Le cancer du sein sans envahissement ganglionnaire. Au-delà des consensus internationaux: une approche pragmatique [Node negative breast cancer. Beyond international consensus: a pragmatic approach].

Apart from therapeutic advances related to new treatments, our practices in the management of early breast cancer have been modified by to key organizational settings (1) mass screening, substantially altering the presentation and epidemiology of breast cancer and (2) the development of guidelines to ensure that any patient management is in agreement with the demonstrated impact in the adjuvant treatment. In daily practice, the impact of screening and guidelines recommendations has put us now in a paradoxical situation: while the majority of non-metastatic breast cancers treated in the hexagon are node negative, most of the results of clinical studies on chemotherapy and targeted therapies today arise from populations predominantly node positive. Therefore, it seemed legitimate to convene a working group around a reflection on the directions of adjuvant chemotherapy in a growing node negative population in order to better respond to the questions of the field oncologists, trying to address the discrepancies between different existing guidelines.

High rate of completion of preventive therapy for latent tuberculosis infection among asylum seekers in a Swiss Canton.

BACKGROUND: Preventive treatment may avoid future cases of tuberculosis among asylum seekers. The effectiveness of preventive treatment depends in large part on treatment completion. METHODS: In a prospective cohort study, asylum seekers of two of the Swiss Canton Vaud migration centres were screened with the Interferon Gamma Release Assay (IGRA). Those with a positive IGRA were referred for medical examination. Individuals with active or past tuberculosis were excluded. Preventive treatment was offered to all participants with positive IGRA but without active tuberculosis. The adherence was assessed during monthly follow-up. RESULTS: From a population of 393 adult migrants, 98 (24.9%) had a positive IGRA. Eleven did not attend the initial medical assessment. Of the 87 examined, eight presented with pulmonary disease (five of them received a full course of antituberculous therapy), two had a history of prior tuberculosis treatment and two had contraindications to treatment. Preventive treatment was offered to 75 individuals (4 months rifampicin in 74 and 9 months isoniazid in one), of whom 60 (80%) completed the treatment. CONCLUSIONS: The vulnerability and the volatility of this population make screening and observance of treatment difficult. It seems possible to obtain a high rate of completion using a short course of treatment in a closely monitored population living in stable housing conditions.

La médecine ambulatoire youth-friendly. [Youth-friendly outpatient care].

Ambulatory pediatric and family medicine takes care of adolescent patients, most of whom regularly consult a physician. Consultations with young people involve issues specifically related to their age. Regarding health care systems and physicians, adolescents' expectations vary from those of adults, not so much in terms of the issues discussed but in terms of the priorities that they give to them. Confidential interviews are not always proposed but are highly appreciated, as are certain personal qualities on the part of the caregivers such as honesty, respect, and friendliness. Finally, easy access to care together with the continuity of care are essential. Prevention of risk behaviors by screening and health education is clearly insufficient. This issue could be approached during the consultation through a psychosocial history. This is a good opportunity to discuss sensitive issues that adolescents seldom bring up themselves. More systematic prevention would probably decrease youth morbidity and mortality, which are both closely related to risk behaviors. To meet these expectations and special health care needs, the World Health Organization has developed the concept of youth-friendly health services. This concept can be applied in both a specialized adolescence center and a pediatric or family practice. Youth-friendly services are still rarely evaluated but seem to bring a clear benefit in terms of patient satisfaction and access to care.

Consommation de cannabis : quels sont les risques ?

Abstract - Cannabis: what are the risks ? Cannabinoids from cannabis have a dual use and display often opposite pharmacological properties depending on the circumstances of use and the administered dose. Cannabinoids constitute mainly a recreative or addictive substance, but also a therapeutic drug. They can be either neurotoxic or neuroprotector, carcinogenic or an anti-cancer drug, hyperemetic or antiemetic, pro-inflammatory or anti-inflammatory... Improvement in in-door cultivation techniques and selection of high yield strains have resulted in a steadily increase of THC content. Cannabis is the most frequently prohibited drug used in Switzerland and Western countries. About half of teenagers have already experimented cannabis consumption. About 10% of cannabis users smoke it daily and can be considered as cannabis-dependant. About one third of these cannabis smokers are chronically intoxicated. THC, the main psychoactive drug interacts with the endocannnabinoid system which is made of cellular receptors, endogenous ligands and a complex intra-cellular biosynthetic, degradation and intra-cellular messengers machinery. The endocannabinoid system plays a major role in the fine tuning of the nervous system. It is thought to be important in memory, motor learning, and synaptic plasticity. At psychoactive dose, THC impairs psychomotor and neurocognitive performances. Learning and memory abilities are diminished. The risk to be responsible of a traffic car accident is slightly increased after administration of cannabis alone and strongly increased after combined use of alcohol and cannabis. With the exception of young children, cannabis intake does not lead to potentially fatal intoxication. However, cannabis exposure can act as trigger for cardiovascular accidents in rare vulnerable people. Young or vulnerable people are more at risk to develop a psychosis at adulthood and/or to become cannabis-dependant. Epidemiological studies have shown that the risk to develop a schizophrenia at adulthood is increased for cannabis smokers, especially for those who are early consumers. Likewise for the risk of depression and suicide attempt. Respiratory disease can be worsen after cannabis smoking. Pregnant and breast-feeding mothers should not take cannabis because THC gets into placenta and concentrates in breast milk. The most sensitive time-period to adverse side-effects of cannabis starts from foetus and extends to adolescence. The reason could be that the endocannabinoid system, the main target of THC, plays a major role in the setup of neuronal networks in the immature brain. The concomitant use of other psychoactive drugs such as alcohol, benzodiazepines or cocaine should be avoided because of possible mutual interactions. Furthermore, it has been demonstrated that a cross-sensitisation exists between most addictive drugs at the level of the brain reward system. Chronic use of cannabis leads to tolerance and withdrawals symptoms in case of cannabis intake interruption. Apart from the aforementioned unwanted side effects, cannabis displays useful and original medicinal properties which are currently under scientific evaluation. At the moment the benefit/risk ratio is not yet well assessed. Several minor phytocannabinoids or synthetic cannabinoids devoid of psychoactive properties could find their way in the modern pharmacopoeia (e.g. ajulemic acid). For therapeutic purposes, special cannabis varieties with unique cannabinoids composition (e.g. a high cannabidiol content) are preferred over those which are currently used for recreative smoking. The administration mode also differs in such a way that inhalation of carcinogenic pyrolytic compounds resulting from cannabis smoking is avoided. This can be achieved by inhaling cannabis vapors at low temperature with a vaporizer device. Résumé Les cannabinoïdes contenus dans la plante de cannabis ont un double usage et possèdent des propriétés opposées suivant les circonstances et les doses employées. Les cannabinoïdes, essentiellement drogue récréative ou d'abus pourraient, pour certains d'entre eux, devenir des médicaments. Selon les conditions d'utilisation, ils peuvent être neurotoxiques ou neuroprotecteurs, carcinogènes ou anticancéreux, hyper-émétiques ou antiémétiques, pro-inflammatoires ou anti-inflammatoires... Les techniques de culture sous serre indoor ainsi que la sélection de variétés de cannabis à fort potentiel de production ont conduit à un accroissement notable des taux de THC. Le cannabis est la drogue illégale la plus fréquemment consommée en Suisse et ailleurs dans le monde occidental. Environ la moitié des jeunes ont déjà expérimenté le cannabis. Environ 10 % des consommateurs le fument quotidiennement et en sont devenus dépendants. Un tiers de ces usagers peut être considéré comme chroniquement intoxiqué. Le THC, la principale substance psychoactive du cannabis, interagit avec le "système endocannabinoïde". Ce système est composé de récepteurs cellulaires, de ligands endogènes et d'un dispositif complexe de synthèse, de dégradation, de régulation et de messagers intra-cellulaires. Le système endocannabinoïde joue un rôle clé dans le réglage fin du système nerveux. Les endocannabinoïdes régulent la mémorisation, l'apprentissage moteur et la plasticité des liaisons nerveuses. À dose psychoactive, le THC réduit les performances psychomotrices et neurocognitives. Les facultés d'apprentissage et de mémorisation sont diminuées. Le risque d'être responsable d'un accident de circulation est augmenté après prise de cannabis, et ceci d'autant plus que de l'alcool aura été consommé parallèlement. À l'exception des jeunes enfants, la consommation de cannabis n'entraîne pas de risque potentiel d'intoxication mortelle. Toutefois, le cannabis pourrait agir comme facteur déclenchant d'accident cardiovasculaire chez de rares individus prédisposés. Les individus jeunes, et/ou vulnérables ont un risque significativement plus élevé de développer une psychose à l'âge adulte ou de devenir dépendant au cannabis. Des études épidémiologiques ont montré que le risque de développer une schizophrénie à l'âge adulte était augmenté pour les consommateurs de cannabis et ceci d'autant plus que l'âge de début de consommation était précoce. Il en va de même pour le risque de dépression. Les troubles respiratoires pourraient être exacerbés par la prise de cannabis. Les femmes enceintes et celles qui allaitent ne devraient pas consommer de cannabis car le THC traverse la barrière hémato-placentaire, en outre, il se concentre dans le lait maternel. La période de la vie la plus sensible aux effets néfastes du cannabis correspond à celle allant du foetus à l'adolescent. Le système endocannabinoïde sur lequel agit le THC serait en effet un acteur majeur orchestrant le développement des réseaux neuronaux dans le cerveau immature. La prise concomitante d'autres psychotropes comme l'alcool, les benzodiazépines ou la cocaïne conduit à des renforcements mutuels de leurs effets délétères. De plus, il a été montré l'existence d'une sensibilité croisée pour la majorité des psychotropes qui agissent sur le système de la récompense, le cannabis y compris, ce qui augmente ainsi le risque de pharmacodépendance. La prise régulière de doses élevées de cannabis entraîne l'apparition d'une tolérance et de symptômes de sevrage discrets à l'arrêt de la consommation. À part les effets négatifs mentionnés auparavant, le cannabis possède des propriétés médicales originales qui sont l'objet d'études attentives. Plusieurs cannabinoïdes mineurs naturels ou synthétiques, comme l'acide ajulémique, pourraient trouver un jour une place dans la pharmacopée. En usage thérapeutique, des variétés particulières de cannabis sont préférées, par exemple celles riches en cannabidiol non psychoactif. Le mode d'administration diffère de celui utilisé en mode récréatif. Par exemple, la vaporisation des cannabinoïdes à basse température est préférée à l'inhalation du "joint".

Comment tes médecins de famille prennent-ils en charge l'hypothyroïdie infraclinique [How do Swiss family physicians treat subclinical hypothyroidism?].

L'hypothyroïdie infraclinique est fréquemment rencontrée et sa prévalence augmente avec l'âge. Les recommandations relatives au dépistage et au traitement de l'hypothyroïdie infraclinique sont controversées. Une enquête internationale auprès des médecins de famille, à laquelle la Suisse a participé, a mis en évidence de fortes variations dans la prise en charge de l'hypothyroïdie infraclinique entre les pays. Ces différences de traitement traduisent avant tout le manque de données fiables quant à la prise en charge de cette condition. L'essai clinique randomisé européen TRUST devrait permettre de clarifier les indications pour le dépistage et la substitution par thyroxine. Une collaboration avec les médecins de famille et le soutien des Instituts universitaires de médecine générale à Lausanne et à Berne pour le recrutement des patients devraient permettre d'obtenir des données directement applicables à une population représentative de la médecine ambulatoire. Subclinical hypothyroidism is a common condition, and its prevalence increases with age. Currently, guidelines regarding the screening and treatment of subclinical hypothyroidism are controversial. An international survey of general practitioners (GPs), to which Swiss GPs also contributed, showed large inter-country variations in treatment strategies for subclinical hypothyroidism. These differences are mainly explained by the lack of strong evidence for the management of this condition. The European randomized-controlled clinical trial TRUST should help clarify recommendations for screening and thyroxin replacement for the elderly with subclinical hypothyroidism. Working in close collaboration with GPs in Switzerland for the recruitment of patients will ensure that the findings from this study will be applicable to primary care settings.

Contribution of multimorbidity to overall mortality in the population-based CoLaus study

Introduction : Multimorbidity (MM) is currently a major health concern for hospitalized patients but little is known about the relative importance of MM in the general population. Accordingly we assessed whether MM could be a good predictor of overall mortality. Method : Data from the population based CoLaus Study: 3239 participants (1731 women, mean age 50+/-9 years) followed for a median time of 5.4 years (range 0.4 to 8.5 years). MM was defined as presenting >=2 morbidities according to Barnett et al. (27 items, measured data). Survival analysis was conducted using Cox regression. Results : During follow-up, 53 (1.6%) participants died. Participants who died had a higher number of morbidities (2.4 +/- 1.6 vs. 1.9 +/- 1.5, p<0.05) and had a higher prevalence of MM (69.8% vs. 55.9%, p<0.05). On bivariate analysis, presence of MM (defined as a yes/no variable) was significantly related with overall mortality: relative risk (RR) of 1.84, 95% confidence interval [1.02; 3.31], p<0.05 (see figure), but this association became non-significant after adjusting for age, gender and smoking: RR=1.68 [0.93; 3.04], p=0.09. Similar results were obtained when using the number of morbidities: RR for an extra morbidity 1.22 [1.05; 1.44], p<0.02; after adjusting for age, gender and smoking, RR=1.16 [0.99; 1.37], p=0.07. Conclusion : During a short 5 year observation period, measured MM in the general population is associated with overall mortality. This association becomes borderline significant after multivariate adjustment. These observations will have to be confirmed during a longer follow-up period. This increased mortality in MM patients may require developing specific strategies of screening and prevention.

2013 Update in addiction medicine for the generalist.

Increasingly, patients with unhealthy alcohol and other drug use are being seen in primary care and other non-specialty addiction settings. Primary care providers are well positioned to screen, assess, and treat patients with alcohol and other drug use because this use, and substance use disorders, may contribute to a host of medical and mental health harms. We sought to identify and examine important recent advances in addiction medicine in the medical literature that have implications for the care of patients in primary care or other generalist settings. To accomplish this aim, we selected articles in the field of addiction medicine, critically appraised and summarized the manuscripts, and highlighted their implications for generalist practice. During an initial review, we identified articles through an electronic Medline search (limited to human studies and in English) using search terms for alcohol and other drugs of abuse published from January 2010 to January 2012. After this initial review, we searched for other literature in web-based or journal resources for potential articles of interest. From the list of articles identified in these initial reviews, each of the six authors independently selected articles for more intensive review and identified the ones they found to have a potential impact on generalist practice. The identified articles were then ranked by the number of authors who selected each article. Through a consensus process over 4 meetings, the authors reached agreement on the articles with implications for practice for generalist clinicians that warranted inclusion for discussion. The authors then grouped the articles into five categories: 1) screening and brief interventions in outpatient settings, 2) identification and management of substance use among inpatients, 3) medical complications of substance use, 4) use of pharmacotherapy for addiction treatment in primary care and its complications, and 5) integration of addiction treatment and medical care. The authors discuss each selected articles' merits, limitations, conclusions, and implication to advancing addiction screening, assessment, and treatment of addiction in generalist physician practice environments.

Monitoring one-year compliance to antihypertension medication in the Seychelles.

OBJECTIVE: To examine the compliance to medication among newly diagnosed hypertensive patients screened from the general population of the Seychelles, a rapidly developing country. METHODS: Among the 1067 participants to a population-based survey for cardiovascular risk factors, hypertension was discovered in 50 (previously unaware of having hypertension and having blood pressure > or = 160/95 mmHg over 3 visits). These 50 patients were placed on a daily one-pill regimen of medication (bendrofluazide, atenolol, or a combination of hydrochlorothiazide and atenolol) and compliance to the regimen was assessed over 12 months using electronic pill containers. Satisfactory compliance was defined as taking the medication on 6 or 7 days a week on average (which corresponds to a mean compliance level of > or = 86%). FINDINGS: In the first month, fewer than half (46%) of the new hypertension patients achieved satisfactory compliance, and only about one-quarter (26%) achieved this level by the twelfth month. Compliance was better among the 23 participants who regularly attended medical follow-up, with nearly three-quarters of these patients (74%) achieving satisfactory compliance during the first month and over one-half (55%) by the twelfth month. There was a direct association between mean 12-month compliance level and having a highly skilled occupation; having good health awareness; and regularly attending medical appointments. In contrast, there was an inverse relationship between mean compliance level and heavy drinking. CONCLUSION: The low proportion of people selected from the general population who were capable of sustaining satisfactory compliance to antihypertension medication may correspond to the maximum effectiveness of medication interventions based on a screening and treatment strategy in the general population. The results stress the need for both high-risk and population approaches to improve hypertension control.

Characterization of MAP1B heavy chain interaction with actin.

Microtubule-associated protein 1B is an essential protein during brain development and neurite outgrowth and was studied by several assays to further characterize actin as a major interacting partner. Tubulin and actin co-immunoprecipitated with MAP1B at similar ratios throughout development. Their identity was identified by mass spectrometry and was confirmed by Western blots. In contrast to previous reports, the MAP1B-actin interaction was not dependent on the MAP1B phosphorylation state, since actin was precipitated from brain tissue throughout development at similar ratios and equal amounts were precipitated before and after dephosphorylation with alkaline phosphatase. MAP1B heavy chain was able to bind actin directly and therefore the N-terminal part of MAP1B heavy chain must also contain an actin-binding site. The binding force of this interaction was measured by atomic force microscopy and values were in the same range as those of MAP1B binding to tubulin or that measured in MAP1B self-aggregation. Aggregation was confirmed by negative staining and electron microscopy. Experiments including COS-7 cells, PC12 cells, cytochalasin D and immunocytochemistry with subsequent confocal laser microscopy, suggested that MAP1B may bind to actin but has no obvious microfilament stabilizing effect. We conclude, that the MAP1B heavy chain has a microtubule-stabilization effect, and contains an actin-binding site that may play a role in the crosslinking of actin and microtubules, a function that may be important in neurite elongation.