Analysis 2.1. Comparison 2 Strength tests (all cancers), Outcome 1 Strength tests (all cancers, 12 weeks of follow-up)............... Analysis 2.2. Comparison 2 Strength tests (all cancers), Outcome 2 Strength tests (all cancers: 12 weeks of follow-up: sensitivity analysis

Liam (2018) Interventions for promoting habitual exercise in people living with and beyond cancer. Cochrane Database of Systematic Reviews (9).

BackgroundNational guidelines (NICE-CG175) recommended 12 weeks of supervised exercise training for men treated with androgen deprivation therapy (ADT) for prostate cancer to counter debilitating adverse effects of castration. As with other chronic conditions where exercise is indicated, it is uncertain if these services are being delivered in the health services. The aim of this multi-centre investigation was to examine what exercise referral is currently available for men on ADT as provided by the NHS and if a supervised, individually-tailored exercise training package (as per the national NICE guidelines CG175) is embedded within prostate cancer care.MethodsA multi-centre investigation of current National Health Service (NHS) care involving a web-based survey of NHS prostate cancer care, five focus groups involving 26 men on ADT and 37 semi-structured interviews with healthcare professionals (HCPs) involved in the management of prostate cancer. Descriptive statistics and thematic analysis evaluated quantitative and qualitative data, respectively. Qualitative methods followed COREQ standards.ResultsHCPs and men on ADT asserted that medical castration has a serious and debilitating impact on many features of men's quality of life. There is support for exercise training programmes as part of cancer care and patients would support their initiation soon after diagnosis. Involving the Multidisciplinary Team (MDT) is proposed as key to this. Critically, traditional values in oncology would need to be overcome for widespread acceptance. Specialist further training for HCPs around behaviour change support could encourage this. Given that these schemes are seen as a fundamental part of cancer care, it is felt the NHS should commission and support provision. 79 representatives of 154 NHS trusts (51%) provided survey data on current delivery: only 17% could provide supervised exercise as per CG175.ConclusionsEvidence-based national exercise guidelines are not being delivered to men on ADT as intended. Traditional values in oncology and the need for NHS financial support are seen as major barriers to provision of current best practice guidelines. Despite this both HCPs and men on ADT are in favour of such programmes being a fundamental part of their cancer care.

Background Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials. Methods In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903. Findings Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment–time interactions were –0·09 (95% CI –0·19 to 0·00) for namilumab and 0·06 (–0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group. Interpretation Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation—as measured by CRP concentration—in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19. Funding Medical Research Council.

Alternative management strategies for localised prostate cancer are required to reduce morbidity and overtreatment. The aim of this study was to evaluate the feasibility, safety and acceptability of exercise training (ET) with behavioural support as a primary therapy for low/intermediate risk localised prostate cancer. Men with low/intermediate-risk prostate cancer were randomised to 12 months of ET or usual care with physical activity advice (UCwA) in a multi-site open label RCT. Feasibility included acceptability, recruitment, retention, adherence, adverse events and disease progression. Secondary outcomes included quality of life and cardiovascular health indices. Of the 50 men randomised to ET (n = 25) or UCwA (n = 25), 92% (n = 46) completed 12 month assessments. Three men progressed to invasive therapy (two in UCwA). In the ET group, men completed mean: 140 mins per week for 12 months (95% CI 129,152 mins) (94% of target dose) at 75% Hrmax. Men in the ET group demonstrated improved body mass (mean reduction: 2.0 kg; 95% CI −2.9,−1.1), reduced systolic (mean: 13 mmHg; 95%CI 7,19) and diastolic blood pressure (mean:8 mmHg; 95% CI 5,12) and improved quality of life (EQ.5D mean:13 points; 95% CI 7,18). There were no serious adverse events. ET in men with low/intermediate risk prostate cancer is feasible and acceptable with a low progression rate to radical treatment. Early signals on clinically relevant markers were found which warrant further investigation.