Real-World Use of Fedratinib for Myelofibrosis Following Prior Ruxolitinib Failure: Patient Characteristics, Treatment Patterns, and Clinical Outcomes.

BACKGROUND: There is a lack of established clinical outcomes for patients with myelofibrosis (MF) receiving fedratinib following ruxolitinib failure. This study examined real-world patient characteristics, treatment patterns, and clinical outcomes of patients with MF treated with fedratinib following ruxolitinib failure in US clinical practice. PATIENTS AND METHODS: This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment. RESULTS: Twenty-four physicians abstracted data for 150 eligible patients. Approximately 55.3% of the patients were male, 68.0% were White, and median age at MF diagnosis was 68 (range, 35-84) years. Median duration of ruxolitinib therapy was 7.6 (range, 0.7-65.5) months. At initiation of fedratinib, 88.0% of patients had palpable spleen and a mean spleen size of 16.0 (standard deviation [SD], 5.9) cm. Spleen size decreased by 19.4% to 13.2 (SD, 7.9) cm at month 3 (P = .0001) and by 53.4% to 7.2 (SD, 7.4) cm at month 6 (P = .01) of fedratinib treatment, respectively. Almost one-third (26.8%) of patients had achieved ≥ 50% spleen reduction by month 6. Mean number of symptoms also decreased significantly at month 3 (P < .0001) and month 6 (P = .01). CONCLUSION: Fedratinib appears to deliver spleen and symptom benefits in real-world patients with MF previously treated with ruxolitinib.

Cadence (steps/min) and relative intensity in 61 to 85-year-olds: the CADENCE-Adults study.

BACKGROUND: We previously demonstrated that a heuristic (i.e., evidence-based, rounded yet practical) cadence threshold of ≥ 100 steps/min was associated with absolutely-defined moderate intensity physical activity (i.e., ≥ 3 metabolic equivalents [METs]) in older adults 61-85 years of age. Although it was difficult to ascertain achievement of absolutely-defined vigorous (6 METs) intensity, ≥ 130 steps/min was identified as a defensible threshold for this population. However, little evidence exists regarding cadence thresholds and relatively-defined moderate intensity indicators, including ≥ 64% heart rate [HR] maximum [HRmax = 220-age], ≥ 40% HR reserve [HRR = HRmax-HRresting], and ≥ 12 Borg Scale Rating of Perceived Exertion [RPE]; or vigorous intensity indicators including ≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE. PURPOSE: To analyze the relationship between cadence and relatively-defined physical activity intensity and identify relatively-defined moderate and vigorous heuristic cadence thresholds for older adults 61-85 years of age. METHODS: Ninety-seven ostensibly healthy adults (72.7 ± 6.9 years; 49.5% women) completed up to nine 5-min treadmill walking bouts beginning at 0.5 mph (0.8 km/h) and progressing by 0.5 mph speed increments (with 2-min rest between bouts). Directly-observed (and video-recorded) steps were hand-counted, HR was measured using a chest-strapped monitor, and in the final minute of each bout, participants self-reported RPE. Segmented mixed model regression and Receiver Operating Characteristic (ROC) curve analyses identified optimal cadence thresholds associated with relatively-defined moderate (≥ 64%HRmax, ≥ 40%HRR, and ≥ 12 RPE) and vigorous (≥ 77%HRmax, ≥ 60%HRR, and ≥ 14 RPE) intensities. A compromise between the two analytical methods, including Youden's Index (a sum of sensitivity and specificity), positive and negative predictive values, and overall accuracy, yielded final heuristic cadences. RESULTS: Across all relatively-defined moderate intensity indicators, segmented regression models and ROC curve analyses identified optimal cadence thresholds ranging from 105.9 to 112.8 steps/min and 102.0-104.3 steps/min, respectively. Comparable values for vigorous intensity indicators ranged between126.1-132.1 steps/min and 106.7-116.0 steps/min, respectively. Regardless of the relatively-defined intensity indicator, the overall best heuristic cadence threshold aligned with moderate intensity was ≥ 105 steps/min. Vigorous intensity varied between ≥ 115 (greater sensitivity) or ≥ 120 (greater specificity) steps/min. CONCLUSIONS: Heuristic cadence thresholds align with relatively-defined intensity indicators and can be useful for studying and prescribing older adults' physiological response to, and/or perceived experience of, ambulatory physical activity. TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258. Registered 24 December 2015.

GGEM: Gender, Geography, and EMployment differences based on mobility levels among lower limb prosthesis users living in the United States.

BACKGROUND: For individuals with a disability, an increase in functional mobility may improve their quality of life and well-being. Greater understanding is needed on how factors such as gender, geography, and employment may play a role in mobility levels among individuals with lower limb amputation. OBJECTIVES: To assess the relationship between gender, geography, and employment status on mobility among lower limb prosthesis users. METHODS: A cross-sectional analysis of 7,524 patient mobility outcomes completed across the United States was performed. The regression model included the independent variables, such as age, gender, region, employment status, and amputation level. Mobility was entered as the dependent variable. RESULTS: Individuals who were employed had 3.6 times the odds of reaching increased mobility (Prosthetic Limb Users' Survey of Mobility ≥ 50) than those unemployed (odds ratio 3.56, 95% confidence interval 3.10-4.09). Gender and geography were significantly associated with mobility as well. CONCLUSIONS: Being employed is associated with greater odds of reaching increased mobility. Addressing factors such as returning to employment may aid in improving mobility levels among prosthesis users.

Factors that influence time to prosthesis receipt after lower limb amputation: A Cox proportional hazard model regression.

BACKGROUND: Early mobility, functional independence, and ambulation are associated benefits after lower limb amputation (LLA), whereas an increased risk of clinical complications is associated with no prosthesis. OBJECTIVE: To describe time to prosthesis receipt after amputation and to assess the impact of patient demographic and health factors on the rate of prosthesis receipt within 12 months post LLA. DESIGN: A retrospective cohort analysis using commercial administrative claims data. Kaplan-Meier and Cox proportional-hazards models were applied to assess time to prosthesis receipt. SETTING: Watson/Truven administrative database 2014-2016. PARTICIPANTS: Adults aged 18-64 years with LLA who maintained their current insurance enrollment for 12 months after amputation. INTERVENTIONS: Independent variables included diabetes/vascular disease status, amputation level, age, gender, and region. MAIN OUTCOME MEASURES: Prosthesis receipt was defined based on the presence of codes billed for prosthesis services. Time was measured in days from date of amputation surgery. RESULTS: Among the sample, 510 individuals maintained insurance enrollment for 12 months after amputation, of which 443 individuals received a prosthesis within that period (79% below knee and 21% above knee). The adjusted average rate of time to prosthesis receipt was 138 (95% confidence interval [CI]: 113-185) days. Individuals with diabetes/vascular disease were 22% (hazard ratio: 1.22, 95% CI: 1.02-1.49) more likely to receive a prosthesis earlier than individuals without diabetes/vascular disease and women received a prosthesis later than men at 141 (95% CI: 126-162) days versus 106 (95% CI: 96-119) days, respectively. CONCLUSIONS: This study expands the understanding of factors that influence the likelihood of receiving a prosthesis along with the timing of prosthesis receipt after LLA among commercially insured adults. At least half of this sample received a prosthesis within 5 months or less. Disparities in timing and access to a prosthesis based on amputation level and gender were noted; future efforts are needed to address these issues.

Stability and Falls Evaluations in AMPutees (SAFE-AMP 2): Reduced functional mobility is associated with a history of injurious falls in lower limb prosthesis users.

BACKGROUND: Injurious falls have a high cost and economic impact on an individual and the health system. Several studies have assessed performance-based functional mobility in lower limb prosthesis (LLP) users and fall risk including fall history. However, limited data exist regarding the relationship between functional mobility and a history of injurious falls in individuals who use a LLP. Such information could inform clinical practice and decision making from prosthesis design to policy. The purpose of this study was to identify factors associated with a history of injurious falls among LLP users using a clinical outcomes database. METHODS: Retrospective (2016-2018) observational study. Logistic regression applied. RESULTS: A final sample of 12,044 LLP users was included for analysis. Within the sample, 1,529 individuals reported a history of an injurious fall within the previous 6 months. Self-reported functional mobility was stratified into low, middle, and high levels: differences were found between levels for history of an injurious fall. The lowest mobility level was associated with 2.29 higher odds of a history of an injurious fall (95% CI: 1.96-2.69) indicating a potentially greater serious fall risk compared to those with higher mobility levels while controlling for covariates (sex, cause of amputation and level of amputation). CONCLUSION(S): Self-reported functional mobility was associated with a history of injurious falls in LLP users. The Prosthetic Limb Users Survey of Mobility is an accessible tool that prosthetists could use to identify individuals with a high risk of falls; this can inform care planning. Rehabilitation plans and prosthesis designs that target LLP users who report low functional mobility may positively impact health outcomes.

Stability and Falls Evaluations in AMPutees (SAFE-AMP 1): Microprocessor knee technology reduces odds of incurring an injurious fall for individuals with diabetic/dysvascular amputation.

Individuals with lower limb amputation have a high incidence of falls. Above-the-knee amputation and diabetes/vascular disease are both risk factors for falls. Microprocessor knee (MPK) technology may reduce falls in this population. The objective was to determine the association between MPKs and reduced injurious falls. A retrospective analysis of injurious falls within a large, national outcomes database was conducted. Inclusion was limited to adult K3 ambulators with unilateral, transfemoral, or knee disarticulation amputation due to diabetes/vascular disease. There were 744 out of 881 individuals that did not receive an MPK. Results showed that 16.3% of non-MPK users experienced an injurious fall compared to 7.3% of MPK users (p = .007). Not having an MPK resulted in significantly increased odds (unadjusted: OR: 2.47, 95% CI: 1.26-4.83, p = .009; adjusted for confounders: OR: 2.52, 95% CI: 1.28-4.94, p = .007) of incurring an injurious fall over a 6-month period. In conclusion, the current study found use of an MPK strongly associated with reduced injurious falls in a population of patients with amputation due to diabetes/vascular disease. The findings strongly support the use of MPK technology to mitigate fall risk, and in particular injurious falls requiring medical intervention.

A catalog of validity indices for step counting wearable technologies during treadmill walking: the CADENCE-adults study.

BACKGROUND: Standardized validation indices (i.e., accuracy, bias, and precision) provide a comprehensive comparison of step counting wearable technologies. PURPOSE: To expand a previously published child/youth catalog of validity indices to include adults (21-40, 41-60 and 61-85 years of age) assessed across a range of treadmill speeds (slow [0.8-3.2 km/h], normal [4.0-6.4 km/h], fast [7.2-8.0 km/h]) and device wear locations (ankle, thigh, waist, and wrist). METHODS: Two hundred fifty-eight adults (52.5 ± 18.7 years, 49.6% female) participated in this laboratory-based study and performed a series of 5-min treadmill bouts while wearing multiple devices; 21 devices in total were evaluated over the course of this multi-year cross-sectional study (2015-2019). The criterion measure was directly observed steps. Computed validity indices included accuracy (mean absolute percentage error, MAPE), bias (mean percentage error, MPE), and precision (correlation coefficient, r; standard deviation, SD; coefficient of variation, CoV). RESULTS: Over the range of normal speeds, 15 devices (Actical, waist-worn ActiGraph GT9X, activPAL, Apple Watch Series 1, Fitbit Ionic, Fitbit One, Fitbit Zip, Garmin vivoactive 3, Garmin vivofit 3, waist-worn GENEActiv, NL-1000, PiezoRx, Samsung Gear Fit2, Samsung Gear Fit2 Pro, and StepWatch) performed at < 5% MAPE. The wrist-worn ActiGraph GT9X displayed the worst accuracy across normal speeds (MAPE = 52%). On average, accuracy was compromised across slow walking speeds for all wearable technologies (MAPE = 40%) while all performed best across normal speeds (MAPE = 7%). When analyzing the data by wear locations, the ankle and thigh demonstrated the best accuracy (both MAPE = 1%), followed by the waist (3%) and the wrist (15%) across normal speeds. There were significant effects of speed, wear location, and age group on accuracy and bias (both p < 0.001) and precision (p ≤ 0.045). CONCLUSIONS: Standardized validation indices cataloged by speed, wear location, and age group across the adult lifespan facilitate selecting, evaluating, or comparing performance of step counting wearable technologies. Speed, wear location, and age displayed a significant effect on accuracy, bias, and precision. Overall, reduced performance was associated with very slow walking speeds (0.8 to 3.2 km/h). Ankle- and thigh-located devices logged the highest accuracy, while those located at the wrist reported the worst accuracy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258. Registered 24 December 2015.

Racial Disparities in Health Care With Timing to Amputation Following Diabetic Foot Ulcer.

OBJECTIVE: To examine variations in timing of lower-limb amputation (LLA) across race/ethnicity and sex among older adults with a diabetic foot ulcer (DFU). It was hypothesized Black/African Americans were more likely to have LLA post-DFU earlier compared with non-Hispanic/Whites, and more men would receive LLA earlier post-DFU compared with women. RESEARCH DESIGN AND METHODS: This was a retrospective cohort analysis of enrolled Medicare fee-for-service (FFS) beneficiaries with a diagnosis of DFU during the study period (2012-2017), allowing up to 5 years post-DFU. Final analytic sample contained 643,287 individuals; the subsample consisted of 68,633 individuals with LLA only. The primary outcome was mutually exclusive groups based on timing of LLA. Multinomial logistic regression was applied to assess likelihood of membership into a group post-DFU based on characteristics such as sex and race/ethnicity. RESULTS: Black/African American beneficiaries had 1.98 (95% CI 1.93-2.03) times the odds of receiving an LLA within 1 year of DFU diagnosis compared with non-Hispanic/White beneficiaries relative to no amputation. Female beneficiaries had increased odds (odds ratio [OR] 1.07, 95% CI 1.02-1.11] between 1 and 3 years and OR 1.08 [95% CI 1.03-1.12] in ≥3 years) of a delayed LLA compared with men among those that underwent LLA. CONCLUSIONS: Notably, these results present novel evidence on timing of LLA between racial groups and sex for Medicare FFS beneficiaries post-DFU. Results may be generalizable to individuals with Medicare FFS and DFU. Clinically more targeted, evidence-based decision making informs care decisions with opportunities to address inequities related to the social determinants of health that may lead to LLA.

OASIS 2: Mobility differences with specific prosthetic feet across procedure codes.

Introduction: Recently, many prosthetic devices were subjected to reimbursement coding review. Several prosthetic feet that were historically coded with the shock-attenuating function were recoded. The purpose of this analysis was to compare patient-reported functional mobility across a range of prosthetic feet using real-world clinical outcomes data. Methods: A retrospective, observational review. A univariate generalized linear model was used to assess mobility across foot categories and between different prosthetic feet coded as L5987 or L5981. Results: The final sample analyzed comprised of 526 individuals and four mutually exclusive categories of feet examined across a total of 10 different prosthetic foot types. The comparison of prosthetic foot categories were significantly different from the control category (i.e. historically L5981). Conclusions: The current data suggest the development of some prosthetic foot designs using advanced materials and geometric designs can provide comparable functional benefits as those with distinct shock absorbing mechanical features. Emphasizing functional performance over visible features may be a pathway towards higher performance for the end user.

Mobility Analysis of AmpuTees (MAAT 7): Normative Mobility Values for Lower Limb Prosthesis Users of Varying Age, Etiology, and Amputation Level.

OBJECTIVE: The aim of the study was to establish normative values of lower limb amputation mobility across primary etiologies based on age and amputation level. DESIGN: This study is a cross-sectional observational analysis of outcomes. A total of 11,995 lower limb prosthesis users were included in the analysis. Participants were grouped by etiology into four categories: cancer, congenital, trauma, and diabetes/dysvascular. Mobility was assessed by using the Prosthetic Limb Users Survey of Mobility. RESULTS: Mobility across seven age groups for the four etiologies was established for both above-the-knee amputation and below-the-knee amputation. Differences were found between age groups for individuals: above-the-knee amputation: cancer (χ 2 (6) = 40.97, P < 0.001), congenital (χ 2 (3) = 9.41, P = 0.024), trauma (χ 2 (6) = 18.89, P = 0.004), and dysvascular (χ 2 (5) = 39.73, P < 0.001; below-the-knee amputation: cancer (χ 2 (6) = 29.77, P < 0.001), trauma (χ 2 (6) = 28.22, P < 0.001), and dysvascular (χ 2 (6) = 144.66, P < 0.001). CONCLUSIONS: The awareness of differences across amputation etiologies extending across the lifespan of ages can assist the goal-setting process as part of prosthetic rehabilitation. In addition, refined normative values provide the ability to benchmark new and innovative changes in clinical practice.

The Role of Earlier Receipt of a Lower Limb Prosthesis on Emergency Department Utilization.

INTRODUCTION: Adverse events after a lower limb amputation (LLA) can negatively affect the rehabilitation process and may lead to emergency department (ED) visits. Earlier receipt of a prosthesis, as compared to delayed or not receiving a prosthesis, may decrease or moderate the risk of increased ED utilization. In addition, adverse events (ie, fall-related injury [FRI]) may be associated with increased health care utilization as measured by ED use. The implication of the timing of prosthesis provision after amputation and reduced ED use is not well established. Obtaining data about ED utilization early post-LLA could assist the rehabilitation team in ensuring timely and appropriate access to improve outcomes. OBJECTIVE: To determine the role that timing of prosthesis receipt has in ED utilization and the association of fall/FRI with health care utilization. DESIGN: Retrospective observational cohort using commercial claims data. A logistic regression model was used to assess factors that influence ED utilization post-LLA. SETTING: Watson/Truven administrative database 2014 to 2016. PARTICIPANTS: The study sample consisted of 510 adults age 18 to 64 years with continuous enrollment for 3 years. INTERVENTIONS: Independent variables included age, sex, diabetes status, amputation level, fall diagnosis, and prosthesis receipt. Fall was defined as presence of a diagnosis code in any outpatient procedure after the amputation date. MAIN OUTCOME MEASURE: ED use after amputation was defined as the presence of procedure codes that billed for ED services (99281 to 99285). RESULTS: Individuals who receive a prosthesis early, within 0 to 3 months, post-LLA were 48% (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.28 to 0.97) less likely to use the ED compared to those who did not receive a prosthesis. Individuals who experienced a fall/FRI had 2.8 (OR 2.86, 95% CI 1.23 to 6.66) times the odds of ED utilization. CONCLUSION: Receipt of a prosthesis reduces the risk of ED use. The current study underscores the value of prostheses during the rehabilitation process after LLA.

Assessment of a Nine-Item Patient-Reported Outcomes Measurement Information System Upper Extremity Instrument Among Individuals With Upper Limb Amputation.

OBJECTIVE: The aim of the study was to assess the validity of a customized nine-item Patient-Reported Outcomes Measurement Information System Upper Extremity instrument being used with individuals with upper extremity amputation to inform potential modifications for clinical efficiency. DESIGN: A sample of 239 adults with upper extremity amputation (mean age = 48 ± 16 yrs; female = 69; prosthesis users = 150) were included. After clinical implementation of the nine-item Patient-Reported Outcomes Measurement Information System Upper Extremity, the following psychometric properties were examined: structural and known-groups validity, differential item functioning, and reliability. RESULTS: The nine-item Patient-Reported Outcomes Measurement Information System Upper Extremity short form demonstrated satisfactory psychometric properties. Convincing evidence of structural validity included no violation of unidimensionality, local independence (all local dependence χ2 < 10), monotonicity (Hij > 0, Hi > 0.3, and H = 0.57), and adequate model fit (P > 0.006). Known-groups analysis demonstrated that the nine-item Patient-Reported Outcomes Measurement Information System Upper Extremity instrument was able to discriminate between prosthesis users and nonprosthesis users and amputation level. The Cronbach's α and item response theory reliability at the selected range of T scores were greater than 0.9 indicating high reliability. No items were flagged for age in differential item functioning. CONCLUSIONS: The customized nine-item Patient-Reported Outcomes Measurement Information System Upper Extremity met the minimum criteria, according to the Patient-Reported Outcomes Measurement Information System plan, for psychometric validity supporting its use within the population of individuals with upper extremity amputation.

Impact of Time to Receipt of Prosthesis on Total Healthcare Costs 12 Months Postamputation.

OBJECTIVE: The objective was to assess the impact of a prosthesis and the timing of prosthesis receipt on total direct healthcare costs in the 12-mo postamputation period. DESIGN: Data on patients with lower limb amputation (n = 510) were obtained from a commercial claims database for retrospective cohort analysis. Generalized linear multivariate modeling was used to determine differences in cost between groups according to timing of prosthesis receipt compared with a control group with no prosthesis. RESULTS: Receipt of a prosthesis between 0 and 3 mos post lower limb amputation yielded a reduced total cost by approximately 0.23 in log scale within 12 mos after amputation when compared with the no-prosthesis group. Despite the included costs of a prosthesis, individuals who received a prosthesis either at 4-6 mos postamputation or 7-9 mos postamputation incurred costs similar to the no-prosthesis group. CONCLUSION: Earlier receipt of a prosthesis is associated with reduced spending in the 12 mos postamputation of approximately $25,000 compared with not receiving a prosthesis. The results of this study suggest that not providing or delaying the provision of a prosthesis increases costs by about 25%.