Adaptive group sequential design for phase II clinical trials: A Bayesian decision theoretic approach

Bayesian decision theoretic approaches (BDTAs) have been widely studied in the literature as tools for designing and conducting phase II clinical trials. However, full Bayesian approaches that consider multiple endpoints are lacking. Since the monitoring of toxicity is a major goal of phase II trials, we propose an adaptive group sequential design using a BDTA, which characterizes efficacy and toxicity as correlated bivariate binary endpoints. We allow trade‐off between the two endpoints. Interim evaluations are conducted group sequentially, but the number of interim looks and the size of each group are chosen adaptively based on current observations. We utilize a loss function consisting of two components: the loss associated with accruing, treating, and monitoring patients, and the loss associated with making incorrect decisions. The performance of our Bayesian modeling, and the operating characteristics of decision rules under a wide range of loss function parameters are evaluated using seven scenarios in a simulation study. Our method is illustrated in the context of a single‐arm phase II trial of bevacizumab, gemcitabine, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma. Copyright © 2009 John Wiley & Sons, Ltd.     

局部PUVA治疗儿童白癜风疗效及安全性观察

目的:观察局部光化学疗法(Psoralen plus UVA,PUVA)治疗儿童白癜风的临床疗效及安全性.方法:采用小型UVA灯(电压220V,电流0.34A,功率25.4w,主波峰长36 5nm,辐照度为1 070uw/cm2)治疗56例白癜风患儿,30次为一个疗程,共观察3个疗程.结果:第一疗程、第二疗程及第三疗程结束后临床显效率分别达39.29%、48.21%和5 5.36%,未发现明显不良反应,其中病程短、局限性及面颈部白癜风患儿疗效佳.结论:局部PUVA治疗儿童白癜风安全、有效、不良反应小,小型UVA灯具有疗效好、治疗方便的优点.     

Risk groups for clinical complications of norovirus infections: an outbreak investigation

Norovirus infections have been described as self-limiting diseases of short duration. An investigation of a norovirus outbreak in a university hospital provided evidence for severe clinical features in patients with several underlying diseases. Clinical outcomes of norovirus infection were defined. Risk-factor analysis targeting underlying diseases and medication was performed using multivariate analyses. In five outbreak wards, 84 patients and 60 nurses were infected (an overall attack rate of 32% in patients, and 76% in nurses). The causative agent was the new variant Grimsby virus. Severe clinical features, including acute renal failure, arrhythmia and signs of acute graft organ rejection in renal transplant patients, were observed in seven (8.3%) patients. In multivariate analyses, cardiovascular disease (OR 17.1, 95% CI 2.17-403) and renal transplant (OR 13.0, 95% CI 1.63-281) were risk-factors for a potassium decrease of >20%. Age >65 years (OR 11.6, 95% CI 1.89-224) was a risk-factor for diarrhoea lasting >2 days. Immunosuppression (OR 5.7, 95% CI 1.78-20.1) was a risk-factor for a creatinine increase of >10%. Norovirus infections in patients with underlying conditions such as cardiovascular disease, renal transplant and immunosuppressive therapy may lead to severe consequences typified by decreased potassium levels, increased levels of C-reactive protein and creatine phosphokinase. In the elderly, norovirus infection may lead to an increased duration of diarrhoea. Therefore patients at risk should be hospitalised early and monitored frequently. Strict preventional measures should be implemented as early as possible to minimise the risk of nosocomial outbreaks.     

2001年与2004年抗菌药物应用情况比较

目的　了解抗菌药物应用的基本情况。方法　将 2 0 0 1年 3月 14 3 0例住院患者病历与 2 0 0 4年 3月的 2 0 66例住院患者病历进行回顾性调查和对比分析。结果　 2 0 0 1年的 14 3 0例中有 948(66 3 % )例 ,和 2 0 0 4年的 2 0 66例有 10 60例 (5 1.3 % ) ,应用了抗菌药物。结论　定期检查考评 ,严格掌握用药指征 ,是加强抗菌药物应用管理的关键。     

Clinical characteristics of rapidly progressive leuko-araiosis

Introduction – 38 patients found to have either pure leuko-araiosis (LA) or LA combined with infarction(s) on computer tomography (CT) in 1989 were re-examined in 1992 in order to evaluate the progression of LA. The follow-up period averaged 3.2 years. Material and methods - The clinical and radiological data on patients in 1989 were collected from hospital records and re-evaluated. The patients were re-examined clinically (including 24 hour ambulatory blood pressure measurement), and neuroradiologically (CT) in 1992 for this study. Results – 11 (29%) patients were found to have significant (rapid) progression of the extent of LA on CT during the follow-up. At baseline, there was no significant difference in the mean number of brain infarctions between the groups with progressing (prLA) and non-progressing LA (nprLA) or between the number of cortical and central infarctions within these groups. At follow-up, the total number of infarctions had increased significantly in both groups, but it was mostly because of the increase in cortical infarctions in the prLA group (p = 0.043) and, conversely, the central ones in the nprLA group (p = 0.011). prLA was found to be related to heart failure (82% vs 37%, p = 0.029) and atrial fibrillation (55% vs 19%, p = 0.047), whereas nprLA was strongly associated with a sudden onset of symptoms (78% vs prLA 18%, p = 0.001) like a-true brain infarction. Other clinical factors, including mean blood pressure and heart rate, did not clearly differentiate between the groups. Conclusion - The results suggest that there are different subgroups of patients with LA associated with various vascular factors. The occurrence of LA is not related to the distribution of infarctions. The progression of LA is not related to the number of brain infarctions or to the simultaneous increase of infarctions on CT.     

Clinical index to predict bacteraemia caused by staphylococci

Abstract. Objectives. To define risk factors associated with bacteraemia caused by Staphylococcus aureus or coagulase-negative staphylococci; and to use them to define patients in need of empiric anti-staphylococcal antibiotic treatment. Design, Derivation set: observational, prospective study; validation set: retrospective analysis of a prospectively collected database. Setting. Derivation set: Beilinson Medical Centre, Petah Tiqva, Israel—a 900-bed university hospital. Validation set: St Thomas's Hospital, London, UK—an 800-bed teaching hospital. Subjects. All episodes of bacteraemia detected at Beilinson Medical Centre between March 1988 and September 1990 (derivation set, n = 1410), and at St Thomas's Hospital during 1987–1990 (validation set, n = 1040). Interventions. None. Main outcome measures. Percentage of staphylococcal bacteraemia in groups of patients defined by the models. Results. The following factors were associated with Staphylococcus aureus bacteraemia: focus of infection (whether high or low risk), haemodialysis, intravenous drug abuse and infection acquired in the orthopaedic ward. A logistic model was used to divide the derivation set into three groups with percentages of Staphylococcus aureus bacteraemia of 1.8%, 13.2% and 33.7% (P < 0.0001); and the validation group 2.5%, 18.2% and 53.2% (P < 0.0001). Factors associated with coagulase-negative staphylococcal bacteraemia were: central or peripheral intravenous catheter as the focus of infection, a preterm neonate, the presence of a central intravenous catheter, low temperature, and a low white blood cell count. A second model including those factors was used to divide the derivation set into three groups with percentages of coagulase-negative staphylococcal bacteraemia of 1.9%, 22.8%, and 43% (P < 0.0001). In the validation set, the percentages were 2.9%, 22.4% and 31.0% (P < 0.001). Conclusions. The present study defines groups at high risk for staphylococcal bloodstream infection, in which empiric treatment should include an anti-staphylococcal drug.     

Students'' assessment of a course in obstetrics and gynaecology

A complete annual entry of 181 students were administered a questionnaire in which they were invited to make value judgements about all aspects of their 3-month course in obstetrics and gynaecology. The resulting performance indicators were used to compare individual staff and clinical firms.     

江西省528例非何杰金氏恶性淋巴瘤回顾性病理分析

本文收集了我省十年(1974—1983)来诊断为恶性淋巴瘤的病例,按免疫功能分类复查了全部切片,最后确诊为非何杰金氏恶性淋巴瘤(NHL)528例,进行了分析。本组NHL在首发部位、类型分布等方面与国内外有所不同。本组NHL首发于淋巴结外的占64.02％,明显高于国内其它省、市,而滤泡型淋巴瘤则低于国内多数地区。T细胞淋巴瘤占14.84％,较国内、外均低。并提出提高制片质量和广泛开展及应用免疫学技术的重要性。     

Can communication skills be assessed independently of their context?

In many examinations, communication skills tend to be treated as if they are a single attribute independent of the context of the communication. However, it is clear that such assessments are confounded by candidates' knowledge or lack of knowledge of the medical issues about which they are communicating. In the 1990 Part One examination for Membership of the Royal New Zealand College of General Practitioners candidates were provided with all the essential knowledge relevant to the problem they were to communicate about. Despite this, performance was still seen to be context specific, demonstrating that such specificity is not purely knowledge related. Candidates completing the examination were observed to share information about the cases with candidates about to commerce. There was no evidence that performance was enhanced by such breaches in examination security.     

How do clinicians learn to request permission for autopsies?

A postal survey of 434 clinicians at four local hospitals was undertaken in order to identify the methods by which clinicians learn how to request permission for hospital autopsies and to assess the preferred techniques and timing of relevant communication skills training. The majority of 128 responding clinicians had learnt through personal experience with some assistance from senior colleagues and peers. Few clinicians appeared to have learnt through formal training. The preferred methods for the provision of communication skills training were training in small groups (such as seminars or tutorials) and observation of clinicians at work. The most desirable time for the provision of this training was considered to be between the beginning of the final undergraduate year and the end of the pre-registration house officer year. The communication skills training provided within medical education is in need of improvement. More emphasis should be given to clinical-task- or situation-specific applications such as requesting permission for autopsies.