Practice guidelines for evaluation of Fever in returning travelers and migrants.

BACKGROUND: Fever upon return from tropical or subtropical regions can be caused by diseases that are rapidly fatal if left untreated. The differential diagnosis is wide. Physicians often lack the necessary knowledge to appropriately take care of such patients. OBJECTIVE: To develop practice guidelines for the initial evaluation of patients presenting with fever upon return from a tropical or subtropical country in order to reduce delays and potential fatal outcomes and to improve knowledge of physicians. TARGET AUDIENCE: Medical personnel, usually physicians, who see the returning patients, primarily in an ambulatory setting or in an emergency department of a hospital and specialists in internal medicine, infectious diseases, and travel medicine. METHOD: A systematic review of the literature--mainly extracted from the National Library of Medicine database--was performed between May 2000 and April 2001, using the keywords fever and/or travel and/or migrant and/or guidelines. Eventually, 250 articles were reviewed. The relevant elements of evidence were used in combination with expert knowledge to construct an algorithm with arborescence flagging the level of specialization required to deal with each situation. The proposed diagnoses and treatment plans are restricted to tropical or subtropical diseases (nonautochthonous diseases). The decision chart is accompanied with a detailed document that provides for each level of the tree the degree of evidence and the grade of recommendation as well as the key points of debate. PARTICIPANTS AND CONSENSUS PROCESS: Besides the 4 authors (2 specialists in travel/tropical medicine, 1 clinical epidemiologist, and 1 resident physician), a panel of 11 European physicians with different levels of expertise on travel medicine reviewed the guidelines. Thereafter, each point of the proposed recommendations was discussed with 15 experts in travel/tropical medicine from various continents. A final version was produced and submitted for evaluation to all participants. CONCLUSION: Although the quality of evidence was limited by the paucity of clinical studies, these guidelines established with the support of a large and highly experienced panel should help physicians to deal with patients coming back from the Tropics with fever.

Online teaching of inflammatory skin pathology by a French-speaking International University Network

INTRODUCTION: Developments in technology, web-based teaching and whole slide imaging have broadened the teaching horizon in anatomic pathology. Creating online learning material including many types of media such as radiologic images, whole slides, videos, clinical and macroscopic photographs, is now accessible to most universities. Unfortunately, a major limiting factor to maintain and update the learning material is the amount of resources needed. In this perspective, a French-national university network was initiated in 2011 to build joint online teaching modules consisting of clinical cases and tests. The network has since expanded internationally to Québec, Switzerland and Ivory Coast. METHOD: One of the first steps of the project was to build a learning module on inflammatory skin pathology for interns and residents in pathology and dermatology. A pathology resident from Québec spent 6 weeks in France and Switzerland to develop the contents and build the module on an e-learning Moodle platform under the supervision of two dermatopathologists. The learning module contains text, interactive clinical cases, tests with feedback, virtual slides, images and clinical photographs. For that module, the virtual slides are decentralized in 2 universities (Bordeaux and Paris 7). Each university is responsible of its own slide scanning, image storage and online display with virtual slide viewers. RESULTS: The module on inflammatory skin pathology includes more than 50 web pages with French original content, tests and clinical cases, links to over 45 virtual images and more than 50 microscopic and clinical photographs. The whole learning module is being revised by four dermatopathologists and two senior pathologists. It will be accessible to interns and residents in the spring of 2014. The experience and knowledge gained from that work will be transferred to the next international resident whose work will be aimed at creating lung and breast pathology learning modules. CONCLUSION: The challenges of sustaining a project of this scope are numerous. The technical aspect of whole-slide imaging and storage needs to be developed by each university or group. The content needs to be regularly updated and its accuracy reviewed by experts in each individual domain. The learning modules also need to be promoted within the academic community to ensure maximal benefit for trainees. A collateral benefit of the project was the establishment of international partnerships between French-speaking universities and pathologists with the common goal of promoting pathology education through the use of multi-media technology including whole slide imaging.

Differential impact of lacunes and microvascular lesions on poststroke depression.

BACKGROUND AND PURPOSE: Previous studies have postulated that poststroke depression (PSD) might be related to cumulative vascular brain pathology rather than to the location and severity of a single macroinfarct. We performed a detailed analysis of all types of microvascular lesions and lacunes in 41 prospectively documented and consecutively autopsied stroke cases. METHODS: Only cases with first-onset depression <2 years after stroke were considered as PSD in the present series. Diagnosis of depression was established prospectively using DSM-IV criteria for major depression. Neuropathological evaluation included bilateral semiquantitative assessment of microvascular ischemic pathology and lacunes; statistical analysis included Fisher exact test, Mann-Whitney U test, and regression models. RESULTS: Macroinfarct site was not related to the occurrence of PSD for any of the locations studied. Thalamic and basal ganglia lacunes occurred significantly more often in PSD cases. Higher lacune scores in basal ganglia, thalamus, and deep white matter were associated with an increased PSD risk. In contrast, microinfarct and diffuse or periventricular demyelination scores were not increased in PSD. The combined lacune score (thalamic plus basal ganglia plus deep white matter) explained 25% of the variability of PSD occurrence. CONCLUSIONS: The cumulative vascular burden resulting from chronic accumulation of lacunar infarcts within the thalamus, basal ganglia, and deep white matter may be more important than single infarcts in the prediction of PSD.

Molecular autopsy in sudden cardiac death and its implication for families: discussion of the practical, legal and ethical aspects of the multidisciplinary collaboration.

Sudden cardiac death (SCD) is a major cause of premature death in young adults and children in developed countries. Standard forensic autopsy procedures are often unsuccessful in determining the cause of SCD. Post-mortem genetic testing, also called molecular autopsy, has revealed that a non-negligible number of these deaths are a result of inherited cardiac diseases, including arrhythmic disorders such as congenital long QT syndrome and Brugada syndrome. Due to the heritability of these diseases, the potential implications for living relatives must be taken into consideration. Advanced diagnostic analyses, genetic counselling, and interdisciplinary collaboration should be integral parts of clinical and forensic practice. In this article we present a multidisciplinary collaboration established in Lausanne, with the goal of properly informing families of these pathologies and their implications for surviving family members. In Switzerland, as in many other countries, legal guidelines for genetic testing do not address the use of molecular tools for post-mortem genetic analyses in forensic practice. In this article we present the standard practice guidelines established by our multidisciplinary team.

Measurement of β-tryptase in postmortem serum in cardiac deaths. [Measurement of beta-tryptase in postmortem serum in cardiac deaths]

Mast cells are well known for their role in hypersensitivity reactions. However, there is increasing evidence that they might also participate in both developing and weakening atherosclerotic plaques, potentially causing plaque instability. Some clinical studies have therefore postulated the existence of relationships between blood β-tryptase levels and acute coronary syndromes. In this study, we investigated postmortem serum β-tryptase levels in a series of 90 autopsy cases with various degrees of coronary atherosclerosis that had undergone medico-legal investigations. β-tryptase concentrations in these cases were compared to levels observed in 6 fatal anaphylaxis cases following contrast material administration. Postmortem serum β-tryptase concentrations in the anaphylactic deaths ranged from 146 to 979 ng/ml. In 9 out of 90 cases of cardiac deaths, β-tryptase levels were higher than clinical reference values of 11.4 ng/ml and ranged from 21 to 65 ng/ml. These results indicate that increased postmortem serum β-tryptase levels can be observed, though not systematically, in cardiac deaths with varying degrees of coronary atherosclerosis disease, thereby suggesting that mast cell activation in this disease cannot be ascertained by postmortem serum β-tryptase measurements.

A satisfaction survey conducted on patients of a medico-legal consultation.

In 2006, a medico-legal consultation service devoted to adult victims of interpersonal violence was set up at the Lausanne University Hospital Centre, Switzerland: the Violence Medical Unit. Patients are received by forensic nurses for support, forensic examination (in order to establish medical report) and community orientation. In 2008, a telephone survey was conducted on patients. The objectives of the survey were to estimate the degree of patients' satisfaction and to document the use of the medical report by six questions. Among the 476 patients admitted to the VMU in 2007, 132 were interviewed. Their overall satisfaction was high with an average mark of 8.7/10. The medical report was used extensively by the interviewed victims (81%) for its primary function - to be produced as evidence. As the consultations are financed by public funds, these results were of interest for advocacy of long-lasting financial support.

Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid.

BACKGROUND: Disturbances in the levels of one-carbon (1C) metabolism metabolites have been associated with a wide variety of neuropsychiatric diseases. Cerebrospinal fluid (CSF) levels of homocysteine (Hcy) and the other 1C metabolites, nor their interrelatedness and putative determinants, have been studied extensively in a healthy population. METHODS: Plasma and CSF samples from 100 individuals free from neuropsychiatric diseases were analyzed (55 male, 45 female; age 50±17 years). In blood, we measured plasma Hcy, serum folate and serum vitamin B12. In CSF, we measured total Hcy, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and 5-methyltetrahydrofolate (5-methylTHF). Highly selective analytical methods like liquid chromatography combined with either mass spectrometry or fluorescence detection were used. RESULTS: CSF Hcy was inversely correlated with CSF 5-methylTHF and positively with plasma Hcy, independent of serum folate status. CSF SAH correlated with age, lower CSF 5-methylTHF and higher CSF Hcy. CSF 5-methylTHF showed independent negative correlations with age and positive correlations with serum folate. CSF SAM did not correlate with any of the 1C metabolites. CONCLUSIONS: Aging is characterized by a reduction in CSF 5-methylTHF levels and increased CSF levels of the potentially neurotoxic transmethylation inhibitor SAH. CSF 5-methylTHF, which is itself determined in part by systemic folate status, is a powerful independent determinant of CSF levels of Hcy and SAH.

Online teaching of inflammatory skin pathology by a French-speaking International University Network.

INTRODUCTION: Developments in technology, web-based teaching and whole slide imaging have broadened the teaching horizon in anatomic pathology. Creating online learning material including many types of media such as radiologic images, whole slides, videos, clinical and macroscopic photographs, is now accessible to most universities. Unfortunately, a major limiting factor to maintain and update the learning material is the amount of resources needed. In this perspective, a French-national university network was initiated in 2011 to build joint online teaching modules consisting of clinical cases and tests. The network has since expanded internationally to Québec, Switzerland and Ivory Coast. METHOD: One of the first steps of the project was to build a learning module on inflammatory skin pathology for interns and residents in pathology and dermatology. A pathology resident from Québec spent 6 weeks in France and Switzerland to develop the contents and build the module on an e-learning Moodle platform under the supervision of two dermatopathologists. The learning module contains text, interactive clinical cases, tests with feedback, virtual slides, images and clinical photographs. For that module, the virtual slides are decentralized in 2 universities (Bordeaux and Paris 7). Each university is responsible of its own slide scanning, image storage and online display with virtual slide viewers. RESULTS: The module on inflammatory skin pathology includes more than 50 web pages with French original content, tests and clinical cases, links to over 45 virtual images and more than 50 microscopic and clinical photographs. The whole learning module is being revised by four dermatopathologists and two senior pathologists. It will be accessible to interns and residents in the spring of 2014. The experience and knowledge gained from that work will be transferred to the next international resident whose work will be aimed at creating lung and breast pathology learning modules. CONCLUSION: The challenges of sustaining a project of this scope are numerous. The technical aspect of whole-slide imaging and storage needs to be developed by each university or group. The content needs to be regularly updated and its accuracy reviewed by experts in each individual domain. The learning modules also need to be promoted within the academic community to ensure maximal benefit for trainees. A collateral benefit of the project was the establishment of international partnerships between French-speaking universities and pathologists with the common goal of promoting pathology education through the use of multi-media technology including whole slide imaging.

2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease.

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on first line/second and further lines of treatment in advanced disease.

Sports practice among adolescents with chronic health conditions ; and, Are adolescents with chronic conditions particularly at risk of bullying ?

RAPPORT DE SYNTHESE : Les deux articles présentés dans ce mémoire de thèse sont le résultat de recherches effectuées au sein du Groupe de Recherche sur la Santé des Adolescents, affilié à l'Unité Multidisciplinaire de Santé des Adolescents du Centre Hospitalier Universitaire Vaudois. Les études qui constituent les présents articles ont pour thème commun la santé des adolescents atteints d'affections chroniques, à savoir d'une maladie chronique et/ou d'un handicap physique. Les données qui ont servi à ces deux études sant issues de l'enquête SMASH02 (Swiss Multicenter Adolescent Survey on Health 2002), une étude transversale multicentrique, menée en 2002 dans les écoles post-obligatoires de la majorité des cantons suisses par l'intermédiaire de questionnaires anonymes. 7548 adolescents de 16 à 20 ans ont été recrutés dans cette enquête, qui porte sur de nombreux aspects de la santé et des modes de vie des adolescents. Les analyses des données ont été effectuées à l'aide du logiciel de statistiques STATA 9 et avec l'aide d'un statisticien de l'université de Lausanne. Le premier article, intitulé "Sport Practice Among Adolescents Witte Chrome Health Conditions", est publié en juin 2009 dans la revue Archives of Pediatrics and Adolescent Medicine. Cette étude compare le niveau d'activité sportive entre les adolescents atteints d'affections chroniques et leurs pairs. L'hypothèse de recherche postule que les adolescents malades chroniques et/ou en situation de handicap pratiquent significativement moins de sport que les autres. Il ressort des analyses statistiques que cette hypothèse n'est vérifiée que si l'on considère les adolescents de sexe masculin. En effet, l'étude montre également que les filles de 16 à 20 ans en général pratiquent significativement moins de sport que leurs pairs masculins. Et le fait d'être atteint d'une affection chronique semble ne pas représenter chez elles un facteur,de risque supplémentaire de diminution de la pratique sportive. Dans ce même article, nous traitons également des éléments perçus par les adolescents comme des barrières à la pratique sportive. Il s'avère que les adolescents atteints d'affections chroniques ne perçoivent pas leur maladie ou leur situation de handicap comme la principale raison de leur faible activité sportive. Ils évoquent plus fréquemment un manque de temps libre ou une préférence pour d'autres activités, soit les mêmes barrières que celles évoquées par leurs pairs. Les conclusions de cette étude doivent rappeler aux professionnels de la santé l'importance d'encourager la pratique sportive chez leurs jeunes patients, particulièrement ceux atteints d'affections chroniques ainsi que les adolescentes en général. Dans le second article, intitulé "Are Adolescents With Chronic Conditions Particularly at Risk of Bullying?", il est question de violence entre adolescents. Plus précisément, nous étudions la prévalence de bullying chez les adolescents atteints d'affections chroniques et leurs pairs. Le terme de bullying, volontairement emprunté à l'Anglais, représente un phénomène complexe, que l'on peut approximer en Français comme une victimisation par les pairs en milieu scolaire. Il résulte de cette étude que le fait d'être atteint d'une affection chronique semble être un facteur de risque significatif de bullying chez les adolescents de 16 à 20 ans. Cette conclusion amène à considérer le problème du bullying dans l'intégration des élèves malades chroniques et en situation de handicap dans le système scolaire principal, notamment par la mise en place de mesures de prévention. Cet article est publié en ligne par la revue Archives of Disease in Childhood en mars 2009.

Isolation and in vitro chondrogenic potential of human foetal spine cells.

Cell therapy for nucleus pulposus (NP) regeneration is an attractive treatment for early disc degeneration as shown by studies using autologous NP cells or stem cells. Another potential source of cells is foetal cells. We investigated the feasibility of isolating foetal cells from human foetal spine tissues and assessed their chondrogenic potential in alginate bead cultures. Histology and immunohistochemistry of foetal tissues showed that the structure and the matrix composition (aggrecan, type I and II collagen) of foetal intervertebral disc (IVD) were similar to adult IVD. Isolated foetal cells were cultured in monolayer in basic media supplemented with 10% Fetal Bovine Serum (FBS) and from each foetal tissue donation, a cell bank of foetal spine cells at passage 2 was established and was composed of around 2000 vials of 5 million cells. Gene expression and immunohistochemistry of foetal spine cells cultured in alginate beads during 28 days showed that cells were able to produce aggrecan and type II collagen and very low level of type I and type X collagen, indicating chondrogenic differentiation. However variability in matrix synthesis was observed between donors. In conclusion, foetal cells could be isolated from human foetal spine tissues and since these cells showed chondrogenic potential, they could be a potential cell source for IVD regeneration.

Zoonotic occupational diseases in forestry workers: Lyme borreliosis, tularemia and leptospirosis in Europe

INTRODUCTION: Forestry workers and other people who come into close contact with wild animals, such as hunters, natural science researchers, game managers or mushroom/berry pickers, are at risk of contracting bacterial, parasitological or viral zoonotic diseases. Synthetic data on the incidence and prevalence of zoonotic diseases in both animals and humans in European forests do not exist. It is therefore difficult to promote appropriate preventive measures among workers or people who come into direct or indirect contact with forest animals. OBJECTIVES: The objectives of this review are to synthesise existing knowledge on the prevalence of the three predominant bacterial zoonotic diseases in Europe, i.e. Lyme borreliosis, tularemia and leptospirosis, in order to draw up recommendations for occupational or public health. METHODS: 88 papers published between 1995-2013 (33 on Lyme borreliosis, 30 on tularemia and 25 on leptospirosis) were analyzed. CONCLUSIONS: The prevalences of these three zoonotic diseases are not negligible and information targeting the public is needed. Moreover, the results highlight the lack of standardised surveys among different European countries. It was also noted that epidemiological data on leptospirosis are very scarce.

Prediction in forensic science: a critical examination of common understandings

In this commentary, we argue that the term 'prediction' is overly used when in fact, referring to foundational writings of de Finetti, the correspondent term should be inference. In particular, we intend (i) to summarize and clarify relevant subject matter on prediction from established statistical theory, and (ii) point out the logic of this understanding with respect practical uses of the term prediction. Written from an interdisciplinary perspective, associating statistics and forensic science as an example, this discussion also connects to related fields such as medical diagnosis and other areas of application where reasoning based on scientific results is practiced in societal relevant contexts. This includes forensic psychology that uses prediction as part of its vocabulary when dealing with matters that arise in the course of legal proceedings.