Patient and hospital-level factors associated with time to surgery after hip fracture in Ireland: Analysis of national audit data 2016-2020.

INTRODUCTION: In hip fracture care, time to surgery (TTS) is a commonly used quality indicator associated with patient outcomes including mortality. This study aimed to identify patient and hospital-level characteristics associated with TTS in Ireland. METHODS: National data from the Irish Hip Fracture Database (IHFD) (2016-2020) were analysed along with hospital-level characteristics obtained from a 2020 organisational survey. Generalised linear model regression was used to explore the association of TTS with case-mix, surgical details, hospital-level staffing and specific protocols recommended to expedite surgery. RESULTS: A total of 14,951 patients with surgically treated hip fracture from 16 hospitals were included (Mean age= 80.6 years (SD=8.8), 70.4% female). Mean TTS was 40.9 h (SD=60.3 h). Case-mix factors associated with longer TTS were male sex and higher American Society of Anaesthesiologists (ASA) grade. Other factors found to be associated with longer TTS included low pre-morbid mobility, inter-hospital transfer, weekday presentation, pre-operative medical physician assessment, intracapsular fracture type, arthroplasty surgery, general anaesthesia, consultant grade of surgeon and lower hospital-level orthopaedic surgical capacity. The oldest age-group and pre-fracture nursing home residence were associated with shorter TTS when adjusted for other case-mix factors. None of four explored protocols for expediting surgery were associated with TTS. CONCLUSION: Patients with more comorbidity experience longer surgical delay after hip fracture in Ireland, in line with international research. Low availability of senior orthopaedic surgeons in Ireland may be delaying hip fracture surgery. Pathway of presentation, including via inter-hospital transfer or hospital bypass, is an important factor that requires further exploration. Further research is required to identify successful system-level protocols and interventions that may expedite hip fracture surgery within this setting.

Interventions for preventing falls in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is one of the most prevalent diseases of the central nervous system with recent prevalence estimates indicating that MS directly affects 2.3 million people worldwide. Fall rates of 56% have been reported among people with MS in a recent meta-analysis. Clinical guidelines do not outline an evidence-based approach to falls interventions in MS. There is a need for synthesised information regarding the effectiveness of falls prevention interventions in MS. OBJECTIVES: The aim of this review was to evaluate the effectiveness of interventions designed to reduce falls in people with MS. Specific objectives included comparing: (1) falls prevention interventions to controls and; (2) different types of falls prevention interventions. SEARCH METHODS: We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group, Cochrane Central Register of Controlled Trials (2018 Issue 9); MEDLINE (PubMed) (1966 to 12 September 2018); Embase (EMBASE.com) (1974 to 12 September 2018); Cumulative Index to Nursing and Allied Health Literature (EBSCOhost) (1981 to 12 September 2018); Latin American and Caribbean Health Science Information Database (Bireme) (1982 to 12 September 2018); ClinicalTrials.gov; and World Health Organization International Clinical Trials Registry Platform; PsycINFO (1806 to 12 September 2018; and Physiotherapy Evidence Database (1999 to 12 September 2018). SELECTION CRITERIA: We selected randomised controlled trials or quasi-randomised trials of interventions to reduce falls in people with MS. We included trials that examined falls prevention interventions compared to controls or different types of falls prevention interventions. Primary outcomes included: falls rate, risk of falling, number of falls per person and adverse events. DATA COLLECTION AND ANALYSIS: Two review authors screened studies for selection, assessed risk of bias and extracted data. We used a rate ratio (RaR) and 95% confidence interval to compare falls rate between groups. For risk of falling, we used a risk ratio (RR) and 95% CI based on the number of fallers in each group. MAIN RESULTS: A total of 839 people with MS (12 to 177 individuals) were randomised in the 13 included trials. The mean age of the participants was 52 years (36 to 62 years). The percentage of women participants ranged from 59% to 85%. Studies included people with all types of MS. Most trials compared an exercise intervention with no intervention or different types of falls prevention interventions. We included two comparisons: (1) Falls prevention intervention versus control and (2) Falls prevention intervention versus another falls prevention intervention. The most common interventions tested were exercise as a single intervention, education as a single intervention, functional electrical stimulation and exercise plus education. The risk of bias of the included studies mixed, with nine studies demonstrating high risk of bias related to one or more aspects of their methodology. The evidence was uncertain regarding the effects of exercise versus control on falls rate (RaR of 0.68; 95% CI 0.43 to 1.06; very low-quality evidence), number of fallers (RR of 0.85; 95% CI 0.51 to 1.43; low-quality evidence) and adverse events (RR of 1.25; 95% CI 0.26 to 6.03; low-quality evidence). Data were not available on quality of life outcomes comparing exercise to control. The majority of other comparisons between falls interventions and controls demonstrated no evidence of effect in favour of either group for all primary outcomes. For the comparison of different falls prevention interventions, the heterogeneity of intervention types across studies prohibited the pooling of data. In relation to secondary outcomes, there was evidence of an effect in favour of exercise interventions compared to controls for balance function with a SMD of 0.50 (95% CI 0.09 to 0.92), self-reported mobility with a SMD of 16.30 (95% CI 9.34 to 23.26) and objective mobility with a SMD of 0.28 (95% CI 0.07 to 0.50). Secondary outcomes were not assessed under the GRADE criteria and results must be interpreted with caution. AUTHORS' CONCLUSIONS: The evidence regarding the effects of interventions for preventing falls in MS is sparse and uncertain. The evidence base demonstrates mixed risk of bias, with very low to low certainty of the evidence. There is some evidence in favour of exercise interventions for the improvement of balance function and mobility. However, this must be interpreted with caution as these secondary outcomes were not assessed under the GRADE criteria and as the results represent data from a small number of studies. Robust RCTs examining the effectiveness of multifactorial falls interventions on falls outcomes are needed.

Difficulties arising in reimbursement recommendations on new medicines due to inadequate reporting of population adjustment indirect comparison methods.

Indirect treatment comparisons are useful to estimate relative treatment effects when head-to-head studies are not conducted. Statisticians at the National Centre for Pharmacoeconomics Ireland (NCPE) and Scottish Medicines Consortium (SMC) assess the clinical and cost-effectiveness of new medicines as part of multidisciplinary teams. We describe some shared observations on areas where reporting of population-adjustment indirect comparison methods is causing uncertainty in our recommendations to decision-making committees when assessing reimbursement of medicines.

Modifying the consistency of food and fluids for swallowing difficulties in dementia.

BACKGROUND: People with dementia can have feeding and swallowing difficulties (dysphagia). Modification of the consistency of food or fluids, or both, is a common management strategy. However, diet modification can affect quality of life and may lead to dehydration and malnutrition. Evidence on the benefits and risks of modifying food and fluids is mandatory to improve the care of people with dementia and dysphagia. OBJECTIVES: To determine the effectiveness and adverse effects associated with modifying the consistency of food and fluids in improving oral intake and eliminating aspiration in adults with dysphagia and dementia. SEARCH METHODS: We searched ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), the Cochrane Library, MEDLINE via Ovid SP, Embase via Ovid SP, PsycINFO via Ovid SP, CINAHL via EBSCOhost, LILACS via BIREME, ClinicalTrials.gov and the World Health Organization (WHO) Portal on 9 May 2018. We also checked the reference lists of relevant articles to identify any additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), quasi-RCTs and cluster-RCTs published in any language that measured any of the outcomes of interest. We included trials with adults with a clinical diagnosis of dementia with symptoms and signs of dysphagia confirmed on instrumental assessment. We included participants with all types, stages and severities of dementia. Control groups received either no intervention or interventions not involving diet modification or modification to sensory properties of food. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed for inclusion all potential studies identified. Data were extracted independently along with assessment of methodological quality using standard Cochrane methods. We contacted study authors for additional unpublished information. MAIN RESULTS: No trials on modification of food met the inclusion criteria. We included two studies that examined modification to fluids. Both were part of the same large multicentre trial and included people with dementia and people with or without dementia and Parkinson's disease. Participation in the second trial was determined by results from the first trial. With unpublished data supplied by study authors, we examined data from participants with dementia only. The first study, a cross-over trial, investigated the immediate effects on aspiration of two viscosities of liquids (nectar thick and honey thick) compared to regular liquids in 351 participants with dementia using videofluoroscopy. Regular liquids with a chin down head posture, as well as regular liquids without any intervention were also compared. The sequence of interventions during videofluoroscopy may have influenced response to intervention. The second study, a parallel designed RCT, compared the effect of nectar and honey thick liquids with a chin down head posture over a three-month period in a subgroup of 260 participants with dementia. Outcomes were pneumonia and adverse intervention effects. Honey thick liquids, which are more consistent with descriptors for 'spoon thick' or 'extremely thick' liquids, showed a more positive impact on immediate elimination of aspiration during videofluoroscopy, but this consistency showed more adverse effects in the second follow-up study. During the second three-month follow-up trial, there were a greater number of incidents of pneumonia in participants receiving honey thick liquids than those receiving nectar thick liquids or taking regular liquids with a chin down posture. There were no deaths classified as 'definitely related' to the type of fluids prescribed. Neither trial addressed quality of life. Risk of bias for both studies is high. The overall quality of evidence for outcomes in this review is low. AUTHORS' CONCLUSIONS: We are uncertain about the immediate and long-term effects of modifying the consistency of fluid for swallowing difficulties in dementia as too few studies have been completed. There may be differences in outcomes depending on the grade of thickness of fluids and the sequence of interventions trialled in videofluoroscopy for people with dementia. Clinicians should be aware that while thickening fluids may have an immediate positive effect on swallowing, the long-term impact of thickened fluids on the health of the person with dementia should be considered. Further high-quality clinical trials are required.

Subtraction multiphase CT angiography: A new technique for faster detection of intracranial arterial occlusions.

OBJECTIVE: To describe and evaluate a novel technical development to improve detection of intracranial vessel occlusions using multiphase CT angiography (MPCTA). MATERIALS AND METHODS: The institutional ethics committee approved the study. Fifty patients (30 consecutive distal (M2 or smaller) anterior circulation occlusions, ten M1 occlusions, ten cases without occlusion) presenting with suspected AIS who underwent MPCTA were included. Post-processing of MPCTA studies created "subtraction" and "delayed enhancement" (DE) datasets. Initially, non-contrast CT and MPCTA studies for each patient were evaluated. Readers' confidence, speed and sensitivity of detection of intracranial vessel occlusions were recorded. After an interval of at least 4 weeks, readers were provided with post-processed images and studies were re-evaluated. RESULTS: While the sensitivity of detection of intracranial vessel occlusions was equal for both conventional MPCTA and subMPCTA, the mean time taken to identify a vessel occlusion decreased by 64 % using subMPCTA (16 s vs. 45 s with conventional MPCTA) (p<0.001). In addition, confidence in interpretation improved (from 4.4 to 4.9) using subMPCTA (p<0.001). CONCLUSION: SubMPCTA is a novel technique that aids in identifying small intracranial vessel occlusions in the suspected AIS patient. SubMPCTA increases confidence in interpretation and reduces the time taken to detect intracranial vessel occlusions. KEY POINTS: • SubMPCTA processes MPCTA data to better demonstrate intracranial arterial occlusions. • SubMPCTA increases confidence and speed of interpretation of MPCTA studies. • SubMPCTA may aid in rapidly differentiating acute ischaemic stroke from stroke mimics.

Harms of off-label erythropoiesis-stimulating agents for critically ill people.

BACKGROUND: Anaemia is a common problem experienced by critically-ill people. Treatment with erythropoiesis-stimulating agents (ESAs) has been used as a pharmacologic strategy when the blunted response of endogenous erythropoietin has been reported in critically-ill people. The use of ESAs becomes more important where adverse clinical outcomes of transfusing blood products is a limitation. However, this indication for ESAs is not licensed by regulatory authorities and is called off-label use. Recent studies concern the harm of ESAs in a critical care setting. OBJECTIVES: To focus on harms in assessing the effects of erythropoiesis-stimulating agents (ESAs), alone or in combination, compared with placebo, no treatment or a different active treatment regimen when administered off-label to critically-ill people. SEARCH METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO via OvidSP, CINAHL, all evidence-based medicine (EBM) reviews including IPA and SCI-Expanded, Conference Proceedings Citation Index- Science, BIOSIS Previews and TOXLINE up to February 2017. We also searched trials registries, checked reference lists of relevant studies and tracked their citations by using SciVerse Scopus. SELECTION CRITERIA: We considered randomized controlled trials (RCTs) and controlled observational studies, which compared scheduled systemic administration of ESAs versus other effective interventions, placebo or no treatment in critically-ill people. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and evaluated the eligibility of retrieved records, extracted data and assessed the risks of bias and quality of the included studies. We resolved differences in opinion by consensus or by involving a third review author. We assessed the evidence using GRADE and created a 'Summary of findings' table. We used fixed-effect or random-effects models, depending on the heterogeneity between studies. We fitted three-level hierarchical Bayesian models to calculate overall treatment effect estimates. MAIN RESULTS: Of the 27,865 records identified, 39 clinical trials and 14 observational studies, including a total of 945,240 participants, were eligible for inclusion. Five studies are awaiting classification. Overall, we found 114 adverse events in 33 studies (30 RCTs and three observational studies), and mortality was reported in 41 studies (32 RCTs and nine observational studies). Most studies were at low to moderate risk of bias for harms outcomes. However, overall harm assessment and reporting were of moderate to low quality in the RCTs, and of low quality in the observational studies. We downgraded the GRADE quality of evidence for venous thromboembolism and mortality to very low and low, respectively, because of risk of bias, high inconsistency, imprecision and limitations of study design.It is unclear whether there is an increase in the risk of any adverse events (Bayesian risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.21; 3099 participants; 9 studies; low-quality evidence) or venous thromboembolism (Bayesian RR 1.04, 95% CI 0.70 to 1.41; 18,917 participants; 18 studies; very low-quality evidence).There was a decreased risk of mortality with off-label use of ESAs in critically-ill people (Bayesian RR 0.76, 95% CI 0.61 to 0.92; 930,470 participants; 34 studies; low-quality evidence). AUTHORS' CONCLUSIONS: Low quality of evidence suggests that off-label use of ESAs may reduce mortality in a critical care setting. There was a lack of high-quality evidence about the harm of ESAs in critically-ill people. The information for biosimilar ESAs is less conclusive. Most studies neither evaluated ESAs' harm as a primary outcome nor predefined adverse events. Any further studies of ESA should address the quality of evaluating, recording and reporting of adverse events.

Topical non-steroidal anti-inflammatory drugs for analgesia in traumatic corneal abrasions.

BACKGROUND: Traumatic corneal abrasions are relatively common and there is a lack of consensus about analgesia in their management. It is therefore important to document the clinical efficacy and safety profile of topical ophthalmic non-steroidal anti-inflammatory drugs (NSAIDs) in the management of traumatic corneal abrasions. OBJECTIVES: To identify and evaluate all randomised controlled trials (RCTs) comparing the use of topical NSAIDs with placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions (including corneal abrasions arising from foreign body removal), to reduce pain, and its effects on healing time. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 30 March 2017), Embase Ovid (1947 to 30 March 2017), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 30 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 30 March 2017, ZETOC (1993 to 30 March 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 30 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 30 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 30 March 2017. We did not use any date or language restrictions in the electronic searches for trials.We checked the reference lists of identified trials to search for further potentially relevant studies. SELECTION CRITERIA: RCTs comparing topical NSAIDs to placebo or any alternative analgesic interventions in adults with traumatic corneal abrasions. DATA COLLECTION AND ANALYSIS: Two review authors independently performed data extraction and assessed risks of bias in the included studies. We rated the certainty of the evidence using GRADE. MAIN RESULTS: We included nine studies that met the inclusion criteria, reporting data on 637 participants.The studies took place in the UK, USA, Israel, Italy, France and Portugal. These studies compared five types of topical NSAIDs (0.1% indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1% diclofenac) to control (consisting of standard care and in four studies used placebo eye drops). Overall, the studies were at an unclear or high risk of bias (particularly selection and reporting bias). None of the included studies reported the primary outcome measures of this review, namely participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours. Four trials, that included data on 481 participants receiving NSAIDs or control (placebo/standard care), reported on the use of 'rescue' analgesia at 24 hours as a proxy measure of pain control. Topical NSAIDs were associated with a reduction in the need for oral analgesia compared with control (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.34 to 0.61; low-certainty evidence). Approximately 4 out of 10 people in the control group used rescue analgesia at 24 hours. No data were available on the use of analgesia at 48 or 72 hours.One trial (28 participants) reported on the proportion of abrasions healed after 24 and 48 hours. These outcomes were similar in both arms of the trial. (at 24 hours RR 1.00 (0.81 to 1.23); at 48 hours RR 1.00 (0.88 to 1.14); low-certainty evidence). In the control group nine out of 10 abrasions were healed within 24 hours and all were healed by 48 hours. Complications of corneal abrasions were reported in 6 studies (609 participants) and were infrequently reported (4 complications, 1 in NSAID groups (recurrent corneal erosion) and 3 in control groups (2 recurrent corneal erosions and 1 corneal abscess), very low-certainty evidence). Possible drug-related adverse events (AEs) were reported in two trials (163 participants), with the number of adverse events low (4 AEs, 3 in NSAID group, including discomfort/photophobia on instillation, conjunctival hyperaemia and urticaria, and 1 in the control group, corneal abscess) very low-certainty evidence. AUTHORS' CONCLUSIONS: The findings of the included studies do not provide strong evidence to support the use of topical NSAIDs in traumatic corneal abrasions. This is important, since NSAIDs are associated with a higher cost compared to oral analgesics. None of the trials addressed our primary outcome measure of participant-reported pain intensity reduction of 30% or more or 50% or more at 24 hours.

Systematic review of risk prediction models for falls after stroke.

BACKGROUND: Falls are a significant cause of morbidity after stroke. The aim of this review was to identify, critically appraise and summarise risk prediction models for the occurrence of falling after stroke. METHODS: A systematic literature search was conducted in December 2014 and repeated in June 2015. Studies that used multivariable analysis to build risk prediction models for falls early after stroke were included. 2 reviewers independently assessed methodological quality. Data relating to model calibration, discrimination (C-statistic) and clinical utility (sensitivity and specificity) were extracted. A narrative review of models was conducted. PROSPERO reference: CRD42014015612. RESULTS: The 12 included articles presented 18 risk prediction models. 7 studies predicted falls among inpatients only and 5 recorded falls in the community. Methodological quality was variable. A C-statistic was reported for 7 models and values ranged from 0.62 to 0.87. Models for use in the inpatient setting most frequently included measures of hemi-inattention, while those predicting community events included falls (or near-falls) history and balance measures most commonly. Only 2 studies reported any form of validation, and none presented a validated model with acceptable performance. CONCLUSIONS: A number of falls-risk prediction models have been developed for use in the acute and subacute stages of stroke. Future research should focus on validating and improving existing models, with reference to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines to ensure quality reporting and expedite clinical implementation.

A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a Bayesian approach.

BACKGROUND: A number of tumour necrosis factor α (TNFα) antagonists (anti-TNFα) are available to treat rheumatoid arthritis. All of these have demonstrated considerable efficacy in placebo controlled trials, but few head-to-head comparisons exist to date. This work's objective is to estimate the relative efficacy among licensed anti-TNFs in patients who have had an inadequate response to methotrexate (MTX). Different outcome measures are used to highlight the advantages of continuous measures in such analyses. METHODS: A systematic review identified randomised controlled trials comparing the efficacy of licensed anti-TNFα agents with placebo at 24 weeks in patients who have had an inadequate response to MTX. Relative efficacy was estimated using Bayesian mixed treatment comparison (MTC) models. Three different outcome measures were used: RR of achieving an American College of Rheumatology (ACR) 20 and ACR50 response and the percentage improvement in Health Assessment Questionnaire (HAQ) score. RESULTS: 16 published trials were included in the analysis. All anti-TNFs show considerably improved efficacy over placebo. The MTC results also provide evidence of some differences in efficacy of the TNFα antagonists. Etanercept appears superior to infliximab and golimumab, and certolizumab to infliximab and adalimumab. ACR results indicate improved efficacy of certolizumab over golimumab. On HAQ analysis, adalimumab, certolizumab, etanercept and golimumab appear superior to infliximab, and etanercept shows improved efficacy compared with adalimumab. CONCLUSIONS: There are differences in efficacy among the TNFα antagonists. In a MTC, a continuous outcome measure has more strength to detect such differences than a binomial outcome measure because of its enhanced sensitivity to change.

Psychological distress as a key component of psychosocial functioning in community-dwelling older people.

OBJECTIVES: To explore the key components representative of measures of psychosocial functioning with a focus on identifying the constituents of psychological distress in an Irish sample of community-dwelling older adults and to examine the relationship between these components and health outcomes such as frailty. METHOD: Cross-sectional observational study at the Technology Research for Independent Living (TRIL) Clinic, a comprehensive geriatric assessment facility in St. James's Hospital, Dublin. In this study, 579 participants were given eight primary assessments (Centre for Epidemiological Studies of Depression, Geriatric Adverse Life Events Scale, Pittsburgh Sleep Quality Index, De Jong-Gierveld Scale, Practitioner Assessment of Network Type, Eysenck Personality Inventory, Hospital Anxiety and Depression Scale, Lubben Social Network Scale) and a broad range of health and demographic secondary assessments. Principal factor analysis identified the core components relating to psychosocial functioning. Following this, the regression factors of these components were correlated with health outcomes. RESULTS: The first of three components identified accounted for 9.08% of the variance and related to a core internal component of psychological distress. The two other components related to external and physiological functioning, specifically social support networks and sleep. Spearman's Rho correlations indicated significant associations of walking speed, age, Berg Balance Scale and living alone with all three components. Additionally, the core component of psychological distress significantly correlated with the Fried Frailty Index, illness co-morbidity, ADL, IADL and nutrition. CONCLUSION: These results characterise the variation in psychosocial functioning in older adults and identifies psychological distress as a core facet of psychosocial functioning which has associations with frailty.

The impact of a revised EQ-5D population scoring on preference-based utility scores in an inflammatory arthritis cohort.

BACKGROUND AND OBJECTIVE: It is well established that there are problems with the EQ-5D. This is due to the original scoring methods used and how negative time trade-off (TTO) values were treated. A revised scoring method has been published. This article applies this to an inflammatory arthritis cohort. The objective is to examine the impact of a revised scoring system for the EQ-5D (UK) TTO on the utility estimates and in the case of rheumatoid arthritis, to explore the impact of using different utility metrics on the incremental cost-effectiveness ratio (ICER) results of an economic model. METHODS: A total of 504 patients with inflammatory arthritis were rescored using revised EQ-5D scoring, which uses an episodic random utility model to deal with negative TTO values. Differences in utility scores were compared and the new mapping coefficients were obtained. These were then used in an economic model to examine the impact on the ICER. RESULTS: In rheumatoid arthritis, the overall change is less for the revised EQ-5D scoring than with the original EQ-5D (TTO) but greater than the SF-6D: EQ-5D UK -0.22 (95% confidence interval [CI] -0.30 to -0.15), revised EQ-5D UK -0.16 (95% CI -0.21 to -0.10) and SF-6D -0.08 (95% CI -0.11 to -0.05). A similar trend is seen in the psoriatic arthritis group. The economic model produced different ICERs, when different utility measures were used; EQ-5D (TTO) €42,402, SF-6D €111,788, and revised EQ-5D (TTO) €57,747. CONCLUSION: In the context of inflammatory arthritis, this article demonstrates that a revised scoring for EQ-5D may have a significant impact on utility estimates and on the output of the economic model.

Percutaneous vascular interventions for acute ischaemic stroke.

BACKGROUND: Most disabling strokes are due to blockage of a large artery in the brain by a blood clot. Prompt removal of the clot with intra-arterial thrombolytic drugs or mechanical devices, or both, can restore blood flow before major brain damage has occurred, leading to improved recovery. However, these so-called percutaneous vascular interventions can cause bleeding in the brain. OBJECTIVES: To assess the safety and efficacy of percutaneous vascular interventions in patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Trials Registers of the Cochrane Stroke Group and Cochrane Peripheral Vascular Diseases Group (last searched May 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 5), MEDLINE (1980 to May 2010), EMBASE (1980 to May 2010) and eight additional databases. We also searched trials registers, screened reference lists, contacted researchers and equipment manufacturers, and handsearched journals and conference proceedings. SELECTION CRITERIA: Randomised, controlled and unconfounded trials of any percutaneous vascular intervention compared with control in patients with definite ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors applied the inclusion criteria, extracted data and assessed trial quality. We obtained both published and unpublished data if available MAIN RESULTS: We included four trials involving 350 patients. Not all trials contributed data to each outcome. The trials tested either intra-arterial urokinase or recombinant pro-urokinase versus an open control. One trial used guidewire-mediated clot disruption in some patients randomised to the intervention group. Most data came from trials that started treatment up to six hours after stroke; one small trial started treatment up to a median of 12.5 hours after stroke. Most data came from trials of middle cerebral artery territory infarction. Compared with non-thrombolytic standard medical treatment, the intervention administered up to six hours after ischaemic stroke significantly increased the proportion of patients with favourable outcome (modified Rankin 0 to 2) three months after stroke (relative risk (RR) 1.47, 95% confidence interval (CI) 1.07 to 2.02). The intervention also significantly increased the risk of symptomatic intracranial haemorrhage within 24 hours of treatment (RR 3.85, 95% CI 0.91 to 16.36). There was no significant heterogeneity between the included trials. AUTHORS' CONCLUSIONS: Overall, intervention results in a significant increase in the proportion of patients with a favourable outcome, despite a significant increase in intracranial haemorrhage. Further trials are needed to confirm or refute these findings and, given the cost and practical difficulties, to establish whether percutaneous techniques are feasible and cost effective in wider clinical practice.

A frailty instrument for primary care: findings from the Survey of Health, Ageing and Retirement in Europe (SHARE).

BACKGROUND: A frailty paradigm would be useful in primary care to identify older people at risk, but appropriate metrics at that level are lacking. We created and validated a simple instrument for frailty screening in Europeans aged ≥50. Our study is based on the first wave of the Survey of Health, Ageing and Retirement in Europe (SHARE, http://www.share-project.org), a large population-based survey conducted in 2004-2005 in twelve European countries. SUBJECTS: SHARE Wave 1 respondents (17,304 females and 13,811 males). MEASURES: five SHARE variables approximating Fried's frailty definition. Analyses (for each gender): 1) estimation of a discreet factor (DFactor) model based on the frailty variables using LatentGOLD. A single DFactor with three ordered levels or latent classes (i.e. non-frail, pre-frail and frail) was modelled; 2) the latent classes were characterised against a biopsychosocial range of Wave 1 variables; 3) the prospective mortality risk (unadjusted and age-adjusted) for each frailty class was established on those subjects with known mortality status at Wave 2 (2007-2008) (11,384 females and 9,163 males); 4) two web-based calculators were created for easy retrieval of a subject's frailty class given any five measurements. RESULTS: Females: the DFactor model included 15,578 cases (standard R2 = 0.61). All five frailty indicators discriminated well (p < 0.001) between the three classes: non-frail (N = 10,420; 66.9%), pre-frail (N = 4,025; 25.8%), and frail (N = 1,133; 7.3%). Relative to the non-frail class, the age-adjusted Odds Ratio (with 95% Confidence Interval) for mortality at Wave 2 was 2.1 (1.4 - 3.0) in the pre-frail and 4.8 (3.1 - 7.4) in the frail. Males: 12,783 cases (standard R2 = 0.61, all frailty indicators had p < 0.001): non-frail (N = 10,517; 82.3%), pre-frail (N = 1,871; 14.6%), and frail (N = 395; 3.1%); age-adjusted OR (95% CI) for mortality: 3.0 (2.3 - 4.0) in the pre-frail, 6.9 (4.7 - 10.2) in the frail. CONCLUSIONS: The SHARE Frailty Instrument has sufficient construct and predictive validity, and is readily and freely accessible via web calculators. To our knowledge, SHARE-FI represents the first European research effort towards a common frailty language at the community level.

Safety and efficacy of IV-TPA for ischaemic stroke in clinical practice--a Bayesian analysis.

BACKGROUND: Observational studies of new treatments in routine practice are clinically important but may be limited by bias. We used a Bayesian approach to interpret and sequentially combine phase 4 studies of IV-TPA within 3 h for acute ischaemic stroke to quantify the cumulative evidence for the efficacy and safety of this therapy in clinical practice. METHODS: Prior probability distributions for favourable outcome (modified Rankin Score, mRS, 0-1), symptomatic intracerebral haemorrhage, and mortality 3 months after IV-TPA were derived from the NINDS trial. Phase 4 studies from observational case series and from regulator-mandated large registries were included. A cumulative analysis was performed to quantify the increase in the total evidence base over time, unadjusted and adjusted for potential bias. RESULTS: The cumulative analysis indicated that IV-TPA <3 h was associated with 3-month favourable outcome in 37.1% (95% credible interval, CrI, 36.1-38.0%, n = 9,578) compared to 26% (95% confidence interval, CI, 19.6-32.9%, n = 165) in placebo-treated patients in NINDS, symptomatic intracranial haemorrhage in 6.6% (95% CrI 5.9-7.4%, n = 10, 834) compared to 6.4% (95% CI 4.0-9.4%) in the NINDS IV-TPA group, and 3-month mortality in 13.6% (95% CrI 12.6-14.8%, n = 9, 901) compared to 20.5% (95% CI 16.0-25.0%, n = 312) in the NINDS placebo group. CONCLUSION: A Bayesian approach provides further confirmatory evidence of the efficacy and safety of IV-TPA for treatment of acute ischaemic stroke within 3 h in diverse clinical practice settings, after adjusting for potential observational bias.

An examination of the relationship between normal range thyrotropin and cardiovascular risk parameters: a study in healthy women.

OBJECTIVE: To investigate the relationship between thyrotropin concentrations within the accepted reference range and cardiovascular risk. DESIGN: Initially, 728 women aged 45-60 years were enrolled over a 12-month period. All participants underwent full cardiovascular assessment, including detailed health questionnaire, sphygomanometry, body mass index (BMI) calculation, fasting glucose and lipid profiling, and measurement of serum thyrotropin concentrations. Patients whose thyrotropin concentrations were within the reference range (0.5-4.5 mU/L) were divided into quartiles (n = 629). The means of cardiovascular risk parameters between the first (n = 158) and fourth (n = 157) quartile were compared. Subsequently, the relationships between thyrotropin concentration and risk parameters for cardiovascular disease were examined. MAIN OUTCOME: This study demonstrates that, within the reference range, increasing thyrotropin concentrations are associated with increasing risk parameters for the development of cardiovascular disease. Subjects with thyrotropin concentrations within the uppermost quartile of the reference range had significantly increased waist circumference, BMI, glucose, triglyceride, and systolic blood pressure measurements when compared to those in the lowermost quartile. Furthermore, significant relationships between thyrotropin and waist circumference, BMI, and fasting glucose and triglycerides concentrations were demonstrated. Finally, independent relationships between thyrotropin and both fasting glucose and triglyceride concentrations were demonstrated. CONCLUSION: Within the reference range, increasing thyrotropin concentrations are associated with increasing cardiovascular risk parameters. Fasting glucose and triglycerides have been shown to be independently associated with thyrotropin concentration.

The effect of the menstrual cycle on electrophysiological and behavioral measures of memory and mood.

Event-related potentials (ERPs) were compared between the menses and ovulatory phase of the menstrual cycle in response to visually presented words, some of which were repeated as part of direct and indirect memory tasks. Twelve spontaneously cycling women were tested during the menses and ovulatory phases. For the direct task, participants had to discriminate between new words and those repeated after a mean of six trials. In the indirect task, subjects were required to discriminate between target and nontarget words. Some of the nontarget words were repeated after a mean of six trials. The ERP repetition effect mean amplitude was significantly greater in response to repeated words at both cycle phases but did not differ across the cycle. P300 amplitude was significantly greater during menses than the ovulatory phase. We conclude that context updating mechanisms as indexed by the P300 are sensitive to cyclic hormonal fluctuations.