Electroencephalographic Correlates of Clinical Severity in the Natural history study of RTT and Related Disorders.

OBJECTIVE: This study was undertaken to characterize quantitative electroencephalographic (EEG) features in participants from the Natural history study of RTT and Related Disorders and to assess the potential for these features to act as objective measures of cortical function for Rett syndrome (RTT). METHODS: EEG amplitude and power features were derived from the resting EEG of 60 females with RTT (median age = 10.7 years) and 26 neurotypical females (median age = 10.6 years). Analyses focus on group differences and within the RTT group, associations between the EEG parameters and clinical severity. For a subset of participants (n = 20), follow-up data were available for assessing the reproducibility of the results and the stability in the parameters over 1 year. RESULTS: Compared to neurotypical participants, participants with RTT had greater amplitude variability and greater low-frequency activity as reflected by greater delta power, more negative 1/f slope, and lower theta/delta, alpha/delta, beta/delta, alpha/theta, and beta/theta ratios. Greater delta power, more negative 1/f slope, and lower power ratios were associated with greater severity. Analyses of year 1 data replicated the associations between 1/f slope and power ratios and clinical severity and demonstrated good within-subject consistency in these measures. INTERPRETATION: Overall, group comparisons reflected a greater predominance of lower versus higher frequency activity in participants with RTT, which is consistent with prior clinical interpretations of resting EEG in this population. The observed associations between the EEG power measures and clinical assessments and the repeatability of these measures underscore the potential for EEG to provide an objective measure of cortical function and clinical severity for RTT. ANN NEUROL 2024.

Mapping the cellular biogeography of human bone marrow niches using single-cell transcriptomics and proteomic imaging.

Non-hematopoietic cells are essential contributors to hematopoiesis. However, heterogeneity and spatial organization of these cells in human bone marrow remain largely uncharacterized. We used single-cell RNA sequencing (scRNA-seq) to profile 29,325 non-hematopoietic cells and discovered nine transcriptionally distinct subtypes. We simultaneously profiled 53,417 hematopoietic cells and predicted their interactions with non-hematopoietic subsets. We employed co-detection by indexing (CODEX) to spatially profile over 1.2 million cells. We integrated scRNA-seq and CODEX data to link predicted cellular signaling with spatial proximity. Our analysis revealed a hyperoxygenated arterio-endosteal neighborhood for early myelopoiesis, and an adipocytic localization for early hematopoietic stem and progenitor cells (HSPCs). We used our CODEX atlas to annotate new images and uncovered mesenchymal stromal cell (MSC) expansion and spatial neighborhoods co-enriched for leukemic blasts and MSCs in acute myeloid leukemia (AML) patient samples. This spatially resolved, multiomic atlas of human bone marrow provides a reference for investigation of cellular interactions that drive hematopoiesis.

Neurodevelopment of children exposed to prolonged anesthesia in infancy: GABA study interim analysis of resting-state brain networks at 2, 4, and 10-months old.

BACKGROUND: Previous studies have raised concerns regarding neurodevelopmental impacts of early exposures to general anesthesia and surgery. Electroencephalography (EEG) can be used to study ontogeny of brain networks during infancy. As a substudy of an ongoing study, we examined measures of functional connectivity in awake infants with prior early and prolonged anesthetic exposures and in control infants. METHODS: EEG functional connectivity was assessed using debiased weighted phase lag index at source and sensor levels and graph theoretical measures for resting state activity in awake infants in the early anesthesia (n = 26 at 10 month visit, median duration of anesthesia = 4 [2, 7 h]) and control (n = 38 at 10 month visit) groups at ages approximately 2, 4 and 10 months. Theta and low alpha frequency bands were of primary interest. Linear mixed models incorporated impact of age and cumulative hours of general anesthesia exposure. RESULTS: Models showed no significant impact of cumulative hours of general anesthesia exposure on debiased weighted phase lag index, characteristic path length, clustering coefficient or small-worldness (conditional R2 0.05-0.34). An effect of age was apparent in many of these measures. CONCLUSIONS: We could not demonstrate significant impact of general anesthesia in the first months of life on early development of resting state brain networks over the first postnatal year. Future studies will explore these networks as these infants grow older.

The infant gut microbiome and cognitive development in malnutrition.

Malnutrition affects 195 million children under the age of five worldwide with long term effects that include impaired cognitive development. Brain development occurs rapidly over the first 36 months of life. Whilst seemingly independent, changes to the brain and gut microbiome are linked by metabolites, hormones, and neurotransmitters as part of the gut-brain axis. In the context of severe malnutrition, the composition of the gut microbiome and the repertoire of biochemicals exchanged via the gut-brain axis vary when compared to healthy individuals. These effects are primarily due to the recognized interacting determinants, macro- and micronutrient deficiencies, infection, infestations and toxins related to poor sanitation, and a dearth of psycho-social stimulation. The standard of care for the treatment of severe acute malnutrition is focused on nutritional repletion and weight restoration through the provision of macro- and micronutrients, the latter usually in excess of recommended dietary allowances (RDA). However, existing formulations and supplements have not been designed to specifically address key recovery requirements for brain and gut microbiome development. Animal model studies indicate that treatments targeting the gut microbiome could improve brain development. Despite this, research on humans targeting the gut microbiome with the aim of restoring brain functionality are scarce. We conclude that there is a need for assessment of cognition and the use of various tools that permit visualization of the brain anatomy and function (e.g., Magnetic resonance imaging (MRI), functional near-infrared spectroscopy (fNIRS), electroencephalogram (EEG)) to understand how interventions targeting the gut microbiome impact brain development.

Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging.

The bone marrow is the organ responsible for blood production. Diverse non-hematopoietic cells contribute essentially to hematopoiesis. However, these cells and their spatial organization remain largely uncharacterized as they have been technically challenging to study in humans. Here, we used fresh femoral head samples and performed single-cell RNA sequencing (scRNA-Seq) to profile 29,325 enriched non-hematopoietic bone marrow cells and discover nine transcriptionally distinct subtypes. We next employed CO-detection by inDEXing (CODEX) multiplexed imaging of 18 individuals, including both healthy and acute myeloid leukemia (AML) samples, to spatially profile over one million single cells with a novel 53-antibody panel. We discovered a relatively hyperoxygenated arterio-endosteal niche for early myelopoiesis, and an adipocytic, but not endosteal or perivascular, niche for early hematopoietic stem and progenitor cells. We used our atlas to predict cell type labels in new bone marrow images and used these predictions to uncover mesenchymal stromal cell (MSC) expansion and leukemic blast/MSC-enriched spatial neighborhoods in AML patient samples. Our work represents the first comprehensive, spatially-resolved multiomic atlas of human bone marrow and will serve as a reference for future investigation of cellular interactions that drive hematopoiesis.

Resting Frontal Gamma Power is Associated with Both Expressive Language and Non-verbal Cognitive Abilities in Young Autistic Children.

Previous research links resting frontal gamma power to key developmental outcomes in young neurotypical (NT) children and infants at risk for language impairment. However, it remains unclear whether gamma power is specifically associated with language or with more general cognitive abilities among young children diagnosed with autism spectrum disorder (ASD). The current study evaluates differences in resting frontal gamma power between young autistic and NT children and tests whether gamma power is uniquely associated with individual differences in expressive language, receptive language and non-verbal cognitive abilities in autistic and NT children. Participants included 48 autistic children and 58 age- and sex-matched NT children (ages 22-60 months). Baseline electroencephalography (EEG) recordings were acquired from each participant. Children also completed the Mullen Scales of Early Learning (MSEL). We found that frontal gamma power at rest did not differ between autistic and NT children. Among autistic children, reduced frontal gamma power was significantly associated with both higher expressive language skills and higher non-verbal cognitive skills, controlling for age and sex. The interaction between frontal gamma power and diagnostic status no longer explained unique variance in expressive language skills after controlling for variance associated with non-verbal cognitive skills across autistic and NT children. Together, these findings suggest that reduced gamma power is associated with both better expressive language and non-verbal cognitive skills among young autistic children. Moreover, associations between high frequency neural activity and cognition are not specific to verbal abilities but reflect neural mechanisms associated with general higher-order cognitive abilities in ASD.

Linking caregiving quality during infancy to brain activity in early childhood and later executive function.

There is no relationship more vital than the one a child shares with their primary caregivers early in development. Yet many children worldwide are raised in settings that lack the warmth, connection, and stimulation provided by a responsive primary caregiver. In this study, we used data from the Bucharest Early Intervention Project (BEIP), a longitudinal study of institutionally-reared and family-reared children, to test how caregiving quality during infancy is associated with average EEG power over the first 3.5 years of life in alpha, beta, and theta frequency bands, and associations with later executive function (EF) at age 8 years. The sample comprised 189 children (129 institutionally-reared; 60 family-reared) who contributed data on observed caregiving quality during infancy (baseline; average age of 22 months), resting EEG power at baseline, 30, and 42 months, and performance-based data on a series of EF tasks at 8 years. Using Bayesian estimation, observed caregiving quality at baseline was marginally linked with higher average alpha and beta power, and lower theta power, from baseline to 42 months. In turn, higher average beta power and lower average theta power were marginally associated with higher EF at 8 years. In indirect effects models, higher caregiving quality at baseline was associated with higher EF at 8 years, with a marginal indirect effect through average theta power from baseline to 42 months. Variation in the quality of the early caregiving environment may be associated with later executive function, which is partially underpinned by individual differences in brain activity during early childhood. RESEARCH HIGHLIGHTS: Examined associations between caregiving quality during infancy, brain activity during early childhood, and executive function during mid-childhood in sample of never-institutionalized and institutionally-reared children. Significant associations between higher quality caregiving during infancy and higher executive function during middle childhood. Marginal associations between caregiving quality during infancy and brain activity during early childhood. Marginal associations between brain activity during early childhood and executive function during mid-childhood.

Perinatal inflammation, fetal growth restriction, and long-term neurodevelopmental impairment in Bangladesh.

BACKGROUND: There are limited data on the impact of perinatal inflammation on child neurodevelopment in low-middle income countries and among growth-restricted infants. METHODS: Population-based, prospective birth cohort study of 288 infants from July 2016-March 2017 in Sylhet, Bangladesh. Umbilical cord blood was analyzed for interleukin(IL)-1α, IL-1ß, IL-6, IL-8, and C-reactive protein(CRP). Child neurodevelopment was assessed at 24 months with Bayley-III Scales of Infant Development. We determined associations between cord blood inflammation and neurodevelopmental outcomes, controlling for potential confounders. RESULTS: 248/288 (86%) live born infants were followed until 24 months, among whom 8.9% were preterm and 45.0% small-for-gestational-age(SGA) at birth. Among all infants, elevated concentrations (>75%) of CRP and IL-6 at birth were associated with increased odds of fine motor delay at 24 months; elevated CRP was also associated with lower receptive communication z-scores. Among SGA infants, elevated IL-1α was associated with cognitive delay, IL-8 with language delay, CRP with lower receptive communication z-scores, and IL-1ß with lower expressive communication and motor z-scores. CONCLUSIONS: In rural Bangladesh, perinatal inflammation was associated with impaired neurodevelopment at 24 months. The associations were strongest among SGA infants and noted across several biomarkers and domains, supporting the neurobiological role of inflammation in adverse fetal development, particularly in the setting of fetal growth restriction. IMPACT: Cord blood inflammation was associated with fine motor and language delays at 24 months of age in a community-based cohort in rural Bangladesh. 23.4 million infants are born small-for-gestational-age (SGA) globally each year. Among SGA infants, the associations between cord blood inflammation and adverse outcomes were strong and consistent across several biomarkers and neurodevelopmental domains (cognitive, motor, language), supporting the neurobiological impact of inflammation prominent in growth-restricted infants. Prenatal interventions to prevent intrauterine growth restriction are needed in low- and middle-income countries and may also result in long-term benefits on child development.

Foster Care Leads to Lower Irritability Among Adolescents with a History of Early Psychosocial Deprivation.

Irritability reflects a propensity for frustration and anger, and is a transdiagnostic symptom of both externalizing and internalizing psychopathology. While early adverse experiences are associated with higher levels of irritability, experiences of early psychosocial deprivation and whether family-based placements can mitigate the impact on subsequent irritability, remain underexplored. The current study examined irritability in 107 16-year-olds with a history of institutional care from a randomized controlled trial of foster care as an alternative to institutional care and 49 community comparison children. At age 16 years, irritability was assessed using parent- and self-report forms of the Affective Reactivity Index. Compared to community adolescents, those with a history of institutional care exhibited significantly elevated irritability levels. Among those who experienced institutional care, those randomized to foster care had lower levels of irritability compared to participants randomized to the care-as-usual group, and this effect persists after controlling for baseline negative emotionality. These findings suggest a causal link between high-quality foster care and lower irritability following psychosocial deprivation. Additionally, longer duration in institutional care and non-family placement at age 16 years were associated with higher levels of irritability, highlighting the role of caregiving in explaining variation in irritability in adolescence. Policies that support long-term, high-quality family placements for children without regular caregivers should be prioritized.

Acute Total Hip Arthroplasty Following Acetabular Fracture is Associated with a High Risk of Revision, Dislocation, and Periprosthetic Fracture.

BACKGROUND: The aim of this study was to compare outcomes between acute, subacute, and delayed arthroplasty for acetabular fractures occurring within one week, from one week to six months, or longer than six months before the index total hip arthroplasty (THA), versus THA without a history of acetabular fracture as a control. METHODS: We analyzed the records of patients undergoing primary THA who were enrolled in a national database for at least two years before and after the index procedure. Patients who had an initial diagnostic code for acetabular fracture occurring less than one week, from one week to six months, or at least more than six months before the THA were classified as acute THA (aTHA), subacute (saTHA), or delayed (dTHA), respectively. The control group was patients undergoing THA who did not have a history of acetabular fracture. There were 430,349 control primary THAs, 462 aTHAs, 675 saTHAs, and 1,162 dTHAs. RESULTS: After adjusting for age, sex, region, and comorbidities, patients who had an aTHA and saTHA experienced statistically significant increased odds of revision, dislocation, and periprosthetic fracture compared to primary THA without a history of acetabular fracture. Similarly, dTHA was associated with increased odds of revision, dislocation, and periprosthetic fractures compared to primary THA. In the multivariate analysis, aTHA had statistically significant higher rates of dislocation when compared to dTHA. CONCLUSION: Patients who had a history of acetabular fractures undergoing aTHA, saTHA, or dTHA have significantly increased rates of revision, periprosthetic fracture, and dislocation compared to primary THA in those who did not have a history of acetabular fractures.

Temperament and sex as moderating factors of the effects of exposure to maternal depression on telomere length in early childhood.

Individual differences in sensitivity to context are posited to emerge early in development and to influence the effects of environmental exposures on a range of developmental outcomes. The goal of the current study was to examine the hypothesis that temperament characteristics and biological sex confer differential vulnerability to the effects of exposure to maternal depression on telomere length in early childhood. Telomere length has emerged as a potentially important biomarker of current and future health, with possible mechanistic involvement in the onset of various disease states. Participants comprised a community sample of children followed from infancy to age 3 years. Relative telomere length was assessed from DNA in saliva samples collected at infancy, 2 years, and 3 years. Maternal depressive symptoms and the child temperament traits of negative affectivity, surgency/extraversion, and regulation/effortful control were assessed via maternal report at each timepoint. Analyses revealed a 3-way interaction among surgency/extraversion, sex, and maternal depressive symptoms, such that higher surgency/extraversion was associated with shorter telomere length specifically among males exposed to elevated maternal depressive symptoms. These findings suggest that temperament and sex influence children's susceptibility to the effects of maternal depression on telomere dynamics in early life.

Parental communicative input as a protective factor in Bangladeshi families living in poverty: A multi-dimensional perspective.

Studies from high-income populations have shown that stimulating, supportive communicative input from parents promote children's cognitive and language development. However, fewer studies have identified specific features of input supporting the healthy development of children growing up in low- or middle-income countries. The current study proposes and tests a multi-dimensional framework for understanding whether and how caregiver communicative input mediates the associations between socio-economic conditions and early development. We also examine how caregiver conceptual scaffolding and autonomy support uniquely and synergistically explain variation in child outcomes. Participants were 71 Bangladeshi families with five-year-olds who were exposed to a range of biological and psychosocial hazards from birth. Caregiver-child interactions during snack sharing and semi-structured play were coded for caregiver conceptual scaffolding, autonomy support, and child engagement. Findings indicate that the two dimensions of input were correlated, suggesting that caregivers who provided richer conceptual scaffolds were simultaneously more supportive of children's autonomy. Notably, conceptual scaffolding and autonomy support each mediated associations between maternal education and child verbal intelligence quotient (IQ) scores. Further, caregivers who supported greater autonomy in their children had children who participated in conversations more actively, and these children in turn had higher performance IQ scores. When considered simultaneously, conceptual scaffolding was associated with verbal IQ over and above autonomy support, whereas autonomy support related to child engagement, controlling for conceptual scaffolding. These findings shed new light on how environmental factors may support early development, contributing to the design of family-centered, culturally authentic interventions. A video abstract of this article can be viewed at https://youtu.be/9v_8sIv7ako RESEARCH HIGHLIGHTS: Studies from high-income countries have identified factors mitigating the impacts of socio-economic risks on development. Such research is scarce in low- and middle-income countries. The present study conceptualized and evaluated caregiver communicative input in Bangladeshi families along two interrelated yet distinct dimensions: conceptual scaffolding and autonomy support. Conceptual scaffolding and autonomy support individually mediated associations between maternal education and child verbal IQ, shedding light on protective factors in families living in poverty. Parents providing richer conceptual scaffolds were simultaneously more supportive of children's autonomy. However, the two dimensions each related to cognition and language through unique pathways.

Multidimensional evaluation of the early emergence of executive function and development in Bangladeshi children using nutritional and psychosocial intervention: A randomized controlled trial protocol.

INTRODUCTION: Reversing malnutrition-induced impairment of cognition and emotional regulation is a critical global gap. We hypothesize that brain-targeted micronutrient supplemented nutritional rehabilitation in children with moderate acute malnutrition, followed by 2 years micronutrient supplementation will impact on the cognition and emotion regulation of these children. METHODS: The primary outcome of this prospective, randomized controlled trial is to study the development of executive functions (EFs) and emotion regulation (ER) in this cohort. Moderate acute malnourished (MAM; WLZ/WHZ <-2 and ≥-3 z-score, and/or 11.5 cm ≤ MUAC < 12.5cm; n = 140)children aged around one year (11m-13m) in Mirpur, Dhaka, Bangladesh will be randomized (1:1) to receive either locally produced Ready to Use Supplementary Food (RUSF) or Enhanced Ready to Use Supplementary Food (E-RUSF) until anthropometric recovery (WLZ/WHZ > -1SD), or for 3 months after enrollment (whichever is earlier). The randomized MAMs groups will be given either Small Quantity Lipid Based Nutrient Supplement (SQLNS) or Enhanced Small Quantity Lipid Based Nutrient Supplement (E-SQLNS), respectively until the end of the 2-year follow up period. Standard psychosocial stimulation will be provided to the MAMs intervention groups. Biological samples will be collected, anthropometric and neurocognitive assessments will be performed at 2 (22m-26m) and 3 (34m-38m) years of age. Two control groups will be recruited: 1), non-malnourished one-year (11m-13m) old children (WLZ/WHZ score>-1SD; n = 70); and 2) three-year (34m-38m) old children (n = 70) with untreated MAM (WHZ <-2 and ≥-3 z-score, and/or 11.5≤MUAC<12.5 cm). The 3-year-old MAM reference group will be assessed once and provided with 2 months of nutritional rehabilitation support (RUSF Nutriset's Plumpy'Sup™).

Patient satisfaction and patient-reported outcomes do not vary by BMI class in total hip arthroplasty.

PURPOSE: Obesity has been identified as a risk factor for postoperative complications in patients undergoing total hip arthroplasty (THA). This study aimed to investigate patient-reported outcomes, pain, and satisfaction as a function of body mass index (BMI) class in patients undergoing THA. METHODS: 1736 patients within a prospective observational study were categorized into BMI classes. Pre- and postoperative Hip disability and Osteoarthritis Outcome Score for Joint Replacement (HOOS JR), satisfaction, and pain scores were compared by BMI class using one-way ANOVA. RESULTS: Healthy weight patients reported the highest preoperative HOOS JR (56.66 ± 13.35) compared to 45.51 ± 14.45 in Class III subjects. Healthy weight and Class III patients reported the lowest (5.65 ± 2.01) and highest (7.06 ± 1.98, p < 0.0001) preoperative pain, respectively. Changes in HOOS JR scores from baseline suggest larger improvements with increasing BMI class, where Class III patients reported an increase of 33.7 ± 15.6 points at 90 days compared to 26.1 ± 17.1 in healthy weight individuals (p = 0.002). Fewer healthy weight patients achieved the minimal clinically important difference (87.4%) for HOOS JR compared to Class II (96.5%) and III (94.7%) obesity groups at 90 days postoperatively. Changes in satisfaction and pain scores were largest in the Class III patients. Overall, no functional outcomes varied by BMI class postoperatively. CONCLUSION: Patients of higher BMI class reported greater improvements following THA. While risk/benefit shared decision-making remains a personalized requirement of THA, this study highlights that utilization of BMI cutoff may not be warranted based on pain and functional improvement.

Function and dysfunction of GEMIN5: understanding a novel neurodevelopmental disorder.

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction (NEDCAM) has resulted in an increased interest in GEMIN5, a multifunction RNA-binding protein. As the largest member of the survival motor neuron complex, GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein. Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder, considerable progress has been made in the brief time since its discovery. In this review, we examine GEMIN5 within the context of NEDCAM, focusing on the structure, function, and expression of the protein specifically in regard to the disorder itself. Additionally, we explore the current animal models of NEDCAM, as well as potential molecular pathways for treatment and future directions of study. This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

Diversity of Backgrounds and Academic Accomplishments for Presidents Elected to Hip and Knee Arthroplasty Societies in the United States.

BACKGROUND: Academic accomplishments and demographics for presidents of hip and knee arthroplasty societies are poorly understood. This study compares the characteristics of presidents nominated to serve the Hip Society, Knee Society, and American Association of Hip and Knee Surgeons. METHODS: This was a cross-sectional study of arthroplasty presidents in the United States (1990 to 2022). Curriculum vitae and academic websites were analyzed for demographic, training, bibliometric, and National Institutes of Health (NIH) funding data. Comparisons were made between organizations and time periods (1990 to 2005 versus 2006 to 2022). RESULTS: There were 97 appointments of 78 unique arthroplasty presidents (80%). Most presidents were male (99%) and Caucasian (95%). There was 1 woman (1%) and 5 non-Caucasian presidents (2% Asian, 3% Hispanic). There were no differences in demographics between the 3 arthroplasty organizations and the 2 time periods (P > .05). Presidents were appointed at 55 ± 10 years old, which was on average 24 years after completion of residency training. Most presidents had arthroplasty fellowship training (68%), and the most common were the Hospital for Special Surgery (21%) and Massachusetts General Hospital (8%). The median h-index was 53 resulting from 191 peer-reviewed publications, which was similar between the 3 organizations (P > .05). There were 2 presidents who had NIH funding (2%), and there were no differences in NIH funding between the 3 organizations (P > .05). CONCLUSIONS: Arthroplasty society presidents have diverse training pedigrees, high levels of scholarly output, and similar demographics. There may be future opportunities to promote diversity and inclusion among the highest levels of leadership in total joint arthroplasty.

Impact of Chronic Opioid Use on Postoperative Mobility Recovery and Patient-Reported Outcomes: A Propensity-Matched Study.

BACKGROUND: Opioid use prior to total joint arthroplasty may be associated with poorer postoperative outcomes. However, few studies have reported the impact on postoperative recovery of mobility. We hypothesized that chronic opioid users would demonstrate impaired objective and subjective mobility recovery compared to nonusers. METHODS: A secondary data analysis of a multicenter, prospective observational cohort study in which patients used a smartphone-based care management platform with a smartwatch for self-directed rehabilitation following hip or knee arthroplasty was performed. Patients were matched 2:1 based on age, body mass index, sex, procedure, Charnley class, ambulatory status, orthopedic procedure history, and anxiety. Postoperative mobility outcomes were measured by patient-reported ability to walk unassisted at 90 days, step counts, and responses to the 5-level EuroQol-5 dimension 5-level, compared by Chi-square and student's t-tests. Unmatched cohorts were also compared to investigate the impact of matching. RESULTS: A total of 153 preoperative chronic opioid users were matched to 306 opioid-naïve patients. Age (61.9 ± 10.5 versus 62.1 ± 10.3, P = .90) and sex (53.6 versus 53.3% women, P = .95) were similar between groups. The proportion of people who reported walking unassisted for 90 days did not vary in the matched cohort (87.8 versus 90.7%, P = .26). Step counts were similar preoperatively and 1-month postoperatively but were lower in opioid users at 3 and 6 months postoperatively (4,823 versus 5,848, P = .03). More opioid users reported moderate to extreme problems with ambulation preoperatively on the 5-level EuroQol-5 dimension 5-level (80.6 versus 69.0%, P = .02), and at 6 months (19.2 versus 9.3%, P = .01). CONCLUSIONS: Subjective and objective measures of postoperative mobility were significantly reduced in patients who chronically used opioid medications preoperatively. Even after considering baseline factors that may affect ambulation, objective mobility metrics following arthroplasty were negatively impacted by preoperative chronic opioid use.