Early vocational rehabilitation and psychological support for trauma patients to improve return to work (the ROWTATE trial): study protocol for an individually randomised controlled multicentre pragmatic trial.

BACKGROUND: Moderately severe or major trauma (injury severity score (ISS) > 8) is common, often resulting in physical and psychological problems and leading to difficulties in returning to work. Vocational rehabilitation (VR) can improve return to work/education in some injuries (e.g. traumatic brain and spinal cord injury), but evidence is lacking for other moderately severe or major trauma. METHODS: ROWTATE is an individually randomised controlled multicentre pragmatic trial of early VR and psychological support in trauma patients. It includes an internal pilot, economic evaluation, a process evaluation and an implementation study. Participants will be screened for eligibility and recruited within 12 weeks of admission to eight major trauma centres in England. A total of 722 participants with ISS > 8 will be randomised 1:1 to VR and psychological support (where needed, following psychological screening) plus usual care or to usual care alone. The ROWTATE VR intervention will be provided within 2 weeks of study recruitment by occupational therapists and where needed, by clinical psychologists. It will be individually tailored and provided for ≤ 12 months, dependent on participant need. Baseline assessment will collect data on demographics, injury details, work/education status, cognitive impairment, anxiety, depression, post-traumatic distress, disability, recovery expectations, financial stress and health-related quality of life. Participants will be followed up by postal/telephone/online questionnaires at 3, 6 and 12 months post-randomisation. The primary objective is to establish whether the ROWTATE VR intervention plus usual care is more effective than usual care alone for improving participants' self-reported return to work/education for at least 80% of pre-injury hours at 12 months post-randomisation. Secondary outcomes include other work outcomes (e.g. hours of work/education, time to return to work/education, sickness absence), depression, anxiety, post-traumatic distress, work self-efficacy, financial stress, purpose in life, health-related quality of life and healthcare/personal resource use. The process evaluation and implementation study will be described elsewhere. DISCUSSION: This trial will provide robust evidence regarding a VR intervention for a major trauma population. Evidence of a clinically and cost-effective VR intervention will be important for commissioners and providers to enable adoption of VR services for this large and important group of patients within the NHS. TRIAL REGISTRATION: ISRCTN: 43115471. Registered 27/07/2021.

The association between nurse staffing and quality of care in emergency departments: A systematic review.

BACKGROUND: The relationship between nurse staffing, skill-mix and quality of care has been well-established in medical and surgical settings, however, there is relatively limited evidence of this relationship in emergency departments. Those that have been published identified that lower nurse staffing levels in emergency departments are generally associated with worse outcomes with the conclusion that the evidence in emergency settings was, at best, weak. METHODS: We searched thirteen electronic databases for potentially eligible papers published in English up to December 2023. Studies were included if they reported on patient outcomes associated with nurse staffing within emergency departments. Observational, cross-sectional, prospective, retrospective, interrupted time-series designs, difference-in-difference, randomised control trials or quasi-experimental studies and controlled before and after studies study designs were considered for inclusion. Team members independently screened titles and abstracts. Data was synthesised using a narrative approach. RESULTS: We identified 16 papers for inclusion; the majority of the studies (n = 10/16) were observational. The evidence reviewed identified that poorer staffing levels within emergency departments are associated with increased patient wait times, a higher proportion of patients who leave without being seen and an increased length of stay. Lower levels of nurse staffing are also associated with an increase in time to medications and therapeutic interventions, and increased risk of cardiac arrest within the emergency department. CONCLUSION: Overall, there remains limited high-quality empirical evidence addressing the association between emergency department nurse staffing and patient outcomes. However, it is evident that lower levels of nurse staffing are associated with adverse events that can result in delays to the provision of care and serious outcomes for patients. There is a need for longitudinal studies coupled with research that considers the relationship with skill-mix, other staffing grades and patient outcomes as well as a wider range of geographical settings. TWEETABLE ABSTRACT: Lower levels of nurse staffing in emergency departments are associated with delays in patients receiving treatments and poor quality care including an increase in leaving without being seen, delay in accessing treatments and medications and cardiac arrest.

Emergency nurses' preference for tools to identify frailty in major trauma patients: A prospective multi-centre cross-sectional study.

BACKGROUND: Frailty is known to be a predictor of poor recovery following trauma and there is evidence that providing early frailty specific care can improve functional and health outcomes. Accurate assessment of frailty is key to its early identification and subsequent provision of specialist care. The aim of this study was to determine the feasibility and acceptability of different frailty screening tools to nurses administering them in the ED in patients admitted following traumatic injury. METHODS: Patients aged 65 and over attending the Emergency Department of five major trauma centres following injury participated in the study between June 2019 and March 2020. Patients were assessed using the clinical frailty scale (CFS), Program of Research to Integrate Services for the Maintenance of Autonomy 7 (PRIMSA7), and the Trauma Specific Frailty Index (TSFI). Nurses were asked to rank ease of use and to state their preference for each of the tools from best to worst. If the tool was not able to be completed fully then free text responses were enabled to identify reasons. Accuracy of the tool in identifying if the patient was frail or not was determined by comparison with frailty determined by a geriatrician. RESULTS: Data were analysed from 372 patients. Completion rates for each of the tools varied, with highest degree of compliance using the CFS (98.9%). TSFI was least likely to be completed with "lack of available information to complete questions" as the most cited reason. Nurses showed a clear preference for the CFS with 57.3% ranking this as first choice (PRISMA-7 32.16%; TSFI 10.54%). Both PRISMA-7 and CFS were both rated highly as 'extremely easy to complete' (PRISMA-7 58.5%, CFS 59.61%). CONCLUSION: Our results suggest that nurses from five centres preferred to use the CFS to assess frailty in ED major trauma patients.

Investigating the effects of frailty on six-month outcomes in older trauma patients admitted to UK major trauma centres: a multi-centre follow up study.

BACKGROUND: Pre-injury frailty is associated with adverse in-hospital outcomes in older trauma patients, but the association with longer term survival and recovery is unclear. We aimed to investigate post discharge survival and health-related quality of life (HRQoL) in older frail patients at six months after Major Trauma Centre (MTC) admission. METHODS: This was a multi-centre study of patients aged ≥ 65 years admitted to five MTCs. Data were collected via questionnaire at hospital discharge and six months later. The primary outcome was patient-reported HRQoL at follow up using Euroqol EQ5D-5 L visual analogue scale (VAS). Secondary outcomes included health status according to EQ5D dimensions and care requirements at follow up. Multivariable linear regression analysis was conducted to evaluate the association between predictor variables and EQ-5D-5 L VAS at follow up. RESULTS: Fifty-four patients died in the follow up period, of which two-third (64%) had been categorised as frail pre-injury, compared to 21 (16%) of the 133 survivors. There was no difference in self-reported HRQoL between frail and not-frail patients at discharge (Mean EQ-VAS: Frail 55.8 vs. Not-frail 64.1, p = 0.137) however at follow-up HRQoL had improved for the not-frail group but deteriorated for frail patients (Mean EQ-VAS: Frail: 50.0 vs. Not-frail: 65.8, p = 0.009). There was a two-fold increase in poor quality of life at six months (VAS ≤ 50) for frail patients (Frail: 65% vs. Not-frail: 30% p < 0.009). Frailty (ß-13.741 [95% CI -25.377, 2.105], p = 0.02), increased age (ß -1.064 [95% CI [-1.705, -0.423] p = 0.00) and non-home discharge (ß -12.017 [95% CI [118.403, 207.203], p = 0.04) were associated with worse HRQoL at follow up. Requirements for professional carers increased five-fold in frail patients at follow-up (Frail: 25% vs. Not-frail: 4%, p = 0.01). CONCLUSIONS: Frailty is associated with increased mortality post trauma discharge and frail older trauma survivors had worse HRQoL and increased care needs at six months post-discharge. Pre-injury frailty is a predictor of poor longer-term HRQoL after trauma and recognition should enable early specialist pathways and discharge planning.

The process of identifying major trauma in the older person in a single major trauma centre: A service evaluation.

BACKGROUND: Diagnosis of major trauma in the older person is increasingly recognised as clinically challenging with recent reports finding that older patients sustaining major trauma are commonly under-recognised and subsequently are not receiving gold standard major trauma care. This paper is a service evaluation of the processes of major trauma (ISS > 15) care for patients > 65 years presenting to a UK major trauma centre. AIM: To identify modifiable factors within the patient journey that might inform future service improvement initiatives. METHODS: TARN audit data and retrospective notes review of 190 patients > 65 presenting to UHS ED from 1st January 2018 - 31st December 2018 who did not receive a level 1 trauma call on arrival were used to achieve the dataset. Descriptive statistics were combined with multiple logistic regression to look for associations between specific process factors and a missed or delayed diagnosis. RESULTS: The evaluation found that, of the cohort not receiving a level 1 trauma call, 42 (22.1%) patients received a level 2 trauma call; 87 (45.7%) patients were seen initially by a senior clinician, with only 31 (16.3%) patients meeting best practice tariff for consultant within 5 min; 60 (31.5%) patients were seen directly in the resuscitation room; 48 (25.2%) patients received a trauma CT scan with only 27 (14.2%) meeting BPT for CT head within 1 h; 142 (74.7%) patients were admitted to a trauma specialty after discharge from ED. A total of 76 (40%) patients had a missed diagnosis of major trauma with 80 (42%) having a delayed diagnosis. Logistic regression showed a significant association between being seen in a standard initial assessment area (referred to as pitstop in this article) vs the resuscitation room as a first location (p = 0.007) with a delayed diagnosis; and a significant association between plain film imaging vs CT imaging (p = 0.000) and no trauma call vs trauma call (p = 0.009) with a missed diagnosis of major trauma. CONCLUSION: The findings of this service evaluation suggest that service improvement initiatives should be aimed at the early stages of the patient journey to improve missed or delayed diagnoses of major trauma in this patient group.

Establishing the research priorities for major trauma in the United Kingdom: A Delphi study of nurses and allied health professionals.

BACKGROUND: Research prioritisation exercises are used to determine which areas of research are important. In major trauma care, nurses and allied health professionals are central to the delivery of evidence-based care but their opinions on research priorities are under-represented in the literature. We aimed to identify the research priorities of major trauma nurses and allied health professionals in the UK. METHODS: A three-round electronic Delphi study was conducted in the UK between November 2019 and May 2021. Round one aimed to generate research questions with rounds two and three questions in order of priority. In stages two and three responses were analysed using descriptive statistics to compute frequencies and proportions for the ranking of each question. RESULTS: Survey rounds were completed by 180, 100 and 91 respondents respectively. The first round generated 285 statements that were condensed into 71 research questions. Analysis of rankings in subsequent rounds prioritised 54 research questions across themes of adult / children's acute care, psychological care and workforce, training and education. DISCUSSION: Nurses and AHPs are well-positioned to determine research priorities in major trauma care. Focusing on these priorities will guide future research and help to build an evidence-base in trauma care.

Configurations and outcomes of acute hospital care for frail and older patients with moderate to major trauma: a systematic review.

OBJECTIVE: To systematically review research on acute hospital care for frail or older adults experiencing moderate to major trauma. SETTING: Electronic databases (Medline, Embase, ASSIA, CINAHL Plus, SCOPUS, PsycINFO, EconLit, The Cochrane Library) were searched using index and key words, and reference lists and related articles hand-searched. INCLUDED ARTICLES: Peer-reviewed articles of any study design, published in English, 1999-2020 inclusive, referring to models of care for frail and/or older people in the acute hospital phase of care following traumatic injury defined as either moderate or major (mean or median Injury Severity Score ≥9). Excluded articles reported no empirical findings, were abstracts or literature reviews, or referred to frailty screening alone. METHODS: Screening abstracts and full text, and completing data extractions and quality assessments using QualSyst was a blinded parallel process. A narrative synthesis, grouped by intervention type, was undertaken. OUTCOME MEASURES: Any outcomes reported for patients, staff or care system. RESULTS: 17 603 references were identified and 518 read in full; 22 were included-frailty and major trauma (n=0), frailty and moderate trauma (n=1), older people and major trauma (n=8), moderate or major trauma (n=7) 0r moderate trauma (n=6) . Studies were observational, heterogeneous in intervention and with variable methodological quality.Specific attention given to the care of older and/or frail people with moderate to major trauma in the North American context resulted in improvements to in-hospital processes and clinical outcomes, but highlights a relative paucity of evidence, particularly in relation to the first 48 hours post-injury. CONCLUSIONS: This systematic review supports the need for, and further research into an intervention to address the care of frail and/or older patients with major trauma, and for the careful definition of age and frailty in relation to moderate or major trauma. INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS PROSPERO: CRD42016032895.

A common transcriptional mechanism involving R-loop and RNA abasic site regulates an enhancer RNA of APOE.

RNA is modified by hundreds of chemical reactions and folds into innumerable shapes. However, the regulatory role of RNA sequence and structure and how dysregulation leads to diseases remain largely unknown. Here, we uncovered a mechanism where RNA abasic sites in R-loops regulate transcription by pausing RNA polymerase II. We found an enhancer RNA, AANCR, that regulates the transcription and expression of apolipoprotein E (APOE). In some human cells such as fibroblasts, AANCR is folded into an R-loop and modified by N-glycosidic cleavage; in this form, AANCR is a partially transcribed nonfunctional enhancer and APOE is not expressed. In contrast, in other cell types including hepatocytes and under stress, AANCR does not form a stable R-loop as its sequence is not modified, so it is transcribed into a full-length enhancer that promotes APOE expression. DNA sequence variants in AANCR are associated significantly with APOE expression and Alzheimer's Disease, thus AANCR is a modifier of Alzheimer's Disease. Besides AANCR, thousands of noncoding RNAs are regulated by abasic sites in R-loops. Together our data reveal the essentiality of the folding and modification of RNA in cellular regulation and demonstrate that dysregulation underlies common complex diseases such as Alzheimer's disease.

Provision of acute care pathways for older major trauma patients in the UK.

BACKGROUND: The introduction of specific pathways of care for older trauma patients has been shown to decrease hospital length of stay and the overall rate of complications. The extent and scope of pathways and services for older major trauma patients in the UK is not currently known. OBJECTIVE: The primary objective of this study was to map the current care pathways and provision of services for older people following major trauma in the UK. METHODS: A cross-sectional survey of UK hospitals delivering care to major trauma patients (major trauma centres and trauma units). Data were collected on respondent and site characteristics, and local definitions of older trauma patients. To explore pathways for older people with major trauma, four clinical case examples were devised and respondents asked to complete responses that best illustrated the admission pathway for each. RESULTS: Responses from 56 hospitals were included in the analysis, including from 25 (84%) of all major trauma centres (MTCs) in the UK. The majority of respondents defined 'old' by chronological age, most commonly patients 65 years and over. The specialty team with overall responsibility for the patient in trauma units was most likely to be acute medicine or acute surgery. Patients in MTCs were not always admitted under the care of the major trauma service. Assessment by a geriatrician within 72 hours of admission varied in both major trauma centres and trauma units and was associated with increased age. CONCLUSIONS: This survey highlights variability in the admitting specialty team and subsequent management of older major trauma patients across hospitals in the UK. Variability appears to be related to patient condition as well as provision of local resources. Whilst lack of standardisation may be a result of local service configuration this has the potential to impact negatively on quality of care, multi-disciplinary working, and outcomes.

Mapping the Patient and Family Liaison Role in UK Helicopter Emergency Medical Services: A Service Evaluation.

OBJECTIVE: Patient and family liaison practitioners are a relatively recent addition to UK helicopter emergency medical services to support patients with their recovery. A service evaluation was completed that mapped the current provision of patient and family liaison practitioner roles in helicopter emergency medical services in the United Kingdom. METHODS: An online survey was distributed to key stakeholders involved with UK helicopter emergency medical service patient and family liaison practitioner roles. Quantitative survey results were described, and open-ended questions were analyzed using content analysis. RESULTS: Twenty UK helicopter emergency medical services responded to the survey. Nine of these services employ patient and family liaison practitioners with 4 additional helicopter emergency medical services planning to initiate the role. There is variation in the employment models used between the services. The patient and family liaison practitioner role provides important benefits to patients and their families, clinicians, and the helicopter emergency medical service. CONCLUSION: Nine UK helicopter emergency medical services employ patient and family liaison practitioners. This role benefits patients, their families, helicopter emergency medical service clinicians, and helicopter emergency medical service charities. Further research is required to understand how the role works in practice and to understand how to maximize the benefits to stakeholders.

RNase H1, the Gold Standard for R-Loop Detection.

RNase H1 has become an essential tool to uncover the physiological and pathological roles of R-loops, three-stranded structures consisting of and RNA-DNA hybrid opposite to a single DNA strand (ssDNA). RNase H1 degrades the RNA portion of the R-loops returning the two DNA strands to double-stranded form (dsDNA). Overexpression of RNase H1 in different systems has helped to address the questions of where R-loops are located, their abundance, and mechanisms of formation, stability, and degradation. In this chapter we review multiple studies that used RNase H1 as an instrument to investigate R-loops multiple functions and their relevance in health and diseases.

FebriDx host response point-of-care testing improves patient triage for coronavirus disease 2019 (COVID-19) in the emergency department.

OBJECTIVES: Patients presenting to hospital with suspected coronavirus disease 2019 (COVID-19), based on clinical symptoms, are routinely placed in a cohort together until polymerase chain reaction (PCR) test results are available. This procedure leads to delays in transfers to definitive areas and high nosocomial transmission rates. FebriDx is a finger-prick point-of-care test (PoCT) that detects an antiviral host response and has a high negative predictive value for COVID-19. We sought to determine the clinical impact of using FebriDx for COVID-19 triage in the emergency department (ED). DESIGN: We undertook a retrospective observational study evaluating the real-world clinical impact of FebriDx as part of an ED COVID-19 triage algorithm. SETTING: Emergency department of a university teaching hospital. PATIENTS: Patients presenting with symptoms suggestive of COVID-19, placed in a cohort in a 'high-risk' area, were tested using FebriDx. Patients without a detectable antiviral host response were then moved to a lower-risk area. RESULTS: Between September 22, 2020, and January 7, 2021, 1,321 patients were tested using FebriDx, and 1,104 (84%) did not have a detectable antiviral host response. Among 1,104 patients, 865 (78%) were moved to a lower-risk area within the ED. The median times spent in a high-risk area were 52 minutes (interquartile range [IQR], 34-92) for FebriDx-negative patients and 203 minutes (IQR, 142-255) for FebriDx-positive patients (difference of -134 minutes; 95% CI, -144 to -122; P < .0001). The negative predictive value of FebriDx for the identification of COVID-19 was 96% (661 of 690; 95% CI, 94%-97%). CONCLUSIONS: FebriDx improved the triage of patients with suspected COVID-19 and reduced the time that severe acute respiratory coronavirus virus 2 (SARS-CoV-2) PCR-negative patients spent in a high-risk area alongside SARS-CoV-2-positive patients.

Resource utilisation for patients brought to a major trauma centre by helicopter.

BACKGROUND: Helicopter Emergency Medical Services (HEMS) allow critical care personnel to attend incidents alongside transporting patients to hospital. The study site is a UK based emergency department and major trauma centre, accepting flights from a wide geographical area. AIMS: To characterise the impact of HEMS on a major trauma centre clinical resources and the impact of the UK regional trauma network launch on HEMS asset provision. METHODS: Flight case-mix data were obtained from Emergency Department (ED) records (non-trauma patients) and from the Trauma Audit and Research Network database (trauma patients). Statistical analysis was in Excel. RESULTS: 432 flights landed at the site between August 2018 and July 2019. 178 flights originated from the incident scene (145 trauma, 26 non-trauma), 107 from other hospitals, and 5 to other hospitals. Hospitalisation was reduced to a median of 6 days. CONCLUSIONS: Primary HEMS trauma patients utilised significant clinical resources but had shorter hospitalisations than those without HEMS intervention. The regional trauma network improved HEMS tasking and utilised critical car cars to provide advanced pre-hospital care locally. Further work should compare HEMS versus ground ambulance to determine the impact of HEMS on patient outcomes and cost implications to both HEMS operators and receiving hospital.

Feasibility and accuracy of ED frailty identification in older trauma patients: a prospective multi-centre study.

BACKGROUND: The burden of frailty on older people is identifiable by its adverse effect on mortality, morbidity and long term functional and health outcomes. In patients suffering from a traumatic injury there is increasing evidence that it is frailty rather than age that impacts greatest on these outcomes and that early identification can guide frailty specific care. The aim of this study was to evaluate the feasibility of nurse-led assessment of frailty in older trauma patients in the ED in patients admitted to major trauma centres. METHODS: Patients age 65 years and over attending the Emergency Departments (ED) of five Major Trauma Centres following traumatic injury were enrolled between June 2019 and March 2020. Patients were assessed for frailty whilst in the ED using three different screening tools (Clinical Frailty Scale [CFS], Program of Research to Integrate Services for the Maintenance of Autonomy 7 [PRIMSA7], and the Trauma Specific Frailty Index [TSFI]) to compare feasibility and accuracy. Accuracy was determined by agreement with geriatrician assessment of frailty. The primary outcome was identification of frailty in the ED using three different assessment tools. RESULTS: We included 372 patients whose median age was 80, 53.8% of whom were female. The most common mechanism of injury was fall from less than 2 m followed by falls greater than 2 m. Completion rates for the tools were variable, 31.9% for TSFI, compared to 93% with PRISMA7 and 98.9% with the CFS. There was substantial agreement when using CFS between nurse defined frailty and geriatrician defined frailty. Agreement was moderate using PRISMA7 and slight using TSFI. CONCLUSIONS: This prospective study has demonstrated that screening for frailty in older major trauma patients within the Emergency Department is feasible and accurate using CFS. TRIAL REGISTRATION: ISRCTN, ISRCTN10671514 . Registered 22 October 2019.

R-Loop Analysis by Dot-Blot.

The three-stranded nucleic acid structure, R-loop, is increasingly recognized for its role in gene regulation. Initially, R-loops were thought to be the by-products of transcription; but recent findings of fewer R-loops in diseased cells made it clear that R-loops have functional roles in a variety of human cells. Next, it is critical to understand the roles of R-loops and how cells balance their abundance. A challenge in the field is the quantitation of R-loops since much of the work relies on the S9.6 monoclonal antibody whose specificity for RNA-DNA hybrids has been questioned. Here, we use dot-blots with the S9.6 antibody to quantify R-loops and show the sensitivity and specificity of this assay with RNase H, RNase T1, and RNase III that cleave RNA-DNA hybrids, single-stranded RNA, and double-stranded RNA, respectively. This method is highly reproducible, uses general laboratory equipment and reagents, and provides results within two days. This assay can be used in research and clinical settings to quantify R-loops and assess the effect of mutations in genes such as senataxin on R-loop abundance.

Death and dying in prehospital care: what are the experiences and issues for prehospital practitioners, families and bystanders? A scoping review.

OBJECTIVE: To identify the factors that shape and characterise experiences of prehospital practitioners (PHPs), families and bystanders in the context of death and dying outside of the hospital environment where PHPs respond. DESIGN: A scoping review using Arksey and O'Malley's five-stage framework. Papers were analysed using thematic analysis. DATA SOURCES: MEDLINE; Embase; CINAHL; Scopus; Social Sciences Citation Index (Web of Science), ProQuest Dissertations & Theses A&I (Proquest), Health Technology Assessment database; PsycINFO; Grey Literature Report and PapersFirst were searched from January 2000 to May 2019. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Qualitative and mixed methods studies reporting the experiences of PHPs, families and bystanders of death and dying in prehospital settings as a result of natural causes, trauma, suicide and homicide, >18 years of age, in Europe, USA, Canada, Australia and New Zealand. RESULTS: Searches identified 15 352 papers of which 51 met the inclusion criteria. The review found substantial evidence of PHP experiences, except call handlers, and papers reporting family and bystander experiences were limited. PHP work was varied and complex, while confident in clinical work, they felt less equipped to deal with the emotion work, especially with an increasing role in palliative and end-of-life care. Families and bystanders reported generally positive experiences but their support needs were rarely explored. CONCLUSIONS: To the best of our knowledge this is the first review that explores the experiences of PHPs, families and bystanders. An important outcome is identifying current gaps in knowledge where further empirical research is needed. The paucity of evidence suggested by this review on call handlers, families and bystanders presents opportunities to investigate their experiences in greater depth. Further research to address the current knowledge gaps will be important to inform future policy and practice.

RNA abasic sites in yeast and human cells.

RNA abasic sites and the mechanisms involved in their regulation are mostly unknown; in contrast, DNA abasic sites are well-studied. We found surprisingly that, in yeast and human cells, RNA abasic sites are prevalent. When a base is lost from RNA, the remaining ribose is found as a closed-ring or an open-ring sugar with a reactive C1' aldehyde group. Using primary amine-based reagents that react with the aldehyde group, we uncovered evidence for abasic sites in nascent RNA, messenger RNA, and ribosomal RNA from yeast and human cells. Mass spectroscopic analysis confirmed the presence of RNA abasic sites. The RNA abasic sites were found to be coupled to R-loops. We show that human methylpurine DNA glycosylase cleaves N-glycosidic bonds on RNA and that human apurinic/apyrimidinic endonuclease 1 incises RNA abasic sites in RNA-DNA hybrids. Our results reveal that, in yeast and human cells, there are RNA abasic sites, and we identify a glycosylase that generates these sites and an AP endonuclease that processes them.

Frailty in major trauma study (FRAIL-T): a study protocol to determine the feasibility of nurse-led frailty assessment in elderly trauma and the impact on outcome in patients with major trauma.

INTRODUCTION: The burden of frailty on older people is easily recognisable by increasing mortality and morbidity, longer hospital stays and adverse discharge locations. In the UK, frailty screening has recently become part of the best practice commissioning tariff within National Health Service England, yet there is no evidence or consensus as to who should carry out this assessment or within which time frame. As major trauma is an increasing burden for older people, there is a need to focus clinician's attention on early identification of frailty in the emergency department (ED) in patients with major trauma as a way to underpin frailty specific major trauma pathways, to optimise recovery and improve patient experience. Throughout the patient with major trauma pathway, nurses are perhaps best placed to conduct timely clinical assessments working with the patient, family and multidisciplinary team to influence ongoing care. This study aims to determine the feasibility of nurse-led assessment of frailty in patients aged 65 years or more admitted to major trauma centres (MTCs). METHODS AND ANALYSIS: This is a prospective observational study conducted across five UK MTCs, enrolling 370 participants over 9 months. The primary aim is to determine the feasibility of nurse-led frailty assessment in MTC EDs in patients aged 65 years or more following traumatic injury. The prevalence of frailty and the best assessment tool for use in the ED will be determined. Other outcome measures include quality of life and frailty assessment 6 months after injury, mortality and discharge outcomes. ETHICS AND DISSEMINATION: The study was given ethical approval by the Social Care Research Ethics Committee (REC no 19/IEC08/0006). Findings will be published in scientific journals and presented to national and international conferences. TRIAL REGISTRATION NUMBER: ISRCTN10671514.

High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase.

Cellular levels of ribonucleoside triphosphates (rNTPs) are much higher than those of deoxyribonucleoside triphosphates (dNTPs), thereby influencing the frequency of incorporation of ribonucleoside monophosphates (rNMPs) by DNA polymerases (Pol) into DNA. RNase H2-initiated ribonucleotide excision repair (RER) efficiently removes single rNMPs in genomic DNA. However, processing of rNMPs by Topoisomerase 1 (Top1) in absence of RER induces mutations and genome instability. Here, we greatly increased the abundance of genomic rNMPs in Saccharomyces cerevisiae by depleting Rnr1, the major subunit of ribonucleotide reductase, which converts ribonucleotides to deoxyribonucleotides. We found that in strains that are depleted of Rnr1, RER-deficient, and harbor an rNTP-permissive replicative Pol mutant, excessive accumulation of single genomic rNMPs severely compromised growth, but this was reversed in absence of Top1. Thus, under Rnr1 depletion, limited dNTP pools slow DNA synthesis by replicative Pols and provoke the incorporation of high levels of rNMPs in genomic DNA. If a threshold of single genomic rNMPs is exceeded in absence of RER and presence of limited dNTP pools, Top1-mediated genome instability leads to severe growth defects. Finally, we provide evidence showing that accumulation of RNA/DNA hybrids in absence of RNase H1 and RNase H2 leads to cell lethality under Rnr1 depletion.