Persistent headaches one year after bacterial meningitis: prevalence, determinants and impact on quality of life.

BACKGROUND: Little is known on headaches long-term persistence after bacterial meningitis and on their impact on patients' quality of life. METHODS: In an ancillary study of the French national prospective cohort of community-acquired bacterial meningitis in adults (COMBAT) conducted between February 2013 and July 2015, we collected self-reported headaches before, at onset, and 12 months (M12) after meningitis. Determinants of persistent headache (PH) at M12, their association with M12 quality of life (SF 12), depression (Center for Epidemiologic Studies Depression Scale) and neuro-functional disability were analysed. RESULTS: Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively. In multivariate analysis, female sex (OR: 2.75 [1.54-4.90]; p < 0.001), pre-existing headaches before meningitis (OR: 2.38 [1.32-4.30]; p < 0.01), higher neutrophilic polynuclei percentage in the CSF of the initial lumbar puncture (OR: 1.02 [1.00-1.04]; p < 0.05), and brain abscess during the initial hospitalisation (OR: 8.32 [1.97-35.16]; p < 0.01) were associated with M12 persistent headaches. Neither the responsible microorganism, nor the corticoids use were associated with M12 persistent headaches. M12 neuro-functional disability (altered Glasgow Outcome Scale; p < 0.01), M12 physical handicap (altered modified Rankin score; p < 0.001), M12 depressive symptoms (p < 0.0001), and M12 altered physical (p < 0.05) and mental (p < 0.0001) qualities of life were associated with M12 headaches. CONCLUSION: Persistent headaches are frequent one year after meningitis and are associated with quality of life alteration. CLINICAL TRIAL: NCT01730690.

Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease.

PURPOSE: Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015. METHODS: This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression. RESULTS: Among the 771 enrolled patients (median age 66 years, IQR [52.0-79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9 years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines. CONCLUSION: We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients. CLINICAL TRIAL: ClinicalTrial. Gov identification number: NCT01730690.

[Therapeutic alliance between sectorial psychiatry inpatients and nurses and aides: A prospective, observational and cross-sectional study]. / Alliance Thérapeutique Entre Les Patients Hospitalisés En Psychiatrie De Secteur Et Les Infirmier(e)s Et Aide-Soignant(e)s: Une Etude Prospective, Observationnelle Et Transversale.

BACKGROUND: Therapeutic alliance represents a rarely studied object when it relates to nurses and care provided by a nursing team in acute care hospitalization. OBJECTIVE: The objective was to study how factors might influence the therapeutic alliance built between nurses and aides and adult inpatients in an acute care unit of sectorial general psychiatry. METHOD: This is a prospective, observational and cross-sectional study using a therapeutic alliance measurement scale. Therapeutic alliance (TA) score was measured with a STAR-P scale in a sample of 240 patients. RESULTS: The median score found is 33.4 (±7.8) out of a maximum theoretical score of 48. The global score of TA in patients aged 60 years old or more is significantly higher than the score of patients between 18 and 29 years old (p=0.021). The lack of external follow-up in the three months after hospital release is not associated with TA global score (p=0.73). If inpatients, no matter what their diseases or types of care are, under legal obligation or not, consider their TA is rather good after their hospital stay. Only sociodemographic factors like age, housing conditions (insecure or sustainable), having a job or not, living alone or with a partner affect TA and follow-up. CONCLUSION: Results evoke concepts of anomie and attachment, that seem to play an important role in the lack of follow-up after hospital stay, and indicate the mandatory global approach to care and an involvement of health professionals as well as social beings, where empathy must find its place.

CONTEXTE: L'alliance thérapeutique représente un objet très peu étudié quand il concerne les infirmiers et les soins prodigués par une équipe infirmière et dans le cadre de l'hospitalisation en soins aigus. OBJECTIF: L'objectif était d'étudier l'influence de facteurs sur l'alliance thérapeutique construite entre les infirmier(e)s et les aides-soignant(e)s et les patients adultes hospitalisés dans un service de soins aigus en psychiatrie générale de secteur. MÉTHODE: Il s'agit d'une étude prospective, observationnelle et transversale utilisant une échelle de mesure de l'alliance thérapeutique. Le score d'alliance thérapeutique (AT) a été mesuré à l'aide de l'échelle STAR-P sur un échantillon de 240 patients. RÉSULTATS: Le score moyen obtenu est de 33,4 (±7,8) sur un score maximum théorique de 48. Le score global d'AT des patients âgés de 60 ans ou plus, est significativement plus élevé que celui des patients ayant entre 18 et 29 ans (p = 0,021). L'absence de suivi ambulatoire au cours des trois mois suivant la sortie d'hospitalisation n'est pas associée au score global d'AT (p = 0,73). Si les patients hospitalisés, quelques soit leurs troubles et les différentes formes de soins, sous obligation légale ou non, jugent plutôt bonne l'AT à l'issue de leur hospitalisation. Seuls des facteurs sociaux-démographiques comme, l'âge, les conditions d'hébergement (précaire ou durable), avoir ou non un emploi, vivre seul ou avec un partenaire influent sur l'AT et le suivi. CONCLUSION: Les résultats convoquent les concepts d'anomie et d'attachement, qui semblent jouer un rôle important dans l'absence de suivi post-hospitalisation, ce qui indiquent la nécessaire approche globale des soins et une implication des professionnels de santé mais aussi du social où l'empathie doit trouver sa place.

Skeletal evolution in Marfan syndrome: growth curves from a French national cohort.

BackgroundTo describe the growth patterns of children affected by Marfan syndrome (MFS) compared with those of unaffected children and to create growth charts.MethodsAn observational study of children referred to the French National MFS Reference Centre. A total of 259 children carrying an FBN1 gene mutation and fulfilling Ghent 1 criteria (MFS group) and 474 mutation-negative sibling controls (non-MFS group) were evaluated. Both groups were compared with French-accepted reference nomograms (Reference group).ResultsBoys and girls from the MFS group were significantly taller than those in the non-MFS group and in the reference group at all ages (P<0.0001). But, MFS children's overgrowth reduced with age. At 17 years of age, the mean height (MFS vs. non-MFS) was 191.2±8.4 cm (+2.9 SD) vs. 182.9±8.1 (+1.6 SD) for boys and 178.3±7.6 cm (+2.7 SD) vs. 169.5±6.8 (+1.2 SD) for girls, respectively. By contrast, the mean BMI of children in the MFS group was similar to those in the non-MFS group and inferior to the values of French general population, evolving around -1 SD.ConclusionGrowth patterns differ in patients with an FBN1 mutation. Knowing the growth parameters should allow physicians to better counsel patients and detect the associated diseases. The provided curves could also help to predict the final height.

Prevalence and treatment of atherogenic dyslipidemia in the primary prevention of cardiovascular disease in Europe: EURIKA, a cross-sectional observational study.

BACKGROUND: Atherogenic dyslipidemia is associated with poor cardiovascular outcomes, yet markers of this condition are often ignored in clinical practice. Here, we address a clear evidence gap by assessing the prevalence and treatment of two markers of atherogenic dyslipidemia: elevated triglyceride levels and low levels of high-density lipoprotein cholesterol. METHODS: This cross-sectional observational study assessed the prevalence of two atherogenic dyslipidemia markers, high triglyceride levels and low high-density lipoprotein cholesterol levels, in the study population from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA; N = 7641; of whom 51.6% were female and 95.6% were White/Caucasian). The EURIKA population included European patients, aged at least 50 years with at least one cardiovascular risk factor but no history of cardiovascular disease. RESULTS: Over 20% of patients from the EURIKA population have either triglyceride or high-density lipoprotein cholesterol levels characteristic of atherogenic dyslipidemia. Furthermore, the proportions of patients with one of these markers were higher in subpopulations with type 2 diabetes mellitus or those already calculated to be at high risk of cardiovascular disease. Approximately 55% of the EURIKA population who have markers of atherogenic dyslipidemia are not receiving lipid-lowering therapy. CONCLUSIONS: A considerable proportion of patients with at least one major cardiovascular risk factor in the primary cardiovascular disease prevention setting have markers of atherogenic dyslipidemia. The majority of these patients are not receiving optimal treatment, as specified in international guidelines, and thus their risk of developing cardiovascular disease is possibly underestimated. TRIAL REGISTRATION: The present study is registered with ClinicalTrials.gov (ID: NCT00882336).

Perip7lakin is a target for autoimmunity in asthma.

The role of autoimmunity targeting epithelial antigens in asthma has been suggested, in particular in non-atopic and severe asthma. Periplakin, a desmosomal component, is involved in epithelial cohesion and intracellular signaling. We detected anti-periplakin IgG antibodies in 47/260 (18 %) patients with asthma, with no association with severity or atopy. In addition, anti-periplakin IgE antibodies were detected in 12 of 138 tested patients (8.7 %) and were more frequently observed in patients with than without nasal polyposis. This study identifies a new autoimmune epithelial target in asthma. Whether periplakin autoimmunity (both IgG and IgE auto-antibodies) is involved in asthma pathogenesis remains to be studied during the disease course of these patients.

Body mass index and response to infliximab in rheumatoid arthritis.

OBJECTIVES: Excess adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetics consequences. Previous studies have suggested that obesity could negatively affect the response to anti-TNF-α agents, notably infliximab (IFX). We aimed to determine whether body mass index (BMI) is involved in the response to IFX in rheumatoid arthritis (RA). METHODS: We retrospectively examined data for 76 RA patients receiving IFX. BMI was calculated before treatment, and change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate, C-reactive protein level, tender and swollen joint count was analysed at 6 months after treatment. The primary outcome was decrease in DAS28 ≥1.2. Secondary outcomes were good response and remission according to EULAR. RESULTS: At baseline, the median [interquartile range] BMI was 26.6 [22.6-30.6] kg/m2. The number of patients with normal weight, overweight and obesity was 25, 29 and 22. In multivariable analyses, IFX treated patients with lower BMI showed a more frequent DAS28 decrease ≥1.2 (25.5 [22.3-28.3] vs. 28.0 [23.2-32.5], p=0.02, odds ratio [OR] 0.88 [95% confidence interval 0.79-0.98]), EULAR good response (25.3 [21.9-27.5] vs. 27.5 [24.3-31.2], p=0.03, OR 0.87 [0.76-0.99]) and EULAR remission, although not significant (25.3 [21.9-26.4] vs. 27.5 [23.2-30.9], p=0.14, OR 0.88 [0.75-1.04]). CONCLUSIONS: Obesity may negatively influence the response to IFX in RA. These data could help physicians to choose biologic agents for obese RA patients.

Emergence of quinolone resistance in the microbiota of hospitalized patients treated or not with a fluoroquinolone.

BACKGROUND: Quinolone resistance is a major global clinical problem. It primarily emerges in microbiota under selective pressure. Studies evaluating the incidence and risk factors for carrying quinolone-resistant bacteria in hospitalized patients treated with fluoroquinolones (FQs) are lacking. METHODS: We prospectively included hospitalized patients treated with FQs. Nasal, throat and rectal swabs were performed before FQ treatment, at the end of FQ treatment and 30 days later. A 'reference group' of patients not receiving FQs was also included to determine the rates of quinolone resistance acquisition not linked to FQ treatment. Prevalence and incidence of quinolone-resistant strains of nasal coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, pharyngeal α-haemolytic streptococci and faecal Escherichia coli, and risk factors for emergence of quinolone resistance in FQ-treated patients were assessed. RESULTS: Four-hundred and fifty-one FQ-treated patients were included, as well as 119 subjects in the 'reference group'. Emergence of quinolone resistance occurred in 110/213 (51.6%), 50/336 (14.9%), 53/290 (18.3%) and 46/336 (13.7%) of FQ-treated patients for CoNS, S. aureus, α-haemolytic streptococci and E. coli, respectively, significantly more than for reference patients for CoNS (23/65; P < 0.05), S. aureus (5/91; P < 0.02) and E. coli (4/84; P < 0.05), but not for α-haemolytic streptococci (15/70; P = 0.55). Emergence of resistance was not associated with the type of FQ received, the duration of therapy or the duration of hospital stay, but was associated with host factors such as immunosuppression and altered performance status. CONCLUSIONS: FQs received during hospitalization account for high rates of emergence of resistance to FQs in clinically relevant bacteria from human microbiota, reflecting the important ecological impact of FQs. Host factors outweighed treatment or hospitalization characteristics as risk factors for carrying quinolone-resistant strains.

Study of phenotype evolution during childhood in Marfan syndrome to improve clinical recognition.

PURPOSE: Because diagnosis of Marfan syndrome is difficult during infancy, we used a large cohort of children to describe the evolution of the Marfan syndrome phenotype with age. METHODS: Two hundred and fifty-nine children carrying an FBN1 gene mutation and fulfilling Ghent criteria were compared with 474 non-Marfan syndrome children. RESULTS: Prevalence of skeletal features changed with aging: prevalence of pectus deformity increased from 43% at 0-6 years to 62% at 15-17 years, wrist signs increased from 28 to 67%, and scoliosis increased from 16 to 59%. Hypermobility decreased from 67 to 47% and pes planus decreased from 73 to 65%. Striae increased from 2 to 84%. Prevalence of ectopia lentis remained stable, varying from 66 to 72%, similar to aortic root dilatation (varying from 75 to 80%). Aortic root dilatation remained stable during follow-up in this population receiving ß-blocker therapy. When comparing Marfan syndrome children with non-Marfan syndrome children, height appeared to be a simple and discriminant criterion when it was >3.3 SD above the mean. Ectopia lentis and aortic dilatation were both similarly discriminating. CONCLUSION: Ectopia lentis and aortic dilatation are the best-discriminating features, but height remains a simple discriminating variable for general practitioners when >3.3 SD above the mean. Mean aortic dilatation remains stable in infancy when children receive a ß-blocker.

C-reactive protein levels in patients at cardiovascular risk: EURIKA study.

BACKGROUND: Elevated C-reactive protein (CRP) levels are associated with high cardiovascular risk, and might identify patients who could benefit from more carefully adapted risk factor management. We have assessed the prevalence of elevated CRP levels in patients with one or more traditional cardiovascular risk factors. METHODS: Data were analysed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov Identifier: NCT00882336), which included patients (aged ≥50 years) from 12 European countries with at least one traditional cardiovascular risk factor but no history of cardiovascular disease. Analysis was also carried out on the subset of patients without diabetes mellitus who were not receiving statin therapy. RESULTS: In the overall population, CRP levels were positively correlated with body mass index and glycated haemoglobin levels, and were negatively correlated with high-density lipoprotein cholesterol levels. CRP levels were also higher in women, those at higher traditionally estimated cardiovascular risk and those with greater numbers of metabolic syndrome markers. Among patients without diabetes mellitus who were not receiving statin therapy, approximately 30% had CRP levels ≥3 mg/L, and approximately 50% had CRP levels ≥2 mg/L, including those at intermediate levels of traditionally estimated cardiovascular risk. CONCLUSIONS: CRP levels are elevated in a large proportion of patients with at least one cardiovascular risk factor, without diabetes mellitus who are not receiving statin therapy, suggesting a higher level of cardiovascular risk than predicted according to conventional risk estimation systems. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00882336.

Restrictive use of Restraints and Delirium Duration in the Intensive Care Unit (R2D2-ICU): protocol for a French multicentre parallel-group open-label randomised controlled trial.

INTRODUCTION: Physical restraint (PR) is prescribed in patients receiving invasive mechanical ventilation in the intensive care unit (ICU) to avoid unplanned removal of medical devices. However, it is associated with an increased risk of delirium. We hypothesise that a restrictive use of PR, as compared with a systematic use, could reduce the duration of delirium in ICU patients receiving invasive mechanical ventilation. METHODS AND ANALYSIS: The Restrictive use of Restraints and Delirium Duration in ICU (R2D2-ICU) study is a national multicentric, parallel-group, randomised (1:1) open-label, controlled, superiority trial, which will be conducted in 10 ICUs. A total of 422 adult patients requiring invasive mechanical ventilation for an expected duration of at least 48 hours and eligible for prescription of PR will be randomly allocated within 6 hours from intubation to either the restrictive PR use group or the systematic PR use group, until day 14, ICU discharge or death, whichever comes first. In both groups, PR will consist of the use of wrist straps. The primary endpoint will be delirium or coma-free days, defined as the number of days spent alive in the ICU without coma or delirium within the first 14 days after randomisation. Delirium will be assessed using the Confusion Assessment Method-ICU twice daily. Key secondary endpoints will encompass agitation episodes, opioid, propofol, benzodiazepine and antipsychotic drug exposure during the 14-day intervention period, along with a core outcome set of measures evaluated 90 days postrandomisation. ETHICS AND DISSEMINATION: The R2D2-ICU study has been approved by the Comité de Protection des Personnes (CPP) ILE DE FRANCE III-PARIS (CPP19.09.06.37521) on June 10th, 2019). Participant recruitment started on 25 January 2021. Results will be published in international peer-reviewed medical journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT04273360.

Aortic event rate in the Marfan population: a cohort study.

BACKGROUND: Optimal management, including timing of surgery, remains debated in Marfan syndrome because of a lack of data on aortic risk associated with this disease. METHODS AND RESULTS: We used our database to evaluate aortic risk associated with standardized care. Patients who fulfilled the international criteria, had not had previous aortic surgery or dissection, and came to our center at least twice were included. Aortic measurements were made with echocardiography (every 2 years); patients were given systematic ß-blockade and advice about sports activities. Prophylactic aortic surgery was proposed when the maximal aortic diameter reached 50 mm. Seven hundred thirty-two patients with Marfan syndrome were followed up for a mean of 6.6 years. Five deaths and 2 dissections of the ascending aorta occurred during follow-up. Event rate (death/aortic dissection) was 0.17%/y. Risk rose with increasing aortic diameter measured within 2 years of the event: from 0.09%/y per year (95% confidence interval, 0.00-0.20) when the aortic diameter was <40 mm to 0.3% (95% confidence interval, 0.00-0.71) with diameters of 45 to 49 mm and 1.33% (95% confidence interval, 0.00-3.93) with diameters of 50 to 54 mm. The risk increased 4 times at diameters ≥50 mm. The annual risk dropped below 0.05% when the aortic diameter was <50 mm after exclusion of a neonatal patient, a woman who became pregnant against our recommendation, and a 72-year-old woman with previous myocardial infarction. CONCLUSIONS: Risk of sudden death or aortic dissection remains low in patients with Marfan syndrome and aortic diameter between 45 and 49 mm. Aortic diameter of 50 mm appears to be a reasonable threshold for prophylactic surgery.

Central or peripheral catheters for initial venous access of ICU patients: a randomized controlled trial.

OBJECTIVES: The vast majority of ICU patients require some form of venous access. There are no evidenced-based guidelines concerning the use of either central or peripheral venous catheters, despite very different complications. It remains unknown which to insert in ICU patients. We investigated the rate of catheter-related insertion or maintenance complications in two strategies: one favoring the central venous catheters and the other peripheral venous catheters. DESIGN: Multicenter, controlled, parallel-group, open-label randomized trial. SETTING: Three French ICUs. PATIENTS: Adult ICU patients with equal central or peripheral venous access requirement. INTERVENTION: Patients were randomized to receive central venous catheters or peripheral venous catheters as initial venous access. MEASUREMENTS AND RESULTS: The primary endpoint was the rate of major catheter-related complications within 28 days. Secondary endpoints were the rate of minor catheter-related complications and a composite score-assessing staff utilization and time spent to manage catheter insertions. Analysis was intention to treat. We randomly assigned 135 patients to receive a central venous catheter and 128 patients to receive a peripheral venous catheter. Major catheter-related complications were greater in the peripheral venous catheter than in the central venous catheter group (133 vs 87, respectively, p=0.02) although none of those was life threatening. Minor catheter-related complications were 201 with central venous catheters and 248 with peripheral venous catheters (p=0.06). 46% (60/128) patients were managed throughout their ICU stay with peripheral venous catheters only. There were significantly more peripheral venous catheter-related complications per patient in patients managed solely with peripheral venous catheter than in patients that received peripheral venous catheter and at least one central venous catheter: 1.92 (121/63) versus 1.13 (226/200), p<0.005. There was no difference in central venous catheter-related complications per patient between patients initially randomized to peripheral venous catheters but subsequently crossed-over to central venous catheter and patients randomized to the central venous catheter group. Kaplan-Meier estimates of survival probability did not differ between the two groups. CONCLUSION: In ICU patients with equal central or peripheral venous access requirement, central venous catheters should preferably be inserted: a strategy associated with less major complications.

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.

Rivaroxaban Prophylaxis in Noncirrhotic Portal Vein Thrombosis.

BACKGROUND: In patients with noncirrhotic chronic portal vein thrombosis (PVT), the benefit of long-term anticoagulation is unknown. We assessed the effects of rivaroxaban on the risk of venous thromboembolism and portal hypertension-related bleeding in such patients. METHODS: In this multicenter, controlled trial, we randomly assigned patients with noncirrhotic chronic PVT without major risk factors for thrombosis to receive either rivaroxaban 15 mg/day or no anticoagulation. The primary end point was 2-year thrombosis-free survival. Secondary end points included the occurrence of site-specific thromboses and major bleeding events. RESULTS: A total of 111 participants were enrolled in the trial, with a mean age of 50.4±13.2 years; 58% of participants were men. An unplanned interim analysis was requested by the independent data safety monitoring board (DSMB) after 10 thrombotic events occurred. The thrombosis incidence rate was 0 per 100 person-years in the rivaroxaban group and 19.71 per 100 person-years (95% confidence interval, 7.49 to 31.92) in the no anticoagulation group (log-rank P=0.0008) after a median follow-up of 11.8 months. Based on the interim analysis, the DSMB recommended switching patients from the no anticoagulation group to anticoagulation. After a median follow-up of 30.3 months (intraquartile range, 24.3 to 47.8), major bleeding occurred in two patients receiving rivaroxaban and in one patient not receiving anticoagulation. No deaths occurred. CONCLUSIONS: After a median follow-up of 11.8 months, among patients with noncirrhotic chronic PVT without major risk factors for thrombosis, daily rivaroxaban reduced the incidence of venous thromboembolism and did not increase major bleeding events. (Funded by grants from the French Ministry of Health and the Association de Malades des Vaisseaux du foie; ClinicalTrials.gov number, NCT02555111.)

Antibiotic use: knowledge and perceptions in two university hospitals.

OBJECTIVES: To investigate knowledge and perceptions about antibiotic prescription in two university hospitals. METHODS: Physicians completed four case vignettes describing infections and a questionnaire. For each vignette, the physicians were asked to determine whether hospital admission and antibiotic treatment were needed; whether a treatment change was needed; and the duration of antibiotic treatment. The questionnaire collected data on beliefs and perceptions regarding antibiotic prescription. RESULTS: Of 412 eligible physicians, 206 agreed to participate. Factors associated with a vignette score above the median were anaesthesiologist/intensivist (adjusted odds ratio, 3.09; P=0.02), perception of inappropriate antibiotic use as risky for the patient (adjusted odds ratio, 2.84; P=0.03) and self-efficacy (adjusted odds ratio, 2.18; P=0.02), whereas being a surgeon was associated with a vignette score lower than the median (adjusted odds ratio, 0.14; P<0.0001). CONCLUSIONS: The high participation rate suggested awareness of antibiotic use. Educational programmes specifically targeted at surgeons are needed. We identified cognitive factors that affect knowledge of antibiotic prescription, and may help in the design of education programmes and interventions aimed at improving antibiotic use.

Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders.

BACKGROUND: TGFBR2 mutations were recognized recently among patients with a Marfan-like phenotype. The associated clinical and prognostic spectra remain unclear. METHODS AND RESULTS: Clinical features and outcomes of 71 patients with a TGFBR2 mutation (TGFBR2 group) were compared with 50 age- and sex-matched unaffected family members (control subjects) and 243 patients harboring FBN1 mutations (FBN1 group). Aortic dilatation was present in a similar proportion of patients in both the TGFBR2 and FBN1 groups (78% versus 79%, respectively) but was highly variable. The incidence and average age for thoracic aortic surgery (31% versus 27% and 35+/-16 versus 39+/-13 years, respectively) and aortic dissection (14% versus 10% and 38+/-12 versus 39+/-9 years) were also similar in the 2 groups. Mitral valve involvement (myxomatous, prolapse, mitral regurgitation) was less frequent in the TGFBR2 than in the FBN1 group (all P<0.05). Aortic dilatation, dissection, or sudden death was the index event leading to genetic diagnosis in 65% of families with TGFBR2 mutations, versus 32% with FBN1 mutations (P=0.002). The rate of death was greater in TGFBR2 families before diagnosis but similar once the disease had been recognized. Most pregnancies were uneventful (without death or aortic dissection) in both TGFBR2 and FBN1 families (38 of 39 versus 213 of 217; P=1). Seven patients (10%) with a TGFBR2 mutation fulfilled international criteria for Marfan syndrome, 3 of whom presented with features specific for Loeys-Dietz syndrome. CONCLUSIONS: Clinical outcomes appear similar between treated patients with TGFBR2 mutations and individuals with FBN1 mutations. Prognosis depends on clinical disease expression and treatment rather than simply the presence of a TGFBR2 gene mutation.

Quality of reporting internal and external validity data from randomized controlled trials evaluating stents for percutaneous coronary intervention.

BACKGROUND: Stents are commonly used to treat patients with coronary artery disease. However, the quality of reporting internal and external validity data in published reports of randomised controlled trials (RCTs) of stents has never been assessed.The objective of our study was to evaluate the quality of reporting internal and external validity data in published reports of RCTs assessing the stents for percutaneous coronary interventions. METHODS: A systematic literature review was conducted. Reports of RCTs assessing stents for percutaneous coronary interventions indexed in MEDLINE and the Cochrane Central Register of Controlled Trials and published between January 2003 and September 2008 were selected. A standardized abstraction form was used to extract data. All analyses were adjusted for the effect of clustering articles by journal. RESULTS: 132 articles were analyzed. The generation of the allocation sequence was adequate in 58.3% of the reports; treatment allocation was concealed in 34.8%. Adequate blinding was reported in one-fifth of the reports. An intention-to-treat analysis was described in 79.5%. The main outcome was a surrogate angiographic endpoint in 47.0%. The volume of interventions per center was described in two reports. Operator expertise was described in five (3.8%) reports. The quality of reporting was better in journals with high impact factors and in journals endorsing the CONSORT statement. CONCLUSION: The current reporting of results of RCTs testing stents needs to be improved to allow readers to appraise the risk of bias and the applicability of the results.

Effect of response format for clinical vignettes on reporting quality of physician practice.

BACKGROUND: Clinical vignettes have been used widely to compare quality of clinical care and to assess variation in practice, but the effect of different response formats has not been extensively evaluated. Our objective was to compare three clinical vignette-based survey response formats - open-ended questionnaire (A), closed-ended (multiple-choice) questionnaire with deceptive response items mixed with correct items (B), and closed-ended questionnaire with only correct items (C) - in rheumatologists' pre-treatment assessment for tumor-necrosis-factor (TNF) blocker therapy. STUDY DESIGN: Prospective randomized study. SETTING: Rheumatologists attending the 2004 French Society of Rheumatology meeting. Physicians were given a vignette describing the history of a fictitious woman with active rheumatoid arthritis, who was a candidate for therapy with TNF blocking agents, and then were randomized to receive questionnaire A, B, or C, each containing the same four questions but with different response formats, that asked about their pretreatment assessment. MEASUREMENTS: Long (recommended items) and short (mandatory items) checklists were developed for pretreatment assessment for TNF-blocker therapy, and scores were expressed on the basis of responses to questionnaires A, B, and C as the percentage of respondents correctly choosing explicit items on these checklists. STATISTICAL ANALYSIS: Comparison of the selected items using pairwise Chi-square tests with Bonferonni correction for variables with statistically significant differences. RESULTS: Data for all surveys distributed (114 As, 118 Bs, and 118 Cs) were complete and available for analysis. The percentage of questionnaire A, B, and C respondents for whom data was correctly complete for the short checklist was 50.4%, 84.0% and 95.0%, respectively, and was 0%, 5.0% and 5.9%, respectively, for the long version. As an example, 65.8%, 85.7% and 95.8% of the respondents of A, B, and C questionnaires, respectively, correctly identified the need for tuberculin skin test (p < 0.0001). CONCLUSION: In evaluating clinical practice with use of a clinical vignette, a multiple-choice format rather than an open-ended format overestimates physician performance. The insertion of deceptive response items mixed with correct items in closed-ended (multiple-choice) questionnaire failed to avoid this overestimation.