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Objectives: We used modified contingent valuation methodology to determine how noninferiority margin sizes influence clinicians' willingness to accept clinical trial results that compare mortality in critically ill children. Methods: We surveyed pediatric infectious diseases and critical care clinicians in Canada, Australia, and New Zealand and randomized respondents to review 1 of 9 mock abstracts describing a noninferiority trial of bacteremic critically ill children assigned to 7 or 14 d of antibiotics. Each scenario showed higher mortality in the 7-d group but met noninferiority criterion. We explored how noninferiority margins and baseline mortality rates influenced respondent acceptance of results. Results: There were 106 survey respondents: 65 (61%) critical care clinicians, 28 (26%) infectious diseases physicians, and 13 (12%) pharmacists. When noninferiority margins were 5% and 10%, 73% (24/33) and 79% (27/33) respondents would accept shorter treatment, compared with 44% (17/39) when the margin was 20% (P = 0.003). Logistic regression adjusted for baseline mortality showed 5% and 10% noninferiority margins were more likely to be associated with acceptance of shorter treatment compared with 20% margins (odds ratio [OR] 3.5, 95% confidence interval [CI]: 1.3–9.6, P = 0.013; OR 5.1, 95% CI: 1.8–14.6, P = 0.002). Baseline mortality was not a significant predictor of acceptance of shorter treatment. Conclusions: Clinicians are more likely to accept shorter treatment when noninferiority margins are ≤10%. However, nearly half of respondents who reviewed abstracts with 20% margins were still willing to accept shorter treatment. This is a novel application of contingent valuation methodology to elicit acceptance of research results among end users of the medical literature. Highlights: Clinicians are more likely to accept shorter treatment durations based on noninferior mortality results when the noninferiority margin is 5% or 10% than if the margin is 20%. However, nearly half of clinicians would still accept shorter-duration treatment as noninferior with margins of 20%. Baseline mortality does not independently predict acceptance of shorter-duration treatment. Contingent valuation is a novel approach to elicit the acceptance of research design parameters from the perspective of endusers of the medical literature. [ABSTRACT FROM AUTHOR]

Objective: To describe antibiotic treatment durations that pediatric infectious diseases (ID) and critical care clinicians usually recommend for bloodstream infections in critically ill children. Design: Anonymous, online practice survey using five common pediatric-based case scenarios of bloodstream infections. Setting: Pediatric intensive care units in Canada, Australia and New Zealand. Participants: Pediatric intensivists, nurse practitioners, ID physicians and pharmacists. Main outcome measures: Recommended treatment durations for common infectious syndromes associated with bloodstream infections and willingness to enrol patients into a trial to study treatment duration. Results: Among 136 survey respondents, most recommended at least 10 days antibiotics for bloodstream infections associated with: pneumonia (65%), skin/soft tissue (74%), urinary tract (64%) and intra-abdominal infections (drained: 90%; undrained: 99%). For central vascular catheter-associated infections without catheter removal, over 90% clinicians recommended at least 10 days antibiotics, except for infections caused by coagulase negative staphylococci (79%). Recommendations for at least 10 days antibiotics were less common with catheter removal. In multivariable linear regression analyses, lack of source control was significantly associated with longer treatment durations (+5.2 days [95% CI: 4.4–6.1 days] for intra-abdominal infections and +4.1 days [95% CI: 3.8–4.4 days] for central vascular catheter-associated infections). Most clinicians (73–95%, depending on the source of bloodstream infection) would be willing to enrol patients into a trial of shorter versus longer antibiotic treatment duration. Conclusions: The majority of clinicians currently recommend at least 10 days of antibiotics for most scenarios of bloodstream infections in critically ill children. There is practice heterogeneity in self-reported treatment duration recommendations among clinicians. Treatment durations were similar across different infectious syndromes. Under appropriate clinical conditions, most clinicians would be willing to enrol patients into a trial of shorter versus longer treatment for common syndromes associated with bloodstream infections. [ABSTRACT FROM AUTHOR]

Objective: To describe the size and variability of non-inferiority margins used in non-inferiority trials of medications with primary outcomes involving mortality, and to examine the association between trial characteristics and non-inferiority margin size., Design: Systematic review., Data Sources: Medline, Medline In Process, Medline Epub Ahead of Print and Embase Classic+Embase databases from January 1989 to December 2019., Eligibility Criteria: Prospective non-inferiority randomised controlled trials comparing pharmacological therapies, with primary analyses for non-inferiority and primary outcomes involving mortality alone or as part of a composite outcome. Trials had to prespecify non-inferiority margins as absolute risk differences or relative to risks of outcome and provide a baseline risk of primary outcome in the control intervention., Results: 3992 records were screened, 195 articles were selected for full text review and 111 articles were included for analyses. 82% of trials were conducted in thrombosis, infectious diseases or oncology. Mortality was the sole primary outcome in 23 (21%) trials, and part of a composite primary outcome in 88 (79%) trials. The overall median non-inferiority margin was an absolute risk difference of 9% (IQR 4.2%-10%). When non-inferiority margins were expressed relative to the baseline risk of primary outcome in control groups, the median relative non-inferiority margin was 1.5 (IQR 1.3-1.7). In multivariable regression analyses examining the association between trial characteristics (medical specialty, inclusion of paediatric patients, mortality as a sole or part of a composite primary outcome, presence of industry funding) and non-inferiority margin size, only medical specialty was significantly associated with non-inferiority margin size., Conclusion: Absolute and relative non-inferiority margins used in published trials comparing medications are large, allowing conclusions of non-inferiority in the context of large differences in mortality. Accepting the potential for large increases in outcomes involving mortality while declaring non-inferiority is a challenging methodological issue in the conduct of non-inferiority trials., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Medication reconciliation reduces potential medication discrepancies and adverse drug events. The role of pharmacy technicians in obtaining best possible medication histories (BPMHs) and performing reconciliation at the admission and transfer interfaces of care for pediatric patients has not been described., Objectives: To compare the completeness and accuracy of BPMHs and reconciliation conducted by a pharmacy technician (pilot study) and by nurses and/or pharmacists (baseline). The severity of identified unintentional discrepancies was rated to determine their clinical importance., Methods: This prospective cohort comparison study involved patients up to 18 years of age admitted to and/or transferred between the Cardiology ward and the Cardiac Critical Care Unit of a pediatric tertiary care teaching hospital. A pharmacy resident conducted two 3-week audits: the first to assess the completeness and accuracy of BPMHs and reconciliation performed by nurses and/or pharmacists and the second to assess the completeness and accuracy of BPMHs and reconciliation performed by a pharmacy technician., Results: The total number of patients was 38 in the baseline phase and 46 in the pilot period. There were no statistically significant differences between the baseline and pilot audits in terms of completion of BPMH (82% [28/34] versus 78% [21/27], p = 0.75) or completion of reconciliation (70% [23/33] versus 75% [15/20], p = 0.76) within 24 h of admission. Completeness of transfer reconciliation was significantly higher during the pilot study than at baseline (91% [31/34] versus 61% [11/18], p = 0.022). No significant differences between the baseline and pilot audits were found in the proportions of patients with at least one BPMH discrepancy (38% [13/34] versus 22% [6/27], p = 0.27), at least one unintentional discrepancy upon admission (21% [7/33] versus 10% [2/20], p = 0.46), or at least one unintentional discrepancy at the transfer interface (6% [1/18] versus 3% [1/34], p = 0.58). None of the 16 unintentional discrepancies were rated as causing severe patient discomfort or clinical deterioration., Conclusions: A trained pharmacy technician can perform admission and transfer medication reconciliation for pediatric patients with completeness and accuracy comparable to those of nurses and pharmacists. Future studies should explore the sustainability and cost-effectiveness of this practice model.

Measurement of renal function is important to optimize drug dosing in critically ill pediatric patients and to prevent dose-related toxicities caused by medications that are eliminated or metabolized by the kidney. In clinical practice, the 24-h creatinine clearance (CrCl) is used as a surrogate marker of renal function. However, a 24-h urine collection period delays the availability of the result and increases the potential for collection errors. This prospective, observational study was performed to determine whether a 12-h CrCl is comparable to the traditional 24-h CrCl and to assess whether CrCl could be reliably predicted by the Schwartz equation, which mathematically estimates a child's GFR. A 24-h urine sample was collected in two 12-h aliquots from 60 catheterized critically ill children (age 2 d to 18 y). CrCl and Schwartz glomerular filtration rate (GFR) estimates were determined for each 12- and 24-h period. Agreement between 12- and 24-h CrCl and between CrCl and Schwartz GFR estimates was assessed using intraclass correlation coefficients (ICCs). An ICC > or =0.8 was considered to indicate excellent agreement. The ICC between the first 12-h CrCl and 24-h CrCl was 0.9605. The ICC between the second 12-h CrCl and 24-h CrCl was 0.9602. The ICC between the 24-h CrCl and Schwartz GFR was only 0.7046. All comparisons of 12- and 24-h CrCl indicated excellent agreement. In summary, the Schwartz equation was not a reliable estimate of renal function in critically ill children, and a 12-h CrCl is just as accurate as the standard 24-h CrCl to assess renal function and guide drug dosing.