Generation and division of excitation energy in heavy-ion collisions studied by measuring charged-particle survival fractions

Charged-particle survival fractions of primary projectile-like fragments from the 40Ar + 197Au reaction at 450 MeV were measured by using a large array of 32 phoswich detectors operating in coincidence with a detector of projectile-like fragments. Differential survival fractions of the primary pickup and stripping reaction products indicate a dependence of the average excitation energy generated in the primary fragments on the direction of the mass transfer

Rate control drugs differ in the prevention of progression of atrial fibrillation

AIMS: We hypothesize that in patients with paroxysmal atrial fibrillation (AF), verapamil is associated with lower AF progression compared to beta blockers or no rate control. METHODS AND RESULTS: In this pre-specified post hoc analysis of the RACE 4 randomized trial, the effect of rate control medication on AF progression in paroxysmal AF was analysed. Patients using Vaughan-Williams Class I or III antiarrhythmic drugs were excluded. The primary outcome was a composite of first electrical cardioversion (ECV), chemical cardioversion (CCV), or atrial ablation. Event rates are displayed using Kaplan–Meier curves and multivariable Cox regression analyses are used to adjust for baseline differences. Out of 666 patients with paroxysmal AF, 47 used verapamil, 383 used beta blockers, and 236 did not use rate control drugs. The verapamil group was significantly younger than the beta blocker group and contained more men than the no rate control group. Over a mean follow-up of 37 months, the primary outcome occurred in 17% in the verapamil group, 33% in the beta blocker group, and 33% in the no rate control group (P = 0.038). After adjusting for baseline characteristics, patients using verapamil have a significantly lower chance of receiving ECV, CCV, or atrial ablation compared to patients using beta blockers [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.19–0.83] and no rate control (HR 0.64, 95% CI 0.44–0.93). CONCLUSION: In patients with newly diagnosed paroxysmal AF, verapamil was associated with less AF progression, as compared to beta blockers and no rate control

Platelet function is disturbed by the angiogenesis inhibitors sunitinib and sorafenib, but unaffected by bevacizumab

Introduction: At the clinical introduction of antiangiogenic agents as anticancer agents, no major toxicities were expected as merely just endothelial cells (ECs) in tumors would be affected. However, several (serious) toxicities became apparent, of which underlying mechanisms are largely unknown. We investigated to what extent sunitinib (multitargeted antiangiogenic tyrosine kinase inhibitor (TKI)), sorafenib (TKI) and bevacizumab [specific antibody against vascular endothelial growth factor (VEGF)] may impair platelet function, which might explain treatment-related bleedings. Materials and methods: In vitro, the influence of sunitinib, sorafenib, and bevacizumab on platelet aggregation, P-selectin expression and fibrinogen binding, platelet–EC interaction, and tyrosine phosphorylation of c-Src was studied by optical aggregation, flow cytometry, real-time perfusion, and western blotting. Ex vivo, platelet aggregation was analyzed in 25 patients upon sunitinib or bevacizumab treatment. Concentrations of sunitinib, VEGF, and platelet and EC activation markers were measured by LC–MS/MS and ELISA. Results: In vitro, sunitinib and sorafenib significantly inhibited platelet aggregation (20 μM sunitinib: 71.3%, p < 0.001; 25 μM sorafenib: 55.8%, p = 0.042). Sorafenib and sunitinib significantly inhibited P-selectin expression on platelets. Exposure to both TKIs resulted in a reduced tyrosine phosphorylation of c-Src. Ex vivo, within 24 h sunitinib impaired platelet aggregation (83.0%, p = 0.001, N = 8). Plasma concentrations of sunitinib, VEGF, and platelet/EC activation markers were not correlated with disturbed aggregation. In contrast, bevacizumab only significantly impaired platelet aggregation in vitro at high c

Patient-reported symptoms and stepwise symptom management in patients on epidermal growth factor inhibitors : A retrospective, descriptive cohort study

Adverse events (AEs) of epidermal growth factor inhibitors (EGFRi) influence well-being with a risk to dose modifications (DMs). Hereby, clinical benefit of treatment might be affected. This retrospective cohort study was set up to gain insight into the suitability and added value of a patient-reported outcome measurement tool (PROM), together with a stepwise intervention management plan for EGFRi-related AEs in daily practice. The primary objective was to gain insight into total treatment duration and DMs, and the secondary objective to gain insight into patient-reported symptoms and well-being as well as healthcare professional-reported AEs. Sixty-eight patients on cetuximab and 19 on panitumumab treatment were included for analysis; 69% had squamous cell carcinoma of head and neck (SCCHN) and 26% metastatic colorectal carcinoma. DMs due to AEs occurred in 39% of the patients and dose discontinuations in 22%. Especially anorexia, dysphagia, oral pain and skin changes led to a decreased well-being. In patients on EGFRi, application of PROMs together with a stepwise symptom management plan enhances early recognition of symptom burden, pro-active symptom management and effect evaluation of interventions performed whereby well-being recovers. Since only SCCHN patients discontinued treatment due to AEs, patient-centred care focused on radiotherapy-related AEs, creates opportunities for amelioration

Patient-reported outcome measures in a pharmacokinetic study with sunitinib, a prospective cohort study

Purpose: During treatment with tyrosine kinase inhibitors, such as sunitinib, patients experience treatment and/or disease-related symptoms. Although application of patient-reported outcome measures (PROMs) enhances early recognition of symptoms, early clinical trials are focused on symptom severity objectified by the Common Terminology Criteria for Adverse Events (CTCAE) in order to evaluate drug safety and to determine a personalized and/or safe dosage range. To gain insight into patient-reported symptoms in addition to healthcare professional-reported adverse events (AEs), a substudy was conducted in an ongoing pharmacokinetic-guided sunitinib dosing study. Methods: In patients for whom sunitinib was considered standard therapy or patients with advanced/metastatic tumors for whom no standard therapy was available, patient-reported symptoms and well-being besides healthcare professional-reported AEs were assessed. Results: Twenty-nine patients were included for analysis. Over 50% of them experienced a decreased well-being, caused by symptoms of mild and moderate intensity. Compared to healthcare professionals, all measured symptoms, with the exception of fatigue and vomiting, were reported statistically significantly more often by patients. Conclusions: Application of PROMs in early clinical trials on personalized or individualized oral targeted anticancer agents is feasible and enhances early recognition of symptom burden due to multiple CTCAE grade 1–2 AEs, just as pro-active symptom management and effect evaluation of interventions performed. Application of PROMs in these trials might be clinically relevant in obtaining dose-limiting toxicities

End-user and Stakeholder Views on Selected Risk Assessment Tools for Marine Oil Spill Preparedness and Response, Including Future Research and Development Needs

Risks in the maritime domain have various sources, of which the transportation of oil and other noxious products is one of key concern to industry and public stakeholders. Operational or accidental releases of oil or other pollutants from ships or offshore facilities into the marine environment can have disastrous effects on the marine ecosystems, while also leading to very significant economical losses. Therefore, national states have implemented various mechanisms for preventing and responding to pollution in the maritime domain, with activities which are often embedded in regional cooperation frameworks clustered around certain sea areas. To support collaborative, harmonized, and risk-informed oil spill Pollution Preparedness and Response (PPR) planning for response authorities, the Baltic Marine Environment Protection Commission (HELCOM), together with its research partners, and with extensive end-user and stakeholder inputs, have developed the OpenRisk Toolbox. This toolbox includes several risk assessment tools and techniques, which can assist in providing answers to a range of PPR risk management questions in a range of organizational contexts. To better understand and ensure the applicability and usefulness of the OpenRisk Toolbox, a workshop was organized where some of these tools were tested. Selected end user and stakeholder views on the perceived usefulness of the tools were collected and analyzed. Another workshop focused on further development needs to implement the tools in organizational practices. This paper first presents the OpenRisk Toolbox, then describes the settings of the workshops. Finally, a summary of the end-user and stakeholder views on the tested tools, and on future development needs, is given.Peer reviewe

Predictive value of each geriatric assessment domain for older patients with cancer : A systematic review

BACKGROUND: A geriatric assessment (GA) is increasingly used to help guide treatment decisions in older patients with cancer. However, there is no consensus regarding which domains should be included in the GA. In addition, the field of geriatric oncology moves very fast and as a result many new studies have been published since the last review in 2015. Therefore, the objective of this systematic review is to evaluate which domains of the GA could predict patient-related treatment outcomes of older patients with cancer and thereby should be included in a GA. METHODS: A systematic literature search was performed for publications in English or Dutch between September 2006 and July 2017 addressing the association between individual domains of the GA and mortality, postoperative complications, or systemic treatment-related outcomes in older patients with cancer. RESULTS: Eight different domains were evaluated in 46 publications, namely functional status, nutritional status, cognition, mood, physical function, fatigue, social support, and falls. All eight domains were predictive for at least one of the investigated outcomes but the results were quite variable across studies. Physical function and nutritional status were the domains most often associated with mortality and systemic treatment-related outcomes, and the domain physical function was most often associated with postoperative complications. CONCLUSION: Overall, this review demonstrates that the GA should minimally consist of physical function and nutritional status, when the aim is to predict patients-related outcomes of older patients with cancer, although the results are quite heterogeneous. For the other domains, the findings are too inconsistent to draw conclusions about their overall predictive ability