from mothers and children born 2010-2012 with a diagnosis of asthma before age 5 years, in Alberta, Canada. The outcome was asthma control within 2 years after diagnosis. Associations between perinatal and early-life factors and risk of partly and uncontrolled asthma were evaluated by multinomial logistic regression. RESULTS: Of 7206 preschoolers with asthma, 52% had controlled, 37% partly controlled and 12% uncontrolled asthma 2 years after diagnosis. Compared with controlled asthma, prenatal antibiotics (adjusted risk ratio (aRR): 1.19; 95% CI 1.06 to 1.33) and smoking (aRR: 1.18; 95% CI 1.02 to 1.37), C-section delivery (aRR: 1.11; 95% CI 1.00 to 1.25), summer birth (aRR: 1.16; 95% CI 1.00 to 1.34) and early-life hospitalisation for respiratory illness (aRR: 2.24; 95% CI 1.81 to 2.76) increased the risk of partly controlled asthma. Gestational diabetes (aRR: 1.41; 95% CI 1.06 to 1.87), C-section delivery (aRR: 1.18; 95% CI 1.00 to 1.39), antibiotics (aRR: 1.32; 95% CI 1.08 to 1.61) and hospitalisation for early-life respiratory illness (aRR: 1.65; 95% CI 1.19 to 2.27) were associated with uncontrolled asthma. CONCLUSION: Maternal perinatal and early-life factors including antibiotics in pregnancy and childhood, gestational diabetes, prenatal smoking, C-section and summertime birth, and hospitalisations for respiratory illness are associated with partly or uncontrolled childhood asthma. These results underline the significance of perinatal health and the lasting effects of early-life experiences on lung development and disease programming.

Flow through the Emergency Department for Patients Presenting with Substance Use Disorder in Alberta, Canada.

INTRODUCTION: Since 2016 the province of Alberta, Canada, has seen a significant increase in substance use disorder (SUD) presentations to the emergency department (ED) with a large surge during the COVID-19 pandemic. In this retrospective study we deconstruct the total length of stay (LOS) in the ED into stages for patients presenting with SUD and estimate the effects of covariates on the time to transition between stages. METHODS: Using the Canadian Coding Standards for International Classification of Diseases, 10th Modification, codes F10.0-F19.9 and T36.0-T50.9, we extracted data from the National Ambulatory Care Reporting System between April 1, 2019-March 31, 2020 on all ED presentations for SUD by Alberta residents. We used a multistate model to deconstruct the EDLOS into eight mutually exclusive states and determine which factors affected the time spent in each state. RESULTS: We analyzed 66,880 presentations (37,530 patients). The mean age was 37.2 years, and 61% were male. The median total LOS in the ED was 6 hours 13 minutes. Patients presenting with methamphetamines (METH) intoxication and patients from low-income neighborhoods had significantly increased transition times between all states. Opposite this, opiate use was associated with faster transition times between almost all states. Metro EDs experienced slower transitions when attempting to discharge or admit patients when compared to urban or rural EDs. Emergency department crowding also had a dramatic effect on physician initial assessment times, while discharge and admission times in patients presenting with SUD were also significantly affected. CONCLUSION: Patients with SUD experience a variety of delays during their ED stay. Those with METH intoxication and those from the lowest income neighborhoods were most likely to experience slower transitions from state to state in the ED and may benefit from a focused approach to improve ED flow.

Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial.

BACKGROUND: People experiencing asthma exacerbations are at increased risk of cardiovascular events. To better understand the relationship between asthma exacerbations and cardiovascular risk, this randomized case-control, cross-over controlled trial assessed the immediate systemic inflammatory and vascular responses to acutely induced pulmonary inflammation and bronchoconstriction in people with asthma and controls. METHODS: Twenty-six people with asthma and 25 controls underwent three airway challenges (placebo, mannitol, and methacholine) in random order. Markers of cardiovascular risk, including serum C-reactive protein, interleukin-6, and tumor necrosis factor, endothelial function (flow-mediated dilation), microvascular function (blood-flow following reactive hyperemia), and arterial stiffness (pulse wave velocity) were evaluated at baseline and within one hour following each challenge. The systemic responses in a) asthma/control and b) positive airway challenges were analyzed. (ClinicalTrials.gov reg# NCT02630511). RESULTS: Both the mannitol and methacholine challenges resulted in clinically significant reductions in forced expiratory volume in 1 second (FEV1) in asthma (-7.6% and -17.9%, respectively). Following positive challenges, reduction in FEV1 was -27.6% for methacholine and -14.2% for mannitol. No meaningful differences in predictors of cardiovascular risk were observed between airway challenges regardless of bronchoconstrictor response. CONCLUSION: Neither acutely induced bronchoconstriction nor pulmonary inflammation and bronchoconstriction resulted in meaningful changes in systemic inflammatory or vascular function. These findings question whether the increased cardiovascular risk associated with asthma exacerbations is secondary to acute bronchoconstriction or inflammation, and suggest that other factors need to be further evaluated such as the cardiovascular impacts of short-acting inhaled beta-agonists.

Examining changes in vascular function, arterial stiffness and systemic inflammation during hospitalization and recovery from an acute exacerbation of chronic obstructive pulmonary disease.

An acute exacerbation of COPD (AECOPD) is associated with increased risk of cardiovascular (CV) events. The elevated risk during an AECOPD may be related to changes in vascular function, arterial stiffness, and systemic inflammation; the time course of these measures and their corresponding recovery are poorly understood. Further, physical activity is reduced during an AECOPD, and physical activity may influence the cardiovascular responses to an AECOPD. The purpose of the study was to examine the acute impact of an AECOPD requiring hospitalization on vascular function, arterial stiffness, and systemic inflammation and examine whether physical activity modulates these variables during recovery. Patients hospitalized for an AECOPD were prospectively recruited and compared to control patients with stable COPD. Vascular function, arterial stiffness, and systemic inflammation (CRP, IL-6) were measured at hospital admission, hospital discharge and within 14 days of discharge. Physical activity was electronically tracked daily while in hospital and for 7 days following discharge using a Fitbit. One hundred and twenty-one patients with an AECOPD requiring hospitalization and 33 control patients with stable COPD were enrolled in the study. Vascular function was significantly lower, and systemic inflammation higher at hospital admission in patients with an AECOPD compared to stable COPD. Significant improvements in vascular function and inflammation were observed within 14 days of hospital discharge; however, vascular function remained lower than stable COPD. Physical activity was low at admission and increased following discharge; however, physical activity was unrelated to measures of vascular function or inflammation at any time point. An AECOPD requiring hospitalization is associated with impaired vascular function that persists during recovery. These findings provide a mechanistic link to help explain the enduring increase in CV risk and mortality following a severe AECOPD event.Clinical trial registration: ClinicalTrials.gov #NCT01949727; Registered: 09/20/2013.

Accuracy of Self-Reported COVID-19 Vaccination Status Compared With a Public Health Vaccination Registry in Québec: Observational Diagnostic Study.

BACKGROUND: The accuracy of self-reported vaccination status is important to guide real-world vaccine effectiveness studies and policy making in jurisdictions where access to electronic vaccine registries is restricted. OBJECTIVE: This study aimed to determine the accuracy of self-reported vaccination status and reliability of the self-reported number of doses, brand, and time of vaccine administration. METHODS: This diagnostic accuracy study was completed by the Canadian COVID-19 Emergency Department Rapid Response Network. We enrolled consecutive patients presenting to 4 emergency departments (EDs) in Québec between March 24, 2020, and December 25, 2021. We included adult patients who were able to consent, could speak English or French, and had a proven COVID-19 infection. We compared the self-reported vaccination status of the patients with their vaccination status in the electronic Québec Vaccination Registry. Our primary outcome was the accuracy of the self-reported vaccination status (index test) ascertained during telephone follow-up compared with the Québec Vaccination Registry (reference standard). The accuracy was calculated by dividing all correctly self-reported vaccinated and unvaccinated participants by the sum of all correctly and incorrectly self-reported vaccinated and unvaccinated participants. We also reported interrater agreement with the reference standard as measured by unweighted Cohen κ for self-reported vaccination status at telephone follow-up and at the time of their index ED visit, number of vaccine doses, and brand. RESULTS: During the study period, we included 1361 participants. At the time of the follow-up interview, 932 participants reported at least 1 dose of a COVID-19 vaccine. The accuracy of the self-reported vaccination status was 96% (95% CI 95%-97%). Cohen κ for self-reported vaccination status at phone follow-up was 0.91 (95% CI 0.89-0.93) and 0.85 (95% CI 0.77-0.92) at the time of their index ED visit. Cohen κ was 0.89 (95% CI 0.87-0.91) for the number of doses, 0.80 (95% CI 0.75-0.84) for the brand of the first dose, 0.76 (95% CI 0.70-0.83) for the brand of the second dose, and 0.59 (95% CI 0.34-0.83) for the brand of the third dose. CONCLUSIONS: We reported a high accuracy of self-reported vaccination status for adult patients without cognitive disorders who can express themselves in English or French. Researchers can use self-reported COVID-19 vaccination data on the number of doses received, vaccine brand name, and timing of vaccination to guide future research with patients who are capable of self-reporting their vaccination data. However, access to official electronic vaccine registries is still needed to determine the vaccination status in certain susceptible populations where self-reported vaccination data remain missing or impossible to obtain. TRIAL REGISTRATION: Clinicaltrials.gov NCT04702945; https://clinicaltrials.gov/ct2/show/NCT04702945.

Intubation practices and outcomes for patients with suspected or confirmed COVID-19: a national observational study by the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN).

OBJECTIVE: Intubation practices changed during the COVID-19 pandemic to protect healthcare workers from transmission of disease. Our objectives were to describe intubation characteristics and outcomes for patients tested for SARS CoV-2 infection. We compared outcomes between patients testing SARS COV-2 positive with those testing negative. METHODS: We conducted a health records review using the Canadian COVID-19 Emergency Department Rapid Response Network (CCEDRRN) registry. We included consecutive eligible patients who presented to one of 47 EDs across Canada between March 1, 2020 and June 20, 2021, were tested for SARS-CoV-2 and intubated in the ED. The primary outcome was the proportion of patients experiencing a post-intubation adverse event during the ED stay. Secondary outcomes included first-pass success, intubation practices, and hospital mortality. We used descriptive statistics to summarize variables with subgroup differences examined using t tests, z tests, or chi-squared tests where appropriate with 95% CIs. RESULTS: Of 1720 patients with suspected COVID-19 who were intubated in the ED during the study period, 337 (19.6%) tested SARS-CoV-2 positive and 1383 (80.4%) SARS-CoV-2 negative. SARS-CoV-2 positive patients presented to hospital with lower oxygen levels than SARS-CoV-2 negative patients (mean pulse oximeter SaO2 86 vs 94%, p < 0.001). In total, 8.5% of patients experienced an adverse event post-intubation. More patients in the SARS-CoV-2 positive subgroup experienced post-intubation hypoxemia (4.5 vs 2.2%, p = 0.019). In-hospital mortality was greater for patients who experienced intubation-related adverse events (43.2 vs 33.2%, p = 0.018). There was no significant difference in adverse event-associated mortality by SARS-CoV-2 status. First-pass success was achieved in 92.4% of all intubations, with no difference by SARS-CoV-2 status. CONCLUSIONS: During the COVID-19 pandemic, we observed a low risk of adverse events associated with intubation, even though hypoxemia was common in patients with confirmed SARS-CoV-2. We observed high rates of first-pass success and low rates of inability to intubate. The limited number of adverse events precluded multivariate adjustments. Study findings should reassure emergency medicine practitioners that system modifications made to intubation processes in response to the COVID-19 pandemic do not appear to be associated with worse outcomes compared to pre-COVID-19 practices.

RéSUMé: OBJECTIF: Les pratiques d'intubation ont changé au cours de la pandémie de COVID-19 afin de protéger le personnel de santé contre la transmission de la maladie. Nos objectifs étaient de décrire les caractéristiques de l'intubation et les résultats pour les patients testés pour l'infection par le CoV-2 du SRAS. Nous avons comparé les résultats entre les patients testés positifs au SARS COV-2 et ceux testés négatifs. MéTHODES: Nous avons effectué un examen des dossiers de santé à l'aide du registre du Réseau canadien d'intervention rapide dans les services d'urgence pour la COVID-19 (RCIRSUC). Nous avons inclus les patients éligibles consécutifs qui se sont présentés à l'un des 47 services d'urgence du Canada entre le 1er mars 2020 et le 20 juin 2021, qui ont été testés pour le SRAS-CoV-2 et qui ont été intubés dans le service d'urgence. Le résultat principal était la proportion de patients ayant subi un événement indésirable après l'intubation pendant leur séjour aux urgences. Les critères de jugement secondaires comprenaient le succès du premier passage, les pratiques d'intubation et la mortalité hospitalière. Nous avons utilisé des statistiques descriptives pour résumer les variables avec des différences de sous-groupes examinées à l'aide de tests t, de tests z ou de tests du chi carré, le cas échéant, avec des IC à 95%. RéSULTATS: Sur les 1720 patients suspects de COVID-19 qui ont été intubés aux urgences pendant la période de l'étude, 337 (19,6%) ont été testés positifs au SARS-CoV-2 et 1383 (80,4%) négatifs au SARS-CoV-2. Les patients positifs au SRAS-CoV-2 se sont présentés à l'hôpital avec des niveaux d'oxygène inférieurs à ceux des patients négatifs pour le SRAS-CoV-2 (oxymètre de pouls moyen SaO2 86% contre 94%, p < 0,001). Au total, 8,5% des patients ont présenté un événement indésirable après l'intubation. Un plus grand nombre de patients du sous-groupe positif au SRAS-CoV-2 ont présenté une hypoxémie post-intubation (4,5% vs 2,2%, p = 0,019). La mortalité hospitalière était plus élevée chez les patients ayant subi des événements indésirables liés à l'intubation (43,2% vs 33,2%, p = 0,018). Il n'y avait pas de différence significative dans la mortalité associée aux événements indésirables selon le statut du SRAS-CoV-2. Le succès du premier passage a été obtenu dans 92,4% de toutes les intubations, sans différence selon le statut SARS-CoV-2 CONCLUSIONS: Pendant la pandémie de COVID-19, nous avons observé un faible risque d'événements indésirables associés à l'intubation, même si l'hypoxémie était fréquente chez les patients atteints de SRAS-CoV-2 confirmé. Nous avons observé des taux élevés de réussite du premier passage et des taux faibles d'incapacité à intuber. Le nombre limité d'événements indésirables a empêché les ajustements multivariés. Les résultats de l'étude devraient rassurer les praticiens de la médecine d'urgence que les modifications apportées aux processus d'intubation en réponse à la pandémie de COVID-19 ne semblent pas être associées à des résultats plus défavorables que les pratiques antérieures à la pandémie de COVID-19.

The burden of incidental SARS-CoV-2 infections in hospitalized patients across pandemic waves in Canada.

Many health authorities differentiate hospitalizations in patients infected with SARS-CoV-2 as being "for COVID-19" (due to direct manifestations of SARS-CoV-2 infection) versus being an "incidental" finding in someone admitted for an unrelated condition. We conducted a retrospective cohort study of all SARS-CoV-2 infected patients hospitalized via 47 Canadian emergency departments, March 2020-July 2022 to determine whether hospitalizations with "incidental" SARS-CoV-2 infection are less of a burden to patients and the healthcare system. Using a priori standardized definitions applied to hospital discharge diagnoses in 14,290 patients, we characterized COVID-19 as (i) the "Direct" cause for the hospitalization (70%), (ii) a potential "Contributing" factor for the hospitalization (4%), or (iii) an "Incidental" finding that did not influence the need for admission (26%). The proportion of incidental SARS-CoV-2 infections rose from 10% in Wave 1 to 41% during the Omicron wave. Patients with COVID-19 as the direct cause of hospitalization exhibited significantly longer LOS (mean 13.8 versus 12.1 days), were more likely to require critical care (22% versus 11%), receive COVID-19-specific therapies (55% versus 19%), and die (17% versus 9%) compared to patients with Incidental SARS-CoV-2 infections. However, patients hospitalized with incidental SARS-CoV-2 infection still exhibited substantial morbidity/mortality and hospital resource use.

Emergency department crowding negatively influences outcomes for adults presenting for chronic obstructive pulmonary disease.

OBJECTIVES: Emergency department (ED) crowding leads to poor outcomes. Patients with respiratory conditions like chronic obstructive pulmonary disease (COPD) are especially vulnerable to crowding-related delays in care. We aimed to assess the associations of ED crowding metrics with outcomes for patients presenting with COPD. METHODS: We conducted a population-based cohort study of adult patients presenting with a diagnosis of COPD to 18 high-volume EDs between 2014 and 2019 in Alberta, Canada. Administrative databases provided date and time data on key stages of the presentation including physician initial assessment and disposition decision. Crowding metrics were calculated using facility-specific median physician initial assessment and length of stay. Patient presentations were grouped by acuity and mixed-effects regression models were fit to adjust for the clustering at the facility level. RESULTS: There were 49,085 presentations for COPD made by 25,734 patients (median age = 73 years). A 1-h increase in the physician initial assessment metric was associated with an increase in physician initial assessment for COPD patients by 23, 53, and 59 min for the high, moderate, and low acuity groups, respectively, adjusted for other predictors. For the low acuity group, this metric was associated with an increased length of stay of 73 min for admitted individuals. Similarly, an increase in the length of stay metric was also associated with an increased likelihood of being admitted for all acuity groups. CONCLUSIONS: For patients with COPD, ED crowding results in delays in assessment increased length of stay, and increased proportion of patients admitted. These results suggest that ED crowding mitigation efforts to provide timely care for patients with COPD are urgently needed. TRIAL REGISTRATION: N/A.

RéSUMé: OBJECTIFS: L'encombrement des services d'urgence entraîne de mauvais résultats. Les patients souffrant de maladies respiratoires telles que la maladie pulmonaire obstructive chronique (MPOC) sont particulièrement vulnérables aux retards de soins liés à l'encombrement. Notre avons cherché à évaluer les associations entre les paramètres d'encombrement des services d'urgence et les résultats pour les patients présentant une MPOC. MéTHODES: Nous avons mené une étude de cohorte basée sur la population de patients adultes se présentant avec un diagnostic de MPOC dans dix-huit services d'urgence à haut volume entre 2014 et 2019 en Alberta, au Canada. Les bases de données administratives ont fourni des données sur la date et l'heure des principales étapes de la présentation, y compris l'évaluation initiale par le médecin et la décision de sortie. Les mesures d'encombrement ont été calculées à partir de l'évaluation initiale médiane du médecin et de la durée du séjour propres à l'établissement. Les présentations des patients ont été regroupées par gravité et des modèles de régression à effets mixtes ont été ajustés pour tenir compte du regroupement au niveau de l'établissement. RéSULTATS: Il y a eu 49 085 présentations pour la MPOC effectuées par 25 734 patients (âge médian = 73 ans). Une augmentation d'une heure de l'évaluation initiale par le médecin était associée à une augmentation de l'évaluation initiale par le médecin pour les patients atteints de MPOC de 23, 53 et 59 min pour les groupes de gravité élevée, modérée et faible, respectivement, après ajustement pour d'autres facteurs prédictifs. Pour le groupe de faible gravité, ce paramètre était associé à une augmentation de la durée de séjour de 73 min pour les personnes admises. De même, une augmentation de la durée du séjour était également associée à une probabilité accrue d'admission pour tous les groupes de gravité. CONCLUSIONS: Pour les patients atteints de MPOC, l'encombrement des urgences entraîne des retards dans l'évaluation, une augmentation de la durée du séjour et une augmentation de la proportion de patients admis. Ces résultats suggèrent qu'il est urgent d'atténuer l'encombrement des urgences afin de fournir des soins en temps opportun aux patients atteints de MPOC. ENREGISTREMENT DE L'ESSAI: N/A.

Prognostic association between d-dimer thresholds and 30-day pulmonary embolism diagnosis among emergency department patients with suspected SARS-CoV-2 infection: a Canadian COVID-19 Emergency Department Rapid Response Network study.

OBJECTIVE: The primary objective was to quantify the prognostic association between various D-dimer thresholds and 30-day PE diagnosis among emergency department (ED) patients with suspected SARS-CoV-2 infection. METHODS: This was a retrospective study of patients enrolled in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) registry from March 1, 2020 to July 2, 2021. We included consecutive adults (≥ 18 years) presenting to 49 EDs with chest pain, shortness of breath, hypoxia, syncope, presyncope, or hemoptysis who were tested for both SARS-CoV-2 and D-dimer at index ED visit. The primary outcome measure was the sensitivity, specificity, and negative predictive value of D-dimer test thresholds for the outcome of 30-day PE diagnosis. RESULTS: Among 10,837 patients included in our study, 404 (3.7%) were diagnosed with PE at 30-days. A standard D-Dimer threshold of 500 ng/mL had a sensitivity of 97.8% (95% confidence interval [CI] 95.8-99.0%), specificity of 40.9% (95% CI 39.9-41.8%), and negative predictive value of 99.8% (95% CI 99.6-99.9%). An age-adjusted D-dimer threshold had a sensitivity of 96.0% (95% CI 93.6-97.7%), specificity of 48.5% (95% CI 47.5-49.4%), and negative predictive value of 99.7% (95% CI 99.5-99.8%). D-dimer testing had slightly lower prognostic performance among SARS-CoV-2 positive compared to SARS-CoV-2 negative patients in predicting 30-day PE diagnosis. CONCLUSIONS: Among ED patients with suspected SARS-CoV-2, the standard 500 ng/mL and age-adjusted D-dimer thresholds were comparable for the prediction of PE at 30-days. The prognostic performance of D-dimer was lower among SARS-CoV-2 positive patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04702945.

RéSUMé: OBJECTIF: L'objectif principal était de quantifier l'association pronostique entre différents seuils de D-dimères et le diagnostic d'EP à 30 jours chez les patients des services d'urgence suspectés d'être infectés par le SRAS-CoV-2. MéTHODES: Il s'agissait d'une étude rétrospective des patients inscrits au registre du réseau canadien de réponse rapide aux urgences COVID-19 (CCEDRRN) du 1er mars 2020 au 2 juillet 2021. Nous avons inclus des adultes consécutifs (>18 ans) se présentant dans 49 services d'urgence pour une douleur thoracique, un essoufflement, une hypoxie, une syncope, une présyncope ou une hémoptysie et qui ont été testés à la fois pour le SRAS-CoV-2 et les D-dimères lors de la visite de référence aux urgences. Le principal critère d'évaluation était la sensibilité, la spécificité et la valeur prédictive négative des seuils du test des D-dimères pour le diagnostic de l'EP à 30 jours. RéSULTATS: Parmi les 10 837 patients inclus dans notre étude, 404 (3,7 %) ont reçu un diagnostic d'EP à 30 jours. Un seuil standard de D-Dimer de 500 ng/mL avait une sensibilité de 97,8 % (intervalle de confiance [IC] à 95 % 95,8-99,0 %), une spécificité de 40,9 % (IC à 95 % 39,9-41,8 %) et une valeur prédictive négative de 99,8 % (IC à 95 % 99,6-99,9 %). Un seuil de D-dimères ajusté à l'âge avait une sensibilité de 96,0% (IC à 95 % 93,6-97,7 %), une spécificité de 48,5% (IC à 95 % 47,5-49,4 %) et une valeur prédictive négative de 99,7 % (IC à 95 % 99,5-99,8 %). Le test des D-dimères avait une performance pronostique légèrement inférieure chez les patients positifs pour le SRAS-CoV-2 par rapport aux patients négatifs pour le SRAS-CoV-2 en ce qui concerne la prédiction du diagnostic d'EP à 30 jours. CONCLUSIONS: Chez les patients des urgences suspectés d'être atteints du SRAS-CoV-2, les seuils standard de 500 ng/ml et les seuils de D-dimères ajustés à l'âge étaient comparables pour la prédiction de l'EP à 30 jours. La performance pronostique des D-dimères était plus faible chez les patients positifs pour le SRAS-CoV-2. ENREGISTREMENT DE L'ESSAI: Clinicaltrials.gov, NCT04702945.

A multi-center, randomized, 12-month, parallel-group, feasibility study to assess the acceptability and preliminary impact of family navigation plus usual care versus usual care on attrition in managing pediatric obesity: a study protocol.

BACKGROUND: Pediatric obesity management can be successful, but some families discontinue care prematurely (i.e., attrition), limiting treatment impact. Attrition is often a consequence of barriers and constraints that limit families' access to obesity management. Family Navigation (FN) can improve access, satisfaction with care, and treatment outcomes in diverse areas of healthcare. To help our team prepare for a future effectiveness trial, the objectives of our randomized feasibility study are to (i) explore children's and caregivers' acceptability of FN and (ii) examine attrition, measures of study rigor and conduct, and responses to FN + Usual Care vs Usual Care by collecting clinical, health services, and health economic data. METHODS: In our 2.5-year study, 108 6-17-year-olds with obesity and their caregivers will be randomized (1:1) to FN + Usual Care or Usual Care after they enroll in obesity management clinics in Calgary and Mississauga, Canada. Our Stakeholder Steering Committee and research team will use Experience-Based Co-Design to design and refine our FN intervention to reduce families' barriers to care, maximizing the intervention dose families receive. FN will be delivered by a navigator at each site who will use logistical and relational strategies to enhance access to care, supplementing obesity management. Usual Care will be offered similarly at both clinics, adhering to expert guidelines. At enrollment, families will complete a multidisciplinary assessment, then meet regularly with a multidisciplinary team of clinicians for obesity management. Over 12 months, both FN and Usual Care will be delivered virtually and/or in-person, pandemic permitting. Data will be collected at 0, 3, 6, and 12 months post-baseline. We will explore child and caregiver perceptions of FN acceptability as well as evaluate attrition, recruitment, enrolment, randomization, and protocol integrity against pre-set success thresholds. Data on clinical, health services, and health economic outcomes will be collected using established protocols. Qualitative data analysis will apply thematic analysis; quantitative data analysis will be descriptive. DISCUSSION: Our trial will assess the feasibility of FN to address attrition in managing pediatric obesity. Study data will inform a future effectiveness trial, which will be designed to test whether FN reduces attrition. TRIAL REGISTRATION: This trial was registered prospectively at ClinicalTrials.gov (# NCT05403658 ; first posted: June 3, 2022).