Working‐correlation‐structure identification in generalized estimating equations

Selecting an appropriate working correlation structure is pertinent to clustered data analysis using generalized estimating equations (GEE) because an inappropriate choice will lead to inefficient parameter estimation. We investigate the well‐known criterion of QIC for selecting a working correlation structure, and have found that performance of the QIC is deteriorated by a term that is theoretically independent of the correlation structures but has to be estimated with an error. This leads us to propose a correlation information criterion (CIC) that substantially improves the QIC performance. Extensive simulation studies indicate that the CIC has remarkable improvement in selecting the correct correlation structures. We also illustrate our findings using a data set from the Madras Longitudinal Schizophrenia Study. Copyright © 2008 John Wiley & Sons, Ltd.     

Assessing ethical problem solving by reasoning rather than decision making

Context The assessment of ethical problem solving in medicine has been controversial and challenging. The purposes of this study were: (i) to create a new instrument to measure doctors’ decisions on and reasoning approach towards resolving ethical problems; (ii) to evaluate the scores generated by the new instrument for their reliability and validity, and (iii) to compare doctors’ ethical reasoning abilities between countries and among medical students, residents and experts. Methods This study used 15 clinical vignettes and the think‐aloud method to identify the processes and components involved in ethical problem solving. Subjects included volunteer ethics experts, postgraduate Year 2 residents and pre‐clerkship medical students. The interview data were coded using the instruments of the decision score and Ethical Reasoning Inventory (ERI). The ERI assessed the quality of ethical reasoning for a particular case (Part I) and for an individual globally across all the vignettes (Part II). Results There were 17 Canadian and 32 Taiwanese subjects. Based on the Canadian standard, the decision scores between Taiwanese and Canadian subjects differed significantly, but made no discrimination among the three levels of expertise. Scores on the ERI Parts I and II, which reflect doctors’ reasoning quality, differed between countries and among different levels of expertise in Taiwan, providing evidence of construct validity. In addition, experts had a greater organised knowledge structure and considered more relevant variables in the process of arriving at ethical decisions than did residents or students. The reliability of ERI scores was 0.70–0.99 on Part I and 0.75–0.80 on Part II. Conclusions Expertise in solving ethical problems could not be differentiated by the decisions made, but could be differentiated according to the reasoning used to make those decisions. The difference between Taiwanese and Canadian experts suggests that cultural considerations come into play in the decisions that are made in the course of providing humane care to patients.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Low HDL‐cholesterol is common in European Type 2 diabetic patients receiving treatment for dyslipidaemia: data from a pan‐European survey

Aims To measure the prevalence of low high‐density lipoprotein (HDL)‐cholesterol (men < 1.03 mmol/l; women < 1.29 mmol/l) in European Type 2 diabetic patients receiving treatment for dyslipidaemia. Methods The pan‐European Survey of HDL‐cholesterol measured lipids and other cardiovascular risk factors in 3866 patients with Type 2 diabetes and 4436 non‐diabetic patients undergoing treatment for dyslipidaemia in 11 European countries. Results Diabetic patients were more likely to be obese or hypertensive than non‐diabetic patients. Most patients received lifestyle interventions (87%) and/or a statin (89%); treatment patterns were similar between groups. Diabetic patients had [means (SD)] lower HDL‐cholesterol [1.22 (0.37) vs. 1.35 mmol/l (0.44) vs. non‐diabetic patients, P < 0.001] and higher triglycerides [2.32 (2.10) vs. 1.85 mmol/l (1.60), P < 0.001]. More diabetic vs. non‐diabetic patients had low HDL‐cholesterol (45% vs. 30%), high triglycerides (≥ 1.7 mmol/l; 57% vs. 42%) or both (32% vs. 19%). HDL‐cholesterol < 0.9 mmol/l was observed in 18% of diabetic and 12% of non‐diabetic subjects. Differences between diabetic and non‐diabetic groups were slightly greater for women. LDL‐ and total cholesterol were lower in the diabetic group [3.02 (1.05) vs. 3.30 mmol/l (1.14) and 5.12 (1.32) vs. 5.38 mmol/l (1.34), respectively, P < 0.001 for each]. Conclusions Low HDL‐cholesterol is common in diabetes: one in two diabetic women has low HDL‐cholesterol and one diabetic man in four has very low HDL‐cholesterol. Management strategies should include correction of low HDL‐cholesterol to optimize cardiovascular risk in diabetes.     

PRENATAL DIAGNOSIS Ⅰ. EARLY DIAGNOSIS OF OPEN NEURAL TUBE DEFECTS BY QUALITATIVE ACETYLCHOLINESTERASE ISOENZYME IN AMNIOTIC FLUID

The measurement of amniotic fluid (AF) acetylcholinesterase isoenzyme (AChEI) is a relatively new method for early diagnosis of open neural tube defects (NTDs). As quantitative methods are of unproven reliability at present, the authors used a high resolving power qualitative method-vertical slab polyaerylamide gel electrophoresis. The benefits of this technique are: simplicity of operation, accuracy, unsophisticated equipment, and easily available reagents. Combined results of 9 NTDs studies revealed that samples from early pregnancy gave more accurate results than those from late pregnancy.