Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy.

Background: The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers.

Methods: We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation.

Association between trauma center type and mortality for injured children with severe traumatic brain injury.

Background: There is conflicting evidence regarding the relationship between trauma center type and mortality for children with traumatic brain injuries. Identification of mortality differences following brain injury across differing trauma center types may result in actionable quality improvement initiatives to standardize care for these children.

Methods: We used Trauma Quality Improvement Program data from 2017 to 2020 to identify children with severe traumatic brain injury (TBI) managed at levels I and II state or American College of Surgeon-verified trauma centers.

The temporal burden of preparing catheters for re-use in adults with spinal cord injury: a cross-sectional study.

Study Design: Cross-sectional OBJECTIVES: Neurogenic lower urinary tract dysfunction is common among people with spinal cord injury (SCI). Although single-use clean intermittent catheterization is recommended to facilitate routine bladder emptying, catheter re-use is common. Barriers associated with the preparation (i.

The Microbiological Burden of Short-Term Catheter Reuse in Individuals with Spinal Cord Injury: A Prospective Study.

Despite the risk of developing catheter-associated urinary tract infections (CAUTI), catheter reuse is common among people with spinal cord injury (SCI). This study examined the microbiological burden and catheter surface changes associated with short-term reuse. Ten individuals with chronic SCI reused their catheters over 3 days.

Differences in Stroke Recurrence Risk Between Atrial Fibrillation Detected on ECG and 14-Day Cardiac Monitoring.

Background: Ischemic stroke and transient ischemic attack (TIA) standard-of-care etiological investigations include an ECG and prolonged cardiac monitoring (PCM). Atrial fibrillation (AF) detected after stroke has been generally considered a single entity, regardless of how it is diagnosed. We hypothesized that ECG-detected AF is associated with a higher risk of stroke recurrence than AF detected on 14-day Holter (PCM-detected AF).

Atrial Dysfunction in Significant Atrial Functional Mitral Regurgitation: Phenotypes and Prognostic Implications.

Background: Atrial functional mitral regurgitation (AFMR) is associated with increased morbidity and mortality. Left atrial (LA) size and function in AFMR are poorly characterized. We aimed to assess LA function by reservoir strain (LASr) and estimated reservoir work (LAWr) and their impact on outcome in AFMR.

In Silico Exploration of Metabolically Active Peptides as Potential Therapeutic Agents against Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is regarded as a fatal neurodegenerative disease that is featured by progressive damage of the upper and lower motor neurons. To date, over 45 genes have been found to be connected with ALS pathology. The aim of this work was to computationally identify unique sets of protein hydrolysate peptides that could serve as therapeutic agents against ALS.

Systemic corticosteroid regimens for prevention of bronchopulmonary dysplasia in preterm infants.

Background: Systematic reviews showed that systemic postnatal corticosteroids reduce the risk of bronchopulmonary dysplasia (BPD) in preterm infants. However, corticosteroids have also been associated with an increased risk of neurodevelopmental impairment. It is unknown whether these beneficial and adverse effects are modulated by differences in corticosteroid treatment regimens related to type of steroid, timing of treatment initiation, duration, pulse versus continuous delivery, and cumulative dose.

Gene Sequencing Identifies Perturbation in Nitric Oxide Signaling as a Nonlipid Molecular Subtype of Coronary Artery Disease.

Background: A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene () are identified in 1% to 2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.

Methods: To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41 081 CAD cases versus 217 115 controls.

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.

Electronic health record-based genome-wide meta-analysis provides insights on the genetic architecture of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a complex disease linked to several chronic diseases. We aimed at identifying genetic variants associated with NAFLD and evaluating their functional consequences. We performed a genome-wide meta-analysis of 4 cohorts of electronic health record-documented NAFLD in participants of European ancestry (8,434 cases and 770,180 controls).

Cardiovascular Safety Profile of Romosozumab: A Pharmacovigilance Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS).

: Cardiovascular safety concerns for major cardiovascular events (MACE) were raised during the clinical trials of romosozumab. We aimed to evaluate the cardiovascular safety profile of romosozumab in a large pharmacovigilance database. All cases reported between January 2019 and December 2020 where romosozumab was reported were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS).

Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants.

Background: Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to prevent or treat a PDA. There are concerns regarding adverse effects of NSAIDs in preterm infants.

Computed Tomography Perfusion-Based Machine Learning Model Better Predicts Follow-Up Infarction in Patients With Acute Ischemic Stroke.

Background And Purpose: Prediction of infarct extent among patients with acute ischemic stroke using computed tomography perfusion is defined by predefined discrete computed tomography perfusion thresholds. Our objective is to develop a threshold-free computed tomography perfusion-based machine learning (ML) model to predict follow-up infarct in patients with acute ischemic stroke.

Methods: Sixty-eight patients from the PRoveIT study (Measuring Collaterals With Multi-Phase CT Angiography in Patients With Ischemic Stroke) were used to derive a ML model using random forest to predict follow-up infarction voxel by voxel, and 137 patients from the HERMES study (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) were used to test the derived ML model.

Thrombectomy vs medical management in low NIHSS acute anterior circulation stroke.

Objective: To undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature.

Methods: We pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6.

Heterozygous Gene Deficiency and Risk of Coronary Artery Disease.

Background: Familial sitosterolemia is a rare Mendelian disorder characterized by hyperabsorption and decreased biliary excretion of dietary sterols. Affected individuals typically have complete genetic deficiency-homozygous loss-of-function (LoF) variants-in the or genes and have substantially elevated plasma sitosterol and LDL (low-density lipoprotein) cholesterol (LDL-C) levels. The impact of partial genetic deficiency of or -as occurs in heterozygous carriers of LoF variants-on LDL-C and risk of coronary artery disease (CAD) has remained uncertain.