Incorporating natural variation into IVF clinic league tables: The Expected Rank

Background  

Rankings based on outcome are often used to present health care provider performance. These rankings do however not reflect that part of the variation in outcome between providers is caused by natural variation, and not by any differences in quality of care. The aim of this study is to compare standard methods for ranking with a novel method that takes into account natural variation.     

Characterizing radial undersampling artifacts for cardiac applications.

The undersampled radial acquisition has been widely employed for accelerated (by a factor R = N(r)/N(p)) cardiac imaging, but the resulting reduction in image quality has not been well characterized. This investigation presents a method of measuring these artifacts through synthetic undersampling of high SNR images (SNR > or = 30). After validating the method in phantoms, the method was applied to a study of short-axis, long-axis, and coronary MRI imaging in healthy subjects. For 60 projections (60 N(p)), the total artifact is approximately 10% for short and long-axis imaging (R = 2.1) and approximately 15% for coronary MRI (R = 3.7). For 60 N(p), the SD of artifact in the region of the heart is 2% for short- and long-axis imaging (R = 2.1) and 3.5% for coronary MRI (R = 3.7). The artifact content is less in the region of the heart than in the periphery. The artifact is very reproducible among subjects for standard views. A study of coronary MRI at progressively fewer projections (at constant scan time) showed that right coronary MRI images were acceptable if total artifact was <6.5% of image content (N(p) > 120, R = 2.1).     

Rationale and design of The Delphi Trial – I(RCT)2: international randomized clinical trial of rheumatoid craniocervical treatment, an intervention-prognostic trial comparing 'early' surgery with conservative treatment [ISRCTN65076841]

Background  

Rheumatoid arthritis is a chronic inflammatory disease, which affects 1% of the population. Hands and feet are most commonly involved followed by the cervical spine. The spinal column consists of vertebrae stabilized by an intricate network of ligaments. Especially in the upper cervical spine, rheumatoid arthritis can cause degeneration of these ligaments, causing laxity, instability and subluxation of the vertebral bodies. Subsequent compression of the spinal cord and medulla oblongata can cause severe neurological deficits and even sudden death. Once neurological deficits occur, progression is inevitable although the rapidity of progression is highly variable. The first signs and symptoms are pain at the back of the head caused by compression of the major occipital nerve, followed by loss of strength of arms and legs. The severity of the subluxation can be observed with radiological investigations (MRI, CT) with a high sensitivity.     

Heart valve dysfunction resulting from cellular rejection in a novel heterotopic transplantation rat model

Abstract Structural failure of heart valve allografts may be related to technical factors or immunological reactions. To circumvent nonimmunological factors a new rat implantation model was developed to study whether alloreactivity results in histopathological changes and valve dysfunction. Syngeneic (WAG‐WAG, DA‐DA) and allogeneic (WAG‐BN, WAG‐DA) transplantation was carried out using this new technique, and the function of explanted valves was assessed 21 days later by retrograde comptence testing. Additionally, grafts were examined using standard histological and immunohistochemical techniques. There was no leakage during retrograde injection in nine of tem syngeneic and two of ten allogeneic grafts. Microscopically, syngeneic valves appeared normal without fibrosis or intimal thickening, although CD8⁺ lymphocytes and macrophages were found in necrotic myocardial rim and adventitia. In contrast, allogeneic valves were deformed and noncellular, with extensive infiltration of CD4⁺, CD8⁺ and CD68⁺ cells in adventitia and media. Absence of fibrosis and intimal thickening in syngeneic transplanted valves indicated circumvention of nonimmunological factors. Allogeneic valve transplantation induces cellular infiltration in the graft with subsequent graft failure.     

Evidence of a marked 25-hydroxyvitamin D deficiency in patients with congenital ichthyosis

BACKGROUND: Vitamin D is essential for bone mineralization, and its deficiency may be the cause of skeletal fractures and osteomalacia. Geographical or ethnic factors may modulate the cutaneous synthesis of vitamin D. We hypothesized that major changes in keratinization may similarly alter the cutaneous synthesis of vitamin D. OBJECTIVES: To explore calciotrophic hormones, parameters of bone remodelling and bone mineral density (BMD) in nine patients with non-bullous congenital ichthyosis. PATIENTS AND METHODS: Six patients were European, three were North African. Four had received acitretin over a long period of time. A complete biological investigation, including serum and urinary calcium and phosphorus, calciotrophic hormones [intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-(OH)D) and 1,25-dihydroxyvitamin D (1,25-(OH)2D)], bone formation and resorption markers, was performed on all patients during the winter season and repeated among four patients after summer. BMD was measured in all patients. RESULTS: All patients had a marked 25-(OH)D deficiency, clearly below the deficiency threshold of 25 nmol/L. Patients from North Africa had a greater deficiency than European patients, perhaps because of the difference in skin pigmentation. iPTH remained normal in European patients but was elevated among the North Africans. After sun exposure, an improvement in vitamin status was visible in only one patient. Bone formation and resorption markers remained normal. Femoral neck osteodensitometry indicated values near the osteopaenic threshold in two young North African females. No deleterious effect of retinoids on vitamin D metabolism was observed. CONCLUSION: Patients, and in particular pigmented patients, with congenital ichthyosis present a severe deficiency in vitamin D. Care provided to protect the skeletal future of these patients involves measuring BMD and prescribing supplementation.     

Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus

BACKGROUND: Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well-being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label. OBJECTIVE: To prepare a series of recommendations agreed by an expert group of dermatologists, relating to the most effective use of etanercept for psoriasis in Europe, within the product license. METHODS: An expert panel of dermatologists from across Europe completed a Delphi survey to address the current use of etanercept in psoriasis in Europe. In June 2005 the results were presented to the expert panel at their nominal group meeting, and a consensus was agreed. RESULTS: It was recommended that, where possible, patients are initiated on the 50 mg twice-weekly (BIW) dose. Etanercept should be given until remission is achieved (maximum 24 weeks) and retreatment should be initiated according to the physician's judgement. Before commencing treatment, contraindications, such as infection or previous malignancy (within 5 years), should be ruled out. CONCLUSIONS: The consensus presented herein provides valuable clarification of use of etanercept according to the label, which may have wider implications relating to the use of all biological therapies in psoriasis.     

Squalene synthase: a critical enzyme in the cholesterol biosynthesis pathway

High levels of plasma low-density lipoprotein cholesterol (LDL-C) are a significant risk factor for heart disease. Statins (3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors) have been extensively used to treat high-plasma LDL-C levels and are effective in preventing heart disease. However, statins can be associated with adverse side effects in some patients and do not work effectively in others. As an alternative to statins, the development of cholesterol-lowering agents that directly inhibit squalene synthase have shown promise. Clinical studies have shown that squalene synthase inhibitors are effective in lowering plasma levels of total cholesterol and LDL-C. Squalene synthase plays an important role in the cholesterol biosynthesis pathway as it is responsible for the flow of metabolites into either the sterol or the non-sterol branches of the pathway. In addition, variants of the squalene synthase gene appear to modulate plasma cholesterol levels in human populations and therefore may be linked to cardiovascular disease. In this review, we examine squalene synthase and the gene that codes for it (farnesyldiphosphate farnesyltransferase 1). In particular, we investigate their role in the regulation of cellular and plasma cholesterol levels, including data that suggest that squalene synthase may be involved in the etiology of hypercholesterolemia.