Authors’ reply to Grundtvig Gram et al.

European Journal of Epidemiology -     

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy‐four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01–1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08–1.98; p = 0.015). Registration on trials was not associated with Gram‐negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML.     

Immunotherapy Use Prior to Liver Transplant in Patients with Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide, and its incidence has increased rapidly in the United States over the past two decades. Liver transplant is considered curative, but is not always possible, and pre-transplant immunotherapy is of great interest as a modality for downstaging the tumor burden. We present a review of the literature on pre-liver transplant immunotherapy use in patients with HCC. Our literature search queried publications in Ovid MEDLINE, Ovid Embase, and Web of Science, and ultimately identified 24 original research publications to be included for analysis. We found that the role of PD-1 and PD-L1 in risk stratification for rejection is of special interest to researchers, and ongoing randomized clinical trials PLENTY and Dulect 2020-1 will provide insight into the role of PD-1 and PD-L1 in liver transplant management in the future. This literature search and the resulting review represents the most thorough collection, analysis, and presentation of the literature on the subject to date.     

Trajectories of reported sleep duration associate with early childhood cognitive development

Study ObjectivesExamine how different trajectories of reported sleep duration associate with early childhood cognition.MethodsCaregiver-reported sleep duration data (n = 330) were collected using the Brief Infant Sleep Questionnaire at 3, 6, 9, 12, 18, and 24 months and Children’s Sleep Habits Questionnaire at 54 months. Multiple group-based day-, night-, and/or total sleep trajectories were derived—each differing in duration and variability. Bayley Scales of Infant and Toddler Development-III (Bayley-III) and the Kaufman Brief Intelligence Test- 2 (KBIT-2) were used to assess cognition at 24 and 54 months, respectively.ResultsCompared to short variable night sleep trajectory, long consistent night sleep trajectory was associated with higher scores on Bayley-III (cognition and language), while moderate/long consistent night sleep trajectories were associated with higher KBIT-2 (verbal and composite) scores. Children with a long consistent total sleep trajectory had higher Bayley-III (cognition and expressive language) and KBIT-2 (verbal and composite) scores compared to children with a short variable total sleep trajectory. Moderate consistent total sleep trajectory was associated with higher Bayley-III language and KBIT-2 verbal scores relative to the short variable total trajectory. Children with a long variable day sleep had lower Bayley-III (cognition and fine motor) and KBIT-2 (verbal and composite) scores compared to children with a short consistent day sleep trajectory.ConclusionsLonger and more consistent night- and total sleep trajectories, and a short day sleep trajectory in early childhood were associated with better cognition at 2 and 4.5 years.     

Erratum: Rhinitis in children less than 6 years of age: current knowledge and challenges

[This corrects the article on p. 115 in vol. 1, PMID: 22053307.].     

Effectiveness of Implementing Evidence‐based Interventions to Reduce C‐spine Image Ordering in the Emergency Department: A Systematic Review

Objectives

Appropriate use of imaging for adult patients with cervical spine (C‐spine) injuries in the emergency department (ED) is a longstanding issue. Guidance for C‐spine ordering exists; however, the effectiveness of the decision support implementation in the ED is not well studied. This systematic review examines the implementation and effectiveness of evidence‐based interventions aimed at reducing C‐spine imaging in adults presenting to the ED with neck trauma.

Methods

Six electronic databases and the gray literature were searched. Comparative intervention studies were eligible for inclusion. Two independent reviewers screened for study eligibility, study quality, and extracted data. The change in imaging was reported using individual odds ratios (ORs) with 95% confidence intervals (CIs) using random effects.

Results

A total of 990 unique citations were screened for relevance of which six before–after studies and one randomized controlled trial were included. None of the studies were assessed as high quality. Interventions consisted primarily of locally developed guidelines or established clinical decision rules such as the NEXUS or the Canadian C‐spine rule. Overall, implementation of interventions aimed at reducing C‐spine image ordering resulted in a statistically significant reduction in imaging (OR = 0.69, 95% CI = 0.51–0.93); however, heterogeneity was high (I² = 82%). Subgroup analysis revealed no differences between studies that specified enrolling alert and stable patients compared to unspecified trauma (p = 0.81) or between studies employing multifaceted versus nonmultifaceted interventions (p = 0.66). While studies generally provided details on implementation strategies (e.g., teaching sessions, pocket cards, posters, computerized decision support) the effectiveness of these implementation strategies were frequently not reported.

Conclusion

There is moderate evidence regarding the effectiveness of interventions to reduce C‐spine image ordering in adult patients seen in the ED with neck trauma. Given the national and international focus on improving appropriateness and reducing unnecessary C‐spine imaging through campaigns such as Choosing Wisely, additional interventional research in this field is warranted.