Construct Validity of the Steep Ramp Test for Assessing Cardiorespiratory Fitness in Patients With Breast Cancer and the Effect of Chemotherapy-Related Symptom Burden.

OBJECTIVE: To investigate the construct validity of the Steep Ramp Test (SRT) by longitudinally comparing the correlation between maximum short exercise capacity of the SRT and direct measurements of peak oxygen consumption (Vo2peak) during or shortly after treatment in patients with breast cancer and the potential effect of chemotherapy-induced symptom burden. DESIGN: Cross-sectional. SETTING: Multicenter. PARTICIPANTS: We used data from 2 studies that included women with breast cancer treated with chemotherapy, resulting in 274 observations. A total of 161 patients (N=161) performed the cardiopulmonary exercise test and the SRT in 2 test sessions on different time points around chemotherapy treatment. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fatigue was assessed with the Multidimensional Fatigue Inventory, and nausea and vomiting and pain by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The longitudinal correlation between the maximum short exercise capacity and Vo2peak was investigated using a linear mixed model. Interaction terms were added to the model to investigate whether the correlation varied by symptom burden. RESULTS: We found a statistically significant moderate correlation between Vo2peak and maximum short exercise capacity (0.61; 95% confidence interval, 0.51-0.70; P<.01) over time. This correlation was slightly attenuated (-0.07; 95% confidence interval, -0.13 to 0.00; P=.04) in patients with chemotherapy-related nausea and vomiting, indicating smaller correlations of Vo2peak with the maximum short exercise capacity with increasing symptom burden. Pain and fatigue did not significantly modify the correlation. CONCLUSIONS: The SRT can only be used as a proxy for changes in aerobic capacity with great caution and with attention for the level of nausea and vomiting.

Rationale and study protocol of the Physical Activity and Dietary intervention in women with OVArian cancer (PADOVA) study: a randomised controlled trial to evaluate effectiveness of a tailored exercise and dietary intervention on body composition, physical function and fatigue in women with ovarian cancer undergoing chemotherapy.

INTRODUCTION: As a consequence of ovarian cancer and its treatment, many women with ovarian cancer have to deal with reduced physical function, fatigue, and loss of weight and/or muscle mass, compromising quality of life. Exercise and dietary interventions can positively influence body composition, physical fitness and function, and fatigue in patients with cancer. However, there are no data from randomised controlled trials on the effectiveness of exercise and dietary interventions in patients with ovarian cancer. Due to a complex disease trajectory, a relatively poor survival and distinct disease-induced and treatment-induced side effects, it is unclear whether exercise and dietary interventions that were shown to be feasible and effective in other types of cancer produce comparable results in patients with ovarian cancer. The aim of this article is to present the design of the multicentre randomised controlled Physical Activity and Dietary intervention in OVArian cancer trial and to describe how the exercise and dietary intervention is tailored to specific comorbidities and disease-induced and treatment-induced adverse effects in patients with ovarian cancer. METHODS AND ANALYSIS: Adult women with primary epithelial ovarian cancer who are scheduled to undergo first-line (neo)adjuvant chemotherapy (n=122) are randomly allocated to a combined exercise and dietary intervention or a usual care control group during chemotherapy. Primary outcomes are body composition, physical function and fatigue. Outcome measures will be assessed before the start of chemotherapy, 3 weeks after completion of chemotherapy and 12 weeks later. The exercise and dietary intervention was tailored to ovarian cancer-specific comorbidities and adverse effects of ovarian cancer and its treatment following the i3-S strategy. ETHICS AND DISSEMINATION: This study has been approved by the medical ethical committee of the Amsterdam UMC (reference: 018). Results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: Netherlands Trial Registry (NTR6300).

From accelerometer output to physical activity intensities in breast cancer patients.

OBJECTIVES: We aimed to investigate accelerometer output corresponding to physical activity intensity cut-points based on percentage of peak oxygen consumption (%VO2peak) and Metabolic Equivalent of Task (MET) value in women treated for breast cancer. DESIGN: Laboratory study. METHODS: Fifty female patients shortly after completion of treatment for breast cancer were included. VO2peak was determined during a cardiopulmonary exercise test. Subsequently, patients performed ten activities with different intensities while wearing an accelerometer on the right hip and a mobile oxycon to assess oxygen consumption. We studied the relationship between energy expenditure (expressed as %VO2peak and MET-value) and accelerometer output (in counts per minute (cpm)) with linear regression analyses. We determined accelerometer output corresponding to physical activity intensity cut-points (40% and 60%VO2peak; 3 and 6 MET) using regression equations. RESULTS: VO2peak was 22.4mL/kg/min (SD 5.2) and resting metabolic rate was 3.1mL/kg/min (SD 0.6). Accelerometer output corresponding to the cut-points for moderate (40% VO2peak) and vigorous intensity (60% VO2peak) were 1123 and 1911, respectively. The analyses based on MET-values resulted in accelerometer output of 1189cpm for the moderate (3 MET) and 2768 cpm for the vigorous intensity cut-point (6 MET). CONCLUSIONS: Accelerometer outputs for moderate and vigorous intensity physical activity were lower than commonly used cut-points (i.e. 1952 and 5724 cpm), irrespective of the method used to express energy expenditure (%VO2peak versus MET-value). Thus, categorizing physical activity intensities based on general-population cut-points, may underestimate physical activity intensities for women treated for breast cancer.

Structured clinical reasoning for exercise prescription in patients with comorbidity.

Purpose: Exercise therapy is an effective intervention in a variety of chronic diseases. The prescription of exercise therapy is usually directed toward an index disease. The presence of comorbidity may require adaptations to the exercise program as intended for the index disease. This paper aims to structure the clinical reasoning process of health professionals when prescribing exercise therapy for the individual patient with an index disease and comorbidity.Methods: We adapted the previously published strategy for developing guidelines and protocols on comorbidity-adapted exercise to a version that can be used for individual exercise prescription.Results: Essential steps and considerations involved in prescribing an exercise program to an individual patient with comorbidity are described. A case description is used as an example of how the proposed strategy leads to clinical decisions.Conclusions: The proposed strategy may have a role in educational and professional development. The advanced clinical expertise needed for safe and effective exercise therapy in patients with a complex health status is emphasized.Implications for RehabilitationThe presence of comorbidity may require adaptations to exercise therapy.We describe the essential steps and considerations involved in prescribing an exercise program to an individual patient with an index disease and comorbidity.The proposed strategy can be used to structure the clinical reasoning process of health professionals.

Cost-Effectiveness of the Transmural Trauma Care Model (TTCM) for the Rehabilitation of Trauma Patients.

OBJECTIVES: To assess the societal cost-effectiveness of the Transmural Trauma Care Model (TTCM), a multidisciplinary transmural rehabilitation model for trauma patients, compared with regular care. METHODS: The economic evaluation was performed alongside a before-and-after study, with a convenience control group measured only afterward, and a 9-month follow-up. Control group patients received regular care and were measured before implementation of the TTCM. Intervention group patients received the TTCM and were measured after its implementation. The primary outcome was generic health-related quality of life (HR-QOL). Secondary outcomes included disease-specific HR-QOL, pain, functional status, and perceived recovery. RESULTS: Eighty-three trauma patients were included in the intervention group and fifty-seven in the control group. Total societal costs were lower in the intervention group than in the control group, but not statistically significantly so (EUR-267; 95 percent confidence interval [CI], EUR-4,175-3011). At 9 months, there was no statistically significant between-group differences in generic HR-QOL (0.05;95 percent CI, -0.02-0.12) and perceived recovery (0.09;95 percent CI, -0.09-0.28). However, mean between-group differences were statistically significantly in favor of the intervention group for disease-specific HR-QOL (-8.2;95 percent CI, -15.0--1.4), pain (-0.84;95CI, -1.42--0.26), and functional status (-20.1;95 percent CI, -29.6--10.7). Cost-effectiveness acceptability curves indicated that if decision makers are not willing to pay anything per unit of effect gained, the TTCM has a 0.54-0.58 probability of being cost-effective compared with regular care. For all outcomes, this probability increased with increasing values of willingness-to-pay. CONCLUSIONS: The TTCM may be cost-effective compared with regular care, depending on the decision-makers willingness to pay and the probability of cost-effectiveness that they perceive as acceptable.

In-Hospital Mobilization, Physical Fitness, and Physical Functioning After Lung Cancer Surgery.

BACKGROUND: Apart from clinical experience and theoretical considerations, there is a lack of evidence that the level of adherence to in-hospital mobilization protocols is related to functional recovery in patients after resection for lung cancer. The objectives of the study were to determine (1) the relationship between adherence to the in-hospital mobilization protocol and physical fitness at hospital discharge and (2) the value of physical fitness measures at discharge in predicting physical functioning 6 weeks and 3 months postoperatively. METHODS: This observational study included 62 patients who underwent surgical resection for lung cancer. Adherence to the in-hospital mobilization protocol was abstracted from patients' records. Physical fitness measures before the operation and at hospital discharge included handgrip strength, 30-second sit-to-stand test, and 6-minute walk test (6MWT). Self-reported physical functioning was assessed preoperatively and 6 weeks and 3 months postoperatively, using the Medical Outcome Study 36-Item Short Form (SF-36) Physical Function subscale (RAND Corp, Santa Monica, CA). Linear regression analyses were used to estimate the relationships of interest, adjusting for potential confounders. RESULTS: Level of adherence to the mobilization protocol was significantly and independently related to handgrip strength, sit-to-stand test, and 6MWT at discharge. Handgrip strength and 6MWT at discharge significantly predicted SF-36 Physical Function at 6 weeks and 3 months postoperatively. The sit-to-stand test only predicted SF-36 Physical Function at 6 weeks. CONCLUSIONS: Suboptimal postoperative mobilization after surgical resection for lung cancer negatively affects physical fitness at discharge. Our results underline the importance of adherence to early postoperative mobilization protocols. Measuring physical fitness at discharge may be useful to inform clinicians on elective referral of patients for postdischarge rehabilitation.

Cost-utility and cost-effectiveness of physical exercise during adjuvant chemotherapy.

INTRODUCTION: A home-based, low-intensity physical activity program (Onco-Move) and a supervised, moderate-to-high intensity, combined resistance and aerobic exercise program (OnTrack) have proven to be effective in maintaining physical fitness and reducing fatigue among breast cancer patients undergoing adjuvant chemotherapy. This study evaluated the cost-utility and cost-effectiveness of Onco-Move and OnTrack. METHODS: A total of 230 patients were randomized to Onco-Move, OnTrack, or usual care (UC). Health outcomes included quality-adjusted life years (QALYs), general and physical fatigue, and physical fitness measured at baseline, end of chemotherapy, and 6-month follow-up. Societal costs included professional and informal health care, work absenteeism, and unpaid productivity costs. Cost data were based on 3-monthly questionnaires, supplemented by medication data obtained from pharmacies. RESULTS: Onco-Move is not likely to be cost-effective due to the relatively high willingness-to-pay necessary to reach reasonable probabilities of cost-effectiveness (QALY, general and physical fatigue). Incremental cost-effectiveness ratios for OnTrack compared to UC were €26,916/QALY, €788/1-point decrease in general fatigue and €1402/1-point decrease in physical fatigue. The probability of OnTrack being cost-effective ranged from 31% at a willingness-to-pay (WTP) of €0-79% at a WTP of €80,000/QALY, 97% at a WTP of €15,000/1-point decrease in general fatigue, and 86% at a WTP of €24,000/1-point decrease in physical fatigue. Both interventions had a low probability of being cost-effective for physical fitness. The probability of cost-effectiveness for both interventions was greater among compliant participants. CONCLUSIONS: Onco-Move is not likely to be cost-effective. Depending on the decision-makers' willingness-to-pay, OnTrack could be considered cost-effective in comparison with UC. Trial registration Clinical trial registration number of the Netherlands Trial Register-NTR2159.

Tailoring exercise interventions to comorbidities and treatment-induced adverse effects in patients with early stage breast cancer undergoing chemotherapy: a framework to support clinical decisions.

PURPOSE: Delivery of exercise interventions to patients with early-stage breast cancer undergoing chemotherapy requires complex clinical decisions. The purpose of this study was to develop a framework to support clinical decisions for tailoring exercise interventions to common comorbidities and cancer treatment-induced adverse effects. METHOD: Tailored exercise prescriptions were developed in four steps, following the i3-S strategy. All steps were based on current best available evidence, complemented with expert opinions. First, common comorbidities and treatment-induced adverse effects were identified. In the subsequent steps, contra-indications and restrictions for exercise were described, along with possible exercise adaptations. In the final step, the obtained information was synthesized into a framework. RESULTS: Prevalent comorbidities were hypertension, heart disease, diabetes mellitus, (osteo)arthritis, chronic obstructive pulmonary disease, and obesity. Adverse effects included conditions induced by pretreatment (e.g., lymphedema as a result of surgery) or by chemotherapy (e.g., reduced blood cell counts). Adaptations to the recommended exercise program were related to exercise tolerance, safety, and hygiene. A framework was proposed to guide clinical decisions during the exercise intervention. CONCLUSION: Comorbidities and adverse effects of breast cancer treatment require exercise adaptations. The proposed framework provides guidance on tailored exercise prescriptions in patients with breast cancer undergoing chemotherapy. Implications for Rehabilitation Exercise is recommended for patients with breast cancer undergoing chemotherapy, but requires complex clinical decisions of the health professional. We identified the most important comorbidities and adverse effects of breast cancer treatment, and the resultant contra-indications and restrictions to exercise. We incorporated these findings into a clinical decision framework that provides suggestions for exercise adaptations in patients with breast cancer undergoing chemotherapy.

Design of the ExCersion-VCI study: The effect of aerobic exercise on cerebral perfusion in patients with vascular cognitive impairment.

There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination ≥22 and Clinical Dementia Rating ≤0.5. Participants are randomized into an aerobic exercise group or a control group. The aerobic exercise program aims to improve cardiorespiratory fitness and takes 14 weeks, with a frequency of three times a week. Participants are provided with a bicycle ergometer at home. The control group receives two information meetings. Primary outcome measure is change in CBF. We expect this study to provide insight into the potential mechanism by which aerobic exercise improves hemodynamic status.

The clinical utility of the GOLD classification of COPD disease severity in pulmonary rehabilitation.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has introduced a four-stage classification of chronic obstructive pulmonary disease (COPD) severity. The present study investigated the discriminatory capacity of the GOLD classification for health status outcomes in patients with COPD. An additional analysis was performed to investigate the discriminatory capacity of a multidimensional staging system, i.e. the Body-Mass Index, Degree of Airflow Obstruction and Dyspnea, and Exercise Capacity Index (BODE index) for the outcome of quality of life. Retrospective analysis was performed on 253 COPD patients (30% stage II, 48% stage III, 22% stage IV), referred for outpatient pulmonary rehabilitation. Pulmonary function, exercise capacity, dyspnoea and quality of life were evaluated. Analyses of variance were used to detect differences between GOLD stages and BODE index quartiles, and scatterplots of individual responses were produced as well. The GOLD classification discriminated between stages for pulmonary function (p<0.001), exercise capacity (p<0.001), dyspnoea (p<0.001) and the activities section (p=0.001) of the St. George Respiratory Questionnaire (SGRQ). The BODE index discriminated between quartiles for the activities section (p<0.001), impacts section (p=0.04) and the total score (p=0.01) of the SGRQ. Scatterplots revealed marked inter-individual variation within each GOLD stage or BODE index quartile, and considerable overlap between stages for all health status outcomes. These findings show that the GOLD classification indeed can be used to discern groups of COPD patients, but due to large inter-individual variability it does not seem adequate as a basis for individual management plans in rehabilitation. The BODE index appeared to discriminate slightly better for quality of life, however, it still leaves a significant part of the variance unexplained.

Effects of exercise training on cardiac performance, exercise capacity and quality of life in patients with heart failure: a meta-analysis.

BACKGROUND: Despite major advances in pharmacological treatment of chronic heart failure (CHF), a number of patients still suffer from dyspnoea, fatigue, diminished exercise capacity and poor quality of life. It is in this context that exercise training is being intensively evaluated for any additional benefit in the treatment of CHF. AIMS: To determine the effect of exercise training in patients with CHF on cardiac performance, exercise capacity and health-related quality of life. A meta-analysis was performed to obtain this goal. METHODS AND RESULTS: After including 35 randomised controlled trials, the methodological quality of each study was assessed, summary effect sizes (SESs) and the concomitant 95% confidence intervals (95% CI) were calculated for each outcome. Quantitative analysis showed statistically significant SESs, at rest, for diastolic blood pressure and end-diastolic volume. During maximal exercise, significant SESs were found for systolic blood pressure, heart rate, cardiac output, peak oxygen uptake, anaerobic threshold and 6-min walking test. The Minnesota Living with Heart Failure Questionnaire improved by an average of 9.7 points. CONCLUSIONS: Exercise training has clinically important effects on exercise capacity and HRQL, and may have small positive effects on cardiac performance during exercise.