Opioid prescription patterns among commercially insured children with and without cerebral palsy.

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.

Comorbidity Clusters Among Adults With Cerebral Palsy: A Latent Class Analysis.

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.

Risk of post-fracture pneumonia and its association with cardiovascular events and mortality in adults with intellectual disabilities.

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.

Perspective: A multi-trait integrative approach to understanding the structural basis of bone fragility for pediatric conditions associated with abnormal bone development.

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.

The age-related association between serum creatinine and cardiorespiratory morbidity and mortality and fractures among adults with cerebral palsy.

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.

Longitudinal Patterns of Postfracture Outpatient Physical Therapy and Occupational Therapy Use and Its Association With 3-Year Mortality Among Adults With Cerebral Palsy.

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.

Policy brief: adaptive cycling equipment for individuals with neurodevelopmental disabilities as durable medical equipment.

- 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.

A Conceptual Approach for Examining Effects of the Adolescent Bone Marrow Milieu on MSC Phenotype.

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 ß-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.

High cardiorespiratory disease burden following a fracture among adults with intellectual disabilities.

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.

Population- and individual-level trajectories of opioid prescription patterns among adults with cerebral palsy: a retrospective cohort study.

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.

5-year fracture risk among children with cerebral palsy.

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.

Trajectories of medication use and polypharmacy among children with cerebral palsy.

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.

Post-fracture rehabilitation pathways and association with mortality among adults with cerebral palsy.

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.

Identifying racial disparities in care for children with spastic cerebral palsy: A single center study.

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.

Post-Fracture Inpatient and Outpatient Physical/Occupational Therapy and Its Association with Survival among Adults with Cerebral Palsy.

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.

Five-year risk of fracture and subsequent fractures among adults with cerebral palsy.

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.

Gender identity and transition: relationships with sleep disorders in US youth.

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.

5-year risk of "adult-onset" chronic diseases during childhood and adolescent transitioning for individuals with cerebral palsy.

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.

Chemotherapy-induced peripheral neuropathy onset is associated with early risk of depression and anxiety in breast cancer survivors.

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.

Preventive Care for Adults With Cerebral Palsy and Other Neurodevelopmental Disabilities: Are We Missing the Point?

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.