Design of the EXercise Intervention after Stem cell Transplantation (EXIST) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of an individualized high intensity physical exercise program on fitness and fatigue in patients with multiple myeloma or (non-) Hodgkin's lymphoma treated with high dose chemotherapy and autologous stem cell transplantation

<p>Abstract</p> <p>Background</p> <p>The use of high-dose chemotherapy combined with autologous stem cell transplantation has improved the outcome of hematologic malignancies. Nevertheless, this treatment can cause persistent fatigue and a reduced global quality of life, role and physical function. Physical exercise interventions may be beneficial for physical fitness, fatigue and quality of life. However, the trials conducted so far to test the effects of physical exercise interventions in this group of patients were of poor to moderate methodological quality and economic evaluations are lacking. Hence there is need for a rigorous, appropriately controlled assessment of the effectiveness of exercise programs in these patients. The aims of the present study are (1) to determine the effectiveness of an individualized high intensity strength and interval training program with respect to physiological and psychological health status in patients with multiple myeloma or (non-)Hodgkin's lymphoma who have recently undergone high dose chemotherapy followed by autologous stem cell transplantation; and (2) to evaluate the cost-effectiveness of this program.</p> <p>Methods</p> <p>A multicenter, prospective, single blind randomized controlled trial will be performed. We aim to recruit 120 patients within an inclusion period of 2 years at 7 hospitals in the Netherlands. The patients will be randomly assigned to one of two groups: (1) intervention plus usual care; or (2) usual care. The intervention consists of an 18-week individualized supervised high-intensity exercise program and counselling. The primary outcomes (cardiorespiratory fitness, muscle strength and fatigue) and secondary outcomes are assessed at baseline, at completion of the intervention and at 12 months follow-up.</p> <p>Discussion</p> <p>The strengths of this study include the solid trial design with clearly defined research groups and standardized outcome measures, the inclusion of an economic evaluation and the inclusion of both resistance and endurance exercise in the intervention program.</p> <p>Trial registration</p> <p>This study is registered at the Netherlands Trial Register (NTR2341)</p

Effects of exercise in patients treated with stem cell transplantation for a hematologic malignancy: a systematic review and meta-analysis

We performed a systematic review and meta-analysis evaluating the effectiveness of exercise interventions compared with usual care on physical fitness, fatigue and health-related quality of life in patients with hematologic malignancies treated with stem cell transplantation. Electronic databases were searched up to June 2012. We included randomized controlled trials comparing exercise with usual care, in which at least 75% of the patients had a hematologic malignancy. Standard mean differences were calculated and pooled to generate summary effect sizes (ES) and 95% confidence intervals (CI). The Cochrane Collaboration Risk of Bias Tool was used to assess the methodological quality of the studies. Eight studies met our inclusion criteria. Exercise had a statistically significant moderately favourable effect on cardiorespiratory fitness (ES=0.53, 95% CI=0.13-0.94), lower extremity muscle strength (ES=0.56, 95% CI=0.18-0.94) and fatigue (ES=0.53, 95% CI=0.27-0.79). Significant small positive effects were found for upper extremity muscle strength, global quality of life, and physical, emotional and cognitive functioning. In conclusion, exercise seems to have beneficial effects in patients treated with stem cell transplantation. However, all studies had at least some risk of bias, and for cardiorespiratory fitness and lower extremity muscle strength substantial heterogeneity in effect sizes were observed. Further high quality research is needed to determine the optimal exercise intervention and clinical implication

Development of a clinical practice guideline for orthodontically induced external apical root resorption

Objectives: To develop a clinical practice guideline on orthodontically induced external apical root resorption (EARR), with evidence-based and, when needed, consensus-based recommendations concerning diagnosis, risk factors, management during treatment, and after-treatment care. Materials and methods: The Appraisal of Guidelines for Research and Evaluation II instrument and the Dutch Method for Evidence-Based Guideline Development were used to develop the guideline. Based on a survey of all Dutch orthodontists, we formulated four clinical questions regarding EARR. To address these questions, we conducted systematic literature searches in MEDLINE and Embase, and we performed a systematic literature review. The quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. After discussing the evidence, a Task Force formulated considerations and recommendations. The drafted guideline was sent for comments to all relevant stakeholders. Results: Eight studies were included. The quality of evidence (GRADE) was rated as low or very low. Only the patient-related risk factors, 'gender' and 'age', showed a moderate quality of evidence. The Task Force formulated 13 final recommendations concerning the detection of EARR, risk factors, EARR management during treatment, and after-treatment care when EARR has occurred. Stakeholder consultation resulted in 51 comments on the drafted guideline. After processing the comments, the final guideline was authorized by the Dutch Association of Orthodontists. The entire process took 3 years. Limitations: The quality of the available evidence was mainly low, and patient-reported outcome measures were lacking. Conclusions/implications: This clinical practice guideline allows clinicians to respond to EARR based on current knowledge, although the recommendations are weak due to low-quality evidence. It may reduce variation between practices and aid in providing patients appropriate information

Health-related physical fitness in patients with multiple myeloma or lymphoma recently treated with autologous stem cell transplantation

Objectives We aimed to examine health-related physical fitness and its demographic and clinical correlates in patients recently treated with autologous stem cell transplantation. Design Cross-sectional study. Methods In 109 patients (multiple myeloma: n = 58, lymphoma: n = 51, median age: 55, range: 19–67 years) maximal exercise testing was conducted to assess cardiorespiratory fitness (VO2peak). Upper and lower extremity muscle strength were assessed with hand grip- and fixed dynamometry and body composition with whole body DXA scans. In addition, we assessed the patients’ demographic and clinical characteristics and examined whether they were associated with health-related physical fitness. Results VO2peak was 21.7 (5.5) mL/min/kg, 26% below reference values. Muscle strength was also reduced when compared with reference values (upper extremity: 90%, lower extremity: 80%) and 73% of our population was classified as overweight or obese. Being female and being older were significantly associated with a lower cardiorespiratory fitness (gender: β = −2.7, 95%CI = −4.6;−0.7 mL/min/kg; age: β = −0.2, 95%CI = −0.3;−0.1 mL/min/kg), upper (gender: β = −17.7, 95%CI = −20.1;−15.3 kg; age: β = −0.2, 95%CI = −0.3;−0.1 kg) and lower (gender: β = −58.3, 95%CI = −73.5;− 43.0 Nm; age: β = −1.7, 95%CI = −2.4;−1.1 Nm) extremity muscle strength. Patients who were non-smoking (β = −5.3, 95%CI = −8.7;−1.9), women (β = 7.2, 95%CI = 4.8;9.6) and diagnosed with multiple myeloma (β = 4.6, 95%CI = 2.2;6.9) had a higher percentage body fat. Conclusions The physical fitness deficits in this population indicate the need for targeted interventions. Trial registration Netherlands Trial Register - NTR234

Live and Incremental Whole-System Migration of Virtual Machines Using Block-Bitmap

In this paper, we describe a whole-system live migration scheme, which transfers the whole system run-time state, including CPU state, memory data, and local disk storage, of the virtual machine (VM). To minimize the downtime caused by migrating large disk storage data and keep data integrity and consistency, we propose a three-phase migration (TPM) algorithm. To facilitate the migration back to initial source machine, we use an incremental migration (IM) algorithm to reduce the amount of the data to be migrated. Block-bitmap is used to track all the write accesses to the local disk storage during the migration. Synchronization of the local disk storage in the migration is performed according to the block-bitmap. Experiments show that our algorithms work well even when I/O-intensive workloads are running in the migrated VM. The downtime of the migration is around 100 milliseconds, close to shared-storage migration. Total migration time is greatly reduced using IM. The block-bitmap based synchronization mechanism is simple and effective. Performance overhead of recording all the writes on migrated VM is very low.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000263868800011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Computer Science, Hardware &amp; ArchitectureEngineering, Electrical &amp; ElectronicEICPCI-S(ISTP)2

Validation and refinement of prediction models to estimate exercise capacity in cancer survivors using the steep ramp test

Objective: To further test the validity and clinical usefulness of the steep ramp test (SRT) in estimating exercise tolerance in cancer survivors by external validation and extension of previously published prediction models for peak oxygen consumption (VO2peak) and peak power output (Wpeak). Design: Cross-sectional study. Setting: Multicenter. Participants: Cancer survivors (NZ283) in 2 randomized controlled exercise trials. Interventions: Not applicable. Main Outcome Measures: Prediction model accuracy was assessed by intraclass correlation coefficients (ICCs) and limits of agreement (LOA). Multiple linear regressionwas used formodel extension. Clinical performancewas judged by the percentage of accurate endurance exercise prescriptions. Results: ICCs of SRT-predicted VO2peak and Wpeak with these values as obtained by the cardiopulmonary exercise test were .61 and .73, respectively, using the previously published prediction models. 95% LOA were _705mL/min with a bias of 190mL/min for VO2peak and _59W with a bias of 5W for Wpeak. Modest improvements were obtained by adding body weight and sex to the regression equation for the prediction of VO2peak (ICC, .73; 95% LOA, _608mL/min) and by adding age, height, and sex for the prediction of Wpeak (ICC, .81; 95% LOA, _48W). Accuracy of endurance exercise prescription improved from 57% accurate prescriptions to 68% accurate prescriptions with the new prediction model for Wpeak. Conclusions: Predictions of VO2peak and Wpeak based on the SRT are adequate at the group level, but insufficiently accurate in individual patients. The multivariable prediction model for Wpeak can be used cautiously (eg, supplemented with a Borg score) to aid endurance exercise prescription

Randomized controlled trial on the effects of a supervised high intensity exercise program in patients with a hematologic malignancy treated with autologous stem cell transplantation : Results from the EXIST study

Background: This single blind, multicenter randomized controlled trial aimed to evaluate the effectiveness of a supervised high intensity exercise program on physical fitness and fatigue in patients with multiple myeloma or lymphoma recently treated with autologous stem cell transplantation. Methods: 109 patients were randomly assigned to the 18-week exercise intervention or the usual care control group. The primary outcomes included physical fitness (VO2peak and Wpeak determined using a cardiopulmonary exercise test; grip strength and the 30s chair stand test) and fatigue (Multidimensional Fatigue Inventory) and were assessed prior to randomization and after completion of the intervention or at similar time points for the control group. Multivariable multilevel linear regression analyses were performed to assess intervention effects. Results: Patients in the intervention group attended 86% of the prescribed exercise sessions. Of the patients in the control group, 47% reported ≥10 physiotherapy sessions, which most likely included supervised exercise, suggesting a high rate of contamination. Median improvements in physical fitness ranged between 16 and 25% in the intervention group and between 12 and 19% in the control group. Fatigue decreased in both groups. There were no significant differences between the intervention and control group. Conclusion: We found no significant beneficial effects of the supervised high intensity exercise program on physical fitness and fatigue when compared to usual care. We hypothesized that the lack of significant intervention effects may relate to suboptimal timing of intervention delivery, contamination in the control group and/or suboptimal compliance to the prescribed exercise intervention. Trial registration: Netherlands Trial Register—NTR2341

Physical activity in patients with cancer: self-report versus accelerometer assessments

Purpose: The level of daily physical activity in patients with cancer is frequently assessed by questionnaires, such as the Physical Activity Scale for the Elderly (PASE). Objective assessments, with for example accelerometers, may be a good alternative. The aim of this study was to investigate the agreement between the PASE questionnaire and accelerometer-assessed physical activity in a large group of patients with different types of cancer. Methods: Baseline accelerometer and PASE questionnaire data of 403 participants from the REACT (Resistance and Endurance Exercise After Chemotherapy, n = 227), the EXIST (Exercise Intervention After Stem-Cell Transplantation, n = 74), and NET-QUBIC (NEtherlands QUality of Life And Biomedical Cohort Studies In Cancer, n = 102) studies were available for the current analyses. Physical activity was assessed by the PASE questionnaire (total score) and accelerometers (total minutes per day > 100 counts). Linear mixed models regression analysis was used to assess the agreement between the PASE questionnaire and accelerometer-assessed physical activity. Results: The mean (SD) PASE score was 95.9 (75.1) points and mean (SD) time in physical activity measured with the accelerometer was 256.6 (78.8) min per day. The agreement between the PASE score and the accelerometer data was significant, but poor (standardized regression coefficient (B) = 0.36, 95%CI = 0.27; 0.44, p < 0.01). Conclusion: Agreement between the PASE questionnaire and accelerometer-assessed physical activity was poor. The poor agreement indicates that they measure different physical activity constructs and cannot be used interchangeably to assess the level of daily physical activity in patients with cancer