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Machine learning is increasingly introduced into medical fields, yet there is limited evidence for its benefit over more commonly used statistical methods in epidemiological studies. We introduce an unsupervised machine learning framework for longitudinal features and evaluate it using sexual behaviour data from the last 20 years from over 3’700 participants in the Swiss HIV Cohort Study (SHCS). We use hierarchical clustering to find subgroups of men who have sex with men in the SHCS with similar sexual behaviour up to May 2017, and apply regression to test whether these clusters enhance predictions of sexual behaviour or sexually transmitted diseases (STIs) after May 2017 beyond what can be predicted with conventional parameters. We find that behavioural clusters enhance model performance according to likelihood ratio test, Akaike information criterion and area under the receiver operator characteristic curve for all outcomes studied, and according to Bayesian information criterion for five out of ten outcomes, with particularly good performance for predicting future sexual behaviour and recurrent STIs. We thus assess a methodology that can be used as an alternative means for creating exposure categories from longitudinal data in epidemiological models, and can contribute to the understanding of time-varying risk factors.

Background. Observational studies showed that the profile of infective endocarditis (IE) significantly changed over the past decades. However, most studies involved referral centers. We conducted a population-based study to control for this referral bias. The objective was to update the description of characteristics of IE in France and to compare the profile of community-acquired versus healthcare-associated IE. Methods. A prospective population-based observational study conducted in all medical facilities from 7 French regions (32% of French individuals aged ≥18 years) identified 497 adults with Duke-Li—definite IE who were first admitted to the hospital in 2008. Main measures included age-standardized and sex-standardized incidence of IE and multivariate Cox regression analysis for risk factors of in-hospital death. Results. The age-standardized and sex-standardized annual incidence of IE was 33.8 (95% confidence interval [CI], 30.8-36.9) cases per million inhabitants. The incidence was highest in men aged 75-79 years. A majority of patients had no previously known heart disease. Staphylococci were the most common causal agents, accounting for 36.2% of cases (Staphylococcus aureus, 26.6%; coagulase-negative staphylococci, 9.7%). Healthcare-associated IE represented 26.7% of all cases and exhibited a clinical pattern significantly different from that of community-acquired IE. S. aureus as the causal agent of IE was the most important factor associated with in-hospital death in community-acquired IE (hazard ratio [HR], 2.82 [95% CI, 1.72-4.61]) and the single factor in healthcare-associated IE (HR, 2.54 [95% CI, 1.33-4.85]). Conclusions. S. aureus became both the leading cause and the most important prognostic factor of IE, and healthcare-associated IE appeared as a major subgroup of the disease.

Introduction In HIV patients, haemophagocytic syndrome (HPS) may occur in the presence of cancer, concomitant viral infection, HIV primo‐infection or at the initiation of highly active antiretroviral therapy (HAART). Hodgkin lymphoma remains a rare cause of HPS. We describe a case of HPS with very high Epstein Barr virus (EBV) load in a HIV patient as initial manifestation of Hodgkin lymphoma. Materials and Methods A 29‐year‐old HIV positive man, successfully treated with HAART with an undetectable viral load and CD4 cells count of 438/µl, was admitted for high fever of unknown origin. Laboratory results showed a pancytopenia with haemoglobin at 82 g/l, lymphocyte count at 0.36G/l and platelets count at 47G/l; a highly elevated ferritine >7500 µg/l; increased lactate dehydrogenase at 885U/l and soluble IL2 receptor (CD25) >60 ng/ml. EBV load was measured and confirmed at 2,600,000 copies/ml. A PET‐CT imaging showed diffuse elevated metabolic activity in the bone marrow and in two lesions in the spleen without lymphadenopathy. Bone marrow and liver biopsies revealed images of haemophagocytosis and lymphocyte depleted Hodgkin lymphoma. Treatment consisted in etoposid, steroids, and R‐ABVD (rituximab, doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy. The patient completed six cycles of chemotherapy. We reviewed the literature in PubMed with the following keywords: HPS, HIV, EBV, Hodgkin lymphoma. Results We identified four publications and two reviews reporting cases of HPS associated with Hodgkin lymphoma in HIV patients with either a positive EBV load either the presence of encoded EBV RNA in tumour cells. Twenty‐two cases (including one pediatric case) were described. Among adults, mostly men, the median age was <50 years and immune suppression was marked with a median CD4 cell count<100 cells/µl, even in patients receiving HAART. When measured, EBV load in the serum was high. Prognosis was poor with a high mortality despite adequate treatment consisting in steroids and chemotherapy, with or without etoposide (Table 1). Conclusions Our case report and the review of literature suggest that physicians should be aware of the association between EBV infection/reactivation and Hodgkin lymphoma as a cause of HPS in HIV patients, even if successfully treated with HAART. The pathogenesis of these three interrelated conditions (viral infection, oncogenesis and immunologic reaction) remains unclear.

Embolic events to the central nervous system are a major cause of morbidity and mortality in patients with infective endocarditis (IE). The appropriate role of valvular surgery in reducing such embolic events is unclear. The purpose of this study was to determine the relationship between the initiation of antimicrobial therapy and the temporal incidence of stroke in patients with IE and to determine if this time course differs from that shown for embolic events in previous studies. Prospective incidence cohort study involving 61 tertiary referral centers in 28 countries. Case report forms were analyzed from 1437 consecutive patients with left-sided endocarditis admitted directly to participating centers. The crude incidence of stroke in patients receiving appropriate antimicrobial therapy was 4.82/1000 patient days in the first week of therapy and fell to 1.71/1000 patient days in the second week. This rate continued to decline with further therapy. Stroke rates fell similarly regardless of the valve or organism involved. After 1 week of antimicrobial therapy, only 3.1% of the cohort experienced a stroke. The risk of stroke in IE falls dramatically after the initiation of effective antimicrobial therapy. The falling risk of stroke in patients with IE as a whole precludes stroke prevention as the sole indication for valvular surgery after 1 week of therapy.

ObjectiveAntiphospholipid (aPL) antibodies may activate platelets and contribute to vegetation growth and embolisation in infective endocarditis (IE). We aimed to determine the value of aPL as predictors of embolic events (EE) in IE.MethodsWe studied 186 patients with definite IE (Duke-Li criteria, all types of IE) from the Nanc-IE prospective registry (2007–2012) who all had a frozen blood sample and at least one imaging procedure to detect asymptomatic or confirm symptomatic EE. Anticardiolipin (aCL) and anti-β2-glycoprotein I (β2GPI) antibodies (IgG and IgM) were assessed after the end of patients’ inclusion. The relationship between antibodies and the detection of EE after IE diagnosis were studied with Kaplan-Meier and Cox multivariate analyses.ResultsAt least one EE was detected in 118 (63%) patients (52 cerebral, 95 other locations) after IE diagnosis in 80 (time interval between IE and EE diagnosis: 5.9±11.3 days). At least one aPL antibody was found in 31 patients (17%).Detection of EE over time after IE diagnosis was more frequent among patients with anti-β2GPI IgM (log-rank P=0.0036) and that of cerebral embolisms, among patients with aCL IgM and anti-β2GPI IgM (log-rank P=0.002 and P<0.0001, respectively).Factors predictive of EE were anti-β2GPI IgM (HR=3.45 (1.47–8.08), P=0.0045), creatinine (2.74 (1.55–4.84), P=0.0005) and vegetation size (2.41 (1.41–4.12), P=0.0014). Those of cerebral embolism were aCL IgM (2.84 (1.22–6.62), P=0.016) and anti-β2GPI IgM (4.77 (1.79–12.74), P=0.0018).ConclusionThe presence of aCL and anti-β2GPI IgM was associated with EE, particularly cerebral ones, and could contribute to assess the embolic risk of IE.

Histoplasmosis is an infectious disease caused by the inhalation of Histoplasma capsulatum spores, a fungus encountered in many diverse areas around the world. Although this infection is often asymptomatic, it may become dramatic in immunocompromised patients. In November 2005, an endocarditis due to Histoplasma capsulatum was diagnosed in a French woman treated for rheumatoid arthritis and who had traveled to South America 2 years earlier. We confirmed the biological diagnosis by mycological, serological, and histological methods. In spite of receiving the appropriate treatment, the patient died 3 months later of cardiac insufficiency. We report here this additional case of Histoplasma endocarditis, by hoping to help rapid and accurate diagnosis of such infections in their early stages of development, in non-endemic areas.

Background. We aimed to compare oral hygiene habits, orodental status, and dental procedures in patients with infective endocarditis (IE) according to whether the IE-causing microorganism originated in the oral cavity. Methods. We conducted an assessor-blinded case-control study in 6 French tertiary-care hospitals. Oral hygiene habits were recorded using a self-administered questionnaire. Orodental status was analyzed by trained dental practitioners blinded to the microorganism, using standardized clinical examination and dental panoramic tomography. History of dental procedures was obtained through patient and dentist interviews. Microorganisms were categorized as oral streptococci or nonoral pathogens using an expert-validated list kept confidential during the course of the study. Cases and controls had definite IE caused either by oral streptococci or nonoral pathogens, respectively. Participants were enrolled between May 2008 and January 2013. Results. Cases (n = 73) were more likely than controls (n = 192) to be aged <65 years (odds ratio [OR], 2.85; 95% CI, 1.41–5.76), to be female (OR, 2.62; 95% CI, 1.20–5.74), to have native valve disease (OR, 2.44; 95% CI, 1.16–5.13), to use toothpicks, dental water jet, interdental brush, and/or dental floss (OR, 3.48; 95% CI, 1.30–9.32), and to have had dental procedures during the prior 3 months (OR, 3.31; 95% CI, 1.18–9.29), whereas they were less likely to brush teeth after meals. The presence of gingival inflammation, calculus, and infectious dental diseases did not significantly differ between groups. Conclusions. Patients with IE caused by oral streptococci differ from patients with IE caused by nonoral pathogens regarding background characteristics, oral hygiene habits, and recent dental procedures, but not current orodental status.

BackgroundBeta-hemolytic streptococci (BHS) are an uncommon cause of infective endocarditis (IE). The aim of this study was to describe the clinical features and outcomes of patients with BHS IE in a large multinational cohort and compare them with patients with viridans streptococcal IE.MethodsThe International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) is a large multinational database that recruited patients with IE prospectively using a standardized data set. Sixty-four sites in 28 countries reported patients prospectively using a standard case report form developed by ICE collaborators.ResultsAmong 1336 definite cases of streptococcal IE, 823 were caused by VGS and 147 by BHS. Patients with BHS IE had a lower prevalence of native valve (P < .005) and congenital heart disease predisposition (P = .002), but higher prevalence of implantable cardiac device predisposition (P < .005). Clinically, they were more likely to present acutely (P < .005) and with fever (P = .024). BHS IE was more likely to be complicated by stroke and other systemic emboli (P < .005). The overall in-hospital mortality of BHS IE was significantly higher than that of VGS IE (P = .001). In univariate analysis, variables associated with in-hospital mortality for BHS IE were age (odds ratio [OR], 1.044; P = .004), prosthetic valve IE (OR, 3.029; P = .022), congestive heart failure (OR, 2.513; P = .034), and stroke (OR, 3.198; P = .009).ConclusionsBHS IE is characterized by an acute presentation and higher rate of stroke, systemic emboli, and in-hospital mortality than VGS IE. Implantable cardiac devices as a predisposing factor were more often found in BHS IE compared with VGS IE.

Objective Whether sex-related differences in the prognosis of infective endocarditis (IE) are due to differences in disease severity or comorbid patterns, physiological specificities or a treatment indication bias is unclear. We conducted an analysis of the pooled database of two population-based cohorts of IE to reassess the relationships between sex, early valve surgery (EVS) and outcome in patients with IE. Methods Demographic and baseline characteristics, complications and outcome were compared in men and women with Duke-definite left-sided IE. A propensity model for EVS was constructed using multivariate logistic regression. Factors associated with 1-year mortality were identified using multivariate Cox models adjusted for EVS factors. Results The study population included 466 (75%) men and 154 (25%) women. Compared with men, women were older (p=0.005), were more often on haemodialysis (p=0.04), more often had a mitral valve IE (50.0% vs 35.8%, p=0.02), less often developed a septic shock (p=0.05), less often underwent EVS (p=0.001) yet had comparable inhospital mortality rates (20.1% vs 20.0%, p=0.96) and similar 1-year survival probability (logrank p=0.68). Female sex was neither associated with EVS (OR 0.76 (95% CI 0.49 to 1.16)) nor mortality (HR 1.17 (95% CI 0.80 to 1.69)). However EVS was associated with an increased risk of death in women in the early postoperative period (HR 8.72 (95% CI 3.42 to 22.24), p=<0.0001). Conclusions Women underwent EVS less often than men. However female sex was independently associated with neither EVS nor 1-year mortality. The reasons for a higher risk of early postoperative mortality in women must still be elucidated.