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.

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.

Adults with Cerebral Palsy Require Ongoing Neurologic Care: A Systematic Review.

Cerebral palsy (CP) neurologic care and research efforts typically focus on children. However, most people with CP are adults. Adults with CP are at increased risk of new neurologic conditions, such as stroke and myelopathy, that require ongoing neurologic surveillance to distinguish them from baseline motor impairments. Neurologic factors could also contribute to the motor function decline, chronic pain, and chronic fatigue that are commonly experienced by adults with CP. Based on a systematic literature review, we suggest (1) guidelines for neurologic surveillance and neurologist referral and (2) clinical research questions regarding the evolving neurologic risks for adults with CP. ANN NEUROL 2021;89:860-871.

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.

The Diagnostic Error Index: A Quality Improvement Initiative to Identify and Measure Diagnostic Errors.

OBJECTIVE: To develop a diagnostic error index (DEI) aimed at providing a practical method to identify and measure serious diagnostic errors. STUDY DESIGN: A quality improvement (QI) study at a quaternary pediatric medical center. Five well-defined domains identified cases of potential diagnostic errors. Identified cases underwent an adjudication process by a multidisciplinary QI team to determine if a diagnostic error occurred. Confirmed diagnostic errors were then aggregated on the DEI. The primary outcome measure was the number of monthly diagnostic errors. RESULTS: From January 2017 through June 2019, 105 cases of diagnostic error were identified. Morbidity and mortality conferences, institutional root cause analyses, and an abdominal pain trigger tool were the most frequent domains for detecting diagnostic errors. Appendicitis, fractures, and nonaccidental trauma were the 3 most common diagnoses that were missed or had delayed identification. CONCLUSIONS: A QI initiative successfully created a pragmatic approach to identify and measure diagnostic errors by utilizing a DEI. The DEI established a framework to help guide future initiatives to reduce diagnostic errors.

Salivary gland ablation: introducing an interventional radiology treatment alternative in the management of sialorrhea.

BACKGROUND: Sialorrhea is common in children with neurological disorders and leads to social isolation, aspiration pneumonia and increased caregiver burden. Sialorrhea management includes anticholinergic medications and a variety of surgeries, but these are limited by side effects, recurrence and risks. OBJECTIVE: We present our method of salivary gland ablation, an interventional radiology treatment for sialorrhea, and report safety and efficacy data from pediatric patients who underwent salivary gland ablation. MATERIALS AND METHODS: Salivary gland ablation uses image-guided sotradecol and ethanol dual-drug injection into the salivary glands. Submandibular and sublingual glands are injected percutaneously using ultrasound. Parotid glands are injected retrograde through Stensen ducts using fluoroscopy. We conducted a retrospective review of the medical records of patients who underwent salivary gland ablation at our institution between 2005 and 2019. Pre- and post-procedure Drooling Frequency and Drooling Severity (DFDS) scale scores were compared and caregiver satisfaction was assessed. We devised two cohorts, one to study patient safety and a subcohort to study clinical efficacy using DFDS scores. RESULTS: One hundred and seventy salivary gland ablation procedures were performed in the 99 patients comprising the safety cohort. Of the procedures, 88.8% resulted in no or minimal complications. Respiratory difficulty, temporary nerve palsy and infection represent the majority of the 11.2% of patients who experienced periprocedural complications. There were no complications resulting in permanent sequelae. Twenty-seven patients met our inclusion criteria for the efficacy subcohort with a mean follow-up time of 5.4 years. DFDS at follow-up decreased from a median score of nine to a seven post-procedure (P=0.000018). The proportion of caregivers who were satisfied with the procedure increased as more glands were ablated, which suggests a causal link between the number of glands ablated and the outcome. CONCLUSION: Salivary gland ablation is a safe and effective procedure with the potential for permanent decrease in symptoms related to sialorrhea.

Capturing At-Home Health and Care Information for Children With Medical Complexity Using Voice Interactive Technologies: Multi-Stakeholder Viewpoint.

Digital health tools and technologies are transforming health care and making significant impacts on how health and care information are collected, used, and shared to achieve best outcomes. As most of the efforts are still focused on clinical settings, the wealth of health information generated outside of clinical settings is not being fully tapped. This is especially true for children with medical complexity (CMC) and their families, as they frequently spend significant hours providing hands-on medical care within the home setting and coordinating activities among multiple providers and other caregivers. In this paper, a multidisciplinary team of stakeholders discusses the value of health information generated at home, how technology can enhance care coordination, and challenges of technology adoption from a patient-centered perspective. Voice interactive technology has been identified to have the potential to transform care coordination for CMC. This paper shares opinions on the promises, limitations, recommended approaches, and challenges of adopting voice technology in health care, especially for the targeted patient population of CMC.

Proteomic investigations of human HERC2 mutants: Insights into the pathobiology of a neurodevelopmental disorder.

HERC2 is a giant protein with E3 ubiquitin ligase activity and other known and suspected functions. Mutations of HERC2 are implicated in the pathogenesis of various cancers and result in severe neurological conditions in Herc2-mutant mice. Recently, a pleotropic autosomal recessive HERC2-associated syndrome of intellectual disability, autism and variable neurological deficits was described; its pathogenetic basis is largely unknown. Using peripheral blood-derived lymphoblasts from 3 persons with homozygous HERC2 variants and 14 age- and gender-matched controls, we performed label-free unbiased HPLC-tandem mass spectrometry-based proteomic analyses to provide insights into HERC2-mediated pathobiology. We found that out of 3427 detected proteins, there were 812 differentially expressed proteins between HERC2-cases vs. controls. 184 canonical pathways were enriched after FDR adjustment, including mitochondrial function, energy metabolism, EIF2 signaling, immune functions, ubiquitination and DNA repair. Ingenuity Pathway Analysis® identified 209 upstream regulators that could drive the differential expression, prominent amongst which were neurodegeneration-associated proteins. Differentially expressed protein interaction networks highlighted themes of immune function/dysfunction, regulation of cell cycle/cell death, and energy metabolism. Overall, the analysis of the HERC2-associated proteome revealed striking differential protein expression between cases and controls. The large number of differentially expressed proteins likely reflects HERC2's multiple domains and numerous interacting proteins. Our canonical pathway and protein interaction network findings suggest derangements of multiple pathways in HERC2-associated disease.

'Learn From Every Patient': implementation and early results of a learning health system.

AIM: The convergence of three major trends in medicine, namely conversion to electronic health records (EHRs), prioritization of translational research, and the need to control healthcare expenditures, has created unprecedented interest and opportunities to develop systems that improve care while reducing costs. However, operationalizing a 'learning health system' requires systematic changes that have not yet been widely demonstrated in clinical practice. METHOD: We developed, implemented, and evaluated a model of EHR-supported care in a cohort of 131 children with cerebral palsy that integrated clinical care, quality improvement, and research, entitled 'Learn From Every Patient' (LFEP). RESULTS: Children treated in the LFEP Program for a 12-month period experienced a 43% reduction in total inpatient days (p=0.030 vs prior 12mo period), a 27% reduction in inpatient admissions, a 30% reduction in emergency department visits (p=0.001), and a 29% reduction in urgent care visits (p=0.046). LFEP Program implementation also resulted in reductions in healthcare costs of 210% (US$7014/child) versus a Time control group, and reductions of 176% ($6596/child) versus a Program Activities control group. Importantly, clinical implementation of the LFEP Program has also driven the continuous accumulation of robust research-quality data for both publication and implementation of evidence-based improvements in clinical care. INTERPRETATION: These results demonstrate that a learning health system can be developed and implemented in a cost-effective manner, and can integrate clinical care and research to systematically drive simultaneous clinical quality improvement and reduced healthcare costs.

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.

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.

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.

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.

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.

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.

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.