Development and use of a flexible data harmonization platform to facilitate the harmonization of individual patient data for meta-analyses.

OBJECTIVE: Harmonizing individual patient data (IPD) for meta-analysis has clinical and statistical advantages. Harmonizing IPD from multiple studies may benefit from a flexible data harmonization platform (DHP) that allows harmonization of IPD already during data collection. This paper describes the development and use of a flexible DHP that was initially developed for the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) study. RESULTS: The DHP that we developed (I) allows IPD harmonization with a flexible approach, (II) has the ability to store data in a centralized and secured database server with large capacity, (III) is transparent and easy in use, and (IV) has the ability to export harmonized IPD and corresponding data dictionary to a statistical program. The DHP uses Microsoft Access as front-end application and requires a relational database management system such as Microsoft Structured Query Language (SQL) Server or MySQL as back-end application. The DHP consists of five user friendly interfaces which support the user to import original study data, to harmonize the data with a master data dictionary, and to export the harmonized data into a statistical software program of choice for further analyses. The DHP is now also adopted in two other studies.

Which exercise prescriptions improve quality of life and physical function in patients with cancer during and following treatment? A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: Certain exercise prescriptions for patients with cancer may improve self-reported quality of life (QoL) and self-reported physical function (PF). We investigated the effects of exercise on QoL and PF in patients with cancer and studied differences in effects between different intervention-related and exercise-related characteristics. DESIGN: We searched four electronic databases to identify randomised controlled trials investigating exercise effects on QoL and PF in patients with cancer. Pooled effects (Hedges' g) were calculated using Comprehensive Meta-Analysis software. Subgroup analyses were conducted based on intervention dimensions, including timing, duration and delivery mode, and exercise dimensions, including frequency, intensity, type and time (FITT factors). RESULTS: We included 74 exercise arms. Patients who were randomised to exercise interventions had significantly improved QoL (g=0.15, 95% CI (0.10 to 0.20), n=67 exercise arms) and PF (g=0.21, 95% CI (0.15 to 0.27), n=59 exercise arms) compared with patients in control groups. We found a significant between-group difference for exercise delivery mode, with significant beneficial effects for supervised exercise interventions (g=0.20, 95% CI (0.14 to 0.26) for QoL and g=0.27, 95% CI (0.20 to 0.33) for PF), but not for unsupervised interventions (g=0.04, 95% CI (-0.06 to 0.13) for QoL and g=0.09, 95% CI (-0.01 to 0.19) for PF). No statistically significant differences in intervention effects were found for variations in intervention timing, duration or exercise FITT factors. Unsupervised exercise with higher weekly energy expenditure was more effective than unsupervised exercise with lower energy expenditure (z=2.34, p=0.02). CONCLUSIONS: Exercise interventions, especially when supervised, have statistically significant and small clinical benefit on self-reported QoL and PF in patients with cancer. Unsupervised exercise intervention effects on PF were larger when prescribed at a higher weekly energy expenditure.

Identifying and sharing data for secondary data analysis of physical activity, sedentary behaviour and their determinants across the life course in Europe: general principles and an example from DEDIPAC.

BACKGROUND: The utilisation of available cross-European data for secondary data analyses on physical activity, sedentary behaviours and their underlying determinants may benefit from the wide variation that exists across Europe in terms of these behaviours and their determinants. Such reuse of existing data for further research requires Findable; Accessible; Interoperable; Reusable (FAIR) data management and stewardship. We here describe the inventory and development of a comprehensive European dataset compendium and the process towards cross-European secondary data analyses of pooled data on physical activity, sedentary behaviour and their correlates across the life course. METHODS: A five-step methodology was followed by the European Determinants of Diet and Physical Activity (DEDIPAC) Knowledge Hub, covering the (1) identification of relevant datasets across Europe, (2) development of a compendium including details on the design, study population, measures and level of accessibility of data from each study, (3) definition of key topics and approaches for secondary analyses, (4) process of gaining access to datasets and (5) pooling and harmonisation of the data and the development of a data harmonisation platform. RESULTS: A total of 114 unique datasets were found for inclusion within the DEDIPAC compendium. Of these datasets, 14 were eventually obtained and reused to address 10 exemplar research questions. The DEDIPAC data harmonisation platform proved to be useful for pooling, but in general, harmonisation was often restricted to just a few core (crude) outcome variables and some individual-level sociodemographic correlates of these behaviours. CONCLUSIONS: Obtaining, pooling and harmonising data for secondary data analyses proved to be difficult and sometimes even impossible. Compliance to FAIR data management and stewardship principles currently appears to be limited for research in the field of physical activity and sedentary behaviour. We discuss some of the reasons why this might be the case and present recommendations based on our experience.

Rigid shoulder taping with physiotherapy in patients with subacromial pain syndrome: A randomized controlled trial.

OBJECTIVE: To assess the effectiveness of individualized physiotherapy in combination with rigid taping compared with individualized physiotherapy alone in patients with subacromial pain syndrome. DESIGN: A prospective randomized trial with concealed allocation. PATIENTS: A total of 140 patients between 18 and 65 years of age from primary physiotherapy settings. METHODS: The intervention group received individualized physiotherapy and shoulder taping. The control group received individualized physiotherapy only. Primary outcomes were: pain intensit (numerical rating scale) and functioning (Simple Shoulder Test). Secondary outcomes were: global perceived effect and patient-specific complaints. Data were collected at baseline, and at 4, 12 and 26 weeks' follow-up. RESULTS: During the 6-month follow-up period multilevel analysis showed a significant difference between groups favouring the control group on pain intensity (p = 0.02), but not on functioning. Regarding secondary outcomes, a significant difference between groups was found favouring the intervention group for global perceived effect (p = 0.02), but not for patient-specific complaints. CONCLUSION: Rigid shoulder taping, as used in this study, cannot be recommended for improving physiotherapy outcomes in people with subacromial pain syndrome.

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=4519 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 (ß=0.15, 95%CI=0.10;0.20) and PF (ß=0.18, 95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (ßdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (ßdifference_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.

Mediators of Exercise Effects on HRQoL in Cancer Survivors after Chemotherapy.

PURPOSE: We investigated the hypothesis that combined resistance and endurance exercise improves cardiorespiratory fitness and muscle strength, thereby reducing fatigue and improving global quality of life (QoL) and physical function among cancer survivors who completed curative treatment including chemotherapy. METHODS: Cancer survivors were assigned to a 12-wk exercise intervention (n = 186) or a wait list control group (n = 91). Data were collected at baseline and after 12 wk. Path analyses using follow-up values adjusted for baseline values, age, and gender were conducted to test if the exercise effects on global QoL and physical function (European Organization Research and Treatment of Cancer Quality of Life questionnaire-Core 30) were mediated by changes in cardiorespiratory fitness (peak V˙O2), hand-grip strength, lower body muscle function (30-s chair stand test), and fatigue (Multidimensional Fatigue Inventory). RESULTS: Compared with the wait list control, exercise increased cardiorespiratory fitness (ß = 1.8; 95% confidence interval (CI), 1.0-2.6 mL·kg·min) and reduced general (ß = -1.0; 95% CI, -1.8 to -0.2) and physical fatigue (ß = -1.5; 95% CI, -2.3 to -0.6). The exercise effect on physical fatigue was mediated by change in cardiorespiratory fitness (ß = -0.2; 95% CI, -0.4 to -0.1). Higher hand-grip strength was significantly associated with lower physical fatigue and better lower body muscle function with lower physical and general fatigue. Lower general fatigue and physical fatigue were significantly associated with higher global QoL (ß = -1.6; 95% CI, -2.2 to -1.1; and ß = -1.7; 95% CI, -2.3 to -1.1, respectively) and physical function (ß = -1.0; 95% CI, -1.3 to -0.7; and ß = -1.2; 95% CI, -1.6 to -0.9, respectively). The models explained 44%-61% of the variance in global QoL and physical function. CONCLUSION: Beneficial effects of exercise on global QoL and physical function in cancer survivors were mediated by increased cardiorespiratory fitness and subsequent reductions in fatigue.

Moderators of the effects of group-based physical exercise on cancer survivors' quality of life.

PURPOSE: This study explored demographic, clinical, and psychological moderators of the effect of a group-based physical exercise intervention on global quality of life (QoL) among cancer survivors who completed treatment. METHODS: Cancer survivors were assigned to a 12-week physical exercise (n = 147) or a wait-list control group (n = 62). The main outcome measure was global QoL, assessed with the EORTC QLQ-C30 at baseline and 12 weeks later. Potential moderators were age, gender, education level, marital status, employment status, type of treatment, time since treatment, the presence of comorbidities, fatigue, general self-efficacy, depression, and anxiety. Linear regression analyses were used to test effect modification of the intervention by each moderator variable using interaction tests (p ≤ 0.10). RESULTS: The physical exercise intervention effect on global QoL was larger for cancer survivors who received radiotherapy (ß = 10.3, 95 % confidence interval (CI) = 4.4; 16.2) than for cancer survivors who did not receive radiotherapy (ß = 1.8, 95 % CI = -5.9; 9.5, p interaction = 0.10), larger for cancer survivors who received a combination of chemoradiotherapy (ß = 13.0, 95 % CI = 6.0; 20.1) than for those who did not receive this combination of treatments (ß = 2.5, 95 % CI = -3.7; 8.7, p interaction = 0.02), and larger for cancer survivors with higher baseline levels of fatigue (ß = 12.6, 95 % CI = 5.7; 19.6) than for those with lower levels (ß = 2.4, 95 % CI = -3.9; 8.7, p interaction = 0.03). No other moderating effects were found. CONCLUSIONS: This study suggests that cancer treatment modality and baseline fatigue levels moderate the effect of a physical exercise program on cancer survivors'global QoL.

Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS): rationale and design for meta-analyses of individual patient data of randomized controlled trials that evaluate the effect of physical activity and psychosocial interventions on health-related quality of life in cancer survivors.

BACKGROUND: Effective interventions to improve quality of life of cancer survivors are essential. Numerous randomized controlled trials have evaluated the effects of physical activity or psychosocial interventions on health-related quality of life of cancer survivors, with generally small sample sizes and modest effects. Better targeted interventions may result in larger effects. To realize such targeted interventions, we must determine which interventions that are presently available work for which patients, and what the underlying mechanisms are (that is, the moderators and mediators of physical activity and psychosocial interventions). Individual patient data meta-analysis has been described as the 'gold standard' of systematic review methodology. Instead of extracting aggregate data from study reports or from authors, the original research data are sought directly from the investigators. Individual patient data meta-analyses allow for adequate statistical analysis of intervention effects and moderators of such effects.Here, we report the rationale and design of the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) Consortium. The primary aim of POLARIS is 1) to conduct meta-analyses based on individual patient data to evaluate the effect of physical activity and psychosocial interventions on the health-related quality of life of cancer survivors; 2) to identify important demographic, clinical, personal, or intervention-related moderators of the effect; and 3) to build and validate clinical prediction models identifying the most relevant predictors of intervention success. METHODS/DESIGN: We will invite investigators of randomized controlled trials that evaluate the effects of physical activity and/or psychosocial interventions on health-related quality of life compared with a wait-list, usual care or attention control group among adult cancer survivors to join the POLARIS consortium and share their data for use in pooled analyses that will address the proposed aims. We are in the process of identifying eligible randomized controlled trials through literature searches in four databases. To date, we have identified 132 eligible and unique trials. DISCUSSION: The POLARIS consortium will conduct the first individual patient data meta-analyses in order to generate evidence essential to targeting physical activity and psychosocial programs to the individual survivor's characteristics, capabilities, and preferences. REGISTRATION PROSPERO: International prospective register of systematic reviews, CRD42013003805.

Taping patients with clinical signs of subacromial impingement syndrome: the design of a randomized controlled trial.

BACKGROUND: Shoulder problems are a common complaint of the musculoskeletal system. Physical therapists treat these patients with different modalities such as exercise, massage, and shoulder taping. Although different techniques have been described, the effectiveness of taping has not yet been established. The aim of this study is to assess the effectiveness and cost-effectiveness of usual physical therapy care in combination with a particular tape technique for subacromial impingement syndrome of the shoulder compared to usual physical therapy care without this tape technique in a primary healthcare setting. METHODS AND DESIGN: An economic evaluation alongside a randomized controlled trial will be conducted. A sample of 140 patients between 18 and 65 years of age with a diagnosis of subacromial impingement syndrome (SAIS) as assessed by physical therapists will be recruited. Eligible patients will be randomized to either the intervention group (usual care in combination with the particular tape technique) or the control group (usual care without this tape technique). In both groups, usual care will consist of individualized physical therapy care. The primary outcomes will be shoulder-specific function (the Simple Shoulder Test) and pain severity (11-point numerical rating scale). The economic evaluation will be performed using a societal perspective. All relevant costs will be registered using cost diaries. Utilities (Quality Adjusted Life Years) will be measured using the EuroQol. The data will be collected at baseline, and 4, 12, and 26 weeks follow-up. DISCUSSION: This pragmatic study will provide information about the effectiveness and cost-effectiveness of taping in patients presenting with clinical signs of SAIS. TRIAL REGISTRATION NUMBER: NTR2575.