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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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Corinne M. Hohl reports financial support was provided by Health Research British Columbia. Danuta M. Skowronski reports financial support to her institution was provided by BCCDC Foundation for Public Health. Danuta M. Skowronski reports financial support to her institution was provided by Public Health Agency of Canada. Christiaan H. Righolt reports a relationship with Pfizer that includes funding grants. Jeffrey C. Kwong is supported by a Clinician-Scientist Award from the University of Toronto Department of Family and Community Medicine. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Symptoms of the Post-COVID-19 Condition are often non-specific making it a challenge to distinguish them from symptoms due to other medical conditions. In this study, we compare the proportion of emergency department patients who developed symptoms consistent with the World Health Organization's Post-COVID-19 Condition clinical case definition between those who tested positive for Severe Acute Respiratory Syndrome Coronavirus-2 infection and time-matched patients who tested negative. Our results show that over one-third of emergency department patients with a proven acute infection meet Post-COVID-19 Condition criteria 3 months post-index visit. However, one in five test-negative patients who claim never having been infected also report symptoms consistent with Post-COVID-19 Condition highlighting the lack of specificity of the clinical case definition. Testing for SARS-CoV-2 during the acute phase of a suspected infection should continue until specific biomarkers of Post-COVID-19 Condition become available for diagnosis and treatment., (© 2024. The Author(s).)

We estimated the operating characteristics of ICD-10 code U07.1, introduced by the World Health Organization in 2020, to identify lab-confirmed SARS-CoV-2. CCEDRRN is a national research registry of adults (March 2020-August 2021) with suspected/confirmed SARS-CoV-2 identified in Canadian emergency departments (EDs) using chart review (symptoms, clinical information, and lab test results including SARS-CoV-2 polymerase chain reaction, PCR results). CCEDRRN data were linked to administrative hospitalization discharge and ED ICD-10 diagnostic codes (accessed centrally via the Canadian Institute for Health Information). We identified ICD-10 diagnostic codes in CCEDRRN participants. We defined lab-confirmed SARS-CoV-2 based on at least one positive PCR in the 0-14 days before the ED presentation and/or during hospitalization (in those admitted from ED). We performed separate analyses for CCEDRRN participants discharged from ED and those hospitalized from the ED. Additional analyses were stratified by province, sex, age, and (for hospitalized patients) timing of the first PCR test. The sensitivity of ICD-10 code U07.1 for a positive SARS-CoV-2 test was 93.6% (95% CI 93.0-94.1%) in those hospitalized from ED and 83.0% (95% CI 82.1-83.9%) in those discharged from the ED. Sensitivity was similar across provinces and demographics, but in each stratified analysis, values were higher in those hospitalized versus those discharged from ED. The ICD-10 diagnostic code for U07.1 within administrative data identified most lab-confirmed SARS-CoV-2 within persons hospitalized from ED, although a significant number of cases discharged from ED were missed. This should be considered when using administrative data for research and public health planning., (© 2024. The Author(s).)

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., (© 2023. The Author(s).)

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., Competing Interests: Drs. Perry and Atzema have peer reviewed mid-career salary support awards from the Heart and Stroke Foundation of Ontario. Dr. Hohl is supported by a Michael Smith Foundation Health Professional Investigator Award. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Hohl et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s), under exclusive licence to Canadian Association of Emergency Physicians (CAEP)/ Association Canadienne de Médecine d'Urgence (ACMU).)

Importance: Early and accurate diagnostic testing for SARS-CoV-2 is essential to initiate appropriate treatment and infection control and prevention measures among patients presenting to the hospital., Objective: To evaluate the diagnostic sensitivity of the SARS-CoV-2 nucleic acid amplification test (NAAT) performed within 24 hours of arrival to the emergency department among a nationally representative sample of patients., Design, Setting, and Participants: This diagnostic study was conducted at 47 hospitals across 7 provinces in Canada participating in the Canadian COVID-19 Rapid Response Emergency Department Network among consecutive eligible patients presenting to a participating emergency department who were tested for SARS-CoV-2 from March 1, 2020, to December 31, 2021. Patients not tested within 24 hours of arrival and those presenting with a positive result from a test performed in the community were excluded., Main Outcomes and Measures: The primary outcome was a positive result from the SARS-CoV-2 NAAT. Outcome measures were the diagnostic sensitivity and yield of the SARS-CoV-2 NAAT., Results: Of 132 760 eligible patients (66 433 women [50.0%]; median age, 57 years [IQR, 37-74 years]), 17 174 (12.9%) tested positive for SARS-CoV-2 within 14 days of their first NAAT. The diagnostic sensitivity of the SARS-CoV-2 NAAT was 96.2% (17 070 of 17 740 [95% CI, 95.9%-96.4%]) among all of the tests performed. Estimates ranged from a high of 97.7% (1710 of 1751 [95% CI, 96.8%-98.3%]) on day 2 of symptoms to a low of 90.4% (170 of 188 [95% CI, 85.3%-94.2%]) on day 11 of symptoms among patients presenting with COVID-19 symptoms. Among patients reporting COVID-19 symptoms, the sensitivity of the SARS-CoV-2 NAAT was 97.1% (11 870 of 12 225 [95% CI, 96.7%-97.3%]) compared with 87.6% (812 of 927 [95% CI, 85.2%-89.6%]) among patients without COVID-19 symptoms. The diagnostic yield of the SARS-CoV-2 NAAT was 12.0% (18 985 of 158 004 [95% CI, 11.8%-12.2%]) and varied from a high of 20.0% (445 of 2229 [95% CI, 18.3%-21.6%]) among patients tested on day 10 after symptom onset to a low of 8.1% (1686 of 20 719 [95% CI, 7.7%-8.5%]) among patients presenting within the first 24 hours of symptom onset., Conclusions and Relevance: This study suggests that the diagnostic sensitivity was high for the first SARS-CoV-2 NAAT performed in the hospital and did not vary significantly by symptom duration. Repeated testing of patients with negative test results should be avoided unless their pretest probability of disease is high.

Objectives: To determine the diagnostic yield of screening patients for SARS-CoV-2 who were admitted with a diagnosis unrelated to COVID-19 and to identify risk factors for positive tests., Design: Cohort from the Canadian COVID-19 Emergency Department Rapid Response Network registry., Setting: 30 acute care hospitals across Canada., Participants: Patients hospitalised for non-COVID-19-related diagnoses who were tested for SARS-CoV-2 between 1 March and 29 December 2020., Main Outcome: Positive nucleic acid amplification test for SARS-CoV-2., Outcome Measure: Diagnostic yield., Results: We enrolled 15 690 consecutive eligible adults who were admitted to hospital without clinically suspected COVID-19. Among these patients, 122 tested positive for COVID-19, resulting in a diagnostic yield of 0.8% (95% CI 0.64% to 0.92%). Factors associated with a positive test included presence of fever, being a healthcare worker, having a positive household contact or institutional exposure, and living in an area with higher 7-day average incident COVID-19 cases., Conclusions: Universal screening of hospitalised patients for COVID-19 across two pandemic waves had a low diagnostic yield and should be informed by individual-level risk assessment in addition to regional COVID-19 prevalence., Trial Registration Number: NCT04702945., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Treatment for coronavirus disease 2019 (COVID-19) evolved between pandemic waves. Our objective was to compare treatments, acute care utilization, and outcomes of COVID-19 patients presenting to emergency departments (ED) across pandemic waves., Methods: This observational study enrolled consecutive eligible COVID-19 patients presenting to 46 EDs participating in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) between March 1 and December 31, 2020. We collected data by retrospective chart review. Our primary outcome was in-hospital mortality. Secondary outcomes included treatments, hospital and ICU admissions, ED revisits and readmissions. Logistic regression modeling assessed the impact of pandemic wave on outcomes., Results: We enrolled 9,967 patients in 8 provinces, 3,336 from the first and 6,631 from the second wave. Patients in the second wave were younger, fewer met criteria for severe COVID-19, and more were discharged from the ED. Adjusted for patient characteristics and disease severity, steroid use increased (odds ratio [OR] 7.4; 95% confidence interval [CI] 6.2-8.9), and invasive mechanical ventilation decreased (OR 0.5; 95% CI 0.4-0.7) in the second wave compared to the first. After adjusting for differences in patient characteristics and disease severity, the odds of hospitalization (OR 0.7; 95% CI 0.6-0.8) and critical care admission (OR 0.7; 95% CI 0.6-0.9) decreased, while mortality remained unchanged (OR 0.7; 95% CI 0.5-1.1)., Interpretation: In patients presenting to cute care facilities, we observed rapid uptake of evidence-based therapies and less use of experimental therapies in the second wave. We observed increased rates of ED discharges and lower hospital and critical care resource use over time. Substantial reductions in mechanical ventilation were not associated with increasing mortality. Advances in treatment strategies created health system efficiencies without compromising patient outcomes., Trial Registration: Clinicaltrials.gov, NCT04702945., (© 2022. The Author(s).)

Background: Repeat exposures to culprit medications are a common cause of preventable adverse drug events. Health information technologies have the potential to reduce repeat adverse drug events by improving information continuity. However, they rarely interoperate to ensure providers can view adverse drug events documented in other systems. We designed ActionADE to enable rapid documentation of adverse drug events and communication of standardized information across health sectors by integrating with legacy systems. We will leverage ActionADE's implementation to conduct two parallel, randomized trials: patients with adverse drug reactions in the main trial and those diagnosed with non-adherence in a secondary trial. Primary objective of the main trial is to evaluate the effects of providing information continuity about adverse drug reactions on culprit medication re-dispensations over 12 months. Primary objective of the secondary trial is to evaluate the effect of providing information continuity on adherence over 12 months., Methods: We will conduct two parallel group, triple-blind randomized controlled trials in participating hospitals in British Columbia, Canada. We will enroll adults presenting to hospital with an adverse drug event to prescribed outpatient medication. Clinicians will document the adverse drug event in ActionADE. The software will use an algorithm to determine patient eligibility and allocate eligible patients to experimental or control. In the experimental arm, ActionADE will transmit information to PharmaNet, where adverse drug event information will be displayed in community pharmacies when re-dispensations are attempted. In the control arm, ActionADE will retain information in the local record. We will enroll 3600 adults with an adverse drug reaction into the main trial. The main trial's primary outcome is re-dispensation of a culprit or same-class medication within 12 months; the secondary trial's primary outcome will be adherence to culprit medication. Secondary outcomes include health services utilization and mortality., Discussion: These studies have the potential to guide policy decisions and investments needed to drive health information technology integrations to prevent repeat adverse drug events. We present an example of how a health information technology implementation can be leveraged to conduct pragmatic randomized controlled trials., Trial Registration: ClinicalTrials.gov NCT04568668 , NCT04574648 . Registered on 1 October 2020.

Objectives: Liver disease is a major cause of morbidity and mortality in sub-Saharan Africa, but its prevalence, distribution and aetiology have not been well characterised. We therefore set out to examine liver function tests (LFTs) and liver fibrosis scores in a rural African population., Design: We undertook a cross-sectional survey of LFTs. We classified abnormal LFTs based on reference ranges set in America and in Africa. We derived fibrosis scores (aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), fibrosis-4, gamma-glutamyl transferase (GGT) to platelet ratio (GPR), red cell distribution width to platelet ratio and S-index). We collected information about alcohol intake, and infection with HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV)., Setting: We studied a population cohort in South-Western Uganda., Participants: Data were available for 8099 adults (median age 30 years; 56% female)., Results: The prevalence of HBV, HCV and HIV infection was 3%, 0.2% and 8%, respectively. The prevalence of abnormal LFTs was higher based on the American reference range compared with the African reference range (eg, for AST 13% vs 3%, respectively). Elevated AST/ALT ratio was significantly associated with self-reported alcohol consumption (p<0.001), and the overall prevalence of AST/ALT ratio >2 was 11% (suggesting alcoholic hepatitis). The highest prevalence of fibrosis was predicted by the GPR score, with 24% of the population falling above the threshold for fibrosis. There was an association between the presence of HIV or HBV and raised GPR (p=0.005) and S-index (p<0.001). By multivariate analysis, elevated LFTs and fibrosis scores were most consistently associated with older age, male sex, being under-weight, HIV or HBV infection and alcohol consumption., Conclusions: Further work is required to determine normal reference ranges for LFTs in this setting, to evaluate the specificity and sensitivity of fibrosis scores and to determine the aetiology of liver disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Evaluate the relationship between naloxone dose (initial and cumulative) and opioid toxicity reversal and adverse events in undifferentiated and presumed fentanyl/ultra-potent opioid overdoses., Methods: We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings (1972 to 2018). We included interventional, observational, and case studies/series reporting on naloxone dose and opioid toxicity reversal or adverse events in people >12 years old., Results: A total of 174 studies (110 case reports/series, 57 observational, 7 interventional) with 26,660 subjects (median age 35 years; 74% male). Heterogeneity precluded meta-analysis. Where reported, we abstracted naloxone dose and proportion of patients with toxicity reversal. Among patients with presumed exposure to fentanyl/ultra-potent opioids, 56.9% (617/1,085) responded to an initial naloxone dose ≤0.4 mg compared with 80.2% (170/212) of heroin users, and 30.4% (7/23) responded to an initial naloxone dose >0.4 mg compared with 59.1% (1,434/2,428) of heroin users. Among patients who responded, median cumulative naloxone doses were higher for presumed fentanyl/ultra-potent opioids than heroin overdoses in North America, both before 2015 (fentanyl/ultra-potent opioids: 1.8 mg [interquartile interval {IQI}, 1.0, 4.0]; heroin: 0.8 mg [IQI, 0.4, 0.8]) and after 2015 (fentanyl/ultra-potent opioids: 3.4 mg [IQI, 3.0, 4.1]); heroin: 2 mg [IQI, 1.4, 2.0]). Where adverse events were reported, 11% (490/4,414) of subjects experienced withdrawal. Variable reporting, heterogeneity and poor-quality studies limit conclusions., Conclusions: Practitioners have used higher initial doses, and in some cases higher cumulative naloxone doses to reverse toxicity due to presumed fentanyl/ultra-potent opioid exposure compared with other opioids. High-quality comparative naloxone dosing studies assessing effectiveness and safety are needed.

Aim: Our objective was to identify preventable adverse drug events and factors contributing to their development., Methods: We performed a retrospective chart review combining data from three prospective multicentre observational studies that assessed emergency department patients for adverse drug events. A clinical pharmacist and physician independently reviewed the charts, extracted data and rated the preventability of each adverse drug event. A third reviewer adjudicated all discordant or uncertain cases. We calculated the proportion of adverse drug events that were deemed preventable, performed multivariable logistic regression to explore the characteristics of patients with preventable events, and identified contributing factors., Results: We reviewed the records of 1 356 adverse drug events in 1 234 patients. Raters considered 869 (64.1%) of adverse drug events probably or definitely preventable. Patients with mental health diagnoses (OR 1.8; 95% CI 1.3-2.5) and diabetes (OR 1.7; 95% CI 1.2-2.4) were more likely to present with preventable events. The medications most commonly implicated in preventable events were warfarin (9.4%), hydrochlorothiazide (4.5%), furosemide (4.0%), insulin (3.9%) and acetylsalicylic acid (2.7%). Common contributing factors included inadequate patient instructions, monitoring and follow-up, and reassessments after medication changes had been made., Conclusions: Our study suggests that patients with mental health conditions and diabetes require close monitoring. Efforts to address the identified contributing factors are needed., (© 2019 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Study Objective: Increasing opioid prescribing has been linked to an epidemic of opioid misuse. Our objective is to synthesize the available evidence about patient-, prescriber-, medication-, and system-level risk factors for developing misuse among patients prescribed opioids for noncancer pain., Methods: We performed a systematic search of the scientific and gray literature for studies reporting on risk factors for prescription opioid misuse. Two reviewers independently reviewed titles, abstracts, and full texts; extracted data; and assessed study quality. We excluded studies with greater than 50% cancer patients, palliative patients, and illicit opioid initiation. When possible, we synthesized the effect sizes of dichotomous risk factors and their associations with opioid misuse, using inverse-variance random-effects meta-analysis. We calculated the mean difference between opioid misusers and nonmisusers for continuous risk factors. When studies lacked homogeneity, we synthesized their results qualitatively., Results: Of 9,629 studies, 65 met our inclusion criteria. Among patients with outpatient opioid prescriptions, the following factors were associated with the development of misuse: any current or previous substance use (odds ratio [OR] 3.55; 95% confidence interval [CI] 2.62 to 4.82), any mental health diagnosis (OR 2.45; 95% CI 1.91 to 3.15), younger age (OR 2.19; 95% CI 1.81 to 2.64), and male sex (OR 1.23; 95% CI 1.10 to 1.36)., Conclusion: Although clinicians should endeavor to offer alternative pain management strategies to all patients, those who are younger, are male patients, and report a history of or current substance use or mental health diagnoses were associated with a greater risk of developing opioid misuse. Clinicians should consider prioritizing alternative pain management strategies for these higher-risk patients., (Copyright © 2019 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Background: North America is in the midst of an unabated opioid overdose epidemic due to the increasing non-medical use of fentanyl and ultra-potent opioids. Naloxone is an effective antidote to opioid toxicity, yet its optimal dosing in the context of fentanyl and ultra-potent opioid overdoses remains unknown. This review aims to determine the relationship between the first empiric dose of naloxone and reversal of toxicity, adverse events, and the total cumulative dose required among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids. Secondary objectives include evaluating the relationship between the cumulative naloxone dose and toxicity reversal and adverse events, among patients with undifferentiated opioid overdoses and those with suspected toxicity from ultra-potent opioids., Methods: To identify studies, we will search MEDLINE, Embase, CENTRAL, DARE, CDAG, CINAHL, Science Citation Index, multiple trial registries, and the gray literature. Included studies will evaluate patients with suspected or confirmed opioid toxicity from undifferentiated opioids and ultra-potent opioids, who received an empiric and possibly additional doses of naloxone. The main outcomes of interest are the relationship between naloxone dose and toxicity reversal and adverse events. We will include controlled and non-controlled interventional studies, observational studies, case reports/series, and reports from poison control centers. We will extract data and assess study quality in duplicate with discrepancies resolved by consensus or a third party. We will use the Downs and Black and Cochrane risk of bias tools for observational and randomized controlled studies. If we find sufficient variation in dose, we will fit a random effects one-stage model to estimate a dose-response relationship. We will conduct multiple subgroup analyses, including by type of opioid used and by suspected high and low prevalence of ultra-potent opioid use based on geographic location and time of the original studies., Discussion: Our review will include the most up-to-date available data including ultra-potent opioids to inform the current response to the opioid epidemic, addressing the limitations of recent reviews. We anticipate limitations relating to study heterogeneity. We will disseminate study results widely to update overdose treatment guidelines and naloxone dosing in Take Home Naloxone programs.

Background: Kidney disease is an important cause of morbidity and mortality globally. However, there are limited data on the prevalence of impaired kidney function in sub-Saharan Africa. We aimed to determine the prevalence of reduced kidney function and associated factors in a rural Ugandan population. Methods: We undertook a study of a representative sample of the General Population Cohort in South-western Uganda. We systematically collected data on cardiovascular disease risk factors, anthropometric measurements and blood tests including haemoglobin, HIV, HbA1c and serum creatinine.  The estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi equation, without the race component of the equation. Results: A total of 5,979/6,397 (93.5%) participants had valid creatinine results. The mean age was 39 years (Range:16-103 years) and 3,627 (60.7%) were female. HIV prevalence was 9.7% and about 40% of the population were pre-hypertensive or hypertensive. The mean serum creatinine level was 0.75 mg/dl (95% CI 0.74-0.75), and the average eGFR was 109.3 ml/min/1.73 m 2 (95% CI 108.8-109.9). The overall prevalence of eGFR <60 ml/min/1.73 m 2 was 1.64% (98/5,979) (95% CI 1.34-1.99).  Additionally, 4,792(80.2%) were classified as normal eGFR (≥90 ml/min/1.73 m 2 ), 1,089(18.2%) as low eGFR (60-89 ml/min/1.73 m 2 ), 91(1.52%) as moderately reduced eGFR (30-59 ml/min/1.73 m 2 ), 4(0.07%) as severely reduced eGFR (15-29 ml/min/1.73 m 2 ), and 3(0.05%) classified as having kidney failure (eGFR<15 ml/min/1.73 m 2 ).  When age-standardised to the WHO Standard Population the prevalence of eGFR<60 ml/min/1.73 m 2 was 1.79%. Age above 35 years and the presence of hypertension (OR 2.86, 95% CI 1.15-7.08) and anaemia (OR 2.14, 95% CI 1.12-4.09) were associated with eGFR<60 ml/min/1.73 m 2 . Conclusion: In a systematic survey of people in rural Uganda, we found a substantial proportion had eGFR<60 ml/min/1.73 m 2 . More population based studies are needed to further characterize kidney disease in sub-Saharan Africa., Competing Interests: No competing interests were disclosed.

Background: Kidney disease is an important cause of morbidity and mortality globally. However, there are limited data on the prevalence of impaired kidney function in sub-Saharan Africa. We aimed to determine the prevalence of reduced kidney function and associated factors in a rural Ugandan population. Methods: We undertook a study of a representative sample of the General Population Cohort in South-western Uganda. We systematically collected data on cardiovascular disease risk factors, anthropometric measurements and blood tests including haemoglobin, HIV, HbA1c and serum creatinine.  The estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi formula, without the race component of the equation. Results: A total of 5,979/6,397 (93.5%) participants had valid creatinine results. The mean age was 39 years (Range: 16-103 years) and 3,627 (60.7%) were female. HIV prevalence was 9.7% and about 40% of the population were pre-hypertensive or hypertensive. The mean serum creatinine level was 0.75 mg/dl (95% CI 0.74-0.75), and the average eGFR was 109.3 ml/min/1.73 m 2 (95% CI 108.8-109.9). The overall prevalence of eGFR <60 ml/min/1.73 m 2 was 1.64% (98/5,979) (95% CI 1.34-1.99).  Additionally, 4,792 (80.2%) were classified as normal eGFR (≥90 ml/min/1.73 m 2 ), 1,089 (18.2%) as low eGFR (60-89 ml/min/1.73 m 2 ), 91 (1.52%) as moderately reduced eGFR (30-59 ml/min/1.73 m 2 ), 4 (0.07%) as severely reduced eGFR (15-29 ml/min/1.73 m 2 ), and 3 (0.05%) classified as having kidney failure (eGFR <15 ml/min/1.73 m 2 ).  When age-standardised to the WHO Standard Population the prevalence of eGFR<60 ml/min/1.73 m 2 was 1.79%. Age above 35 years and the presence of hypertension (OR 2.86, 95% CI 1.15-7.08) and anaemia (OR 2.14, 95% CI 1.12-4.09) were associated with eGFR<60 ml/min/1.73 m 2 . Conclusion: In a systematic survey of people in rural Uganda, we found a substantial proportion had eGFR<60 ml/min/1.73 m 2 , and this was strongly associated with high blood pressure and anaemia., Competing Interests: No competing interests were disclosed.

Background: Chronic kidney disease (CKD) is an important cause of morbidity and mortality globally. However, there are limited data on the prevalence of impaired kidney function in sub-Saharan Africa. We aimed to determine the prevalence of CKD and associated factors in a rural Ugandan population. Methods: We undertook a study of a representative sample of the General Population Cohort in South-western Uganda. We systematically collected data on cardiovascular disease risk factors, anthropometric measurements and blood tests for haemoglobin, HIV, HbA1c, Hepatitis B and C and serum creatinine.  The estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi formula, without the race component of the equation. Results: A total of 5,979/6,397 (93.5%) participants had valid creatinine results. The mean age was 39 years (Range: 16-103 years) and 3,627 (60.7%) were female. HIV prevalence was 9.7% and about 40% of the population were pre-hypertensive or hypertensive. The mean serum creatinine level was 0.75 mg/dl (95% CI 0.74-0.75), and the average eGFR was 109.3 ml/min/1.73 m 2 (95% CI 108.8-109.9). The overall prevalence of CKD (eGFR <60 ml/min/1.73 m 2 ) was 1.64% (98/5,979) (95% CI 1.34-1.99).  Additionally, 4,792 (80.2%) were classified as normal (eGFR ≥90 ml/min/1.73 m 2 ), 1,089 (18.2%) as low (eGFR 60-89 ml/min/1.73 m 2 ), 91 (1.52%) as moderate (eGFR 30-59 ml/min/1.73 m 2 ), 4 (0.07%) as severe (eGFR 15-29 ml/min/1.73 m 2 ), and 3 (0.05%) classified as having kidney failure (eGFR <15 ml/min/1.73 m 2 ).  When age-standardised to the WHO Standard Population the prevalence of CKD was 1.79%. Age above 35 years (OR 78.3, 95% CI 32.3-189), and the presence of hypertension (OR 2.98, 95% CI 1.47-6.02) and anaemia (OR 2.47, 95% CI 1.37-4.42) were associated with CKD. Conclusion: We found a substantial prevalence of CKD in rural Uganda, strongly associated with high blood pressure and anaemia., Competing Interests: No competing interests were disclosed.

Background: Opioid addiction prevention has become an urgent public health priority, with several countries declaring a state of emergency due to rising death tolls from opioid abuse. Reducing the risk of developing addiction among opioid-naïve patients exposed to prescribed opioids during the process of medical care may be an important primary prevention strategy. Our objective is to synthesize the available evidence about factors associated with the development of addiction among patients first exposed to prescribed opioids, with a focus on opioid-naïve patients., Methods: We will perform a systematic search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and other databases in collaboration with a health information specialist using a comprehensive search strategy. We will also supplement our search with a scan of the grey literature to identify relevant ongoing and unpublished studies. We will include studies reporting on risk factors for opioid addiction in patients prescribed opioid analgesic therapy through a prescription from a licensed medical professional, with a focus on opioid-naïve patients. We will exclude studies focusing on patients who are first exposed to illicit opioids, those who use prescription opioids for cancer pain, and/or who are palliative. Two reviewers will independently review titles, abstracts, and full texts for inclusion and exclusion criteria. They will then extract data from included full texts using standardized piloted data extraction forms and assess study quality through risk of bias assessment. We will synthesize the effect sizes of risk factors derived from clinically homogenous studies with similar designs and the remaining ones qualitatively., Discussion: Understanding risk factors for opioid addiction among patients who require analgesia has the potential to inform clinical care and opioid prescribing guidelines aiming to reduce opioid addiction. We will also use this information as a starting point for developing interventions for primary prevention.