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

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

A system-wide approach to explaining variation in potentially avoidable emergency admissions: national ecological study

Background Some emergency admissions can be avoided if acute exacerbations of health problems are managed by the range of health services providing emergency and urgent care. Aim To identify system-wide factors explaining variation in age sex adjusted admission rates for conditions rich in avoidable admissions. Design National ecological study. Setting 152 emergency and urgent care systems in England. Methods Hospital Episode Statistics data on emergency admissions were used to calculate an age sex adjusted admission rate for conditions rich in avoidable admissions for each emergency and urgent care system in England for 2008–2011. Results There were 3 273 395 relevant admissions in 2008–2011, accounting for 22% of all emergency admissions. The mean age sex adjusted admission rate was 2258 per year per 100 000 population, with a 3.4-fold variation between systems (1268 and 4359). Factors beyond the control of health services explained the majority of variation: unemployment rates explained 72%, with urban/rural status explaining further variation (R2=75%). Factors related to emergency departments, hospitals, emergency ambulance services and general practice explained further variation (R2=85%): the attendance rate at emergency departments, percentage of emergency department attendances converted to admissions, percentage of emergency admissions staying less than a day, percentage of emergency ambulance calls not transported to hospital and perceived access to general practice within 48 h. Conclusions Interventions to reduce avoidable admissions should be targeted at deprived communities. Better use of emergency departments, ambulance services and primary care could further reduce avoidable emergency admissions

Enterprise IoT Security and Scalability : How Unikernels can Improve the Status Quo

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Pharmacological thromboprophylaxis to prevent venous thromboembolism in patients with temporary lower limb immobilization after injury : systematic review and network meta‐analysis

Background Thromboprophylaxis has the potential to reduce venous thromboembolism (VTE) following lower limb immobilization due to injury. Objectives We aimed to estimate the effectiveness of thromboprophylaxis, compare different agents and identify any factors associated with effectiveness. Methods We undertook a systematic review and network meta‐analysis (NMA) of randomised trials reporting VTE or bleeding outcomes that compared thromboprophylactic agents to each other or to no pharmacological prophylaxis, for this indication. An NMA was undertaken for each outcome or agent used, and a series of study level network meta‐regressions examined whether population characteristics, type of injury, treatment of injury or duration of thromboprophylaxis were associated with treatment effect. Results Data from 6857 participants across 13 randomised trials showed that, compared to no treatment, low molecular weight heparin (LMWH) reduced the risk of any VTE (OR 0.52; 95% CrI 0.37, 0.71), clinically detected deep vein thrombosis (DVT) (OR 0.39; 95% CrI 0.12, 0.94) and pulmonary embolism (PE) (OR 0.16; 95% CrI 0.01, 0.74), while fondaparinux reduced the risk of any VTE (OR 0.13; 95% CrI 0.05, 0.30) and clinically detected DVT (OR 0.10; 95% CrI 0.01, 0.86), with inconclusive results for PE (OR 0.40; 95% CrI 0.01, 7.53). Conclusions Thromboprophylaxis with either fondaparinux or LMWH appears to reduce the odds of both asymptomatic and clinically detected VTE in people with temporary lower limb immobilization following an injury. Treatment effects vary by outcome and are not always conclusive. We were unable to identify any treatment effect modifiers other than thromboprophylactic agent used

Developing and assessing the acceptability of an epilepsy first aid training intervention for patients who visit UK emergency departments: A multi-method study of patients and professionals

Epilepsy affects around 1% of the UK population; 40% of whom experience two or more seizures annually. However, most Emergency Department (ED) visits by people with epilepsy (PWE) are clinically unnecessary. Evidence highlights that with correct training, seizures can be safely managed by patients and their families within the community. Arguably therefore, PWE who frequently visit the ED might benefit from a self-management intervention that improves their own and their families' confidence and ability in managing seizures. Currently, no such intervention is available for PWE attending the ED. A collaborative approach (patients, carers, health professionals) was adopted to develop a patient-focused, self-management intervention. An existing group-based seizure management course, offered by the Epilepsy Society, was adapted. Collaborative feedback was sought via a base-line document review, one-to-one semi-structured interviews, and focus group discussions. The applied framework provided a systematic approach from development through to implementation. Participant feedback overall was extremely positive. People with epilepsy who visit the ED reported a positive view of epilepsy seizure first aid training and associated educational materials. Their feedback was then used to develop the optimized intervention presented here. Strengths and perceived barriers to successful implementation and participation, as well as the practical and psychosocial benefits, were identified. We describe the developed intervention together with the process followed. This description, while being project-specific, provides a useful template to assist in the development of interventions more generally. Ongoing evaluation will determine the effects of the training intervention on participants' behavior

Multiple metabolomics of uropathogenic E. coli reveal different information content in terms of metabolic potential compared to virulence factors.

No single analytical method can cover the whole metabolome and the choice of which platform to use may inadvertently introduce chemical selectivity. In order to investigate this we analysed a collection of uropathogenic Escherichia coli. The selected strains had previously undergone extensive characterisation using classical microbiological methods for a variety of metabolic tests and virulence factors. These bacteria were analysed using Fourier transform infrared (FT-IR) spectroscopy; gas chromatography mass spectrometry (GC-MS) after derivatisation of polar non-volatile analytes; as well as reversed-phase liquid chromatography mass spectrometry in both positive (LC-MS(+ve)) and negative (LC-MS(-ve)) electrospray ionisation modes. A comparison of the discriminatory ability of these four methods with the metabolic test and virulence factors was made using Procrustes transformations to ascertain which methods produce congruent results. We found that FT-IR and LC-MS(-ve), but not LC-MS(+ve), were comparable with each other and gave highly similar clustering compared with the virulence factors tests. By contrast, FT-IR and LC-MS(-ve) were not comparable to the metabolic tests, and we found that the GC-MS profiles were significantly more congruent with the metabolic tests than the virulence determinants. We conclude that metabolomics investigations may be biased to the analytical platform that is used and reflects the chemistry employed by the methods. We therefore consider that multiple platforms should be employed where possible and that the analyst should consider that there is a danger of false correlations between the analytical data and the biological characteristics of interest if the full metabolome has not been measured

Evaluating alcohol intoxication management services: the EDARA mixed-methods study

Background: Front-line health-care services are under increased demand when acute alcohol intoxication is most common, which is in night-time environments. Cities have implemented alcohol intoxication management services to divert the intoxicated away from emergency care. Objectives: To evaluate the effectiveness, cost-effectiveness and acceptability to patients and staff of alcohol intoxication management services and undertake an ethnographic study capturing front-line staff’s views on the impact of acute alcohol intoxication on their professional lives. Methods: This was a controlled mixed-methods longitudinal observational study with an ethnographic evaluation in parallel. Six cities with alcohol intoxication management services were compared with six matched control cities to determine effects on key performance indicators (e.g. number of patients in the emergency department and ambulance response times). Surveys captured the impact of alcohol intoxication management services on the quality of care for patients in six alcohol intoxication management services, six emergency departments with local alcohol intoxication management services and six emergency departments without local alcohol intoxication management services. The ethnographic study considered front-line staff perceptions in two cities with alcohol intoxication management services and one city without alcohol intoxication management services. Results: Alcohol intoxication management services typically operated in cities in which the incidence of acute alcohol intoxication was greatest. The per-session average number of attendances across all alcohol intoxication management services was low (mean 7.3, average minimum 2.8, average maximum 11.8) compared with the average number of emergency department attendances per alcohol intoxication management services session (mean 78.8), and the number of patients diverted away from emergency departments, per session, required for services to be considered cost-neutral was 8.7, falling to 3.5 when ambulance costs were included. Alcohol intoxication management services varied, from volunteer-led first aid to more clinically focused nurse practitioner services, with only the latter providing evidence for diversion from emergency departments. Qualitative and ethnographic data indicated that alcohol intoxication management services are acceptable to practitioners and patients and that they address unmet need. There was evidence that alcohol intoxication management services improve ambulance response times and reduce emergency department attendance. Effects are uncertain owing to the variation in service delivery. Limitations: The evaluation focused on health service outcomes, yet evidence arose suggesting that alcohol intoxication management services provide broader societal benefits. There was no nationally agreed standard operating procedure for alcohol intoxication management services, undermining the evaluation. Routine health data outcomes exhibited considerable variance, undermining opportunities to provide an accurate appraisal of the heterogenous collection of alcohol intoxication management services. Conclusions: Alcohol intoxication management services are varied, multipartner endeavours and would benefit from agreed national standards. Alcohol intoxication management services are popular with and benefit front-line staff and serve as a hub facilitating partnership working. They are popular with alcohol intoxication management services patients and capture previously unmet need in night-time environments. However, acute alcohol intoxication in emergency departments remains an issue and opportunities for diversion have not been entirely realised. The nurse-led model was the most expensive service evaluated but was also the most likely to divert patients away from emergency departments, suggesting that greater clinical involvement and alignment with emergency departments is necessary. Alcohol intoxication management services should be regarded as fledgling services that require further work to realise benefit. Future work: Research could be undertaken to determine if a standardised model of alcohol intoxication management services, based on the nurse practitioner model, can be developed and implemented in different settings. Future evaluations should go beyond the health service and consider outcomes more generally, especially for the police. Future work on the management of acute alcohol intoxication in night-time environments could recognise the partnership between health-care, police and ambulance services and third-sector organisations in managing acute alcohol intoxication. Trial registration: Current Controlled Trials ISRCTN63096364

Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation

Background Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis. Objectives To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research. Data sources Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field. Review methods Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services. Results Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra®, Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84–89% and specificity of 46–55%. Limitations Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling. Conclusions Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain. Future work Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis. Study registration This study is registered as PROSPERO CRD42017058688. Funding The National Institute for Health Research Health Technology Assessment programme