The second Newborn Sequencing in Genomic Medicine and Public Health study was a randomized, controlled trial of the effectiveness of rapid whole-genome or -exome sequencing (rWGS or rWES, respectively) in seriously ill infants with diseases of unknown etiology.Here we report comparisons of analytic and diagnostic performance. Of 1,248 ill inpatient infants, 578 (46%) had diseases of unknown etiology. 213 infants (37% of those eligible) were enrolled within 96 h of admission. 24 infants (11%) were very ill and received ultrarapid whole-genome sequencing (urWGS). The remaining infants were randomized, 95 to rWES and 94 to rWGS. The analytic performance of rWGS was superior to rWES, including variants likely to affect protein function, and ClinVar pathogenic/likely pathogenic variants (p < 0.0001). The diagnostic performance of rWGS and rWES were similar (18 diagnoses in 94 infants [19%] versus 19 diagnoses in 95 infants [20%], respectively), as was time to result (median 11.0 versus 11.2 days, respectively). However, the proportion diagnosed by urWGS (11 of 24 [46%]) was higher than rWES/rWGS (p ¼ 0.004) and time to result was less (median 4.6 days, p < 0.0001). The incremental diagnostic yield of reflexing to trio after negative proband analysis was 0.7% (1 of 147). In conclusion, rapid genomic sequencing can be performed as a first-tier diagnostic test in inpatient infants. urWGS had the shortest time to result, which was important in unstable infants, and those in whom a genetic diagnosis was likely to impact immediate management. Further comparison of urWGS and rWES is warranted because genomic technologies and knowledge of variant pathogenicity are evolving rapidly.

Pentosanpolysulfate appears to be a potent inhibitor of allergic and nonimmune mast cell stimulation, which is an alternative explanation of its benefit in interstitial cystitis.

1 Mast cells derive from the bone marrow and are responsible for the development of allergic and possibly in¯ammatory reactions. Mast cells are stimulated by immunoglobulin E (IgE) and speci®c antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to secrete numerous pro-in¯ammatory molecules that include histamine, cytokines and proteolytic enzymes. 2 Chondroitin sulphate, a major constituent of connective tissues and of mast cell secretory granules, had a dose-dependent inhibitory eect on rat peritoneal mast cell release of histamine induced by the mast cell secretagogue compound 48/80 (48/80). This inhibition was stronger than that of the clinically available mast cell`stabilizer' disodium cromoglycate (cromolyn). Inhibition by chondroitin sulphate increased with the length of preincubation and persisted after the drug was washed o, while the eect of cromolyn was limited by rapid tachyphylaxis. 3 Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this eect was weaker in umbilical cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). Oligo-and monosaccharides were not as eective as the polysaccharides. 4 Inhibition, documented by light and electron microscopy, involved a decrease of intracellular calcium ion levels shown by confocal microscopy and image analysis. Autoradiography at the ultrastructural level showed that chondroitin sulphate was mostly associated with plasma and perigranular membranes.5 Chondroitin sulphate appears to be a potent mast cell inhibitor of allergic and nonimmune stimulation with potential clinical implications.

Background Non-attendance at paediatric urology outpatient appointments results in the patient's failure to receive medical care and wastes health care resources.

The Epic electronic health record (EHR) platform supports structured data entry systems (SDES), which allow developers, with input from users, to create highly customized patient-record templates in order to maximize data completeness and to standardize structure. There are many potential advantages of using discrete data fields in the EHR to capture data for secondary analysis and epidemiological research, but direct data acquisition from clinicians remains one of the largest obstacles to leveraging the EHR for secondary use. Physician resistance to SDES is multifactorial. A 35-item questionnaire based on Unified Theory of Acceptance and Use of Technology, was used to measure attitudes, facilitation, and potential incentives for adopting SDES for clinical documentation among 25 pediatric specialty physicians and surgeons. Statistical analysis included chi-square for categorical data as well as independent sample t-tests and analysis of variance for continuous variables. Mean scores of the nine constructs demonstrated primarily positive physician attitudes toward SDES, while the surgeons were neutral. Those under 40 were more likely to respond that facilitating conditions for structured entry existed as compared to the two older age groups (p = .02). Pediatric surgeons were significantly less positive than specialty physicians about SDES effects on Performance (p = .01) and the effect of Social Influence (p = .02); but in more agreement that use of forms was voluntary (p = .02). Attitudinal differences likely reflect medical training, clinical practice workflows, and division specific practices. Identified resistance indicate efforts to increase SDES adoption should be discipline-targeted rather than a uniform approach.

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Shunted hydrocephalus has a negative impact on the perception of quality of life, an effect that may be attenuated by age. Further study and more-specific measurement tools are needed to better understand health-related quality of life in children with spina bifida.

Background The patient portal interface with individual electronic health records (EHR) was introduced as a tool to enhance participatory medicine. Recent studies suggest adults from racial and ethnic minorities as well as non-English speakers face disproportionate barriers to adoption; however, little data are available for pediatric patients. Objective The purpose of this study was to examine patient portal offers and activation patterns among pediatric urology patients at two geographically diverse tertiary pediatric hospitals. Methods Retrospective analysis of 2011 to 2016 electronic portal audit records was conducted among patients aged 18 and younger with at least one outpatient urology clinic visit at two tertiary academic pediatric hospitals and their affiliated networks. Differences in utilization among parents/caregivers and adolescents were examined using multivariate analysis. Results Of 44,608 individuals seen in a participating urology department during the study period, 21,815 (48.9%) were offered a code for patient portal activation; of these, 8,605 (19.3% of total eligible individuals) activated portal access. Logistic regression demonstrated associations between an offer and site (p < 0.001), being female (p < 0.001), being Asian or white (p < 0.05), being non-Hispanic (p < 0.001), and reporting English as preferred language (p < 0.001). Activating patient portal access was associated with site (p < 0.001), being Asian or white (p < 0.001), and reporting English as preferred language (p < 0.001). Conclusion This study found that demographic variations in portal began with demographic differences in which patients were offered an activation code. Fewer than half of those given an access code activated their account. Preferred language, race/ethnicity, and clinic location were associated with likelihood of portal activation. Although patients are increasingly expected to schedule appointments, manage correspondence, request prescription refills, obtain authorizations and referrals, and communicate with the medical team using the portal, this study suggests that in the pediatric specialty setting many patients and caregivers are not offered the opportunity to access these tools.