Dissociating sensitivity from bias in the Mini Profile of Music Perception Skills.

The Mini Profile of Music Perception Skills (Mini-PROMS) is a rapid performance-based measure of musical perceptual competence. The present study was designed to determine the optimal way to evaluate and score the Mini-PROMS results. Two traditional methods for scoring the Mini-PROMS, the weighted composite score and the parametric sensitivity index (d'), were compared with nonparametric alternatives, also derived from signal detection theory. Performance estimates using the traditional methods were found to depend on response bias (e.g., confidence), making them suboptimal. The simple nonparametric alternatives provided unbiased and reliable performance estimates from the Mini-PROMS and are therefore recommended instead.

Clinical features and outcomes of hospitalised patients with COVID-19 and Parkinsonian disorders: A multicentre UK-based study.

BACKGROUND: Parkinson's disease has been identified as a risk factor for severe Coronavirus disease 2019 (COVID-19) outcomes. However, whether the significant high risk of death from COVID-19 in people with Parkinson's disease is specific to the disease itself or driven by other concomitant and known risk factors such as comorbidities, age, and frailty remains unclear. OBJECTIVE: To investigate clinical profiles and outcomes of people with Parkinson's disease and atypical parkinsonian syndromes who tested positive for COVID-19 in the hospital setting in a multicentre UK-based study. METHODS: A retrospective cohort study of Parkinson's disease patients with a positive SARS-CoV-2 test admitted to hospital between February 2020 and July 2021. An online survey was used to collect data from clinical care records, recording patient, Parkinson's disease and COVID-19 characteristics. Associations with time-to-mortality and severe outcomes were analysed using either the Cox proportional hazards model or logistic regression models, as appropriate. RESULTS: Data from 552 admissions were collected: 365 (66%) male; median (inter-quartile range) age 80 (74-85) years. The 34-day all-cause mortality rate was 38.4%; male sex, increased age and frailty, Parkinson's dementia syndrome, requirement for respiratory support and no vaccination were associated with increased mortality risk. Community-acquired COVID-19 and co-morbid chronic neurological disorder were associated with increased odds of requiring respiratory support. Hospital-acquired COVID-19 and delirium were associated with requiring an increase in care level post-discharge. CONCLUSIONS: This first, multicentre, UK-based study on people with Parkinson's disease or atypical parkinsonian syndromes, hospitalised with COVID-19, adds and expands previous findings on clinical profiles and outcomes in this population.

Relational memory function in schizophrenia: Electrophysiological evidence for early perceptual and late associative abnormalities.

We used event-related potentials (ERPs) to examine encoding and retrieval during episodic memory in people with schizophrenia (SZ) and biological relatives of SZ (SZr). To isolate contextual from item-specific aspects of memory, we employed the Relational and Item-Specific Encoding (RISE) task. Twenty two healthy controls (HCs), 22 SZ, and 19 SZr, encoded visual depictions of objects when displayed alone (item-specific) or in pairs (relational encoding), and were later tested on recognition of specific objects and whether pairs of objects had appeared together. An early posterior component (P2) during encoding predicted later recognition and was diminished in SZ. A late negative potential (LNP) over left frontal brain regions during recognition was larger for relationally encoded objects than new and item-specific encoded objects in HCs. This pattern was absent for SZ and SZr. Smaller P2 and LNP components were associated with greater self-reported cognitive-perceptual abnormalities. Early posterior brain responses likely relevant to perceptual functions supporting memory formation were diminished in schizophrenia. Late frontal electrophysiological responses associated with relational aspects of memory appear diminished in SZ and SZr, potentially reflecting the influence of genetic liability for schizophrenia on brain functions supporting episodic memory.

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease: A Randomized Clinical Trial.

Importance: Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. Objective: To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. Design, Setting, and Participants: This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Interventions: Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. Main Outcomes and Measures: The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Results: Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. Conclusions and Relevance: In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. Trial Registration: ISRCTN Identifier: 16108482.

Multicentre, randomised controlled feasibility study to compare a 10-week physiotherapy programme using an interactive exercise training device to improve walking and balance, to usual care of children with cerebral palsy aged 4-18 years: the ACCEPT study protocol.

INTRODUCTION: Children with cerebral palsy (CP) frequently undertake physiotherapy programmes to improve walking and balance. They often require adult support to exercise in a functional position. A novel interactive exercise trainer has been devised to enable children to exercise with against resistance in a functional position, but its efficacy has yet to be proved. A novel protocol has been developed to determine whether a randomised controlled trial (RCT) is feasible. AIM: To establish whether it is feasible to conduct an RCT to assess the effectiveness of a 10-week physiotherapy intervention using an interactive trainer in children with CP. METHODS AND ANALYSIS: This study is multicentre randomised controlled feasibility trial with an embedded qualitative study. Forty children with CP, Gross Motor Function Classification System (GMFCS) I-III will be recruited from community paediatric physiotherapy caseloads. Participants will be randomised to 10 weeks of training with the interactive training device or to usual physiotherapy care. The mediolateral motion of the centre of mass estimate and Paediatric Balance Scale will be explored as potential primary outcomes measures, tested at baseline, 10 weeks and follow-up at 20 weeks. The views of child participants, their parents and physiotherapists will be gained through e-diaries and qualitative interviews.Feasibility will be determined by examining recruitment and retention rates, completeness of, adherence to the intervention, appropriateness of outcome measures and effectiveness of blinding. Results will be reported in accordance to Consolidated Standards of Reporting Trials (CONSORT) guidelines. ETHICS AND DISSEMINATION: Physiotherapists, children and parents have informed trial design and information leaflets. Results will be disseminated via publications, conferences and to families. This study has approval from North of Scotland Research Ethics Committee (20/NS/0018). TRIAL REGISTRATION NUMBER: ISRCTN80878394.

Resource users as land-sea links in coastal and marine socioecological systems.

Coastal zones, which connect terrestrial and aquatic ecosystems, are among the most resource-rich regions globally and home to nearly 40% of the global human population. Because human land-based activities can alter natural processes in ways that affect adjacent aquatic ecosystems, land-sea interactions are increasingly recognized as critical to coastal conservation planning and governance. However, the complex socioeconomic dynamics inherent in coastal and marine socioecological systems (SESs) have received little consideration. Drawing on knowledge generalized from long-term studies in Caribbean Nicaragua, we devised a conceptual framework that clarifies the multiple ways socioeconomically driven behavior can link the land and sea. In addition to other ecosystem effects, the framework illustrates how feedbacks resulting from changes to aquatic resources can influence terrestrial resource management decisions and land uses. We assessed the framework by applying it to empirical studies from a variety of coastal SESs. The results suggest its broad applicability and highlighted the paucity of research that explicitly investigates the effects of human behavior on coastal SES dynamics. We encourage researchers and policy makers to consider direct, indirect, and bidirectional cross-ecosystem links that move beyond traditionally recognized land-to-sea processes.

Los Usuarios de Recursos como Conexiones entre la Tierra y el Mar dentro de los Sistemas Socioecológicos Marinos y Costeros Resumen Las zonas costeras, que conectan los ecosistemas terrestres y acuáticos, se encuentran entre las regiones más ricas en recursos a nivel mundial y además albergan a casi el 40% de la población humana de todo el mundo. Ya que las actividades humanas terrestres pueden alterar los procesos naturales de manera que terminan por afectar a los ecosistemas acuáticos adyacentes, cada vez se reconoce más a las interacciones tierra-mar como críticas para la planeación de la conservación y la gestión costera. Sin embargo, las complejas dinámicas socioeconómicas inherentes a los sistemas socioecológicos (SES) marinos y costeros han recibido poca atención. Con el conocimiento generalizado a partir de los estudios a largo plazo realizados en el Caribe de Nicaragua como punto de partida, diseñamos un marco conceptual que clarifica las múltiples formas en las que el comportamiento con origen socioeconómico puede conectar a la tierra y al mar. Sumado a otros efectos de los ecosistemas, el marco conceptual ilustró cómo los comentarios resultantes de los cambios ocurridos en los recursos acuáticos pueden influir sobre las decisiones de manejo de recursos terrestres y de uso de suelo. Evaluamos el marco conceptual mediante su aplicación a los estudios empíricos de una variedad de SES costeros. Los resultados sugirieron su aplicabilidad generalizada y resaltaron la escasez de investigaciones busquen específicamente los efectos del comportamiento humano sobre las dinámicas de los SES costeros. Alentamos a los investigadores y a los formuladores de políticas a considerar las conexiones directas, indirectas y bidireccionales entre ecosistemas que van más allá de los procesos de tierra a mar reconocidos tradicionalmente.

The fisheries governance tool: A practical and accessible approach to evaluating management systems.

The Fisheries Governance Tool (FGT) is a comprehensive, evidence-based diagnostic tool that fishery managers, environmental organizations, funders, investors, and other key stakeholders can use to track progress against sustainability goals, identify gaps and challenges that impede continued improvement, and set targets for improvement. The diagnostic tool was developed following a thorough review of existing evaluation and assessment schemes and builds upon many of the credible and widely accepted guidelines and assessment tools currently available. It is built on the premise that the most comprehensive and informative measures of country or regional performance requires evaluation of evidence across three components: 1) the laws and policies governing fisheries, 2) the capacity to implement those policies, and 3) the functioning and performance of the fishery management system and fisheries. The Tool's reliance on empirical evidence allows for an objective, repeatable and rigorous evaluation. Driving this work has been recognition of the importance of identifying and strengthening the enabling conditions for good fisheries management. The FGT offers a unique integrated evaluation of enabling factors and outcomes across the triple bottom line of ecological sustainability, economic efficiency and social/community well-being, with measures spanning a range of identifiable performance levels. Measures identify the building blocks of sound and durable management that lead to more sustainable and responsible fisheries. The Tool was refined through consultation with experts from around the world. The public version of the FGT can be downloaded and allows users to enter data and visualize the results, providing a diagnosis of their management system. The Tool is available in several languages.

Need for recovery and physician well-being in emergency departments: national survey findings.

BACKGROUND AND IMPORTANCE: Need for recovery (NFR) describes an individual's need to physically and psychologically recuperate following a period of work. Physicians working in emergency departments (EDs) have higher NFR scores than other occupational groups. Increased NFR may precede occupational burnout and identification provides opportunities for early interventions. OBJECTIVE: To identify the incidence of well-being characteristics for ED physicians and to determine if NFR score is associated with these characteristics, whilst adjusting for potential confounders. DESIGN: This is a secondary analysis of a survey study. Responses to 11 items were summated into the NFR score, from 0 (lowest NFR) to 100. Additional items (n = 44) explored well-being, demographic and occupational characteristics. SETTING AND PARTICIPANTS: Physicians working within 112 EDs in the UK and Ireland were surveyed in June-July 2019. OUTCOME MEASURE AND ANALYSIS: The outcome measure was self-perceptions of well-being including; current burnout, risk of future burnout and feeling overwhelmed at work. Descriptive statistics are presented alongside findings of a multiple regression analysis. MAIN RESULTS: In 4365 participants, the self-perceived incidence of current burnout, high risk of future burnout and feeling overwhelmed at work more than once a week was 24.8, 62.7 and 45.1%, respectively. For every unfavourable response of the NFR scale there was an increase in odds of 34.0% (95% CI, 31.0-37.1) for frequency of feeling overwhelmed; 53.8% (95% CI, 47.5-60.4) for current burnout; 56.2% (95% CI, 51.1-61.6) for high risk of future burnout. CONCLUSION: This study confirms an association between increased NFR score and self-perceived well-being characteristics. Factors previously reported to reduce NFR could therefore be important initiatives to improve well-being of the ED workforce.

The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial.

STUDY OBJECTIVE: Epistaxis is a common emergency department (ED) presentation and, if simple first aid measures fail, can lead to a need for anterior nasal packing. Tranexamic acid is an agent that contributes to blood clot stability. The aim of this study is to investigate the effectiveness of topical intranasal tranexamic acid in adult patients presenting to the ED with persistent epistaxis, and whether it reduces the need for anterior nasal packing. METHODS: From May 5, 2017, to March 31, 2019, a double-blind, placebo-controlled, multicenter, 1:1, randomized controlled trial was conducted across 26 EDs in the United Kingdom. Participants with spontaneous epistaxis, persisting after simple first aid and the application of a topical vasoconstrictor, were randomly allocated to receive topical tranexamic acid or placebo. The primary outcome was the need for anterior nasal packing of any kind during the index ED attendance. Secondary outcome measures included hospital admission, need for blood transfusion, recurrent epistaxis, and any thrombotic events requiring any hospital reattendance within 1 week. RESULTS: The study sample consisted of 496 participants with spontaneous epistaxis, persisting after simple first aid and application of a topical vasoconstrictor. In total, 211 participants (42.5%) received anterior nasal packing during the index ED attendance, including 111 of 254 (43.7%) in the tranexamic acid group versus 100 of 242 (41.3%) in the placebo group. The difference was not statistically significant (odds ratio 1.107; 95% confidence interval 0.769 to 1.594; P=.59). Furthermore, there were no statistically significant differences between tranexamic acid and placebo for any of the secondary outcome measures. CONCLUSION: In patients presenting to an ED with atraumatic epistaxis that is uncontrolled with simple first aid measures, topical tranexamic acid applied in the bleeding nostril on a cotton wool dental roll is no more effective than placebo at controlling bleeding and reducing the need for anterior nasal packing.

The Use of Postoperative Antibiotics Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis: A Systematic Review and Meta-analysis.

BACKGROUND: Endoscopic sinus surgery is performed for medically recalcitrant chronic rhinosinusitis. There is no universally accepted strategy regarding post-operative antibiotics despite the high rates of usage worldwide. The aim of this study was to analyse patient-reported and objective outcomes behind antibiotic use following endoscopic sinus surgery. METHODS: A search of electronic databases was performed. Eligible randomised controlled trials (RCTs) and observational trials were included. The primary outcome was patient reported outcome measures. Secondary outcomes were local infections, endoscopy scores and adverse events. Meta-analysis was performed. RESULTS: Of 1045 publications identified, 7 were included in the qualitative synthesis and 5 RCTs were included in meta-analysis. Antibiotic regimens varied between studies in terms of antibiotic selection, timing commenced and duration of use. Meta-analysis suggested no significant difference between placebo and antibiotics in patient reported outcome measures (standardised mean difference (SMD) -0.215, 95% confidence interval (CI) -0.637 to 0.207) or endoscopic scores (SMD -2.86, 95% CI -0.846 to 0.273). There was no consistent definition in reporting of infection; therefore, this outcome cannot be comprehensively considered. No severe adverse events were attributable to antibiotics. CONCLUSIONS: From the studies analysed, there is no level 1 evidence to suggest that antibiotics improved patient outcomes following sinus surgery. However, there was significant heterogeneity in outcome measures and no clear data exists regarding the effects of antibiotics on postoperative infections. The available evidence at present is not enough to make a recommendation in either direction. Further designed larger RCTs are required to investigate these questions in more detail.

Need for recovery amongst emergency physicians in the UK and Ireland: a cross-sectional survey.

OBJECTIVES: To determine the need for recovery (NFR) among emergency physicians and to identify demographic and occupational characteristics associated with higher NFR scores. DESIGN: Cross-sectional electronic survey. SETTING: Emergency departments (EDs) (n=112) in the UK and Ireland. PARTICIPANTS: Emergency physicians, defined as any registered physician working principally within the ED, responding between June and July 2019. MAIN OUTCOME MEASURE: NFR Scale, an 11-item self-administered questionnaire that assesses how work demands affect intershift recovery. RESULTS: The median NFR Score for all 4247 eligible, consented participants with a valid NFR Score was 70.0 (95% CI: 65.5 to 74.5), with an IQR of 45.5-90.0. A linear regression model indicated statistically significant associations between gender, health conditions, type of ED, clinical grade, access to annual and study leave, and time spent working out-of-hours. Groups including male physicians, consultants, general practitioners (GPs) within the ED, those working in paediatric EDs and those with no long-term health condition or disability had a lower NFR Score. After adjusting for these characteristics, the NFR Score increased by 3.7 (95% CI: 0.3 to 7.1) and 6.43 (95% CI: 2.0 to 10.8) for those with difficulty accessing annual and study leave, respectively. Increased percentage of out-of-hours work increased NFR Score almost linearly: 26%-50% out-of-hours work=5.7 (95% CI: 3.1 to 8.4); 51%-75% out-of-hours work=10.3 (95% CI: 7.6 to 13.0); 76%-100% out-of-hours work=14.5 (95% CI: 11.0 to 17.9). CONCLUSION: Higher NFR scores were observed among emergency physicians than reported in any other profession or population to date. While out-of-hours working is unavoidable, the linear relationship observed suggests that any reduction may result in NFR improvement. Evidence-based strategies to improve well-being such as proportional out-of-hours working and improved access to annual and study leave should be carefully considered and implemented where feasible.

Continuous Free Cortisol Profiles in Healthy Men.

CONTEXT: In humans, approximately 95% of circulating cortisol is bound to corticosteroid-binding globulin and albumin. It is only the free fraction that is biologically active and can activate signaling pathways via glucocorticoid hormone receptors in cells. Microdialysis is a well-established technique that enables the sampling of molecules in different compartments of the body, including extracellular fluid. This is the first study validating a rapid sampling microdialysis method measuring free cortisol in the subcutaneous and blood compartments of healthy volunteers. METHODS: Healthy nonsmoking volunteers (42 men, aged 18-24 years; body mass index 18-25 kg/m2) received placebo (saline), 250 µg Synacthen, or 1 mg dexamethasone with 10-minute sampling to measure total and free cortisol (subcutaneous, intravenous, and saliva) for an hour before and 4 hours after administration. RESULTS: Following stimulation by Synacthen, total serum cortisol and free cortisol in both compartments rose significantly, achieving and maintaining maximum levels between 2 and 3 hours following the stimulus. A decline in cortisol levels was evident after the administration of dexamethasone or placebo, but there was a clear pulsatile activity around lunchtime in the latter group, which was prominent in the blood compartment (total and free cortisol). There was good correlation between serum total and free cortisol (subcutaneous and intravenous) in the Synacthen and dexamethasone groups with no significant delay (less than 5 minutes) between total and free cortisol. CONCLUSIONS: This seminal study demonstrated the dynamic responses of total blood cortisol and microdialysis derived free cortisol in blood, subcutaneous tissue, and saliva in men.

Simvastatin as a neuroprotective treatment for Parkinson's disease (PD STAT): protocol for a double-blind, randomised, placebo-controlled futility study.

INTRODUCTION: Parkinson's disease (PD) is a progressive neurodegenerative condition affecting approximately 185,000 people in the UK. No drug has been proven to slow disease progression. Epidemiological and pre-clinical data support simvastatin, a widely used cholesterol-lowering drug with a well-established safety profile, having neuroprotective properties. The aim of this study (Simvastatin as a neuroprotective treatment for PD (PD STAT)) is to determine whether simvastatin has the potential to slow PD progression. The study is part of the International Linked Clinical Trials initiative coordinated by The Cure Parkinson's Trust. This paper describes the protocol for the PD STAT study. METHODS AND ANALYSIS: PD STAT is a double-blind, randomised, placebo-controlled, multi-centre, parallel group, futility trial in patients with PD of mild-moderate severity. 235 participants have been recruited and randomly allocated in a 1:1 ratio to receive either oral simvastatin or matched placebo. Treatment involves a 1-month low-dose phase (40 mg daily), followed by a 23-month high-dose phase (80 mg daily) and ends with a 2-month washout period. Participants are reviewed at clinic visits at 1 month, 6, 12, 18, 24 and 26 months post-baseline, with interim telephone follow-up to monitor for adverse events.The primary outcome is the change in the Movement Disorder Society Unified Parkinson's Disease Rating Scale part III motor subscale score in the practically defined OFF medication state (OFF state) between baseline and 24 months. Primary analysis will be on a modified intention to treat basis and will include only those participants who progress to the high-dose phase of the study. ETHICS AND DISSEMINATION: The protocol has been approved by the North East-Newcastle and North Tyneside 2 Research Ethics Committee. The results will be disseminated via research articles in peer-reviewed journals and presentations at local, national and international scientific meetings, as well as disseminated via patient groups, websites and networks. A summary of the study findings will be posted to participants at the end of the study. TRIAL REGISTRATION: ISRCTN16108482 (prospectively registered); EudraCT 2015-000148-40; ClinicalTrials.gov NCT02787590; Pre-results.

The holistic assessment and care planning in partnership intervention study (HAPPI): A protocol for a feasibility, cluster randomized controlled trial.

AIM: During an initial phase of this research, an e-Delphi survey was conducted to gain consensus among stakeholders on the components of a nurse-led assessment and care planning intervention for older people who live with frailty in primary care. This feasibility randomized controlled trial (fRCT) will test the proposed intervention and its implementation and determine methods for the design of a conclusive randomized controlled trial. METHODS: The fRCT, with embedded qualitative study, aims to recruit 60 participants. Moderately and severely frail older people will be identified using the electronic frailty index (eFI) and the intervention will be delivered by senior community nurses. The control participants will receive usual primary care for frailty. The study is funded by the National Institute of Health Research (NIHR; funding granted in May 2016, ref: ICA-CDRF-2016-02-018) and received NHS and University Research Ethics Committee approval in 2018. DISCUSSION: There is evidence that the delivery of complex interventions for community-dwelling older people can reduce care home and hospital admissions and falls, there is less evidence for the benefit of any specific type or intensity of intervention or the additional benefits of targeting the frail population. This trial will determine feasibility of the intervention, define recruitment and retention parameters and trial logistics, and decide outcome measures. IMPACT: This study aims to address the limitations of current research by using a systematic method of frailty diagnosis and participant identification, trialling implementation of a person-centred intervention, and testing of feasibility parameters. TRIAL REGISTRATION NUMBER: ISRCTN: 74345449.

A self-management programme to reduce falls and improve safe mobility in people with secondary progressive MS: the BRiMS feasibility RCT.

BACKGROUND: Balance, mobility impairments and falls are common problems for people with multiple sclerosis (MS). Our ongoing research has led to the development of Balance Right in MS (BRiMS), a 13-week home- and group-based exercise and education programme intended to improve balance and encourage safer mobility. OBJECTIVE: This feasibility trial aimed to obtain the necessary data and operational experience to finalise the planning of a future definitive multicentre randomised controlled trial. DESIGN: Randomised controlled feasibility trial. Participants were block randomised 1 : 1. Researcher-blinded assessments were scheduled at baseline and at 15 and 27 weeks post randomisation. As is appropriate in a feasibility trial, statistical analyses were descriptive rather than involving formal/inferential comparisons. The qualitative elements utilised template analysis as the chosen analytical framework. SETTING: Four sites across the UK. PARTICIPANTS: Eligibility criteria included having a diagnosis of secondary progressive MS, an Expanded Disability Status Scale (EDSS) score of between ≥ 4.0 and ≤ 7.0 points and a self-report of two or more falls in the preceding 6 months. INTERVENTIONS: Intervention - manualised 13-week education and exercise programme (BRiMS) plus usual care. Comparator - usual care alone. MAIN OUTCOME MEASURES: Trial feasibility, proposed outcomes for the definitive trial (including impact of MS, mobility, quality of life and falls), feasibility of the BRiMS programme (via process evaluation) and economic data. RESULTS: A total of 56 participants (mean age 59.7 years, standard deviation 9.7 years; 66% female; median EDSS score of 6.0 points, interquartile range 6.0-6.5 points) were recruited in 5 months; 30 were block randomised to the intervention group. The demographic and clinical data were broadly comparable at baseline; however, the intervention group scored worse on the majority of baseline outcome measures. Eleven participants (19.6%) withdrew or were lost to follow-up. Worsening of MS-related symptoms unrelated to the trial was the most common reason (n = 5) for withdrawal. Potential primary and secondary outcomes and economic data had completion rates of > 98% for all those assessed. However, the overall return rate for the patient-reported falls diary was 62%. After adjusting for baseline score, the differences between the groups (intervention compared with usual care) at week 27 for the potential primary outcomes were MS Walking Scale (12-item) version 2 -7.7 [95% confidence interval (CI) -17.2 to 1.8], MS Impact Scale (29-item) version 2 (MSIS-29vs2) physical 0.6 (95% CI -7.8 to 9) and MSIS-29vs2 psychological -0.4 (95% CI -9.9 to 9) (negative score indicates improvement). After the removal of one outlier, a total of 715 falls were self-reported over the 27-week trial period, with substantial variation between individuals (range 0-93 falls). Of these 715 falls, 101 (14%) were reported as injurious. Qualitative feedback indicated that trial processes and participant burden were acceptable, and participants highlighted physical and behavioural changes that they perceived to result from undertaking BRiMS. Engagement varied, influenced by a range of condition- and context-related factors. Suggestions to improve the utility and accessibility of BRiMS were highlighted. CONCLUSIONS: The results suggest that the trial procedures are feasible and acceptable, and retention, programme engagement and outcome completion rates were sufficient to satisfy the a priori progression criteria. Challenges were experienced in some areas of data collection, such as completion of daily diaries. FUTURE WORK: Further development of BRiMS is required to address logistical issues and enhance user-satisfaction and adherence. Following this, a definitive trial to assess the clinical effectiveness and cost-effectiveness of the BRiMS intervention is warranted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13587999. 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. 27. See the NIHR Journals Library website for further project information.

People with secondary progressive multiple sclerosis (SPMS) often have problems with walking and balance, which lead them to fall. Undertaking exercise and learning about falls prevention could help reduce injury risk and improve mobility. We developed a mobility, balance and falls programme called Balance Right in MS (BRiMS). Before testing its effectiveness in a large-scale trial, we needed to conduct a small-scale version of the trial. We asked people with SPMS who had balance and mobility problems to be assigned by chance to undertake the BRiMS programme plus their usual care, or to continue with usual care only. Questionnaires were used to ask people about their mobility, falls and quality of life, and we measured their balance and activity levels. We interviewed participants about BRiMS and being in the trial, and collected information about costs. Fifty-six people entered the trial from three areas of the south-west and from Ayrshire. At completion of the study we were able to review 44 people. The key measures were completed by 98% of those we assessed, but only around half (62%) of the diaries detailing falls were returned. As this was a feasibility trial, the numbers were too small for us to look at differences between the groups. Participants liked the BRiMS programme; some did a lot of exercise and learning activities, but most did not manage the amount we asked them to do. People reported feeling a little overwhelmed by the educational content of BRiMS, and that this should be reduced in future. They told us that they felt that their balance had improved and that they fell less frequently after the BRiMS programme. Our assessment of the trial methods we used showed that it would be possible to conduct a full-scale trial using this design, but that we need to adapt the BRiMS programme further to make it more user-friendly.

Transmural unipolar electrogram change occurs within 7 s at the left atrial posterior wall during pulmonary vein isolation.

BACKGROUND: To assess occurrence of a histologically validated measure of transmural (TM) atrial ablation-pure R unipolar electrogram (UE) morphology change-at first-ablated left atrial posterior wall (LAPW) sites during contact force (CF)-guided pulmonary vein isolation (PVI). METHODS: Objectively annotated VISITAG™ Module and CARTOREPLAY™ (Biosense Webster Inc., Diamond Bar, CA, USA) UE morphology data were retrospectively analyzed in 23 consecutive patients undergoing PVI under general anesthesia. RESULTS: PVI without spontaneous/dormant recovery was achieved in all, employing 16.3 (3.2) min of radiofrequency (RF; 30 W) energy. All first-ablated LAPW sites demonstrated RS UE morphology preablation, with RF-induced pure R UE morphology change in 98%. Time to pure R UE morphology was significantly shorter at left-sided LAPW sites (4.9 [2.1] vs 6.7 [2.5] s; P = .02), with significantly greater impedance drop (median 13.5 vs 9.9 Ω; P = .003). Importantly, neither first-site RF duration (14.9 vs 15.0 s) nor maximum ablation catheter tip distance moved (during RF) was significantly different, yet the mean CF was significantly higher at right-sided sites (16.5 vs 11.2 g; P = .002). Concurrent impedance and objectively annotated bipolar electrogram (BE) data demonstrated ∼6-8 Ω impedance drop and ∼30% BE decrease at the time of first pure R UE morphology change. CONCLUSIONS: Using objective ablation site annotation, UE morphology evidence of TM RF effect was demonstrated far sooner than considered biologically possible according to the "conventional" 20-40 s RF per-site approach, with significantly greater ablative effect evident at left-sided sites. This novel methodology represents a scientifically more rigorous foundation toward future research into the biological effects of RF ablation in vivo.

National prospective observational study of inpatient management of adults with epistaxis - a National Trainee Research Collaborative delivered investigation.

BACKGROUND: There is a paucity of high-quality evidence relating to the management of epistaxis severe enough to require admission to a hospital. Previous studies of interventions for epistaxis have suffered from small sample sizes. They lacked the power to allow analysis of the effect of an intervention on epistaxis control that is independent of the condition severity or additional interventions given. OBJECTIVE: To determine the effect of specialist treatments on the successful management of severe epistaxis METHODOLOGY: Secondary analysis of data collected from a national multi-centre audit of patients with epistaxis over 30 days in 2016. Data were entered prospectively, and patients were followed up for 30 days following hospital discharge. 1402 adults admitted for inpatient management of epistaxis were identified in 113 participating UK hospitals, with data entered prospectively during the 30-day audit window. Exposure variables assessed included treatment instigated at first ENT review, intervention strategy during hospitalization, disease factors (e.g. severity), patient risk factors (e.g. co-morbidities, medications) and treatment factors (grade of doctor, therapies initiated during hospital stay). Main Outcomes include treatment time (time from first ENT review to time haemostasis was achieved and patient was safe for hospital discharge) and 30-day hospital readmission rate. RESULTS: 834 patients had sufficient data for inclusion. Patients who did not receive nasal cautery at first specialist review had a treatment time greater than double the time of those who were cauterised: Adjusted ratio (aR) 2.5 (95% CI 1.7-3.3), after controlling for age, bleeding severity, and whether they received a nasal pack or not. Only 30% of patients received management that complied with new national guidance, but those that did were 87% more likely to be achieve haemostasis before those that did not, even after controlling for bleeding severity. Type of treatment, whether initial intervention or management strategy, did not affect 30-day re-attendance. CONCLUSIONS: Analysis of national audit data suggest that cautery at first specialist review, and management according to national guidance can reduce hospital treatment times without compromising 30-day re-attendance. Future work should investigate why early nasal cautery is infrequently used, and how service delivery can be optimised to allow widespread implementation of evidence-based management for epistaxis.

Home visits: A new screening tool for frailty? A retrospective exploratory study.

BACKGROUND: In the United Kingdom, the new NHS contract for primary care mandates that practices use the Electronic Frailty Index (EFI) to screen for frailty and apply clinical judgment, based on knowledge of the patient, to decide whether they have a diagnosis of frailty. EFI has not yet been validated for this purpose. Many primary care clinicians would agree that although not formally investigated, there seems to be a strong association between being housebound or in institutional care and having a diagnosis of frailty. Although being housebound or in institutional care is not commonly coded in primary care computer record systems (IT), this cohort of patients do require home visits if they become unwell. Home visits are coded and it is simple to run a search on primary care IT to generate a list of older people who have received a home over given period. AIM: This study assessed whether being housebound and requiring home visits could form a new screening tool for frailty. DESIGN AND SETTING: Retrospective cohort study from 1/3/15 to 29/2/16. Primary care, South Devon. METHOD: Medical records of 154 patients over 65 years of age were evaluated. Patients were divided into two groups: a group (n = 82) that had received a home visit and a second group consisting of a randomized sample of patients (n = 72) with similar baseline characteristics who had not. Patient records were analyzed by two clinicians to determine whether a frailty syndrome was present. Researchers were blinded to each other's results. An arbitrator determined the frailty status on disagreement. RESULTS: Home visits have a sensitivity of 87.23% [95% confidence interval (CI): 74.35%-95.17%] and specificity of 61.68% (95% CI: 51.78%-70.92%). For frailty, Cohen's Kappa showed fair interobserver reliability. CONCLUSION: This study suggests that home visits are a good screen for frailty; the data are easy to retrieve from primary care IT and could be used as a valid screening tool to assist with identifying frailty in primary care.

Coastal livelihood transitions under globalization with implications for trans-ecosystem interactions.

Anthropogenic threats to natural systems can be exacerbated due to connectivity between marine, freshwater, and terrestrial ecosystems, complicating the already daunting task of governance across the land-sea interface. Globalization, including new access to markets, can change social-ecological, land-sea linkages via livelihood responses and adaptations by local people. As a first step in understanding these trans-ecosystem effects, we examined exit and entry decisions of artisanal fishers and smallholder farmers on the rapidly globalizing Caribbean coast of Nicaragua. We found that exit and entry decisions demonstrated clear temporal and spatial patterns and that these decisions differed by livelihood. In addition to household characteristics, livelihood exit and entry decisions were strongly affected by new access to regional and global markets. The natural resource implications of these livelihood decisions are potentially profound as they provide novel linkages and spatially-explicit feedbacks between terrestrial and marine ecosystems. Our findings support the need for more scientific inquiry in understanding trans-ecosystem tradeoffs due to linked-livelihood transitions as well as the need for a trans-ecosystem approach to natural resource management and development policy in rapidly changing coastal regions.

Agroforestry Practices Promote Biodiversity and Natural Resource Diversity in Atlantic Nicaragua.

Tropical forest conversion to pasture, which drives greenhouse gas emissions, soil degradation, and biodiversity loss, remains a pressing socio-ecological challenge. This problem has spurred increased interest in the potential of small-scale agroforestry systems to couple sustainable agriculture with biodiversity conservation, particularly in rapidly developing areas of the tropics. In addition to providing natural resources (i.e. food, medicine, lumber), agroforestry systems have the potential to maintain higher levels of biodiversity and greater biomass than lower diversity crop or pasture systems. Greater plant diversity may also enhance soil quality, further supporting agricultural productivity in nutrient-limited tropical systems. Yet, the nature of these relationships remains equivocal. To better understand how different land use strategies impact ecosystem services, we characterized the relationships between plant diversity (including species richness, phylogenetic diversity, and natural resource diversity), and soil quality within pasture, agroforests, and secondary forests, three common land use types maintained by small-scale farmers in the Pearl Lagoon Basin, Nicaragua. The area is undergoing accelerated globalization following the 2007 completion of the region's first major road; a change which is expected to increase forest conversion for agriculture. However, farmer agrobiodiversity maintenance in the Basin was previously found to be positively correlated with affiliation to local agricultural NGOs through the maintenance of agroforestry systems, despite these farmers residing in the communities closest to the new road, highlighting the potential for maintaining diverse agroforestry agricultural strategies despite heightened globalization pressures. We found that agroforestry sites tended to have higher surface soil %C, %N, and pH relative to neighboring to secondary forest, while maintaining comparable plant diversity. In contrast, pasture reduced species richness, phylogenetic diversity, and natural resource diversity. No significant relationships were found between plant diversity and the soil properties assessed; however higher species richness and phylodiversity was positively correlated with natural resource diversity. These finding suggest that small, diversified agroforestry systems may be a viable strategy for promoting both social and ecological functions in eastern Nicaragua and other rapidly developing areas of the tropics.