Relationship between plasma tissue Factor Pathway Inhibitor (TFPI) levels, thrombin generation and clinical risk of bleeding in patients with severe haemophilia A or B.

INTRODUCTION: Bleeding severity in severe haemophilic patients, with low thrombin generation (TG) capacity, can vary widely between patients, possibly reflecting differences in tissue factor pathway inhibitor (TFPI) level. AIM: To compare free TFPI (fTFPI) levels in patients with severe haemophilia A (sHA) and severe haemophilia B (sHB) and to investigate in these patients as a whole the relationships between bleeding and TG potential, between TG potential and fTFPI level and between fTFPI level and bleeding tendency. METHODS: Data on bleeding episodes retrospectively recorded during follow-up visits over 5-10 years were collected and used to calculate the annualised joint bleeding rate (AJBR). fTFPI levels and basal TG parameters were determined in platelet-poor plasma (PPP) and platelet-rich plasma (PRP) using calibrated automated tomography (CAT). RESULTS: Mean fTFPI levels did not differ significantly between sHA (n = 34) and sHB (n = 19) patients. Mean values of endogenous thrombin potential (ETP) and thrombin peak (peak) in PPP and PRP were two-fold higher when fTFPI levels < 9.4 versus > 14.3 ng/mL. In patients treated on demand, ETP and peak in PRP were doubled when AJBR was ≤ 4.9 $ \le 4.9$ , AJBR being halved in patients with a low fTFPI level (9.4 ng/mL). In patients on factor prophylaxis, no association was found between TG parameters and either fTFPI level or AJBR. CONCLUSION: In patients treated on demand, bleeding tendency was influenced by fTFPI levels, which in turn affected basal TG potential. In patients on prophylaxis, bleeding tendency is probably determined primarily by the intensity of this treatment.

Inferior vena cava filters in pregnancy: Safe or sorry?

Background: Potential hazards of vena cava filters include migration, tilt, perforation, fracture, and in-filter thrombosis. Due to physiological changes during pregnancy, the incidence of these complications might be different in pregnant women. Aim: To evaluate the use and safety of inferior vena cava filters in both women who had an inferior vena cava filter inserted during pregnancy, and in women who became pregnant with an inferior vena cava filter in situ. Methods: We performed two searches in the literature using the keywords "vena cava filter", "pregnancy" and "obstetrics". Results: The literature search on women who had a filter inserted during pregnancy yielded 11 articles compiling data on 199 women. At least one filter complication was reported in 33/177 (19%) women and included in-filter thrombosis (n = 14), tilt (n = 6), migration (n = 5), perforation (n = 2), fracture (n = 3), misplacement (n = 1), air embolism (n = 1) and allergic reaction (n = 1). Two (1%) filter complications led to maternal deaths, of which at least one was directly associated with a filter insertion. Filter retrieval failed in 9/149 (6%) women. The search on women who became pregnant with a filter in situ resulted in data on 21 pregnancies in 14 women, of which one (6%) was complicated by uterine trauma, intraperitoneal hemorrhage and fetal death caused by perforation of the inferior vena cava filter. Conclusion: The risks of filter complications in pregnancy are comparable to the nonpregnant population, but could lead to fetal or maternal death. Therefore, only in limited situations such as extensive thrombosis with a contraindication for anticoagulants, inferior vena filters should be considered in pregnant women.

External validation of the MidiCAT variant of thrombography: Comparison with calibrated automated thrombography and study of the centrifugation scheme.

Introduction: To perform Calibrated Automated Thrombography (CAT), the use of reduced plasma volumes (referred to as "MidiCAT") makes it possible to more efficiently use limited volumes of valuable biobanked plasma samples and decreases expenses for reagents. It is, however, unclear whether the MidiCAT procedure is suitable when thrombin generation (TG) is studied in the presence of added thrombomodulin (TG-TM). Moreover, a simplified centrifugation scheme would facilitate biobanking, if appropriate, for more sensitive coagulation studies. We aimed to compare the results of "MidiCAT" (halved plasma and reagent volumes) with those from regular CAT, in the absence or presence of TM, as well as to study the impact of a single-centrifugation scheme for plasma preparation before freezing. Materials and methods: Plasma samples were prepared from the citrated blood from 20 Geneva hospital diverse patients without gross coagulation abnormalities with a single- or double-centrifugation scheme. Samples were kept frozen at -80°C and thawed just before the TG assay in duplicate under two conditions: 1 pM tissue factor (TF) or 5 pM TF + TM. Results and discussion: (1) We externally validated "MidiCAT" and also extended the validation to TG-TM. Whatever the method (CAT or MidiCAT), intra-assay (assessed with duplicates) CV was below 6% (1 pM TF) or below 10% (5 pM TF + TM) for ETP. Agreement between the MidiCAT and CAT results was satisfactory; the p coefficients were above 0.95 for ETP and above 0.90 for most other parameters; biases for ETP were +10.0% (1 pM FT) and +13.5% (5 pM + TM). (2) The centrifugation scheme markedly affected the results obtained in the presence of TM, whereas the bias and limit of agreement (difference plots) were low for the no TM condition. The bias in the presence of TM was obvious, more marked with plasma samples sensitive to TM when double centrifuged: the lower the ETP-TM, the greater the relative difference between the ETP-TM of plasma samples prepared with just single centrifugation and the reference plasma samples. Thus, a single-centrifugation procedure, as is often used for plasma biobanking, is suitable for TG study only if it is not performed in the presence of TM.

Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Pregnancy-related venous thromboembolism is a leading cause of maternal morbidity and mortality, and thromboprophylaxis is indicated in pregnant and post-partum women with a history of venous thromboembolism. The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy and the post-partum period is uncertain. METHODS: In this open-label, randomised, controlled trial (Highlow), pregnant women with a history of venous thromboembolism were recruited from 70 hospitals in nine countries (the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA, and Russia). Women were eligible if they were aged 18 years or older with a history of objectively confirmed venous thromboembolism, and with a gestational age of 14 weeks or less. Eligible women were randomly assigned (1:1), before 14 weeks of gestational age, using a web-based system and permuted block randomisation (block size of six), stratified by centre, to either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks post partum. The primary efficacy outcome was objectively confirmed venous thromboembolism (ie, deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), as determined by an independent central adjudication committee, in the intention-to-treat (ITT) population (ie, all women randomly assigned to treatment). The primary safety outcome was major bleeding which included antepartum, early post-partum (within 24 h after delivery), and late post-partum major bleeding (24 h or longer after delivery until 6 weeks post partum), assessed in all women who received at least one dose of assigned treatment and had a known end of treatment date. This study is registered with ClinicalTrials.gov, NCT01828697, and is now complete. FINDINGS: Between April 24, 2013, and Oct 31, 2020, 1339 pregnant women were screened for eligibility, of whom 1110 were randomly assigned to weight-adjusted intermediate-dose (n=555) or fixed low-dose (n=555) low-molecular-weight heparin (ITT population). Venous thromboembolism occurred in 11 (2%) of 555 women in the weight-adjusted intermediate-dose group and in 16 (3%) of 555 in the fixed low-dose group (relative risk [RR] 0·69 [95% CI 0·32-1·47]; p=0·33). Venous thromboembolism occurred antepartum in five (1%) women in the intermediate-dose group and in five (1%) women in the low-dose group, and post partum in six (1%) women and 11 (2%) women. On-treatment major bleeding in the safety population (N=1045) occurred in 23 (4%) of 520 women in the intermediate-dose group and in 20 (4%) of 525 in the low-dose group (RR 1·16 [95% CI 0·65-2·09]). INTERPRETATION: In women with a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and post-partum periods was not associated with a lower risk of recurrence than fixed low-dose low-molecular-weight heparin. These results indicate that low-dose low-molecular-weight heparin for thromboprophylaxis during pregnancy is the appropriate dose for the prevention of pregnancy-related recurrent venous thromboembolism. FUNDING: French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer.

Prediction of venous thromboembolism in patients with multiple myeloma treated with lenalidomide, bortezomib, dexamethasone, and transplantation: Lessons from the substudy of IFM/DFCI 2009 cohort.

BACKGROUND: Venous thromboembolism (VTE) is a concern for patients with newly diagnosed multiple myeloma. OBJECTIVES: We aimed to evaluate VTE incidence, risk factors, and risk score. PATIENTS/METHODS: We performed a substudy of the "Intergroupe Francophone du Myelome 2009" randomized controlled trial. RESULTS: We assessed 700 patients receiving lenalidomide/bortezomib/dexamethasone, followed or not by autologous hematopoietic stem cell transplantation. VTE incidence at 6 months was 4.8% (95% confidence interval [CI]: 3.3-6.9%) and 1.5% (95% CI: 0.8-2.9%) from 6 to 12 months. Using multivariate analysis we confirmed history of VTE (odds ratio 5.1 [1.6-16.7], P = .007) as a strong VTE-related risk factor, invalidated erythropoietin exposure (0.6 [0.2-1.7], P = .3) as risk factor, and added two new risk factors: fracture at diagnosis (2.6 [1.3-5.5], P = .01), and serum gamma globulin level > 27 g/L (2.8 [1.2-6.8,] P = .02). Moreover, we noticed that VTE occurred earlier in patients with gamma globulin levels >27 g/L, suggesting a need to revisit the thromboprophylaxis timeframe. Heparin administration was associated with a decreased risk (0.3 [0.1-0.7], P = .005) but failed to erase the risk regardless of dose. The area under the receiver operating characteristic curve of the IMPEDE VTE score was 0.67, as previously reported, confirming our cohort was well representative. CONCLUSIONS: Prospective studies are warranted in light of these results to improve VTE risk stratification and to design adapted thromboprophylaxis in terms of timing and dose.

Slope analysis for the prediction of fluid responsiveness by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients.

OBJECTIVE: Assessment of fluid responsiveness is problematic in intensive care unit patients. Lung recruitment maneuvers (LRM) can be used as a functional test to predict fluid responsiveness. We propose a new test to predict fluid responsiveness in mechanically ventilated patients by analyzing the variations in central venous pressure (CVP) and systemic arterial parameters during a prolonged sigh breath LRM without the use of a cardiac output measuring device. DESIGN: Prospective observational cohort study. SETTING: Intensive Care Unit, Saint-Etienne University Central Hospital. PATIENTS: Patients under mechanical ventilation, equipped with invasive arterial blood pressure, CVP, pulse contour analysis (PICCO™), requiring volume expansion, with no right ventricular dysfunction. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CVP, systemic arterial parameters and stroke volume (SV) were recorded during prolonged LRM followed by a 500 mL fluid expansion to asses fluid responsiveness. 25 patients were screened and 18 patients analyzed. 9 patients were responders to volume expansion and 9 were not. Evaluation of hemodynamic parameters suggested the use of a linear regression model. Slopes for systolic arterial pressure, pulse pressure (PP), CVP and SV were all significantly different between responders and non-responders during the pressure increase phase of LRM (STEP-UP) (p = 0.022, p = 0.014, p = 0.006 and p = 0.038, respectively). PP and CVP slopes during STEP-UP were strongly predictive of fluid responsiveness with an AUC of 0.926 (95% CI, 0.78 to 1.00), sensitivity = 100%, specificity = 89% and an AUC = 0.901 (95% CI, 0.76 to 1.00), sensibility = 78%, specificity = 100%, respectively. Combining sensitivity of PP and specificity of CVP, prediction of fluid responsiveness can be achieved with 100% sensitivity and 100% specificity (AUC = 0.96; 95% CI, 0.90 to 1.00). One patient showed inconclusive values using the grey zone approach (5.5%). CONCLUSIONS: In patients under mechanical ventilation with no right heart dysfunction, the association of PP and CVP slope analysis during a prolonged sigh breath LRM seems to offer a very promising method for prediction of fluid responsiveness without the use and associated cost of a cardiac output measurement device. TRIAL REGISTRATION: NCT04304521 , IRBN902018/CHUSTE. Registered 11 March 2020, Fluid responsiveness predicted by a stepwise PEEP elevation recruitment maneuver in mechanically ventilated patients (STEP-PEEP).

Diuretic vs. placebo in intermediate-risk acute pulmonary embolism: a randomized clinical trial.

AIMS: The role of diuretics in patients with intermediate-risk pulmonary embolism (PE) is controversial. In this multicentre, double-blind trial, we randomly assigned normotensive patients with intermediate-risk PE to receive either a single 80 mg bolus of furosemide or a placebo. METHODS AND RESULTS: Eligible patients had at least a simplified PE Severity Index (sPESI) ≥1 with right ventricular dysfunction. The primary efficacy endpoint assessed 24 h after randomization included (i) absence of oligo-anuria and (ii) normalization of all sPESI items. Safety outcomes were worsening renal function and major adverse outcomes at 48 hours defined by death, cardiac arrest, mechanical ventilation, or need of catecholamine. A total of 276 patients underwent randomization; 135 were assigned to receive the diuretic, and 141 to receive the placebo. The primary outcome occurred in 68/132 patients (51.5%) in the diuretic and in 49/132 (37.1%) in the placebo group (relative risk = 1.30, 95% confidence interval 1.04-1.61; P = 0.021). Major adverse outcome at 48 h occurred in 1 (0.8%) patients in the diuretic group and 4 patients (2.9%) in the placebo group (P = 0.19). Increase in serum creatinine level was greater in diuretic than placebo group [+4 µM/L (-2; 14) vs. -1 µM/L (-11; 6), P < 0.001]. CONCLUSION: In normotensive patients with intermediate-risk PE, a single bolus of furosemide improved the primary efficacy outcome at 24 h and maintained stable renal function. In the furosemide group, urine output increased, without a demonstrable improvement in heart rate, systolic blood pressure, or arterial oxygenation.ClinicalTrials.gov identifier NCT02268903.

Heparin-induced Thrombocytopenia Diagnosis: A Retrospective Study Comparing Heparin-induced Platelet Activation Test to 14 C-serotonin Release Assay.

Laboratory confirmation of heparin-induced thrombocytopenia (HIT) is of crucial importance and remains challenging and relies on platelet functional assays highlighting the presence of heparin-dependent platelet-activating antibodies in patient serum or plasma. Platelet functional assays using washed platelets include the 14 C-serotonin release assay (SRA), usually described as the gold standard, and the heparin-induced platelet activation assay (HIPA). Since its first comparison with SRA there has been no additional published study regarding HIPA diagnostic performances compared with SRA. Aim of our retrospective study was to compare the concordance between HIPA and SRA in HIT suspected-patients with positive anti-PF4/heparin antibodies between October 2010 and October 2015. Fifty-five HIT-suspected patients who beneficiated from both HIPA and SRA were included. Positive and negative percent agreements were 83.8% (95% CI 68.0-93.8%) and 66.7% (95% CI 41.0-86.7%), respectively. Overall percent agreement was 78.2% (95% CI 65.0-92.2%). Agreement was higher in patients who underwent cardiopulmonary bypass with extracorporeal circulation circuit for cardiac surgery. We also confirm that the use of a minimum of 2 platelet donors to establish positive HIT diagnosis and 4 platelet donors to exclude HIT diagnosis allows obtaining a good agreement with SRA. Although HIPA and SRA were performed with different platelet donors and in different laboratories, HIPA had a good positive agreement with SRA for HIT diagnosis, showing that HIPA is a useful functional assay that does not require radioactivity and could be developed worldwide to improve HIT diagnosis.

Heparin-induced thrombocytopenia: Construction of a pretest diagnostic score derived from the analysis of a prospective multinational database, with internal validation.

BACKGROUND: Diagnosis of heparin-induced thrombocytopenia (HIT) requires pretest probability assessment and dedicated laboratory assays. OBJECTIVE: To develop a pretest score for HIT. DESIGN: Observational; analysis of prospectively collected data of hospitalized patients suspected with HIT (ClinicalTrials.gov NCT00748839). SETTING: Thirty-one tertiary hospitals in France, Switzerland, and Belgium. PATIENTS: Patients tested for HIT antibodies (2280 evaluable), randomly allocated to derivation and validation cohorts. MEASUREMENTS: Independent adjudicators diagnosed HIT based on the prospectively collected data and serotonin release assay results. RESULTS: Heparin-induced thrombocytopenia was diagnosed in 234 (14.7%) and 99 (14.5%) patients in the two cohorts. Eight features were associated with HIT (in brackets, points assigned for score calculation of the score): unfractionated heparin (1); therapeutic-dose heparin (1); cardiopulmonary bypass (cardiac surgery) (2); major trauma (3); 5- to 21-day interval from anticoagulation initiation to suspicion of HIT (4); ≥40% decrease in platelet count over ≤6 days (3); thrombotic event, arterial (3) or venous (3). The C-statistic was 0.79 (95% CI, 0.76-0.82). In the validation cohort, the area under the receiver operating characteristic curve was 0.77 (95% CI, 0.74-0.80). Three groups of scores were defined; HIT prevalence reached almost 30% in the high-probability group. LIMITATION: The performance of the score may depend on settings and practices. CONCLUSION: The objective, easy-to-collect, clinical features of HIT we evidenced were incorporated into a pretest score, which may guide clinical decisions regarding diagnostic testing and anticoagulation.

Functional Flow Cytometric Assay for Reliable and Convenient Heparin-Induced Thrombocytopenia Diagnosis in Daily Practice.

Reliable laboratory diagnosis of heparin-induced thrombocytopenia (HIT) remains a major clinical concern. Immunoassays are highly sensitive, while confirmatory functional tests (based on heparin-dependent platelet activation) lack standardization. We evaluated the diagnostic performance of a functional flow cytometric assay (FCA) based on the detection of heparin-dependent platelet activation with an anti-p-selectin. A total of 288 patients were included (131 HIT-positive and 157 HIT-negative) with a HIT diagnosis established by expert opinion adjudication (EOA) considering clinical data and local laboratory results. The FCA was centrally performed in a single laboratory on platelet-rich plasma, using a very simple four-color fluorometer. The results were standardized according to the Heparin Platelet Activation (HEPLA) index. The serotonin release assay (SRA) was performed in the four French reference laboratories. Based on the final HIT diagnosis established by EOA, the sensitivity and specificity of the FCA were 88 and 95%, respectively, values very similar to those of the SRA (88 and 97%, respectively). This study showed that the FCA, based on easily implementable technology, may be routinely used as a reliable confirmatory test for HIT diagnosis.

PHILEOS (haemoPHILia and ostEoporOSis) Study: protocol of a multicentre prospective case-control study.

INTRODUCTION: Two meta-analyses showed lower bone mineral density (BMD) in patients with haemophilia (haemophilia type and severity were often not specified) compared with healthy controls. This finding could be related to reduced mobility and sedentary lifestyle, and/or hepatitis C or HIV infection. The aim of this study is to determine osteoporosis prevalence in patients with haemophilia classified in function of the disease type (A or B) and severity, and to evaluate the potential role of regular prophylactic factor replacement (early vs delayed initiation) in preserving or restoring BMD. METHODS AND ANALYSIS: The haemoPHILia and ostEoporOSis Study is a prospective, controlled, multicentre study that will include patients in France (13 haemophilia treatment centres), Belgium (1 centre) and Romania (1 centre). In total, 240 patients with haemophilia and 240 matched healthy controls will be recruited (1:1). The primary objective is to determine osteoporosis prevalence in patients with severe haemophilia A and B (HA and HB) without prophylaxis, compared with healthy controls. Secondary outcomes include: prevalence of osteoporosis and osteopenia in patients with mild, moderate and severe HA or HB with prophylaxis (grouped in function of their age at prophylaxis initiation), compared with healthy subjects; BMD in patients with HA and HB of comparable severity; correlation between BMD and basal factor VIII/IX levels and thrombin potential; and quantification of plasmatic markers of bone remodelling (formation and resorption) in patients with haemophilia. ETHICS AND DISSEMINATION: The protocol was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2019-A03358-49). The results of this study will be actively disseminated through scientific publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04384341.

Intention to participate in a COVID-19 vaccine clinical trial and to get vaccinated against COVID-19 in France during the pandemic.

INTRODUCTION: The world is facing the COVID-19 pandemic. The development of a vaccine is challenging. We aimed to determine the proportion of people who intend to get vaccinated against COVID-19 in France or to participate in a vaccine clinical trial. METHODS: We conducted an anonymous on-line survey from the 26th of March to the 20th of April 2020. Primary endpoints were the intention to get vaccinated against COVID-19 if a vaccine was available or participate in a vaccine clinical trial. RESULTS: Three thousand two hundred and fifty nine individuals answered the survey; women accounted for 67.4% of the respondents. According to their statements, 2.512 participants (77.6%, 95% CI 76.2-79%) will certainly or probably agree to get vaccinated against COVID-19. Older age, male gender, fear about COVID-19, being a healthcare worker and individual perceived risk were associated with COVID-19 vaccine acceptance. Vaccine hesitancy was associated with a decrease in COVID-19 vaccine acceptance. One thousand and five hundred and fifty respondents (47.6% 95% CI 45.9-49.3%) will certainly or probably agree to participate in a COVID-19 vaccine clinical trial. Older age, male gender, being a healthcare worker and individual perceived risk were associated with potential acceptance to participate in a COVID-19 vaccine clinical trial. Vaccine hesitancy was associated with refusal for participation in a COVID-19 vaccine clinical trial. CONCLUSIONS: Nearly 75% and 48% of the survey respondents were respectively likely to accept vaccination or participation in a clinical trial against COVID-19. Vaccine hesitancy will be the major barrier to COVID-19 vaccine uptake.

Comparative Analysis of a French Prospective Series of 144 Patients with Heparin-Induced Thrombocytopenia (FRIGTIH) and the Literature.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatments, and only a few large patient cohorts have been reported. In this study, biological and clinical data from 144 French patients with HIT were analyzed in comparison with the literature. METHODS: The diagnosis of HIT was confirmed in all patients by an immunoassay combined with serotonin release assay. In the literature, only cohorts of at least 20 HIT patients published from 1992 were selected for a comparative analysis. RESULTS: Two-thirds of patients were hospitalized in surgery and most were treated with unfractionated heparin (83.2% vs. 16.8% with low molecular weight heparin only). Thrombotic events in 54 patients (39.7%) were mainly venous (41/54). However, arterial thrombosis was more frequent after cardiac surgery (13.2% vs. 2.4% in other surgeries, p = 0.042) with a shorter recovery time (median = 3 vs. 5 days, p < 0.001). The mortality rate was lower in our series than in the 22 selected published studies (median = 6.3% vs. 15.9%). Three genetic polymorphisms were also studied and homozygous subjects FcγRIIA RR were more frequent in patients with thrombosis (37.8 vs. 18.2% in those without thrombosis, p = 0.03). CONCLUSION: This study shows that the mortality rate due to HIT has recently decreased in France, possibly due to earlier diagnosis and improved medical care. It also confirms the strong association between polymorphism FcγRIIA H131R and thrombosis in HIT.

Impact of take-home messages written into slide presentations delivered during lectures on the retention of messages and the residents' knowledge: a randomized controlled study.

BACKGROUND: Lectures with slide presentations are widely used to teach evidence-based medicine to large groups. Take-home messages (THMs) are poorly identified and recollected by students. We investigated whether an instruction to list THMs in written form on slides would improve the retention thereof by residents, and the residents' level of knowledge, 1 month after lectures. METHODS: Prospective blinded randomized controlled study was conducted. Twelve lectures (6 control and 6 intervention lectures) were delivered to 73 residents. For the intervention lectures, the lecturers were instructed to incorporate clear written THMs into their slide presentations. The outcomes were ability of resident to recollect THMs delivered during a lecture (as assessed by accordance rate between the lecturers' and residents' THMs) and knowledge (as assessed by multiple choice questions (MCQs)). RESULTS: Data for 3738 residents' THMs and 3410 MCQs were analyzed. The intervention did not significantly increase the number of THMs written on slides (77% (n = 20/26), 95% CI 56-91 vs 64% (n = 18/28), 95% CI 44-81, p = 0.31) nor THMs retention (13% (n = 238/1791), 95% CI 12-15 vs 17% (n = 326/1947), 95% 15-18, p = 0.40) nor knowledge (63.8 ± 26.2 vs 61.1 ± 31.4 /100 points, p = 0.75). In multivariable analyses performed with all THMs written on slides from the two groups, a superior knowledge was associated with notetaking during lectures (OR 1.88, 95% CI 1.41-2.51) and THMs retention (OR 2.17, 95% CI 1.54-3.04); and THMs retention was associated with written THMs (OR 2.94, 95% CI 2.20-3.93). CONCLUSIONS: In lectures delivered to residents, a third of the THMs were not in written form. An intervention based on an explicit instruction to lecturers to provide THMs in written form in their slide presentations did not result in increased use of written THMs into the slide presentation or improvement of the THMs retention or level of knowledge. However, we showed that there was a strong positive association between writing THMs on a slide, retention of THMs and residents' knowledge. Further researches are needed to assess interventions to increase written THMs in lectures by faculty. TRIAL REGISTRATION: ClinicalTrials.gov NCT01795651 (Fev 21, 2013).

[Use and management of proton pump inhibitors: An observational study]. / Utilisation et gestion des inhibiteurs de la pompe à protons : une étude observationnelle.

INTRODUCTION: Proton pump inhibitors (PPIs) have improved the management and prevention of digestive diseases, leading to a heavy prescription of this therapy. In 2015, nearly one quarter of the French population had consumed a PPI and half of them were long-term users. The main objective of this study was to analyze, in patients hospitalized in several medical departments, the adequacy of long-term PPI prescriptions to recommendations. METHOD: The Use and management of proton pump inhibitors: an observational study project (UTOPPIA) is a longitudinal observational study conducted at the University Hospital of Saint-Étienne in the departments of hepato-gastroenterology, infectious and tropical diseases, internal medicine, vascular medicine and nephrology. All patients with PPI treatment on their usual outpatient prescription were interviewed. RESULTS: Over a 3-month period, 334 of hospitalized patients (30.7%) had received a long-term PPI prescription and 181 patients (54.2%) could be included in the study for a total of 274 indications. Ninety-nine patients (54.7%) had a long-term PPI prescription in accordance with the recommendations. The most frequent indication (70 prescriptions) was the prescription of an antiplatelet drug or anticoagulant for subjects at high risk of bleeding in 70 prescriptions. Fifty-three PPI treatments were amended during the hospital stay, including 9 discontinuations. The justification for the change was documented in the patients' chart in only 17% of cases. Individual interviews of patients revealed that 75.1% of them were in favour of discontinuing their PPI treatment. CONCLUSIONS: About one-third of hospitalized patients in medical wards in France have long-term PPI treatment and half of these prescriptions do not comply with good practice recommendations. A majority of patients report being willing to try to stop PPI therapy.

Graduated compression stockings in prevention of venous thromboembolism among acutely ill medical patients aged over 75 years: a French national survey.

Background: The thromboprophylactic efficacy of graduated compression stockings (GCS) has not yet been demonstrated in acutely ill medical patients, and guidelines vary considerably. Older acutely ill medical patients appear to constitute a distinctive population presenting high risks of both thrombosis and bleeding. Objective: To evaluate the practices and beliefs of a panel of French geriatricians regarding GCS management in acutely ill medical patients aged over 75 years. Methods: A survey was designed to study French geriatric practice concerning GCS use for thromboprophylaxis. Results: A total of 111 geriatricians answered the questionnaire. Among the responders, 46% declared frequent or very frequent prescription of GCS for preventing venous thromboembolism (VTE) in acutely ill, hospitalized medical patients, 54% declaring that they frequently re-evaluated GCS prescription during the patient's hospitalization. The main reason reported for discontinuing GCS use was patient request. Regarding complications of GCS, 87% of responders declared having already noted adverse effects with the use of GCS, although 80% estimated the risk of complications to be low or very low. In the context considered, the efficacy of wearing GCS was believed to be high or very high for 73% of responders. GCS prescription was judged to be in accordance with evidence-based medicine for 69%. Conclusion: There is a gap between the frequent use of GCS to prevent VTE in older patients presenting an acute medical illness and the availability of data concerning their efficacy, safety, and management by nurses. Prospective trials including clinical and cost effectiveness are needed.