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In this phase 3 trial, among infants with spinal muscular atrophy, those who received nusinersen were more likely to achieve major motor milestones and less likely to need permanent assisted ventilation than those who underwent a sham procedure.

The small molecule risdiplam increased the expression of SMN protein in blood in 21 infants with type 1 spinal muscular atrophy. Post hoc clinical features of sitting ability and respiratory status were reported.

In infants with genetically diagnosed spinal muscular atrophy, risdiplam therapy before the development of symptoms led to improved motor milestones and survival at 12 and 24 months. Treatment-related adverse events were mild.

This study examined deaths due to unintentional injuries among children in Japan to identify the age groups and sexes at most risk, and the types of injuries, so that effective forms of targeted intervention can be devised. Among children aged 0–14 years, deaths whose underlying causes had been classified under code V01-X59 of the ICD-10 were defined as deaths of children caused by unintentional injuries. Using data from the Vital Statistics 2000–2009 for analysis, we examined the changes in mortality and trends in terms of sex, age, and cause of death. Mortality decreased by 46.2%, from 933 in 2000 to 502 in 2009. The mortality rate among children aged 1–4 years decreased by almost half. The total number of deaths during this decade was 7,362 (boys: 4,690, girls: 2,672). Among the causes of death, the majority were due to “transport accidents”, followed by “other accidental threats to breathing”, and “accidental drowning and submersion”. The characteristics observed in terms of sex, age, and cause of death—that is, deaths from suffocation among infants aged less than 1 year, drowning deaths among boys, and transport accidents involving pedestrians and cyclists—must be addressed as targets for future intervention.

Introduction: Childhood mortality is an important health indicator that reflects the overall health status of a population. Despite the decrease in global childhood mortality rates over the past decades, it still remains an important public health issue in Qatar.Methods: The data from 2004-2016 were extracted from the Qatar Ministry of Public Health Birth and Death Database. International Classification of Diseases (ICD-10) was used for coding the causes of death. The childhood mortality rate was defined as the probability of a child dying between the first and the fifth birthday, expressed as the number of deaths per 1,000 children surviving to 12 months of age. The sex ratio was calculated by dividing the mortality rate of males by that of females. Mann-Kendall trend test was performed to examine time trends. Relative risks were calculated to examine differences by nationality (Qatari and non-Qatari) and sex.Results: A significant decrease in mortality rate of children aged one to five was observed from 1.76 to 1.05 per 1000 children between 2004 and 2016 (Kendall tau=-0.6, p=0.004). Three prominent causes of mortality were motor vehicle accidents, congenital malformations of the circulatory system, and accidental drowning/submersion. A statistically non-significant decrease in childhood mortality from motor vehicle accidents was oberved for all nationalities (total (Kendall tau=-0.03), Qatari (Kendall tau=-0.14), and non-Qatari (Kendall tau=-0.12)). A significant decrease was seen for total accidental drowning and submersion (Kendall tau=-0.54, p=0.012), while no statistically significant decrease was seen for total congenital malformations of the circulatory system (Kendall tau=-0.36, NS). The Qatari population did have a significant decrease in childhood mortality due to congenital malformations of the circulatory system (Kendall tau=-0.67, p=0.003) and accidental drowning and submersion (Kendall tau=-0.55, p=0.016).Conclusion: The study is a first attempt to evaluate childhood mortality statistics from Qatar and could be useful in supporting Qatar’s ongoing national health strategy programs.

Spinal muscular atrophy type 1 (SMA1) is a debilitating neurodegenerative disease resulting from survival motor neuron 1 gene ( SMN1 ) deletion/mutation. Onasemnogene abeparvovec (formerly AVXS-101) is a gene therapy that restores SMN production via one-time systemic administration. The present study demonstrates widespread biodistribution of vector genomes and transgenes throughout the central nervous system (CNS) and peripheral organs, after intravenous administration of an AAV9-mediated gene therapy. Two symptomatic infants with SMA1 enrolled in phase III studies received onasemnogene abeparvovec. Both patients died of respiratory complications unrelated to onasemnogene abeparvovec. One patient had improved motor function and the other died shortly after administration before appreciable clinical benefit could be observed. In both patients, onasemnogene abeparvovec DNA and messenger RNA distribution were widespread among peripheral organs and in the CNS. The greatest concentration of vector genomes was detected in the liver, with an increase over that detected in CNS tissues of 300–1,000-fold. SMN protein, which was low in an untreated SMA1 control, was clearly detectable in motor neurons, brain, skeletal muscle and multiple peripheral organs in treated patients. These data support the fact that onasemnogene abeparvovec has effective distribution, transduction and expression throughout the CNS after intravenous administration and restores SMN expression in humans. Biodistribution analysis of two patients with spinal muscular atrophy shows widespread onasemnogene abeparvovec DNA, mRNA and SMN protein throughout the central nervous system and peripheral organs following intravenous gene therapy administration.

In a large community-randomized trial, biannual azithromycin distributions significantly reduced postneonatal childhood mortality in sub-Saharan African sites. Here, we present a prespecified secondary analysis showing that much of the protective effect was in the first 3 months postdistribution. Distributing more frequently than biannually could be considered if logistically feasible.

Background Spinal muscular atrophy is a rare neuromuscular disorder with a spectrum of severity related to age at onset and the number of SMN2 gene copies. Infantile-onset (≤ 6 months of age) is the most severe spinal muscular atrophy and is the leading monogenetic cause of infant mortality; patients with later-onset (> 6 months of age) spinal muscular atrophy can survive into adulthood. Nusinersen is a new treatment for spinal muscular atrophy. Objective The objective of this study was to evaluate the cost effectiveness of nusinersen for the treatment of patients with infantile-onset spinal muscular atrophy and later-onset spinal muscular atrophy in Sweden. Methods One Markov cohort health-state transition model was developed for each population. The infantile-onset and later-onset models were based on the efficacy results from the ENDEAR phase III trial and the CHERISH phase III trial, respectively. The cost effectiveness of nusinersen in both models was compared with standard of care in Sweden. Results For a time horizon of 40 years in the infantile-onset model and 80 years in the later-onset model, treatment with nusinersen resulted in 3.86 and 9.54 patient incremental quality-adjusted life-years and 0.02 and 2.39 caregiver incremental quality-adjusted life-years and an incremental cost of 21.9 and 38.0 million SEK (Swedish krona), respectively. These results translated into incremental cost-effectiveness ratios (including caregiver quality-adjusted life-years) of 5.64 million SEK (€551,300) and 3.19 million SEK (€311,800) per quality-adjusted life-year gained in the infantile-onset model and later-onset model, respectively. Conclusions Treatment with nusinersen resulted in overall survival and quality-adjusted life-year benefits but with incremental costs above 21 million SEK (€2 million) [mainly associated with maintenance treatment with nusinersen over a patient’s lifespan]. Nusinersen was not cost effective when using a willingness-to-pay threshold of 2 million SEK (€195,600), which has been considered in a recent discussion by the Dental and Pharmaceutical Benefits Agency as a reasonable threshold for rare disease. Nonetheless, nusinersen gained reimbursement in Sweden in 2017 for paediatric patients (below 18 years old) with spinal muscular atrophy type I–IIIa.

Despite significant strides made in childhood survival during the last 75 years, India bears the largest burden of congenital heart disease (CHD) in the world. The care of a child with CHD requires multidisciplinary collaboration and development of distinct training opportunities in developing countries to ensure outcomes similar to those achieved in high-income countries. We present a commentary on the current state of pediatric cardiac critical care in India and propose pathways to fulfil the unmet needs of Indian children. The aim is to achieve self-reliance in pediatric cardiac services and to move towards optimal outcome and intact survival of children with CHD.

Background Child health, especially childhood mortality, is one of the critical indicators of human development. No child mortality is desirable, but it is still high in Bangladesh. We aimed to assess the effect of the child's desired status on childhood morbidity and mortality in Bangladesh. Methods We used the data from the nationally representative cross-sectional Bangladesh Demographic and Health Survey (BDHS) 2017–18 and restricted the analyses to children born in the past five years preceding the survey. We estimated the undesired status (excess in boy, girl, both, and parity) by subtracting an ideal number of children from the total live birth. We measured childhood mortality (perinatal, early neonatal, neonatal, post-neonatal, infant, child, and under-five mortality), morbidity (fever, diarrhea, cough, and acute respiratory infectious-ARI), nutritional problems (stunting, wasting, underweight, and low birth weight), and treatments (postnatal care, treatment for fever, diarrhea/cough, and vitamin A supplementation). Finally, we utilized the chi-square test and multilevel mixed-effects logistic regression analyses. Results The prevalence of undesired children was 19.2%, 21.5%, 3.7%, and 25.4% for boys, girls, both boys and girls, and parity, respectively. Age, education, residence, division, and wealth index were significantly associated with undesired children. The prevalence of under-five mortality was 3.3% among desired children, almost double (5.4%) among undesired children. The likelihood of under-five mortality was [adjusted odds ratio (aOR): 2.05, p  ≤ 0.001] higher among undesired children. Despite lower under-five mortality among higher socioeconomic status, the relative contribution of undesired children to under-fiver mortality was substantial. The undesired girl children were associated with an increased likelihood of moderately wasting (aOR: 1.28, p  = 0.072), severely underweight (aOR: 1.41, p  = 0.066), and low birth weight (aOR: 1.50, p  ≤ 0.05). Moreover, the undesired children were 19% ( p  ≤ 0.05) more likely to be infected with fever. The undesired children had lower treatment for diarrhea and fever/cough and were less likely to get vitamin A supplementation (aOR: 0.71, p  ≤ 0.001). Conclusions The share of childhood morbidity, mortality, and malnutrition were higher among undesired children. Every child should be wanted, and no unwanted pregnancies are desirable; thereby, the government should reemphasize the proper use of family planning methods to reduce child mortality and malnutrition.