Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

Barriers and facilitators related to self-management of shoulder pain: a systematic review and qualitative synthesis.

OBJECTIVE: The objective of this review was to identify barriers and facilitators related to self-management from the perspectives of people with shoulder pain and clinicians involved in their care. DATA SOURCES: CINAHL, MEDLINE, PsycINFO, SPORTDiscus, Embase, ProQuest Health, Web of Science, and Scopus were searched from inception to March 2022. REVIEW METHODS: A meta-aggregative approach to the synthesis of qualitative evidence was used. Two independent reviewers identified eligible articles, extracted the data, and conducted a critical appraisal. Two reviewers independently identified and developed categories, with validation by two further researchers. Categories were discussed among the wider research team and a comprehensive set of synthesized findings was derived. RESULTS: Twenty studies were included. From the perspective of patients, three synthesized findings were identified that influenced self-management: (1) support for self-management, including subthemes related to patient-centred support, knowledge, time, access to equipment, and patient digital literacy; (2) personal factors, including patient beliefs, patient expectations, patient motivation, pain, and therapeutic response; and (3) external factors, including influence of the clinician and therapeutic approach. From the perspective of clinicians, two synthesized findings were identified that influenced self-management: (1) support for self-management, including education, patient-centred support, patient empowerment, time, and clinician digital literacy; and (2) preferred management approach, including clinician beliefs, expectations, motivation, therapeutic approach, and therapeutic response. CONCLUSION: The key barriers and facilitators were patient-centred support, patient beliefs, clinician beliefs, pain, and therapeutic response. Most of the included studies focused on exercise-based rehabilitation, and therefore might not fully represent barriers and facilitators to broader self-management.

Are Corticosteroid Injections Associated With Secondary Adrenal Insufficiency in Adults With Musculoskeletal Pain? A Systematic Review and Meta-analysis of Prospective Studies.

BACKGROUND: Corticosteroid injection is a common treatment for individuals experiencing musculoskeletal pain, and it is part of the management of numerous orthopaedic conditions. However, there is concern about offering corticosteroid injections for musculoskeletal pain because of the possibility of secondary adrenal insufficiency. QUESTIONS/PURPOSES: In this systematic review and meta-analysis of prospective studies, we asked: (1) Are corticosteroid injections associated with secondary adrenal insufficiency as measured by 7-day morning serum cortisol? (2) Does this association differ depending on whether the shot was administered in the spine or the appendicular skeleton? METHODS: We searched the Allied and Complementary Medicine (AMED), Embase, EmCare, MEDLINE, CINAHL, and Web of Science from inception to January 22, 2021. We retrieved 4303 unique records, of which 17 were eventually included. Study appraisal was via the Downs and Black tool, with an average quality rating of fair. A Grading of Recommendations, Assessment, Development, and Evaluations assessment was conducted with the overall certainty of evidence being low to moderate. Reflecting heterogeneity in the study estimates, a pooled random-effects estimate of cortisol levels 7 days after corticosteroid injection was calculated. Fifteen studies or subgroups (254 participants) provided appropriate estimates for statistical pooling. A total of 106 participants received a spine injection, and 148 participants received an appendicular skeleton injection, including the glenohumeral joint, subacromial bursa, trochanteric bursa, and knee. RESULTS: Seven days after corticosteroid injection, the mean morning serum cortisol was 212 nmol/L (95% confidence interval 133 to 290), suggesting that secondary adrenal insufficiency was a possible outcome. There is a difference in the secondary adrenal insufficiency risk depending on whether the injection was in the spine or the appendicular skeleton. For spinal injection, the mean cortisol was 98 nmol/L (95% CI 48 to 149), suggesting secondary adrenal insufficiency was likely. For appendicular skeleton injection the mean cortisol was 311 nmol/L (95% CI 213 to 409) suggesting hypothalamic-pituitary-adrenal axis integrity was likely. CONCLUSION: Clinicians offering spinal injections should discuss the possibility of short-term secondary adrenal insufficiency with patients, and together, they can decide whether the treatment remains appropriate and whether mitigation strategies are needed. Clinicians offering appendicular skeleton injections should not limit care because of concerns about secondary adrenal insufficiency based on the best available evidence, and clinical guidelines could be reviewed accordingly. Further research is needed to understand whether age and/or sex determine risk of secondary adrenal insufficiency and what clinical impact secondary adrenal insufficiency has on patients undergoing spinal injection. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Mechanical thrombectomy: can it be safely delivered out of hours in the UK?

BACKGROUND: Mechanical thrombectomy was approved by NICE as a treatment for stroke in 2016. However, most of the evidence is from studies conducted during working hours. Only few centres in the UK perform thrombectomies out-of-hours. The Royal Stoke University Hospital (RSUH) has offered thrombectomies over 24 h (24/7) since 2010. The aim of this service review is to compare the outcomes for patients treated in regular working hours to those treated outside normal working hours within this unit. METHODS: This retrospective service analysis includes all patients treated with mechanical thrombectomy at RSUH since the start of the service in January 2010 to June 2019. Data on key demographics, timings, procedural complications, and long-term outcomes including death and disability at 90 days were collected. In-hours was defined as the time between 8:00-17:00 h, Monday to Friday; out-of-hours was defined as any time outside this period. RESULTS: In total, 516 mechanical thrombectomies were performed in this time period; data were available on 501 of these. Successful recanalization (TICI 2b/3) was achieved in 86% of patients. By 90 days 96 (19%) had died and 234 (47%) were functionally independent (modified Rankin Scale score ≤ 2). 211 (42%) of the procedures were performed in-hours and 290 (58%) out-of-hours. Door-to-CT and door-to-groin times were significantly longer out-of-hours than in-hours, but thrombectomy duration was significantly shorter. There were no significant differences in complications and short- and long-term outcomes. CONCLUSION: Mechanical thrombectomy was delivered safely and effectively 24/7 in this UK hospital, with no difference in clinical outcomes.

Do We Need Rights in Bioethics Discourse?

Moral rights feature prominently and are relied on substantially in debates in bioethics. Conceptually, however, duties can perform the logical work of rights, but not vice versa, and reference to rights is therefore inessential. Normatively, rights, like duties, depend on more basic moral values or principles, and attempts to establish the logical priority of rights over duties or the reverse are misguided. In practical decision making, however, an analysis in terms of duties is more fruitful than one based on rights. A right may function as a proxy term for a consequentialist rule, or for a deontological constraint, but does not thereby enrich these concepts. Rights may also help in a purely expressive sense and may assist an initial focusing on a moral conflict. However, their role in bioethics discourse is more one of convenience than of necessity. Moreover, unless rights are firmly founded on fundamental moral values, their use encourages rhetoric rather than argument.

Effect on Hospital Length of Stay of Tourniquet Use During Internal Fixation of Ankle Fractures: Randomized Controlled Trial.

Approximately 50% of ankle fractures require internal fixation. A tourniquet is often used to create a bloodless operative field, but its effect on hospital length of stay (LOS) is unclear. This article reports a parallel-group observer-blinded randomized trial of the effect of tourniquet use on LOS. One hundred eighty-eight adult patients requiring internal fixation of ankle fracture were randomized to surgery with or without a tourniquet. LOS was analyzed on intention-to-treat principles using Poisson regression. As a secondary outcome, duration of operation was analyzed by analysis of covariance. Mean LOS was 1.79 ± 1.50 days in the tourniquet group and 1.65 ± 1.11 days in the no-tourniquet group. The covariate-adjusted rate ratio for LOS (reference group: no tourniquet) was 1.084 (95% confidence interval 0.871, 1.348; p = .470). Sensitivity analyses (unadjusted intention-to-treat analysis and as-treated analysis) gave similar nonsignificant results. The covariate-adjusted mean difference in duration of operation was 3.03 minutes (95% confidence interval -4.96, 11.02; p = .455), favoring the tourniquet group; sensitivity analyses again gave similar results. Adverse events did not differ significantly between groups. In conclusion, the use of a tourniquet during internal fixation does not significantly influence hospital LOS, of which preinjury medical condition of the patient appears to be the most important determinant.

Rationale and design of BISTRO: a randomized controlled trial to determine whether bioimpedance spectroscopy-guided fluid management maintains residual kidney function in incident haemodialysis patients.

BACKGROUND: Preserved residual kidney function (RKF) and normal fluid status are associated with better patient outcomes in incident haemodialysis patients. The objective of this trial is to determine whether using bioimpedance technology in prescribing the optimal post-dialysis weight can reduce the rate of decline of RKF and potentially improve patient outcomes. METHODS/DESIGN: 516 pateints commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine volume >500 ml per day or per the shorter inter-dialytic period will be consented and enrolled into a pragmatic, open-label, randomized controlled trial. The intervention is incorporation of bioimpedance spectroscopy (BI) determination of normally hydrated weight to set a post-dialysis target weight that limits volume depletion, compared to current standard practice. Clinicians and participants will be blinded to BI measures in the control group and a standardized record capturing management of fluid status will be used in all participants. Primary outcome is preservation of residual kidney function assessed as time to anuria (≤100 ml/day or ≤200 ml urine volume in the short inter-dialytic period). A sample size of 516 was based upon a cumulative incidence of 30% anuria in the control group and 20% in the treatment group and 11% competing risks (death, transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes include rate of decline in small solute clearance, significant adverse events, hospitalization, loss of vascular access, cardiovascular events and interventions, dialysis efficacy and safety, dialysis-related symptoms and quality of life. Economic evaluation will be carried out to determine the cost-effectiveness of the intervention. Analyses will be adjusted for patient characteristics and dialysis unit practice patterns relevant to fluid management. DISCUSSION: This trial will establish the added value of undertaking BI measures to support clinical management of fluid status and establish the relationship between fluid status and preservation of residual kidney function in incident haemodialysis patients. TRIAL REGISTRATION: ISCCTN Number: 11342007 , completed 26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University.

Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke: The Stroke Oxygen Study Randomized Clinical Trial.

Importance: Hypoxia is common in the first few days after acute stroke, is frequently intermittent, and is often undetected. Oxygen supplementation could prevent hypoxia and secondary neurological deterioration and thus has the potential to improve recovery. Objective: To assess whether routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation. Design, Setting, and Participants: In this single-blind randomized clinical trial, 8003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015). Interventions: Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93% or less and at 2 L/min if oxygen saturation was greater than 93%. Main Outcomes and Measures: The primary outcome was reported using the modified Rankin Scale score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The modified Rankin Scale score was analyzed by ordinal logistic regression, which yields a common odds ratio (OR) for a change from one disability level to the next better (lower) level; OR greater than 1.00 indicates improvement. Results: A total of 8003 patients (4398 (55%) men; mean [SD] age, 72 [13] years; median National Institutes of Health Stroke Scale score, 5; mean baseline oxygen saturation, 96.6%) were enrolled. The primary outcome was available for 7677 (96%) participants. The unadjusted OR for a better outcome (calculated via ordinal logistic regression) was 0.97 (95% CI, 0.89 to 1.05; P = .47) for oxygen vs control, and the OR was 1.03 (95% CI, 0.93 to 1.13; P = .61) for continuous vs nocturnal oxygen. No subgroup could be identified that benefited from oxygen. At least 1 serious adverse event occurred in 348 (13.0%) participants in the continuous oxygen group, 294 (11.0%) in the nocturnal group, and 322 (12.1%) in the control group. No significant harms were identified. Conclusions and Relevance: Among nonhypoxic patients with acute stroke, the prophylactic use of low-dose oxygen supplementation did not reduce death or disability at 3 months. These findings do not support low-dose oxygen in this setting. Trial Registration: ISRCTN Identifier: ISRCTN52416964.

Safety and effect of metoclopramide to prevent pneumonia in patients with stroke fed via nasogastric tubes trial.

BACKGROUND AND PURPOSE: Pneumonia is a major cause of mortality and morbidity in patients with stroke fed via nasogastric tubes and may be because of vomiting and gastro-oesophageal regurgitation. The aim of the study was to assess whether regular treatment with metoclopramide, a D2-receptor antagonist with antiemetic and gastric prokinetic actions, could reduce the rate of aspiration and pneumonia. METHODS: Patients with no signs of pneumonia within 7 days of stroke onset and 48 hours of insertion of a nasogastric tube were recruited into a double-blind randomized placebo-controlled trial. Participants received metoclopramide 10 mg or placebo 3× daily via the nasogastric tube for 21 days or until nasogastric feeds were discontinued. Clinical signs of pneumonia were recorded daily. Pneumonia was diagnosed if the patient had relevant clinical signs, high inflammatory markers, and new infiltrates on the chest radiograph. RESULTS: Sixty patients (mean age, 78 years; 38 women; mean National Institutes for Health Stroke Scale score, 19.25) were randomized in a 1:1 ratio. There were significantly more episodes of pneumonia in the placebo group than in the metoclopramide group (rate ratio, 5.24; P<0.001). There were also significant differences in favor of metoclopramide in the rate of aspiration, oxygen saturation, highest inflammatory markers, and National Institutes for Health Stroke Scale. There was no significant difference in mortality between the groups. CONCLUSIONS: This study suggests that metoclopramide may reduce the rate of pneumonia and may improve other clinical outcomes in patients with subacute stroke fed via nasogastric tube. These findings need to be confirmed in larger randomized and blinded trials. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrialsregister.eu. EudraCT no: 2006-002570-22, URL: http://www.controlled-trials.com/ISRCTN18034911/18034911.

The nature and ethics of natural experiments.

Natural experiments are an important methodology often used to answer research questions that would, otherwise, be impossible to address, or employed because of ethical concerns about the use of randomisation to interventions that carry known risks. The UK Medical Research Council (MRC) recently produced an extremely useful document discussing the nature and significance of natural experiments within medical and public health research. In this paper, however, we suggest that the MRC document's definition of the term 'natural experiment' is insufficiently precise. In response, we offer a taxonomy of different types of natural experiments and related methods, and explore the ethical implications of these different types. We argue that while the ethical issues that may arise within natural experiments in relation to risks of harm or informed consent may differ from those within the randomised controlled trial, they are not thereby less pressing. The implications of the argument are explored and recommendations made for those involved in research governance.

Bias, precision and statistical power of analysis of covariance in the analysis of randomized trials with baseline imbalance: a simulation study.

BACKGROUND: Analysis of variance (ANOVA), change-score analysis (CSA) and analysis of covariance (ANCOVA) respond differently to baseline imbalance in randomized controlled trials. However, no empirical studies appear to have quantified the differential bias and precision of estimates derived from these methods of analysis, and their relative statistical power, in relation to combinations of levels of key trial characteristics. This simulation study therefore examined the relative bias, precision and statistical power of these three analyses using simulated trial data. METHODS: 126 hypothetical trial scenarios were evaluated (126,000 datasets), each with continuous data simulated by using a combination of levels of: treatment effect; pretest-posttest correlation; direction and magnitude of baseline imbalance. The bias, precision and power of each method of analysis were calculated for each scenario. RESULTS: Compared to the unbiased estimates produced by ANCOVA, both ANOVA and CSA are subject to bias, in relation to pretest-posttest correlation and the direction of baseline imbalance. Additionally, ANOVA and CSA are less precise than ANCOVA, especially when pretest-posttest correlation ≥ 0.3. When groups are balanced at baseline, ANCOVA is at least as powerful as the other analyses. Apparently greater power of ANOVA and CSA at certain imbalances is achieved in respect of a biased treatment effect. CONCLUSIONS: Across a range of correlations between pre- and post-treatment scores and at varying levels and direction of baseline imbalance, ANCOVA remains the optimum statistical method for the analysis of continuous outcomes in RCTs, in terms of bias, precision and statistical power.

Identifying vulnerability in grief: psychometric properties of the Adult Attitude to Grief Scale.

PURPOSE: Grief is a reaction to a significant loss that can profoundly affect all aspects of life and capacity to function well. The consequences can vary from severe psychological distress through to physical disturbances and significant social problems. This study sought to identify a measure of vulnerability in grief, by examining the psychometric properties of the Adult Attitude to Grief (AAG) scale in a sample of 168 people seeking help in their bereavement. METHODS: The factor structure of the scale, its internal consistency, its construct validity and optimum classification cutoffs were tested. RESULTS: Confirmatory factor analysis broadly supported the factor structure of the AAG, but identified one item that could profitably be reworded. Internal consistency of the three subscales was acceptable. Construct validity and discriminative validity were supported by correlations with allied constructs (depression and anxiety) and a significant difference between scores for clients with Prolonged Grief Disorder and those without. A correlation with counsellors' own clinical ratings of vulnerability demonstrated criterion-related validity of the AAG. Using receiver operating characteristic methods, optimum cutoff scores on the scale were identified for the classification of different levels of vulnerability. CONCLUSION: The AAG was found to be a psychometrically promising tool for identifying vulnerability in grief.

Transcutaneous electrical nerve stimulation as adjunct to primary care management for tennis elbow: pragmatic randomised controlled trial (TATE trial).

STUDY QUESTION: Can transcutaneous electrical nerve stimulation (TENS), as a patient controlled adjunct to primary care management for tennis elbow, provide superior pain relief to primary care management alone. SUMMARY ANSWER: TENS conferred no additional clinical benefit over primary care management consisting of information and advice on analgesia and exercise for patients with tennis elbow, probably partly owing to poor adherence to treatment recommendations. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: A need exists for safe, self administered interventions to provide pain relief for patients with tennis elbow. TENS as an adjunct to primary care management failed to show any additional pain relief compared with primary care management alone.

Heart rate and perceived muscle pain responses to a functional walking test in McArdle disease.

The aim of this study was to assess a 12-min self-paced walking test in patients with McArdle disease. Twenty patients (44.7 ± 11 years; 11 female) performed the walking test where walking speed, distance walked, heart rate (HR) and perceived muscle pain (Borg CR10 scale) were measured. Median (interquartile range) distance walked was 890 m (470-935). From 1 to 6 min, median walking speed decreased (from 75.0 to 71.4 m∙min(-1)) while muscle pain and %HR reserve increased (from 0.3 to 3.0 and 37% to 48%, respectively). From 7 to 12 min, walking speed increased to 74.2 m∙min(-1), muscle pain decreased to 1.6 and %HR reserve remained between 45% and 48%. To make relative comparisons, HR and muscle pain were divided by walking speed and expressed as ratios. These ratios rose significantly between 1 and 6 min (HR:walking speed P = .001 and pain:walking speed P < .001) and similarly decreased between 6 and 11 min (P = .002 and P = .001, respectively). Peak ratios of HR:walking speed and pain:walking speed were inversely correlated to distance walked: rs (HR) = -.82 (P < .0001) and rs (pain) = -.55 (P = .012). Largest peak ratios were found in patients who walked < 650 m. A 12-min walking test can be used to assess exercise capacity and detect the second wind in McArdle disease.

Older People's Perceptions of Remaining Physically Active and Living With Chronic Pain.

Active aging, using the conventional sense of activity, might be difficult to achieve for people with chronic musculoskeletal pain (CMP). Given that a large number of older people will develop CMP, it is important to consider a broader conceptualization of activity and how this might fit into discourses of aging. We report findings from a study of the experiences of chronic pain in the daily life of 60 older people. In this article we focus on the role and meanings of physical activity for those older people. We develop a typology of styles-deliberate, strategic, and natural-to show how people approached physical activity and how its meaning differed for individuals in different contexts and across their life course. We suggest a more balanced perspective of aging in which "slowing down" might also be a desirable outcome for some older people with CMP but is not incompatible with well-being.

Impact of the Preservation of Residual Kidney Function on Hemodialysis Survival: Results from the BISTRO Trial.

BACKGROUND: Preservation of residual kidney function (RKF) in dialysis patients has been associated with improved survival. RKF in the BISTRO trial was relatively well preserved and here we describe its association with survival during the trial and extended follow-up. METHODS: RKF, measured as the average urea and creatinine clearance (GFR) or 24-hour urine volume was assessed at baseline, one, two and three months and three-monthly up to 2 years in incident haemodialysis patients. Time to event survival data or competing events (transplantation, modality change) were obtained for 50 months post enrolment via data linkage with the UK Renal Registry. Cox proportional hazards regression survival models, including those incorporating change in GFR from baseline as a time-varying variable and joint regression models for longitudinal and survival data (longitudinal models for GFR or urine volume) were used to explore the relationship of RKF preservation with survival. Analyses were adjusted for age, sex, comorbidity and ethnicity. RESULTS: 2919 measures of RKF were made in 387 patients from 32 UK dialysis units. Higher age and comorbidity score associated with increased mortality in all models. Baseline GFR reduced the risk of death (Hazard Ratio: 0.918 95%CI: 0.844, 0.999) per ml/min/1.73m2. A greater fall in GFR and urine volume from baseline was associated with a non-significant increased risk of death as visualised on spline plots. In the joint survival models higher GFR (adjusted HR: 0.88 95%CI 0.80, 0.97) or urine volume (adjusted HR: 0.75 95%CI 0.57, 0.95 per L) at any time point associated with better survival. CONCLUSIONS: Lower RKF during the first two years of haemodialysis is associated with an increased death risk for up to 50 months following dialysis initiation. This adds to a growing body of evidence that interventions to preserve RKF should be developed and tested in clinical trials.

Cost-effectiveness of bioimpedance-guided fluid management in patients undergoing haemodialysis: the BISTRO RCT.

Background: The BioImpedance Spectroscopy to maintain Renal Output randomised controlled trial investigated the effect of bioimpedance spectroscopy added to a standardised fluid management protocol on the risk of anuria and preservation of residual kidney function (primary trial outcomes) in incident haemodialysis patients. Despite the economic burden of kidney disease, the cost-effectiveness of using bioimpedance measurements to guide fluid management in haemodialysis is not known. Objectives: To assess the cost-effectiveness of bioimpedance-guided fluid management against current fluid management without bioimpedance. Design: Within-trial economic evaluation (cost-utility analysis) carried out alongside the open-label, multicentre BioImpedance Spectroscopy to maintain Renal Output randomised controlled trial. Setting: Thirty-four United Kingdom outpatient haemodialysis centres, both main and satellite units, and their associated inpatient hospitals. Participants: Four hundred and thirty-nine adult haemodialysis patients with > 500 ml urine/day or residual glomerular filtration rate > 3 ml/minute/1.73 m2. Intervention: The study intervention was the incorporation of bioimpedance technology-derived information about body composition into the clinical assessment of fluid status in patients with residual kidney function undergoing haemodialysis. Bioimpedance measurements were used in conjunction with usual clinical judgement to set a target weight that would avoid excessive fluid depletion at the end of a dialysis session. Main outcome measures: The primary outcome measure of the BioImpedance Spectroscopy to maintain Renal Output economic evaluation was incremental cost per additional quality-adjusted life-year gained over 24 months following randomisation. In the main (base-case) analysis, this was calculated from the perspective of the National Health Service and Personal Social Services. Sensitivity analyses explored the impact of different scenarios, sources of resource use data and value sets. Results: The bioimpedance-guided fluid management group was associated with £382 lower average cost per patient (95% CI -£3319 to £2556) and 0.043 more quality-adjusted life-years (95% CI -0.019 to 0.105) compared with the current fluid management group, with neither values being statistically significant. The probability of bioimpedance-guided fluid management being cost-effective was 76% and 83% at commonly cited willingness-to-pay threshold of £20,000 and £30,000 per quality-adjusted life-year gained, respectively. The results remained robust to a series of sensitivity analyses. Limitations: The missing data level was high for some resource use categories collected through case report forms, due to COVID-19 disruptions and a significant dropout rate in the informing BioImpedance Spectroscopy to maintain Renal Output trial. Conclusions: Compared with current fluid management, bioimpedance-guided fluid management produced a marginal reduction in costs and a small improvement in quality-adjusted life-years. Results from both the base-case and sensitivity analyses suggested that use of bioimpedance is likely to be cost-effective. Future work: Future work exploring the association between primary outcomes and longer-term survival would be useful. Should an important link be established, and relevant evidence becomes available, it would be informative to determine whether and how this might affect longer-term costs and benefits associated with bioimpedance-guided fluid management. Funding details: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number HTA 14/216/01 (NIHR136142).

'Bioimpedance' is a measure of how difficult it is for an electric current to pass through a biological object. Bioimpedance is used in devices that assess fluid status (over- or under-hydration) because it is very sensitive to the amount of water in tissue. Bioimpedance can be used in addition to clinical judgement when deciding how much water should be removed from someone with kidney failure during a dialysis treatment session. This is the first study to examine whether using this treatment represents a cost-effective use of National Health Service resources. We carried out an economic evaluation within a large randomised controlled trial in patients with kidney disease undergoing haemodialysis. We calculated the additional costs and quality-adjusted life-years (a measure that combines quality and quantity of life) using established methods. Over 2 years, our study showed that taking into account bioimpedance measurements about target weight resulted in slightly lower costs and marginally more quality-adjusted life-years, although there is uncertainty around these findings.

Effects of mobilization and tactile stimulation on chronic upper-limb sensorimotor dysfunction after stroke.

OBJECTIVE: To explore the effects of Mobilization and Tactile Stimulation (MTS) and patterns of recovery in chronic stroke (>12mo) when upper limb (UL) "performance" has reached a clear plateau. DESIGN: Replicated single-system experimental study with 8 single cases using A-B-A design (baseline-intervention-withdrawal phases); length of baseline randomly determined; intervention phase involved 6 weeks of daily MTS to the contralesional UL. SETTING: Community setting, within participants' place of residence. PARTICIPANTS: Individual stroke survivors (N=8; male-to-female ratio, 3:1; age range, 49-76y; 4 with left hemiplegia, 4 with right hemiplegia) discharged from ongoing therapy, more than 1 year post stroke (range, 14-48mo). Clinical presentations were varied across the sample. INTERVENTIONS: Participants received up to 1 hour of daily (Monday to Friday) treatment with MTS to the UL for 6 weeks during the intervention (B) phase. MAIN OUTCOME MEASURES: Motor function (Action Research Arm Test [ARAT]) and motor impairment (Motricity Index [MI] arm section) of the UL. RESULTS: UL performance was stable during baseline for all participants. On visual analysis, improvements in motor impairment were seen in all participants, and clinically significant improvements in motor function were seen in 4 of 8 participants during the intervention phase. Latency between onset of intervention and improvement ranged from 5 to 31 days (ARAT) and from 0 to 28 days (MI). Improvements in performance were maintained on withdrawal of the intervention. Randomization tests were not significant. CONCLUSIONS: MTS appears to improve UL motor impairment and functional activity many months, even years, after stroke onset. Improvement can be immediate, but more often there is latency between the start of intervention and improvement; recovery can be distal to proximal.