Predictors of abstinence maintenance after cocaine inpatient detoxification: A prospective study.

BACKGROUND AND OBJECTIVES: Cocaine is a highly addictive substance, and with no approved medication for cocaine use disorder (CUD), leading to a heavy burden. Despite validated psychosocial treatments, relapse rates after detoxification are very high in CUD. Few consistent factors can predict abstinence after detoxification. Our study, therefore, aimed at identifying factors predicting abstinence among CUD patients after inpatient detoxification. METHODS: Eighty-one CUD inpatients were included during detoxification and characterized for clinical and sociodemographic data at baseline and at a follow-up of 3 months after discharge, including a standard measure of their abstinence duration from cocaine. We performed Cox univariate analyzes to determine the factors associated with abstinence maintenance, followed by a multivariate Cox regression to identify independent predictors. RESULTS: Abstinence maintenance was shorter in patients injecting cocaine (hazard ratio [HR] = 5.16, 95% confidence interval [CI]: 2.01-13.27, p < .001) and using cocaine heavily in the month before inclusion (HR = 1.03, 95% CI: 1.00-1.06, p = .046). Conversely, abstinence maintenance was longer in patients with longer inpatient detoxification stays (HR = 0.96, 95% CI: 0.94-0.99, p = .015) and prescribed with selective serotonin reuptake inhibitors (SSRIs) (HR = 0.30, 95% CI: 0.16-0.56, p < .001). DISCUSSION AND CONCLUSIONS: Patients with severe CUD may require longer inpatient stays to achieve abstinence. Regarding SSRI prescription, more specific studies are needed to provide stronger recommendations about their use in clinical practice. SCIENTIFIC SIGNIFICANCE: Our findings suggest several modifiable factors to improve inpatient treatment response in CUD. As there are no specific recommendations about the optimal duration of inpatient stay, our results could pave the way for evidence-based guidelines.

Plasma tau, NfL, GFAP and UCHL1 as candidate biomarkers of alcohol withdrawal-associated brain damage: A pilot study.

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) levels were higher in the presence of signs of Wernicke's encephalopathy (n = 9). In the preclinical study, NfL and GFAP levels were assessed in the alcohol deprivation effect (ADE) procedure (N = 17) and control Wistar rats (N = 15). Furthermore, ADE rats were prospectively assessed: after 24 h (T1) and 3 weeks of AC (T2) (paired-samples Wilcoxon and Mann-Whitney tests). The NfL level was higher in the ADE model than in the control rats at both T1 and T2 (p = 0.033 and p = 1.3 × 10-3 ) and higher at T2 than at T1 (p = 0.040). Plasma tau, NfL and UCHL1 are potential biomarkers of brain suffering during alcohol withdrawal.

Cerebrospinal Fluid Biomarkers in Patients With Alcohol Use Disorder and Persistent Cognitive Impairment.

BACKGROUND: The prevalence of cognitive impairment is high among alcohol-dependent patients. Although the clinical presentation of alcohol-related cognitive disorder (ARCD) may resemble that of Alzheimer's disease (AD), the prognosis and treatment of the 2 diseases are different. Cerebrospinal fluid (CSF) biomarkers (tau, phosphorylated tau, and amyloid ß) have high diagnostic accuracy in AD and are currently being used to discriminate between psychiatric disorders and AD, but are not used to diagnose ARCD. The aim of this study was to characterize CSF biomarkers in a homogeneous, cognitively impaired alcohol-dependent population. METHODS: This single-center study was conducted in an addiction medicine department of a Parisian Hospital. We selected patients with documented persistent cognitive impairment whose MoCA (Montreal Cognitive Assessment) score was below 24/30 after at least 1 month of documented inpatient abstinence from alcohol. We measured the CSF biomarkers (tau, phosphorylated tau, and amyloid ß 1-42 and 1-40) in 73 highly impaired alcohol-dependent patients (Alcohol Use Disorders Identification Test score over 11 for women and 12 for men) with. RESULTS: Patients' average age was 60 ± 9.1 years and 45 (61.6%) had a normal CSF profile, 8 (11.0%) had a typical CSF AD profile, and 20 (27.4%) had an intermediate CSF profile. CONCLUSIONS: This study revealed a high prevalence of AD in alcohol-dependent patients with persistent cognitive deficits and several anomalies in their CSF profiles. Thus, it is important to consider AD in the differential diagnosis of persistent cognitive deficits in patients with alcohol dependence and to use CSF biomarkers in addition to imaging and neuropsychological testing to evaluate alcohol-related cognitive impairment.

Brain 18FDG-PET pattern in patients with alcohol-related cognitive impairment.

PURPOSE: Brain positron emission tomography using 18F-fluorodeoxyglucose (18FDG-PET) provides a metabolic assessment of brain function that is useful for differential diagnosis among several neurodegenerative diseases manifested by cognitive impairment (CI). The purpose of the study is to describe the pattern of 18FDG-PET abnormalities in patients with CI related to alcohol use disorder. METHODS: Patients admitted to the addiction medicine department of a university hospital in Paris between January 2017 and October 2018 with a confirmed diagnosis of alcohol-related cognitive impairment (ARCI) or Wernicke encephalopathy (WE) were included. Brain 18FDG-PET uptake was measured after at least 1 month of monitored abstinence from alcohol. Standardized uptake values were obtained for 13 regions of interest (ROI) and normalized to the pons. Individual patients' ROI Z-scores were calculated from healthy sex- and age-matched controls provided by Cortex ID software. RESULTS: Twenty-five patients were included in the analysis (20 males and 5 females; mean age 57.6 years (45-76 years old)). The group consisted of 19 ARCI and 6 WE cases. The mean hypometabolism was most severe in the prefrontal medial cortex (PFM) (- 2.80 (± 1.30)), the prefrontal lateral cortex (- 2.20 (± 1.35)), and the anterior cingulate cortex (- 2.24 (± 1.19)). Hypometabolism (Z-score < - 2) was most frequent in the PFM (72.0% of the sample, N = 18). Other regions were also affected (with 5.32/13 hypometabolic ROIs on average (SD = 4.16, range 0-13)). The Z-scores in the 13 ROIs did not differ significantly between the ARCI and WE patients (p ≥ 0.05). CONCLUSIONS: Predominant prefrontal and cingulate cortex hypometabolism was the most frequent brain 18FDG-PET pattern in our sample of patients with ARCI and WE.

[Temporary approval for intranasal naloxone: Setting up in a French addiction center]. / Pratique de l'ATU de cohorte de la naloxone intranasale (Nalscue®) : mise en place dans un CSAPA parisien.

Intranasal naloxone aims at preventing opioid overdose related deaths in active drug users. In France, it has been available since July 2016 through a temporary approval which requires a hospital-based pharmacy and a nominative registration of each patient. We present the characteristics of the first patients who could receive this prescription in our hospital-based addiction center and how they used naloxone during follow-up. Results favor a larger dispensing of naloxone. Patients' as well as peers' and families' education is needed.

Hospital Stay and Engagement in Outpatient Follow-Up After Alcohol Emergency Detox: A 1-Year Comparison Study.

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 ± 16 vs. 14 ± 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 ± 6 vs. 4.5 ± 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.

Brain alterations in Cocaine Use Disorder: Does the route of use matter and does it relate to the treatment outcome?

AIMS: Cocaine Use Disorder (CUD) is an important health issue, associated with structural brain abnormalities. However, the impact of the route of administration and their predictive value for relapse remain unknown. METHODS: We conducted an anatomical MRI study in 55 CUD patients (26 CUD-Crack and 29 CUD-Hydro) entering inpatient detoxification, and 38 matched healthy controls. In patients, a 3-months outpatient follow-up was carried out to specify the treatment outcome status (relapser when cocaine was consumed once or more during the past month). A Voxel-Based Morphometry approach was used. RESULTS: Compared with controls, CUD patients had widespread gray matter alterations, mostly in frontal and temporal cortices, but also in the cerebellum and several sub-cortical structures. We then compared CUD-Crack with CUD-Hydro patients and found that crack-cocaine use was associated with lower volume in the right inferior and middle temporal gyri, and the right fusiform gyrus. Cerebellar vermis was smaller during detoxification in subsequent relapsers compared to three-months abstainers. CONCLUSIONS: Patients with CUD display widespread cortical and subcortical brain shrinkage. Patients with preferential crack-cocaine use and subsequent relapsers showed specific gray matter volume deficits, suggesting that different patterns of cocaine use and different clinical outcome are associated with different brain macrostructure.

Hospitalized cocaine detoxification patients in Paris, France: Increased patient levels and changing population characteristics since 2011.

AIM OF THE STUDY: The past twenty years have seen a rise in cocaine-related statistics in France, including cocaine use in the general population, emergency ward presentations of acute cocaine intoxication, cocaine use disorders related outpatient appointments and cocaine-related deaths. This study's objectives were to describe trends in patients' admission for specific cocaine detoxification as well as changes in patients' characteristics in the Assistance publique-Hôpitaux de Paris (AP-HP) hospitals group located in Paris region, France. METHODS: We reviewed the international classification of diseases 10th edition (ICD-10) discharge codes of the AP-HP hospitals group between 2011 and 2021. In addition, medical reports of the largest addiction medicine ward were also analysed for changes across the years 2009, 2014, 2019 and 2022. RESULTS: The regional database showed an almost 3-fold increase in cocaine-related disorders discharge codes between 2011 and 2019. This occurred due to a rise in hospital stays for cocaine dependence or cocaine acute intoxication prior to the fall in levels of inpatient stays associated with the coronavirus disease 2019 (COVID-19) pandemic. The in-depth analysis of inpatients' stays in the specialized addiction medicine ward also showed an increase in admissions for cocaine detoxification programs, with a prevalence of 1.19% in 2009 to 15.73% in 2022 (P=1.44×10-20). Inpatient characteristics showed significant changes, especially in 2022, namely: more daily users, less intravenous administration and less comorbid illicit substances use disorders, with heightened levels of cured hepatitis C patients (P<0.05). Inpatient prescriptions were primarily dopaminergic antagonists with sedatives properties (cyamemazine, loxapine and chlorpromazine), dopamine-receptors partial agonist (aripiprazole) and serotonin reuptake inhibitors. CONCLUSION: The referral to hospital care for cocaine detoxification has increased in Paris region since 2011, coupled with changes in inpatients' characteristics. This trend has significant implications for the management of inpatient hospital services.

Biomarkers of Relapse in Cocaine Use Disorder: A Narrative Review.

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 to predict abstinence. CONCLUSION: Several biomarkers have been shown to have predictive value. Prospective studies using combined multimodal assessments are now warranted.

Patients With Severe Alcohol-Related Cognitive Impairment Improve in Flexibility When Abstinence Is Maintained: A Comparative Study With Alzheimer's Disease.

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 occurred at 12.8 (± 2.9) months (p < 10-3), the mean age was 72.3 (± 8.4) years (p < 10-3), and 10 were men. ARCI patients significantly improved on one executive function test (TMT-B; p < 0.05), while AD patients have worsened memory subtests on Free-and-Cued-Selective-Reminding Test (p < 0.05). These tests showed a statistically different change between severe ARCI and AD group (p < 0.05). Severe ARCI patients have improved in executive functioning, discernible on the TMT-B test, in specific care setting, including abstinence maintenance and rehabilitation. The disease progression was different from that observed in AD patients.

Brainstem responses can predict death and delirium in sedated patients in intensive care unit.

OBJECTIVES: In critically ill patients, the assessment of neurologic function can be difficult because of the use of sedative agents. It is not known whether neurologic signs observed under sedation can predict short-term outcomes. The objective of this study was to assess whether abnormal brainstem responses within the first 24 hrs of sedation are associated with mortality and altered mental status postsedation. DESIGN: Observational prospective study including an initial single-center and a subsequent multicenter study to develop and then validate the prognostic models. SETTING: Three mixed and two medical intensive care units. PATIENTS: Mechanically ventilated intensive care unit patients sedated with midazolam (± sufentanyl). INTERVENTIONS: Neurologic examination including the Glasgow Coma Scale, the Assessment to Intensive Care Environment score, cranial nerve examination, response to noxious stimuli, and the cough reflex was performed. MEASUREMENTS AND MAIN RESULTS: Seventy-two patients were included in the initial group and 72 in a subsequent validation study. Neurologic responses were independent of sedative dose. Twenty-two patients in the development cohort and 21 (29%) in the validation group died within 28 days of inclusion. Adjusted for Simplified Acute Physiology Score II score, absent cough reflex was independently associated with 28-day mortality in the development (adjusted odds ratio [OR], 7.80; 95% confidence interval [CI], 2.00-30.4; p = .003) and validation groups (adjusted OR, 5.44; 95% CI, 1.35-22.0; p = .017). Absent oculocephalic response, adjusted for Simplified Acute Physiology Score II score, was independently associated with altered mental status after the withdrawal of sedation in the development (adjusted OR, 4.54; 95% CI, 1.34-15.4; p = .015) and validation groups (adjusted OR, 6.10; 95% CI, 1.18-25.5; p = .012). CONCLUSIONS: Assessment of brainstem responses is feasible in sedated critically ill patients and loss of selected responses is predictive of mortality and altered mental status.

Clinical Trials of Cannabidiol for Substance Use Disorders: Outcome Measures, Surrogate Endpoints, and Biomarkers.

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. Furthermore, 12 excluded studies in cannabis, tobacco, and opioid use disorders are described. Interpretation: Primary outcomes were validated withdrawal symptoms scales and drug use reduction in the three RCTs. In the short-term or crossover studies, the outcome measures were visual analog scales for subjective states; self-rated scales for withdrawal, craving, anxiety, or psychotomimetic symptoms; and laboratory tasks of drug-induced craving, effort expenditure, attentional bias for substance, impulsivity, or anxiety to serve as surrogate endpoints for treatment efficacy. Of note, ongoing studies are now adding peripheral biomarkers of the endocannabinoid system status to predict treatment response. Conclusion: The outcome measures and biomarkers assessed in the ongoing CBD trials for substance use disorders are improving.

BNP worsens 12 days after alcohol cessation while other cardiovascular risk biomarkers improve: An observational study.

Subjects with alcohol use disorder (AUD) display a high prevalence of cardiovascular risk factors (CRFs), and 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 inpatients 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 at day 12, BNP and other CRFs: hemodynamic and electromyographic variables, lipid, homocysteine level, and liver enzymes at entry and at 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 60 g-750 g, 44 current tobacco smokers). BNP was significantly increased (11.8 pg/mL [±16.2] to 35.5 pg/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 was confirmed. However, the increase of BNP at day 12 supports its investigation as a possible relevant biomarker of cardiac function in alcohol withdrawal.

Ascorbic Acid Deficiency Prevalence and Associated Cognitive Impairment in Alcohol Detoxification Inpatients: A Pilot Study.

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 was available for 53 patients (mean MoCA score: 25.7 (±3.3)). In multivariate analysis, the natural logarithm of AA (ß = 1.18, p = 0.037) and sedative use disorder (ß = -2.77, p = 0.046) were associated with the MoCA score. AAD and AAI are frequent in inpatients admitted for alcohol detoxification. A low level of AA was associated with cognitive impairment in the early period of abstinence.

COVID-19 in adults with dementia: clinical features and risk factors of mortality-a clinical cohort study on 125 patients.

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 was 22.4%. Chronic kidney disease and CRP at admission were independent factors of death. Persisting confusion, mood and behavioural disorders were observed in survivors (19.2%). CONCLUSION: COVID-19 in demented individuals is associated with severe outcome in SARS-CoV-2 infection and is characterised by specific clinical features and complications, with confusion and delirium at the forefront. COVID-19 testing should be considered in front of any significant change from baseline.

COVID-19 in Older Adults: A Series of 76 Patients Aged 85 Years and Older with COVID-19.

BACKGROUND: Clinical presentation and risk factors of death in COVID-19 in oldest adults have not been well characterized. OBJECTIVES: To describe clinical features and outcome of COVID-19 in patients older than 85 years and study risk factors for mortality. DESIGN: Prospective cohort. PARTICIPANTS AND SETTING: Patients 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. MEASUREMENTS: Clinical and laboratory findings were collected. Cox survival analysis was performed to explore factors associated with death. RESULTS: From 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 initial fall was reported in 25.0% of cases, and digestive symptoms were reported in 22.4% of cases. COVID-19 was severe in 51.3% of cases, moderate in 32.9%, and mild in 15.8%. Complications included acute respiratory syndrome (28.9%), cardiac decompensation (14.5%), and hypotensive shock (9.0%). Fatality at 21 days was 28.9%, after a median course of disease of 13 (8-17) days. Males were overrepresented in nonsurvivors (68.2%). In survivors, median length of stay was 12 (9-19.5) days. Independent predictive factors of death were C-reactive protein level at admission and lymphocyte count at nadir. CONCLUSION: Specific clinical features, multiorgan injury, and high case fatality rate are observed in older adults with COVID-19. However, rapid diagnosis, appropriate care, and monitoring seem to improve prognosis.

An observational study of benzodiazepine prescription during inpatient alcohol detoxification for patients with vs. without chronic pretreatment with high-dosage baclofen.

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 vs. without steady-state pretreatment 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 vs. 310 ± 133 mg (t-test = 0.440, P = 0.661) in matched controls. Steady-state high-dose baclofen before an inpatient alcohol cessation hospitalization does not lower the needed benzodiazepine dose in the management of alcohol withdrawal symptoms.

Population pharmacokinetics of oral baclofen at steady-state in alcoholic-dependent adult patients.

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 determine mean values for clearance (CL/F), volume of distribution (V/F) and absorption rate constant at 8.0 L/h, 44.5 L and 2.23 h-1 , respectively. Inter-individual variability on CL/F and V/F was 27.4 and 86% for the parameters. None of the demographic and biological covariates significantly decreased inter-individual variability. A proportional relationship between oral dose and plasma baclofen exposure indicated a linear pharmacokinetics of baclofen even at doses over 120 mg/day. Our large population study evidenced a linear pharmacokinetics of oral baclofen even at high daily doses with an inter-individual variability of baclofen exposure that could not be explained by demographic and biological data.

Distribution of Cerebrospinal Fluid Biomarker Profiles in Patients Explored for Cognitive Disorders.

BACKGROUND: CSF Alzheimer's disease (AD) biomarkers allow classifying individuals based on their levels of amyloid and neurodegeneration pathologies. OBJECTIVE: To investigate the distribution of AD biomarker profiles from patients suffering from cognitive disorders. METHODS: 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. RESULTS: 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 observed more frequently in men and the distribution was stable across age and MMSE. The SNAP profile showed no association with gender or age, was less frequent in patients with lower MMSE, and had a lower repartition than the one previously reported in asymptomatic populations. CONCLUSIONS: While A+/N+ patients had the clinical characteristics typically observed in AD, A+/N-patients had a different epidemiological pattern (higher frequency in men, no association with advanced age or lower MMSE). The SNAP profile was less frequent than previously reported in the general elderly population, suggesting that this profile is not a frequent cause of memory impairment in this population.