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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 (VO 2 peak) 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, VO 2 peak 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 VO 2 peak ≥ 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., (© 2022. The Author(s).)

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., (© 2022. The Author(s).)

Background: Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO 2 ) 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 VO 2 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 VO 2 , with a value < 85% of predicted defined as impaired peak VO 2 . 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 VO 2 (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 VO 2 . However, those with reduced peak VO 2 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.

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 VO 2 , < 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.

Background: Prostate cancer is the most commonly diagnosed cancer in men in developed countries. Androgen deprivation therapy (ADT) is a systemic treatment shown to increase survival in selected patients with prostate cancer. The use of ADT continues to increase for all stages and grades of prostate cancer despite known treatment-induced adverse effects. The primary aim of this study is to examine the efficacy of a targeted, multi-component resistance and impact-loading exercise programme together with a daily protein-, calcium- and vitamin D-enriched supplement on bone health in men treated with ADT for prostate cancer. Secondary aims are to determine the effects of this intervention on measures of total body and regional body composition, cardiometabolic risk, inflammatory markers, health-related quality of life and cognitive function., Methods: This study is a two-arm randomised controlled trial. Men currently treated with ADT for prostate cancer will be randomised to either a 52-week, community-based, exercise training and nutritional supplementation intervention (n = 51) or usual care control (n = 51). Participants will be assessed at baseline, 26 weeks and 52 weeks for all measures. The primary outcome measures are proximal femur and lumbar spine areal bone mineral density (BMD). Secondary outcomes comprise: changes in tibial and radial bone structure and strength, total body and regional body composition, muscle strength and function, as well as cardiometabolic health, catabolic/inflammatory and anabolic/anti-inflammatory cytokines, health-related quality of life and cognitive function., Discussion: This study investigates whether a multi-component intervention incorporating a targeted bone and muscle-loading programme in combination with a protein-, calcium- and vitamin D-enriched supplement can ameliorate multiple adverse effects of ADT when compared to usual care. The results will contribute to the development of exercise training and nutrition guidelines for optimising overall health in men treated with ADT for prostate cancer., Trial Registration: Australia New Zealand Clinical Trial Registry (ANZCTR), ID: ACTRN12614000317695 . Registered on 25 march 2014.

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.

Background: Clinical practice guidelines globally recommend lifestyle modification including diet and exercise training as first-line treatment for obesity. The clinical benefits of exercise training in adults with obesity is well-documented; however, there is no strong evidence for the effectiveness of exercise training for weight loss in class II and class III obesity. The purpose of the randomised controlled trial described in this protocol article is to examine the effect of exercise training, in addition to a very low energy diet (VLED), in clinically severe obese women for changes in body composition, physical function, quality of life, and markers of cardiometabolic risk., Methods/design: Sixty women, aged 18-50 years with a body mass index (BMI) greater than 34.9 kg.m(2) and at least one obesity-related co-morbidity, will be recruited for this 12-month study. Participants will be randomised to either exercise plus energy restriction (n = 30), or energy restriction alone (n = 30). All participants will follow an energy-restricted individualised diet incorporating a VLED component. The exercise intervention group will also receive exercise by supervised aerobic and resistance training and a home-based exercise programme totalling 300 minutes per week. Primary outcome measures include body composition and aerobic fitness. Secondary outcome measures include: physical function, cardiometabolic risk factors, quality of life, physical activity, and mental health. All outcome measures will be conducted at baseline, 3, 6 and 12 months., Discussion: Previous research demonstrates various health benefits of including exercise training as part of a healthy lifestyle at all BMI ranges. Although clinical practice guidelines recommend exercise training as part of first-line treatment for overweight and obesity, there are few studies that demonstrate the effectiveness of exercise in class II and class III obesity. The study aims to determine whether the addition of exercise training to a VLED provides more favourable improvements in body composition, physical function, quality of life, and markers of cardiometabolic risk for women with clinically severe obesity, compared to VLED alone., Trial Registration: Australian New Zealand Clinical Trials Registry ( ACTRN12611000694910 ). Date registered: 4 July 2011.

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.