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Objective: To evaluate the relationship between diabetes care and types of comorbidity, classified by the degree to which their treatment is concordant with that for diabetes.Research Design and Methods: Retrospective cohort study (fiscal year [FY] 2001 to FY 2004) of 42,826 veterans with new-onset diabetes in FY 2003. Veterans were classified into five chronic comorbid illness groups (CCIGs): none, concordant only, discordant only, both concordant and discordant, and dominant. Five diabetes-related care measures were assessed in FY 2004 (guideline-consistent testing and treatment goals for HbA(1c) and LDL cholesterol and diabetes-related outpatient visits). Analyses included logistic regressions adjusting for age, race, sex, marital status, priority code, and interaction between CCIGs and visit frequency.Results: Only 20% of patients had no comorbidities. Mean number of visits per year ranged from 7.8 (no CCIG) to 17.5 (dominant CCIG). In unadjusted analyses, presence of any illness was associated with equivalent or better care. In the fully adjusted model, we found interaction between CCIG and visit frequency. When visits were <7 per year, the odds of meeting the goal of HbA(1c) <8% were similar in the concordant (odds ratio 0.96 [95% CI 0.83-1.11]) and lower in the discordant (0.90 [0.81-0.99]) groups compared with the no comorbidity group. Among patients with >24 visits per year, these odds were insignificant. Dominant CCIG was associated with substantially reduced care for glycemic control for all visit categories and for lipid management at all but the highest visit category.Conclusions: Our study indicates that diabetes care varies by types of comorbidity. Concordant illnesses result in similar or better care, regardless of visit frequency. Discordant illnesses are associated with diminished care: an effect that decreases as visit frequency increases. [ABSTRACT FROM AUTHOR]

Objective: To examine how service accessibility measured by geographic distance affects service sector choices for veterans who are dually eligible for veterans affairs (VA) and Medicare services and who are diagnosed with mental health and/or substance abuse (MH/SA) disorders.Data Sources: Primary VA data sources were the Patient Treatment (acute care), Extended Care (long-term care), and Outpatient Clinic files. VA cost data were obtained from (1) inpatient and outpatient cost files developed by the VA Health Economics and Resource Center and (2) outpatient VA Decision Support System files. Medicare data sources were the denominator, Medicare Provider Analysis Review (MEDPAR), Provider-of-Service, Outpatient Standard Analytic and Physician/Supplier Standard Analytic files. Additional sources included the Area Resource File and Census Bureau data.Study Design: We identified dually eligible veterans who had either an inpatient or outpatient MH/SA diagnosis in the VA system during fiscal year (FY)'99. We then estimated one- and two-part regression models to explain the effects of geographic distance on both VA and Medicare total and MH/SA costs.Principal Findings: Results provide evidence for substitution between the VA and Medicare, demonstrating that poorer geographic access to VA inpatient and outpatient clinics decreased VA expenditures but increased Medicare expenditures, while poorer access to Medicare-certified general and psychiatric hospitals decreased Medicare expenditures but increased VA expenditures.Conclusions: As geographic distance to VA medical facility increases, Medicare plays an increasingly important role in providing mental health services to veterans. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although difficulties in applying risk-adjustment measures to mental health populations are increasingly evident, a model designed specifically for patients with psychiatric disorders has never been developed. OBJECTIVE: Our objective was to develop and validate a case-mix classification system, the 'PsyCMS,' for predicting concurrent and future mental health (MH) and substance abuse (SA) healthcare costs and utilization. SUBJECTS: Subjects included 914,225 veterans who used Veterans Administration (VA) healthcare services during fiscal year 1999 (FY99) with any MH/SA diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes 290.00-312.99, 316.00-316.99). METHODS: We derived diagnostic categories from ICD-CM codes using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition definitions, clinical input, and empiric analyses. Weighted least-squares regression models were developed for concurrent (FY99) and prospective (FY00) MH/SA costs and utilization. We compared the predictive ability of the PsyCMS with several case-mix systems, including adjusted clinical groups, diagnostic cost groups, and the chronic illness and disability payment system. Model performance was evaluated using R-squares and mean absolute prediction errors (MAPEs). RESULTS: Patients with MH/SA diagnoses comprised 29.6% of individuals seen in the VA during FY99. The PsyCMS accounted for a distinct proportion of the variance in concurrent and prospective MH/SA costs (R=0.11 and 0.06, respectively), outpatient MH/SA utilization (R=0.25 and 0.07), and inpatient MH/SA utilization (R=0.13 and 0.05). The PsyCMS performed better than other case-mix systems examined with slightly higher R-squares and lower MAPEs. CONCLUSIONS: The PsyCMS has clinically meaningful categories, demonstrates good predictive ability for modeling concurrent and prospective MH/SA costs and utilization, and thus represents a useful method for predicting mental health costs and utilization. [ABSTRACT FROM AUTHOR]

Background: The Patient Safety Indicators (PSIs), an administrative data-based tool developed by the Agency for Healthcare Research and Quality, are increasingly being used to screen for potential in-hospital patient safety problems. Although the Veterans Health Administration (VA) is a national leader in patient safety, accurate information on the epidemiology of patient safety events in the VA is still unavailable.Objectives: Our objectives were to: (1) apply the AHRQ PSI software to VA administrative data to identify potential instances of compromised patient safety; (2) determine occurrence rates of PSI events in the VA; and (3) examine the construct validity of the PSIs.Methods: We examined differences between observed and risk-adjusted PSI rates in the VA, compared VA and non-VA PSI rates, and investigated the construct validity of the PSIs by examining correlations of the PSIs with other outcomes of VA hospitalizations.Results: We identified 11,411 PSI events in the VA nationwide in FY'01. Observed PSI rates per 1000 discharges ranged from 0.007 for "transfusion reaction" to 155.5 for "failure to rescue." There were significant, although small, differences between VA and non-VA risk-adjusted PSI rates. Hospitalizations with PSI events had longer lengths of stay, higher mortality, and higher costs than those without PSI events.Conclusions: Our results suggest that the PSIs may be useful as a patient safety screening tool in the VA. Our PSI rates were consistent with the national incidence of low rates; however, differences between VA and non-VA rates suggest that inadequate case-mix adjustment may be contributing to these findings. [ABSTRACT FROM AUTHOR]

BACKGROUND: Racial disparities have been widely documented in medical care, but variations in dental care have not been well examined. OBJECTIVES: To determine if there is racial variation in use of root canal therapy versus tooth extraction across different levels of dental insurance coverage and adjusting for other factors known to influence treatment decisions. METHODS: Within 3 different categories of insurance coverage, we examined whether there were racial differences in the provision of the tooth-sparing treatment of root canal therapy (vs. tooth extraction) among 54,423 users of outpatient Veterans Affairs dental care in 1998. Regression analyses adjusted for the severity of tooth- and gum-related disease, age, sex, medical and psychiatric comorbidities, prior use of preventive dental services, tooth extraction and root canal therapy, and clustering by geographic region. RESULTS: In the adjusted regression models, black patients and those with unknown race were less likely overall to receive root canal therapy than whites, whereas Asians were more likely. Among patients with eligibility for continuing and comprehensive dental care, blacks were less likely and Asians more likely to receive root canals than whites. For patients covered only for emergency dental care, Hispanics had a higher likelihood of receiving root canal therapy. Among all other types of coverage, there were no significant racial differences in the care received. CONCLUSION: We observed substantial racial variations in the provision of root canal therapy among patients treated in Department of Veterans Affairs dental clinics. Future research should identify the causes of such variations. [ABSTRACT FROM AUTHOR]

Background: Retaining teeth improves oral health and quality of life. Thus, receipt of a root canal (vs. a tooth extraction) is a useful indicator of the quality of dental care. However, use of this quality measure without adjusting for the severity of oral disease could lead to spurious conclusions.Objectives: This paper describes the development of a dental severity adjustment methodology.Research Design: Retrospective study.Subjects: 54,423 users of Department of Veterans Affairs (VA) dental care who had either root canal therapy or a tooth extraction at a VA facility in Fiscal year 1998.Measures: International Classification of Disease Clinical Modification codes for dental diagnoses and comorbid medical conditions. We modeled the effects of dental disease severity in logistic regression models of the probability of receiving a root canal, using both conceptual and Modified Delphi-Panel derived models, adjusting for age, and medical comorbidities.Results: Conceptual and Modified Delphi models performed similarly. The dental disease severity adjustments increased the fit in models of the probability of receiving a root canal (C-statistic = 0.822 for the conceptual model and 0.804 for the Modified Delphi Panel model) compared with the model including comorbid medical conditions alone (C-statistic = 0.561).Conclusions: Risk adjustment for dental disease severity improves the fit of models of the probability of receiving a root canal. Studies of the quality of dental care should consider employing risk-adjusted models. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that the agreement among radiologists interpreting a test set of mammograms is relatively low. However, data available from real-world settings are sparse. We studied mammographic examination interpretations by radiologists practicing in a community setting and evaluated whether the variability in false-positive rates could be explained by patient, radiologist, and/or testing characteristics.Methods: We used medical records on randomly selected women aged 40-69 years who had had at least one screening mammographic examination in a community setting between January 1, 1985, and June 30, 1993. Twenty-four radiologists interpreted 8734 screening mammograms from 2169 women. Hierarchical logistic regression models were used to examine the impact of patient, radiologist, and testing characteristics. All statistical tests were two-sided.Results: Radiologists varied widely in mammographic examination interpretations, with a mass noted in 0%-7.9%, calcification in 0%-21.3%, and fibrocystic changes in 1.6%-27.8% of mammograms read. False-positive rates ranged from 2.6% to 15.9%. Younger and more recently trained radiologists had higher false-positive rates. Adjustment for patient, radiologist, and testing characteristics narrowed the range of false-positive rates to 3.5%-7.9%. If a woman went to two randomly selected radiologists, her odds, after adjustment, of having a false-positive reading would be 1.5 times greater for the radiologist at higher risk of a false-positive reading, compared with the radiologist at lowest risk (95% highest posterior density interval [similar to a confidence interval] = 1.17 to 2.08).Conclusion: Community radiologists varied widely in their false-positive rates in screening mammograms; this variability range was reduced by half, but not eliminated, after statistical adjustment for patient, radiologist, and testing characteristics. These characteristics need to be considered when evaluating false-positive rates in community mammographic examination screening. [ABSTRACT FROM AUTHOR]

Background: The cumulative risk of a false-positive mammogram can be substantial. We studied which variables affect the chance of a false-positive mammogram and estimated cumulative risks over nine sequential mammograms.Methods: We used medical records of 2227 randomly selected women who were 40-69 years of age on July 1, 1983, and had at least one screening mammogram. We used a Bayesian discrete hazard regression model developed for this study to test the effect of patient and radiologic variables on a first false-positive screening and to calculate cumulative risks of a false-positive mammogram.Results: Of 9747 screening mammograms, 6. 5% were false-positive; 23.8% of women experienced at least one false-positive result. After nine mammograms, the risk of a false-positive mammogram was 43.1% (95% confidence interval [CI] = 36.6%-53.6%). Risk ratios decreased with increasing age and increased with number of breast biopsies, family history of breast cancer, estrogen use, time between screenings, no comparison with previous mammograms, and the radiologist's tendency to call mammograms abnormal. For a woman with highest-risk variables, the estimated risk for a false-positive mammogram at the first and by the ninth mammogram was 98.1% (95% CI = 69.3%-100%) and 100% (95% CI = 99.9%-100%), respectively. A woman with lowest-risk variables had estimated risks of 0.7% (95% CI = 0.2%-1.9%) and 4.6% (95% CI = 1. 1%-12.5%), respectively.Conclusions: The cumulative risk of a false-positive mammogram over time varies substantially, depending on a woman's own risk profile and on several factors related to radiologic screening. By the ninth mammogram, the risk can be as low as 5% for women with low-risk variables and as high as 100% for women with multiple high-risk factors. [ABSTRACT FROM AUTHOR]

OBJECTIVE. To describe the epidemiology, management, and outcomes of children with fever in pediatric primary care practice. PATIENTS. A cohort of 20 585 children 3 to 36 months of age cared for in 11 pediatric offices of a health maintenance organization between 1991 and 1994. METHODS. Using automated medical records we identified all office visits with temperatures >/=38 degrees C for a random sample of 5000 children, and analyzed diagnoses conferred, laboratory tests performed, and antibiotics prescribed. We also determined the frequency of in-person and telephone follow-up after initial visits for fever. Finally, we reviewed hospital claims data for the entire cohort of 20 585 to identify cases of meningitis, meningococcal sepsis, and death from infection. RESULTS. Among 3819 initial visits of an illness episode, 41% of children had no diagnosed bacterial or specific viral source. Of these, 13% with a temperature of 38 degrees C to 39 degrees C and 36% with a temperature of >/=39 degrees C received laboratory testing. Almost half (43%) received some documented follow-up care in the subsequent 7 days. Among the 26 970 child-years of observation in the entire cohort, 15 children (56 per 100 000 child-years) were treated for bacterial meningitis or meningococcal sepsis. Five had an office visit for fever in the week before hospitalization, but only 1 had documented fever >/=39 degrees C and received neither laboratory testing for occult bacteremia nor treatment with an antibiotic. CONCLUSION. The majority of febrile children in ambulatory settings were diagnosed with a bacterial infection and treated with an antibiotic. Of highly febrile children without a source, 36% received laboratory testing consistent with published expert recommendations, and short-term follow-up was common. Meningitis or death after an office visit for fever without a source was predictably rare. These data suggest that increased testing and/or treatment of febrile children beyond the rates observed here are unlikely to affect population rates of meningitis substantially. [ABSTRACT FROM AUTHOR]

Abstract Background Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical setting, we aimed to develop an assay that could reliably measure fragments of degraded titin in serum and potentially be used in the assessment of cardiac muscle damage. Methods A competitive ELISA was developed to specifically measure levels of the titin sequence 12670’ NVTVEARLIK 12679’, derived by the degradation of titin by matrix metalloproteinase (MMP)-12. Serum samples from 90 individuals were divided into 3 equally sized groups. One group had been diagnosed with acute myocardial infarction (AMI) while the remaining two were asymptomatic individuals either with CT-scan signs of coronary calcium (CT-plusCa) or without coronary calcium (CT-noCa). Results Mean geometric levels of the titin fragment in the CT-noCa group were 506.5 ng/ml (±43.88). The CT-plusCa group showed 50.6% higher levels of the marker [763 ng/ml (±90.14)] (P Conclusions The titin-12670 fragment is present in both individuals with undiagnosed and diagnosed CVD. The statistically significant increase in level of the marker in the AMI group is indicative that this neoepitope biomarker may be a useful serological marker in AMI.

Abstract Background Abdominal aortic calcifications (AAC) predict cardiovascular mortality. A new scoring model for AAC, the Morphological Atherosclerotic Calcification Distribution (MACD) index may contribute with additional information to the commonly used Aortic Calcification Severity (AC24) score, when predicting death from cardiovascular disease (CVD). In this study we investigated associations of MACD and AC24 with traditional metabolic-syndrome associated risk factors at baseline and after 8.3 years follow-up, to identify biological parameters that may account for the differential performance of these indices. Methods Three hundred and eight healthy women aged 48 to 76 years, were followed for 8.3 ± 0.3 years. AAC was quantified using lumbar radiographs. Baseline data included age, weight, blood pressure, blood lipids, and glucose levels. Pearson correlation coefficients were used to test for relationships. Results At baseline and across all patients, MACD correlated with blood glucose (r2 = 0.1, P< 0.001) and to a lesser, but significant extent with traditional risk factors (p < 0.01) of CVD. In the longitudinal analysis of correlations between baseline biological parameters and the follow-up calcification assessment using radiographs we found LDL-cholesterol, HDL/LDL, and the ApoB/ApoA ratio significantly associated with the MACD (P< 0.01). In a subset of patients presenting with calcification at both baseline and at follow-up, all cholesterol levels were significantly associated with the MACD (P< 0.01) index. AC24 index was not correlated with blood parameters. Conclusion Patterns of calcification identified by the MACD, but not the AC24 index, appear to contain useful biological information perhaps explaining part of the improved identification of risk of cardiovascular death of the MACD index. Correlations of MACD but not the AC24 with glucose levels at baseline suggest that hyperglycemia may contribute to unique patterns of calcification indicated by the MACD.

Abstract Background Aortic calcification is a major risk factor for death from cardiovascular disease. We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta. Methods 308 postmenopausal women aged 48-76 were followed for 8.3 ± 0.3 years, with deaths related to cardiovascular disease, cancer, or other causes being recorded. From lumbar X-rays at baseline the number (NCD), size, morphology and distribution of aortic calcification lesions were scored and combined into one Morphological Atherosclerotic Calcification Distribution (MACD) index. The hazard ratio for mortality was calculated for the MACD and for three other commonly used predictors: the EU SCORE card, the Framingham Coronary Heart Disease Risk Score (Framingham score), and the gold standard Aortic Calcification Severity score (AC24) developed from the Framingham Heart Study cohorts. Results All four scoring systems showed increasing age, smoking, and raised triglyceride levels were the main predictors of mortality after adjustment for all other metabolic and physical parameters. The SCORE card and the Framingham score resulted in a mortality hazard ratio increase per standard deviation (HR/SD) of 1.8 (1.51-2.13) and 2.6 (1.87-3.71), respectively. Of the morphological x-ray based measures, NCD revealed a HR/SD >2 adjusted for SCORE/Framingham. The MACD index scoring the distribution, size, morphology and number of lesions revealed the best predictive power for identification of patients at risk of mortality, with a hazard ratio of 15.6 (p < 0.001) for the 10% at greatest risk of death. Conclusions This study shows that it is not just the extent of aortic calcification that predicts risk of mortality, but also the distribution, shape and size of calcified lesions. The MACD index may provide a more sensitive predictor of mortality from aortic calcification than the commonly used AC24 and SCORE/Framingham point card systems.

Abstract Background We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. Methods Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination. Results Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. Conclusion Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. Trial Registration Trial registration number: NCT00205777; Trial registration date: September 16, 2005

Abstract Background Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture. The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular matrix (ECM) of atherosclerotic plaques by cathepsin K mediated processes. Methods We 1) cultured human macrophages on ECM and measured cathepsin K generated fragments of type I collagen (C-terminal fragments of Type I collagen (CTX-I) 2) investigated the presence of CTX-I in human coronary arteries and 3) finally investigated the clinical potential by measuring circulating CTX-I in women with and without radiographic evidence of aortic calcified atherosclerosis. Results Immune-histochemistry of early and advanced lesions of coronary arteries demonstrated co-localization of Cathepsin-K and CTX-I in areas of intimal hyperplasia and in shoulder regions of advanced plaques. Treatment of human monocytes with M-CSF or M-CSF+LDL generated macrophages and foam cells producing CTX-I when cultured on type I collagen enriched matrix. Circulating levels of CTX-I were not significantly different in women with aortic calcifications compared to those without. Conclusions Human macrophage foam cells degrade the atherosclerotic plaques though cathepsin K mediated processes, resulting in increase in levels of CTX-I. Serum CTX-I was not elevated in women with aortic calcification, likely due to the contribution of CTX-I from osteoclastic bone resorption which involves Cathepsin-K. The human macrophage model system may be used to identify important pathway leading to excessive proteolytic plaque remodeling and plaque rupture.

Abstract Background Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in breast and prostate cancer patients is associated with an increase in cartilage degradation and to test in vitro whether osteoclasts or cathepsin K alone generate CTXII from human bone. Methods The study included 132 breast and prostate cancer patient, where presence of bone metastases was graded according to the Soloway score. Total bone resorption (CTXItotal) and cartilage degradation (CTXII) were determined. Results Breast and prostate cancer patients with bone metastases revealed significant increased levels of CTXItotal at Soloway scores 1 and higher compared to patients without bone metastases (p < 0.001). CTXII was statistically elevated at score 3 and 4 (p < 0.01). CTXII/CTXItotal significantly decreased at score 3 and 4 (p < 0.001). Levels of CTXItotal, CTXII and CTXII/CTXItotal changed +900%, +130%, and -90%, respectively at Soloway score 4 compared to score 0. The in vitro experiments revealed that osteoclasts released CTXI fragments but not CTXII from bone specimens. The same was observed for cathepsin K. Conclusion Data suggest that an uncoupling between bone resorption and cartilage degradation occurs in breast and lung cancer patient.

Bone-anchored limbs (BALs) are socket prosthesis alternatives, directly fixing to residual bone via osseointegrated implant. There is a need to quantify multi-level effects of rehabilitation for transfemoral BAL users (i.e. changes in joint loading and movement patterns). Our primary objective was determining feasibility of using optimal control to predict gait biomechanics compared to ground-truth experimental data from transfemoral BAL users. A secondary objective was examining biomechanical effects from estimated changes in hip abductor muscle strength. We developed and validated a workflow for predicting gait biomechanics in four transfemoral BAL users and investigated the biomechanical effects of altered hip abductor strengths.

Background: A bone-anchored limb (BAL) is an alternative to a traditional socket-type prosthesis for people with transfemoral amputation. Early laboratory-based evidence suggests improvement in joint and limb loading mechanics during walking with a BAL compared to socket prosthesis use. However, changes in cumulative joint and limb loading measures, which may be predictive of degenerative joint disease progression, remain unknown., Research Question: Do cumulative total limb and hip joint loading during walking change using a BAL for people with unilateral transfemoral amputation, compared to prior socket prosthesis use?, Methods: A case-series cohort of eight participants with prior unilateral transfemoral amputation who underwent BAL hardware implantation surgery were retrospectively analyzed (4 M/4 F; BMI: 27.7 ± 3.1 kg/m 2 ; age: 50.4 ± 10.2 years). Daily step count and whole-body motion capture data were collected before (using socket prosthesis) and one-year after BAL hardware implantation. Cumulative total limb and hip joint loading and between-limb loading symmetry metrics were calculated during overground walking at both time points and compared using Cohen's d effect sizes., Results: One year after BAL hardware implantation, participants demonstrated bilateral increases in cumulative total limb loading (amputated: d = -0.65; intact: d = -0.72) and frontal-plane hip moment (amputated: d = -1.29; intact: d = -1.68). Total limb loading and hip joint loading in all planes remained asymmetric over time, with relative overloading of the intact limb in all variables of interest at the one-year point., Significance: Despite increases in cumulative total limb and hip joint loading, between-limb loading asymmetries persist. Habitual loading asymmetry has been implicated in contributing to negative long-term joint health and onset or progression of degenerative joint diseases. Improved understanding of methods to address habitual loading asymmetries is needed to optimize rehabilitation and long-term joint health as people with transfemoral amputation increase physical activity when using a BAL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known conflicting financial or personal interests that could have appeared to inappropriately influence the results presented in this work., (Published by Elsevier B.V.)

Objective: Conventional total knee arthroplasty (TKA) rehabilitation has little impact on sedentary lifestyles that have negative long-term health consequences. The purpose of this trial was to determine the effect of telehealth-based physical activity behavior change intervention on physical activity and functional outcomes following TKA., Methods: This study was a 2-arm, parallel randomized controlled superiority trial at a regional Veterans Affairs medical center. The participants were 92 US military Veterans (mean age = 65.7 [SD =7.8] y) undergoing unilateral TKA. The Physical Activity Behavior Change (PABC) intervention included telehealth-based self-management training (ten 30-minute sessions) delivered over 12 weeks. The control intervention included telehealth-based health education sessions that matched PABC frequency and duration. Both groups participated in standardized conventional outpatient rehabilitation. Physical activity, measured as average daily step count, was the primary outcome. Secondary outcomes were Life-Space Assessment questionnaire, 30-Second Chair-Stand test, Timed Up-and-Go Test, Six-Minute Walk test, Western Ontario and McMaster Universities Osteoarthritis Index, and Veterans RAND 12-Item Health Survey. The Self Efficacy for Exercise scale and daily time spent in different postures (sitting/lying, standing, stepping) were exploratory variables. Outcomes were measured at baseline (before surgery), mid-intervention (8 weeks after surgery), after the intervention (14 weeks after surgery; primary endpoint), and follow-up (38 weeks after surgery)., Results: The PABC group had an estimated 931 (95% CI = 42-1819) more daily steps than the control group from baseline to 14 weeks, though a between-group effect was not sustained at 38 weeks. There were no group differences in secondary outcomes. Participants included only military veterans using Veteran's Health Administration services. The intervention targeted self-management and did not include peer support., Conclusions: The PABC intervention improved physical activity for Veterans recovering from unilateral TKA at 14 weeks after surgery, though the effect was not sustained at 38 weeks. Physical function improved with rehabilitation but was not different between groups, indicating that physical function was not a primary driver of physical activity behavior., Impact: Conventional TKA rehabilitation has a negligible effect on free-living physical activity, which is relevant to long-term health outcomes. This trial identified telehealth physical activity self-management as effective in addressing activity behaviors, separate from conventional rehabilitation strategies., (© The Author(s) 2024. 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.)

Objective: The purpose of this study will be to determine the efficacy of low intensity lower extremity resistance training with and without blood flow restriction (BFR) on quadriceps muscle strength and thickness in veterans with advanced multiple sclerosis (MS)., Methods: This will be an assessor-blinded, 2-group (1 to 1 allocation) randomized controlled trial targeting an enrollment of 58 participants with advanced MS as defined by Patient-Determined Disease Steps scale levels 4 to 7. Both groups will complete 10 weeks of twice weekly low-load resistance training (20%-30% of 1-repetition max) targeting knee and hip extension, knee flexion, and ankle plantarflexion. The intervention group will perform all training using BFR, with limb occlusion pressures between 60% and 80% of maximal limb occlusion pressure. Primary outcomes will be quadriceps muscle strength and thickness. Secondary outcomes will include knee flexion and ankle plantarflexion strength, functional mobility, physical activity, and patient-reported measures. All outcomes will be assessed at baseline before the intervention, immediately after the intervention, and at a 2-month follow-up assessment. The change between groups postintervention and after the 2-month follow-up will be reported for all outcomes. All analyses will assume a 2-sided test of hypothesis (α = .05)., Impact: There is very little evidence for the efficacy of exercise interventions in people with MS who have advanced mobility disability. Resistance training with BFR may be an important approach for people with advanced MS who may not tolerate more conventional, moderate-to-high intensity resistance training. The results of this study will inform clinicians regarding exercise decisions for people with advanced MS and future investigations on the role of BFR in people with MS., (© Published by Oxford University Press on behalf of the American Physical Therapy Association 2024.)

For some individuals with severe socket-related problems, prosthesis osseointegration directly connects a prosthesis to the residual limb creating a bone-anchored limb (BAL). We compared dynamic gait stability and between-limb stability symmetry, as measured by the Margin of Stability (MoS) and the Normalized Symmetry Index (NSI), for people with unilateral transfemoral amputation before and one-year after BAL implantation. The MoS provides a mechanical construct to assess dynamic gait stability and infer center of mass and limb control by relating the center of mass and velocity to the base of support. Before and one-year after BAL implantation, 19 participants walked overground at self-selected speeds. We quantified dynamic gait stability anteriorly and laterally at foot strike and at the minimum lateral MoS value. After implantation, we observed decreased lateral MoS at foot strike for the amputated (MoS mean(SD) %height; pre: 6.6(2.3), post: 5.9(1.3), d = 0.45) and intact limb (pre: 6.2(1.2), post: 5.8(1.0), d = 0.38) and increased between-limb MoS symmetry at foot strike (NSI mean(SD) %; anterior-pre: 10.3(7.3), post: 8.4(3.6), d = 0.23; lateral-pre: 18.8(12.4), post: 12.4(4.9), d = 0.47) and at minimum lateral stability (pre: 28.1(18.1), post: 19.2(6.8), d = 0.50). Center of mass control using a BAL resulted in dynamic gait stability more similar between limbs and may have reduced the adoption of functional asymmetries. We suggest that improved between-limb MoS symmetry after BAL implantation is likely due to subtle changes in individual limb MoS values at self-selected walking speeds resulting in an overall positive impact on fall risk through improved center of mass and prosthetic limb control., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Jason W. Stoneback is a paid consultant for AQ Solutions. No additional competing financial or non-financial interests which could or appear to influence the interpretation or presentation of this work are declared]., (Published by Elsevier Ltd.)

Background: Individuals with end-stage knee osteoarthritis (OA) walk at a lower intensity (ie, slower step cadence) contributing to worse physical function. Previous literature reports daily step counts and sedentary time, with little information regarding stepping bouts or cadence. Determining relationships between daily higher stepping cadence duration and clinical outcomes can move the field toward optimal daily stepping prescription., Objective: To quantify daily physical activity patterns of individuals with end-stage knee OA and determine the contribution of high stepping cadence to explain functional capacity variability., Design: Cross-sectional analysis., Setting: Veterans Administration medical center., Participants: U.S. military veterans (n = 104; age: 67.1 years [7.2]; mean [SD]; male [89.3%]) with end-stage knee OA were enrolled., Intervention: Not applicable., Main Outcome Measure: Functional capacity (6-Minute Walk Test [6MWT]). Physical activity (activPAL wearable sensor; cadence and time sitting, standing, and stepping), pain (Western Ontario and McMaster Universities Osteoarthritis Index-pain subscale) sociodemographic variables, and comorbidities (body mass index and Functional Comorbidity Index) are the main explanatory variables., Results: Participants' wake time was mainly sitting (11.0 h/day) in ≥60-minute bouts (29.7% ± 12.7 of sitting time). Standing (3.4 hours/day) and stepping (1.4 h/day) primarily occurred in 0-5 minute bouts (standing: 87.7% ± 14.4 of standing time, stepping: 98.7% ± 12.7 of stepping time) and stepping cadence was predominantly incidental (1-19 spm; 52.9% ± 9.6 of total stepping time). Backward elimination model results indicated shorter medium-to-brisk cadence bout duration, older age, and higher pain significantly explained shorter 6MWT distance ( Adj R 2 =0.24, p < .01)., Conclusions: Individuals with knee OA spend most of their waking hours sitting, while standing and stepping occurs in short bouts at very low stepping cadence. Decreased time in high stepping cadence is associated with lower functional capacity. Future studies should explore if increasing the daily time spent in higher step cadence can improve functional capacity in this population., (© 2023 American Academy of Physical Medicine and Rehabilitation.)

Individuals with unilateral transtibial amputation (TTA) using socket prostheses demonstrate asymmetric joint biomechanics during walking, which increases the risk of secondary comorbidities (e.g., low back pain (LBP), osteoarthritis (OA)). Bone-anchored limbs are an alternative to socket prostheses, yet it remains unknown how they influence multi-joint loading. Our objective was to determine the influence of bone-anchored limb use on multi-joint biomechanics during walking. Motion capture data (kinematics, ground reaction forces) were collected during overground walking from ten participants with unilateral TTA prior to (using socket prostheses) and 12-months after bone-anchored limb implantation. Within this year, each participant completed a rehabilitation protocol that guided progression of loading based on patient pain response and optimized biomechanics. Musculoskeletal models were developed at each testing timepoint (baseline or 12-months after implantation) and used to calculate joint kinematics, internal joint moments, and joint reaction forces (JRFs). Analyses were performed during three stance periods on each limb. The between-limb normalized symmetry index (NSI) was calculated for joint moments and JRF impulses. Discrete (range of motion (ROM), impulse NSI) dependent variables were compared before and after implantation using paired t-tests with Bonferroni-Holm corrections while continuous (ensemble averages of kinematics, moments, JRFs) were compared using statistical parametric mapping (p < 0.05). When using a bone-anchored limb, frontal plane pelvic (residual: pre = 9.6 ± 3.3°, post = 6.3 ± 2.5°, p = 0.004; intact: pre = 10.2 ± 3.9°, post = 7.9 ± 2.6°, p = 0.006) and lumbar (residual: pre = 15.9 ± 7.0°, post = 10.6 ± 2.5°, p = 0.024, intact: pre = 17.1 ± 7.0°, post = 11.4 ± 2.8°, p = 0.014) ROM was reduced compared to socket prosthesis use. The intact limb hip extension moment impulse increased (pre = -11.0 ± 3.6 Nm*s/kg, post = -16.5 ± 4.4 Nm*s/kg, p = 0.005) and sagittal plane hip moment impulse symmetry improved (flexion: pre = 23.1 ± 16.0 %, post = -3.9 ± 19.5 %, p = 0.004, extension: pre = 29.2 ± 20.3 %, post = 8.7 ± 22.9 %, p = 0.049). Residual limb knee extension moment impulse decreased compared to baseline (pre = 15.7 ± 10.8 Nm*s/kg, post = 7.8 ± 3.9 Nm*s/kg, p = 0.030). These results indicate that bone-anchored limb implantation alters multi-joint biomechanics, which may impact LBP or OA risk factors in the TTA population longitudinally., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: People with lower-limb loss participate in less physical activity than able-bodied individuals, which increases the mortality risk and incidence of metabolic syndromes. This study evaluated the effect of lower-limb prosthesis osseointegration on physical activity, including daily steps and stepping cadence., Methods: Free-living walking activity was assessed from 14 patients scheduled to undergo prosthesis osseointegration at two time points (within 2 weeks prior to osseointegration surgery and 12-months following). Daily step count, stepping time, number of walking bouts, average step cadence per bout, maximum step cadence per bout, and time spent in bands of step cadence were compared before and after osseointegration., Results: Twelve months after prosthesis osseointegration, participants increased daily steps, daily stepping time, average step cadence, and maximum cadence per walking bout compared to pre-osseointegration., Conclusions: Participants engaged in more daily steps, higher stepping cadence, and longer bouts at higher cadence one year following osseointegration compared to when using a socket prosthesis. As a novel intervention that is becoming more common, it is important to understand walking activity outcomes as these are critical for long-term health.

Background: After lower limb amputation, several prosthesis design options exist. However, prosthesis design decisions do not always reflect a prosthesis user's needs, values, and preferences., Objective: To develop a patient decision aid (PDA) prototype for prosthetists and new prosthesis users facing prosthesis design decisions after lower limb amputation, and to assess its usability, accuracy, and comprehensibility., Study Design: Exploratory mixed methods., Methods: PDA development was informed by a qualitative needs assessment and guided by the International Patient Decision Aid Standards. The PDA was evaluated by steering groups of experienced prosthesis users and prosthetic professionals (prosthetists and researchers) to test usability, accuracy, and comprehensibility through focus groups, individual interviews, and rating on a Likert scale ranging from 1 to 10., Results: The resulting PDA included 6 sections: (1) Amputation and Early Recovery, (2) Communication, (3) Values, (4) Prosthesis Design, (5) Preferences, and (6) Prosthetic Journey. Usability, accuracy, and comprehensibility were rated as 9.2, 9.6, and 9.6, respectively, by prosthetic professionals, and 9.4, 9.6, and 9.6, respectively, by prosthesis users., Discussion: The PDA incorporated guidance by relevant stakeholders and was rated favorably, emphasizing a need for shared decision-making support in prosthesis design. One challenge was determining the amount of information in the PDA, highlighting the diversity in end users' informational needs. Future iterations of the PDA should undergo beta testing in clinical settings., Conclusions: A standardized, iterative method was used to develop a PDA for new lower limb prosthesis users and prosthetists when considering prosthesis design decisions. The PDA was considered useable, accurate, and comprehensible., (Copyright © 2024 International Society for Prosthetics and Orthotics.)

» Patient-reported outcome measures (PROMs) are essential for measuring quality and functional outcomes after implantation of osseointegrated bone anchored limbs for patients with lower extremity amputation.» Using a novel assessment criterion with 8 domains, this study assessed all commonly used PROMs for their efficiency and comprehensiveness.» Comprehensiveness was scored according to the presence or absence of PROM questions related to these 8 domains (maximum score = 60): mobility (15 items), prosthesis (14 items), pain (10 items), psychosocial status (10 items), independence/self-care (4 items), quality of life/satisfaction (4 items), osseoperception (1 item), general information (1 item), and vitality (1 item).» The efficiency scores were calculated by dividing the comprehensiveness score by the total number of questions answered by the patients with higher scores being deemed more efficient.» The most comprehensive PROMs were Orthotics and Prosthetics User's Survey-Lower Extremity Functional Status (OPUS-LEFS) (score = 36), Prosthesis Evaluation Questionnaire (PEQ) (score = 31), and Questionnaire for Persons with a Transfemoral Amputation (score = 27).» The most efficient PROMs were the OPUS-LEFS (score = 1.8) and European Quality of Life (score = 1.4)., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B76)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Patients with transfemoral amputation (TFA) are at an increased risk of secondary musculoskeleteal comorbidities, primarily due to asymmetric joint loading. Amputated limb muscle weakness is also prevalent in the TFA population, yet all factors that contribute to muscle strength and thus joint loading are not well understood. Our objective was to bilaterally compare gluteus medius (GMED) muscle factors (volume, fatty infiltration, moment arm) that all contribute to joint loading in patients with TFA. Quantitative magnetic resonance (MR) images of the hip were collected from eight participants with unilateral TFA (2M/6F; age: 47.3 ± 14.7 y/o; BMI: 25.4 ± 5.3 kg/m 2 ; time since amputation: 20.6 ± 15.0 years) and used to calculate normalized GMED muscle volume and fatty infiltration. Six participants participated in an instrumented gait analysis session that collected whole-body kinematics during overground walking. Subject-specific musculoskeletal models were used to calculate bilateral GMED (anterior, middle, posterior) moment arms and frontal plane hip joint angles across three gait cycles. Differences in volume, fatty infiltration, hip adduction-abduction angle, and peak moment arms were compared between limbs using paired Cohen's d effect sizes. Volume was smaller by 36.3 ± 18.8% (d = 1.7) and fatty infiltration was greater by 6.4 ± 7.8% (d = 0.8) in the amputated limb GMED compared to the intact limb. The amputated limb GMED abduction moment arms were smaller compared to the intact limb for both overground walking (anterior: d = 0.9; middle: d = 0.1.2) and during normal range of motion (anterior: d = 0.8; middle: d = 0.8) while bilateral hip adduction-abduction angles were similar during overground walking (d = 0.5). These results indicate that in patients with TFA, the amputated limb GMED is biomechanically disadvantaged compared to the intact limb, which may contribute to the etiology of secondary comorbidities. This population might benefit from movement retraining to lengthen the amputated limb GMED abduction moment arm during gait., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Background: Low back pain (LBP) is more prevalent in patients with transfemoral amputation using socket prostheses than able-bodied individuals, in part due to altered spinal loading caused by aberrant lumbopelvic movement patterns. Early evidence surrounding bone-anchored limb functional outcomes is promising, yet it remains unknown if this novel prosthesis influences LBP or movement patterns known to increase its risk., Research Question: How are self-reported measures of LBP and lumbopelvic movement coordination patterns altered when using a unilateral transfemoral bone-anchored limb compared to a socket prosthesis?, Methods: Fourteen patients with unilateral transfemoral amputation scheduled to undergo intramedullary hardware implantation for bone-anchored limbs due to failed socket use were enrolled in this longitudinal observational cohort study (7 F/7 M, Age: 50.2±12.0 years). The modified Oswestry Disability Index (mODI) (self-reported questionnaire) and whole-body motion capture during overground walking were collected before (with socket prosthesis) and 12-months following bone-anchored limb implantation. Lumbopelvic total range of motion (ROM) and continuous relative phase (CRP) segment angles were calculated during 10 bilateral gait cycles. mODI, total ROM, CRP and CRP variabilities were compared between time points., Results: mODI scores were significantly reduced 12-months after intramedullary hardware implantation for the bone-anchored limb (P = 0.013). Sagittal plane trunk and pelvis total ROM during gait were reduced after implantation (P = 0.001 and P < 0.001, respectively). CRP values were increased (more anti-phase) in the sagittal plane during single limb stance and reduced (more in-phase) in the transverse plane during pre-swing of the amputated limb gait cycle (P << 0.001 and P = 0.029, respectively). No differences in CRP values were found in the frontal plane., Significance: Decreases in mODI scores and lumbopelvic ROM, paired with the changes in lumbopelvic coordination, indicate that bone-anchored limbs may reduce LBP symptoms and reduce compensatory movement patterns for people with unilateral transfemoral amputation., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Total hip arthroplasty (THA) is a common orthopedic procedure that alleviates pain for millions of individuals. Yet, persistent physical function deficits, perhaps associated with movement compensations, are observed after THA. These deficits negatively affect quality of life and health for many individuals. Functional strength integration (FSI) techniques combine muscle strength training with specific movement retraining to improve physical function. This study aimed to determine if FSI would improve functional performance through remediation of movement compensations for individuals after THA., Methods: A double-blind randomized controlled trial was conducted. Ninety-five participants were randomized to either the FSI or control (CON) group for an 8-week intervention. The FSI protocol included exercise to improve muscular control and stability around the hip to minimize movement compensation during daily activity. The CON protocol included low-load resistance exercise, range-of-motion activities, and patient education. Functional performance, muscle strength, and self-reported outcomes were measured preoperatively, midway and after intervention, and 6 months after THA. Change from preoperative assessment to each time point was measured, and between-group differences were assessed., Results: There were minimal differences in outcomes between groups at the first postoperative assessment. There were no statistically significant between-group differences in the later assessments, including the primary endpoint. Both groups improved functional outcomes throughout the study period., Conclusion: The FSI intervention did not result in greater improvements in function after THA compared to the CON intervention. Future work should further investigate additional biomechanical outcomes, timing of the FSI protocol, effective dosing, and patient characteristics predictive of success with FSI., Impact: Recovery after THA is complex, and individuals after THA are affected by persistent movement deficits that affect morbidity and quality of life. The present study suggests that either approach to THA rehabilitation could improve outcomes for patients, and that structured rehabilitation programs may benefit individuals after THA., (Published by Oxford University Press on behalf of American Physical Therapy Association 2023.)

Objective: The aim of this study was to understand therapist-identified factors influencing clinical adoption of a telehealth walking self-management intervention for individuals with lower limb amputation., Methods: Semi-structured focus groups were completed with actively practicing physical and occupational therapists treating populations that are medically complex. A qualitative explorative design was employed with conventional content analysis and iterative independent parallel coding using 2 analysts. Themes and subthemes were generated with a consensus building process identifying patterns and collapsing codes to represent participant perspectives., Results: Thematic saturation was met after 5 focus groups (24 therapists). Therapists were on average 34 years old and predominantly female (n = 19; 79%) physical therapists (n = 17; 71%). Three primary facilitator and barrier themes were identified for intervention adoption: system, therapist, and person. System considerations included telehealth support and interprofessional care coordination. Therapist facilitators included self-management programming that overlapped with standard of care and personalization methods. However, limited behavioral theory training was a therapist level barrier. Finally, person factors such as patient activation could influence both positively and negatively. Person facilitators included social support and barriers included the complex health condition., Conclusion: System, therapist, and person facilitators and barriers must be considered to maximize the adoption of similar telehealth walking self-management interventions and prior to larger scale implementation of the current intervention for individuals with lower limb amputation., Impact: A telehealth walking self-management intervention has potential impact for individuals with lower limb amputation and must be considered in terms of optimizing system, therapist, and person level facilitators and barriers to implementation., (© 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.)

Objective: This randomized controlled superiority trial will determine if an 18-month telehealth walking exercise self-management program produces clinically meaningful changes in walking exercise sustainability compared to attention-control education for veterans living with lower-limb amputation., Methods: Seventy-eight participants with lower-limb amputation (traumatic or nontraumatic) aged 50 to 89 years will be enrolled. Two groups will complete 6 one-on-one intervention sessions, and 6 group sessions over an 18-month intervention period. The experimental arm will receive a self-management program focusing on increasing walking exercise and the control group will receive attention-control education specific to healthy aging. Daily walking step count (primary outcome) will be continuously monitored using an accelerometer over the 18-month study period. Secondary outcomes are designed to assess potential translation of the walking exercise intervention into conventional amputation care across the Veteran Affairs Amputation System of Care. These secondary outcomes include measures of intervention reach, efficacy, likelihood of clinical adoption, potential for clinical implementation, and ability of participants to maintain long-term exercise behavior., Impact: The unique rehabilitation paradigm used in this study addresses the problem of chronic sedentary lifestyles following lower-limb amputation through a telehealth home-based walking exercise self-management model. The approach includes 18 months of exercise support from clinicians and peers. Trial results will provide rehabilitation knowledge necessary for implementing clinical translation of self-management interventions to sustain walking exercise for veterans living with lower-limb amputation, resulting in a healthier lifestyle., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early stages of PD., Objective: To investigate the relationship between chronotropic incompetence, orthostatic blood pressure change (supine - standing), and exercise performance (maximal oxygen consumption, VO2peak) in individuals with early PD within 5 years of diagnosis not on dopaminergic medications., Methods: We performed secondary analyses of heart rate and blood pressure data from the Study in Parkinson's Disease of Exercise (SPARX)., Results: 128 individuals were enrolled into SPARX (63.7±9.3 years; 57.0% male, 0.4 years since diagnosis [median]). 103 individuals were not taking chronotropic medications, of which 90 had a normal maximal heart rate response to exercise testing (155.3±14.0 bpm; PDnon-chrono) and 13 showed evidence of chronotropic incompetence (121.3±11.3 bpm; PDchrono, p < 0.05). PDchrono had decreased VO2peak compared to PDnon-chrono (19.7±4.5 mL/kg/min and 24.3±5.8 mL/kg/min, respectively, p = 0.027). There was a positive correlation between peak heart rate during exercise and the change in systolic blood pressure from supine to standing (r = 0.365, p < 0.001)., Conclusions: A subgroup of individuals with early PD not on dopaminergic medication had chronotropic incompetence and decreased VO2peak, which may be related to autonomic dysfunction. Evaluation of both heart rate responses to incremental exercise and orthostatic vital signs may serve as biomarkers of early autonomic impairment and guide treatment. Further studies should investigate whether cardiovascular autonomic dysfunction affects the ability to exercise and whether exercise training improves autonomic dysfunction.

Stroke is the main cause of acquired disability in adults. Exercise reduces the risk for stroke and protects against functional loss after stroke. An exercise-induced reduction in key risk factors probably contributes to the protective effect, but direct effects on the brain may also contribute to stroke protection. We previously reported that exercise increases angiogenesis and neurogenesis through activation of the lactate receptor HCA 1 . Here we exposed young adult wild-type mice and HCA 1 knockout mice to interval exercise at high or medium intensity, or to intraperitoneal injections of L-lactate or saline for seven weeks before we induced experimental stroke by permanent occlusion of the distal medial cerebral artery (dMCA). The resulting cortical atrophy measured three weeks after stroke was unaffected by exercise or L-lactate pre-treatments, and independent of HCA 1 activation. Our results suggest that the beneficial effect of exercise prior to stroke where no reperfusion occurs is limited in individuals who do not carry risk factors., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: People with lower-limb amputation (LLA) are routinely prescribed a socket prosthesis; however, many socket prosthesis users experience severe complications with the fit of their prosthesis including residual limb wounds and pain. Osseointegration is a procedure that creates a direct connection between the bone and prosthetic limb through a bone-anchored prosthesis, eliminating the need for a socket interface. It is offered as a secondary procedure to people with LLA who experience significant complications with socket prostheses., Objectives: To evaluate change in disability and function 1 year postosseointegration compared with preosseointegration in people with LLA., Study Design: Single group, pretest, and post-test., Methods: Twelve participants (9 transfemoral and 3 transtibial amputations, age: 44 ± 10 years, 7 female participants, 14 ± 12 years since amputation) with unilateral LLA underwent osseointegration with press-fit implants. Disability was measured with the World Health Organization Disability Assessment Schedule 2.0, and function was measured with both Prosthetic Limb Users Mobility Survey and the Activities-Specific Balance Confidence Scale. Questionnaires were administered preosseointegration and 1 year postosseointegration. Paired t tests assessed change in outcomes between time points., Results: Postosseointegration, participants demonstrated reduced disability measured with World Health Organization Disability Assessment Schedule 2.0 (%Δ = -52.6, p = 0.01), improved mobility measured with Prosthetic Limb Users Mobility Survey (%Δ = 21.8, P < 0.01), and improved balance confidence measured with the Activities-Specific Balance Confidence Scale (%Δ = 28.4, P < 0.01)., Conclusions: Participants report less disability and greater function in their prosthesis postosseointegration. Osseointegration is a novel procedure for people experiencing complications with their socket prosthesis, and this study is the first to show improvements in disability postosseointegration., (Copyright © 2022 International Society for Prosthetics and Orthotics.)

Background and Purpose: This study's purpose was to investigate the reliability, validity, and responsiveness of the Patient-Specific Functional Scale (PSFS) for measuring mobility-related goals in people with multiple sclerosis (MS)., Methods: Data from 32 participants with MS who underwent 8 to 10 weeks of rehabilitation were analyzed (Expanded Disability Status Scale scores 1.0-7.0). For the PSFS, participants identified 3 mobility-related areas where they had difficulty and rated them at baseline, 10 to 14 days later (before starting intervention), and immediately after intervention. Test-retest reliability and response stability of the PSFS were calculated using the intraclass correlation coefficient (ICC 2,1 ) and minimal detectable change (MDC 95 ), respectively. Concurrent validity of the PSFS was determined with the 12-item Multiple Sclerosis Walking Scale (MSWS-12) and the Timed 25-Foot Walk Test (T25FW). PSFS responsiveness was determined using Cohen's d , and minimal clinically important difference (MCID) was calculated based on patient-reported improvements on a Global Rating of Change (GRoC) scale., Results: The PSFS total score demonstrated moderate reliability (ICC 2,1 = 0.70, 95% CI: 0.46 to 0.84) and the MDC was 2.1 points. At baseline, the PSFS was fairly and significantly correlated with the MSWS-12 ( r = -0.46, P = 0.008) but not with the T25FW. Changes in the PSFS were moderately and significantly correlated with the GRoC scale (ρ = 0.63, P < 0.001), but not with MSWS-12 or T25FW changes. The PSFS was responsive ( d = 1.7), and the MCID was 2.5 points or more to identify patient-perceived improvements based on the GRoC scale (sensitivity = 0.85, specificity = 0.76)., Discussion and Conclusions: This study supports the use of the PSFS as an outcome measure in people with MS to assess mobility-related goals.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A423 )., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Academy of Neurologic Physical Therapy, APTA.)

People with unilateral transfemoral amputation using socket prostheses are at increased risk for developing osteoarthritis in both the residual hip and intact lower-limb joints. Osseointegrated prostheses are a surgical alternative to socket prostheses that directly attach to the residual femur via a bone-anchored implant, however their multi-joint loading effect is largely unknown. Our objective was to establish how osseointegrated prostheses influence joint loading during walking. Motion capture data (kinematics, ground reaction forces) were collected from 12 participants at baseline, with socket prostheses, and 12-months after prosthesis osseointegration during overground walking at self-selected speeds. Subject-specific musculoskeletal models were developed at each timepoint relative to osseointegration. Internal joint moments were calculated using inverse dynamics, muscle and joint reaction forces (JRFs) were estimated with static optimization. Changes in internal joint moments, JRFs, and joint loading-symmetry were compared using statistical parametric mapping (p≤ 0.05) before and after osseointegration. Amputated limb hip flexion moments and anterior JRFs decreased during terminal stance (p = 0.002, <0.001; respectively), while amputated limb hip abduction moments increased during mid-stance (p < 0.001), amputated hip rotation moment changed from internal to external throughout early stance (p < 0.001). Intact limb hip extension and knee flexion moments (p = 0.028, 0.032; respectively), superior and resultant knee JRFs (p = 0.046, 0.049; respectively) decreased during the loading response following prosthesis osseointegration. These results may indicate that the direct loading transmission of these novel prostheses create a more typical mechanical environment in bilateral joints, which is comparable with loading observed in able-bodied individuals and could decrease the risk of development or progression of osteoarthritis., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The clinical utility of the Trendelenburg Test remains unknown in people with multiple sclerosis (MS)., Objective: To measure (1) intra-rater reliability, (2) agreement of goniometer-assessed Trendelenburg pelvis-on-femur angle (POF) with motion capture, and (3) concurrent validity of Trendelenburg POF and hip abduction strength with POF during walking and step negotiation., Methods: Trendelenburg POF was measured in 20 people with MS using goniometry and motion analysis. In addition, peak POF was measured using motion analysis during walking, step ascent, and step descent. Intra-rater reliability of goniometer-assessed Trendelenburg POF and agreement with motion analysis-assessed POF were analyzed. Pearson's r was used to determine the relationships between Trendelenburg POF and hip abduction strength with peak POF during each functional activity., Results: Goniometer-assessed Trendelenburg POF demonstrated very strong reliability (ICC: 0.948), strong agreement with 3D motion analysis (ICC: 0.792), correlated moderately with peak POF during walking ( r = 0.519) and step ascent ( r = 0.572), and weakly with step descent ( r = 0.463). Hip abductor strength correlated weakly with peak POF during step ascent ( r = -0.307) and negligibly during walking ( r = -0.270) and step descent ( r = -0.249)., Conclusions: Goniometer-assessed Trendelenburg POF was reliable, agreed with motion analysis, and may provide insight into hip abduction muscle performance during functional activities in people with MS.

Background: Dissatisfaction with socket prostheses has led to the development of bone-anchored prostheses through osseointegration for people with transfemoral amputation, eliminating the need for a prosthetic socket. Gait deviations of transfemoral prosthesis users may be linked to increased risk of osteoarthritis, and it remains unknown if gait biomechanics change following osseointegration. The purpose of this case series was to evaluate the longitudinal changes in joint kinetics one year post-osseointegration in patients with transfemoral amputation during walking., Methods: Knee, hip, and trunk internal moments were evaluated in the prosthetic and intact limbs during walking at a self-selected speed in four participants pre- and one-year post-osseointegration. Longitudinal changes were quantified using the percent change (%∆) in peak joint moments between the two time points and Cohen's d (d) effect size was used to determine the magnitude of effect on joint moments during walking one year following osseointegration., Findings: Participants demonstrated increased peak knee extension moment (224 ± 308%∆, d = -1.31) in the prosthetic limb, while demonstrating reduced peak knee extension moment (-43 ± 34%∆, d = 1.82) in the intact limb post-osseointegration. Participants demonstrated bilateral reduction of peak hip extension moment (prosthetic: -22 ± 37%∆, d = 0.86; intact: -29 ± 10%∆, d = 1.27) and bilateral increase of peak hip abduction moment (prosthetic: 45 ± 40%∆, d = 1.20; intact: 23 ± 44%∆, d = 0.74) post-osseointegration. Participants demonstrated reduced peak trunk moments on both the prosthetic (extension: -31 ± 16%∆, d = 1.51; lateral flexion: -21 ± 20%∆, d = 0.63) and intact side (extension: -7 ± 22%∆, d = 0.38; lateral flexion: -22 ± 18%∆, d = 1.12) post-osseointegration., Interpretation: This case series suggests improved gait symmetry in individuals with transfemoral amputation one year following osseointegration, justifying future investigation., Competing Interests: Declaration of Competing Interest Dr. Jason Stoneback serves as a consultant for Revivo, an osseointegration device company, and Exer Al, a software company that investigates rehabilitation in osseointegration. Dr. Stoneback is a stake shareholder and receives funding from Exer Al. All other authors declare that they have no known conflicting financial interests or personal relationships that have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: More than half of patients with lower-limb amputation who use socket prostheses experience at least one fall annually. These falls are primarily attributed to reduced proprioception which negatively affects balance. A promising alternative to socket prostheses are osseointegrated prostheses that involve direct fixation of the prosthetic limb to the residual limb through a bone-anchored implant, yet its effect on balance remains unknown., Research Question: Do osseointegrated prostheses change static and dynamic balance, as well as patient reported measures of balance confidence, compared to a socket prosthesis?, Methods: A sample of 10 patients with unilateral transfemoral amputation scheduled to undergo prosthesis osseointegration were enrolled (6 F/4 M, BMI: 26.7 ± 2.9 kg/m 2 , Age: 46.1 ± 6.3 years). Motion capture data during quiet standing (eyes opened and eyes closed) and overground walking at a self-selected speed, and the Activities-Specific Balance Confidence (ABC) scale, were collected before (with socket prosthesis) and 12-months following osseointegration. Postural sway via the center of pressure (COP), variability of spatiotemporal parameters, and ABC scores were compared using a repeated measures design before and after osseointegration., Results: Following prosthesis osseointegration, COP path length and 95 % confidence ellipse area were reduced during quiet standing (d = 0.75, P = 0.09; d = 0.52, P = 0.29, respectively) and the variability of step width and length were reduced during overground walking (d = 0.50, P = 0.06; d = 0.72, P = 0.06, respectively). Furthermore, patients reported significantly improved ABC scores with an osseointegrated prosthesis compared to a socket prosthesis (d = -1.36, P = 0.01)., Significance: Improvements in postural sway, reductions in gait variability, and greater balance confidence indicate that osseointegrated prostheses improve balance for people with unilateral transfemoral amputation., Competing Interests: Conflict of Interest Statement The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Little has been published about the process of decision-making between prosthetists and people with lower limb amputation (LLA). The purpose of this study is to identify decisions and factors influencing decision-making in prosthetic rehabilitation from the perspectives of prosthetists and prosthesis users, to identify barriers and opportunities for shared decision-making (SDM)., Methods: Qualitative semi-structured individual interviews were conducted with 13 prosthetists and 14 prosthesis users from three clinics in three states of the Rocky Mountain and Southwest regions of the United States. Transcripts were analyzed using thematic analysis., Results: Four main themes were identified: perceived decision points, importance of relationship, balancing competing priorities, and experience . Contrasts between perceptions of prosthetists and prosthesis users were related to prosthesis design decisions, and the purpose of communication (e.g., goals for a prosthesis vs. goals informing prosthesis design). Both prosthetists and prosthesis users described balancing priorities that contribute to prosthetic rehabilitation decisions, and the role of experience for informing realistic expectations and preferences necessary for participating in decision-making., Conclusion: Opportunities for improving SDM between prosthetists and prosthesis users include (1) clarifying key rehabilitation decisions, (2) identifying the purpose of initial communications, (3) support for balancing priorities, and (4) utilizing experience to achieve informed preferences.IMPLICATIONS FOR REHABILITATIONMany people with lower limb amputation experience poor physical function and psychosocial outcomes, which may be further compounded by under informed prosthesis-user expectations for function with a prosthesis.Shared decision-making offers an opportunity for improving realistic prosthesis-user expectations, reducing healthcare costs, and improving prosthesis-user satisfaction and adherence to care plans.Opportunities for improving shared decision-making between prosthetists and prosthesis-users include (1) clarifying key rehabilitation decisions, (2) identifying the purpose of initial communications, (3) support for balancing priorities, and (4) utilizing experience to achieve informed preferences.

Background: Prosthesis design is complex and multiple appropriate options exist for any individual with lower-limb amputation. However, there is insufficient evidence for guiding decision-making. Shared decision-making (SDM) offers an opportunity to incorporate patient-specific values and preferences where evidence is lacking for prosthesis design decisions. To develop resources to facilitate SDM, and consistent with the International Patient Decision Aid Standards, it is necessary to identify the decisional needs of prosthetists and prosthesis users for prosthesis design decisions., Objectives: To assess the needs of prosthetists and new prosthesis users for SDM about the first prosthesis design., Study Design: Qualitative descriptive design., Methods: Six focus groups were conducted with 38 prosthetists. Individual semistructured interviews were conducted with 17 new prosthesis users. Transcripts were analyzed using directed content analysis, with codes defined a priori using existing frameworks for SDM: the Three Talk Model for SDM and the Ottawa Decision Support Framework., Results: Four main themes were identified among prosthetists and prosthesis users: acknowledging complexity in communication, clarifying values, recognizing the role of experience to inform preferences , and understanding the prosthetic journey ., Conclusions: Resources that support SDM for the first prosthesis design should consider methods for identifying individual communication needs, support with clarifying values, and resources such as experience for achieving informed preferences, within the context of the overall course of rehabilitation and recovery following lower-limb amputation. The themes identified in this work can inform SDM to promote collaborative discussion between prosthetists and new prosthesis users when making prosthesis design decisions., (Copyright © 2022 International Society for Prosthetics and Orthotics.)