A multi-institutional analysis of perioperative outcomes in 106 men who underwent radical prostatectomy for distant metastatic prostate cancer at presentation

Current trials are investigating radical intervention in men with metastatic prostate cancer. However, there is a lack of safety data for radical prostatectomy as therapy in this setting.To examine perioperative outcomes and short-term complications after radical prostatectomy for locally resectable, distant metastatic prostate cancer.A retrospective case series from 2007 to 2014 comprising 106 patients with newly diagnosed metastatic (M1) prostate cancer from the USA, Germany, Italy, and Sweden.Radical prostatectomy and extended pelvic lymphadenectomy.Descriptive statistics were used to present margin status, continence, and readmission, reoperation, and overall complication rates at 90 d, as well as for 21 specific complications. Kaplan-Meier plots were used to estimate survival function. Intercenter variability and M1a/ M1b subgroups were examined.Some 79.2% of patients did not suffer any complications; positive-margin (53.8%), lymphocele (8.5%), and wound infection (4.7%) rates were higher in our cohort than in a meta-analysis of open radical prostatectomy performed for standard indications. At a median follow-up of 22.8 mo, 94/106 (88.7%) men were still alive. The study is limited by its retrospective design, differing selection criteria, and short follow-up.Radical prostatectomy for men with locally resectable, distant metastatic prostate cancer appears safe in expert hands for meticulously selected patients. Overall and specific complication rates related to the surgical extirpation are not more frequent than when radical prostatectomy is performed for standard indications, and the use of extended pelvic lymphadenectomy in all of this cohort compared to its selective use in localized/locally advanced prostate cancer accounts for any extra morbidity.Men presenting with advanced prostate cancer that has spread beyond the prostate are increasingly being considered for treatments directed at the prostate itself. On the basis of results for our international series of 106 men, surgery appears reasonably safe in this setting for certain patients

The mediating effect of changes in hand impairments on hand function in patients with rheumatoid arthritis: exploring the mechanisms of an effective exercise programme

Objective: To determine whether the effect of the ‘Strengthening And stretching for Rheumatoid Arthritis of the Hand’ (SARAH) exercise programme on hand function was mediated by changes in the proposed active ingredients: strength, dexterity, and/or range of motion. Methods: The SARAH intervention included exercises hypothesized to improve potential mediators of grip strength, pinch strength, wrist flexion, wrist extension, finger flexion, finger extension, thumb opposition, and dexterity, which would theoretically improve self-reported hand function. All variables were measured at baseline and at 4 and 12 months. Structural equation modelling was used to assess mediation on change in hand function via change in potential mediators. Results: Change in grip strength partially mediated change in hand function. Grip strength mediated 19.4% (95% confidence interval: 0.9% to 37.8%) of the treatment effect. Discussion: Improvements in grip strength at 4 months are likely to mediate improved hand function at 12 months. The role of joint mobility exercises is less clear and is likely influenced by the choice of measurement tools for both mobility and function outcomes. More robust measurements of wrist and hand mobility for patients with rheumatoid arthritis may be necessary to determine the relationship between this variable and self-reported hand function. Conclusion: Using a large trial dataset, we have demonstrated that techniques used to target grip strength are key active ingredients of the SARAH exercise programme and mediate its effect

Multifactorial and multiple component interventions for preventing falls in older people living in the community

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects (benefits and harms) of multifactorial interventions and multiple component interventions for preventing falls in older people living in the community

Aerobic and strength training exercise programme for cognitive impairment in people with mild to moderate dementia : the DAPA RCT

Background Approximately 670,000 people in the UK have dementia. Previous literature suggests that physical exercise could slow dementia symptom progression. Objectives To estimate the clinical effectiveness and cost-effectiveness of a bespoke exercise programme, in addition to usual care, on the cognitive impairment (primary outcome), function and health-related quality of life (HRQoL) of people with mild to moderate dementia (MMD) and carer burden and HRQoL. Design Intervention development, systematic review, multicentred, randomised controlled trial (RCT) with a parallel economic evaluation and qualitative study. Setting 15 English regions. Participants People with MMD living in the community. Intervention A 4-month moderate- to high-intensity, structured exercise programme designed specifically for people with MMD, with support to continue unsupervised physical activity thereafter. Exercises were individually prescribed and progressed, and participants were supervised in groups. The comparator was usual practice. Main outcome measures The primary outcome was the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog). The secondary outcomes were function [as measured using the Bristol Activities of Daily Living Scale (BADLS)], generic HRQoL [as measured using the EuroQol-5 Dimensions, three-level version (EQ-5D-3L)], dementia-related QoL [as measured using the Quality of Life in Alzheimer’s Disease (QoL-AD) scale], behavioural symptoms [as measured using the Neuropsychiatric Inventory (NPI)], falls and fractures, physical fitness (as measured using the 6-minute walk test) and muscle strength. Carer outcomes were HRQoL (Quality of Life in Alzheimer’s Disease) (as measured using the EQ-5D-3L) and carer burden (as measured using the Zarit Burden Interview). The economic evaluation was expressed in terms of incremental cost per quality-adjusted life-year (QALY) gained from a NHS and Personal Social Services perspective. We measured health and social care use with the Client Services Receipt Inventory. Participants were followed up for 12 months. Results Between February 2013 and June 2015, 494 participants were randomised with an intentional unequal allocation ratio: 165 to usual care and 329 to the intervention. The mean age of participants was 77 years [standard deviation (SD) 7.9 years], 39% (193/494) were female and the mean baseline ADAS-Cog score was 21.5 (SD 9.0). Participants in the intervention arm achieved high compliance rates, with 65% (214/329) attending between 75% and 100% of sessions. Outcome data were obtained for 85% (418/494) of participants at 12 months, at which point a small, statistically significant negative treatment effect was found in the primary outcome, ADAS-Cog (patient reported), with a mean difference of –1.4 [95% confidence interval (CI) –2.62 to –0.17]. There were no treatment effects for any of the other secondary outcome measures for participants or carers: for the BADLS there was a mean difference of –0.6 (95% CI –2.05 to 0.78), for the EQ-5D-3L a mean difference of –0.002 (95% CI –0.04 to 0.04), for the QoL-AD scale a mean difference of 0.7 (95% CI –0.21 to 1.65) and for the NPI a mean difference of –2.1 (95% CI –4.83 to 0.65). Four serious adverse events were reported. The exercise intervention was dominated in health economic terms. Limitations In the absence of definitive guidance and rationale, we used a mixed exercise programme. Neither intervention providers nor participants could be masked to treatment allocation. Conclusions This is a large well-conducted RCT, with good compliance to exercise and research procedures. A structured exercise programme did not produce any clinically meaningful benefit in function or HRQoL in people with dementia or on carer burden

Problems persist in reporting of methods and results for the WOMAC measure in hip and knee osteoarthritis trials

Purpose The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a commonly used outcome measure for osteoarthritis. There are different versions of the WOMAC (Likert, visual analogue or numeric scales). A previous review of trials published before 2010 found poor reporting and inconsistency in how the WOMAC was used. This review explores whether these problems persist. Methods This systematic review included randomised trials of hip and/or knee osteoarthritis published in 2016 that used the WOMAC. Data were extracted on the version used, score range, analysis and results of the WOMAC, and whether these details were clearly reported. Results This review included 62 trials and 41 reported the WOMAC total score. The version used and item range for the WOMAC total score were unclear in 44% (n = 18/41) and 24% (n = 10/41) of trials, respectively. The smallest total score range was 0–10 (calculated by averaging 24 items scored 0–10); the largest was 0–2400 (calculated by summing 24 items scored 0–100). All trials reported the statistical analysis methods but only 29% reported the between-group mean difference and 95% confidence interval. Conclusion Details on the use and scoring of the WOMAC were often not reported. We recommend that trials report the version of the WOMAC and the score range used. The between-group treatment effect and corresponding confidence interval should be reported. If all the items of the WOMAC are collected, the total score and individual subscale scores should be presented. Better reporting would facilitate the interpretation, comparison and synthesis of the WOMAC score in trials

First large-scale study of antimicrobial susceptibility data, and genetic resistance determinants, in Fusobacterium necrophorum highlighting the importance of continuing focused susceptibility trend surveillance

Objectives: The objective of the study was to explore antimicrobial resistance gene determinant, and phenotypic antibiotic susceptibility, data for Fusobacterium necrophorum from a collection of UK strains. In addition, antimicrobial resistance genes detected in publicly available assembled whole genome sequences were investigated for comparison.Methods: Three hundred and eighty five F. necrophorum strains (1982-2019) were revived from cryovials (Prolab). Subsequent to sequencing (Illumina) and quality checking, 374 whole genomes were available for analysis. These genomes, in addition to publicly available assembled F. necrophorum genetic data, were interrogated using BioNumerics (bioMérieux; v 8.1), for the presence of known antimicrobial resistance genes (ARGs). Agar dilution susceptibility results for 313 F. necrophorum isolates (2016-2021) were also examined.Results: The phenotypic antibiotic test data for the 313 contemporary strains demonstrated potential resistance to penicillin, without increased dosing, in only three isolates. Otherwise, all strains were susceptible to ceftriaxone, clindamycin, co-amoxiclav, meropenem, metronidazole, penicillin and piperacillin/tazobactam, using EUCAST (v 11.0) interpretive guidance. The tet(O), tet(M), tet(40), aph(3’)-III, ant(6)-la and blaOXA-85 ARGs were present in publicly available assembled genomes. tet(M), tet(32), erm(A) and erm(B) were found within the UK strains, with correspondingly raised clindamycin and tetracycline minimum inhibitory concentrations.Conclusions: Current antibiotics recommended for the treatment of infections caused by F. necrophorum, including Lemierre’s disease, are likely to be effective in most cases. However, with evidence of potential ARG transmission from oral bacteria, and the detection of a transposon-mediated beta-lactamase resistance determinant in F. necrophorum, surveillance of both phenotypic and genotypic antimicrobial susceptibility trends must continue, and increase.<br/

Physiotherapist-delivered cognitive behavioural interventions are effective for low back pain, but can they be replicated in clinical practice? A systematic review

Purpose: To determine if physiotherapist-led cognitive-behavioural (CB) interventions are effective for low back pain (LBP) and described sufficiently for replication. Method: RCTs of patients with LBP treated by physiotherapists using a CB intervention were included. Outcomes of disability, pain and quality of life were assessed using the GRADE approach. Intervention reporting was assessed using the Template for Intervention Description and Replication. Results: Of 1898 titles, 5 RCTs (n=1,390) were identified. Compared to education and/or exercise interventions, we found high quality evidence that CB had a greater effect (SMD; 95% CI) on reducing disability (-0.19; -0.32, -0.07), pain (- 0.21; -0.33, -0.09); and moderate quality evidence of little difference in quality of life (-0.06; -0.18 to 0.07). Sufficient information was provided on dose, setting and provider; but not content and procedural information. Studies tended to report the type of CB component used (e.g. challenging unhelpful thoughts) with little detail on how it was operationalised. Moreover, access to treatment manuals, patient materials and provider training was lacking. Conclusions: With additional training, physiotherapists can deliver effective CB interventions. However, without training or resources, successful translation and implementation remains unlikely. Researchers should improve reporting of procedural information, provide relevant materials and offer accessible provider training

RECREATE:A study protocol for a multi-centre pilot cluster Randomised Controlled Trial (cRCT) in UK stroke services evaluating an intervention to reduce sedentary behaviour in stroke survivors (Get Set Go) with embedded process and economic evaluations

Introduction: Sedentary behaviour (sitting or lying during waking hours without being otherwise active) is strongly associated with adverse health outcomes, including all-cause, cancer, and cardiovascular mortality in adults. Stroke survivors are consistently reported as being more sedentary than healthy age-matched controls, spending more hours sedentary daily and sustaining longer unbroken bouts of sedentary time. An evidence-based and clinically feasible intervention (‘Get Set Go’) was developed. A pragmatic definitive trial to evaluate Get Set Go was planned; however, due to the unprecedented effects of the COVID-19 pandemic on National Health Service (NHS) services this study was reduced in size and scope to become an external pilot trial. We report the protocol for this external pilot trial, which aims to undertake a preliminary exploration of whether Get Set Go is likely to improve ability to complete extended activities of daily living in the first year post-stroke and inform future trial designs in stroke rehabilitation. Methods and analysis: This study is a pragmatic multi-centre, two-arm, external pilot cluster Randomised Controlled Trial (cRCT) with embedded process and economic evaluations. UK-based stroke services will be randomized 1:1 to the intervention (usual care plus Get Set Go) or control (usual care) arm. Fifteen stroke services will recruit 300-400 stroke in-patient and carer participants, with follow-up at six, 12 and 24 months. The proposed primary endpoint is stroke survivor self-reported Nottingham Extended Activities of Daily Living (NEADL) scale. Endpoint analyses will be exploratory and provide preliminary estimates of intervention effect. The process evaluation will provide valuable information on intervention fidelity, acceptability, and how it can be optimised. Ethics and dissemination: The study has been approved by Yorkshire &amp; The Humber-Bradford Leeds Research Ethics Committee (Ref: 19/YH/0403). Results will be disseminated through journal publications and conference presentations. Trial registration: This trial was registered prospectively on 01/04/2020 (ISRCTN ref: 82280581). <br/

Assessing physiotherapists’ communication skills for promoting patient autonomy for self-management: reliability and validity of the communication evaluation in rehabilitation tool

Purpose: To assess the inter-rater reliability and concurrent validity of the Communication Evaluation in Rehabilitation Tool, which aims to externally assess physiotherapists’ competency in using Self-Determination Theory-based communication strategies in practice. Materials and Methods: Audio recordings of initial consultations between 24 physiotherapists and 24 patients with chronic low back pain in four hospitals in Ireland were obtained as part of a larger randomised controlled trial. Three raters, all of whom had PhDs in psychology and expertise in motivation and physical activity, independently listened to the 24 audio recordings and completed the 18-item Communication Evaluation in Rehabilitation Tool. Inter-rater reliability between all three raters was assessed using intraclass correlation coefficients. Concurrent validity was assessed using Pearson’s r correlations with a reference standard, the Health Care Climate Questionnaire. Results: The total score for the Communication Evaluation in Rehabilitation Tool is an average of all 18 items. Total scores demonstrated good inter-rater reliability (ICC=0.8) and concurrent validity with the Health Care Climate Questionnaire total score (range: r=0.7-0.88). Item-level scores of the Communication Evaluation in Rehabilitation Tool identified five items that need improvement. Conclusion: Results provide preliminary evidence to support future use and testing of the Communication Evaluation in Rehabilitation Tool

Anti-Tumour Necrosis Factor therapy for Dupuytren’s disease: a randomised dose response proof of concept phase 2a clinical trial

Background: Dupuytren’s disease is a common fibrotic condition of the hand that causes irreversible flexion contractures of the fingers, with no approved therapy for early stage disease. Our previous analysis of surgically-excised tissue defined tumour necrosis factor (TNF) as a potential therapeutic target. Here we assessed the efficacy of injecting nodules of Dupuytren’s disease with a TNF inhibitor. Methods: Patients were randomised to receive adalimumab on one occasion in dose cohorts of 15mg in 0.3ml, 35mg in 0.7ml, or 40mg in 0.4ml, or an equivalent volume of placebo in a 3:1 ratio. Two weeks later the injected tissue was surgically excised and analysed. The primary outcome measure was levels of mRNA expression for a-smooth muscle actin (ACTA2). Secondary outcomes included levels of a-SMA and collagen proteins. The trial was registered with ClinicalTrial.gov (NCT03180957) and the EudraCT (2015-001780-40). Findings: We recruited 28 patients, 8 assigned to the 15mg, 12 to the 35mg and 8 to the 40mg adalimumab cohorts. There was no change in mRNA levels for ACTA2, COL1A1, COL3A1 and CDH11. Levels of a-SMA protein expression in patients treated with 40mg adalimumab (1.09 ± 0.09 ng per μg of total protein) were significantly lower (p=0.006) compared to placebo treated patients (1.51 ± 0.09 ng/μg). The levels of procollagen type I protein expression were also significantly lower (p<0.019) in the sub group treated with 40mg adalimumab (474 ± 84 pg/μg total protein) compared with placebo (817 ± 78 pg/μg). There were two serious adverse events, both considered unrelated to the study drug. Interpretation: In this dose-ranging study, injection of 40mg of adalimumab in 0.4ml resulted in down regulation of the myofibroblast phenotype as evidenced by reduction in expression of a-SMA and type I procollagen proteins at 2 weeks. These data form the basis of an ongoing phase 2b clinical trial assessing the efficacy of intranodular injection of 40mg adalimumab in 0.4ml compared to an equivalent volume of placebo in patients with early stage Dupuytren’s disease