Linking AM-PAC Cognition to PROMIS Cognitive Function.

OBJECTIVE: To link the Activity Measure for Post-Acute Care (AM-PAC) Applied Cognition to the Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Function, allowing for a common metric across scales. DESIGN: Cross-sectional survey study. SETTING: Outpatient rehabilitation clinics. PARTICIPANTS: Consecutive sample of 500 participants (N=500) aged ≥18 years presenting for outpatient therapy (physical, occupation, speech). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: AM-PAC Medicare and Generic Cognition short forms and PROMIS Cognitive Function items representing the PROMIS Cognitive Function item bank. RESULTS: The calibration of 25 AM-PAC cognition items with 11 fixed PROMIS cognitive function item parameters using item-response theory indicated that items were measuring the same underlying construct (cognition). Both scales measured a wide range of functioning. The AM-PAC Generic Cognitive assessment showed more reliability with lower levels of cognition, whereas the PROMIS Cognitive Function full-item bank was more reliable across a larger distribution of scores. Data were appropriate for a fixed-anchor item response theory-based crosswalk and AM-PAC Cognition raw scores were mapped onto the PROMIS metric. CONCLUSIONS: The crosswalk developed in this study allows for converting scores from the AM-PAC Applied Cognition to the PROMIS Cognitive Function scale.

Combining the AM-PAC "6-Clicks" and the Morse Fall Scale to Predict Individuals at Risk for Falls in an Inpatient Rehabilitation Hospital.

OBJECTIVE: To determine the effect of adding the Activity Measure for Post-Acute Care (AM-PAC) Inpatient '6-Clicks' Short Forms to the Morse Fall Scale (MFS) to assess fall risk. Falls that occur in a rehabilitation hospital result in increased morbidity and mortality, increased cost, and negatively affect reimbursement. Identifying individuals at high risk for falls would enable targeted fall prevention strategies and facilitate appropriate resource allocation to address this critical patient safety issue. DESIGN: We used a retrospective observational design and repeated k-fold cross-validation (10 repeats and 10 folds) of logistic regression models with falls regressed onto: MFS alone, AM-PAC basic mobility and applied cognitive scales alone, and MFS and AM-PAC combined. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS: After exclusions, 2007 patients from an inpatient setting (N=2007; 131 experienced a fall). Primary diagnoses included 602 individuals with stroke (30%), 502 with brain injury (25%), 321 with spinal cord injury (16%), and 582 with other diagnoses (29%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Experience of a fall during inpatient stay. RESULTS: The MFS at admission was associated with falls (area under the curve [AUC], 0.64). Above and beyond the MFS, AM-PAC applied cognitive and basic mobility at admission were also significantly associated with falls (combined model AUC, 0.70). Although MFS and applied cognition showed linear associations, there was evidence for a nonlinear association with AM-PAC basic mobility. CONCLUSIONS: The AM-PAC basic mobility and AM-PAC applied cognitive scales showed associations with falls above and beyond the MFS. More work is needed to validate model predictions in an independent sample with truly longitudinal data; prediction accuracy would also need to be substantially improved. However, the current data do suggest that the AM-PAC has the potential to reduce the burden of fall management by focusing resources on a smaller cohort of patients identified as having a high fall risk.

Improving Outcomes for Critically Ill Cardiovascular Patients Through Increased Physical Therapy Staffing.

OBJECTIVE: To examine the effect of increasing physical therapy (PT) staff in a cardiovascular intensive care unit (CVICU) on temporal measures of PT interventions and on outcomes important to patients and hospitals. DESIGN: Retrospective pre/post subgroup analysis from a quality improvement initiative. SETTING: Academic medical center. PARTICIPANTS: Cardiovascular patients in either a baseline (N=52) or quality improvement period (N=62) with a CVICU length of stay (LOS) ≥7 days and use of any one of the following: mechanical ventilation, continuous renal replacement therapy, or mechanical circulatory support. INTERVENTIONS: The 6-month quality improvement initiative increased CVICU-dedicated PT staff from 2 to 4. MAIN OUTCOME MEASURES: Changes in physical therapy delivery were examined using the frequency and daily duration of PT intervention. Post-CVICU LOS was the primary outcome. CVICU LOS, mobility change, and discharge level of care were secondary outcomes. A secondary analysis of hospital survivors was also conducted. RESULTS: Compared to those in the baseline period, cardiovascular patients in the quality improvement period participated in PT for an additional 9.6 minutes (95% confidence interval [CI]: 1.9, 17.2) per day for all patients and 15.1 minutes (95% CI: 7.6, 22.6) for survivors. Post-CVICU LOS decreased 2.2 (95% CI: -6.0, 1.0) days for all patients and 2.6 days (95% CI: -5.3, 0.0) for survivors. CVICU LOS decreased 3.6 days (95% CI: -6.4, -0.8) for all patients and 3.1 days (95% CI: -6.4, -0.9) for survivors. Differences in mobility change and discharge level of care were not significant. CONCLUSIONS: Additional CVICU-dedicated PT staff was associated with increased PT treatment and reductions in CVICU and post-CVICU LOS. The effects of each were greatest for hospital survivors.

Skeletal muscle ceramides and relationship with insulin sensitivity after 2 weeks of simulated sedentary behaviour and recovery in healthy older adults.

KEY POINTS: Insulin sensitivity (as determined by a hyperinsulinaemic-euglyceamic clamp) decreased 15% after reduced activity. Despite not fully returning to baseline physical activity levels, insulin sensitivity unexpectedly, rebounded above that recorded before 2 weeks of reduced physical activity by 14% after the recovery period. Changes in insulin sensitivity in response to reduced activity were primarily driven by men but, not women. There were modest changes in ceramides (nuclear/myofibrillar fraction and serum) following reduced activity and recovery but, in the absence of major changes to body composition (i.e. fat mass), ceramides were not related to changes in inactivity-induced insulin sensitivity in healthy older adults. ABSTRACT: Older adults are at risk of physical inactivity as they encounter debilitating life events. It is not known how insulin sensitivity is affected by modest short-term physical inactivity and recovery in healthy older adults, nor how insulin sensitivity is related to changes in serum and muscle ceramide content. Healthy older adults (aged 64-82 years, five females, seven males) were assessed before (PRE), after 2 weeks of reduced physical activity (RA) and following 2 weeks of recovery (REC). Insulin sensitivity (hyperinsulinaemic-euglyceamic clamp), lean mass, muscle function, skeletal muscle subfraction, fibre-specific, and serum ceramide content and indices of skeletal muscle inflammation were assessed. Insulin sensitivity decreased by 15 ± 6% at RA (driven by men) but rebounded above PRE by 14 ± 5% at REC. Mid-plantar flexor muscle area and leg strength decreased with RA, although only muscle size returned to baseline levels following REC. Body fat did not change and only minimal changes in muscle inflammation were noted across the intervention. Serum and intramuscular ceramides (nuclear/myofibrillar fraction) were modestly increased at RA and REC. However, ceramides were not related to changes in inactivity-induced insulin sensitivity in healthy older adults. Short-term inactivity induced insulin resistance in older adults in the absence of significant changes in body composition (i.e. fat mass) are not related to changes in ceramides.

Focus on the Quadruple Aim: Development of a Resiliency Center to Promote Faculty and Staff Wellness Initiatives.

DEFINING THE PROBLEM: A growing body of evidence highlights the need for wellness programs to support health care professionals. Although much of the existing literature centers on practicing physicians and physician trainees, there is growing awareness that these challenges are not unique to physicians and affect all members of the health care team. Traumatic and stressful events will always be a part of health care; how these events are addressed on a personal and team level is essential to the success of a health care system. A Resiliency Center was developed on the basis of the specific concerns and strengths of local stakeholders to support the well-being of employees at University of Utah Health. INITIAL APPROACH: The initial approach to evaluating and supporting faculty wellness began concurrent with planning for the Resiliency Center in 2016. Stakeholders were brought together by leaders in Health Sciences to propose a Resiliency Center. Initial data gathering was performed with several survey tools, including the American Medical Association's Mini Z. PLANNED INITIATIVES: The Resiliency Center, which is housed in the Office of Wellness and Integrative Health, is intended to serve as an overarching structure to help coordinate the faculty and staff wellness initiatives currently in existence and fill identified gaps. The four pillars of the Center are wellness initiatives, communication skills training, peer support, and an on-site Employee Assistance Program. NEXT STEPS: The current focus is on program development and outreach, with plans to measure the impact of the Center.

Eccentric versus traditional resistance exercise for older adult fallers in the community: a randomized trial within a multi-component fall reduction program.

BACKGROUND: Addressing muscle deficits within a multi-component exercise fall reduction program is a priority, especially for the highest risk older adults, i.e., those who have fallen previously. Eccentric resistance exercise with its high-force producing potential, at a low energetic cost, may be ideally-suited to address muscle impairments in this population. The purpose of this study was to compare the effects of resistance exercise via negative, eccentrically-induced, work (RENEW) versus traditional (TRAD) resistance exercise on mobility, balance confidence, muscle power and cross sectional area, as well as the number of days high fall risk older adults survived without a fall event over a 1 year period. METHODS: Randomized, two group, four time point (over 1 year) clinical trial testing RENEW versus TRAD as part of a 3 month multi-component exercise fall reduction program (MCEFRP). Primary outcomes of mobility, balance confidence, muscle power output and cross sectional area were analyzed using mixed effects modeling. The secondary outcomes of days to fall and days to near-fall were analyzed using survival analysis. RESULTS: The MCEFRP did have an effect on fall risk factors considered reversible with exercise interventions though there was no differential effect of RENEW versus TRAD (p = 0.896) on mobility, balance confidence, muscle power and cross sectional area. There were also no group differences in the number of days survived without a fall (p = 0.565) or near-fall (p = 0.678). Despite 100% of participants having at least one fall in the year prior to the MCEFRP, however, after 3 months of exercise and 9 months of follow-up <50% had experienced a fall or near fall. CONCLUSIONS: There were no differential effects of RENEW or TRAD as components of a MCEFRP on the primary or secondary outcomes. The two modes of resistance exercise had identical effects on fall risk and fall-free survival. TRIAL REGISTRATION: NCT01080196 ; March 2, 2010 (retrospectively registered).

Supervised exercise improves cutaneous reinnervation capacity in metabolic syndrome patients.

OBJECTIVE: Unmyelinated cutaneous axons are vulnerable to physical and metabolic injury, but also capable of rapid regeneration. This balance may help determine risk for peripheral neuropathy associated with diabetes or metabolic syndrome. Capsaicin application for 48 hours induces cutaneous fibers to die back into the dermis. Regrowth can be monitored by serial skin biopsies to determine intraepidermal nerve fiber density (IENFD). We used this capsaicin axotomy technique to examine the effects of exercise on cutaneous regenerative capacity in the setting of metabolic syndrome. METHODS: Baseline ankle IENFD and 30-day cutaneous regeneration after thigh capsaicin axotomy were compared for participants with type 2 diabetes (n = 35) or metabolic syndrome (n = 32) without symptoms or examination evidence of neuropathy. Thirty-six participants (17 with metabolic syndrome) then joined twice weekly observed exercise and lifestyle counseling. Axotomy regeneration was repeated in month 4 during this intervention. RESULTS: Baseline distal leg IENFD was significantly reduced for both metabolic syndrome and diabetic groups. With exercise, participants significantly improved exercise capacity and lower extremity power. Following exercise, 30-day reinnervation rate improved (0.051 ± 0.027 fibers/mm/day before vs 0.072 ± 0.030 after exercise, p = 0.002). Those who achieved improvement in more metabolic syndrome features experienced a greater degree of 30-day reinnervation (p < 0.012). INTERPRETATION: Metabolic syndrome was associated with reduced baseline IENFD and cutaneous regeneration capacity comparable to that seen in diabetes. Exercise-induced improvement in metabolic syndrome features increased cutaneous regenerative capacity. The results underscore the potential benefit to peripheral nerve function of a behavioral modification approach to metabolic improvement.

Age-related differences in lean mass, protein synthesis and skeletal muscle markers of proteolysis after bed rest and exercise rehabilitation.

Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge (BED REST). This was followed by 8 weeks of high intensity resistance exercise (REHAB). Leg lean mass (via dual-energy X-ray absorptiometry; DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after essential amino acid (EAA) ingestion on three occasions: before (PRE), after bed rest and after rehabilitation. Samples were assessed for protein synthesis, mTORC1 signalling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after bedrest (P < 0.05) and was restored after rehabilitation. EAA-induced mTORC1 signalling and protein synthesis increased before bed rest in both age groups (P < 0.05). Although both groups had blunted mTORC1 signalling, increased REDD2 and MURF1 mRNA after bedrest, only older adults had reduced EAA-induced protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P < 0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short-term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults.

Exercise as Therapy for Diabetic and Prediabetic Neuropathy.

Length-dependent neuropathy is the most common and costly complication of diabetes and frequently causes injury primarily to small-diameter cutaneous nociceptive fibers. Not only persistent hyperglycemia but also metabolic, endocrine, and inflammatory effects of obesity and dyslipidemia appear to play an important role in the development of diabetic neuropathy. Rational therapies aimed at direct control of glucose or its increased entry into the polyol pathway, oxidative or nitrosative stress, advanced glycation end product formation or signaling, microvascular ischemia, or adipocyte-derived toxicity have each failed in human trials of diabetic neuropathy. Aerobic exercise produces salutary effects in many of these pathogenic pathways simultaneously and, in both animal models and human trials, has been shown to improve symptoms of neuropathy and promote re-growth of cutaneous small-diameter fibers. Behavioral reduction in periods of seated, awake inactivity produces multimodal metabolic benefits similar to exercise, and the two strategies when combined may offer sustained benefit to peripheral nerve function.

Resistance strength training exercise in children with spinal muscular atrophy.

INTRODUCTION: Preliminary evidence in adults with spinal muscular atrophy (SMA) and in SMA animal models suggests exercise has potential benefits in improving or stabilizing muscle strength and motor function. METHODS: We evaluated feasibility, safety, and effects on strength and motor function of a home-based, supervised progressive resistance strength training exercise program in children with SMA types II and III. Up to 14 bilateral proximal muscles were exercised 3 times weekly for 12 weeks. RESULTS: Nine children with SMA, aged 10.4 ± 3.8 years, completed the resistance training exercise program. Ninety percent of visits occurred per protocol. Training sessions were pain-free (99.8%), and no study-related adverse events occurred. Trends in improved strength and motor function were observed. CONCLUSIONS: A 12-week supervised, home-based, 3-day/week progressive resistance training exercise program is feasible, safe, and well tolerated in children with SMA. These findings can inform future studies of exercise in SMA.

Exercise and medication effects on persons with Parkinson disease across the domains of disability: a randomized clinical trial.

BACKGROUND AND PURPOSE: Hypokinesia and bradykinesia as movement deficits of Parkinson disease are thought to be mediated by both basal ganglia dysfunction and a loss of muscle mass and strength commensurate with aging and decreased levels of physical activity. For these reasons, we sought to utilize resistance training as a means to increase muscle force and minimize hypokinesia and bradykinesia in persons with Parkinson disease and examine the effects of exercise and medication on Body Structure and Function (muscle force production and muscle cross-sectional area), Activity (mobility), and Participation (Health Status) outcomes. METHODS: Forty-two participants were enrolled in a 12-week randomized clinical trial that compared 2 active exercise interventions: a standard care control group (Active Control) and an experimental group that underwent Resistance Exercise via Negative Eccentric Work (RENEW). RESULTS: Participants in both groups improved in muscle force production and mobility as a result of exercise and medication (P < 0.02). There were no significant interaction or between-group differences and no significant changes in muscle cross-sectional area or health status were observed. Effect sizes for exercise and medication combined exceeded the effect sizes of either intervention in isolation. DISCUSSION AND CONCLUSIONS: Taken together, these results point to the complementary effects of exercise and medication on the Body Structure and Function and Activity outcomes but little effect on Participation outcomes.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A92).

Low Physical Function in Maintenance Hemodialysis Patients Is Independent of Muscle Mass and Comorbidity.

OBJECTIVES: It is unknown whether muscle wasting accounts for impaired physical function in adults on maintenance hemodialysis (MHD). DESIGN: Observational study. SETTING: Outpatient dialysis units and a fall clinic. SUBJECTS: One hundred eight MHD and 122 elderly nonhemodialysis (non-HD) participants. EXPOSURE VARIABLE: Mid-thigh muscle area was measured by magnetic resonance imaging. MAIN OUTCOME MEASURE: Physical function was measured by distance walked in 6 minutes. RESULTS: Compared with non-HD elderly participants, MHD participants were younger (49.2 ± 15.8 vs. 75.3 ± 7.1 years; P < .001) and had higher mid-thigh muscle area (106.2 ± 26.8 vs. 96.1 ± 21.1 cm2; P = .002). However, the distance walked in 6 minutes was lower in MHD participants (322.9 ± 110.4 vs. 409.0 ± 128.3 m; P < .001). In multiple regression analysis adjusted for demographics, comorbid conditions, and mid-thigh muscle area, MHD patients walked significantly less distance (-117 m; 95% confidence interval: -177 to -56 m; P < .001) than the non-HD elderly. CONCLUSIONS: Even when compared with elderly non-HD participants, younger MHD participants have poorer physical function that was not explained by muscle mass or comorbid conditions. We speculate that the uremic milieu may impair muscle function independent of muscle mass. The mechanism of impaired muscle function in uremia needs to be established in future studies.

Sedentary Behavior in Individuals With Diabetic Chronic Kidney Disease and Maintenance Hemodialysis.

OBJECTIVE: The objective of this study was to examine whether more advanced kidney failure is associated with sedentary behavior and whether demographics, comorbidity, nutritional, and inflammatory markers explain this association. DESIGN: Observational study. SETTING: Outpatients recruited from outpatient clinics and dialysis units. SUBJECTS: One hundred sixty patients with chronic kidney disease (CKD) or receiving maintenance hemodialysis (MHD). METHODS: Standardized questionnaires including Baecke physical activity questionnaire, standardized anthropometry examination, and blood draw. MAIN OUTCOME MEASURE: Sedentary behavior (defined as answering "very often" for "during leisure time I watch television" or answering "never" for "during leisure time I walk") and being physically active (top 25th percentile of the total Baecke score). RESULTS: Nineteen percent of CKD and 50% of MHD patients were sedentary (P < .001) and 38.8% of CKD and 11.3% of MHD patients were physically active. In separate multivariable logistic regression models, compared with CKD patients, MHD patients were more sedentary (odds ratio 3.84; 95% confidence interval, 1.18-12.51) and less physically active (odds ratio 0.07; 95% confidence interval 0.01-0.40) independent of demographics, comorbidity, smoking, body size, serum high sensitivity C-reactive protein (hsCRP) and albumin. Congestive heart failure, peripheral vascular disease, and higher body mass index were independently associated with sedentary behavior, whereas younger age, lower body mass index, lower serum hsCRP, and higher serum albumin were associated with being physically active. CONCLUSIONS: Sedentary behavior is highly prevalent among diabetic CKD or MHD patients. The strong association of MHD status with sedentary behavior is not explained by demographics, smoking, comorbidity, nutritional, and inflammatory markers. Interventions targeting obesity might improve sedentary behavior and physical activity, whereas interventions targeting inflammation might improve physical activity in these populations.

Effects of practice on variability of muscle force.

The motor skill required to decrease the variability in muscle force steadiness can be challenging. The purposes of this study were to determine whether muscle force steadiness improved following repeated trials and whether the number of trials varied for healthy younger adults, healthy older adults, and older adults who have fallen to obtain stable muscle force steadiness measures. Sixty participants performed 30 concentric and eccentric contractions of the knee extensors on an isokinetic dynamometer. Each group had significant improvements in muscle force steadiness and obtained stable measures within six to nine trials. Healthy younger and older adults, and older adults who have fallen, can improve muscle force steadiness. These findings provide a framework for methodological approaches when testing steadiness in varying populations.

Morphology versus function: the relationship between lumbar multifidus intramuscular adipose tissue and muscle function among patients with low back pain.

OBJECTIVE: To explore the bivariate and multivariate relations between fatty degeneration of the lumbar multifidus muscle (LMM) and LMM function among patients with low back pain (LBP). DESIGN: Cross-sectional clinical study. SETTING: Hospital. PARTICIPANTS: Patients with LBP (N=70) referred for lumbar spine magnetic resonance imaging. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: LMM morphology and function were measured at the L4/L5 and L5/S1 spinal levels bilaterally. Quantitative measures of LMM intramuscular adipose tissue (IMAT) were derived from T1-weighted magnetic resonance images. Function was assessed with ultrasound imaging by measuring change in LMM thickness during a submaximal contraction task. The study participants self-reported their level of LBP-related disability (Modified Oswestry Index), pain intensity (numerical pain rating scale), and physical activity (International Physical Activity Questionnaire). Bivariate and multivariate relations between LMM morphology and function were explored with correlational and hierarchical linear regression analyses, respectively. Additionally, we explored for possible covariates with potential to modify the relation between LMM IMAT and function. RESULTS: There were 70 participants (12 women) enrolled in the study (mean age, 45.4±11.9y). A high level of physical activity was reported by 45.5% of participates. Age, sex, and physical activity level demonstrated variable relations with LMM IMAT and LMM function. There were no significant bivariate or multivariate relations between LMM IMAT and LMM function. CONCLUSIONS: We observed higher levels of physical activity and LMM function and less LMM IMAT than previous studies involving patients with LBP. There was no relation between LMM morphology and function in this cohort of patients with LBP. Issues specific to LMM measurement and recommendations for future research are discussed.

Muscle force steadiness in older adults before and after total knee arthroplasty.

The ability to control submaximal muscle forces has been shown to be associated with age-related decreases in physical function, such as increased tendency to fall. This study compared quadriceps muscle force steadiness (MFS) in individuals with knee OA before and after total knee arthroplasty (TKA) to an age-matched group of controls. Lower extremity MFS was measured in 13 subjects with knee OA before and at six months after TKA (TKA-GROUP) and compared to an age-matched control group (CONTROL-GROUP). MFS was significantly more impaired in the TKA-GROUP at the pre-operative, but not post-operative visit, and significantly improved between the pre-operative and post-operative visits. Further research is warranted to evaluate the relation between this MFS measurement and physical functional performance in those at high risk for falling.

Evaluation of the Effectiveness of a Bilingual Nutrition Education Program in Partnership with a Mobile Health Unit.

There are limited reports of community-based nutrition education with culinary instruction that measure biomarkers, particularly in low-income and underrepresented minority populations. Teaching kitchens have been proposed as a strategy to address social determinants of health, combining nutrition education, culinary demonstration, and skill building. The purpose of this paper is to report on the development, implementation, and evaluation of Journey to Health, a program designed for community implementation using the RE-AIM planning and evaluation framework. Reach and effectiveness were the primary outcomes. Regarding reach, 507 individuals registered for the program, 310 participants attended at least one nutrition class, 110 participants completed at least two biometric screens, and 96 participants attended at least two health coaching appointments. Participants who engaged in Journey to Health realized significant improvements in body mass index, blood pressure, and triglycerides. For higher risk participants, we additionally saw significant improvements in total and LDL cholesterol. Regarding dietary intake, we observed a significant increase in cups of fruit and a decrease in sugar sweetened beverages consumed per day. Our findings suggest that Journey to Health may improve selected biometrics and health behaviors in low-income and underrepresented minority participants.

Physical function and gait speed in patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) who are treated with dialysis have impaired physical functioning that is associated with poor outcomes. Gait speed is an important measure of mobility that predicts adverse events and mortality in older people. Gait speed is low in patients with CKD, and those treated with hemodialysis average below cut-points known to indicate increased risk of reduced survival and adverse health events. Measurement of gait speed in patients with CKD may be valuable in identifying those at risk for adverse events, including disability and mortality.

Disuse-induced muscle fibrosis, cellular senescence, and senescence-associated secretory phenotype in older adults are alleviated during re-ambulation with metformin pre-treatment.

Muscle inflammation and fibrosis underlie disuse-related complications and may contribute to impaired muscle recovery in aging. Cellular senescence is an emerging link between inflammation, extracellular matrix (ECM) remodeling and poor muscle recovery after disuse. In rodents, metformin has been shown to prevent cellular senescence/senescent associated secretory phenotype (SASP), inflammation, and fibrosis making it a potentially practical therapeutic solution. Thus, the purpose of this study was to determine in older adults if metformin monotherapy during bed rest could reduce muscle fibrosis and cellular senescence/SASP during the re-ambulation period. A two-arm controlled trial was utilized in healthy male and female older adults (n = 20; BMI: <30, age: 60 years+) randomized into either placebo or metformin treatment during a two-week run-in and 5 days of bedrest followed by metformin withdrawal during 7 days of recovery. We found that metformin-treated individuals had less type-I myofiber atrophy during disuse, reduced pro-inflammatory transcriptional profiles, and lower muscle collagen deposition during recovery. Collagen content and myofiber size corresponded to reduced whole muscle cellular senescence and SASP markers. Moreover, metformin treatment reduced primary muscle resident fibro-adipogenic progenitors (FAPs) senescent markers and promoted a shift in fibroblast fate to be less myofibroblast-like. Together, these results suggest that metformin pre-treatment improved ECM remodeling after disuse in older adults by possibly altering cellular senescence and SASP in skeletal muscle and in FAPs.

Intramuscular adipose tissue and central activation in older adults.

INTRODUCTION: Intramuscular adipose tissue (IMAT) is a potential contributor to declining force production and may be related to impaired central activation; therefore, the purpose of this report is to describe IMAT composition and its association with central activation in older adults. The central activation ratio (CAR) of the knee extensors was assessed using a superimposition technique in 15 older adults (29 legs) along with the cross-sectional area of IMAT and lean tissue. RESULTS: IMAT and CAR are inversely related in older adults (r = -0.51, P = 0.005), and many subjects with high IMAT have deficits in central activation, whereas those with low IMAT have normal central activation. CONCLUSIONS: These novel findings may assist in unraveling why muscle force production and lean tissue cross-sectional area are not strongly linked, as the ability to centrally activate muscle appears to be unrelated to lean muscle area and may be dependent in part on IMAT levels.