Performance and comparison of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease formulae in estimating glomerular filtration rate in a Chinese Type 2 diabetic population.

AIMS: Our aim was to assess performances of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease (MDRD) formulae in estimating glomerular filtration rate (GFR) in Chinese diabetic populations and their association with vascular risks. METHODS: A total of 1009 patients with Type 2 diabetes were categorized into low estimated GFR groups (GFR < 60 ml/min/1.73 m(2)) and control groups by the two equations. The performances of these formulae were assessed at different stages of kidney function. Carotid artery intima-media thickness (IMT) and the prevalence of diabetic retinopathy or albuminuria were compared among the groups. The ability of these formulae to identify established vascular risk markers using sensitivity, specificity, positive and negative predictive values were also compared. RESULTS: The prevalence of low estimated GFR was 32.7% with the Cockcroft-Gault formula and 5.2% with the MDRD formula, respectively. In low estimated GFR subjects by the MDRD formula, IMT was significantly thicker than those by the Cockcroft-Gault formula (1.2 mm vs. 1.0 mm; P < 0.05), with a higher prevalence of albuminuria (78.4 vs. 52.8%, P < 0.05) and diabetic retinopathy (46.5 vs. 30.5%; P < 0.05). The Cockcroft-Gault formula gave a specificity of 71.7% and a sensitivity of 37.0%, and the MDRD formula gave a specificity of 96.6% and a sensitivity of 7.9% in estimating low GFR relevant for established vascular risks. CONCLUSIONS: These formulae performed differently in Chinese diabetic populations. The simplified MDRD formula is minimally superior to the Cockcroft-Gault formula for its high specificity and positive predictive values in estimating low GFR relevant for vascular risks.     

Pathophysiological aspects of brain edema

Summary Two mayor types of brain edema, related to two different pathomechanisms, can be recognized: 1)cytotoxic type-where the main feature is the swelling of cellular elements of brain parenchyma and 2)vasogenic type-where an increased vascular permeability leading to accumulation of edema fluid inthe extracellular spaces plays the principal role. In this type of edema, there is a close interrelationship between extravasation of serum proteins and retention of water in the brain tissue. In theischemic brain edema both cytotoxic and vasogenic mechanisms are involved. A biphasic opening of the blood-brain barrier, associated with vasogenic edema, is observed following release of major cerebral artery occlusion. The first opening of the barrier is related to a reactive hyperemia which follows promptly recirculation. The second opening, recognizable after a delay, is associated with a severe ischemic brain tissue injury.Dedicated to Prof. F. Seitelberger on the occasion of his seventieth birthday     

Systematic review of methods to diagnose infection in foot ulcers in diabetes.

AIM: To undertake a systematic review of the diagnostic performance of clinical examination, sample acquisition and sample analysis in infected foot ulcers in diabetes. METHODS: Nineteen electronic databases plus other sources were searched. To be included, studies had to fulfil the following criteria: (i) compare a method of clinical assessment, sample collection or sample analysis with a reference standard; (ii) recruit diabetic individuals with foot ulcers; (ii) present 2 x 2 diagnostic data. Studies were critically appraised using a 12-item checklist. RESULTS: Three eligible studies were identified, one each on clinical examination, sample collection and sample analysis. For all three, study groups were heterogeneous with respect to wound type and a small proportion of participants had foot ulcers due to diabetes. No studies identified an optimum reference standard. Other methodological problems included non-blind interpretation of tests and the time lag between index and reference tests. Individual signs or symptoms of infection did not prove to be useful tests when assessed against punch biopsy as the reference standard. The wound swab did not perform well when assessed against tissue biopsy. Semiquantitative analysis of wound swab might be a useful alternative to quantitative analysis. The limitations of these findings and their impact on recommendations from relevant clinical guidelines are discussed. CONCLUSION: Given the importance of this topic, it is surprising that only three eligible studies were identified. It was not possible to describe the optimal methods of diagnosing infection in diabetic patients with foot ulceration from the evidence identified in this systematic review.     

急诊抗菌药物的使用调查与分析

目的考察了解急诊抗菌药物的使用情况。方法随机抽取2008年7—12月的急诊处方2700张，对其中抗菌药物的应用情况进行统计分析。结果急诊抗菌药物使用率49．1％，药物应用形式以单用为主（占66．3％）；给药途径以口服和静脉注射为主。不合理用药处方占抗菌药物处方的10．8％，分别在选药方案、给药方案、溶媒使用、联合应用等方面存在问题。结论我院急诊抗菌药物的应用基本合理，但仍存在一定问题，需进一步加强管理。     

Immunological responses to pneumococcal vaccine in frail older people

Advanced age has been associated with a wide range of defects in both the innate and adaptive immune systems including diminished specific antibody responses that increase the risk of invasive pneumococcal disease (IPD) and limit the effectiveness of vaccines. However, the elderly are a heterogeneous group and measures of overall frailty may be a better indicator of disease susceptibility (or vaccine response) than chronological age alone.     

Estimated research and development costs of rotavirus vaccines

Diseases like rotavirus afflict both upper- and lower-income countries, but most serious illnesses and deaths occur among the latter. It is a vital public health issue that vaccines for these types of global diseases can recover research and development (R&D) costs from high-priced markets quickly so that manufacturers can offer affordable prices to lower-income nations. Cost recovery depends on how high R&D costs are, and this study attempts to replace high, unverified estimates with lower, more verifiable estimates for two new vaccines, RotaTeq (Merck) and Rotarix (GlaxoSmithKline or GSK), based on detailed searches of public information and follow-up interviews with senior informants. We also offer a new perspective on “cost of capital” as a claim for recovery from public bodies. Our estimates suggest that companies can recover all fixed costs quickly from affluent markets and thus can offer these vaccines to lower-income countries at prices they can afford. Better vaccines are a shared project between companies and public health agencies; greater transparency and consistency in reporting of R&D costs is needed so that fair prices can be established.     

Medical management of Crohn's disease: A guide for radiologists

The choice of therapies for Crohn's disease has expanded greatly over the past 30 years. Increasingly it is important that we attempt to identify subgroups of patients who will benefit most from each type of therapy. This article reviews the therapeutic options currently available, organized by the goal the practitioner hopes to achieve. Imaging is one critical way of aiding the classification of Crohn's disease by attempting to accurately determine the location, extent and, most importantly, the nature of the disease.     

Simultaneous versus sequential optimal design for pharmacokinetic-pharmacodynamic models with FO and FOCE considerations

We consider nested multiple response models which are used extensively in the area of pharmacometrics. Given the conditional nature of such models, differences in predicted responses are a consequence of different assumptions about how the models interact. As such, sequential versus simultaneous and First Order (FO) versus First Order Conditional Estimation (FOCE) techniques have been explored in the literature where it was found that the sequential and FO approaches can produce biased results. It is therefore of interest to determine any design consequences between the various methods and approximations. As optimal design for nonlinear mixed effects models is dependent upon initial parameter estimates and an approximation to the expected Fisher information matrix, it is necessary to incorporate any influence of nonlinearity (or parameter-effects curvature) into our exploration. Hence, sequential versus simultaneous design with FO and FOCE considerations are compared under low, typical and high degrees of nonlinearity. Additionally, predicted standard errors of parameters are also compared to empirical estimates formed via a simulation/estimation study in NONMEM. Initially, design theory for nested multiple response models is developed and approaches mentioned above are investigated by considering a pharmacokinetic–pharmacodynamic model found in the literature. We consider design for situations where all responses are continuous and extend this methodology to the case where a response may be a discrete random variable. In particular, for a binary response pharmacodynamic model, it is conjectured that such responses will offer little information about all parameters and hence a sequential optimization, in the form of product design optimality, may yield near optimal designs.