Etampes

Infections due to Pseudomonas aeruginosa isolates with acquired resistances to all first-line antipseudomonal beta-lactams and fluoroquinolones (difficult-to-treat isolates - DTR), pose serious therapeutical challenges, especially in critically ill and/or immunocompromised patients. Certain new beta-lactam/beta-lactamase inhibitor combinations (BL/BLI (beta lactamine/ beta lactamase inhibitor) - i.e., ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, others) and cefiderocol have shown promising results for the treatment of infections due to DTR P. aeruginosa. However, multicenter data on their real-life utilization in this indication are still scarce. The ADDICT study is a prospective, multicenter cohort study including unselected patients with DTR P. aeruginosa infection requiring definite intravenous antimicrobial therapy. The primary objective of the study is to investigate the clinical efficacy of available options (new BL/BLI, cefiderocol or older agents such as aminoglycosides and colistin) in this population. Secondary objectives are to compare the clinical and microbiological efficacy of available options in infections due to DTR P. aeruginosa with in vitro susceptibility to more than one last-resort drug, to compare the incidence of non-ecological adverse events observed with these drugs, to assess the incidence of resistance emergence under therapy and to elucidate the molecular mechanisms of resistance emergence, to assess the benefits and risks of combination therapy in this indication, to compare the acquisition rates of multidrug-resistant bacteria other than DTR P. aeruginosa, and Clostridioides difficile infection, to compare Day-28 and in-hospital all-cause mortality rates. Patients will be recruited in 60 hospital centers contributing to four French networks of research in infectious diseases and critical care (CRICS-TRIGGERSEP, ReaRezo, OutcomeRéa, RENARCI - PROMISE metanetwork). Clinical variables will be collected through an electronic case-report form. DTR P. aeruginosa isolates will be sent to the National Reference Center of Antimicrobial Resistance in P. aeruginosa for centralized analyses (extended antimicrobial susceptibility testing, MLST, whole-genome sequencing of successive isolates if resistance emergence under therapy).

The study will be a prospective multicentre, randomized, open-label comparative continuous vs. intermittent pivotal βL antibiotic infusion strategies and combination vs. monotherapy trial conducted with a 2X2 factorial design. Patients will be randomized to one of four of the following treatment groups in a 1:1:1:1 ratio. Randomization will be stratified on the centre and the initial βL administered (meropenem versus other) to receive (i) βL antibiotic either as a continuous infusion: CID group or as intermittent infusion: IID group, and (ii) either at most 1 dose (short duration) : AMT group or 5 days (long duration) : ACT group of aminoglycoside * Arm A: continuous infusion dosing of a pivotal βL-AB (Antibiotics) (CID group) AND AG (Aminoglycoside) infusion for 5 days (long duration) as appropriate combination therapy (ACT group) * Arm B: intermittent infusion dosing of a pivotal βL-AB (IID = control group) AND AG infusion for 5 days (long duration) as appropriate combination therapy (ACT = group) * Arm C: continuous infusion dosing of a pivotal βL-AB (CID group) AND AG infusion at most 1 dose (AMT group) * Arm D: intermittent infusion dosing of a pivotal βL-AB (IID = group) AND AG infusion at most 1 dose (AMT group) The primary objective of the study is to compare the 30-day mortality of patients with hospital-acquired sepsis in the ICU according to the mode of administration of the pivotal βL antibiotic (CID group vs. IID group). The primary endpoint is the mortality rate at day 30 between CID and IID groups while the Co-primary objective is to compare the MAKE 30 (Major Adverse Kidney Events within 30 days) between patients that will receive an appropriate monotherapy with βL (AMT group) or an appropriate combination therapy with βL and 5 days of AG (ACT group). moreover, The co-primary criterion is the percentage of patients with a MAKE 30, i.e. when patients met one of the following criteria within day 30: in-hospital mortality, receipt of renal replacement therapy (RRT) or persistent renal dysfunction (discharge serum creatinine/baseline serum creatinine ≥200%) between AMT and ACT groups.

Unipolar major depressive disorder is the leading cause of disability worldwide. The most commonly used treatments for major depressive episodes (MDE) are antidepressant medications. However, they have limited efficacy and their onset of action is long, ranging between 2 to 6 weeks. During this period, hospitalization can become necessary, especially for severe MDE. It is crucial to improve the early effectiveness of treatments for these patients in order to alleviate their suffering, limit complications (suicidal risk), and reduce hospitalization durations (approximately 1000 euros per day). The efficacy of intravenous ketamine has been demonstrated in pharmaco-resistant depression but remains to be proven in non-pharmaco-resistant severe MDE. Additionally, PET imaging using \[11C\]UCB-J, which allows the in vivo study of synaptic density in the human brain, has shown significant decreases in synaptic density in unipolar patients with severe MDE. Furthermore, a single ketamine infusion was found to enhance synaptogenesis

The NUTRIREA-4 trial will test the hypothesis that an individually tailored rehabilitation program combining nutritional therapy, physiotherapy, and physical activity and started early in the ICU then continued uninterruptedly throughout the post-ICU stay and at home after hospital discharge improves the long-term outcomes of critical-illness survivors, compared to usual care. From ICU admission to recovery at home, the trial patients will receive either usual care or the early extended rehabilitation program. Usual care will consist in nutritional support and physiotherapy according to usual local practice in each participating ICU. The early extended program will consist of nutritional therapy, physiotherapy, and physical activity according to a standardized protocol tailored to general- and muscle-health improvements achieved in each individual patient over time.

The smoking rate among people with mental disorders is higher than in the general population. Greater exposure to the harmful effects of tobacco partly explains the major inequality in life expectancy observed among people with mental disorders who, depending on the disorder and the study, live 10 to 20 years less than the general population, a gap mainly due to the occurrence of cardiovascular and respiratory pathologies, notably bronchial cancers. While studies found that people under psychiatric care are as motivated as others to stop smoking, the literature also shows that psychiatric care systems tolerate, underestimate and even encourage smoking among users, despite the fact that psychiatric care, whether at hospital or in an ambulatory setting, is conducive to changes in smoking behaviour and to the implementation of a smoking cessation approach, notably because of anti-smoking regulations in hospitals. In addition, withdrawal symptoms is stronger in this population and smoking cessation would therefore need to be adapted. Against this backdrop, a smoking cessation intervention ('Tabapsy') was co-constructed with the various stakeholders (users with mental disorders, mental health professionals and general practitioners). Its aim is to encourage and support smoking cessation among people with mental disorders followed in ambulatory psychiatry by medical psychological centers (CMP). It consists of two parts: a campaign to promote smoking cessation within the CMP, and the setting up of an intervention to help people stop smoking. The latter comprises of: 1. A general information meeting, to encourage motivation to start smoking cessation; 2. An assessment workshop, to evaluate level of dependence using validated tests and establish a personalized cessation program based on the results obtained; 3. Five thematic workshops to support cessation, covering 1/ nicotine replacement treatments, electronic cigarettes and other drug treatments available for smoking cessation, 2/ emotional management, 3/ weight gain, 4/ physical activities, and 5/ manual occupations; 4. Peer support groups, based on the sharing of experiences, to encourage mutual aid and solidarity between people with mental disorders who are trying to quit smoking. The intervention also relies on a facilitator specifically recruited to set up the intervention and run the various workshops in the CMP. It is complemented by a website that will contain all the resources and information presented during the meetings/workshops. The primary objective of the study is to evaluate the effectiveness of the "Tabapsy" intervention on short-term smoking cessation (cessation for at least 7 days) at 3 months among regular smokers followed by adult psychiatric CMPs. Secondary objectives include assessing its cost-effectiveness and implementation. A cluster-randomized controlled trial will be carried out to evaluate the intervention. The cluster is the "psychiatric sector", i.e., the public care entity responsible for organizing the mental health care of a population within a pre-specified geographical area (including hospital and ambulatory care) in France. A psychiatric sector may include one or multiple CMPs depending on the size of the population it serves. Psychiatric sectors will be randomized into one of two groups (intervention or usual practice). It will be supplemented by a qualitative study to study the implementation of the intervention. All regular smokers (at least one cigarette a day) who agree to participate will be asked to complete questionnaires on a WebApp at inclusion, and again at 3 and 6 months. Additional questionnaires will be available in the intervention group. Questions will focus on user characteristics, tobacco consumption, level of nicotine dependence, motivation to quit, use of cessation aids, level of mental and physical well-being, smoking-related knowledge and representations, and in the intervention group, participation in the intervention and satisfaction. 6,250 participants will be included over 12 months, in 22 participating sectors.

Community-acquired pneumonia (CAP) that is of sufficient severity to require admission to an intensive care unit (ICU) is associated with substantial mortality. Patients with pneumonia who are being treated in an ICU will receive therapy that consists of many different treatments, as many as 20 or 30. These treatments act together to treat both the infection and its effects on the body. When treating a patient, doctors choose from many different treatments, most of which are known or believed to be safe and effective. However, doctors don't always know which treatment option is the better one, as individuals or groups of individuals may respond differently. This study aims to help doctors understand which treatments work best. This clinical study has been designed in a way that allows the information from patients already in the study to help new patients joining the study. Most studies aren't able to do that. REMAP-CAP has been designed to: * Evaluate multiple treatment strategies, at the same time, in the same patient. * Reach platform conclusions when sufficient data is accrued, rather than when a pre-specified sample size is reached * Utilise data that is already accrued to increase the likelihood that patients within the trial are randomised to treatments that are more likely to be beneficial * New questions can be substituted into the trial as initial questions are answered, meaning that the trial can be perpetual or open-ended * Interactions between interventions in different domains can be evaluated It is reasonable to presume that any pandemic respiratory infection of major significance to public health will manifest as life-threatening respiratory infection including Severe Acute Respiratory illness and severe Community Acquired Pneumonia (CAP) with concomitant admission to hospital, and for some patients, admission to an Intensive Care Unit (ICU). Previous pandemics and more localized outbreaks of respiratory emerging infections have resulted in severe CAP and ICU admission. Previous pandemics and outbreaks of emerging infectious diseases have outlined the urgent need for evidence, preferably from Randomized Controlled Trials (RCTs), to guide best treatment. However, there are substantial challenges associated with being able to organize such trials when the time of onset of a pandemic and its exact nature are unpredictable. As an adaptive platform trial that enrolls patients during the interpandemic period, REMAP-CAP is ideally positioned to adapt, in the event of a respiratory pandemic, to evaluate existing treatments as well as novel approaches.

Context Alcohol use disorders (AUDs) are reported in 10-32% of hospitalized medical patients \[Nielsen et al. 1994; Smothers et al. 2004; Dolman and Hawkes 2005; Doering-Silveira et al. 2014\], in 23 % of hospitalized medical patients and in 25-50% of hospitalized psychiatric patients in France \[Paille \& Reynaud 2015\]. A hospital admission may result in an abrupt cessation of alcohol consumption for individuals with AUD and thus provide a risk period for alcohol withdrawal syndrome. Even though the majority of patients at risk of AWS will develop only minor or uncomplicated withdrawal symptoms, up to 20% of patients develop symptoms associated with complicated alcohol withdrawal, including withdrawal seizures and delirium tremens \[Maldonado et al., 2010\]. Complicated alcohol withdrawal syndrome is associated with increased in-hospital morbidity and mortality, increased lengths of stay, inflated costs of care, and worsened cognitive functioning. Due to lack of any similar previously existing tools, Maldonado et al. developed the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) \[Maldonado et al. 2014, 2015\]. The PAWSS scale has excellent psychometric characteristics and predictive value of complicated alcohol withdrawal among medically ill hospitalized patients using a PAWSS cutoff of 4, the tool's sensitivity was 93.1% and specificity was 99.5%. The PAWSS scale is recommended by the American Society of Addiction Medicine for alcohol withdrawal management, (ASAM 2020, www.asam.org). There is no scale available to identify the patients at risk of complicated withdrawal In France. The PAWSS is not a withdrawal severity scale such as the CIWA-AR or Cushman scale, which are scored during withdrawal, but a scale designed to screen beforehand, prior to withdrawal, patients at high risk for the most severe complications (Delirium tremens and seizures), and thus to take appropriate therapeutic measures. It also has the advantage of being able to guide patients towards the most suitable scheduled withdrawal modalities for their condition. The PAWSS can therefore greatly assist clinicians in directing patients to either outpatient or hospital withdrawal in more or less intensive care, with a minimum of risk. Its use would allow earlier management to limit the sequelae, especially cognitive and those related to seizures. The PAWSS scale includes an initial screener question and can be used with patients who are not currently exhibiting signs of withdrawal. If a patient does indeed endorse recent intake of alcohol, this must be followed by 10 questions contained in the second part of PAWSS, assessing known risk factors for withdrawal and current clinical status. The PAWSS is heavily based on self-report of alcohol intake and history provided by patients, as the literature suggests that interviews by clinicians can provide the most accurate information on alcohol abuse and relapse, as compared to collateral information or selected laboratory data. Objectives The primary objective is to validate the French version of the PAWSS scale (PRSAC) in a population of patients with AUD. The secondary objectives are 1) to confirm the optimal cut-off score of 4 for the PRSAC scale, 2) to evaluate PRSAC scale reproducibility in predicting the risk of complicated alcohol withdrawal syndrome and 3) to identify an optimal strategy for benzodiazepine use following the application of PRSAC scale. Hypothesis Are the psychometric properties of the French version of the PAWSS scale (PRSAC) comparable to those of the English version in a population of alcohol use disorders subjects? Methods This study is a multicentric non-interventional prospective cohort study. Subject evaluation included during 3 days. Day 1: Collection of consent and clinical data, DSM-5 criterion for alcohol use disorders, AUDIT, PRSAC scale (twice by two investigators), and CIWA-AR scale every 8 hours. Day 2 and Day 3: administration of CIWA-AR scale every 8 hours. Inclusion criteria Male or female, aged 18 to 60 years Subjects with DSM-5 criteria for moderate to severe alcohol use disorders (AUD) Subjects hospitalized for AUD or another condition with AUD. Subjects who understand French and affiliated to the social security system Non-inclusion criteria Subject with a neurological disorder, impairing cognition (epilepsy, dementia,…) Subjects unable to understand the questionnaire and to give consent or not volunteering for the study Subject under guardianship or curatorship Study location Academic substance abuse treatment and Psychiatry departments of: Barthélemy Durand Hospital at Etampes, France Paul Brousse hospital in Villejuif, France Rouen university hospital, France Caen university hospital, France Martinique university hospital, France Results \& Outcome Confirmation of the psychometric qualities of the French version of the PAWSS scale.