Advanced breast cancer and its prevention by screening.

In discussions on breast cancer screening, much attention has been focussed on the possible morbidity generated by screening. Favourable effects like the prevention of advanced disease seem underestimated, probably because quantification is that difficult. To analyse the amount of care and treatment given to women with advanced breast cancer, we report on patients followed from first recurrence until death using patient files and national sources. A random sample of 60 female cases from computerised registries of two cancer centres and a sample of 20 cases from a non-computerised hospital registry was taken. A total of 68 patient files were sufficiently documented. A woman with advanced breast cancer is estimated to have a 39% loss in utility compared to a healthy woman (range 27-45%). Hormonal treatment is the main modality during 14 and chemotherapy during 4 months. Total medical cost from diagnosis of advanced disease until death amounts to 17,100 US dollars, or 21,000 when including extramural cost. The effect of breast cancer screening by preventing the occurrence of advanced disease is quantified. The resulting gain in quality of life contributes 70% of the total gain in quality of life. In the long run, almost half of the annual cost of screening will be offset by savings in the cost for advanced disease. Only the changes in palliative surgery and/or radiotherapy will be small in contrast to primary treatment changes. Besides the mortality reduction, screening is justified by the improvements in quality of life and cost savings for women prevented from reaching advanced disease

The application of the tracer method with peer observation and formative feedback for professional development in clinical practice:a scoping review

INTRODUCTION: The tracer method, commonly used for quality assessment, can also be used as a tool for peer observation and formative feedback on professional development. This scoping review describes how, by whom, and with what effect the tracer method is applied as a formative professional development instrument between healthcare professionals of equal status and aims to identify the types of scientific evidence for this use of the tracer method. METHODS: The authors searched four electronic databases for eligible articles, which were screened and assessed for eligibility by two independent researchers. From eligible studies, data were extracted to summarize, collate, and make a narrative account of the findings. RESULTS: The electronic search yielded 1757 unique studies, eight of which were included as valid and relevant to our aim: five qualitative, two mixed methods, and one quantitative study. Seven studies took place in hospitals and one in general practice. The tracer method was used mainly as a form of peer observation and formative feedback. Most studies evaluated the tracer method’s feasibility and its impact on professional development. All but one study reported positive effects: participants described the tracer method generally as being valuable and worth continuing. DISCUSSION: Although the body of evidence is small and largely limited to the hospital setting, using the tracer method for peer observation and formative feedback between healthcare professionals of equal status appears sufficiently useful to merit further rigorous evaluation and implementation in continuous professional development in healthcare. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s40037-021-00693-6) contains supplementary material, which is available to authorized users

Two Decades of Research on Euthanasia from the Netherlands. What Have We Learnt and What Questions Remain?

Two decades of research on euthanasia in the Netherlands have resulted into clear insights in the frequency and characteristics of euthanasia and other medical end-of-life decisions in the Netherlands. These empirical studies have contributed to the quality of the public debate, and to the regulating and public control of euthanasia and physician-assisted suicide. No slippery slope seems to have occurred. Physicians seem to adhere to the criteria for due care in the large majority of cases. Further, it has been shown that the majority of physicians think that the euthanasia Act has improved their legal certainty and contributes to the carefulness of life-terminating acts. In 2005, eighty percent of the euthanasia cases were reported to the review committees. Thus, the transparency envisaged by the Act still does not extend to all cases. Unreported cases almost all involve the use of opioids, and are not considered to be euthanasia by physicians. More education and debate is needed to disentangle in these situations which acts should be regarded as euthanasia and which should not. Medical end-of-life decision-making is a crucial part of end-of-life care. It should therefore be given continuous attention in health care policy and medical training. Systematic periodic research is crucial for enhancing our understanding of end-of-life care in modern medicine, in which the pursuit of a good quality of dying is nowadays widely recognized as an important goal, in addition to the traditional goals such as curing diseases and prolonging life

The identification of small molecule inhibitors that reduce invasion and metastasis of aggressive cancers

Transformed epithelial cells can activate programs of epithelial plasticity and switch from a sessile, epithelial phenotype to a motile, mesenchymal phenotype. This process is linked to the acquisition of an invasive phenotype and the formation of distant metastases. The development of compounds that block the acquisition of an invasive phenotype or revert the invasive mesenchymal phenotype into a more differentiated epithelial phenotype represent a promising anticancer strategy. In a high-throughput assay based on E-cadherin (re)induction and the inhibition of tumor cell invasion, 44,475 low molecular weight (LMW) compounds were screened. The screening resulted in the identification of candidate compounds from the PROAM02 class. Selected LMW compounds activated E-cadherin promoter activity and inhibited cancer cell invasion in multiple metastatic human cancer cell lines. The intraperitoneal administration of selected LMW compounds reduced the tumor burden in human prostate and breast cancer in vivo mouse models. Moreover, selected LMW compounds decreased the intra-bone growth of xenografted human prostate cancer cells. This study describes the identification of the PROAM02 class of small molecules that can be exploited to reduce cancer cell invasion and metastases. Further clinical evaluation of selected candidate inhibitors is warranted to address their safety, bioavailability and antitumor efficacy in the management of patients with aggressive cancers.Prostatic carcinom

Molecular and cellular signatures underlying superior immunity against Bordetella pertussis upon pulmonary vaccination

Mucosal immunity is often required for protection against respiratory pathogens but the underlying cellular and molecular mechanisms of induction remain poorly understood. Here, systems vaccinology was used to identify immune signatures after pulmonary or subcutaneous immunization of mice with pertussis outer membrane vesicles. Pulmonary immunization led to improved protection, exclusively induced mucosal immunoglobulin A (IgA) and T helper type 17 (Th17) responses, and in addition evoked elevated systemic immunoglobulin G (IgG) antibody levels, IgG-producing plasma cells, memory B cells, and Th17 cells. These adaptive responses were preceded by unique local expression of genes of the innate immune response related to Th17 (e.g., Rorc) and IgA responses (e.g., Pigr) in addition to local and systemic secretion of Th1/Th17-promoting cytokines. This comprehensive systems approach identifies the effect of the administration route on the development of mucosal immunity, its importance in protection against Bordetella pertussis, and reveals potential molecular correlates of vaccine immunity to this reemerging pathogen.Drug Delivery Technolog