Compounds known to be successful in the treatment of alcohol use disorder include the aversive agent, Disulfiram, the glutamatergic NMDA receptor antagonist, Acamprosate, and the opioid receptor antagonists, Naltrexone and Nalmefene. Although all four are effective in maintaining abstinence or reduction of alcohol consumption, only a small percentage of patients receive pharmacological treatment. In addition, many other medications have been investigated for their therapeutic potential in the treatment of alcohol use disorder. In this review we summarize and compare Baclofen, Gabapentin, Topiramate, Ondansetron, Varenicline, Aripiprazole, Quetiapine, Clozapine, Antidepressants, Lithium, Neuropeptide Y, Neuropeptide S, Corticotropin-releasing factor antagonists, Oxytocin, PF-05190457, Memantine, Ifenprodil, Samidorphan, Ondelopran, ABT-436, SSR149415, Mifepristone, Ibudilast, Citicoline, Rimonabant, Surinabant, AM4113 and Gamma-hydroxybutyrate While some have shown promising results in the treatment of alcohol use disorder, others have disappointed and should be excluded from further investigation. Here we discuss the most promising results and highlight medications that deserve further preclinical or clinical study. Effective, patient-tailored treatment will require greater understanding provided by many more preclinical and clinical studies.

Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review

Alcohol use disorder (AUD) accounts for millions of acute care encounters annually in the United States. Hospitalization represents a vital opportunity to intervene pharmacologically, but low medication adherence is a significant barrier. Two single-dose, adherence-independent interventions are well suited for pre-discharge administration: intravenous (IV) ketamine and intramuscular (IM) naltrexone. Their feasibility and readmission-reducing efficacy in hospital settings are not well-established.A 3-arm, open-label randomized trial was conducted at our safety-net medical hospital among high-utilization inpatients with severe AUD. Consented adults (age 18-65) were randomized to (1) IV ketamine (KET) 0.5 mg/kg over 40 min, (2) IM naltrexone (NTX) 380 mg once, or (3) linkage alone (LA). The primary clinical outcome was 30-day all-cause hospital readmission rate. All were provided enhanced linkage to outpatient addiction clinic.We consented and randomized 44 participants (n = 13, 14, 17 for KET, NTX, LA, respectively), with a mean of 3.2 past-year hospitalizations. Compared to the LA arm, both the KET arm (RR 0.37, p = 0.17) and NTX arm (RR 0.52, p = 0.27) had a lower 30-day readmission rate, though the differences were nonsignificant. Immediate acceptability ratings of KET and NTX were 9.50 and 9.17 out of 10, respectively. No serious adverse events or illicit ketamine use was reported.Both interventions are feasible and showed promise in reducing readmissions for high-utilization AUD inpatients. Despite randomization, baseline characteristics may have differed in ways that biased against the control arm. Additional pragmatic studies-with larger sample size, blinding, and robust follow-up data collection-are needed to verify findings and better understand mediating factors.gov Identifier NCT04562779. Registered 24 September 2020. https://clinicaltrials.gov/ct2/show/NCT04562779. 

/pdf/single-dose-intravenous-ketamine-or-intramuscular-naltrexone-2i4elifi.pdf

Single-dose intravenous ketamine or intramuscular naltrexone for high-utilization inpatients with alcohol use disorder: pilot trial feasibility and readmission rates

RATIONALE
Investigations show that medications for alcohol use disorders (MAUD) reduce heavy drinking and relapses. However, only 1.6% of individuals with alcohol use disorders (AUD) receive MAUD across care settings. The epidemiology of MAUD prescribing in the acute care setting is incompletely described. We hypothesized that MAUD would be under prescribed in inpatient acute care hospital settings compared to the outpatient, emergency department (ED), and inpatient substance use treatment settings.


METHODS
We evaluated electronic health record (EHR) data from adult patients with an International Classification of Diseases, 10th revision (ICD-10) alcohol-related diagnosis in the University of Colorado Health (UCHealth) system between January 1, 2016 and 31 December, 2019. Data from patients with an ICD-10 diagnosis code for opioid use disorder and those receiving MAUD prior to their first alcohol-related episode were excluded. The primary outcome was prescribing of MAUD, defined by prescription of naltrexone, acamprosate, and/or disulfiram. We performed bivariate and multivariate analyses to identify independent predictors of MAUD prescribing at UCHealth.


RESULTS
We identified 48,421 unique patients with 136,205 alcohol-related encounters at UCHealth. Encounters occurred in the ED (42%), inpatient acute care (17%), inpatient substance use treatment (18%), or outpatient primary care (12%) settings. Only 2270 (5%) patients received MAUD across all settings. Female sex and addiction medicine consults positively predicted MAUD prescribing. In contrast, encounters outside inpatient substance use treatment, Hispanic ethnicity, and black or non-white race were negative predictors of MAUD prescribing. Compared to inpatient substance use treatment, inpatient acute care hospitalizations for AUD was associated with a 93% reduced odds of receiving MAUD.


CONCLUSIONS
AUD-related ED and inpatient acute care hospital encounters in our healthcare system were common. Nevertheless, prescriptions for MAUD were infrequent in this population, particularly in inpatient settings. Our findings suggest that the initiation of MAUD for patients with alcohol-related diagnoses in acute care settings deserves additional evaluation.

Medication prescribing for alcohol use disorders during alcohol-related encounters in a Colorado regional healthcare system.

(1) Antibiotics are an important weapon in the fight against serious bacterial infections and are considered a common cause of drug-induced liver injury (DILI). The hepatotoxicity of many drugs, including antibiotics, is poorly analyzed in human in vitro models. (2) A standardized assay with a human hepatoma cell line was used to test the hepatotoxicity of various concentrations (Cmax, 5× Cmax, and 10× Cmax) of antibiotics. In an ICU, the most frequently prescribed antibiotics, ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, meropenem, rifampicin, tigecycline, and vancomycin, were incubated with HepG2/C3A cells for 6 days. Cell viability (XTT assay, LDH release, and vitality), albumin synthesis, and cytochrome 1A2 activity were determined in cells. (3) In vitro, vancomycin, rifampicin, and tigecycline showed moderate hepatotoxic potential. The antibiotics ampicillin, cefepime, cefuroxime, levofloxacin, linezolid, and meropenem were associated with mild hepatotoxic reactions in test cells incubated with the testes Cmax concentration. Rifampicin and cefuroxime showed significantly negative effects on the viability of test cells. (4) Further in vitro studies and global pharmacovigilance reports should be conducted to reveal underlying mechanism of the hepatotoxic action of vancomycin, rifampicin, tigecycline, and cefuroxime, as well as the clinical relevance of these findings.

/pdf/influence-of-antibiotics-on-functionality-and-viability-of-hsu7a45s.pdf

Influence of Antibiotics on Functionality and Viability of Liver Cells In Vitro

This cohort study investigates the association of medications for alcohol use disorder initiated at hospital discharge with return to hospital or death after alcohol-related hospitalizations.

Outcomes After Initiation of Medications for Alcohol Use Disorder at Hospital Discharge

Naltrexone Initiation in the Inpatient Setting for Alcohol Use Disorder: A Systematic Review of Clinical Outcomes.

Linezolid is a frequently prescribed antibiotic for chronic infection suppression, such as in prosthetic joint infections. While well tolerated, its prolonged use can increase the risk of rare and serious side effects. We present a case of linezolid toxicity presenting with a constellation of adverse effects including bone marrow suppression, lactic acidosis, and drug-induced liver injury. Our case highlights the increased risk of acute multiorgan failure in patients using the antibiotic for extended durations, notably those with preexisting comorbidities.

Linezolid use and drug-induced liver injury.

Bloodstream infections in patients with transcatheter aortic valve replacement.

Bloodstream Infection Following Cardiac Valve Repair: A Population-Based Study

/pdf/correction-to-spiritual-care-of-inpatients-focusing-on-4nw4dop6yj.pdf

Correction to: Spiritual Care of Inpatients Focusing on Outcomes and the Role of Chaplaincy Services: A Systematic Review.

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