Efficacy and tolerability of adjunctive lacosamide in pediatric patients with focal seizures.

Objective: To evaluate efficacy and tolerability of adjunctive lacosamide in children and adolescents with uncontrolled focal (partial-onset) seizures.

Methods: In this double-blind trial (SP0969; NCT01921205), patients (age ≥4-<17 years) with uncontrolled focal seizures were randomized (1:1) to adjunctive lacosamide/placebo. After a 6-week titration, patients who reached the target dose range for their weight (<30 kg: 8-12 mg/kg/d oral solution; ≥30-<50 kg: 6-8 mg/kg/d oral solution; ≥50 kg: 300-400 mg/d tablets) entered a 10-week maintenance period.

Predicting overweight and obesity in young adulthood from childhood body-mass index: comparison of cutoffs derived from longitudinal and cross-sectional data.

Background: Historically, cutoff points for childhood and adolescent overweight and obesity have been based on population-specific percentiles derived from cross-sectional data. To obtain cutoff points that might better predict overweight and obesity in young adulthood, we examined the association between childhood body-mass index (BMI) and young adulthood BMI status in a longitudinal cohort.

Methods: In this study, we used data from the International Childhood Cardiovascular Cohort (i3C) Consortium (which included seven childhood cohorts from the USA, Australia, and Finland) to establish childhood overweight and obesity cutoff points that best predict BMI status at the age of 18 years.

Enabling Global Clinical Collaborations on Identifiable Patient Data: The Minerva Initiative.

The clinical utility of computational phenotyping for both genetic and rare diseases is increasingly appreciated; however, its true potential is yet to be fully realized. Alongside the growing clinical and research availability of sequencing technologies, precise deep and scalable phenotyping is required to serve unmet need in genetic and rare diseases. To improve the lives of individuals affected with rare diseases through deep phenotyping, global big data interrogation is necessary to aid our understanding of disease biology, assist diagnosis, and develop targeted treatment strategies.

Metalloprotease inhibitor TIMP proteins control FGF-2 bioavailability and regulate skeletal growth.

Regulated growth plate activity is essential for postnatal bone development and body stature, yet the systems regulating epiphyseal fusion are poorly understood. Here, we show that the tissue inhibitors of metalloprotease (TIMP) gene family is essential for normal bone growth after birth. Whole-body quadruple-knockout mice lacking all four TIMPs have growth plate closure in long bones, precipitating limb shortening, epiphyseal distortion, and widespread chondrodysplasia.

Epidemiology of childhood death in Australian and New Zealand intensive care units.

Purpose: Data on childhood intensive care unit (ICU) deaths are needed to identify changing patterns of intensive care resource utilization. We sought to determine the epidemiology and mode of pediatric ICU deaths in Australia and New Zealand (ANZ).

Methods: This was a retrospective, descriptive study of multicenter data from pediatric and mixed ICUs reported to the ANZ Pediatric Intensive Care Registry and binational Government census.

Persistence of the immune response after 4CMenB vaccination, and the response to an additional booster dose in infants, children, adolescents, and young adults.

The multicomponent meningococcal serogroup B vaccine, 4CMenB, has demonstrated effectiveness in preventing invasive MenB disease in infants and in controlling MenB outbreaks. The need for/timing of additional booster doses is not yet established. We reviewed eight studies that evaluated antibody persistence and booster following primary 4CMenB vaccination of infants, children, adolescents, and young adults.

Predictors of Unlikely Bacterial Pneumonia and Adverse Pneumonia Outcome in Children Admitted to a Hospital in Central Vietnam.

Background: Pneumonia is the leading cause of antibiotic use and hospitalization in Vietnam. There is a need for better prediction of unlikely bacterial pneumonia and adverse pneumonia outcome in order to guide hospital admission and improve rational antibiotic use.

Methods: All children under 5 admitted with pneumonia (per clinician assessment) to the Da Nang Hospital for Women and Children were prospectively enrolled.

Emerging challenges in pharmacotherapy research on attention-deficit hyperactivity disorder-outcome measures beyond symptom control and clinical trials.

Although pharmacological therapies are recommended as a key component in the treatment of attention-deficit hyperactivity disorder, their use continues to prompt intense debate. Despite considerable research efforts, several gaps in the knowledge base and several questions over the quality of evidence exist. Particular issues surrounding pharmacological treatments include uncertainties about long-term effectiveness and safety, safety profiles in adults, and the comparative effectiveness of different medications.

Immunogenicity and Safety of a Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine 6 Years After MenC Priming as Toddlers.

Background: We assessed immunogenicity, antibody persistence and safety of the meningococcal serogroups A, C, W and Y-tetanus toxoid (TT) conjugate vaccine (MenACWY-TT) in children primed as toddlers with MenC vaccine.

Methods: This open, multicenter extension study enrolled children 84-95 months of age who had received one dose of the combined Haemophilus influenzae type b (Hib)-MenC-TT conjugate vaccine (HibMenC group) or Hib-TT and monovalent MenC (MCC)-CRM197 vaccines (Hib+MCC group) at 12-18 months of age, in the primary study. All participants received one dose of MenACWY-TT.

Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features.

Background: Fragile X syndrome (FXS) is a common monogenic cause of intellectual disability with autism features. While it is caused by loss of the 1 product (FMRP), mosaicism for active and inactive alleles, including alleles termed premutation (PM: 55-199 CGGs), is not uncommon. Importantly, both PM and active full mutation (FM: ≥ 200 CGGs) alleles often express elevated levels of mRNA that are thought to be toxic.

Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia.

Purpose: The purpose of this study was to expand the genetic architecture of neurodevelopmental disorders, and to characterize the clinical features of a novel cohort of affected individuals with variants in ZNF142, a CH domain-containing transcription factor.

Methods: Four independent research centers used exome sequencing to elucidate the genetic basis of neurodevelopmental phenotypes in four unrelated families. Following bioinformatic filtering, query of control data sets, and secondary variant confirmation, we aggregated findings using an online data sharing platform.

Genetic or Other Causation Should Not Change the Clinical Diagnosis of Cerebral Palsy.

High throughput sequencing is discovering many likely causative genetic variants in individuals with cerebral palsy. Some investigators have suggested that this changes the clinical diagnosis of cerebral palsy and that these individuals should be removed from this diagnostic category. Cerebral palsy is a neurodevelopmental disorder diagnosed on clinical signs, not etiology.

Clinical and Molecular Differences between 4-Year-Old Monozygous Male Twins Mosaic for Normal, Premutation and Fragile X Full Mutation Alleles.

This study describes monozygotic (MZ) male twins with fragile X syndrome (FXS), mosaic for normal size (NS: <44 CGGs), premutation (PM: 55–199 CGG) and full mutation (FM alleles ≥ 200) alleles, with autism. At 4 years of age chromosomal microarray confirmed monozygosity with both twins showing an XY sex complement. Normal size (30 CGG), PM (99 CGG) and FM (388–1632 CGGs) alleles were detected in Twin 1 (T1) by standard polymerase chain reaction (PCR) and Southern blot testing, while only PM (99 CGG) and FM (672–1025) alleles were identified in Twin 2 (T2).

Characterisation of children hospitalised with pneumonia in central Vietnam: a prospective study.

Pneumonia is the most common reason for paediatric hospital admission in Vietnam. The potential value of using the World Health Organization (WHO) case management approach in Vietnam has not been documented.We performed a prospective descriptive study of all children (2-59 months) admitted with "pneumonia" (as assessed by the admitting clinician) to the Da Nang Hospital for Women and Children to characterise their disease profiles and assess risk factors for an adverse outcome.

Leigh syndrome caused by mutations in is associated with a better prognosis.

Objectives: Mitochondrial methionyl-tRNA formyltransferase (MTFMT) is required for the initiation of translation and elongation of mitochondrial protein synthesis Pathogenic variants in have been associated with Leigh syndrome (LS) and mitochondrial multiple respiratory chain deficiencies. We sought to elucidate the spectrum of clinical, neuroradiological and molecular genetic findings of patients with bi-allelic pathogenic variants in .

Methods: Retrospective cohort study combining new cases and previously published cases.

Withdrawal Aversion and the Equivalence Test.

If a doctor is trying to decide whether or not to provide a medical treatment, does it matter ethically whether that treatment has already been started? Health professionals sometimes find it harder to stop a treatment (withdraw) than to refrain from starting the treatment (withhold). But does that feeling correspond to an ethical difference? In this article, we defend equivalence-the view that withholding and withdrawal of treatment are ethically equivalent when all other factors are equal. We argue that preference for withholding over withdrawal could represent a form of cognitive bias-withdrawal aversion.

Bridging the knowledge-practice gap in tuberculosis contact management in a high-burden setting: a mixed-methods protocol for a multicenter health system strengthening study.

Background: People in close contact with tuberculosis should have screening and appropriate management, as an opportunity for active case detection and prevention. However, implementation of tuberculosis contact screening and management is limited in high-burden settings. Behaviour change is needed across three levels of the healthcare system-policymakers, healthcare providers, and patients.

Identifying Important Outcomes for Young People With CKD and Their Caregivers: A Nominal Group Technique Study.

Rationale & Objective: Chronic kidney disease (CKD) has wide-ranging and long-term consequences for young people and their families. The omission of outcomes that are important to young people with CKD and their caregivers limits knowledge to guide shared decision making. We aimed to identify the outcomes that are important to young people with CKD and their caregivers.