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.

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.

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.

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.

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.

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.

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.

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.

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.

Randomized Trial-PrEscription of intraDialytic exercise to improve quAlity of Life in Patients Receiving Hemodialysis.

INTRODUCTION: Whether clinically implementable exercise interventions in people receiving hemodialysis (HD) therapy improve health-related quality of life (HRQoL) remains unknown. The PrEscription of intraDialytic exercise to improve quAlity of Life (PEDAL) study evaluated the clinical benefit and cost-effectiveness of a 6-month intradialytic exercise program. METHODS: In a multicenter, single-blinded, randomized, controlled trial, people receiving HD were randomly assigned to (i) intradialytic exercise training (exercise intervention group [EX]) and (ii) usual care (control group [CON]). Primary outcome was change in Kidney Disease Quality of Life Short-Form Physical Component Summary (KDQOL-SF 1.3 PCS) from baseline to 6 months. Cost-effectiveness was determined using health economic analysis; physiological impairment was evaluated by peak oxygen uptake; and harms were recorded. RESULTS: We randomized 379 participants; 335 and 243 patients (EX n = 127; CON n = 116) completed baseline and 6-month assessments, respectively. Mean difference in change PCS from baseline to 6 months between EX and CON was 2.4 (95% confidence interval [CI]: -0.1 to 4.8) arbitrary units (P = 0.055); no improvements were observed in peak oxygen uptake or secondary outcome measures. Participants in the intervention group had poor compliance (47%) and poor adherence (18%) to the exercise prescription. Cost of delivering intervention ranged from US$598 to US$1092 per participant per year. The number of participants with harms was similar between EX (n = 69) and CON (n = 56). A primary limitation was the lack of an attention CON. Many patients also withdrew from the study or were too unwell to complete all physiological outcome assessments. CONCLUSIONS: A 6-month intradialytic aerobic exercise program was not clinically beneficial in improving HRQoL as delivered to this cohort of deconditioned patients on HD.

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.

Exercise programme to improve quality of life for patients with end-stage kidney disease receiving haemodialysis: the PEDAL RCT.

BACKGROUND: Whether or not clinically implementable exercise interventions in haemodialysis patients improve quality of life remains unknown. OBJECTIVES: The PEDAL (PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease) trial evaluated the clinical effectiveness and cost-effectiveness of a 6-month intradialytic exercise programme on quality of life compared with usual care for haemodialysis patients. DESIGN: We conducted a prospective, multicentre randomised controlled trial of haemodialysis patients from five haemodialysis centres in the UK and randomly assigned them (1 : 1) using a web-based system to (1) intradialytic exercise training plus usual-care maintenance haemodialysis or (2) usual-care maintenance haemodialysis. SETTING: The setting was five dialysis units across the UK from 2015 to 2019. PARTICIPANTS: The participants were adult patients with end-stage kidney disease who had been receiving haemodialysis therapy for > 1 year. INTERVENTIONS: Participants were randomised to receive usual-care maintenance haemodialysis or usual-care maintenance haemodialysis plus intradialytic exercise training. MAIN OUTCOME MEASURES: The primary outcome of the study was change in Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score (from baseline to 6 months). Cost-effectiveness was determined using health economic analysis and the EuroQol-5 Dimensions, five-level version. Additional secondary outcomes included quality of life (Kidney Disease Quality of Life Short Form, version 1.3, generic multi-item and burden of kidney disease scales), functional capacity (sit-to-stand 60 and 10-metre Timed Up and Go tests), physiological measures (peak oxygen uptake and arterial stiffness), habitual physical activity levels (measured by the International Physical Activity Questionnaire and Duke Activity Status Index), fear of falling (measured by the Tinetti Falls Efficacy Scale), anthropometric measures (body mass index and waist circumference), clinical measures (including medication use, resting blood pressure, routine biochemistry, hospitalisations) and harms associated with intervention. A nested qualitative study was conducted. RESULTS: We randomised 379 participants; 335 patients completed baseline assessments and 243 patients (intervention, n = 127; control, n = 116) completed 6-month assessments. The mean difference in change in physical component summary score from baseline to 6 months between the intervention group and control group was 2.4 arbitrary units (95% confidence interval -0.1 to 4.8 arbitrary units; p = 0.055). Participants in the intervention group had poor compliance (49%) and very poor adherence (18%) to the exercise prescription. The cost of delivering the intervention ranged from £463 to £848 per participant per year. The number of participants with harms was similar in the intervention (n = 69) and control (n = 56) groups. LIMITATIONS: Participants could not be blinded to the intervention; however, outcome assessors were blinded to group allocation. CONCLUSIONS: On trial completion the primary outcome (Kidney Disease Quality of Life Short Form, version 1.3, physical component summary score) was not statistically improved compared with usual care. The findings suggest that implementation of an intradialytic cycling programme is not an effective intervention to enhance health-related quality of life, as delivered to this cohort of deconditioned patients receiving haemodialysis. FUTURE WORK: The benefits of longer interventions, including progressive resistance training, should be confirmed even if extradialytic delivery is required. Future studies also need to evaluate whether or not there are subgroups of patients who may benefit from this type of intervention, and whether or not there is scope to optimise the exercise intervention to improve compliance and clinical effectiveness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN83508514. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 40. See the NIHR Journals Library website for further project information.

Although the benefits of exercise in the general population are well recognised, we do not know if offering cycling exercise during haemodialysis is an effective way to improve quality of life, and if this would be a cost-effective way to provide exercise training for this patient population. To determine whether or not this type of exercise training is effective, and provides value for money, this study compared cycling during haemodialysis treatment, three times per week for 6 months, with usual care that does not include routine delivery of any exercise training. Five regions of the UK were included in the study. We compared the results from the two groups at the start of the study and at 6 months, after correcting for age and diabetes status. We also assessed the economic impact of delivering the cycling during haemodialysis programme and interviewed people from different regions of the UK in both groups. The baseline assessments revealed a deconditioned population in the study. There was no difference in quality of life or any physical function measures between the group that performed cycling during haemodialysis and the usual-care group. Compliance with the exercise intervention was very poor. Interviews with patients showed that patient engagement with the exercise training was linked to the presence of an exercise culture, and leadership to provide this, in the renal unit. An economic evaluation showed that delivering cycling during haemodialysis would not be value for money when delivered to a deconditioned haemodialysis population. Ways to engage patients with exercise training during their haemodialysis treatment should be explored further.

The PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease trial: study design and baseline data for a multicentre randomized controlled trial.

BACKGROUND: Exercise interventions designed to improve physical function and reduce sedentary behaviour in haemodialysis (HD) patients might improve exercise capacity, reduce fatigue and lead to improved quality of life (QOL). The PrEscription of intraDialytic exercise to improve quAlity of Life study aimed to evaluate the effectiveness of a 6-month intradialytic exercise programme on QOL and physical function, compared with usual care for patients on HD in the UK. METHODS: We conducted a prospective, pragmatic multicentre randomized controlled trial in 335 HD patients and randomly (1:1) assigned them to either (i) intradialytic exercise training plus usual care maintenance HD or (ii) usual care maintenance HD. The primary outcome of the study was the change in Kidney Disease Quality of Life Short Form (KDQOL-SF 1.3) Physical Component Score between baseline and 6 months. Additional secondary outcomes included changes in peak aerobic capacity, physical fitness, habitual physical activity levels and falls (International Physical Activity Questionnaire, Duke's Activity Status Index and Tinetti Falls Efficacy Scale), QOL and symptom burden assessments (EQ5D), arterial stiffness (pulse wave velocity), anthropometric measures, resting blood pressure, clinical chemistry, safety and harms associated with the intervention, hospitalizations and cost-effectiveness. A nested qualitative study investigated the experience and acceptability of the intervention for both participants and members of the renal health care team. RESULTS: At baseline assessment, 62.4% of the randomized cohort were male, the median age was 59.3 years and 50.4% were white. Prior cerebrovascular events and myocardial infarction were present in 8 and 12% of the cohort, respectively, 77.9% of patients had hypertension and 39.4% had diabetes. Baseline clinical characteristics and laboratory data for the randomized cohort were generally concordant with data from the UK Renal Registry. CONCLUSION: The results from this study will address a significant knowledge gap in the prescription of exercise interventions for patients receiving maintenance HD therapy and inform the development of intradialytic exercise programmes both nationally and internationally. TRIAL REGISTRATION: ISRCTN N83508514; registered on 17 December 2014.

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.

Association of postural balance and falls in adult patients receiving haemodialysis: A prospective cohort study.

BACKGROUND: Static postural balance performance is often impaired in people receiving haemodialysis (HD) for the treatment of stage-5 chronic kidney disease (CKD-5). However, the question as to whether lower postural balance is associated with adverse clinical outcomes such as falls has not been addressed yet. RESEARCH QUESTION: We conducted a prospective cohort study to explore the association between static postural balance and falls in people receiving HD. We hypothesised that higher postural sway would be associated with increased odds of falling. METHODS: Seventy-five prevalent CKD-5 patients receiving HD (age: 61.8 ± 13.4 years) from three Renal Units were enrolled in this prospective cohort study. At baseline, postural balance was assessed with a force platform in eyes open (EO) and eyes closed (EC) conditions. Centre of pressure (CoP) measures of range, velocity and area were taken for the analysis. Falls experienced by study participants were prospectively recorded during 12 months of follow-up. Secondary outcomes included timed-up and go, five-repetition sit-to-stand test and the Tinetti falls efficacy scale (FES). RESULTS: In multivariable logistic regression analysis, higher CoP range in medial-lateral direction during EC was associated with increased odds of falling (OR: 1.04, 95 %CI: 1.00-1.07, p = 0.036). In ROC curve analysis, CoP velocity in EO exhibited the greatest prognostic accuracy (AUC: 0.69, 95 %CI: 0.55-0.82), however this was not statistically different from CoP measures of area and range. None of the postural balance measures exceeded the prognostic accuracy of the FES (AUC: 0.70, 95 %CI: 0.58-0.83, p = 0.005). SIGNIFICANCE: This prospective cohort study showed that higher postural sway in medial-lateral direction was associated with increased odds of falling in people receiving HD. CoP measures of range, velocity and area displayed similar prognostic value in discriminating fallers from non-fallers. The overall utility of static posturography to detect future fall-risk may be limited in a clinical setting.

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).

Test-retest reliability and minimal detectable change of ankle kinematics and spatiotemporal parameters in MS population.

BACKGROUND: Many people with multiple sclerosis (pwMS) experience walking impairments often including foot drop, evident as either reduced dorsiflexion at initial contact and/or at the swing phase of the gait cycle. To measure even subtle differences in ankle kinematics, 3D gait analysis is considered a 'gold' standard. However, the psychometric properties of ankle kinematics in the MS population have not yet been examined. OBJECTIVE: The aim of the study was to examine test-retest relative and absolute reliability of sagittal ankle kinematics and spatiotemporal parameters in two groups of pwMS with different levels of walking impairment. METHODS: Two groups of pwMS underwent 3D gait analysis on two occasions 7-14 days apart. Group A consisted of 21 (14 female) people with Expanded Disability Status Scale (EDSS) 1-3.5 and group B consisted of 28 participants (14 female) with EDSS 4-6. The Intraclass Correlation Coefficient (ICC2,2), standard error of measurement (SEM) and minimal detectable change (MDC95%) were calculated for peak dorsiflexion (DF) in swing, ankle angle at initial contact (IC), gait profile score (GPS), walking speed, cadence and step length. RESULTS: Both groups presented 'excellent' ICC values (>0.75) for DF in swing, IC and step length of most and least affected limbs, walking speed and cadence, with GPS for both limbs exhibiting 'fair' to 'good' ICCs (0.489-0.698). The MDC95% values for all ankle kinematic parameters in group A were lower (1.9°-4.2°) than those in group B (2.2°-7.7°). CONCLUSION: The present results suggest that ankle kinematic and spatiotemporal parameters derived from 3D gait analysis are reliable outcome measures to be used in the MS population. Further, this study provides indices of reliability that can be applied to both clinical decision making and in the design of studies aimed at treating foot drop in people with MS.

Baroreflex function, haemodynamic responses to an orthostatic challenge, and falls in haemodialysis patients.

BACKGROUND: Stage 5 chronic kidney disease patients on haemodialysis (HD) often present with dizziness and pre-syncopal events as a result of the combined effect of HD therapy and cardiovascular disease. The dysregulation of blood pressure (BP) during orthostasis may be implicated in the aetiology of falls in these patients. Therefore, we explored the relationship between baroreflex function, the haemodynamic responses to a passive orthostatic challenge, and falls in HD patients. METHODS: Seventy-six HD patients were enrolled in this cross-sectional study. Participants were classified as "fallers" and "non-fallers" and completed a passive head up tilting to 60o (HUT-60°) test on an automated tilt table. ECG signals, continuous and oscillometric BP measurements and impedance cardiography were recorded. The following variables were derived from these measurements: heart rate (HR) stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), number of baroreceptor events, and baroreceptor effectiveness index (BEI). RESULTS: The forty-four participants who were classified as fallers (57.9%) had a lower number of baroreceptor events (6.5±8.5 vs 14±16.7, p = .027) and BEI (20.8±24.2% vs 33.4±23.3%, p = .025). In addition, fallers experienced a significantly larger drop in systolic (-6.4±10.9 vs -0.4±7.7 mmHg, p = .011) and diastolic (-2.7±7.3 vs 1.8±6 mmHg, p = .027) oscillometric BP from supine to HUT-60° compared with non-fallers. None of the variables taken for the analysis were significantly associated with falls in multivariate logistic regression analysis. CONCLUSIONS: This cross-sectional comparison indicates that, at rest, HD patients with a positive history of falls present with a lower count of baroreceptor sequences and BEI. Short-term BP regulation warrants further investigation as BP drops during a passive orthostatic challenge may be implicated in the aetiology of falls in HD.

Ankle Kinematics and Temporal Gait Characteristics over the Duration of a 6-Minute Walk Test in People with Multiple Sclerosis Who Experience Foot Drop.

Foot drop is a common gait impairment in people with MS (pwMS) but in some foot drop may only occur after a period of prolonged walking and may be a sign of motor fatigability. The purpose of the study was to explore whether, for pwMS, an adapted six-minute walk test (6minWT) would result in an increase in foot drop as measured using electrogoniometry. Sagittal ankle kinematics were recorded for fifteen participants (10 females and 5 males, aged 37-64) with MS (EDSS 4-6) throughout the 6minWT. Ankle kinematics and temporal stride parameters were compared between the first and last 10 gait cycles of the 6minWT. Peak dorsiflexion in swing was significantly reduced at the end of the 6minWT compared to the start, with six of the fifteen participants having a decrease of two degrees or more. Statistically significant changes in temporal stride parameters suggested a decrease in walking speed. Our results suggest that with the protocol used in this study it is feasible to identify patients who experience increased foot drop as a result of a prolonged exercise task.