Statin treatment is associated with improved prognosis in patients with AF-related stroke.

BACKGROUND/OBJECTIVES: The most recent ACC/AHA guidelines recommend high-intensity statin therapy in ischemic stroke patients of presumably atherosclerotic origin. On the contrary, there is no specific recommendation for the use of statin in patients with non-atherosclerotic stroke, e.g. strokes related to atrial fibrillation (AF). We investigated whether statin treatment in patients with AF-related stroke is associated with improved survival and reduced risk for stroke recurrence and future cardiovascular events. METHODS: All consecutive patients registered in the Athens Stroke Registry with AF-related stroke and no history of coronary artery disease nor clinically manifest peripheral artery disease were included in the analysis and categorized in two groups depending on whether statin was prescribed at discharge. The primary outcome was overall mortality; the secondary outcomes were stroke recurrence and a composite cardiovascular endpoint comprising of recurrent stroke, myocardial infarction, aortic aneurysm rupture or sudden cardiac death during the 5-year follow-up. RESULTS: Among 1602 stroke patients, 404 (25.2%) with AF-related stroke were included in the analysis, of whom 102 (25.2%) were discharged on statin. On multivariate Cox-proportional-hazards model, statin treatment was independently associated with a lower mortality (hazard-ratio (HR): 0.49, 95%CI:0.26-0.92) and lower risk for the composite cardiovascular endpoint during the median 22months follow-up (HR: 0.44, 95%CI:0.22-0.88), but not with stroke recurrence (HR: 0.47, 95%CI:0.22-1.01, p: 0.053). CONCLUSIONS: In this long-term registry of patients with AF-related stroke, statin treatment was associated with improved survival and reduced risk for future cardiovascular events.

Mortality associated with diabetes mellitus in comparison with history of cardiovascular disease in older women.

Current treatment guidelines consider diabetes to be equivalent to existing cardiovascular disease (CVD), but few data exist about the relative importance of these risk factors for total and CVD mortality in older women.We studied 9704 women aged >= 65 years enrolled in a prospective cohort study (Study of Osteoporotic Fracture) during a mean follow-up of 13 years and compared all-cause and CVD mortality among non-diabetic women without and with history of CVD at baseline and diabetic women without and with history of CVD. Diabetes mellitus and CVD were defined as self-report of physician diagnoses. Cause of death was adjudicated from death certificates and medical records when available. Ascertainment of vital status was 99% complete. Multivariate Cox hazard models adjusted for age, smoking, physical activity, systolic blood pressure, waist girth and education were used to compare mortality among the four groups with non-diabetic women without CVD as the referent group. At baseline mean age was 71.7 } 5.3 years, 7.0% reported diabetes mellitus and 14.5% reported prior CVD. 4257 women died during follow-up, 36.6% were attributed to CVD. Compared to non-diabetic women without prior CVD, the risk of CVD mortality was elevated among both non-diabetic women with CVD (HR = 1.82, 95% CI: 1.60-2.07, P <0.001) and diabetic women without prior CVD (HR = 2.24, CI: 1.87-2.69, P <0.001). CVD mortality was highest among diabetic women with CVD (HR = 3.41, CI: 2.61-4.45, P <0.001). Compared to non-diabetic women with CVD, diabetic women without prior CVD had a significantly higher adjusted HR for total and CVD mortality (P < 0.001 and P <0.05 respectively). Older diabetic women without prior CVD have a higher risk of all-cause and CVD mortality compared to nondiabetic women with pre-existing CVD. For older women, these data support the equivalence of prior CVD and diabetes mellitus in current guidelines for the prevention of CVD in primary care.

Molecular mechanisms of follicular associated epithelium differentiation

Les muqueuses respiratoires, genitales et digestives sont continuellement exposées aux antigènes de l?alimentation, à la flore intestinale et aux pathogènes. Cela implique une activité immunologique intense et finement régulée dans ces tissus. On admet que la modulation de ces réponses immunitaires muqueuses s?effectue dans des organes sentinels spécifiques appelés o-MALT (organized mucosal associated lymphoid tissues). Ces processus de modulation et la biologie de ces sites immuno-inducteurs sont peu connus. Ceci est pourtant d?une grande relevance si l?on veut faire un design rationnel de drogues et de vaccins muqueux. Dans l?intestin grèle, ces organes sont composés de follicules multiples et sont appelés plaques de Peyer. Ils sont constitués de follicules enrichis en cellules B comprenant ou non un centre germinatif, de regions interfolliculaires comprenant des cellules T, et d?une région en d ome riche en cellules dendritiques, cellules B naives et cellules T CD4+, surmontée par un epithelium specialisé, le FAE (epithelium associé aux follicules). Le FAE contient des cellules M spécialisées dans le transport de macromolécules et micro-organismes de la lumière intestinale au tissu lymphoide sous-jacent. Ce transport des antigènes est une condition obligatoire pour induire une réponse immunitaire. Les cellules du FAE, outre les cellules M, expriment un programme de différenciation distinct de celui des cellules associées aux villosités. Ceci est characterisé par une baisse des fonctions digestives et de défenses, et l?expression constitutive des chimiokines: CCL20 et CCL25. Le but de l?étude présentée ici est de rechercher les facteurs cellulaires et/ou moléculaire responsables de cette différenciation. Certaines études ont démontré l?importance du contact entre le compartiment mésenchymateux et l?épithelium pour la morphogenèse de ce dernier. En particulier, les molécules de la matrice extracellulaire peuvent activer des gènes clefs qui, à leur tour, vont controler l?adhésion et la differenciation cellulaire. Dans l?intestin, les cellules mésenchymateuses différencient en myofibroblastes qui participent à l?élaboration de la matrice extracellulaire. Dans cette étude, nous avons décrit les différences d?expression de molécules de la matrices sous le FAE et les villosités. Nous avons également montré une absence de myofibroblastes sous le FAE. Suite à plusieurs évidences expérimentales, certains ont proposé une influence des composés présents dans la lumière sur la différenciation et/ou la maturation des plaques de Peyer. La chimiokine CCL20, capable de recruter des cellules initiatrices de la réponse immunitaire, constitue notre seul marqueur positif de FAE. Nous avons pu montrer que la flagelline, un composé du flagelle bactérien, était capable d?induire l?expression de CCL20 in vitro et in vivo. Cet effet n?est pas limité aux cellules du FAE mais est observé sur l?ensemble de l?épithelium intestinal. Molecular mechanisms of FAE differenciation. La signalement induit par la lymphotoxine ß est critique pour l?organogenèse des plaques de Peyer, car des souris déficientes pour cette molécules ou son récepteur n?ont ni plaque de Peyer, ni la plupart des ganglions lymphatiques. Nous avons obtenus plusieurs évidences que la lymphotoxine ß était impliquée dans la régulation du gène CCL20 in vitro et in vivo.<br/><br/>Mucosal surfaces of the respiratory, genital and digestive systems are exposed to food antigens, normal bacterial flora and oral pathogens. This justifies an intense and tuned immunological activity in mucosal tissues. The modulation of immune responses in the mucosa is thought to occur in specific sentinel sites, the organized mucosa associated lymphoid tissues (o-MALT). This immune modulation and the biology of these immune-inductive sites are poorly understood but highly important and relevant in the case of drugs and vaccines design. In the small intestine, these organs (gut associated lymphoid tissue : GALT) consists of single or multiple lymphoid follicles, the so-called Peyer?s patches (PP), with typical B cell-enriched follicles and germinal centers, inter-follicular T cell areas, and a dome region enriched in dendritic cells, naive B cells, and CD4+ T cells under a specialized follicle associated epithelium (FAE). To trigger protective immunity, antigens have to cross the mucosal epithelial barrier. This is achieved by the specialized epithelial M cells of the FAE that are able to take up and transport macromolecules and microorganisms from the environment into the underlying organized lymphoid tissue. The ontogeny of M cells remains controversial: some data are in favor of a distinct cell lineage, while others provide evidence for the conversion of differentiated enterocytes into M cells. In this study we mapped the proliferative, M cells and apoptotic compartments along the FAE. Enterocytes acquire transient M cell features as they leave the crypt and regain enterocyte properties as they move towards the apoptotic compartment at the apex of the FAE, favouring the hypothesis of a plastic phenotype. The follicle-associated epithelium (FAE) is found exclusively over lymphoid follicles in mucosal tissues, including Peyer?s patches. The enterocytes over Peyer?s patches express a distinct phenotype when compared to the villi enterocytes, characterized by the down regulation of digestive and defense functions and the constitutive expression of chemokines, i.e. CCL20 and CCL25. The purpose of this study was to investigate and identify the potential cells and/or molecules instructing FAE differentiation. Contact between the epithelial and the mesenchymal cell compartment is required for gut morphogenesis. Extracellular matrix molecules (ECM) can activate key regulatory genes which in turn control cell adhesion and differentiation. In the gut, mesenchymal cells differentiate into myofibroblats that participate to the elaboration of ECM. We have described a differential expression of extracellular matrix components under the FAE, correlating with the absence of subepithelial myofibroblats. Molecular mechanisms of FAE differenciation. Different studies proposed an influence of the luminal compartment in the differentiation and/or the maturation of PP. CCL20, a chemokine able to recruit cells that initiate adaptive immunity constitutes our first positive FAE molecular marker. We have shown that CCL20 gene expression is inducible in vitro and in vivo in intestinal epithelium by flagellin, a component of bacterial flagella. This effect was not restricted to the FAE. Lymphotoxin ß (LTß) signaling is critical for PPs organogenesis as LT deficient mice as well as LTß-receptor-/- mice lack PPs and most of the lymph nodes (LN). The continuous signaling via LTßR-expressing cells appears necessary for the maintenance throughout the life of PP architecture. We obtained in vitro and in vivo evidence that LTß signalling is involved in CCL20 gene expression.

Murine model of pneumonia caused by Parachlamydia acanthamoebae

The role of Parachlamydia acanthamoebae as an agent of pneumonia is suggested by sero-epidemiological studies, molecular surveys and by the permissivity of macrophages, lung fibroblasts and pneumocytes to this obligate intracellular bacteria. We thus developed a murine model of pneumonia due to Parachlamydia. Mice were inoculated intratracheally with Parachlamydia acanthamoebae. Pneumonia-associated mortality was of 50% 5 days post-inoculation. Lungs histopathology was characterized by purulent and interstitial pneumonia. The presence of Parachlamydia in the lesions was demonstrated by PCR, immunohistochemistry and electron microscopy. Moreover, living Parachlamydia could be recovered from the lungs of infected mice using amoebal co-culture. All control mice inoculated with heat-inactivated bacteria were free of symptoms and survived. Thus, we demonstrated that Parachlamydia induce a severe pneumonia in mice. This animal model, which confirms the third and fourth Koch postulates, may be suitable to test in vivo efficient therapeutic regimens against Parachlamydia.

A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder.

BACKGROUND: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD. METHODS: Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case-control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity. RESULTS: In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P <0.001) but explained only a modest amount of variance. Adding 'traditional' risk factors to GRS significantly improved the predictive ability with the area under the curve (AUC) in the ROC analysis, increasing from 0.58 to 0.66 (95% CI, 0.62-0.68; χ(2) = 27.68; P <0.0001). Although there was no formal evidence of interaction between depression status and GRS, there was further improvement in AUC in the ROC analysis when depression status was added to the model (AUC = 0.71; 95% CI, 0.68-0.73; χ(2) = 28.64; P <0.0001). We further found that the GRS accounted for more variance of BMI in depressed patients than in healthy controls. Again, GRS discriminated obesity better in depressed patients compared to healthy controls. We later replicated these analyses in two independent samples (GSK-Munich and PsyCoLaus) and found similar results. CONCLUSIONS: A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity.

Low C-reactive protein values at admission predict mortality in patients with severe community-acquired pneumonia caused by Streptococcus pneumoniae that require intensive care management.

PURPOSE: To identify risk factors associated with mortality in patients with severe community-acquired pneumonia (CAP) caused by S. pneumoniae who require intensive care unit (ICU) management, and to assess the prognostic values of these risk factors at the time of admission. METHODS: Retrospective analysis of all consecutive patients with CAP caused by S. pneumoniae who were admitted to the 32-bed medico-surgical ICU of a community and referral university hospital between 2002 and 2011. Univariate and multivariate analyses were performed on variables available at admission. RESULTS: Among the 77 adult patients with severe CAP caused by S. pneumoniae who required ICU management, 12 patients died (observed mortality rate 15.6 %). Univariate analysis indicated that septic shock and low C-reactive protein (CRP) values at admission were associated with an increased risk of death. In a multivariate model, after adjustment for age and gender, septic shock [odds ratio (OR), confidence interval 95 %; 4.96, 1.11-22.25; p = 0.036], and CRP (OR 0.99, 0.98-0.99 p = 0.034) remained significantly associated with death. Finally, we assessed the discriminative ability of CRP to predict mortality by computing its receiver operating characteristic curve. The CRP value cut-off for the best sensitivity and specificity was 169.5 mg/L to predict hospital mortality with an area under the curve of 0.72 (0.55-0.89). CONCLUSIONS: The mortality of patients with S. pneumoniae CAP requiring ICU management was much lower than predicted by severity scores. The presence of septic shock and a CRP value at admission <169.5 mg/L predicted a fatal outcome.

Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific long non-coding RNAs.

AIM: Heart disease is recognized as a consequence of dysregulation of cardiac gene regulatory networks. Previously, unappreciated components of such networks are the long non-coding RNAs (lncRNAs). Their roles in the heart remain to be elucidated. Thus, this study aimed to systematically characterize the cardiac long non-coding transcriptome post-myocardial infarction and to elucidate their potential roles in cardiac homoeostasis. METHODS AND RESULTS: We annotated the mouse transcriptome after myocardial infarction via RNA sequencing and ab initio transcript reconstruction, and integrated genome-wide approaches to associate specific lncRNAs with developmental processes and physiological parameters. Expression of specific lncRNAs strongly correlated with defined parameters of cardiac dimensions and function. Using chromatin maps to infer lncRNA function, we identified many with potential roles in cardiogenesis and pathological remodelling. The vast majority was associated with active cardiac-specific enhancers. Importantly, oligonucleotide-mediated knockdown implicated novel lncRNAs in controlling expression of key regulatory proteins involved in cardiogenesis. Finally, we identified hundreds of human orthologues and demonstrate that particular candidates were differentially modulated in human heart disease. CONCLUSION: These findings reveal hundreds of novel heart-specific lncRNAs with unique regulatory and functional characteristics relevant to maladaptive remodelling, cardiac function and possibly cardiac regeneration. This new class of molecules represents potential therapeutic targets for cardiac disease. Furthermore, their exquisite correlation with cardiac physiology renders them attractive candidate biomarkers to be used in the clinic.

Chromosome 7 gain and DNA hypermethylation at the HOXA10 locus are associated with expression of a stem cell related HOX-signature in glioblastoma.

BACKGROUND: HOX genes are a family of developmental genes that are expressed neither in the developing forebrain nor in the normal brain. Aberrant expression of a HOX-gene dominated stem-cell signature in glioblastoma has been linked with increased resistance to chemo-radiotherapy and sustained proliferation of glioma initiating cells. Here we describe the epigenetic and genetic alterations and their interactions associated with the expression of this signature in glioblastoma. RESULTS: We observe prominent hypermethylation of the HOXA locus 7p15.2 in glioblastoma in contrast to non-tumoral brain. Hypermethylation is associated with a gain of chromosome 7, a hallmark of glioblastoma, and may compensate for tumor-driven enhanced gene dosage as a rescue mechanism by preventing undue gene expression. We identify the CpG island of the HOXA10 alternative promoter that appears to escape hypermethylation in the HOX-high glioblastoma. An additive effect of gene copy gain at 7p15.2 and DNA methylation at key regulatory CpGs in HOXA10 is significantly associated with HOX-signature expression. Additionally, we show concordance between methylation status and presence of active or inactive chromatin marks in glioblastoma-derived spheres that are HOX-high or HOX-low, respectively. CONCLUSIONS: Based on these findings, we propose co-evolution and interaction between gene copy gain, associated with a gain of chromosome 7, and additional epigenetic alterations as key mechanisms triggering a coordinated, but inappropriate, HOX transcriptional program in glioblastoma.

A prospective observational study comparing a non-operator dependent automatic PWV analyser to pulse pressure, in assessing arterial stiffness in hemodialysis.

BACKGROUND: Chronic kidney disease (CKD) accelerates vascular stiffening related to age. Arterial stiffness may be evaluated measuring the carotid-femoral pulse wave velocity (PWV) or more simply, as recommended by KDOQI, monitoring pulse pressure (PP). Both correlate to survival and incidence of cardiovascular disease. PWV can also be estimated on the brachial artery using a Mobil-O-Graph; a non-operator dependent automatic device. The aim was to analyse whether, in a dialysis population, PWV obtained by Mobil-O-Graph (MogPWV) is more sensitive for vascular aging than PP. METHODS: A cohort of 143 patients from 4 dialysis units has been followed measuring MogPWV and PP every 3 to 6 months and compared to a control group with the same risk factors but an eGFR > 30 ml/min. RESULTS: MogPWV contrarily to PP did discriminate the dialysis population from the control group. The mean difference translated in age between the two populations was 8.4 years. The increase in MogPWV, as a function of age, was more rapid in the dialysis group. 13.3% of the dialysis patients but only 3.0% of the control group were outliers for MogPWV. The mortality rate (16 out of 143) was similar in outliers and inliers (7.4 and 8.0%/year). Stratifying patients according to MogPWV, a significant difference in survival was seen. A high parathormone (PTH) and to be dialysed for a hypertensive nephropathy were associated to a higher baseline MogPWV. CONCLUSIONS: Assessing PWV on the brachial artery using a Mobil-O-Graph is a valid and simple alternative, which, in the dialysis population, is more sensitive for vascular aging than PP. As demonstrated in previous studies PWV correlates to mortality. Among specific CKD risk factors only PTH is associated with a higher baseline PWV. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02327962.

Statins are associated with decreased mortality risk after status epilepticus.

BACKGROUND AND PURPOSE: Statins display anti-inflammatory and anti-epileptogenic properties in animal models, and may reduce the epilepsy risk in elderly humans; however, a possible modulating role on outcome in patients with status epilepticus (SE) has not been assessed. METHODS: This cohort study was based on a prospective registry including all consecutive adults with incident SE treated in our center between April 2006 and September 2012. SE outcome was categorized at hospital discharge into 'return to baseline', 'new disability' and 'mortality'. The role of potential predictors, including statins treatment on admission, was evaluated using a multinomial logistic regression model. RESULTS: Amongst 427 patients identified, information on statins was available in 413 (97%). Mean age was 60.9 (±17.8) years; 201 (49%) were women; 211 (51%) had a potentially fatal SE etiology; and 191 (46%) experienced generalized-convulsive or non-convulsive SE in coma. Statins (simvastatin, atorvastatin or pravastatin) were prescribed prior to admission in 76 (18%) subjects, mostly elderly. Whilst 208 (50.4%) patients returned to baseline, 58 (14%) died. After adjustment for established SE outcome predictors (age, etiology, SE severity score), statins correlated significantly with lower mortality (relative risk ratio 0.38, P = 0.046). CONCLUSION: This study suggests for the first time that exposure to statins before an SE episode is related to its outcome, involving a possible anti-epileptogenic role. Other studies are needed to confirm this intriguing finding.

Preferred Spatial Frequencies for Human Face Processing Are Associated with Optimal Class Discrimination in the Machine

Psychophysical studies suggest that humans preferentially use a narrow band of low spatial frequencies for face recognition. Here we asked whether artificial face recognition systems have an improved recognition performance at the same spatial frequencies as humans. To this end, we estimated recognition performance over a large database of face images by computing three discriminability measures: Fisher Linear Discriminant Analysis, Non-Parametric Discriminant Analysis, and Mutual Information. In order to address frequency dependence, discriminabilities were measured as a function of (filtered) image size. All three measures revealed a maximum at the same image sizes, where the spatial frequency content corresponds to the psychophysical found frequencies. Our results therefore support the notion that the critical band of spatial frequencies for face recognition in humans and machines follows from inherent properties of face images, and that the use of these frequencies is associated with optimal face recognition performance.

APOE status modulates the changes in network connectivity induced by brain stimulation in non-demented elders.

Behavioral consequences of a brain insult represent an interaction between the injury and the capacity of the rest of the brain to adapt to it. We provide experimental support for the notion that genetic factors play a critical role in such adaptation. We induced a controlled brain disruption using repetitive transcranial magnetic stimulation (rTMS) and show that APOE status determines its impact on distributed brain networks as assessed by functional MRI (fMRI).Twenty non-demented elders exhibiting mild memory dysfunction underwent two fMRI studies during face-name encoding tasks (before and after rTMS). Baseline task performance was associated with activation of a network of brain regions in prefrontal, parietal, medial temporal and visual associative areas. APOE ε4 bearers exhibited this pattern in two separate independent components, whereas ε4-non carriers presented a single partially overlapping network. Following rTMS all subjects showed slight ameliorations in memory performance, regardless of APOE status. However, after rTMS APOE ε4-carriers showed significant changes in brain network activation, expressing strikingly similar spatial configuration as the one observed in the non-carrier group prior to stimulation. Similarly, activity in areas of the default-mode network (DMN) was found in a single component among the ε4-non bearers, whereas among carriers it appeared disaggregated in three distinct spatiotemporal components that changed to an integrated single component after rTMS. Our findings demonstrate that genetic background play a fundamental role in the brain responses to focal insults, conditioning expression of distinct brain networks to sustain similar cognitive performance.

Factors associated with durable response to infliximab in Crohn's disease 5 years and beyond : a multicenter international cohort

BACKGROUND: Infliximab (IFX) has been used for over a decade worldwide. Less is known about the natural history of IFX use beyond a few years and which patients are more likely to sustain benefits. METHODS: Patients with Crohn's disease (CD) exposed to IFX from Massachusetts General Hospital, Boston, Saint-Antoine Hospital, Paris, and the Swiss IBD Cohort Study were identified through retrospective and prospective data collection, complemented by chart abstraction of electronic medical records. We compared long-term users of IFX (>5 yr of treatment, long-term users of infliximab [LTUI]), with non-LTUI patients to identify prognostic factors. RESULTS: We pooled data on 1014 patients with CD from 3 different databases, of whom 250 were defined as LTUI. The comparison group comprised 290 patients with CD who discontinued IFX: 48 primary nonresponses, 95 loss of responses, and 147 adverse events. Factors associated with LTUI were colonic involvements and an earlier age at the start of IFX. The prevalence of active smokers and obese patients differed markedly, but inversely, between American and European centers but did not impact outcome. The discontinuation rate was stable around 3% to 6%, each year from years 3 to 10. CONCLUSIONS: Young age at start of IFX and colonic CD are factors associated with a beneficial long-term use of IFX. After 5 years of IFX, there is still a 3% to 5% discontinuation rate annually. Several factors associated with a good initial response such as nonsmoker and shorter disease duration at IFX initiation do not seem associated with a longer term response.

Fatigue prolongée ou chronique d'origine indéterminée : prise en charge pharmacologique et non pharmacologique

Bien que la fatigue prolongée ou chronique soit une plainte très fréquente en médecine de premier recours, une cause biomédicale évidente n'est souvent pas retrouvée. Dans une telle situation, pour les femmes entre 18 et 50 ans avec un taux de ferritine inférieur à 50 µg/l en l'absence d'anémie, un traitement de fer peut être associé à une amélioration de la fatigue. Un traitement adapté est également important en cas de dépression, d'anxiété ou d'insomnie. Dans les autres situations, la prise en charge est essentiellement non pharmacologique sous forme de conseils d'hygiène de vie, d'empathie, de thérapie cognitivo-comportementale ainsi que d'exercices physiques progressifs et adaptés. Although prolonged or chronic fatigue is a very common complaint in primary care medicine, a biomedical obvious cause is often not found. In such a case, for women between 18 and 50 years with a ferritin level of less than 50 µg/l in the absence of anaemia, an iron supplementation may be associated with an improvement in fatigue. Appropriate treatment is also important for depression, anxiety or insomnia. In other cases, the approach is essentially non-pharmacological in the form of lifestyle advice, empathy and cognitive behavioural therapy as well as progressive and adapted physical exercises.

Rainfall is a risk factor for sporadic cases of Legionella pneumophila Pneumonia

It is not known whether rainfall increases the risk of sporadic cases of Legionella pneumonia. We sought to test this hypothesis in a prospective observational cohort study of non-immunosuppressed adults hospitalized for community-acquired pneumonia (1995-2011). Cases with Legionella pneumonia were compared with those with non-Legionella pneumonia. Using daily rainfall data obtained from the regional meteorological service we examined patterns of rainfall over the days prior to admission in each study group. Of 4168 patients, 231 (5.5%) had Legionella pneumonia. The diagnosis was based on one or more of the following: sputum (41 cases), antigenuria (206) and serology (98). Daily rainfall average was 0.556 liters/m2 in the Legionella pneumonia group vs. 0.328 liters/m2 for non-Legionella pneumonia cases (p = 0.04). A ROC curve was plotted to compare the incidence of Legionella pneumonia and the weighted median rainfall. The cut-off point was 0.42 (AUC 0.54). Patients who were admitted to hospital with a prior weighted median rainfall higher than 0.42 were more likely to have Legionella pneumonia (OR 1.35; 95% CI 1.02-1.78; p = .03). Spearman Rho correlations revealed a relationship between Legionella pneumonia and rainfall average during each two-week reporting period (0.14; p = 0.003). No relationship was found between rainfall average and non-Legionella pneumonia cases (−0.06; p = 0.24). As a conclusion, rainfall is a significant risk factor for sporadic Legionella pneumonia. Physicians should carefully consider Legionella pneumonia when selecting diagnostic tests and antimicrobial therapy for patients presenting with CAP after periods of rainfall.