Julien Azuar - Academia.edu (original) (raw)

Papers by Julien Azuar

Addiction Biology

In this translational study, we investigated the plasma tau protein, neurofilament light chain (N... more In this translational study, we investigated the plasma tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and ubiquitin carboxy‐terminal hydrolase L1 (UCHL1), which are established biomarkers of neurological injury, as predictive biomarkers of alcohol withdrawal‐associated brain toxicity. In the clinical study, patients with severe alcohol use disorder (AUD) on D1 of hospitalization for alcohol cessation (AC) (N = 36) were compared to severe AUD patients with at least 3 months of abstinence (N = 16). Overall, patients were 40 men (76.9%), aged 49.8 years [SD ±9.9]. Tau, NfL, GFAP and UCHL1 levels were measured using SIMOA and analysed with a quasipoisson regression model adjusted for age and sex. The NfL level was higher in the AC group (p = 0.013). In the AC group, the tau (p = 0.021) and UCHL1 (p = 0.021) levels were positively associated with the dose of diazepam per weight, and the tau (p = 0.045), NfL (p = 4.9 × 10−3) and UCHL1 (p = 0.036) lev...

Brain Sciences

Introduction: Cocaine use disorder is a chronic disease with severe consequences and a high relap... more Introduction: Cocaine use disorder is a chronic disease with severe consequences and a high relapse rate. There is a critical need to explore the factors influencing relapse in order to achieve more efficient treatment outcomes. Furthermore, there is a great need for easy-to-measure, repeatable, and valid biomarkers that can predict treatment response or relapse. Methods: We reviewed the available literature on the Pubmed database concerning the biomarkers associated with relapse in CUD, including central nervous system-derived, genetic, immune, oxidative stress, and “other” biomarkers. Results: Fifty-one articles were included in our analysis. Twenty-five imaging brain anatomic and function assessment studies, mostly using fMRI, examined the role of several structures such as the striatum activity in abstinence prediction. There were fewer studies assessing the use of neuropsychological factors, neurotrophins, or genetic/genomic factors, immune system, or oxidative stress measures ...

Frontiers in Psychiatry

Background: Cannabidiol (CBD) is a cannabinoid of potential interest for the treatment of substan... more Background: Cannabidiol (CBD) is a cannabinoid of potential interest for the treatment of substance use disorders. Our aim was to review the outcome measures, surrogate endpoints, and biomarkers in published and ongoing randomized clinical trials.Methods: We conducted a search in PubMed, Web of Science, PMC, PsycINFO, EMBASE, CENTRAL Cochrane Library, “clinicalTrials.gov,” “clinicaltrialsregister.eu,” and “anzctr.org.au” for published and ongoing studies. Inclusion criteria were randomized clinical trials (RCTs) examining the use of CBD alone or in association with other cannabinoids, in all substance use disorders. The included studies were analyzed in detail and their qualities assessed by a standardized tool (CONSORT 2010). A short description of excluded studies, consisting in controlled short-term or single administration in non-treatment-seeking drug users, is provided.Findings: The screening retrieved 207 published studies, including only 3 RCTs in cannabis use disorder. Furt...

Frontiers in Psychology

The disease progression of severe alcohol-related cognitive impairment (ARCI) is debated. The aim... more The disease progression of severe alcohol-related cognitive impairment (ARCI) is debated. The aim of this study was to compare the cognitive change of patients with severe ARCI in inpatient setting to that of patients with Alzheimer’s disease (AD). Fifteen consecutive patients with severe ARCI were recruited between 2013 and 2015. They received inpatient detoxification, neurological assessment, and inpatient cognitive rehabilitation in specialized facilities. Twelve patients, with documented AD matched on sex and initial cognitive impairment severity, were selected. All have benefited from two neuropsychological assessments. The neurocognitive change was tested in both groups with pair-wised Wilcoxon tests. ARCI and AD patients’ time course was compared with Mann–Whitney–Wilcoxon test. In ARCI group, first assessment occurred at 2.9 (± 2.2) months of abstinence and follow-up 6.5 (± 2.9) months later, the mean age was 56.5 (± 7.4) years, and 12 were men. In AD group, follow-up occurr...

Elsevier Masson, Apr 11, 2018

Antioxidants, 2021

Malnutrition has been reported in alcohol use disorder patients as having a possible influence on... more Malnutrition has been reported in alcohol use disorder patients as having a possible influence on cognitive function. The aim of this study was to analyse the prevalence of ascorbic acid (AA) deficiency in inpatients admitted for alcohol detoxification and the associated factors, including cognitive impairment in the early period of abstinence. A retrospective chart review was conducted. The AA level was categorised into three groups: deficiency (AAD) (<2 mg/L), insufficiency (AAI) (2–5 mg/L) and normal level. The cognitive impairment was screened using the Montreal Cognitive Assessment (MoCA). Ninety-six patients were included (74 men; mean age 49.1 years (±11.5)). Twenty-seven AAD (28.1%) and twenty-two AAI (22.9%) were observed. In multivariate analysis, risk factors for AAD versus normal AA level were men (OR 17.8, 95%CI (1.63–194)), compensated cirrhosis (OR 9.35, 95%CI (1.60–54.6)) and street homelessness (OR 5.76, 95%CI (1.24–26.8) versus personal housing). The MoCA score ...

Hors urgence somatique, l’hospitalisation est rarement proposee au patient alcoolodependant admis... more Hors urgence somatique, l’hospitalisation est rarement proposee au patient alcoolodependant admis aux urgences, au motif qu’un sevrage en alcool doit etre motive et travaille en amont. Dans cette etude retrospective, il n’existe pas difference significative dans l’adhesion au suivi addictologique (represente par le nombre de consultations honorees sur l’annee suivant la sortie) entre 2 groupes de 60 patients, le premier recrute par les urgences, le second en hospitalisation programmee. Les patients du premier groupe sont significativement plus âges, ont plus de comorbidites somatiques, ont moins souvent un emploi et necessitent un sejour plus long. Les facteurs predictifs de leur venue a au moins 1 consultation sont le sexe feminin, le fait d’avoir un domicile et un medecin traitant declare. Ceux predictifs de leur venue a au moins 5 consultations sont une alcoolodependance plus recente et l’existence d’un suivi addictologique anterieur. Ni la demande de sevrage en urgence, ni le fa...

Alzheimer's Research & Therapy, 2021

Background There is limited evidence on the characteristics and outcome of patients with dementia... more Background There is limited evidence on the characteristics and outcome of patients with dementia hospitalised for novel coronavirus infection (COVID-19). Method We conducted a prospective study in 2 gerontologic COVID units in Paris, France, from March 14, 2020, to May 7, 2020. Patients with dementia hospitalised for confirmed COVID-19 infection were systematically enrolled. A binary logistic regression analysis was performed to identify factors associated with mortality at 21 days. Results We included 125 patients. Median age was 86 (IQI 82–90); 59.4% were female. Most common causes of dementia were Alzheimer’s disease, mixed dementia and vascular dementia. 67.2% had ≥ 2 comorbidities; 40.2% lived in a long-term care facility. The most common symptoms at COVID-19 onset were confusion and delirium (82.4%), asthenia (76.8%) and fever (72.8%) before polypnea (51.2%) and desaturation (50.4%). Falls were frequent at the initial phase of the disease (35.2%). The fatality rate at 21 days...

Journal of the American Geriatrics Society, 2020

BACKGROUNDClinical presentation and risk factors of death in COVID‐19 in oldest adults have not b... more BACKGROUNDClinical presentation and risk factors of death in COVID‐19 in oldest adults have not been well characterized.OBJECTIVESTo describe clinical features and outcome of COVID‐19 in patients older than 85 years and study risk factors for mortality.DESIGNProspective cohort.PARTICIPANTS AND SETTINGPatients aged 85 years and older, admitted in noncritical care units at the University Hospital Lariboisière Fernand‐Widal (Paris, France) for confirmed severe acute respiratory syndrome coronavirus 2 infection were included and followed up for 21 days.MEASUREMENTSClinical and laboratory findings were collected. Cox survival analysis was performed to explore factors associated with death.RESULTSFrom March 14 to April 11, 2020, 76 patients (median age = 90 (86–92) years; women = 55.3%) were admitted for confirmed COVID‐19. Of the patients, 64.5% presented with three or more comorbidities. Most common symptoms were asthenia (76.3%), fever (75.0%) and confusion and delirium (71.1%). An ini...

La Revue de Médecine Interne, 2021

The management of alcohol withdrawal syndrome is a frequent work in both community medicine and h... more The management of alcohol withdrawal syndrome is a frequent work in both community medicine and hospital wards. One of the most severe complications of alcohol withdrawal is Delirium Tremens (DT). The purpose of this development is to update knowledge on this complication in terms of diagnosis, evaluation and therapeutic approaches. It also proposes a reflection on the trajectory of care during and after DT.

Alcohol, 2021

Subjects with alcohol use disorder (AUD) display a high prevalence of cardiovascular risk factors... more Subjects with alcohol use disorder (AUD) display a high prevalence of cardiovascular risk factors (CRFs), a high incidence of cardiovascular diseases associated with an earlier mortality. Abstinence has long-term cardiovascular and global health benefits. However, few studies have examined the short-term effect of alcohol cessation on cardiac function and key CRFs. The aim of the study was to assess brain natriuretic peptide (BNP) and other CRFs on admission for alcohol cessation and 12 days later, in inpatient with AUD. A retrospective chart review of inpatients hospitalized for alcohol cessation was conducted. Patients who did not relapse at day-12 were included. We compared, at entry and day-12, BNP and other CRFs: hemodynamic and electromyographic variables, lipid, homocysteine level and liver enzymes at entry and day-12. Wilcoxon, Student tests and repeated measures ANOVA were conducted. Fifty-five patients were included (38 males, mean age 50.5 years, alcohol per day 60g to 750g, 44 current tobacco smokers). BNP was significantly increased (11.8pg/mL [±16.2] to 35.5pg/mL [±47.6], p<0.001). Repeated measure ANOVA showed a significant between-subject effect (p=0.024) but no significant interaction between BNP variation and having a BNP at entry > 10 pg/mL (p=0.092). In contrast, a significant improvement on 8 of 13 other CRFs and liver enzymes measures was observed (p≤0.05). A rapid improvement of several CRFs is confirmed. However the increase of BNP at day 12 supports its investigation as a possible relevant biomarker of cardiac function in alcohol withdrawal.

French Journal of Psychiatry, 2019

Rationnel La cocaine est la deuxieme drogue illicite la plus utilisee en France et en Europe, mai... more Rationnel La cocaine est la deuxieme drogue illicite la plus utilisee en France et en Europe, mais il n’existe pas de traitement de substitution, et la majorite des patients rechutent apres un sevrage. Il n’existe pas de marqueurs predictifs de la reussite du sevrage qui puissent etre mesures a l’entree. Parmi les facteurs cognitifs qui influencent la rechute dans les addictions, on compte notamment le biais attentionnel vers la substance, c’est-a-dire la tendance a faire plus attention aux stimuli lies a la substance [1] , [2] . On compte egalement la flexibilite cognitive, c’est-a-dire la capacite a changer de comportement pour s’adapter aux changements de l’environnement [3] . Objectif Nous avons voulu tester la valeur predictive de deux mesures cognitives, le biais attentionnel vers la cocaine et la flexibilite cognitive, dans le maintien d’abstinence de cocaine apres sevrage. Methodes Sujets des patients (n = 52) hospitalises pour un sevrage de cocaine a l’hopital Fernand-Widal (Paris) ont participe a cette etude. Design de l’etude Dans les 48 heures suivant l’entree en hospitalisation, nous avons mesure le biais attentionnel par une tâche de Stroop adaptee a la cocaine, et la flexibilite cognitive par une tâche de renversement d’apprentissage. Les patients ont ensuite ete suivis de facon prospective dans les 3 mois suivant la sortie. Analyse statistique Pour le Stroop, exprime comme un ralentissement du temps de reponse des patients lors de l’exposition a des indices rappelant la cocaine, l’association avec la duree d’abstinence sera testee par une correlation de Spearman. Pour le renversement d’apprentissage, exprime par une probabilite de changement immediat de strategie apres un feedback negatif, l’association avec la duree d’abstinence sera testee par une correlation de Spearman. Resultats attendus Sur les 52 sujets evalues a l’entree en sevrage, 38 ont ete suivi prospectivement jusqu’au bout des trois mois, et le temps moyen d’abstinence apres la sortie etait de 28 ± 32 jours. Les resultats des tâches cognitives seront discutes en fonction de la litterature.

Revue d'Épidémiologie et de Santé Publique, 2018

Background.-General practitioners (GPs) are fully concerned with the care of patients suffering f... more Background.-General practitioners (GPs) are fully concerned with the care of patients suffering from addiction and must have the support of a specialized network. The aim of the study was to evaluate the prevalence of the addict follow-up care by GPs, their use of addictological care facilities and their needs in communicating with specialists. Methods.-Private and salaried GPs working in the 9th, 10th, 18th and 19th districts of Paris were contacted by phone, and a questionnaire was sent to those who agreed to respond. Results.-One hundred and thirty-eight GPs responded (median age 57 years, 38.4% women, 54% in private practice). In total, 78.9% received at least one patient weekly for alcohol dependence, 38.1% received at least one patient monthly for opiates and 40.2% for cannabis. They managed ambulatory alcohol (46.8%) and tobacco (65.0%) withdrawal schemes. Among GPs, 86.1% worked with the support of an addictological care facility structure, 69.6% reported lack of specialists for at least one product and 75.4% for at least one specific situation. Conclusion.-The majority of GPs in north Paris providing care for patients with substance use disorder, worked with addictological care facilities structures. However, they noticed a lack of specialists with whom to communicate. Optimizations are proposed to facilitate interaction.

Revue d'Épidémiologie et de Santé Publique, 2019

Aim.-Cannabis use, as well as the prevalence of cannabis use disorder, are not known among the po... more Aim.-Cannabis use, as well as the prevalence of cannabis use disorder, are not known among the population attending general practices in France. We wanted to describe the characteristics of current cannabis users, estimate cannabis use disorder and self-rating of cannabis dependence, and describe medical conditions associated with cannabis use in a general practice in Paris. Methods.-An anonymous questionnaire was proposed to every patient aged 18-65 in a general practice during three months from June to August 2014. Cannabis use in the last six months was recorded and cannabis use disorder was assessed according to three different means: answering yes to the question: do you feel like you are dependent on cannabis? or answering yes to the question: do you smoke cannabis in the first 5 minutes after awakening? or CUDIT score ! 8 points. Results.-Two hundred and fifty-eight questionnaires were analyzed. Cannabis use in the past six months was found in 54 subjects (21%). Subjective feeling of cannabis dependence was endorsed by 18 subjects (6.9%). Cannabis use in the first 5 minutes after awakening was found in five subjects (1.9%) and 23 (8.9%) had a CUDIT score ! 8 points. Cannabis smokers had more often addictive and psychiatric associated medical conditions. Conclusion.-General practitioners could ask about cannabis use and self-rated cannabis use disorder because it is frequent and patients with cannabis use disorder deserve specific care.

Journal of Alzheimer's disease : JAD, Jan 23, 2018

CSF Alzheimer's disease (AD) biomarkers allow classifying individuals based on their levels o... more CSF Alzheimer's disease (AD) biomarkers allow classifying individuals based on their levels of amyloid and neurodegeneration pathologies. To investigate the distribution of AD biomarker profiles from patients suffering from cognitive disorders. We analyzed 3001 patients with cognitive disorders and referred by 18 French memory clinics located in and around Paris. Patients were classified as normal, amyloidosis (A+/N-), amyloidosis and neurodegeneration (A+/N+) or suspected non-AD pathophysiology (SNAP), according to their CSF levels of biomarkers. Analysis were performed for the overall population and stratified by gender, age quintiles, and Mini-Mental State Examination (MMSE) score quintiles. Results were compared to previous findings in cohorts of healthy elderly adults. 37% of the sample were classified as A+/N+, 22% were classified A+/N-, and 15% as SNAP. The A+/N+ profile was associated with female gender, advanced age, and lower MMSE score, while the A+/N-profile was obse...

Fundamental & clinical pharmacology, 2017

Baclofen has been proposed for few years to help treating alcohol dependence at higher doses than... more Baclofen has been proposed for few years to help treating alcohol dependence at higher doses than those used in neurology. Baclofen pharmacokinetics has been previously well described at low oral or intravenous doses but remains poorly investigated with such high oral doses. We here describe dose regimens of baclofen in 143 alcohol-dependent patients treated with steady-state oral doses of baclofen. Plasma baclofen levels were measured in blood samples using liquid chromatography coupled with tandem mass spectrometry. One hundred and forty-nine baclofen concentrations were sampled 30 min to 15 h after the last dose, and baclofen pharmacokinetics was determined using population pharmacokinetics approach. Our population, whose average age and BMI were 51.5 years and 25.5 kg/m2 , respectively, was composed of two-thirds of men. Daily baclofen doses ranged from 15 to 250 mg and 26% were higher than 120 mg. A one-compartment model with first-order absorption and elimination allowed to de...

Fundamental & clinical pharmacology, Jan 10, 2017

High dose baclofen is prescribed as a maintenance treatment to reduce alcohol use in patients wit... more High dose baclofen is prescribed as a maintenance treatment to reduce alcohol use in patients with alcohol use disorder. Nevertheless, some patients still have massive alcohol intakes and require inpatient alcohol withdrawal. to compare the oral dose of benzodiazepine prescribed to manage alcohol withdrawal symptoms in patients with versus without steady state pre-treatment with high dose baclofen. Retrospective chart review study. Prescribed benzodiazepine dose expressed in diazepam-equivalent was compared between groups. Thirty-one patients were assessed in the high dose maintenance baclofen group and compared to 31 matched patients not receiving baclofen. No statistically significant difference was evident between groups regarding levels of benzodiazepines prescribed. The mean diazepam-equivalent dose during the first 7 days was 294 ± 149 mg in the baclofen group versus 310 ± 133 mg (t test =.440, p=.661) in matched controls. steady-state high dose baclofen before an inpatient al...

Alcoholism: Clinical and Experimental Research, 2016

Background: Inpatient alcohol detoxifications are only proposed after motivational outpatient enc... more Background: Inpatient alcohol detoxifications are only proposed after motivational outpatient encounters because detoxification directly from the emergency department (ED) is believed to be associated with early dropout and poor adherence to outpatient follow-up. The aim of this prospective follow-up study was to test the feasibility of unscheduled (UP) alcohol detoxification directly from the ED and to compare the 1-year follow-up of these patients to that of scheduled (SP) patients. Methods: A quasi-naturalistic prospective follow-up study of 120 patients: 60 consecutively admitted patients referred directly by the ED for alcohol detoxification (UP) were compared to 60 consecutively admitted patients who had undergone the usual preparation for an inpatient detoxification program (SP). The length of hospitalization (in days) and attendance to postdischarge outpatient visits during the first year was compared. Results: UP patients were older, less frequently employed, and had more somatic comorbidities compared with SP patients. The UP length of stay was significantly longer (20 AE 16 vs. 14 AE 6, p = 0.04). No difference in their postdischarge attendance was observed; the number of patients attending 1 session (57% UP vs. 65% SP, p = 0.227) and 5 sessions (22% UP vs. 32% SP, p = 0.151) and the mean number of postdischarge visits attended were comparable between the UP and SP groups (2.7 AE 6 vs. 4.5 AE 6; Mann-Whitney U = 1,517, p = 0.124). Conclusions: We did not find that UP patients who had been admitted for alcohol detoxification had a significantly higher dropout rate or lower postdischarge addiction treatment attendance. Because they may have several advantages, detoxification programs directly linked with EDs should be further evaluated.

Annales françaises de médecine d'urgence, 2016