Creating Adjusted Scores Targeting mobiLity Empowerment (CASTLE 1): determination of normative mobility scores after lower limb amputation for each year of adulthood.

PURPOSE: As United States healthcare transitions from traditional fee-for-service models to value-based care, there is increased need to demonstrate quality care through clinical outcomes. Therefore, the purpose of this study was to create equations to calculate an expected mobility score for lower limb prosthesis users specific to their age, etiology, and amputation level to provide benchmarks to qualify good outcomes. MATERIALS AND METHODS: A retrospective cross-sectional analysis of outcomes collected during clinical care was performed. Individuals were grouped based on amputation level (unilateral above-knee (AKA) or below-knee (BKA)) and etiology (trauma or diabetes/dysvascular (DV)). The mean mobility score (PLUS-M® T-score) for each year of age was calculated. AKAs were further stratified into having a microprocessor knee (MPK) or non-microprocessor (nMPK) for secondary analysis. RESULTS: As expected, average prosthetic mobility declined with age. Overall, BKAs had higher PLUS-M T-scores compared to AKAs and trauma etiologies had higher scores compared to DV. For AKAs, those with a MPK had higher T-scores compared to those with a nMPK. CONCLUSIONS: Results from this study provide average mobility for adult patients across every year of life. This can be leveraged to create a mobility adjustment factor to qualify good outcomes in lower limb prosthetic care.IMPLICATIONS FOR REHABILITATIONNormative values of mobility are needed to qualify good outcomes in prosthetic care as healthcare shifts towards value-based care.Understanding where an individual is relative to others with similar characteristics (e.g., age, etiology, gender, amputation level, and device type) can provide clinicians with better benchmarks for individual goal-setting.The ability to generate predicted mobility scores specific to each individual can create a mobility adjustment factor to better qualify good outcomes.

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.

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.

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.

Subsurface microbial communities as a tool for characterizing regional-scale groundwater flow.

Subsurface microbial community distribution patterns are influenced by biogeochemical and groundwater fluxes and may inform hydraulic connections along groundwater-flow paths. This study examined the regional-scale microbial community of the Death Valley Regional Flow System and evaluated whether subsurface communities can be used to identify groundwater-flow paths between recharge and discharge areas. Samples were collected from 36 sites in three groundwater basins: Pahute Mesa-Oasis Valley (PMOV), Ash Meadows (AM), and Alkali Flat-Furnace Creek Ranch (AFFCR). Microbial diversity within and between communities varied by location, and communities were separated into two overall groups that affiliated with the AM and PMOV/AFFCR basins. Network analysis revealed patterns between clusters of common microbes that represented groundwaters with similar geochemical conditions and largely corroborated hydraulic connections between recharge and discharge areas. Null model analyses identified deterministic and stochastic ecological processes contributing to microbial community assemblages. Most communities were more different than expected and governed by dispersal limitation, geochemical differences, or undominating processes. However, certain communities from sites located within or near the Nevada National Security Site were more similar than expected and dominated by homogeneous dispersal or selection. Overall, the (dis)similarities between the microbial communities of DVRFS recharge and discharge areas supported previously documented hydraulic connections between: (1) Spring Mountains and Ash Meadows; (2) Frenchman and Yucca Flat and Amargosa Desert; and (3) Amargosa Desert and Death Valley. However, only a portion of the flow path between Pahute Mesa and Oasis Valley could be supported by microbial community analyses, likely due to well-associated artifacts in samples from the two Oasis Valley sites. This study demonstrates the utility of combining microbial data with hydrologic, geologic, and water-chemistry information to comprehensively characterize groundwater systems, highlighting both strengths and limitations of this approach.

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.

Mobility Analysis of AmpuTees (MAAT 6): Mobility, Satisfaction, and Quality of Life among Long-Term Dysvascular/Diabetic Prosthesis Users-Results of a Cross-Sectional Analysis.

OBJECTIVE: The aim of this study was to establish the mobility, satisfaction, and quality of life (QoL) among prosthesis users with dysvascular/diabetic amputation at both acute and long-term phases of prosthetic rehabilitation. METHODS: This is a multisite, cross-sectional outcomes analysis. A total of 341 individuals met the inclusion/exclusion criteria. Individuals were grouped into acute phases (0-3 months [n = 24], 4-6 months [n = 72]) and chronic phases (24-36 months [n = 91], 37-48 months [n = 53], 49-60 months [n = 47], and 60-84 months [n = 54]) after amputation. Mobility was measured with the Prosthetic Limb Users Survey of Mobility (PLUS-M), whereas QoL and satisfaction (Sat) were reported using 10-point scales adapted from the Prosthesis Evaluation Questionnaire-Well-Being (PEQ-WB). Composite PEQ-WB scores were also compared. RESULTS: The average mobility, QoL, and Sat among prosthesis users was, respectively, 44.8 ± 10.6, 7.6 ± 2.2, and 7.6 ± 2.2. There were no observed differences in mobility (F 5,330 = 1.52, P = 0.18), QoL (F 5,333 = 0.78, P = 0.57), or PEQ-WB (F 5,335 = 1.618, P = 0.155) between any groups. For Sat, there was a group difference (F 5,334 = 2.44, P = 0.03) as individuals appear to experience an initial increase in Sat with receipt of a prosthesis (0-3 months) compared with 25 to 36 months (P = 0.005), 49 to 60 months (P = 0.008), and 61 to 84 months (P = 0.009). CONCLUSIONS: Those individuals with amputation secondary to dysvascular disease and diabetes who continue to participate in prosthetic rehabilitation appear to experience levels of mobility, Sat, and QoL 7 years after amputation comparable to that reported in the first 6 months postamputation. There may be a modest increase in Sat with receipt of an initial prosthesis, potentially due to an increased optimism for one's situation. Notably, the mobility levels observed in the dysvascular population through a range of long-term postamputation periods remain within a single standard deviation of the population mean for individuals with a lower-limb amputation using a prosthesis for mobility.

The intersection of stress, sex and immunity in fishes.

While sexual dimorphism in immune responses has been documented in other vertebrates, evidence for a similar phenomenon in fish is lacking. Here, we review the relationship between immunity, stress, spawning, and sex hormones in fish to gain a better understanding of sex-based differences in fish immune responses and its consequences for aquaculture. It is well known that there is a strong link between the stress response and immune function in fish. In addition, research to date has demonstrated that sexual dimorphism in the stress response exists in many species; yet, the relationship between the sexual dimorphic stress responses and immune function has rarely been explored together. Aside from stress, spawning is also known to trigger changes in fish immune responses. Estrogens and androgens have been shown to modulate the immune system which could account for differences between the two sexes of fish when spawning; however, evidence regarding the sexual dimorphism of these changes varies between fishes and is likely related to the spawning strategy employed by a given species. Sex hormones are also used in aquaculture practices to produce monosex populations, and exposure to these hormones early in development has been shown to impact the development of immune organs in several fishes. While female fish are generally thought to be more robust than males, aquaculture practices should also consider the role that maternal stress has on the immune function of the offspring and what role this plays in compromising the immune response of farmed fish.

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.

OASIS 1: Retrospective analysis of four different microprocessor knee types.

INTRODUCTION: Microprocessor knee analyses to date have been primarily limited to microprocessor knees as a category rather than comparisons across different models. The purpose of the current analysis was to compare outcomes from four common knee models. METHODS: A retrospective analysis of clinical outcomes was performed. Outcomes for functional mobility, quality of life, satisfaction with amputee status, and injurious falls were compared. Specific knee types represented were C-Leg (Ottobock), Orion (Blatchford), Plié (Freedom Innovations), and Rheo (Össur). RESULTS: Outcomes from 602 individuals were included. No significant differences were noted for functional mobility (H = 2.91, p = 0.406) or satisfaction (H = 4.43, p = 0.219). For quality of life, differences existed for C-Leg versus Plié (p = 0.010). For injurious falls, C-Leg (χ2 (1,137) = 10.99, p < 0.001) and Orion (χ2 (1,119) = 4.34, p = 0.037) resulted in significantly reduced injurious falls compared to non-microprocessor knee users. C-Leg (H = 19.63, p < 0.001) and Plié (H = 14.04, p = 0.003) users saw declines with advanced aging. CONCLUSIONS: Our data indicate relative parity among the 4 microprocessor knees with regard to functional mobility and satisfaction. In contrast to mobility, neither satisfaction nor quality of life values reflected declines with aging. Finally, when compared to non-microprocessor knees, significant differences were observed across the microprocessor knee types in relation to the reduction of injurious falls.Keywords: MPK, mobility, quality of life, falls, amputee, outcomes.

Mobility analysis of amputees (MAAT 3): Matching individuals based on comorbid health reveals improved function for above-knee prosthesis users with microprocessor knee technology.

The objective of this cross-sectional observational study was to determine whether the use of a microprocessor knee for individuals with an above-the-knee amputation results in improved functional mobility compared to their peers of matched comorbid-health with a non-microprocessor knee, and to inform how this compares to the mobility observed in below-knee prosthesis users. A sample of 450 individuals with lower limb amputation were divided into three groups (n = 150 each). The groups included: nonmicroprocessor knee users (NMPK, age: 57.6 ± 17.2 years), microprocessor knee users (MPK, age: 56.5 ± 13.8 years), and below-knee prosthesis users (BKA, age: 58.4 ± 12.2 years). Primary outcome measure was functional mobility measured through Prosthetic Limb Users' Survey of Mobility (PLUS-M®). Results showed MPK mobility (48.49 ± 0.86) was greater than NMPK (43.49 ± 0.86, p < 0.001), but less than BKA (52.11 ± 0.86, p = 0.003). These results persisted when removing potential confounding effects of age, body mass index, cause of amputation, and comorbid health (MPK: 47.15 ± 0.97; NMPK: 43.47 ± 0.88; BKA: 52.61 ± 0.91). In conclusion, these results show the use of a MPK can improve functional mobility for individuals with an above-knee amputation.

Mobility Analysis of AmpuTees (MAAT 4): classification tree analysis for probability of lower limb prosthesis user functional potential.

Purpose: To develop a predictive model to inform the probability of lower limb prosthesis users' functional potential for ambulation.Materials and Methods: A retrospective analysis of a database of outcomes for 2770 lower limb prosthesis users was used to inform a classification and regression tree analysis. Gender, age, height, weight, body mass index adjusted for amputation, amputation level, cause of amputation, comorbid health status and functional mobility score [Prosthetic Limb Users Survey of Mobility (PLUS-M™)] were entered as potential predictive variables. Patient K-Level was used to assign dependent variable status as unlimited community ambulator (i.e., K3 or K4) or limited community/household ambulator (i.e., K1 or K2). The classification tree was initially trained from 20% of the sample and subsequently tested with the remaining sample.Results: A classification tree was successfully developed, able to accurately classify 87.4% of individuals within the model's training group (standard error 1.4%), and 81.6% within the model's testing group (standard error 0.82%). Age, PLUS-M™ T-score, cause of amputation and body weight were retained within the tree logic.Conclusions: The resultant classification tree has the ability to provide members of the clinical care team with predictive probabilities of a patient's functional potential to help assist care decisions.Implications for RehabilitationClassification and regression tree analysis is a simple analytical tool that can be used to provide simple predictive models for patients with a lower limb prosthesis.The resultant classification tree had an 81.6% (standard error 0.82%) accuracy predicting functional potential as an unlimited community ambulator (i.e., K3 or K4) or limited community/ household ambulator (i.e., K1 or K2) in an unknown group of 2770 lower limb prosthesis users.The resultant classification tree can assist with the rehabilitation team's care planning providing probabilities of functional potential for the lower limb prosthesis user.

Targeted isolation and cultivation of uncultivated bacteria by reverse genomics.

Most microorganisms from all taxonomic levels are uncultured. Single-cell genomes and metagenomes continue to increase the known diversity of Bacteria and Archaea; however, while 'omics can be used to infer physiological or ecological roles for species in a community, most of these hypothetical roles remain unvalidated. Here, we report an approach to capture specific microorganisms from complex communities into pure cultures using genome-informed antibody engineering. We apply our reverse genomics approach to isolate and sequence single cells and to cultivate three different species-level lineages of human oral Saccharibacteria (TM7). Using our pure cultures, we show that all three Saccharibacteria species are epibionts of diverse Actinobacteria. We also isolate and cultivate human oral SR1 bacteria, which are members of a lineage of previously uncultured bacteria. Reverse-genomics-enabled cultivation of microorganisms can be applied to any species from any environment and has the potential to unlock the isolation, cultivation and characterization of species from as-yet-uncultured branches of the microbial tree of life.

Mobility analysis of AmpuTees (MAAT 5): Impact of five common prosthetic ankle-foot categories for individuals with diabetic/dysvascular amputation.

INTRODUCTION: Diabetes and vascular disease represent the most common etiologies for lower limb amputations. In lower limb loss rehabilitation, the prosthetic ankle-foot mechanism is the most common major component needed to restore function. The purpose of this study was to examine the impact of five common prosthetic ankle-foot mechanisms on functional mobility in a large sample of individuals with amputation due to diabetes/dysvascular disease. METHODS: A retrospective analysis of the Prosthetic Limb Users' Survey of Mobility (PLUS-M®) captured in the patient care setting. A total of 738 individuals were included and subsequently subdivided into five groups based on the ankle-foot mechanism of their current prosthesis. Groups were compared using a general linear univariate model with age, body mass index, comorbid health status, time since amputation, and amputation level entered as covariates. RESULTS: The microprocessor ankle-foot group had the highest mobility (F4,728 = 3.845, p=0.004), which was followed by the vertical loading pylon type ankle-foot, the hydraulic ankle-foot, the flex-walk-type ankle-foot, and lastly the flex-foot-type ankle-foot. CONCLUSION: These results demonstrate that the selection of different prosthetic ankle-foot technology directly impacts functional mobility for the patient with an amputation due to diabetes and/or vascular disease.

Mobility Analysis of AmpuTees II: Comorbidities and Mobility in Lower Limb Prosthesis Users.

OBJECTIVE: The aim of the study was to determine the impact of comorbidities on mobility in patients with lower limb prostheses. DESIGN: Cohort database chart review was conducted to examine mobility in lower limb prosthesis users grouped according to comorbidities. Regression models were used to determine significant predictor comorbidities for mobility. General linear univariate models were implemented to investigate differences in mobility among cohorts (N = 596). RESULTS: Patient age and history of stroke, peripheral vascular disease, and anxiety/panic disorders were predictors of decreased mobility. After adjusting for covariates, the differences in mobility reported by patients older than 65 yrs was compared with those younger than 65 yrs; in addition, we compared those with a history of peripheral vascular disease with those without. The comparative analyses for both categories did not satisfy the minimal clinically important difference. There were no significant differences when comparing overall comorbid health after adjusting for covariates. CONCLUSIONS: Clinicians should consider patient age and history of stroke, peripheral vascular disease, or anxiety/panic disorders when optimizing a lower limb prosthesis users' mobility because these variables may be predictive of modest but clinically meaningful decreased prosthetic mobility. By contrast, common comorbid health conditions such as arthritis, chronic obstructive pulmonary disease, congestive heart failure, and diabetes do not seem predictive of decreased mobility among lower limb prosthesis users.

Effect of hemin, baicalein and heme oxygenase-1 (HO-1) enzyme activity inhibitors on Cd-induced accumulation of HO-1, HSPs and aggresome-like structures in Xenopus kidney epithelial cells.

Cadmium is a highly toxic environmental pollutant that can cause many adverse effects including cancer, neurological disease and kidney damage. Aquatic amphibians are particularly susceptible to this toxicant as it was shown to cause developmental abnormalities and genotoxic effects. In mammalian cells, the accumulation of heme oxygenase-1 (HO-1), which catalyzes the breakdown of heme into CO, free iron and biliverdin, was reported to protect cells against potentially lethal concentrations of CdCl2. In the present study, CdCl2 treatment of A6 kidney epithelial cells, derived from the frog, Xenopus laevis, induced the accumulation of HO-1, heat shock protein 70 (HSP70) and HSP30 as well as an increase in the production of aggregated protein and aggresome-like structures. Treatment of cells with inhibitors of HO-1 enzyme activity, tin protoporphyrin (SnPP) and zinc protoporphyrin (ZnPP), enhanced CdCl2-induced actin cytoskeletal disorganization and the accumulation of HO-1, HSP70, aggregated protein and aggresome-like structures. Treatment of cells with hemin and baicalein, which were previously shown to provide cytoprotection against various stresses, induced HO-1 accumulation in a concentration-dependent manner. Also, treatment of cells with hemin and baicalein suppressed CdCl2-induced actin dysregulation and the accumulation of aggregated protein and aggresome-like structures. This cytoprotective effect was inhibited by SnPP. These results suggest that HO-1-mediated protection against CdCl2 toxicity includes the maintenance of actin cytoskeletal and microtubular structure and the suppression of aggregated protein and aggresome-like structures.