Towards understanding and reducing late side effects of radiotherapy in breast cancer patients

The goal of this dissertation was to gain insight in the different aspects of several late side effects in breast cancer patients who had breast-saving treatment. It appears that a higher dose of radiation (a photon boost instead of an electron boost), a larger radiation area and supplementary chemotherapies are risk factors for a cosmetically less attractive breast. Additionally, we found that our Voluntary moderately Deep Inspiration Breath Hold technique (patient holds their breath during radiation) is a simple and valuable way to reduce the radiated heart volume and therefore later-occurring cardiac damage. Lastly, we demonstrated the structural registration of late side effects through patient questionnaires ensures patients who need extra care are identified. Structural registration also makes the development of prognostic models possible as well as outcome data comparison among centres

A capability perspective on sustainable employability:A Dutch focus group study on organizational, work and personal conversion factors

Objective In the field of work, there is a shift towards more value-based approaches to study the sustainable employability of the present-day worker. The capability approach offers a value based and innovative conceptualisation and framework of sustainable employability characterized by contextuality, normativity and diversity. The capabilities of Dutch employees have been established and validated, yet it is not known which conversion factors on a personal, work and organizational level enable employees to achieve value in work in different Dutch occupational sectors. Methods Our qualitative approach included seven focus groups in different occupational sectors including elderly care, higher education, insurance work, facility management and the oil-, car- and chemical industry. Each focus group included 5–11 participants and took approximately one and a half hour. A qualitative content analysis was used to analyse the data, by combining deductive and inductive coding respectively. Deductive coding involved assigning themes to the conversion of resources into capabilities at the organizational, work and personal level. Results On the organizational conversion level, important themes were cultural aspects, power relations, shortage of personnel and policies for self-management. On the work conversion level, social contacts, communication and workload, tasks and schedules were identified. Social contacts were described as a work value in itself, but also conditional for achieving other work values. On the personal conversion level, experienced work stress, motivation and the ability to achieve values informally within the company. Conclusion From our findings it follows that focus groups are sensitive to identify conversion factors on all three levels of conversion. In addition, companies and their employees might effectively increase work capabilities by being sensitive to all three conversion levels simultaneously. Further research is necessary to study the effect of a capability-based intervention at the work floor

AGREE-S: AGREE II extension for surgical interventions - United European Gastroenterology and European Association for Endoscopic Surgery methodological guide

The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument has been developed to inform the methodology, reporting and appraisal of clinical practice guidelines. Evidence suggests that the quality of surgical guidelines can be improved, and the structure and content of AGREE II can be modified to help enhance the quality of guidelines of surgical interventions

Prognostic value of plasma lactate levels in a retrospective cohort presenting at a university hospital emergency department

OBJECTIVES: The prognostic value of lactate in the setting of an emergency department (ED) has not been studied extensively. The goal of this study was to assess 28-day mortality in ED patients in whom lactate was elevated (≥4.0 mmol/L), <4.0 mmol/L or not determined and to study the impact of the underlying cause of hyperlactatemia, that is, type A (tissue hypoxia) or type B (non-hypoxia), on mortality. DESIGN: Retrospective study. SETTING: A secondary and tertiary referral centre in the Netherlands. MATERIALS AND METHODS: All internal medicine patients with hyperlactatemia (≥4.0 mmol/L) at the ED between January 2011 and October 2014 were included in this study. Samples of patients with lactate levels <4.0 mmol/L and of patients in whom no lactate was measured were included as a reference. RESULTS: In 1144 of 19 822 patients (5.8%), lactate was measured. Hyperlactatemia (n=197) was associated with a higher 28-day mortality than in those with lactate <4.0 mmol/L (40.6% vs 18.5%; p<0.001) and in those without lactate measurements (9.5%). Type A hyperlactatemia, present in 84% of those with hyperlactatemia, was associated with higher mortality than type B hyperlactatemia (45.8% vs 12.5%, p=0.001). CONCLUSIONS: This study demonstrates that the prognostic value of lactate depends largely on the underlying cause and the population in whom lactate has been measured. Prospective studies are required to address the true added value of lactate at the ED

American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the Use of Epoetin and Darbepoetin in Adult Patients With Cancer

This guideline update addresses two clinical questions: (1) What are the defining features of patients with a malignancy who are appropriate candidates for ESA treatment? (2) For patients who are appropriate candidates for treatment with ESAs, what are the optimal approaches to ESA therapy

An evidence-based assessment of the clinical significance of drug-drug interactions between disease-modifying antirheumatic drugs and non-antirheumatic drugs according to rheumatologists and pharmacists

Background: Clinically relevant drug-drug interactions (DDIs) must be recognized in a timely manner and managed appropriately to prevent adverse drug reactions or therapeutic failure. Because the evidence for most DDIs is based on case reports or poorly documented clinical information, there is a need for better assessment of their clinical relevance. - \ud Objective: This study evaluates the interdisciplinary agreement between rheumatologists and clinical (hospital) pharmacists in assessing the clinical relevance of DDIs with disease-modifying antirheumatic drugs (DMARDs) and non-DMARD medications. - \ud Methods: Potential DDIs were identified from the medical literature using MEDLINE and EMBASE for the years 1968–2009. The following search terms were used for the key word, title, and abstract sections of the publications: interaction(s), DMARD, disease-modifying antirheumatic drug(s), antirheumatic, rheumatology, rheumatoid arthritis, and the names of the individual DMARDs of interest (abatacept, adalimumab, anakinra, auranofin, aurothioglucose, aurothiomalate, d-penicillamine, etanercept, gold, [hydroxy]-chloroquine, interleukin-1 receptor antagonist, IL1-RA, infliximab, leflunomide, methotrexate, rituximab, and sulfasalazine/sulphasalazine). Reference lists of the retrieved publications were searched for further information on potential DDIs. All pharmacodynamic or pharmacokinetic DDIs between a DMARD and a non-DMARD identified were included in the study, with the exception of evidence regarding DMARD doses higher than used in the treatment of rheumatoid arthritis and interactions with phytothera-peutic or homeopathic preparations. Using a standard information set for each DDI (eg, from product labeling, textbooks, and the medical literature), a group of rheumatologists and a group of clinical pharmacists independently assessed whether the individual drug-DMARD combinations interacted and whether they required immediate intervention. Both groups consisted of 3 members (2 men and 1 woman), aged 40 to 60 years, who had >5 years of clinical experience and were currently involved in clinical practice in large, nonacademic teaching hospitals in the Netherlands. - \ud Results: Forty potential DDIs with DMARDs were retrieved and assessed by the 2 groups. For 30 (75%) of these, rheumatologists and clinical pharmacists agreed about the requirement for immediate intervention. Specifically, 17 drug combinations (43%) were judged to interact and to require immediate intervention, and 13 combinations (33%) were judged either not to interact or to interact but not to require immediate intervention. For 10 combinations (25%), rheu-matologists and clinical pharmacists were not in agreement. Overall, agreement between the groups was good (κ = 0.80) for judging whether the drug combinations were interactions, and agreement was fair (κ = 0.39) for judging whether immediate intervention was required. Prospective analysis of the data showed that rheumatologists tended to recommend immediate intervention more often when the adverse reaction to the DDI involved an increased risk of tox-icity of the DMARD. In contrast, clinical pharmacists more often advocated immediate intervention when the adverse reaction involved decreased effectiveness of the DMARD. - \ud Conclusion: For a subset of DMARD-drug combinations, rheumatologists and clinical pharmacists differed in their assessments of clinical relevance

Signaling by the Matrix Proteoglycan Decorin Controls Inflammation and Cancer Through PDCD4 and MicroRNA-21.

International audienceThe mechanisms linking immune responses and inflammation with tumor development are not well understood. Here, we show that the soluble form of the extracellular matrix proteoglycan decorin controls inflammation and tumor growth through PDCD4 (programmed cell death 4) and miR-21 (microRNA-21) by two mechanisms. First, decorin acted as an endogenous ligand of Toll-like receptors 2 and 4 and stimulated production of proinflammatory molecules, including PDCD4, in macrophages. Second, decorin prevented translational repression of PDCD4 by decreasing the activity of transforming growth factor-β1 and the abundance of oncogenic miR-21, a translational inhibitor of PDCD4. Moreover, increased PDCD4 abundance led to decreased release of the anti-inflammatory cytokine interleukin-10, thereby making the cytokine profile more proinflammatory. This pathway operates in both pathogen-mediated and sterile inflammation, as shown here for sepsis and growth retardation of established tumor xenografts, respectively. Decorin was an early response gene evoked by septic inflammation, and protein concentrations of decorin were increased in the plasma of septic patients and mice. In cancer, decorin reduced the abundance of anti-inflammatory molecules and increased that of proinflammatory molecules, thereby shifting the immune response to a proinflammatory state associated with reduced tumor growth. Thus, by stimulating proinflammatory PDCD4 and decreasing the abundance of miR-21, decorin signaling boosts inflammatory activity in sepsis and suppresses tumor growth