Assessment of the cytotoxicity and genotoxicity properties of Uvaria chamae P. Beauv (Annonaceae) and Morinda lucida Benth (Rubiaceae) in mice

The toxicity profile of medicinal plants is an important preclinical requirement in the development of phytomedicines. The cytotoxic and genotoxic effects of the leaf of Uvaria chamae P. Beauv (Annonaceae) and stem bark of Morinda lucida Benth (Rubiaceae) were investigated in order to provide information on their safety as antimalarial plants. The methanol extract of U. chamae and ethanol (70%) extract of M. lucida were separately orally administered (125, 250, and 750?mg/kg/day) to mice for 10 consecutive days. Cyclophosphamide (50?mg/kg, single dose) and distilled water were used as positive and negative controls, respectively. The mice were injected with colchicine (0.04%) intra-peritoneally 24?h after the last administration of the extracts and the bone marrows harvested. Giemsa-stained slides of bone marrow cells were microscopically assessed for dividing cells to determine the mitotic index (MI) and scored for chromosomal aberrations (CA) according to standard methods. chamae exhibited dose-dependent cytotoxicity. At 750?mg/kg, the MI was significantly (p?M. lucida was not significantly different (p?>?0.05) from that of the negative control. The total CA observed from treatment with both plants at all doses were significantly (p?U. chamae showed both cytotoxicity and genotoxicity while M. lucida exerted only genotoxic effect. Nevertheless, the two plants should be used with caution in antimalarial therapy.     

Dibucaine in Ionic-Gradient Liposomes: Biophysical,Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC.     

The prevalence of constipation at admission and after 1 week of palliative care: a multi-center study

Aim: To assess the prevalence and intensity of constipation in advanced-cancer patients referred to palliative care, and to assess changes after 1 week of specialist palliative care.

Methods: This was a prospective multi-center study in advanced patients for a period of 1 year. At admission (T0), age, gender, primary tumor, concomitant diseases, Karnofsky status, Palliative prognostic score (PaP), Edmonton Symptom Assessment scale (ESAS), Memorial Delirium Assessment Scale (MDAS), and bowel function index (BFI) were collected. In BFI, high values represent severe constipation. The use of medication was also recorded, as well as possible causes of constipation. The same parameters were recorded 1 week after admission for palliative care (T7).

Results: A total of 246 patients were screened for constipation. The mean BFI at T0 was 42.4 (SD?=?26.92). One hundred and sixty-three patients (66.3%) had a BFI >28. The mean BFI at T7 was 35.7 (SD?=?28.8), with a significant decrease from T0 to T7 (p?=?.000). A significant decrease of BFI in patients with a BFI >28 was reported (p?=?.000). In patients with a BFI ≤28 there was a significant worsening of constipation (p?=?.000). In patients with a BFI >28 at T0 there was a significant increase in the use of laxatives at T7 in comparison with patients having a BFI ≤28 (p?=?.002). In patients with a BFI ≤28 at T0, who had a significant worsening of BFI (Δ?>?12), the use of laxatives was significantly lower in comparison to patients who had a BFI >28 (p?=?.000). In the multivariate analysis, dehydration and the use of benzodiazepines were independently associated with higher BFI scores.

Conclusion: Constipation is present in approximately two-thirds of patients, and is principally associated with dehydration and the use of benzodiazepines. Patients with normal bowel function at initial assessment may see a worsening in their condition a week later due to lack of prevention or subsequent under-treatment.     

基于大数据的基本医疗保险参保人欺诈风险评估

目的:构造基本医疗保险参保人欺诈风险预测模型,发现欺诈行为的主要特征,进而建立风险评估指标体系,以期为医保基金智能监管提供决策支持。方法:利用183万多条我国基本医疗保险诊疗历史记录的大规模真实数据,应用XGBoost算法和EasyEnsemble方法构造基本医疗保险参保人欺诈风险评估集成模型。在此基础上,利用特征重要度计算进一步识别和量化欺诈行为人的潜在特征以构造欺诈风险评估指标体系。结果:模型预测结果的准确性为83%;阳性与阴性预测值的加权平均值为95%;参保人欺诈的可能性能够被正确评估的概率为85%;其中,实际产生欺诈行为的所有参保人中,有82%的人员能通过本模型正确识别;各项费用发生金额、各阶段费用发生金额以及各类项目的数量等是区分欺诈与正常参保人的重要指标。结论:基于XGBoost集成模型构建的基本医疗保险参保人欺作风险评估指标体系能够有效地用于识别潜在欺诈人员。建立健全的风险评估指标体系并开发基于医保大数据的智能化监控系统,对于提高医保管理服务水平,保障医保基金安全以及维护社会医保的公平性有重要作用。     

2型糖尿病患者体质量指数与甲状旁腺素、 25羟维生素D的相关性研究

摘要：目的 探讨 2 型糖尿病（T2DM）患者体质量指数（BMI）与甲状旁腺素（PTH）、25 羟维生素 D［25（OH）D］的 相关性。方法 收集首都医科大学附属北京朝阳医院内分泌科住院治疗的 2 型糖尿病患者 110 例,BMI 在 18.5～ 23.9 kg/m2患者作为正常体质量组（n=24）,BMI 在 24.0～27.9 kg/m2患者作为超重组（n=47）,BMI≥28.0 kg/m2患者作为 肥胖组（n=39）。记录患者年龄、性别、吸烟史、BMI、腹围和臀围。采集清晨空腹外周血,通过全自动生物化学分析仪 检测总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、三酰甘油（TG）、血清白蛋白 （ALB）、尿素氮（BUN）、血肌酐（Cr）、血清钙（Ca2+）、血清磷（P）、游离脂肪酸（FFA）、空腹血糖（FPG）和空腹胰岛素 （FINS）。高效液相色谱法测定糖化血红蛋白（HbA1c）。采用乳胶增强免疫透射比浊法测定超敏 C 反应蛋白（hs CRP）。采用免疫化学发光法测定 PTH、25（OH）D。计算稳态模型胰岛素抵抗指数（HOMA-IR）。利用简化肾脏病膳 食改善公式（MDRD）估算肾小球滤过率（eGFR）。比较 3 组间 PTH、25（OH）D 及各指标的差异,多重线性逐步回归 分析 BMI 与 PTH、25（OH）D 等指标的相关性。结果 与正常体质量组比较,超重组的腹围、臀围、FINS 明显升高 （P＜0.05）;肥胖组的腹围、臀围、PTH、FINS、HOMA-IR 明显升高（P＜0.05）。与超重组比较,肥胖组的腹围、臀围、 hs-CRP、PTH 明显升高（P＜0.05）。多元线性逐步回归分析结果提示,BMI 与臀围（β=0.293）、腹围（β=0.060）、FINS （β=0.026）、PTH（β=0.019）呈正相关（P＜0.05）。结论 T2DM 患者 BMI 与 PTH 密切相关,与 25（OH）D 无关。     

Associations of Body Mass Index and Waist Circumference with 3-Year All-Cause Mortality Among the Oldest Old: Evidence from a Chinese Community-Based Prospective Cohort Study

Objective

Current international and national guidelines for body mass index (BMI) and waist circumference (WC) have been recommended to all adults. However, whether recommendations applied to the oldest old (aged 80+) is poorly known. The study objective was to investigate the relation of BMI and WC with 3-year all-cause mortality among the oldest old.

Assessment of Skeletal Muscle Mass in Older People: Comparison Between 2 Anthropometry-Based Methods and Dual-Energy X-ray Absorptiometry

Objectives

Sarcopenia is a common geriatric syndrome, whose diagnosis implies the assessment of muscle mass. Dual-energy x-ray absorptiometry (DXA) is the reference method for clinical practice, but it is not universally available. We compared DXA with 2 anthropometry-based methods to assess muscle mass in older adults.

Being overweight or obese as a risk factor for acute liver injury secondary to acute acetaminophen overdose

Purpose

Increased incidences of hepatotoxicity have been observed in obese patients with acute acetaminophen overdose. We evaluate whether the status of being overweight or obese is associated with increase in the development of hepatotoxicity and acute liver injury (ALI) in patients with acute acetaminophen overdose.

Methods

This was a retrospective cohort study comparing the risk of hepatotoxicity and ALI between overweight or obese patients (body mass index [BMI] ≥ 25) and normal BMI patients (BMI ≤ 24.9) presenting with acute acetaminophen overdose at Siriraj Hospital during January 2004 to June 2012. All patients were treated with intravenous N‐acetylcysteine. Psi parameters were calculated. High psi was defined as psi of ≥5.0 mM‐hour. Data were analyzed using multinomial logistic regressions, odds ratio (OR), stratified OR, and 95% confidence interval (CI).

Results

There were 197 patients who fulfilled the criteria for analysis, 35 (17.8%) were obese, 24 (12.2%) were overweight, and 138 (70%) were normal BMI cases. Hepatotoxicity and ALI developed in 25 (12.7%) and 40 (20.3%) cases, respectively. Multinomial logistic regression revealed that the overweight‐obesity status and log₁₀(psi value) were significant risk factors of ALI, with OR (95% CI) of 2.68 (1.21‐5.95) and 1.74 (1.27‐2.38), respectively, while only log₁₀(psi) was a significant risk factor of hepatotoxicity with OR (95% CI) 378.51 (39.49‐3627.99). From stratification, overweight‐obesity had significant odds ratios for ALI in strata with low acetaminophen concentration, early initiation of N‐acetylcysteine and low psi.

Conclusion

We conclude that being overweight or obese is an independent risk factor of ALI in acute acetaminophen overdoses.     

Sample size calculations for blinding assessment

Blinding is a critical component in randomized clinical trials along with treatment effect estimation and comparisons between the treatments. Various methods have been proposed for the statistical analyses of blinding-related data, but there is little guidance for determining the sample size for this type of data, especially if blinding assessment is done in pilot studies. In this paper, we try to fill this gap and provide simple methods to address sample size calculations for a “new” study with different research questions and scenarios. The proposed methods are framed in terms of estimation/precision or statistical testing to allow investigators to choose the best suited method for their goals. We illustrate the methods using worked examples with real data.     

On evaluation of consistency in multi-regional clinical trials

In recent years, multi-regional clinical trials (MRCT) that conduct clinical trials simultaneously in Asian Pacific region, Europe, and the United States have become very popular for global pharmaceutical development. The main purpose of multi-regional clinical trials is to shorten the time for pharmaceutical development and regulatory submission, and approval around the world. In practice, however, clinical results observed from some regions (sub-population) may not be consistent with the results from other regions and/or all regions combined (entire population). The inconsistency observed may be due to ethnic differences in different regions, differences in medical practice, time points of assessment, or by random chance due to small sample size for the region. Some regional regulatory agencies require consistency evaluation between local country results and overall results. However, the challenge is there is no detailed guidance on the definition of ‘consistency’ and methodology to evaluate it. Therefore, the questions are: how to evaluate consistency and what statistical methods are appropriate to be used for consistency evaluation? In this article, several statistical tests for consistency (similarity) between clinical results observed from a specific sub-population and the entire population are proposed. These methods are compared through extensive simulation. As most published articles discussed consistency evaluation for superiority situations, we have discussed consistency evaluation for non-inferiority situation in this article through a simulated example concerning consistency in some countries. Recommendations of the statistical methods to be used for consistency evaluation are given. Other aspects that should be considered for consistency evaluation are also provided.