Challenges and opportunities related to the creation of a unique society of specialists in general internal medicine in 2015

A common training plan in general internal medicine was a brave enterprise started in 2011 in accordance with the common objectives of the Swiss Society of General Medicine and the Swiss Society of Internal Medicine. The next challenge will be the dissolution of the two Societies and therefore the creation of an unique new association in 2015. This is an extraordinary opportunity to bring together the specific qualities of each association and to create a new society. Issues, objectives and secondary benefits expected from the creation of the largest national society of a medical discipline are explored as a joint discussion in this article.

DNA-based diagnosis of rare diseases in veterinary medicine: a 4.4 kb deletion of ITGB4 is associated with epidermolysis bullosa in Charolais cattle.

BACKGROUND Rare diseases in livestock animals are traditionally poorly diagnosed. Other than clinical description and pathological examination, the underlying causes have, for the most part, remained unknown. A single case of congenital skin fragility in cattle was observed, necropsy, histological and ultrastructural examinations were carried out and whole genome sequencing was utilized to identify the causative mutation. RESULTS A single purebred female Charolais calf with severe skin lesions was delivered full-term and died spontaneously after birth. The clinical and pathological findings exactly matched the gross description given by previous reports on epitheliogenesis imperfecta and epidermolysis bullosa (EB) in cattle. Histological and ultrastructural changes were consistent with EB junctionalis (EBJ). Genetic analysis revealed a previously unpublished ITGB4 loss-of-function mutation; the affected calf was homozygous for a 4.4 kb deletion involving exons 17 to 22, and the dam carried a single copy of the deletion indicating recessive inheritance. The homozygous mutant genotype did not occur in healthy controls of various breeds but some heterozygous carriers were found among Charolais cattle belonging to the affected herd. The mutant allele was absent in a representative sample of unrelated sires of the German Charolais population. CONCLUSION This is the first time in which a recessively inherited ITGB4 associated EBJ has been reported in cattle. The identification of heterozygous carriers is of importance in avoiding the transmission of this defect in future. Current DNA sequencing methods offer a powerful tool for understanding the genetic background of rare diseases in domestic animals having a reference genome sequence available.

European undergraduate curriculum in geriatric medicine developed using an international modified Delphi technique.

INTRODUCTION the rise in the number of older, frail adults necessitates that future doctors are adequately trained in the skills of geriatric medicine. Few countries have dedicated curricula in geriatric medicine at the undergraduate level. The aim of this project was to develop a consensus among geriatricians on a curriculum with the minimal requirements that a medical student should achieve by the end of medical school. METHODS a modified Delphi process was used. First, educational experts and geriatricians proposed a set of learning objectives based on a literature review. Second, three Delphi rounds involving a panel with 49 experts representing 29 countries affiliated to the European Union of Medical Specialists (UEMS) was used to gain consensus for a final curriculum. RESULTS the number of disagreements following Delphi Rounds 1 and 2 were 81 and 53, respectively. Complete agreement was reached following the third round. The final curriculum consisted of detailed objectives grouped under 10 overarching learning outcomes. DISCUSSION a consensus on the minimum requirements of geriatric learning objectives for medical students has been agreed by European geriatricians. Major efforts will be needed to implement these requirements, given the large variation in the quality of geriatric teaching in medical schools. This curriculum is a first step to help improve teaching of geriatrics in medical schools, and will also serve as a basis for advancing postgraduate training in geriatrics across Europe.

Taking personalized medicine seriously: Biomarker approaches in phase IIb/III studies in major depression and schizophrenia

The success rate in the development of psychopharmacological compounds is insufficient. Two main reasons for failure have been frequently identified: 1) treating the wrong patients and 2) using the wrong dose. This is potentially based on the known heterogeneity among patients, both on a syndromal and a biological level. A focus on personalized medicine through better characterization with biomarkers has been successful in other therapeutic areas. Nevertheless, obstacles toward this goal that exist are 1) the perception of a lack of validation, 2) the perception of an expensive and complicated enterprise, and 3) the perception of regulatory hurdles. The authors tackle these concerns and focus on the utilization of biomarkers as predictive markers for treatment outcome. The authors primarily cover examples from the areas of major depression and schizophrenia. Methodologies covered include salivary and plasma collection of neuroendocrine, metabolic, and inflammatory markers, which identified subgroups of patients in the Netherlands Study of Depression and Anxiety. A battery of vegetative markers, including sleep-electroencephalography parameters, heart rate variability, and bedside functional tests, can be utilized to characterize the activity of a functional system that is related to treatment refractoriness in depression (e.g., the renin-angiotensin-aldosterone system). Actigraphy and skin conductance can be utilized to classify patients with schizophrenia and provide objective readouts for vegetative activation as a functional marker of target engagement. Genetic markers, related to folate metabolism, or folate itself, has prognostic value for the treatment response in patients with schizophrenia. Already, several biomarkers are routinely collected in standard clinical trials (e.g., blood pressure and plasma electrolytes), and appear to be differentiating factors for treatment outcome. Given the availability of a wide variety of markers, the further development and integration of such markers into clinical research is both required and feasible in order to meet the benefit of personalized medicine. This article is based on proceedings from the "Taking Personalized Medicine Seriously-Biomarker Approaches in Phase IIb/III Studies in Major Depression and Schizophrenia" session, which was held during the 10th Annual Scientific Meeting of the International Society for Clinical Trials Meeting (ISCTM) in Washington, DC, February 18 to 20, 2014.

Towards personalized medicine: Chemosensitivity assays of patient lung cancer cell spheroids in a perfused microfluidic platform

Cancer is responsible for millions of deaths worldwide and the variability in disease patterns calls for patient-specific treatment. Therefore, personalized treatment is expected to become a daily routine in prospective clinical tests. In addition to genetic mutation analysis, predictive chemosensitive assays using patient's cells will be carried out as a decision making tool. However, prior to their widespread application in clinics, several challenges linked to the establishment of such assays need to be addressed. To best predict the drug response in a patient, the cellular environment needs to resemble that of the tumor. Furthermore, the formation of homogeneous replicates from a scarce amount of patient's cells is essential to compare the responses under various conditions (compound and concentration). Here, we present a microfluidic device for homogeneous spheroid formation in eight replicates in a perfused microenvironment. Spheroid replicates from either a cell line or primary cells from adenocarcinoma patients were successfully created. To further mimic the tumor microenvironment, spheroid co-culture of primary lung cancer epithelial cells and primary pericytes were tested. A higher chemoresistance in primary co-culture spheroids compared to primary monoculture spheroids was found when both were constantly perfused with cisplatin. This result is thought to be due to the barrier created by the pericytes around the tumor spheroids. Thus, this device can be used for additional chemosensitivity assays (e.g. sequential treatment) of patient material to further approach the personalized oncology field.

International Frameworks for Disaster Risk Reduction: Useful Guidance for Sustainable Mountain Development?

In recent decades, a number of global frameworks have been developed for disaster risk reduction (DRR). The Hyogo Framework for Action 2005–2015 and its successor document, the Sendai Framework for Disaster Risk Reduction, adopted in Japan in March 2015, provide general guidance for reducing risks from natural hazards. This is particularly important for mountainous areas, but DRR for mountain areas and sustainable mountain development received little attention in the recent policy debate. The question remains whether the Hyogo and Sendai frameworks can provide guidance for sustainable mountain development. This article evaluates the 2 frameworks in light of the special challenges of DRR in mountain areas and argues that, while the frameworks offer valuable guidance, they need to be further adapted for local contexts—particularly for mountain areas, which require special attention because of changing risk patterns like the effects of climate change and high land-use pressure.

Sudden cardiac death in forensic medicine – Swiss recommendations for a multidisciplinary approach

Sudden cardiac death (SCD) is by definition unexpected and cardiac in nature. The investigation is almost invariably performed by a forensic pathologist. Under these circumstances the role of the forensic pathologist is twofold: (1.) to determine rapidly and efficiently the cause and manner of death and (2.) to initiate a multidisciplinary process in order to prevent further deaths in existing family members. If the death is determined to be due to "natural" causes the district attorney in charge often refuses further examinations. However, additional examinations, i.e. extensive histopathological investigations and/or molecular genetic analyses, are necessary in many cases to clarify the cause of death. The Swiss Society of Legal Medicine created a multidisciplinary working group together with clinical and molecular geneticists and cardiologists in the hope of harmonising the approach to investigate SCD. The aim of this paper is to close the gap between the Swiss recommendations for routine forensic post-mortem cardiac examination and clinical recommendations for genetic testing of inherited cardiac diseases; this is in order to optimise the diagnostic procedures and preventive measures for living family members. The key points of the recommendations are (1.) the forensic autopsy procedure for all SCD victims under 40 years of age, (2.) the collection and storage of adequate samples for genetic testing, (3.) communication with the families, and (4.) a multidisciplinary approach including cardiogenetic counselling.

Integrated Disaster Reduction Approach: LforS Learning and Simulation Game

Main objective of the game is to increase the coping capacity of players and familiarise them with the Integrated Disaster Reduction Approach. The game is intended to prepare for and introduce the players to a subsequent Learning for Sustainability capacity building workshop for community leaders. The game represents a typical emergency situation resulting from a natural disaster. Before and after the event, adequate measures help to prevent or minimise potential damages. Once a disaster has occurred, concerted actions and immediate measures need to be taken to rescue as much as possible (human lives, livestock, material) and safeguard the village against further damage and losses. In the course of the game, each playing team can proof its knowledge on adequate measures that have to be taken in order to avoid or reduce losses related to natural disasters. Such measures relate to assessment and monitoring of risks, prevention and mitigation measures, preparedness and response as well as recovery and reconstruction.