International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

Integrating cancer into crisis: a global vision for action from WHO and partners.

More than a billion people live in fragile, conflict-affected, and vulnerable settings requiring humanitarian support, where cancer is a substantial health issue. Despite its substantial effect on populations, cancer care remains underprioritised in emergency preparedness and response frameworks and humanitarian operational planning. This Policy Review summarises the perspectives and actionable recommendations from the First Global High-Level Technical Meeting on Non-communicable Diseases in Humanitarian Settings, with a focus on cancer.

Neonatal Seizures and Associated Neurobehavioral Profiles in Preschool Age Children.

Background: Neonatal seizures are common with acute brain injury. Up to 25% of survivors develop postneonatal epilepsy. We hypothesized postneonatal epilepsy diagnosed by age 24 months would increase risk for early markers of neurobehavioral disorders than acute provoked neonatal seizures alone.

International Multicenter Cohort Study on Beta-Blocker-Free Treatment Strategies for Catecholaminergic Polymorphic Ventricular Tachycardia Patients.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare, potentially life-threatening genetic heart disease. Nonselective beta-blockers (BBs) are highly effective in reducing CPVT-triggered arrhythmic events. However, some patients suffer from unacceptable BB side effects and might require strategies without a BB.

Endpoint Selection in Randomized Clinical Trials for Hypertrophic Cardiomyopathy.

Randomized clinical trials (RCTs) for hypertrophic cardiomyopathy (HCM) have long been challenging caused by the condition's rarity, low event rates, and diverse clinical presentations. However, recent advances in targeted therapies have sparked increased interest in HCM research. Despite this, designing effective RCTs remains complex, particularly in identifying clinically meaningful endpoints.

Fish oil lipid emulsion compared with soybean oil lipid emulsion in pediatric patients with parenteral nutrition-associated cholestasis: A cost-effectiveness study.

Objectives: Evidence indicates that, in pediatric patients with parenteral nutrition-associated cholestasis (PNAC), the use of a 100% fish oil lipid emulsion (FOLE) increased the likelihood of PNAC resolution and reduced the likelihood of liver transplantation compared with a 100% soybean oil lipid emulsion (SOLE). To evaluate the potential economic benefit, we conducted a cost-effectiveness analysis comparing FOLE with SOLE.

Study Design: A discrete event simulation model evaluated cost-effectiveness by simulating clinical outcomes and estimating associated healthcare costs in pediatric patients with PNAC receiving parenteral nutrition (PN) with FOLE (1 g/kg) or SOLE (1.

Multi-omics approaches reveal that diffuse midline gliomas present altered DNA replication and are susceptible to replication stress therapy.

Background: The fatal diffuse midline gliomas (DMG) are characterized by an undruggable H3K27M mutation in H3.1 or H3.3.

Clinical utility of receptor status prediction in breast cancer and misdiagnosis identification using deep learning on hematoxylin and eosin-stained slides.

Background: Molecular profiling of estrogen receptor (ER), progesterone receptor (PR), and ERBB2 (also known as Her2) is essential for breast cancer diagnosis and treatment planning. Nevertheless, current methods rely on the qualitative interpretation of immunohistochemistry and fluorescence in situ hybridization (FISH), which can be costly, time-consuming, and inconsistent. Here we explore the clinical utility of predicting receptor status from digitized hematoxylin and eosin-stained (H&E) slides using machine learning trained and evaluated on a multi-institutional dataset.

Global burden of tuberculous meningitis in children aged 0-14 years in 2019: a mathematical modelling study.

Background: Tuberculous meningitis is fatal if untreated and can lead to lifelong neurological sequelae. However, to our knowledge, there are no data on the number of children affected by this disease. We aimed to estimate the global disease burden and attributable mortality of childhood tuberculous meningitis by WHO regions, age groups, treatment status, and HIV status in 2019.

Evaluating post-cardiac arrest blood pressure thresholds associated with neurologic outcome in children: Insights from the pediRES-Q database.

Background: Current Pediatric Advanced Life Support Guidelines recommend maintaining blood pressure (BP) above the 5th percentile for age following return of spontaneous circulation (ROSC) after cardiac arrest (CA). Emerging evidence suggests that targeting higher thresholds, such as the 10th or 25th percentiles, may improve neurologic outcomes. We aimed to evaluate the association between post-ROSC BP thresholds and neurologic outcome, hypothesizing that maintaining mean arterial pressure (MAP) and systolic blood pressure (SBP) above these thresholds would be associated with improved outcomes at hospital discharge.

A Systematic Review of Human Paenibacillus Infections and Comparison of Adult and Pediatric Cases.

Background: Neonatal infections due to Paenibacillus species have increasingly been reported over the last few years.

Methods: We performed a structured literature review of human Paenibacillus infections in pediatric and adult patients to compare the epidemiology of infections between these distinct patient populations.

Results: Forty reports describing 177 infections were included.

Failure to oxygenate during cardiopulmonary bypass; treatment options and intervention algorithm.

Membrane oxygenator failure remains a concern for perfusion teams. Successful outcomes for this low-frequency, high-risk intervention are predicated on having written institutional protocols for both the oxygenator change-out procedure as well as how often the procedure is practiced by staff perfusionists. A recent review of peer-reviewed journal articles, textbooks and online resources revealed a lack of a unified intervention algorithm for failure to oxygenate during cardiopulmonary bypass (CPB).

Practical strategies to improve MRI operations and workflow in pediatric radiology.

Magnetic resonance imaging (MRI) is an essential tool in pediatric imaging. It offers detailed, high-contrast images without ionizing radiation, making it particularly suitable for children. Creating an efficient MRI service is challenging given the balancing priorities of image quality and scan time and the overlying logistical challenges, including MRI safety protocols, the need for sedation in certain patient populations, and flexibility to accommodate patients at different phases of care.

Sex-specific cytokine, chemokine, and growth factor signatures in T1D patients and progressors.

Numerous studies have reported altered cytokine levels in type 1 diabetes (T1D) patients, yet findings remain inconsistent. In this pilot study, we tested the hypothesis that circulating immune markers exhibit sex-based differences in T1D, both prior to and after disease onset. We analyzed 47-48 cytokine, chemokine, and growth factor levels in two cohorts.

Determining the time to cholangiocarcinoma in pediatric-onset PSC-IBD.

Primary sclerosing cholangitis (PSC) is a risk factor for cholangiocarcinoma. When a child is diagnosed with both PSC and inflammatory bowel disease (IBD), evidence-based information on counseling families and risk management of developing cholangiocarcinoma is limited. In this case series (PubMed/collaborators), we included patients with PSC-IBD who developed cholangiocarcinoma and contacted authors to determine an event curve specifying the time between the second diagnosis (IBD or PSC) and a diagnosis of cholangiocarcinoma.

Constrained Multivariate Functional Principal Components Analysis for Novel Outcomes in Eye-Tracking Experiments.

Individuals with autism spectrum disorder (ASD) tend to experience greater difficulties with social communication and sensory information processing. Of particular interest in ASD biomarker research is the study of visual attention, effectively quantified in eye tracking (ET) experiments. Eye tracking offers a powerful, safe, and feasible platform for gaining insights into attentional processes by measuring moment-by-moment gaze patterns in response to stimuli.

Lessons learned on information retrieval in electronic health records: a comparison of embedding models and pooling strategies.

Objectives: Applying large language models (LLMs) to the clinical domain is challenging due to the context-heavy nature of processing medical records. Retrieval-augmented generation (RAG) offers a solution by facilitating reasoning over large text sources. However, there are many parameters to optimize in just the retrieval system alone.

Rhabdoid Tumor of the Kidney and Soft Tissues: Results from National Wilms Tumor Study-5 and Children's Oncology Group Study AREN0321.

Purpose: National Wilms Tumor Study-5 (NWTS-5) and AREN0321 evaluated the outcomes of children with rhabdoid tumor of the kidney (RTK) and malignant rhabdoid tumor of soft tissues (MRT).

Patients And Methods: Eligible patients with RTK were enrolled prospectively on NWTS-5 (1995-2002) and treated with carboplatin and etoposide alternating with cyclophosphamide (Regimen RTK). Patients with RTK or MRT were enrolled on AREN0321 (2005-2012) and received vincristine, doxorubicin, and cyclophosphamide alternating with carboplatin, cyclophosphamide, and etoposide (Regimens UH-1 or dose-reduced Revised UH-1).

Platelet characteristics in extremely preterm infants after fatty acid supplementation: a randomized controlled trial.

Background: Two risk factors for severe retinopathy of prematurity (ROP) in extremely preterm infants are thrombocytopenia and low levels of arachidonic acid (AA) and docosahexaenoic acid (DHA). To date, these risk factors have not been linked.

Method: Infants born < 28 weeks gestational age (GA) from 2016 to 2019 were randomized to postnatal enteral AA/DHA supplementation or standard care (controls).

Brain volumes, cognitive, and adaptive skills in school-age children with Down syndrome.

Background: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.

Randomized controlled trials - The what, when, how and why.

Randomized controlled trials (RCTs) are at the top of the pyramid of evidence as they offer the best answer on the efficacy of a new treatment. RCTs are true experiments in which participants are randomly allocated to receive a certain intervention (experimental group) or a different intervention (comparison group), or no treatment at all (control or placebo group). Randomization, along with other methodological features such as blinding and allocation concealment, safeguard against biases.