Use of a wearable accelerometer to evaluate physical frailty in people receiving haemodialysis.

BACKGROUND: Physical frailty is a major health concern among people receiving haemodialysis (HD) for stage-5 chronic kidney disease (CKD-5). Wearable accelerometers are increasingly being recommended to objectively monitor activity levels in CKD-5 and recent research suggests they may also represent an innovative strategy to evaluate physical frailty in vulnerable populations. However, no study has yet explored whether wearable accelerometers may be utilised to assess frailty in the context of CKD-5-HD. Therefore, we aimed to examine the diagnostic performance of a research-grade wearable accelerometer in evaluating physical frailty in people receiving HD. METHODS: Fifty-nine people receiving maintenance HD [age = 62.3 years (SD = 14.9), 40.7% female] participated in this cross-sectional study. Participants wore a uniaxial accelerometer (ActivPAL) for seven consecutive days and the following measures were recorded: total number of daily steps and sit-to-stand transitions, number of daily steps walked with cadence < 60 steps/min, 60-79 steps/min, 80-99 steps/min, 100-119 steps/min, and ≥ 120 steps/min. The Fried phenotype was used to evaluate physical frailty. Receiver operating characteristics (ROC) analyses were performed to examine the diagnostic accuracy of the accelerometer-derived measures in detecting physical frailty status. RESULTS: Participants classified as frail (n = 22, 37.3%) had a lower number of daily steps (2363 ± 1525 vs 3585 ± 1765, p = 0.009), daily sit-to-stand transitions (31.8 ± 10.3 vs 40.6 ± 12.1, p = 0.006), and lower number of steps walked with cadence of 100-119 steps/min (336 ± 486 vs 983 ± 797, p < 0.001) compared to their non-frail counterparts. In ROC analysis, the number of daily steps walked with cadence ≥ 100 steps/min exhibited the highest diagnostic performance (AUC = 0.80, 95% CI: 0.68-0.92, p < 0.001, cut-off ≤ 288 steps, sensitivity = 73%, specificity = 76%, PPV = 0.64, NPV = 0.82, accuracy = 75%) in detecting physical frailty. CONCLUSIONS: This study provided initial evidence that a wearable accelerometer may be a useful tool in evaluating physical frailty in people receiving HD. While the total number of daily steps and sit-to-stand transitions could significantly discriminate frailty status, the number of daily steps walked with cadences reflecting moderate to vigorous intensity of walking may be more useful in monitoring physical frailty in people receiving HD.

The effect of intravenous iron supplementation on exercise capacity in iron-deficient but not anaemic patients with chronic kidney disease: study design and baseline data for a multicentre prospective double-blind randomised controlled trial.

BACKGROUND: Many people living with chronic kidney disease (CKD) are iron deficient, even though they may not be anaemic. The Iron and Muscle study aims to evaluate whether iron supplementation reduces symptoms of fatigue, improves muscle metabolism, and leads to enhanced exercise capacity and physical function. We report here the trial design and baseline characteristics. METHODS: This is a prospective, double-blind multicentre randomised controlled trial (RCT) including 75 non-dialysis stage 3-4 CKD patients with iron deficiency but without anaemia. Patients were randomly (1:1) assigned to either: i) intravenous iron therapy, or ii) placebo, with concurrent recruitment of eight CKD non-iron deficient participants and six healthy volunteers. The primary outcome of the study is the six-minute walk test (6MWT) distance between baseline and four-weeks. An additional exercise training programme for patients in both groups was initiated and completed between 4 and 12 weeks, to determine the effect of iron repletion compared to placebo treatment in the context of patients undertaking an exercise programme. Additional secondary outcomes include fatigue, physical function, muscle strength, muscle metabolism, quality of life, resting blood pressure, clinical chemistry, safety and harms associated with the iron therapy intervention and the exercise training intervention, and hospitalisations. All outcomes were conducted at baseline, 4, and 12 weeks, with a nested qualitative study, to investigate the experience of living with iron deficiency and intervention acceptability. The cohort have been recruited and baseline assessments undertaken. RESULTS: Seventy-five individuals were recruited. 44% of the randomised cohort were male, the mean (SD) age was 58 (14) years, and 56% were White. Body mass index was 31 (7) kg/m2; serum ferritin was 59 (45) µg/L, transferrin saturation was 22 (10) %, and haemoglobin was 125 (12) g/L at randomisation for the whole group. Estimated glomerular filtration rate was 35 (12) mL/min/1.73 m2 and the baseline 6MWT distance was 429 (174) m. CONCLUSION: The results from this study will address a substantial knowledge gap in the effects of intravenous iron therapy, and offer potential clinical treatment options, to improve exercise capacity, physical function, fatigue, and muscle metabolism, for non-dialysis patients with CKD who are iron-deficient but not anaemic. It will also offer insight into the potential novel effects of an 8-week exercise training programme. TRIAL REGISTRATION: EudraCT: 2018-000,144-25 Registered 28/01/2019.

Leisure Time Physical Activity in Children and Young People With Cerebral Palsy: A Population-Based Study.

PURPOSE: To describe leisure time physical activity in children and young people with cerebral palsy and identify barriers and facilitators to participation. METHODS: Leisure time physical activity participation was derived from a national cerebral palsy register and associated factors were analyzed. Barriers and facilitators to participation were investigated through a survey. RESULTS: Leisure time physical activity participation was recorded. Outcomes of participation decreased with increasing Gross Motor Function Classification System level. Leisure time physical activity "not in club" for 11- to 18-year-olds was significantly lower than for those aged 5 to 10 years for Gross Motor Function Classification System level II. The survey supported that disability and disliking help were common barriers and parental encouragement and enjoyment were common facilitators. CONCLUSIONS: Data from the register and survey provide insight into factors influencing leisure time physical activity participation in young people with cerebral palsy and how to increase.

Screening tools to expedite assessment of frailty in people receiving haemodialysis: a diagnostic accuracy study.

BACKGROUND: Frailty is associated with multiple adverse outcomes in stage-5 chronic kidney disease (CKD-5) and upwards of one third of people receiving haemodialysis (HD) are frail. While many frailty screening methods are available in both uremic and non-uremic populations, their implementation in clinical settings is often challenged by time and resource constraints. In this study, we explored the diagnostic accuracy of time-efficient screening tools in people receiving HD. METHODS: A convenience sample of 76 people receiving HD [mean age = 61.1 years (SD = 14), 53.9% male] from three Renal Units were recruited for this cross-sectional study. Frailty was diagnosed by means of the Fried phenotype. Physical performance-based screening tools encompassed handgrip strength, 15-ft gait speed, timed up and go (TUG), and five-repetition sit to stand (STS-5) tests. In addition, participants completed the SF-36 Health Survey, the short-form international physical activity questionnaire and the Tinetti falls efficacy scale (FES) as further frailty-related measures. Outcome measures included the area under the curve (AUC), sensitivity, specificity, positive (PPV) and negative predictive values (NPV). The diagnostic performance of screening tools in assessing fall-risk was also investigated. RESULTS: Overall, 36.8% of participants were classified as frail. All the examined instruments could significantly discriminate frailty status in the study population. Gait speed [AUC = 0.89 (95%CI: 0.81-0.98), sensitivity = 75%, specificity = 93%] and TUG [AUC = 0.90 (95%CI: 0.80-0.99), sensitivity = 89%, specificity = 85%] exhibited the highest diagnostic accuracy. There was a significant difference in gait speed AUC (20%, p = 0.013) between participants aged 65 years or older (n = 36) and those under 65 years of age (n = 40), with better discriminating performance in the younger sub-group. The Tinetti FES was the only instrument showing good diagnostic accuracy (AUCs≥0.80) for both frailty (sensitivity = 82%, specificity = 79%) and fall-risk (sensitivity = 82%, specificity = 71%) screening. CONCLUSIONS: This cross-sectional study revealed that time- and cost-efficient walking performance measures can accurately be used for frailty-screening purposes in people receiving HD. While self-selected gait speed had an excellent performance in people under 65 years of age, TUG may be a more suitable screening method for elderly patients (≥65 years). The Tinetti FES may be a clinically useful test when physical testing is not achievable.

Minimum accelerometer wear-time for reliable estimates of physical activity and sedentary behaviour of people receiving haemodialysis.

BACKGROUND: Low levels of physical activity are implicated in low life expectancies of people receiving maintenance haemodialysis. Accelerometers are increasingly being used to quantify activity behaviours of this population but guidance to quality-assure such data is lacking. The objective of this study was to provide data processing and reduction recommendations to ensure accelerometer-derived outcomes are sufficiently reliable for interpretative analysis. METHODS: Seventy people receiving maintenance haemodialysis (age 55.9 ± 15.7 years, 34% women, 23% diabetic) from a single outpatient renal unit volunteered for the study. Participants wore Actigraph GT3x and ActivPAL monitors during waking hours over seven days. Reliability of accelerometer output (normalised to wear-time) was assessed via intraclass correlation coefficient (ICC). The Spearman-Brown prophecy formula was subsequently applied to the ICCs to derive the minimum required accelerometer wear-time for each behavioural outcome. RESULTS: Monitor wear compliance was greater on dialysis compared to non-dialysis days (90% v 77%). Participants were significantly more active on non-dialysis days compared to dialysis days but there were no significant differences in estimated behaviours between days within the same condition. Average measure ICCs for all accelerometer outcomes were high (range 0.76-0.96). Computations indicated that habitual physical activity and sedentary behaviour could be estimated with a minimum reliability level of 0.80 from one dialysis day and two non-dialysis days, and at least eight hours monitor wear per day. Applying this rubric allowed 90% of participant data to be retained for further analysis. CONCLUSIONS: Regardless of accelerometer, one dialysis and two non-dialysis days data with a minimum of eight hours wear each day should enable habitual activity of people receiving maintenance haemodialysis to be characterised with acceptable reliability. These recommendations reconcile the tension between wear-time criteria stringency and retention of an adequately representative sample.

The relative importance of frailty, physical and cardiovascular function as exercise-modifiable predictors of falls in haemodialysis patients: a prospective cohort study.

BACKGROUND: Stage 5 chronic kidney disease (CKD-5) patients on haemodialysis (HD) are at high risk of accidental falls. Previous research has shown that frailty is one of the primary contributors to the increased risk of falling in this clinical population. However, HD patients often present with abnormalities of cardiovascular function such as baroreflex impairment and orthostatic dysregulation of blood pressure (BP) which may also be implicated in the aetiology of falling. Therefore, we aimed to explore the relative importance of frailty and cardiovascular function as potential exercise-modifiable predictors of falls in these patients. METHODS: Ninety-three prevalent CKD-5 patients on HD from three Renal Units were recruited for this prospective cohort study, which was conducted between October 2015 and August 2018. At baseline, frailty status was assessed using the Fried's frailty phenotype, while physical function was evaluated through timed up and go (TUG), five repetitions chair sit-to-stand (CSTS-5), objectively measured physical activity, and maximal voluntary isometric strength. Baroreflex and haemodynamic function at rest and in response to a 60° head-up tilt test (HUT-60°) were also assessed by means of the Task Force Monitor. The number of falls experienced was recorded once a month during 12 months of follow-up. RESULTS: In univariate negative binomial regression analysis, frailty (RR: 4.10, 95%CI: 1.60-10.51, p = 0.003) and other physical function determinants were associated with a higher number of falls. In multivariate analysis however, only worse baroreflex function (RR: 0.96, 95%CI: 0.94-0.99, p = 0.004), and orthostatic decrements of BP to HUT-60° (RR: 0.93, 95%CI: 0.87-0.99, p = 0.033) remained significantly associated with a greater number of falls. Eighty falls were recorded during the study period and the majority of them (41.3%) were precipitated by dizziness symptoms, as reported by participants. CONCLUSIONS: This prospective study indicates that cardiovascular mechanisms implicated in the short-term regulation of BP showed a greater relative importance than frailty in predicting falls in CKD-5 patients on HD. A high number of falls appeared to be mediated by a degree of cardiovascular dysregulation, as evidenced by the predominance of self-reported dizziness symptoms. TRIAL REGISTRATION: ClinicalTrials.gov (trial registration ID: NCT02392299; date of registration: March 18, 2015).

Selective voluntary motor control measures of the lower extremity in children with upper motor neuron lesions: a systematic review.

AIM: Recovery and trainability of impaired selective voluntary motor control (SVMC) of the lower extremity in children with upper motor neuron lesions has received little attention. To facilitate an evidence-based debate about this topic, this review evaluates the evidence level of the psychometric properties of SVMC measures. METHOD: MEDLINE, Embase, CINAHL, PsycINFO, Scopus, Cochrane and PEDro databases were systematically searched up to July 2016. Two independent raters scored the methodological quality in accordance to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The overall level of evidence was scored according to Cochrane criteria. RESULTS: We identified 3590 studies, of which 17 were included. COSMIN scores ranged from 'poor' to 'excellent' for studies investigating measurement properties of the Selective Motor Control test, modified Trost test, Gillette's Selective Motor Control test, Selective Control Assessment of the Lower Extremity (SCALE), kinematic measures, electromyography, and torque steadiness. Studies assessing the SCALE scored highest on COSMIN items. Evidence levels for SCALE's validity and reliability properties were moderate, while for the other SVMC measures these ranged from unknown to moderate. Responsiveness was not assessed. INTERPRETATION: Further psychometric studies of SVMC measures are needed to provide a scientific contribution to the ongoing debate of SVMC trainability.

Construct validity and reliability of the Selective Control Assessment of the Lower Extremity in children with cerebral palsy.

AIM: Assessing impaired selective voluntary movement control in children with cerebral palsy (CP) has gained increasing interest. We investigated construct validity and intra- and interrater reliability of the Selective Control Assessment of the Lower Extremity (SCALE). METHOD: Thirty-nine children (21 males, 18 females) with spastic CP, mean age 12 years 6 months [range 6y 11mo-19y 9mo], Gross Motor Function Classification System (GMFCS) levels I to IV, participated. Differences in SCALE scores were determined on joint levels and between patients categorized according to their limb distribution and GMFCS levels. SCALE scores were correlated with the Fugl-Meyer Assessment, Manual Muscle Test, and Modified Ashworth Scale. To determine reliability, the SCALE was applied once and recorded on video. RESULTS: SCALE scores differed significantly between the less and more affected leg (p<0.001) and between most leg joints. Total SCALE scores differed significantly between GMFCS levels I and II. Correlations with Fugl-Meyer Assessment, Manual Muscle Test, and Modified Ashworth Scale were 0.88, 0.88, and -0.55 respectively. Intraclass correlation coefficients were all above 0.9, with the minimal detectable change below 2 points. INTERPRETATION: The SCALE appears to be a valid and reliable tool to assess selective voluntary movement control of the legs in children with spastic CP.

Effect of exercise training on estimated GFR, vascular health, and cardiorespiratory fitness in patients with CKD: a pilot randomized controlled trial.

BACKGROUND: Exercise capacity, which is predictive of all-cause mortality and cardiovascular disease risk, is reduced significantly in patients with non-dialysis-dependent chronic kidney disease. This pilot study examined the effect of moderate-intensity exercise training on kidney function and indexes of cardiovascular risk in patients with progressive chronic kidney disease stages 3 to 4. STUDY DESIGN: Single-blind, randomized, controlled, parallel trial. SETTING & PARTICIPANTS: 20 patients (aged 18-80 years; 17 men) randomly assigned to rehabilitation (n=10) or usual care (n=10). Participants were included if they were 18 years or older and had evidence of rate of decline in creatinine-based estimated glomerular filtration rate (eGFRcr)≥2.9mL/min/1.73m(2) per year for 12 months preintervention. Patients were excluded if they had unstable medical conditions or had recently started regular exercise. INTERVENTION: The rehabilitation group received resistance and aerobic training (3 days per week) for a 12-month period. The usual care group received standard care. OUTCOMES: Kidney function assessed by comparing mean rate of change in eGFRcr (mL/min/1.73m(2) per year) from a 12-month preintervention period against the 12-month intervention period. Pulse wave velocity (PWV), peak oxygen uptake (Vo2peak), and waist circumference assessed at 0, 6, and 12 months. MEASUREMENTS: eGFR assessed using creatinine, cystatin C (eGFRcys), and a combination of both values (eGFRcr-cys). RESULTS: 18 participants (rehabilitation, 8; usual care, 10) completed the study. A significant mean difference in rate of change in eGFRcr (+7.8±3.0 [95% CI, 1.1-13.5] mL/min/1.73m(2) per year; P=0.02) was observed between the rehabilitation and usual care groups, with the rehabilitation group demonstrating a slower decline. No significant between-group mean differences existed in absolute eGFRcr, eGFRcr-cys, or eGFRcys at 12 months of study intervention. Significant between-group mean differences existed in PWV (-2.30 [95% CI, -3.02 to -1.59] m/s), waist circumference (-7.1±12.8 [95% CI, -12.4 to -3.2] cm), and Vo2peak (5.7 [95% CI, 1.34-10.10] mL/kg/min). Change in eGFRcr was correlated inversely with PWV (r=-0.5; P=0.04) at 12 months. LIMITATIONS: Small sample size, inconsistency between primary and secondary measures of kidney function. CONCLUSIONS: The effect of a 1-year exercise intervention on progression of kidney disease is inconclusive. A larger study with longer follow-up may be necessary.

Aerobic or Resistance Training and Pulse Wave Velocity in Kidney Transplant Recipients: A 12-Week Pilot Randomized Controlled Trial (the Exercise in Renal Transplant [ExeRT] Trial).

BACKGROUND: Cardiovascular disease remains the leading cause of death in kidney transplant recipients. This pilot study examined the potential effect of aerobic training or resistance training on vascular health and indexes of cardiovascular risk in kidney transplant recipients. STUDY DESIGN: Single-blind, randomized, controlled, parallel trial. SETTING & PARTICIPANTS: 60 participants (mean age, 54 years; 34 men) were randomly assigned to aerobic training (n=20), resistance training (n=20), or usual care (n=20). Participants were included if they had a kidney transplant within 12 months prior to baseline assessment. Patients were excluded if they had unstable medical conditions or had recently started regular exercise. INTERVENTION: Aerobic training and resistance training were delivered 3 days per week for a 12-week period. The usual-care group received standard care. OUTCOMES & MEASUREMENTS: Pulse wave velocity, peak oxygen uptake (Vo2peak), sit-to-stand 60, isometric quadriceps force, and inflammatory biomarkers were assessed at 0 and 12 weeks. RESULTS: The anticipated 60 participants were recruited within 12 months. 46 participants completed the study (aerobic training, n=13; resistance training, n=13; and usual care, n=20), resulting in a 23% attrition rate. Analyses of covariance, adjusted for baseline values, age, and dialysis vintage pretransplantation, revealed significant mean differences between aerobic training and usual care in pulse wave velocity of -2.2±0.4 (95% CI, -3.1 to -1.3) m/s (P<0.001) and between resistance training and usual care of -2.6±0.4 (95% CI, -3.4 to -1.7) m/s (P<0.001) at 12 weeks. Secondary analyses indicated significant improvements in Vo2peak in the aerobic training group and in Vo2peak, sit-to-stand 60, and isometric muscle force in the resistance training group compared with usual care at 12 weeks. There were no reported adverse events, cardiovascular events, or hospitalizations as a result of the intervention. LIMITATIONS: Pilot study, small sample size, no measure of endothelial function. CONCLUSIONS: Both aerobic training and resistance training interventions appear to be feasible and clinically beneficial in this patient population.

Exercise counselling practices for patients with chronic kidney disease in the UK: a renal multidisciplinary team perspective.

BACKGROUND: Patients with chronic kidney disease (CKD) have elevated cardiovascular disease (CVD) risk. Physical activity (PA) is a strong and independent CVD risk factor, and despite the fact that current clinical practice guidelines recommend simultaneous treatment of multiple risk factors for optimum management of CKD, PA is rarely addressed by renal care teams. The aim of this observational cross-sectional survey was to document current exercise/PA practices across renal units in the UK, and capture views and experiences regarding the provision of PA/exercise options for patients with CKD. METHODS: An 18-item online survey questionnaire regarding exercise counselling practice patterns was administered to 565 multidisciplinary renal care professionals. RESULTS: 142 individuals (25% response rate) completed the questionnaire. Overall, 42% of respondents discussed and encouraged PA, but only 18 and 11% facilitated implementation of PA for their patients. Nephrologists (p < 0.003) were more likely to prescribe or recommend PA compared to professionals with a nursing background and believed that specific renal rehabilitation services, including an active PA/exercise component, should be available to all patients (p < 0.01). The most commonly reported barriers for the development and implementation of PA/exercise options included lack of funding, time, and knowledgeable personnel, such as physiotherapists or other exercise professionals. CONCLUSION: Beliefs and attitudes towards PA amongst members of the renal multidisciplinary team are encouraging. However there is a big gap between believing in the benefits of PA and promoting/implementing PA for patient benefit. This gap needs to be minimised by at least trying to address some of the reported barriers.

Are tactile function and body awareness of the foot related to motor outcomes in children with upper motor neuron lesions?

Introduction: Somatosensory function can be reduced in children with Upper Motor Neuron (UMN) lesions. Therefore, we investigated relationships between somatosensory functions of the foot and motor outcomes in children with UMN lesions. Method: In this cross-sectional study, we assessed the Tactile Threshold (TT) with monofilaments and body awareness with Tactile Localisation Tasks for spatial-related action (TLTaction) and structural-related perception (TLTperception) body representation at the foot sole. Furthermore, we assessed four motor outcomes: the Selective Control Assessment of the Lower Extremity (SCALE), the modified Timed Up and Go test (mTUG), the Gillette Functional Assessment Questionnaire (FAQ), and the Functional Mobility Scale (FMS). Spearman's correlations (ρ) were applied to assess relationships between the somatosensory function of the foot sole and the applied motor outcomes. Results: Thirty-five children with UMN lesions, on average 11.7 ± 3.4 years old, participated. TLTperception correlated significantly with all lower limb motor outcomes (|ρ|=0.36-0.57; p < 0.05), but TLTaction (|ρ|=0.00-0.27; p = 0.15-0.97, and TT did not (|ρ|=0.01-0.83; p = 0.73-0.94). TLTperception correlated strongly with the Gross Motor Function Classification System (|ρ|=0.62; p = 0.001) in children with cerebral palsy (n = 24). Discussion: Assessing structural body representation of the foot sole should be considered when addressing lower limb motor impairments, including gait, in children with upper motor neuron lesions. Our results suggest that the assessment of tactile function and spatial body representation may be less related to lower limb motor function.

Exercise therapy in individuals with chronic kidney disease: a systematic review and synthesis of the research evidence.

Chronic kidney disease (CKD) is becoming a serious health problem throughout the world and is one of the most potent known risk factors for cardiovascular disease (CVD) which is considered the leading cause of morbidity and mortality in this cohort of patients. Additional independent risk factors for poor health outcomes among many include diabetes, physical inactivity and physical dysfunction. Physical inactivity partly contributes to the accelerated deterioration of physical function in people in all stages of CKD, to levels that significantly impact on clinically and patient important outcomes such as morbidity, employment, quality of life (QoL) and ultimately survival. Ongoing research aims to determine the effectiveness and impact of exercise rehabilitation on reducing/managing the risk of CVD, alleviating physical function limitations, preventing disability and enhancing QoL. Current research also aims to elucidate the mechanisms via which exercise therapy may contribute to clinically relevant benefits.

Feasibility of randomized controlled trials and long-term implementation of interventions: Insights from a qualitative process evaluation of the PEDAL trial.

Introduction: A multi-site randomized controlled trial was carried out between 2015 and 2019 to evaluate the impacts on quality of life of an intradialytic exercise programme for people living with chronic kidney disease. This included a qualitative process evaluation which gave valuable insights in relation to feasibility of the trial and of the intervention in the long-term. These can inform future clinical Trial design and evaluation studies. Methods: A constructivist phenomenological approach underpinned face-to-face, semi-structured interviews. Purposive recruitment ensured inclusion of participants in different arms of the PEDAL Trial, providers with different roles and trial team members from seven Renal Units in five study regions. Following ethical review, those willing took part in one interview in the Renal Unit. Audio-recorded interviews were transcribed (intelligent verbatim) and inductively thematically analyzed. Results: Participants (n = 65) (Intervention arm: 26% completed; 13% who did not; Usual care arm: 13%; 46% women; 54% men; mean age 60 year) and providers (n = 39) were interviewed (23% PEDAL Trial team members). Three themes emerged: (1) Implementing the Intervention; (2) Implementing the trial; and (3) Engagement of the clinical team. Explanatory theory named "the Ideal Scenario" was developed, illustrating complex interactions between different aspects of intervention and trial implementation with the clinical context. This describes characteristics likely to optimize trial feasibility and intervention sustainability in the long-term. Key aspects of this relate to careful integration of the trial within the clinical context to optimize promotion of the trial in the short-term and engagement and ownership in the long-term. Strong leadership in both the clinical and trial teams is crucial to ensure a proactive and empowering culture. Conclusion: Novel explanatory theory is proposed with relevance for Implementation Science. The "Ideal Scenario" is provided to guide trialists in pre-emptive and ongoing risk analysis relating to trial feasibility and long-term intervention implementation. Alternative study designs should be explored to minimize the research-to-practice gap and optimize the likelihood of informative findings and long-term implementation. These might include Realist Randomized Controlled Trials and Hybrid Effectiveness-Implementation studies.

A Randomized Trial of Intravenous Iron Supplementation and Exercise on Exercise Capacity in Iron-Deficient Nonanemic Patients With CKD.

Introduction: Patients with chronic kidney disease (CKD) are often iron deficient, even when not anemic. This trial evaluated whether iron supplementation enhances exercise capacity of nonanemic patients with CKD who have iron-deficiency. Methods: Prospective, multicenter double-blind randomized controlled trial of nondialysis patients with CKD and iron-deficiency but without anemia (Hemoglobin [Hb] >110 g/l). Patients were assigned 1:1 to intravenous (IV) iron therapy, or placebo. An 8-week exercise program commenced at week 4. The primary outcome was the mean between-group difference in 6-minute walk test (6MWT) at 4 weeks. Secondary outcomes included 6MWT at 12 weeks, transferrin saturation (TSAT), serum ferritin (SF), Hb, renal function, muscle strength, functional capacity, quality of life, and adverse events at baseline, 4 weeks, and at 12 weeks. Mean between-group differences were analyzed using analysis of covariance models. Results: Among 75 randomized patients, mean (SD) age for iron therapy (n = 37) versus placebo (n = 38) was 54 (16) versus 61 (12) years; estimated glomerular filtration rate (eGFR) (34 [12] vs. 35 [11] ml/min per 1.73 m2], TSAT (23 [12] vs. 21 [6])%; SF (57 [64] vs. 62 [33]) µg/l; Hb (122.4 [9.2] vs. 127 [13.2] g/l); 6MWT (384 [95] vs. 469 [142] meters) at baseline, respectively. No significant mean between-group difference was observed in 6MWT distance at 4 weeks. There were significant increases in SF and TSAT at 4 and 12 weeks (P < 0.02), and Hb at 12 weeks (P = 0.009). There were no between-group differences in other secondary outcomes and no adverse events attributable to iron therapy. Conclusion: This trial did not demonstrate beneficial effects of IV iron therapy on exercise capacity at 4 weeks. A larger study is needed to confirm if IV iron is beneficial in nondialysis patients with CKD who are iron-deficient.

Evaluation of a pragmatic exercise rehabilitation programme in chronic kidney disease.

BACKGROUND: Physical activity has the potential to positively impact upon aerobic and functional ability, and the quality of life of all chronic kidney disease (CKD) patients independent of the stage of the disease process. Physical activity is recommended in a number of national CKD guidelines, but its incorporation into routine care has been slow. The translation of research-led physical activity programmes into an established procedure appears to be a particular obstacle. This study included 263 patients, consecutively referred over a 4-year period, to a pragmatic 12-week renal rehabilitation (RR) programme delivered within a National Health Service (NHS). METHODS: One hundred and thirty-one patients were assessed and started the RR programme. Anxiety and depression were measured using the hospital anxiety and depression (HAD) scale. The self-reported level of fitness was measured with the Duke's activity status index (DASI), and exercise capacity was assessed with the incremental shuttle walk test (ISWT), sit-to-stand transfers in 60 s (STS60), timed up and go (TUAG) and stair-climb descent (SCD) tests. All measures were assessed at baseline and at 12 weeks. Attendance and completion of the RR programme were recorded for all patients. RESULTS: There were significant improvements in exercise capacity and functional ability ranging from 21 to 44%, and significant improvements in anxiety (15%) and depression (29%) in the 77 patients who completed the RR programme. The self-reported level of fitness was found to be significantly associated with completion (P = 0.01), with older participants showing a trend towards being more likely to complete (P= 0.07). Fifty-four patients, out of the 131 patients who commenced the RR programme, failed to complete 12 or more of the 24 scheduled sessions. Patients requiring haemodialysis (HD) treatment constituted the largest number of dropouts/non-completers (49%) in the study. CONCLUSIONS: This study demonstrates that a pragmatically constructed, NHS-delivered exercise-based RR can substantially improve both physical function and mental well-being for the wide range of CKD patients who regularly participated (55%). Compliance/adherence data indicate that this type of rehabilitation programme is particularly well received by pre-dialysis (PD) CKD and post-transplantation patients.

Resistance Exercise in People With Stage-3 Chronic Kidney Disease: Effects of Training Frequency (Weekly Volume) on Measures of Muscle Wasting and Function.

Background: Resistance training (RT) is a proven anabolic intervention in people living with and without chronic kidney disease (CKD). To date, there is a dearth of knowledge regarding the dose-response relationship of RT in the non-dialysis dependent CKD population. Therefore, we aimed to explore the effects of RT frequency (weekly volume) on established measures of muscle wasting and function in CKD. Methods: Twenty people with stage-3 CKD (CKD-3) were allocated to either a low frequency (one-session per week, RT1) or higher frequency (three-sessions per week, RT3) 12-week RT programme consisting of lower extremity strengthening exercises. The two RT programmes were not volume matched. Assessment outcomes before and after the intervention included measures of total and regional body composition, muscle size and architecture, strength, physical function, and uraemic symptoms. Results: Significant improvements over time in muscle size and architecture, strength, physical function, and uraemic symptoms were observed for both RT1 and RT3. Compared to RT1, participants who performed RT3 showed greater increases in vastus lateralis (VL) anatomical cross-sectional area (30.8% vs. 13.2%, p < 0.001) and pennation angle (36.3% vs. 17.5%, p = 0.008) after 12 weeks. In either group, there were no significant changes over time in mid-VL fascicle length, nor in measures of total body composition and upper arm muscle strength. Conclusion: Despite the group differences observed in the VL physiological adaptations, the strength and physical function responses, as well as the reductions of uraemic symptoms, were similar whether training once or thrice weekly. Therefore, performing RT just once per week may be an effective pre-habilitation strategy for people with CKD-3.

Validity and reliability of high-resolution ultrasound imaging for the assessment of regional body composition in stage 5 chronic kidney disease patients undergoing continuous ambulatory peritoneal dialysis.

BACKGROUND: Accurate measurement of muscle mass is an important research and clinical tool. High-resolution ultrasound (US) has shown potential as a method to assess muscle and fat mass at specific anatomical sites. However, there is limited evidence for the reliability of US to measure muscle size in patients receiving continuous ambulatory peritoneal dialysis (CAPD). Therefore, we examined the validity and reliability of an US method compared to a gold standard comparison for the assessment of a quadriceps muscle in this clinical population. METHODS: Twenty people receiving CAPD (mean age = 56.5 ± 16.7 years) at a single dialysis unit were assessed on two occasions, 7 days apart. Measures of the mid-thigh, such as vastus lateralis (VL) anatomical cross-sectional area (ACSA), VL muscle thickness and subcutaneous fat thickness were compared for US reliability and validity compared to magnetic resonance imaging (MRI) measures. RESULTS: US had high validity against gold standard MRI measures, with intraclass correlation coefficients (ICC) equating to VL ACSA of 0.95, VL thickness of 0.99 and fat thickness of 0.98. The US measurements also exhibited high intra-rater reliability (ICCs: VL thickness = 0.98, total muscle thickness = 0.97 and fat thickness = 0.99) in measuring body composition at the mid-VL site in the study population. CONCLUSIONS: Valid assessment of regional body composition can be achieved via high-resolution US in patients receiving CAPD. The validity and reliability of the US in repeated measures (in comparison to the gold standard MRI) warrant further investigation in the wider chronic kidney disease population.

Validity and reliability of an electromyography-based similarity index to quantify lower extremity selective voluntary motor control in children with cerebral palsy.

Objective: To quantify selective voluntary motor control (SVMC) objectively and more precisely, we combined the "Selective Control Assessment of the Lower Extremity" (SCALE) with surface electromyography. The resulting Similarity Index (SI) measures the similarity of muscle activation patterns. This study evaluated the preliminary validity and reliability of this novel SISCALE measure in children with cerebral palsy (CP). Methods: We investigated concurrent validity by correlating the SISCALE of 24 children with CP (median age 10.6 years) with comparator assessments. For discriminative validity, the patients' SISCALE scores were compared to 31 neurologically intact age-matched peers. Test-retest reliability was quantified using intraclass correlation coefficients (ICC) and minimal detectable change (MDC) values. Results: The SISCALE correlated strongly with the SCALE (ρ = 0.90, p < .001) and the Gross Motor Function Classification System (ρ = -0.74, p < .001). SISCALE scores were significantly lower in children with CP compared to healthy peers. Test-retest reliability appeared good (for the more and less affected leg, ICC ≥ 0.84, and MDC ≤ 0.17). Conclusions: Validity and reliability of the SISCALE leg and total scores lay within clinically acceptable ranges. Further clinimetric analyses should include responsiveness. Significance: A neurophysiology-based assessment could contribute to a more refined assessment of SVMC impairments.

Exercise-induced changes in gait kinematics in multiple sclerosis with minimal neurological disability.

BACKGROUND: Exercise-induced gait deterioration is a frequently encountered symptom that limits ambulation throughout the clinical course, becoming more prominent with increasing neurological disability in people with MS (pwMS). OBJECTIVE: We attempted to objectively document exercise-induced gait changes in pwMS with minimal neurological disability and stable disease. METHODS: Gait kinematics and spatio-temporal parameters were recorded using 3D motion analysis before and after a 20-minute treadmill walk (Group A, n=15)/run (Group B, n=15) at a self-selected speed in pwMS and compared with healthy controls (n=15). RESULTS: Gait analysis revealed a significant decrease in peak ankle dorsiflexion in swing of the most affected leg, post-exercise task, in both Group A (EDSS 2.5-3.5) and Group B (EDSS 1-2.5) and not in healthy controls. Fourteen out of 30 MS participants showed an exercise-induced gait deterioration, based on minimal detectable change. Pre-exercise gait parameters in Group A showed a significantly higher peak dorsiflexion in swing with shorter step length and higher cadence, whereas Group B was comparable to healthy controls. CONCLUSION: The detection of exercise-induced gait deterioration (foot drop) in pwMS with minimal neurological disability and stable disease indicates the potential of gait kinematics, before and after an exercise task, to monitor subtle neurological deficits from an early stage of MS.