Development and validation of a stakeholder-driven, self-contained electronic informed consent platform for trio-based genomic research studies.

Increasingly long and complex informed consents have yielded studies demonstrating comparatively low participant comprehension and satisfaction with traditional face-to-face approaches. In parallel, interest in electronic consents for clinical and research genomics has steadily increased, yet limited data are available for trio-based genomic discovery studies. We describe the design, development, implementation, and validation of an electronic iConsent application for trio-based genomic research deployed to support genomic studies of cerebral palsy. iConsent development incorporated stakeholder perspectives including researchers, patient advocates, institutional review board members, and genomic data-sharing considerations. The iConsent platform integrated principles derived from prior electronic consenting research and elements of multimedia learning theory. Participant comprehension was assessed in an interactive teachback format. The iConsent application achieved nine of ten proposed desiderata for effective patient-focused electronic consenting for genomic research. Overall, participants demonstrated high comprehension and retention of key human subjects' considerations. Enrollees reported high levels of satisfaction with the iConsent, and we found that participant comprehension, iConsent clarity, privacy protections, and study goal explanations were associated with overall satisfaction. Although opportunities exist to optimize iConsent, we show that such an approach is feasible, can satisfy multiple stakeholder requirements, and can realize high participant satisfaction and comprehension while increasing study reach.

Cerebral palsy research network community registry adult surveys on function & pain: Successes, challenges, and future directions.

NARRATIVE SUMMARY: The formation of a patient-reported outcomes registry to provide information about functional changes and pain among adults with cerebral palsy (CP) was identified as a priority to address the gap in knowledge and practice about aging and CP. The Cerebral Palsy Research Network collaborated with consumers, clinicians, and researchers to create an interactive internet platform, MyCP, to host a Community Registry. MyCP also provides educational programming, access to webinars and community forums, and fitness opportunities. The registry hosts surveys on function and pain for adults with CP, which provide cross-sectional and longitudinal data about these important issues. Surveys include previously validated measures with normative values that have been used with other populations and investigator developed questions. Enrollment in the registry is growing but needs to reflect the population of adults with CP, which limits generalizability. Future initiatives involve strategies to increase consumer engagement and enrollment.

Feasibility and utility of in-home body weight support harness system use in young children treated for spinal muscular atrophy: A single-arm prospective cohort study.

PURPOSE: This single-arm prospective cohort study aimed to evaluate the feasibility and utility of in-home body weight support harness system (BWSS) use in children treated for spinal muscular atrophy (SMA). METHODS: Individuals with 2 or 3 copies of SMN2 who received pharmacotherapeutic treatment, had head control, and weight <50lbs were enrolled. Families were provided a BWSS and documented use. Motor outcome assessments were completed at baseline, month 3 and month 6. Families provided feedback in an end of study survey. RESULTS: All 32 participants (2.9 (SD 1.9) yrs), improved or remained stable on all outcomes. Average reported frequency of use was 4.1(2.3) hrs/week. Controlling for other covariates, frequency of use explained over 70% of the variability in change scores. Family feedback was overwhelmingly positive. CONCLUSION: Use of in-home BWSS is a safe, feasible and useful option to increase exercise dosage after treatment in SMA and may help optimize motor abilities. TRIAL REGISTRATION: Study registered with: Clinicaltrials.gov Clinicaltrials.gov identifier: NCT05715749.

Adults with cerebral palsy and functional decline: A cross-sectional analysis of patient-reported outcomes from a novel North American registry.

BACKGROUND: Adults with cerebral palsy (CP) have unique healthcare needs and risks, including high risk of functional decline. Understanding functional decline is an area of priority for CP research. OBJECTIVE: Describe factors associated with patient-reported changes in function among adults with CP living in the community. METHODS: Cross-sectional analysis of adult patient-reported outcomes collected by the CP Research Network (CPRN) Community Registry. RESULTS: Participants included 263 respondents (76% female (n = 200); mean age 42 years (SD 14); 95% White (n = 249); 92% non-Hispanic (n = 241)). Many reported functional changes, most commonly a decline in gross motor function since childhood (n = 158, 60%). Prevalence of gross motor decline varied significantly by Gross Motor Function Classification System (GMFCS) level (p < 0.001), but neither hand function decline (p = 0.196) nor communication decline (p = 0.994) differed by GMFCS. All types of decline increased with increasing age, with statistically significant differences between age groups (p < 0.001 gross motor; p = 0.003 hand function; p = 0.004 communication). Those with spastic CP (n = 178) most commonly reported gross motor functional decline (n = 108/178, 60.7%). However, the prevalence of gross motor decline did not significantly differ between those with spastic CP and those without spastic CP (p = 0.789). CONCLUSIONS: Many adults in the CPRN Community Registry reported functional decline, most commonly in gross motor function. Functional decline across domains increased with age. Further research into risk stratification and preventive and rehabilitative measures is needed to address functional decline across the lifespan.

Continued safety and long-term effectiveness of onasemnogene abeparvovec in Ohio.

5q spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by absence of the SMN1 gene with three FDA approved genetic therapies which significantly improve outcomes. The AAV9 mediated gene replacement therapy, onasemnogene abeparvovec, has the greatest potential for side effects. Here we report the safety and outcomes from 46 children treated with onasemnogene abeparvovec in the state of Ohio between December 2018 and January 2023. In our cohort, onasemnogene abeparvovec treatment remained safe and no child experienced any significant adverse events, including thrombotic microangiopathy, liver failure or death. All children experienced benefit, although the benefit in those with 2 copies of SMN2 was variable. 79 % of the children treated when symptomatic had a SMN2 modifying therapy added on. With careful screening and post treatment monitoring, onasemnogene abeparvovec is safe and effective for children with SMA in the state of Ohio, but more work needs to be done to ensure optimal outcomes for all children with 2 copies of SMN2.

Adults with cerebral palsy and chronic pain experience: A cross-sectional analysis of patient-reported outcomes from a novel North American registry.

BACKGROUND: Chronic pain is common among adults with cerebral palsy (CP) and an area of priority for research and treatment. OBJECTIVE: Describe the pain experience and its functional and quality of life impact among adults with CP with chronic pain in the community. METHODS: Cross-sectional analysis of adult patient-reported outcomes collected by the Cerebral Palsy Research Network Community Registry. RESULTS: Among all participants in the Community Registry, n = 205 reported having chronic pain, and 73 % of those (n = 149) completed the Chronic Pain Survey Bundle (75 % female; mean age 43 years (SD 14 years); 94 % White; 91 % non-Hispanic). Back and weight-bearing joints of lower extremities were most frequently reported as painful. There were no differences in average pain severity scores between varying GMFCS levels (H = 6.25, p = 0.18) and age groups (H = 3.20, p = 0.36). Several nonpharmacologic interventions were most frequently reported as beneficial. Participants with moderate to severe average pain scores (5-10) had higher levels of pain interference (p < 0.01) and depression (p < 0.01), and lower levels of satisfaction with social roles (p < 0.01) and lower extremity function (p < 0.01). Pain interference was significantly positively correlated with depression, and negatively correlated with upper and lower extremity function and satisfaction with social roles. CONCLUSIONS: Chronic pain is experienced by adults with CP of varying ages and functional levels and is associated with several adverse quality of life and functional outcomes. Improved understanding of chronic pain in this population will facilitate the development and study of treatment interventions optimizing health, function, participation, and quality of life.

Examining the Role of Sublingual Atropine for the Treatment of Sialorrhea in Patients with Neurodevelopmental Disabilities: A Retrospective Review.

Sialorrhea is common in children with neurodevelopmental disabilities (NDD) and is reported in >40% of children with cerebral palsy (CP). It causes a range of complications, including significant respiratory morbidity. This single-center retrospective chart review aims to document sublingual atropine (SLA) utilization to guide further study in establishing its role in secretion management for children with NDD. A chart review was completed for patients with NDD ≤ 22 years of age treated with SLA at a free-standing children's hospital between 1 January 2016 and 1 June 2021. Descriptive statistics were generated to summarize findings. In total, 190 patients were identified, of which 178 met inclusion criteria. The average starting dose for SLA was 1.5 mg/day, or 0.09 mg/kg/day when adjusted for patient weight. Eighty-nine (50%) patients were prescribed SLA first line for secretion management while 85 (48%) patients tried glycopyrrolate prior to SLA. SLA was used after salivary Botox, ablation, and/or surgery in 16 (9%) patients. This study investigates SLA as a potential pharmacologic agent to treat sialorrhea in children with NDD. We identify a range of prescribing patterns regarding dosing, schedule, and place in therapy, highlighting the need for further evidence to support and guide its safe and efficacious use.

Newborn screening for Duchenne muscular dystrophy: A two-year pilot study.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an X-linked disorder resulting in progressive muscle weakness and atrophy, cardiomyopathy, and in late stages, cardiorespiratory impairment, and death. As treatments for DMD have expanded, a DMD newborn screening (NBS) pilot study was conducted in New York State to evaluate the feasibility and benefit of NBS for DMD and to provide an early pre-symptomatic diagnosis. METHODS: At participating hospitals, newborns were recruited to the pilot study, and consent was obtained to screen the newborn for DMD. The first-tier screen measured creatine kinase-MM (CK-MM) in dried blood spot specimens submitted for routine NBS. Newborns with elevated CK-MM were referred for genetic counseling and genetic testing. The latter included deletion/duplication analysis and next-generation sequencing (NGS) of the DMD gene followed by NGS for a panel of neuromuscular conditions if no pathogenic variants were detected in the DMD gene. RESULTS: In the two-year pilot study, 36,781 newborns were screened with CK-MM. Forty-two newborns (25 male and 17 female) were screen positive and referred for genetic testing. Deletions or duplications in the DMD gene were detected in four male infants consistent with DMD or Becker muscular dystrophy. One female DMD carrier was identified. INTERPRETATION: This study demonstrated that the state NBS program infrastructure and screening technologies we used are feasible to perform NBS for DMD. With an increasing number of treatment options, the clinical utility of early identification for affected newborns and their families lends support for NBS for this severe disease.

Comparison of Gross Motor Outcomes Between Children With Cerebral Palsy From Appalachian and Non-Appalachian Counties.

PURPOSE: This study evaluated gross motor outcomes between children with cerebral palsy from non-Appalachian and Appalachian counties in the United States. METHODS: For this retrospective, matched-case controlled study, data were sourced from electronic medical record and compared between groups. Groups were matched by age and Gross Motor Function Classification System (GMFCS) level. RESULTS: Children from Appalachian counties had significantly higher Gross Motor Function Measure, 66 (GMFM-66) scores and had a cerebral palsy diagnosis reported in the electronic medical record significantly later compared with children from non-Appalachian counties, controlling for age and GMFCS level. CONCLUSION: Although it has been documented that families and children from Appalachian counties have poorer overall health outcomes, motor development may not be affected. Our study found that children with cerebral palsy from Appalachian counties scored significantly higher on the GMFM-66 across GMFCS levels.

Epilepsy and proxy-reported health-related quality of life in children and young people with non-ambulatory cerebral palsy.

AIM: To assess the association between epilepsy characteristics and proxy-reported health-related quality of life (HRQoL) in children and young people with non-ambulatory cerebral palsy (CP) and seizures. METHOD: This was a cross-sectional study of 164 children and young people (74 females, 90 males; mean age 10 years 6 months, range 2-21 years, SD 5 years 5 months). Caregivers completed the Child Health Index of Life with Disabilities (CPCHILD) in an outpatient setting. We utilized univariable linear regression and multivariable modeling to study relationships between variables and CPCHILD scores. RESULTS: Gross Motor Function Classification System levels were 37% IV and 63% V. Sociodemographic factors included the Child Opportunity Index (median 51, interquartile range [IQR] 25-80). A median of 2 (IQR 1-3) antiseizure medications (ASMs) were used, and days with seizures ranged from 0 (30%) to 28 (20%) days in the previous 4 weeks. Total CPCHILD scores decreased 2.3 points for each ASM (95% confidence interval [CI] -4.1 to -0.42). Compared to persons with focal epilepsy, those with generalized epilepsy had lower total CPCHILD scores (-5.7; 95% CI -11 to -0.55). Number of days with seizures was not associated with total CPCHILD scores. INTERPRETATION: Proxy-reported HRQoL was affected by epilepsy-specific features in children and young people with severe CP. WHAT THIS PAPER ADDS: Health-related quality of life (HRQoL) was lower with increasing numbers of antiseizure medications. Overall quality of life (QoL) scores were lower by a similar amount, independent of seizure frequency. HRQoL was lower in persons with recent hospital admissions for epilepsy.

Reduction of Very Rapid Emergency Transfers to the Pediatric Intensive Care Unit.

Introduction: Emergency transfers are associated with increased inpatient pediatric mortality. Therefore, interventions to improve system-level situational awareness were utilized to decrease a subset of emergency transfers that occurred within four hours of admission to an inpatient medical-surgical unit called very rapid emergency transfers (VRET). Specifically, we aimed to increase the days between VRET from non-ICU inpatient units from every 10 days to every 25 days over 1 year. Methods: Using the Model for Improvement, we developed an interdisciplinary team to reduce VRET. The key drivers targeted were the admission process from the emergency department and ambulatory clinics, sepsis recognition and communication, and expansion of our situational awareness framework. Days between VRET defined the primary outcome metric for this improvement project. Results: After six months of interventions, our baseline improved from a VRET every 10 days to every 79 days, followed by another shift to 177 days, which we sustained for 3 years peaking at 468 days between events. Conclusion: Interventions targeting multiple admission sources to improve early recognition and communication of potential clinical deterioration effectively reduced and nearly eliminated VRET at our organization.

Providing a Primary Care Medical Home for Children and Youth With Cerebral Palsy.

Cerebral palsy (CP) is the most common motor disorder of childhood, with prevalence estimates ranging from 1.5 to 4 in 1000 live births. This clinical report seeks to provide primary care physicians with guidance to detect children with CP; collaborate with specialists in treating the patient; manage associated medical, developmental, and behavioral problems; and provide general medical care to their patients with CP.

Pancreatitis in the Complex Care Population: Presentation, Incidence, and Severity.

OBJECTIVES: To describe the incidence and presentation of pancreatitis in Children with Medical Complexity (CMC) while evaluating severity of disease and outlining risk factors. METHODS: This was a retrospective chart review between January 2010 and December 2019 of patients seen in the complex care clinic at Nationwide Children's Hospital (NCH) and Cincinnati Children's Hospital Medical Center (CCHMC). Data collected included sex, underlying diagnosis, family history of pancreatitis, type of pancreatitis, signs/symptoms, abdominal imaging, severity of attack, and presence of various risk factors associated with pancreatitis. Severity and diagnosis of pancreatitis was determined based on North American Society for Pediatric Gastroenterology, Hepatology and Nutrition criteria. RESULTS: One hundred and twelve patients from both institutions were included, 62% from NCH, median age 11.5 [interquartile range (IQR): 5-16 years], 50% male. Most patients were less than 18 years of age with a median age of 8 years (IQR: 4-13 years). Underlying diagnoses included seizures (67%), cerebral palsy/spastic quadriplegia (65%), diabetes (3.6%), and mitochondrial disease (3%). Majority of patients were found to have multiple underlying diagnoses (88%). Incidence of pancreatitis for both institutions was 336 of 100,000 patients/year which is significantly higher than the general pediatric population ( P < 0.0001). Majority of first episodes of pancreatitis were mild (82%) with abdominal pain as the predominant symptom (50%). Adult patients were more likely to have pancreatitis related to medication use than pediatric patients (70% vs 38%, respectively P = 0.007). CONCLUSIONS: Individuals in the CMC population at our institutions have a high incidence of pancreatitis with unique risk factors compared to the general pediatric/young adult populations.

Feeding tube use is associated with severe scoliosis in patients with cerebral palsy and limited ambulatory ability.

PURPOSE: Cerebral palsy (CP) is the most common motor disorder in childhood. Scoliosis is a common complication of CP that can reach clinically severe levels, but predictors for scoliosis in CP are not well understood. Some variables identified in the literature involve the severity of the brain injury and the presence of hip deformity. We aimed to identify associations with developing severe scoliosis in a prospective cohort of patients with cerebral palsy at higher risk for severe curve progression. METHODS: This study reviewed a prospectively collected database at a tertiary children's hospital. We evaluated a panel of potential associations with severe scoliosis-including age, sex, Gross Motor Function Classification System (GMFCS) class, history of hip surgery, epilepsy, and feeding tube presence-in a population of children with limited ambulatory ability defined as GMFCS level IV or V CP. Univariate analysis and multivariate logistic regression with stepwise selection was used for analysis. RESULTS: Descriptive analysis showed that female sex, higher GMFCS class, history of hip surgery, non-upright seating, pelvic obliquity, presence of epilepsy, and presence of a feeding tube were associated with an increased risk for scoliosis. Multivariate logistic regression analysis revealed that the presence of a feeding tube was associated with severe scoliosis even when controlling for GMFCS and age. CONCLUSIONS: Feeding tube use may stratify risk for severe scoliosis progression in patients with GMFCS IV or V CP.

"Hey Siri, Help Me Take Care of My Child": A Feasibility Study With Caregivers of Children With Special Healthcare Needs Using Voice Interaction and Automatic Speech Recognition in Remote Care Management.

Background: About 23% of households in the United States have at least one child who has special healthcare needs. As most care activities occur at home, there is often a disconnect and lack of communication between families, home care nurses, and healthcare providers. Digital health technologies may help bridge this gap. Objective: We conducted a pre-post study with a voice-enabled medical note taking (diary) app (SpeakHealth) in a real world setting with caregivers (parents, family members) of children with special healthcare needs (CSHCN) to understand feasibility of voice interaction and automatic speech recognition (ASR) for medical note taking at home. Methods: In total, 41 parents of CSHCN were recruited. Participants completed a pre-study survey collecting demographic details, technology and care management preferences. Out of 41, 24 participants completed the study, using the app for 2 weeks and completing an exit survey. The app facilitated caregiver note-taking using voice interaction and ASR. An exit survey was conducted to collect feedback on technology adoption and changes in technology preferences in care management. We assessed the feasibility of the app by descriptively analyzing survey responses and user data following the key focus areas of acceptability, demand, implementation and integration, adaptation and expansion. In addition, perceived effectiveness of the app was assessed by comparing perceived changes in mobile app preferences among participants. In addition, the voice data, notes, and transcriptions were descriptively analyzed for understanding the feasibility of the app. Results: The majority of the recruited parents were 35-44 years old (22, 53.7%), part of a two-parent household (30, 73.2%), white (37, 90.2%), had more than one child (31, 75.6%), lived in Ohio (37, 90.2%), used mobile health apps, mobile note taking apps or calendar apps (28, 68.3%) and patient portal apps (22, 53.7%) to track symptoms and health events at home. Caregivers had experience with voice technology as well (32, 78%). Among those completed the post-study survey (in Likert Scale 1-5), ~80% of the caregivers agreed or strongly agreed that using the app would enhance their performance in completing tasks (perceived usefulness; mean = 3.4, SD = 0.8), the app is free of effort (perceived ease of use; mean = 3.2, SD = 0.9), and they would use the app in the future (behavioral intention; mean = 3.1, SD = 0.9). In total, 88 voice interactive patient notes were generated with the majority of the voice recordings being less than 20 s in length (66%). Most noted symptoms and conditions, medications, treatment and therapies, and patient behaviors. More than half of the caregivers reported that voice interaction with the app and using transcribed notes positively changed their preference of technology to use and methods for tracking symptoms and health events at home. Conclusions: Our findings suggested that voice interaction and ASR use in mobile apps are feasible and effective in keeping track of symptoms and health events at home. Future work is suggested toward using integrated and intelligent systems with voice interactions with broader populations.

A study of Reiki therapy on unpleasant symptoms in children with cerebral palsy.

Children with Cerebral Palsy (CP) commonly experience unpleasant symptoms such as pain, anger, and sadness. The purpose of this quasi-experimental study, guided by the Theory of Unpleasant Symptoms (TOUS), was to examine the practicality and impact of delivering Reiki Therapy (RT) in homes over an 8-week intervention phase to children with CP. Thirteen pediatric participants were recruited, ranging in age from 5 to 16 years. Reiki Therapy was administered by a Level 3 Reiki Therapist in the home for 8 consecutive weeks. Parents completed on-line questionnaires addressing their children's unpleasant symptoms. Hair cortisol was measured as an indicator of stress. Nearly all study procedures were completed by the participants, indicating that the methods are feasible for a larger study. Reiki Therapy significantly decreased pain while lying down (3.09 vs. 2.00; p = .002) but not while sitting (2.55 vs. 2.09; p = .40). Anger symptoms showed a trend towards improvement in the participants. These preliminary findings demonstrate that Reiki is a therapeutic modality worthy of further investigation in the CP pediatric population.

Defining Persistent Total Parenteral Nutrition Use in Patients with Neurologic Impairment.

Background: Patients with neurologic impairment (NI) experience gastrointestinal symptoms as one of three common problems associated with NI, including occasional persistent total parenteral nutrition (TPN) use. Objective: To describe the incidence of persistent TPN use in patients with NI. Design: Retrospective chart review on patients 0-38 years old enrolled in the Complex Health Care Program from January 2011 to October 2015. Setting/Subjects: This study occurred in a United States pediatric tertiary care hospital. Two hundred and eight participants were included based on NI, utilizing a surgical feeding tube, and having encounters with a dietitian. Measurements: The primary outcome was incidence of persistent TPN use in patients with NI. Secondary outcomes included mortality rate, hospitalization frequency, time-to-TPN initiation, and describing symptoms preceding persistent TPN use. Results: Median number of admissions was 4 for 168 hospitalized patients (59% male, 58% White). One hundred twenty-five patients required admission for unplanned bowel rest with average length-of-stay of 7.3 days. Twenty-six patients required TPN initiation. Average time-to-TPN was two years since enrollment. Mortality rate was 14% (n = 28). TPN initiation (odds ratio [OR]: 3.99; 95% confidence interval [CI]: 1.16-13.8) was significantly associated with increased OR of mortality. Conclusions: Our study demonstrates a substantial population of patients with NI and surgical feeding tube are affected by persistent feeding intolerance. We propose that persistent TPN use may be a risk factor for mortality. Additional research is needed to delineate relationships between persistent TPN use, hospitalizations, and mortality.

Lessons learned in the development of a nurse-led family centered approach to developing a holistic comprehensive clinic and integrative holistic care plan for children with cerebral palsy.

CLINICAL PROBLEM: Children with cerebral palsy (CP) typically receive care from multiple specialty providers including Developmental Pediatrics, Orthopedics, Physical Medicine, Occupational Therapy, Physical Therapy, Speech Therapy, Clinical Social Work, Clinical Nutrition, Nursing and Orthotists, which often require many individual visits to the hospital annually. The potential for conflicting plans of care is increased by this fragmented approach, which may lead to duplication of services and increased healthcare costs. SOLUTION: To address the problem and alleviate burden for families, the Comprehensive Cerebral Palsy Program implemented a nurse-led comprehensive interdisciplinary team approach to provide optimal care coordination to patients and families, using an Integrative Holistic Care Plan (IHCP). During an annual 3-4 hour Comprehensive CP Clinic appointment, a team of specialists meets with the family, and a holistic, evidence-based plan of care is developed. The family-centered care plan includes summaries of each discipline's plan of care with individualized goals, recommendations, and evidence-based outcomes. After the visit, the plan of care is communicated with the family, primary care provider, and other community providers to ensure continuity of care. RESULTS: Early in the program and electronic IHCP development stage, clinical, and financial outcomes were improved. In addition to significant cost savings, family satisfaction surveys showed continuous improvement in the areas of access, communication, and coordination of care. PRACTICE IMPLICATIONS: Nurses working in interdisciplinary clinics are in a position to facilitate improved outcomes by developing and implementing a family-centered care plan that provides a comprehensive holistic approach to impacting the areas of quality, effectiveness, and efficiency of care delivery. The use of an IHCP decreases fragmentation of care and duplication of services leading to healthcare cost savings and enhanced patient satisfaction.