Sensory unpleasantness of very-high frequency sound and audible ultrasound.

Audible very-high frequency sound (VHFS) and ultrasound (US) have been rated more unpleasant than lower frequency sounds when presented to listeners at similar sensation levels (SLs). In this study, 17 participants rated the sensory unpleasantness of 14-, 16-, and 18-kHz tones and a 1-kHz reference tone. Tones were presented at equal subjective loudness levels for each individual, corresponding to levels of 10, 20, and 30 dB SL measured at 1 kHz. Participants were categorized as either "symptomatic" or "asymptomatic" based on self-reported previous symptoms that they attributed to exposure to VHFS/US. In both groups, subjective loudness increased more rapidly with sound pressure level for VHFS/US than for the 1-kHz reference tone, which is consistent with a reduced dynamic range at the higher frequencies. For loudness-matched tones, participants rated VHFS/US as more unpleasant than that for the 1-kHz reference. These results suggest that increased sensory unpleasantness and reduced dynamic range at high frequencies should be considered when designing or deploying equipment which emits VHFS/US that could be audible to exposed people.

Just go with your body? A conversation analytic study of the transition from first to second stage of labor in UK midwife-led care.

BACKGROUND: The transition from first to second stage of labor is poorly understood. While the onset of second stage is defined by cervical measurement, dilation cannot be directly sensed or externally observed. Thus, uncertainty exists when women report pushing urges before dilation is confirmed. This study aimed to explore how sensations of pushing and uncertainty over progress are interactionally managed. METHODS: We audio/video recorded the labors of 37 women in two midwife-led units in England. Our analysis focused on a subset of 28 recordings that featured discussion of transition from first to second stage of labor. The interactions between midwives, laboring women and their birth partners were transcribed and analyzed using conversation analysis. RESULTS: We identified a 'pushing until proven otherwise' rule granting temporary, contingent authority to bodily urges to push while tracking progress over time. Specifically, midwives supported reported pushing sensations without insisting on examinations. Caution was occasionally expressed in distinguishing between irresistible and forced pushing. Across multiple contractions, midwives watched and waited for alignment of sensations with signs of descent. Where signs of progress were absent over time, examinations were treated as clinically indicated. DISCUSSION: Thus, a complex interplay of women's sensations and midwifery expertise produced care. Compared to past research, our analysis demonstrates increased validation of embodied experience in contemporary midwife-led practice. However, uncertainty still requires navigation through collaborative work. We evidence how this navigation is accomplished in real-time interactions.

The arrhythmic substrate of hypertrophic cardiomyopathy using ECG imaging.

Introduction: Patients with hypertrophic cardiomyopathy (HCM) are at risk for lethal ventricular arrhythmia, but the electrophysiological substrate behind this is not well-understood. We used non-invasive electrocardiographic imaging to characterize patients with HCM, including cardiac arrest survivors. Methods: HCM patients surviving ventricular fibrillation or hemodynamically unstable ventricular tachycardia (n = 17) were compared to HCM patients without a personal history of potentially lethal arrhythmia (n = 20) and a pooled control group with structurally normal hearts. Subjects underwent exercise testing by non-invasive electrocardiographic imaging to estimate epicardial electrophysiology. Results: Visual inspection of reconstructed epicardial HCM maps revealed isolated patches of late activation time (AT), prolonged activation-recovery intervals (ARIs), as well as reversal of apico-basal trends in T-wave inversion and ARI compared to controls (p < 0.005 for all). AT and ARI were compared between groups. The pooled HCM group had longer mean AT (60.1 ms vs. 52.2 ms, p < 0.001), activation dispersion (55.2 ms vs. 48.6 ms, p = 0.026), and mean ARI (227 ms vs. 217 ms, p = 0.016) than structurally normal heart controls. HCM ventricular arrhythmia survivors could be differentiated from HCM patients without a personal history of life-threatening arrhythmia by longer mean AT (63.2 ms vs. 57.4 ms, p = 0.007), steeper activation gradients (0.45 ms/mm vs. 0.36 ms/mm, p = 0.011), and longer mean ARI (234.0 ms vs. 221.4 ms, p = 0.026). A logistic regression model including whole heart mean activation time and activation recovery interval could identify ventricular arrhythmia survivors from the HCM cohort, producing a C statistic of 0.76 (95% confidence interval 0.72-0.81), with an optimal sensitivity of 78.6% and a specificity of 79.8%. Discussion: The HCM epicardial electrotype is characterized by delayed, dispersed conduction and prolonged, dispersed activation-recovery intervals. Combination of electrophysiologic measures with logistic regression can improve differentiation over single variables. Future studies could test such models prospectively for risk stratification of sudden death due to HCM.

Three and twelve-month analysis of the PROM-Q study: comparison of patient-reported outcome measures using the BREAST-Q questionnaire in pre- vs. sub-pectoral implant-based immediate breast reconstruction.

PURPOSE: Implant-based breast reconstruction (IBR) is being increasingly performed with implant placed above the pectoral muscle (pre-pectoral), instead of below the pectoral muscle (sub-pectoral). Currently, there is a lack of comparative data on clinical and patient-perceived outcomes between pre- vs. sub-pectoral IBR. We investigated whether this difference in surgical approach influenced clinical or patient-perceived outcomes. METHODS: This prospective non-randomised longitudinal cohort study (ClinicalTrials.gov identifier: NCT04842240) recruited patients undergoing immediate IBR at the Leeds Breast Unit (Sep 2019-Sep 2021). Data collection included patient characteristics and post-operative complications. Patient-Reported Outcome Measures were collected using the BREAST-Q questionnaire at baseline, 2 weeks, 3- and 12-months post-surgery. RESULTS: Seventy-eight patients underwent IBR (46 patients pre-pectoral; 59% vs. 32 patients sub-pectoral; 41%). Similar complication rates were observed (15.2% pre-pectoral vs. 9.4% sub-pectoral; p = 0.44). Overall implant loss rate was 3.8% (6.5% pre-pectoral vs. 0% sub-pectoral; p = 0.13). Respective median Breast-Q scores for pre- and sub-pectoral IBR at 3 months were: breast satisfaction (58 vs. 48; p = 0.01), psychosocial well-being (60 vs. 57; p = 0.9), physical well-being (68 vs. 76; p = 0.53), and Animation Q scores (73 vs. 76; p = 0.45). Respective Breast-Q scores at 12 months were: breast satisfaction (58 vs. 53; p = 0.3), psychosocial well-being (59 vs. 60; p = 0.9), physical well-being (68 vs. 78; p = 0.18), and Animation Q scores (69 vs. 73; p = 0.4). CONCLUSIONS: This study demonstrates equivalent clinical and patient-perceived outcomes between pre- and sub-pectoral IBR. The study findings can be utilised to aid informed decision making regarding either surgical option.

My hearing explained for children: exploring use of this discussion tool in clinical practice.

OBJECTIVE: To explore the clinical use of 'My Hearing Explained for Children' (MHEfC) with children aged 8-11 years, from the perspectives of the child, parents and audiologist. DESIGN: A mixed methods randomised control trial. Participants completed evaluation questionnaires after their appointment. Statistical and thematic analyses were used to examine the rating scale and open response elements of the questionnaires respectively. STUDY SAMPLE: 45 families participated, 24 randomised to MHEfC and 21 to standard care. RESULTS: Use of MHEfC increased the appointment duration by 8.2 minutes (95% CI 4.1 to 14.2 minutes), which was acceptable to parents (96%) and audiologists (67%). It promoted conversation around 'behavioural and communication tactics', 'specific listening situations' and 'listening effort' at the expense of 'anatomy/physiology/aetiology'. MHEfC positively impacted the discussion of test results (54%); ease of finding joint solutions to problems (71%); and the nature of issues and management options discussed (54%). Parental satisfaction with discussion was high on both pathways, so some parents and audiologists questioned MHEfC necessity and recommended targeted use in future. CONCLUSIONS: MHEfC was acceptable to children (70%) and parents (86%). It successfully promoted child-centred topics of discussion and can positively impact discussion outcomes.

Embedding a novel screening programme for sexually transmitted infections (chlamydia and gonorrhoea) within an ambulatory emergency surgical assessment unit: an observational cohort study.

BACKGROUND: A number of females with pelvic inflammatory disease will present to general surgical services with non-specific abdominal pain. Screening for sexually transmitted infections (STI) as an underlying cause is not routinely offered. We therefore established an STI screening programme for young females presenting to a same day emergency ambulatory surgical clinic as part of the diagnostic pathway. Data outlining the incidence and prevalence of STIs as the underlying cause of lower abdominal pain were collected. METHODS: We conducted an observational cohort study. Self-collected vulvovaginal swabs for chlamydia and gonorrhoea were offered as part of a standardised diagnostic pathway for all females meeting inclusion criteria presenting with abdominal pain. Positive results were referred to our local sexual health team for treatment and contact tracing. RESULTS: The cohort comprised 297 eligible patients; 259 participated, 20 patients declined testing and 18 samples were rejected as inadequate in the laboratory. 5.4% of swab results were positive (2 gonorrhoea and 12 chlamydia). All patients with positive swabs had presented with lower abdominal pain and of these only 21% had a documented sexual history. CONCLUSION: Undiagnosed STIs are prevalent, with significant fertility and public health risks. Young females seeking medical assessment for abdominal pain provide an opportunistic screening cohort with a likely subset of patients presenting with abdominal pain as a direct result of an STI. Our results demonstrate a high incidence of positive tests, suggesting further training of surgeons to include a sexual history in assessment of females with abdominal pain is vital.

"We all see things through a different lens based on our life experiences": co-production of a web-based implementation toolkit with stakeholders across the health and social care system.

Background: Implementing new innovations across the health and social care system is complex, involving many factors that in recent years have been compounded by Covid-19. While a plethora of implementation tools and frameworks are available, there are limitations in terms of their design and accessibility. Co-production is a valuable mechanism for developing tools that have utility and accessibility for those tasked with using them in health and social care organisations and there is growing acknowledgement of increasing the role of co-production in implementation science. This paper provides novel insight into co-production practices and relevance to implementation science by reporting findings from a study to co-produce a web-based implementation toolkit (WIT) that is accessible, usable and designed to support adaptive implementation across health and social care systems. Key themes relating to the process of co-production are outlined and the value of using co-production in implementation processes are discussed. Methods: A web-based survey (n = 36) was conducted with a range of stakeholders across health and social care. Findings identified a need for WIT. Survey respondents were invited to express interest in becoming part of a co-production group and to take part in three online interactive workshops to co-produce WIT. Workshops took place with the group (n = 12) and focused on key developmental stages of WIT. Results: Online co-production workshops were integral to the development and refinement of WIT. Benefits of using this process identified three interrelated themes: (i) Co-designing key features of the toolkit, (ii) Co-producing a toolkit with utility for users across health and social care settings, (iii) Co-producing a toolkit to support the implementation journey. Our approach of undertaking co-production as a dialogic process enabled generation of these themes. To illuminate discussion of these themes we draw upon iterative co-development of the "active ingredients" of key components (e.g., interactive Implementation Wheel) and functions (e.g., interactive "pop-up" definitions of keyword) and features (e.g., case studies) of WIT. Conclusion: Using a co-production approach with a range of end-users across health and social care systems, highlights the benefits of understanding implementation processes for users in these settings. User-centred design and processes for ensuring accessibility readily support the translation of implementation into rapidly changing health and social care systems to benefit outcomes for patients, their families, carers, service users and practitioners.

Long-term risk prediction after major lower limb amputation: 1-year results of the PERCEIVE study.

BACKGROUND: Decision-making when considering major lower limb amputation is complex and requires individualized outcome estimation. It is unknown how accurate healthcare professionals or relevant outcome prediction tools are at predicting outcomes at 1-year after major lower limb amputation. METHODS: An international, multicentre prospective observational study evaluating healthcare professional accuracy in predicting outcomes 1 year after major lower limb amputation and evaluation of relevant outcome prediction tools identified in a systematic search of the literature was undertaken. Observed outcomes at 1 year were compared with: healthcare professionals' preoperative predictions of death (surgeons and anaesthetists), major lower limb amputation revision (surgeons) and ambulation (surgeons, specialist physiotherapists and vascular nurse practitioners); and probabilities calculated from relevant outcome prediction tools. RESULTS: A total of 537 patients and 2244 healthcare professional predictions of outcomes were included. Surgeons and anaesthetists had acceptable discrimination (C-statistic = 0.715), calibration and overall performance (Brier score = 0.200) when predicting 1-year death, but performed worse when predicting major lower limb amputation revision and ambulation (C-statistics = 0.627 and 0.662 respectively). Healthcare professionals overestimated the death and major lower limb amputation revision risks. Consultants outperformed trainees, especially when predicting ambulation. Allied healthcare professionals marginally outperformed surgeons in predicting ambulation. Two outcome prediction tools (C-statistics = 0.755 and 0.717, Brier scores = 0.158 and 0.178) outperformed healthcare professionals' discrimination, calibration and overall performance in predicting death. Two outcome prediction tools for ambulation (C-statistics = 0.688 and 0.667) marginally outperformed healthcare professionals. CONCLUSION: There is uncertainty in predicting 1-year outcomes following major lower limb amputation. Different professional groups performed comparably in this study. Two outcome prediction tools for death and two for ambulation outperformed healthcare professionals and may support shared decision-making.

Talking cervixes: How times materialise during the first stage of labour.

The clock occupies a prominent position in many feminist and midwifery critiques of the medicalisation of labour and birth. Concern has long focused on the production of standardised 'progress' during labour via the expectation that once in 'established' labour, birthing people's cervixes should dilate at a particular rate, measurable in centimetres and clock time. In this article we draw on 37 audio- or video-recordings of women labouring in two UK midwife-led units in NHS hospital settings to develop a more nuanced critique of the way in which times materialise during labour. Mobilising insights from literature that approaches time as relational we suggest that it is helpful to explore the making of times during labour as multiple, uncertain and open-ended. This moves analysis of time during labour and birth beyond concern with particular forms of time (such as the clock or the body) towards understanding how times are constituted through interactions (for example, between midwives, cervixes, clocks, people in labour and their birth partners), and what they do.

Understanding how to create healthier places: A qualitative study exploring the complex system of urban development decision-making.

Tackling complex system challenges like creating healthy environments requires understanding priorities and structures affecting multiple actors. This qualitative study, involving 132 multi-sectoral stakeholders spanning the urban development decision-making system, explores how to influence healthier place-making. Using thematic analysis we develop themes around competing stakeholder priorities; structural 'rules' and influential relationships; and justifying a focus on health, requiring greater clarity and consensus around definitions of 'healthy' urban development. Building on the socio-ecological model we highlight how a multi-faceted approach is required for change at multiple levels in the complex system to target individual actor motivations, organisational priorities and structural 'rules'.

The Relation Between Discipline Identity and Academic Achievement Within a Marketized Higher Education Context: A Serial Mediation Model of Approaches to Learning and Course Complaints.

Social-psychological dimensions of learning are under-researched, but they affect student achievement. Within a marketized higher education context in England, United Kingdom, this study examined whether the relation between students' social identities as members of their discipline and academic achievement could be further understood by considering the mediating roles of approaches to learning and frequency of making course complaints. Undergraduates (N = 679) completed a questionnaire to assess these constructs. As expected, approaches to learning and course complaining both acted as serial mediators of the link between discipline identification and academic achievement: stronger discipline identification was related to more deep approaches to learning, less complaining, and higher achievement, whereas weaker discipline identification was related to more surface approaches to learning, more complaining, and lower achievement. The findings suggest that addressing these social-psychological aspects of learning could improve students' academic achievement.

Short-term risk prediction after major lower limb amputation: PERCEIVE study.

BACKGROUND: The accuracy with which healthcare professionals (HCPs) and risk prediction tools predict outcomes after major lower limb amputation (MLLA) is uncertain. The aim of this study was to evaluate the accuracy of predicting short-term (30 days after MLLA) mortality, morbidity, and revisional surgery. METHODS: The PERCEIVE (PrEdiction of Risk and Communication of outcomE following major lower limb amputation: a collaboratIVE) study was launched on 1 October 2020. It was an international multicentre study, including adults undergoing MLLA for complications of peripheral arterial disease and/or diabetes. Preoperative predictions of 30-day mortality, morbidity, and MLLA revision by surgeons and anaesthetists were recorded. Probabilities from relevant risk prediction tools were calculated. Evaluation of accuracy included measures of discrimination, calibration, and overall performance. RESULTS: Some 537 patients were included. HCPs had acceptable discrimination in predicting mortality (931 predictions; C-statistic 0.758) and MLLA revision (565 predictions; C-statistic 0.756), but were poor at predicting morbidity (980 predictions; C-statistic 0.616). They overpredicted the risk of all outcomes. All except three risk prediction tools had worse discrimination than HCPs for predicting mortality (C-statistics 0.789, 0.774, and 0.773); two of these significantly overestimated the risk compared with HCPs. SORT version 2 (the only tool incorporating HCP predictions) demonstrated better calibration and overall performance (Brier score 0.082) than HCPs. Tools predicting morbidity and MLLA revision had poor discrimination (C-statistics 0.520 and 0.679). CONCLUSION: Clinicians predicted mortality and MLLA revision well, but predicted morbidity poorly. They overestimated the risk of mortality, morbidity, and MLLA revision. Most short-term risk prediction tools had poorer discrimination or calibration than HCPs. The best method of predicting mortality was a statistical tool that incorporated HCP estimation.

Hughes abdominal closure versus standard mass closure to reduce incisional hernias following surgery for colorectal cancer: the HART RCT.

BACKGROUND: Incisional hernias can cause chronic pain and complications and affect quality of life. Surgical repair requires health-care resources and has a significant associated failure rate. A prospective, multicentre, single-blinded randomised controlled trial was conducted to investigate the clinical effectiveness and cost-effectiveness of the Hughes abdominal closure method compared with standard mass closure following surgery for colorectal cancer. The study randomised, in a 1 : 1 ratio, 802 adult patients (aged ≥ 18 years) undergoing surgical resection for colorectal cancer from 28 surgical departments in UK centres. INTERVENTION: Hughes abdominal closure or standard mass closure. MAIN OUTCOME MEASURES: The primary outcome was the incidence of incisional hernias at 1 year, as assessed by clinical examination. Within-trial cost-effectiveness and cost-utility analyses over 1 year were conducted from an NHS and a social care perspective. A key secondary outcome was quality of life, and other outcomes included the incidence of incisional hernias as detected by computed tomography scanning. RESULTS: The incidence of incisional hernia at 1-year clinical examination was 50 (14.8%) in the Hughes abdominal closure arm compared with 57 (17.1%) in the standard mass closure arm (odds ratio 0.84, 95% confidence interval 0.55 to 1.27; p = 0.4). In year 2, the incidence of incisional hernia was 78 (28.7%) in the Hughes abdominal closure arm compared with 84 (31.8%) in the standard mass closure arm (odds ratio 0.86, 95% confidence interval 0.59 to 1.25; p = 0.43). Computed tomography scanning identified a total of 301 incisional hernias across both arms, compared with 100 identified by clinical examination at the 1-year follow-up. Computed tomography scanning missed 16 incisional hernias that were picked up by clinical examination. Hughes abdominal closure was found to be less cost-effective than standard mass closure. The mean incremental cost for patients undergoing Hughes abdominal closure was £616.45 (95% confidence interval -£699.56 to £1932.47; p = 0.3580). Quality of life did not differ significantly between the study arms at any time point. LIMITATIONS: As this was a pragmatic trial, the control arm allowed surgeon discretion in the approach to standard mass closure, introducing variability in the techniques and equipment used. Intraoperative randomisation may result in a loss of equipoise for some surgeons. Follow-up was limited to 2 years, which may not have been enough time to see a difference in the primary outcome. CONCLUSIONS: Hughes abdominal closure did not significantly reduce the incidence of incisional hernias detected by clinical examination and was less cost-effective at 1 year than standard mass closure in colorectal cancer patients. Computed tomography scanning may be more effective at identifying incisional hernias than clinical examination, but the clinical benefit of this needs further research. FUTURE WORK: An extended follow-up using routinely collected NHS data sets aims to report on incisional hernia rates at 2-5 years post surgery to investigate any potential mortality benefit of the closure methods. Furthermore, the proportion of incisional hernias identified by a computed tomography scan (at 1 and 2 years post surgery), but not during clinical examination (occult hernias), proceeding to surgical repair within 3-5 years after the initial operation will be explored. TRIAL REGISTRATION: This trial is registered as ISRCTN25616490. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 34. See the NIHR Journals Library website for further project information.

Bowel cancer treatment involves surgery for the majority of patients. A complication of this surgery is the formation of a hernia at the site of the incision in the abdominal wall, known as an incisional hernia. The lining of the abdomen, fat or the intestine can squeeze through the gap and form a lump under the skin. An incisional hernia can form any time after surgery and can cause serious complications and pain, and can also affect the patient's quality of life. Surgery to correct incisional hernias is not always successful, so finding a way of preventing them is important. This research compares the traditional way of sewing up the abdomen, where the two sides are brought together in one layer with a continuous thread, with an alternative method called the Hughes abdominal closure method/Hughes repair. In the Hughes repair, a series of horizontal and vertical stitches are arranged to spread the load and ease the tension across the wound. A total of 802 patients from 28 sites in the UK were recruited to the trial. Half of the patients were randomly allocated to have traditional abdominal closure and half were randomised to have Hughes abdominal closure. All were followed up for 1 year after surgery to assess whether or not an incisional hernia had occurred. We also assessed quality of life during follow-up, and we compared the costs and benefits of each procedure to see which option was the better value for money. By comparing the results from the two methods, it was hoped that the best method of abdominal closure to reduce the risk of an incisional hernia occurring would be found. The analysis of the data suggested that the risk of an incisional hernia was no different with either closure method. Furthermore, Hughes abdominal closure was more expensive and provided less value for money than standard abdominal closure.

Clinical and cost-effectiveness of paramedic administered fascia iliaca compartment block for emergency hip fracture (RAPID 2)-protocol for an individually randomised parallel-group trial.

BACKGROUND: Approximately 75,000 people fracture a hip each year in the UK. This painful injury can be devastating-with a high associated mortality rate-and survivors likely to be more dependent and less mobile. Pain relief at the scene of injury is known to be inadequate. Intravenous morphine is usually given by paramedics, but opioids are less effective for dynamic pain and can cause serious side effects, including nausea, constipation, delirium and respiratory depression. These may delay surgery, require further treatment and worsen patient outcomes. We completed a feasibility study of paramedic-provided fascia iliaca compartment block (FICB), testing the intervention, trial methods and data collection. The study (RAPID) demonstrated that a full trial was feasible. In this subsequent study, we aim to test safety, clinical and cost-effectiveness of paramedic-provided FICB as pain relief to patients with suspected hip fracture in the prehospital environment. METHODS: We will conduct a pragmatic multi-centre individually randomised parallel-group trial, with a 1:1 allocation between usual care (control) and FICB (intervention). Hospital clinicians in five sites (paired ambulance services and receiving hospitals) in England and Wales will train 220 paramedics to administer FICB. The primary outcome is change in pain score from pre-randomisation to arrival at the emergency department. One thousand four hundred patients are required to find a clinically important difference between trial arms in the primary outcome (standardised statistical effect ~ 0.2; 90% power, 5% significance). We will use NHS Digital (England) and the SAIL (Secure Anonymised Information Linkage) databank (Wales) to follow up patient outcomes using routine anonymised linked data in an efficient study design, and questionnaires to capture patient-reported outcomes at 1 and 4 months. Secondary outcomes include mortality, length of hospital stay, job cycle time, prehospital medications including morphine, presence of hip fracture, satisfaction, mobility, and NHS costs. We will assess safety by monitoring serious adverse events (SAEs). DISCUSSION: The trial will help to determine whether paramedic administered FICB is a safe, clinically and cost-effective treatment for suspected hip fracture in the pre-hospital setting. Impact will be shown if and when clinical guidelines either recommend or reject the use of FICB in routine practice in this context. TRIAL REGISTRATION: ISRCTN15831813 . Registered on 22 September 2021.

Automated next-generation profiling of genomic alterations in human cancers.

The lack of validated, distributed comprehensive genomic profiling assays for patients with cancer inhibits access to precision oncology treatment. To address this, we describe elio tissue complete, which has been FDA-cleared for examination of 505 cancer-related genes. Independent analyses of clinically and biologically relevant sequence changes across 170 clinical tumor samples using MSK-IMPACT, FoundationOne, and PCR-based methods reveals a positive percent agreement of >97%. We observe high concordance with whole-exome sequencing for evaluation of tumor mutational burden for 307 solid tumors (Pearson r = 0.95) and comparison of the elio tissue complete microsatellite instability detection approach with an independent PCR assay for 223 samples displays a positive percent agreement of 99%. Finally, evaluation of amplifications and translocations against DNA- and RNA-based approaches exhibits >98% negative percent agreement and positive percent agreement of 86% and 82%, respectively. These methods provide an approach for pan-solid tumor comprehensive genomic profiling with high analytical performance.

PrEdiction of Risk and Communication of outcomE followIng major lower limb amputation: a collaboratiVE study (PERCEIVE)-protocol for the PERCEIVE qualitative study.

INTRODUCTION: Deciding whether to proceed with a major lower limb amputation is life-changing and complex, and it is crucial that the right decision is made at the right time. However, medical specialists are known to poorly predict risk when assessing patients for major surgery, and there is little guidance and research regarding decisions about amputation. The process of shared decision-making between doctors and patients during surgical consultations is also little understood. Therefore, the aim of this study is to analyse in depth the communication, consent, risk prediction and decision-making process in relation to major lower limb amputation. METHODS AND ANALYSIS: Consultations between patients and surgeons at which major lower limb amputation is discussed will be audio-recorded for 10-15 patients. Semi-structured follow-up interviews with patients (and relatives/carers) will then be conducted at two time points: as soon as possible/appropriate after a decision has been reached regarding surgery, and approximately 6 months later. Semi-structured interviews will also be conducted with 10-15 healthcare professionals working in the UK National Health Service (NHS) involved in amputation decision-making. This will include surgeons, anaesthetists and specialist physiotherapists at 2-4 NHS Health Boards/Trusts in Wales and England. Discourse analysis will be used to analyse the recorded consultations; interviews will be analysed thematically. Finally, workshops will be held with patients and healthcare professionals to help synthesise and interpret findings. ETHICS AND DISSEMINATION: The study has been approved by Wales REC 7 (20/WA/0351). Study findings will be published in international peer-reviewed journal(s) and presented at national and international scientific meetings. Findings will also be disseminated to a wide NHS and lay audience via presentations at meetings and written summaries for key stakeholder groups.

The PERCEIVE quantitative study: PrEdiction of Risk and Communication of outcome following major lower-limb amputation: protocol for a collaboratiVE study.

BACKGROUND: Accurate prediction of outcomes following surgery with high morbidity and mortality rates is essential for informed shared decision-making between patients and clinicians. It is unknown how accurately healthcare professionals predict outcomes following major lower-limb amputation (MLLA). Several MLLA outcome-prediction tools have been developed. These could be valuable in clinical practice, but most require validation in independent cohorts before routine clinical use can be recommended. The primary aim of this study is to evaluate the accuracy of healthcare professionals' predictions of outcomes in adult patients undergoing MLLA for complications of chronic limb-threatening ischaemia (CLTI) or diabetes. Secondary aims include the validation of existing outcome-prediction tools. METHOD: This study is an international, multicentre prospective observational study including adult patients undergoing a primary MLLA for CLTI or diabetes. Healthcare professionals' accuracy in predicting outcomes at 30-days (death, morbidity and MLLA revision) and 1-year (death, MLLA revision and ambulation) will be evaluated. Sixteen existing outcome-prediction tools specific to MLLA will be examined for validity. Data collection began on 1 October 2020; the end of follow-up will be 1 May 2022. The C-statistic, Hosmer-Lemeshow test, reclassification tables and Brier score will be used to evaluate the predictive performance of healthcare professionals and prediction tools, respectively. STUDY REGISTRATION AND DISSEMINATION: This study will be registered locally at each centre in accordance with local policies before commencing data collection, overseen by local clinician leads. Results will be disseminated to all centres, and any subsequent presentation(s) and/or publication(s) will follow a collaborative co-authorship model.

Isolation and Identification of Inter-Species Enterovirus Recombinant Genomes.

Positive-strand RNA virus evolution is partly attributed to the process of recombination. Although common between closely genetically related viruses, such as within species of the Enterovirus genus of the Picornaviridae family, inter-species recombination is rarely observed in nature. Recent studies have shown recombination is a ubiquitous process, resulting in a wide range of recombinant genomes and progeny viruses. While not all recombinant genomes yield infectious progeny virus, their existence and continued evolution during replication have critical implications for the evolution of the virus population. In this study, we utilised an in vitro recombination assay to demonstrate inter-species recombination events between viruses from four enterovirus species, A-D. We show that inter-species recombinant genomes are generated in vitro with polymerase template-switching events occurring within the virus polyprotein coding region. However, these genomes did not yield infectious progeny virus. Analysis and attempted recovery of a constructed recombinant cDNA revealed a restriction in positive-strand but not negative-strand RNA synthesis, indicating a significant block in replication. This study demonstrates the propensity for inter-species recombination at the genome level but suggests that significant sequence plasticity would be required in order to overcome blocks in the virus life cycle and allow for the production of infectious viruses.

A Multicenter External Validation of a Score Model to Predict Risk of Events in Patients With Brugada Syndrome.

A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the United Kingdom and retrospectively scored according to a score model by Sieira et al. Data were compiled summatively over follow-up to mimic regular risk re-evaluation as per current guidelines. Sudden cardiac death survivor data were considered perievent to ascertain the utility of the score before cardiac arrest. Scores were compared with actual outcomes. Sensitivity in our cohort was 22.7%, specificity was 57.6%, and C-index was 0.58. In conclusion, up to 75% of cardiac arrest survivors in this cohort would not have been offered a defibrillator if evaluated before their event. This casts doubt on the utility of the score model for primary prevention of sudden death. Inherent issues with modern risk scoring strategies decrease the likelihood of success even in robustly designed tools such as the Sieira score model.