Current definitions of advanced multimorbidity: a protocol for a scoping review.

INTRODUCTION: People living with and dying from multimorbidity are increasing in number, and ensuring quality care for this population is one of the major challenges facing healthcare providers. People with multimorbidity often have a high burden of palliative and end-of-life care needs, though they do not always access specialist palliative care services. A key reason for this is that they are often not identified as being in the last stages of their life by current healthcare providers and systems.This scoping review aims to identify and present the available evidence on how people with multimorbidity are currently included in research, policy and clinical practice. METHODS AND ANALYSIS: Scoping review methodology, based on Arksey and O'Malley's framework, will be undertaken and presented using the Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Reviews. Search terms have been generated using the key themes of 'multimorbidity', 'end of life' and 'palliative care'. Peer-reviewed research will be obtained through systematic searching of Medline, EMBASE, CINAHL, Scopus and PsycINFO. Grey literature will be searched in a systematic manner. Literature containing a definition for adults with multimorbidity in a terminal phase of their illness experience will be included. After screening studies for eligibility, included studies will be described in terms of setting and characteristics as well as using inductive content analysis to highlight the commonalities in definitions. ETHICS AND DISSEMINATION: Ethical approval is not required for this scoping review. The findings of the scoping review will be used internally as part of SPB's PhD thesis at the University of St Andrews through the Multimorbidity Doctoral Training Programme for Health Professionals, which is supported by the Wellcome Trust (223499/Z/21/Z) and published in an open access, peer-reviewed journal for wider dissemination.

Duration of External Neck Stabilisation (DENS) following odontoid fracture in older or frail adults: protocol for a randomised controlled trial of collar versus no collar.

INTRODUCTION: Fractures of the odontoid process frequently result from low impact falls in frail or older adults. These are increasing in incidence and importance as the population ages. In the UK, odontoid fractures in older adults are usually managed in hard collars to immobilise the fracture and promote bony healing. However, bony healing does not always occur in older adults, and bony healing is not associated with quality of life, functional, or pain outcomes. Further, hard collars can cause complications such as skin pressure ulcers, swallowing difficulties and difficulties with personal care. We hypothesise that management with no immobilisation may be superior to management in a hard collar for older or frail adults with odontoid fractures. METHODS AND ANALYSES: This is the protocol for the Duration of External Neck Stabilisation (DENS) trial-a non-blinded randomised controlled trial comparing management in a hard collar with management without a collar for older (≥65 years) or frail (Rockwood Clinical Frailty Scale ≥5) adults with a new odontoid fracture. 887 neurologically intact participants with any odontoid process fracture type will be randomised to continuing with a hard collar (standard care) or removal of the collar (intervention). The primary outcome is quality of life measured using the EQ-5D-5L at 12 weeks. Secondary outcomes include pain scores, neck disability index, health and social care use and costs, and mortality. ETHICS AND DISSEMINATION: Informed consent for participation will be sought from those able to provide it. We will also include those who lack capacity to ensure representativeness of frail and acutely unwell older adults. Results will be disseminated via scientific publication, lay summary, and visual abstract. The DENS trial received a favourable ethical opinion from the Scotland A Research Ethics Committee (21/SS/0036) and the Leeds West Research Ethics Committee (21/YH/0141). TRIAL REGISTRATION NUMBER: NCT04895644.

The 4 'A's test for detecting delirium in acute medical patients: a diagnostic accuracy study.

BACKGROUND: Delirium is a common and serious neuropsychiatric syndrome, usually triggered by illness or drugs. It remains underdetected. One reason for this is a lack of brief, pragmatic assessment tools. The 4 'A's test (Arousal, Attention, Abbreviated Mental Test - 4, Acute change) (4AT) is a screening tool designed for routine use. This project evaluated its usability, diagnostic accuracy and cost. METHODS: Phase 1 - the usability of the 4AT in routine practice was measured with two surveys and two qualitative studies of health-care professionals, and a review of current clinical use of the 4AT as well as its presence in guidelines and reports. Phase 2 - the 4AT's diagnostic accuracy was assessed in newly admitted acute medical patients aged ≥ 70 years. Its performance was compared with that of the Confusion Assessment Method (CAM; a longer screening tool). The performance of individual 4AT test items was related to cognitive status, length of stay, new institutionalisation, mortality at 12 weeks and outcomes. The method used was a prospective, double-blind diagnostic test accuracy study in emergency departments or in acute general medical wards in three UK sites. Each patient underwent a reference standard delirium assessment and was also randomised to receive an assessment with either the 4AT (n = 421) or the CAM (n = 420). A health economics analysis was also conducted. RESULTS: Phase 1 found evidence that delirium awareness is increasing, but also that there is a need for education on delirium in general and on the 4AT in particular. Most users reported that the 4AT was useful, and it was in widespread use both in the UK and beyond. No changes to the 4AT were considered necessary. Phase 2 involved 785 individuals who had data for analysis; their mean age was 81.4 (standard deviation 6.4) years, 45% were male, 99% were white and 9% had a known dementia diagnosis. The 4AT (n = 392) had an area under the receiver operating characteristic curve of 0.90. A positive 4AT score (> 3) had a specificity of 95% [95% confidence interval (CI) 92% to 97%] and a sensitivity of 76% (95% CI 61% to 87%) for reference standard delirium. The CAM (n = 382) had a specificity of 100% (95% CI 98% to 100%) and a sensitivity of 40% (95% CI 26% to 57%) in the subset of participants whom it was possible to assess using this. Patients with positive 4AT scores had longer lengths of stay (median 5 days, interquartile range 2.0-14.0 days) than did those with negative 4AT scores (median 2 days, interquartile range 1.0-6.0 days), and they had a higher 12-week mortality rate (16.1% and 9.2%, respectively). The estimated 12-week costs of an initial inpatient stay for patients with delirium were more than double the costs of an inpatient stay for patients without delirium (e.g. in Scotland, £7559, 95% CI £7362 to £7755, vs. £4215, 95% CI £4175 to £4254). The estimated cost of false-positive cases was £4653, of false-negative cases was £8956, and of a missed diagnosis was £2067. LIMITATIONS: Patients were aged ≥ 70 years and were assessed soon after they were admitted, limiting generalisability. The treatment of patients in accordance with reference standard diagnosis limited the ability to assess comparative cost-effectiveness. CONCLUSIONS: These findings support the use of the 4AT as a rapid delirium assessment instrument. The 4AT has acceptable diagnostic accuracy for acute older patients aged > 70 years. FUTURE WORK: Further research should address the real-world implementation of delirium assessment. The 4AT should be tested in other populations. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53388093. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 40. See the NIHR Journals Library website for further project information. The funder specified that any new delirium assessment tool should be compared against the CAM, but had no other role in the study design or conduct of the study.

Delirium is the sudden onset of confusion that can happen when someone is unwell. It is common in older people who go into hospital, and it is upsetting for both the patients and their families. Delirium is important to diagnose, because people with delirium do less well than those without, and it is often treatable. The ideal way to diagnose delirium is with a full assessment by a specialist, but this is expensive and time-consuming. We therefore developed a short test called the 4 'A's Test (4AT). The four 'A's stand for Arousal, Attention, Abbreviated Mental Test ­ 4, and Acute change. First, we interviewed hospital staff about delirium and the 4AT. We found that the 4AT was already widely used and that people found it easy to use. We then tested how the 4AT performed in practice. A total of 785 recently admitted patients aged ≥ 70 years participated, of whom around one in eight had delirium. A researcher carried out the full standard delirium assessment on each patient and then a different researcher carried out the 4AT. A normal 4AT score reliably ruled out delirium. An abnormal score was also reasonably effective in detecting delirium, but staff still needed to follow up such patients with a full assessment. People with higher 4AT scores stayed in hospital longer and were more likely to die, and their treatment was more expensive. We conclude that the 4AT is a useful test to rule out delirium or to see if more detailed testing is required. It could help treat patients correctly and quickly. This would save money and improve outcomes.

Delirium detection in older acute medical inpatients: a multicentre prospective comparative diagnostic test accuracy study of the 4AT and the confusion assessment method.

BACKGROUND: Delirium affects > 15% of hospitalised patients but is grossly underdetected, contributing to poor care. The 4 'A's Test (4AT, www.the4AT.com ) is a short delirium assessment tool designed for routine use without special training. The primary objective was to assess the accuracy of the 4AT for delirium detection. The secondary objective was to compare the 4AT with another commonly used delirium assessment tool, the Confusion Assessment Method (CAM). METHODS: This was a prospective diagnostic test accuracy study set in emergency departments or acute medical wards involving acute medical patients aged ≥ 70. All those without acutely life-threatening illness or coma were eligible. Patients underwent (1) reference standard delirium assessment based on DSM-IV criteria and (2) were randomised to either the index test (4AT, scores 0-12; prespecified score of > 3 considered positive) or the comparator (CAM; scored positive or negative), in a random order, using computer-generated pseudo-random numbers, stratified by study site, with block allocation. Reference standard and 4AT or CAM assessments were performed by pairs of independent raters blinded to the results of the other assessment. RESULTS: Eight hundred forty-three individuals were randomised: 21 withdrew, 3 lost contact, 32 indeterminate diagnosis, 2 missing outcome, and 785 were included in the analysis. Mean age was 81.4 (SD 6.4) years. 12.1% (95/785) had delirium by reference standard assessment, 14.3% (56/392) by 4AT, and 4.7% (18/384) by CAM. The 4AT had an area under the receiver operating characteristic curve of 0.90 (95% CI 0.84-0.96). The 4AT had a sensitivity of 76% (95% CI 61-87%) and a specificity of 94% (95% CI 92-97%). The CAM had a sensitivity of 40% (95% CI 26-57%) and a specificity of 100% (95% CI 98-100%). CONCLUSIONS: The 4AT is a short, pragmatic tool which can help improving detection rates of delirium in routine clinical care. TRIAL REGISTRATION: International standard randomised controlled trial number (ISRCTN) 53388093 . Date applied 30/05/2014; date assigned 02/06/2014.

Principal results of a randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with a 12 h regimen of N-acetylcysteine for paracetamol overdose (POP trial).

BACKGROUND: The POP Trial was a phase 1, open-label, rising-dose, randomised study that explored the safety and tolerability of calmangafodipir (superoxide dismutase mimetic) co-treatment with n-acetylcysteine (NAC) for paracetamol overdose. METHODS: Patients were recruited at the Royal Infirmary of Edinburgh (8th June 2017-10th May 2018). Inclusion criterion: adults within 24 h of a paracetamol overdose that required NAC. Within each of 3 sequential cohorts, participants were randomly assigned, with concealed allocation, to NAC and a single intravenous calmangafodipir dose (n = 6) or NAC alone (n = 2). Calmangafodipir doses were 2, 5, or 10 µmol/kg. Participants, study and clinical teams were not blinded. The primary outcome was safety and tolerability. Secondary outcomes were alanine transaminase (ALT), international normalised ratio (INR), keratin-18, caspase-cleaved keratin-18 (ccK18), microRNA-122, and glutamate dehydrogenase (GLDH). (Clinicaltrials.gov:NCT03177395). FINDINGS: All 24 participants received their allocated drug doses and were analysed. Primary endpoints: all participants experienced ≥1 adverse event (AE), most commonly gastrointestinal. Patients experiencing ≥1 serious adverse event (SAE): NAC alone, 2/6; NAC + calmangafodipir (2 µmol/kg), 4/6; NAC + calmangafodipir (5 µmol/kg), 2/6; NAC + calmangafodipir (10 µmol/kg), 3/6. No AEs or SAEs were probably or definitely calmangafodipir-related. Secondary safety outcomes demonstrated no differences between groups. With NAC alone, 2/6 had ALT > 100 U/L; with NAC + calmangafodipir, 0/18. No INR difference. Keratin-18 and ccK18 increased in the NAC alone group more than with calmangafodipir (baseline to 20 h fold change, NAC + calmangafodipir (5 µmol/kg) compared to NAC alone: 0.48 (95%CI 0.28-0.83)). microRNA-122 changes were similar to K18, GLDH was frequently undetected. INTERPRETATION: Calmangafodipir was tolerated when combined with NAC and may reduce biomarkers of paracetamol toxicity.

Protocol for validation of the 4AT, a rapid screening tool for delirium: a multicentre prospective diagnostic test accuracy study.

INTRODUCTION: Delirium is a severe neuropsychiatric syndrome of rapid onset, commonly precipitated by acute illness. It is common in older people in the emergency department (ED) and acute hospital, but greatly under-recognised in these and other settings. Delirium and other forms of cognitive impairment, particularly dementia, commonly coexist. There is a need for a rapid delirium screening tool that can be administered by a range of professional-level healthcare staff to patients with sensory or functional impairments in a busy clinical environment, which also incorporates general cognitive assessment. We developed the 4 'A's Test (4AT) for this purpose. This study's primary objective is to validate the 4AT against a reference standard. Secondary objectives include (1) comparing the 4AT with another widely used test (the Confusion Assessment Method (CAM)); (2) determining if the 4AT is sensitive to general cognitive impairment; (3) assessing if 4AT scores predict outcomes, including (4) a health economic analysis. METHODS AND ANALYSIS: 900 patients aged 70 or over in EDs or acute general medical wards will be recruited in three sites (Edinburgh, Bradford and Sheffield) over 18 months. Each patient will undergo a reference standard delirium assessment and will be randomised to assessment with either the 4AT or the CAM. At 12 weeks, outcomes (length of stay, institutionalisation and mortality) and resource utilisation will be collected by a questionnaire and via the electronic patient record. ETHICS AND DISSEMINATION: Ethical approval was granted in Scotland and England. The study involves administering tests commonly used in clinical practice. The main ethical issues are the essential recruitment of people without capacity. Dissemination is planned via publication in high impact journals, presentation at conferences, social media and the website www.the4AT.com. TRIAL REGISTRATION NUMBER: ISRCTN53388093; Pre-results.

Detection of physiological deterioration by the SNAP40 wearable device compared to standard monitoring devices in the emergency department: the SNAP40-ED study.

BACKGROUND: In recent years, there has been increasing focus on the earlier detection of deterioration in the clinical condition of hospital patients with the aim of instigating earlier treatment to reverse this deterioration and prevent adverse outcomes. This is especially important in the ED, a dynamic environment with large volumes of undifferentiated patients, which carries inherent patient risk. SNAP40 is an innovative medical-grade device that can be worn on the upper arm that continuously monitors patients' vital signs including relative changes in systolic blood pressure, respiratory rate, heart rate, movement, blood oxygen saturation and temperature. It uses automated risk analysis to potentially allow clinical staff to easily and quickly identify high-risk patients. The aim of this study is to investigate whether the SNAP40 device is able to identify deterioration in the vital sign physiology of an ED patient earlier than current standard monitoring and observation charting techniques. METHODS/DESIGN: Single centre, teaching hospital ED open label, prospective, observational cohort study recruiting 250 high acuity participants aged 16 years or over presenting to the ED. Participants will be approached and enrolled in the ED and after consent will have the SNAP40 wearable monitoring device attached which will be used alongside standard care monitoring. Participants will be observed throughout their time in the ED. Any SNAP40 device alarm, standard monitoring alarms or standard practice vital sign observations indicating a deterioration in a patient's vital sign physiology (defined as an increase in NEWS score) will be recorded. Primary outcome is time to detection of deterioration. Secondary outcomes include staff time spent performing observations and responding to standard monitoring alarms, clinical escalation of care when deterioration is detected and participants and staff rating of experience of both SNAP40 and current monitoring. DISCUSSION: The SNAP40-ED study aims to recruit 250 patients. It will be the first study to compare the ability of a novel ambulatory monitoring device to detect deterioration compared to standard care in the ED. It may allow the earlier detection of deterioration in the clinical condition of ED patients and therefore earlier treatment to reverse this deterioration and prevent adverse outcomes. TRIAL REGISTRATION: NCT03179267 ClinicalTrials.gov. Registered on June 17, 2017.

Introduction of paramedic led Echo in Life Support into the pre-hospital environment: The PUCA study.

OBJECTIVES: Can pre-hospital paramedic responders perform satisfactory pre-hospital Echo in Life Support (ELS) during the 10-s pulse check window, and does pre-hospital ELS adversely affect the delivery of cardiac arrest care. METHODS: Prospective observational study of a cohort of ELS trained paramedics using saved ultrasound clips and wearable camera videos. RESULTS: Between 23rd June 2014 and 31st January 2016, seven Resuscitation Rapid Response Unit (3RU) paramedics attended 45 patients in Lothian suffering out-of-hospital CA where resuscitation was attempted and ELS was available and performed. 80% of first ELS attempts by paramedics produced an adequate view which was excellent/good or satisfactory in 68%. 44% of views were obtained within the 10-s pulse check window with a median time off the chest of 17 (IQR 13-20) seconds. A decision to perform ELS was communicated 67% of the time, and the 10-s pulse check was counted aloud in 60%. A manual pulse check was observed in around a quarter of patients and the rhythm on the monitor was checked 38% of the time. All decision changing scans involved a decision to stop resuscitation. CONCLUSIONS: Paramedics are able to obtain good ELS views in the pre-hospital environment but this may lead to longer hands off the chest time and possibly less pulse and monitor checking than is recommended. Future studies will need to demonstrate either improved outcomes or a benefit from identifying patients in whom further resuscitation and transportation is futile, before ELS is widely adopted in most pre-hospital systems.

Researching participant recruitment times.

Conducting research in emergency departments is relatively new, and there are a number of ethical and practical challenges to recruiting patients in these settings. In 2008, the Emergency Medicine Research Group Edinburgh (EMERGE) was set up at the Royal Infirmary of Edinburgh emergency department to support researchers and encourage the growth of research in emergency medicine. As part of a review of their working methods, the group's clinical nurse researchers undertook a small study to identify participant recruitment times. The results showed a significant difference between perceived and actual recruitment times, which has implications for planning staff numbers and budgets. This article describes the evaluation process and methods of data collection, and discusses the results.