Disease and psychological status in ankylosing spondylitis.

Objectives. Psychological factors may be important in the assessment and management of ankylosing spondylitis (AS). Our primary objective was to describe associations between disease and psychological status in AS, using AS-specific assessment tools and questionnaires. Our secondary objectives were to identify patient subgroups based on such associations and to determine the stability of the measures over time. Methods. A total of 110 patients were assessed at 6-monthly intervals up to four times using tools to measure disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Metrology Index (BASMI)], psychological [Hospital Anxiety and Depression Questionnaire (HADS), Health Locus of Control—Form C Questionnaire (HLC-C)] and generic health [Short form (SF)-36] status. Results. Eighty-nine participants completed all four assessments. Throughout the study, BASDAI, BASFI and BASMI scores correlated significantly with anxiety, depression, internality and health status, but not with levels of belief in chance or powerful others. Clinically anxious or depressed subgroups had significantly worse BASDAI and BASFI, but not BASMI, scores. BASMI scores were the least closely linked to psychological status. Mean scores for disease, psychological and health status were clinically stable over the 18 months period. Conclusions. Disease status scores in AS correlated significantly with anxiety, depression, internality and health status. Interpretation of AS disease scores should take an account of psychological status and the choice of measures used. These findings have important potential applications in AS management and monitoring, including the identification of patients for biological therapies

Can emergency medicine research benefit from adaptive design clinical trials?

Background: Adaptive design clinical trials use preplanned interim analyses to determine whether studies should be stopped or modified before recruitment is complete. Emergency medicine trials are well suited to these designs as many have a short time to primary outcome relative to the length of recruitment. We hypothesised that the majority of published emergency medicine trials have the potential to use a simple adaptive trial design. Methods: We reviewed clinical trials published in three emergency medicine journals between January 2003 and December 2013. We determined the proportion that used an adaptive design as well as the proportion that could have used a simple adaptive design based on the time to primary outcome and length of recruitment. Results: Only 19 of 188 trials included in the review were considered to have used an adaptive trial design. A total of 154/165 trials that were fixed in design had the potential to use an adaptive design. Conclusions: Currently, there seems to be limited uptake in the use of adaptive trial designs in emergency medicine despite their potential benefits to save time and resources. Failing to take advantage of adaptive designs could be costly to patients and research. It is recommended that where practical and logistical considerations allow, adaptive designs should be used for all emergency medicine clinical trials

Periodic cometary showers: Real or imaginary?

Since the initial reports in 1980, a considerable body of chemical and physical evidence has been accumulated to indicate that a major impact event occurred on earth 65 million years ago. The effects of this event were global in extent and have been suggested as the cause of the sudden demise or mass extinction of a large percentage of life, including the dinosaurs, at the end of the geologic time period known as the Cretaceous. Recent statistical analyses of extinctions in the marine faunal record for the last 250 million years have suggested that mass extinctions may occur with a periodicity of every 26 to 30 million years. Following these results, other workers have attempted to demonstrate that these extinction events, like that at the end of the Cretaceous, are temporally correlated with large impact events. A recent scenario suggests that they are the result of periodic showers of comets produced by either the passage of the solar system through the galactic plane or by perturbations of the cometary cloud in the outer solar system by a, as yet unseen, solar companion. This hypothesized solar companion has been given the name Nemesis

Effect of herbage density, height and age on nutrient and invertebrate generalist predator abundance in permanent and temporary pastures

© 2020 by the authors. The aim of this research was to assess differences in the quantity and quality of herbage and invertebrate generalist predator abundance among permanent and temporary pastures. Two permanent pastures and four temporary ley pastures (either one year or two years since being sown) were monitored weekly for 10 weeks in the spring. Permanent pastures included a diverse range of native UK grass species, and temporary ley pastures were predominantly perennial ryegrass (Lolium perenne) with or without white clover (Trifolium repens). Weekly measurements of herbage height (in centimeters), herbage cover (fresh and dry matter in kg per hectare) and herbage density (fresh and dry matter in kg per hectare per centimeter) were obtained for each field, along with lycosid spider and carabid beetle abundance. Weekly pasture samples were used to obtain nutrient concentrations of dry matter, crude protein, neutral detergent fibre (NDF), acid detergent fibre (ADF), ash, oil, sugars, digestible organic matter in the dry matter (DOMD) and metabolisable energy (ME) in the herbage as a measure of forage quality for grazing or harvesting. A linear mixed model was used to assess the effect of sward age, herbage density and height on herbage production, nutrient concentrations and invertebrate abundance. Although this study showed that permanent pastures were associated with lower nutrient concentrations of crude protein, ash, oil and ME compared to younger and predominantly perennial ryegrass pastures, the older pastures were associated with higher carabid numbers. Furthermore, permanent pastures had a higher density of dry matter herbage compared to younger pastures, and more dense and taller swards were associated with higher lycosid numbers. The study suggests that within pastures of 3 to 20 cm height, increasing the height and density of swards increases both ME and oil concentrations in herbage, therefore enhancing forage nutrient quality. Older and more permanent pastures can be beneficial for plant and invertebrate generalist predator populations, and still provide a useful source of nutrients for forage production

Retrospective single-centre descriptive study of the characteristics, management and outcomes of adult patients with suspected sepsis in the emergency department

Background: Guidelines for adults presenting to the emergency department (ED) with suspected sepsis recommend protocols and bundles that promote rapid and potentially intensive treatment, but give little consideration of how patient characteristics, such as age, functional status and comorbidities, might influence management. This study aimed to describe the characteristics, management and outcomes of adults attending the ED with suspected sepsis, and specifically describe the prevalence of comorbidities, functional impairment and escalations of care. Methods: We undertook a single-centre retrospective observational study involving medical record review of a random sample of adults admitted to an ED between February 2018 and January 2019 with suspected sepsis. Descriptive statistics were used with 95% confidence intervals (CIs) for key proportions. Results: We included 509 patients (median age 74 years), of whom 49.3% met the Sepsis-3 criteria. Less than half of the patients were living at home independently (42.5%) or could walk independently (41.5%), 19.3% were care home residents and 89.2% of patients had one or more comorbidity. 22% had a pre-existing do not attempt resuscitation order. 6.5% were referred to intensive care, and 34.3% of the 13.2% who died in-hospital had an escalation plan explicitly documented. Conclusion: Adults with suspected sepsis have substantial functional limitations, comorbidities and treatment directives that should be considered in guidelines, especially recommendations for escalation of care

A qualitative exploration of patient flow in a developing Caribbean emergency department

Objectives Emergency departments (EDs) are complex adaptive systems and improving patient flow requires understanding how ED processes work. This is important for developing countries where flow concerns are compounded by resource constraints. The Caribbean is one region with developing emergency care systems and limited research in the area. This study aimed to explore the patient flow process in an emergency department in Trinidad and Tobago, identifying organizational factors influencing patient flow. Methods Multiple qualitative methods, including non-participant observations, observational process mapping and informal conversational interviews were used to explore patient flow. The process maps were generated from the observational process mapping. Thematic analysis was used to analyze the data. Setting The study was conducted at a major tertiary level emergency department in Trinidad and Tobago. Participants Patient and staff journeys in the emergency department were observed. Results Six broad categories were identified- 1) ED organizational work processes, 2) ED design and layout, 3) material resources, 4) nursing staff levels, roles, skill mix and use 5) non-clinical ED staff and 6) external clinical and non-clinical departments. The study findings were combined with existing literature to produce a model of factors influencing ED patient flow. Barriers and facilitators to patient flow were highlighted. Conclusion The knowledge gained may be used to strengthen the emergency care system in the local context. The model of ED patient flow may be used to systematically examine factors influencing patient flow, informing policy and practice. However, the study findings should be validated in other settings

Composite outcomes in clinical prediction modeling: are we trying to predict apples and oranges?

Composite outcomes are widely used in clinical research. Existing literature has considered the pros and cons of composite outcomes in clinical trials, but their extensive use in clinical prediction has received much less attention. Clinical prediction assists decision-making by directing patients with higher risks of adverse outcomes toward interventions that provide the greatest benefits to those at the greatest risk. In this article, we summarize our existing understanding of the advantages and disadvantages of composite outcomes, consider how these relate to clinical prediction, and highlight the problem of key predictors having markedly different associations with individual components of the composite outcome. We suggest that a “composite outcome fallacy” may occur when a clinical prediction model is based on strong associations between key predictors and one component of a composite outcome (such as mortality) and used to direct patients toward intervention when these predictors actually have an inverse association with a more relevant component of the composite outcome (such as the use of a lifesaving intervention). We propose that clinical prediction scores using composite outcomes should report their accuracy for key components of the composite outcome and examine for inconsistencies among predictor variables

'Seizure First Aid Training' for people with epilepsy who attend emergency departments, and their family and friends: study protocol for intervention development and a pilot randomised controlled trial.

INTRODUCTION: People with chronic epilepsy (PWE) often make costly but clinically unnecessary emergency department (ED) visits. Offering them and their carers a self-management intervention that improves confidence and ability to manage seizures may lead to fewer visits. As no such intervention currently exists, we describe a project to develop and pilot one. METHODS AND ANALYSIS: To develop the intervention, an existing group-based seizure management course that has been offered by the Epilepsy Society within the voluntary sector to a broader audience will be adapted. Feedback from PWE, carers and representatives from the main groups caring for PWE will help refine the course so that it addresses the needs of ED attendees. Its behaviour change potential will also be optimised. A pilot randomised controlled trial will then be completed. 80 PWE aged ≥16 who have visited the ED in the prior 12 months on ≥2 occasions, along with one of their family members or friends, will be recruited from three NHS EDs. Dyads will be randomised to receive the intervention or treatment as usual alone. The proposed primary outcome is ED use in the 12 months following randomisation. For the pilot, this will be measured using routine hospital data. Secondary outcomes will be measured by patients and carers completing questionnaires 3, 6 and 12 months postrandomisation. Rates of recruitment, retention and unblinding will be calculated, along with the ED event rate in the control group and an estimate of the intervention's effect on the outcome measures. ETHICS AND DISSEMINATION: Ethical approval: NRES Committee North West-Liverpool East (Reference number 15/NW/0225). The project's findings will provide robust evidence on the acceptability of seizure management training and on the optimal design of a future definitive trial. The findings will be published in peer-reviewed journals and presented at conferences. TRIAL REGISTRATION NUMBER: ISRCTN13 871 327

Detection of Protein Glycosylation Using Tip-Enhanced Raman Scattering

The correct glycosylation of biopharmaceutical glycoproteins and their formulations is essential for them to have the desired therapeutic effect on the patient. It has recently been shown that Raman spectroscopy can be used to quantify the proportion of glycosylated protein from mixtures of native and glycosylated forms of bovine pancreatic ribonuclease (RNase). Here we show the first steps toward not only the detection of glycosylation status but the characterization of glycans themselves from just a few protein molecules at a time using tip-enhanced Raman scattering (TERS). While this technique generates complex data that are very dependent on the protein orientation, with the careful development of combined data preprocessing, univariate and multivariate analysis techniques, we have shown that we can distinguish between the native and glycosylated forms of RNase. Many glycoproteins contain populations of subtly different glycoforms; therefore, with stricter orientation control, we believe this has the potential to lead to further glycan characterization using TERS, which would have use in biopharmaceutical synthesis and formulation research