Design and Assessment of a Mobile Health Care Solution for the Military Pediatrician: The DHA Pediatrics App.

INTRODUCTION: Mobile health technology design and use by patients and clinicians have rapidly evolved in the past 20 years. Nevertheless, the technology has remained in silos of practices, patients, and individual institutions. Uptake across integrated health systems has lagged. MATERIALS AND METHODS: In 2015, the authors designed a mobile health application (App) aimed at augmenting the capabilities of clinicians who care for children within the Military Health System (MHS). This App incorporated a curated, system-based collection of Clinical Practice Guidelines, access to emergency resuscitation cards, call buttons for local market subspecialty and inpatient teams, links to residency academic calendars, and other web-based resources. Over the next 5 years, three Plan-Do-Study-Act cycles facilitated multiple enhancements for the App which eventually transitioned from the Android/iOS stores to a web browser. The "People At the Centre of Mobile Application Development" tool which has validity evidence captured user experience. The team assessed the App's global effectiveness using Google Analytics. A speed test measured time saved and accuracy of task completion for clinicians using the App compared to non-users. Finally, MHS medical librarians critiqued the App using a questionnaire with validity evidence. The Walter Reed National Military Medical Center Institutional Review Board reviewed the study and deemed it exempt. RESULTS: Clinician respondents (n = 68 complete responses across six MTFs, 51% graduate medical trainees representing a 7.4% response rate of active duty pediatrician forces) perceived the App to have appropriate qualities of efficiency, effectiveness, learnability, memorability, errors, satisfaction, and cognitive properties following App use in clinical practice. Google Analytics demonstrated more than 1,000 unique users on the App from May 1, 2020 to January 20, 2021. There were 746 instances (26% of all sessions) when a user navigated between more than one military treatment facility. App users were faster and more accurate at task completion during a digital scavenger hunt. Medical librarians measured the App to have acceptable usefulness, accuracy, authority, objectivity, timeliness, functionality, design, security, and value. CONCLUSIONS: The App appears to be an effective tool to extend a clinician's capabilities and inter-professional communication between world-wide users and six MHS markets. This App was designed-and used-for a large health care network across a wide geographic footprint. Next steps are establishing an enduring chain of App champions for continued updates and sharing the App's code with other military medical disciplines and interested civilian centers.

Association of Autism Spectrum Disorders With Neonatal Hyperbilirubinemia.

Autism spectrum disorders (ASD) are a common neurodevelopmental disorder of unknown etiology. Studies suggest a link between autism and neonatal jaundice. A 1:3 matched case-control study was conducted with children enrolled in the Military Health System born between October 2002 and September 2009. Diagnostic and procedure codes were used for identifying ASD and hyperbilirubinemia. Two definitions for hyperbilirubinemia were evaluated: an inpatient admission with a diagnosis of jaundice and treatment with phototherapy. A total of 2917 children with ASD and 8751 matched controls were included in the study. After adjustment, there remained an association between ASD in children and an admission with a diagnosis of jaundice (odds ratio = 1.18; 95% confidence interval = 1.06-1.31; P = .001) and phototherapy treatment (odds ratio = 1.33; 95% confidence interval = 1.04-1.69; P = .008). Children who develop ASD are more likely to have an admission with a diagnosis of jaundice in the neonatal period and more likely to require treatment for this jaundice.

Effects of herbal supplements on the bioactivation of chemotherapeutic agents.

OBJECTIVES: The aim of this study was to investigate the impact of commercially available, over-the-counter herbal supplements (St John's wort, black cohosh and ginger root extract) on the metabolic activation of tamoxifen and irinotecan. METHODS: Co-incubation of each drug and supplement combination over a range of concentrations was conducted in human liver microsomes and the decrease in the rate of active metabolite formation was monitored using high-performance liquid chromatography tandem mass spectrometry. Data was analysed using non-linear regression analysis and Dixon plots to determine the dominant mechanism of inhibition and to estimate the Ki and IC50 values of the commercial supplements. KEY FINDINGS: The data suggest that black cohosh was the strongest inhibitor tested in this study for both CYP450 and carboxyesterase mediated biotransformation of tamoxifen and irinotecan, respectively, to their active metabolites. St John's wort was a stronger inhibitor compared with ginger root extract for tamoxifen (CYP mediated pathway), while ginger root extract was a stronger inhibitor compared with St John's wort for the carboxyesterase mediated pathway. CONCLUSIONS: Commercially available supplements are widely used by patients and their potential impact on the efficacy of the chemotherapy is often unknown. The clinical significance of these results needs to be evaluated in a comprehensive clinical trial.

Preclinical pharmacokinetics, metabolism, and toxicity of azurin-p28 (NSC745104) a peptide inhibitor of p53 ubiquitination.

PURPOSE: Characterize the preclinical pharmacokinetics, metabolic profile, multi-species toxicology, and antitumor efficacy of azurin-p28 (NSC 745104), an amphipathic, 28 amino acid fragment (aa 50-77) of the copper containing redox protein azurin that preferentially enters cancer cells and is currently under development for treatment of p53-positive solid tumors. METHODS: An LC/MS/MS assay was developed, validated, and applied to liver microsomes, serum, and tumor cells to assess cellular uptake and metabolic stability. Pharmacokinetics was established after administration of a single intravenous dose of p28 in preclinical species undergoing chronic toxicity testing. Antitumor efficacy was assessed on human tumor xenografts. A human therapeutic dose was predicted based on efficacy and pharmacokinetic parameters. RESULTS: p28 is stable, showed tumor penetration consistent with selective entry into tumor cells and significantly inhibited p53-positive tumor growth. Renal clearance, volume of distribution, and metabolic profile of p28 was relatively similar among species. p28 was non-immunogenic and non-toxic in mice and non-human primates (NHP). The no observed adverse effect level (NOAEL) was 120 mg/kg iv in female mice. A NOAEL was not established for male mice due to decreased heart and thymus weights that was reversible and did not result in limiting toxicity. In contrast, the NOAEL for p28 in NHP was defined as the highest dose (120 mg/kg/dose; 1,440 mg/m(2)/dose) studied. The maximum-tolerated dose (MTD) for subchronic administration of p28 to mice is >240 mg/kg/dose (720 mg/m(2)/dose), while the MTD for subchronic administration of p28 to Cynomolgous sp. is >120 mg/kg (1,440 mg/m(2)/dose). The efficacious (murine) dose of p28 was 10 mg/kg ip per day. CONCLUSIONS: p28 does not exhibit preclinical immunogenicity or toxicity, has a similar metabolic profile among species, and is therapeutic in xenograft models.