The effect of RaceRunning on cardiometabolic disease risk factors and functional mobility in young people with moderate-to-severe cerebral palsy:A feasibility study

Introduction: There is consistent evidence that people with cerebral (CP) do not engage in the recommended physical activity guidelines for the general population from a young age. Participation in moderate-to-vigorous physical activity is particularly reduced in people with CP who have moderate-to-severe disability. RaceRunning is a growing disability sport that provides an opportunity for people with moderate-to-severe disability to participate in physical activity in the community. It allows those who are unable to walk independently, to propel themselves using a RaceRunning bike, which has a breastplate for support but no pedals. The aim of this study is to examine the feasibility and acceptability of RaceRunning for young people with moderate-to-severe CP and the feasibility of conducting a definitive study of the effect of RaceRunning on cardiometabolic disease risk factors and functional mobility. Methods and analysis: Twenty-five young people (age 5-21 yr) with CP or acquired brain injury affecting co-ordination will be included in this single arm intervention study. Participants will take part in one RaceRunning session each week for 24 weeks. Outcomes assessed at baseline, 12 and 24 weeks include body mass index, waist circumference, blood pressure, muscle strength, cardiorespiratory fitness, physical activity and sedentary behaviour, functional mobility, activity competence and psychosocial impact. Adverse events will be systematically recorded throughout the 24 weeks. Focus groups will be conducted with participants and/or parents to explore their views and experiences of taking part in RaceRunning. Ethics and dissemination: Approval has been granted by Queen Margaret University Research Ethics Committee (REC) and the South East of Scotland REC. Results will be disseminated through peer-reviewed journals and distributed to people with CP and their families through RaceRunning and Athletic Clubs, NHS trusts, and organisations for people with disabilities

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. CONCLUSIONS: 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

Long-term pulse wave velocity outcomes with aerobic and resistance training in kidney transplant recipients - A pilot randomised controlled trial

Background This pilot study examined long-term pulse wave velocity (PWV) and peak oxygen uptake (VO2peak) outcomes following a 12-week moderate-intensity aerobic or resistance training programme in kidney transplant recipients. Method Single-blind, bi-centre randomised controlled parallel trial. 42 out of 60 participants completed a 9-month follow-up assessment (Aerobic training = 12, Resistance training = 10 and usual care = 20). Participants completed 12 weeks of twice-weekly supervised aerobic or resistance training. Following the 12-week exercise intervention, participants were transitioned to self-managed community exercise activity using motivational interviewing techniques. Usual care participants received usual encouragement for physical activity during routine clinical appointments in the transplant clinic. PWV, VO2peak, blood pressure and body weight were assessed at 12 weeks and 12 months, and compared to baseline. Results ANCOVA analysis, covarying for baseline values, age, and length of time on dialysis pretransplantation, revealed a significant mean between-group difference in PWV of -1.30 m/ sec (95%CI -2.44 to -0.17, p = 0.03) between resistance training and usual care groups. When comparing the aerobic training and usual care groups at 9-month follow-up, there was a mean difference of -1.05 m/sec (95%CI -2.11 to 0.017, p = 0.05). A significant mean between-group difference in relative VO2peak values of 2.2 ml/kg/min (95% CI 0.37 to 4.03, p = 0.02) when comparing aerobic training with usual care was revealed. There was no significant between group differences in body weight or blood pressure. There were no significant adverse effects associated with the interventions. Conclusions Significant between-group differences in 9-month follow-up PWV existed when comparing resistance exercise intervention with usual care. A long-term between-group difference in VO2peak was only evident when comparing aerobic intervention with usual care. This pilot study, with a small sample size, did not aim to elucidate mechanistic mediators related to the exercise interventions. It is however suggested that a motivational interviewing approach, combined with appropriate transition to community training programmes, could maintain the improvements gained from the 12-week exercise interventions and further research in this area is therefore warranted. 2017 O'Connor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.sch_phy12pub4670pub

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

Achieving consensus on psychosocial and physical rehabilitation management for people living with kidney disease

From Crossref journal articles via Jisc Publications RouterHistory: epub 2023-05-19, issued 2023-05-19Article version: AMPublication status: PublishedPelagia Koufaki - ORCID: 0000-0002-1406-3729 https://orcid.org/0000-0002-1406-3729Background People living with chronic kidney disease (CKD) need to be able to live well with their condition. The provision of psychosocial interventions (psychological, psychiatric, and social care) and physical rehabilitation management is variable across England, as well as the rest of the United Kingdom. There is a need for clear recommendations for standards of psychosocial and physical rehabilitation care for people living with CKD, and guidance for the commissioning and measurement of these services. The NHS England Renal Services Transformation Programme (RSTP) supported a programme of work and modified Delphi process to address the management of psychosocial and physical rehabilitation care as part of a larger body of work to formulate a comprehensive commissioning toolkit for renal care services across England. We sought to achieve expert consensus regarding the psychosocial and physical rehabilitation management of people living with CKD in England and the rest of the UK. Method A Delphi consensus method was used to gather and refine expert opinions of senior members of the kidney multi-disciplinary team (MDT) and other key stakeholders in the UK. An agreement was sought on 16 statements reflecting aspects of psychosocial and physical rehabilitation management for people living with CKD. Results Twenty-six expert practitioners and other key stakeholders, including lived experience representatives, participated in the process. The consensus (>80% affirmative votes) amongst the respondents for all 16 statements was high. Nine recommendation statements were discussed and refined further to be included in the final iteration of the ‘Systems’ section of the NHS England RSTP commissioning toolkit. These priority recommendations reflect pragmatic solutions that can be implemented in renal care and include recommendations for a holistic well-being assessment for all people living with CKD who are approaching dialysis, or who are at listing for kidney transplantation, which includes the use of validated measurement tools to assess the need for further intervention in psychosocial and physical rehabilitation management. It is recommended that the scores from these measurement tools be included in the NHS England Renal Data Dashboard. There was also a recommendation for referral as appropriate to NHS Talking therapies, psychology, counselling or psychotherapy, social work or liaison psychiatry for those with identified psychosocial needs. The use of digital resources was recommended to be used in addition to face-to-face care to provide physical rehabilitation, and all healthcare professionals should be educated to recognise psychosocial and physical rehabilitation needs and refer/sign-post people with CKD to appropriate services. Conclusion There was high consensus amongst senior members of the kidney MDT and other key stakeholders, including those with lived experience, in the UK on all aspects of the psychosocial and physical rehabilitation management of people living with CKD. The results of this process will be used by NHS England to inform the ‘Systems’ section of the commissioning toolkit and data dashboard and to inform the National Standards of Care for people living with CKD.inpressinpres

Epigenetic and metabolic reprogramming of fibroblasts in Crohn's disease strictures reveals histone deacetylases as therapeutic targets.

BACKGROUND & AIMS: No effective therapeutic intervention exists for intestinal fibrosis in Crohn's disease [CD]. We characterised fibroblast subtypes, epigenetic and metabolic changes, and signalling pathways in CD fibrosis to inform future therapeutic strategies. METHODS: We undertook immunohistochemistry, metabolic, signalling pathway and Epigenetic [Transposase-Accessible Chromatin using sequencing] analyses associated with collagen production in CCD-18Co intestinal fibroblasts and primary fibroblasts isolated from stricturing [SCD] and non-stricturing [NSCD] CD small intestine. SCD/ NSCD fibroblasts were cultured with TGFβ and valproic acid [VPA]. RESULTS: Stricturing CD was characterised by distinct histone deacetylase [HDAC] expression profiles, particularly HDAC1, HDAC2, and HDAC7. As a proxy for HDAC activity, reduced numbers of H3K27ac+ cells were found in SCD compared to NSCD sections. Primary fibroblasts had increased extracellular lactate [increased glycolytic activity] and intracellular hydroxyproline [increased collagen production] in SCD compared to NSCD cultures. The metabolic effect of TGFβ-stimulation was reversed by the HDAC inhibitor VPA. SCD fibroblasts appear "metabolically primed" and responded more strongly to both TGFβ and VPA. Treatment with VPA revealed TGFβ-dependent and independent Collagen-I production in CCD-18Co cells and primary fibroblasts. VPA altered the epigenetic landscape with reduced chromatin accessibility at the COL1A1 and COL1A2 promoters. CONCLUSIONS: Increased HDAC expression profiles, H3K27ac hypoacetylation, a significant glycolytic phenotype, and metabolic priming, characterise SCD-derived as compared to NSCD fibroblasts. Our results reveal a novel epigenetic component to Collagen-I regulation and TGFβ-mediated CD fibrosis. HDAC inhibitor therapy may 'reset' the epigenetic changes associated with fibrosis

The effect of RaceRunning on cardiometabolic disease risk factors and functional mobility in young people with moderate-to-severe cerebral palsy: protocol for a feasibility study

Copyright © Author(s) (or their employer(s)) 2020. Introduction: There is consistent evidence that people with cerebral (CP) do not engage in the recommended physical activity guidelines for the general population from a young age. Participation in moderate-to-vigorous physical activity is particularly reduced in people with CP who have moderate-to-severe disability. RaceRunning is a growing disability sport that provides an opportunity for people with moderate-to-severe disability to participate in physical activity in the community. It allows those who are unable to walk independently, to propel themselves using a RaceRunning bike, which has a breastplate for support but no pedals. The aim of this study is to examine the feasibility and acceptability of RaceRunning for young people with moderate-to-severe CP and the feasibility of conducting a definitive study of the effect of RaceRunning on cardiometabolic disease risk factors and functional mobility. Methods and analysis: Twenty-five young people (age 5-21 yr) with CP or acquired brain injury affecting co-ordination will be included in this single arm intervention study. Participants will take part in one RaceRunning session each week for 24 weeks. Outcomes assessed at baseline, 12 and 24 weeks include body mass index, waist circumference, blood pressure, muscle strength, cardiorespiratory fitness, physical activity and sedentary behaviour, functional mobility, activity competence and psychosocial impact. Adverse events will be systematically recorded throughout the 24 weeks. Focus groups will be conducted with participants and/or parents to explore their views and experiences of taking part in RaceRunning. Ethics and dissemination: Approval has been granted by Queen Margaret University Research Ethics Committee (REC) and the South East of Scotland REC. Results will be disseminated through peer-reviewed journals and distributed to people with CP and their families through RaceRunning and Athletic Clubs, NHS trusts, and organisations for people with disabilities. Trial registration number: ClinicalTrials.gov Identifier: NCT04034342. Protocol version 1.0; pre-results.Action Medical Research and Chartered Society of Physiotherapy Charitable Trust.Joint award from Action Medical Research and Chartered Society of Physiotherapy Charitable Trust

Evidence of Increased Muscle Atrophy and Impaired Quality of Life Parameters in Patients with Uremic Restless Legs Syndrome

BACKGROUND: Restless Legs Syndrome is a very common disorder in hemodialysis patients. Restless Legs Syndrome negatively affects quality of life; however it is not clear whether this is due to mental or physical parameters and whether an association exists between the syndrome and parameters affecting survival. METHOD#ENTITYSTARTX003BF;LOGY/PRINCIPAL FINDINGS: Using the Restless Legs Syndrome criteria and the presence of Periodic Limb Movements in Sleep (PLMS/h >15), 70 clinically stable hemodialysis patients were assessed and divided into the RLS (n = 30) and non-RLS (n = 40) groups. Physical performance was evaluated by a battery of tests: body composition by dual energy X ray absorptiometry, muscle size and composition by computer tomography, while depression symptoms, perception of sleep quality and quality of life were assessed through validated questionnaires. In this cross sectional analysis, the RLS group showed evidence of thigh muscle atrophy compared to the non-RLS group. Sleep quality and depression score were found to be significantly impaired in the RLS group. The mental component of the quality of life questionnaire appeared significantly diminished in the RLS group, reducing thus the overall quality of life score. In contrast, there were no significant differences between groups in any of the physical performance tests, body and muscle composition. CONCLUSIONS: The low level of quality of life reported by the HD patients with Restless Legs Syndrome seems to be due mainly to mental health and sleep related aspects. Increased evidence of muscle atrophy is also observed in the RLS group and possibly can be attributed to the lack of restorative sleep

The effect of a novel, digital physical activity and emotional well-being intervention on health-related quality of life in people with chronic kidney disease: trial design and baseline data from a multicentre prospective, wait-list randomised controlled trial (kidney BEAM)

BACKGROUND: Physical activity and emotional self-management has the potential to enhance health-related quality of life (HRQoL), but few people with chronic kidney disease (CKD) have access to resources and support. The Kidney BEAM trial aims to evaluate whether an evidence-based physical activity and emotional wellbeing self-management programme (Kidney BEAM) leads to improvements in HRQoL in people with CKD. METHODS: This was a prospective, multicentre, randomised waitlist-controlled trial, with health economic analysis and nested qualitative studies. In total, three hundred and four adults with established CKD were recruited from 11 UK kidney units. Participants were randomly assigned to the intervention (Kidney BEAM) or a wait list control group (1:1). The primary outcome was the between-group difference in Kidney Disease Quality of Life (KDQoL) mental component summary score (MCS) at 12 weeks. Secondary outcomes included the KDQoL physical component summary score, kidney-specific scores, fatigue, life participation, depression and anxiety, physical function, clinical chemistry, healthcare utilisation and harms. All outcomes were measured at baseline and 12 weeks, with long-term HRQoL and adherence also collected at six months follow-up. A nested qualitative study explored experience and impact of using Kidney BEAM. RESULTS: 340 participants were randomised to Kidney BEAM (n = 173) and waiting list (n = 167) groups. There were 96 (55%) and 89 (53%) males in the intervention and waiting list groups respectively, and the mean (SD) age was 53 (14) years in both groups. Ethnicity, body mass, CKD stage, and history of diabetes and hypertension were comparable across groups. The mean (SD) of the MCS was similar in both groups, 44.7 (10.8) and 45.9 (10.6) in the intervention and waiting list groups respectively. CONCLUSION: Results from this trial will establish whether the Kidney BEAM self management programme is a cost-effective method of enhancing mental and physical wellbeing of people with CKD. TRIAL REGISTRATION: NCT04872933. Registered 5th May 2021