Conditional estimation of sensitivity and specificity from a phase 2 biomarker study allowing early termination for futility

Development of a disease screening biomarker involves several phases. In phase 2 its sensitivity and specificity is compared with established thresholds for minimally acceptable performance. Since we anticipate that most candidate markers will not prove to be useful and availability of specimens and funding is limited, early termination of a study is appropriate, if accumulating data indicate that the marker is inadequate. Yet, for markers that complete phase 2, we seek estimates of sensitivity and specificity to proceed with the design of subsequent phase 3 studies. We suggest early stopping criteria and estimation procedures that adjust for bias caused by the early termination option. An important aspect of our approach is to focus on properties of estimates conditional on reaching full study enrollment. We propose the conditional‐UMVUE and contrast it with other estimates, including naïve estimators, the well‐studied unconditional‐UMVUE and the mean and median Whitehead‐adjusted estimators. The conditional‐UMVUE appears to be a very good choice. Copyright © 2008 John Wiley & Sons, Ltd.     

The impact of new screening protocol on individuals at increased risk of colorectal cancer

OBJECTIVE: Screening colonoscopy has been shown to reduce mortality and cancer stage in hereditary nonpolyposis colorectal cancer (HNPCC) individuals. However, the benefit of screening in intermediate risk groups is unknown. The most recent national guidelines have recommended a reduction of screening frequency for the intermediate risk group. Therefore, this study aims to compare the results of colonoscopic screening in HNPCC and intermediate risk groups and assess the effect of the most recent screening protocol recommendations. METHOD: A total of 244 individuals; 108 from HNPCC families (28 mismatch repair gene carriers) and 136 from intermediate risk families were referred for regular colonoscopic screening by the Regional Genetics Service. Findings from 417 colonoscopies performed between 1992 and 2003 were evaluated. RESULTS: A total of three cancers, 39 adenomas and 41 hyperplastic polyps were found in the HNPCC group compared with one cancer, 22 adenomas and 19 hyperplasic polyps in the intermediate risk group. If the recent screening guidelines for the intermediate group were applied, then 89 (44%) fewer colonoscopies would have been performed. Although no cancers would have been missed, six adenomas (mean size = 5.7 mm, range 2-10 mm) with two graded as severely dysplasic and six hyperplastic polyps would not have been detected. CONCLUSION: The detection rate and distribution of adenomas were similar in both groups. If the new colonoscopic screening recommendations for the intermediate risk group had been applied, a small number of significant lesions would have been missed.     

Physical activity consultation for people with Type 2 diabetes: evidence and guidelines.

Physical activity is an important, but often underused, therapeutic strategy within diabetes care. To date, little is known about the best way to promote physical activity in diabetes care. Physical activity consultation is an intervention designed to promote physical activity behaviour change. This article provides guidelines on how to conduct a physical activity consultation with people who have Type 2 diabetes, and reviews the evidence surrounding the effectiveness of this intervention in this population. The trans-theoretical model is the underlying theory of behaviour change for the physical activity consultation intervention. The review identifies research which supports the use of this model for understanding physical activity behaviour in people with Type 2 diabetes. The review outlines a number of modifiable variables associated with physical activity behaviour change in this population. How each of these variables is addressed within the guidelines for conducting a physical activity consultation is identified. Finally, limited but consistent research highlights the effectiveness of physical activity consultation for promoting physical activity in people with Type 2 diabetes.     

循证护理在糖尿病皮肤损害临床实践中的应用

目的　应用循证护理 (EBN) ,探索糖尿病皮肤损害有效干预方法 ,减少残疾及死亡率 ,提高病人生活质量。方法　通过临床评估确定护理诊断 ,查阅文献 ,选择最佳护理证据 ,制定护理干预措施。结果　通过治疗及护理干预 ,2 2例糖尿病患者皮肤损害 ,显效 2 1例 ,有效 1例 ,转科 1例 ,出院时患者无并发症。结论　循证护理应用于临床 ,使传统护理经验走向护理科学发展 ;促进护士主动学习 ,提高护士综合素质 ;优质护理服务于个体化 ;解决患者现存的、潜在的护理问题 ,提高患者生存质量。     

All-cause and cardiovascular mortality in diabetic subjects increases significantly with reduced estimated glomerular filtration rate (eGFR): 10 years' data from the South Tees Diabetes Mortality study.

AIMS: To investigate the association between estimated glomerular filtration rate (eGFR) and total and cardiovascular mortality in a population-based cohort of diabetic subjects. METHODS: A longitudinal study using a population-based district diabetes register comprising 3288 subjects in South Tees, UK. The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) study equation. Patients were stratified by baseline eGFR into five stages as per the National Kidney Foundation guidelines: Stage 1, eGFR > 90; Stage 2, eGFR 60-89; Stage 3, eGFR 30-59; Stage 4, eGFR 15-29; and Stage 5, eGFR < 15 ml/min per 1.73 m(2). Main outcome was all-cause and cardiovascular mortality between 1 January 1994 and 31 July 2004. RESULTS: At baseline, mean age (58.4 years) differed between groups. Persons with lower eGFR were older (P < 0.001). Thirty-six percent (n = 1193, males 56%) had died by 10 years (cardiovascular cause in 60%). Median follow-up was 10.5 years amounting to 28 342 person years. Stages 4 and 5 (eGFR 相似文献   

Effects of self-management training in Type 2 diabetes: a randomized, prospective trial.

AIMS: The efficacy of three education programmes for Type 2 diabetic patients was tested in a randomized trial. A didactic-oriented training programme (treatment A) was compared with a self-management-oriented programme delivered in group sessions (treatment B). The latter programme was compared with a more individualized approach (treatment C). METHODS: One hundred and eighty-one Type 2 diabetic patients (age 55.6 +/- 6.3 years, diabetes duration 6.6 +/- 6.2 years, HbA(1c) 7.8 +/- 1.6%, female 49.7%) took part. Efficacy was assessed 3 months (t1) after baseline (t0) and at a follow-up 15 months (t2) after baseline. RESULTS: The fall in HbA(1c) in treatment B at t1 was sustained at t2 (t0 8.1 +/- 1.8%, t1 7.3 +/- 1.7%, t2 7.4 +/- 1.9%). In treatment A, HbA(1c) was unchanged throughout (t0 7.6 +/- 1.5%, t1 7.5 +/- 1.3%, t2 7.7 +/- 1.7%; treatment A vs. treatment B; P < 0.05). With the more individualized approach of treatment C, there was a fall in HbA(1c) at t1, but this was not sustained at t2 (t0 7.8 +/- 1.6%, t1 7.1 +/- 1.3%, t2 7.6 +/- 1.6%; treatment B vs. treatment C; P = 0.73). There were also significant benefits in treatment B subjects compared with treatment A in further medical (body mass index and fasting blood glucose), psychological (control, irritability and hunger dependency of eating behaviour, and trait anxiety) and behavioural (exercise) variables. There were no significant benefits of the more individualized treatment C compared with group treatment B. No significant differences were found regarding triglyceride levels, high-density lipoprotein, diabetes-related knowledge, negative well-being, urine or blood glucose levels or foot care. CONCLUSION: Self-management training had a significantly higher medium-term efficacy than didactic diabetes education. The group sessions were more effective than a more individualized approach.     

Psychosocial factors associated with poor diabetes self-care management in a specialized Center in Mexico City

To examine the relationship between demographic, clinical and psychosocial variables and diabetes self-care management in Mexican type 2 diabetic patients. Cross-sectional study of 176 consecutive patients with type 2 diabetes aged 30-75 years, attending a tertiary health-care center in Mexico City. A brief medical history and previously validated questionnaires were completed. The study group consisted of 64 males/112 females, aged 55 +/- 11 years, mean diabetes duration of 12 +/- 8 years and HbA1c of 9.0 +/- 2.0%, 78.4% reported following the correct dose of diabetes pills or insulin, 58% ate the recommended food portions, and 44.3% did exercise three or more times per week. A good adherence to these three recommendations was observed in only 26.1% of the patients. These patients considered as a group were characterized by a greater knowledge about the disease (P < 0.00001), regular home blood glucose monitoring (P < 0.01), an inner perception of better diabetes control (P = 0.007), good health (P = 0.004) and better communication with their physician (P < 0.02). A poor adherence to two or the three main diabetes care recommendations was associated with a depressive state (OR 2.38, 95% CI 1.1-4.9, P < 0.01) and a history of excessive alcohol intake (OR 4.03, 95% CI 1.1-21.0, P = 0.03). Poor adherence to standard diabetes care recommendations is frequently observed in patients with type 2 diabetes attending a specialized health care center in Mexico City. Depression must be identified and treated effectively.     

Maternal glycated haemoglobin, pre-gestational weight, pregnancy weight gain and risk of large-for-gestational-age babies: a Danish cohort study of 209 singleton Type 1 diabetic pregnancies.

AIMS: To examine the association between maternal glycated haemoglobin in the second half of diabetic pregnancies and the relative risk of delivering large-for-gestational-age (LGA) babies, controlling for maternal body mass index (BMI) before pregnancy, weight gain, age, White class and smoking habits. METHODS: We identified all pregnant diabetic women in North Jutland County, Denmark from 1985 to 2003. Data on HbA(1c) values from the 20th gestational week to term were collected from medical records and the babies were classified as large, normal or small for gestational age. The association between glycated haemoglobin (HbA(1c)) and relative risk of delivering an LGA baby was quantified based on logistic regression models and stratified analysis controlling for the five covariates. RESULTS: We included 209 singleton pregnancies with assessable HbA(1c) values of which 59%[95% confidence interval (CI) 52-65%] terminated with an LGA baby. Increasing levels of HbA(1c), BMI and weight gain were all associated with increasing risk of delivering an LGA baby. Analyses stratified according to maternal BMI showed that the association between HbA(1c) and risk of delivering an LGA baby was restricted to pregnancies with pre-pregnancy BMI > 23 kg/m(2). We found no association between HbA(1c) and risk of delivering an LGA baby in pregnancies with lower BMI. CONCLUSION: The positive association between glycated haemoglobin and birth of an LGA baby seems to be restricted to women with BMI > 23 kg/m(2).     

尿视黄醇结合蛋白在2型糖尿病肾病早期诊断中的意义

目的　探讨检测尿视黄醇结合蛋白 (RBP)在糖尿病肾病 (DN)早期诊断中的临床意义。方法　分别对 4 2例 2型糖尿病患者及 36例健康对照者用酶联免疫法 (ELISA)测定尿RBP ,用放射免疫法测定尿α1 微球蛋白 (α1 M )、β2 微球蛋白 (β2 M)。结果　糖尿病组三种尿微量蛋白排泄量明显高于健康对照组 ,且以尿RBP敏感性最高。结论　尿RBP的检测可敏感反映早期糖尿病患者肾小管损伤。     

Proposed diagnostic thresholds for gestational diabetes mellitus according to a 75-g oral glucose tolerance test. Maternal and perinatal outcomes in 3260 Danish women.

AIMS: To study if established diagnostic threshold values for gestational diabetes based on a 75-g, 2-h oral glucose tolerance test can be supported by maternal and perinatal outcomes. METHODS: Historical cohort study of 3260 pregnant women examined for gestational diabetes on the basis of risk indicators. Information on oral glucose tolerance test results and clinical outcomes were collected from medical records. RESULTS: There was an increased risk of delivering a macrosomic infant in women with 2-h capillary blood glucose of 7.8-8.9 mmol/l compared with women with 2-h glucose < 7.8 mmol/l. Despite treatment, 2-h glucose of 9.0-11.0 mmol/l and > or = 11.1 mmol/l were both associated with increased rates of macrosomia, spontaneous preterm delivery, hypertensive complications, and neonatal hypoglycaemia. Adverse outcomes tended to be more frequent in women with 2-h glucose > or = 11.1 mmol/l than in women with 2-h glucose of 9.0-11.0 mmol/l. CONCLUSIONS: The risk for several maternal and perinatal complications increased with the diagnostic threshold for 2-h glucose. Large-scale blinded studies are needed to clarify the question of a clinically meaningful diagnosis of gestational diabetes mellitus. Until these results are available, a 2-h threshold level of 9.0 mmol/l after a 75-g oral glucose tolerance test seems acceptable.