Purpose The Trials within Cohorts (TwiCs) design aims to overcome problems faced in conventional RCTs. We evaluated the TwiCs design when estimating the effect of exercise on quality of life (QoL)... Show morePurpose The Trials within Cohorts (TwiCs) design aims to overcome problems faced in conventional RCTs. We evaluated the TwiCs design when estimating the effect of exercise on quality of life (QoL) and fatigue in inactive breast cancer survivors. Methods UMBRELLA Fit was conducted within the prospective UMBRELLA breast cancer cohort. Patients provided consent for future randomization at cohort entry. We randomized inactive patients 12-18 months after cohort enrollment. The intervention group (n = 130) was offered a 12-week supervised exercise intervention. The control group (n = 130) was not informed and received usual care. Six-month exercise effects on QoL and fatigue as measured in the cohort were analyzed with intention-to-treat (ITT), instrumental variable (IV), and propensity scores (PS) analyses. Results Fifty-two percent (n = 68) of inactive patients accepted the intervention. Physical activity increased in patients in the intervention group, but not in the control group. We found no benefit of exercise for dimensions of QoL (ITT difference global QoL: 0.8, 95% CI = - 2.2; 3.8) and fatigue, except for a small beneficial effect on physical fatigue (ITT difference: - 1.1, 95% CI = - 1.8; - 0.3; IV: - 1.9, 95% CI = - 3.3; - 0.5, PS: - 1.2, 95% CI = - 2.3; - 0.2). Conclusion TwiCs gave insight into exercise intervention acceptance: about half of inactive breast cancer survivors accepted the offer and increased physical activity levels. The offer resulted in no improvement on QoL, and a small beneficial effect on physical fatigue. Show less
BackgroundAn efficient diagnostic pathway and early stage diagnosis for cancer patients is widely pursued. This study aims to chart the duration of the diagnostic pathway for patients with... Show moreBackgroundAn efficient diagnostic pathway and early stage diagnosis for cancer patients is widely pursued. This study aims to chart the duration of the diagnostic pathway for patients with symptomatic oesophageal and gastric cancer, to identify factors associated with long duration and to assess the association of duration with tumour stage at diagnosis.MethodsThis was a retrospective cohort study, using electronic health records of six routine primary care databases covering about 640,000 patients, partly linked to the Netherlands Cancer Registry. Symptomatic patients with oesophageal and gastric cancer (2010-2015) that presented in primary care were included. Duration of four diagnostic intervals was determined: patient interval; first symptoms to primary care consultation, primary care interval; consultation to referral, secondary care interval; referral to diagnosis, and the diagnostic interval; consultation to diagnosis. Characteristics associated with 'long duration' (>= P75 duration) were assessed using log-binomial regression. Median durations were stratified for tumour stages.ResultsAmong 312 symptomatic patients with upper gastrointestinal cancer, median durations were: patient interval: 29 days (interquartile interval 15-73), primary care interval: 12 days (interquartile interval 1-43), secondary care interval: 13 days (interquartile interval 6-29) and diagnostic interval: 31 days (11-74). Patient interval duration was comparable for patients with and without alarm symptoms. Absence of cancer-specific alarm symptoms was associated with 'long duration' of primary care interval and secondary care interval: relative risk 5.0 (95% confidence interval 2.7-9.1) and 2.1 (95% confidence interval 1.3-3.7), respectively. Median diagnostic interval duration for local stage disease was 51 days (interquartile interval 13-135) versus 27 days (interquartile interval 11-71) for advanced stage (p = 0.07).ConclusionIn the diagnostic pathway of upper gastrointestinal cancers, the longest interval is the patient interval. Reducing time to diagnosis may be achieved by improving patients' awareness of alarm symptoms and by diagnostic strategies which better identify cancer patients despite low suspicion. Show less
Gal, R.; Monninkhof, E.M.; Gils, C.H. van; Groenwold, R.H.H.; Bongard, D.H.J.G. van den; Peeters, P.H.M.; ... ; May, A.M. 2019
Objectives: The Trials within Cohorts (TwiCs) design is an alternative for pragmatic randomized controlled trials (RCTs) and might overcome disadvantages such as difficult recruitment, dropout... Show moreObjectives: The Trials within Cohorts (TwiCs) design is an alternative for pragmatic randomized controlled trials (RCTs) and might overcome disadvantages such as difficult recruitment, dropout after randomization to control, and contamination. We investigated the applicability of the TwiCs design in an exercise oncology study regarding the recruitment process, representativeness of the study sample, contamination, participation, and dropout.Methods: The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA) Fit TwiCs evaluates an exercise intervention in inactive breast cancer patients. Eligible patients participating in the prospective UMBRELLA were identified and randomized. Patients randomized to the intervention (n = 130) were offered the intervention, whereas controls (n = 130) were not informed.Results: Fifty-two percent (n = 68) accepted the intervention. Because this rate was lower than expected, a larger sample size was required than initially estimated (n = 166). However, recruitment of 260 patients was still completed by one researcher within 30 months. Unselective eligibility screening and randomization before invitation improved representativeness. Disadvantage of the design might be inclusion of ineligible patients when cohort information is limited. Furthermore, the design faced higher noncompliance in the intervention group, but prevention of contamination.Conclusion: The TwiCs design improved logistics in recruitment and prevented contamination, but noncompliance due to refusal of the intervention was higher compared with conventional pragmatic exercise oncology RCTs, which may dilute the estimated intervention effect. (C) 2019 The Authors. Published by Elsevier Inc. Show less
