Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study.

Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R2 adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.

How to Identify Potential Candidates for HIV Pre-Exposure Prophylaxis: An AI Algorithm Reusing Real-World Hospital Data.

HIV Pre-Exposure Prophylaxis (PrEP) is effective in Men who have Sex with Men (MSM), and is reimbursed by the social security in France. Yet, PrEP is underused due to the difficulty to identify people at risk of HIV infection outside the "sexual health" care path. We developed and validated an automated algorithm that re-uses Electronic Health Record (EHR) data available in eHOP, the Clinical Data Warehouse of Rennes University Hospital (France). Using machine learning methods, we developed five models to predict incident HIV infections with 162 variables that might be exploited to predict HIV risk using EHR data. We divided patients aged 18 or more having at least one hospital admission between 2013 and 2019 in two groups: cases (patients with known HIV infection in the study period) and controls (patients without known HIV infection and no PrEP in the study period, but with at least one HIV risk factor). Among the 624,708 admissions, we selected 156 cases (incident HIV infection) and 761 controls. The best performing model for identifying incident HIV infections was the combined model (LASSO, Random Forest, and Generalized Linear Model): AUC = 0.88 (95% CI: 0.8143-0.9619), specificity = 0.887, and sensitivity = 0.733 using the test dataset. The algorithm seems to efficiently identify patients at risk of HIV infection.

[HIV infection, from a death sentence to a chronic disease]. / Infection par le VIH, de la mort annoncée à la maladie chronique.

The accessibility of antiretroviral treatments has revolutionised the life expectancy of people living with HIV. The efficacy of these treatments, while essential, must nevertheless be accompanied by the prevention and close monitoring of comorbidities such as certain cancers, diabetes or cardiovascular diseases. Finally, the support provided to people living with HIV must also take into account the stigmatisation to which they are still subjected.

Impact of age on care pathways of people living with HIV followed up in hospital.

The aging population of people living with human immunodeficiency virus (HIV) (PLWH) is exposed to a widening spectrum of non-AIDS-defining diseases. Thus, our objective was to compare the health care offered to PLWH according to age. We conducted a multicenter cross-sectional study on PLWH who consulted at one of 59 French HIV reference centers from 15th to 19th October 2012. Using our survey questionnaires, PLWH self-reported the medical care they received, whether or not tied to HIV infection monitoring, during the previous year. A total of 650 PLWH participated in the survey (median age 48 years, Interquartile range (IQR) 40-54), of which 95 were aged 60 years or over (14.5%). Compared to younger PLWH, 60-and-over PLWH were more often under complementary health insurance cover and less socially deprived based on the French EPICES (Evaluation of Precarity and Inequalities in Health Examination Centers) score. The elderly PLWH presented more comorbidities and less coinfections with hepatitis viruses. During health care, therapeutic education was less often offered to older PLWH (14% vs. 26%, p = .01), but this difference was mainly explained by sociodemographic factors and clinical status. Over the previous 6 months, 74% of PLWH who were followed up in hospital had also consulted another doctor, with a mean of 3.75 consultations (±4.18) without difference between age groups. After adjustment for sociodemographic factors and comorbidities, PLWH over 60 years were more likely to have consulted medical specialists as outpatients in the last 6 months (odds ratio [OR] = 2.63 [1.11-6.20]). Whatever their age, 13% of PLWH had been refused care on disclosure of their HIV status, and 27% of PLWH still did not disclose their HIV status to some caregivers. Coordinated health care throughout patients' lives is crucial, as health-care pathways evolve toward outpatient care as the patients get older.

Benefits of management strategy adjustments during an outbreak of enterovirus meningitis in adults.

Enteroviruses (EVs) are the most common identifiable cause of the aseptic meningitis syndrome. Widespread seasonal outbreaks of EV meningitis result in a high financial cost to the community, in part because of the difficulty of discriminating between viral and bacterial meningitis. During a nationwide outbreak of EV meningitis due to echovirus 30 in France we tested the hypothesis that a management strategy including early testing of cerebrospinal fluid (CSF) by means of EV PCR in all adult patients with acute aseptic meningitis on admission might reduce the duration of hospitalization and thus the expenditure on health resources. We compared the characteristics of adult patients with acute aseptic meningitis seen in our institution before (n = 21) and after (n = 27) implementation of this strategy. The strategy was cost-effective in that it significantly reduced (i) the mean duration of hospital stay (from 103 to 80 h; p = 0.04); and (ii) the mean duration of antibacterial treatment (from 115 to 69 h; p = 0.02). Systematic testing of CSF in adult patients with aseptic meningitis by means of EV PCR may be cost-effective during an outbreak of EV meningitis.