Birmingham City Hospital

BACKGROUND: Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism (TE) in patients with atrial fibrillation (AF) are largely derived from risk factors identified from trial cohorts. Thus, many potential risk factors have not been included. METHODS: We refined the 2006 Birmingham/National Institute for Health and Clinical Excellence (NICE) stroke risk stratification schema into a risk factor-based approach by reclassifying and/or incorporating additional new risk factors where relevant. This schema was then compared with existing stroke risk stratification schema in a real-world cohort of patients with AF (n = 1,084) from the Euro Heart Survey for AF. RESULTS: Risk categorization differed widely between the different schemes compared. Patients classified as high risk ranged from 10.2% with the Framingham schema to 75.7% with the Birmingham 2009 schema. The classic CHADS(2) (Congestive heart failure, Hypertension, Age > 75, Diabetes, prior Stroke/transient ischemic attack) schema categorized the largest proportion (61.9%) into the intermediate-risk strata, whereas the Birmingham 2009 schema classified 15.1% into this category. The Birmingham 2009 schema classified only 9.2% as low risk, whereas the Framingham scheme categorized 48.3% as low risk. Calculated C-statistics suggested modest predictive value of all schema for TE. The Birmingham 2009 schema fared marginally better (C-statistic, 0.606) than CHADS(2). However, those classified as low risk by the Birmingham 2009 and NICE schema were truly low risk with no TE events recorded, whereas TE events occurred in 1.4% of low-risk CHADS(2) subjects. When expressed as a scoring system, the Birmingham 2009 schema (CHA(2)DS(2)-VASc acronym) showed an increase in TE rate with increasing scores (P value for trend = .003). CONCLUSIONS: Our novel, simple stroke risk stratification schema, based on a risk factor approach, provides some improvement in predictive value for TE over the CHADS(2) schema, with low event rates in low-risk subjects and the classification of only a small proportion of subjects into the intermediate-risk category. This schema could improve our approach to stroke risk stratification in patients with AF.

Minimum inhibitory concentrations (MICs) are defined as the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation, and minimum bactericidal concentrations (MBCs) as the lowest concentration of antimicrobial that will prevent the growth of an organism after subculture on to antibiotic-free media. MICs are used by diagnostic laboratories mainly to confirm resistance, but most often as a research tool to determine the in vitro activity of new antimicrobials, and data from such studies have been used to determine MIC breakpoints. MBC determinations are undertaken less frequently and their major use has been reserved for isolates from the blood of patients with endocarditis. Standardized methods for determining MICs and MBCs are described in this paper. Like all standardized procedures, the method must be adhered to and may not be adapted by the user. The method gives information on the storage of standard antibiotic powder, preparation of stock antibiotic solutions, media, preparation of inocula, incubation conditions, and reading and interpretation of results. Tables giving expected MIC ranges for control NCTC and ATCC strains are also supplied.

AIMS: We aimed to investigate the prevalence and incidence of atrial fibrillation (AF) in a large European population-based study. METHODS AND RESULTS: The study is part of the Rotterdam study, a population-based prospective cohort study among subjects aged 55 years and above. The prevalence at baseline was assessed in 6808 participants. Incidence of AF was investigated during a mean follow-up period of 6.9 years in 6432 persons. We identified 376 prevalent and 437 incident cases. Overall prevalence was 5.5%, rising from 0.7% in the age group 55-59 years to 17.8% in those aged 85 years and above. The overall incidence rate was 9.9/1000 person-years. The incidence rate in the age group 55-59 years was 1.1/1000 person-years, rose to 20.7/1000 person-years in the age group 80-84 years and stabilized in those aged 85 years and above. Prevalence and incidence were higher in men than in women. The lifetime risk to develop AF at the age of 55 years was 23.8% in men and 22.2% in women. CONCLUSION: In this prospective study in a European population, the prevalence and incidence of AF increased with age and were higher in men than in women. The high lifetime risk to develop AF was similar to North American epidemiological data.

BACKGROUND: inhibitor and aspirin reduces the risk of thrombosis and stroke but increases the risk of bleeding. The effectiveness and safety of anticoagulation with rivaroxaban plus either one or two antiplatelet agents are uncertain. METHODS: inhibitor for 12 months (group 1), very-low-dose rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months (group 2), or standard therapy with a dose-adjusted vitamin K antagonist (once daily) plus DAPT for 1, 6, or 12 months (group 3). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to Thrombolysis in Myocardial Infarction [TIMI] criteria or bleeding requiring medical attention). RESULTS: The rates of clinically significant bleeding were lower in the two groups receiving rivaroxaban than in the group receiving standard therapy (16.8% in group 1, 18.0% in group 2, and 26.7% in group 3; hazard ratio for group 1 vs. group 3, 0.59; 95% confidence interval [CI], 0.47 to 0.76; P<0.001; hazard ratio for group 2 vs. group 3, 0.63; 95% CI, 0.50 to 0.80; P<0.001). The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups (Kaplan-Meier estimates, 6.5% in group 1, 5.6% in group 2, and 6.0% in group 3; P values for all comparisons were nonsignificant). CONCLUSIONS: inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT for 1, 6, or 12 months was associated with a lower rate of clinically significant bleeding than was standard therapy with a vitamin K antagonist plus DAPT for 1, 6, or 12 months. The three groups had similar efficacy rates, although the observed broad confidence intervals diminish the surety of any conclusions regarding efficacy. (Funded by Janssen Scientific Affairs and Bayer Pharmaceuticals; PIONEER AF-PCI ClinicalTrials.gov number, NCT01830543 .).

OBJECTIVES: To evaluate the individual risk factors composing the CHADS(2) (Congestive heart failure, Hypertension, Age ≥ 75 years, Diabetes, previous Stroke) score and the CHA(2)DS(2)-VASc (CHA(2)DS(2)-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism. DESIGN: Registry based cohort study. SETTING: Nationwide data on patients admitted to hospital with atrial fibrillation. Population All patients with atrial fibrillation not treated with vitamin K antagonists in Denmark in the period 1997-2006. MAIN OUTCOME MEASURES: Stroke and thromboembolism. RESULTS: Of 121,280 patients with non-valvular atrial fibrillation, 73,538 (60.6%) fulfilled the study inclusion criteria. In patients at "low risk" (score = 0), the rate of thromboembolism per 100 person years was 1.67 (95% confidence interval 1.47 to 1.89) with CHADS(2) and 0.78 (0.58 to 1.04) with CHA(2)DS(2)-VASc at one year's follow-up. In patients at "intermediate risk" (score = 1), this rate was 4.75 (4.45 to 5.07) with CHADS(2) and 2.01 (1.70 to 2.36) with CHA(2)DS(2)-VASc. The rate of thromboembolism depended on the individual risk factors composing the scores, and both schemes underestimated the risk associated with previous thromboembolic events. When patients were categorised into low, intermediate, and high risk groups, C statistics at 10 years' follow-up were 0.812 (0.796 to 0.827) with CHADS(2) and 0.888 (0.875 to 0.900) with CHA(2)DS(2)-VASc. CONCLUSIONS: The risk associated with a specific risk stratification score depended on the risk factors composing the score. CHA(2)DS(2)-VASc performed better than CHADS(2) in predicting patients at high risk, and those categorised as low risk by CHA(2)DS(2)-VASc were truly at low risk for thromboembolism.

AIMS: Since atrial fibrillation (AF) is associated with increased risks of cardiovascular and cerebrovascular complications, estimations on the number of individuals with AF are relevant to healthcare planning. We aimed to project the number of individuals with AF in the Netherlands and in the European Union from 2000 to 2060. METHODS AND RESULTS: Age- and sex-specific AF prevalence estimates were obtained from the prospective community-based Rotterdam Study. Population projections for the Netherlands and the European Union were obtained from the European Union's statistics office. In the age stratum of 55-59 years, the prevalence of AF was 1.3% in men (95% CI: 0.4-3.6%) and 1.7% in women (95% CI: 0.7-4.0%). The prevalence of AF increased to 24.2% in men (95% CI: 18.5-30.7%), and 16.1% in women (95% CI: 13.1-19.4%), for those >85 years of age. This age- and sex-specific prevalence remained stable during the years of follow-up. Furthermore, we estimate that in the European Union, 8.8 million adults over 55 years had AF in 2010 (95% CI: 6.5-12.3 million). We project that this number will double by 2060 to 17.9 million (95% CI: 13.6-23.7 million) if the age- and sex-specific prevalence remains stable. CONCLUSION: We estimate that from 2010 to 2060, the number of adults 55 years and over with AF in the European Union will more than double. As AF is associated with significant morbidities and mortality, this increasing number of individuals with AF may have major public health implications.

AIMS: The impact of some risk factors for stroke and bleeding, and the value of stroke and bleeding risk scores, in atrial fibrillation (AF), has been debated, as clinical trial cohorts have not adequately tested these. Our objective was to investigate risk factors for stroke and bleeding in AF, and application of the new CHA(2)DS(2)-VASc and HAS-BLED schemes for stroke and bleeding risk assessments, respectively. METHODS AND RESULTS: We used the Swedish Atrial Fibrillation cohort study, a nationwide cohort study of 182 678 subjects with a diagnosis of AF at any Swedish hospital between 1 July 2005 and 31 December 2008, who were prospectively followed for an average of 1.5 years (260 000 years at risk). With the use of the National Swedish Drug Registry, all patients who used an oral anticoagulant anytime during follow-up were identified. Most of the analyses were made on a subset of 90 490 patients who never used anticoagulants. Risk factors for stroke, the composite thromboembolism endpoint (stroke, TIA, or systemic embolism), and bleeding, and the performance of published stroke and bleeding risk stratification schemes were investigated. On multivariable analysis, significant associations were found between the following 'new' risk factors and thromboembolic events; peripheral artery disease [hazard ratio (HR) 1.22 (95% CI 1.12-1.32)], 'vascular disease' [HR 1.14 (1.06-1.23)], prior myocardial infarction [HR 1.09 (1.03-1.15)], and female gender [HR 1.17 (1.11-1.22)]. Previous embolic events, intracranial haemorrhage (ICH), hypertension, diabetes, and renal failure were other independent predictors of the composite thromboembolism endpoint, while thyroid disease (or hyperthyroidism) was not an independent stroke risk factor. C-statistics for the composite thromboembolic endpoint with the CHADS(2) and CHA(2)DS(2)-VASc schemes were 0.66 (0.65-0.66) and 0.67 (0.67-0.68), respectively. On multivariable analysis, age, prior ischaemic stroke or thromboembolism, prior major bleeding events, and hypertension were significant predictors of ICH and major bleeding. Heart failure, diabetes, renal failure, liver disease, anaemia or platelet/coagulation defect, alcohol abuse, and cancer were other significant predictors for major bleeding, but not ICH. The ability for predicting ICH and major bleeding with both bleeding risk schemes (HEMORR(2)HAGES, HAS-BLED) were similar, with c-statistics of ~0.6. CONCLUSION: Several independent risk factors (prior ICH, myocardial infarction, vascular disease, and renal failure) predict ischaemic stroke and/or the composite thromboembolism endpoint in AF, but thyroid disease (or hyperthyroidism) was not an independent risk factor for stroke. There is a better performance for CHA(2)DS(2)-VASc over CHADS(2) schemes for the composite thromboembolism endpoint. While both tested bleeding risk schemes have similar predictive value, the HAS-BLED score has the advantage of simplicity.

There is a lack of consensus among studies on the possible risks of stroke from cigarette smoking; because of this a meta-analysis was conducted. All published data on the association were sought and the relative risk for each study obtained whenever possible. The pooled relative risks were calculated by using estimates of the precision of the individual relative risks to weight their contribution to the meta-analysis. Thirty two separate studies were analysed. The overall relative risk of stroke associated with cigarette smoking was 1.5 (95% confidence interval 1.4 to 1.6). Considerable differences were seen in relative risks among the subtypes: cerebral infarction 1.9, cerebral haemorrhage 0.7, and subarachnoid haemorrhage 2.9. An effect of age on the relative risk was also noted; less than 55 years 2.9, 55-74 years 1.8, and greater than or equal to 75 years 1.1. A dose response between the number of cigarettes smoked and relative risk was noted, and there was a small increased risk in women compared with men. Ex-smokers under the age of 75 seemed to retain an appreciably increased risk of stroke (1.5); for all ages the relative risk in ex-smokers was 1.2. The meta-analysis provides strong evidence of an excess risk of stroke among cigarette smokers. Stroke should therefore be added to the list of diseases related to smoking.

Editor—One of the priorities in the national service framework for coronary heart disease summarised by Mayor1 was “improved use of effective medicines after heart attack—especially aspirin, β blockers, and statins—so that 80-90% of people discharged from hospital after a heart attack will be prescribed these drugs.” This is the recommendation in the executive summary, which taken at face value implies that all three drugs should be prescribed before a patient leaves hospital. In contrast, the recommendation in the main document is that aspirin and β blocker treatment should be started in hospital and statin treatment left for “continuing care.” Statin treatment was not started at the time of infarction in any of the large secondary prevention studies. The shortest times from infarction to inclusion were six months in the Scandinavian simvastatin survival study (4S),2 and three months in the cholesterol and recurrent events (CARE) study3 and the long term intervention with pravastatin in ischaemic disease (LIPID) study.4 Thus the common practice of starting treatment before discharge is not strictly evidence based and statin treatment may be harmful immediately after myocardial infarction. Starting treatment before discharge, however, ensures that the drug is prescribed and simplifies audit. A further recommendation in the main document is “give statins to lower serum cholesterol concentrations either to less than 5 mmol/l (low density lipoprotein cholesterol below 3 mmol/l) or by 30% (whichever is greater).” I find this ambiguous because a percentage change cannot be compared to a concentration, but I presume that the intention is to exclude from treatment those with a total cholesterol concentration under 5 mmol/l on admission. An audit of my own patients with myocardial infarction showed that statin treatment was not appropriate in 22% for this reason. The main document states that patients with acute myocardial infarction should usually receive the recommended interventions unless contraindicated. Surely all patients without intolerance or contradindications should receive aspirin and β blockers. Similarly, all patients with a total cholesterol concentration greater than or equal to 5 mmol/l should be treated with a statin, but they may number less than 80% of the total. Whether the 80-90% standard above applies to all patients or to those without contraindications is not clear. These ambiguities need to be clarified or the results of comparative audit will be meaningless. The criteria for audit should be as rigorous as those for clinical trials.

With the increasing manufacture of expensive systems for the measurement of ambulatory blood pressure there is a need for potential purchasers to be able to satisfy themselves that the systems have been evaluated according to agreed criteria. The British Hypertension Society has, therefore, drawn up a protocol of requirements for the evaluation of these devices. This protocol incorporates many features of the American National Standard for Non-Automated Sphygmomanometers but includes many additional features, such as strict criteria for observer training, interdevice variability testing before and after a month of ambulatory use, and a new system of analysis which permits the test system to be graded. It is recommended that manufacturers of ambulatory blood pressure measuring devices should obtain an unbiased evaluation according to a recognized standard before a device is marketed.

The changes that have been made to the previous version of the recommendations (version 6) are as follows: medium and incubation condition for testing Acinetobacter spp. (Tables 1 and 6); use of cefoxitin as an indicator antibiotic for detecting methicillin/oxacillin/cefoxitin resistance in coagulase-negative staphylococci (Tables 1, 6 and 11); MIC breakpoint for co-trimoxazole based on the trimethoprim concentration in a 1:19 combination with sulfamethoxazole (Tables 7, 10, 11, 12, 15, 16 and 19); advice on the use of azithromycin for the treatment of infections with Salmonella typhi (footnote to Table 7); amendment to the recommendation for cefuroxime for the treatment of infections with Proteus mirabilis (footnote Table 7); MIC and zone diameter breakpoints for Stenotrophomonas maltophilia only (Table 10); MIC breakpoints for daptomycin (Tables 11 and 15); clarification for staphylococci that the neomycin zone diameter breakpoints are for topical use only and differentiate the isolates outside the 'wild-type' population in Table 11; clarification for beta-haemolytic streptococci that the linezolid zone diameter breakpoints relate to an MIC breakpoint of 2 mg/L as no data for the intermediate category are currently available (Table 15); clarification that strains with reduced susceptibility to fluoroquinolones give no zone of inhibition with a 30 microg nalidixic acid disc (Tables 16 and 21); erythromycin is no longer used for therapy of Neisseria gonorrhoeae, but may be tested for epidemiological purposes (Table 17); clarification that the ciprofloxacin zone diameter breakpoint for Neisseria meningitidis relates to the MIC breakpoint of 0.03 mg/L as no data for the intermediate category are currently available; clarification that the ciprofloxacin zone diameter breakpoints for Campylobacter spp. relate to an MIC breakpoint of 0.5 mg/L as no data for the intermediate category are currently available; clarification that for ciprofloxacin and vancomycin zone diameter breakpoints for coryneform organisms relate to an MIC breakpoint of 0.5 and 4 mg/L, respectively, as no data for the intermediate category are currently available; MIC and zone diameter breakpoints for Gram-negative rods isolated from urinary tract infections have been expanded to include Klebsiella spp.; and a definition of coliforms is also included (Table 26).

Despite increased global aid for development and health – from 5.6 billion United States dollars (US$) in 1990 to US$ 21.8 billion in 20071 – donors and wider society have become sceptical about the benefits of this aid. This is reflected in a call recently issued by the Bill and Melinda Gates Foundation’s Grand Challenges Explorations programme for innovative ways to better convey to the public the benefits of global aid.2 Poor tracking of programme outcomes and of funding for global health by both donors and recipients, a problem widely recognized, contributes to the growing doubts.3-4 A United Nations High Level Meeting (UNHLM) held in September 2011 focussed attention on noncommunicable diseases (NCDs).5 Almost two thirds of all deaths in the world are caused by NCDs, many of which are preventable,6 yet NCDs have received relatively little attention and funding.7 They were excluded from the Millennium Development Goals.8 Although the lack of measurable “hard” outcomes (e.g. targets for reduction in mortality or increased access to medicines) emanating from the UNHLM disappointed many, media coverage of the meeting undoubtedly put the spotlight on NCDs. Encouragingly, the UNHLM revealed singularity of purpose across the global health community.5 Participants agreed that identifying common NCD risk factors and integrating approaches for NCD control are crucial, but saw as the greatest challenge the implementation of broader health system changes in low- and low-middle income countries to produce more sustainable, long-term effects.5-6 Failure to learn from the past and to scrutinize the factors currently hindering efforts to control communicable diseases and improve maternal and child health, including non-transparent tracking of programme funding and finances, will undermine efforts to combat NCDs. Better metrics and improved monitoring and reporting of health outcomes, funding and finances will facilitate programme success. NCD control and monitoring of programme funding should occur at the country and regional levels, since insufficient data on global health financing makes comprehensive auditing of funds nearly impossible. On a global scale, reported increases in health funding may be overblown and there may be no way to know whether the funds really reach the intended recipients.3 The shaky economy may lead to reduced health aid for several countries and create the need for improved monitoring and efficiency.3,4 There are also potential conflicts of interest among the many parties involved in the multi-billion dollar industry that global health represents.4 When Sridhar & Batniji tracked funding from the major global health donors, such as The World Bank and the Global Fund, they found that “the pluralism of global health institutions and the informal alliances on which power in global health rests make a unified and fully coordinated health system highly unlikely”.3 Inadequate coordination and bureaucracy have plagued global health aid and the NCD community must take heed. Lessons can be more widely shared and previous mistakes more easily avoided through coordination of methods and data across countries. New efforts to control NCDs should be worked into the existing health-care infrastructure and global programmes.7 Transparency in funding, programme delivery and outcome data, as well as local ownership, will enable improved monitoring and a global health architecture actively prepared for change instead of passively reactive to it. The data collected by donors and aid recipients on the global burden of disease and on financing requirements must be standardized to enable monitoring and comparisons across health programmes and systems. Common data gathering mechanisms for all diseases and global health programmes, as well as improved monitoring of the data furnished by both funders and recipients, will ensure better tracking of finances, resources and, ultimately, outcomes. This will in turn heighten accountability and responsibility on all sides. Country-level ownership of NCD programmes will make governments and local players more inclined to “buy into” policy-making and planning and will put financial and outcome data within the public’s reach. Despite a call for “a quantitative, scientific framework to guide health-care scale-up in developing countries”,9 the scale-up of NCD prevention and treatment programmes is hampered by lack of measurable targets and disagreement on the policies and interventions required. Evidence-based global health interventions relevant to low- and low-middle income settings sometimes conflicts with quick, pragmatic policy-making.10 New research is necessary to design the best evidence-based policies for the control of NCDs, but a thorough understanding of the policies’ sociopolitical and cultural ramifications should underlie their design and implementation.10 Importantly, inadequate tracking and non-transparency of NCD programme finances, funding and outcomes detract from programme acceptability in social and political spheres. In summary, reliable monitoring of funding is required, since without it, the empirical research and data to shape NCD policy-making and scale up NCD programmes will be shaky from the outset. The importance of studying the lessons learnt from yesterday’s and today’s global health programmes cannot be over-stressed. Finally, intra- and inter-national cooperation is fundamental when designing and implementing NCD-related policies, and although both donors and recipients are responsible for tracking funding, neutral parties such as the World Health Organization have a key role to play.

A hypercoagulable or prothrombotic state of malignancy occurs due to the ability of tumor cells to activate the coagulation system. It has been estimated that hypercoagulation accounts for a significant percentage of mortality and morbidity in cancer patients. Prothrombotic factors in cancer include the ability of tumor cells to produce and secrete procoagulant/fibrinolytic substances and inflammatory cytokines, and the physical interaction between tumor cell and blood (monocytes, platelets, neutrophils) or vascular cells. Other mechanisms of thrombus promotion in malignancy include nonspecific factors such as the generation of acute phase reactants and necrosis (i.e., inflammation), abnormal protein metabolism (i.e., paraproteinemia), and hemodynamic compromise (i.e., stasis). In addition, anticancer therapy (i.e., surgery/chemotherapy/hormone therapy) may significantly increase the risk of thromboembolic events by similar mechanisms, e.g., procoagulant release, endothelial damage, or stimulation of tissue factor production by host cells. However, not all of the mechanisms for the production of a hypercoagulable state of cancer are entirely understood. In this review, we attempt to describe what is currently accepted about the pathophysiology of the hypercoagulable state of cancer. We also discuss whether or not to screen patients with idiopathic deep venous thrombosis for an underlying malignancy, and whether this would be beneficial to patients. It is hoped that a better understanding of these mechanisms will ultimately lead to the development of more targeted treatment to prevent thromboembolic complications in cancer patients. It is also hoped that antithrombotic strategies may also have a positive effect on the process of tumor growth and dissemination.

Using a silver staining technique, nucleolar organizer region-associated proteins (Ag-NORs) have been studied in paraffin sections of 90 non-Hodgkin's lymphomas, five palatine tonsils and five 'reactive' lymph nodes. The method was readily applicable to these preparations and the Ag-NORs were enumerated with ease. A significant difference was found between the numbers of Ag-NORs in the nuclei of low-grade lymphomas (from a mean of 1 to 1.5 per nucleus) and those of high-grade lymphomas (a mean of 4.4 to 6.8 per nucleus). The Ag-NOR regions were often observed in nuclei in areas where nucleoli themselves were not visible. It is suggested that this method, previously largely the province of the cytogeneticist, should find widespread applications in the field of tumour histopathology.

International audience

There is mounting evidence to support the influence of inflammation in the pathogenesis of atrial fibrillation (AF). Indeed, AF is associated with increased levels of known inflammatory markers, even after adjustment for confounding factors. The renin-angiotensin-aldosterone system (RAAS) appears to play a key role in this process. Atrial biopsies from patients with AF have also confirmed the presence of inflammation. Furthermore, there is preliminary evidence to support a number of drug therapies that have the potential to reduce the clinical burden of AF. In this review, we present an overview of the evidence supporting a link between inflammation and AF, and some of the drug therapies, such as the angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, steroids, fish oils, and vitamin C, that might be efficacious in the prevention of AF by modulating inflammatory pathways.

BACKGROUND/AIMS: Uveitis is a major cause of visual morbidity in the working age group. The authors investigated the duration, degree, and causes of visual loss in uveitis patients with the aim of better defining the visual morbidity and identifying potential risk factors. METHODS: A retrospective, non-interventional, observational survey of 315 consecutive patients attending a tertiary referral uveitis service. RESULTS: The mean duration of follow up was 36.7 months. Reduced vision (< or =6/18) was found in 220/315 (69.95%) of the patients with a subset of 120 patients having vision < or =6/60. Unilateral visual loss occurred in 109 (49.54%), while 111 (50.45%) had bilateral loss. The mean duration of visual loss was 21 months. Of the 148 patients with pan-uveitis, 125 (84.45%) had reduced vision, with 66 (53%) having vision < or =6/60. Main causes of visual loss were cystoid macular oedema (CMO) (59/220, 26.8%), cataract (39/220, 17.7%), and combination of CMO and cataract (44/220, 20%). The following were predictive of a poorer visual prognosis: pan-uveitis (p = 0.0005), bilateral inflammation (p = 0.0005), increasing duration of reduced vision (p = 0.0005), an Indian or Pakistani ethnic background (p = 0.004), and increasing patient age (p = 0.02). CONCLUSION: Prolonged visual loss occurred in two thirds of uveitis patients, with 70 (22%) patients meeting the criteria for legal blindness at some point in their follow up. Older patients with bilateral inflammation and an increasing duration of reduced vision are at the greatest risk of severe visual loss (< or =6/60). CMO and cataract were responsible for visual loss in 64.5% of patients.

.Whilst there is increasing realization that inappropri-ate platelet activation plays a prime role in the increas-ing heart disease burden of society, there is still nogenerally accepted ideal measure of platelet activationthat would indicate a state of ‘high risk’. There is also aneed for the objective assessment of the relative effec-tiveness and safety of antiplatelet agents. Furthermore,despite the great success of aspirin, it is clearly far fromperfect

The adhesion molecule P-selectin (CD62P) is of interest because of its role in modulating interactions between blood cells and the endothelium, and also because of the possible use of the soluble form as a plasma predictor of adverse cardiovascular events. Although present on the external cell surface of both activated endothelium and activated platelets, it now seems clear that most, if not all, of the measured plasma P-selectin is of platelet origin. P-selectin is partially responsible for the adhesion of certain leukocytes and platelets to the endothelium. Animal models have also shown the important role of P-selectin in the process of atherogenesis. For example, increased P-selectin expression has been demonstrated on active atherosclerotic plaques; in contrast, fibrotic inactive plaques lack P-selectin expression, and animals lacking P-selectin have a decreased tendency to form atherosclerotic plaques. Increased levels of soluble P-selectin in the plasma have also been demonstrated in a variety of cardiovascular disorders, including coronary artery disease, hypertension and atrial fibrillation, with some relationship to prognosis. The objective of this review is to provide an overview of the current literature on this molecule and thus present a concise view of its potential in dissecting the pathophysiology of atherosclerosis. In doing so we shall focus primarily on human biology but will note a small number of excellent lessons provided by non-human work.

The trends in treatment and outcome of 13,560 patients with pancreatic cancer, and in incidence of the disease, in the West Midlands health region were determined between 1957 and 1986 using data from the West Midlands Region Cancer Registry. Patients were divided into those diagnosed in the first 20 years (1957-1976, n = 7888) and the most recent 10 years (1977-1986, n = 5672). The disease was more common in men and the incidence increased up to 1970 after which it levelled off. In the 1977-1986 period a lower proportion of patients had laparotomy alone (825 (14.5 per cent) versus 1552 (19.7 per cent)), a similar proportion had bypass surgery (2010 (35.4 per cent) versus 2760 (35.0 per cent)), while a greater proportion had supportive care (2710 (47.8 per cent) versus 3368 (42.7 per cent)) but the resection rates were the same (145 (2.6 per cent) versus 208 (2.6 per cent)). The 30-day mortality rates between the two periods improved for resection (40 (27.6 per cent) versus 94 (45.2 per cent)), bypass surgery (436 (21.7 percent) versus 691 (25.0 per cent)) and laparotomy (372 (45.1 per cent) versus 873 (56.3 per cent)). The 12-month survival rate for bypass did not significantly differ during the study (14.9 per cent versus 12.4 per cent) but there was a significant improvement in the 5-year survival for resection (9.7 per cent versus 2.6 per cent, P < 0.015). The resection rates were low and 30-day mortality rates for surgery were high compared with those of other published series.