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Abstract Background Acne vulgaris has increased in women over the past 10 years; it currently affects 20–30% of women. The physiopathology of adult female acne is distinguished from that of teenagers essentially by two factors: hormonal and inflammatory. On a therapeutic plan, the four types of systemic treatment approved for female acne include cyclines (leading to bacterial resistance); zinc salts (less effective than cyclines); and antiandrogens (risks of phlebitis). The last alternative is represented by isotretinoin, but its use in women of childbearing potential is discouraged because of the teratogen risks. In this context, spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at the sebaceous gland and inhibits luteinizing hormone (LH) production at the pituitary level. It has no isotretinoin constraints and does not lead to bacterial resistance. Currently, very few studies have been performed in a limited number of patients: the studies showed that at low doses (lower than 200 mg/day), spironolactone can be effective against acne. In that context, it is clearly of interest to perform the first double-blind randomized study of spironolactone versus cyclines, which remains the moderate acne reference treatment, and to demonstrate the superiority of spironolactone’s efficacy in order to establish it as an alternative to cyclines. Methods Two hundred female patients will be included. They must have acne vulgaris with at least 10 inflammatory lesions and no more than 3 nodules. After randomization, the patients will be treated by spironolactone or doxycycline for 3 months and after placebo. The study will be blind for the first 6 months and open for the last 6 months. Discussion The treatment frequently used in female acne is systemic antibiotics with many courses, as it is a chronic inflammatory disease. In the context of the recent World Health Organisation (WHO) revelation about the serious, worldwide threat to public health of antibiotic resistance, this trial could give the physician another alternative in the treatment of adult female acne instead of using isotretinoin, which is more complex to manage. Trial registration ClinicalTrials.gov: NCT03334682 . Registered on 7 November 2017.

Abstract Background Depression is a debilitating and costly disease for our society, especially in the case of treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy in treatment-resistant unipolar and non-psychotic depression. It can be applied according to two therapeutic strategies after an initial rTMS cure: a further rTMS cure can be performed at the first sign of relapse or recurrence, or systematic maintenance rTMS (M-rTMS) can be proposed. TMS adjuvant to treatment as usual (TAU) could improve long-term prognosis. However, no controlled study has yet compared the cost-effectiveness of these two additional rTMS therapeutic strategies versus TAU alone. Methods/design This paper focuses on the design of a health-economic, prospective, randomized, double-blind, multicenter study with three parallel arms carried out in France. This study assesses the cost-effectiveness of the adjunctive and maintenance low frequency rTMS on the right dorsolateral prefrontal cortex versus TAU alone. A total of 318 patients suffering from a current TRD will be enrolled. The primary endpoint is to investigate the incremental cost-effectiveness ratio (ICER) (ratio costs / quality-adjusted life-years [QALY] measured by the Euroqol Five Dimension Questionnaire) over 12 months in a population of patients assigned to one of three arms: systematic M-rTMS for responders (arm A); additional new rTMS cure in case of mood deterioration among responders (arm B); and a placebo arm (arm C) in which responders are allocated in two subgroups: sham systematic M-rTMS and supplementary rTMS course in case of mood deterioration. ICER and QALYs will be compared between arm A or B versus arm C. The secondary endpoints in each three arms will be: ICER at 24 months; the cost-utility ratio analysis at 12 and 24 months; 5-year budget impact analysis; and prognosis factors of rTMS. The following criteria will be compared between arm A or B and arm C: rates of responders; remission and disease-free survival; clinical evolution; tolerance; observance; treatment modifications; hospitalization; suicide attempts; work stoppage; marital / professional statues; and quality of life at 12 and 24 months. Discussion The purpose of our study is to check the cost-effectiveness of rTMS and we will discuss its economic impact over time. In the case of significant decrease in the depression costs and expenditures associated with a good long-term prognosis (sustained response and remission) and tolerance, rTMS could be considered as an efficient treatment within the armamentarium for resistant unipolar depression. Trial registration ClinicalTrials.gov, NCT03701724 . Registered on 10 October 2018. Protocol Amendment Version 2.0 accepted on 29 June 2019.

Abstract Background Whether they are injected peri- or intraocularly, corticosteroids are still essential tools in the therapeutic arsenal for treating inflammatory macular oedema. A few years ago, however, only triamcinolone acetonide was available to ophthalmologists. While this compound was initially developed for rheumatological or dermatological use, it has been increasingly deployed in ophthalmology, despite still being off-label. In 2011, the system for delivery of dexamethasone from a biodegradable, injectable implant into the vitreous cavity obtained approval for use in inflammatory macular oedema. While the efficacy and safety of triamcinolone in macular oedema, including inflammatory oedema, have already been studied, there are currently no publications on subconjunctival triamcinolone injections, which are simple, effective and well tolerated. To date, the dexamethasone 700 μg implant has been authorized for the treatment of noninfectious intermediate and posterior uveitis, but there have been no studies to evaluate the efficacy and safety of the different peri- and intraocular strategies, including the treatment of inflammatory macular oedema. Methods This protocol is therefore designed to compare the efficacy and safety of peri- and intraocular corticosteroid injections in the treatment of inflammatory macular oedema. In this ongoing study, 142 patients will be included, and the oedematous eye will be randomised to treatment with either subconjunctival triamcinolone injection or an intravitreal implant containing 700 μg dexamethasone. Follow-up is planned for 6 months with monthly visits. Each visit will include visual acuity measurement, a slit lamp examination, fundoscopy, intraocular pressure measurement, laser flare measurement (if available) and spectral domain optical coherence tomography. Discussion The results of this trial will have a real impact on public health if it is shown that a Kenacort retard® (i.e. triamcinolone) injection costing just €2.84 and performed in the physician’s office (with no additional overhead costs) is at least as effective as the dexamethasone 700 μg implant (Ozurdex®; costing approximately €960 with the injection performed in a dedicated room), with no increased side effects. Trial registration ClinicalTrials.gov, NCT02556424. Registered on 22 September 2015.

BackgroundDeprescribing benzodiazepines and related drugs (BZDR) is a challenge due to a lack of time on physicians’ part, a lack of involvement of other health professionals, and the need for adapted tools. This study is based on primary care collaboration, by evaluating the effectiveness of a joint intervention between general practitioners and community pharmacists on the implementation of BZDR deprescribing in older adults.MethodsThis is a cluster randomized controlled trial in which each cluster will be formed by a physician-pharmacist pair. Within a cluster allocated to the intervention, the pharmacist will be trained in motivational interviewing (MI), and will offer the patient 3 interviews after inclusion by the physician. They will base their intervention on validated deprescribing guidelines. The pharmacist will receive methodological support during the first interviews. Interprofessional collaboration will be encouraged by writing reports for the physician after each interview. The following implementation outcomes will be evaluated: acceptability/adoption, appropriateness, cost, and fidelity. They will be measured by means of sociological interviews, observations, logbooks, and cost-utility analysis. Focus groups with physicians and pharmacists will be carried out to identify levers and barriers experienced in this collaboration. Observations will be conducted with pharmacists to assess their approach of the MIs. Effectiveness outcomes will be based on medication (discontinuation or reduction of BZDR) and clinical outcomes (such as quality of life, insomnia or anxiety), assessed by health insurance databases and validated questionnaires.DiscussionThis study will determine whether collaboration in primary care between physicians and pharmacists, as well as training and coaching of pharmacists in motivational interviewing, allows the implementation of BZDR deprescribing in the older adults.This study will provide an understanding of the processes used to implement deprescribing guidelines, and the contribution of collaborative practice in implementing BZDR discontinuation. The cluster methodology will allow to assess the experience of the relationship between the different primary care actors, and the related obstacles and levers.The results obtained will make it possible to produce guidelines on the involvement of community pharmacists in the management of substance abuse in older adults, or even to legislate new missions or care pathways.Clinical trial registrationClinicalTrials.gov, identifier, NCT05765656.

ObjectivesTo investigate the potential impact of the syndromic multiplex FilmArray® Pneumonia plus Panel (FAPP) on the antimicrobial treatment guidance of patients with ventilated hospital-acquired pneumonia (VHAP).MethodsRespiratory fluids from 100 adult patients with VHAP, receiving invasive mechanical ventilation in three intensive care units from one French university hospital, were tested prospectively using FAPP. Conventional cultures were performed in parallel as routine practice. Clinicians were left blinded to the FAPP results. Antimicrobial therapies based on FAPP results were simulated by independent blinded experts according to a predefined algorithm and compared to 1) those prescribed in practice according to local guidelines (real-life), and 2) those that complied with the international ERS/ESICM/ESCMID/ALAT recommendations. The primary endpoint was the number of days of broad-spectrum antimicrobial therapy. Secondary endpoints were the rates of microbiological treatment failure and cost-effectiveness ratio.ResultsThe predicted median duration of broad-spectrum antibiotics was 0 [0-1.25] day in the FAPP-based simulation, versus 2 [0-6] days in real-life (p

Abstract Background Threatened preterm delivery (TPD) is the leading cause of inpatient admissions during pregnancy. The ability to predict the risk of imminent preterm delivery is thus a major priority in obstetrics. The aim of our study is to assess the diagnostic performance of the test to detect the placental alpha microglobulin 1 (PAMG-1) for the prediction of delivery within 7 days in women with TPD. Methods This is a prospective multicenter diagnostic study. Inclusion criteria are singleton pregnancy, gestational age between 24 + 0 and 33 + 6 weeks inclusive, cervical measurement 25 mm or less assessed by transvaginal ultrasound (with or without uterine contractions), clinically intact membranes and cervical dilatation

Introduction Depression is among the most widespread psychiatric disorders in France. Psychiatric disorders are associated with considerable social costs, amounting to €22.6 billion for treatment and psychotropic medication in 2011. Treatment as usual (TAU), mainly consisting of pharmacotherapy and psychotherapy, is effective for only a third of patients and in most cases fails to prevent treatment resistance and chronicity. Transcranial direct current stimulation (tDCS) consists in a non-invasive and painless application of low-intensity electric current to the cerebral cortex through the scalp. Having proved effective in depressed patients, it could be used in combination with TAU to great advantage. The objective is to compare, for the first time ever, the cost-utility of tDCS-TAU and of TAU alone for the treatment of a depressive episode that has been refractory to one or two drug treatments.Methods and analysis This paper, based on the DISCO study protocol, focuses on the design of a prospective, randomised, controlled, open-label multicentre economic study to be conducted in France. It will include 214 patients with unipolar or bipolar depression, assigning them to two parallel arms: group A (tDCS-TAU) and group B (TAU alone). The primary outcome is the incremental cost-effectiveness ratio, that is, the ratio of the difference in cost between each strategy to the difference in their effects. Their effects will be expressed as numbers of quality-adjusted life-years, determined through administration of the EuroQol Five-Dimension questionnaire over a 12-month period to patients (EQ-5D-5L). Expected benefits are the reduction of treatment resistance and suicidal ideation as well as social and professional costs of depression. Should depression-related costs fall significantly, tDCS might be considered an efficient treatment for depression.Ethics and dissemination This protocol has been approved by a French ethics committee, the CPP-–Est IV (Comité de Protection des Personnes–Strasbourg). Data are to be published in peer-reviewed medical journals.Trial registration number RCB 2018-A00474-51; NCT03758105