Loss of function,missense, and intronic variants in NOTCH1 confer different risks for left ventricular outflow tract obstructive heart defects in two European cohorts

Loss of function variants in NOTCH1 cause left ventricular outflow tract obstructive defects (LVOTO). However, the risk conferred by rare and noncoding variants in NOTCH1 for LVOTO remains largely uncharacterized. In a cohort of 49 families affected by hypoplastic left heart syndrome, a severe form of LVOTO, we discovered predicted loss of function NOTCH1 variants in 6% of individuals. Rare or low-frequency missense variants were found in 16% of families. To make a quantitative estimate of the genetic risk posed by variants in NOTCH1 for LVOTO, we studied associations of 400 coding and noncoding variants in NOTCH1 in 1,085 cases and 332,788 controls from the UK Biobank. Two rare intronic variants in strong linkage disequilibrium displayed significant association with risk for LVOTO amongst European-ancestry individuals. This result was replicated in an independent analysis of 210 cases and 68,762 controls of non-European and mixed ancestry. In conclusion, carrying rare predicted loss of function variants in NOTCH1 confer significant risk for LVOTO. In addition, the two intronic variants seem to be associated with an increased risk for these defects. Our approach demonstrates the utility of population-based data sets in quantifying the specific risk of individual variants for disease-related phenotypes.     

Dexamethasone as an adjuvant for peripheral nerve blockade: a randomised,triple-blinded crossover study in volunteers

Background

The efficacy of dexamethasone in extending the duration of local anaesthetic block is uncertain. In a randomised controlled triple blind crossover study in volunteers, we tested the hypothesis that neither i.v. nor perineurally administered dexamethasone prolongs the sensory block achieved with ropivacaine.

Clinical and subclinical cardiovascular disease in female SLE patients: Interplay between body mass index and bone mineral density

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Congenital high airway obstruction syndrome (CHAOS): Natural history,prenatal management strategies,and outcomes at a single comprehensive fetal center

PurposeCongenital high airway obstruction syndrome (CHAOS) is a devastating fetal condition of complete airway discontinuity resulting in significant hydrops and extreme lung hyperplasia. It is universally fatal with survival reported only in the rare spontaneous fistulization or EXIT intervention (Ex Utero Intrapartum Treatment). Even in these cases, mortality remains high, and current investigations are targeting prenatal interventions. This report describes our experience with management and fetal interventions for CHAOS, including laser laryngotomy.MethodsWe retrospectively reviewed all patients diagnosed with CHAOS at a single academic institution between 2006 and 2017.ResultsFifteen patients were identified. Eight had obstruction at the trachea and seven at the larynx. In the laryngeal obstructions, three expired shortly after birth, and one survived after spontaneous fistulization and subsequent EXIT to tracheostomy. The remaining three underwent in-utero treatment with laser laryngotomy. One had preterm premature rupture of membranes (PPROM), delivered 3 days post-operatively, and died. Two underwent EXIT to tracheostomy with one surviving to discharge and is currently 2 years old.ConclusionOur study demonstrates the outcomes of a large series of patients diagnosed with CHAOS. While mortality remains high, options for fetal intervention are being explored to allow alterations in the prenatal natural history and improve postnatal outcomes.Type of StudyRetrospective Treatment Study.Level of EvidenceLevel IV.     

Knowledge of the Brain Death Concept in Dominican Immigration Residents in Spain and Florida

The Latin American population has a double way of immigration, one toward the United States by proximity and another toward Spain by sociocultural affinity. This population increase is affecting organ donation and transplantation in receiving countries.

Effects of Price,Information, and Transactions Cost Interventions to Raise Voluntary Enrollment in a Social Health Insurance Scheme: A Randomized Experiment in the Philippines

A cluster randomized experiment was undertaken testing two sets of interventions encouraging enrollment in the Individually Paying Program (IPP), the voluntary component of the Philippines' social health insurance program. In early 2011, 1037 unenrolled IPP‐eligible families in 179 randomly selected intervention municipalities were given an information kit and offered a 50% premium subsidy valid until the end of 2011; 383 IPP‐eligible families in 64 control municipalities were not. In February 2012, the 787 families in the intervention sites who were still IPP‐eligible but had not enrolled had their vouchers extended, were resent the enrollment kits and received SMS reminders. Half the group also received a ‘handholding’ intervention: in the endline interview, the enumerator offered to help complete the enrollment form, deliver it to the insurer's office in the provincial capital, and mail the membership cards. The main intervention raised the enrollment rate by 3 percentage points (ppts) (p = 0.11), with an 8 ppt larger effect (p < 0.01) among city‐dwellers, consistent with travel time to the insurance office affecting enrollment. The handholding intervention raised enrollment by 29 ppts (p < 0.01), with a smaller effect (p < 0.01) among city‐dwellers, likely because of shorter travel times, and higher education levels facilitating unaided completion of the enrollment form. Copyright © The World Bank Health Economics © 2015 John Wiley & Sons, Ltd.