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Objective: To explore the trajectory of scleroderma disease activity in women who experienced a pregnancy after systemic sclerosis diagnosis compared to nulliparous women. Methods: We analyzed data from the Canadian Scleroderma Research Group registry by identifying nulliparous women and women with ⩾1 pregnancy after systemic sclerosis diagnosis. Patient characteristics were compared between groups at registry entry. Controlling for age, smoking, and time since systemic sclerosis diagnosis, generalized estimating equations tested the effect of pregnancy on force vital capacity, diffusing capacity of the lungs for carbon monoxide, right ventricular systolic pressure, glomerular filtration rate, antibody status, active digital ulcers, physician global assessment of activity, and severity over 9 years. Results: At registry entry, numbers of women in the nulliparous and pregnancy after systemic sclerosis diagnosis groups were 153 and 45, respectively. Corresponding numbers at 6 and 9 years were 48 and 21, and 18 and 9, respectively. The prevalence of anti-topoisomerase positivity was 18.3% in nulliparous and 12.5% in pregnancy after systemic sclerosis diagnosis. Baseline differences included mean (Standard deviation) age of diagnosis (nulliparous: 38.8 (14.0), pregnancy after systemic sclerosis diagnosis: 22.6 (6.8) years, p Conclusion: Results demonstrated that having ⩾1 pregnancy after systemic sclerosis diagnosis did not appear to significantly impact long-term renal, respiratory, or global function outcomes. While this offers a hopeful message to systemic sclerosis patients planning a pregnancy, physicians and patients should remain vigilant for potential post-partum complications.

It is unclear whether D-dimer is a disease-specific marker for COVID-19 or part of the general inflammatory response alongside C-reactive protein (CRP) and other acute-phase reactants. We extracted data of patients hos-pitalized with COVID-19 for demographics, comorbidities, biochemical data, and outcomes. Using multivari-able logistic regression, the value of D-dimer in predicting intensive care unit (ICU) admission or mortality was measured. Of 1175 patients, 263 were admitted to the ICU and 226 died. CRP predicted both ICU admission and mortality [Odds ratios (ORs) with 95% confidence interval 1.01 (1.01–1.01) and 1.00 (1.00–1.01), respectively] but D-dimer was not predictive of either outcome [ORs 1.02 (0.97–1.06) and 0.99 (0.93–1.06)]. This suggests D-dimer levels are not independently predictive of COVID-19 severity or mortality. Our results confirm find-ings from smaller cohorts and demonstrate the inflammatory characteristics of COVID in the Canadian context. RésuméOn ne sait pas exactement si le D-dimère est un marqueur propre à la COVID-19 ou s’il fait partie de la réponse inflammatoire générale au même titre que la protéine C réactive et autres réactifs de phase aiguë. Nous avons extrait les données relatives aux caractéristiques démographiques, aux affections comorbides, aux analyses bio-chimiques et aux issues de patients hospitalisés en raison de la COVID-19. À l’aide d’une régression logistique multivariable, nous avons mesuré l’utilité du D-dimère dans la prédiction de l’admission à l’unité des soins intensifs (USI) ou de la mortalité. Sur 1175 patients, 263 ont été admis à l’USI et 226 sont décédés. La protéine C réactive a permis de prédire l’admission à l’USI (rapport de cotes [RC] = 1,01; intervalle de confiance [IC] à 95 % de 1,01 à 1,01) et la mortalité (RC = 1,00; IC à 95 % de 1,00 à 1,01), mais le D-dimère n’a pas permis de prédire l’une ou l’autre issue (RC = 1,02; IC à 95 % de 0,97 à 1,06 pour l’admission à l’USI et RC = 0,99; IC à 95 % de 0,93 à 1,06 pour la mortalité). D’après ces résultats, les taux de D-dimère ne sont pas des prédicteurs indépendants de la gravité de la COVID-19 ou de la mortalité. Nos résultats confirment les résultats de cohortes plus petites et démontrent les caractéristiques inflammatoires de la COVID-19 dans le contexte canadien.

Despite the known clinical importance of hypoxemia and pneumonia, there is a paucity of evidence for these variables with respect to risk of mortality and short-term outcomes among those hospitalised with COVID-19.ObjectiveDescribe the prevalence and clinical course of patients hospitalised with COVID-19 based on oxygenation and pneumonia status at presentation and determine the incidence of emergent hypoxaemia or radiographic pneumonia during admission.MethodsA retrospective study was conducted using a Canadian regional registry. Patients were stratified according to hypoxaemia/pneumonia phenotype and prevalence. Clinical parameters were compared between phenotypes using χ2and one-way Analysis of variance (ANOVA). Cox analysis estimated adjusted Hazard Ratios (HR) for associations between disease outcomes and phenotypes.ResultsAt emergency department (ED) admission, the prevalence of pneumonia and hypoxaemia was 43% and 50%, respectively, and when stratified to phenotypes: 28.2% hypoxaemia+/pneumonia+, 22.2% hypoxaemia+/pneumonia−, 14.5% hypoxaemia−/pneumonia+and 35.1% hypoxaemia−/pneumonia−. Mortality was 31.1% in the hypoxaemia+/pneumonia−group and 26.3% in the hypoxaemia+/pneumonia+group. Hypoxaemia with pneumonia and without pneumonia predicted higher probability of death. Hypoxaemia either ConclusionMortality in COVID-19 infection is predicted by hypoxaemia with or without pneumonia and was greatest in patients who initially presented with hypoxaemia. The emergence of hypoxaemia was predicted by radiographic pneumonia. Patients with early and emergent hypoxaemia had similar mortality but were less likely to be admitted to ICU. There may be delayed identification of hypoxaemia, which prevents timely escalation of care.

To perform a descriptive analysis of individuals with suspected Polyarteritis nodosa (PAN) referred for second opinion imaging consultation. A retrospective observational cohort study was performed at a single institution. A consecutive sample was performed of individuals who underwent a second opinion CT or MR angiography subspecialty radiologist consultation between January 2008 and September 2019 for suspected abdominal medium vessel vasculitis. Demographic, clinical, and imaging data were collected. Clinical and imaging findings were reported for PAN, small vessel vasculitis, and “non-vasculitis” groups. Agreement and diagnostic accuracy between final clinical and second opinion imaging diagnoses for PAN were determined. Two-tailed t-tests with a significant p-value

Objectives Health guidelines are a key knowledge translation tool produced and used by numerous stakeholders worldwide. Effective participation in guideline development groups or development groups is crucial for guideline success, yet little guidance exists for members of these groups. In this study, we present the Guideline Participant Tool (GPT) to support effective participation in guideline groups, in particular those using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Study Design and Setting We used a mixed methods and iterative approach to develop a tool to support guideline participation. We used the findings of a published systematic review to develop an initial list of items for considerations for guideline participants. Then, we refined this list through key informant interviews with guideline chairs, sponsors, and participants. Finally, we validated the GPT in three guideline groups with 26 guideline group members. Results The initial list of items based on 37 articles from the existing systematic review included 15 themes and 61 items for a draft tool. Ten key informant interviews helped us refine the list to include the following themes: selection of participants, guideline group process, and tool format. 26 respondents completed the validation survey from three guideline groups. Refinement of the tool ultimately generated a GPT with 33 items for participant consideration before, during, and in follow-up to guideline group meetings. Conclusion The GPT contains helpful guidance for all guideline participants, particularly those without previous guideline experience. Future research should further explore the need for additional tools to support guideline participants and identify and develop strategies for improving guideline members’ participation in guideline groups. This work will be incorporated into INGUIDE.org guideline training and credentialing efforts by the Guidelines International Network and McMaster University.

Pneumorrhachis is often associated with trauma or postsurgical changes; few cases are reported as a result of infectious causes in adults. Here, we describe a 61-year-old male with a history of ren...

Objectives Imaging modalities have become common in evaluating patients for a possible diagnosis of GCA. This study seeks to contextualize how temporal arterial magnetic resonance angiography (TA-MRA) can be used in facilitating the diagnosis of GCA. Methods A retrospective cohort study was performed on patients who had been previously referred to a rheumatologist for evaluation of possible GCA in Hamilton, Ontario, Canada. Data including clinical features, inflammatory markers, imaging, and biopsy results were extracted. Multivariable logistic regression model to predict the diagnosis of GCA. Using these models, the utility of TA-MRA in series with or in parallel to clinical evaluation was demonstrated across the cohort as well as in subgroups defined by biopsy and imaging status. Results In total 268 patients had complete data. Those diagnosed with biopsy- and/or imaging-positive GCA were more likely to demonstrate classic features including jaw claudication and vision loss. Clinical multivariable modelling allowed for fair discriminability [receiver operating characteristic (ROC) 0.759, 95% CI: 0.703, 0.815] for diagnosing GCA; there was excellent discriminability in facilitating the diagnosis of biopsy-positive GCA (ROC 0.949, 0.898–1.000). When used in those with a pre-test probability of 50% or higher, TA-MRA had a positive predictive value of 93.0%; in those with a pre-test probability of 25% or less TA-MRA had a negative predictive value of 89.5%. Conclusion In those with high disease probability, TA-MRA can effectively rule in disease (and replace temporal artery biopsy). In those with low to medium probability, TA-MRA can help rule out the disease, but this continues to be a challenging diagnostic population.

Giant cell arteritis (GCA) is the most common large-vessel vasculitis that primarily affects older individuals.1Prompt diagnosis and treatment with empiric glucocorticoids (GCs) is important because GCA can lead to ischemic complications, including visual loss.1,2

Introduction COVID-19 is an international public health crisis with more than 132 million infections worldwide. Beyond acute infection, emerging data indicate patients diagnosed with COVID-19 may experience persistent sequelae similar to survivors of sepsis or acute respiratory syndromes, including mobility limitations and fatigue. However, there is limited evidence on the trajectory of functional recovery in those hospitalised with COVID-19. The primary aim of the Coronavirus Registry Functional Recovery (COREG-FR) study is to understand the trajectory of functional recovery among individuals hospitalised for COVID-19 over the medium (up to 6 months) and longer term (6–12 months) that will guide clinical care and optimal management of serious COVID-19 illness and recovery. Methods and analysis COREG-FR is a multicentre longitudinal cohort study. We will enrol a minimum of 211 adults age 18 years and older with COVID-19 from five hospitals. Participants will be followed from admission to hospital as an inpatient, to hospital discharge, and at 3-month, 6-month, 9-month and up to 12-month post-hospital discharge. We will conduct telephone interviews at ward admission and discharge, and telephone interviews plus in-person assessments of physical function and lung function at all remaining follow-ups. Our primary outcome is the Activity Measure for Post-Acute Care mobility scale measured at all time points. We will conduct linear mixed effects regression analyses to explore determinants of functional outcomes after COVID-19 illness. Subgroup analyses based on age (≤65 vs >65 years), frailty status (Clinical Frailty Scale score ≤4 vs >5) and variants of concern will be conducted. Ethics and dissemination COREG-FR has been approved by Research Ethics Boards at participating sites. We will disseminate this work through peer-reviewed manuscripts, presentations at national and international meetings and through the established COREG website (www.coregontario.ca). COREG-FR is designed as a data platform for future studies evaluating COVID-19 recovery. Trial registration number NCT04602260; Pre-results.

Background: Functional status is a patient-important, patient-centered measurement. The utility of functional status measures to inform post-discharge patient needs is unknown. We sought to examine the utility of routinely collected functional status measures gathered from older hospitalized patients to predict a panel of post-discharge outcomes.Methods: In this population-based retrospective cohort study, Adults 65+ who experienced an acute hospitalization between 4 November 2008 and 16 March 2016 in Ontario, Canada and received an assessment of functional status at discharge using the Health Outcomes for Better Information and Care (HOBIC) tool were included. Multivariable regression analysis was used to determine the relationship between functional status and emergency department (ED) presentation, hospital readmission, long term care facility (LTCF) admission or wait listing (‘LTCF readiness’), and death at 180 days from discharge.Results: A total of 80,020 patients were included. 38,928 (48.6%) re-presented to the ED, 24,222 (30.3%) were re-admitted, 5,037 (6.3%) were LTCF ready, and 9,047 (11.3%) died at 180 days. Beyond age, functional status at discharge was the factor most associated with LTCF readiness (Odds Ratio [OR] 4.11; 95% Confidence Interval [CI]: 3.70-4.57) and death (OR 3.99; 95% CI: 3.67-4.35). Functional status also had a graded relationship with each outcome and improved the discriminability of the models predicting death and LTCF readiness (pConclusion: Routinely collected functional status at discharge meaningfully improves models to predict long term care home readiness and death. The routine assessment of functional status can inform post-discharge care and service planning for older adults.

Background: The incidence of acute kidney injury (AKI) in patients with COVID-19 and its association with mortality and disease severity is understudied in the Canadian population. Objective: To determine the incidence of AKI in a cohort of patients with COVID-19 admitted to medicine and intensive care unit (ICU) wards, its association with in-hospital mortality, and disease severity. Our aim was to stratify these outcomes by out-of-hospital AKI and in-hospital AKI. Design: Retrospective cohort study from a registry of patients with COVID-19. Setting: Three community and 3 academic hospitals. Patients: A total of 815 patients admitted to hospital with COVID-19 between March 4, 2020, and April 23, 2021. Measurements: Stage of AKI, ICU admission, mechanical ventilation, and in-hospital mortality. Methods: We classified AKI by comparing highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We calculated the unadjusted and adjusted odds ratio for the stage of AKI and the outcomes of ICU admission, mechanical ventilation, and in-hospital mortality. Results: Of the 815 patients registered, 439 (53.9%) developed AKI, 253 (57.6%) presented with AKI, and 186 (42.4%) developed AKI in-hospital. The odds of ICU admission, mechanical ventilation, and death increased as the AKI stage worsened. Stage 3 AKI that occurred during hospitalization increased the odds of death (odds ratio [OR] = 7.87 [4.35, 14.23]). Stage 3 AKI that occurred prior to hospitalization carried an increased odds of death (OR = 5.28 [2.60, 10.73]). Limitations: Observational study with small sample size limits precision of estimates. Lack of nonhospitalized patients with COVID-19 and hospitalized patients without COVID-19 as controls limits causal inferences. Conclusions: Acute kidney injury, whether it occurs prior to or after hospitalization, is associated with a high risk of poor outcomes in patients with COVID-19. Routine assessment of kidney function in patients with COVID-19 may improve risk stratification. Trial registration: The study was not registered on a publicly accessible registry because it did not involve any health care intervention on human participants.

Objectives: Risk prediction scores are important tools to support clinical decision-making for patients with coronavirus disease (COVID-19). The objective of this paper was to validate the 4C mortality score, originally developed in the United Kingdom, for a Canadian population. Methods: We conducted an external validation study within a registry of COVID-19 positive emergency department visits and hospital admissions in the Kitchener-Waterloo and Hamilton regions of southern Ontario between March 4 and January 9, 2020. We examined the validity of the 4C score to prognosticate in-hospital mortality using the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals calculated via bootstrapping. Results: The study included 560 individuals, of whom 115 (20.5%) died in-hospital. Median age was 69 years and 281 individuals (51%) were male. The AUC of the 4C score was 0.83, 95% confidence interval 0.79-0.87. Mortality rates across the pre-defined risk groups were 0% (Low), 3.2% (Intermediate), 25.9% (High), and 59.5% (Very High). The AUC was 0.80 (0.76-0.85) among hospital inpatients. Interpretation: The 4C score is a valid tool to prognosticate mortality from COVID-19 in Canadian emergency departments and hospitals.

Objectives To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU. Design The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. Setting The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology. Interventions We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. Measurements and main results In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence. Conclusions Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.

BACKGROUND: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19). PURPOSE: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19. DATA SOURCES: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020. STUDY SELECTION: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included. DATA EXTRACTION: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews). DATA SYNTHESIS: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs. LIMITATION: Direct studies in COVID-19 are limited and poorly reported. CONCLUSION: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers. PRIMARY FUNDING SOURCE: World Health Organization. (PROSPERO: CRD42020178187).

IntroductionHome care clients are increasingly medically complex, have limited access to effective chronic disease management and have very high emergency department (ED) visitation rates. There is a need for more appropriate and targeted supportive chronic disease management for home care clients. We aim to evaluate the effectiveness and preliminary cost effectiveness of a targeted, person-centred cardiorespiratory management model.Methods and analysisThe Detection of Indicators and Vulnerabilities of Emergency Room Trips (DIVERT) — Collaboration Action Research and Evaluation (CARE) trial is a pragmatic, cluster-randomised, multicentre superiority trial of a flexible multicomponent cardiorespiratory management model based on the best practice guidelines. The trial will be conducted in partnership with three regional, public-sector, home care providers across Canada. The primary outcome of the trial is the difference in time to first unplanned ED visit (hazard rate) within 6 months. Additional secondary outcomes are to identify changes in patient activation, changes in cardiorespiratory symptom frequencies and cost effectiveness over 6 months. We will also investigate the difference in the number of unplanned ED visits, number of inpatient hospitalisations and changes in health-related quality of life. Multilevel proportional hazard and generalised linear models will be used to test the primary and secondary hypotheses. Sample size simulations indicate that enrolling 1100 home care clients across 36 clusters (home care caseloads) will yield a power of 81% given an HR of 0.75.Ethics and disseminationEthics approval was obtained from the Hamilton Integrated Research Ethics Board as well as each participating site’s ethics board. Results will be submitted for publication in peer-reviewed journals and for presentation at relevant conferences. Home care service partners will also be informed of the study’s results. The results will be used to inform future support strategies for older adults receiving home care services.Trial registration numberNCT03012256.

ObjectiveWhile research suggests that higher continuity of primary and specialty physician care can improve patient outcomes, their effects have rarely been examined and compared concurrently. We investigated associations between continuity of primary and specialty physician care and emergency department visits and hospital admissions among community-dwelling older adults with complex care needs.MethodsWe conducted a retrospective cohort study of home care patients in Ontario, Canada, from October 2014 to September 2016. We measured continuity of primary and specialty physician care over the two years prior to a home care assessment and categorized them into low, medium, and high groups using terciles of the distribution. We used Cox regression models to concurrently test the associations between continuity of primary and specialty care and risk of an emergency department visit and hospital admission within six months of assessment, controlling for potential confounders. We examined interactions between continuity of care and count of chronic conditions, count of physician specialties seen, functional impairment, and cognitive impairment.ResultsOf 178,686 participants, 49% had an emergency department visit during follow-up and 27% had a hospital admission. High vs. low continuity of primary care was associated with a reduced risk of an emergency department visit (HR = 0.90 (0.89-0.92)) as was continuity of specialty care (HR = 0.93 (0.91-0.95)). High vs. low continuity of primary care was associated also with a reduced risk of a hospital admission (HR = 0.94 (0.92-0.96)) as was continuity of specialty care (HR = 0.92 (0.90-0.94)). The effect of continuity of specialty care was moderately stronger among patients who saw four or more physician specialties.ConclusionHigher continuity of primary physician and specialty physician care had independent, protective effects of similar magnitude against emergency department use and hospital admissions. Improving continuity of specialty care should be a priority alongside improving continuity of primary care in complex, older adult populations with significant specialist use.

The central flaw of Riediger and Bomback’s[1][1] argument is the suggestion that public health solutions are narrow in scope: no single strategy is ever universally effective or equitable. Continuing the connection between tobacco and sugar-sweetened goods, tobacco consumption has been effectively

The mu and delta types of opioid receptors form heteromers that exhibit pharmacological and functional properties distinct from those of homomeric receptors. To characterize these complexes in the brain, we generated antibodies that selectively recognize the mu-delta heteromer and blocked its in vitro signaling. With these antibodies, we showed that chronic, but not acute, morphine treatment caused an increase in the abundance of mu-delta heteromers in key areas of the central nervous system that are implicated in pain processing. Because of its distinct signaling properties, the mu-delta heteromer could be a therapeutic target in the treatment of chronic pain and addiction.