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Background Treatment of oesophageal cancer is associated with significant morbidity which has an impact on longer term survival. Prehabilitation has been shown to reduce post-operative morbidity and mortality. The aim of this study was to undertake a cost-utility analysis to determine if, based on quality adjusted life-years, prehabilitation should be universally implemented in patients undergoing treatment for oesophageal cancer. Methods Patients with oesophageal cancer who were recruited to a randomised control trial were retrospectively analysed. Three-years follow-up was available for calculating overall survival. Costs were calculated based on network, staging, and treatment algorithms. QALYs were calculated as a matrix cost of treatment, quality of life, and overall survival. Overall survival was calculated from time of diagnosis to death or censorship at three-years follow up. Results Thirty-nine patients were randomised to prehabilitation (n=20, 51%) or standard care (n=19, 49%). The median cost per patient for treatment was £46,770.16 (Inter quartile range (IQR) 41,907.21–58,984.21). The overall cost per patient in the prehabilitation group was lower, £44,382.99 (IQR 42,022.86–54,068.23), when compared with standard care per patient £51,538.07 (IQR41,907.21–68,734.33). The mean survival was 24.7 months in the prehab group compared with 27.7 months in the control group (p=0.523). The cost per-QALY for the prehabilitation group was £24,899.06 compared with £25,781.71 in the standard care group. Conclusions In the setting of a randomised control trial, prehabilitation is clinically effective with observed reductions in total treatment costs and a cheaper cost per QALY.

Background: Sarcopenia (low skeletal muscle mass), myosteatosis (low skeletal muscle radiation-attenuation) and fitness are independently associated with postoperative outcomes in oesophago-gastric cancer. This study aimed to investigate (1) the effect of neoadjuvant therapy (NAT) on sarcopenia, myosteatosis and cardiopulmonary exercise testing (CPET), (2) the relationship between these parameters, and (3) their association with postoperative morbidity and survival.Methods: Body composition analysis used single slice computed tomography (CT) images from chest (superior to aortic arch) and abdominal CT scans (third lumbar vertebrae). Oxygen uptake at anaerobic threshold (VO2 at AT) and at peak exercise (VO2 Peak) were measured using CPET. Measurements were performed before and after NAT and an adjusted regression model assessed their association.Results: Of the 184 patients recruited, 100 underwent surgical resection. Following NAT skeletal muscle mass, radiation-attenuation and fitness reduced significantly (p < 0.001). When adjusted for age, sex, and body mass index, only pectoralis muscle mass was associated with VO2 Peak (p = 0.001). VO2 at AT and Peak were associated with 1-year survival, while neither sarcopenia nor myosteatosis were associated with morbidity or survival.Conclusion: Skeletal muscle and CPET variables reduced following NAT and were positively associated with each other. Cardiorespiratory function significantly contributes to short-term survival after oesophago-gastric cancer surgery.Keywords: body composition; myosteatosis; neoadjuvant therapy; oxygen uptake; physical fitness; sarcopenia.

Background: Surgical resection remains the primary curative treatment for intra-cavity cancer. Low physical fitness and psychological factors such as depression are predictive of post–operative morbidity, mortality and length of hospital stay. Prolonged post-operative morbidity is associated with persistently elevated risk of premature death. We aim to investigate whether a structured, responsive exercise training programme, a psychological support programme or combined exercise and psychological support, delivered between treatment decision and major intra-cavity surgery for cancer, can reduce length of hospital stay, compared with standard care. Methods: WesFit is a pragmatic, 2x2 factorial-design, multi-centre, randomised-controlled trial, with planned recruitment of N=1560. Participants will be randomised to one of four groups. Group 1 (control) will receive usual pre-operative care, Group 2 (exercise) patients will undergo 2/3 aerobic, high-intensity interval training sessions per week supervised by personal trainers. Group 3 (psychological support) patients are offered 1 session per week at a local cancer support centre. Group 4 will receive both exercise and psychological support. All patients undergo baseline and pre-operative cardiopulmonary exercise testing, complete self-report questionnaires and will be followed up at 30 days, 12 weeks and 12 months post-operatively. Primary outcome is post-operative length-of-stay. Secondary outcomes include disability-adjusted survival at 1-year postoperatively, post-operative morbidity, and health-related quality of life. Exploratory investigations include objectively measured changes in physical fitness assessed by cardiopulmonary exercise test, disease-free and overall mortality at 1-year postoperatively, longer-term physical activity behaviour change, pre-operative radiological tumour regression, pathological tumour regression, pre and post-operative body composition analysis, health economics analysis and nutritional characterisation and its relationship to post-operative outcome. Conclusions: The WesFit trial will be a randomised controlled study investigating whether a high-intensity exercise training programme +/- psychological intervention results in improvements in clinical and patient reported outcomes in patients undergoing major inter-cavity resection of cancer. ClinicalTrials.gov registration: NCT03509428 (26/04/2018)

IntroductionPhysical activity (PA) and replete nutritional status are key to maintaining independence and improving frailty status among frail older adults. In response to the COVID-19 pandemic, healthcare has increasingly turned to virtual modes of delivery and there is interest in the use of trained volunteers to deliver PA and nutrition interventions. We aim to evaluate the feasibility and acceptability of training hospital volunteers to deliver an online intervention, comprising exercise, behaviour change and nutrition support, to older people with frailty after discharge from hospital.MethodsWe will use a quasi-experimental mixed methods approach. Hospital volunteers (n=6) will be trained to deliver an online, 3-month, multimodal intervention to frail (Clinical Frailty Scale ≥5) adults ≥65 years (n=30) after discharge from hospital. Feasibility will be assessed by determining the number of volunteers recruited, trained and retained at the end of the study; the proportion of intervention sessions delivered; participant recruitment, retention and adherence to the intervention. To determine the acceptability of the intervention, interviews will be conducted among a purposive sample of older adults, and volunteers. Secondary outcomes will include physical function, appetite, well-being, quality of life, anxiety and depression, self-efficacy for managing chronic disease and PA. Outcomes will be measured at baseline, 3 months and 6 months.AnalysisDescriptive statistics will be used to describe feasibility and adherence to the intervention. Secondary outcomes at baseline will be compared at 3 and 6 months. Interviews will be transcribed verbatim and analysed using thematic analysis.Ethics and disseminationHealth Research Authority ethical approval was obtained on 30 May 2022 (reference: 22/WA/0155). Results will be disseminated through peer-reviewed journal articles, volunteer organisations, National Health Service communication systems and social media platforms. A toolkit will be developed to facilitate roll out of volunteer training.Trial registration numberNCT05384730.

Background The use of preoperative cardiopulmonary exercise testing (CPET) to evaluate the risk of adverse perioperative outcomes is increasingly prevalent. CPET-derived information enables personalised perioperative care and enhances shared decision-making. Sex-related differences in physical fitness are reported in non-perioperative literature. However, little attention has been paid to sex-related differences in the context of perioperative CPET. Aim We explored differences in the physical fitness variables reported in a recently published multi-centre study investigating CPET before colorectal surgery. We also report the inclusion rate of females in published perioperative CPET cohorts that are shaping guidelines and clinical practice. Methods We performed a post hoc analysis of the trial data of 703 patients who underwent CPET prior to major elective colorectal surgery. We also summarised the female inclusion rate in peer-reviewed published reports of perioperative CPET. Results Fitness assessed using commonly used perioperative CPET variables—oxygen consumption at anaerobic threshold (AT) and peak exercise—was significantly higher in males than in females both before and after correction for body weight. In studies contributing to the development of perioperative CPET, 68.5% of the participants were male. Conclusion To our knowledge, this is the first study to describe differences between males and females in CPET variables used in a perioperative setting. Furthermore, there is a substantial difference between the inclusion rates of males and females in this field. These findings require validation in larger cohorts and may have significant implications for both sexes in the application of CPET in the perioperative setting.

Opinion piece in the BJS talking about developing an implementation framework for Prehabilitation services across the NHS

Multimodal prehabilitation aims to improve preoperative health in ways that reduce surgical complications and expedite post-operative recovery. However, the extent to which preoperative health has been affected by the COVID-19 pandemic is unclear and evidence for the mitigating effects of prehabilitation in this context has not been elucidated. The COVID-19 pandemic has forced a rapid reorganization of perioperative pathways. Delayed diagnosis and surgery have caused a backlog of cases awaiting surgery increasing the risk of more complex procedures due to disease progression. Poor fitness and preoperative deconditioning are predictive of surgical complications and may be compounded by pandemic-related restrictions to accessing supportive services. The COVID-19 pandemic has forced a rapid reorganization of perioperative pathways. This narrative review aims to summarize the understanding of the effects of the COVID-19 pandemic on preoperative health and related behaviors and their implication for the need and delivery for prehabilitation to engender improved surgical outcomes. A literature search of Medline was conducted for articles related to preoperative health, prehabilitation, and surgical outcomes published between December 1, 2020 and January 31, 2021. Additional hand searches for relevant publications within the included literature were also conducted through October 15, 2021.The COVID-19 pandemic, and measures designed to reduce the spread of the virus, have resulted in physical deconditioning, deleterious dietary changes, substance misuse, and heightened anxiety prior to surgery. Due to the adverse health changes prior to surgery, and often protracted waiting time for surgery, there is likely an elevated risk of peri- and post-operative complications. A small number of prehabilitation services and research programmes have been rapidly adapted or implemented to address these needs.During the COVID-19 pandemic to date, people undergoing surgery have faced a triple threat posed by extended wait times for surgery, reduced access to supportive services, and an elevated risk of poor outcomes. It is imperative that healthcare providers find ways to employ evidence-based prehabilitation strategies that are accessible and safe to mitigate the negative impact of the pandemic on surgical outcomes. Attention should be paid to cohorts most affected by established health inequities and further exacerbated by the pandemic.

Background Neoadjuvant cancer treatment is associated with improved survival following major oesophagogastric cancer surgery. The impact of neoadjuvant chemo/chemoradiotherapy on physical fitness and operative outcomes is however unclear. This study aims to investigate the impact of neoadjuvant chemo/chemoradiotherapy on fitness and post-operative mortality. Methods Patients with oesophagogastric cancer scheduled for chemo/chemoradiotherapy and surgery were recruited to a prospective, blinded, multi-centre, observational cohort study. Primary outcomes were changes in fitness with chemo/chemoradiotherapy, measured using cardiopulmonary exercise testing and its association with mortality one-year after surgery. Patients were followed up for re-admission at 30-days, in-hospital morbidity and quality of life (exploratory outcomes). Results In total, 384 patients were screened, 217 met the inclusion criteria, 160 consented and 159 were included (72% male, mean age 65 years). A total of 132 patients (83%) underwent chemo/chemoradiotherapy, 109 (71%) underwent chemo/chemoradiotherapy and two exercise tests, 100 (63%) completed surgery and follow-up. A significant decline in oxygen uptake at anaerobic threshold and oxygen uptake peak was observed following chemo/chemoradiotherapy: -1.25ml.kg-1.min-1 (-1.80 to - 0.69) and -3.02ml.kg-1.min-1 (-3.85 to -2.20); p

Redox dysregulation and oxidative stress have been implicated in asthma pathogenesis. Exercise interventions improve symptoms and reduce inflammation in asthma patients, but the underlying mechanisms remain unclear. We hypothesized that a personalised exercise intervention would improve asthma control by reducing lung inflammation through modulation of local and systemic reactive species interactions, thereby increasing antioxidant capacity. We combined deep redox metabolomic profiling with clinical assessment in an exploratory cohort of six female patients with symptomatic asthma and studied their responses to a metabolically targeted exercise intervention over 12 weeks. Plasma antioxidant capacity and circulating nitrite levels increased following the intervention (p = 0.028) and lowered the ratio of reduced to oxidised glutathione (p = 0.029); this was accompanied by improvements in physical fitness (p = 0.046), symptoms scores (p = 0.020), quality of life (p = 0.046), lung function (p = 0.028), airway hyperreactivity (p = 0.043), and eosinophilic inflammation (p = 0.007). Increased physical fitness correlated with improved plasma antioxidant capacity (p = 0.019), peak oxygen uptake and nitrite changes (p = 0.005), the latter also associated with reductions in peripheral blood eosinophil counts (p = 0.038). Thus, increases in “redox resilience” may underpin the clinical benefits of exercise in asthma. An improved understanding of exercise-induced alterations in redox regulation offers opportunities for greater treatment personalisation and identification of new treatment targets.

Group pre-operative education has usually been limited to conditioning expectations and providing education. Prehabilitation has highlighted modifiable lifestyle factors that are amenable to change and may improve clinical outcomes. We instituted a pre-operative ‘Fit-4-Surgery School’ for patients scheduled for major surgery, to educate and promote healthy behaviour. We evaluated patients’ views having attended the school, and after surgery we asked how it had changed their behaviour with a lifestyle questionnaire. The school was launched in May 2016 and was attended by 586/1017 (58%) of invited patients. Patients who did not attend: lived further away, median (IQR [range]) 8 (4–19 [0–123]) miles vs. 5 (3–14 [0–172]) miles, p < 0.001; and were more deprived, Index of Multiple Deprivation Rank decile median (IQR [range]), 6 (4–8 [1–10]) vs. 7 (4–9 [1–10]), p = 0.04. Of the 492/586 (84%) participants who completed an evaluation questionnaire, 462 (94%) would recommend the school to a friend having surgery and 296 (60%) planned lifestyle changes. After surgery, 232/586 (40%) completed a behavioural change questionnaire, 106 (46%) of whom reported changing at least one lifestyle factor, most commonly by increasing exercise. The pre-operative school was acceptable to patients.

To review the recent literature around patient-centric prehabilitation in oncology patients and propose a conceptual framework to inform development of interdisciplinary prehabilitation services leading to focused, individualized prehabilitation interventions.A review of recent peer-reviewed literature, national guidance, and government strategy on prehabilitation in oncology patients.Patient- centric prehabilitation is key to improving patient's experiences of cancer throughout the cancer journey while improving population health and reducing financial costs. Successful personalized prehabilitation interventions are comprised of an interplay between individual interdisciplinary roles, as illustrated in the conceptual framework. The role of the nurse underpins this whole process in patient screening, assessment, implementation of the intervention, and patient reassessment, ensuring care is dynamic and tailored to patient need.The review has discussed the key role that nurses play in the process but warrants more research in the area. The conceptual framework provides a basis to develop interdisciplinary prehabilitation services underpinned by the nurse's role. The review advocates the use of educational interventions to equip all health professionals with prehabilitation knowledge to enable interdisciplinary prehabilitation services to be developed.

Background The EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of (1) the exercise prehabilitation programme on psychological health; and (2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and psychological health. Methods Between October 2013 and December 2016, adults with locally advanced rectal cancer undergoing standardised NCRT and surgery were recruited to a multi-centre trial. Patients underwent cardiopulmonary exercise testing (CPET) and completed HRQoL questionnaires (EORTC-QLQ-C30 and EQ-5D-5L) pre-NCRT and post-NCRT (week 0/baseline). At week 0, patients were randomised to exercise prehabilitation or usual care (no intervention). CPET and HRQoL questionnaires were assessed at week 0, 3, 6 and 9, whilst semi-structured interviews were assessed at week 0 and week 9. Changes in oxygen uptake at anaerobic threshold (VO2 at AT (ml kg−1 min−1)) between groups were compared using linear mixed modelling. Results Thirty-eight patients were recruited, mean age 64 (10.4) years. Of the 38 patients, 33 were randomised: 16 to usual care and 17 to exercise prehabilitation (26 males and 7 females). Exercise prehabilitation significantly improved VO2 at AT at week 9 compared to the usual care. The change from baseline to week 9, when adjusted for baseline, between the randomised groups was + 2.9 ml kg −1 min −1; (95% CI 0.8 to 5.1), p = 0.011. Conclusion A 9-week exercise prehabilitation programme significantly improved fitness following NCRT. These findings have informed the WesFit trial (NCT03509428) which is investigating the effects of community-based multimodal prehabilitation before cancer surgery. Trial registration ClinicalTrials.gov NCT01914068. Registered 1 August 2013.

Background Body composition assessment, measured using single-slice computed tomography (CT) image at L3 level, and aerobic physical fitness, objectively measured using cardiopulmonary exercise testing (CPET), are each independently used for perioperative risk assessment. Sarcopenia (i.e. low skeletal muscle mass), myosteatosis [i.e. low skeletal muscle radiation attenuation (SM-RA)], and impaired objectively measured aerobic fitness (reduced oxygen uptake) have been associated with poor post-operative outcomes and survival in various cancer types. However, the association between CT body composition and physical fitness has not been explored. In this study, we assessed the association of CT body composition with selected CPET variables in patients undergoing hepatobiliary and pancreatic surgery. Methods A pragmatic prospective cohort of 123 patients undergoing hepatobiliary and pancreatic surgery were recruited. All patients underwent preoperative CPET. Preoperative CT scans were analysed using a single-slice CT image at L3 level to assess skeletal muscle mass, adipose tissue mass, and muscle radiation attenuation. Multivariate linear regression was used to test the association between CPET variables and body composition. Main outcomes were oxygen uptake at anaerobic threshold (V?O-2 at AT), oxygen uptake at peak exercise (V?O-2 peak), skeletal muscle mass, and SM-RA. Results Of 123 patients recruited [77 men (63%), median age 66.9 +/- 11.7, median body mass index 27.3 +/- 5.2], 113 patients had good-quality abdominal CT scans available and were included. Of the CT body composition variables, SM-RA had the strongest correlation with V?O-2 peak (r = 0.57, P

Purpose To evaluate the role of prehabilitation interventions in adult patients before elective major surgery. Recent findings Exercise training before elective adult major surgery is feasible and safe. Efficacy has been determined but the clinical effectiveness remains uncertain. Early data suggest a reduction in morbidity, length of stay, and an improvement in the quality of life. Nutritional and psychological interventions are less well evaluated, and when they are, it is often in combination with exercise interventions as part of multimodal prehabilitation. Summary Studies evaluating multimodal prehabilitation interventions before elective major surgery in adults are producing encouraging early results, but definitive clinical effectiveness is currently very limited. Future research should focus on refining interventions, exploring mechanisms, establishing minimum dosage, interrogating interactions between therapies, and urgent implementation of large-scale clinical effectiveness studies.

BackgroundThe EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of 1) the exercise prehabilitation programme on psychological health; and 2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and psychological health.MethodsBetween October 2013 and December 2016, adults with locally advanced rectal cancer undergoing standardised NCRT and surgery were recruited to a multi-centre trial. Patients underwent cardiopulmonary exercise testing (CPET) and HRQoL questionnaires (EORTC-QLQ-C30 and EQ-5D-5L) pre-NCRT and post-NCRT (week 0/baseline). At week 0, patients were randomised to exercise prehabilitation or usual care (no intervention). CPET and HRQoL questionnaires were assessed at week 0, 3, 6 and 9, whilst semi structured interviews were assessed at week 0 and week 9. Changes in oxygen uptake at anaerobic threshold (VO2 at AT (ml.kg− 1.min− 1)) between groups was compared using linear mixed modelling.ResultsThirty-eight patients were recruited, mean age 64 (10.4) years. Of the 38 patients, 33 were randomised: 16 to usual care and 17 to exercise prehabilitation (26 male and seven female). Exercise prehabilitation significantly improved VO2 at AT compared to the usual care. The change from baseline to week 9, when adjusted for baseline, between the randomised groups was + 2.9 ml.kg− 1.min− 1; 95% CI (0.8 to 5.1); p = 0.011.ConclusionA 9-week exercise prehabilitation programme significantly rescued fitness following NCRT. These findings have informed the WesFit trial (NCT03509428) which is investigating the effects of community-based multimodal prehabilitation before cancer surgery.Trial registrationClinicalTrials.gov NCT01914068. Registered 1 August 2013, https://clinicaltrials.gov/ct2/show/NCT01914068.

The field of cancer survivorship has significantly advanced person-centered care throughout the cancer continuum. Within cancer survivorship, the last decade has seen remarkable growth in the investigation of prehabilitation comprising pre-treatment interventions to prevent or attenuate the burden of oncologic therapies. While the majority of evidence remains in the surgical setting, prehabilitation is being adapted to target modifiable risk factors that predict poor treatment outcomes in patients receiving other systemic and localized anti-tumor treatments. Here, we propose a multiphasic approach for prehabilitation across the cancer continuum, as a conceptual framework, to encompass the variability in cancer treatment experiences while adopting the most inclusive definition of the cancer survivor.

Background Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. Methods In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg−1 min−1 and peak oxygen consumption (VO2 peak) >16 ml kg−1 min−1, cut-points that represent a reduced risk of postoperative complications. Results Five questions were identified to have dominance in predicting AT>11 ml kg−1 min−1 and VO2 peak>16 ml.kg−1min−1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg−1.min−1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO2 peak>16 ml.kg−1.min−1 and VO2 peak Conclusions The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management.

The use of perioperative cardiopulmonary exercise testing (CPET) to evaluate the risk of adverse perioperative events and inform the perioperative management of patients undergoing surgery has increased over the last decade. CPET provides an objective assessment of exercise capacity preoperatively and identifies the causes of exercise limitation. This information may be used to assist clinicians and patients in decisions about the most appropriate surgical and non-surgical management during the perioperative period. Information gained from CPET can be used to estimate the likelihood of perioperative morbidity and mortality, to inform the processes of multidisciplinary collaborative decision making and consent, to triage patients for perioperative care (ward vs critical care), to direct preoperative interventions and optimization, to identify new comorbidities, to evaluate the effects of neoadjuvant cancer therapies, to guide prehabilitation and rehabilitation, and to guide intraoperative anaesthetic practice. With the rapid uptake of CPET, standardization is key to ensure valid, reproducible results that can inform clinical decision making. Recently, an international Perioperative Exercise Testing and Training Society has been established (POETTS www.poetts.co.uk) promoting the highest standards of care for patients undergoing exercise testing, training, or both in the perioperative setting. These clinical cardiopulmonary exercise testing guidelines have been developed by consensus by the Perioperative Exercise Testing and Training Society after systematic literature review. The guidelines have been endorsed by the Association of Respiratory Technology and Physiology (ARTP).

There is a consistent relationship between physical activity, physical fitness, and health across almost all clinical contexts, including the perioperative setting. Physiological measurements obtained during physical exercise may be used to infer the risk of adverse outcome after major surgery. In particular, data obtained from perioperative cardiopulmonary exercise testing have an expanding role in perioperative care. Such information may be used to inform a variety of changes in clinical practice, including interventions that may reduce the risk of perioperative adverse events. Specifically, for patients undergoing major cancer surgery there is a complex interplay between different cancer treatments, including neoadjuvant therapies (chemo- and chemo- plus radiotherapy), surgery, and physical fitness, and the modulation of these relationships by perioperative exercise interventions. Preoperative cardiopulmonary exercise testing provides an objective evaluation of physical fitness and has been used to provide an individualized risk profile in order to guide collaborative decision-making, inform the consent process, characterize and optimize co-morbidities, and to triage patients to perioperative care. Furthermore, studies evaluating exercise interventions aimed at increasing preoperative exercise capacity have established that training improves physical fitness. However, to date, this literature is largely composed of feasibility and pilot studies with small sample sizes, which are in general underpowered to assess clinical outcomes. Adequately powered prospective multicentre studies are needed to characterize the most effective means of improving patient fitness before surgery and to evaluate the impact of such improvements on surgical and disease-specific (e.g. cancer) outcomes.

IntroductionThe impact of the COVID-19 pandemic (caused by the SARS-CoV-2 virus) on individuals with cancer has been profound. It has led to increased anxiety, distress and deconditioning due to reduced physical activity. We aim to investigate whether SafeFit, a multimodal intervention of physical activity, nutrition and psychological support delivered virtually by cancer exercise specialists (CES), can improve physical and emotional functionings during the COVID-19 pandemic.Methods and analysisA phase III non-randomised intervention trial, target recruitment of 1050 adults with suspected or confirmed diagnosis of cancer. All recruited participants will receive the multimodal intervention delivered by CES for 6 months. Sessions will be delivered 1-to-1 using telephone/video conferencing consultations. CES will work with each participant to devise a personalised programme of (1) physical activity, (2) basic dietary advice and (3) psychological support, all underpinned by behaviour change support.Primary outcomePhysical and emotional functioning as measured by the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-C30). Secondary outcomes: overall quality of life measured by EORTC-QLQ-C30 and EQ-5D-5L, health economics, patient activation, self-efficacy to self-manage chronic disease, distress, impact of COVID-19 on emotional functioning, self-reported physical activity, functional capacity and nutrition. Adherence to the intervention will also be measured and a process evaluation conducted.Ethics and disseminationEthical approval was obtained from the Health Research Authority (reference number 20/NW/0254). Results of this trial will be disseminated through publication of peer-reviewed articles, presentations at scientific conferences, and to the public and people with cancer in collaboration with our patient and public involvement representatives and partners.Trial registration numberNCT04425616.

Background: Neoadjuvant cancer treatment is associated with improved survival following major oesophagogastric cancer surgery. The impact of neoadjuvant chemo/chemoradiotherapy on physical fitness and operative outcomes is however unclear. This study aims to investigate the impact of neoadjuvant chemo/chemoradiotherapy on fitness and post-operative mortality. Methods: Patients with oesophagogastric cancer scheduled for chemo/chemoradiotherapy and surgery were recruited to a prospective, blinded, multi-centre, observational cohort study. Primary outcomes were changes in fitness with chemo/chemoradiotherapy, measured using cardiopulmonary exercise testing and its association with mortality one-year after surgery. Patients were followed up for re-admission at 30-days, in-hospital morbidity and quality of life (exploratory outcomes). Results: In total, 384 patients were screened, 217 met the inclusion criteria, 160 consented and 159 were included (72% male, mean age 65 years). A total of 132 patients (83%) underwent chemo/chemoradiotherapy, 109 (71%) underwent chemo/chemoradiotherapy and two exercise tests, 100 (63%) completed surgery and follow-up. A significant decline in oxygen uptake at anaerobic threshold and oxygen uptake peak was observed following chemo/chemoradiotherapy: -1.25ml.kg-1.min-1 (-1.80 to -0.69) and -3.02ml.kg-1.min-1 (-3.85 to -2.20); p Conclusion: Chemo/chemoradiotherapy prior to oesophagogastric cancer surgery reduced physical fitness. Lower baseline fitness was associated with reduced overall survival at one-year. Careful consideration of fitness prior to chemo/chemoradiotherapy and surgery is urgently needed.

Physical activity (PA) levels are low in patients with lung cancer. Emerging evidence supports the use of interventions to increase PA in this population. We aimed to (1) identify and synthesize outcome measures which assess PA levels in patients with lung cancer and (2) to evaluate, synthesize and compare the psychometric properties of these measures. A systematic review of articles from searches was conducted of five electronic databases and personal records. Eligible studies were those which assessed PA using either performance-based or patient-reported measures. For aim 2, studies identified in aim 1 reporting on at least one psychometric property (validity, reliability, responsiveness or measurement error) were included. Two independent reviewers assessed eligibility and risk of bias with the COnsensus-based Standards for the selection of health status Measurement INstruments. Thirty-four studies using 21 different measures of PA were identified. Seventeen studies used performance-based measures. The Godin Leisure Time Exercise Questionnaire (GLTEQ) was the most frequently used patient-reported measure. Psychometric properties were reported for 13 of these measures and most frequently for movement sensors. Two studies reported on properties of the GLTEQ. Quality ratings for risk of bias were low. There is significant heterogeneity amongst studies regarding method of PA measurement along the lung cancer continuum. Greater consensus could be achieved by using a consensus approach such as a Delphi process. Future studies should include assessment of psychometric properties of the measurement tool being used. Currently, it is recommended where feasible, both performance-based and patient-reported measurements of PA should be undertaken.

Introduction and objectives Exercise intervention may modulate the inflammation responsible for asthma, offering clinical benefit beyond functional improvement. Interval training is tolerated in asthmatics, and may also improve symptom control. This proof of concept study has recruited sub optimally controlled, untrained asthmatics to a 12-week Interval Training Programme to ascertain feasibility and safety, and effect on symptom control, airway and systemic inflammation, and physical fitness. Methods Participants completed thrice weekly 30-minute interval exercise training sessions for 12 weeks. The training intensities were prescribed based on oxygen uptake (VO2) at anaerobic threshold (AT) and peak exercise. Lung function, blood, exhaled breath, saliva, sputum and symptom questionnaires were sampled at baseline, 3, 6 and 12 weeks. Results Early results (n=6) suggest safety and tolerability, with improvement in symptom scores using the Asthma Control Questionnaire score (Friedman p=0.003) and Asthma Quality of Life Questionnaire score (Friedman p=0.02). This improvement in symptoms was associated with reductions in peripheral blood total white cell count (Friedman p=0.02), neutrophil count (Friedman p=0.04), eosinophil count (Friedman p=0.0017), and lymphocyte count (Friedman p=0.04). There was a significant improvement in pre-bronchodilator FVC (Friedman p=0.04) but not FEV1, with a trend for reduction in percentage bronchodilator reversibility (Wilcoxon signed rank p=0.09). The training intervention did not significantly improve physical fitness, assessed by VO2 at anaerobic threshold (Friedman p=0.37) or peak (Friedman p=0.15). BMI did not significantly change (Friedman p=0.18) and exhaled nitric oxide (FeNO) did not significantly improve (Friedman p=0.5). Conclusions This interim analysis suggests exercise intervention in sub optimally controlled asthma is tolerated and beneficial for symptom control, with associated improvement in inflammatory parameters and lung function. The stability of BMI suggests the improvements in inflammatory markers are not a result of reduced adipose tissue related systemic inflammation. The stability of FeNO and significant reductions in total white cell and neutrophil count suggest the improvement in symptoms and inflammation are not due to improved adherence to inhaled corticosteroids. Prescribed training programmes may provide a cost-effective, disease modifying treatment adjunct in poorly controlled asthma.

Introduction: Exercise intervention may modulate the inflammatory basis for asthma, offering clinical benefit beyond functional improvement. Interval training is tolerated in asthmatics, and may improve symptom control. Aims and Objectives: This proof of concept study has recruited poorly controlled asthmatics to a 12-week Interval Training Programme to ascertain if it is feasible and safe, improves symptom control, airway and systemic inflammation, and physical fitness. Methods: Participants were sampled at baseline and 3, 6 and 12 weeks of training. Results: Early results (n=7) suggest safety and tolerability, with improvement between baseline and week 3. Wilcoxon signed rank showed that Asthma Control Questionnaire score improved significantly (mdn=2 [IQR=1.8,2.3] vs mdn=1.63 [IQR=1.37,1.96], p=0.028). Asthma Quality of Life Questionnaire score improved significantly (mdn=4.97 [IQR=4.46,5.3] vs median 5.5 [IQR=5.09,5.84] p=0.018), but was not associated with improved physical fitness, assessed by VO2 at anaerobic threshold (mdn=10.1 [IQR=9.25,11.35] vs 9.7ml/kg/min [IQR=8.6,14]; p=0.46) and VO2peak (mdn= 21.30 [IQR=12.80,25.40] vs 22.8ml/kg/min [IQR=13.80,28.80]; p=0.86). There were no statistically significant improvements in FeNO (median=37.75 [IQR=27.63,66] vs median=36 [IQR=20,82], p=0.39) or peripheral blood eosinophilia (mdn=0.2 [IQR=0.2,0.38] vs mdn=0.3 [IQR=0.2,0.4], p=0.57). Conclusion: These interim data suggests even a short exercise intervention in poorly controlled asthma is tolerated and beneficial for symptom control, which may precede improvement in markers of inflammation. Prescribed training programmes may provide a cost-effective treatment adjunct in poorly controlled asthma.

Purpose: We evaluate the effect of an exercised prehabilitation programme on tumour response in rectal cancer patients following neoadjuvant chemoradiotherapy (NACRT). Patients and Methods: Rectal cancer patients with (MRI-defined) threatened resection margins who completed standardized NACRT were prospectively studied in a post hoc, explorative analysis of two previously reported clinical trials. MRI was performed at Weeks 9 and 14 post-NACRT, with surgery at Week 15. Patients undertook a 6-week preoperative exercise-training programme. Oxygen uptake (VO2) at anaerobic threshold (AT) wasmeasured at baseline (pre-NACRT), after completion of NACRT and at week 6 (post-NACRT). Tumour related outcome variables: MRI tumour regression grading (ymrTRG) at Week 9 and 14; histopathological T-stage (ypT); and tumour regression grading (ypTRG)) were compared. Results: 35 patients (26 males) were recruited. 26 patients undertook tailored exercise-training with 9 unmatched controls. NACRT resulted in a fall in VO2 at AT −2.0 ml/kg −1 /min −1 (−1.3,−2.6), p < 0.001. Exercise was shown to reverse this effect. VO2 at AT increased between groups, (post-NACRT vs. week 6) by +1.9 ml/kg −1 /min −1 (0.6, 3.2), p = 0.007. A significantly greater ypTRG in the exercise group at the time of surgery was found (p = 0.02). Conclusion: Following completion of NACRT, exercise resulted in significant improvements in fitness and augmented pathological tumour regression.

Introduction Many asthmatics remain symptomatic despite optimized medical therapy. New treatments are needed that are scalable at minimal cost. Pulmonary rehabilitation is established in respiratory disease, and emerging data suggests that prescribed exercise intervention may modulate the immune and inflammatory basis for asthma, offering clinical benefit beyond functional capacity improvement. High-intensity interval training (HIIT) seems better tolerated in asthmatics than constant work-rate training, but HIIT with strength training has not been assessed in terms of immunomodulatory potential, and mechanistic work is needed to explain these responses to exercise. Methods This study will randomise ten suboptimally controlled asthma patients to a 12 week HIIT Structured Responsive Exercise Training Programme (SRETP) or SRETP with strength training, which allows adaptation of the programme as fitness improves. Participants will be assessed at 3, 6 and 12 weeks to ascertain if SRETP is feasible, safe and tolerable, improves symptom control, modifies airway and systemic inflammation, and physiology in asthmatic patients. An interim analysis of the first 5 patients is presented. Results Early results suggest safety and tolerability. Wilcoxon signed rank tests between Baseline and Week 3 showed that ACQ score improved significantly (median=2.00 [IQR=1.82–2.38] vs median=1.50 [IQR=1.00–1.83], p=0.043). There were no statistically significant improvements in airways inflammation as assessed by FeNO (median=44.50 [IQR=29.00–87.25] vs median=49 [IQR=21.25–92.50], p=0.686), peripheral blood eosinophilia (n=4, median=0.30 [IQR=0.20–0.50] vs median=0.35 [IQR=0.30–0.48], p=0.102), or aerobic fitness as assessed by VO2 at anaerobic threshold (AT) (n=4, median=10.90 [IQR=9.55–20.25] vs 11.00 ml/kg/min [IQR=9.48–22.35]; p=0.285) and VO2peak (n=4, median=21.80 [IQR=17.15–33.45] vs 23.00 ml/kg/min [IQR=15.73–35.68]; p=0.465) Conclusion This interim data suggests even a very short period of exercise intervention is tolerated and beneficial for symptom control in sub-optimally controlled asthma. Further data will allow assessment of whether this precedes improvement in markers of inflammation, and current results are due to early subclinical cellular improvements in inflammation, or whether symptoms improve independent of any reduction in inflammation. We aim to further investigate this response to exercise training in asthma in a fully powered, observational mechanistic study. Prescribed exercise training programmes may provide a cost-effective treatment adjunct for suboptimally controlled asthmatics.

Increasingly end-organ injury is being demonstrated late after institution of the Fontan circulation, particularly liver fibrosis and cirrhosis. The exact mechanisms for these late phenomena remain largely elusive. Hypothesizing that exercise induces precipitous systemic venous hypertension and insufficient cardiac output for the exercise demand, that is, a possible mechanism for end-organ injury, we sought to demonstrate the dynamic exercise responses in systemic venous perfusion (SVP) and concurrent end-organ perfusion. Ten stable Fontan patients and 9 control subjects underwent incremental cycle ergometry-based cardiopulmonary exercise testing. SVP was monitored in the right upper limb, and regional tissue oxygen saturation was monitored in the brain and kidney using near-infrared spectroscopy. SVP rose profoundly in concert with workload in the Fontan group, described by the regression equation 15.97 + 0.073 watts per mm Hg. In contrast, SVP did not change in healthy controls. Regional renal (p0.01) and cerebral tissue saturations (p0.001) were significantly lower and decrease more rapidly in Fontan patients. We conclude that in a stable group of adult patients with Fontan circulation, high-intensity exercise was associated with systemic venous hypertension and reduced systemic oxygen delivery. This physiological substrate has the potential to contribute to end-organ injury.

Background In single-centre studies, postoperative complications are associated with reduced fitness. This study explored the relationship between cardiorespiratory fitness variables derived by cardiopulmonary exercise testing (CPET) and in-hospital morbidity after major elective colorectal surgery. Methods Patients underwent preoperative CPET with recording of in-hospital morbidity. Receiver operating characteristic (ROC) curves and logistic regression were used to assess the relationship between CPET variables and postoperative morbidity. Results Seven hundred and three patients from six centres in the UK were available for analysis (428 men, 275 women). ROC curve analysis of oxygen uptake at estimated lactate threshold (V˙o2 at θ^L) and at peak exercise (V˙o2peak) gave an area under the ROC curve (AUROC) of 0·79 (95 per cent c.i. 0·76 to 0·83; P < 0·001; cut-off 11·1 ml per kg per min) and 0·77 (0·72 to 0·82; P < 0·001; cut-off 18·2 ml per kg per min) respectively, indicating that they can identify patients at risk of postoperative morbidity. In a multivariable logistic regression model, selected CPET variables and body mass index (BMI) were associated significantly with increased odds of in-hospital morbidity (V˙o2 at θ^L 11·1 ml per kg per min or less: odds ratio (OR) 7·56, 95 per cent c.i. 4·44 to 12·86, P < 0·001; V˙o2peak 18·2 ml per kg per min or less: OR 2·15, 1·01 to 4·57, P = 0·047; ventilatory equivalents for carbon dioxide at estimated lactate threshold (V˙E/V˙co2 at θ^L) more than 30·9: OR 1·38, 1·00 to 1·89, P = 0·047); BMI exceeding 27 kg/m2: OR 1·05, 1·03 to 1·08, P < 0·001). A laparoscopic procedure was associated with a decreased odds of complications (OR 0·30, 0·02 to 0·44; P = 0·033). This model was able to discriminate between patients with, and without in-hospital morbidity (AUROC 0·83, 95 per cent c.i. 0·79 to 0·87). No adverse clinical events occurred during CPET across the six centres. Conclusion These data provide further evidence that variables derived from preoperative CPET can be used to assess risk before elective colorectal surgery.

Background Small airways disease (SAD) is considered pivotal in the pathology of COPD. There are numerous publications describing physiological and Computed Tomography (CT) imaging markers to detect SAD. However, there is no agreed gold standard and limited understanding of the clinical associations of these measures to disease outcomes. Methods We conducted a systematic review using Embase, Medline and Pubmed to explore the relationship between physiological and CT SAD measures in COPD (GOLD Stages 1–4). Furthermore, evidence linking these physiological measures with defined clinical outcomes such as health status, functional assessment and exacerbation frequency were summarised. Results The search yielded 1160 abstracts of which 21 met the search criteria. Eight studies examined physiological and CT measures while 13 publications identified physiological measures and clinical outcomes. Strong correlations were seen between CT and physiological measures of SAD. Varying associations between physiological measures and defined clinical outcomes were noted. Conclusions Physiological and CT measures of SAD correlate and infer similar information. Physiological measures of SAD may offer valuable insight into clinical expression of the disease. A consensus on the standardisation and recommendation of tests to measure SAD is needed in order to better understand any clinical benefits of targeted drug therapy to the small airways.

Aerobic exercise improves prognosis and quality of life (QoL) following completion of chemotherapy. However, the safety and efficacy of aerobic exercise during chemotherapy is less certain. A systematic review was performed of randomised trials of adult patients undergoing chemotherapy, comparing an exercise intervention with standard care. From 253 abstracts screened, 33 unique trials were appraised in accordance with PRISMA guidance, including 3257 patients. Interventions included walking, jogging or cycling, and 23 were of moderate intensity (50–80% maximum heart rate). Aerobic exercise improved, or at least maintained fitness during chemotherapy. Moderately intense exercise, up to 70–80% of maximum heart rate, was safe. Any reported adverse effects of exercise were mild and self-limiting, but reporting was inconsistent. Adherence was good (median 72%). Exercise improved QoL and physical functioning, with earlier return to work. Two out of four studies reported improved chemotherapy completion rates. Four out of six studies reported reduced chemotherapy toxicity. There was no evidence that exercise reduced myelosuppression or improved response rate or survival. Exercise during chemotherapy is safe and should be encouraged because of beneficial effects on QoL and physical functioning. More research is required to determine the impact on chemotherapy completion rates and prognosis.

Summary Background Functional capacity is an important component of risk assessment for major surgery. Doctors' clinical subjective assessment of patients' functional capacity has uncertain accuracy. We did a study to compare preoperative subjective assessment with alternative markers of fitness (cardiopulmonary exercise testing [CPET], scores on the Duke Activity Status Index [DASI] questionnaire, and serum N-terminal pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting death or complications after major elective non-cardiac surgery. Methods We did a multicentre, international, prospective cohort study at 25 hospitals: five in Canada, seven in the UK, ten in Australia, and three in New Zealand. We recruited adults aged at least 40 years who were scheduled for major non-cardiac surgery and deemed to have one or more risk factors for cardiac complications (eg, a history of heart failure, stroke, or diabetes) or coronary artery disease. Functional capacity was subjectively assessed in units of metabolic equivalents of tasks by the responsible anaesthesiologists in the preoperative assessment clinic, graded as poor ( 10). All participants also completed the DASI questionnaire, underwent CPET to measure peak oxygen consumption, and had blood tests for measurement of NT pro-BNP concentrations. After surgery, patients had daily electrocardiograms and blood tests to measure troponin and creatinine concentrations until the third postoperative day or hospital discharge. The primary outcome was death or myocardial infarction within 30 days after surgery, assessed in all participants who underwent both CPET and surgery. Prognostic accuracy was assessed using logistic regression, receiver-operating-characteristic curves, and net risk reclassification. Findings Between March 1, 2013, and March 25, 2016, we included 1401 patients in the study. 28 (2%) of 1401 patients died or had a myocardial infarction within 30 days of surgery. Subjective assessment had 19·2% sensitivity (95% CI 14·2–25) and 94·7% specificity (93·2–95·9) for identifying the inability to attain four metabolic equivalents during CPET. Only DASI scores were associated with predicting the primary outcome (adjusted odds ratio 0·96, 95% CI 0·83–0·99; p=0·03). Interpretation Subjectively assessed functional capacity should not be used for preoperative risk evaluation. Clinicians could instead consider a measure such as DASI for cardiac risk assessment. Funding Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.