Neurodevelopmental disorders (NDDs) affect more than 3% of children and are attributable to single-gene mutations at more than 1000 loci. Traditional methods yield molecular diagnoses in less than ...one-half of children with NDD. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) can enable diagnosis of NDD, but their clinical and cost-effectiveness are unknown. One hundred families with 119 children affected by NDD received diagnostic WGS and/or WES of parent-child trios, wherein the sequencing approach was guided by acuity of illness. Forty-five percent received molecular diagnoses. An accelerated sequencing modality, rapid WGS, yielded diagnoses in 73% of families with acutely ill children (11 of 15). Forty percent of families with children with nonacute NDD, followed in ambulatory care clinics (34 of 85), received diagnoses: 33 by WES and 1 by staged WES then WGS. The cost of prior negative tests in the nonacute patients was $19,100 per family, suggesting sequencing to be cost-effective at up to $7640 per family. A change in clinical care or impression of the pathophysiology was reported in 49% of newly diagnosed families. If WES or WGS had been performed at symptom onset, genomic diagnoses may have been made 77 months earlier than occurred in this study. It is suggested that initial diagnostic evaluation of children with NDD should include trio WGS or WES, with extension of accelerated sequencing modalities to high-acuity patients.
Background
In children, height is an essential element of a pediatric assessment, yet this measure is less likely to occur in nonambulatory children or those with unique disabilities. There is ...compelling support for surrogate measures; however, many of these are accompanied by limitations.
Objective
This study was conducted to evaluate whether the U.S. Food and Drug Administration (FDA)–cleared Mercy TAPE could be adopted for height estimation.
Design
Development and external validation of a height‐estimation method were conducted with retrospectively collected data in nonrehabilitation children. Testing of the model was performed prospectively in a pediatric rehabilitation population.
Setting
U.S. pediatric rehabilitation outpatient clinic.
Participants
Data from 19 407 children were used to develop the model. Data from an independent cohort of 1472 children were used for external validation, and the model was tested in 195 pediatric rehabilitation patients. Of the 195 patients, 57% required no wheelchair, 18% could ambulate independently for short distances, 17% could ambulate with an assistive device, and 8% were full‐time wheelchair users.
Interventions
Not applicable.
Main Outcome Measurements
Relative error (RE), percentage error (PE), and percent predicted within 10% and 20% of actual height.
Results
Height estimated with the modified Mercy TAPE was highly predictive of actual height in nonrehabilitation children in the United States (RE mean ± SD: 1.1 ± 5.7 cm; PE mean ± SD: 1.0 ± 4.7%). In rehabilitation patients, height was underestimated to a greater extent (RE mean ± SD: 3.0 ± 7.4 cm; PE mean ± SD: −2.1 ± 5.6%).
Conclusions
The Mercy TAPE offers a reasonable approximation of height in ambulatory children, although it slightly underestimates height in the pediatric rehabilitation population. Consequently, this and other surrogate measures may be less suited to examining growth against a reference ambulatory population and more suited to following individual children over time.
The objective of this study was to analyze the effects on patient access by decreasing missed appointments after hiring a clinic coordinator using medical informatics.
A single-center retrospective ...analysis of the rates of missed appointments before and after hiring a clinic coordinator in a multidisciplinary spinal differences clinic were analyzed using a commercially available business software system (SAP® Business Objects). The total number of clinic visits was collected for each month to determine the access available for patients.
The median number of missed appointments per clinic by month before employing the clinic coordinator was higher than in the two years following implementation (p < 0.0005). No differences were seen in the number of available appointment slots per month indicating no new clinics were needed to improve patient access (p = 0.551). Projected billing amounts prior to hiring the clinic coordinator indicated that $91,520 was lost in the 2 years prior to hiring this coordinator compared to $30,160 lost during the 2 years following the creation of this position (p = 0.0009).
Hiring a clinic coordinator decreased the rate of missed appointments and was a cost-efficient intervention to improve patient access and provide effective patient care in a multidisciplinary setting.
Without a structured health-care transition (HCT) process, youths with chronic conditions face increased morbidity, care gaps, and dissatisfaction. This article documents the process and outcomes of ...implementing a standardized approach in a large children's hospital.
Children's Mercy Kansas City adopted Got Transition's Six Core Elements of Health Care Transition and established a system-wide implementation plan, between 2015 and 2019, involving leadership buy-in, consumer engagement, infrastructure improvements, and quality improvement efforts. Outcomes measured included the number of youths aged 12–21 years receiving transition readiness assessments and participating in goal setting, receiving counseling, and receiving a transfer order, if appropriate. Also, Division-specific process outcome surveys were conducted annually using Got Transition's Current Assessment of HCT Activities.
A total of 8,099 unique patients received a structured HCT intervention using the Six Core Element approach over the 5-year period. From 2015 to 2019 the average annual growth was: 207% for completion of transition readiness and goals assessments, 243% for charting of HCT discussions, and 105% for transfer orders. In 2015, 3/20 (15%) divisions were implementing this HCT intervention; in 2019, 17/20 (85%) divisions were implementing it, representing a 467% growth. Division participation in measuring HCT implementation also increased by 89% from 9/20 in 2016 to 17/20 in 2019. The average Current Assessment of HCT Activities scores increased by 35% from 14.55/32 to 19.67/32 during that time.
This hospital-wide program demonstrates that a standardized HCT process can be successfully implemented in a diverse group of outpatient pediatric primary and subspecialty care settings.
To identify the underlying genetic cause in 2 sisters affected with progressive lower extremity spasticity, neuropathy, and early-onset deafness.
Whole-exome sequencing was performed, and segregation ...testing of variants was investigated using targeted Sanger sequencing. An inherited paternal mosaic mutation was further evaluated through quantitative analysis of the ratio of mutant vs wild-type allele in genomic DNA from various tissues, including blood, dermal fibroblasts, and saliva.
A novel heterozygous nonsense mutation (c.1140C>A; p.Y380X) in
was identified in the affected sisters. Paternal mosaicism was suspected based on a small chromatogram peak, which was less than the heterozygous peak of the mutated allele. Consistent with mosaicism, the mosaic paternal samples had notable variability in the ratio of mutant vs wild-type allele in various tissues (compared with the fully heterozygous daughter), with the highest paternal mutant levels in saliva (32.7%) and lowest in dermal fibroblasts (13.9%). Targeted clinical re-examination of the father revealed a sensorimotor neuropathy that was previously clinically unrecognized.
These findings expand the phenotypic spectrum of
-related neurocristopathy. Mutations in
should be considered in patients presenting with a complicated form of hereditary spastic paraplegia that includes neuropathy and deafness. Diagnostic workup may be complicated, as
mutations can present in a mosaic state, with a mild clinical manifestation.
Duchenne muscular dystrophy is a progressive muscle disease characterized by increasing muscle weakness and death by the third decade.
mdx mice exhibit the underlying muscle disease but appear ...physically normal with ordinary lifespans, possibly due to compensatory expression of utrophin. In contrast, double mutant mice (
mdx/utrn
−/−), deficient for both dystrophin and utrophin die by ∼3 months and suffer from severe muscle weakness, growth retardation, and severe spinal curvature. The capacity of human retinal dystrophin (Dp260) to compensate for the missing 427
kDa muscle dystrophin was tested in
mdx/utrn
−/− mice. Functional outcomes were assessed by histology, EMG, MRI, mobility, weight and longevity. MCK-driven transgenic expression of Dp260 in
mdx/utrn
−/− mice converts their disease course from a severe, lethal muscular dystrophy to a viable, mild myopathic phenotype. This finding is relevant to the design of exon-skipping therapeutic strategies since Dp260 lacks dystrophin exons 1–29.
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