Exercise for the Prevention of Anthracycline-Induced Functional Disability and Cardiac Dysfunction: The BREXIT Study.

BACKGROUND: Breast cancer survivors treated with anthracycline-based chemotherapy (AC) have increased risk of functional limitation and cardiac dysfunction. We conducted a 12-month randomized controlled trial in 104 patients with early-stage breast cancer scheduled for AC to determine whether 12 months of exercise training (ExT) could attenuate functional disability (primary end point), improve cardiorespiratory fitness (VO2peak), and prevent cardiac dysfunction. METHODS: Women 40 to 75 years of age with stage I to III breast cancer scheduled for AC were randomized to 3 to 4 days per week aerobic and resistance ExT for 12 months (n=52) or usual care (UC; n=52). Functional measures were performed at baseline, at 4 weeks after AC (4 months), and at 12 months, comprising: (1) cardiopulmonary exercise testing to quantify VO2peak and functional disability (VO2peak ≤18.0 mL·kg-1·min-1); (2) cardiac reserve (response from rest to peak exercise), quantified with exercise cardiac magnetic resonance measures to determine changes in left and right ventricular ejection fraction, cardiac output, and stroke volume; (3) standard-of-care echocardiography-derived resting left ventricular ejection fraction and global longitudinal strain; and (4) biochemistry (troponin and BNP [B-type natriuretic peptide]). RESULTS: Among 104 participants randomized, greater study attrition was observed among UC participants (P=0.031), with 93 women assessed at 4 months (ExT, n=49; UC, n=44) and 87 women assessed at 12 months (ExT, n=49; UC, n=38). ExT attenuated functional disability at 4 months (odds ratio, 0.32 [95% CI, 0.11-0.94]; P=0.03) but not at 12 months (odds ratio, 0.27 [95% CI, 0.06-1.12]; P=0.07). In a per-protocol analysis, functional disability was prevented entirely at 12 months among participants adherent to ExT (ExT, 0% versus UC, 20%; P=0.005). Compared with UC at 12 months, ExT was associated with a net 3.5-mL·kg-1·min-1 improvement in VO2peak that coincided with greater cardiac output, stroke volume, and left and right ventricular ejection fraction reserve (P<0.001 for all). There was no effect of ExT on resting measures of left ventricular function. Postchemotherapy troponin increased less in ExT than in UC (8-fold versus 16-fold increase; P=0.002). There were no changes in BNP in either group. CONCLUSIONS: In women with early-stage breast cancer undergoing AC, 12 months of ExT did not attenuate functional disability, but provided large, clinically meaningful benefits on VO2peak and cardiac reserve. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12617001408370.

Mental health and quality of life during weight loss in females with clinically severe obesity: a randomized clinical trial.

The purpose of this investigation was to explore the effects of dietary weight loss intervention, with and without the addition of exercise on health-related quality of life, depressive symptoms, and anxiety. As part of the EMPOWER study for women, sixty premenopausal women (BMI of 40.4 ± 6.7) were randomized to energy restriction only (ER) or to exercise plus energy restriction (EXER) for 12 months. Health-related quality of life was assessed using the SF-36, depressive symptoms were assessed using the Beck Depression Inventory II (BDI), and anxiety symptoms using the Spielberger state and trait anxiety questionnaire. All measures were completed at baseline, 3, 6 and 12 months. At 12 months, there were significant (p < 0.05) group-by-time interactions favouring the EXER group for five of the eight domains and the mental component summary score. At 12 months, a significant group-by-time interaction favouring the EXER group is reported for both state and trait anxiety (p = .005 and p = .001, respectively). At 12 months, there was a significant group-by-time interaction for depressive symptoms favouring EXER (p < 0.05). Within-group changes for BDI scores were improved at all follow-up time points in the EXER group. Exercise training confers an additional benefit to energy restriction in the absence of additional weight loss at 12 months for health-related quality of life, depressive symptoms, and state and trait anxiety scores when compared to energy restriction only. Exercise and an energy-restricted diet improve health-related quality of life and mental health. Exercise may protect mental health without further weight loss for women with severe obesity.

Oral digoxin effects on exercise performance, K+ regulation and skeletal muscle Na+ ,K+ -ATPase in healthy humans.

We investigated whether digoxin lowered muscle Na+ ,K+ -ATPase (NKA), impaired muscle performance and exacerbated exercise K+ disturbances. Ten healthy adults ingested digoxin (0.25 mg; DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105%peak-workrate , 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ and 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , 90% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ to fatigue) trials using a double-blind, crossover, randomised, counter-balanced design. Arterial (a) and antecubital venous (v) blood was sampled (FF, LC) and muscle biopsied (LC, rest, 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ , fatigue, 3 h after exercise). In DIG, in resting muscle, [3 H]-ouabain binding site content (OB-Fab ) was unchanged; however, bound-digoxin removal with Digibind revealed total ouabain binding (OB+Fab ) increased (8.2%, P = 0.047), indicating 7.6% NKA-digoxin occupancy. Quadriceps muscle strength declined in DIG (-4.3%, P = 0.010) but fatiguability was unchanged. During LC, in DIG (main effects), time to fatigue and [K+ ]a were unchanged, whilst [K+ ]v was lower (P = 0.042) and [K+ ]a-v greater (P = 0.004) than in CON; with exercise (main effects), muscle OB-Fab was increased at 67% V O 2 peak ${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ (per wet-weight, P = 0.005; per protein P = 0.001) and at fatigue (per protein, P = 0.003), whilst [K+ ]a , [K+ ]v and [K+ ]a-v were each increased at fatigue (P = 0.001). During FF, in DIG (main effects), time to fatigue, [K+ ]a , [K+ ]v and [K+ ]a-v were unchanged; with exercise (main effects), plasma [K+ ]a , [K+ ]v , [K+ ]a-v and muscle K+ efflux were all increased at fatigue (P = 0.001). Thus, muscle strength declined, but functional muscle NKA content was preserved during DIG, despite elevated plasma digoxin and muscle NKA-digoxin occupancy, with K+ disturbances and fatiguability unchanged. KEY POINTS: The Na+ ,K+ -ATPase (NKA) is vital in regulating skeletal muscle extracellular potassium concentration ([K+ ]), excitability and plasma [K+ ] and thereby also in modulating fatigue during intense contractions. NKA is inhibited by digoxin, which in cardiac patients lowers muscle functional NKA content ([3 H]-ouabain binding) and exacerbates K+ disturbances during exercise. In healthy adults, we found that digoxin at clinical levels surprisingly did not reduce functional muscle NKA content, whilst digoxin removal by Digibind antibody revealed an ∼8% increased muscle total NKA content. Accordingly, digoxin did not exacerbate arterial plasma [K+ ] disturbances or worsen fatigue during intense exercise, although quadriceps muscle strength was reduced. Thus, digoxin treatment in healthy participants elevated serum digoxin, but muscle functional NKA content was preserved, whilst K+ disturbances and fatigue with intense exercise were unchanged. This resilience to digoxin NKA inhibition is consistent with the importance of NKA in preserving K+ regulation and muscle function.

Preventing the adverse cardiovascular consequences of allogeneic stem cell transplantation with a multi-faceted exercise intervention: the ALLO-Active trial protocol.

BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) is a potentially lifesaving treatment for high-risk hematological malignancy, but survivors experience markedly elevated rates of cardiovascular disease and associated functional impairment. Mounting evidence suggests regular exercise, combined with a reduction in sedentary time through replacement with light exercise may be a useful therapeutic strategy for the prevention of cardiovascular comorbidities. However, this type of intervention has yet to be evaluated in patients undergoing allo-SCT. The ALLO-Active study will evaluate the efficacy of a ~ 4 month multi-faceted exercise intervention, commenced upon admission for allo-SCT, to preserve peak oxygen uptake (VO2peak) and peak cardiac output, compared with usual care. The study will also evaluate the effect of the intervention on functional independence, quality of life, and symptoms of fatigue. METHODS: Sixty adults with hematological malignancy scheduled for allo-SCT will be randomly assigned to usual care (n = 30) or the exercise and sedentary behaviour intervention (n = 30). Participants assigned to the intervention will complete a thrice weekly aerobic and progressive resistance training program and concomitantly aim to reduce daily sedentary time by 30 min with short, frequent, light-intensity exercise bouts. Participants will undergo testing prior to, immediately after inpatient discharge, and 12 weeks after discharge. To address aim 1, VO2peak and peak cardiac output (multiple primary outcomes, p < 0.025) will be assessed via cardiopulmonary exercise testing and exercise cardiac magnetic resonance imaging, respectively. Secondary outcomes include functional independence (defined as VO2peak ≥ 18.mL.kg-1.min-1), quality of life, and fatigue (assessed via validated questionnaire). Exploratory outcomes will include indices of resting cardiac, vascular, and skeletal muscle structure and function, cardiovascular biomarkers, anxiety and depression, transplant outcomes (e.g., engraftment, graft-versus-host disease), and habitual physical activity, sedentary time, and sleep. DISCUSSION: Multi-faceted exercise programs are a promising approach for ameliorating the cardiovascular consequences of allo-SCT. If this intervention proves to be effective, it will contribute to the development of evidence-based exercise guidelines for patients undergoing allo-SCT and assist with optimising the balance between acute cancer management and long-term health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ID: 12619000741189 . Registered 17 May 2019.

The influence of adiposity on the interactions between strength, physical function and cognition among older adults in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study.

BACKGROUND: Being overweight or obese may be associated with lower physical and cognitive function, but in late-adulthood (≥ 65 years) evidence is mixed. This study aimed to investigate how being overweight or obese affected interactions between muscle strength, function and cognition in Australians aged ≥ 50 years, and whether interactions varied according to age (i.e. ≥ 50-65 vs > 65 years). METHODS: This study included 2368 adults [mean (standard deviation) age: 63 (7) years; 56% female] from the 2011/2012 Australian Diabetes, Obesity and Lifestyle (AusDiab) follow-up. Physical function was assessed via timed up-and-go (TUG) and muscle strength from knee extensor strength (KES). Cognition was assessed using Mini-Mental-State Exam (MMSE), Spot-the-Word (STW), California Verbal Learning Test (CVLT) and Symbol-Digit-Modalities Test (SDMT). Beta binomial regression was used to evaluate how being overweight or obese influenced strength, physical and cognitive function associations. RESULTS: Being overweight or obese did not affect strength-cognition associations regardless of sex or age. With slower physical function; obese females showed better STW (odds ratio [OR] 95% CI]: 1.070 [1.016, 1.127], P = 0.011); obese men better MMSE (OR [95% CI]: 1.157 [1.012, 1.322], P = 0.033); and obese men aged > 65 better CVLT (OR [95% CI]: 1.122 [1.035, 1.217], P = 0.019) and MMSE (OR [95% CI]: 1.233 [1.049, 1.449], P = 0.017) compared to normal weight participants. CONCLUSION: Slower physical function was associated with better performance in some cognitive domains in obese, but not in non-obese adults aged ≥ 50 years. These findings suggest some benefits of obesity to aspects of cognition when physical function is slower, but longitudinal follow-up studies are needed.

Prescribing Exercise in Early-Stage Breast Cancer During Chemotherapy: A Simple Periodized Approach to Align With the Cyclic Phases of Chemotherapy.

ABSTRACT: Bigaran, A, Howden, EJ, Foulkes, S, Janssens, K, Beaudry, R, Haykowsky, MJ, La Gerche, A, Fraser, SF, and Selig, SE. Prescribing exercise in early-stage breast cancer during chemotherapy: a simple periodized approach to align with the cyclic phases of chemotherapy. J Strength Cond Res 36(10): 2934-2941, 2022-To evaluate whether a periodized aerobic and resistance training plan aligned to the anthracycline chemotherapy (AC) cycles would be well tolerated, feasible, and attenuate the decline in peak oxygen uptake (V̇o2peak) in breast cancer (BC) patients. Twenty-eight women with early-stage BC treated with AC self-selected to undertake exercise training (EX 47 ± 9 years, n = 14) or usual care (53 ± 9 years, n = 14) for 12 weeks as part of a nonrandomized controlled trial. The periodized EX was aligned to the cyclic phases of AC, including AC taper and nontaper weeks. Outcome measures included cardiopulmonary exercise testing. Attendance and adherence variables (relative dose intensity [RDI] and volume load) were calculated to quantify the dose of EX completed relative to the amount of EX prescribed. The mean session attendance was 76% (range 46-88%). The mean ± SD prescribed and completed dose of aerobic training was 332.3 ± 48.7 MET h·wk-1 and 380.6 ± 53.2 MET h·wk-1 (p = 0.02), equating to a mean RDI of 89 ± 17%. For resistance training, the prescribed and completed cumulative dose was 128,264 ± 54,578 and 77,487 ± 26,108 kg (p < 0.001), equating to an RDI of 60 ± 11%. Adherence to the AC taper week RDI (52 ± 14%) for resistance training was significantly lower than the non-AC taper week (72 ± 8%, p = 0.02). The most frequent cause for EX interruption was hospitalization (35%), whereas AC-related illness was the most common cause for missed (57%) or modified EX sessions (64%). This periodized approach was mostly well tolerated for patients with BC. We speculate that a periodized approach may be both more palatable and useful, although this requires further investigation in a randomized controlled trial.

Health-related quality of life, fatigue and health behaviours in Australian adolescent and young adult cancer survivors.

INTRODUCTION: Current knowledge of the long-term health behaviours and well-being of adolescent and yong adult (AYA) cancer survivors is limited. The aim of this study was to evaluate the health behaviours of AYA cancer survivors compared to Australian normative data and describe their health-related quality of life (HR-QoL) and levels of fatigue. METHOD: A cross-sectional online survey of participants aged 15-25 years at diagnosis and 2-7 years post treatment completion was conducted at a comprehensive cancer centre. Validated questionnaires assessed health behaviours and functioning including current physical activity (PA) levels, diet quality, fatigue (FACIT-F) and HR-QoL (AQoL-6D, Short Form 36v2 [SF-36v2]) were compared to Australian normative data. RESULTS: Ninety individuals completed the survey (26% response rate) with a mean age of 25.4 years and median time post treatment of 61 months (24-85 months). Compared to normative data, a higher proportion of AYA cancer survivors was consuming the recommended daily serves of fruit and vegetables (16.7% vs. 3.9%, p < .0001), had a lower presence of overweight or obesity (46.7% vs. 57.7%, p = .04) and lower percentage of current smokers (2.2% vs. 16.7%, p < .0001). However, AYA cancer survivors reported increased fatigue (t[df = 596] = -4.1, p < .0001) and reduced HR-QoL compared to normative data (t[df = 533] = 9.2, p < .0001) along with a higher proportion suffering from one or more chronic health conditions (65% vs. 40%, p < .0001). CONCLUSION: AYA cancer survivors from a single Australian institution, who were on average 5 years post treatment, exhibited better health behaviours compared to Australian normative data, but still below recommended guidelines. However, they continue to experience issues with fatigue and reduced HR-QoL, especially in those not meeting the PA guidelines.

Hemodynamic and perceptual responses to blood flow-restricted exercise among patients undergoing dialysis.

End-stage kidney disease is associated with reduced exercise capacity, muscle atrophy, and impaired muscle function. While these may be improved with exercise, single modalities of exercise do not traditionally elicit improvements across all required physiological domains. Blood flow-restricted exercise may improve all of these physiological domains with low intensities traditionally considered insufficient for these adaptions. Investigation of this technique appeals, but is yet to be evaluated, in patients undergoing dialysis. With the use of a progressive crossover design, 10 satellite patients undergoing hemodialysis underwent three exercise conditions over 2 wk: two bouts (10 min) of unrestricted cycling during two consecutive hemodialysis sessions (condition 1), two bouts of cycling with blood flow restriction while off hemodialysis on 2 separate days (condition 2), and two bouts of cycling with blood flow restriction during two hemodialysis sessions (condition 3). Outcomes included hemodynamic responses (heart rate and blood pressure) throughout all sessions, participant-perceived exertion and discomfort on a Borg scale, and evaluation of ultrafiltration rates and dialysis adequacy (Kt/V) obtained post hoc. Hemodynamic responses were consistent regardless of condition. Significant increases in heart rate, systolic blood pressure, and mean arterial blood pressure (P < 0.05) were observed postexercise followed by a reduction in blood pressures during the 60-min recovery (12, 5, and 11 mmHg for systolic, diastolic, and mean arterial pressures, respectively). Blood pressures returned to predialysis ranges following the recovery period. Blood flow restriction did not affect ultrafiltration achieved or Kt/V. Hemodynamic safety and tolerability of blood flow restriction during aerobic exercise on hemodialysis is comparable to standard aerobic exercise.

Exercise as a diagnostic and therapeutic tool for preventing cardiovascular morbidity in breast cancer patients- the BReast cancer EXercise InTervention (BREXIT) trial protocol.

BACKGROUND: Anthracycline chemotherapy (AC) is an efficacious (neo) adjuvant treatment for early-stage breast cancer (BCa), but is associated with an increased risk of cardiac dysfunction and functional disability. Observations suggest that regular exercise may be a useful therapy for the prevention of cardiovascular morbidity but it is yet to be interrogated in a large randomised trial. The primary aims of this study are to: 1) determine if 12-months of ET commenced at the onset of AC can reduce the proportion of BCa patients with functional disability (peak VO2, < 18 ml/kg/min), and 2) compare current standard-of-care for detecting cardiac dysfunction (resting left-ventricular ejection fraction assessed from 3-dimensional echocardiography) to measures of cardiac reserve (peak exercise cardiac output assessed from exercise cardiac magnetic resonance imaging) for predicting the development of functional disability 12-months following AC. Secondary aims are to assess the effects of ET on VO2peak, left ventricular morphology, vascular stiffness, cardiac biomarkers, body composition, bone mineral density, muscle strength, physical function, habitual physical activity, cognitive function, and multidimensional quality of life. METHODS: One hundred women with early-stage BCa (40-75 years) scheduled for AC will be randomized to 12-months of structured exercise training (n = 50) or a usual care control group (n = 50). Participants will be assessed at baseline, 4-weeks following completion of AC (4-months) and at 12-months for all measures. DISCUSSION: Women diagnosed with early-stage BCa have increased cardiac mortality. More sensitive strategies for diagnosing and preventing AC-induced cardiovascular impairment are critical for reducing cardiovascular morbidity and improving long-term health outcomes in BCa survivors. TRIAL REGISTRATION: Australia & New Zealand Clinical Trials Registry (ANZCTR), ID: 12617001408370 . Registered on 5th of October 2017.

Exercise cardiovascular magnetic resonance reveals reduced cardiac reserve in pediatric cancer survivors with impaired cardiopulmonary fitness.

BACKGROUND: Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO2) is associated with impaired cardiac reserve (defined as the increase in cardiac function from rest to peak exercise) and heart failure risk, but it is unclear whether this relationship exists in pediatric cancer survivors. This study sought to investigate the presence of reduced peak VO2 in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac haemodynamics and systolic function during exercise. METHODS: Twenty pediatric cancer survivors (8-24 years; 10 male) treated with anthracycline chemotherapy ± radiation underwent cardiopulmonary exercise testing to quantify peak VO2, with a value < 85% of predicted defined as impaired peak VO2. Resting cardiac function was assessed using 2- and 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate, stroke volume index (SVI) and cardiac index (CI) using exercise cardiovascular magnetic resonance (CMR). RESULTS: Twelve of 20 survivors (60%) had reduced peak VO2 (70 ± 16% vs. 97 ± 14% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired peak VO2. However, those with reduced peak VO2 had diminished cardiac reserve, with a lesser increase in CI and SVI during exercise (Interaction P < 0.01 for both), whilst the heart rate response was similar (P = 0.71). CONCLUSIONS: Whilst exercise intolerance is common among pediatric cancer survivors, it is poorly explained by resting measures of cardiac function. In contrast, impaired exercise capacity is associated with impaired haemodynamics and systolic functional reserve measured during exercise. Consequently, measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure.

Exercise and Nutritional Approaches to Combat Cancer-Related Bone and Muscle Loss.

PURPOSE OF REVIEW: The aim of this narrative review is to summarise recent literature on the effects of exercise and nutrition interventions alone or in combination on muscle and bone loss in people with cancer. RECENT FINDINGS: There is emerging evidence to support the inclusion of targeted exercise and nutrition strategies to counter loss of muscle and bone associated with cancer treatments. Although research in this field is advancing, the optimal exercise and nutrition prescription to combat cancer-related bone and muscle loss remain unknown. This review identifies specific components of nutrition and exercise interventions that are promising although require further exploration through studies designed to determine the effect on muscle and bone. A focused research effort is required to elucidate the full potential of exercise and nutrition intervention for people with cancer at risk of bone and muscle loss.

Exercise interventions for improving objective physical function in patients with end-stage kidney disease on dialysis: a systematic review and meta-analysis.

Patients with end-stage kidney disease on dialysis have increased mortality and reduced physical activity, contributing to impaired physical function. Although exercise programs have demonstrated a positive effect on physiological outcomes such as cardiovascular function and strength, there is a reduced focus on physical function. The aim of this review was to determine whether exercise programs improve objective measures of physical function indicative of activities of daily living for patients with end-stage kidney disease on dialysis. A systematic search of Medline, Embase, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature identified 27 randomized control trials. Only randomized control trials using an exercise intervention or significant muscular activation in the intervention, a usual care, nonexercising control group, and at least one objective measure of physical function were included. Participants were ≥18 yr of age, with end-stage kidney disease, undergoing hemo- or peritoneal dialysis. Systematic review of the literature and quality assessment of the included studies used the Cochrane Collaboration's tool for assessing risk bias. A meta-analysis was completed for the 6-min walk test. Data from 27 studies with 1,156 participants showed that exercise, regardless of modality, generally increased 6-min walk test distance, sit-to-stand time or repetitions, and grip strength as well as step and stair climb times or repetitions, dynamic mobility, and short physical performance battery scores. From the evidence available, exercise, regardless of modality, improved objective measures of physical function for end-stage kidney disease patients undergoing dialysis. It is acknowledged that further well-designed randomized control trials are required.

Does Use of Androgen Deprivation Therapy (ADT) in Men with Prostate Cancer Increase the Risk of Sarcopenia?

Androgen deprivation therapy (ADT) for prostate cancer (PCa) can compromise muscle health. Hence, we aimed to quantify the prevalence of sarcopenia (i.e., compromised lean mass, muscle strength, and physical function) in ADT-treated (> 12 week) men (n = 70) compared to similarly aged non-ADT-treated PCa (n = 52) and healthy controls (n = 70). Lean and fat mass were quantified by dual-energy X-ray absorptiometry. Muscle strength and function were measured using handgrip dynamometry and gait speed, respectively. Sarcopenia was defined as low adjusted appendicular lean mass [ALM; height-adjusted (ALMI), body mass index-adjusted (ALMBMI) and height and fat mass-adjusted (ALMHFM)] with weak handgrip strength and/or slow gait speed according to the following criteria: European Working Group on Sarcopenia in Older People [EWGSOP; both 2010 (EWGSOP1) and 2018 (EWGSOP2)], Foundation for the National Institutes of Health (FNIH) and International Working Group on Sarcopenia (IWGS). Overall the prevalence of sarcopenia was low and did not differ between the three groups. Only two (3.2%) ADT-treated men presented with sarcopenia as per EWGSOP1 and FNIH criteria, whereas no cases were observed using EWGSOP2 and IWGS criteria. The prevalence of low ALMBMI was greater in ADT-treated men (32%) compared to PCa (15%; P = 0.037) and healthy controls (7.1%; P < 0.001). Similarly, low ALMHFM was greater in ADT-treated men (29%) compared to healthy controls only (13%; P = 0.019). There was also a low prevalence of weak muscle strength and slow gait speed (0.0-11%) in all men, with no differences between the groups. Based on these findings, an adiposity-based adjustment of ALM is recommended to quantify risk of adverse outcomes associated with ADT in these men.

Does exercise training augment improvements in quality of life induced by energy restriction for obese populations? A systematic review.

OBJECTIVE: Obesity is associated with a decline in health-related quality of life (HRQOL), while weight loss and exercise training have a positive influence. The aim of this systematic review was to compare the effects of energy restriction (ER) alone intervention to diet and exercise intervention on HRQOL. METHODS: MEDLINE, CINAHL and PsycINFO databases were searched for randomised controlled trials examining HRQOL through lifestyle interventions which examined ER and energy restriction plus exercise in obese adults. RESULTS: Nine hundred and fifty-two papers were assessed for inclusion in this review with nine being deemed suitable. This review indicates that four studies provide evidence to support the role of exercise in addition to ER to improve HRQOL in adults with obesity. The findings of this review are limited due to the limited number of studies as well as substantial heterogeneity in ER, exercise prescription variables and outcome measures utilised within studies. CONCLUSIONS: A definitive conclusion regarding the capacity of exercise to facilitate greater improvement in HRQOL than diet alone, or, to formulate an exercise prescription for obese adults to address HRQOL is not feasible based on the existing evidence. Future studies should utilise comparable HRQOL assessment tools along with ensuring full reporting of results.

Efficacy of blood flow restriction exercise during dialysis for end stage kidney disease patients: protocol of a randomised controlled trial.

BACKGROUND: Exercise during haemodialysis improves strength and physical function. However, both patients and clinicians are time poor, and current exercise recommendations add an excessive time burden making exercise a rare addition to standard care. Hypothetically, blood flow restriction exercise performed during haemodialysis can provide greater value for time spent exercising, reducing this time burden while producing similar or greater outcomes. This study will explore the efficacy of blood flow restriction exercise for enhancing strength and physical function among haemodialysis patients. METHODS: This is a randomised controlled trial design. A total of 75 participants will be recruited from haemodialysis clinics. Participants will be allocated to a blood flow restriction cycling group, traditional cycling group or usual care control group. Both exercising groups will complete 3 months of cycling exercise, performed intradialytically, three times per week. The blood flow restriction cycling group will complete two 10-min cycling bouts separated by a 20-min rest at a subjective effort of 15 on a 6 to 20 rating scale. This will be done with pressurised cuffs fitted proximally on the active limbs during exercise at 50% of a pre-determined limb occlusion pressure. The traditional cycling group will perform a continuous 20-min bout of exercise at a subjective effort of 12 on the same subjective effort scale. These workloads and volumes are equivalent and allow for comparison of a common blood flow restriction aerobic exercise prescription and a traditional aerobic exercise prescription. The primary outcome measures are lower limb strength, assessed by a three repetition maximum leg extension test, as well as objective measures of physical function: six-minute walk test, 30-s sit to stand, and timed up and go. Secondary outcome measures include thigh muscle cross sectional area, body composition, routine pathology, quality of life, and physical activity engagement. DISCUSSION: This study will determine the efficacy of blood flow restriction exercise among dialysis patients for improving key physiological outcomes that impact independence and quality of life, with reduced burden on patients. This may have broader implications for other clinical populations with similarly declining muscle health and physical function, and those contraindicated to higher intensities of exercise. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Register: ACTRN12616000121460.

Effects of a clinician referral and exercise program for men who have completed active treatment for prostate cancer: A multicenter cluster randomized controlled trial (ENGAGE).

BACKGROUND: The purpose of this study was to determine the efficacy of a clinician referral and exercise program in improving exercise levels and quality of life for men with prostate cancer. METHODS: This was a multicenter cluster randomized controlled trial in Melbourne, Australia comprising 15 clinicians: 8 clinicians were randomized to refer eligible participants (n = 54) to a 12-week exercise program comprising 2 supervised gym sessions and 1 home-based session per week, and 7 clinicians were randomized to follow usual care (n = 93). The primary outcome was self-reported physical activity; the secondary outcomes were quality of life, anxiety, and symptoms of depression. RESULTS: A significant intervention effect was observed for vigorous-intensity exercise (effect size: Cohen's d, 0.46; 95% confidence interval [CI], 0.09-0.82; P = .010) but not for combined moderate and vigorous exercise levels (effect size: d, 0.08; 95% CI, -0.28 to 0.45; P = .48). Significant intervention effects were also observed for meeting exercise guidelines (≥150 min/wk; odds ratio, 3.9; 95% CI, 1.9-7.8; P = .002); positive intervention effects were observed in the intervention group for cognitive functioning (effect size: d, 0.34; 95% CI, -0.02 to 0.70; P = .06) and depression symptoms (effect size: d, -0.35; 95% CI, -0.71 to 0.02; P = .06). Eighty percent of participants reported that the clinician's referral influenced their decision to participate in the exercise program. CONCLUSIONS: The clinician referral and 12-week exercise program significantly improved vigorous exercise levels and had a positive impact on mental health outcomes for men living with prostate cancer. Further research is needed to determine the sustainability of the exercise program and its generalizability to other cancer populations.

Risk factors for low muscle mass, malnutrition, and (probable-) sarcopenia in adults with or without a history of cancer in the UK Biobank.

BACKGROUND AND AIMS: Early identification of people at risk of cancer-related malnutrition, low muscle mass (LMM) and sarcopenia is crucial to mitigate the impact of adverse outcomes. This study investigated risk factors associated with LMM, malnutrition and (probable-) sarcopenia and whether these varied in people with or without a history of cancer. METHODS: Participants in the UK Biobank, with or without a history of cancer, who completed the Oxford WebQ at the baseline assessment were included. LMM was estimated from fat-free mass derived from bioelectrical impedance analysis, and low muscle strength from handgrip strength, and used to identify probable or confirmed sarcopenia following the European Working Group on Sarcopenia in Older People 2 definition. The Global Leadership Initiative on Malnutrition criteria were applied to determine malnutrition. Generalised linear models were used to estimate prevalence ratios (PR) for associations between risk factors (clinical, functional, nutritional) and study outcomes. RESULTS: Overall, 50,592 adults with (n = 2,287, mean ± SD 59.7 ± 7.1 years) or without (n = 48,305, mean ± SD 55.8 ± 8.2 years) cancer were included. For all participants (PRs [cancer, without cancer]), slow walking pace (PR 1.85; 1.99), multimorbidity (PR 1.72; 1.51), inflammation (PR 2.91; 2.07), and low serum 25(OH)D (PR 1.85, 1.44) were associated with higher prevalence of LMM, while higher energy intake (PR 0.55; 0.49) was associated with lower prevalence. Slow walking pace (PR 1.54 [cancer], 1.51 [without cancer]) and higher protein intake (PR 0.18 [cancer]; 0.11 [without cancer]) were associated with increased or decreased prevalence of malnutrition, respectively regardless of cancer status. Multimorbidity was the only common factor associated with higher prevalence (PR 1.79 [cancer], 1.68 [without cancer]) of (probable-)sarcopenia in all participants. CONCLUSION: Risk factors for LMM and malnutrition were similar in adults with and without cancer, although these varied between LMM and malnutrition. These findings have implications for the future of risk stratification, screening and assessment for these conditions and the development or modification of existing screening tools.

The impact of an exercise physiologist coordinated resistance exercise program on the physical function of people receiving hemodialysis: a stepped wedge randomised control study.

BACKGROUND: Exercise during hemodialysis treatments improves physical function, markers of cardiovascular disease and quality of life. However, exercise programs are not a part of standard therapy in the vast majority of hemodialysis clinics internationally. Hemodialysis unit-based accredited exercise physiologists may contribute to an increased intradialytic exercise uptake and improved physical function. METHODS AND DESIGN: This is a stepped wedge cluster randomised controlled trial design. A total of 180 participants will be recruited from 15 community satellite hemodialysis clinics in a large metropolitan Australian city. Each clinic will represent a cluster unit. The stepped wedge design will consist of three groups each containing five randomly allocated cluster units, allocated to either 12, 24 or 36 weeks of the intervention. The intervention will consist of an accredited exercise physiologist-coordinated program consisting of six lower body resistance exercises using resistance elastic bands and tubing. The resistance exercises will include leg abduction, plantar flexion, dorsi flexion, straight-leg/bent-knee raise, knee extension and knee flexion. The resistance training will incorporate the principle of progressive overload and completed in a seated position during the first hour of hemodialysis treatment. The primary outcome measure is objective physical function measured by the 30-second sit to stand test. Secondary outcome measures include the 8-foot timed-up-and-go test, the four square step test, quality of life, cost-utility analysis, uptake and involvement in community activity, self-reported falls, fall's confidence, medication use, blood pressure and morbidity (hospital admissions). DISCUSSION: The results of this study are expected to determine the efficacy of an accredited exercise physiologist supervised resistance training on the physical function of people receiving hemodialysis and the cost-utility of exercise physiologists in hemodialysis centres. This may contribute to intradialytic exercise as standard therapy using an exercise physiologist workforce model. TRIAL REGISTRATION: Current Controlled Trials ACTRN12612001223820.

Effectiveness of combined nutrition and exercise interventions on body weight, lean mass, and fat mass in adults diagnosed with cancer: a systematic review and meta-analysis.

CONTEXT: Changes in body weight and composition (fat and lean mass) are prominent side effects of cancer treatment. Nutrition and exercise interventions are both key strategies to protect against these adverse effects, yet their impact when combined has not been comprehensively reviewed in adults with cancer. OBJECTIVE: This systematic review and meta-analysis aims to assess the effects of combined nutrition and exercise interventions on body weight and composition in adults with cancer. DATA SOURCES: Four databases were searched until January 2021. Combined nutrition and exercise randomized controlled trials that detailed the nutrition and exercise prescription and reported body weight and composition outcomes were eligible. DATA EXTRACTION: Risk of bias was assessed through the Cochrane Collaboration tool. The number of participants, mean values, and standard deviations of the outcome variables were extracted. Mean differences (MDs) were pooled using random-effects models. Predetermined subgroup analyses included cancer type, intervention intent, exercise modality, and use of behavior change strategies. DATA ANALYSIS: Twenty-three RCTs were included. Nutrition plus exercise interventions significantly reduced body weight (MD -  2.13 kg; 95%CI, - 3.07 to - 1.19), fat mass (MD - 2.06 kg; 95%CI, - 3.02 to - 1.09), and lean mass (MD - 0.43; 95%CI, - 0.82 to - 0.04). Subgroup analyses in women with breast cancer showed that weight loss interventions and interventions incorporating behavior change strategies significantly reduced body weight and fat mass but also reduced lean mass. Interventions aiming to maintain body weight showed no changes in body weight, as intended. CONCLUSION: Combined nutrition and exercise interventions successfully reduce body weight and fat mass in adults with cancer but also reduce lean mass. In contrast, weight loss-focused interventions are associated mostly with reduced lean mass. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020161805.

Low muscle mass, malnutrition, sarcopenia, and associations with survival in adults with cancer in the UK Biobank cohort.

BACKGROUND: Low muscle mass (MM) is a common component of cancer-related malnutrition and sarcopenia, conditions that are all independently associated with an increased risk of mortality. This study aimed to (1) compare the prevalence of low MM, malnutrition, and sarcopenia and their association with survival in adults with cancer from the UK Biobank and (2) explore the influence of different allometric scaling (height [m2 ] or body mass index [BMI]) on low MM estimates. METHODS: Participants in the UK Biobank with a cancer diagnosis within 2 years of the baseline assessment were identified. Low MM was estimated by appendicular lean soft tissue (ALST) from bioelectrical impedance analysis derived fat-free mass. Malnutrition was determined using the Global Leadership in Malnutrition criteria. Sarcopenia was defined using the European Working Group on Sarcopenia in Older People criteria (version 2). All-cause mortality was determined from linked national mortality records. Cox-proportional hazards models were fitted to estimate the effect of low MM, malnutrition, and sarcopenia on all-cause mortality. RESULTS: In total, 4122 adults with cancer (59.8 ± 7.1 years; 49.2% male) were included. Prevalence of low MM (8.0% vs. 1.7%), malnutrition (11.2% vs. 6.2%), and sarcopenia (1.4% vs. 0.2%) was higher when MM was adjusted using ALST/BMI compared with ALST/height2 , respectively. Low MM using ALST/BMI identified more cases in participants with obesity (low MM 56.3% vs. 0%; malnutrition 50% vs. 18.5%; sarcopenia 50% vs. 0%). During a median 11.2 (interquartile range: 10.2, 12.0) years of follow up, 901 (21.7%) of the 4122 participants died, and of these, 744 (82.6%) deaths were cancer-specific All conditions were associated with a higher hazard of mortality using either method of MM adjustment: low MM (ALST/height2 : HR 1.9 [95% CI 1.3, 2.8], P = 0.001; ALST/BMI: HR 1.3 [95% CI 1.1, 1.7], P = 0.005; malnutrition (ALST/height2 : HR 2.5 [95% CI 1.1, 1.7], P = 0.005; ALST/BMI: HR 1.3 [95% CI 1.1, 1.7], P = 0.005; sarcopenia (ALST/height2 : HR 2.9 [95% CI 1.3, 6.5], P = 0.013; ALST/BMI: HR 1.6 [95% CI 1.0, 2.4], P = 0.037). CONCLUSIONS: In adults with cancer, malnutrition was more common than low MM or sarcopenia, although all conditions were associated with a higher mortality risk, regardless of the method of adjusting for MM. In contrast, adjustment of low MM for BMI identified more cases of low MM, malnutrition, and sarcopenia overall and in participants with obesity compared with height adjustment, suggesting it is the preferred adjustment.