Risk factors associated with 1-week revisit among emergency department patients with alcohol withdrawal.

BACKGROUND: Approximately one-quarter of emergency department (ED) visits for alcohol withdrawal result in unscheduled 1-week ED return visits, but it is unclear what patient and clinical factors may impact this outcome METHODS: From January 1, 2015, to December 31, 2018, at three urban EDs in Vancouver, Canada, we studied patients who were discharged with a primary or secondary diagnosis of alcohol withdrawal. We performed a structured chart review to ascertain patient characteristics, ED treatments, and the outcome of an ED return within 1 week of discharge. We used univariable and multivariable Bayesian binomial regression to identify characteristics associated with being in the upper quartile of 1-week ED revisits. RESULTS: We collected 935 ED visits among 593 unique patients. Median age was 45 years (interquartile range 34 to 55 years) and 71% were male. The risk of a 1-week ED revisit was 15.0% (IQR 12.3; 19.5%). After adjustment, factors independently associated with a high risk for return included any prior ED visit within 30 days, no fixed address, initial blood alcohol level > 45 mmol/L, and initial Clinical Institute Withdrawal Assessment-alcohol revised score > 23. These factors explained 41% of the overall variance in revisits. CONCLUSION: Among discharged ED patients with alcohol withdrawal, we describe high-risk patient characteristics associated with 1-week ED revisits, and these findings may assist clinicians to facilitate appropriate discharge planning with access to integrated follow-up support.

RéSUMé: CONTEXTE: Environ un quart des visites aux urgences pour sevrage alcoolique se traduit par un retour non programmé aux urgences pendant une semaine, mais les facteurs cliniques et relatifs aux patients qui peuvent avoir une incidence sur ce résultat ne sont pas clairs. MéTHODES: Du 1er janvier 2015 au 31 décembre 2018, dans trois urgences urbaines de Vancouver, au Canada, nous avons étudié les patients qui sont sortis avec un diagnostic primaire ou secondaire de sevrage alcoolique. Nous avons procédé à une analyse structurée des dossiers afin de déterminer les caractéristiques des patients, les traitements aux urgences et l'issue d'un retour aux urgences dans la semaine suivant la sortie. Nous avons utilisé une régression binomiale bayésienne univariable et multivariable pour identifier les caractéristiques associées au fait d'être dans le quartile supérieur des visites aux urgences à une semaine. RéSULTATS: Nous avons recueilli 935 visites aux urgences parmi 593 patients uniques. L'âge médian était de 45 ans (intervalle interquartile de 34 à 55 ans) et 71 % étaient des hommes. Le risque d'une nouvelle visite aux urgences à une semaine était de 15,0% (IQR 12,3 ; 19,5%). Après ajustement, les facteurs indépendamment associés à un risque élevé de retour comprenaient toute visite antérieure à l'urgence dans les 30 jours, aucune adresse fixe, le taux d'alcoolémie initial > 45 mmol/L, et l'évaluation initiale du sevrage de l'Institut clinique ­ cote d'alcoolémie révisée > 23. Ces facteurs expliquaient 41 % de la variance globale des visites. CONCLUSIONS: Parmi les patients sortants des urgences en sevrage alcoolique, nous décrivons les caractéristiques des patients à haut risque associés à la réadmission aux urgences après une semaine de sevrage alcoolique. Ces résultats peuvent aider les cliniciens à planifier de manière appropriée la sortie de l'hôpital et à accéder à un suivi intégré.

Lorazepam Versus Diazepam in the Management of Emergency Department Patients With Alcohol Withdrawal.

STUDY OBJECTIVE: Alcohol withdrawal is a common emergency department (ED) presentation. Although benzodiazepines reduce symptoms of withdrawal, there is little ED-based evidence to assist clinicians in selecting appropriate pharmacotherapy. We compare lorazepam with diazepam for the management of alcohol withdrawal to assess 1-week ED and hospital-related outcomes. METHODS: From January 1, 2015, to December 31, 2018, at 3 urban EDs in Vancouver, Canada, we studied patients with a discharge diagnosis of alcohol withdrawal. We excluded individuals presenting with a seizure or an acute concurrent illness. We performed a structured chart review to ascertain demographics, ED treatments, and outcomes. Patients were stratified according to initial management with lorazepam versus diazepam. The primary outcome was hospital admission, and secondary outcomes included in-ED seizures and 1-week return visits for discharged patients. RESULTS: Of 1,055 patients who presented with acute alcohol withdrawal, 898 were treated with benzodiazepines. Median age was 47 years (interquartile range 37 to 56 years) and 73% were men. Baseline characteristics were similar in the 2 groups. Overall, 69 of 394 patients (17.5%) receiving lorazepam were admitted to the hospital compared with 94 of 504 patients receiving diazepam (18.7%), a difference of 1.2% (95% confidence interval -4.2% to 6.3%). Seven patients (0.7%; 95% confidence interval 0.3% to 1.4%) had an in-ED seizure, but all seizures occurred before receipt of benzodiazepines. Among patients discharged home, 1-week return visits occurred for 78 of 325 (24.0%) who received lorazepam and 94 of 410 (23.2%) who received diazepam, a difference of 0.8% (95% confidence interval -5.3% to 7.1%). CONCLUSION: In our sample of ED patients with acute alcohol withdrawal, patients receiving lorazepam had an admission rate similar to that of those receiving diazepam. The few in-ED seizures occurred before medication administration. For discharged patients, the 1-week ED return visit rate of nearly 25% could warrant enhanced follow-up and community support.

Elimination of mitochondrial DNA is not required for herpes simplex virus 1 replication.

UNLABELLED: Infection with herpes simplex virus type 1 (HSV-1) results in the rapid elimination of mitochondrial DNA (mtDNA) from host cells. It is known that a mitochondrial isoform of the viral alkaline nuclease (UL12) called UL12.5 triggers this process. However, very little is known about the impact of mtDNA depletion on viral replication or the biology of HSV-1 infections. These questions have been difficult to address because UL12.5 and UL12 are encoded by overlapping transcripts that share the same open reading frame. As a result, mutations that alter UL12.5 also affect UL12, and UL12 null mutations severely impair viral growth by interfering with the intranuclear processing of progeny viral genomes. Therefore, to specifically assess the impact of mtDNA depletion on viral replication, it is necessary to eliminate the activity of UL12.5 while preserving the nuclear functions of UL12. Previous work has shown that the human cytomegalovirus alkaline nuclease UL98 can functionally substitute for UL12 during HSV-1 replication. We found that UL98 is unable to deplete mtDNA in transfected cells and therefore generated an HSV-1 variant in which UL98 coding sequences replace the UL12/UL12.5 open reading frame. The resulting virus was severely impaired in its ability to trigger mtDNA loss but reached titers comparable to those of wild-type HSV-1 in one-step and multistep growth experiments. Together, these observations demonstrate that the elimination of mtDNA is not required for HSV-1 replication in cell culture. IMPORTANCE: Herpes simplex virus types 1 and 2 destroy the DNA of host cell mitochondria, the powerhouses of cells. Epstein-Barr virus, a distantly related herpesvirus, has a similar effect, indicating that mitochondrial DNA destruction is under positive selection and thus confers a benefit to the virus. The present work shows that mitochondrial DNA destruction is not required for efficient replication of herpes simplex virus type 1 in cultured Vero kidney epithelial cells, suggesting that this activity likely benefits the virus in other cell types or in the intact human host.