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Background: The prison environment is a place of high consumption of benzodiazepines (BZDs) due to the anxiety and sleep disturbances, mental disorders, detoxification and trafficking., Objective: The study aims to explore experiences of health and social care professionals on the use of BZDs in prisons, as well as the barriers and enablers to their deprescribing., Method: Semistructured individual interviews with professionals working in a prison setting were performed between March and April 2022, based on an interview guide. They were recorded and transcribed using the NVivo software. A qualitative analysis using an inductive approach based on a thematic analysis was performed., Results: Sixteen health professionals were interviewed, including psychiatrists, general practitioners, nurses, pharmacists, psychologists, musicologists and pharmacy technicians. The identified barriers to deprescribing BZDs were problems of coordination between prescribers, lack of time and alternatives. Concerning the enablers, therapeutic education groups, staff's awareness of the irrelevance of some medication and multi-professional advice were identified., Discussion: This study highlights the similarities in deprescribing difficulties between prison and other settings. Some of the levers identified in our study have shown their effectiveness in different settings., Conclusion: Deprescribing is done most of the time in good conditions but requires an additional delay compared to the outside environment., (© 2023 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objectives: Today, the involvement of patients in their care is essential. As the population ages increases, the number of patients with chronic diseases is increasing. In the vascular medicine and surgery departments, patients are polymedicated and mostly suffer from several chronic diseases. Approximately 50% of patients with a chronic disease are not adherent. Among the factors that can influence therapeutic adherence are the beliefs and representations of patients.To evaluate the beliefs and representations of chronic treatments in patients with multiple medications and hospitalised in a vascular medicine and surgery department, and to evaluate the medication adherence, the knowledge and the importance patients attach to their treatments., Design: Observational, prospective and a single-centre study., Setting: The study was conducted in a French tertiary hospital centre of around 3000 beds in 9 institutions., Participants: Adult polymedicated (ie, minimum of five chronic treatments) patients hospitalised in a vascular medicine and surgery department were included after application of the exclusion criteria., Methods: Patient interviews were carried out in the department and were based on three interviewer-administered questionnaires (a global questionnaire, the Belief Medical Questionnaire and the GIRERD questionnaire)., Results: Our study showed that patients perceived their treatments as beneficial rather than worrying. A correlation between medication adherence and beliefs was observed. 'Non-adherent'patients had a more negative overall view of medication than 'adherent' patients. The level of compliance and knowledge of our patients was low. Only 11% of the patients were 'good adherent', 16% of the patients could perfectly name their treatment and 36% knew all the indications., Conclusion: Knowledge of treatment representation and beliefs are central to understanding patient behaviour. Considering patients' representations will allow the identification of levers, and the development of actions and educational tools adapted to improve their adherence, their knowledge and therefore their drug management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Setting: Health measures taken during the pandemic deeply modified the clinical research practices. At the same time, the demand for the results of the COVID-19 trials was urgent. Thus, the objective of this article is to share Inserm's experience in ensuring quality control in clinical trials in this challenging context., Objectives: DisCoVeRy is a phase III randomized study that aimed at evaluating the safety and efficacy of 4 therapeutic strategies in hospitalized COVID-19 adult patients. Between March, 22nd 2020 and January, 20th 2021, 1309 patients were included. In order to guarantee the best quality of data, the Sponsor had to adapt to the current sanitary measures and to their impact on clinical research activity, notably by adapting Monitoring Plan objectives, involving the research departments of the participating hospitals and a network of clinical research assistants (CRAs)., Results: Overall, 97 CRAs were involved and performed 909 monitoring visits. The monitoring of 100% of critical data for all patients included in the analysis was achieved, and despite of the pandemic context, a conform consent was recovered for more than 99% of patients. Results of the study were published in May and September 2021., Discussion/conclusion: The main monitoring objective was met thanks to the mobilization of considerable personnel resources, within a very tight time frame and external hurdles. There is a need for further reflection to adapt the lessons learned from this experience to the context of routine practice and to improve the response of French academic research during a future epidemic., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CFL, VT, ADI, VPS, NM, ADE, AM, FM, DB and FA have nothing to disclose. CB has received consulting fees from MYLAN and Da Volterra and participated on a DSMB for 4Living Biotech. MH has received funding from The Belgian Centre for Knowledge (KCE), the Fonds-Erasme-COVID-19-Université Libre de Bruxelles and an EU-Horizon 2020 grant, payement or honoraria for lectures from Pfizer, Gilead and INSM, support for attending meetings and/or travel from Pfizer and Gilead, participated on a DSMB for Gilead and is President of the Belgian Society of Infectious Diseases and Clinical Microbiology and expert for Belgian Taskforce on COVID therapeutics. The institution employing AF, CD, HE, JS, SCC, MD and SLM received support from the French government, the European Commission, the Region Ile de France, Gilead Sciences, Inc., Sanofi, Merck group and AbbVie for the DisCoVeRy study., (Copyright © 2023. Published by Elsevier Inc.)

The current COVID-19 pandemic was an exceptional health situation, including for drug use. As there was no known effective drug for COVID-19 at the beginning of the pandemic, different drug candidates were proposed. In this article, we present the challenges for an academic Safety Department to manage the global safety of a European trial during the pandemic. The National Institute for Health and Medical Research (Inserm) conducted a European multicenter, open-label, randomized, controlled trial involving three repurposed and one-in development drugs (lopinavir/ritonavir, IFN-β1a, hydroxychloroquine, and remdesivir) in adults hospitalized with COVID-19. From 25 March 2020 to 29 May 2020, the Inserm Safety Department had to manage 585 Serious Adverse Events (SAEs) initial notification and 396 follow-up reports. The Inserm Safety Department's staff was mobilized to manage these SAEs and to report Expedited safety reports to the competent authorities within the legal timeframes. More than 500 queries were sent to the investigators due to a lack of or incoherent information on SAE forms. At the same time, the investigators were overwhelmed by the management of patients suffering from COVID-19 infection. These particular conditions of missing data and lack of accurate description of adverse events made evaluation of the SAEs very difficult, particularly the assessment of the causal role of each investigational medicinal product. In parallel, working difficulties were accentuated by the national lockdown, frequent IT tool dysfunctions, delayed implementation of monitoring and the absence of automatic alerts for SAE form modification. Although COVID-19 is a confounding factor per se, the delay in and quality of SAE form completion and the real-time medical analysis by the Inserm Safety Department were major issues in the quick identification of potential safety signals. To conduct a high-quality clinical trial and ensure patient safety, all stakeholders must take their roles and responsibilities., (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Objectives: We evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in coronavirus 2019 disease (COVID-19) inpatients requiring oxygen and/or ventilatory support., Methods: We conducted a phase III multicentre, open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), an add-on to the Solidarity trial (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO seven-point ordinal scale. Secondary outcomes included quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in respiratory specimens and pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, trials of which were stopped prematurely., Results: The intention-to-treat population included 583 participants-lopinavir/ritonavir (n = 145), lopinavir/ritonavir-IFN-β-1a (n = 145), hydroxychloroquine (n = 145), control (n = 148)-among whom 418 (71.7%) were male, the median age was 63 years (IQR 54-71), and 211 (36.2%) had a severe disease. The day-15 clinical status was not improved with the investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.83, (95% confidence interval (CI) 0.55-1.26, p 0.39), lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.04, p 0.08), and hydroxychloroquine versus control, aOR 0.93 (95%CI 0.62-1.41, p 0.75). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of serious adverse events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms., Conclusion: In adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a and hydroxychloroquine improved neither the clinical status at day 15 nor SARS-CoV-2 clearance in respiratory tract specimens., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Few data are available on plasma concentrations of antiretroviral therapy (ARV) during intermittent treatment., Objective: To compare plasma concentrations in OFF vs ON treatment periods at several time points during treatment., Methods: During a successful 48-week multicenter study (ANRS 162-4D trial) of 4 days with treatment (ON) followed by 3 days without treatment (OFF) in adults treated by two nucleoside analogues and a third agent belonging to a boosted protease-inhibitor (PI, darunavir [DRV], atazanavir [ATV], lopinavir [LPV]) or a non-nucleoside-reverse-transcriptase inhibitor (NNRTI, efavirenz [EFV], etravirine [ETR], rilpivirine [RPV]) conducted in 100 patients (96% success), we determined the plasma concentrations of ARV. Blood samples were collected for analysis at inclusion (W0, 7/7 strategy for all patients), W16 and W40 (ON) and at W4, W8, W12, W24, W32 and W48 (OFF)., Results: A total of 866 samples was analysed. Plasma concentrations were not statistically lower after 4 days (ON) vs 7/7 days of treatment except for RPV (-30 ng/mL at 4/7, P = 0.003). Significant lower plasma concentrations were observed for OFF vs ON except for ETR (n = 5, P = 0.062). Overall, 87.1% of ON concentrations (ATV 92.1%, DRV 51.1%, LPV 62.5%, EFV 94.4%, ETR 100% and RPV 94.9%) and 21.8% of OFF concentrations (ATV 1.4%, DRV 0.0%, LPV 0.0%, EFV 16.0%, ETR 92.6% and RPV 39.0%) were above the theoretical limit of efficacy of the molecule. In the OFF period, 85.8% of PI concentrations were under the limit of quantification, while 98.0% of NNRTI concentrations were quantifiable., Conclusion: Despite low/undetectable PI/NNRTI plasma concentrations in the OFF period, patients maintained an undetectable viral load. The mechanistic explanation should be investigated., (© 2020 British Pharmacological Society.)

One health (OH) approaches have increasingly been used in the last decade in the fight against zoonotic neglected tropical diseases (NTDs). However, descriptions of such collaborations between the human, animal and environmental health sectors are still limited for French-speaking tropical countries. The objective of the current survey was to explore the diversity of OH experiences applied to research, surveillance and control of NTDs by scientists from French-speaking countries, and discuss their constraints and benefits. Six zoonotic NTDs were targeted: echinococcoses, trypanosomiases, leishmaniases, rabies, Taenia solium cysticercosis and leptospiroses. Invitations to fill in an online questionnaire were sent to members of francophone networks on NTDs and other tropical diseases. Results from the questionnaire were discussed during an international workshop in October 2019. The vast majority (98%) of the 171 respondents considered OH approaches relevant although only 64% had implemented them. Among respondents with OH experience, 58% had encountered difficulties mainly related to a lack of knowledge, interest and support for OH approaches by funding agencies, policy-makers, communities and researchers. Silos between disciplines and health sectors were still strong at both scientific and operational levels. Benefits were reported by 94% of respondents with OH experience, including increased intellectual stimulation, stronger collaborations, higher impact and cost-efficiency of interventions. Recommendations for OH uptake included advocacy, capacity-building, dedicated funding, and higher communities' involvement. Improved research coordination by NTD networks, production of combined human-animal health NTD impact indicators, and transversal research projects on diagnostic and reservoirs were also considered essential., Competing Interests: The authors have declared that no competing interests exist.

Phytotherapy is the main complementary medicine for which patients afflicted with cancer have recourse but the associated consumption of phytotherapy products gives rise to a risk of interaction with anticancer agents. The aim of this prospective study was to measure the prevalence of the consumption of phytotherapy products as well as their interactions with anticancer agents in a cohort of patients from January 2018 to August 2019. Patients hospitalized in the conventional hematology unit and outpatients who had their prescriptions for oral anticancer agents filled at the hospital pharmacy were questioned about consumption of phytotherapy products by pharmacy externs trained in pharmaceutical interviews. Among the 110 hospitalized patients who answered the questionnaire, 40% (n = 44) used phytotherapy and 5 of them continued to consume it during the cycles of injectable chemotherapy. As a result, 10 interactions were found between the plants and the anticancer agents (prevalence of 27%). Among the 59 outpatients, 17% (n = 10) consumed phytotherapy. Eight interactions were identified (prevalence of 80%). The potential consequences were an increase or a decrease in the concentration of the anticancer agents and an increase in the risk of bleeding, hepatoxicity, and hypokalemia. The consumption of phytotherapy was unknown by a health professional for 44% of hospitalized patients and 60% of the outpatients. The risk of interactions between plants and anticancer agents is not negligible and professionals should be cognizant of this in their daily practice. The availability of tools for training and detection of interactions is indispensable for managing patients undergoing onco-hematology treatments.

Importance: Individuals living with schizophrenia are affected by cardiometabolic, endocrine, and motor adverse effects of current antipsychotic medications. Lumateperone is a serotonin, dopamine, and glutamate modulator with the potential to treat schizophrenia with few adverse effects., Objective: To examine the efficacy and safety of lumateperone for the short-term treatment of schizophrenia., Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, phase 3 clinical trial was conducted from November 13, 2014, to July 20, 2015, with data analyses performed from August 13 to September 15, 2015. Patients with schizophrenia who were aged 18 to 60 years and were experiencing an acute exacerbation of psychosis were enrolled from 12 clinical sites in the United States., Interventions: Patients were randomized 1:1:1 (150 patients in each arm) to receive lumateperone tosylate, 60 mg; lumateperone tosylate, 40 mg (equivalent to 42 or 28 mg, respectively, of the active moiety lumateperone); or placebo once daily for 4 weeks., Main Outcomes and Measures: The prespecified primary efficacy end point was mean change from baseline to day 28 in the Positive and Negative Syndrome Scale (PANSS) total score vs placebo. The key secondary efficacy measure was the Clinical Global Impression-Severity of Illness (CGI-S) score. The PANSS subscale scores, social function, safety, and tolerability were also assessed., Results: The study comprised 450 patients (mean [SD] age, 42.4 [10.2] years; 346 [77.1%] male; mean [SD] baseline PANSS score, 89.8 [10.3]; mean [SD] baseline CGI-S score, 4.8 [0.6]). In the prespecified modified intent-to-treat efficacy analysis (n = 435), 42 mg of lumateperone met the primary and key secondary efficacy objectives, demonstrating a statistically significant improvement vs placebo from baseline to day 28 on the PANSS total score (least-squares mean difference [LSMD], -4.2; 95% CI, -7.8 to -0.6; P = .02; effect size [ES], -0.3) and the CGI-S (LSMD, -0.3; 95% CI, -0.5 to -0.1; P = .003; ES, -0.4). For 28 mg of lumateperone, the LSMD from baseline to day 28 was -2.6 (95% CI, -6.2 to 1.1; P = .16; ES, -0.2) on the PANSS total score and -0.2 (95% CI, -0.5 to 0.0; P = .02; ES, -0.3) on the CGI-S. Both lumateperone doses were well tolerated without clinically significant treatment-emergent motor adverse effects or changes in cardiometabolic or endocrine factors vs placebo., Conclusions and Relevance: Lumateperone demonstrated efficacy for improving the symptoms of schizophrenia and had a favorable safety profile., Trial Registration: ClinicalTrials.gov identifier: NCT02282761.

Objectives: High rates of clinical acute rejection after kidney transplantation have been reported in people living with HIV (PLHIV), probably as a consequence of drug interactions. We therefore investigated the incidence of acute rejection within 6 months of transplantation in HIV-infected recipients treated with a protease-inhibitor-free raltegravir-based regimen., Methods: The Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS) 153 TREVE (NCT01453192) study was a prospective multicentre single-arm trial in adult PLHIV awaiting kidney transplantation, with viral load < 50 HIV-1 RNA copies/mL, CD4 T-cell count > 200 cells/μL, and HIV-1 strains sensitive to raltegravir, aiming to demonstrate 6-month clinical acute rejection rates < 30%. Time to transplantation was compared with that for uninfected subjects matched for age, sex and registration date., Results: In total, 61 participants were enrolled in the study, and 26 underwent kidney transplantation. Two participants experienced clinical acute rejection, corresponding to an estimated clinical acute rejection rate of 8% [95% confidence interval (CI) 2-24%] at 6 and 12 months post-transplantation. HIV infection remained under control in all but one participant, who temporarily stopped antiretroviral treatment. Median time to transplantation was longer in PLHIV than in controls (4.3 versus 2.8 years, respectively; P = 0.002) and was not influenced by blood group., Conclusions: Acute rejection rates were low after kidney transplantation in PLHIV treated with a raltegravir-based regimen. However, PLHIV have poorer access to transplantation than HIV-uninfected individuals after registration on the waiting list., (© 2019 British HIV Association.)

Dopamine D 2 receptor occupancy (D 2 RO) is a key feature of all currently approved antipsychotic medications. However, antipsychotic efficacy associated with high D 2 RO is often limited by side effects such as motor disturbances and hyperprolactinemia. Lumateperone (ITI-007) is a first-in-class selective and simultaneous modulator of serotonin, dopamine and glutamate in development for the treatment of schizophrenia and other disorders. The primary objective of the present study was to determine D 2 RO at plasma steady state of 60 mg ITI-007, a dose that previously demonstrated antipsychotic efficacy in a controlled trial, administered orally open-label once daily in the morning for two weeks in patients with schizophrenia (N = 10) and after at least a two-week washout period from standard of care antipsychotics. D 2 RO was determined using positron emission tomography with 11 C-raclopride as the radiotracer. Mean peak dorsal striatal D 2 RO was 39% at 60 mg ITI-007 occurring 1 h post-dose. Lumateperone was well-tolerated with a favorable safety profile in this study. There were no clinically significant changes in vital signs, ECGs, or clinical chemistry laboratory values, including prolactin levels. There were no adverse event reports of akathisia or other extrapyramidal motor side effects; mean scores on motor function scales indicated no motor disturbances with lumateperone treatment. This level of occupancy is lower than most other antipsychotic drugs at their efficacious doses and likely contributes to the favorable safety and tolerability profile of lumateperone with reduced risk for movement disorders and hyperprolactinemia. If approved, lumateperone may provide a new and safe treatment option for individuals living with schizophrenia.

Background: In the ANRS 165 DARULIGHT study (NCT02384967) carried out in HIV-infected patients, the use of a darunavir/ritonavir-containing regimen with a switch to a reduced dose of darunavir maintained virological efficacy (≤50 copies/mL) for 48 weeks with a good safety profile., Objectives: To assess the total and unbound blood plasma pharmacokinetics of darunavir and associated antiretrovirals, and their penetration into semen before and after dose reduction., Patients and Methods: Patients receiving a darunavir/ritonavir (800/100 mg q24h)-containing regimen for >6 months with plasma HIV-RNA ≤50 copies/mL for >12 months were switched to 400/100 mg darunavir/ritonavir q24h at week 0. A 24 h intensive pharmacokinetic blood sampling and a trough seminal sampling were performed before (week 0) and after (week 12) dose reduction. Individual pharmacokinetic parameter estimates were obtained using non-linear mixed-effect modelling for darunavir/ritonavir in blood plasma and used to test for bioequivalence, whereas darunavir/ritonavir in seminal plasma and NRTIs were analysed using a non-compartmental approach., Results and Conclusions: Fifteen patients completed the intensive pharmacokinetic analysis. There was no significant decrease in total and unbound darunavir blood plasma exposure despite a 50% decrease in darunavir daily dose from 800 to 400 mg (AUC0-24 = 65 563 versus 52 518 ng·h/mL; P = 0.25). A decrease in apparent oral clearance (CL/F) of both darunavir and ritonavir at week 12 suggests a modification of the initial darunavir/ritonavir daily dose balance (800/100 to 400/100 mg), in favour of a reduced inducer effect of darunavir on cytochrome P450 and efflux transporters compared with the standard dose.

Objectives: To assess whether low-dose ritonavir-boosted darunavir (darunavir/r) in combination with two NRTIs could maintain virological suppression in patients on a standard regimen of darunavir/r + two NRTIs., Design: A multicentre, Phase II, non-comparative, single-arm, open-label study., Setting: Tertiary care hospitals in France., Subjects: One hundred HIV-1-infected adults with no darunavir or NRTI resistance-associated mutations (RAMs) and a plasma HIV RNA level ≤50 copies/mL for ≥12 months on once-daily darunavir/r (800/100 mg) + two NRTIs for ≥6 months were switched to darunavir/r 400/100 mg with the same NRTIs., Primary Outcome Measure: Proportion of patients with treatment success: plasma HIV RNA level ≤50  copies/mL up to 48 weeks without any change in the study regimen, in a modified ITT (mITT) analysis., Results: At baseline, most patients were male (78%), with a median age of 43 years, median duration of HIV RNA ≤50 copies/mL of 35 months and median CD4 T cell count of 633 cells/mm3. Seventy-six percent received tenofovir/emtricitabine and 24% abacavir/lamivudine. Five patients were excluded from the mITT analysis. The rate of treatment success through to week 48 was 91.6% (87/95; 95% CI 84.1%-96.3%). No RAM was detected in three amplifiable genotypes. A total of 212 adverse events (AEs) occurred in 64 patients (64%); 9 AEs were serious, none leading to treatment discontinuation., Conclusions: In HIV-infected patients well suppressed with darunavir/r (800/100 mg) and two NRTIs, a reduction of the darunavir dose to 400 mg/day maintained virological efficacy and was safe over 48 weeks.

Background: Intermittent treatment could improve the convenience, tolerability and cost of ART, as well as patients' quality of life. We conducted a 48 week multicentre study of a 4-days-a-week antiretroviral regimen in adults with controlled HIV-1-RNA plasma viral load (VL)., Methods: Eligible patients were adults with VL < 50 copies/mL for at least 1 year on triple therapy with a ritonavir-boosted PI (PI/r) or an NNRTI. The study protocol consisted of the same regimen taken on four consecutive days per week followed by a 3 day drug interruption. The primary outcome was the proportion of participants remaining in the strategy with VL < 50 copies/mL up to week 48. The study was designed to show an observed success rate of > 90%, with a power of 87% and a 5% type 1 error. The study was registered with ClinicalTrials.gov (NCT02157311) and EudraCT (2014-000146-29)., Results: One hundred patients (82 men), median age 47 years (IQR 40-53), were included. They had been receiving ART for a median of 5.1 (IQR 2.9-9.3) years and had a median CD4 cell count of 665 (IQR 543-829) cells/mm3. The ongoing regimen included PI/r in 29 cases and NNRTI in 71 cases. At 48 weeks, 96% of participants (95% CI 90%-98%) had no failure while remaining on the 4-days-a-week regimen. Virological failure occurred in three participants, who all resumed daily treatment and became resuppressed. One participant stopped the strategy. No severe treatment-related events occurred., Conclusions: Antiretroviral maintenance therapy 4 days a week was effective for 48 weeks in 96% of patients, leading to potential reduction of long-term toxicities, high adherence to the antiretroviral regimen and drug cost saving.

Purpose: To describe, in patients treated for infectious keratitis, the microorganisms identified and their antibiotic susceptibility over a period of 18 months., Method: Retrospective, descriptive, non-comparative study. Medical and biological data were extracted from the patients' file treated with strengthened antibiotic eye drops at Angers University Hospital between January 2015 and June 2016. The main elements noted were the bacteria involved and their susceptibility to antibiotics. Patients' visual acuity at the start and end of treatment was compared., Results: Forty-eight patients were included. Almost one bacterium was identified in 31 patients, totalling 43 pathogens of 24 different species. The most frequently found microorganisms were Gram-positive cocci (55.8%), including Staphylococcus Aureus (14.0%) and Epidermidis (14.0%). All Gram-negative bacilli amounted to 30.2% of the identified bacteria, including 9.3% of Pseudomonas aeruginosa. None of the Gram-positive cocci were resistant to vancomycin and all Gram-negative bacilli were susceptible to ceftazidime and amikacin. Following treatment with at least one of the three antibiotic eye drops produced by our pharmacy (amikacin at 50mg/mL, ceftazidime at 50mg/mL and vancomycin at 25mg/mL), patients' visual acuity was significantly improved (P=0.043)., Conclusion: The study helped identify the bacterial ecology of patients admitted for infectious keratitis. Among the bacteria identified, none were found to be resistant to any of the three strengthened antibiotic eye drops produced by the hospital pharmacy. These eye drops allowed for a rapid and effective treatment of patients and the improvement of their visual acuity before even identifying the bacteria., (Copyright © 2017 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012., Methods: Affected individuals were identified from a national register of hereditary eye diseases at the National Eye Clinic (NEC), a tertiary low vision rehabilitation center for the entire Danish population. The assembling of LHON pedigrees was based on the reconstruction of published families and newly diagnosed cases from 1980 to 2012 identified in the files of NEC. Genealogic follow-up on the maternal ancestry of all affected individuals was performed to identify a possible relation to an already known maternal line. A full genotypic characterization of the nation-based LHON cohort is provided., Results: Forty different lines were identified. The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population., Conclusions: Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines.

Background: Standard first-line antiretroviral therapy for HIV-1 infection includes two nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs), but these drugs have limitations. We assessed the 96 week efficacy and safety of an NtRTI-sparing regimen., Methods: Between August, 2010, and September, 2011, we enrolled treatment-naive adults into this randomised, open-label, non-inferiority trial in treatment-naive adults in 15 European countries. The composite primary outcome was change to randomised treatment before week 32 because of insufficient virological response, no virological response by week 32, HIV-1 RNA concentration 50 copies per mL or higher at any time after week 32; death from any cause; any new or recurrent AIDS event; or any serious non-AIDS event. Patients were randomised in a 1:1 ratio to receive oral treatment with 400 mg raltegravir twice daily plus 800 mg darunavir and 100 mg ritonavir once daily (NtRTI-sparing regimen) or tenofovir-emtricitabine in a 245 mg and 200 mg fixed-dose combination once daily, plus 800 mg darunavir and 100 mg ritonavir once daily (standard regimen). This trial was registered with ClinicalTrials.gov, number NCT01066962., Findings: Of 805 patients enrolled, 401 received the NtRTI-sparing regimen and 404 the standard regimen, with median follow-up of 123 weeks (IQR 112-133). Treatment failure was seen in 77 (19%) in the NtRTI-sparing group and 61 (15%) in the standard group. Kaplan-Meier estimated proportions of treatment failure by week 96 were 17·8% and 13·8%, respectively (difference 4·0%, 95% CI -0·8 to 8·8). The frequency of serious or treatment-modifying adverse events were similar (10·2 vs 8·3 per 100 person-years and 3·9 vs 4·2 per 100 person-years, respectively)., Interpretation: Our NtRTI-sparing regimen was non-inferior to standard treatment and represents a treatment option for patients with CD4 cell counts higher than 200 cells per μL., Funding: European Union Sixth Framework Programme, Inserm-ANRS, Gilead Sciences, Janssen Pharmaceuticals, Merck Laboratories., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: NEAT001/ANRS143 was an open-label, randomized, non-inferiority study comparing raltegravir+darunavir/r(RGV+DRV/r) vs. tenofovir/emtricitabine+darunavir/r (TDF/FTC+DRV/r) in HIV-infected antiretroviral naïve adults. Primary efficacy outcome was a composite of virological and clinical events by week 96., Materials and Methods: Clinical trial units collected and translated supporting documentation (SD) related to the investigator-reported events. A coordinator checked events and SD for consistency and completeness. The Endpoint Review Committee (ERC) determined if clinical events met pre-defined diagnostic criteria in categories "confirmed" or "probable". The ERC of 12 experienced, independent clinicians served in groups of three conducting individual reviews in writing, blinded to treatment arm. Differences of opinion were adjudicated in a second review by direct dialogue between reviewers. "Confirmed" events required adequate SD like laboratory, radiographic or pathology diagnostic reports. "Probable" events were typically based on clinical criteria., Results: Of the 164 serious and 3,964 adverse events reported in the study, 133 qualified for endpoint review, for a total of 153 adjudications:, Conclusions: Blinded endpoint review prevented unacceptably high false positive event rates documenting that real-time ascertainment of clinical endpoints is crucial for appropriateness of the overall results. Non-confirmed events jeopardize the statistical power in this and probably all kinds of clinical studies. The rejection rate was not indicative of poor study conduct - on the contrary over-reporting prevented missing events, which would have adversely impacted the trial. Adequacy of SD and investigator training on possible differences in event criteria in daily pragmatic clinical management compared to protocol defined criteria is essential.

Social inequalities in health remain a major problem in France despite recent efforts to improve access to prevention and care. In France, the reduction of inequalities involves many actors, including the Instances régionales d'education et de promotion de la santé (IREPS, the Regional Authorities for Health Education and Promotion). This paper focuses on health education for deaf and hard of hearing youth. The educational team responsible for providing health education among this population has highlighted the dangers of internet use among deaf and hard of hearing youth. The overall objective is to "promote the critical and responsible use of the Internet", focusing in particular on social and technical skills. The project is a long-term intervention based on the active involvement of the educational team and the participating youth. Another objective of the project is to enable participants to contribute to online resources. This has involved using QR codes to create digital resources. The study found high levels of satisfaction among all the participants. These findings provide further evidence of the importance of providing health education to deaf and hard of hearing people.

Energy conservation of the scattering from one-dimensional strongly rough dielectric surfaces is investigated using the Kirchhoff approximation with single reflection and by taking the shadowing phenomenon into account, both in reflection and transmission. In addition, because no shadowing function in transmission exists in the literature, this function is presented here in detail. The model is reduced to the high-frequency limit (or geometric optics). The energy conservation criterion is investigated versus the incidence angle, the permittivity of the lower medium, and the surface rms slope.

Based on sequencing data and results obtained from applying a tailored mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, we report that the G allele of the mitochondrial DNA (mtDNA) polymorphism at nucleotide position 11719 is associated with the European mtDNA haplogroup cluster HV, and that 11719A is therefore the ancestral allele.

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

The Eskimo-Aleut language phylum is distributed from coastal Siberia across Alaska and Canada to Greenland and is well distinguished from the neighboring Na Dene languages. Genetically, however, the distinction between Na Dene and Eskimo-Aleut speakers is less clear. In order to improve the genetic characterization of Eskimos in general and Greenlanders in particular, we have sequenced hypervariable segment I (HVS-I) of the mitochondrial DNA (mtDNA) control region and typed relevant RFLP sites in the mtDNA of 82 Eskimos from Greenland. A comparison of our data with published sequences demonstrates major mtDNA types shared between Na Dene and Eskimo, indicating a common Beringian history within the Holocene. We further confirm the presence of an Eskimo-specific mtDNA subgroup characterized by nucleotide position 16265G within mtDNA group A2. This subgroup is found in all Eskimo groups analyzed so far and is estimated to have originated <3,000 years ago. A founder analysis of all Eskimo and Chukchi A2 types indicates that the Siberian and Greenland ancestral mtDNA pools separated around the time when the Neo-Eskimo culture emerged. The Greenland mtDNA types are a subset of the Alaskan mtDNA variation: they lack the groups D2 and D3 found in Siberia and Alaska and are exclusively A2 but at the same time lack the A2 root type. The data are in agreement with the view that the present Greenland Eskimos essentially descend from Alaskan Neo-Eskimos. European mtDNA types are absent in our Eskimo sample.

An analytical approach of the two-dimensional emissivity of a rough sea surface in the infrared band is presented. The emissivity characterizes the intrinsic radiation of the sea surface. Because the temperature measured by the infrared camera depends on the emissivity, the emissivity is a relevant parameter for retrieving the sea-surface temperature from remotely sensed radiometric measurements, such as from satellites. This theory is developed from the first-order geometrical-optics approximation and is based on recent research. The typical approach assumes that the slope in the upwind direction is greater than the slope in the crosswind direction, involving the use of a one-dimensional shadowing function with the observed surface assumed to be infinite. We introduce the two-dimensional shadowing function and the surface observation length parameters that are included in the modeling of the two-dimensional emissivity.