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Daniel G Whitney,1,2 Edward A Hurvitz,1 Michelle S Caird3 1Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA; 2Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA; 3Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USACorrespondence: Daniel G Whitney University of Michigan, 325 E. Eisenhower Pkwy, Ann Arbor, MI, 48108, USATel +1 734-936-7175Email dgwhit@umich.eduPurpose: The efficacy of osteoporosis medication on reducing the risk of non-trauma fracture (NTFx) among adults with cerebral palsy (CP) has not been comprehensively investigated. There are many logistical and biological factors that may reduce this efficacy, and therefore requires attention. The purpose of this propensity score-matched, observational cohort study was to determine if osteoporosis medication was associated with NTFx risk attenuation among adults with CP and compared to adults without CP.Materials and Methods: Data from 07/01/2011 to 09/30/2015 were extracted from Optum Clinformatics® Data Mart. Claims identified adults (≥ 18 years), CP, osteoporosis medication, pre-index NTFx (6-months), and post-index NTFx (12-months). CP without osteoporosis medication (CPMeds-) and without CP with Meds (non-CPMeds+; reflects “background” population) served as controls and were matched (6:1 ratio) to adults with CP with Meds (CPMeds+; n=306). The Meds groups were further stratified by the initiation of their medication as new users or consistent users. Changes in the prevalence of NTFx from pre- to post-index periods were examined with risk ratios (RR) and the change was compared among groups using the ratio of the RR (RRR) via difference-in-difference analysis.Results: New users with CP had: a larger risk attenuation of any NTFx compared to CPMeds- (RRR=0.39; 95% CI=0.22– 0.71), which was consistent for vertebral column/hip and lower extremities; a larger risk attenuation for NTFx of the lower extremities compared to consistent users with CP (RRR=0.22; 95% CI=0.05– 0.93); and a similar risk attenuation of any NTFx compared to new users without CP (RRR=0.81; 95% CI=0.45– 1.43), which was consistent for vertebral column/hip and lower extremities.Conclusion: The findings suggest that osteoporosis medication is associated with clinically meaningful risk attenuation of NTFx, especially for new users with CP.Keywords: cerebral palsy, fracture, osteoporosis medication

Daniel G Whitney,1,2 Mary Schmidt,1 Sarah Bell,1 Hal Morgenstern,3– 5 Richard A Hirth2,6,7 1Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA; 2Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA; 3Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 4Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 5Department of Urology, School of Medicine, University of Michigan, Ann Arbor, MI, USA; 6Department of Health Management and Policy, University of Michigan School of Public Health, Ann Arbor, MI, USA; 7Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USACorrespondence: Daniel G Whitney Tel +1 734-936-7175Email dgwhit@umich.eduPurpose: Due to complex medical profiles, adults with neurodevelopmental disabilities (NDDs) may have a heightened risk for early development of chronic kidney disease (CKD) and accelerated CKD progression to advanced stages and kidney failure. The purpose of this study was to estimate the incidence rate of advanced CKD for adults with NDDs and compare the incidence rate to adults without NDDs.Patients and Methods: Data were used from the Optum Clinformatics® Data Mart to conduct this retrospective cohort study. The calendar year 2013 was used to identify eligible participants: individuals ≥ 18 years of age and without advanced CKD. Participants were followed from 01/01/2014 to advanced CKD, loss to follow-up, death, or end of the study period (12/31/2017), whichever came first. Diagnostic, procedure, and diagnosis-related group codes identified NDDs (intellectual disabilities, cerebral palsy, autism spectrum disorders), incident cases of advanced CKD (CKD stages 4+), diabetes, cardiovascular diseases, and hypertension present in the year 2013. Crude incidence rates (IR) of advanced CKD and IR ratios (IRR), comparing adults with vs without NDDs (with 95% CI) were estimated. Then, Cox regression estimated the hazard ratio (HR and 95% CI) for advanced CKD, comparing adults with NDDs to adults without NDDs while adjusting for covariates.Results: Adults with NDDs (n=33,561) had greater crude IR of advanced CKD (IRR=1.32; 95% CI=1.24– 1.42) compared to adults without NDDs (n=6.5M). The elevated rate of advanced CKD among adults with NDDs increased after adjusting for demographics (HR=2.19; 95% CI=2.04– 2.34) and remained elevated with further adjustment for hypertension and diabetes (HR=2.01; 95% CI=1.87– 2.15) plus cardiovascular disease (HR=1.84; 95% CI=1.72– 1.97). Stratified analyses showed that the risk of advanced CKD was greater for all NDD subgroups.Conclusion: Study findings suggest that adults with NDDs have a greater risk of advanced CKD than do adults without NDDs, and that difference is not explained by covariates used in our analysis.Keywords: chronic kidney disease, neurodevelopmental disabilities, intellectual disabilities, cerebral palsy, autism spectrum disorders

Daniel G Whitney,1,2 Neil S Kamdar,2–5 Sophia Ng,2 Edward A Hurvitz,1 Mark D Peterson1,21Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA; 2Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA; 3Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA; 4Department of Surgery, University of Michigan, Ann Arbor, MI, USA; 5Department of Emergency Medicine, University of Michigan, Ann Arbor, MI, USAPurpose: Individuals with cerebral palsy (CP) are susceptible to early development of high-burden medical conditions, which may place a considerable strain on health care resources. However, little is known about the prevalence of high-burden medical conditions or health care resource utilization among adults with CP. The purpose of this study was to determine the prevalence of high-burden medical conditions and health care resource utilization and costs among adults with CP, as compared to adults without CP.Patients and methods: Cross-sectional data from the 2016 Optum Clinformatics®, Data Mart, a de-identified nationwide claims database of beneficiaries from a single private payer in the US. ICD-10-CM diagnosis codes were used to identify all medical conditions among beneficiaries with and without CP who were between 18 and 64 years of age. Medical and outpatient pharmacy claims were used to identify annual all-cause health care resource utilization and health care costs as standardized reimbursement and patient out-of-pocket costs.Results: Adults with CP (n=5,555) had higher prevalence and odds of all medical conditions compared to adults without CP (OR=1.3–5.8; all P

Daniel G Whitney,1 Edward A Hurvitz,1 Jennifer M Ryan,2,3 Maureen J Devlin,4 Michelle S Caird,5 Zachary P French,1 Elie C Ellenberg,1 Mark D Peterson1 1Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA; 2Department of Epidemiology and Public Health Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland; 3Department of Clinical Sciences, Brunel University London, Uxbridge, UK; 4Department of Anthropology, University of Michigan, Ann Arbor, MI, USA; 5Department of Orthopedic Surgery, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA Purpose: Individuals with cerebral palsy (CP) are at increased risk for frailty and chronic disease due to factors experienced throughout the lifespan, such as excessive sedentary behaviors and malnutrition. However, little is known about noncommunicable diseases (NCDs) and multimorbidity profiles in young adults with CP. The study objective was to compare NCD and multimorbidity profiles between young adults with and without CP.Methods: A clinic-based sample of adults (18–30 years) with (n=452) and without (n=448) CP was examined at the University of Michigan Medical Center. The prevalence and predictors of 13 NCDs were evaluated, including existing diagnoses or historical record of musculoskeletal, cardiometabolic, and pulmonary morbidities. The level of motor impairment was determined by the Gross Motor Function Classification System (GMFCS) and stratified by less vs more severe motor impairment (GMFCS I–III vs IV–V). Logistic regression was used to determine the odds of NCD morbidity and multimorbidity in adults with CP compared to adults without CP, and for GMFCS IV–V compared to GMFCS I–III in those with CP, after adjusting for age, sex, body mass index, and smoking.Results: Adults with CP had a higher prevalence of osteopenia, osteoporosis, hypertension, myocardial infarction, hyperlipidemia, asthma, and multimorbidity compared to adults without CP, and higher odds of musculoskeletal (odds ratio [OR]: 6.97) and cardiometabolic morbidity (OR: 1.98), and multimorbidity (OR: 2.67). Adults with CP with GMFCS levels IV–V had a higher prevalence of osteopenia/osteoporosis, osteoarthritis, hypertension, other cardiovascular conditions, pulmonary embolism, and multimorbidity, and higher odds of musculoskeletal (OR: 3.41), cardiometabolic (OR: 2.05), pulmonary morbidity (OR: 1.42), and multimorbidity (OR: 3.45) compared to GMFCS I–III.Conclusion: Young adults with CP have a higher prevalence of chronic NCDs and multimorbidity compared to young adults without CP, which is pronounced in those with more severe motor impairment. These findings reiterate the importance of early screening for prevention of NCDs in CP. Keywords: cerebral palsy, noncommunicable disease, multimorbidity, osteoporosis, osteoarthritis, cardiovascular disease, diabetes, pulmonary disease

Background: Children with non-ambulatory cerebral palsy (CP) frequently develop progressive neuromuscular scoliosis and require surgical intervention. Due to their comorbidities, they are at high risk for developing peri- and post-operative complications. The objectives of this study were to compare stepwise and LASSO variable selection techniques for consistency in identifying predictors when modelling these post-operative complications and to identify potential predictors of respiratory complications and infections following spine surgery among children with CP., Methods: In this retrospective cohort study, a large administrative claims database was queried to identify children who met the following criteria: 1) ≤ 25 years old, 2) diagnosis of CP, 3) underwent surgery during the study period, 4) had ≥ 12-months pre-operative, and 5) ≥ 3-months post-operative continuous health plan enrollment. Outcome measures included the development of a post-operative respiratory complication (e.g., pneumonia, aspiration pneumonia, atelectasis, pleural effusion, pneumothorax, pulmonary edema) or an infection (e.g., surgical site infection, urinary tract infection, meningitis, peritonitis, sepsis, or septicemia) within 3 months of surgery. Codes were used to identify CP, surgical procedures, medical comorbidities and the development of post-operative respiratory complications and infections. Two approaches to variable selection, stepwise and LASSO, were compared to determine which potential predictors of respiratory complications and infection development would be identified using each approach., Results: The sample included 220 children. During the 3-month follow-up, 21.8% (n = 48) developed a respiratory complication and 12.7% (n = 28) developed an infection. The prevalence of 11 variables including age, sex and 9 comorbidities were initially considered to be potential predictors based on the intended outcome of interest. Model discrimination utilizing LASSO for variable selection was slightly improved over the stepwise regression approach. LASSO resulted in retention of additional comorbidities that may have meaningful associations to consider for future studies, including gastrointestinal issues, bladder dysfunction, epilepsy, anemia and coagulation deficiency., Conclusions: Potential predictors of the development of post-operative complications were identified in this study and while identified predictors were similar using stepwise and LASSO regression approaches, model discrimination was slightly improved with LASSO. Findings will be used to inform future research processes determining which variables to consider for developing risk prediction models., (© 2024. The Author(s).)

Background: Lymphedema is a chronic and progressive condition but is understudied among adults with cerebral palsy (CP)., Objective: To compare the 2-year incidence of lymphedema between adults with versus without CP before and after accounting for multimorbidity, cancer diagnosis/treatment, and lymph node/channel surgery., Design: Retrospective cohort study., Setting: Nationwide commercial claims data from January 1, 2011 to December 31, 2017., Participants: Adults ≥18 years old with and without CP with at least 12 months of continuous health plan enrollment, defined as the baseline period, were included for analysis. The 12-month baseline period was used to establish information on preexisting lymphedema (for exclusion), presence of cancer, including radiation treatment and lymph node surgery, and the Whitney Comorbidity Index (WCI)., Interventions: Not applicable., Main Outcome Measure: The 2-year incidence rate (IR) and IR ratio (IRR) of lymphedema were evaluated. Cox regression estimated the hazard ratio (HR) of 2-year lymphedema after adjusting for age, gender, WCI, cancer diagnosis/treatment, and lymph node/channel surgery., Results: The 2-year IR of lymphedema was 5.73 (95% confidence interval [CI] = 4.59-6.88) for adults with CP (n = 9922) and 1.81 (95% CI = 1.79-1.83) for adults without CP (n = 12,932,288); the IRR was 3.17 (95% CI = 2.59-3.87) and the adjusted HR was 2.43 (95% CI = 1.98-2.98). There was evidence of effect modification by gender, age, and WCI score. All HRs were elevated, but men with versus without CP had higher HRs than women with versus without CP; HRs for adults with versus without CP were higher for younger participants and those with lower WCI scores., Conclusions: Adults with CP had a higher 2-year rate of lymphedema compared with those without CP. Men with CP had a disproportionately higher rate than women with CP when compared with their gender-based reference cohorts without CP., (© 2024 American Academy of Physical Medicine and Rehabilitation.)

Background: Children with cerebral palsy (CP) have a high risk of fracture; yet, little is known about their post-fracture health outcomes. A fracture is an unplanned event in contrast to surgeries or procedures where there is a pre-operative period to optimize body composition and health and planned post-operative follow-up care. Fractures may be associated with significant outcomes due to the unplannable nature and reactionary care. The objective of this study was to determine if fractures were associated with an increased rate of short-term adverse health outcomes among children with CP, and if these associations were dependent on age., Methods: This retrospective cohort study used commercial claims from 01/01/2001-12/31/2018. The primary cohort was children 2-18 years old with CP and an incident fracture (CP + Fx). Comparison cohorts were propensity score matched 1:1 to CP + Fx on demographic and health-related indicators: CP without fractures (CPw/oFx); without CP with (w/oCP + Fx) or without (w/oCPw/oFx) a fracture. The incidence rate (IR) and IR ratios (IRR) of 30-day and 31-90-day pneumonia and 90-day emergency department (ED) visit were estimated. Cox regression tested for effect modification by age and sex., Results: The CP + Fx cohort (n = 1670) had higher IRs of 30-day pneumonia (IRR range, 1.53-4.54) and 90-day ED visit (IRR range, 1.45-2.37) (all P < 0.05), and higher IRs of 31-90-day pneumonia but this did not reach statistical significance (IRR, 1.41 to 2.32, all P > 0.05). Notably, there was evidence of effect modification by age. The rate of 30-day pneumonia became more problematic for CP + Fx with older age relative to comparison cohorts and for 90-day ED visit compared to CPw/oFx. The rate of 90-day ED visit for CP + Fx was more problematic at younger ages compared to w/oCP + Fx., Conclusions: Fractures among children with CP were associated with an increased rate of short-term pneumonia and ED visit, which was more problematic with older age., Competing Interests: Declaration of competing interest All authors declare there is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: While research has provided key insights into mortality rates and risks for individuals with cerebral palsy (CP), clinically useable mortality risk estimates remain unreported for adults with CP, especially by key patient-level factors., Objective: The objective of this study was to generate clinically useable mortality risk estimates among adults with CP to inform clinical decision making., Methods: This retrospective cohort study, using a fee-for-service Medicare database, identified adults ≥18-years-old with CP from 01/01/2008-12/31/2010 and followed through 12/31/2019 for death. Mortality risk at 1-, 3-, 5-, and 9-year intervals were selected based on common clinical length of time to reasonably benefit from preventive care. Sex-stratified analyses assessed risk estimates by narrow age group (18-25/26-34/35-44/45-54/55-64/65-74/≥75 years old) and multi-morbidity group (Whitney Comorbidity Index score 0-2/3/4-6/≥7)., Results: Of 24,767 adults with CP, n = 12,962 were men (mean [SD] age = 48.3 [15.0] years) and n = 11,805 were women (age = 49.7 [15.8] years). Loss to follow-up was rare. 1-year risk was similar between men and women (3.4 % vs. 3.3 %), but increased slightly more for men than women through 9-years (30.1 % vs. 28.0 %). As expected, the mortality risk increased with older age and higher WCI scores. The probability of death (and survival) is presented per age and multi-morbidity group for men and women with CP., Conclusions: Mortality risk estimates were reported at clinically relevant intervals by age, sex, and multi-morbidity status. This information can be used to weigh harm-to-benefit ratios of screening and treatment strategies based on mortality expectancy estimates., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Despite the need, measuring glomerular filtration rate (mGFR) is not routinely performed for adults with cerebral palsy (CP), possibly due to unknown feasibility given the secondary complications of CP. This study aimed to assess the feasibility and reliability of mGFR and explore factors associated with eGFR-mGFR discordance among young adults with mild-to-moderate CP., Methods: This single-center, cross-sectional study included 18- to 40-year-olds with CP gross motor function classification system (GMFCS) I-III. The participants were excluded if they were pregnant/lactating, had cognitive impairments, or had contraindications to mGFR. A routine clinical protocol for mGFR and eGFR was used. mGFR feasibility was assessed based on the number of participants who completed testing. mGFR reliability was assessed using the coefficient of variation (CV) across the four 30 min intervals. The association between age, sex, and GMFCS and the percentage of eGFR-mGFR discordance was assessed., Results: Of the 19 participants enrolled, 18 completed the testing [mean age (SD), 29.9 (7.4) years, n  = 10 female participants, n  = 10/3/5 for GMFCS I/II/III] and most ( n  = 15) of the participants had an mGFR >90 mL/min; 14 participants (77.8%) had a CV <20%, 2 had a CV between 20 and 25%, and 2 had a CV >50%. eGFR overestimated mGFR by a median (interquartile range) of approximately 17.5% (2-38%); the full range of mis-estimation was -20.5 to 174.3%. Increasing age and GMFCS levels exhibited notable, but weak-to-modest, associations with a larger eGFR-mGFR discordance., Discussion: Obtaining mGFR was feasible and reasonably reliable within this small sample. eGFR overestimated mGFR by a notable amount, which may be associated with patient-level factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Whitney, Oliverio, Kreschmer, Bolde, Hurvitz and Wong.)

Introduction: Adults with cerebral palsy are at risk for early multimorbidity onset, but little is known about the composition of multimorbidity profiles or how these profiles present across adulthood. The objective of this study was to identify multimorbidity profiles and association with mortality among adults with cerebral palsy., Methods: This retrospective cohort study used a random 20% fee-for-service Medicare database from January 1, 2008 to December 31, 2019 from adults aged ≥18 years with cerebral palsy. Latent class analyses using 4-class models were conducted within each age cohort (young adults aged 18-39 years, middle adulthood aged 40-64 years, and older adults aged ≥65 years) to determine patterns of 30 comorbidities defined using the International Classification of Diseases, Ninth Revision codes, identified from January 1, 2008 to December 31, 2010, and their association with mortality through December 31, 2019 (up to 11 years of follow-up); statistical analysis was performed in 2023., Results: Three classes were relatively consistent in the composition of comorbidities across young (n=7,020), middle (n=13,554), and older (n=4,193) cohorts: (1) low morbidity (low proportion of all comorbidities) representing 50.1% (young), 41.4% (middle), and 30.9% (older) of the cohorts; (2) neurologic multimorbidity (e.g., epilepsy, intellectual disabilities) representing 26.0% (young), 26.6% (middle), and 14.7% (older) of the cohorts; and complex multimorbidity (e.g., cardiorespiratory, nutritional, musculoskeletal, neurologic) representing 26.0% (young), 26.6% (middle), and 14.7% (older) of the cohorts. The fourth class varied by young (mental health disorders), middle (hypertension), and older (hypertension and osteoarthritis) age cohorts. Compared with the low morbidity class, other classes had an increased mortality rate for each age cohort (hazard ratio range=1.34-5.58, all p<0.001)., Conclusions: Findings provide insight into varied multimorbidity profiles and associations with mortality across the life course for adults with cerebral palsy., (Copyright © 2024 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: This study aimed to describe opioid prescription patterns for children with vs. without cerebral palsy (CP)., Methods: This cohort study used commercial claims from 01/01/2015-12/31/2016 and included children aged 2-18 years old with and without CP. Opioid prescription patterns (proportion exposed, number of days supplied) were described. A zero-inflated generalized linear model compared the proportion exposed to opioids in the follow-up year (2016) and, among those exposed, the number of days supplied opioids between cohorts before and after adjusting for age, gender, race, U.S. region of residence, and the number of co-occurring neurological/neurodevelopmental disabilities (NDDs)., Results: A higher proportion of children with (n = 1,966) vs. without (n = 1,219,399) CP were exposed to opioids (12.1% vs. 5.3%), even among the youngest age group (2-4 years: 9.6% vs. 1.8%), and had a greater number of days supplied (median [interquartile range], 8 [5-13] vs. 6 [4-9] days; P < 0.05). Comparing children with opioid exposure with vs. without CP, a greater number of days supplied was identified for older age, Asian race/ethnicity, and without co-occurring NDDs, and a lower number of days supplied was observed for Black race/ethnicity and with ≥1 co-occurring NDDs., Conclusion: Children with CP are more likely to be exposed to opioids and have a higher number of days supplied.

Aim: To determine the feasibility and reliability of measuring grip strength and its association with anthropometrics and diseases among adolescents and adults (≥16 years old) with cerebral palsy (CP)., Method: In this cross-sectional study, individuals with CP, classified in Gross Motor Function Classification System (GMFCS)/Manual Ability Classification System (MACS) levels I to V, were recruited to measure grip strength, anthropometrics, and self-reported current/history of disease during a routine clinical visit. Feasibility was determined as the proportion recruited/consented/completed testing. Test-retest reliability of three maximal effort trials per side was assessed. Linear regression determined associations of grip strength with anthropometrics after adjusting for age, sex, and GMFCS. The predictive ability of GMFCS alone, grip strength alone, GMFCS + grip strength, and GMFCS × grip strength for diseases was compared., Results: Of 114 individuals approached, 112 participated and 111 successfully completed all tasks. There was good to excellent reliability of test-retest grip strength between trials for dominant and non-dominant sides for the entire cohort and when stratified by each GMFCS and MACS level (intraclass correlation coefficient range 0.83-0.97). Sex, GMFCS, MACS, body mass, and waist circumference were associated with grip strength (p < 0.05), but not hip circumference, waist:hip ratio, or triceps skinfold thickness. Modeling grip strength with GMFCS had a higher predictive value for relevant diseases than GMFCS alone., Interpretation: Grip strength is a feasible and reliable measurement for CP, and is associated with some demographics and anthropometric measures. Grip strength, in addition to the GMFCS, enhanced prediction of disease outcomes., What This Paper Adds: Measurement of hand grip strength is clinically feasible for adolescents/adults with cerebral palsy. Grip strength has good to excellent test-retest reliability across Gross Motor Function Classification System (GMFCS) and Manual Ability Classification System (MACS) levels. Grip strength is associated with sex, weight, waist circumference, GMFCS, and especially MACS. Grip strength, in addition to GMFCS, shows promise for enhancing disease prediction in this cohort., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Objective: Fragility fractures are associated with an increased risk of pneumonia, which is a leading cause of death in adults with intellectual disabilities; however, the timing and complications of post-fracture pneumonia are underinvestigated. The objectives of this study were to determine the 30-day pneumonia rate post-fracture and the association of post-fracture pneumonia with mortality and cardiovascular events among adults with intellectual disabilities., Methods: This retrospective cohort study was conducted using Medicare and commercial claims from 01 January 2011 to 31 December 2016. Incidence of pneumonia 30 days after a fragility fracture among adults ≥18 years old with intellectual disabilities (Fx cohort) was compared to the incidence among matched adults with intellectual disabilities without fractures (w/oFx cohort) and the general population of patients with an incident fragility fracture (GP+Fx). For the Fx cohort, Cox regression was used to examine the adjusted association of time-varying pneumonia (within 30 days post-fracture) with mortality and incidence of cardiovascular events 0-30, 31-365, and 366-730 days post-fracture., Results: There was a high-early rate of pneumonia within 30 days post-fracture for young, middle-aged, and elderly adults with intellectual disabilities ( n = 6,183); this rate was 2.2- to 6.1-fold higher than the rate among the w/oFx ( n = 12,366) and GP+Fx ( n = 363,995) cohorts (all P < 0.05). For the Fx cohort, post-fracture 30-day incidence of pneumonia was associated with an increased 30-day rate of mortality (adjusted HR [aHR] = 5.19; 95% confidence interval [CI] = 3.68-7.32), heart failure (aHR = 2.96; 95% CI = 1.92-4.56), and cerebrovascular disease (aHF = 1.48; 95% CI = 0.93-2.35; P = 0.098), with sustained effects to 1 year for heart failure (aHR = 1.61; 95% CI = 1.19-2.17) and 2 years for mortality (aHR = 1.39; 95% CI = 1.06-1.83), and without evidence of effect modification by age., Discussion: Adults with intellectual disabilities are vulnerable to post-fracture pneumonia within 30 days, and complications arising from this, across the adult lifespan, and not only during the elderly years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Whitney, Erickson and Berri.)

Bone development is a highly orchestrated process that establishes the structural basis of bone strength during growth and functionality across the lifespan. This developmental process is generally robust in establishing mechanical function, being adaptable to many genetic and environmental factors. However, not all factors can be fully accommodated, leading to abnormal bone development and lower bone strength. This can give rise to early-onset bone fragility that negatively impacts bone strength across the lifespan. Current guidelines for assessing bone strength include measuring bone mineral density, but this does not capture the structural details responsible for whole bone strength in abnormally developing bones that would be needed to inform clinicians on how and when to treat to improve bone strength. The clinical consequence of not operationalizing how altered bone development informs decision making includes under-detection and missed opportunities for early intervention, as well as a false positive diagnosis of fragility with possible resultant clinical actions that may actually harm the growing skeleton. In this Perspective, we emphasize the need for a multi-trait, integrative approach to better understand the structural basis of bone growth for pediatric conditions with abnormal bone development. We provide evidence to showcase how this approach might reveal multiple, unique ways in which bone fragility develops across and within an array of pediatric conditions that are associated with abnormal bone development. This Perspective advocates for the development of new translational research aimed at informing better ways to optimize bone growth, prevent fragility fractures, and monitor and treat bone fragility based on the child's skeletal needs., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Serum creatinine may be an objective biomarker of salient health issues in adults with cerebral palsy (CP). The objective was to assess the age-related association between serum creatinine with 3-year risk of cardiorespiratory morbidity/mortality and fracture among adults with CP., Patients and Methods: This retrospective cohort study used medical records between Jan. 1, 2012 and Oct. 2, 2022 from adults ≥18 years old with CP. The association between baseline serum creatinine with the 3-year risk of all-cause mortality, respiratory/cardiovascular morbidity/mortality, and fracture was assessed by age and sex using logistic regression. The discriminative ability of serum creatinine alone and in conjunction with other variables was assessed., Results: Over the 3-year follow-up, 8.3% of 1368 adults with CP had all-cause mortality, 25.6% had respiratory morbidity/mortality, 12.4% had cardiovascular morbidity/mortality, and 8.9% sustained a fracture. The association between serum creatinine with outcomes was dependent on age. For younger adults, lower creatinine had a higher odds ratio (OR) for all-cause mortality, respiratory morbidity/mortality, and fracture. For 51-60 year olds, higher creatinine had a higher OR for cardiovascular morbidity/mortality. Serum creatinine alone had modest prediction of outcomes, and generally improved prediction when added to models that included sex and co-occurring intellectual disabilities and epilepsy (c-statistic range, 0.54-0.84)., Conclusions: Lower serum creatinine may reflect frailty while higher levels may reflect kidney dysfunction, helping to explain the differential associations by age. Serum creatinine may be a useful biomarker as part of risk prediction models for these salient health issues for adults with CP., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2023 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Objective: Fragility fractures are common among adults with cerebral palsy (CP), but clinical rehabilitation use after fracture and its effect on long-term health outcomes have not been sufficiently studied. The objectives of this study were to identify patterns of the use of physical therapy, occupational therapy, or both in the 6-month postfracture period and the association with 3-year mortality in adults with CP., Methods: This retrospective cohort study included adults who were ≥18 years old, had CP, and had sustained an incident fragility fracture between January 1, 2014, and December 31, 2016, as identified from a random 20% Medicare fee-for-service dataset. Six-month outpatient physical therapy or occupational therapy use patterns after fracture were identified using group-based trajectory modeling. Cox regression determined the association between physical therapy or occupational therapy use trajectory patterns and mortality from 6 months to 3 years after fracture, adjusting for confounders. Effect modification by key characteristics was tested, including age, sex, and the modified Whitney Comorbidity Index (mWCI), which is a CP-specific comorbidity index that better captures overall medical complexity., Results: Of the 2429 participants included, the majority (73.2%) were characterized as having little to no probability of physical therapy or occupational therapy use, whereas 16.0 and 10.7% were characterized as having early initiation and later initiation, respectively. Compared to the mortality rate for the little to no physical therapy or occupational therapy group, the mortality rates were 26% lower for the early physical therapy or occupational therapy initiation group (hazard ratio [HR] = 0.74; 95% CI = 0.55-1.00) and were 20% lower for the later initiation group (HR = 0.80; 95% CI = 0.57-1.12). There was effect modification by the mWCI. The mortality rate was lower when the early initiation and later initiation groups were compared to the little to no initiation group across all mWCI values examined (median and interquartile range), but the effect was stronger (ie, lower mortality rate) for lower mWCI values for both early initiation and later initiation groups., Conclusion: Most adults with CP underutilize outpatient physical therapy or occupational therapy services within 6 months postfracture. Early or later initiation versus little to no physical therapy or occupational therapy use was associated with a lower HR of mortality, although the effect was stronger and statistically significant among those with less medical complexity., Impact: Throughout their lives, the use of rehabilitation services in individuals with CP, including physical therapy and occupational therapy, dramatically declines despite the need for continued rehabilitation across their lifespans. This study characterized longitudinal physical therapy or occupational therapy use patterns in the 6 months following a fragility fracture among adults with CP and found that nearly 3 in 4 adults with CP had little to no physical therapy or occupational therapy use during this critical window to optimize postfracture health and function. Further, those who more regularly used physical therapy or occupational therapy services, regardless of the timing of initiation (early vs later), had significantly improved survival up to 3 years after fracture, suggesting the need for greater access to and delivery of clinical rehabilitation services., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Adults with intellectual disabilities have a greater risk for fragility fractures that begin to accumulate early in the adult lifespan, which may contribute to accelerated health declines. The objective was to determine if fragility fractures were associated with an increased 2-year rate of cardiorespiratory diseases among adults with intellectual disabilities., Method: This retrospective cohort study used nationwide administrative claims data from 01/01/2011-12/31/2016 from the Medicare fee-for-service database. 2-year incidence of cardiorespiratory diseases were compared between adults ≥18 years old with intellectual disabilities with (n = 6183) vs. without (n = 67,842) an incident fragility fracture after confounder adjustment using Cox regression., Results: Fracture at the vertebral column, hip, non-proximal femur, tibia/fibula, and multiple sites had an elevated hazard ratio (HR) compared to those with no fracture for pneumonia, respiratory failure, heart failure, and cerebrovascular disease (HR range, 1.15-2.09, all P < 0.05), while humerus and radius/ulna fracture were associated with an elevated HR for congestive heart failure and cerebrovascular disease (HR range, 1.38-1.72, all P < 0.05)., Conclusions: Fragility fractures were associated with an increased incidence of cardiorespiratory diseases among adults with intellectual disabilities., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

- Durable medical equipment (DME) policies require that the equipment be medically necessary; however, adaptive cycling equipment (bicycles and tricycles) are usually not deemed medically necessary. - Individuals with neurodevelopmental disabilities (NDD) are at high risk for secondary conditions, both physical and mental, that can be mitigated by increasing physical activity. - Significant financial costs are associated with the management of secondary conditions. - Adaptive cycling can provide improved physical health of individuals with NDD potentially reducing costs of comorbidities. - Expanding DME policies to include adaptive cycling equipment for qualifying individuals with NDD can increase access to equipment. - Regulations to ensure eligibility, proper fitting, prescription, and training can optimize health and wellbeing. - Programs for recycling or repurposing of equipment are warranted to optimize resources., Competing Interests: The authors received a small honorarium for the preparation of this policy brief from Rifton, Inc and Rifton, Inc covered article publication costs. The views presented in this policy brief are the views of the authors and in no way did the honorarium influence the synthesis of the literature, policy recommendations, or conclusions reported in this brief., (© 2023 Gannotti, O'Neil, Fragala-Pinkham, Gorton and Whitney.)

Background: There is little epidemiologic evidence on opioid prescription among adults with cerebral palsy (CP)., Aim: To describe the population- and individual-level opioid prescription patterns for adults with versus without CP., Method: This retrospective cohort study used commercial claims (Optum's de-identified Clinformatics® Data Mart Database) from the USA from 01/01/2011-12/31/2017 from adults ≥ 18 years old with CP and matched adults without CP. For the population-level analysis, monthly estimates of opioid exposure were described for adults ≥ 18 years old with CP and matched adults without CP. For the individual-level analysis, group based trajectory modelling (GBTM) was used to identify groups of similar individual-level monthly opioid exposure patterns for adults with CP and matched adults without CP for 1-year starting from their first opioid exposure month., Results: For the population-level, adults with (n = 13,929) versus without (n = 278,538) CP had a higher prevalence of opioid exposure (~ 12%, ~ 8%) and days supplied (median, ~ 23, ~17) monthly over 7 years. For the individual-level, there were 6 trajectory groups for CP (n = 2099) and 5 for non-CP (n = 10,361). Notably, 14% of CP (comprising 4 distinct trajectory groups) and 8% (comprising 3 distinct groups) of non-CP had variably high monthly opioid volume for extended periods; exposure was higher for CP. The remaining had low/absent opioid exposure trajectories; for CP (non-CP), 55.7% (63.3%) had nearly absent exposure and 30.4% (28.9%) had consistently low exposure to opioids., Conclusion: Adults with versus without CP were more likely to be exposed to opioids and for a longer duration, which may alter the risk-benefit balance of opioids., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Children with bone fragility often exhibit elevated bone marrow lipid levels, which may affect mesenchymal stem cell (MSC) differentiation potential and ultimately bone strength via cell-autonomous and/or non-cell-autonomous factors. Here, we use standard co-culture techniques to study biological effects of bone marrow cell-derived secretome on MSC. Bone marrow was collected during routine orthopedic surgery, and the entire marrow cell preparation, with or without red blood cell (RBC) reduction, was plated at three different densities. Conditioned medium (secretome) was collected after 1, 3, and 7 days. ST2 cells, a murine MSC line, were then cultured in the secretomes. Exposure to the secretomes was associated with reductions of up to 62% in MSC MTT outcomes that depended on the duration of secretome development, as well as marrow cell plating density. Reduced MTT values were not associated with diminished cell number and viability assessed using Trypan Blue exclusion. Expression of pyruvate dehydrogenase kinase 4 was modestly elevated, and β-actin levels were transiently reduced in ST2 cells exposed to secretome formulations that had elicited maximal reductions in MTT outcomes. The findings from this study can inform the design of future experimental studies to examine contributions of cell-autonomous and non-cell-autonomous factors in the bone marrow to MSC differentiation potential, bone formation, and skeletal growth. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Background: Epidemiologic evidence documenting fracture risk as children with cerebral palsy (CP) age throughout growth is lacking to inform on when to implement fracture prevention strategies. The objective was to characterize the 5-year risk of fractures by each year of age among <1-13 year olds with CP and effects by patient-level factors., Methods: This retrospective cohort study used commercial administrative claims from 01/01/2001 to 12/31/2018 from children <1-13 years old with ≥5 years of insurance enrollment. Fractures were examined during the 5-year follow-up. For the CP cohort, the association between 5-year fracture rate and patient-level factors was assessed using Cox regression., Results: Children with (n = 5559) vs. without (n = 2.3 million) CP had a higher 5-year fracture risk at the vertebral column, hip, and lower extremities at almost each year of age, but lower 5-year fracture risk at the upper extremities after 6 years old (all P < 0.05). Among children with CP, the 5-year fracture rate was elevated for co-occurring neurological conditions and non-ambulatory status at the vertebral column, hip, and lower extremities (hazard ratio [HR] range, 1.44-2.39), and higher for males at the upper extremities (HR = 1.29) (all P < 0.05)., Conclusions: This study provides novel epidemiologic evidence of 5-year fracture risk for each year of age for children with CP., Impact: This study provides novel epidemiologic evidence of 5-year fracture risk for each year of age across important developmental stages for children with vs. without cerebral palsy (CP). Children with vs. without CP were more likely to fracture at the vertebral column, hip, lower extremities, and humerus and less likely to fracture at the forearm and hands. The age-related 5-year fracture risk was associated with clinically relevant patient-level factors, but in different ways by fracture region. Study findings may be used to enhance clinical detection of at-risk children and strategize when to implement fracture prevention efforts for children with CP., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Purpose: Existing evidence identifies racial and ethnic disparities impacting the prevalence and severity of cerebral palsy (CP). There is a paucity of literature examining the impact on associated treatment., Methods: In this retrospective cohort study, an institutional database search identified outpatient encounters for pediatric patients with spastic CP. Additional filters were used to determine treatments received. For each treatment, the proportion of African American (AA) patients receiving treatment was compared to the proportion of Caucasian (C) patients receiving the same treatment., Results: 3,686 children with spastic CP were seen in outpatient clinics associated with an academic tertiary hospital over a 21-year period. There was no significant difference between the proportion of any treatment compared to the entire sample for AA or C patients., Conclusion: In this sample, there was no significant evidence of a racial disparity for AA patients receiving treatments for spasticity. This data is limited by several factors. Further research is needed to determine whether pediatric patients with disabilities are receiving equitable care. Clinicians should consider systematically monitoring their practices to identify areas of bias or inequity in accessing care.

Objective: Rehabilitation may mitigate the high mortality rates and health declines post-fracture for adults with cerebral palsy, but this is understudied. The objectives were to characterize the post-fracture rehabilitation pathways and identify their association with 1-year survival among adults with cerebral palsy., Methods: A retrospective cohort study of adults with cerebral palsy with a fragility fracture with continuous health plan enrollment ≥1-year prior to and ≥1 day after their fracture date was performed using a random 20% Medicare fee-for-service dataset. Participants were categorized as a home discharge or inpatient rehabilitation admission post-fracture. For the home discharge cohort, weekly exposure to outpatient physical/occupational therapy (PT/OT) was examined up to 6-month post-fracture. Cox regression examined the association between time-varying PT/OTuse within 6-month post-fracture and mortality from 30 days to 1-year post-fracture before and after adjusting for confounders (e.g. medical complexity)., Results: Of 3598 adults with cerebral palsy with an incident fragility fracture, 74% were discharged home without inpatient rehabilitation; they were younger, but more medically complex compared to the 26% admitted to inpatient rehabilitation. Among the home discharge cohort (n = 2662), 43.1% initiated PT/OTwithin 6-month post-fracture, and cumulative PT/OTexposure post-fracture was associated with improved survival; for example, per 3 weeks of PT/OTexposure, the adjusted mortality rate was 40% lower (95% confidence interval (CI) = 0.41-0.89)., Conclusions: Most adults with cerebral palsy with a fragility fracture were discharged home rather than to inpatient rehabilitation, and only 43.1% of that group initiated outpatient PT/OTwithin 6 months post-fracture. Receiving outpatient PT/OTwas associated with improved 1-year survival.

BACKGROUND: Children with cerebral palsy (CP) may have chronic exposure to polypharmacy to address several medical needs, but there is little research on the topic to inform surveillance methods and clinical practice. OBJECTIVE: To identify the trajectories of medication number and pediatric polypharmacy (≥2 concurrent medications) exposure over 3.5 years among children with CP. METHODS: This cohort study used commercial claims from January 1, 2015, to December 31, 2018 (4-year period). Children with CP, aged 5-18 years by January 1, 2016, and with continuous health plan enrollment for all 4 years, were included and categorized as with or without co-occurring neurological/ RESULTS: Of the 1,252 children with CP, 600 were in the CP only cohort (mean [SD]; age, 11.4 [4.1] years; 46.0% female) and 652 were in the CP + NDDs cohort (age, 11.9 [4.1] years; 41.3% female; 32.7% had ≥2 of the NDDs). For the primary GBTM, 3 trajectory groups were identified for CP only: on average, no prescribed medications (69.7% of the cohort), 1 medication/month (24.8%), and 4 medications/month (5.5%). Five trajectory groups were identified for CP + NDDs: 0 (22.4%), 1 (25.6%), 2 (25.2%), 4 (18.4%), and 6 (8.4%) prescribed medications/month. For the secondary GBTM, 3 trajectory groups were identified for CP only: 80.5% were characterized as negligible probability of polypharmacy exposure, 10.8% as low probability, and 8.7% as high probability. Five trajectory groups were identified for CP + NDDs: 37.9% as negligible probability of polypharmacy exposure, 32.8% as constantly high probability, and 29.2% as changing probability (eg, increasing/decreasing). CONCLUSIONS: Children with CP are chronically exposed to differing levels of polypharmacy. Findings can help establish polypharmacy surveillance practices. Studies need to determine if polypharmaceutical strategies are balanced to optimize health and development for children with CP. DISCLOSURES: Dr Whitney is supported by the University of Michigan Office of Health Equity and Inclusion Diversity Fund. The funding source had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

Objective: The objective was to assess for an association between chemotherapy-induced peripheral neuropathy (CIPN) onset and development of depression and anxiety in breast cancer (BrCa) survivors., Methods: A retrospective observational cohort was used and identified from Optum's De-identified Clinformatics® Data Mart Database years 2012-2015. Three groups of women were derived based on BrCa and CIPN status: BrCa+/CIPN+ (n = 244), BrCa+/CIPN- (n = 8870), and BrCa-/CIPN- (n = 1,125,711). The ratio of the prevalence ratios (RPR) determined if the change in risk of depression and anxiety from the 12-month preindex period to postindex period I (0-6 months) and II (7-12 months) was different for BrCa+/CIPN+ compared to BrCa+/CIPN- and BrCa-/CIPN-., Results: The adjusted RPR for depression was significantly elevated for BrCa+/CIPN+ compared to BrCa+/CIPN- and BrCa-/CIPN- for postindex periods I (RPR = 1.35 [1.10,1.65] and 1.33 [1.08,1.63], respectively) and II (RPR = 1.53 [1.21,1.94] and 1.50 [1.17,1.93], respectively). The RPR for anxiety was significantly elevated for BrCa+/CIPN+ compared to BrCa+/CIPN- and BrCa-/CIPN- for postindex periods I (RPR = 1.37 [1.12,1.67] and 1.31 [1.06,1.61], respectively) and II (RPR = 1.41 [1.13,1.76] and 1.28 [1.02,1.62], respectively)., Conclusions: Among BrCa survivors, CIPN onset is associated with a subsequent increased 12-month risk of depression and anxiety. Depression and anxiety screening should be considered in BrCa+/CIPN+ survivors, particularly given their known impact on fall risk. The observed association between CIPN and an increased risk of depression and anxiety should be further studied in prospective studies., (© 2022 John Wiley & Sons Ltd.)

Study Objectives: Transgender or gender-nonconforming (TGNC) identity is associated with higher burden of sleep disorders relative to cisgender identity. However, the role of gender-affirming therapy (GAT) in sleep disorders is poorly understood. This study examined relationships between TGNC identity, transition, and sleep disorders among TGNC and cisgender youth., Methods: This retrospective cross-sectional study utilized a large US-based administrative claims database (deidentified Optum Clinformatics Data Mart Database) to identify youth aged 12-25 years who obtained a diagnosis of TGNC identity and those who pursued GAT. Descriptive statistics estimated distributions of demographic and health characteristics by gender identity. Unadjusted and age-adjusted logistic regression models were used to examine associations between TGNC identity, GAT, and sleep disorders., Results: This study included 1,216,044 youth, of which 2,603 (0.2%) were identified as TGNC. Among the 1,387 TGNC who pursued GAT, 868 and 519 were identified as transmasculine and transfeminine, respectively. Adjusted analysis showed increased odds of insomnia (odds ratio = 5.4, 95% confidence interval 4.7, 6.2), sleep apnea (odds ratio = 3.0, 95% confidence interval 2.3, 4.0), and other sleep disorders (odds ratio = 3.1, 95% confidence interval 2.5, 3.9) in TGNC relative to cisgender youth. Decreased odds of any sleep disorder were observed in the TGNC youth on GAT (odds ratio = 0.5, 95% confidence interval 0.4, 0.7) relative to those not on GAT., Conclusions: This study demonstrated a high burden of sleep disorders in TGNC youth in comparison to cisgender. However, GAT may confer a protective effect on sleep disorders among TGNC youth. Longitudinal assessments of sleep disorders prior to and post-GAT are needed to uncover their temporal relationships., Citation: Gavidia R, Whitney DG, Hershner S, Selkie EM, Tauman R, Dunietz GL. Gender identity and transition: relationships with sleep disorders in US youth. J Clin Sleep Med . 2022;18(11):2553-2559., (© 2022 American Academy of Sleep Medicine.)

Physical and/or occupational therapy (PT/OT) may improve post-fracture health and survival among adults with cerebral palsy (CP), but this has not been studied in the inpatient setting. The objective was to quantify the association between acute inpatient and outpatient PT/OT use with 1-year mortality among adults with CP. This was a retrospective cohort study of adults with CP with an incident fragility fracture admitted to an acute care or rehabilitation facility using a random 20% Medicare fee-for-service dataset. Acute care/rehabilitation PT/OT was measured as the average PT/OT cost/day for the length of stay (LOS). Weekly exposure to outpatient PT/OT was examined up to 6 months post-fracture. Cox regression examined the adjusted association between the interaction of acute care/rehabilitation average PT/OT cost/day and LOS with 1-year mortality. A separate Cox model added time-varying outpatient PT/OT. Of 649 adults with CP, average PT/OT cost/day was associated with lower mortality rate for LOS < 17 days (HR range = 0.78−0.93), and increased mortality rate for LOS > 27 days (HR ≥ 1.08) (all, p < 0.05). After acute care/rehabilitation, 44.5% initiated outpatient PT/OT, which was associated with lower mortality rate (HR = 0.52; 95% CI = 0.27−1.01). Post-fracture inpatient and outpatient PT/OT were associated with improved 1-year survival among adults with CP admitted to acute care/rehabilitation facilities.

Background: Epidemiologic evidence documenting the incidence of fracture and subsequent fractures among adults with cerebral palsy (CP) is lacking, which could inform fracture prevention efforts. The objective was to characterize the 5-year rate of initial and subsequent fragility fractures among adults with CP., Methods: This retrospective cohort study used Medicare claims from 01/01/2008-12/31/2019 from adults ≥18 years old with CP ( n  = 44,239) and elderly ≥65 years old without CP ( n  = 2,176,463) as a comparison. The incidence rate (IR), IR ratio (IRR), and site distribution were estimated for the initial and subsequent fragility fractures over 5-years by sex and age., Results: The IR of fragility fracture at any site over the 5-year follow-up was similar for 18-30-year-old men with CP (IR = 5.2; 95%CI = 4.4-5.9) and 30-34-year-old women with CP (IR = 6.3; 95%CI = 5.3-7.2) compared to the same sex youngest-old (65-74 years old) without CP (IRR = 1.09 and 0.94, respectively, both P  > 0.05), and increased with older age for those with CP. The number of fragility fractures and IR of subsequent fragility fractures was similar for young men and middle-aged women with CP compared to elderly without CP, and increased with older age for those with CP. The proportion of fragility fracture at the tibia/fibula decreased while the vertebral column and multiple simultaneous sites (most involved hip/lower extremities) increased with older age., Conclusion: Young and middle-aged adults with CP had similar-to-worse initial and subsequent fragility fracture profiles compared to the general elderly population- a well characterized group for bone fragility. Findings emphasize the need for fracture prevention efforts at younger ages for CP, possibly by ~5 decades younger., Competing Interests: None., (© 2022 The Authors.)

Purpose: To evaluate clinically relevant fracture characteristics by age, sex, and ambulatory status among individuals with cerebral palsy., Methods: Fracture location, energy of fracture, and activities that lead to a fracture were assessed among a clinic-based sample of children (0-17 years; n  = 57) and adults (18-70 years; n  = 58) with cerebral palsy that sustained a fracture by sex and gross motor function classification system (GMFCS) I-III vs. IV/V., Results: Proportion of fractures that were low-energy was 67-99% for children and 69-84% for adults. ∼2/3rds of fractures were at the lower extremities, with the distal femur being the most common site for children (44%) and the foot/ankle for adults (40%); however, there were age, sex, and ambulatory effects, such that 43% of adults GMFCS IV/V and 32% of women had a distal femur fracture. GMFCS I-III were more likely to fracture from functionally complex activities, while GMFCS IV/V were more likely to fracture from wheelchair/transfers/limb-stuck and incidental findings., Conclusions: The majority of fractures were low-energy and occurred in the lower extremities, with effects by age, sex, and GMFCS. Activities that led to a fracture also differed by age and GMFCS, which can be used to design fracture prevention interventions in addition to bolstering skeletal mass and architecture.Implications for rehabilitationSkeletal fragility is a major problem for individuals with cerebral palsy (CP) across the lifespan leading to an increased risk of fragility fractures.Rehabilitation is a prime clinical intervention to prevent fractures from occurring and improving post-fracture healing and function; yet, effective rehabilitation interventions require knowledge of fracture characteristics, such as where fractures are occurring and the activities that lead to the fracture event specific to individuals with CP.Using a clinic-based sample of 0-70 year olds with CP, we describe salient fracture characteristics based on age, sex, and ambulatory status to enhance translation into clinical and rehabilitation practice.

Epidemiologic evidence documenting risk of chronic diseases as children with cerebral palsy age throughout growth is lacking to inform prevention strategies. The objective was to characterize the 5-year risk of chronic diseases that are typically associated with advanced aging among < 1-13 year olds with cerebral palsy and effects by patient-level factors. This retrospective cohort study used nationwide commercial administrative claims from 01/01/2001-12/31/2018 from children < 1-13 years old with ≥ 5 years of mostly continuous insurance enrollment. The 5-year risk of chronic diseases was examined for the entire cohort with and without cerebral palsy and then by baseline age group (<1-2, 3-5, 6-8, 9-11, 12-13 years old), including cardiorespiratory, metabolic, kidney, and liver diseases, cancer, depression, and osteoarthritis. For cerebral palsy, the association between 5-year chronic disease rate and patient-level factors was assessed using Cox regression. Children with (n = 5,559) vs without (n = 2.3 million) cerebral palsy had a higher 5-year risk of all chronic diseases when comparing the entire cohorts (relative risk, 1.19 to 64.26, all P  < 0.05) and most chronic diseases when comparing cohorts for each age group. Among children with cerebral palsy, there were effects by gender, co-occurring intellectual disabilities and/or epilepsy, and wheelchair use for some chronic diseases, which can help to identify at-risk children. This study provides novel epidemiologic evidence of 5-year risk of "adult-onset" chronic diseases for children with cerebral palsy during important developmental stages, and associated patient-level factors (to enhance clinical detection). Findings may inform when to implement prevention strategies and who may be more at risk., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author.)

Background: Adults with cerebral palsy (CP) experience functional declines. Clinical rehabilitation may preserve function for this population., Objective: To identify longitudinal physical/occupational therapy use and associated factors among adults with CP, to inform health promotion strategies., Methods: A retrospective cohort study including adults ≥ 18 years of age with CP was performed using a random 20% Medicare fee-for-service dataset. Participants with continuous medicare enrolment from 01/01/2016-12/31/2018 were included: 2016 was the one-year baseline period; 2017-2018 was the two-year follow-up. Therapy included an indication of physical, occupational, or other forms of therapy. Two-year therapy use patterns were identified using group-based trajectory modeling. Multivariable multinomial logistic regression models identified associations between baseline characteristics with trajectory groups., Results: Of 17,441, 7231 (41.5%) adults with CP had therapy use across the three-year period, and six longitudinal therapy trajectories were identified: the majority (42.5%) were low-consistent users, 13.4% moderate-consistent users, 4.4% high-consistent users, and the remaining variable users. Associations between baseline characteristics (e.g., age, sex, comorbidities) with trajectory groups varied. For example, using the low-consistent users as the reference, Black versus White were 49% less likely, Northeast versus South residency were 7.52-fold more likely, and co-occurring neurologic conditions versus CP only were up to 118% more likely to be high-consistent users (all, P < 0.05). Bone fragility and some chronic comorbidities were associated with moderate consistent users., Conclusions: The majority of adults with CP were not using physical/occupational therapy. Of those that did, there were unique longitudinal trajectories which associated differently with demographics and comorbidities., Competing Interests: Conflicts of interest Neil Kamdar reports consulting services for the University of New Mexico and Lucent Surgical related to algorithm development within electronic medical records. All other authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Fractures represent a triple threat to adults with cerebral palsy (CP): common, accumulate early in adulthood, and are consequential to health. An economic evaluation of fractures in CP is needed to highlight priorities for allocating resources to clinical and public health programs aimed at preventing fractures and their disease sequela., Objective: To identify short-term healthcare costs associated with fractures among adults with CP., Methods: A retrospective cohort study was performed using Optum's de-identified Clinformatics® Data Mart Database from 01/01/2011-12/31/2017. The primary cohort included adults ≥ 18 years old with CP with an incident fracture (CP+Fx), and cost estimates were compared with: CP without fractures (CPw/oFx) and without CP+Fx (w/oCP+Fx). A difference-in-difference (DiD) analysis compared the change in pharmacy and medical costs between cohorts from the one-year baseline period through the one-year post-index period in three-month quarters., Results: CP+Fx (n = 855) had higher mean costs in the baseline and follow-up periods compared with CPw/oFx (n = 5667) and w/oCP+Fx (n = 588,042). The first post-index quarter DiD estimate suggests that CP+Fx accumulated an excess $6462 (95%CI = $3810-$9021) compared with w/oCP+Fx and $17,197 (95%CI = $14,418-$19,833) compared with CPw/oFx. The CP+Fx cohort had higher DiD estimates in the other follow-up quarters, but they were not statistically significant compared with CPw/oFx. When stratified by fracture site, vertebral column fractures for CP+Fx vs. w/oCP+Fx accumulated an excess $25,226 (95%CI = $12,639-$37,417)., Conclusions: Fractures, especially of the vertebral column, were associated with high healthcare costs among adults with CP. Studies are needed to identify cost-effective opportunities to utilize available resources to prevent fractures and their costly sequela for CP., Competing Interests: Conflicts of interest All authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To determine the association between severity of cerebral palsy with serum creatinine (sCr) and sCr-based equations to estimate glomerular filtration rate (eGFR), a marker of renal function., Methods: A clinic-based sample of 30-64 year-olds with cerebral palsy was examined and stratified by motor impairment: gross motor function classification system (GMFCS) I/II ( n  = 79), GMFCS III ( n  = 78), and GMFCS IV/V ( n  = 137). sCr, which is influenced by muscle mass, was obtained and sCr-based eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations., Results: sCr was lower with increasing GMFCS. The opposite pattern was observed for eGFR: GMFCS IV/V had significantly higher eGFR derived from MDRD compared to other GMFCS groups; GMFCS III had significantly higher eGFR compared to GMFCS I/II. The pattern was similar for CKD-EPI derived eGFR., Conclusions: According to widely used clinical assessment methods for renal function, higher severity of cerebral palsy among adults is associated with better renal function, which is incongruent with their other biological systems. This paradoxical relationship is likely driven by lower muscle rather than true renal function, and thus, sCr-based eGFR may overestimate renal function, especially for GMFCS IV/V. Further prospective studies are needed.Implications for rehabilitationCommon methods of clinical assessment may over-estimate renal function for adults with cerebral palsy (CP), potentially giving a false positive for normal renal health due to their reliance on muscle mass.This study of a clinic-based sample of middle-aged adults with CP highlights the paradoxical relationship between severity of CP and renal function, which is likely driven by methodological limitations in the presence of low muscle mass rather than actual better renal function.It is recommended that clinicians have a high suspicion of abnormal renal function and the need for a nephrology consultation, especially with changes in creatinine levels, even within the normal range.Rehabilitation for adults with CP must have a strong focus on muscle and kidney health, especially for patients with more severe forms of CP.

Background: For adults with cerebral palsy (CP), fragility fractures may be a risk factor for pneumonia, a leading cause of death for this population; yet, the timing and complications are unknown. The objectives were to determine the 30-day pneumonia rate post-fracture and its association with mortality and incident cardiovascular events among adults with CP., Methods: This retrospective cohort study used nationwide administrative claims data from 01/01/2012-12/31/2017 from a random 20% sample of the Medicare fee-for-service and Optum Clinformatics® Data Mart. Cohorts included ≥18 years of age with CP with an incident fragility fracture (CP + Fx) and comparison cohorts: CP without fractures (CPw/oFx) and without CP with an incident fragility fracture (w/oCP + Fx). Incidence rate (IR) of pneumonia 30-days post-fracture and IR ratios were estimated by age group: 18-40, 41-64, and ≥ 65 years. For CP + Fx, Cox regression examined the association between time-varying pneumonia (within 30-days post-fracture) with mortality and incidence of cardiovascular events 0-30-days and 31-365-days post-fracture., Results: There were 3688 CP + Fx (mean [SD] age, 58.2 [14.9]; 56.4% women), 29,429 CPw/oFx (50.3 [15.8]; 45.9% women), and 363,995 w/oCP + Fx (65.9 [18.3]; 65.5% women). The IR of 30-day pneumonia for CP + Fx was similar across age groups (IR per 100 person-months, 8.4-11.0) and 1.77-16.18-fold higher (all P < 0.05) than comparison cohorts. Peri/post-fracture pneumonia was associated with an increased rate of mortality (30-day-adjusted HR [aHR] = 5.89, 95%CI = 3.54-9.81; 31-365-day aHR = 2.89, 95%CI = 2.13-3.92), congestive heart failure 0-30-days (aHR = 3.64, 95%CI = 2.01-6.57) and 31-365-days (time-dependent), myocardial infarction 31-365-days (aHR = 2.03, 95%CI = 1.11-3.71), and cerebrovascular disease 0-30-days (time-dependent), without evidence of effect modification by age, sex, or fracture site., Conclusions: Adults with CP are particularly vulnerable to 30-day risk of post-fracture pneumonia and its complications across the adult lifespan and not just in the elderly years., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Preventive care techniques are cornerstones of primary care for people with neurodevelopmental disabilities such as cerebral palsy (CP). However, well-established methods evaluating health constructs may not be applied in the same way for adults with CP, as compared to the general population, due to differences in anatomy/physiology, leading to missed opportunities for interventions, medication modifications, and other primary/secondary prevention goals. One barrier to care prevention comes from misinterpretation of values to capture health constructs, even when measurements are accurate. In this Perspective, we emphasize the need for differential interpretation of values from commonly used clinical measures that assess for well-known medical issues among adults with CP obesity risk, bone health, and kidney health. We provide technical, but simple, evidence to showcase why the underlying assumptions of how some measures relate to the health construct being assessed may not be appropriate for adults with CP, which may apply to other neurodevelopmental conditions across the lifespan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Whitney, Rabideau, Mckee and Hurvitz.)

Aim: To understand associations among bone mineral density (BMD), bone mineral content (BMC), and bone area, and their association with fractures in adults with cerebral palsy (CP)., Method: This retrospective cohort study included 78 adults with CP with a hip dual energy X-ray absorptiometry (DXA) from 1st December 2012 to 3rd May 2021 performed at the University of Michigan. Data-driven logistic regression techniques identified which, if any, DXA-derived bone traits (e.g. age/sex/ethnicity-based z-scores) were associated with fracture risk by sex and severity of CP. BMC-area associations were examined to study the structural mechanisms of fragility., Results: Femoral neck area was associated with lower age-adjusted odds ratios (ORs) of fracture history (OR 0.72; 95% confidence interval [CI] 0.49-1.06; p=0.098), while higher BMD was associated with higher odds of incident fracture (OR 3.08; 95% CI 1.14-8.33; p=0.027). Females with fracture had lower area than females without fracture but similar BMC, whereas males with fracture had larger area and higher BMC than males without fracture. The paradoxical BMD-fracture association may be due to artificially elevated BMD from BMC-area associations that differed between females and males (sex interaction, p˂0.05): males had higher BMC at lower area values and lower BMC at higher area values compared to females., Interpretation: BMD alone may not be adequate to evaluate bone strength for adults with CP. Further research into associations (or integration) between BMC and area is needed., (© 2021 Mac Keith Press.)

Children with autism spectrum disorder (ASD) have a higher prevalence of pain compared to those without ASD. Pain is a leading cause of morbidity and disability worldwide and may contribute to adverse health outcomes in people with ASD, thus warranting further research on this special population. The present study used data from 1,423 children with ASD and 46,023 children without ASD and their mothers from the combined 2016-2017 National Survey of Children's Health. Mothers reported child pain and ASD status and their own mental health status. Mothers reporting a status of "Fair or Poor" were considered as having maternal mental health conditions (MMHCs) for the purposes of this study. Children with and without ASD who had mothers with MMHCs had higher odds of pain compared to children with mothers without MMHCs. These increased odds did not attenuate as a result of controlling for co-occurring neurological conditions, which have been associated with increased pain in children with ASD. Thus, parent mental health may alter perception and/or reports of pain on behalf of children with and without ASD. Future research should include more detailed assessments of parent mental health and clinical assessments of children in order to explore the role of parent mental health in the experiences of pain and other symptoms present in children with ASD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Luke P. Grosvenor et al.)

Objective: Aging with cerebral palsy is accompanied by a declining health and function status across neurological and non-neurological systems. There is a need to understand the shared pathophysiology among comorbidities for adults with cerebral palsy, to inform clinical assessment and guidelines for interventions to improve healthful aging. To begin defining multimorbidity, this study identified the most common comorbidity combinations and their association with mortality among a representative sample of adults with cerebral palsy. Methods: Data from 2016 to 2018 were used from a random 20% sample from the fee-for-service Medicare database. Adults ≥18 years with cerebral palsy and 25 neurological and non-neurological comorbidities were obtained from 2016. Principal component (PC) analysis identified the most common comorbidity combinations, defined as individual PCs. Cox regression estimated the hazard ratio (HR) of 2-year mortality including all PCs and demographics in a single model. To facilitate comparisons, PC scores were transformed into quintiles (reference: lowest quintile). Results: Among the 16,728 adults with cerebral palsy, the most common comorbidity combinations (PCs) in order were: cardiorespiratory diseases, dysphagia, and fluid/electrolyte disorders; metabolic disorders (e.g., diabetes, renal disease, hypertension); neurologic-related disorders (e.g., dementia, cerebrovascular disease); gastrointestinal issues; and orthopedic-related disorders. During the 2-year follow-up, 1,486 (8.9%) died. In the adjusted model, most PCs were associated with an elevated mortality rate, especially the first PC (5th quintile HR = 3.91; 95%CI = 3.29-4.65). Discussion: This study identified the most common comorbidity combinations for adults with cerebral palsy, many of them were deadly, which may inform on the underlying pathophysiology or shared characteristics of multimorbidity for this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Whitney, Schmidt and Hurvitz.)

As individuals with cerebral palsy (CP) age, they face unique challenges which complicate their ability to access and receive appropriate health care. These problems exist at the level of the health care system, the clinician, and the individual. At the system level, there is an inadequate number of professionals who are informed of and interested in the care of adults with CP. Pediatric clinicians prefer treating children, and adult caregivers are not knowledgeable about and may feel less competent about CP. Pediatric care does not translate well to the adult population, and information about best practices for adults is just starting to develop. Differences in the physiologic development of individuals with CP render well-established clinical protocols for risk screening of chronic diseases less effective. Moreover, lack of supportive resources decreases a caregiver's sense of self-efficacy in treating this population. The patient's ability to navigate these barriers is complicated by the high prevalence of comorbid cognitive impairment and mental health issues including anxiety, depression, and other psychiatric disorders; a bidirectional relationship between challenges in navigating care/needs and comorbid mental health conditions appears likely. Many patients have additional barriers related to social determinants of health, such as access to transportation, accessible health care facilities, and other personal and environmental factors that may impede health maintenance and wellness. Increasing and disseminating knowledge, harnessing the power of new technologies such as telemedicine, and addressing mental health issues are some of the methods that are available to help adults with CP navigate this road., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hurvitz, Whitney, Waldron-Perrine, Ryan, Haapala, Schmidt, Gray and Peterson.)

Objective: Recent evidence shows that adults with cerebral palsy (CP) have an increased risk for kidney disease, but nothing is known about how kidney disease integrates with their overall health. To begin understanding the importance of kidney health, the objective was to determine if kidney disease is associated with mortality among adults with CP after accounting for comorbidities common to CP and kidney disease. Methods: Data from 2016 to 2018 from adults ≥18 years with CP were used from a random 20% sample fee-for-service Medicare database. Kidney disease in 2016 was ascertained as chronic kidney disease (CKD) stages 1-4, end stage kidney disease (ESKD), nephritic and nephrotic syndrome, and renal osteodystrophy. A modified version of the Whitney Comorbidity Index (modWCI) was used, which includes 24 comorbidities relevant to CP and kidney disease. Mortality rate ratio (MRR) through the year 2018 was estimated for each kidney disease and Cox regression estimated the hazard ratio (HR) of mortality after adjusting for demographics, co-occurring neurological conditions, and the modWCI. Results: Prevalence of kidney disease was 7.3% among 16,728 adults with CP. MRR was elevated for any kidney disease (MRR = 3.14; 95%CI = 2.76-3.58) and most subtypes (MRR = 2.21-3.56; all p < 0.05). The adjusted HR of mortality remained elevated for any kidney disease (HR = 1.25; 95%CI = 1.09-1.45) and ESKD (HR = 1.38; 95%CI = 1.10-1.74). Discussion: Kidney disease, especially ESKD, is associated with mortality among adults with CP independent of comorbidities that are relevant to CP and kidney disease. Findings suggest that nephrology care should be considered as part of routine clinical care for this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Whitney and Oliverio.)

Objective: The objective of this study was to determine whether two commonly prescribed antiseizure medications (ASMs), levetiracetam (LEV) and oxcarbazepine (OXC), were associated with an increased risk of fragility fracture in children with epilepsy when initiating therapy during a crucial period of bone development, namely, pre- and midpuberty., Methods: Claims data from January 1, 2009 to December 31, 2018 were extracted from the Optum Clinformatics Data Mart. Children aged 4-13 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1-year baseline (e.g., pre-ASM exposure) and 4 years of follow-up. Children with epilepsy who were ASM naïve were grouped based on whether ASM treatment initiation included LEV or OXC. The comparison group included children without epilepsy and without ASM exposure. Crude incidence rate (IR; n per 1000 person-years) and IR ratio (IRR; with 95% confidence interval [CI]) were estimated for nontrauma fracture (NTFx), a claims-based proxy for fragility fracture, for up to 4 years of follow-up. Cox proportional hazards regression estimated the hazard ratio (HR; with 95% CI) after adjusting for demographic variables, motor impairment, and baseline fracture., Results: The crude IR (95% CI) of NTFx was 21.5 (21.2-21.8) for non-ASM-users without epilepsy (n = 271 346), 19.8 (12.3-27.2) for LEV (n = 358), and 34.4 (21.1-47.7) for OXC (n = 203). Compared to non-ASM-users, the crude IRR of NTFx was similar for LEV (IRR = .92, 95% CI = .63-1.34) and elevated for OXC (IRR = 1.60, 95% CI = 1.09-2.35); the crude IRR of NTFx was elevated for OXC compared to LEV (IRR = 1.74, 95% CI = 1.02-2.99). The findings were consistent after adjusting for covariates, except when comparing OXC to LEV (HR = 1.71, 95% CI = .99-2.93), which was marginally statistically insignificant (p = .053)., Significance: Initiating OXC, but not LEV, therapy among 4-13-year-olds with epilepsy is associated with an elevated risk of fragility fracture. Studies are needed to determine whether these children could benefit from adjunct bone fragility therapies., (© 2021 International League Against Epilepsy.)

Study Objectives: To examine, among girls and boys, associations between site-specific extremity fracture and sleep apnea diagnosis or treatment., Methods: A cross-sectional analysis of claims data from 2016 to 2018 for children aged 2-18 years. Children with sleep apnea, continuous positive airway pressure, adenotonsillectomy, and fracture were identified using International Classification of Diseases, 10th Revision, Current Procedural Terminology, and Healthcare Common Procedure Coding System codes. We examined sex-stratified associations between site-specific fracture, sleep apnea, and sleep apnea treatment., Results: Among 2,327,104 children, 9,547 (0.41%) had sleep apnea and nearly 61% were treated. Girls with sleep apnea, treated or untreated, had increased odds of lower, but not upper, extremity fracture compared to those without sleep apnea (treated 1.56, 95% confidence interval 1.11, 2.21; untreated odds ratio 1.63, 95% confidence interval 1.09, 2.44). Only boys untreated for sleep apnea had increased odds of lower extremity fracture in comparison to those without a diagnosis of sleep apnea (odds ratio 1.65, 95% confidence interval 1.20, 2.27). Interestingly, boys treated for sleep apnea but not those untreated, in comparison to boys without sleep apnea, had different (reduced) odds of upper extremity fracture (odds ratio 0.74, 95% confidence interval 0.59, 0.95)., Conclusions: These large datasets provide evidence that both boys and girls with untreated sleep apnea have higher odds of lower extremity fractures. However, treatment for sleep apnea was associated with improved odds of lower extremity fracture only in boys. Upper extremity data were less clear. These data are cross-sectional and cannot show causality, but they suggest that treatment for sleep apnea may lower risk for extremity fractures in boys., Citation: Matlen LB, Whitney DG, Whibley D, Jansen EC, Chervin RD, Dunietz GL. Obstructive sleep apnea and fractures in children and adolescents. J Clin Sleep Med . 2021;17(9):1853-1858., (© 2021 American Academy of Sleep Medicine.)

Background: Skeletal fragility is a major burden for individuals with cerebral palsy (CP), but little is known clinically about when to prevent fractures or monitor bone health for this population. Critical periods of bone health (CPBH) are important windows for intervention to augment bone growth or mitigate bone loss. However, CPBH from the general population may not align with the needs or timing of skeletal fragility for individuals with CP. The objective of this study was to identify discrepancies when evaluating individuals with CP using CPBH across the lifespan from the general population, and propose new CP-specific CPBH., Methods: Data from 2016 administrative claims databases were used, including the Optum's De-identified Clinformatics® Data Mart Database and a random 20% sample of the Medicare fee-for-service database from the Centers for Medicare and Medicaid Services. Sex-stratified fracture prevalence was compared between individuals with and without CP across the lifespan starting at 2 years of age using age groups to capture important stages of development and 3-4-year age bands in adulthood (up to >80 years). Sex-specific CPBH from the general population included: rapid bone accrual, peak bone mass, menopause, and elderly., Results: There were 23,861 individuals with CP and 9,976,161 individuals without CP. CPBH from the general population did not align with the timing of skeletal fragility for CP. For example, fractures were rare and decreased throughout the CPBH of peak bone mass for males without CP, but males with CP had a greater relative fracture risk (2.9-5.6-fold higher) and a substantially increased rate of fracture (CP-slope 14× higher than non-CP-slope). For females with CP, fracture risk was increased by 18-21 years, with additional inflection points (e.g., decade before menopause and again by 57-60 years). For males with CP, fracture risk in mid-life exhibited a pattern similar to elderly males without CP., Conclusions: This study identified discrepancies in evaluating fracture risk for individuals with CP if using established CPBH from the general population. We therefore propose new CP- and sex-specific CPBH for fracture monitoring and prevention., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Adults with epilepsy have an increased risk of fragility fractures, which contributes to an accelerated rate of premature morbidity and mortality. In the general population, osteoporosis treatment has shown improvements in health and survival, possibly through improving skeletal robustness; however, the effect of osteoporosis medication on survival among adults with epilepsy has not been investigated. The purpose of this propensity score-matched, observational cohort study was to determine if osteoporosis medication was associated with mortality risk among adults with epilepsy. An exploratory analysis then examined the association between the type of osteoporosis medication with mortality., Methods: Data from 01/01/2012-09/30/2017 was extracted from Optum Clinformatics® Data Mart. Adults ≥50 years of age with epilepsy that were treatment naïve for and initiated osteoporosis medication (EP new users) were the primary group of interest, and were compared to adults with epilepsy that were not prescribed osteoporosis medication (EP no users) and adults without epilepsy that were treatment naïve for and initiated osteoporosis medication (w/o EP new users). Comparison groups were matched 1:4 to EP new users (n = 733; comparison groups, n = 2932) for demographics, glucocorticoid and antiseizure medication, prior 12-month fracture, and the Elixhauser comorbidity index. Crude incidence rate (IR) and IR ratio (IRR and 95% confidence intervals [CI]) was estimated for mortality for up to 3 years of follow-up. For new users, the association between type of osteoporosis medication (bisphosphonates vs. others) and mortality was explored using Cox proportional hazards regression after adjusting for all covariates., Results: For new users, the majority of the prescribed osteoporosis medications were bisphosphonates (~83%). The incidence of mortality for EP new users was lower compared to EP no users (IRR = 0.69; 95%CI = 0.52-0.93), but elevated compared to w/o EP new users (IRR = 1.42; 95%CI = 1.04-1.94). Comparing bisphosphonates to other medications for new users (P for EP group interaction = 0.089), EP new users showed a lower fully adjusted hazard ratio for mortality (HR = 0.56; 95%CI = 0.30-1.04), but was marginally insignificant (P = 0.066), while w/o EP new users showed no evidence of an association (HR = 1.09; 95%CI = 0.72-1.65)., Conclusions: Osteoporosis medication initiation was associated with a lower 3-year risk of mortality among adults with epilepsy. The exploratory analysis revealed potential evidence of a unique protective effect of bisphosphonates as compared to other osteoporosis medications on 3-year mortality for adults with epilepsy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Anti-seizure medication (ASM) is necessary to manage epilepsy and often prescribed to children and adolescents, but can lead to iatrogenic effects, including bone fragility by altering bone metabolism. Disrupting bone metabolism during crucial developmental stages could have a lasting adverse effect on bone health. Therefore, the objective of this propensity score-matched, observational cohort study was to determine if age when initiating ASM therapy across developmental stages (from pre- to post-puberty) for individuals with epilepsy was associated with an increased risk of fragility fracture., Methods: Data from 01/01/2011 to 12/31/2018 were extracted from Optum Clinformatics® Data Mart. Children aged 4-21 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1-year baseline and 4-years of follow-up. The primary group of interest included new ASM users (i.e., treatment naïve) with epilepsy. The comparison group, no ASM users without epilepsy, was matched 1:14 to new ASM users with epilepsy for demographics and baseline fracture. To provide a proxy for developmental stages, age was categorized as 4-6 (pre-puberty), 7-10 (early puberty), 11-13 (mid-puberty), 14-17 (late puberty), and 18-21 (post-puberty). Crude incidence rate (IR; per 1000 person years) and IR ratio (IRR and 95% confidence intervals [CI]) were estimated for non-trauma fracture (NTFx) for up to 4-years of follow-up., Results: Prior to stratifying by age group, the crude NTFx IR (95% CI) of 20.6 (16.5-24.8) for new ASM users with epilepsy (n = 1205) was 34% higher (IRR = 1.34; 95% CI = 1.09-1.66) than the crude NTFx IR (95% CI) of 15.4 (14.4-16.3) for no ASM users without epilepsy. The groups exhibited a different pattern of NTFx incidence with age, with new ASM users showing a more dramatic increase and peaking at 11-13 years, then decreasing with the older age groups. The crude IR and IRR were elevated for new ASM users with epilepsy compared to no ASM users without epilepsy for each age group (10% to 55% higher), but was only statistically significant for 11-13 years (IRR = 1.55; 95% CI = 1.02-2.36)., Conclusions: Children with epilepsy initiating ASM therapy may be vulnerable to fragility fracture, especially when initiating ASM around the time of puberty. Clinicians should be aware of this age-related association and consider age-appropriate adjunct bone fragility therapies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Lysosomal acid lipase (LAL) is essential for cholesteryl ester (CE) and triacylglycerol (TAG) hydrolysis in the lysosome. Clinically, an autosomal recessive LIPA mutation causes LAL deficiency (LALD), previously described as Wolman Disease or Cholesteryl Ester Storage Disease (CESD). LAL-D is associated with ectopic lipid accumulation in the liver, small intestine, spleen, adrenal glands, and blood. Considering the importance of unesterified cholesterol and fatty acids in bone metabolism, we hypothesized that LAL is essential for bone formation, and ultimately, skeletal health. To investigate the role of LAL in skeletal homeostasis, we used LAL-deficient ( -/- ) mice, in vitro osteoblast cultures, and novel clinical data from LAL-D patients. Both male and female LAL -/- mice demonstarted lower trabecular and cortical bone parameters , which translated to reduced biomechanical properties. Further histological analyses revealed that LAL -/- mice had fewer osteoblasts, with no change in osteoclast or marrow adipocyte numbers. In studying the cell-autonomous role of LAL, we observed impaired differentiation of LAL -/- calvarial osteoblasts and in bone marrow stromal cells treated with the LAL inhibitor lalistat. Consistent with LAL's role in other tissues, lalistat resulted in profound lipid puncta accumulation and an altered intracellular lipid profile. Finally, we analyzed a large de-identified national insurance database (i.e. 2016/2017 Optum Clinformatics®) which revealed that adults (≥18 years) with CESD (n = 3076) had a higher odds ratio (OR = 1.21; 95% CI = 1.03-1.41) of all-cause fracture at any location compared to adults without CESD (n = 13.7 M) after adjusting for demographic variables and osteoporosis. These data demonstrate that alterations in LAL have significant clinical implications related to fracture risk and that LAL's modulation of lipid metabolism is a critical for osteoblast function., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite the greater risk of an array of morbidities, little is known about when morbidities occur for adults with cerebral palsy. The objective of this study is to determine the timecourse of morbidity risk/development for adults with cerebral palsy and the effect by patient-level factors., Methods: Cross-sectional data from 2016 were used from a random 20% sample from the fee-for-service Medicare database. Diagnosis codes identified adults aged ≥18 years with cerebral palsy and 16 clinically relevant morbidities. Qualitative and quantitative approaches identified the age where each morbidity became exceedingly prevalent. The effect of the timecourse by sex, race, and co-occurring intellectual disabilities and epilepsy was examined. Data were sequestered and analyzed in 2020., Results: Among 16,818 adults with cerebral palsy, the prevalence of most morbidities was already high among those aged 18-30 years, and all morbidities increased with age except liver disease and anxiety. Hypertension and diabetes exhibited a positive linear trend with age. Of the morbidities that did not exhibit a linear trend, the qualitative and quantitative approaches were consistent considering that the cardiorespiratory diseases, osteoarthritis, renal disease, and dementia became exceedingly more prevalent at age >50 years, whereas the threshold was >60 years for depression, cancer, and metastatic cancer. There were interactions with sex, race, and co-occurring intellectual disabilities and epilepsy for some of the morbidities., Conclusions: Morbidity prevalence is already elevated early in adulthood among individuals living with cerebral palsy, with an abrupt increase by age 50 years. Preventive efforts should be adopted early in the lifespan and not later than age 50 years for adults with cerebral palsy., (Copyright © 2021 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To validate the Whitney Comorbidity Index (WCI), which was recently developed to monitor disease status for adults with cerebral palsy (CP), and to identify WCI scores associated with an increased mortality risk using a representative sample of adults with CP., Method: Data from 2016 to 2018 were used from a random 20% sample from the fee-for-service Medicare database for this retrospective cohort study. The WCI was examined as unweighted (WCI unw ) and weighted (WCI w ) among adults at least 18 years old with CP. Cox regression models were developed with mortality as the outcome after adjusting for demographics. A concordance statistic (C-statistic) of at least 0.70 was considered as showing sufficient validity. The hazard ratio of mortality for each WCI score was estimated. Secondary analyses were performed for subgroups with co-occurring epilepsy and/or intellectual disabilities., Results: For the entire group (n=16 728) and subgroups, the WCI showed sufficient validity (C-statistic 0.73-0.81). For the entire group, the mortality rate was elevated for a score of 1 compared with 0 from the WCI unw (hazard ratio 3.06; 95% confidence interval [CI] 1.52-6.17) and WCI w (hazard ratio 4.08; 95% CI 1.69-9.85), and became larger with each WCI score. Results were similar for the subgroups., Interpretation: The WCI is a valid marker for health/disease status for adults with CP. Several WCI score thresholds were identified to assist in clinical decision making for preventive medicine and intervention implementation. What this paper adds The Whitney Comorbidity Index (WCI) is valid among 16 728 adults with CP. The WCI is valid for those with co-occurring epilepsy and/or intellectual disabilities. Thresholds of the WCI score were identified to assist clinical decision making., (© 2021 Mac Keith Press.)