Evaluation of a Novel Protocol for Assessment and Treatment of Alcohol Withdrawal Syndrome in Psychiatric Inpatients.

BACKGROUND AND OBJECTIVES: Despite the high incidence of alcohol withdrawal syndrome (AWS) in psychiatric inpatients, standardized methods for assessing and treating AWS have been studied only once before in this population. We evaluated a novel AWS assessment and treatment protocol designed for psychiatric inpatients. METHODS: This retrospective cohort study evaluated outcomes before and after implementation of the protocol. We collected consecutive data on patients (N = 138) admitted to inpatient psychiatric units at a single center. Participants were patients admitted for nonsubstance-related psychiatric reasons, who were also at risk for developing AWS. Those who developed AWS were treated with either (a) treatment as usual (TAU) or (b) a novel standardized protocol. The primary outcome was duration of benzodiazepine treatment for symptoms of alcohol withdrawal. Secondary outcomes included cumulative benzodiazepine dose administered, treatment duration, and incidence of complications. RESULTS: Of 138 participants, 83 received TAU and 55 were assessed and treated with the novel protocol. Median duration of benzodiazepine treatment following protocol implementation was 19.7 hours (interquartile range [IQR], 0-46) prior to implementation (TAU) and 0 hours (IQR, 0-15) following protocol implementation (protocol group) (P < .0001). Median benzodiazepine dose (in diazepam equivalents) administered to participants was 30 mg (IQR, 0-65) for TAU and 5 mg (IQR, 0-30) for the protocol group (P < .001). Adverse events before and after implementation occurred in 4.8% and 0%, respectively (P = .15). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: This study provides preliminary evidence for the efficacy and safety of a novel standardized AWS protocol for psychiatric inpatients. This is the first known study assessing an AWS assessment and treatment protocol designed for psychiatric inpatients. (Am J Addict 2020;29:500-507).

Helicobacter pylori increases proteasome-mediated degradation of p27(kip1) in gastric epithelial cells.

Helicobacter pylori infection is associated with increased gastric epithelial cell turnover and is a risk factor for noncardia gastric cancer. H. pylori reduces the expression of p27 protein, a cyclin-dependent kinase inhibitor of the G(1) to S-phase cell cycle transition and gastric tumor suppressor gene. Although cell cycle dysregulation associated with decreased p27 may contribute to gastric carcinogenesis, how H. pylori reduces p27 in gastric epithelial cells remains unknown. In the present study, we investigated the mechanisms of the p27 decrease, using AGS and MKN28 gastric epithelial cells cocultured with H. pylori strains under conditions of defined cell cycle distribution. The expression of p27 protein was reduced by H. pylori in a dose- and time-dependent manner. Northern blot and pulse-chase analyses revealed that this reduction was not regulated at a transcriptional level but by accelerated p27 degradation via a proteasome-dependent pathway. Despite up-regulation of the proteasome-dependent degradation of p27 protein, neither threonine 187-phosphorylated p27 nor skp2 (the ubiquitin ligase for p27) were increased. Furthermore, H. pylori impaired p27 ubiquitination and did not increase global proteasomal function. These results indicate that H. pylori increases the degradation of p27 through a proteasomal pathway distinct from the physiological pathway that degrades p27 during cell cycle progression. Putative virulence genes of H. pylori (cagA, cagE, or vacA) played no role in reducing p27 expression. Increased degradation of p27 by H. pylori through a proteasome-dependent, ubiquitin-independent pathway may contribute to the increased risk of gastric cancer associated with chronic H. pylori infection.