The clinical course of Duchenne muscular dystrophy in the corticosteroid treatment era: a systematic literature review

Abstract Background Duchenne muscular dystrophy (DMD) is a severe rare progressive inherited neuromuscular disorder, leading to loss of ambulation (LOA) and premature mortality. The standard of care for patients with DMD has been treatment with corticosteroids for the past decade; however a synthesis of contemporary data describing the clinical course of DMD is lacking. The objective was to summarize age at key clinical milestones (loss of ambulation, scoliosis, ventilation, cardiomyopathy, and mortality) in the corticosteroid-treatment-era. Methods A systematic review was conducted using MEDLINE and EMBASE. The percentage experiencing key clinical milestones, and the mean or median age at those milestones, was synthesized from studies from North American populations, published between 2007 and 2018. Results From 5637 abstracts, 29 studies were included. Estimates of the percentage experiencing key clinical milestones, and age at those milestones, showed heterogeneity. Up to 30% of patients lost ambulation by age 10 years, and up to 90% by 15 years of age. The mean age at scoliosis onset was approximately 14 years. Ventilatory support began from 15 to 18 years, and up to half of patients required ventilation by 20 years of age. Registry-based estimates suggest that 70% had evidence of cardiomyopathy by 15 years and almost all by 20 years of age. Finally, mortality rates up to 16% by age 20 years were reported; among those surviving to adulthood mortality was up to 60% by age 30 years. Conclusions Contemporary natural history studies from North America report that LOA on average occurs in the early teens, need for ventilation and cardiomyopathy in the late teens, and death in the third or fourth decade of life. Variability in rates may be due to differences in study design, treatment with corticosteroids or other disease-modifying agents, variations in clinical practices, and dystrophin mutations. Despite challenges in synthesizing estimates, these findings help characterize disease progression among contemporary North American DMD patients

Effects of parental and household smoking on the risk of respiratory syncytial virus (RSV) hospitalisation in late-preterm infants and the potential impact of RSV prophylaxis

OBJECTIVE: To assess the impact of household smoking and palivizumab prophylaxis on the risk of respiratory syncytial virus (RSV) hospitalisation in late-preterm (32-35 weeks' gestational age) infants. METHODS: Familial smoking and other RSV risk factor data from the FLIP, FLIP-2 and IMpact studies and datasets from France, Germany and Italy, together with palivizumab prophylaxis data from the FLIP-2 and IMpact studies, were analysed using cross-correlation and Bayesian meta-analytical modelling employing Markov Chain Monte Carlo sampling. RESULTS: There were 2.35 times (95% confidence interval [CI] 1.37-4.02) as many hospitalisations amongst infants from smoking compared with those from non-smoking families. Among non-prophylaxed infants, there were 2.53 times (95% CI 1.27-4.94) as many RSV hospitalisations from smoking than from non-smoking families and that excess hospitalisation was reduced to 1.03 times (95% CI 0.38-2.99) amongst prophylaxed infants. Familial smoking correlates significantly (p\u2009<\u20090.01) with other RSV risk factors: positive correlation with number of school-age siblings, history of family atopy, family wheeze and gestational age; negative correlation with birth weight and breast feeding. CONCLUSIONS: Late-preterm infants from smoking families appear to be at heightened risk for severe RSV infection requiring hospitalisation of which the risk may be reduced with RSV prophylaxis

Liver-specific case fatality due to chronic hepatitis C virus infection: A systematic review

Despite reports that mortality is increasing, overall case fatality due to hepatitis C virus (HCV) is thought to be low. Given the variability in published rates, we aimed to synthesize estimates of liver-specific case fatality and all-cause mortality in chronic HCV according to follow-up duration, sustained viral response (SVR) to treatment, and liver disease severity. A systematic review was conducted of studies published in English from 2003 to 2013, reporting liver-specific case fatality estimates from HCV-infected samples. Thirty-five eligible articles were identified; 26 also presented estimates of all-cause mortality. Among community-based samples, liver-specific case fatality ranged from 0.3% over 5.7 years to 9.2% over 8.2 years of follow-up; and of all-cause mortality, from 4.0% over 5.7 years, to 23.0% over 8.2 years of follow-up. Estimates were higher among clinic-based samples and those with more severe liver disease. Among treated patients achieving SVR, liver-specific case fatality was low: up to 1.4% over 11.5 years of follow-up among samples with any severity of liver disease. Estimates were higher among those without SVR: up to 14.0% over 10 years of followup among samples with any severity of liver disease, and higher still among samples with more severe liver disease. The proportion of deaths attributable to liver-specific causes ranged from 55 to 85% among those with severe liver disease. Published estimates of fatality are high among certain populations of chronic HCV patients, with liver-specific causes being an important contributor. Understanding current HCV mortality rates is important for quantifying the total burden of HCV disease

The influence of birth weight amongst 33-35 weeks gestational age (wGA) infants on the risk of respiratory syncytial virus (RSV) hospitalisation: a pooled analysis

OBJECTIVE: To investigate the association between birth weight and respiratory syncytial virus (RSV) hospitalisation during the first year of life in 33\ub0-356 weeks' gestational age (wGA) infants. STUDY DESIGN: Pooled analysis of data (n\u2009=\u20091218) from Spain, Germany, France and Italy. RESULT: RSV hospitalised infants overall had a significantly higher birth weight than non-hospitalised infants (2.24 versus 2.14\u2009kg; p\u2009<\u20090.001) for both males (2.25 versus 2.18\u2009kg; p\u2009=\u20090.049) and females (2.22 versus 2.11\u2009kg, p\u2009=\u20090.007). The effect was significant only in 34 wGA infants (33 wGA: hospitalised 1.95\u2009kg versus non-hospitalised 1.95\u2009kg, p\u2009=\u20090.976; 34 wGA: 2.26 versus 2.14\u2009kg, p\u2009=\u20090.007; 35 wGA: 2.37 versus 2.29\u2009kg, p\u2009=\u20090.070), particularly female 34 wGA infants (female: 2.24 versus 2.08\u2009kg, p\u2009=\u20090.019; male: 2.27 versus 2.20, p\u2009=\u20090.191). Birth weight was shown to be an independent risk factor for RSV hospitalisation. CONCLUSIONS: In 33-35 wGA infants, a higher birth weight appeared independently associated with an increased risk of RSV hospitalisation