Mutation of a Single Amino Acide Residue in the Basic Region of the Epstein-Barr Virus (EBV) Lytic Cycle Switch Protein Zta (BZLF1) Prevents Reactivation of EBV from Latency

Zta, the product of the BZLF1 gene carried by Epstein-Barr virus (EBV), is crucial for reactivation of EBV from latency. Zta is a member of the bZIP family of transcription factors, and in common with many of these, Zta possesses a conserved cysteine residue in its basic region (C189) and a further cysteine residue in its ZIP region (C222). We demonstrate that C189 is required to reactivate EBV from latency but C222 is not and that this single amino acid affects two independent functions of Zta, (i) binding to a Zta-responsive site and (ii) manipulating the cell cycle

Risk Factors for Hospital Readmission and Death After Discharge of Older Adults from Acute Geriatric Units: Taking the Rank of Admission into Account

International audienceObjective: To analyze the impact of the number of hospital readmissions on the risks of further hospital readmission and death after adjustment for a range of risk factors. Methods: We performed a multicentre prospective study of the DAMAGE cohort in the Hauts-de-France region of France. Patients aged 75 and over hospitalized initially in an acute geriatric unit (AGU) were included and followed up for 12 months. The risk of hospital readmission was analyzed using a Cox model, and its extension for recurrent events and the risk of death were analyzed using a Cox model for time-dependent variables. Results: A total of 3081 patients were included (mean (SD) age: 86.4 (5.5)). In the multivariate analysis, the relative risk (95% confidence interval [CI]) of hospital readmission rose progressively to 2.66 (1.44; 5.14), and the risk of death rose to 2.01 (1.23; 3.32) after five hospital admissions, relative to a patient with no hospital readmissions. The number of hospital readmissions during the follow-up period was the primary risk factor and the best predictor of the risk of hospital readmission and the risk of death. Conclusion: Hospital readmission is the primary risk factor for further hospital readmissions and for death in older subjects discharged from an AGU

Transition to Comfort Care Only and End-of-Life Trajectories in an Acute Geriatric Unit: A Secondary Analysis of the DAMAGE Cohort.

International audienceOBJECTIVES: Comfort care for a dying patient increases the quality of the end of life. End-of-life situations are frequently managed in acute geriatric units (AGUs), and transition to comfort care only is often necessary. However, the frequency of transition to comfort care and the latter's putative link with the end-of-life trajectory (sudden death, cancer, organ failure, and frailty with or without dementia) have not previously been studied in acute geriatric units. We sought to (1) describe end-of-life trajectories and the transition to comfort care only, and (2) analyse the relationship between the two, prior to death in an AGU. DESIGN: A secondary analysis of a subgroup of the DAMAGE cohort (a prospective multicentre cohort of 3509 patients aged 75~years and over and admitted consecutively to an AGU). SETTING/PARTICIPANTS: DAMAGE patients who died in an AGU after a stay of at least 48~hours. METHODS: Data on the end-of-life trajectory and the transition to comfort care only were extracted from medical records. RESULTS: Of the 177 included patients, 123 (69.5%) transitioned to comfort care only in the AGU. A frailty trajectory (in patients living with dementia or not) accounted for nearly 70% of deaths. Paradoxically, only frailty among people living without dementia was not significantly associated with a more frequent transition to comfort care [odds ratio (95% confidence interval): 1.44 (0.44-4.76), relative to a patient dying suddenly]. CONCLUSIONS AND IMPLICATIONS: Transition to comfort care only is frequent in AGUs and is linked to the end-of-life trajectory (except for frail patients living without dementia). The frailty trajectory is one of the most frequent, and, therefore, physicians must be aware of the need to improve practice in this context

Development of a Predictive Score for Mortality at 3- and 12-Month after Discharge from an Acute Geriatric Unit as a Trigger for Advanced Care Planning

International audienceBACKGROUND: There is a need for a mortality score that can be used to trigger advanced care planning among older patients discharged from acute geriatric units (AGUs). OBJECTIVE: To develop a prognostic score for 3- and 12-month mortality after discharge from an AGU, based on a comprehensive geriatric assessment, in-hospital events, and the exclusion of patients already receiving palliative care. METHODS: DAMAGE is a French multicentre, prospective, cohort study. The broad inclusion criteria ensured that the cohort is representative of patients treated in an AGU. The DAMAGE participants underwent a comprehensive geriatric assessment, a daily clinical check-up, and follow-up visits 3 and 12 months after discharge. Multivariable logistic regression models were used to develop a prognostic score for the derivation and validation subsets. RESULTS: 3509 patients were assessed and 3112 were included. The patient population was very older and frail or dependant, with a high proportion of deaths at 3 months (n=455, 14.8%) and at 12 months (n=1014, 33%). The score predicted an individual risk of mortality ranging from 1% to 80% at 3 months and between 5% and 93% at 12 months, with an area under the receiving operator characteristic curve in the validation cohort of 0.728 at 3 months and 0.733 at 12 months. CONCLUSIONS: Our score predicted a broad range of risks of death after discharge from the AGU. Having this information at the time of hospital discharge might trigger a discussion on advanced care planning and end-of-life care with very old, frail patients