Dropout from exercise trials among cancer survivors—An individual patient data meta-analysis from the POLARIS study

Introduction: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. Methods: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. Results: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI &gt;28.4 kg/m2, performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI &gt;28.4 kg/m2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m2 exercising during (5.2%) or post (9.5%) treatment. Conclusions: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects.</p

Moderators of Exercise Effects on Cancer-related Fatigue:A Meta-analysis of Individual Patient Data

PURPOSE: Fatigue is a common and potentially disabling symptom in patients with cancer. It can often be effectively reduced by exercise. Yet, effects of exercise interventions might differ across subgroups. We conducted a meta-analysis using individual patient data of randomized controlled trials (RCT) to investigate moderators of exercise intervention effects on cancer-related fatigue. METHODS: We used individual patient data from 31 exercise RCT worldwide, representing 4366 patients, of whom 3846 had complete fatigue data. We performed a one-step individual patient data meta-analysis, using linear mixed-effect models to analyze the effects of exercise interventions on fatigue (z score) and to identify demographic, clinical, intervention- and exercise-related moderators. Models were adjusted for baseline fatigue and included a random intercept on study level to account for clustering of patients within studies. We identified potential moderators by testing their interaction with group allocation, using a likelihood ratio test. RESULTS: Exercise interventions had statistically significant beneficial effects on fatigue (β = -0.17; 95% confidence interval [CI], -0.22 to -0.12). There was no evidence of moderation by demographic or clinical characteristics. Supervised exercise interventions had significantly larger effects on fatigue than unsupervised exercise interventions (βdifference = -0.18; 95% CI -0.28 to -0.08). Supervised interventions with a duration ≤12 wk showed larger effects on fatigue (β = -0.29; 95% CI, -0.39 to -0.20) than supervised interventions with a longer duration. CONCLUSIONS: In this individual patient data meta-analysis, we found statistically significant beneficial effects of exercise interventions on fatigue, irrespective of demographic and clinical characteristics. These findings support a role for exercise, preferably supervised exercise interventions, in clinical practice. Reasons for differential effects in duration require further exploration

Targeting exercise interventions to patients with cancer in need:An individual patient data meta-analysis

Background: Exercise effects in cancer patients often appear modest, possibly because interventions rarely target patients most in need. This study investigated the moderator effects of baseline values on the exercise outcomes of fatigue, aerobic fitness, muscle strength, quality of life (QoL), and self-reported physical function (PF) in cancer patients during and post-treatment. Methods: Individual patient data from 34 randomized exercise trials (n = 4519) were pooled. Linear mixed-effect models were used to study moderator effects of baseline values on exercise intervention outcomes and to determine whether these moderator effects differed by intervention timing (during vs post-treatment). All statistical tests were two-sided. Results: Moderator effects of baseline fatigue and PF were consistent across intervention timing, with greater effects in patients with worse fatigue (Pinteraction = .05) and worse PF (Pinteraction = .003). Moderator effects of baseline aerobic fitness, muscle strength, and QoL differed by intervention timing. During treatment, effects on aerobic fitness were greater for patients with better baseline aerobic fitness (Pinteraction = .002). Post-treatment, effects on upper (Pinteraction &lt; .001) and lower (Pinteraction = .01) body muscle strength and QoL (Pinteraction &lt; .001) were greater in patients with worse baseline values. Conclusion: Although exercise should be encouraged for most cancer patients during and post-treatments, targeting specific subgroups may be especially beneficial and cost effective. For fatigue and PF, interventions during and post-treatment should target patients with high fatigue and low PF. During treatment, patients experience benefit for muscle strength and QoL regardless of baseline values; however, only patients with low baseline values benefit post-treatment. For aerobic fitness, patients with low baseline values do not appear to benefit from exercise during treatment

Effects and moderators of exercise on muscle strength, muscle function and aerobic fitness in patients with cancer:A meta-analysis of individual patient data

To optimally target exercise interventions for patients with cancer, it is important to identify which patients benefit from which interventions. Design We conducted an individual patient data meta-analysis to investigate demographic, clinical, intervention-related and exercise-related moderators of exercise intervention effects on physical fitness in patients with cancer. Data sources We identified relevant studies via systematic searches in electronic databases (PubMed, Embase, PsycINFO and CINAHL). Eligibility criteria We analysed data from 28 randomised controlled trials investigating the effects of exercise on upper body muscle strength (UBMS) and lower body muscle strength (LBMS), lower body muscle function (LBMF) and aerobic fitness in adult patients with cancer. Results Exercise significantly improved UBMS (β=0.20, 95% Confidence Interval (CI) 0.14 to 0.26), LBMS (β=0.29, 95% CI 0.23 to 0.35), LBMF (β=0.16, 95% CI 0.08 to 0.24) and aerobic fitness (β=0.28, 95% CI 0.23 to 0.34), with larger effects for supervised interventions. Exercise effects on UBMS were larger during treatment, when supervised interventions included ≥3 sessions per week, when resistance exercises were included and when session duration was >60 min. Exercise effects on LBMS were larger for patients who were living alone, for supervised interventions including resistance exercise and when session duration was >60 min. Exercise effects on aerobic fitness were larger for younger patients and when supervised interventions included aerobic exercise. Conclusion Exercise interventions during and following cancer treatment had small effects on UBMS, LBMS, LBMF and aerobic fitness. Demographic, intervention-related and exercise-related characteristics including age, marital status, intervention timing, delivery mode and frequency and type and time of exercise sessions moderated the exercise effect on UBMS, LBMS and aerobic fitness.Sin financiación12.022 JCR (2019) Q1, 1/85 Sport Sciences3.712 SJR (2019) Q1, 48/2754 Medicine (miscellaneous), 1/284 Orthopedics and Sports Medicine, 1/207 Physical Therapy, Sports Therapy and Rehabilitation, 2/125 Sports ScienceNo data IDR 2019UE

Dropout from exercise trials among cancer survivors-An individual patient data meta-analysis from the POLARIS study

INTRODUCTION: The number of randomized controlled trials (RCTs) investigating the effects of exercise among cancer survivors has increased in recent years; however, participants dropping out of the trials are rarely described. The objective of the present study was to assess which combinations of participant and exercise program characteristics were associated with dropout from the exercise arms of RCTs among cancer survivors. METHODS: This study used data collected in the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study, an international database of RCTs investigating the effects of exercise among cancer survivors. Thirty-four exercise trials, with a total of 2467 patients without metastatic disease randomized to an exercise arm were included. Harmonized studies included a pre and a posttest, and participants were classified as dropouts when missing all assessments at the post-intervention test. Subgroups were identified with a conditional inference tree. RESULTS: Overall, 9.6% of the participants dropped out. Five subgroups were identified in the conditional inference tree based on four significant associations with dropout. Most dropout was observed for participants with BMI >28.4 kg/m 2 , performing supervised resistance or unsupervised mixed exercise (19.8% dropout) or had low-medium education and performed aerobic or supervised mixed exercise (13.5%). The lowest dropout was found for participants with BMI >28.4 kg/m 2 and high education performing aerobic or supervised mixed exercise (5.1%), and participants with BMI ≤28.4 kg/m 2 exercising during (5.2%) or post (9.5%) treatment. CONCLUSIONS: There are several systematic differences between cancer survivors completing and dropping out from exercise trials, possibly affecting the external validity of exercise effects

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects and moderators of exercise on quality of life and physical function in patients with cancer:An individual patient data meta-analysis of 34 RCTs

This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics. Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4,519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions. Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18,95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions. In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

American College of Sports Medicine Roundtable Report on Physical Activity, Sedentary Behavior, and Cancer Prevention and Control

INTRODUCTION: The American College of Sports Medicine convened an International Multidisciplinary Roundtable on Exercise and Cancer in March 2018 to evaluate and translate the evidence linking physical activity and cancer prevention, treatment, and control. This article discusses findings from the Roundtable in relation to the biologic and epidemiologic evidence for the role of physical activity in cancer prevention and survival. RESULTS: The evidence supports that there are a number of biologically plausible mechanisms, whereby physical activity can influence cancer risk, and that physical activity is beneficial for the prevention of several types of cancer including breast, colon, endometrial, kidney, bladder, esophageal, and stomach. Minimizing time spent in sedentary behavior may also lower risk of endometrial, colon and lung cancers. Conversely, physical activity is associated with higher risk of melanoma, a serious form of skin cancer. Further, physical activity before and after a cancer diagnosis is also likely to be relevant for improved survival for those diagnosed with breast and colon cancer; with data suggesting that postdiagnosis physical activity provides greater mortality benefits than prediagnosis physical activity. CONCLUSIONS: Collectively, there is consistent, compelling evidence that physical activity plays a role in preventing many types of cancer and for improving longevity among cancer survivors, although the evidence related to higher risk of melanoma demonstrates the importance of sun safe practices while being physically active. Together, these findings underscore the importance of physical activity in cancer prevention and control. Fitness and public health professionals and health care providers worldwide are encouraged to spread the message to the general population and cancer survivors to be physically active as their age, abilities, and cancer status will allow.</p

American College of Sports Medicine Roundtable Report on Physical Activity, Sedentary Behavior, and Cancer Prevention and Control.

IntroductionThe American College of Sports Medicine convened an International Multidisciplinary Roundtable on Exercise and Cancer in March 2018 to evaluate and translate the evidence linking physical activity and cancer prevention, treatment, and control. This article discusses findings from the Roundtable in relation to the biologic and epidemiologic evidence for the role of physical activity in cancer prevention and survival.ResultsThe evidence supports that there are a number of biologically plausible mechanisms, whereby physical activity can influence cancer risk, and that physical activity is beneficial for the prevention of several types of cancer including breast, colon, endometrial, kidney, bladder, esophageal, and stomach. Minimizing time spent in sedentary behavior may also lower risk of endometrial, colon and lung cancers. Conversely, physical activity is associated with higher risk of melanoma, a serious form of skin cancer. Further, physical activity before and after a cancer diagnosis is also likely to be relevant for improved survival for those diagnosed with breast and colon cancer; with data suggesting that postdiagnosis physical activity provides greater mortality benefits than prediagnosis physical activity.ConclusionsCollectively, there is consistent, compelling evidence that physical activity plays a role in preventing many types of cancer and for improving longevity among cancer survivors, although the evidence related to higher risk of melanoma demonstrates the importance of sun safe practices while being physically active. Together, these findings underscore the importance of physical activity in cancer prevention and control. Fitness and public health professionals and health care providers worldwide are encouraged to spread the message to the general population and cancer survivors to be physically active as their age, abilities, and cancer status will allow