Showing papers by "St Thomas' Hospital published in 2009"

Echocardiographic Assessment of Valve Stenosis: EAE/ASE Recommendations for Clinical Practice

Abstract: Abbreviations: AR aortic regurgitation, AS aortic stenosis, AVA aortic valve area, CSA cross sectional area, CWD continuous wave Doppler, D diameter, HOCM hypertrophic obstructive cardiomyopathy, LV left ventricle, LVOT left ventricular outflow tract, MR mitral regurgitation, MS mitral stenosis, MVA mitral valve area, DP pressure gradient, RV right ventricle, RVOT right ventricular outflow tract, SV stroke volume, TEE transesophageal echocardiography, T1/2 pressure half-time, TR tricuspid regurgitation, TS tricuspid stenosis, V velocity, VSD ventricular septal defect, VTI velocity time integral

Recommendations for Evaluation of Prosthetic Valves With Echocardiography and Doppler Ultrasound. A Report From the American Society of Echocardiography's Guidelines and Standards Committee and the Task Force on Prosthetic Valves, Developed in Conjunction With the American College of Cardiology Cardiovascular Imaging Committee, Cardiac Imaging Committee of the American Heart Association

Abstract: A Report From the American Society of Echocardiography’s Guidelines and Standards Committee and the Task Force on Prosthetic Valves, Developed in Conjunction With the American College of Cardiology Cardiovascular Imaging Committee, Cardiac Imaging Committee of the American Heart Association, the European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography and the Canadian Society of Echocardiography, Endorsed by the American College of Cardiology Foundation, American Heart Association, European Association of Echocardiography, a registered branch of the European Society of Cardiology, the Japanese Society of Echocardiography, and Canadian Society of Echocardiography

Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice

Abstract: AR = aortic regurgitation AS = aortic stenosis AVA = aortic valve area CSA = cross sectional area CWD = continuous wave Doppler D = diameter HOCM = hypertrophic obstructive cardiomyopathy LV = left ventricle LVOT = left ventricular outflow tract MR = mitral regurgitation MS = mitral stenosis MVA = mitral valve area ΔP = pressure gradient RV = right ventricle RVOT = right ventricular outflow tract SV = stroke volume TEE = transesophageal echocardiography T 1/2 = pressure half-time TR = tricuspid regurgitation TS = tricuspid stenosis V = velocity VSD = ventricular septal defect VTI =velocity time integral Valve stenosis is a common heart disorder and an important cause of cardiovascular morbidity and mortality. Echocardiography has become the key tool for the diagnosis and evaluation of valve disease, and is the primary non-invasive imaging method for valve stenosis assessment. Clinical decision-making is based on echocardiographic assessment of the severity of valve stenosis, so it is essential that standards be adopted to maintain accuracy and consistency across echocardiographic laboratories when assessing and reporting valve stenosis. The aim of this paper was to detail the recommended approach to the echocardiographic evaluation of valve stenosis, including recommendations for specific measures of stenosis severity, details of data acquisition and measurement, and grading of severity. These recommendations are based on the scientific literature and on the consensus of a panel of experts. This document discusses a number of proposed methods for evaluation of stenosis severity. On the basis of a comprehensive literature review and expert consensus, these methods were categorized for clinical practice as:

Dissociation of Aortic Pulse Wave Velocity With Risk Factors for Cardiovascular Disease Other Than Hypertension: A Systematic Review

Abstract: Carotid-femoral pulse wave velocity (cfPWV), a measure of large artery stiffness, is an important predictor of cardiovascular events. This has been attributed to it being an integrative measure of the impact of cardiovascular risk factors on the arterial wall. Pulse wave velocity is strongly associated with age and blood pressure. However, findings with regard to its relation with other risk factors have been inconsistent. We performed a systematic review of cross-sectional published literature reporting independent associations of cfPWV in multivariable regression models. Articles were selected from a PubMed search using a prespecified search strategy. Studies were included if they did the following: (1) measured cfPWV; (2) reported on associations with cfPWV from regression models; and (3) considered age and blood pressure in the model. From 637 retrieved articles, 65 met our inclusion criteria, and 12 studies were included from reference searches. Age and blood pressure were consistently independently associated with cfPWV (91% and 90% of studies, respectively). Diabetes mellitus was associated with cfPWV in 52% studies, but the strength of the association was low. The majority of studies found no independent association between cfPWV and sex, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, smoking, or body mass index. The contribution of risk factors other than age and blood pressure to cfPWV is, thus, small or insignificant. The prognostic value of cfPWV may relate to a process of arterial ageing unrelated to classic risk factors other than hypertension.

Risk factors for delayed presentation and referral of symptomatic cancer: evidence for common cancers

Abstract: It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation. We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these. Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results. Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately.

The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins.

Abstract: Population based studies have demonstrated that having a first degree relative with a hip fracture is predictive of future hip fractures. Postmenopausal bone mineral density (BMD), ultrasound of calcaneus and hip axis length are associated with hip fracture, with the association for ultrasound and hip axis length being independent of BMD. The aim of this study was to determine the genetic component of these three important risk factors. We performed a classical twin study using 500 normal female twins, 128 identical and 122 non-identical pairs, aged 50 to 70 years. We measured bone mineral density at multiple sites, hip axis length (distance from the inner rim of the acetabulum to the greater trochanter), broadband ultrasound attenuation and velocity of sound of the calcaneus. Bone density had a strong genetic component at all sites with estimates of heritability ranging from 0.46 to 0.84. Hip axis length and velocity of sound had major genetic components with estimates of 0.62 and 0.61 respectively, which remained virtually unchanged after adjustment for bone mineral density. Broadband ultrasound attenuation had a moderate genetic component with an estimate of 0.53, which was reduced further to 0.45 after adjustment for BMD. In summary, all three bone measurements, which are independently associated with hip fracture, are independently heritable. This study suggests that a combination of different genetic factors acting on the structure, dimensions and density of bone may explain the importance of family history as a risk factor for hip fracture.

Diagnosis of recurrent laryngeal nerve palsy after thyroidectomy: a systematic review.

Abstract: Summary Background: Recurrent laryngeal nerve palsy (RLNP) is a recognised possible complication after thyroid surgery. It may present with a variety of symptoms, such as voice change and respiratory symptoms. However, it may remain undetected and the true incidence may be under-reported. The aim of this study was to determine the reported incidence of temporary and permanent palsy after thyroid surgery using different vocal assessment methods. Methods: A Medline search was performed. A systematic review was undertaken which included 27 articles and 25,000 patients. Results: The average incidence of temporary RLNP after thyroid operations is 9.8% and the incidence of permanent RLNP is 2.3%. The RLNP rate varied according to the method of examining the larynx and ranged from 26% to 2.3%. Most of the reviewed studies recommend a follow-up period up to 1 year to assess and evaluate RLNP. Conclusion: Our study has identified that different methods are used to diagnose RNLP and that a wide variety of reported RLNP rates exist. We propose establishment of a ‘gold standard’ for assessing the voice after thyroidectomy to reduce reporting bias.

Pathogenesis of chronic urticaria

Abstract: Summary Chronic urticaria is defined as the presence of urticaria (hives) for at least 6 weeks with the assumption that it occurs daily or close to it. If we eliminate physical urticarias and urticarial vasculitis from consideration, the remainder can be divided into autoimmune chronic urticaria (45%) and idiopathic chronic urticaria (55%). The autoimmune subgroup is associated with the IgG anti-IgE receptor α subunit in 35–40% of patients and IgG anti-IgE in an additional 5–10%. These autoantibodies have been shown to activate blood basophils and cutaneous mast cells in vitro with augmentation of basophil activation by complement and release of C5a, in particular. Binding methods (immunoblot and ELISA) yield positives in many autoimmune diseases as well as occasional normal subjects or patients with other forms of urticaria but most such sera are non-functional. Activation of basophils or mast cells causing histamine release is quite specific for chronic urticaria and defines the autoimmune subgroup. Although pathogenicity is not formally proven, the antibodies cause wealing upon intradermal injection, and removal of the autoantibody leads to remission. A cellular infiltrate is seen to be characterized by mast cell degranulation and infiltration of CD4+ T lymphocytes, monocytes, neutrophils, eosinophils, and basophils. The intensity of the infiltrate and clinical severity of the disease (including accompanying angio-oedema) is more severe in the autoimmune subpopulation. This latter group also has a higher evidence of human leucocyte antigen DR alleles associated with autoimmunity and a 25% incidence of antithyroid antibodies with diagnosed hypothyroidism in some. Hypo-responsiveness of patients' basophils to anti-IgE and hyperresponsiveness to serum defines another subpopulation (at least 50%) that overlaps the idiopathic and autoimmune subgroups. Hypo-responsiveness to anti-IgE has been shown to be associated with elevated levels of cytoplasmic phosphatases that inhibit degranulation. Reversal of the abnormality is seen with disease remission. Further work will be needed to distinguish whether this is a cause or a consequence of persistent urticaria and to further assess the relationship (or lack thereof) of altered responsiveness (decreased or increased) with the presence or absence of activating autoantibodies.

Public awareness of cancer in Britain: a population-based survey of adults

Abstract: To assess public awareness of cancer warning signs, anticipated delay and perceived barriers to seeking medical advice in the British population. We carried out a population-based survey using face-to-face, computer-assisted interviews to administer the cancer awareness measure (CAM), a newly developed, validated measure of cancer awareness. The sample included 2216 adults (970 males and 1246 females) recruited as part of the Office for National Statistics Opinions Survey using stratified probability sampling. Awareness of cancer warning signs was low when open-ended (recall) questions were used and higher with closed (recognition) questions; but on either measure, awareness was lower in those who were male, younger, and from lower socio-economic status (SES) groups or ethnic minorities. The most commonly endorsed barriers to help seeking were difficulty making an appointment, worry about wasting the doctor's time and worry about what would be found. Emotional barriers were more prominent in lower SES groups and practical barriers (e.g. too busy) more prominent in higher SES groups. Anticipated delay was lower in ethnic minority and lower SES groups. In multivariate analysis, higher symptom awareness was associated with lower anticipated delay, and more barriers with greater anticipated delay. A combination of public education about symptoms and empowerment to seek medical advice, as well as support at primary care level, could enhance early presentation and improve cancer outcomes.

2009 EANM parathyroid guidelines

Abstract: The present guidelines were issued by the Parathyroid Task Group of the European Association of Nuclear Medicine. The main focus was imaging of primary hyperparathyroidism. Dual-tracer and single-tracer parathyroid scintigraphy protocols were discussed as well as the various modalities of image acquisition. Primary hyperparathyroidism is an endocrine disorder with high prevalence, typically caused by a solitary parathyroid adenoma, less frequently (about 15%) by multiple parathyroid gland disease (MGD) and rarely (1%) by parathyroid carcinoma. Patients with MGD may have a double adenoma or hyperplasia of three or all four parathyroid glands. Conventional surgery has consisted in routine bilateral neck exploration. The current trend is toward minimally invasive surgery. In this new era, the success of targeted parathyroid surgery depends not only on an experienced surgeon, but also on a sensitive and accurate imaging technique. Recognizing MGD is the major challenge for pre-operative imaging, in order to not direct a patient towards inappropriate minimal surgery. Scintigraphy should also report on thyroid nodules that may cause confusion with a parathyroid adenoma or require concurrent surgical resection. The two main reasons for failed surgery are ectopic glands and undetected MGD. Imaging is mandatory before re-operation, and scintigraphy results should be confirmed with a second imaging technique (usually US for a neck focus, CT or MRI for a mediastinal focus). Hybrid SPECT/CT instruments should be most helpful in this setting. SPECT/CT has a major role for obtaining anatomical details on ectopic foci. However, its use as a routine procedure before target surgery is still investigational. Preliminary data suggest that SPECT/CT has lower sensitivity in the neck area compared to pinhole imaging. Additional radiation to the patient should also be considered. The guidelines also discuss aspects related to radio-guided surgery of hyperparathyroidism and imaging of chronic kidney disease patients with secondary hyperparathyroidism.

Long-term outcomes from the English national comparative audit of surgery for nasal polyposis and chronic rhinosinusitis.

Abstract: Objectives/Hypothesis: We present a large, prospective cohort study following patients who underwent surgery for chronic rhinosinusitis (CRS), with or without nasal polyps, in hospitals in England and Wales. Five-year outcomes will be reported, and we will revisit a previous analysis of the effectiveness of extensive surgery in the treatment of nasal polyposis. Methods: Baseline clinical data was collected for 3,128 patients undergoing surgery for CRS (with or without nasal polyps). Outcomes are described in terms of the proportion of patients undergoing revision surgery and mean Sino-Nasal Outcome Test (SNOT-22) scores. Results: A total of 1,459 (52.2%) patients responded to 5-year follow-up. Revision surgery rates increased at each time point. Of the patients responding, 279 patients (19.1%) had undergone further surgery during the 5 years since their original operation. Of the patients with polyps, 20.6% had undergone revision compared to 15.5% of patients with CRS alone. The mean SNOT-22 score for all patients was 28.2 (standard deviation [SD] = 22.4) at 5 years after surgery. This is remarkably similar to the results observed at 3 months (25.5), 12 months (27.7), and 36 months (27.7), and represents a 14-point improvement over the baseline score. Polyp patients report better SNOT-22 scores at 5 years (mean = 26.2; SD = 21.6) than patients with CRS alone (mean = 33.3; SD = 23.7). Of the patients who had originally received simple polypectomy, 21.2% had undergone revision surgery compared to 20.0% of patients who had also received additional sinus surgery. The difference in unadjusted revision surgery rates is not statistically significant (χ2 = 0.22; P = .64). However, the difference becomes statistically significant when a multivariate logistic regression is used to adjust for baseline characteristics, with patients undergoing additional sinus surgery being less likely to undergo further surgery within the study period (adjusted odds ratio = 0.66; P = .04). Conclusions: We have shown sinonasal surgery to be safe and effective in reducing the symptoms associated with CRS over a 5-year period. The reduction in symptoms is large, with no significant decline in symptomatic improvement from 12 to 60 months postsurgery. However, revision surgery rates approach 20% over this time, and patients should be counseled accordingly prior to surgery. Laryngoscope, 2009

The size of the prize for earlier diagnosis of cancer in England

Abstract: This supplement presents a wide range of observations, reviews, novel research and analyses underpinning the National Awareness and Early Diagnosis Initiative (NAEDI). The preceding three papers present and discuss different aspects of the data from European cancer survival comparison studies. I conclude here by attempting to quantify the extent to which delayed diagnosis in England accounts for observed survival differences and by outlining areas for further research. Analysis of indirect evidence related to late diagnosis, surgical intervention rates and utilisation of radiotherapy and chemotherapy in England and other European countries in the late 1990s for breast, colorectal and lung cancer. Late diagnosis was almost certainly a major contributor to poor survival in England for all three cancers. Low surgical intervention rates are very likely to have contributed to low survival rates for lung cancer and possibly for the other two cancers. Any differences in the use of radiotherapy or chemotherapy are likely to have had only a minor impact on survival differences. Between 5000 and 10000 deaths within 5 years of diagnosis could be avoided every year in England if efforts to promote earlier diagnosis and appropriate primary surgical treatment are successful. Detailed international benchmarking studies are to be recommended.

The National Awareness and Early Diagnosis Initiative in England: assembling the evidence.

Abstract: A National Awareness and Early Diagnosis Initiative (NAEDI) has been established in England as part of the Government's strategy to improve cancer outcomes. One of the early priorities for this initiative has been to assemble the diverse evidence linking late diagnosis with poor survival and avoidable deaths. This supplement brings together new perspectives on existing research in this area together with findings from recently commissioned research. This paper describes a provisional model, the 'NAEDI pathway', for testing hypotheses relating to late diagnosis and its impact. Key findings from other papers in this supplement are also highlighted.

Development of a measurement tool to assess public awareness of cancer.

Abstract: BACKGROUND: We aimed to develop and validate a measurement tool to assess cancer awareness in the general population: the cancer awareness measure (CAM).METHODS: Items assessing awareness of cancer warning signs, risk factors, incidence, screening programmes and attitudes towards help seeking were extracted from the literature or generated by expert groups. To determine reliability, the CAM was administered to a university participant panel (n = 148), with a sub-sample (n = 94) completing it again 2 weeks later. To establish construct validity, CAM scores of cancer experts (n = 12) were compared with those of non-medical academics (n = 21). Finally, university students (n = 49) were randomly assigned to read either a cancer information leaflet or a leaflet with control information before completing the measure, to ensure the CAM was sensitive to change.RESULTS: Cognitive interviewing indicated that the CAM was being interpreted as intended. Internal reliability (Cronbach's alpha = 0.77) and test-retest reliability (r = 0.81) were high. Scores for cancer experts were significantly higher than those for non-medical academics (t(31) 6.8, P < 0.001). CAM scores were higher among students who received an intervention leaflet than the control leaflet (t(47) 4.8, P < 0.001).CONCLUSIONS: These studies show the psychometric properties of the CAM and support its validity as a measure of cancer awareness in the general population. British Journal of Cancer (2009) 101, S13-S17. doi: 10.1038/sj.bjc.6605385 www.bjcancer.com (C) 2009 Cancer Research UK

Interventions to promote cancer awareness and early presentation: systematic review

Abstract: BACKGROUND: Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. METHODS: We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities. RESULTS: We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma. CONCLUSION: Interventions delivered to individuals may increase cancer awareness. Interventions delivered to communities may promote cancer awareness and early presentation, although the evidence is limited.

The Euro-Phospholipid project: epidemiology of the antiphospholipid syndrome in Europe.

Abstract: The Euro-Phospholipid project started in 1999 with a multicentre, consecutive and prospective design. A total cohort of 1000 patients with antiphospholipid syndrome (APS), derived from 13 countries (Belgium, Bulgaria, Denmark, France, Germany, Greece, Hungary, Israel, Italy, the Netherlands, Portugal, Spain and United Kingdom), has been followed since then. This project allowed the identification of the prevalence and characteristics of the main clinical and immunological manifestations at the onset and during the evolution of APS and demonstrated that it is possible to recognize more homogeneous subsets of clinical significance. Patients with APS associated with systemic lupus erythematosus (SLE) had more episodes of arthritis, livedo reticularis and more frequently exhibited thrombocytopenia and leucopenia. Female patients had more episodes of arthritis and livedo reticularis - both connected with the higher prevalence of migraine and SLE-related APS in women, while male patients had more myocardial infarction, epilepsy and lower limb arterial thrombosis. Childhood onset patients presented more episodes of chorea and jugular vein thrombosis, whereas older onset patients were more frequently male and had more strokes and angina pectoris, but less frequently livedo reticularis.

The Euro-lupus project: epidemiology of systemic lupus erythematosus in Europe.

Abstract: The Euro-lupus project provides updated information on the epidemiologic characteristics of systemic lupus erythematosus (SLE) at the change of the millennium and defines several clinical and immunological prognostic factors. The Euro-lupus cohort is composed of 1000 patients with SLE who have been followed prospectively since 1991. Among other findings, this project has shown that a) the age at onset of the disease, the gender and the autoantibody pattern, among other factors, modify the disease expression and define some specific SLE subsets; b) most of the SLE inflammatory manifestations are less common after long-term evolution of the disease, thus probably reflecting the effect of therapy as well as the progressive remission of the disease in many patients and c) a more prominent role of thrombotic events is becoming evident affecting both morbidity and mortality in SLE.

An artificial di-iron oxo-protein with phenol oxidase activity

Abstract: Here we report the de novo design and NMR structure of a four-helical bundle di-iron protein with phenol oxidase activity. The introduction of the cofactor-binding and phenol-binding sites required the incorporation of residues that were detrimental to the free energy of folding of the protein. Sufficient stability was, however, obtained by optimizing the sequence of a loop distant from the active site.

Promoting Global Research Excellence in Severe Sepsis (PROGRESS): lessons from an international sepsis registry.

Abstract: The PROGRESS Registry (Promoting Global Research Excellence in Severe Sepsis) was designed to provide comparative data reflecting everyday clinical practice, thereby allowing participating institutions to explore and benchmark medical interventions in severe sepsis. PROGRESS was an international, noninterventional, prospective, observational registry collecting data that describe the management and outcomes of severe sepsis patients in intensive care units (ICUs). Patients were enrolled who had been diagnosed with severe sepsis (suspected or proven infection and ≥ 1 acute sepsis-induced organ dysfunction) at the participating institutions, where de-identified data were entered directly into a secured website. PROGRESS was governed by an independent international medical advisory board. PROGRESS took place in 276 ICUs in 37 countries, and 12,881 patients were identified as having severe sepsis. There was considerable variation among countries in enrollment levels, provision of standard treatment and supportive therapies, and ICU and hospital outcomes. Eight countries accounted for 65.2% of the enrolled patients. Males (59.3%) and Caucasian (48.6%) patients predominated the patient cohort. Diagnosis of severe sepsis was prior to ICU admission in 45.7% of patients, at ICU admission in 29.1% of patients, and after ICU admission in the remainder. Globally, ICU and hospital mortality rates were 39.2% and 49.6%, respectively. The mean length of ICU and hospital stay was 14.6 days and 28.2 days, respectively. The PROGRESS international sepsis registry demonstrates that a large web-based sepsis registry is feasible. Wide variations in outcomes and use of sepsis therapies were observed between countries. These results also suggest that additional opportunities exist across countries to improve severe sepsis outcomes.

3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology.

Abstract: Purpose. To study the distribution and predominant orientations of fibrillar collagen at different depths throughout the entire thickness of the human cornea. This information will form the basis of a full three-dimensional reconstruction of the preferred orientations of corneal lamellae. Methods. Femtosecond laser technology was used to delaminate the central zones of five human corneas into three separate layers (anterior, mid, and posterior stroma), each with predetermined thicknesses. Wide-angle x-ray diffraction was used to study the gross collagen fibril orientation and distribution within each layer. Results. The middle and posterior parts of the human cornea demonstrated a preferential orthogonal arrangement of collagen fibrils, directed along the superior–inferior and nasal–temporal meridians, with an increase in the number of lamellae toward the periphery. However, the anterior cornea (33% of total corneal thickness) showed no systematic preferred lamellar orientation. Conclusions. In the posterior two thirds of the human cornea, collagen lies predominantly in the vertical and horizontal meridians (directed toward the four major rectus muscles), whereas collagen in the anterior third of the cornea is more isotropic. The predominantly orthogonal arrangement of collagen in the mid and posterior stroma may help to distribute strain in the cornea by allowing it to withstand the pull of the extraocular muscles, whereas the more isotropic arrangement in the anterior cornea may play an important role in the biomechanics of the cornea by resisting intraocular pressure while at the same time maintaining corneal curvature.

Hand eczema classification: a cross‐sectional, multicentre study of the aetiology and morphology of hand eczema

Abstract: Hand eczema is a long-lasting disease with a high prevalence in the background population. The disease has severe, negative effects on quality of life and sometimes on social status. Epidemiological studies have identified risk factors for onset and prognosis, but treatment of the disease is rarely evidence based, and a classification system for different subdiagnoses of hand eczema is not agreed upon. Randomized controlled trials investigating the treatment of hand eczema are called for. For this, as well as for clinical purposes, a generally accepted classification system for hand eczema is needed. The present study attempts to characterize subdiagnoses of hand eczema with respect to basic demographics, medical history and morphology. Clinical data from 416 patients with hand eczema from 10 European patch test clinics were assessed. A classification system for hand eczema is proposed. It is suggested that this classification be used in clinical work and in clinical trials. (Less)

Prevalence of vertebral fracture in women and the relationship with bone density and symptoms : the chingford study

Abstract: A population survey was performed to estimate the prevalence of vertebral fractures in women aged 45–69 and to determine their relationship to bone density and symptoms. Subjects were 1035 women aged 45–69 (mean 55.4 years, response rate 77%) from the age-sex register of a large 11,000-person general practice in Chingford, London. Thoracic and lumbar spine x-rays were read by a semiautomated quantitative method. Vertebral fractures were diagnosed using a variety of morphometric methods, including a new method we recently developed and the published methods of Melton and Eastell. These methods all detect abnormal ratios between anterior, central, or posterior vertebral height and between observed posterior vertebral height and values predicted from the posterior height of adjacent vertebrae. Bone mineral density (BMD) of lumbar spine L1–4 and neck of femur was measured by dual-energy x-ray absorptiometry (DXA). Using our method, 147, 14.2% (95% CI 12.0–16.2%) of the 1035 women, had minor fractures (at least two vertebral ratios 2–2.99 SD below the mean) and 20, 1.9% (95% CI 1.2–3.0%) of the total, had severe fractures (at least two ratios more than 3 SD below the mean). In the 147 women with minor fractures, bone density of the spine was not significantly lower than in the other 868 women, and reported back pain or loss of height was no more common. Women with multiple minor fractures did have lower bone density, by 0.4 SD. In the 20 women with severe fracture, bone density was significantly lower, by 0.6 SD. Loss of height was more common, but back pain was not. Using the method of Melton the prevalence of deformity was 10.2% and, for the Eastell 3 and 4 SD method, 9.7 and 1.3%, respectively, which is similar to published data from the Rochester population. Minor vertebral deformities are common in postmenopausal women, but they are not usually associated with pain, loss of height, or (unless multiple) reduced bone density. This suggests that they may not be of clinical or pathologic importance. Severe deformities associated with low bone density are rare in U.K. women under the age of 70.

Safety of Sildenafil Citrate: Review of 67 Double-Blind Placebo-Controlled Trials and the Postmarketing Safety Database

Abstract: Aim: To review special safety topics associated with sildenafil and to document the tolerability of 50- and 100-mg doses, overall and by age, in men with erectile dysfunction (ED).

The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial.

Abstract: To determine if statin therapy reduces the incidence of severe sepsis and the levels of inflammatory cytokines in patients with acute bacterial infection. Double-blind placebo controlled randomized clinical trial. Department of medicine and medical intensive care unit in a tertiary university medical center. A total of 83 patients with suspected or documented bacterial infection were enrolled. We randomly assigned 42 patients to receive 40 mg of simvastatin orally, followed by 20 mg of simvastatin, and 41 to receive matching placebo. The study was prematurely terminated due to slow recruitment rate. Here we report the analysis of the secondary outcome: change in cytokines levels at 72 h. Both groups were evenly matched in terms of co-morbidity and severity of illness on admission. Four of the 83 patients enrolled developed severe sepsis, two in each group. No difference was observed in other clinical variables and there were no mortalities. Cytokine levels were randomly assessed in 40 patients (20 in each group). Both TNF-α and IL-6 levels were significantly reduced in the simvastatin group (p = 0.02 and p = 0.02, respectively), while no such difference was observed in the placebo group (p = 0.35 and 0.39, respectively). Statin therapy may be associated with a reduction in the levels of inflammatory cytokines in patients with acute bacterial infections. Large controlled trials will determine if this reduction will translate into a clinical benefit.