BACKGROUNDSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODSWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTSIn the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P = 0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P = 0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONSAmong infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)

Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non‐invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence‐based physiotherapy care to people with CF in Australia and New Zealand.

In young children with CF, GOR is primarily acidic and proximal migration is common. Physiotherapy in the head-down position does not appear to exacerbate GOR. The impact of GOR on lung disease remains to be elucidated.

Background Children with cystic fibrosis (CF) are routinely managed in a multidisciplinary clinic at tertiary pediatric centers. However, children with bronchiectasis may not be managed in the same way. We sought to compare the management model and clinical outcomes of children with bronchiectasis with children diagnosed with CF, in a single pediatric center. Methods We identified patients with bronchiectasis from hospital medical records at an urban tertiary pediatric hospital and identified a sex‐ and age‐matched CF patient at the same center to compare lung function, nutritional status, frequency of physiotherapy and respiratory physician visits, and number of microbiological samples taken for bacterial culture. Results Twenty‐two children with bronchiectasis were identified, mean (standard deviation [SD]) age was 11 (3) years. The most common known etiology for bronchiectasis was postinfective (6 of 22) but was unknown in 8 of 22. The cohort with bronchiectasis had poorer lung function (FEV1 mean [SD] percent predicted 78.6 [20.5] vs 94.5 [14.7], P = .005) and had less outpatient reviews by the respiratory physician (P < .001) and respiratory physiotherapist (P < .001) when compared to those with CF. Nutritional parameters did not differ between the groups. Many children (10 of 22, 45%) with bronchiectasis did not have any microbiological respiratory tract samples taken for evaluation. Conclusion Children with bronchiectasis at this institution have poorer lung function than children with CF, and are deserving of improved multidisciplinary care.