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.

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.

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.

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.

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.