Effectiveness of a web-based health risk assessment with individually-tailored feedback on lifestyle behaviour: study protocol

<p>Abstract</p> <p>Background</p> <p>Physical inactivity, unhealthy dietary habits, smoking and high alcohol consumption are recognized risk factors for cardiovascular disease and cancer. Web-based health risk assessments with tailored feedback seem promising in promoting a healthy lifestyle. This study evaluates the effectiveness of a web-based health risk assessment with individually-tailored feedback on lifestyle behaviour, conducted in a worksite setting.</p> <p>Methods/Design</p> <p>The web-based health risk assessment starts with a questionnaire covering socio-demographic variables, family and personal medical history, lifestyle behaviour and psychological variables. Prognostic models are used to estimate individual cardiovascular risks. In case of high risk further biometric and laboratory evaluation is advised. All participants receive individually-tailored feedback on their responses to the health risk assessment questionnaire. The study uses a quasi-experimental design with a waiting list control group. Data are collected at baseline (T0) and after six months (T1). Within each company, clusters of employees are allocated to either the intervention or the control group. Primary outcome is lifestyle behaviour, expressed as the sum of five indicators namely physical activity, nutrition, smoking behaviour, alcohol consumption, and symptoms of burnout. Multilevel regression analysis will be used to answer the main research question and to correct for clustering effects. Baseline differences between the intervention and control group in the distribution of characteristics with a potential effect on lifestyle change will be taken into account in further analyses using propensity scores.</p> <p>Discussion</p> <p>This study will increase insight into the effectiveness of health risk assessments with tailored feedback and into conditions that may modify the effectiveness. This information can be used to design effective interventions for lifestyle behaviour change among employees.</p> <p>Trial registration</p> <p>Dutch Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=NTR8148">NTR8148</a>.</p

Phase II Feasibility and Biomarker Study of Neoadjuvant Trastuzumab and Pertuzumab With Chemoradiotherapy for Resectable Human Epidermal Growth Factor Receptor 2-Positive Esophageal Adenocarcinoma:TRAP Study

PURPOSE: Approximately 15% to 43% of esophageal adenocarcinomas (EACs) are human epidermal growth factor receptor 2 (HER2) positive. Because dual-agent HER2 blockade demonstrated a survival benefit in breast cancer, we conducted a phase II feasibility study of trastuzumab and pertuzumab added to neoadjuvant chemoradiotherapy (nCRT) in patients with EAC. PATIENTS AND METHODS: Patients with resectable HER2-positive EAC received standard nCRT with carboplatin and paclitaxel and 41.4 Gy of radiotherapy, with 4 mg/kg of trastuzumab on day 1, 2 mg/kg per week during weeks 2 to 6, and 6 mg/kg per week during weeks 7, 10, and 13 and 840 mg of pertuzumab every 3 weeks. The primary end point was feasibility, defined as ≥ 80% completion of treatment with both trastuzumab and pertuzumab. An exploratory comparison of survival with a propensity score-matched cohort receiving standard nCRT was performed, as were exploratory pharmacokinetic and biomarker analyses. RESULTS: Of the 40 enrolled patients (78% men; median age, 63 years), 33 (83%) completed treatment with trastuzumab and pertuzumab. No unexpected safety events were observed. R0 resection was achieved in all patients undergoing surgery, with pathologic complete response in 13 patients (34%). Three-year progression-free and overall survival (OS) were 57% and 71%, respectively (median follow-up, 32.1 months). Compared with the propensity score-matched cohort, a significantly longer OS was observed with HER2 blockade (hazard ratio, 0.58; 95% CI, 0.34 to 0.97). Results of pharmacokinetic analysis and activity on [18F]fluorodeoxyglucose positron emission tomography scans did not correlate with survival or pathologic response. Patients with HER2 3+ overexpression or growth factor receptor-bound protein 7 (Grb7) -positive tumors at baseline demonstrated significantly better survival (P = .007) or treatment response (P = .016), respectively. CONCLUSION: Addition of trastuzumab and pertuzumab to nCRT in patients with HER2-positive EAC is feasible and demonstrates potentially promising activity compared with historical controls. HER2 3+ overexpression and Grb7 positivity are potentially predictive for survival and treatment response, respectively

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative

Background: The increasing sub-classification of cancer patients due to more detailed molecular classification of tumors, and limitations of current trial designs, require innovative research designs. We present the design, governance and current standing of three comprehensive nationwide cohorts including pancreatic, esophageal/gastric, and colorectal cancer patients (NCT02070146). Multidisciplinary collection of clinical data, tumor tissue, blood samples, and patient-reported outcome (PRO) measures with a nationwide coverage, provides the infrastructure for future and novel trial designs and facilitates research to improve outcomes of gastrointestinal cancer patients. Material and methods: All patients aged ≥18 years with pancreatic, esophageal/gastric or colorectal cancer are eligible. Patients provide informed consent for: (1) reuse of clinical data; (2) biobanking of primary tumor tissue; (3) collection of blood samples; (4) to be informed about relevant newly identified genomic aberrations; (5) collection of longitudinal PROs; and (6) to receive information on new interventional studies and possible participation in cohort multiple randomized controlled trials (cmRCT) in the future. Results: In 2015, clinical data of 21,758 newly diagnosed patients were collected in the Netherlands Cancer Registry. Additional clinical data on the surgical procedures were registered in surgical audits for 13,845 patients. Within the first two years, tumor tissue and blood samples were obtained from 1507 patients; during this period, 1180 patients were included in the PRO registry. Response rate for PROs was 90%. The consent rate to receive information on new interventional studies and possible participation in cmRCTs in the future was >85%. The number of hospitals participating in the cohorts is steadily increasing. Conclusion: A comprehensive nationwide multidisciplinary gastrointestinal cancer cohort is feasible and surpasses the limitations of classical study designs. With this initiative, novel and innovative studies can be performed in an efficient, safe, and comprehensive setting

Thrombin-Fibrin(ogen) Interactions, Host Defense and Risk of Thrombosis

Fibrinogen is a well-known risk factor for arterial and venous thrombosis. Its function is not restricted to clot formation, however, as it partakes in a complex interplay between thrombin, soluble plasma fibrinogen, and deposited fibrin matrices. Fibrinogen, like thrombin, participates predominantly in hemostasis to maintain vascular integrity, but executes some important pleiotropic effects: firstly, as observed in thrombin generation experiments, fibrin removes thrombin from free solution by adsorption. The adsorbed thrombin is protected from antithrombins, notably α2-macroglobulin, and remains physiologically active as it can activate factors V, VIII, and platelets. Secondly, immobilized fibrinogen or fibrin matrices activate monocytes/macrophages and neutrophils via Mac-1 interactions. Immobilized fibrin(ogen) thereby elicits a pro-inflammatory response with a reciprocal stimulating effect of the immune system on coagulation. In contrast, soluble fibrinogen prohibits recruitment of these immune cells. Thus, while fibrin matrices elicit a procoagulant response, both directly by protecting thrombin and indirectly through the immune system, high soluble fibrinogen levels might protect patients due to its immune diminutive function. The in vivo influence of the ‘protective’ plasma fibrinogen versus the ‘pro-thrombotic’ fibrin matrices on thrombosis should be explored in future research

The needs of patients with cardiovascular disease and healthcare professionals with regard to communication and collaboration on work participation and return-to-work.

Applied Ergonomics and Desig

Supporting work participation for clients with cardiovascular disease: Exploring the patients' experiences and needs using client experience journey mapping.

Applied Ergonomics and Desig

Extensive variability of work participation outcomes measured in randomized controlled trials: a systematic review

OBJECTIVE: To investigate how work participation outcomes in randomized controlled trials are measured internationally and across disciplines. STUDY DESIGN AND SETTING: We identified trials that reported on work participation in Medline, Embase, PsycINFO and Cochrane Central published between 2014 and 2019. Screening, selection, and data extraction were done by two authors independently. We grouped outcomes into four categories ("employment status", "absence from work", "at-work productivity loss," and "employability") and created subcategories according to how the outcome was measured. RESULTS: From 10,022 database hits we selected 269 trials reporting on 435 work participation outcomes. Authors used inconsistent outcome terminology to describe the measured constructs. Grouped in four main categories we identified 70 outcomes that reported on "employment status", 196 on "absence from work" and return-to-work, 132 on "at-work productivity loss," and 37 on "employability" outcomes. Variability in measurement methods existed across all categories. Employment status and absenteeism measures consisted mostly of clinimetrically unvalidated tools. "At-work productivity loss" and "employability" were measured by at least 41 different questionnaires. CONCLUSION: Extensive variability exists among trials in the measurement of outcomes, measurement methods and measurement instruments that focus on work participation. This study is a first step towards the development of a Core Outcome Set for work participation

Extensive variability of work participation outcomes measured in randomized controlled trials: a systematic review

OBJECTIVE: To investigate how work participation outcomes in randomized controlled trials are measured internationally and across disciplines. STUDY DESIGN AND SETTING: We identified trials that reported on work participation in Medline, Embase, PsycINFO and Cochrane Central published between 2014 and 2019. Screening, selection, and data extraction were done by two authors independently. We grouped outcomes into four categories ("employment status", "absence from work", "at-work productivity loss," and "employability") and created subcategories according to how the outcome was measured. RESULTS: From 10,022 database hits we selected 269 trials reporting on 435 work participation outcomes. Authors used inconsistent outcome terminology to describe the measured constructs. Grouped in four main categories we identified 70 outcomes that reported on "employment status", 196 on "absence from work" and return-to-work, 132 on "at-work productivity loss," and 37 on "employability" outcomes. Variability in measurement methods existed across all categories. Employment status and absenteeism measures consisted mostly of clinimetrically unvalidated tools. "At-work productivity loss" and "employability" were measured by at least 41 different questionnaires. CONCLUSION: Extensive variability exists among trials in the measurement of outcomes, measurement methods and measurement instruments that focus on work participation. This study is a first step towards the development of a Core Outcome Set for work participation

Rotational Thromboelastometry in High-Risk Patients on Dual Antithrombotic Therapy After Percutaneous Coronary Intervention

Aims: Patients using antithrombotic drugs after percutaneous coronary intervention (PCI) are at risk for bleeding and recurrent ischemia. We aimed to explore routine and tissue plasminogen activated (tPA) ROTEM results in a post-PCI population on dual antithrombotic treatment. Methods and Results: In this prospective cohort, 440 patients treated with double antithrombotic therapy after recent PCI and with ≥3 risk factors for either ischemic or bleeding complications were included and compared with a control group (n = 95) consisting of perioperative patients not using antithrombotic medication. Laboratory assessment, including (tPA) ROTEM, was performed one month post-PCI and bleeding/ischemic complications were collected over a five-month follow-up. Patients were stratified by antithrombotic regimen consisting of a P2Y12 inhibitor with either aspirin (dual antiplatelet therapy; DAPT, n = 323), a vitamin K antagonist (VKA, n = 69) or a direct oral anticoagulant (DOAC, n = 48). All post-PCI patients had elevated ROTEM clot stiffness values, but only the DAPT group additionally presented with a decreased fibrinolytic potential as measured with tPA ROTEM. Patients receiving anticoagulants had prolonged clotting times (CT) when compared to the control and DAPT group; EXTEM and FIBTEM CT could best discriminate between patients (not) using anticoagulants (AUC > 0.97). Furthermore, EXTEM CT was significantly prolonged in DAPT patients with bleeding complications during follow-up (68 [62–70] vs. 62 [57–68], p = 0.030). Conclusion: ROTEM CT has high potential for identifying anticoagulants and tPA ROTEM could detect a diminished fibrinolytic potential in patients using DAPT. Furthermore, the ability of EXTEM CT to identify patients at risk for bleeding may be promising and warrants further research