Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

Abstract   We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score >2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15–2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN.     

Design of clinical trials for chronic diseases: implications for periodontal disease

In order to make effective use of the statistical theory of design of clinical trials for chronic diseases such as periodontal disease, certain issues must be considered. Any clinical trial requires that the disease definition be well-specified; that patient eligibility be explicit; that the observation times be explicit; that the duration and endpoint of therapy be specified; that the duration of subsequent followup observation be specified; and that the unit of observation (e.g., tooth, set of teeth, patient) be defined. In a chronic disease, the potential biases that can readily be introduced by self-selection of patients who enter the trial and/or who return for subsequent observation become more important, because subjects are required to remain on treatment and/or observation for prolonged periods. Further, the cyclical nature of some chronic diseases may require special attention to baseline definitions of active disease and disease outcome. These issues are illustrated with examples from clinical trials of hypertension, breast cancer screening, and Polycythemia Vera. Implications for periodontal disease are discussed.     

导航辅助脊柱胸腰段椎弓根钉植入的临床应用

目的探讨临床运用计算机影像导航技术引导脊柱胸腰段椎弓根钉植入的准确性。方法2003年5月-2007年5月，29例患者接受116枚计算机影像导航技术引导脊柱胸腰段椎弓根钉植入手术治疗，T10-T1250枚胸椎弓根钉，L1-L3 66枚腰椎弓根钉。术中记录椎弓根钉植入所需时间及C-臂透视工作次数，椎弓根钉植入完成后，即行C-臂正侧位摄片并与导航路径进行比较测量。术后CT进行椎弓根层面扫描，根据椎弓根钉与椎弓根皮质问关系分为四级：A=在椎弓根内；B=突破皮质，〈2mm；C=突破皮质，2-4mm；C=突破皮质，〉4mm。结果术后CT椎弓根位置扫描显示：A级101枚（87．07％）；B级10枚（8．62％）；C级2枚（1．72％）；D级3枚（2．59％）。1枚椎弓根钉植入平均所需时间：2．73±0．64min（1．15～4．02min）。下胸椎9枚（7．75％）胸椎弓根钉突破皮质，上腰椎6枚（5．17％）腰椎弓根钉突破皮质，且临床观察未发现与椎弓根钉突破皮质相关的神经血管等并发症。植入的椎弓根钉C-臂正侧位摄片与导航路径吻合比较，进钉点均差2．6mm（最大3．1mm），角度均差3．3°（最大5．4°）。结论计算机影像导航辅助脊柱胸腰段椎弓根钉植入，提供二维、多平面实时显示，保证了脊柱胸腰段椎弓根钉植入的准确性及安全性，明显减少放射线的暴露强度。     

A simple method for screening assessment of acute toxicity of chemicals

We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD₅₀ values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD₅₀ values reported in the literature. Our toxicological data also showed that LD₅₀ values were about 2–2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD₅₀ of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD₅₀ values of chemicals and for screening for necessity for classical full LD₅₀ test using many animals.This work was supported by a grant from Ministry of Health and Welfare in Japan (No. 467 and 511)     

浙江省某乡村慢性肾脏病的流行病学研究

目的 研究我国南方某农村人群中慢性肾脏病（CKD）的患病率及相关因素。方法 对浙江省东阳市某乡村18岁以上的常住居民慢性肾脏病情况及相关因素进行调查和检测。结果 获得完整资料的居民占该村18岁以上自然人口的76．2％。将该村自然人口按年龄性别构成校正后，白蛋白尿发生率为10．4％；肾小球滤过率〈60ml·min^-1·（1．73m^2）^-1的发生率为3．0％；血尿发生率为1．4％。本研究中40岁以上调查对象与北京市某社区及NHANESⅢ中40岁以上调查对象相比，高血压及糖尿病的患病率较低，白蛋白尿和肾功能下降的发生率介于2者之间。多因素Logistic回归提示，年龄增加10岁、糖代谢异常及收缩压水平与白蛋白尿的发生独立相关；女性、年龄增加10岁、高尿酸血症与肾功能下降独立相关；年龄增加10岁及吸烟与血尿独立相关。结论 在该经济快速发展的南方乡村，CKD的疾病谱和相关因素已经与我国大城市和发达国家类似。此外，该人群可能另有导致CKD高发的特殊原因，需进一步研究。     

The value of different resistance parameters in distinguishing biopsy-proved dysfunction of renal allografts

The data concerning the value of duplex sonography in diagnosingparenchymatous renal allograft dysfunction are controversial.Most early studies did not take into consideration the manyfactors influencing resistance parameters. We therefore performeda prospective, biopsy-controlled study with exclusion of allknown sources of error regarding resistance parameters. Furthermorewe investigated the value of a new resistance parameter, thesystolic deceleration percentage. Forty-seven duplex sonographicstudies were performed on 43 patients (30 male, 13 female, medianage 47 years, range 7–70). Fourteen studies were doneon normally functioning grafts (control group) an average of33 days after transplantation. Thirty-three studies were performedon dysfunctional grafts immediately prior to biopsy. Graftswhich had been transplanted more than a year previously or withvascular findings or any other clinical or sonographic pathologyprobably explaining function deterioration were excluded. Inall patients, the resistive index (RI), pulsatility index (PI)and systolic deceleration percentage (DP) were calculated inthe main renal artery and in the interlobar artery. Of the 33grafts with dysfunction, nine had vascular rejection (VR), 11interstitial rejection (IR), 11 cyclosporin A toxicity (CAT)and two other histologies (OR). The mean RI in normal grafts(NO) was 0.71±0.06 in the main artery and 0.68±0.06in the interlobar artery, in VR 0.86±0.12 and 0.80±0.18,in IR 0.72±0.05 and 0.70±0.07, in CAT 0.67±0.06and 0.65±0.07 and in OR 0.64±0.07 and 0.60±0.01.For PI, the values were 1.45±0.23 and 1.41±0.28(NO), 3.5±2.13 and 2.92±2.16 (VR), 1.55±0.26and 1.46±0.33 (IR), 1.32±0.25 and 1.27±0.26(CAT) and 1.30±0.34 and 1.13±0.04 (OR). For DPwe calculated 28±5% and 29±6% (NO), 43±14%and 36±6% (VR), 29±9% and 27±9% (IR), 31±8%and 32±7% (CAT ) and 32±4% and 28±3% (OR).The sensitivity/specificity for VR with a cutoff mean+2 SD was0.44/1 for RI, 0.55/0.97 for PI and 0.33/0.89 for DP. It wasconcluded that:(1) despite the high selection of our patientgroup, diagnostic accuracy of duplex sonography for diagnosingparenchymatous function disorder in renal allograft remainsinsufficient; (2) in vascular rejection only, the resistanceparameters differ significantly from the values of normal allografts;(3) the higher the cutoff of resistance parameters, the betterthe specificity and the worse the sensitivity for diagnosingvascular rejection; (4) of all investigated resistance parameters,the RI is the most practical due to a simple measurement technique.     

Diagnostic Validity of Fecal Occult Blood Tests for Detecting Gastroenterological Cancers

In order to estimate the diagnostic validity of chemical fecal occult blood tests, i.e. orthotolidine (Shionogi A) and guajac (Shionogi B) slides for detecting cancers of the esophagus, stomach and colorectum, the authors followed up all the examinees (n=3,449) of comprehensive medical check-ups at the Center for Adult Diseases, Osaka, by means of record linkage to the Osaka Cancer Registry's files. Then, diagnostic validity was calculated based on the results of two years' follow-up. Sensitivity for the respective cancers was 20.0%, 11.8% and 62.5% for Shionogi A, and 20.0%, 5.9% and 43.8% for Shionogi B slides. Likelihood ratio for the respective cancers was 1.4, 0.8 and 4.5 for Shionogi A, and 3.3, 1.0 and 7.5 for Shionogi B. Specificity was analogous among the three cancer sites, being 86% for Shionogi A and 94% for Shionogi B. These results suggest that the diagnostic validity of chemical occult blood tests for detecting cancers of the esophagus and the stomach is very poor, and therefore imply that close examinations of these sites for screening positives is unnecessary in mass screenings for colorectal cancer.