A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers.

BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions. LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

Genome-wide Association Study and Meta-analysis on Alcohol-Associated Liver Cirrhosis Identifies Genetic Risk Factors.

BACKGROUND AND AIMS: Only a minority of heavy drinkers progress to alcohol-associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. APPROACH AND RESULTS: We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy-drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome-wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta-analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome-wide significant risk association of rs738409 in patatin-like phospholipase domain containing 3 (PNPLA3) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10-17 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10-10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas-associated factor family member 2 (FAF2) (OR = 0.61 [del(T) allele], P = 2.56 × 10-8 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta-analysis (without conditioning) confirmed genome-wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13. Two other previously known loci (SERPINA1 and SUGP1/TM6SF2) were also genome-wide significant in the meta-analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. CONCLUSIONS: Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.

Patient consultations during SARS-CoV-2 pandemic: a mixed-method cross-sectional study in 16 European countries.

INTRODUCTION: Remote consultations help reduce contact between people and prevent cross-contamination. Little is known about the changes in consultation in European rural primary care during the SARS-CoV-2 (COVID-19) pandemic. The purpose of this mixed-methods cross-sectional study was to find out more about the effects of the pandemic on changes in patient consultations in European rural primary care. METHODS: A key informant survey from 16 member countries of the European Rural and Isolated Practitioners Association (EURIPA) was undertaken using a self-developed questionnaire. The steering committee of this project, called EURIPA Covid-19 study, developed a semi-structured questionnaire with 68 questions, 21 of which included free-text comments. Proportions were calculated for dichotomized or categorized data, and means were calculated for continuous data. Multivariate analysis by logistic regression model was used to assess the association of multiple variables. RESULTS: A total of 406 questionnaires from primary care providers (PCPs) in 16 European countries were collected; 245 respondents (60.5%) were females, 152 PCPs were rural (37.5%), 124 semi-rural (30.5%). Mean age of the respondents was 45.9 years (standard deviation (SD) 11.30) while mean seniority (length of experience) was 18.2 years (SD 11.6). A total of 381 (93.8%) respondents were medical doctors. Significant differences were found between countries in adopting alternative arrangements to face-to-face consultation: remote teleconsultation is well appreciated by both healthcare professionals and patients, but the most common way of remote consultation remains telephone consultation. A factor significantly inversely associated with the adoption of video consultation was the seniority of the PCP (odds ratio 1.19, 95% confidence interval 1.02-1.40, p=0.03). CONCLUSION: Telephone consultation is the most common form of remote consultation. The adoption of video-consultation is inversely related to the seniority of the informants.

Obesity, Diabetes, Coffee, Tea, and Cannabis Use Alter Risk for Alcohol-Related Cirrhosis in 2 Large Cohorts of High-Risk Drinkers.

INTRODUCTION: Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. METHODS: We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. RESULTS: The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10-18) and higher premorbid body mass index (26.37 ± 0.16 kg/m2) than controls (24.44 ± 0.18 kg/m2, P = 5.77 × 10-15). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. DISCUSSION: If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.

Anticoagulants' Safety and Effectiveness in General Practice: A Nationwide Prospective Cohort Study.

PURPOSE: Most real-world studies on anticoagulants have been based on health insurance databases or performed in secondary care. The aim of this study was to compare safety and effectiveness between patients treated with vitamin K antagonists (VKAs) and patients treated with direct oral anticoagulants (DOACs) in a general practice setting. METHODS: The CACAO study (Comparison of Accidents and their Circumstances with Oral Anticoagulants) is a multicenter prospective cohort study conducted among ambulatory patients taking an oral anticoagulant. Participants were patients from the study's cross-sectional phase receiving oral anticoagulants because of nonvalvular atrial fibrillation, for secondary prevention of venous thromboembolism, or both. They were followed as usual for 1 year by their general practitioners, who collected data on changes in therapy, thromboembolic events, bleeding, and deaths. All events were adjudicated by an independent committee. We used a propensity score and a Cox regression model to derive hazard ratios. RESULTS: Between April and December 2014, a total of 3,082 patients were included. At 1 year, 42 patients (1.7%) had experienced an arterial or venous event; 151 (6.1%) had experienced bleeding, including 47 (1.9%) who experienced major bleeding; and 105 (4.1%) had died. There was no significant difference between the VKA and DOAC groups regarding arterial or venous events, or major bleeding. The VKA group had a lower risk of overall bleeding (hazard ratio = 0.65; 95% CI, 0.43-0.98) but twice the risk of death (hazard ratio = 1.98; 95% CI, 1.15-3.42). CONCLUSIONS: VKAs and DOACs had fairly similar safety and effectiveness in general practice. The substantially higher incidence of deaths with VKAs is consistent with known data from health insurance databases and calls for further research to understand its cause.

A Novel Microflow Phantom Dedicated to Ultrasound Microvascular Measurements.

Tumor microvascularization is a biomarker of response to antiangiogenic treatments and is accurately assessed by ultrasound imaging. Imaging modes used to visualize slow flows include Power Doppler imaging, dynamic contrast-enhanced ultrasonography, and more recently, microvascular Doppler. Flow phantoms are used to evaluate the performance of Doppler imaging techniques, but they do not have a steady flow and sufficiently small channels. We report a novel device for robust and stable microflow measurements and the study of the microvascularization. Based on microfluidics technology, the prototype features wall-less cylindrical channels of diameters ranging from as small as 147 up to 436 µm, cast in a soft silicone polymer and perfused via a microfluidic flow pressure controller. The device was assessed using flow rates from 49 to 146 µL/min, with less than 1% coefficient of variation over three minutes, corresponding to velocities of 6 to 142 mm/s. This enabled us to evaluate and confirm the reliability of the Superb Microvascular Imaging Doppler mode compared with the Power Doppler mode at these flow rates in the presence of vibrations mimicking physiological motion.

[Contribution of therapeutic patient education to addiction medicine]. / Ce que l’éducation thérapeutique peut apporter à l’addictologie.

TPE can improve the efficacy of addiction medicine, for the benefit of patients and staff. It can help the patient withdraw from addiction, or at least achieve a better quality of life with this chronic condition..

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.

A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry.

BACKGROUND: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis. METHODS: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239). RESULTS: A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis. CONCLUSIONS: PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.

Should HIV-infected patients be screened for silent myocardial ischaemia using gated myocardial perfusion SPECT?

PURPOSE: A higher prevalence of cardiovascular risk factors (CRFs) in HIV-infected patients, together with chronic infection and treatments, has resulted in an increased risk of silent myocardial ischaemia (SMI). The objective of this study was to evaluate whether myocardial SPECT should be used for screening HIV-infected patients with no clinical symptoms of coronary artery disease. METHODS: The prevalence of SMI detected by myocardial SPECT was determined in 94 HIV-infected patients with a normal clinical cardiovascular examination in relation to anthropomorphic parameters, CRFs, inflammatory and HIV infection status, and treatment. RESULTS: Coronary artery disease was detected in nine patients (eight with ischaemia, one with myocardial infarction), corresponding to 9.6 % positivity. All but two of the scintigraphic diagnoses of ischaemia were confirmed by coronarography. Univariate analysis revealed that the overall number of CRFs and the combination of gender and age were associated with a diagnosis of SMI (p < 0.05). According to multivariate analysis, the only independent parameter significantly associated with the scintigraphic diagnosis of SMI was the combination of gender and age (p = 0.01). All the positive myocardial SPECT scans were in men older than 52 years with at least two other CRFs. In this subpopulation of 47 patients, the prevalence of SMI detected by myocardial SPECT reached 19.2 %. CONCLUSION: In male HIV-infected patients older than 52 years and with at least two other CRFs, screening for SMI using myocardial SPECT was about four times more likely to be positive than in the general population. This may motivate physicians to advise these patients to undergo more systematic screening for SMI using this technique.

Chemsex in HIV pre-exposure prophylaxis users: Assessment of mood disorders and addictive behavior.

The assessment of mood disorders and addiction linked to the practice of chemsex is of interest given the psychoactive substances used. The aim of this study was to assess risky sexual and addictive behavior to chemsex and related anxiety/depression symptoms in individuals receiving HIV pre-exposure prophylaxis (PrEP). In this cross-sectional study, all adults presenting for PrEP renewal at French sexual health centers were enrolled from January 2018 to March 2019. Participants completed a questionnaire on chemsex (i.e., the use of psychoactive substances before/during sex), including adapted Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) to chemsex addiction (questions of ASSIST were modified to focus on chemsex). Anxiety/depression was assessed with the Hospital Anxiety and Depression Scale. In the last 3 months before enrollment, 39.8% (94/236) of participants reported chemsex. The main psychoactive substances consumed during chemsex were cathinones (74.6%), gamma-hydroxybutyrate (66.3%), and other psychostimulants (60%). The median score of the chemsex-focused ASSIST was 8 [IQR25-75 : 3-15]; 72.2% of participants had a score justifying at least a brief intervention (>4). In multivariate analyses, anxiety and cathinones consumption were associated with an ASSIST score >4: OR 13.65 (95% CI 1.68-662.7), P = 0.0062, and OR 8.468 (95% CI 2.066-43.059), P = 0.0014, respectively. The level of addiction to the practice of chemsex can be difficult to estimate for the user, and the ASSIST makes it possible to evaluate this addiction and to direct the subjects toward specialized consultations of addictology, sexual health, or PrEP renewals. The implementation of the modified ASSIST in these consultations can allow early systematic screening and counseling.

Suppression of HIV-1 replication by microRNA effectors.

The rate of HIV-1 gene expression is a key step that determines the kinetics of virus spread and AIDS progression. Viral entry and gene expression were described to be the key determinants for cell permissiveness to HIV. Recent reports highlighted the involvement of miRNA in regulating HIV-1 replication post-transcriptionally. In this study we explored the role of cellular factors required for miRNA-mediated mRNA translational inhibition in regulating HIV-1 gene expression. Here we show that HIV-1 mRNAs associate and co-localize with components of the RNA Induced Silencing Complex (RISC), and we characterize some of the proteins required for miRNA-mediated silencing (miRNA effectors). RCK/p54, GW182, LSm-1 and XRN1 negatively regulate HIV-1 gene expression by preventing viral mRNA association with polysomes. Interestingly, knockdown of RCK/p54 or DGCR8 resulted in virus reactivation in PBMCs isolated from HIV infected patients treated with suppressive HAART.

3-D-Printed Phantom Fabricated by Photopolymer Jetting Technology for High-Frequency Ultrasound Imaging.

In the field of high-frequency ultrasound imaging ( MHz), tools for characterizing the performance of imaging systems are lacking. Indeed, commercial phantoms are often inadequate for this frequency range. The development of homemade phantoms on the laboratory scale is often required but is hindered by the difficulty in making very small structures that must be distributed with high accuracy in 3-D space. We propose investigating the use of 3-D photopolymer printing to create resolution and calibration phantoms designed for high-frequency ultrasound imaging. The quality and importance of these phantoms are discussed from the point of view of ultrasound parameters and imaging. First, the compressional wave group velocity, acoustic impedance, and attenuation of six photopolymerized materials were measured using temporal and spectral methods in a substitution experimental setup. Measurements were performed on printed samples using a broadband-focused single-element transducer covering a large frequency range (15-55 MHz). Two 3-D phantoms incorporating different shapes and dimensions were designed and printed. Finally, 3-D acoustic images were obtained using either a mechanically driven single-element transducer or a high-frequency commercial imaging system. Three-dimensional printing enabled us to generate phantoms suitable for high-frequency imaging with complex geometry inclusions and with a surrounding material having acoustic properties close to those of human skin. The calculated SNR between the inclusion and surrounding media is approximately 50 dB. In conclusion, 3-D printing is a useful tool for directly, easily, and rapidly manufacturing ultrasound phantoms for ultrasound imaging system assessments and computational calibration or validation.

Psychoactive substances, alcohol and tobacco consumption in HIV-infected outpatients.

OBJECTIVES: To assess the alcohol consumption, tobacco addiction and psychoactive substance use (PSU) of people living with HIV (PLHIV). DESIGN: Cross-sectional study in an HIV outpatient unit. METHODS: Autoquestionnaire systematically proposed to all patients during their usual clinical care visit during a 6-months period, for alcohol (AUDIT test), tobacco (Short Fagerstrom Test) and PSU (ASSIST V3.0 test). RESULTS: Of 1334 distributed questionnaires, 1018 PLHIV responded: 76.8% were men [528 patients were MSM), and the median age was 49 years (interquartile range: 42-46). A prevalence of excessive alcohol drinking was found in 22% [95% confidence interval (CI) 19.5-24.7%] and 44.6% (CI 41.5-47.7%) were current smokers, with high dependence in 29.1% (CI 24.9-33.7%). The prevalence of PSU was 37.8% (CI 34.8-41%) in the past 3 months: cannabis 27.7%, poppers 16.4%, cocaine 8.9%, psychotropic medications 7.1%, gamma-hydroxybutyrate/gamma-butyrolactone (GHB/GBL) 4.7%, stimulants 3.1%, synthetic cathinones 2.7%, hallucinogens 1.5%. In the past 3 months, PSU was more prevalent in MSM than in non-MSM patients (46 versus 30%, P < 0.001). MSM consumed significantly more inhaled solvents (poppers) 31.0 versus 1.1%, GHB/GBL 7.8 versus 0.8%, stimulants 5.0 versus 1.1%, synthetic cathinones 4.9 versus 0.3%, and hallucinogens 2.3 versus 0.5%. CONCLUSION: Given the high prevalence of PSU and other addictions (alcohol and smoking) among PLHIV, and particularly among MSM, a systematic screening of PSU and other addictions should be part of routine clinical care.

Evaluation of laboratory tests for cirrhosis and for alcohol use, in the context of alcoholic cirrhosis.

Laboratory tests can play an important role in assessment of alcoholic patients, including for evaluation of liver damage and as markers of alcohol intake. Evidence on test performance should lead to better selection of appropriate tests and improved interpretation of results. We compared laboratory test results from 1578 patients between cases (with alcoholic cirrhosis; 753 men, 243 women) and controls (with equivalent lifetime alcohol intake but no liver disease; 439 men, 143 women). Comparisons were also made between 631 cases who had reportedly been abstinent from alcohol for over 60 days and 364 who had not. ROC curve analysis was used to estimate and compare tests' ability to distinguish patients with and without cirrhosis, and abstinent and drinking cases. The best tests for presence of cirrhosis were INR and bilirubin, with areas under the ROC curve (AUCs) of 0.91 ± 0.01 and 0.88 ± 0.01, respectively. Confining analysis to patients with no current or previous ascites gave AUCs of 0.88 ± 0.01 for INR and 0.85 ± 0.01 for bilirubin. GGT and AST showed discrimination between abstinence and recent drinking in patients with cirrhosis, including those without ascites, when appropriate (and for GGT, sex-specific) limits were used. For AST, a cut-off limit of 85 units/L gave 90% specificity and 37% sensitivity. For GGT, cut-off limits of 288 units/L in men and 138 units/L in women gave 90% specificity for both and 40% sensitivity in men, 63% sensitivity in women. INR and bilirubin show the best separation between patients with alcoholic cirrhosis (with or without ascites) and control patients with similar lifetime alcohol exposure. Although AST and GGT are substantially increased by liver disease, they can give useful information on recent alcohol intake in patients with alcoholic cirrhosis when appropriate cut-off limits are used.

Evaluation of high resolution ultrasound as a tool for assessing the 3D volume of blood clots during in vitro thrombolysis.

Thrombosis is a major cause of several diseases, i.e. myocardial infarction, cerebral stroke and pulmonary embolism. Thrombolytic therapies are required to induce fast and efficient recanalization of occluded vessels. To evaluate the in vitro efficacy of these thrombolytic strategies, measuring clot dissolution is essential. This study aimed to evaluate and validate high resolution ultrasound as a tool to assess the exact volume of clots in 3D and in real time during in vitro thrombolytic drug testing. This new method was validated by measuring the effects of concentration range of recombinant tissue type plasminogen activator on a blood clot during complete occlusion or 70% stenosis of a vessel. This study shows that high resolution ultrasound imaging allows for a real-time assessment of the 3D volume of a blood clot with negligible inter- and intra-operator variabilities. The conclusions drawn from this study demonstrate the promising potential of high resolution ultrasound imaging for the in vitro assessment of new thrombolytic drugs.

Areas of improvement in anticoagulant safety. Data from the CACAO study, a cohort in general practice.

BACKGROUND: Real-world studies on anticoagulants are mostly performed on health insurance databases, limited to reported events, and sometimes far from every-day issues in family practice. We assess the presence of data for safe monitoring of oral anticoagulants in general practice, and compare patients' knowledge of taking an anticoagulant between vitamin K antagonists (VKA) and direct anticoagulants (DOAC), and the general practitioner's perception of their adherence to anticoagulation. METHODS: The CACAO study is a national cohort study, conducted by general practitioners on ambulatory patients under oral anticoagulant. In the first phase, investigators provided safety data available from medical records at inclusion. They also evaluated patients' knowledge about anticoagulation and graded their perception of patients' adherence. RESULTS: Between April and December 2014, 463 general practitioners included 7154 patients. Renal and hepatic function tests were respectively unavailable in 109 (7.5%) and 359 (24.7%) DOAC patients. Among patients with atrial fibrillation, 345 patients (6.9%) had a questionable indication of anticoagulant (CHA2DS2-Vasc<2). One hundred and thirty-three VKA patients (2.3%) and 70 DOAC patients (4.9%) answered they took no anticoagulant (p<0.0001). According to general practitioners' perception, 430 patients (6.1%) were classified as "not very" or "not adherent", with no difference between groups. CONCLUSIONS: Our results highlight the efforts needed to improve anticoagulant safety in daily practice: decreasing the rate of unknown biological data in patients with DOACs or the rate of patients with VKA with no strong indication of anticoagulation, and improving patient knowledge with regard to their anticoagulant. Patients' adherence seems highly over-estimated by the general practitioners. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02376777.

Rapid bacterial identification using evanescent-waveguide oligonucleotide microarray classification.

Bacterial identification relies primarily on culture-based methodologies and requires 48-72 h to deliver results. We developed and used i) a bioinformatics strategy to select oligonucleotide signature probes, ii) a rapid procedure for RNA labelling and hybridization, iii) an evanescent-waveguide oligoarray with exquisite signal/noise performance, and iv) informatics methods for microarray data analysis. Unique 19-mer signature oligonucleotides were selected in the 5'-end of 16s rDNA genes of human pathogenic bacteria. Oligonucleotides spotted onto a Ta(2)O(5)-coated microarray surface were incubated with chemically labelled total bacterial RNA. Rapid hybridization and stringent washings were performed before scanning and analyzing the slide. In the present paper, the eight most abundant bacterial pathogens representing >54% of positive blood cultures were selected. Hierarchical clustering analysis of hybridization data revealed characteristic patterns, even for closely related species. We then evaluated artificial intelligence-based approaches that outperformed conventional threshold-based identification schemes on cognate probes. At this stage, the complete procedure applied to spiked blood cultures was completed in less than 6 h. In conclusion, when coupled to optimal signal detection strategy, microarrays provide bacterial identification within a few hours post-sampling, allowing targeted antimicrobial prescription.

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.