Incident Hepatitis C Virus Infections in the Swiss HIV Cohort Study : changes in treatment uptake and outcomes between 1991 and 2013

Background: The hepatitis C virus (HCV) epidemic is evolving rapidly in patients infected with human immunodeficiency virus (HIV). We aimed to describe changes in treatment uptake and outcomes of incident HCV infections before and after 2006, the time-point at which major changes in HCV epidemic became apparent. Methods.  We included all adults with an incident HCV infection before June 2012 in the Swiss HIV Cohort Study, a prospective nationwide representative cohort of individuals infected with HIV. We assessed the following outcomes by time period: the proportion of patients starting an HCV therapy, the proportion of treated patients achieving a sustained virological response (SVR), and the proportion of patients with persistent HCV infection during follow-up. Results.  Of 193 patients with an HCV seroconversion, 106 were diagnosed before and 87 after January 2006. The proportion of men who have sex with men increased from 24% before to 85% after 2006 (P < .001). Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (P < .001). Treatment was started during early infection in 22% of patients before and 91% after 2006 (P < .001). An SVR was achieved in 78% and 29% (P = .01) of patients treated during early and chronic HCV infection. The probability of having a detectable viral load 5 years after diagnosis was 0.67 (95% confidence interval [CI], 0.58-0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16-0.35) in the other group (P < .001). Conclusions. In recent years, increased uptake and earlier initiation of HCV therapy among patients with incident infections significantly reduced the proportion of patients with replicating HCV.

Surgery for unruptured arteriovenous malformations of the brain is better than conservative management for selected cases : a prospective cohort study

Object. The aim of this study was to identify patients who are likely to benefit from surgery for unruptured brain arterriovenous malformations (ubAVMs). Methods. The authors' database was interrogated for the risk and outcome of hemorrhage after referral and the out- come from surgery. Furthermore, the outcome from surgery incorporated those cases excluded from surgery because of perceived greater risk (sensitivity analysis). Finally, a comparison was made for the authors' patients between the natural history and surgery. Data were collected for 427 consecutively enrolled patients with ubAVMs in a database that in- cluded patients who were conservatively managed. Kaplan-Meier analysis was performed on patients observed for more than 1 day to determine the risk of hemorrhage. Variables that may influence the risk of first hemorrhage were assessed using Cox proportional hazard regression models and Kaplan-Meier life table analyses from referral until the first occur- rence of the following: hemorrhage, treatment, or last review. The outcome from surgery (leading to a new permanent neurological deficit with last review modified Rankin Scale [mRS] score > 1) was determined. Further sensitivity analy- sis was made to predict risk from surgery for the total ubAVM cohort by incorporating outcomes of surgical cases as well as cases excluded from surgery because of perceived risk, and assuming an adverse outcome for these excluded cases. Results. A total of 377 patients with a ubAVM were included in the analysis of the risk of hemorrhage. The 5-year risk of hemorrhage for ubAVM was 11.5%. Hemorrhage resulted in an mRS score > 1 in 14 cases (88% [95% CI 63%-98%]). Patients with Spetzler-Ponce Class A ubAVMs treated by surgery (n = 190) had a risk from surgery of 1.6% (95% CI 0.3%-4.8%) for a permanent neurological deficit leading to an mRS score > 1 and 0.5% (95% CI< 0.1%-3.2%) for a permanent neurological deficit leading to an mRS score > 2. Patients with Spetzler-Ponce Class B ubAVMs treated by surgery (n = 107) had a risk from surgery of 14.0% (95% CI 8.6%-22.0%) for a permanent neurological deficit leading to an mRS score > 1. Sensitivity analysis of Spetzler-Ponce Class B ubAVMs, including those in patients excluded from surgery, showed that the true risk for surgically eligible patients may have been as high as 15.6% (95% CI 9.9%-23.7%) for mRS score > 1, had all patients who were perceived to have a greater risk experienced an adverse outcome. Patients with Spetzler-Ponce Class C ubAVMs treated by surgery (n = 44) had a risk from surgery of 38.6% (95% CI 25.7%-53.4%) for a permanent neurological deficit leading to an mRS score >1. Sensitivity analysis of Class C ubAVMs, including those harbored by patients excluded from surgery, showed that the true risk for surgically eligible patients may have been as high as 60.9% (95% CI 49.2%-71.5%) for mRS score > 1, had all patients who were perceived to have a greater risk experienced an adverse outcome. Conclusion. Surgical outcomes for Spetzler-Ponce Class ubAVMs are better than those for conservative management.

CoDiab-VD: protocol of a prospective population-based cohort study on diabetes care in Switzerland.

BACKGROUND: Diabetes represents an increasing health burden worldwide. In 2010, the Public Health Department of the canton of Vaud (Switzerland) launched a regional diabetes programme entitled "Programme cantonal Diabète" (PcD), with the objectives to both decrease the incidence of diabetes and improve care for patients with diabetes. The cohort entitled CoDiab-VD emerged from that programme. It specifically aimed at following quality of diabetes care over time, at evaluating the coverage of the PcD within this canton and at assessing the impact of the PcD on care of patients with diabetes. METHODS/DESIGN: The cohort CoDiab-VD is a prospective population-based cohort study. Patients with diabetes were recruited in two waves (autumn 2011--summer 2012) through community pharmacies. Eligible participants were non-institutionalised adult patients (≥ 18 years) with diabetes diagnosed for at least one year, residing in the canton of Vaud and coming to a participating pharmacy with a diabetes-related prescription. Women with gestational diabetes, people with obvious cognitive impairment or insufficient command of French were not eligible. Self-reported data collected, included the following primary outcomes: processes-of-care indicators (annual checks) and outcomes of care such as HbA1C, (health-related) quality of life measures (Short Form-12 Health Survey--SF-12, Audit of Diabetes-Dependent Quality of Life 19--ADDQoL) and Patient Assessment of Chronic Illness Care (PACIC). Data on diabetes, health status, healthcare utilisation, health behaviour, self-management activities and support, knowledge of, or participation to, campaigns/activities proposed by the PcD, and socio-demographics were also obtained. For consenting participants, physicians provided few additional pieces of information about processes and laboratory results. Participants will be followed once a year, via a mailed self-report questionnaire. The core of the follow-up questionnaires will be similar to the baseline one, with the addition of thematic modules adapting to the development of the PcD. Physicians will be contacted every 2 years. DISCUSSION: CoDiab-VD will allow obtaining a broad picture of the care of patients with diabetes, as well as their needs regarding their chronic condition. The data will be used to evaluate the PcD and help prioritise targeted actions. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier NCT01902043, July 9, 2013.

Increases in condomless sex in the Swiss HIV Cohort Study.

Condomless sex is a key driver of sexually transmitted diseases. In this study, we assess the long-term changes (2000-2013) of the occurrence of condomless sex among human immunodeficiency virus (HIV)-infected individuals enrolled in the Swiss HIV Cohort study. The frequencies with which HIV-infected individuals reported condomless sex were either stable or only weakly increasing for 2000-2008. For 2008-2013, these rates increased significantly for stable relationships among heterosexuals and men who have sex with men (MSM) and for occasional relationships among MSM. Our results highlight the increasing public health challenge posed by condomless sex and show that condomless sex has been increasing even in the most recent years.

Contrast : a concept in language and its development in Medieval Spanish

The purpose of this PhD thesis is to investigate a semantic relation present in the connection of sentences (more specifically: propositional units). This relation, which we refer to as contrast, includes the traditional categories of adversatives - predominantly represented by the connector but in English and pero in Modern Spanish - and concessives, prototypically verbalised through although / aunque. The aim is to describe, analyse and - as far as possible - to explain the emergence and evolution of different syntactic schemes marking contrast during the first three centuries of Spanish (also referred to as Castilian) as a literary language, i.e., from the 13th to the 15th century. The starting point of this question is a commonplace in syntax, whereby the semantic and syntactic complexity of clause linkage correlates with the degree of textual elaboration. In historical linguistics, i.e., applied to the phylogeny of a language, it is commonly referred to as the parataxis hypothesis A crucial part of the thesis is dedicated by the definition of contrast as a semantic relation. Although the label contrast has been used in this sense, mainly in functional grammar and text linguistics, mainstream grammaticography and linguistics remain attached to the traditional categories adversatives and concessives. In opposition to this traditional view, we present our own model of contrast, based on a pragma-semantic description proposed for the analysis of adversatives by Oswald Ducrot and subsequently adopted by Ekkehard König for the analysis of concessives. We refine and further develop this model in order for it to accommodate all, not just the prototypical instances of contrast in Spanish, arguing that the relationship between adversatives and concessives is a marked opposition, i.e., that the higher degree of semantic and syntactic integration of concessives restricts some possible readings that the adversatives may have, but that this difference is almost systematically neutralised by contextual factors, thus justifying the assumption of contrast as a comprehensive onomasiological category. This theoretical focus is completed by a state-of-the-question overview attempting to account for all relevant forms in which contrast is expressed in Medieval Spanish, with the aid of lexicographic and grammaticographical sources, and an empirical study investigating the expression of corpus in a corpus study on the textual functions of contrast in nine Medieval Spanish texts: Cantar de Mio Cid, Libro de Alexandre, Milagros de Nuestra Sehora, Estoria de Espana, Primera Partida, Lapidario, Libro de buen amor, Conde Lucanor, and Corbacho. This corpus is analysed using quantitative and qualitative tools, and the study is accompanied by a series of methodological remarks on how to investigate a pragma-semantic category in historical linguistics. The corpus study shows that the parataxis hypothesis fails to prove from a statistical viewpoint, although a qualitative analysis shows that the use of subordination does increase over time in some particular contexts.

Chronological order of appearance of extraintestinal manifestations relative to the time of IBD diagnosis in the Swiss Inflammatory Bowel Disease Cohort

BACKGROUND: Data evaluating the chronological order of appearance of extraintestinal manifestations (EIMs) relative to the time of inflammatory bowel disease (IBD) diagnosis is currently lacking. We aimed to assess the type, frequency, and chronological order of appearance of EIMs in patients with IBD. METHODS: Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. RESULTS: The data on 1249 patients were analyzed (49.8% female, median age: 40 [interquartile range, 30-51 yr], 735 [58.8%] with Crohn's disease, 483 [38.7%] with ulcerative colitis, and 31 [2.5%] with indeterminate colitis). A total of 366 patients presented with EIMs (29.3%). Of those, 63.4% presented with 1, 26.5% with 2, 4.9% with 3, 2.5% with 4, and 2.7% with 5 EIMs during their lifetime. Patients presented with the following diseases as first EIMs: peripheral arthritis 70.0%, aphthous stomatitis 21.6%, axial arthropathy/ankylosing spondylitis 16.4%, uveitis 13.7%, erythema nodosum 12.6%, primary sclerosing cholangitis 6.6%, pyoderma gangrenosum 4.9%, and psoriasis 2.7%. In 25.8% of cases, patients presented with their first EIM before IBD was diagnosed (median time 5 mo before IBD diagnosis: range, 0-25 mo), and in 74.2% of cases, the first EIM manifested itself after IBD diagnosis (median: 92 mo; range, 29-183 mo). CONCLUSIONS: In one quarter of patients with IBD, EIMs appeared before the time of IBD diagnosis. Occurrence of EIMs should prompt physicians to look for potential underlying IBD.

Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy.

Inherited retinal dystrophies present extensive phenotypic and genetic heterogeneity, posing a challenge for patients' molecular and clinical diagnoses. In this study, we wanted to clinically characterize and investigate the molecular etiology of an atypical form of autosomal recessive retinal dystrophy in two consanguineous Spanish families. Affected members of the respective families exhibited an array of clinical features including reduced visual acuity, photophobia, defective color vision, reduced or absent ERG responses, macular atrophy and pigmentary deposits in the peripheral retina. Genetic investigation included autozygosity mapping coupled with exome sequencing in the first family, whereas autozygome-guided candidate gene screening was performed by means of Sanger DNA sequencing in the second family. Our approach revealed nucleotide changes in CDHR1; a homozygous missense variant (c.1720C > G, p.P574A) and a homozygous single base transition (c.1485 + 2T > C) affecting the canonical 5' splice site of intron 13, respectively. Both changes co-segregated with the disease and were absent among cohorts of unrelated control individuals. To date, only five mutations in CDHR1 have been identified, all resulting in premature stop codons leading to mRNA nonsense mediated decay. Our work reports two previously unidentified homozygous mutations in CDHR1 further expanding the mutational spectrum of this gene.

Epidemiology and outcome of fungemia in a cancer Cohort of the Infectious Diseases Group (IDG) of the European Organization for Research and Treatment of Cancer (EORTC 65031).

BACKGROUND: Anti-cancer treatment and the cancer population have evolved since the last European Organisation for Research and Treatment of Cancer (EORTC) fungemia survey, and there are few recent large epidemiological studies. METHODS: This was a prospective cohort study including 145 030 admissions of patients with cancer from 13 EORTC centers. Incidence, clinical characteristics, and outcome of fungemia were analyzed. RESULTS: Fungemia occurred in 333 (0.23%; 95% confidence interval [CI], .21-.26) patients, ranging from 0.15% in patients with solid tumors to 1.55% in hematopoietic stem cell transplantation recipients. In 297 evaluable patients age ranged from 17 to 88 years (median 56 years), 144 (48%) patients were female, 165 (56%) had solid tumors, and 140 (47%) had hematological malignancies. Fungemia including polymicrobial infection was due to: Candida spp. in 267 (90%), C. albicans in 128 (48%), and other Candida spp. in 145 (54%) patients. Favorable overall response was achieved in 113 (46.5%) patients by week 2. After 4 weeks, the survival rate was 64% (95% CI, 59%-70%) and was not significantly different between Candida spp. Multivariable logistic regression identified baseline septic shock (odds ratio [OR] 3.04, 95% CI, 1.22-7.58) and tachypnoea as poor prognostic factors (OR 2.95, 95% CI, 1.66-5.24), while antifungal prophylaxis prior to fungemia (OR 0.20, 95% CI, .06-.62) and remission of underlying cancer (OR, 0.18; 95% CI, .06-.50) were protective. CONCLUSIONS: Fungemia, mostly due to Candida spp., was rare in cancer patients from EORTC centers but was associated with substantial mortality. Antifungal prophylaxis and remission of cancer predicted better survival.

Transient detectable viremia and the risk of viral rebound in patients from the Swiss HIV Cohort Study.

BACKGROUND: Temporary increases in plasma HIV RNA ('blips') are common in HIV patients on combination antiretroviral therapy (cART). Blips above 500 copies/mL have been associated with subsequent viral rebound. It is not clear if this relationship still holds when measurements are made using newer more sensitive assays. METHODS: We selected antiretroviral-naive patients that then recorded one or more episodes of viral suppression on cART with HIV RNA measurements made using more sensitive assays (lower limit of detection below 50 copies/ml). We estimated the association in these episodes between blip magnitude and the time to viral rebound. RESULTS: Four thousand ninety-four patients recorded a first episode of viral suppression on cART using more sensitive assays; 1672 patients recorded at least one subsequent suppression episode. Most suppression episodes (87 %) were recorded with TaqMan version 1 or 2 assays. Of the 2035 blips recorded, 84 %, 12 % and 4 % were of low (50-199 copies/mL), medium (200-499 copies/mL) and high (500-999 copies/mL) magnitude respectively. The risk of viral rebound increased as blip magnitude increased with hazard ratios of 1.20 (95 % CI 0.89-1.61), 1.42 (95 % CI 0.96-2.19) and 1.93 (95 % CI 1.24-3.01) for low, medium and high magnitude blips respectively; an increase of hazard ratio 1.09 (95 % CI 1.03 to 1.15) per 100 copies/mL of HIV RNA. CONCLUSIONS: With the more sensitive assays now commonly used for monitoring patients, blips above 200 copies/mL are increasingly likely to lead to viral rebound and should prompt a discussion about adherence.

High hepatic and extrahepatic mortality and low treatment uptake in HCV-coinfected persons in the Swiss HIV cohort study between 2001 and 2013.

BACKGROUND & AIMS: The landscape of HCV treatments is changing dramatically. At the beginning of this new era, we highlight the challenges for HCV therapy by assessing the long-term epidemiological trends in treatment uptake, efficacy and mortality among HIV/HCV-coinfected people since the availability of HCV therapy. METHODS: We included all SHCS participants with detectable HCV RNA between 2001 and 2013. To identify predictors for treatment uptake uni- and multivariable Poisson regression models were applied. We further used survival analyses with Kaplan-Meier curves and Cox regression with drop-out as competing risk. RESULTS: Of 12,401 participants 2107 (17%) were HCV RNA positive. Of those, 636 (30%) started treatment with an incidence of 5.8/100 person years (PY) (95% CI 5.3-6.2). Sustained virological response (SVR) with pegylated interferon/ribavirin was achieved in 50% of treated patients, representing 15% of all participants with replicating HCV-infection. 344 of 2107 (16%) HCV RNA positive persons died, 59% from extrahepatic causes. Mortality/100 PY was 2.9 (95% CI 2.6-3.2) in untreated patients, 1.3 (1.0-1.8) in those treated with failure, and 0.6 (0.4-1.0) in patients with SVR. In 2013, 869/2107 (41%) participants remained HCV RNA positive. CONCLUSIONS: Over the last 13years HCV treatment uptake was low and by the end of 2013, a large number of persons remain to be treated. Mortality was high, particularly in untreated patients, and mainly due to non-liver-related causes. Accordingly, in HIV/HCV-coinfected patients, integrative care including the diagnosis and therapy of somatic and psychiatric disorders is important to achieve mortality rates similar to HIV-monoinfected patients.

Assessing the Paradox Between Transmitted and Acquired HIV Type 1 Drug Resistance Mutations in the Swiss HIV Cohort Study From 1998 to 2012.

BACKGROUND: Transmitted human immunodeficiency virus type 1 (HIV) drug resistance (TDR) mutations are transmitted from nonresponding patients (defined as patients with no initial response to treatment and those with an initial response for whom treatment later failed) or from patients who are naive to treatment. Although the prevalence of drug resistance in patients who are not responding to treatment has declined in developed countries, the prevalence of TDR mutations has not. Mechanisms causing this paradox are poorly explored. METHODS: We included recently infected, treatment-naive patients with genotypic resistance tests performed ≤1 year after infection and before 2013. Potential risk factors for TDR mutations were analyzed using logistic regression. The association between the prevalence of TDR mutations and population viral load (PVL) among treated patients during 1997-2011 was estimated with Poisson regression for all TDR mutations and individually for the most frequent resistance mutations against each drug class (ie, M184V/L90M/K103N). RESULTS: We included 2421 recently infected, treatment-naive patients and 5399 patients with no response to treatment. The prevalence of TDR mutations fluctuated considerably over time. Two opposing developments could explain these fluctuations: generally continuous increases in the prevalence of TDR mutations (odds ratio, 1.13; P = .010), punctuated by sharp decreases in the prevalence when new drug classes were introduced. Overall, the prevalence of TDR mutations increased with decreasing PVL (rate ratio [RR], 0.91 per 1000 decrease in PVL; P = .033). Additionally, we observed that the transmitted high-fitness-cost mutation M184V was positively associated with the PVL of nonresponding patients carrying M184V (RR, 1.50 per 100 increase in PVL; P < .001). Such association was absent for K103N (RR, 1.00 per 100 increase in PVL; P = .99) and negative for L90M (RR, 0.75 per 100 increase in PVL; P = .022). CONCLUSIONS: Transmission of antiretroviral drug resistance is temporarily reduced by the introduction of new drug classes and driven by nonresponding and treatment-naive patients. These findings suggest a continuous need for new drugs, early detection/treatment of HIV-1 infection.

Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study.

BACKGROUND: Ribavirin (RBV) is an essential component of most current hepatitis C (HCV) treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN) to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR). METHODS: We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS) participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT) 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24) and IL28B genotype (CC versus CT/TT). RESULTS: SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80]) and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73]), regardless of treatment phase, and IL28B genotype. CONCLUSION: In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.

Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF Cohort.

INTRODUCTION: Approximately 2% of lung adenocarcinomas have BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations, including V600E and other types. Vemurafenib, dabrafenib, and sorafenib as BRAF inhibitors are currently tested in clinical trials, but access for patients is limited. The aim of this study was to document the clinical course of patients treated outside of clinical trials. METHODS: We conducted a retrospective multicenter cohort study in Europe of patients with advanced BRAF-mutant lung cancer treated with known BRAF inhibitors. Data were anonymized and centrally assessed for age, gender, smoking, histology, stage, local molecular diagnostic results, systemic therapies, and survival. Best response was assessed locally by RECIST1.1. RESULTS: We documented 35 patients treated in 17 centers with vemurafenib, dabrafenib, or sorafenib. Median age was 63 years (range 42-85); gender was balanced; 14 (40%) were never smokers; all (100%) had adenocarcinoma; 29 (83%) had V600E; 6 (17%) had other mutations; one of them had a concomitant KRAS mutation. Thirty (86%) patients had chemotherapy in the first line. Overall survival with first-line therapy was 25.3 months for V600E and 11.8 months for non-V600E. Thirty-one patients received one BRAF inhibitor, and four received a second inhibitor. Overall response rate with BRAF therapy was 53%, and disease control rate was 85%. Median progression-free survival with BRAF therapy was 5.0 months, and overall survival was 10.8 months. CONCLUSIONS: These results confirm the activity of targeted therapy in patients with BRAF-mutant lung adenocarcinoma. Further trials are warranted to study combination therapies and drug resistance mechanisms.

Biomarkers of Host Response Predict Primary End-Point Radiological Pneumonia in Tanzanian Children with Clinical Pneumonia: A Prospective Cohort Study.

BACKGROUND: Diagnosing pediatric pneumonia is challenging in low-resource settings. The World Health Organization (WHO) has defined primary end-point radiological pneumonia for use in epidemiological and vaccine studies. However, radiography requires expertise and is often inaccessible. We hypothesized that plasma biomarkers of inflammation and endothelial activation may be useful surrogates for end-point pneumonia, and may provide insight into its biological significance. METHODS: We studied children with WHO-defined clinical pneumonia (n = 155) within a prospective cohort of 1,005 consecutive febrile children presenting to Tanzanian outpatient clinics. Based on x-ray findings, participants were categorized as primary end-point pneumonia (n = 30), other infiltrates (n = 31), or normal chest x-ray (n = 94). Plasma levels of 7 host response biomarkers at presentation were measured by ELISA. Associations between biomarker levels and radiological findings were assessed by Kruskal-Wallis test and multivariable logistic regression. Biomarker ability to predict radiological findings was evaluated using receiver operating characteristic curve analysis and Classification and Regression Tree analysis. RESULTS: Compared to children with normal x-ray, children with end-point pneumonia had significantly higher C-reactive protein, procalcitonin and Chitinase 3-like-1, while those with other infiltrates had elevated procalcitonin and von Willebrand Factor and decreased soluble Tie-2 and endoglin. Clinical variables were not predictive of radiological findings. Classification and Regression Tree analysis generated multi-marker models with improved performance over single markers for discriminating between groups. A model based on C-reactive protein and Chitinase 3-like-1 discriminated between end-point pneumonia and non-end-point pneumonia with 93.3% sensitivity (95% confidence interval 76.5-98.8), 80.8% specificity (72.6-87.1), positive likelihood ratio 4.9 (3.4-7.1), negative likelihood ratio 0.083 (0.022-0.32), and misclassification rate 0.20 (standard error 0.038). CONCLUSIONS: In Tanzanian children with WHO-defined clinical pneumonia, combinations of host biomarkers distinguished between end-point pneumonia, other infiltrates, and normal chest x-ray, whereas clinical variables did not. These findings generate pathophysiological hypotheses and may have potential research and clinical utility.

Schistosomiase aiguë au retour de voyage. Enseignements tirés d'une cohorte de 42 voyageurs exposés [Acute schistosomiasis: lessons learned from a cohort of 42 exposed travelers].

La schistosomiase aiguë est une pathologie régulièrement rencontrée chez les voyageurs. En raison de sa longue période d'incubation, de ses manifestations aspécifiques et de la résolution spontanée des symptômes, elle peut facilement ne pas être reconnue par un médecin peu familier des pathologies tropicales. En décembre 2011, une femme de retour de Madagascar, où elle avait été en contact avec de l'eau douce, a été hospitalisée pour un état fébrile d'origine indéterminé. Une schistosomiase aiguë a été diagnostiquée. Un dépistage chez tous les voyageurs de son groupe a révélé une séroconversion chez 78% des participants.Cet article cherche à rediscuter les mesures préventives et diagnostiques à la lumière des enseignements tirés de l'étude de cette cohorte de 42 voyageurs exposés à la schistosomiase. Acute schistosomiasis is a regularly encountered disease in travelers. Because of the temporal delay, its unspecific presentation and the spontaneous resolution, acute schistosomiasis can easily remain unrecognized by physicians who are not familiar with tropical pathologies. In December 2011, a female traveler was admitted to the hospital with undetermined fever after having returned from Madagascar where she bathed in fresh water. Acute schistosomiasis was diagnosed and infection was suspected among other travelers of her group. Seroconversion was confirmed among 78% of participants. This article intends to clarify the preventive and diagnostic strategies based on the lessons learned from this cluster of 42 travelers exposed to schistosomiasis.