Prevention of delirium (POD) for older people in hospital: study protocol for a randomised controlled feasibility trial

Background: Delirium is the most frequent complication among older people following hospitalisation. Delirium may be prevented in about one-third of patients using a multicomponent intervention. However, in the United Kingdom, the National Health Service has no routine delirium prevention care systems. We have developed the Prevention of Delirium Programme, a multicomponent delirium prevention intervention and implementation process. We have successfully carried out a pilot study to test the feasibility and acceptability of implementation of the programme. We are now undertaking preliminary testing of the programme. Methods/Design: The Prevention of Delirium Study is a multicentre, cluster randomised feasibility study designed to explore the potential effectiveness and cost-effectiveness of the Prevention of Delirium Programme. Sixteen elderly care medicine and orthopaedic/trauma wards in eight National Health Service acute hospitals will be randomised to receive the Prevention of Delirium Programme or usual care. Patients will be eligible for the trial if they have been admitted to a participating ward and are aged 65 years or over. The primary objectives of the study are to provide a preliminary estimate of the effectiveness of the Prevention of Delirium Programme as measured by the incidence of new onset delirium, assess the variability of the incidence of new-onset delirium, estimate the intracluster correlation coefficient and likely cluster size, assess barriers to the delivery of the Prevention of Delirium Programme system of care, assess compliance with the Prevention of Delirium Programme system of care, estimate recruitment and follow-up rates, assess the degree of contamination due to between-ward staff movements, and investigate differences in financial costs and benefits between the Prevention of Delirium Programme system of care and standard practice. Secondary objectives are to investigate differences in the number, severity and length of delirium episodes (including persistent delirium); length of stay in hospital; inhospital mortality; destination at discharge; health-related quality of life and health resource use; physical and social independence; anxiety and depression; and patient experience. Discussion: This feasibility study will be used to gather data to inform the design of a future definitive randomised controlled trial. Trial registration: ISRCTN01187372. Registered 13 March 2014

Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase IIo processing in transcription-coupled nucleotide-excision repair

UV-sensitive syndrome (UVSS) is a genodermatosis characterized by cutaneous photosensitivity without skin carcinoma1, 2, 3, 4. Despite mild clinical features, cells from individuals with UVSS, like Cockayne syndrome cells, are very UV sensitive and are deficient in transcription-coupled nucleotide-excision repair (TC-NER)2, 4, 5, which removes DNA damage in actively transcribed genes6. Three of the seven known UVSS cases carry mutations in the Cockayne syndrome genes ERCC8 or ERCC6 (also known as CSA and CSB, respectively)7, 8. The remaining four individuals with UVSS, one of whom is described for the first time here, formed a separate UVSS-A complementation group1, 9, 10; however, the responsible gene was unknown. Using exome sequencing11, we determine that mutations in the UVSSA gene (formerly known as KIAA1530) cause UVSS-A. The UVSSA protein interacts with TC-NER machinery and stabilizes the ERCC6 complex; it also facilitates ubiquitination of RNA polymerase IIo stalled at DNA damage sites. Our findings provide mechanistic insights into the processing of stalled RNA polymerase and explain the different clinical features across these TC-NER–deficient disorders