Faculty Bibliography

BACKGROUND:Children born very preterm (VPT) are at high risk for attention problems. This study's purpose was to describe the Conners Kiddie Continuous Performance Test (K-CPT) assessment in children born VPT, including rates of clinically elevated scores, change over time, and associations between K-CPT scores and parent reported attention problems. METHODS:We studied 305 children from a multi-site study of children born VPT who completed at least one K-CPT assessment at age 5, 6, and/or 7 years. Parent-reported ADHD symptoms and diagnosis were also collected. We calculated K-CPT completion rates, mean scores, and rates of clinically elevated scores at each timepoint. Linear mixed models examined change over time in K-CPT scores. Correlations and generalized linear models investigated associations between K-CPT scores and ADHD symptoms and diagnoses. RESULTS:K-CPT scores showed expected age-related improvements from age 5-7, with significant intra- and inter-individual variability. Up to 1/3 of children had clinically elevated attention problems and another 1/3 had subclinical elevations. K-CPT scores were modestly correlated with parent-rated ADHD symptoms and children with a parent-reported ADHD diagnosis performed worse on nearly all K-CPT metrics. CONCLUSION/CONCLUSIONS:Performance-based measures like the K-CPT can be useful for research and clinical practice in VPT populations. IMPACT/CONCLUSIONS:Attention problems are a specific area of weakness for children born very preterm. Performance-based tests of attention have benefits and drawbacks compared to parent report measures yet are understudied in this population. We examined one performance-based measure (the Conners Kiddie Continuous Performance Test [K-CPT]) in 305 children born very preterm. We observed improving task scores from age 5-7 years with significant intra- and inter-individual variability, a sizable proportion of children with clinically and subclinically elevated scores, and modest associations between K-CPT scores and parent reported attention problems. The K-CPT could be a useful clinical and research tool in this population.

OBJECTIVE:To compare regional splanchnic oxygenation (SrSO2) levels and clinical outcomes between infants who received minimal enteral nutrition (MEN) during Therapeutic Hypothermia (TH), and those who did not. STUDY DESIGN/METHODS:A prospective, interventional cohort study with a historic control group at two Regional Perinatal Centers (NCT05471336). RESULTS:Participant demographics and clinical illness severity were similar between MEN (n = 40) and control (n = 40) groups. There were no significant safety events. SrSO2 levels were normal in both groups throughout. Subjects that received MEN experienced fewer central line days (5.8 v 6.9, p = 0.005) and higher rates of human milk feeding (77% v 46%, p = 0.010), and achieved full oral feeds sooner (9.9 v 13.4 days, p = 0.043). CONCLUSION/CONCLUSIONS:Splanchnic tissue oxygenation was normal in both groups, and similar between groups throughout TH. Providing MEN during TH appears safe and effective, resulting in several important clinical benefits.

BACKGROUND:Limited literature exists on labor and delivery outcomes after bariatric surgery. This study assesses the impact of prior bariatric surgery on peripartum outcomes. METHODS:We queried the National Inpatient Sample (2016-2020) for labor and delivery admissions, categorizing them into three cohorts: prior bariatric surgery (BaS), obesity without prior bariatric surgery, and controls without obesity. We used a multivariate regression model, adjusting for confounders, to compare peripartum outcomes. RESULTS:We identified 22,685 BaS cases, 2.1 million pregnant controls with obesity, and 16.37 million pregnant controls without obesity. Compared to controls with obesity, the BaS cohort had lower rates of cesarean delivery [43% vs 46.8%, adjusted odds ratio (aOR) 0.72, p < 0.001], fetal distress [aOR 0.79, p < 0.001), post-partum hemorrhage (aOR 0.67, p < 0.001), fetal disproportion (aOR 0.36, p < 0.001), and premature rupture of membranes (aOR 0.88, p = 0.04). Compared to controls without obesity, the BaS group had higher rates of cesarean delivery (43% vs 29.57%, aOR 1.43, p < 0.001), breech presentation (aOR 1.4, p < 0.001), thromboembolic events (aOR 2.47, p = 0.01), and pregnancy termination (aOR 1.59, p = 0.048), but lower rates of assisted delivery (aOR 0.54, p < 0.001), fetal disproportion (aOR 0.56, p = 0.025), PROM (aOR 0.87, p = 0.024), and placenta previa (aOR 0.63, p = 0.019). The BaS group had longer hospitalizations (3.11 vs 2.56 days, p < 0.001) and higher hospitalization charges ($25,941 vs $20,760, p < 0.001) compared to controls without obesity. CONCLUSION/CONCLUSIONS:Pregnancy after bariatric surgery is associated with lower odds of cesarean delivery and postpartum complications, relative to the general population with obesity. This underscores the positive impact of bariatric surgery on peripartum outcomes.

BACKGROUND:The prognostic impact of cohesin mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is controversial. METHODS:In patients with AML and MDS who underwent next-generation sequencing at the authors' center during 2017-2023, the authors assessed the landscape of cohesin mutations and the impact of co-occurring mutations on overall survival (OS) and compared outcomes between patients with cohesin mutations and those with wild-type (WT) cohesin genes. RESULTS:The study included 83 patients, 36 with cohesin mutations (STAG2, n = 28; SMC1A, n = 7; SMC3, n = 3; co-expression of cohesin mutations, n = 2) and 47 with WT cohesin genes. Of the 36 patients with cohesin mutations, 17 (47%) had AML (six de novo and 11 secondary), and 19 (53%) had MDS. Patients who had STAG2 mutations had better median OS than patients who had only SMC1A and SMC3 mutations (26 vs. 10 months; p = .043). SRSF2 mutation was the most frequent co-occurring mutation (n = 12; 33%) and was associated with worse median OS than WT SRSF2 (13 vs. 43 months; p = .016). Seven patients (19%) with cohesin mutations underwent hematopoietic transplantation; their median OS was 70 months. Compared with the WT cohesin group, patients who had cohesin mutations were more likely to have adverse-risk AML (82% vs. 53%). The median OS was similar among patients with adverse-risk AML in the cohesin-mutation and WT cohesin groups (10 vs. 14 months, respectively; p = .9). CONCLUSIONS:The current study provides insight into the prognostic impact of cohesin mutations and co-occurring mutations in patients with myeloid malignancies.

OBJECTIVES/OBJECTIVE:Numerous real-world evidence (RWE) guidance documents have been published by many regulatory agencies, health technology assessment agencies, and academic groups.These guidances are largely focused on generating unbiased treatment effect estimates from real-world data (RWD) for use in approval and coverage decisions. One of the most prominently cited documents, is a joint ISPOR/ISPE Task Force guidance on the use of RWD for Hypothsis Evaluating Treatment Effectiveness (HETE) Studies. However there are a variety of uses of RWD that existing guidance does not explicitly address. Our goal was to assess existing guidance for its relevance to a range of non-HETE analyses. METHODS:In this paper, we delineate categories of non-HETE applications of RWD. This range of applications includes various types of non-HETE RWD analyses as well as the use of RWD as inputs into other types of analyses such as health economic modeling or simulation studies that are not typically considered RWD studies. We then map existing guidance documents to the categories of non-HETE studies to help identify existing resources for analysts interested in conducting these types of analyses. RESULTS:We identified 13 published guidance documents for detailed review, including documents that outline best practices, provide checklists, or are structured templates. They were selected for their prominence, recency, specific reference to "fit-for-purpose" RWE generation, or their relevance to specific analysis categories. CONCLUSIONS:We conclude that existing guidance documents, even though they were largely developed for HETE studies, are highly useful for the broad range of non-HETE RWD analyses as well.

High-density microelectrode arrays have opened new possibilities for systems neuroscience, but brain motion relative to the array poses challenges for downstream analyses. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from action potential data, DREDge enables automated, high-temporal-resolution motion tracking in local field potential data. In human intraoperative recordings, DREDge's local field potential-based tracking reliably recovered evoked potentials and single-unit spike sorting. In recordings of deep probe insertions in nonhuman primates, DREDge tracked motion across centimeters of tissue and several brain regions while mapping single-unit electrophysiological features. DREDge reliably improved motion correction in acute mouse recordings, especially in those made with a recent ultrahigh-density probe. Applying DREDge to recordings from chronic implantations in mice yielded stable motion tracking despite changes in neural activity between experimental sessions. These advances enable automated, scalable registration of electrophysiological data across species, probes and drift types, providing a foundation for downstream analyses of these rich datasets.