CSF ß-Amyloid and Tau Biomarker Changes in Veterans With Mild Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Moderate-to-severe traumatic brain injuries (TBI) have been reported to increase the risk of Alzheimer disease (AD). Whether mild TBI (mTBI) in veterans confers a similar increased risk of AD is less known. This study investigated early AD changes using CSF biomarkers in veterans with blast mTBI. METHODS: This was a cross-sectional case-control study of veterans with mTBI and non-mTBI veterans and civilians from 2 study sources. Blast-mTBI veterans had at least 1 war zone blast or combined blast/impact mTBI meeting Veterans Affairs (VA) and Department of Defense (DoD) criteria for mTBI. Non-mTBI participants had no lifetime history of TBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of the CSF. CSF biomarkers were measured using MesoScale Discovery assays for Aß40 and Aß42 and INNOTEST ELISAs for phosphorylated tau181 (p-tau181) and total tau (t-tau). RESULTS: Our sample comprised 51 participants with mTBI and 85 non-mTBI participants with mean (SD) ages 34.0 (10.1) and 33.5 years (8.9), respectively. All participants but 1 (99%) were male. Differences in CSF AD biomarkers between mTBI and non-mTBI groups were age dependent and most pronounced at older ages (omnibus test p ≤ 0.08). At age 50 years, the mTBI group had lower mean [95% CI] CSF Aß42 and Aß40 than the non-mTBI group by 154 [-12 to 319] and 1864 [610-3,118] pg/mL, respectively. By contrast, CSF p-tau181 and t-tau mean levels remained relatively constant with age in participants with mTBI, while tending to be higher at older ages for the non-mTBI group. The mTBI group also demonstrated poorer cognitive performance at older ages (omnibus p < 0.08): at age 50 years, the mean TMT-B time was higher by 34 seconds [10-58] and the mean CVLT-II short-delay recall was lower by 4.2 points [1.9-6.6]. Poorer verbal memory and verbal fluency performance were associated with lower CSF Aß42 (p ≤ 0.05) in older participants. DISCUSSION: CSF Aß levels decreased in middle-aged veterans with blast-related mTBI. These data suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes known to portend AD onset, thus raising concern that veterans with blast-related mTBI may develop a dementing disorder later in life.

Military Sexual Trauma As a Risk Factor for Treatment Non-Response from an Online, Self-Management Posttraumatic Stress Disorder Treatment for Women Veterans.

Women veterans are exposed to high rates of trauma, including military sexual trauma (MST), and face unique barriers to posttraumatic stress disorder (PTSD) treatment. Telehealth interventions that are tailored to women veterans' unique lived experiences may improve treatment engagement and outcomes. It is important to ascertain how beneficial new telehealth interventions are in the context of different patient characteristics and trauma types, particularly for lower-intensity telehealth interventions (e.g., web-based programs or apps). This secondary analysis of a randomized clinical trial conducted in a sample of 102 women veterans examines predictors of treatment response to a self-management, telehealth intervention for PTSD: Delivery of Self Training and Education for Stressful Situations-Women Veterans (DESTRESS-WV). In the trial, women veterans with PTSD received either an online cognitive behavioral intervention with phone coaching, or phone monitoring alone. We examined associations between baseline patient characteristics (demographics, trauma types, and clinical symptoms) and treatment outcome at post-treatment, 3 months, and 6 months, focusing on the association between treatment outcome and MST. Our primary outcomes were changes in PTSD (PTSD Symptom Checklist, Version 5, PCL-5) and depression (8-item Patient Health Questionnaire, PHQ-8) in the full sample, adjusting for treatment condition. Women veterans who identified MST as the primary trauma for which they were seeking PTSD treatment experienced a nearly nine-point lesser improvement on the PCL-5 than those seeking PTSD treatment for other trauma types (e.g., childhood abuse, combat trauma; p = .0073). Similar patterns were found for depression symptoms. To our knowledge, this is the first study to examine the association between trauma type and treatment outcomes within the context of a self-management, telehealth treatment for PTSD. While the study was not powered to examine differential treatment response for patient subgroups, our exploratory findings suggest that gaps remain in providing effective PTSD care for women veterans who experienced MST.Trial registration: The trial and analysis plan were preregistered in ClinicalTrials.gov (Identifier: NCT02917447).

The development of rating scales to evaluate experiential prosthetic foot preference for people with lower limb amputation.

BACKGROUND: Selection of a foot is an important aspect of prosthetic prescription and vital to maximizing mobility and functional goals after lower limb amputation. Development of a standardized approach to soliciting user experiential preferences is needed to improve evaluation and comparison of prosthetic feet. OBJECTIVE: To develop rating scales to assess prosthetic foot preference and to evaluate use of these scales in people with transtibial amputation after trialing different prosthetic feet. DESIGN: Participant-blinded, repeated measures crossover trial. SETTING: Veterans Affairs and Department of Defense Medical Centers, laboratory setting. PARTICIPANTS: Seventy-two male prosthesis users with unilateral transtibial amputation started, and 68 participants completed this study. INTERVENTIONS: Participants trialed three mobility-level appropriate commercial prosthetic feet briefly in the laboratory. MAIN OUTCOME MEASURES: "Activity-specific" rating scales were developed to assess participants' ability with a given prosthetic foot to perform typical mobility activities (eg, walking at different speeds, on inclines, and stairs) and "global" scales to rate overall perceived energy required to walk, satisfaction, and willingness to regularly use the prosthetic foot. Foot preference was determined by comparing the rating scale scores, after laboratory testing. RESULTS: The greatest within-participant differences in scores among feet were observed in the "incline" activity, where 57% ± 6% of participants reported 2+ point differences. There was a significant association (p < .05) between all "activity-specific" rating scores (except standing) and each "global" rating score. CONCLUSIONS: The standardized rating scales developed in this study could be used to assess prosthetic foot preference in both the research and clinical settings to guide prosthetic foot prescription for people with lower limb amputation capable of a range of mobility levels.

Prospective Multicenter Study of Salto Talaris Ankle Arthroplasty With Minimum 4-Year Follow-Up.

BACKGROUND: Total ankle arthroplasty (TAA) continues to be investigated as a primary treatment for end-stage ankle arthritis. The objective of this study is to report mid- to long-term results of the Salto Talaris TAA using prospectively collected patient-reported outcomes and implant survival rates with 4- to 13-year follow-up. METHODS: This was a retrospective study of prospectively collected data from 2 multicenter cohort studies from 3 centers. Three hundred fourteen subjects who received a Salto Talaris TAA from 2005 to 2015 were included in the study. Follow-up ranged 4-13 years following index procedure. Outcomes included 36-Item Short Form Health Survey (SF-36) mental and physical component summary scores, pain scores, and adverse events including additional surgeries, revision, or removal of components. RESULTS: Significant improvements were seen in pain and physical function scores at 2-year follow-up and were generally maintained through most recent follow-up. The survival rate of the prosthesis was >95% (n = 30/32 at >10 years, n = 272/282 at 4.5-10 years). Thirteen patients (4.1%) underwent revision or removal of their prosthesis. Time to revision ranged from 2 months to 6.5 years following the index procedure. Twenty-two patients (7.0%) had additional surgery that did not involve revision or removal of components. CONCLUSION: Treatment of end-stage ankle arthritis with this implant provided patients with improved pain and functional outcome scores at mid- to long-term follow-up. The significant improvements reported at 2-4 years appeared to endure through the extended follow-up period. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Randomized controlled pilot trial of prazosin for prophylaxis of posttraumatic headaches in active-duty service members and veterans.

OBJECTIVE: Evaluate the efficacy and tolerability of prazosin for prophylaxis of headaches following mild traumatic brain injury in active-duty service members and military veterans. BACKGROUND: Prazosin is an alpha-1 adrenoreceptor antagonist that reduces noradrenergic signaling. An open-label trial in which prazosin reduced headache frequency in veterans following mild traumatic brain injury provided the rationale for this pilot study. METHODS: A 22-week parallel-group randomized controlled trial  which included 48 military veterans and active-duty service members with mild traumatic brain injury-related headaches was performed. The study design was based on International Headache Society consensus guidelines for randomized controlled trials for chronic migraine. Following a pre-treatment baseline phase, participants with at least eight qualifying headache days per 4 weeks were randomized 2:1 to prazosin or placebo. After a 5-week titration to a maximum possible dose of 5 mg (morning) and 20 mg (evening), participants were maintained on the achieved dose for 12 weeks. Outcome measures were evaluated in 4-week blocks during the maintenance dose phase. The primary outcome measure was change in 4-week frequency of qualifying headache days. Secondary outcome measures were percent participants achieving at least 50% reduction in qualifying headache days and change in Headache Impact Test-6 scores. RESULTS: Intent-to-treat analysis of randomized study participants (prazosin N = 32; placebo N = 16) demonstrated greater benefit over time in the prazosin group for all three outcome measures. In prazosin versus placebo participants, reductions from baseline to the final rating period for 4-week headache frequency were -11.9 ± 1.0 (mean ± standard error) versus -6.7 ± 1.5, a prazosin minus placebo difference of -5.2 (-8.8, -1.6 [95% confidence interval]), p = 0.005 and for Headache Impact Test-6 scores were -6.0 ± 1.3 versus +0.6 ± 1.8, a difference of -6.6 (-11.0, -2.2), p = 0.004. The mean predicted percent of participants at 12 weeks with ≥50% reduction in headache days/4 weeks, baseline to final rating, was 70 ± 8% for prazosin (21/30) versus 29 ± 12% for placebo (4/14), odds ratio 5.8 (1.44, 23.6), p = 0.013. The trial completion rate of 94% in the prazosin group (30/32) and 88% in the placebo group (14/16) indicated that prazosin was generally well tolerated at the administered dose regimen. Morning drowsiness/lethargy was the only adverse effect that differed significantly between groups, affecting 69% of the prazosin group (22/32) versus 19% of the placebo group (3/16), p = 0.002. CONCLUSIONS: This pilot study provides a clinically meaningful efficacy signal for prazosin prophylaxis of posttraumatic headaches. A larger randomized controlled trial is needed to confirm and extend these promising results.

Performance of a condensed protocol to assess limbic-predominant age-related TDP-43 encephalopathy neuropathologic change.

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is a dementia-related proteinopathy common in the elderly population. LATE-NC stages 2 or 3 are consistently associated with cognitive impairment. A condensed protocol (CP) for the assessment of Alzheimer disease neuropathologic change and other disorders associated with cognitive impairment, recommended sampling of small brain portions from specific neuroanatomic regions that were consolidated, resulting in significant cost reduction. Formal evaluation of the CP for LATE-NC staging was not previously performed. Here, we determined the ability of the CP to identify LATE-NC stages 2 or 3. Forty brains donated to the University of Washington BioRepository and Integrated Neuropathology laboratory with known LATE-NC status were resampled. Slides containing brain regions required for LATE-NC staging were immunostained for phospho-TDP-43 and reviewed by 6 neuropathologists blinded to original LATE-NC diagnosis. Overall group performance distinguishing between LATE-NC stages 0-1 and 2-3 was 85% (confidence interval [CI]: 75%-92%). We also used the CP to evaluate LATE-NC in a hospital autopsy cohort, in which LATE-NC was more common in individuals with a history of cognitive impairment, older age, and/or comorbid hippocampal sclerosis. This study shows that the CP can effectively discriminate higher stages of LATE-NC from low or no LATE-NC and that it can be successfully applied in clinical practice using a single tissue block and immunostain.

The effect of diabetes and tissue depth on adipose chamber size and plantar soft tissue features.

BACKGROUND: Plantar ulceration is a serious complication of diabetes. However, the mechanism of injury initiating ulceration remains unclear. The unique structure of the plantar soft tissue includes superficial and deep layers of adipocytes contained in septal chambers, however, the size of these chambers has not been quantified in diabetic or non-diabetic tissue. Computer-aided methods can be leveraged to guide microstructural measurements and differences with disease status. METHODS: Adipose chambers in whole slide images of diabetic and non-diabetic plantar soft tissue were segmented with a pre-trained U-Net and area, perimeter, and minimum and maximum diameter of adipose chambers were measured. Whole slide images were classified as diabetic or non-diabetic using the Axial-DeepLab network, and the attention layer was overlaid on the input image for interpretation. RESULTS: Non-diabetic deep chambers were 90 %, 41 %, 34 %, and 39 % larger in area (26,954 ± 2428 µm2 vs 14,157 ± 1153 µm2), maximum (277 ± 13 µm vs 197 ± 8 µm) and minimum (140 ± 6 µm vs 104 ± 4 µm) diameter, and perimeter (405 ± 19 µm vs 291 ± 12 µm), respectively, than the superficial (p < 0.001). However, there was no significant difference in these parameters in diabetic specimens (area 18,695 ± 2576 µm2 vs 16627 ± 130 µm2, maximum diameter 221 ± 16 µm vs 210 ± 14 µm, minimum diameter 121 ± 8 µm vs 114 ± 7 µm, perimeter 341 ± 24 µm vs 320 ± 21 µm). Between diabetic and non-diabetic chambers, only the maximum diameter of the deep chambers differed (221 ± 16 µm vs 277 ± 13 µm). The attention network achieved 82 % accuracy on validation, but the attention resolution was too coarse to identify meaningful additional measurements. CONCLUSIONS: Adipose chamber size differences may provide a basis for plantar soft tissue mechanical changes with diabetes. Attention networks are promising tools for classification, but additional care is required when designing networks for identifying novel features. DATA AVAILABILITY: All images, analysis code, data, and/or other resources required to replicate this work are available from the corresponding author upon reasonable request.

Correlates of Conversion from Mild Cognitive Impairment to Dementia with Lewy Bodies: Data from the National Alzheimer's Coordinating Center.

BACKGROUND: Many patients with dementia with Lewy bodies (DLB) miss out on the best standards of care and psychosocial support due to diagnostic delays or inaccuracies following symptom onset. OBJECTIVE: This study seeks to identify baseline characteristics in individuals with mild cognitive impairment (MCI) that correlate with eventual conversion to DLB or Alzheimer's disease (AD). METHODS: Baseline neuropsychological and neuropsychiatric data were analyzed in National Alzheimer's Coordinating Center participants who completed the Uniform Data Set between 2006 and 2020 and subsequently converted from MCI to DLB or AD (n = 1632). RESULTS: Only 6% of participants with MCI converted to DLB. Among those who converted to DLB, multidomain amnestic MCI (aMCI) was the most common subtype at study entry. As part of logistic regression analyses, odds ratios (ORs) were estimated for conversion to DLB versus AD based on study-entry characteristics, adjusting for age, sex, education, and years to diagnosis. The strongest predictors of conversion to DLB (p≤0.0001) were nonamnestic MCI versus aMCI (OR 8.2, CI [5.0, 14]), multidomain MCI versus single-domain MCI (OR 2.7, CI [1.7. 4.2]), male sex (OR 4.2, CI [2.5, 7.1]), and presence of nighttime behaviors (OR 4.4 CI [2.8, 6.9]). CONCLUSION: A diagnosis of prodromal DLB should be considered in individuals with MCI who present with prominent executive/visuospatial deficits, neuropsychiatric symptoms, and less memory impairment. Early diagnosis of DLB may guide treatment planning, including the avoidance of antipsychotic medications in patients who develop psychotic symptoms, caregiver support, and initiation of early treatment(s) once medications become available.

Low cumulative disease activity is associated with higher bone mineral density in a majority Latinx and Asian US rheumatoid arthritis cohort.

OBJECTIVE: Prior studies have found conflicting results when evaluating the association between rheumatoid arthritis (RA) disease activity and bone mineral density (BMD). Whether or not cumulative RA disease activity is associated with BMD remains unanswered. METHODS: Data were from the University of California San Francisco RA Cohort from years 2006-2018. Those with BMD measures and at least two study visits prior to BMD measure were included in the study. The association between low cumulative disease activity, as measured by DAS28ESR, with the primary outcome of femoral neck BMD was assessed using multivariable linear regression. Sensitivity analyses were performed substituting CDAI for the disease activity measure as well as total hip and lumbar spine BMD as outcomes. RESULTS: 161 participants with RA were studied. The cohort was 62.4 ± 10.2 years old and 88% female. Hispanic/Latino (N = 73, 45%) and Asian (N = 59, 37%) were the most common racial/ethnic groups in our cohort. Mean RA duration was 10.5 ± 7.3 years and 83% were ACPA positive. Low disease activity was independently associated with higher femoral neck BMD compared to the moderate/high disease activity group (ß= 0.071 [95%CI: 0.021 to 0.122], p = 0.020). The relationship between low cumulative disease activity was similar when CDAI and other BMD sites were substituted in the multivariable models. CONCLUSION: Low cumulative disease activity as measured by DAS28ESR was associated with higher femoral neck BMD, independent of traditional osteoporosis risk factors (e.g., age, sex, BMI) in a unique RA cohort. Results were similar when evaluating cumulative low CDAI and other BMD sites.

Self-perceived irritability among OEF/OIF/OND veterans with a history of deployment-related mTBI: Associations with prospective memory and quality of life.

Objective: Examine relationships between self-perceived irritability, prospective memory, and quality of life (QOL) following mild traumatic brain injury (mTBI). Methods: 75 OEF/OIF/OND-era Veterans (56 deployment-related mTBI; 19 no history of TBI), were administered a battery of neuropsychological tests and self-report measures of mood and QOL. Self-perceived irritability was measured using the Neurobehavioral Symptom Inventory. Prospective memory (PM) was measured using the Memory for Intentions Test (MIST). Results: Self-perceived irritability was significantly higher for Veterans with, versus without, a history of deployment-related mTBI. Among Veterans with a history of mTBI, self-perceived irritability was inversely associated with PM performance, even after adjusting for PTSD severity. Greater self-perceived irritability was also associated with higher depressive symptoms and reduced QOL for perceived physical health, psychological health, social support, and environmental factors; however, only social support remained significant after adjusting for PTSD severity. Depression symptom severity was not significantly associated with PM, suggesting that PM may be uniquely related to self-perceived irritability rather than mood dysregulation more generally. Conclusions: Findings provide preliminary evidence of a relationship between PM and self-perceived irritability in Veterans with a history of mTBI. PM and irritability may be related via their mutual reliance on high-level cognitive control. Results illustrate possible cognitive and affective factors contributing to psychological and interpersonal challenges for this population. Future investigations with larger and more diverse samples are needed to replicate findings and explore potential mechanisms linking irritability and PM following mTBI.

The Impact of Coronal Plane Deformity on Ankle Arthrodesis and Arthroplasty.

BACKGROUND: Ankle coronal plane deformity represents a complex 3-dimensional problem, and comparative data are lacking to guide treatment recommendations for optimal treatment of end-stage ankle arthritis with concomitant coronal plane deformity. METHODS: In total, 224 patients treated for end-stage ankle arthritis were enrolled in an observational trial. Of 112 patients followed more than 2 years, 48 patients (19 arthrodesis, 29 arthroplasty) had coronal plane deformity and were compared to 64 patients without coronal plane deformity (18 arthrodesis, 46 arthroplasty) defined as greater than 10 degrees of varus or valgus. The arthroplasty implants used had different internal constraints to intracomponent coronal plane tilting. Patients completed Musculoskeletal Functional Assessment (MFA) and SF-36 preoperatively and at 3, 6, 12, 24, and 36 months postoperatively. Measures included change in SF-36 and MFA, as well as compared reoperation rates and pain scales. RESULTS: For the groups with coronal plane ankle deformity, the median for the arthrodesis group was 19.0 degrees and the median for the arthroplasty group was 16.9 degrees. In the deformity cohort during the follow-up period, we had 7 major reoperations: 2 in the arthrodesis group and 5 in the arthroplasty group, all with the less constrained implant design. MFA, vitality, and social function of the SF-36 improved for all groups. Patients without preoperative deformities had greater improvement with fusion or replacement at both 2 and 3 years. There was no difference in improvement between those patients with coronal deformity who received arthroplasty vs arthrodesis. CONCLUSION: Patients with and without coronal plane deformity may benefit from ankle arthroplasty and arthrodesis, although greater improvements may be expected in those without preoperative deformity. In this study, at final follow-up of 3 years, overall we found no meaningful difference in patient-reported outcomes between the patients with preoperative coronal plane deformities whether they had a fusion or a replacement as treatment for end-stage ankle arthritis. LEVEL OF EVIDENCE: Level II, comparative study.

Comparing 4-Year Changes in Patient-Reported Outcomes Following Ankle Arthroplasty and Arthrodesis.

BACKGROUND: The rate of total ankle arthroplasty (TAA) is increasing relative to ankle arthrodesis (AA) for patients seeking surgical treatment for end-stage ankle arthritis. Patients and providers would benefit from a more complete understanding of the rate of improvement, the average length of time to achieve maximal function and minimal pain, and whether there is a greater decline in function or an increase in pain over time following TAA compared with AA. The objectives of this study were to compare treatment changes in overall physical and mental function and ankle-specific function, as well as pain intensity at 48 months after TAA or AA in order to determine if the improvements are sustained. METHODS: This was a multisite prospective cohort study that included 517 participants (414 TAA and 103 AA) who presented for surgical treatment. Participants were compared 48 months after surgery using the Foot and Ankle Ability Measure (FAAM) Activities of Daily Living and Sports subscales (0 to 100 points), the Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) scores (0 to 100 points), and pain scores (0 to 10 points). RESULTS: Both groups achieved significant improvement in the 2 FAAM measures, the SF-36 PCS score, and all of the pain measures at 48 months after surgey (p < 0.001). Mean improvements from baseline in patients undergoing TAA for the FAAM Activities of Daily Living, FAAM Sports, and SF-36 scores were at least 9 points, 8 points, and 3.5 points, respectively, which were higher than in those undergoing AA. Mean improvements in worst and average pain were at least 0.9 point higher in patients undergoing TAA than in those undergoing AA at 12, 24, and 36 months. These differences were attenuated by 48 months. For both treatments, all improvements from baseline to 24 months had been maintained at 48 months. CONCLUSIONS: When both procedures are performed by the same group of surgeons, patients who undergo TAA or AA for end-stage ankle arthritis have significant improvement in overall function, ankle-specific function, and pain at 48 months after surgery, with better functional improvement in the TAA group. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Ankle fusion and replacement gait similar post-surgery, but still exhibit differences versus controls regardless of footwear.

Persons with ankle osteoarthritis (AOA) often seek surgical intervention to alleviate pain and restore function; however, recent research has yielded no superior choice between the two primary options: fusion and replacement. One factor yet to be considered is the effect of footwear on biomechanical outcomes. Comparisons of AOA biomechanics to a normative population are also sparse. The objectives of this study were to (1) determine how footwear uniquely affected gait in persons with ankle fusion and replacement and (2) provide context for AOA biomechanics via comparisons to a healthy adult sample. Thirty-four persons with AOA performed overground walking trials barefoot and shod before surgical intervention and then received either an ankle fusion (n = 14) or replacement (n = 20). Two and/or three years post-surgery, patients returned for gait analysis. Nineteen controls performed the same gait procedures during a single study visit. Spatiotemporal variables and peak angles, internal moments, powers, and forces were calculated to quantify gait behavior. Overall, the two surgical groups performed similarly to each other but demonstrated marked differences from controls both pre- and post-surgery. No significant differences were detected when examining the effect of footwear. The motion of the midfoot with respect to the hindfoot and forefoot may be instrumental in gait biomechanics following an ankle fusion or replacement and should be considered in future investigations.

The effect of prosthetic foot stiffness on foot-ankle biomechanics and relative foot stiffness perception in people with transtibial amputation.

BACKGROUND: Prosthetic feet are available in a range of stiffness categories, however, there is limited evidence to guide optimal selection during prosthetic foot prescription. The aim of this study was to determine the effect of commercial prosthetic foot stiffness category on foot-ankle biomechanics, gait symmetry, community ambulation, and relative foot stiffness perception. METHODS: Participants were fit in randomized order with three consecutive stiffness categories of a commonly-prescribed prosthetic foot. Prosthetic foot roll-over shape and ankle push-off power and work were determined via data collected during walking in a motion analysis laboratory. Step activity was recorded during community use of each foot. Self-reported perception of relative foot stiffness was assessed with an ad hoc survey. FINDINGS: Seventeen males with transtibial amputation completed the study. Prosthetic foot roll-over radius increased with increased prosthetic foot stiffness categories (p < 0.001). Both prosthetic ankle push-off peak power and work decreased with increased foot stiffness categories (p = 0.002). There was no association between prosthetic foot stiffness category and step length symmetry or steps per day. When assessed post-accommodation, there was no association between relative foot stiffness perception and the stiffness category across prosthetic foot conditions. INTERPRETATION: Prosthetic foot stiffness category was significantly associated with changes in prosthetic foot-ankle biomechanical variables, however, was not associated with changes in gait symmetry or community ambulation. Relative prosthetic foot stiffness perception after accommodation was generally inconsistent with the order of prosthetic foot stiffness categories. CLINICAL RELEVANCE: While there were quantifiable differences in prosthetic foot-ankle biomechanics across stiffness categories, no significant differences were detected in gait symmetry or mean daily step count in the community. Furthermore, after community use, participants perceptions of relative stiffness across feet were generally inconsistent with the order of prosthetic foot stiffness categories. These findings raise questions as to whether changes in commercial prosthetic foot stiffness category (within a clinically relevant range) affect subjective and objective measures relevant to successful outcomes from prosthetic foot prescription.

Neuropathy, claw toes, intrinsic muscle volume, and plantar aponeurosis thickness in diabetic feet.

BACKGROUND: The objective of this study was to explore the relationships between claw toe deformity, peripheral neuropathy, intrinsic muscle volume, and plantar aponeurosis thickness using computed tomography (CT) images of diabetic feet in a cross-sectional analysis. METHODS: Forty randomly-selected subjects with type 2 diabetes were selected for each of the following four groups (n = 10 per group): 1) peripheral neuropathy with claw toes, 2) peripheral neuropathy without claw toes, 3) non-neuropathic with claw toes, and 4) non-neuropathic without claw toes. The intrinsic muscles of the foot were segmented from processed CT images. Plantar aponeurosis thickness was measured in the reformatted sagittal plane at 20% of the distance from the most inferior point of the calcaneus to the most inferior point of the second metatarsal. Five measurement sites in the medial-lateral direction were utilized to fully characterize the plantar aponeurosis thickness. A linear mixed-effects analysis on the effects of peripheral neuropathy and claw toe deformity on plantar aponeurosis thickness and intrinsic muscle volume was performed. RESULTS: Subjects with concurrent neuropathy and claw toes had thicker mean plantar aponeurosis (p < 0.006) and may have had less mean intrinsic muscle volume (p = 0.083) than the other 3 groups. The effects of neuropathy and claw toes on aponeurosis thickness were synergistic rather than additive. A similar pattern may exist for intrinsic muscle volume, but results were not as conclusive. A negative correlation was observed between plantar aponeurosis thickness and intrinsic muscle volume (R2 = 0.323, p < 0.001). CONCLUSIONS: Subjects with concurrent neuropathy and claw toe deformity were associated with the smallest intrinsic foot muscle volumes and the thickest plantar aponeuroses. Intrinsic muscle atrophy and plantar aponeurosis thickening may be related to the development of claw toes in the presence of neuropathy.

Effectiveness and Safety of Ankle Arthrodesis Versus Arthroplasty: A Prospective Multicenter Study.

BACKGROUND: Newer designs and techniques of total ankle arthroplasty (TAA) have challenged the assumption of ankle arthrodesis (AA) as the primary treatment for end-stage ankle arthritis. The objective of this study was to compare physical and mental function, ankle-specific function, pain intensity, and rates of revision surgery and minor complications between these 2 procedures and to explore heterogeneous treatment effects due to age, body mass index (BMI), patient sex, comorbidities, and employment on patients treated by 1 of these 2 methods. METHODS: This was a multisite prospective cohort study comparing outcomes of surgical treatment of ankle arthritis. Subjects who presented after nonoperative management had failed received either TAA or AA using standard-of-treatment care and rehabilitation. Outcomes included the Foot and Ankle Ability Measure (FAAM), Short Form-36 (SF-36) Physical and Mental Component Summary (PCS and MCS) scores, pain, ankle-related adverse events, and treatment success. RESULTS: Five hundred and seventeen participants underwent surgery and completed a baseline assessment. At 24 months, the mean improvement in FAAM activities of daily living (ADL) and SF-36 PCS scores was significantly greater in the TAA group than in the AA group, with a difference between groups of 9 points (95% confidence interval [CI] = 3, 15) and 4 points (95% CI = 1, 7), respectively. The crude incidence risks of revision surgery and complications were greater in the AA group; however, these differences were no longer significant after adjusting for age, sex, BMI, and Functional Comorbidity Index (FCI). The treatment success rate was greater after TAA than after AA for those with an FCI of 4 (80% versus 62%) and not fully employed (81% versus 58%) but similar for those with an FCI score of 2 (81% versus 77%) and full-time employment (79% versus 78%). CONCLUSIONS: At 2-year follow-up, both AA and TAA were effective. Improvement in several patient-reported outcomes was greater after TAA than after AA, without a significant difference in the rates of revision surgery and complications. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Step Activity After Surgical Treatment of Ankle Arthritis.

BACKGROUND: Ambulatory activity is reduced in patients with ankle arthritis. In this study, we measured step activity over time in 2 treatment groups and secondarily compared step activity with results of patient-reported outcome measures (PROMs). METHODS: Patients who were treated with either ankle arthrodesis or ankle arthroplasty wore a step activity monitor preoperatively and at 6, 12, 24, and 36 months postoperatively. Changes from preoperative baseline in total steps per day and per-day metrics of low, medium, and high-activity step counts were measured in both treatment groups. Step activity was compared with each subject's PROM scores as reported on the Musculoskeletal Function Assessment (MFA) and the Short Form-36 (SF-36) physical function and bodily pain subscales. RESULTS: Of the 3 activity levels, combined group high-activity step counts showed the greatest increase (mean of 278 steps [95% confidence interval (CI), 150 to 407 steps], a 46% improvement from preoperatively). At 6 months, the mean high-activity step improvement for the arthroplasty group was 194 steps compared with a mean decline of 44 steps for the arthrodesis group (mean 238-step difference [95% CI, -60 to 536 steps]). By 36 months postoperatively, the greater improvement in high-activity steps for the arthroplasty versus the arthrodesis group was no longer present. There were no significant pairwise differences in improvement based on surgical treatment method at any individual follow-up time point. For a within-patient increase of 1,000 total steps, there was a mean change in the MFA, SF-36 physical function, and SF-36 bodily pain scores of -1.8 (95% CI, -2.4 to -1.2), 3.8 (95% CI, 2.8 to 4.8), and 2.8 (95% CI, 1.8 to 3.9), respectively (p < 0.0001 for all associations). There was no evidence that the association differed by study visit, or by study visit and surgical procedure interaction (p > 0.10). CONCLUSIONS: Surgical treatment of ankle arthritis significantly improves ambulatory activity, with greater change occurring at high activity levels. Improvement may occur more quickly following arthroplasty than arthrodesis, but at 3 years, we detected no significant difference between the 2 procedures. Step counts, while associated with PROMs, do not parallel them, and thus may be a useful supplementary measure, particularly in longitudinal studies. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Variables associated with subjective cognitive change among Iraq and Afghanistan war Veterans with blast-related mild traumatic brain injury.

Introduction: This study investigated variables associated with subjective decline in executive function among Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND) following a history of blast-related mild traumatic brain injury (mTBI). Method: Fifty-six male U.S. Veterans (MAge = 35.3 ± 8.8 years) with a history of blast-related mTBI (6.6 ± 3.2 years post injury) completed a battery of self-report questionnaires and neuropsychological measures. Participants rated current and retrospectively estimated pre-mTBI executive function difficulties on the Frontal Systems Behavior Scale (FrSBe). A difference score (post- minus pre-mTBI ratings) was the dependent variable (∆FrSBe). Linear regression models examined variables predicting ∆FrSBe, including: pre-injury characteristics (education, premorbid intelligence), injury-related characteristics (number of blast exposures, losses of consciousness), post-injury clinical symptoms (PTSD Checklist-Military version; Pittsburgh Sleep Quality Index), and post-injury neuropsychological performances on executive function measures (Trail Making Test Part B; Controlled Oral Word Association Test; Auditory Consonant Trigrams; Wisconsin Card Sorting Test). Results: While 11% of participants had a clinically elevated pre-injury FrSBe total score, 82% had a clinically elevated post-injury FrSBe total score. Only self-reported PTSD symptom severity independently predicted perceived change in executive function. Conclusions: Many OEF/OIF/OND Veterans with a history of blast-related mTBI experience subjective decline in executive function following injury. Perceived executive function decline was associated with higher PTSD symptom severity, aligning with previous research associating PTSD with cognitive complaints. Results did not support a correspondence between perceived cognitive change and neuropsychological performances.

Cognitive Self-Efficacy and Mental Health Ratings after a Memory Skills Group for Older Veterans with PTSD.

Objectives: Mental health factors, such as PTSD, can exacerbate typical age-related cognitive changes and lead individuals to have subjective concerns for which few interventions presently exist. This study evaluates self-reported mental health outcomes following a psychoeducational memory skills program designed for veterans over 50 with subjective memory concerns in the context of PTSD. It was hypothesized that outcomes would improve following program participation and that baseline cognitive self-efficacy would moderate improvements in self-reported depression and life satisfaction. Methods: Veterans (n = 101, age ≥ 51) participated in an 8-week memory skills program and completed baseline and post-program assessment data as part of a quality improvement project. Results: Life satisfaction and cognitive self-efficacy demonstrated significant improvement following participation in the memory skills program. Cognitive self-efficacy was found to significantly modify change in depressive symptoms. Conclusions: We found improvement in mental health outcomes following participation in a psychoeducational memory skills program, with differential impact on depressive symptoms for those with low baseline cognitive self-efficacy. Clinical Implications: Participation in this intervention led to improved life satisfaction and cognitive self-efficacy. Cognitive self-efficacy, in turn, appeared to have implications for improving depressive symptomology and may be a useful target of memory skills education.