Antiosteoporosis Medication Prescriptions After Fragility Fractures.

This cohort study assesses prescribing rates for antiosteoporosis medication following a fragility fracture and factors associated with filling a prescription after a fracture among patients in Ontario, Canada.

Seeing the Truth About Double Blinding.

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.

Edible Cannabis Legalization and Cannabis Poisonings in Older Adults.

This cross-sectional study examines the association between edible cannabis legalization and emergency department visits for cannabis poisonings in older adults.

New Persistent Opioid Use After Childbirth.

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.

A Dose of Reality About Dose-Response Relationships.

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.

Prescription of oxycodone versus codeine after childbirth and risk of persistent opioid use: a population-based cohort study.

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.

Association Between Diabetes and Mortality Among Adult Patients Hospitalized With COVID-19: A Cohort Study of Hospitalized Adults in Ontario, Canada, and Copenhagen, Denmark.

OBJECTIVES: Diabetes has been reported to be associated with an increased risk of death among patients with COVID-19. However, the available studies lack detail on COVID-19 illness severity and measurement of relevant comorbidities. METHODS: We conducted a multicentre, retrospective cohort study of patients 18 years of age and older who were hospitalized with COVID-19 between January 1, 2020, and November 30, 2020, in Ontario, Canada, and Copenhagen, Denmark. Chart abstraction emphasizing comorbidities and disease severity was performed by trained research personnel. The association between diabetes and death was measured using Poisson regression. The main outcome measure was in-hospital 30-day risk of death. RESULTS: Our study included 1,133 hospitalized patients with COVID-19 in Ontario and 305 in Denmark, of whom 405 and 75 patients, respectively, had pre-existing diabetes. In both Ontario and Denmark, patients with diabetes were more likely to be older; have chronic kidney disease, cardiovascular disease, and higher troponin levels; and be receiving antibiotics, when compared with adults without diabetes. In Ontario, 24% (n=96) of adults with diabetes died compared with 15% (n=109) of adults without diabetes. In Denmark, 16% (n=12) of adults with diabetes died in hospital compared with 13% (n=29) of those without diabetes. In Ontario, the crude mortality ratio among patients with diabetes was 1.60 (95% confidence interval [CI], 1.24 to 2.07) and in the adjusted regression model it was 1.19 (95% CI, 0.86 to 1.66). In Denmark, the crude mortality ratio among patients with diabetes was 1.27 (95% CI, 0.68 to 2.36) and in the adjusted model it was 0.87 (95% CI, 0.49 to 1.54). Meta-analysis of the 2 rate ratios from each region resulted in a crude mortality ratio of 1.55 (95% CI, 1.22 to 1.96) and an adjusted mortality ratio of 1.11 (95% CI, 0.84 to 1.47). CONCLUSION: The presence of diabetes was not strongly associated with in-hospital COVID-19 mortality independent of illness severity and other comorbidities.

Pedestrian Deaths During the COVID-19 Pandemic.

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.

Maternal opioid treatment after delivery and risk of adverse infant outcomes: population based cohort study.

OBJECTIVE: To examine whether maternal opioid treatment after delivery is associated with an increased risk of adverse infant outcomes. DESIGN: Population based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: 865 691 mother-infant pairs discharged from hospital alive within seven days of delivery from 1 September 2012 to 31 March 2020. Each mother who filled an opioid prescription within seven days of discharge was propensity score matched to a mother who did not. MAIN OUTCOME MEASURES: The primary outcome was hospital readmission of infants for any reason within 30 days of their mother filling an opioid prescription (index date). Infant related secondary outcomes were any emergency department visit, hospital admission for all cause injury, admission to a neonatal intensive care unit, admission with resuscitation or assisted ventilation, and all cause death. RESULTS: 85 675 mothers (99.8% of the 85 852 mothers prescribed an opioid) who filled an opioid prescription within seven days of discharge after delivery were propensity score matched to 85 675 mothers who did not. Of the infants admitted to hospital within 30 days, 2962 (3.5%) were born to mothers who filled an opioid prescription compared with 3038 (3.5%) born to mothers who did not. Infants of mothers who were prescribed an opioid were no more likely to be admitted to hospital for any reason than infants of mothers who were not prescribed an opioid (hazard ratio 0.98, 95% confidence interval 0.93 to 1.03) and marginally more likely to be taken to an emergency department in the subsequent 30 days (1.04, 1.01 to 1.08), but no differences were found for any other adverse infant outcomes and there were no infant deaths. CONCLUSIONS: Findings from this study suggest no association between maternal opioid prescription after delivery and adverse infant outcomes, including death.

Effect of Ward-Based High-Flow Nasal Cannula (HFNC) Oxygen Therapy on Critical Care Utilization During the COVID-19 Pandemic: A Retrospective Cohort Analysis.

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.

The use of loop diuretics in the context of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

AIMS: Addressing volume expansion may improve the management of hypertension across the pregnancy continuum. We conducted a systematic review to summarize the evidence on the use of loop diuretics in the context of hypertensive disorders during pregnancy and the postpartum period. METHODS AND RESULTS: Medline, Embase, Cochrane library, ClinicalTrials.gov, and Google Scholar were searched for original research articles published up to 29 June 2021. Of the 2801 results screened, 15 studies were included: eight randomized controlled trials, six before-after studies, and one cohort study. Based on random effects meta-analysis of before-after studies, antepartum use of loop diuretics was associated with lower DBP [mean difference -17.73 mmHg, (95% confidence intervals -34.50 to -0.96); I2 = 94%] and lower cardiac output [mean difference -0.75 l/min, (-1.11 to -0.39); I2 = 0%], with no difference in SBP, mean arterial pressure, heart rate, or total peripheral resistance. Meta-analysis of randomized controlled trials revealed that postpartum use of loop diuretics was associated with decreased need for additional antihypertensive patients [relative risk 0.69, (0.50-0.97); I2 = 14%], and an increased duration of hospitalization [mean difference 8.80 h, (4.46-13.14); I2 = 83%], with no difference in the need for antihypertensive therapy at hospital discharge, or persistent postpartum hypertension. CONCLUSION: Antepartum use of loop diuretics lowered DBP and cardiac output, while their postpartum use reduced the need for additional antihypertensive medications. There was insufficient evidence to suggest a clear benefit. Future studies focusing on women with hypertensive pregnancy disorders who may most likely benefit from loop diuretics are required.

Adverse Fetal Outcomes and Maternal Mortality Following Nonobstetric Abdominopelvic Surgery in Pregnancy: A Systematic Review and Meta-analysis.

OBJECTIVE: To quantify the absolute risks of adverse fetal outcomes and maternal mortality following nonobstetric abdominopelvic surgery in pregnancy. SUMMARY BACKGROUND DATA: Surgery is often necessary in pregnancy, but absolute measures of risk required to guide perioperative management are lacking. METHODS: We systematically searched MEDLINE, EMBASE, and EvidenceBased Medicine Reviews from January 1, 2000, to December 9, 2020, for observational studies and randomized trials of pregnant patients undergoing nonobstetric abdominopelvic surgery. We determined the pooled proportions of fetal loss, preterm birth, and maternal mortality using a generalized linear random/mixed effects model with a logit link. RESULTS: We identified 114 observational studies (52 [46%] appendectomy, 34 [30%] adnexal, 8 [7%] cholecystectomy, 20 [17%] mixed types) reporting on 67,111 pregnant patients. Overall pooled proportions of fetal loss, preterm birth, and maternal mortality were 2.8% (95% CI 2.2-3.6), 9.7% (95% CI 8.3-11.4), and 0.04% (95% CI 0.02-0.09; 4/10,000), respectively. Rates of fetal loss and preterm birth were higher for pelvic inflammatory conditions (eg, appendectomy, adnexal torsion) than for abdominal or nonurgent conditions (eg, cholecystectomy, adnexal mass). Surgery in the second and third trimesters was associated with lower rates of fetal loss (0.1%) and higher rates of preterm birth (13.5%) than surgery in the first and second trimesters (fetal loss 2.9%, preterm birth 5.6%). CONCLUSIONS: Absolute risks of adverse fetal outcomes after nonobstetric abdom- inopelvic surgery vary with gestational age, indication, and acuity. Pooled estimates derived here identify high-risk clinical scenarios, and can inform implementation of mitigation strategies and improve preoperative counselling.

Variation in the risk of death due to COVID-19: An international multicenter cohort study of hospitalized adults.

BACKGROUND: There is wide variation in mortality among patients hospitalized with COVID-19. Whether this is related to patient or hospital factors is unknown. OBJECTIVE: To compare the risk of mortality for patients hospitalized with COVID-19 and to determine whether the majority of that variation was explained by differences in patient characteristics across sites. DESIGN, SETTING, AND PARTICIPANTS: An international multicenter cohort study of hospitalized adults with laboratory-confirmed COVID-19 enrolled from 10 hospitals in Ontario, Canada and 8 hospitals in Copenhagen, Denmark between January 1, 2020 and November 11, 2020. MAIN OUTCOMES AND MEASURES: Inpatient mortality. We used a multivariable multilevel regression model to compare the in-hospital mortality risk across hospitals and quantify the variation attributable to patient-level factors. RESULTS: There were 1364 adults hospitalized with COVID-19 in Ontario (n = 1149) and in Denmark (n = 215). In Ontario, the absolute risk of in-hospital mortality ranged from 12.0% to 39.8% across hospitals. Ninety-eight percent of the variation in mortality in Ontario was explained by differences in the characteristics of the patients. In Denmark, the absolute risk of inpatients ranged from 13.8% to 20.6%. One hundred percent of the variation in mortality in Denmark was explained by differences in the characteristics of the inpatients. CONCLUSION: There was wide variation in inpatient COVID-19 mortality across hospitals, which was largely explained by patient-level factors, such as age and severity of presenting illness. However, hospital-level factors that could have affected care, including resource availability and capacity, were not taken into account. These findings highlight potential limitations in comparing crude mortality rates across hospitals for the purposes of reporting on the quality of care.

Prenatal electrocardiogram testing and postpartum depression: A population-based cohort study.

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.

Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE).

OBJECTIVES: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19. DESIGN: Multicentre pragmatic randomised clinical trial. SETTING: 15 hospitals in Canada and the United States from May 2020 until May 2021. PARTICIPANTS: Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis. INTERVENTION: Patients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position). MAIN OUTCOME MEASURES: The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen. RESULTS: The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomisation was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomisation. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care. CONCLUSION: Among non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning. STUDY REGISTRATION: ClinicalTrials.gov NCT04383613.