Time is of the Essence: Achieving Prompt and Effective Antimicrobial therapy of Bloodstream infection With Advanced Hospital Information Systems.

The early administration of appropriate antibiotic therapy is crucial for the survival of patients with bacteremia. Current research focuses on improving analytical times through technology while there have been very few efforts to improve post-analytical times even though they represent 40% of the time between blood taking and appropriate treatment administration. One of the clues is the efficiency and appropriateness of the result communication system. Here, we review all delays in the whole process with the aim of improving time to appropriate treatment administration. We discuss causes for long times to adjust treatment once microbiological results are released. We argue that that the pervasive health information system in this organization serves as both a bottleneck and a rigid framework to focus on. Finally, we explore how should be conceived the next generation hospital information systems to effectively assist the doctors in treating patients with bacteremia.

Description of an outbreak of hemorrhagic fever with renal syndrome in the southern Jura Mountains, France, in 2021.

OBJECTIVE: The aim of our study was to describe the 2021 Hemorrhagic Fever with Renal Syndrome (HFRS) outbreak in the southern Jura Mountains. PATIENTS AND METHODS: We included all laboratory-confirmed cases of HFRS reported between April and September 2021 in the three local hospitals. RESULTS: A total of 90 patients were enrolled in the study: 73 hospitalized and 17 non-hospitalized patients. Transient myopia was only reported in non-hospitalized patients. Forty (44.4 %) patients underwent medical imaging before hantavirus diagnosis. Twenty-one patients (28.8 %) had a plasma creatinine level > 353.6 µmol/L, no patient developed severe metabolic disorder. Only one patient was dialyzed. A pacemaker was implanted before diagnosis of HFRS due to severe bradycardia in one patient. Sudden death was reported in one patient. CONCLUSION: This hantavirus epidemic led to numerous hospitalizations, one dialysis treatment, and one death. Early diagnosis by rapid test could avoid unnecessary investigations.

Post-exposure prophylaxis completion and condom use in the context of potential sexual exposure to HIV.

OBJECTIVES: Post-exposure prophylaxis (PEP) care remains a challenge for individuals with potential sexual exposure to HIV in terms of PEP completion and ongoing risk behaviours. METHODS: A retrospective analysis was carried out on data from the French Dat'AIDS prevention cohort (NCT03795376) for individuals evaluated for PEP between 2004 and 2017. A multivariable analysis was performed of predictors of both PEP completion and condom use [odds ratios (ORs)] and their associated probabilities (P, with P > 95% being clinically relevant). RESULTS: Overall, 29 060 sexual exposures to HIV were evaluated for PEP [36% in men who have sex with men (MSM) and 64% in heterosexuals]. Overall, 12 different PEP regimens were offered in 19 240 cases (46%). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) was the preferred backbone (n = 14 304; 74%). We observed a shift from boosted protease inhibitor-based regimens to nonnucleoside reverse transcriptase inhibitor- or integrase inhibitor-based regimens in recent years. Overall, 20% of PEP prescriptions were prematurely discontinued. Older age, MSM, intercourse with a sex worker, rape and intercourse with a known HIV-infected source patient were factors associated with increased rates of PEP completion (OR > 1; P > 98%). None of the 12 PEP regimens was associated with premature discontinuation. We also found 12 774 cases of unprotected sexual intercourse (48%). Condom use decreased (OR < 1; P > 99%) with the year of exposure, and was lower in MSM and rape victims. Condom use increased (OR > 1, P > 99%) with age, and was higher in those who had intercourse with a sex worker or with a female partner and in those with knowledge of the partner's HIV status. CONCLUSIONS: We provide new insights into how rates of condom use and PEP completion might be improved in those receiving PEP by targeting certain groups of individuals for interventions. In particular, youth and MSM at risk should be linked in a prevention-to-care continuum.

Implant retention and high rate of treatment failure in hematogenous acute knee and hip prosthetic joint infections.

OBJECTIVES: Only few studies evaluated hematogenous prosthetic joint infections. We aimed to describe the characteristics of these infections and factors associated with management failure. METHODS: We selected hematogenously-acquired infections, defined by the occurrence of infectious symptoms more than a year after implantation among records of patients treated for hip and knee prosthetic joint infections at Montpellier University Hospital between January 2004 and May 2015. Failure was defined by death due to prosthesis-related infection, need for prosthesis removal in case of conservative treatment, or recurrence of infectious signs on a new prosthesis. RESULTS: Forty-seven patients with hematogenous prosthetic joint infection were included (33 knee infections and 14 hip infections). Infectious agents were streptococci (43%), Staphylococcus aureus (43%), Gram-negative bacilli (13%), and Listeria monocytogenes (2%). Thirty-one patients were initially treated with debridement and implant retention and 15 with prosthesis removal (three with one-stage surgery, 10 with two-stage surgery). The median duration of antibiotic therapy was 66.5 days. The overall failure rate was 52% (24/48), 71% (22/31) with implant retention strategy, 13% (2/15) with prosthesis removal, and 63% (12/19) in case of Staphylococcus aureus infection. Conservative treatment was appropriate (arthrotomy on a well-implanted prosthesis without sinus tract and symptom onset <21 days) in 13/31 patients (42%) with a failure rate still high at 69% (9/13). The only factor associated with failure was conservative surgical treatment. CONCLUSION: The high risk of failure of conservative treatment for hematogenous prosthetic joint infections should lead to considering prosthesis replacement as the optimal strategy, particularly with Staphylococcus aureus.

Potential lung cancer screening outcomes using different age and smoking thresholds in the ANRS-CO4 French Hospital Database on HIV cohort.

OBJECTIVES: In most lung screening programmes, only subjects ≥ 55 years old and smoking ≥ 30 pack-years are eligible to undergo chest low-dose computed tomography. Whether the same criteria should apply to people living with HIV (PLHIV) is uncertain, given the increased lung cancer risks associated with immunodeficiency and high rates of smoking. We assessed different outcomes obtained from simulating one round of lung cancer screening in PLHIV using different age and smoking thresholds for eligibility. METHODS: Data from the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS)-CO4 French Hospital Database on HIV (FHDH) cohort of PLHIV and a national representative survey of PLHIV in care in 2011 (the ANRS-VESPA2 [enquête sur les personnes atteintes] study) were used to estimate the maximum proportion of incident lung cancers occurring between 2012 and 2016 that would have potentially been detected by screening in 2011. Secondary outcomes were numbers of eligible subjects in the cohort and numbers of subjects needed to screen (NNS) to detect one lung cancer. RESULTS: Among 77819 PLHIV in 2011 (median age 46 years; 66% men), 285 subjects subsequently developed lung cancer. Adoption of the US Preventive Services Task Force (USPSTF) recommendations (55-80 years; ≥ 30 pack-years) would have detected 31% of lung cancers at most. Lowering the minimum age to 50 and 45 years would have detected 49% and 60% of cancers, respectively, but would have greatly increased the number of eligible subjects and the NNS to detect one case of lung cancer. CONCLUSIONS: Use of the USPSTF criteria would have detected only a minority of lung cancers in a large French cohort of PLHIV in 2011. Screening PLHIV at younger ages (45 or 50 years) and/or the use of lower smoking thresholds (20 pack-years) may be beneficial, despite the consequently higher numbers of eligible subjects and NNS to detect one case of lung cancer, and should be evaluated in future studies.

Electrotransfer of CpG free plasmids enhances gene expression in skin.

Skin is a very suitable target for gene therapy and DNA vaccination due to its accessibility, its surface and its ability to produce transgenes. Gene electrotransfer (GET) to the skin is under development for clinical applications for DNA vaccine or local treatment such as wound healing. Local treatments are effective if the expression of the plasmid affects only the local environment (skin) by inducing an efficient concentration over a prolonged period. In this study, we evaluate the control of expression in the skin of a plasmid coding a fluorescent protein by its CpG (cytosine-phosphate-guanine motif) content. Two fluorescent reporter genes are evaluated: tdTomato and GFP. The expression is followed on the long term by in vivo fluorescence imaging. Our results show that GET mediated expression in the skin can be controlled by the CpG content of the plasmid. Long term expression (>120 days) can be obtained at high level with CpG-free constructs associated with a proper design of the electrodes where the field distribution mediating the gene electrotransfer is present deep in the skin.

Distinct Profiles of Consumers of Psychoactive Substances in People Attending French Sexual Transmitted Infections Centers.

The objective of this cross-sectional survey was to assess the prevalence of psychoactive substance use (PSU) in people attending 11 French Sexual Transmitted Infection Centers, and to specify their profiles (PSU and link with risky sexual behaviors) using the ascending hierarchical clustering method. Among the 5220 individuals who completed the survey, 55.6% were men and the median age was 24 years [IQR: 20-31]. Among the participants, 2751 (52.7%) reported PSU at least once in their life. Ascending hierarchical clustering identified seven distinct profiles of participants based on their PSU. This study shows a high prevalence of PSU and alcohol consumption in this young population. Moreover, subgroup analysis allowed identifying groups of psychoactive substance users who presented specific risks or vulnerabilities and who should be priority targets for interventions, particularly sexual minority groups.

Implementing screening, brief intervention and referral to treatment in a French cohort of people living with HIV: a pilot study.

OBJECTIVES: Screening, brief intervention and referral to treatment (SBIRT) is an evidence-based practice used to identify, reduce and prevent problematic use and abuse of, and dependence on, tobacco, alcohol and psychoactive substances. To date, the pertinence of this practice among people living with HIV (PLHIV) is unknown. In this pilot study, we aimed to assess the acceptability of SBIRT in a cohort of HIV-infected out-patients who were asked about their consumption of alcohol, tobacco and psychoactive substances. METHODS: A monocentric study was performed at the University Hospital of Montpellier. In a 6-month period, 20 trained physicians screened for the consumption of alcohol [using the Alcohol Use Disorders Identification Test (AUDIT)], tobacco (using the Short Fagerstrom Test) and psychoactive substances [using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) V3.0] via an auto-questionnaire and proposed a brief intervention to patients with misusage. RESULTS: One thousand and eighteen PLHIV completed the questionnaire, and 861 [84.6%; 95% confidence interval (CI) 82.2-86.7%] PLHIV returned it to the physician. Among the latter, 650 patients wished to discuss the answers with their physician (75.5%; 95% CI 72.5-78.3%), and brief interventions were realized in 405 patients (62.3%). CONCLUSIONS: SBIRT is a simple screening and harm reduction tool that is well accepted by PLHIV in out-patient clinics. This method could be implemented in routine HIV care to screen and manage patients systematically for harmful substance use.

Which antiretrovirals should be prescribed as first-line treatments? Changes over the past 10 years in France.

OBJECTIVE: To describe the changes in first-line antiretroviral (ART) regimens in France between 2005 and 2015 and patients' characteristics related to the use of protease inhibitors in 2015. METHODS: We extracted all patients starting ART between 2005 and 2015 from a large prospective cohort. Regimens were classified as three nucleoside reverse transcriptase inhibitors (NRTI), or two NRTIs with a boosted protease inhibitor (bPI), with a non-nucleoside reverse transcriptase inhibitor (NNRTI), or with an INSTI. Patients' characteristics at the time of initiation were collected. A multinomial logit model was fitted to analyze characteristics related to the choice of regimen in 2015. RESULTS: We analyzed data from 15,897 patients. The proportion of patients starting with (i) a bPI decreased from 60% before 2014 to 38.1% in 2015; (ii) an NNRTI decreased from 30% to 17.8% in 2015; (iii) an INSTI gradually increased to 39.4% in 2015. In 2015, patients with an initial viral load ˃5 log copies/mL were less likely to receive NNRTI (OR=0.08) or INSTI regimens (OR=0.69) than bPIs. Patients with initial CD4+ T cell count ˂200/mm3 were less likely to receive an NNRTI (OR=0.28) or an INSTI regimen (OR=0.52) than a bPI. Women were less likely to receive an NNRTI (OR=0.79) or an INSTI regimen (OR=0.71) than a bPI; although this depended on age. CONCLUSION: The use of bPI as first-line ART declined sharply in France from 2005 to 2015. bPI remained of preferential use in patients with high viral load, low CD4+ T cell count, and in women.

No relationship between late HIV diagnosis and social deprivation in newly diagnosed patients in France.

OBJECTIVES: The aim of the study was to determine whether there is a relationship between social deprivation and time of HIV diagnosis in France. METHODS: Prospectively collected data from a multicentre database were used in the study. Patients with a first HIV diagnosis between 1 January 2014 and 31 December 2015 were selected from the database. Deprivation was measured using the European Deprivation Index (EDI), which is an ecological index constructed from the address of residence and based on the smallest geographical census unit, in which individuals are classified so as to be comparable with national quintiles. Time of diagnosis was classified as being at an early, intermediate, late, or advanced stage of disease. Age, gender, distance from home to HIV centre, most probable route of infection, and hepatitis B or C coinfection were considered in the analysis. Because of a strong interaction between gender and most probable route of infection, we constructed a 'population' variable: men who have sex with men (MSM), heterosexual men and women. RESULTS: Of 1421 newly diagnosed patients, 44% were diagnosed either late or at an advanced stage of disease, and 46.3% were in the highest deprivation quintile. Using multivariate logistic regression, 'population' [odds ratio (OR) 0.62 (95% confidence interval (CI) 0.48-0.78) for MSM compared with women] and age [OR 1.39 (95% CI 1.07-1.80), 1.72 (1.32-2.23) and 1.86 (1.40-2.47) for the second, third and fourth quartiles, respectively, compared with the first quartile] were found to be related to late diagnosis. EDI level was not related to late HIV diagnosis. CONCLUSIONS: 'Population' seems to be more relevant than EDI to define evidence-based interventions to limit late diagnosis.

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Investigation of pre-XDR Beijing Mycobacterium tuberculosis transmission to a healthcare worker in France, 2016.

A case of occupational contamination of a healthcare worker by a pre-extensively drug-resistant (pre-XDR) Beijing strain of Mycobacterium tuberculosis at the University Hospital of Montpellier, France is reported. The index case was identified using genetic fingerprinting of isolates. This report underscores the risk of healthcare-associated contamination by pre-XDR tuberculosis (TB) in low-incidence countries and the importance of molecular tools for TB care. It also calls for increased vigilance in the management of multi-drug-resistant/XDR TB patients.

Cytochrome 2B6 polymorphism and efavirenz-induced central nervous system symptoms : a substudy of the ANRS ALIZE trial.

OBJECTIVES: Single nucleotide polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been associated with high interindividual variation in efavirenz pharmacokinetics. However, clinical data on the relationship of CYP2B6 polymorphisms with the occurrence of efavirenz-induced central nervous system (CNS) symptoms are limited. METHODS: We analysed four polymorphisms in the CYP2B6 (516 G>T), CYP3A5 (6986 A>G) and ATP-binding cassette, sub-family B, member 1 (ABCB1) (2677 G>T/A and 3435 C>T) genes in HIV-infected adults virologically suppressed on a protease inhibitor-based regimen who switched to a regimen containing emtricitabine, didanosine and efavirenz in the setting of the ANRS ALIZE trial. Kaplan-Meier methods and Cox regression analysis were used to investigate their association with efavirenz plasma levels and CNS events up to 48 months after switching. RESULTS: In total, 191 patients with a median age of 41 years, who were 87% male and 85% Caucasian, were enrolled in the study. Variant allelic frequencies were 0.49, 0.93, 0.59 and 0.63 for CYP2B6 516, CYP3A5 392, ABCB1 2677 and ABCB1 3435, respectively. The median efavirenz plasma concentration (MEPC) was 2.2 mg/L [interquartile range (IQR) 1.7-2.8 mg/L] and was significantly higher in patients with the deficient CYP2B6 516T. Overall, 242 CNS events were reported in 104 individuals (54%). No correlation was found between MEPC and CNS events. The occurrence of a first CNS event was lower in patients with the CYP2B6 516 G/G genotype vs. CYP2B6 516 T genotypes [50% (IQR: 40-60%) vs. 66% (IQR: 56-75%), respectively; P = 0.02]. In an adjusted Cox regression model, there was a tendency towards a higher risk of a first CNS event among carriers of the variant CYP2B6 516 T allele (relative risk 1.4 [95% CI, 0.99-2.1]; P?=?.06), compared with noncarriers. CONCLUSIONS: The deficient CYP2B6 516 T allele is associated with higher efavirenz plasma drug levels and more frequent CNS-related symptoms.

Impact of T cell activation, HIV replication and hepatitis C virus infection on neutrophil CD64 expression.

BACKGROUND: Overexpression of the Fc receptor CD64 on neutrophils is associated with innate immune response and bacterial infections. During HIV infection a large set of immune disorders including T-lymphocyte over-activation, microbial translocation, impairment of neutrophil functions, and immunodeficiency may interplay with neutrophil CD64 expression. METHODS: Associations of neutrophil CD64 expression with CD8+ T cell activation, CD4+ T cells number, HIV, and HCV replications were investigated in HIV infected patients using a standardized method. RESULTS: Higher neutrophil CD64 expression was observed in HIV infected subjects compared to healthy controls (0.91 vs. 0.75, P < 0.001). Among 115 HIV infected patients, nine (8.8%) had a CD64 expression over the clinical threshold as calculated against bead standard (i.e., 1.5). HIV viremic patients were more likely to have an index above 1.5 (OR: 6.68, P values: 0.01). A trend for correlation between CD64 expression and CD8 T cell activation was observed (P values: 0.08). Blood CD4+ T lymphocyte depletion and HCV replication did not affect neutrophil CD64 expression. CONCLUSIONS: HIV infection and HIV replication are associated with up-regulation of neutrophil CD64. CD64 overexpression above the clinical threshold was observed in a minor proportion of HIV infected individuals treated by antiretroviral therapy and may be a marker of neutrophil activation related to non-AIDS-linked comorbidities. © 2016 International Clinical Cytometry Society.

MACVIA-LR (Fighting Chronic Diseases for Active and Healthy Ageing in Languedoc-Roussillon): A Success Story of the European Innovation Partnership on Active and Healthy Ageing.

The Région Languedoc Roussillon is the umbrella organisation for an interconnected and integrated project on active and healthy ageing (AHA). It covers the 3 pillars of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA): (A) Prevention and health promotion, (B) Care and cure, (C) and (D) Active and independent living of elderly people. All sub-activities (poly-pharmacy, falls prevention initiative, prevention of frailty, chronic respiratory diseases, chronic diseases with multimorbidities, chronic infectious diseases, active and independent living and disability) have been included in MACVIA-LR which has a strong political commitment and involves all stakeholders (public, private, patients, policy makers) including CARSAT-LR and the Eurobiomed cluster. It is a Reference Site of the EIP on AHA. The framework of MACVIA-LR has the vision that the prevention and management of chronic diseases is essential for the promotion of AHA and for the reduction of handicap. The main objectives of MACVIA-LR are: (i) to develop innovative solutions for a network of Living labs in order to reduce avoidable hospitalisations and loss of autonomy while improving quality of life, (ii) to disseminate the innovation. The three years of MACVIA-LR activities are reported in this paper.

[Seoul hantavirus infection-associated hemorrhagic fever with renal syndrome in France: A case report]. / Fièvre hémorragique à syndrome rénal associée à l'hantavirus Séoul en France : une observation.

INTRODUCTION: Rodents are hantavirus hosts. In Europe, hantaviruses are responsible for human infections resulting in hemorrhagic fever with renal syndrome. Thousands of Puumala virus infections are reported annually in Europe, whereas human Seoul virus infections are rarely detected. CASE REPORT: We report the case of a 38-year-old patient who presented initially with flu-like symptoms and transitory blurred vision. He developed thrombocytopenia, acute renal failure, and elevated aminotransferases levels during the disease course, but the outcome was favorable with a full recovery. Afterwards, the hantavirus serology results were indicative of Seoul virus infection. CONCLUSION: This report serves to remind physicians to consider diagnosing hantavirus infection when observing the association of fever, acute renal failure and thrombocytopenia. Transitory blurred vision is a specific element to indicate this diagnosis.

Diagnosing pelvic osteomyelitis beneath pressure ulcers in spinal cord injured patients: a prospective study.

There is no consensus on a diagnostic strategy for osteomyelitis underlying pressure ulcers. We conducted a prospective study to assess the accuracy of multiple bone biopsies and imaging to diagnose pelvic osteomyelitis. Patients with clinically suspected osteomyelitis beneath pelvic pressure ulcers were enrolled. Bone magnetic resonance imaging (MRI) and surgical bone biopsies (three or more for microbiology and one for histology per ulcer) were performed. Bacterial osteomyelitis diagnosis relied upon the association of positive histology and microbiology (at least one positive culture for non-commensal microorganisms or three or more for commensal microorganisms of the skin). From 2011 to 2014, 34 patients with 44 pressure ulcers were included. Bacterial osteomyelitis was diagnosed for 28 (82.3%) patients and 35 (79.5%) ulcers according to the composite criterion. Discrepancy was observed between histology and microbiology for 5 (11.4%) ulcers. Most common isolates were Staphylococcus aureus (77.1%), Peptostreptococcus (48.6%) and Bacteroides (40%), cultured in three or more samples in 42.9% of ulcers for S. aureus and ≥20% for anaerobes. Only 2.8% of ulcers had three or more positive specimens with coagulase-negative staphylococci, group B Streptococcus, and nil with enterococci and Pseudomonas aeruginosa. Staphylococcus aureus, Proteus and group milleri Streptococcus were recovered from one sample in 22.8%, 11.4% and 11.4% of ulcers, respectively. Agreement was poor between biopsies and MRI (κ 0.2). Sensitivity of MRI was 94.3% and specificity was 22.2%. The diagnosis of pelvic osteomyelitis relies on multiple surgical bone biopsies with microbiological and histological analyses. At least three bone samples allows the detection of pathogens and exclusion of contaminants. MRI is not routinely useful for diagnosis.