Outcome after conservative management or intervention for unruptured brain arteriovenous malformations

Neurosurger

Transcutaneous electrical nerve stimulation for the management of tennis elbow: a pragmatic randomized controlled trial: the TATE trial (ISRCTN 87141084)

<p>Abstract</p> <p>Background</p> <p>Tennis elbow is a common and often extremely painful musculoskeletal condition, which has considerable impact on individuals as well as economic implications for healthcare utilization and absence from work. Many management strategies have been studied in clinical trials. Whilst corticosteroid injections offer short term pain relief, this treatment is unpleasant and is used with caution due to an associated high risk of pain recurrence in the long term. Systematic reviews conclude that there is no clear and effective treatment for symptoms of pain in the first 6 weeks of the condition. There is a clear need for an intervention that is acceptable to patients and provides them with effective short-term pain relief without increasing the risk of recurrence. Transcutaneous electrical nerve stimulation (TENS) is an inexpensive, non-invasive, non-pharmacological form of analgesia that is commonly used in the treatment of pain. TENS has very few contraindications and is simple to apply. It also benefits from being patient controlled, thereby promoting self-management. This study aims to assess the effectiveness, in terms of pain relief, and cost-effectiveness of a self-management package of treatment that includes TENS.</p> <p>Methods/Design</p> <p>The design of the study will be a two-group pragmatic randomized clinical trial. 240 participants aged 18 years and over with tennis elbow will be recruited from 20-30 GP practices in Staffordshire, UK. Participants are to be randomized on a 1:1 basis to receive either primary care management (standard GP consultation, medication, advice and education) or primary care management with the addition of TENS, over 6 weeks. Our primary outcome measure is average intensity of elbow pain in the past 24 hours (0-10 point numerical rating scale) at 6 weeks. Secondary outcomes include pain and limitation of function, global assessment of change, days of sick leave, illness perceptions, and overall health status. A cost-effectiveness analysis will also be performed. Patient adherence and satisfaction data will be collected at 6 weeks, 6 months and 12 months by postal questionnaire. A diary will also be completed for the first 2 weeks of treatment. Clinical effectiveness and cost-effectiveness analyses will be carried out using an intention-to-treat approach as the primary analysis.</p> <p>Discussion</p> <p>This paper presents detail on the rationale, design, methods and operational aspects of the trial.</p> <p>Trial registration</p> <p>Current Controlled Trials. ISRCTN87141084</p

Ir-LBP, an Ixodes ricinus Tick Salivary LTB4-Binding Lipocalin, Interferes with Host Neutrophil Function

BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins that can interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: We previously identified 14 new lipocalin genes in the tick Ixodes ricinus. One of them codes for a protein that specifically binds leukotriene B4 with a very high affinity (Kd: +/-1 nM), similar to that of the neutrophil transmembrane receptor BLT1. By in silico approaches, we modeled the 3D structure of the protein and the binding of LTB4 into the ligand pocket. This protein, called Ir-LBP, inhibits neutrophil chemotaxis in vitro and delays LTB4-induced apoptosis. Ir-LBP also inhibits the host inflammatory response in vivo by decreasing the number and activation of neutrophils located at the tick bite site. Thus, Ir-LBP participates in the tick's ability to interfere with proper neutrophil function in inflammation. CONCLUSIONS/SIGNIFICANCE: These elements suggest that Ir-LBP is a "scavenger" of LTB4, which, in combination with other factors, such as histamine-binding proteins or proteins inhibiting the classical or alternative complement pathways, permits the tick to properly manage its blood meal. Moreover, with regard to its properties, Ir-LBP could possibly be used as a therapeutic tool for illnesses associated with an increased LTB4 production.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Incidental Findings on Brain MR Imaging in Older Community-Dwelling Subjects Are Common but Serious Medical Consequences Are Rare:A Cohort Study

Incidental findings in neuroimaging occur in 3% of volunteers. Most data come from young subjects. Data on their occurrence in older subjects and their medical, lifestyle and financial consequences are lacking. We determined the prevalence and medical consequences of incidental findings found in community-dwelling older subjects on brain magnetic resonance imaging.Prospective cohort observational study.Single centre study with input from secondary care.Lothian Birth Cohort 1936, a study of cognitive ageing.Incidental findings identified by two consultant neuroradiologists on structural brain magnetic resonance imaging at age 73 years; resulting medical referrals and interventions.PREVALENCE OF INCIDENTAL FINDINGS BY INDIVIDUAL CATEGORIES: neoplasms, cysts, vascular lesions, developmental, ear, nose or throat anomalies, by intra- and extracranial location; visual rating of white matter hyperintensities and brain atrophy.There were 281 incidental findings in 223 (32%) of 700 subjects, including 14 intra- or extracranial neoplasms (2%), 15 intracranial vascular anomalies (2%), and 137 infarcts or haemorrhages (20%). Additionally, 153 had moderate/severe deep white matter hyperintensities (22%) and 176 had cerebral atrophy at, or above, the upper limit of normal (25%) compared with a normative population template. The incidental findings were unrelated to white matter hyperintensities or atrophy; about a third of subjects had both incidental findings and moderate or severe WMH and a quarter had incidental findings and atrophy. The incidental findings resulted in one urgent and nine non-urgent referrals for further medical assessment, but ultimately in no new treatments.In community-dwelling older subjects, incidental findings, including white matter hyperintensities and atrophy, were common. However, many findings were not of medical importance and, in this age group, most did not result in further assessment and none in change of treatment

Change in stroke incidence, mortality, case-fatality, severity, and risk factors in Oxfordshire, UK from 1981 to 2004 (Oxford Vascular Study)

Background The incidence of stroke is predicted to rise because of the rapidly ageing population. However, over the past two decades, findings of randomised trials have identified several interventions that are effective in prevention of stroke. Reliable data on time-trends in stroke incidence, major risk factors, and use of preventive treatments in an ageing population are required to ascertain whether implementation of preventive strategies can offset the predicted rise in stroke incidence. We aimed to obtain these data. Methods We ascertained changes in incidence of transient ischaemic attack and stroke, risk factors, and premorbid use of preventive treatments from 1981–84 (Oxford Community Stroke Project; OCSP) to 2002–04 (Oxford Vascular Study; OXVASC). Findings Of 476 patients with transient ischaemic attacks or strokes in OXVASC, 262 strokes and 93 transient ischaemic attacks were incident events. Despite more complete case-ascertainment than in OCSP, age-adjusted and sex-adjusted incidence of first-ever stroke fell by 29% (relative incidence 0·71, 95% CI 0·61–0·83, p=0·0002). Incidence declined by more than 50% for primary intracerebral haemorrhage (0·47, 0·27–0·83, p=0·01) but was unchanged for subarachnoid haemorrhage (0·83, 0·44–1·57, p=0·57). Thus, although 28% more incident strokes (366 vs 286) were expected in OXVASC due to demographic change alone (33% increase in those aged 75 or older), the observed number fell (262 vs 286). Major reductions were recorded in mortality rates for incident stroke (0.63, 0.44–0.90, p=0.02) and in incidence of disabling or fatal stroke (0·60, 0·50–0·73, p<0·0001), but no change was seen in case-fatality due to incident stroke (17·2% vs 17·8%; age and sex adjusted relative risk 0·85, 95% CI 0·57-1·28, p=0·45). Comparison of premorbid risk factors revealed substantial reductions in the proportion of smokers, mean total cholesterol, and mean systolic and diastolic blood pressures and major increases in premorbid treatment with antiplatelet, lipid-lowering, and blood pressure lowering drugs (all p<0.0001). Interpretation The age-specific incidence of major stroke in Oxfordshire has fallen by 40% over the past 20 years in association with increased use of preventive treatments and major reductions in premorbid risk factors

Learning from OCTET - Exploring the Acceptability of Clinical Trials Management Methods

Background Conducting research can be time consuming, difficult and challenging. Guidance and pragmatic advice focusing on randomised controlled trial conduct are available but do not necessarily constitute comprehensive guidance. A successful trial is one that recruits to time and target and collects high quality data within the originally agreed budget. Standardised trial management tools have outlined key project management elements for a successful trial as a method of ensuring good practice in research trials: initiation, planning, execution, monitoring, and closure. Lessons are also frequently learnt during the development and conduct of trialsbut rarely shared for the benefit of others. For the wider research team, the key focus will always be on the execution and delivery of a study. The aim of this study was to evaluate the acceptability of clinical trials management methods, focusing on study execution and monitoring, as implemented in the National Institute for Health Research Health Technology Assessment Programme funded Obsessive Compulsive Treatment Efficacy Trial (OCTET). Methods Workshops, questionnaires and semi-structured interviews were used to explore acceptability of trial management methods with members of the OCTET Trial research team. Nine members participated in the focus group, 10 completed a questionnaire and 20 were interviewed as part of qualitative work for the main OCTET study. Data was collected and analysed using thematic analysis. Results Six key themes were identified: support; communication; processes; resources; training and ethos. Clear and open communication,enthusiasm and accessibility of the trial managers and Chief Investigator were consistently noted as an important facet of the successful running of the trial. Clear resources and training materials were also found to be crucial in helping staff to work within the trial setting. Constructive suggestions were also made for improvement of these resources, for example including both checklists and flowcharts within trial processes. Conclusion Organisation, openness, and positivity are crucial for executing a trial successfully, whilst clear and focused processes and resources are essential in monitoring and controlling the trial progress. Although derived from a single study, these findings are likely to be applicable to the successful conduct of all trials. Trial managers should consider developing these elements when setting up a study. Trial Registration: Clinical Trial Registry: ISRCTN73535163, Date of Registration: 05.04.2011, Prospective registration. Key Words: Randomised controlled trial, project management, trial management, qualitativ

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study

Background: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. Methods: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. Findings: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75–84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio &gt;1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28–4·7) and 7·0% (1·2–13·0). Interpretation: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. Funding: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network