Severe junctional epidermolysis bullosa (JEB) is a rare, incurable, autosomal recessive blistering disorder with a uniformly poor prognosis. We present the case of a female infant diagnosed shortly after birth with genetically confirmed severe JEB, whose family prioritized comfort-focused care and memory-making over life-prolonging interventions. Her interdisciplinary care centered on symptom relief, bonding, and alignment with family values. This case underscores the importance of early diagnosis and values-based decision-making in managing rare, life-limiting conditions like severe JEB.

BACKGROUND AND OBJECTIVES Children with medical complexity (CMC) often receive polypharmacy (≥5 concurrent medications), increasing the risk of medication-related problems. Little is known about how caregivers of CMC manage the responsibility of polypharmacy in outpatient settings. This study aims to use caregivers’ lived experiences to develop a data-informed conceptual model of key factors influencing outpatient polypharmacy management. METHODS This study recruited caregivers of CMC with polypharmacy receiving care at a tertiary pediatric complex care clinic using purposeful sampling. Grounded theory methodology was applied to semistructured interviews with caregivers to explore their subjective experiences managing polypharmacy. Interview guide development included the input of family partners. Constant comparative analysis via iterative open, axial, and selective coding was used to develop a novel grounded theory model. Negative case analysis and investigator triangulation bolstered methodological rigor. RESULTS Interviews with 21 caregivers revealed 4 overarching themes and 9 related subthemes. Major themes include: (1) considerable psychosocial burden of managing complex and high-stakes medication regimens, (2) variable quality of health care system interactions, and (3) need for adaptation to dynamic medication landscapes for CMC, which together converge to influence (4) day-to-day decision-making and home medication strategies impacting real-world regimen adherence. Themes inform the development of a model of factors that caregivers find most influential to polypharmacy management. CONCLUSIONS The resulting model underscores a need for patient- and caregiver-centered interventions to provide clinical pharmacotherapy support, reduce caregiver burden, and improve medication management processes among CMC.

Epidermolysis bullosa (EB) impacts the skin and other organ systems, and the management of affected patients is complex and requires coordinated care. Severe EB simplex, junctional EB, and recessive dystrophic EB are effectively multisystem disorders affecting the epithelia and other organ systems with a range of complications. This article describes our center's approach to providing a comprehensive, holistic, and patient-centered approach to care of patients with EB in our multidisciplinary EB clinic. Teams from dermatology, pediatrics, occupational and physical therapy, nutrition, social work, and pain psychology work collaboratively to manage the cutaneous, extracutaneous, and psychosocial needs of these patients.

BACKGROUND:Pediatric polypharmacy is often necessary for symptom and disease management in children with medical complexity (CMC) but can result in medication-related problems. Little is known about how pediatric care teams coordinate efforts to manage polypharmacy. This limits the pragmatic design of interventions to comprehensively manage pediatric polypharmacy. OBJECTIVES:In a large outpatient pediatric complex care program for CMC, we sought to understand 1) how pediatric polypharmacy is managed by a multidisciplinary team, 2) associated challenges, and 3) opportunities for improvement. METHODS:We conducted a qualitative pilot study of pediatric clinicians with prescribing and nonprescribing roles. Thematic content analysis was used to synthesize findings across participants and identify key themes. RESULTS:We interviewed 16 clinicians representing prescribing (n = 9) and nonprescribing (n = 7) clinicians. Three of the following overarching themes emerged: 1) pediatric polypharmacy poses unique safety risks for CMC; 2) polypharmacy management requires careful collaboration between distinct clinical roles to accomplish numerous medication-related tasks; and 3) multiple prescribers across subspecialties complicates polypharmacy management, including challenges in identifying responsibility for certain medications. Clinicians described myriad challenges across different levels of the healthcare system (patient, clinic, hospital, and system) and endorsed the need for a pediatric pharmacist to help mitigate these challenges. CONCLUSION:Interventions to manage pediatric polypharmacy for CMC will require a multilevel approach including the 1) curation of accessible highly centralized medication documentation, 2) delegation of certain medication-related tasks based on clinical expertise, and 3) coordination of medication management activities across health care organizations and settings of care. Integrated pediatric pharmacist support could address many of these needs.

This cross-sectional study analyzed outpatient prescription medication use and cost among children in Colorado and identified those who would qualify for medication therapy management under Centers for Medicare and Medicaid guidelines.

Pediatric home health care represents a vital system of care for children with disability and medical complexity, encompassing services provided by family caregivers and nonfamily home health care providers and the use of durable medical equipment and supplies. Home health care is medically necessary for the physiologic health of children with disability and medical complexity and for their participation and function within home, school, and community settings. While the study of pediatric home health care in the United States has increased in the last decade, its research remains primarily methodologically limited to observational studies. Dedicated funding and research efforts are needed to transform American home health care research to address multifaceted outcomes valued by families and providers as well as payers and government programs. In this paper, we review the recent literature in pediatric home health care and then propose an actional agenda that could address its missing evidence base. We posit that pediatricians should partner with family caregiving experts and patients to advance knowledge about child and family health outcomes, home health care use, new models of care, and optimal approaches to education and training while also considering meaningful approaches to address disparities. The creation of an American pediatric home health care data-sharing consortium, patient registry, and reproducible access and quality measures is also needed. Most importantly, efforts should center on patient- and family-centered health priorities, with the goal of ensuring equitable outcomes for every child and family.

Inherited epidermolysis bullosa (EB) is a group of rare and complex genetic disorders characterized by fragility of the skin and mucous membranes. Specifically, the gastrointestinal tract is commonly involved with a range of complications, one of the most disabling being oesophageal strictures (OS). OS manifest with progressive dysphagia, which in turn contributes to malnutrition, chronic anaemia and growth delay, with high impact on the quality of life of patients and their families. DEBRA International has supported the development of clinical practice guidelines (CPGs) for different aspects of EB care. The present CPG aims to provide healthcare professionals and affected individuals and their caregivers with recommendations on diagnostic procedures, preventive measures and treatment of OS. An international multidisciplinary panel comprising clinical experts and patient and public involvement (PPI) representatives developed the CPG, following an international PPI survey and literature review. The GRADE methodology was adopted to define PICO (population, intervention, comparison, outcome) questions, implement a literature appraisal process and prepare recommendations. Three recommendations are focused on OS diagnosis, and seven on preventive nonpharmacological (diet, oral care and therapeutic education) and pharmacological measures (topical corticosteroids) and treatment procedures. Treatment focuses particularly on oesophageal dilatation and how to delay and manage disease relapses. It is expected that this CPG will contribute to improving the quality and equity of care for individuals affected with EB, and will hopefully foster clinical research to increase evidence, in particular on noninvasive OS treatment to prevent complications and delay relapses.

OBJECTIVE: Children with medical complexity (CMC), a subgroup of children with special health care needs (CSHCN) with the most serious medical conditions and disabilities, are at risk for negative effects from poor oral health. CSHCN have high rates of poor oral health, including cavities. This study aimed to compare oral health status between CMC and CSHCN. METHODS: This was a cross-sectional analysis of the 2016-17 National Survey of Child Health data. CMC and CSHCN were identified using validated algorithms. The primary outcome was oral health status; secondary outcomes included dental service use. Bivariate analyses compared the prevalence and service use by medical complexity status. Multivariable logistic regression assessed oral health outcomes by complexity, adjusting for influencing variables. RESULTS: Of 16,178 CSHCN ages 1 to 17 years, 6% were CMC and 94% were non-CMC CSHCN. Compared to CSHCN, CMC had a higher prevalence of fair/poor teeth conditions (19% vs 9%; P < 0.001) and higher odds for fair/poor teeth conditions after adjusting for socioeconomic factors (adjusted odds ratio [aOR]: 1.54; 95% confidence interval [CI]: 1.01-2.34). There was no statistically significant difference between groups when assessing cavities, toothache, or receipt of most preventive dental services. C ONCLUSIONS : One in 5 CMC are reported by caregivers as having poor oral health, including cavities, despite high rates of receiving preventive dental services. After adjusting for so- cioeconomic factors, medical complexity remained associated with fair or poor teeth conditions. Understanding potentially modifiable targets could further help families of CMC prior- itize dental needs and potentially reduce negative effects on overall health.

Importance:Children requiring care in a pediatric intensive care unit (PICU) are known to have increased risk of subsequent mortality. Children with severe neurologic impairment (SNI)-who carry neurologic or genetic diagnoses with functional impairments and medical complexity-are frequently admitted to PICUs. Although recurrent PICU critical illness episodes (PICU-CIEs) are assumed to indicate a poor prognosis, the association between recurrent PICU-CIEs and mortality in this patient population is poorly understood. Objective:To assess the association between number of recent PICU-CIEs and survival among children with severe neurologic impairment. Design, Setting, and Participants:This population-based retrospective cohort study used health administrative data from April 1, 2002, to March 31, 2020, on 4774 children born between 2002 and 2019 with an SNI diagnosis code in an Ontario, Canada, hospital record before 16 years of age and a first PICU-CIE from 2002 to 2019. Data were analyzed from November 2021 to June 2023. Exposure:Pediatric intensive care unit critical illness episodes (excluding brief postoperative PICU admissions). Main Outcome and Measures:One-year survival conditioned on the number and severity (length of stay >15 days or use of invasive mechanical ventilation) of PICU-CIEs in the preceding year. Results:In Ontario, 4774 children with SNI (mean [SD] age, 2.1 [3.6] months; 2636 [55.2%] <1 year of age; 2613 boys [54.7%]) were discharged alive between 2002 and 2019 after their first PICU-CIE. Ten-year survival after the initial episode was 81% (95% CI, 79%-82%) for children younger than 1 year of age and 84% (95% CI, 82%-86%) for children 1 year of age or older; the age-stratified curves converged by 15 years after the initial episode at 79% survival (95% CI, 78%-81% for children <1 year and 95% CI, 75%-84% for children ≥1 year). Adjusted for age category and demographic factors, the presence of nonneurologic complex chronic conditions (adjusted hazard ratio [AHR], 1.70 [95% CI, 1.43-2.02]) and medical technology assistance (AHR, 2.32 [95% CI, 1.92-2.81]) were associated with increased mortality. Conditional 1-year mortality was less than 20% regardless of number or severity of recent PICU-CIEs. Among children with high-risk PICU-CIEs, 1-year conditional survival decreased from 90% (95% CI, 89%-91%) after the first PICU-CIE to 81% (95% CI, 77%-86%) after the fourth PICU-CIE. Conclusions and Relevance:This cohort study of children with SNI demonstrated a modest dose-dependent association between PICU-CIEs and short-term mortality. These data did not support the conventional wisdom that recurrent PICU admissions are associated with subsequent high mortality risk.

Background This study will pilot-test the mobile app, Medication Safety @HOME—Meds@HOME intervention to improve medication administration accuracy, reduce preventable adverse drug events, and ultimately improve chronic care management for children with medical complexity (CMC). The Meds@HOME app was co-designed with CMC families, secondary caregivers (SCGs), and health professionals to support medication management for primary caregivers (PCGs) and SCGs of CMC. We hypothesize that Meds@HOME will improve caregivers’ medication administration accuracy, reduce preventable adverse drug events, and ultimately improve chronic care management. Objective This study aims to evaluate the effectiveness of Meds@HOME on medication administration accuracy for PCGs and SCGs. Methods This study will recruit up to 152 PCGs and 304 SCGs of CMC who are prescribed at least 1 scheduled high-risk medication and receive care at the University of Wisconsin American Family Children’s Hospital. PCGs will be randomly assigned, for the 6-month trial, to either the control group (not trialing Meds@HOME) or the intervention group (trialing Meds@HOME) using 1:1 ratio. The Meds@HOME app allows caregivers to create a child profile, store medication and care instructions, and receive reminders for upcoming and overdue care routines and medication refills. Surveys completed both at the start and end of the trial measure demographics, medication delivery knowledge, confidence in the CMC’s caregiving network, and comfort with medical information. Univariate and multivariate generalized estimation equations will be used for primary statistical analysis. The primary outcome is the PCG’s rate of medication administration accuracy measured as correct identification of each of the following for a randomly selected high-risk medication: indication, formulation, dose, frequency, and route at baseline and after 6 months. Secondary outcomes include SCG medication administration accuracy (indication, formulation, dose, frequency, and route), count of University of Wisconsin hospital and emergency department encounters, PCG-reported medication adherence, count of deaths, and PCG medication confidence and understanding. Results Recruitment for this study began on November 29, 2023. As of May 15, 2024, we have enrolled 94/152 (62%) PCGs. We expect recruitment to end by August 1, 2024, and the final participant will complete the study by January 28, 2025, at which point we will start analyzing the complete responses. We expect publication of results at the end of 2025. Conclusions The Meds@HOME mobile app provides a promising strategy for improving PCG medication safety for CMC who take high-risk medications. In addition, this protocol highlights novel procedures for recruiting SCGs of CMC. In the future, this app could be used more broadly across diverse caregiving networks to navigate complex medication routines and promote medication safety. Trial Registration ClinicalTrials.gov NCT05816590; https://clinicaltrials.gov/study/NCT05816590 International Registered Report Identifier (IRRID) DERR1-10.2196/60621

BACKGROUND AND OBJECTIVES Drug–drug interactions (DDIs) can cause adverse drug events, but little is known about DDI exposure in children in the outpatient setting. This study aimed to determine the prevalence of major DDI exposure and factors associated with higher DDI exposure rates among children in an outpatient setting. METHODS We performed a cross-sectional study of children aged 0 to 18 years with ≥1 ambulatory encounter, and ≥2 dispensed outpatient prescriptions study using the 2019 Marketscan Medicaid database. DDIs (exposure to a major DDI for ≥1 day) and the adverse physiologic effects of each DDI were identified using DrugBank’s interaction database. Primary outcomes included the prevalence and rate of major DDI exposure. We used logistic regression to assess patient characteristics associated with DDI exposure. We examined the rate of DDI exposures per 100 children by adverse physiologic effects category, and organ-level effects (eg, heart rate-corrected QT interval prolongation). RESULTS Of 781 019 children with ≥2 medication exposures, 21.4% experienced ≥1 major DDI exposure. The odds of DDI exposure increased with age and with medical and mental health complexity. Frequently implicated drugs included: Clonidine, psychiatric medications, and asthma medications. The highest adverse physiologic effect exposure rate per 100 children included: Increased drug concentrations (14.6), central nervous system depression (13.6), and heart rate-corrected QT interval prolongation (9.9). CONCLUSIONS One in 5 Medicaid-insured children with ≥2 prescription medications were exposed to major DDIs annually, with higher exposures in those with medical or mental health complexity. DDI exposure places children at risk for negative health outcomes and adverse drug events, especially in the harder-to-monitor outpatient setting.

A pediatrician caring for patients with a rare and life-limiting disease learns from his mentor the benefits of acknowledging that his story and his patients' stories are inextricably intertwined.

Importance There are an increasing number of medications with a high level of evidence for pharmacogenetic-guided dosing (PGx drugs). Knowledge of the prevalence of dispensings of PGx drugs and their associated genes may allow hospitals and clinical laboratories to determine which pharmacogenetic tests to implement. Objectives To investigate the prevalence of outpatient dispensings of PGx drugs among Medicaid-insured youths, determine genes most frequently associated with PGx drug dispenses, and describe characteristics of youths who were dispensed at least 1 PGx drug. Design, Setting, and Participants This serial cross-sectional study includes data from 2011 to 2019 among youths aged 0 to 17 years in the Marketscan Medicaid database. Data were analyzed from August to December 2022. Main Outcomes and Measures PGx drugs were defined as any medication with level A evidence as determined by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The number of unique youths dispensed each PGx drug in each year was determined. PGx drugs were grouped by their associated genes for which there was CPIC level A evidence to guide dosing, and a dispensing rate (No. of PGx drugs/100 000 youths) was determined for each group for the year 2019. Demographics were compared between youths dispensed at least 1 PGx drug and those not dispensed any PGx drugs. Results The number of Medicaid-insured youths queried ranged by year from 2 078 683 youths in 2011 to 4 641 494 youths in 2017, including 4 126 349 youths (median [IQR] age, 9 [5-13] years; 2 129 926 males [51.6%]) in 2019. The proportion of Medicaid-insured youths dispensed PGx drugs increased from 289 709 youths (13.9%; 95% CI, 13.8%-14.0%) in 2011 to 740 072 youths (17.9%; 95% CI, 17.9%-18.0%) in 2019. Genes associated with the most frequently dispensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.7-9226.3 drugs], 8731.5 drugs [95% CI, 8702.5-8759.5 drugs], and 3426.8 drugs [95% CI, 3408.1-3443.9 drugs] per 100 000 youths, respectively). There was a higher percentage of youths with at least 1 chronic medical condition among youths dispensed at least 1 PGx drug (510 445 youths [69.0%; 95% CI, 68.8%-69.1%]) than among 3 386 277 youths dispensed no PGx drug (1 381 544 youths [40.8%; 95% CI, 40.7%-40.9%) (P < .001) in 2019. Conclusions and Relevance In this study, there was an increasing prevalence of dispensings for PGx drugs. This finding suggests that pharmacogenetic testing of specific drug-gene pairs should be considered for frequently prescribed PGx drugs and their implicated genes.

The most common bacteria isolated from wound cultures in patients recorded in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD) are Staphylococcus aureus and Pseudomonas aeruginosa. Given the prevalence of P. aeruginosa in this patient population and prior research implicating P. aeruginosa's potential role in carcinogenesis, we sought to further analyze patients with recorded wound cultures positive for Pseudomonas aeruginosa in the EBCCOD. We provide a descriptive analysis of this subset of patients and highlight potential avenues for future longitudinal studies that may have significant implications in our wound care management for patients with epidermolysis bullosa.

Objective: Polypharmacy increases the risk of drug- drug interactions and adverse drug events. As obesity and rates of obesity-associated comorbid chronic conditions continue to rise, an improved understanding of whether children with obesity experience higher risk of polypharmacy is needed. This study aimed to compare chronic medication polypharmacy prevalence among children with and without a diagnosis of obesity.Methods: We performed a cross-sectional examination of prescription data for children aged 2- 18 years prescribed >= 1 chronic medication using the 2019 Marketscan Medicaid database. Children with documented obesity were identified using medical visit diagnosis codes. Chronic medications included any >= 30 -day prescription with >= 2 dispensed refills. Polypharmacy was defined as the prescription of >= 2 chronic medications for >= 1 overlapping days. Chi-squared tests compared polypharmacy prevalence and the distribution of chronic medication classes between children with and without obesity. Logistic regression determined the adjusted odds ratio (aOR) of polypharmacy for children with obesity, adjusting for relevant demographic and clinical differences.Results: Of 634,671 included children, 12.2% had documented obesity. More than one -half (52.7%) of children with obesity experienced polypharmacy compared with 47.6% of children without obesity (aOR 1.06 [95% confidence interval 1.04- 1.08]). Chronic medication prescriptions, particularly for psychiatric and asthma medications, were more commonly prescribed among children with obesity than those without obesity.Conclusions: Children with documented obesity have higher polypharmacy prevalence than children without obesity. Clinicians must be aware of this risk and minimize inappropriate polypharmacy whenever possible. Future work should examine the consequences of polypharmacy, including drug- drug interactions and adverse drug events in children with obesity.

BACKGROUND:Children with medical complexity (CMC) are uniquely vulnerable to medication errors and preventable adverse drug events because of their extreme polypharmacy, medical fragility, and reliance on complicated medication schedules and routes managed by undersupported family caregivers. There is an opportunity to improve CMC outcomes by designing health information technologies that support medication administration accuracy, timeliness, and communication within CMC caregiving networks. OBJECTIVES:The present study engaged family caregivers, secondary caregivers, and clinicians who work with CMC in a codesign process to identify: (1) medication safety challenges experienced by CMC caregivers and (2) design requirements for a mobile health application to improve medication safety for CMC in the home. METHODS:Study staff recruited family caregivers, secondary caregivers, and clinicians from a children's hospital-based pediatric complex care program to participate in virtual codesign sessions. During sessions, the facilitator-guided codesigners in generating and converging upon medication safety challenges and design requirements. Between sessions, the research team reviewed notes from the session to identify design specifications and modify the prototype. After design sessions concluded, each session recording was reviewed to confirm that all designer comments had been captured. RESULTS:A total of N = 16 codesigners participated. Analyses yielded 11 challenges to medication safety and 11 corresponding design requirements that fit into three broader challenges: giving the right medication at the right time; communicating with others about medications; and accommodating complex medical routines. Supporting quotations from codesigners and prototype features associated with each design requirement are presented. CONCLUSION:This study generated design requirements for a tool that may improve medication safety by creating distributed situation awareness within the caregiving network. The next steps are to pilot test tools that integrate these design requirements for usability and feasibility, and to conduct a randomized control trial to determine if use of these tools reduces medication errors.

This Viewpoint discusses how the International Classification of Diseases, 11th Revision (ICD-11), made available in January 2022, will affect the US health care system.

Children with medical complexity (CMC) often rely upon the use of multiple medications to sustain quality of life and control substantial symptom burden. Pediatric polypharmacy (≥ 5 concurrent medications) is prevalent and increases the risk of medication-related problems (MRPs). Although MRPs are associated with pediatric morbidity and healthcare utilization, polypharmacy is infrequently assessed during routine clinical care for CMC. The aim of this randomized controlled trial is to determine if a structured pharmacist-led Pediatric Medication Therapy Management (pMTM) intervention reduces MRP counts, as well as the secondary outcomes of symptom burden and acute healthcare utilization. This is a hybrid type 2 randomized controlled trial assessing the effectiveness of pMTM compared to usual care in a large, patient-centered medical home for CMC. Eligible patients include all children ages 2–18 years old, with ≥ 1 complex chronic condition, and with ≥ 5 active medications, as well as their English-speaking primary caregivers. Child participants and their primary parental caregivers will be randomized to pMTM or usual care before a non-acute primary care visit and followed for 90 days. Using generalized linear models, the overall effectiveness of the intervention will be evaluated using total MRP counts at 90 days following pMTM intervention or usual care visit. Following attrition, a total of 296 CMC will contribute measurements at 90 days, which provides > 90

Background Anemia is a common complication of severe forms of epidermolysis bullosa (EB). To date, there are no guidelines outlining best clinical practices to manage anemia in the EB population. The objective of this manuscript is to present the first consensus guidelines for the diagnosis and management of anemia in EB. Results Due to the lack of high-quality evidence, a consensus methodology was followed. An initial survey exploring patient preferences, concerns and symptoms related to anemia was sent to EB patients and their family members. A second survey was distributed to EB experts and focused on screening, diagnosis, monitoring and management of anemia in the different types of EB. Information from these surveys was collated and used by the panel to generate 26 consensus statements. Consensus statements were sent to healthcare providers that care for EB patients through EB-Clinet. Statements that received more than 70% approval (completely agree/agree) were adopted. Conclusions The end result was a series of 6 recommendations which include 20 statements that will help guide management of anemia in EB patients. In patients with moderate to severe forms of EB, the minimum desirable level of Hb is 100 g/L. Treatment should be individualized. Dietary measures should be offered as part of management of anemia in all EB patients, oral iron supplementation should be used for mild anemia; while iron infusion is reserved for moderate to severe anemia, if Hb levels of > 80–100 g/L (8–10 g/dL) and symptomatic; and transfusion should be administered if Hb is < 80 g/L (8 g/dL) in adults and < 60 g/L (6 g/dL) in children.

Common data models solve many challenges of standardizing electronic health record (EHR) data but are unable to semantically integrate all of the resources needed for deep phenotyping. Open Biological and Biomedical Ontology (OBO) Foundry ontologies provide computable representations of biological knowledge and enable the integration of heterogeneous data. However, mapping EHR data to OBO ontologies requires significant manual curation and domain expertise. We introduce OMOP2OBO, an algorithm for mapping Observational Medical Outcomes Partnership (OMOP) vocabularies to OBO ontologies. Using OMOP2OBO, we produced mappings for 92,367 conditions, 8611 drug ingredients, and 10,673 measurement results, which covered 68–99% of concepts used in clinical practice when examined across 24 hospitals. When used to phenotype rare disease patients, the mappings helped systematically identify undiagnosed patients who might benefit from genetic testing. By aligning OMOP vocabularies to OBO ontologies our algorithm presents new opportunities to advance EHR-based deep phenotyping.