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.

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.

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.

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.

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.

Prescription of macrolides vs penicillin during pregnancy was linked to major malformations in offspring.

SOURCE CITATION: Fan H, Gilbert R, O'Callaghan F, Li L. Associations between macrolide antibiotics prescribing during pregnancy and adverse child outcomes in the UK: population based cohort study. BMJ. 2020;368:m331. 32075790.

A Web-based Multimedia Program Before Colonoscopy Increased Knowledge and Decreased Anxiety, Sedation Requirement, and Procedure Time.

GOALS: Assess the impact of a web-based multimedia patient engagement program on patient anxiety, perception and knowledge about the colonoscopy in addition to procedure outcomes. BACKGROUND: The success of patients coming for a colonoscopy for colorectal cancer screening is dependent in part on patients' understanding of the preparation and of the procedure. Patients were randomized to use either our institution's standard preprocedure colonoscopy packet or a web-based multimedia patient engagement program (Emmi Solutions) before their scheduled procedure. On the day of colonoscopy, all participants completed a survey including questions to assess knowledge and perception of colonoscopy, in addition to the State Trait Anxiety Inventory. We also collected procedure data including medication doses and procedure time. STUDY RESULTS: Patients in the experimental group correctly answered knowledge questions (82%) more often than the control group (74%) (P=0.0003). More than half (58%) of patients in the experimental group felt this intervention reduced their anxiety about the procedure, and the State Trait Anxiety Inventory anxiety score was lower in the experimental group (P=0.026). Patients who viewed the program required less midazolam (3.66 vs. 4.46 mg, P=0.0035) and total procedure time was shorter (24.8 vs. 29 min, P=0.024). CONCLUSIONS: A web-based multimedia patient engagement program watched before colonoscopy decreased patient anxiety, medication requirements, and procedure time while increasing knowledge. This intervention could help patients understand and feel more comfortable about colonoscopy leading to increased screening rates while increasing efficiency and decreasing recovery time.