Anemia and bleeding in patients receiving anticoagulant therapy for venous thromboembolism: comment.

Kuperman et al. found that patients with anemia had a higher risk of major bleeding (RR 2.84; 95% CI 2.52-3.39) in RIETE database. Anemia appeared to be an independent predictive factor for major bleeding [hazard ratio (HR) 1.95; 95% CI 1.72-2.20] in this registry. Unfortunately, selection bias due to enrolled patients does not allowed us to use these major results in ambulatory care. The aim of SCORE study was to refine bleeding risk estimation in French vitamin K antagonist (VKA) treated patients and to identifying one or several parameters of prognostic significance. We conducted a prospective, multi-center cohort study of 962 consecutive outpatients from private angiologic offices, clinics and hospitals enrolled in grenoble angiologic network for thromboembolic diseases between May 2009 and December 2010, followed during 1 year by their general practitioner. Main outcome was the occurrence of major bleeding or clinically non major relevant bleeding (CNMRB). Incidence rates major bleeding and CNMRB were 2.86 (95% CI 1.95-4.2) events per 100 patient-years and 12% (95% CI 9.89-14.11) respectively. Cox multivariate analyses showed that only anemia was strongly associated with a risk of major bleeding (HR 6.1; 95% CI 2.7-13.8; p = 0.001). Logistic regression analyses performed in CNMRB showed that anemia, prior gastro-intestinal bleeding and antiplatelet drug use were strongly associated with a risk of CNMRB at 1 year, respectively OR 2.53, 95% CI (1.4-4.56); p = 0.002, OR 3.32, 95% CI (1.51-7.31); p = 0.003 and OR 1.77, 95% CI (1.1-2.83); p = 0.017. These new data were consistent between major and CRNM bleeding in VKA treated patients. The key role of anemia should be confirmed in other prospective cohort studies, with different anticoagulants use such as direct oral anticoagulant in ambulatory care settings.

Factors affecting dementia screening by general practitioners in community-dwelling elderly populations: a large cross-sectional study in 2 areas of France.

In patients aged 75 years and above, dementia is associated with increased expenditure and high morbimortality. Although the incidence of dementia is well known, it is often underrecognized in primary care. We conducted a cross-sectional study in 2 areas in the southeast of France to identify the factors affecting dementia-screening implementation by the French general practitioners (GPs). In May 2008, an anonymized survey was sent by e-mail and/or post to all GPs with a large clinic practice. Two months later, reminder letters were sent. Overall, 493 GPs answered (26.8%) to self-reported behavior. Of these, 73.2% felt that annual screening was useful, although only 24.5% implemented it each year and 17.5% implemented it every 2 to 5 years. Factors that favorably influenced screening practices were: the older age of the GPs; belief in the usefulness of annual dementia screening; increased frequency of follow-up visits by elderly patients; and the proportion of dementia in the GP's practice. The main barrier to annual screening was the social problems encountered in the medical care of 75-year-old patients. Regardless of the differences in European national health policies or health care systems, all GPs encounter the same difficulties when dealing with elderly dementia patients.

Cytokine profiles in adults with imported malaria.

The increase in worldwide travel is making imported malaria a growing health concern in non-endemic countries. Most data on the pathophysiology of malaria come from endemic areas. Little is known about cytokine profiles during imported malaria. This study aimed at deciphering the relationship between cytokine host response and malaria severity among imported cases in France. This study reports cytokine profiles in adults with Plasmodium falciparum malaria included in the PALUREA prospective study conducted between 2006 and 2010. The patients were classified as having uncomplicated malaria (UM) or severe malaria (SM), with this last further categorized as very severe malaria (VSM) or less severe malaria (LSM). At hospital admission, eight blood cytokines were assayed in duplicate using Luminex® technology: interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-10, tumor necrosis factor (TNF)α, interferon (IFN)γ, and macrophage migration inhibitory factor (MIF). These assays were repeated on days 1 and 2 in the SM group. Of the 278 patients, 134 had UM and 144 SM. At hospital admission, over half the patients had undetectable levels of IL-1α, IL-1ß, IL-2, IL-4, IFNγ, and TNFα, while IL-10 and MIF were significantly higher in the SM vs. the UM group. Higher IL-10 was significantly associated with higher parasitemia (R = 0.32 [0.16-0.46]; P = 0.0001). In the SM group, IL-10 elevation persisting from admission to day 2 was significantly associated with subsequent nosocomial infection. Of eight tested cytokines, only MIF and IL-10 were associated with disease severity in adults with imported P. falciparum malaria. At admission, many patients had undetectable cytokine levels, suggesting that circulating cytokine assays may not be helpful as part of the routine evaluation of adults with imported malaria. Persisting high IL-10 concentration was associated with subsequent nosocomial infection, suggesting its possible interest in immune monitoring of most severe patients.

Reasons for seeking care and adherence to pretravel preparation in expatriate or long-term travelers' children in the tropics: A French prospective study.

BACKGROUND: Studies on pediatric travelers' health rarely address expat or long-term travelers' children. METHOD: To investigate reasons for seeking care and adherence to pretravel preparation, we prospectively enrolled French children 0-15 years old, either expatriates or staying >6 months in tropical areas, who attended a French health center in Africa, Central America or Southern Pacific regions from October 01, 2011 to October 31, 2012. A standardized questionnaire was completed by a general practitioner at each visit, then anonymized and included in our database. RESULTS: 464 questionnaires were collected from 367 children (sex ratio M/F: 1:1). Median age was 6.4 years (IQR: 3.6; 10.3). Reasons for seeking care were mostly infections (n = 378), of which 12 (3.2%) were tropical. There were no deaths, but one child with tuberculosis was repatriated. Coverage was high for routine immunization, but less for travel-related vaccines. Personal antivectorial protection was significantly lower in children aged >5 y or in non-malarial areas. Where indicated, malarial chemoprophylaxis was prescribed to only one third of the children, of whom 60% were poorly compliant. Advice regarding measures against diarrhea was followed significantly more for stays <2 yrs. CONCLUSION: Mild cosmopolitan illnesses predominated but protection against tropical threats should be optimized before and during the stay.

Outpatient healthcare and clinical trials in the care pathway: Organisational and regulatory aspects and tools.

Clinical research in outpatient healthcare, particularly in general practice, which is the first line of contact with the population, is now a public health issue. However, this type of research has specific characteristics that differentiate it from clinical research conducted in a hospital setting and requires an adaptation of its conditions of practice: in terms of organisation, the development of research in outpatient healthcare relies on the appropriation of its fundamentals by the investigators, which implies their presentation, upstream, from the initial cycle, and the participation of practitioners in training modules adapted to research in primary care, such as those already organised by several GIRCI (Groupement Inter régional de la Recherche Clinique et de l'Innovation [French Interregional Clusters for Clinical Research and Innovation]). To compensate for the fragmented nature of their location, on the model of the EMRCs (équipes mobiles de recherche clinique [mobile clinical research teams]) in oncology, mobile research teams should enable general medical practices to participate in clinical trials. This presupposes, on the one hand, the allocation of earmarked funding to ensure the sustainability of a base of dedicated personnel and, on the other hand, the impetus of a national dynamic through the setting up of a multi-organisation thematic institute for "research in primary care" associated, at the operational level, with a national scale investigation network supported by a platform of excellence. The use of digital tools and innovations (telemedicine; data collection via connected tools; e-consent; electronic signature) which make it possible to digitise and relocate all or part of the research procedures for both the participant and the investigation teams. An adaptation of the legal framework in order to bring the place of research closer to the patient and not the other way round, which means moving the equipment and investigations closer to the patient. Taking into account the acceptability of the patient, thus limiting the disruption that may be caused by his or her participation in a research protocol and motivating the practitioner by valuing his or her contribution and providing all the guarantees of scientific relevance and independence of practice. In view of the contextual analysis, positive feedback and the availability of organisational and digital support points facilitating the delocalisation and digitisation of the conduct of research activity as close as possible to the patient and his or her doctor, the round table concluded that opportunities exist today which favour the development of clinical research in general practice. It is important to seize this opportunity and make the most of it without delay.

Scalp eschar and neck lymphadenopathy caused by Bartonella henselae after Tick Bite.

Rickettsia slovaca and Rickettsia raoultii have been associated with a syndrome characterized by scalp eschar and neck lymphadenopathy following tick bites. However, in many cases, the causative agent remains undetermined. We report 3 cases of this syndrome caused by Bartonella henselae, and we propose the term "SENLAT" to collectively describe this clinical entity.

Doxycycline failure in lymphogranuloma venereum.

Lymphogranuloma venereum (LGV) cases are currently re-emerging in the homosexual community, particularly in HIV-seropositive patients. The standard treatment for this infection, which is caused by Chlamydia trachomatis L1, L2 and L3 serotypes, is a 3-week doxycycline regimen. The case is reported of a male patient presenting with LGV, who was rapidly cured with moxifloxacin treatment after failure of extended treatment with cyclines. This fluoroquinolone is known to be highly active in vitro on the LGV pathogenic agent. Thus it may be a useful alternative when doxycycline treatment results in failure.

Fatal cardiotoxicity related to halofantrine: a review based on a worldwide safety data base.

BACKGROUND: Halofantrine (HF) was considered an effective and safe treatment for multi-drug resistant falciparum malaria until 1993, when the first case of drug-associated death was reported. Since then, numerous studies have confirmed cardiac arrythmias, possibly fatal, in both adults and children. The aim of the study was to review fatal HF related cardiotoxicity. METHODS: In addition, to a systematic review of the literature, the authors have had access to the global safety database on possible HF related cardiotoxicity provided by GlaxoSmithKline. RESULTS: Thirty-five cases of fatal cardiotoxicity related to HF, including five children, were identified. Females (70%) and patients from developing countries (71%) were over-represented in this series. Seventy-four percent of the fatal events occurred within 24 hours of initial exposure to HF. Twenty six patients (74%) had at least one predisposing factor for severe cardiotoxicity, e.g., underlying cardiac disease, higher than recommended doses, or presence of a concomitant QT-lengthening drug. All (100%) of the paediatric cases had either a contraindication to HF or an improper dose was given. In six cases there was no malaria. CONCLUSION: A distinction should be made between common but asymptomatic QT-interval prolongation and the much less common ventricular arrhythmias, such as torsades de pointes, which can be fatal and seem to occur in a very limited number of patients. The majority of reported cardiac events occurred either in patients with predisposing factors or with an improper dose.Therefore, in the rare situations in which HF is the only therapeutic option, it can still be given after carefully checking for contraindications, such as underlying cardiac disease, bradycardia, metabolic disorders, personal or family history of long QT-interval or concomitant use of another QT-prolonging drug (e.g., mefloquine), especially in females.

Pathological rupture of the spleen in malaria: analysis of 55 cases (1958-2008).

BACKGROUND: Splenic rupture during acute malaria is rare but underreported. Because splenic rupture occurs mostly in non-immune adults, ongoing malaria elimination efforts may paradoxically increase the proportion of Plasmodium-infected patients suffering from this life-threatening complication. The pathogenesis and optimal patient management are still debated. METHOD: We collected and analysed reports of pathological rupture of the spleen associated with malaria published over the last 50 years in five languages. RESULTS: Fifty-five cases were reported, due to Plasmodium falciparum (n=26), Plasmodium vivax (n=23), Plasmodium ovale (n=2), Plasmodium malariae (n=2), or P. vivax-falciparum (n=2), and occurred in travellers (n=24), locals (n=21), expatriates (n=6) or migrants (n=4). Median age was 31.5 years and sex ratio M/F 3.2. Splenic rupture was complete with hemoperitoneum (n=50), or partial (n=5). Death occurred in 12 patients (22%), 8 of whom from early irreversible collapse (n=7) or unexpected death (n=1). Death rate was higher among travellers than in other patients (9/24, 38%, versus 3/31, 10%, p=0.01). Clinical features of P. falciparum- or P. vivax-associated splenic rupture were strikingly similar. Treatment included in-hospital medical observation without surgery (conservative management, n=14), immediate splenectomy (n=29), delayed splenectomy (n=4), or none (patients dying at admission, n=8). The type of treatment, conservative or not, had no influence on prognosis. The median duration of malaria symptoms before diagnosis was longer in our review (5-6 days) than in previous reports on imported malaria (3-4 days), suggesting that early diagnosis and therapy of malaria may reduce the incidence of splenic rupture. CONCLUSIONS: Abdominal pain, collapse, or fainting is warning symptoms. Fourteen published observations support conservative management in carefully selected patients. Spleen preservation likely reduces the risk of future severe malaria attacks in patients with potential further exposition to Plasmodium sp., and also that of overwhelming sepsis in all.

Epidemiology of Early-onset Bacterial Neonatal Infections in Madagascar.

BACKGROUND: Little is known about early-onset neonatal bacterial infections (EONBI) in Madagascar. Our aim was to determine their epidemiology to improve their management. METHODS: Inborn neonates at risk for EONBI and admitted in the neonatal unit of 2 tertiary hospitals in Antananarivo, Madagascar, were included in a prospective study from April 2012 to March 2013. Using a clinical algorithm, blood culture, gastric fluid culture and C-reactive protein dosage were performed in newborns at high risk of infection, that is, peri partum fever, prematurity <35 weeks' gestation or birth weight <2000 g, or presenting with clinical signs of infection. EONBI was defined as a bacteremia occurring within the first week of life. RESULTS: Among 307 neonates, 75 (24.4%) had an EONBI caused by 1 (n = 59) or 2 (n = 16) bacteria (91 isolates). Gram-negative bacteria were predominant (n = 62, 82.7%), including Enterobacter cloacae (n = 26), Klebsiella pneumoniae (n = 14), Escherichia coli (n = 7) and Proteus mirabilis (n = 2). Group B Streptococcus, Acinetobacter baumanii and Enterococcus sp. represented 3.6%, 8.2% and 12.1% of the isolates, respectively. All E. cloacae and 12/14 (85.7%) K. pneumoniae were extended-spectrum ß-lactamase producers. At all, 41/91 (45.1%) bacteria were multidrug-resistant (MDR) and 34/75 (45.3%) newborns had an EONBI caused by an MDR bacteria. Neonatal asphyxia was the only factor associated with multidrug resistance (odds ratio: 4.52; CI: 1.20-16.94; P = 0.025). The EONBI-related mortality (n = 20/75, 26.7%) rose up to 38.2% (n = 13/34) in case of MDR bacteria. CONCLUSIONS: The epidemiology of EONBIs in Madagascar is comparable to that found in many low-income countries. Prevention, including improvement of hygiene during resuscitation for neonatal asphyxia, is likely to be more effective in reducing EONBI-related morbidity and mortality than using new antibiotics to counter resistance.

Outcome of life-threatening malaria in African children requiring endotracheal intubation.

BACKGROUND: Little is known about children undergoing critical care for malaria. The purpose of this survey was to evaluate the outcome in African children requiring endotracheal intubation for life-threatening malaria. METHODS: All children with a primary diagnosis of severe malaria (2000 WHO definition) requiring endotracheal intubation, hospitalised over a five-year period, within a tertiary-care hospital in Dakar, Senegal, were enrolled in a retrospective cohort study. RESULTS: 83 consecutive patients were included (median PRISM h24 score: 14; IQR: 10-19, multiple organ dysfunctions: 91.5%). The median duration of ventilation was 36 hrs (IQR: 4-72). Indications for intubation were deep coma (Glasgow score

Severe imported malaria in children in France. A national retrospective study from 1996 to 2005.

BACKGROUNDS: Malaria is a leading cause of imported febrile illnesses in pediatric travelers, but few studies have addressed severe imported pediatric malaria. We aimed to determine the risk factors and the features of imported pediatric severe malaria. METHODS: We conducted a retrospective, descriptive study using the French National Reference Center for Imported Malaria database, in children aged 0-15 years who were hospitalized with a falciparum malaria from January 1st 1996 to December 31th 2005. Uncomplicated and severe cases of falciparum malaria were compared to identify risk factors for severe cases. In the hospitals that reported more than five severe cases during the study period, we evaluated severe cases for prognostic factors and assessed the accuracy WHO criteria for predicting severity. Given the rarity of deaths, adverse outcomes were defined as requiring major therapeutic procedures (MTPs)-e.g., sedation, mechanical ventilation, nasal oxygen therapy, blood transfusions, hemodialysis, fluid resuscitation-or pediatric intensive care unit (PICU) admission. RESULTS: Of 4150 pediatric malaria cases included in the study, 3299 were uncomplicated and 851 (20.5%) were severe. Only one death was recorded during this period. Predictors for severe falciparum malaria were: age <2 years (OR = 3.2, 95% CI = 2.5-4.0, p <0.0001) and a travel in the Sahelian region (OR = 1.7, 95% CI = 1.3-2.0, p = 0.0001). Of 422 severe malaria cases, a stay in a Sahelian region, lack of chemoprophylaxis, age <2 years or thrombocytopenia <100 x 10^3/mm^3 predicted adverse outcomes. Except for the hyperparasitemia threshold of 4%, the main WHO 2000 criteria for severe malaria reliably predicted adverse outcomes. In our study, the threshold of parasitemia most predictive of a poor outcome was 8%. CONCLUSION: In imported pediatric malaria, children younger than 2 years deserve particular attention. The main WHO 2000 criteria for severity are accurate, except for the threshold of hyperparasitemia, which should be revised.

Prevalence of Mycoplasma pneumoniae Infection in Malagasy Children.

BACKGROUND: Childhood community-acquired pneumonia is a leading cause of childhood morbidity in low-income countries. The etiologic agents are usually Staphylococcus aureus, Streptococcus pneumoniae and Mycoplasma pneumoniae. M. pneumoniae was recognized as a cofactor in asthmatic disease. High asthma prevalence was reported in Madagascar. Our aim was to clarify the prevalence of M. pneumoniae infection in this country and its relationship with asthma. METHODS: A prospective study was conducted in 351 children (from 2 to 16 years of age) from January 2012 to December 2014. According to the clinical symptoms, children were enrolled in 3 groups: "control group" (CG, n = 106), "asthma group" (n = 129) and "pneumonia group" (n = 116). The IgG and IgM M. pneumoniae status was evaluated by an enzyme-linked immunosorbent assay. Clinical signs of infection, socioeconomic data and antimicrobial treatment were recorded. RESULTS: The overall prevalence of M. pneumoniae infection was 18.2%. The multivariate analysis demonstrated that M. pneumoniae infection was significantly more frequent in the CG [pneumonia group vs. CG: odds ratio = 0.45 (0.21-0.91), P = 0.037 and asthma group vs. CG: odds ratio = 0.39 (0.18-0.87), P = 0.021]. The C-reactive protein value was significantly higher in children with M. pneumonia-positive serology (85 vs. 61 mg/L, P = 0.03). Of note, 99 (41%) children received antibiotics before attending. CONCLUSIONS: We report a prevalence of 18.2% for M. pneumoniae infection in children in Madagascar. The prevalence of M. pneumoniae infection was higher in the control patients than in asthmatic ones.

Evaluation of Pediatric Risk of Mortality (PRISM) scoring in African children with falciparum malaria.

OBJECTIVE: Little is known about the use of generic severity scores in severe childhood infectious diseases. The purpose of this prospective study was to evaluate the performance of the Pediatric Risk of Mortality (PRISM) scoring system in predicting the outcome of falciparum malaria in African children. DESIGN, SETTING, PATIENTS: All children admitted to a 120-bed pediatric ward in a tertiary care hospital in Dakar, Senegal, with a primary diagnosis of acute malaria were assigned a PRISM score after 24 hrs or at time of death. INTERVENTIONS: None. RESULTS: PRISM discrimination, evaluated by areas under receiver operating characteristic curves (AUC), was good both for all acute malaria cases (n = 311; lethality, 9%; AUC, 0.89; 95% confidence interval [CI], 0.85-0.92) and for severe malaria cases (n = 233; lethality, 12%; AUC, 0.86; 95% CI, 0.81-0.90). However, the number of children who died was greater than the number of deaths predicted by PRISM (standardized mortality ratio, 2.16; 95% CI, 1.46-2.87). CONCLUSION: This discrepancy observed in five classes of expected mortality (Hosmer-Lemeshow chi-square test, p < .001) may have been due to chance (sample size too small for a valid test), to a lower standard of care in Dakar than in the American hospitals where PRISM was designed, or to a failure of PRISM to classify risk in severe malaria.

Barriers to and promoters of screening for falls in elderly community-dwelling patients by general practitioners: a large cross-sectional survey in two areas of France.

The objective was to determine the factors affecting French GPs' implementation of annual screening for falls among patients of 75 years old and over. We conduct a cross-sectional study in two areas in the South-east of France (Savoie and Isère). An anonymized survey was sent by e-mail and/or post in May 2008 to all GPs with a large practice. Reminder letters were sent to GPs who hadn't answered between June and July 2008. Potentials barriers were measured by dichotomous scale. On GPs characteristics (socio-demographic, knowledge, attitude and practice), a multiple logistic regression was performed to identify others factors affecting falls screening. 493 questionnaires were analyzed (26.8%). 65.3% of respondents considered annual screening for falls to be useful, though only 28.8% of them implemented it each year and 9.3% every two to five years. Barriers to achieving annual screening included patient selecting (56.3%), forgetting to screen (26.6%), unsuitable working conditions (18.5%), lack of time (13.3%), of knowledge (13.3%), or of financial compensation (11.1%). Perception of the usefulness of annual screening for falls (OR=5.38 (2.07-14.08); p=0.001), satisfaction with medical care for falls (OR=1.34 (1.09-1.65); p=0.006) and increased consultation time (OR=2.65 (1.37-5.13); p=0.004), were found to have a significant impact on the implementation of annual screening for falls. Asking your patient each year if s/he has had any falls, inquiring about gait and balance disturbance is not time consuming. Finally, to improve a health-related quality of life, GPs should consider fall assessment as a fundamental feature of medical care.

Acute meningitis owing to phlebotomus fever Toscana virus imported to France.

Acute lymphocytic meningitis, seen in France in summer, is often due to enteroviruses. Arboviruses as West Nile and tick-borne encephalitis do exist in Europe, but other viruses are rarely considered in patients unless they have had recent tropical travel. Toscana virus infection, which is endemic, especially in Italy,1-3 has been documented in some European travelers returning from Italy,4-6 but surprisingly was not documented in France until recently.7 We report a case of meningitis caused by Toscana virus imported to France.

Prognostic value of thrombocytopenia in African children with falciparum malaria.

Thrombocytopenia is a common finding in malaria, but its prognostic value has not been addressed in children. The relationship between thrombocytopenia (platelet count < 100,000/mm3 on admission) and severity and outcome was investigated prospectively in children hospitalized with falciparum malaria in Dakar, Senegal, an area that is hypoendemic for malaria. Of 288 falciparum cases, 215 matched the 2000 World Health Organization definition of severe malaria. Median platelet counts were lower (98,000/mm3 versus 139,000/mm3; P < 0.02) among severe cases than in mild cases, and in children who died than among those who recovered (68,500/mm3 versus 109,000/mm3; P < 0.002). In severe cases, children presenting with a platelet count < 100,000/mm3 were more likely to die (odds ratio [OR] = 6.31, 95% confidence interval [CI] = 2.0-26.0). Moreover, multivariate analysis identified thrombocytopenia as an independent predictor of death (OR = 13.3, 95% CI = 3.2-55.1). Our data show an association between thrombocytopenia and either severity or prognosis in childhood falciparum malaria.

Epidemiological and clinical aspects of blackwater fever among African children suffering frequent malaria attacks.

Blackwater fever (BWF), one of the commonest causes of death of Europeans living in Africa at the beginning of the twentieth century, but rarely diagnosed since the 1950s, is related to Plasmodium falciparum malaria but there is considerable debate and controversy about its aetiology. From 1990 to 2000, the whole population of Dielmo, a village in Senegal, was involved in a prospective study of malaria. Three cases of BWF occurred in 3 children aged 4, 7 and 10 years, belonging to a subgroup of children who suffered malaria attacks every 4 to 6 weeks over many years, who had received repeated quinine treatment. The spread of chloroquine resistance, by increasing the use of more toxic alternative drugs, may expose endemic populations to a high incidence of severe side effects of antimalarials.