Search

Competing Interests: Competing interests:: Jonathan Zipursky and Tali Bogler are medical advisors for First Exposure; Cynthia Maxwell is the medical director. Jonathan Zipursky reports payments from law firms for medicolegal opinions on the safety and effectiveness of drugs unrelated to the current work. No other competing interests were declared.

Randomized clinical trials provide reassurances that confounding factors are balanced at baseline whereas blinding is essential to assure the balance of extraneous factors thereafter. This article provides a three-part taxonomy of pitfalls that can arise because of inadequate blinding in clinical trials. We introduce a cautionary framework for readers interpreting a blinded randomized trial for evidence-based medicine. Each pitfall is illustrated with a relevant example of a potential bias resulting from knowledge of group assignment. Several pitfalls occur during the conduct of the study including inadequate blinding of the intervention group, control group, or responsible clinicians. Additional pitfalls relate to data analysis including unsubstantiated assertions of blinding and subverted tests for blinding. Further pitfalls arise due to surrounding oversight including unblinding of research ethics boards and scientific reviewers. These caveats are sources of misunderstanding when observing the apparent connection between a clinical intervention and patient outcomes. An awareness of specific pitfalls might help advance the interpretation and application of blinded randomized clinical trials to inform evidence-based medical care., Competing Interests: Declarations:. Conflict of Interest:: The authors declare that they do not have a conflict of interest., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Alcohol sales increased at the onset of the coronavirus disease 2019 (Covid-19) pandemic, while alcohol-related emergency department (ED) visits decreased. It is unknown whether these patterns of alcohol use persisted or led to delayed effects on health., Methods: We conducted a cross-sectional time series analysis of alcohol sales and alcohol-related adverse events in Ontario, Canada. We obtained 6 years of alcohol sales data from the largest regional alcohol distributor. We obtained monthly counts of alcohol-related ED visits, hospital admissions, and toxicity deaths. We defined our exposure as the start of the Covid-19 pandemic (March 1, 2020). We used linear mixed models to compare mean monthly alcohol sales and adverse events during prepandemic and pandemic periods. We used univariate Poisson regression models to generate incident rate ratios for alcohol-related adverse events comparing the prepandemic (February 28, 2016, to February 29, 2020) and pandemic (March 1, 2020, to February 26, 2022) periods., Results: Alcohol sales increased, on average, by CA$43.5 million per month (95% confidence interval [CI], CA$26.1 million to CA$60.9 million; P<0.01) during the pandemic years compared with the prepandemic period. We observed a 7% increase (95% CI, 5 to 8) in the proportion of alcohol-related ED visits during the pandemic years, due to a modest decrease in alcohol-related ED visits and a larger decrease in all-cause ED visits. Overall, an average increase of 191 alcohol-related admissions occurred per month (95% CI, 101 to 282). We also observed an average increase of eight toxicity deaths per month (95% CI, 4 to 12)., Conclusions: Alcohol sales and alcohol-related adverse events increased during the Covid-19 pandemic.

Observational research can be strengthened by examining potential dose-response relationships that correlate a clinical intervention with a patient outcome. Despite being a classic criterion for establishing causality, dose-response testing can be difficult to interpret in clinical medicine due to multiple diverse pitfalls. This review introduces a cautionary framework for investigators considering dose-response relationships in observational research to support evidence-based medicine. Each pitfall is illustrated with a specific example relevant when analyzing a dose-response relationship. Several pitfalls stem from faulty interpretation including confounding by indication and fallible range selection. Additional pitfalls relate to improper analysis including fitting a nonlinear model and misclassification error. Further pitfalls arise in special situations including subjective self-report and artifacts from survival bias. These caveats are common sources of misunderstanding in analyses that examine the link between varying exposures and the intensity of clinical outcomes. Awareness of specific pitfalls, we suggest, might help advance the conduct, application, and translation of dose-response relationships in observational research to inform evidence-based medical care., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Objective: To examine factors associated with new persistent opioid use after childbirth., Methods: We conducted a population-based cohort study of individuals who initiated opioid therapy within 7 days of discharge from hospital after delivery between September 1, 2013, and September 30, 2021. The primary outcome was new persistent opioid use , which was defined as one or more prescriptions for an opioid within 90 days of the first postpartum prescription and one or more subsequent opioid prescriptions in the 91-365 days afterward. We used multivariable logistic regression to assess patient-, pregnancy-, and prescription-related factors associated with new persistent opioid use after delivery., Results: We identified 118,694 unique deliveries after which opioids were initiated, including 99,399 cesarean (83.7%) and 19,295 vaginal (16.3%) deliveries. Among mothers who initiated an opioid after delivery, 1,282 (10.8/1,000 deliveries) met our definition of new persistent opioid use in the subsequent year. Rates of new persistent opioid use were appreciably higher after vaginal (16.0/1,000) compared with cesarean (9.8/1,000) deliveries. Each additional 30 morphine milligram equivalents in the initial opioid prescription was associated with an increased risk of new persistent use after cesarean (adjusted odds ratio [aOR] 1.06, 95% CI 1.04-1.08) and vaginal (aOR 1.05, 95% CI 1.02-1.08) delivery. A concomitant benzodiazepine prescription after cesarean delivery was associated with a markedly increased risk of persistent opioid use (aOR 2.69, 95% CI 1.60-4.52)., Conclusion: Among people who filled an opioid prescription after delivery, about 1% displayed evidence of persistent opioid use in the subsequent year. Initial prescriptions for large quantities of opioids and a concurrent benzodiazepine prescription may be important modifiable risk factors to prevent new persistent opioid use after delivery., Competing Interests: Financial Disclosure Jonathan S. Zipursky has received payments for medicolegal opinions regarding the safety and effectiveness of analgesics, including opioids. David N. Juurlink is an unpaid member of Physicians for Responsible Opioid Prescribing (PROP), which is sometimes cast as an “anti-opioid” group but is invested in safer and more evidence-based opioid prescribing. Dr. Juurlink is also a member of the American College of Medical Toxicology. Both PROP and ACMT have publicly available positions related to opioid prescribing. He has received payment for lectures and medicolegal opinions regarding the safety and effectiveness of analgesics, including opioids. Tara Gomes is supported by a Canada Research Chair in Drug Policy Research and Evaluation and has received funding from the Ontario MOH. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Oxycodone is increasingly prescribed for postpartum analgesia in lieu of codeine owing to concerns regarding the neonatal safety of codeine during lactation. We examined whether initiation of oxycodone after delivery was associated with an increased risk of persistent opioid use relative to initiation of codeine., Methods: We conducted a population-based cohort study of people who filled a prescription for either codeine or oxycodone within 7 days of discharge from hospital after delivery between Sept. 1, 2012, and June 30, 2020. The primary outcome was persistent opioid use, defined as 1 or more additional prescriptions for an opioid within 90 days of the first postpartum prescription and 1 or more additional prescriptions in the 91 to 365 days thereafter. We used inverse probability of treatment weighting to assess the risk of persistent postpartum opioid use, comparing people who initiated oxycodone with those who initiated codeine., Results: Over the 8-year study period, we identified 70 607 people who filled an opioid prescription within 7 days of discharge from hospital: 21 308 (30.2%) received codeine and 49 299 (69.8%) oxycodone. Compared with people who filled a prescription for codeine, receipt of oxycodone was not associated with persistent opioid use (relative risk [RR] 1.04, 95% confidence interval [CI] 0.91-1.20). We found an association between a prescription for oxycodone and persistent use after vaginal delivery (RR 1.63, 95% CI 1.31-2.03), but not after cesarean delivery (RR 0.85, 95% CI 0.73-1.00)., Interpretation: Initiation of oxycodone (v. codeine) was not associated with an increased risk of persistent opioid use, except after vaginal delivery., Competing Interests: Competing interests: Jonathan Zipursky has received payments from private law firms for medicolegal opinions on the safety and effectiveness of analgesics, including opioids. Dr. Zipursky is supported by the University of Toronto Department of Medicine Clinician Scientist Training Program and a Canadian Institutes of Health Research (CIHR) Banting and Best Doctoral Award. David Juurlink reports receiving payment for expert testimony from multiple law firms related to analgesics, including opioids; an honorarium for a lecture on pain management from Texas Tech University Health Sciences Center; and reimbursement for travel costs for presentations and scientific meetings from CIHR, Stanford University and Texas Tech University Health Sciences Center. Dr. Juurlink is an unpaid member of Physicians for Responsible Opioid Prescribing (PROP), a nongovernmental organization with the goal of promoting opioid stewardship. Tara Gomes reports receiving grant and contract funding from the Ontario Ministry of Health, the Public Health Agency of Canada, the Ontario College of Pharmacists and the Government of Canada (paid to institution in support of Dr. Gomes’ research program). A Tier 2 Canada Research Chair supports Dr. Gomes’ salary. Dr. Gomes has also received payment for travel and a stipend for participating in the Drugs and Therapeutics Advisory Committee from Indigenous Services Canada. Muhammad Mamdani reports receiving grant funding from Roche, examining drug use for multiple sclerosis. Dr. Mamdani has also received honoraria as a member of the scientific advisory board of SaNotize. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: Hospitals expanded critical care capacity during the COVID-19 pandemic by treating COVID-19 patients with high-flow nasal cannula oxygen therapy (HFNC) in non-traditional settings, including general internal medicine (GIM) wards. The impact of this practice on intensive care unit (ICU) capacity is unknown., Objective: To describe how our hospital operationalized the use of HFNC on GIM wards, assess its impact on ICU capacity, and examine the characteristics and outcomes of treated patients., Design: Retrospective cohort study of all patients treated with HFNC on GIM wards at a Canadian tertiary care hospital., Participants: All patients admitted with COVID-19 and treated with HFNC on GIM wards from December 28, 2020, to June 13, 2021, were included., Main Measures: We combined administrative data on critical care occupancy daily with chart-abstracted data for included patients to establish the total number of patients receiving ICU-level care at our hospital per day. We also collected data on demographics, medical comorbidities, illness severity, COVID-19 treatments, HFNC care processes, and patient outcomes., Key Results: We treated 124 patients with HFNC on the GIM wards (median age 66 years; 48% female). Patients were treated with HFNC for a median of 5 days (IQR 3 to 8); collectively, they received HFNC for a total of 740 hospital days, 71% of which were on GIM wards. At peak ICU capacity strain (144%), delivering HFNC on GIM wards added 20% to overall ICU capacity by managing up to 14 patients per day. Patients required a median maximal fraction of inspired oxygen of 80% (IQR 60 to 95). There were 18 deaths (15%) and 85 patients (69%) required critical care admission; of those, 40 (47%) required mechanical ventilation., Conclusions: With appropriate training and resources, treatment of COVID-19 patients with HFNC on GIM wards appears to be a feasible strategy to increase critical care capacity., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

A 47-Year-Old Man with Fever and RashA 47-year-old man presented for evaluation of fevers, rash, and diffuse muscle aches. How do you approach the evaluation, and what is the differential diagnosis?

Background: Cardiovascular symptoms in pregnancy may be a clue to psychological distress. We examined whether electrocardiogram testing in pregnant women is associated with an increased risk of subsequent postpartum depression., Methods: We conducted a population-based cohort study of pregnant women who delivered in Ontario, Canada comparing women who received a prenatal ECG to women who did not., Results: In total, 3,238,218 women gave birth during the 25-year study period of whom 157,352 (5%) received an electrocardiogram during prenatal care. Receiving an electrocardiogram test was associated with a one-third relative increase in the odds of postpartum depression (odds ratio 1.34; 95% confidence interval 1.29-1.39, p  < 0.001)., Conclusion: The association between prenatal electrocardiogram testing and postpartum depression suggests a possible link of organic disease with mental illness, and emphasizes that cardiovascular symptoms may be a clinical clue to the presence of an underlying mood disorder., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JSZ has received fees for medicolegal opinions unrelated to the published work., (© The Author(s) 2021.)

The COVID pandemic provides a natural experiment examining how a 50-60% reduction in pedestrian activity might lead to a reduction in pedestrian deaths. We assessed whether the reduction in pedestrian deaths was proportional to a one-to-one matching presumed in statistics correlating mobility with fatality. The primary analysis examined New York (largest city in US), and the validation analysis examined Toronto (largest city in Canada). We identified pedestrian activity in each location from the Apple Mobility database, normalized to the baseline in January 2020. We calculated monthly pedestrian deaths from the Vision Zero database in each city with baseline data from 3 prior years. We found a large initial reduction in pedestrian deaths during the lockdown in New York that was transient and not statistically significant during the summer and autumn despite sustained reductions in pedestrian activity. Similarly, we found a large initial reduction in pedestrian deaths during the lockdown in Toronto that was transient and not sustained. Together, these data suggest the substantial reductions in pedestrian activity during the COVID pandemic have no simple correlation with pedestrian fatality counts in the same locations. An awareness of this finding emphasizes the role of unmeasured modifiable individual factors beyond pedestrian infrastructure or other structural contributors., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. All authors have no financial or personal relationships or affiliations that could influence the decisions and work on this manuscript., (Copyright © 2021 The Author(s).)

Competing Interests: Intérêts concurrents: Jonathan Zipursky déclare avoir reçu des honoraires pour des opinions médicolégales sur l’innocuité et l’efficacité des médicaments indépendamment des travaux soumis. Aucun autre intérêt concurrent n’a été déclaré.

Competing Interests: Competing interests: Jonathan Zipursky reports receiving payments from private law firms for medicolegal opinions regarding the safety and effectiveness of drugs, outside the submitted work. No other competing interests were declared.

Opioids are commonly prescribed following childbirth, but data are lacking on trends in postpartum opioid prescribing over time. We examined whether a highly publicized 2006 case report questioning the safety of codeine during lactation was associated with changes in postpartum opioid prescribing. We conducted a cross-sectional time series analysis of all publicly funded prescriptions for opioids to postpartum women in Ontario, Canada, from April 1, 2000, to March 31, 2017. The intervention was the publication of a case report in 2006 attributing the death of a breastfeeding neonate to maternal codeine use. The primary outcome was the rate of opioid prescribing to postpartum women. Among postpartum women eligible for prescription drug coverage, 17.5% filled an opioid prescription in the third quarter of 2006 (immediately prior to the intervention), with codeine representing 89.8% of all prescriptions. By the fourth quarter of 2010, only 12.2% of postpartum women filled an opioid prescription, representing a decline of 30% (P < 0.01), with codeine representing 71.9% of all prescriptions. During this period, we observed sizeable relative increases in the proportion of opioid prescriptions filled for morphine, hydromorphone, and oxycodone. By 2017, among women prescribed opioids post partum, 39.0% filled a prescription for codeine, while the remainder filled prescriptions for oxycodone (18.6%), morphine (25.5%), and hydromorphone (16.9%). A highly publicized case report questioning the safety of maternal codeine use during breastfeeding was associated with significant changes in opioid prescribing to postpartum women, including a decline in overall opioid prescribing and a shift from codeine to stronger opioids., (© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

Competing Interests: Competing interests: Jonathan Zipursky reports payments for medicolegal opinions regarding the safety and effectiveness of drugs, outside the submitted work. No other competing interests were declared.

Competing Interests: Intérêts concurrents: Jonathan Zipursky déclare des honoraires personnels pour avoir fourni des avis médicolégaux, indépendamment des travaux soumis. Aucun autre intérêt concurrent n’a été déclaré.

Competing Interests: Competing interests: Jonathan Zipursky reports personal fees from providing medicolegal opinions, outside the submitted work. No other competing interests were declared.

Competing Interests: Intérêts concurrents: Aucun déclaré. Déclaration d’intérêts: Tali Bogler est mariée à Nathan Stall, rédacteur associé pour le CMAJ, qui n’a pas participé au processus ayant mené au choix de cet article.

Competing Interests: Competing interests: None declared.

Competing Interests: Intérêts concurrents: Aucun déclaré.

Competing Interests: Competing interests: None declared.

Background: Poisoning in pregnancy can cause maternal and neonatal morbidity and mortality, but few data detail such events. Herein, we describe poisoning exposures in pregnant women identified by a large Canadian Poison Centre. Methods: This retrospective study evaluated poisoning exposures in pregnant women aged 12-60 years, reported to the Ontario Poison Centre from 2010 to 2017. Exposures were identified from the Poison Centre database by calls received, in which the patient was also reported to be pregnant. We collected patient demographics (age, trimester, and location), as well as information about the poisoning exposure (number and type of substances, route of exposure, reason for exposure, decontamination, and treatment recommendations). Results: There were 1716 cases of poisoning exposures during pregnancy over the eight-year study period, representing 0.28% of all 619,539 calls over the period. Median maternal age was 29 years (IQR 25-33), and exposures were most frequent in the second trimester of pregnancy (41%). Unintentional exposures ( n  = 1397) accounted for 81% of all calls. Of the 18% of calls ( n  = 305) for intentional exposures, 71% ( n  = 219) were suspected attempted suicides. Intentional exposures were more frequent in the first (OR 2.64, 95% CI 1.85-3.76) and second trimesters (OR 1.61, 95% CI 1.13-2.28), relative to third trimester. The associated risk of intentional exposures was more likely in women aged ≤19 years (OR 21.41, 95% CI 12.75-35.94) and 20-29 years (OR 3.72, 95% CI 2.70-5.14), relative to women ≥30 years old. Conclusions: Intentional poisoning exposures in pregnancy most commonly involve young women in the first two trimesters. Population-based studies are needed to further examine risk factors for overdose, poisoning, and self-harm in pregnancy, as well as perinatal outcomes.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Background: Conducting postcall morning handoffs using a resident handoff bundle such as I-PASS can prove challenging. This may delay recognizing and acting on clinically important patient issues that arose overnight., Objective: We developed and implemented the I-CATCH morning handoff bundle and evaluated its impact on the proportion of overnight patient issues handed off from the on-call resident to the daytime team., Methods: We evaluated the I-CATCH ( I dentify patient; C haracterize situation; A ction-what was done overnight?; T o do for the team in the morning; C onfirm the H andoff) handoff bundle from November 2015 to May 2016 on general internal medicine wards at 1 academic teaching hospital. The bundle entailed staff/resident training, structured communication, and dedicated handoff space and time. We compared handoffs of overnight on-call issues by evening resident to daytime medical team before and after implementation, and used statistical process control to analyze adherence to the mnemonic., Results: We observed 435 handoffs (242 pre- and 193 postimplementation) over 63 days. There was no significant association between I-CATCH implementation and proportion of on-call overnight issues handed off (OR = 0.96; 95% confidence interval [CI] 0.52-1.47; P = .85). Running the list by going through patients one-by-one (OR = 1.74; 95% CI 1.1-2.77; P = .019), progress note documentation (OR = 3.80; 95% CI 2.19-6.60; P < .001), and direct handoff (OR = 4.84; 95% CI 1.43-16.42; P = .011) correlated with an increased likelihood of morning handoff., Conclusions: Implementing the I-CATCH bundle did not improve handoff of overnight issues to the daytime team., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Competing Interests: Competing interests: None declared.

A 79-year-old man presented to hospital with scald burns to the perineum after a syncopal episode while in a hot bathtub. Admission ECG was misdiagnosed as possible ventricular fibrillation with high-frequency irregular waveforms in lead V2 at a rate exceeding 1000 cycles per minute, corresponding to intervening skeletal muscle contractions unrelated to the heart. Follow-up ECG showed full resolution of the irregular waveforms. Muscle fasciculations are a benign cause of ECG artefact and can easily be mistaken for serious cardiac arrhythmias. While most muscle fasciculations detected on ECG are benign, in the correct clinical circumstance these waveforms indicate an underlying neuromuscular disorder. The patient underwent surgical skin grafting with no perioperative cardiac complications and no further syncope in hospital., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Heart failure is a significant cause of morbidity and mortality, yet patient risk stratification may be difficult. Prevention or treatment of atrial fibrillation (AF) may be an important strategy in these patients that could positively affect their outcome. It has been demonstrated that in patients with systolic dysfunction, prolonged QRS duration (QRSd), an easily measured electrocardiographic parameter, is associated with AF., Hypothesis: Prolonged QRSd is associated with an increase in prevalence of AF in patients with heart failure with preserved ejection fraction(HFPEF)., Methods: Between February 2006 and February 2009, 718 patients were discharged with a diagnosis of HF from the Dartmouth-Hitchcock Medical Center. Of these, 206 had EF ≥50% by echocardiography performed within 72 hours of admission. After exclusions, 82 patients remained, of which 25 had AF and 57 had sinus rhythm. Characteristics of the AF and sinus-rhythm patients were compared in this pilot study., Results: After adjustment for age, prior diagnosis of HF, and left atrial area, there was a nonsignificant trend (odds ratio: 2.2, 95% CI of 0.3-17.2) for a QRSd >120 ms to be associated with AF., Conclusions: Similar to results in patients with systolic dysfunction, patients with preserved EF may have an association between a prolonged QRSd and AF., (© 2017 Wiley Periodicals, Inc.)