The effectiveness of parenteral agents to mitigate relapses after severe acute migraine headache presentations: A systematic review and network analysis.

OBJECTIVES: To compare the effectiveness of parenteral agents to reduce relapse in patients with acute migraine and identify factors that predict relapse. BACKGROUND: Following discharge from emergency settings, many patients with acute migraine will experience a relapse in pain; severe relapses may result in re-visits to emergency settings. METHODS: A comprehensive literature search, updated to 2023, was conducted to identify randomized controlled trials assessing the effectiveness of parenteral agents on relapse outcomes in patients with acute migraine discharged from emergency settings. Two independent reviewers completed study selection, quality assessment, and data extraction. A traditional meta-analysis compared parenteral corticosteroids to placebo; a frequentist network analysis assessed direct and indirect comparisons. Results are reported as risk ratios (RRs) and 95% confidence intervals (CIs). The review protocol was registered with the International Prospective Register of Systematic Reviews (identifier: CRD42018099493). RESULTS: From 8949 citations, a total of 53 unique studies were included involving 6167 patients. Most studies had a high or unclear risk of bias. Corticosteroids significantly reduced relapses compared to placebo (RR 0.67, 95% CI 0.52-0.88; I2 = 0%). Patients receiving lidocaine (RR 0.10, 95% CI 0.01-0.82), sedatives/hypnotics (RR 0.33, 95% CI 0.14-0.75), ergot agents (RR 0.44, 95% CI 0.25-0.75), neuroleptics (RR 0.47, 95% CI 0.31-0.71), opioids (RR 0.58; 95% CI 0.35-0.94), or corticosteroids (RR 0.64, 95% CI 0.47-0.86) were significantly less likely to relapse. Lidocaine (RR 0.09, 95% CI 0.01-0.71), combination therapy (RR 0.12, 95% CI 0.02-0.74), or adding corticosteroids (RR 0.61, 95% CI 0.44-0.84) were more likely to reduce severe relapses. Longer duration of headache and residual pain at discharge were significantly associated with higher relapses. DISCUSSION: Corticosteroids remain the recommended first-line option to reduce relapse outcomes. Some parenteral agents typically provided for pain relief including ergot agents, neuroleptics, or combination therapy may effectively reduce relapse; however, opioids are not recommended due to safety concerns. Additional research is needed for some lesser studied, albeit promising, agents including lidocaine and propofol. Effective pain control in emergency settings prior to discharge and duration of headache may play a role in the success of such treatments and further investigations could provide further insight regarding how and why some parenteral agents are effective in mitigating relapse events.

The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis.

OBJECTIVES: To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine. BACKGROUND: Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear. METHODS: Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096). RESULTS: A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics. CONCLUSIONS: Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs.

Social Determinants of Health and Pediatric Emergency Department Outcomes: A Systematic Review and Meta-Analysis of Observational Studies.

STUDY OBJECTIVE: Social determinants of health contribute to disparities in pediatric health and health care. Our objective was to synthesize and evaluate the evidence on the association between social determinants of health and emergency department (ED) outcomes in pediatric populations. METHODS: This review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Equity Extension guidelines. Observational epidemiological studies were included if they examined at least 1 social determinant of health from the PROGRESS-Plus framework in relation to ED outcomes among children <18 years old. Effect direction plots were used for narrative results and pooled odds ratios (pOR) with 95% confidence intervals (CI) for meta-analyses. RESULTS: Fifty-eight studies were included, involving 17,275,090 children and 103,296,839 ED visits. Race/ethnicity and socioeconomic status were the most reported social determinants of health (71% each). Black children had 3 times the odds of utilizing the ED (pOR 3.16, 95% CI 2.46 to 4.08), whereas visits by Indigenous children increased the odds of departure prior to completion of care (pOR 1.58, 95% CI 1.39 to 1.80) compared to White children. Public insurance, low income, neighborhood deprivation, and proximity to an ED were also predictors of ED utilization. Children whose caregivers had a preferred language other than English had longer length of stay and increased hospital admission. CONCLUSION: Social determinants of health, particularly race, socioeconomic deprivation, proximity to an ED, and language, play important roles in ED care-seeking patterns of children and families. Increased utilization of ED services by children from racial minority and lower socioeconomic status groups may reflect barriers to health insurance and access to health care, including primary and subspecialty care, and/or poorer overall health, necessitating ED care. An intersectional approach is needed to better understand the trajectories of disparities in pediatric ED outcomes and to develop, implement, and evaluate future policies.

Understanding Experiences of Headache-Sufferers Attending Emergency Departments Through Photovoice.

OBJECTIVE: Our aim was to explore the experiences of individuals receiving emergency department (ED) care for acute headaches. BACKGROUND: Patients with headache exacerbations commonly present to EDs. This study explored the experiences of adult patients during the exacerbation period, specifically using photovoice. METHODS: Recruited from two urban EDs in Alberta, Canada, participants with primary headaches took photographs over 3-4 weeks and subsequently completed a 60-90 minute, one-on-one, in-person photo-elicitation interview. Interviews were audio recorded, transcribed and thematically analyzed alongside photographs. RESULTS: Eight participants (six women) completed the study. The average age was 42 years (standard deviation: 16). Five themes emerged: (1) the struggle for legitimacy in light of the invisibility of their condition; (2) the importance of hope, hopelessness and fear in the day-to-day life of participants; (3) the importance of agency and becoming "your own advocate"; (4) the struggle to be and be seen as themselves despite the encroachment of their headaches; and (5) the realities of "good" and "bad" care in the ED. Participants highlighted examples of good care, specifically when they felt seen and believed. Additionally, some expressed the acute care space itself being a beacon of hope in the midst of their crisis. Others felt dismissed because providers "know it's not life or death." CONCLUSIONS: This study highlighted the substantial emotional impact that primary headaches have on the lives of participants, particularly during times of exacerbation and while seeking acute care. This provides insight for acute care settings and practitioners on how to effectively engage with this population.

Physician Management and CT Ordering in the Emergency Department for Primary Headaches.

OBJECTIVE: Management of primary headache (PHA) varies across emergency departments (ED), yet there is widespread agreement that computed tomography (CT) scans are overused. This study assessed emergency physicians' (EPs) PHA management and their attitudes towards head CT ordering. METHODS: A cross-sectional study was undertaken with EPs from one Canadian center. Drivers of physicians' perceptions regarding the appropriateness of CT ordering for patients with PHA were explored. RESULTS: A total of 73 EPs (70% males; 48% with <10 years of practice) participated in the study. Most EPs (88%) did not order investigations for moderate-severe primary headaches; however, CT was the common investigation (47%) for headaches that did not improve. Computed tomography ordering was frequently motivated by the need for specialist consultation (64%) or admission (64%). A small proportion (27%) believed patients usually/frequently expected a scan. Nearly half of EPs (48%) identified patient imaging expectations/requests as a barrier to reducing CT ordering. Emergency physicians with CCFP (EM) certification were less likely to perceive CT ordering for patients with PHA as appropriate. Conversely, those who identified the possibility of missing a condition as a major barrier to limiting their CT use were more likely to perceive CT ordering for patients with PHA as appropriate. CONCLUSIONS: Emergency physicians reported consistency and evidence-based medical management. They highlighted the complexities of limiting CT ordering and both their level of training and their perceived barriers for limiting CT ordering seem to be influencing their attitudes. Further studies could elucidate these and other factors influencing their practice.

Canadian Association of Radiologists Thoracic Imaging Referral Guideline.

The Canadian Association of Radiologists (CAR) Thoracic Expert Panel consists of radiologists, respirologists, emergency and family physicians, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 24 clinical/diagnostic scenarios, a rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 30 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop 48 recommendation statements across the 24 scenarios. This guideline presents the methods of development and the referral recommendations for screening/asymptomatic individuals, non-specific chest pain, hospital admission for non-thoracic conditions, long-term care admission, routine pre-operative imaging, post-interventional chest procedure, upper respiratory tract infection, acute exacerbation of asthma, acute exacerbation of chronic obstructive pulmonary disease, suspect pneumonia, pneumonia follow-up, immunosuppressed patient with respiratory symptoms/febrile neutropenia, chronic cough, suspected pneumothorax (non-traumatic), clinically suspected pleural effusion, hemoptysis, chronic dyspnea of non-cardiovascular origin, suspected interstitial lung disease, incidental lung nodule, suspected mediastinal lesion, suspected mediastinal lymphadenopathy, and elevated diaphragm on chest radiograph.

Emergency Department Visits During Pregnancy.

STUDY OBJECTIVE: Pregnant women often seek care in an emergency department (ED). We sought to describe the frequency, characteristics, and factors associated with increased ED visits during pregnancy. METHODS: We conducted a retrospective cohort study using administrative health data of all pregnancies resulting in a live birth at 20 or more weeks of gestation in Alberta, Canada, from 2011 to 2017. The primary outcome was the occurrence of any ED visit during pregnancy. The secondary outcomes were ED visit characteristics and discharge disposition. We calculated rate ratios (RRs) and 95% confidence intervals (CIs) for associations between sociodemographic and clinical factors and increased ED visits during pregnancy using random-effect negative binomial regression adjusting for multiple pregnancies per person during the study period. RESULTS: We included 255,929 pregnancies from 193,965 women. Of all the pregnancy episodes followed, 37.3% (95% CI 37.1 to 37.5) had at least 1 ED visit, resulting in a total of 226,811 ED visits and an overall ED visit rate of 94.0 visits per 100 pregnancies (95% CI 93.6 to 94.3). Most visits were nonobstetric (46.4%) and resulted in ED discharge (85.3%). Increased ED visits were associated with living in remote (RR 6.9; 95 %CI 6.7 to 7.1) or rural (RR 3.4; 95% CI 3.4 to 3.5) areas, younger age (RR 1.9; 95% CI 1.8 to 2.0), intensive prenatal care (RR 1.5; 95% CI 1.5 to 1.5), major/moderate health conditions (RR 1.6; 95% CI 1.6 to 1.6), mental health conditions (RR 1.6; 95% CI 1.5 to 1.6), and high antepartum risk score (RR 1.1; 95% CI 1.1 to 1.1). CONCLUSION: Approximately 1 in 3 women in our sample visited the ED during pregnancy. A higher number of visits occurred in those with rural/remote residence, younger maternal age, and concomitant health conditions.

Role of sex and gender in concussion outcome differences among patients presenting to the emergency department: a systematic review.

OBJECTIVE: This systematic review aimed to identify research involving adults presenting to the emergency department (ED) with a concussion to document the reporting of sex and/or gender according to the Canadian Institutes of Health Research (CIHR) guidelines, the prevalence of sex and gender-based analysis (SGBA) and to summarise sex and/or gender-based differences in ED presentation, management and outcomes. DESIGN: Systematic review. METHODS: Electronic databases and grey literature were searched to identify studies that recruited adult patients with concussion from the ED. Two independent reviewers identified eligible studies, assessed quality and extracted data. A descriptive summary of the evidence was generated, and sex and/or gender reporting was examined for accuracy according to standardised criteria. RESULTS: Overall, 126 studies were included in the analyses. A total of 80 (64%) studies reported sex and/or gender as demographic information, of which 51 (64%) included sex and/or gender in their analysis; however, 2 (3%) studies focused on an SGBA. Sex was more accurately reported in alignment with CIHR definitions than gender (94% vs 12%; p<0.0001). In total, 25 studies used an SGBA for outcomes of interest. Males and females experience different causes of concussion, 60% of studies documented that females had less frequent CT scanning while in the ED, and 57% of studies reported that postconcussion syndrome was more prevalent in females and women. CONCLUSION: This systematic review highlighted that sex is reported more accurately than gender, approximately half of studies did not report either sex and/or gender as demographic information, and one-third of studies did not include SGBA. There were important sex and gender differences in the cause, ED presentation, management and outcomes of concussions. PROSPERO REGISTRATION NUMBER: CRD42021258613.

You exhaust me! Air pollution exposure near schools during pick-up and drop-off times.

Background: Public and healthcare practitioner awareness of climate change and the longitudinal health impacts of air pollution is growing; however, it is not always clear how to implement practical and feasible steps that individuals and communities can take to help decrease air pollution and protect children, and it can be challenging to request and enforce behaviour changes that the public associates with perceived personal inconvenience. In this context, it is important to consider common, chronic exposures that increase children's risks, especially when straightforward solutions with minimal negative impact where significant evidence-based positive results are available. Aims: This article provides simple tips that healthcare providers, parents, and communities can use to advocate for decreased idling in school zones to improve air quality in and around schools.

A randomized trial of ketorolac and metoclopramide for migraine in the emergency department.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of a common monotherapy (intravenous [iv] metoclopramide) compared to a combination strategy (adding iv ketorolac to metoclopramide) in children presenting for acute treatment of migraine headache in the emergency department (ED). METHODS: Children aged 5-17 years presenting for acute treatment of migraine headache at two pediatric EDs were enrolled in a double-blind randomized controlled trial. Children were randomly assigned to receive iv metoclopramide 0.2 mg/kg) and placebo or iv metoclopramide (0.2 mg/kg) and ketorolac (0.5 mg/kg). The primary outcome was a mean change in pain from baseline to 120 min via a 100 mm Visual Analog Scale (VAS). Follow-up was conducted 24-h after discharge. RESULTS: Fifty-three children were randomized and included in the analysis (monotherapy group [metoclopramide + placebo], n = 27; and ketorolac group [metoclopramide + ketorolac], n = 26); mean age was 12.9 ± 2.7 years and baseline pain severity on VAS was 67.3 ± 2.7 mm. The mean change in pain intensity at 120 min was -44 mm (SD: 24; 95% confidence interval [CI]: 32-57) for the monotherapy group and -36 mm (SD: 24; 95% CI: 23-49) for the ketorolac group, with a mean difference between groups of 8 mm (95% CI: -9-25; p = 0.360). Seventeen percent of the children (9/53; 95% CI: 7-27%) were pain-free at discharge. There was no difference in headache recurrence or adverse events between groups. CONCLUSIONS: The approach of combining iv metoclopramide with ketorolac failed to improve pain scores in children presenting for acute treatment of migraine headache in the ED compared to metoclopramide monotherapy. Most patients were discharged with residual pain. Further comparative studies are needed to test alternative ED treatments for migraine in children or adolescents.

Emergency Department Visits During the Postpartum Period: A Canadian Cohort Study.

STUDY OBJECTIVE: Challenges in transitioning from obstetric to primary care in the postpartum period may increase emergency department (ED) visits. This study described the frequency, characteristics, and predictors of maternal ED visits in the postpartum period. METHODS: Retrospective cohort study of all live-birth pregnancies occurring in Alberta (Canada) between 2011 and 2017. Individual-level health and ED utilization data was linked across 5 population health databases. We calculated age-standardized ED visit rates in the postpartum period and used negative binomial regression models to assess the outcome of any ED visit in the postpartum period associated with relevant sociodemographic and clinical factors. Results were reported using rate ratios (RRs) and 95% confidence intervals (95% CIs). RESULTS: Data on 255,929 pregnancies from 193,965 individuals were analyzed. During the study period, 44.7% of pregnancies had 1 or more ED visits; 29.7% of visits occurred within 6 weeks after delivery. Increased postpartum ED visits were associated with living in remote (RR, 2.8; 95% CI, 2.6 to 2.9) or rural areas (RR, 2.3; 95% CI, 2.3 to 2.4), age less than 20 years (RR, 2.5; 95% CI, 2.4 to 2.6), mental (RR, 1.6; 95% CI, 1.6 to 1.7) and major/moderate health conditions (RR, 1.5; 95% CI, 1.5 to 1.6), multiparity 4 or more (RR, 2.0; 95% CI, 1.9 to 2.1), cesarean delivery (RR, 1.4; 95% CI, 1.4 to 1.4), and intensive prenatal care (RR, 1.4; 95% CI, 1.4 to 1.5). CONCLUSION: Almost one third of ED visits in the postpartum occurred within 6 weeks immediately after delivery. Potential gaps in equitable access and quality of prenatal care should be bridged by appropriate transitions to primary care in the postpartum period.

Sports-Related Concussions in Adults Presenting to Canadian Emergency Departments.

OBJECTIVE: To document the occurrence and recovery outcomes of sports-related concussions (SRCs) presenting to the Emergency Department (ED) in a community-based sample. DESIGN: A prospective observational cohort study was conducted in 3 Canadian hospitals. SETTING: Emergency Department. PATIENTS: Adults (≥17 years) presenting with a concussion to participating EDs with a Glasgow Coma Scale score ≥13 were recruited. INTERVENTIONS: Patient demographics (eg, age and sex), clinical characteristics (eg, history of depression or anxiety), injury characteristics (eg, injury mechanisms and loss of consciousness and duration), and ED management and outcomes (eg, imaging, consultations, and ED length of stay) were collected. MAIN OUTCOME MEASURES: Patients' self-reported persistent concussion symptoms, return to physical activity status, and health-related quality of life at 30 and 90 days after ED discharge. RESULTS: Overall, 248 patients were enrolled, and 25% had a SRC. Patients with SRCs were younger and reported more physical activity before the event. Although most of the patients with SRCs returned to their normal physical activities at 30 days, postconcussive symptoms persisted in 40% at 90 days of follow-up. After adjustment, there was no significant association between SRCs and persistent symptoms; however, patients with concussion from motor vehicle collisions were more likely to have persistent symptoms. CONCLUSION: Although physically active individuals may recover faster after a concussion, patients returning to their physical activities before full resolution of symptoms are at higher risk of persistent symptoms and further injury. Patient-clinician communications and tailored recommendations should be encouraged to guide appropriate acute management of concussions.

Personalised risk prediction following emergency department assessment for syncope.

BACKGROUND: Published risk tools do not provide possible management options for syncope in the emergency department (ED). Using the 30-day observed risk estimates based on the Canadian Syncope Risk Score (CSRS), we developed personalised risk prediction to guide management decisions. METHODS: We pooled previously reported data from two large cohort studies, the CSRS derivation and validation cohorts, that prospectively enrolled adults (≥16 years) with syncope at 11 Canadian EDs between 2010 and 2018. Using this larger cohort, we calculated the CSRS calibration and discrimination, and determined with greater precision than in previous studies the 30-day risk of adjudicated serious outcomes not identified during the index ED evaluation depending on the CSRS and the risk category. Based on these findings, we developed an on-line calculator and pictorial decision aids. RESULTS: 8233 patients were included of whom 295 (3.6%, 95% CI 3.2% to 4.0%) experienced 30-day serious outcomes. The calibration slope was 1.0, and the area under the curve was 0.88 (95% CI 0.87 to 0.91). The observed risk increased from 0.3% (95% CI 0.2% to 0.5%) in the very-low-risk group (CSRS -3 to -2) to 42.7% (95% CI 35.0% to 50.7%), in the very-high-risk (CSRS≥+6) group (Cochrane-Armitage trend test p<0.001). Among the very-low and low-risk patients (score -3 to 0), ≤1.0% had any serious outcome, there was one death due to sepsis and none suffered a ventricular arrhythmia. Among the medium-risk patients (score +1 to+3), 7.8% had serious outcomes, with <1% death, and a serious outcome was present in >20% of high/very-high-risk patients (score +4 to+11) including 4%-6% deaths. The online calculator and the pictorial aids can be found at: https://teamvenk.com/csrs CONCLUSIONS: 30-day observed risk estimates from a large cohort of patients can be obtained for management decision-making. Our work suggests very-low-risk and low-risk patients may be discharged, discussion with patients regarding investigations and disposition are needed for medium-risk patients, and high-risk patients should be hospitalised. The online calculator, accompanied by pictorial decision aids for the CSRS, may assist in discussion with patients.

Emergency department crowding negatively influences outcomes for adults presenting with asthma: a population-based retrospective cohort study.

BACKGROUND: Access to emergency department (ED) services is important for patients with acute asthma; however, ED crowding may impact the quality of care and compromise outcomes. We examine the association between ED crowding metrics and individual patient outcomes for adults presenting with asthma. METHODS: This population-based retrospective cohort study extracted all ED presentations made by patients aged 18 to 55 years to 18 high-volume EDs in Alberta from April 2014 to March 2019. Physician initial assessment (PIA) time and ED length of stay (LOS) for discharged and admitted patients were calculated. Other metrics and patient outcomes were also obtained. Linear and generalized linear models were fit for continuous and categorical outcomes. Cox proportional hazards models were used for time-to-event outcomes. RESULTS: There were 17,724 ED presentations by 12,569 adults. The median age was 33 years, and females (58.7%) made more presentations. ED crowding affected the PIA time for all triage groups. For the high acuity group (Canadian Triage and Acuity Scale [CTAS] 1/2), 1 h increase in median facility-specific PIA was associated with 26 min (95%CI: 24,28) increase; for the moderate acuity (CTAS 3) and low acuity (CTAS 4/5) groups, the individual-level PIA increased by 54 min (95%CI: 53,55) and 61 min (95%CI: 59,63), respectively adjusted by other predictors. Increases in facility PIA resulted in increase in odds of admissions for the high acuity group and increase odds of left without completion of care for the moderate and low acuity groups. CONCLUSION: The care provided for patients from all triage groups was impacted when EDs experienced crowding. Effective interventions are needed to mitigate ED crowding and improve care and outcomes for this important patient group.

Electrical versus pharmacological cardioversion for emergency department patients with acute atrial fibrillation (RAFF2): a partial factorial randomised trial.

BACKGROUND: Acute atrial fibrillation is the most common arrythmia treated in the emergency department. Our primary aim was to compare conversion to sinus rhythm between pharmacological cardioversion followed by electrical cardioversion (drug-shock), and electrical cardioversion alone (shock-only). Our secondary aim was to compare the effectiveness of two pad positions for electrical cardioversion. METHODS: We did a partial factorial trial of two protocols for patients with acute atrial fibrillation at 11 academic hospital emergency departments in Canada. We enrolled adult patients with acute atrial fibrillation. Protocol 1 was a randomised, blinded, placebo-controlled comparison of attempted pharmacological cardioversion with intravenous procainamide (15 mg/kg over 30 min) followed by electrical cardioversion if necessary (up to three shocks, each of ≥200 J), and placebo infusion followed by electrical cardioversion. For patients having electrical cardioversion, we used Protocol 2, a randomised, open-label, nested comparison of anteroposterior versus anterolateral pad positions. Patients were randomly assigned (1:1, stratified by study site) for Protocol 1 by on-site research personnel using an online electronic data capture system. Randomisation for Protocol 2 occurred 30 min after drug infusion for patients who had not converted and was stratified by site and Protocol 1 allocation. Patients and all research and emergency department staff were masked to treatment allocation for Protocol 1. The primary outcome was conversion to normal sinus rhythm for at least 30 min at any time after randomisation and up to a point immediately after three shocks. Protocol 1 was analysed by intention to treat and Protocol 2 excluded patients who did not receive electrical cardioversion. This study is registered at ClinicalTrials.gov, number NCT01891058. FINDINGS: Between July 18, 2013, and Oct 17, 2018, we enrolled 396 patients, and none were lost to follow-up. In the drug-shock group (n=204), conversion to sinus rhythm occurred in 196 (96%) patients and in the shock-only group (n=192), conversion occurred in 176 (92%) patients (absolute difference 4%; 95% CI 0-9; p=0·07). The proportion of patients discharged home was 97% (n=198) versus 95% (n=183; p=0·60). 106 (52%) patients in the drug-shock group converted after drug infusion only. No patients had serious adverse events in follow-up. The different pad positions in Protocol 2 (n=244), had similar conversions to sinus rhythm (119 [94%] of 127 in anterolateral group vs 108 [92%] of 117 in anteroposterior group; p=0·68). INTERPRETATION: Both the drug-shock and shock-only strategies were highly effective, rapid, and safe in restoring sinus rhythm for patients in the emergency department with acute atrial fibrillation, avoiding the need for return to hospital. The drug infusion worked for about half of patients and avoided the resource intensive procedural sedation required for electrical cardioversion. We also found no significant difference between the anterolateral and anteroposterior pad positions for electrical cardioversion. Immediate rhythm control for patients in the emergency department with acute atrial fibrillation leads to excellent outcomes. FUNDING: Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research.

Th2 cell markers in peripheral blood increase during an acute asthma exacerbation.

BACKGROUND: Allergic asthma is characterized by type 2 inflammation. We have shown the presence of increased type 2 inflammation in patients with severe asthma and those with frequent exacerbations. However, it is not known whether increased type 2 inflammation drives asthma exacerbations. This study aims to determine Th2 immune parameters in patients presenting to the emergency department (ED) with an acute asthma exacerbation and correlate these parameters with clinical and physiological measures of asthma. METHODS: Sixteen adults presenting to the ED with acute asthma exacerbations were recruited after giving informed consent. Ten patients returned 2 weeks later for follow-up. Physiological parameters, asthma control (ACQ6), asthma quality of life (AQLQ) questionnaires, and venous blood were collected during both visits. An immune cell profiling was performed by whole blood flow cytometry: CD4+ T cells, Th2 cells (CD4+ CRTh2+ T cells and % of CD4+ T cells expressing CRTh2), eosinophils and innate lymphoid cells (ILC2). RESULTS: During exacerbation, peripheral blood Th2 cell numbers correlated with ACQ6 and AQLQ scores, while ILC2 and eosinophil numbers did not. Subjects had higher % of CD4+ T cells expressing CRTh2 and worse FEV1 during exacerbation compared with the follow-up. The decrease in the % of CD4+ T cells expressing CRTh2 seen during the follow-up visit correlated with the improvement in lung function. CONCLUSIONS: These data suggest that Th2 cells in peripheral blood may be a sensitive measure of increasing symptoms in patients with asthma exacerbations and may serve as a biomarker of an asthma exacerbation.

Emergency department crowding negatively influences outcomes for children presenting with asthma: a population-based retrospective cohort study.

BACKGROUND: Emergency department (ED) crowding may delay assessment and management and compromise outcomes. The association between the crowding metric time to physician initial assessment (PIA) and outcomes for children presenting for acute asthma is examined. METHODS: A population-based retrospective cohort of all presentations to 18 high-volume EDs during 2010-2014 in Alberta, Canada was created. Hourly, facility-specific median PIAs were calculated. Physician claims and hospitalizations data were linked for children (2-17 years) presenting for asthma. RESULTS: Twenty-five thousand three hundred and eighty-three presentations (16,053 children) were made for asthma. Crowding was common in all hospitals and affected PIA more for lower acuity presentations. For every 1-h increase in median facility PIA, the individual-level PIA increased by 13 min (95% CI: 12, 14) for high, 43 min (95% CI: 42, 44) for moderate, and 60 min (95% CI: 58, 61) for the low acuity groups, when adjusted by predictors. Similarly, length of stay increased by 6, 36, and 45 min for the high, moderate, and low acuity groups, respectively. Increased PIA resulted in more departures prior to completion of care for the lower acuity groups. CONCLUSIONS: Crowding adversely affects short-term outcomes of less ill children more than those who are more ill. When EDs experience increased crowding, care to patients with asthma is delayed; effective strategies to reduce crowding and delays to care are urgently needed. IMPACT: For children presenting to EDs for asthma, increased time to physician initial assessment adversely affects short-term outcomes of patients with less severe presentations to a greater extent compared to those who are most severe. Times to physician initial assessment are below recommended benchmarks; however, delays in care exist that impact LOS, odds of admission, and premature patient departures. Pediatric patients with severe asthma are seen quickly and their outcomes are excellent. Since crowding adversely affects short-term outcomes of pediatric patients with asthma, efforts to reduce ED crowding and assess patients with asthma in a more timely manner are needed.

Efficacy and safety outcomes of proposed randomized controlled trials investigating hydroxychloroquine and chloroquine during the early stages of the COVID-19 pandemic.

AIMS: To assess whether randomized clinical trials (RCTs) proposed to evaluate the treatment of patients with COVID-19 with hydroxychloroquine (HQ) or chloroquine early in the pandemic included plans to measure outcomes that would translate into meaningful efficacy/effectiveness and safety outcomes. METHODS: The World Health Organization International Clinical Trials Registry Platform database was searched for registers of RCTs evaluating HQ or chloroquine, alone or in combination, compared with other treatments for patients diagnosed with COVID-19. The final search was performed on 8 April 2020. RESULTS: Among 51 registered RCTs (median sample size 262; interquartile range: 100, 520), 34 (67%) reported a clinical outcome, 12 (24%) a surrogate outcome, and 5 (10%) a combination of clinical and surrogate outcomes as primary endpoints. Six (15%) trials included the World Health Organization scale for clinical improvement as a primary clinical outcome. Clinical improvement and mortality accounted for 45% of the unique domains among 18 clinical outcome domains of efficacy. Twenty-four (47%) RCTs did not describe plans to assess safety outcomes; when assessed, safety outcomes were determined in generic terms of total, severe or serious adverse events. CONCLUSION: The RCTs investigating HQ or chloroquine during the early stages of the COVID-19 pandemic included heterogeneous and insufficient approaches to measure efficacy/effectiveness and safety relevant to patients and clinical practice. These findings provide insights to inform clinical and regulatory decisions that can be drawn about the efficacy/effectiveness and safety of these agents in patients with COVID-19. Trialists need to adapt quickly to the research progress on COVID-19, ensuring that core outcome measures are assessed in ongoing RCTs.

Peripheral blood intermediate monocyte protease-activated receptor-2 expression increases during asthma exacerbations and after inhalation allergen challenge.

BACKGROUND: Myeloid cells, especially dendritic cells and macrophages, play important roles in asthma pathophysiology. Monocytes (Mo) and macrophages express protease-activated receptor-2 (PAR-2), a proinflammatory serine protease receptor implicated in the pathophysiology of allergic airway inflammation. We have revealed that patients with severe asthma and those with a history of frequent asthma exacerbations exhibit increased PAR-2 expression on peripheral blood monocytes. OBJECTIVE: To determine PAR-2 expression on peripheral blood intermediate monocytes (IMMo) in subjects with increased airway inflammation, either as a result of an asthma exacerbation or after an inhalation allergen challenge. METHODS: A total of 16 adults who presented to the emergency department with asthma exacerbations were recruited after giving an informed consent. After 2 weeks, 10 patients returned for follow-up. A total of 11 patients with mild asthma treated only with as-needed bronchodilators were recruited and underwent inhalation allergen challenge after providing an informed consent. Immune cell profiling was performed by whole blood flow cytometry in both groups of patients. RESULTS: PAR-2 expression in peripheral blood IMMo increased in patients with an asthma exacerbation compared with those with stable disease, but this expression decreased after treatment of the asthma exacerbation. Subjects with mild asthma had an increase in percentages of IMMo expressing PAR-2 after an allergen challenge. Patients who presented to the emergency department had lower dendritic cell and dendritic cell subset numbers in peripheral blood during exacerbation compared with after treatment. CONCLUSION: Increased PAR-2 expression on Mo during periods of increased airway inflammation may initiate a positive feedback loop leading to systemic inflammatory changes.

Elevated Blood Pressures Are Common in the Emergency Department but Are They Important? A Retrospective Cohort Study of 30,278 Adults.

STUDY OBJECTIVE: We determine the frequency of elevated blood pressure (BP) readings in the emergency department (ED), the proportion of patients with prior or subsequent diagnosis of hypertension assigned in other settings, and the association between ED BP levels and cardiovascular outcomes after ED discharge. METHODS: This was a retrospective cohort study using electronic medical records for all adults treated and released from a large-volume ED in 2016 that were linked to administrative records for all health care encounters in the province for 2 years before and after the index ED visit. The primary outcome measure was a composite of stroke or transient ischemic attack, acute coronary syndrome, new heart failure, or death. RESULTS: Of 30,278 adults treated and released from the ED, 14,717 (48.6%) had elevated BP readings; 10,732 (72.9%) had no prior diagnosis of hypertension. Of the 3,480 patients with no prior diagnosis of hypertension but an ED BP greater than or equal to 160/100 mm Hg, 907 (26.1%) subsequently received a diagnosis of chronic hypertension or were prescribed antihypertensive therapy in other settings within 2 years. Among patients without a history of hypertension, those with an ED BP greater than or equal to 160/100 mm Hg were more likely to meet the composite outcome (stroke, transient ischemic attack, acute coronary syndrome, heart failure, or death) in the subsequent year (3.3% versus 2.5%) or 2 years (5.9% versus 3.8%) than those with ED BPs 120 to 139/80 to 89 mm Hg; however, after adjusting for age, sex, diabetes, atrial fibrillation, and prior cardiovascular disease, their risk was not elevated (adjusted hazard ratio 0.84; 95% confidence interval 0.71 to 1.004 during 2 years). CONCLUSION: Elevated BP readings in the ED are common and are often the first time hypertension is detected; however, they were not associated with adverse cardiovascular outcomes within 2 years of the visit.