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This discussion provides commentary on the paper by Ethan M. Alt, Xiuya Chang, Xun Jiang, Qing Liu, May Mo, H. Amy Xia, and Joseph G. Ibrahim entitled "LEAP: the latent exchangeability prior for borrowing information from historical data". The authors propose a novel method to bridge the incorporation of supplemental information into a study while also identifying potentially exchangeable subgroups to better facilitate information sharing. In this discussion, we highlight the potential relationship with other Bayesian model averaging approaches, such as multisource exchangeability modeling, and provide a brief numeric case study to illustrate how the concepts behind latent exchangeability prior may also improve the performance of existing methods. The results provided by Alt et al. are exciting, and we believe that the method represents a meaningful approach to more efficient information sharing., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Biometric Society.)

Aims: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS., Methods and Results: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity., Conclusion: Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history., Competing Interests: Conflict of interest: M.J.A. is a consultant for Abbott, Boston Scientific, Bristol Myers Squibb, Daiichi Sankyo, Invitae, Medtronic, Tenaya Therapeutics, and UpToDate. M.J.A. and Mayo Clinic are involved in equity/intellectual property/royalty relationships with AliveCor, Anumana, ARMGO Pharma, Pfizer, and Thryv Therapeutics. A.A.M.W. is a consultant for Thryv Therapeutics with minor financial interest. S.P.E. is involved with Spaulding Research with minor financial interest., (Published by Oxford University Press on behalf of the European Society of Cardiology 2023.)

Gastroesophageal reflux disease (GERD) is primarily diagnosed based on symptoms and response to a proton-pump inhibitor (PPI) trial. Gold standard testing requires an invasive endoscopic procedure, often with ambulatory pH monitoring. Salivary pepsin is a potential noninvasive modality for GERD diagnosis. This study aimed to assess diagnostic performance of salivary pepsin thresholds for GERD and determine optimal collection protocol of saliva in an external validation cohort. Over 10 months, adults with symptoms of GERD undergoing esophagogastroduodenoscopy with wireless pH-monitoring off PPI were enrolled. Saliva was self-collected by participants over 4 days across three different time points: fasting ante meridiem (AM), post-prandial, and bedtime (PM). Pepsin levels were calculated via Peptest. Pepsin variability and agreement were determined using linear mixed effects models and intraclass correlation. Validation of diagnostic threshold and performance characteristics were evaluated by receiver-operator curve analysis. Twenty participants enrolled in the study; 50% with physiologic acid exposure (acid exposure time < 4% no GERD) and 50% with elevated acid exposure (GERD). Mean pepsin concentrations were significantly lower in the AM (22.6 ± 25.2 ng/mL) compared to post-prandial (44.5 ± 36.7 ng/mL) and PM (55.4 ± 47.0 ng/mL). Agreement between pepsin concentrations across 3 days was substantial for AM samples (kappa 0.61), with lower agreement for post-prandial and PM samples. A single AM pepsin concentration of 25 ng/mL was 67% accurate for GERD with 56% sensitivity and 78% specificity. This validation study highlights fair accuracy and performance characteristics of a single fasting AM salivary pepsin concentration for the diagnosis of GERD., (© The Author(s) 2022. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Children who sustain moderate to large surface area burns present in a hypermetabolic state with increased caloric and protein requirements. A policy was implemented at our institution in 2017 to initiate enteral nutrition (EN) in pediatric burn patients within 4 hours of admission. The authors hypothesize that early EN (initiated within 4 hours of admission) is more beneficial than late EN (initiated ≥ 4 hours from admission) for pediatric burn patients and is associated with decreased rates of pneumonia, increased calorie and protein intake, fewer feeding complications, a shorter Intensive Care Unit (ICU) length of stay (LOS), and a reduced hospital LOS. Children who sustained a total body surface area (TBSA) burn injury ≥ 10% between 2011 and 2018 were identified in a prospectively maintained burn registry at Children's Hospital Colorado. Patients were stratified into two groups for comparison: early EN and late EN. The authors identified 132 pediatric burn patients who met inclusion criteria, and most (60%) were male. Approximately half (48%) of the study patients were in the early EN group. The early EN group had lower rates of underfeeding during the first week (P = .014) and shorter ICU LOS (P = .025). Achieving and sustaining adequate nutrition in pediatric burn patients with moderate to large surface area burn injuries are critical to recovery. Early EN in pediatric burn patients is associated with decreased underfeeding and reduced ICU LOS. The authors recommend protocols to institute feeding for patients with burns ≥ 10% TBSA within 4 hours of admission at all pediatric burn centers., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Traditional paradigms for clinical translation are challenged in settings where multiple contemporaneous therapeutic strategies have been identified as potentially beneficial. Platform trials have emerged as an approach for sequentially comparing multiple trials using a single protocol. The Ebola virus disease outbreak in West Africa represents one recent example which utilized a platform design. Specifically, the PREVAIL II master protocol sequentially tested new combinations of therapies against the concurrent, optimal standard of care (oSOC) strategy. Once a treatment demonstrated sufficient evidence of benefit, the treatment was added to the oSOC for all future comparisons (denoted as segments throughout the manuscript). In the interest of avoiding bias stemming from population drift, PREVAIL II considered only within-segment comparisons between the oSOC and novel treatments and failed to leverage data from oSOC patients in prior segments. This article describes adaptive design methodology aimed at boosting statistical power through Bayesian modeling and adaptive randomization. Specifically, the design uses multi-source exchangeability models to combine data from multiple segments and adaptive randomization to achieve information balance within a segment. When compared to the PREVAIL II design, we demonstrate that our proposed adaptive platform design improves power by as much as 51% with limited type-I error inflation. Further, the adaptive platform effectuates more balance with respect to the distribution of acquired information among study arms, with more patients randomized to experimental regimens., (© 2018, The International Biometric Society.)

Bayesian hierarchical models produce shrinkage estimators that can be used as the basis for integrating supplementary data into the analysis of a primary data source. Established approaches should be considered limited, however, because posterior estimation either requires prespecification of a shrinkage weight for each source or relies on the data to inform a single parameter, which determines the extent of influence or shrinkage from all sources, risking considerable bias or minimal borrowing. We introduce multisource exchangeability models (MEMs), a general Bayesian approach for integrating multiple, potentially non-exchangeable, supplemental data sources into the analysis of a primary data source. Our proposed modeling framework yields source-specific smoothing parameters that can be estimated in the presence of the data to facilitate a dynamic multi-resolution smoothed estimator that is asymptotically consistent while reducing the dimensionality of the prior space. When compared with competing Bayesian hierarchical modeling strategies, we demonstrate that MEMs achieve approximately 2.2 times larger median effective supplemental sample size when the supplemental data sources are exchangeable as well as a 56% reduction in bias when there is heterogeneity among the supplemental sources. We illustrate the application of MEMs using a recently completed randomized trial of very low nicotine content cigarettes, which resulted in a 30% improvement in efficiency compared with the standard analysis.