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.)
The Pediatric Eating Assessment Tool was shown to be a valid and reliable tool to determine penetration/aspiration risk in children. Implications for rehabilitation The pediatric eating assessment tool: a new dyphagia-specific outcome survey for children. The Pediatric Version of the Eating Assessment Tool is a dysphagia specific, parent report outcome instrument to determine penetration/aspiration risk in children. The Pediatric Version of the Eating Assessment Tool has good internal consistency, test-retest reliability and criterion-based validity. The Pediatric Version of the Eating Assessment Tool may be utilized as a clinical instrument to assess the need for further instrumental evaluation of swallowing function in children.
This study aimed to develop a chewing performance scale that classifies chewing from normal to severely impaired and to investigate its validity and reliability. The study included the developmental phase and reported the content, structural, criterion validity, interobserver and intra-observer reliability of the chewing performance scale, which was called the Karaduman Chewing Performance Scale (KCPS). A dysphagia literature review, other questionnaires and clinical experiences were used in the developmental phase. Seven experts assessed the steps for content validity over two Delphi rounds. To test structural, criterion validity, interobserver and intra-observer reliability, two swallowing therapists evaluated chewing videos of 144 children (Group I: 61 healthy children without chewing disorders, mean age of 42·38 ± 9·36 months; Group II: 83 children with cerebral palsy who have chewing disorders, mean age of 39·09 ± 22·95 months) using KCPS. The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was used for criterion validity. The KCPS steps arranged between 0-4 were found to be necessary. The content validity index was 0·885. The KCPS levels were found to be different between groups I and II (χ(2) = 123·286, P < 0·001). A moderately strong positive correlation was found between the KCPS and the subscales of the BPFAS (r = 0·444-0·773, P < 0·001). An excellent positive correlation was detected between two swallowing therapists and between two examinations of one swallowing therapist (r = 0·962, P < 0·001; r = 0·990, P < 0·001, respectively). The KCPS is a valid, reliable, quick and clinically easy-to-use functional instrument for determining the level of chewing function in children.
Both pharyngeal swallowing disorders, such as penetration and aspiration, and esophageal disorders and reflux may result in recurrent pneumonia in pediatric patients. Thus, all phases of deglutition should be considered and followed up during swallowing evaluation.
Cerebral palsy (CP) is a group of permanent sensorimotor impairments. Children with CP have various feeding difficulties including chewing disorder, which may affect their nutritional status. Functional Chewing Training (FuCT) was designed as a holistic approach to improve chewing function by providing postural alignment, sensory and motor training, and food and environmental adjustments. This study aimed to investigate the effect of FuCT on chewing function in children with CP. This study was designed as a double-blind, randomised controlled trial. Eighty CP children with chewing disorder were randomised and split between the FuCT group (31 males, 19 females; mean age 3·5 ± 1·9 years) and the control group (16 males, 14 females; 3·4 ± 2·3 years) receiving traditional oral motor exercises. Each group received the training programme for 12 weeks with weekly follow-up and with two evaluations at baseline and end of 12 weeks. Chewing function was evaluated by analysing video recordings and scored with the Karaduman Chewing Performance Scale (KCPS). The Behavioral Pediatrics Feeding Assessment Scale (BPFAS) was used to evaluate feeding behaviours of children. A significant improvement was observed in KCPS scores at 12 weeks after training in the FuCT group (P < 0·001), but no change was found in the control group (P = 0·07). A significant improvement was detected in all parameters of BPFAS at 12 weeks after training in the FuCT group (P < 0·001) and in four parameters of BPFAS in the control group (P = 0·02, P = 0·02). FuCT is an effective method to improve chewing function compared with traditional oral motor exercises.
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