研究设计时混杂控制策略的结构分类

混杂影响着人群因果关系的发生。依据混杂因素是否已知、可测量及已测量,可将其分为4类情形。基于有向无环图,对混杂的控制策略分为两类：①混杂路径打断法,又可分为单路径和双路径打断法,分别对应于暴露完全干预法、限制法和分层法;②混杂路径保留法,分别对应于暴露不完全干预法（工具变量设计或不完美的随机对照试验）、中间变量法和匹配法。其中,随机对照试验、工具变量设计或孟德尔随机化设计、中间变量分析可满足4类混杂的控制,而限制法、分层法和匹配法仅适用于已知、可测量并已测量的混杂。识别不同类型混杂的控制机制,有助于在研究设计阶段提出应对措施,是获得正确因果效应估计的前提。     

基于人畜疫情分层的血吸虫病流行区综合治理投入与效果评价Ⅱ2006-2013年湖沼垸内型地区疫情变化与费用投入关联分析

目的研究湖沼垸内型血吸虫病流行区血吸虫病疫情变化与经费投入和防治费用的关联性,为优化血吸虫病防治策略提供参考。方法选择江陵县为研究区,采用直线相关与回归法分析当地2006-2013年血吸虫病疫情;采用两阶段最小二乘法与路径递归模型分析经费投入与防治费用对当地疫情变化的可能影响。结果 2006-2013年,江陵县人群校正感染率、耕牛存栏数与钉螺面积分别下降了77.42%、76.34%和19.43%;钉螺感染率与人群血检、粪检阳性率及耕牛感染率均呈显著相关,且与耕牛感染率呈直线回归关系(P均0.05)。各级投入与人群血检和粪检阳性率、耕牛和钉螺感染率,以及各类费用与人群粪检阳性率、耕牛和钉螺感染率的回归模型均有统计学意义(P均0.05),但各类费用与人群血检阳性率回归模型无统计学意义(P0.05);影响人群血检阳性率、人群粪检阳性率、耕牛感染率和钉螺感染率的分别为县级投入、综合治理费用、人工费用与查治病费用、国家级投入与查治病费用(P均0.05)。结论 2006-2013年,江陵县血吸虫病疫情变化与各级投入、防治费用均有关联;各疫情指标相互显著相关的现象提示应开展综合性监测体系研究。     

左氧氟沙星750mg注射液5日短程疗法治疗社区获得性肺炎的多中心临床研究

目的：比较左氧氟沙星750 mg注射液5 d短程疗法与500 mg注射液7-14 d常规疗法治疗社区获得性肺炎（CAP）疗效和安全性差异。方法本临床试验为随机对照、开放、非劣效性多中心临床试验。CAP患者被随机分配到左氧氟沙星750 mg组治疗5 d或500 mg组治疗7-14 d ,两组均接受静脉给药治疗,观察其临床表现、实验室检查、影像学改变及微生物学检查等,比较两组安全性和疗效差异。结果10个研究中心共入选病例241例。其中全分析集（FAS ）223例,包括750 mg组111例,500 mg组112例。符合方案分析集（PPS）211例,包括750 mg组107例,500 mg组104例。安全性分析集（SS）241例,包括750 mg组121例,500 mg组120例。FAS 750 mg组疗程中位数为5．0 d ,500 mg组疗程中位数为9．0 d。750 mg组总剂量中位数为3750 mg ,500 mg组总剂量中位数为4500 mg。FAS第4次随访750 mg组有效率为86．2％,500 mg组有效率为84．7％,两组综合疗效评价相比为非劣效。FAS 750 mg组可进行微生物疗效评价者共40例,获病原菌41株,500 mg组可行微生物疗效评价者共49例,获病原菌51株,两组细菌清除率均为100％。另外,750 mg组和500 mg组的非典型病原体的临床有效率均为100％。对750 mg组安全性观察结果显示,临床不良反应最常见为注射部位瘙痒、疼痛和充血等,其次为失眠、恶心、皮疹等。较常见的实验室指标异常为中性粒细胞比率降低、白细胞总数降低、ALT升高、AST升高等。以上不良反应多属轻微,患者可耐受,与500 mg组相比,因药物中止试验和不良反应发生率差异无统计学意义,提示两组安全性相仿。结论左氧氟沙星750 mg注射液5 d短程疗法治疗CAP与左氧氟沙星500 mg注射液7-14 d常规疗程相比,其临床和微生物疗效相仿,不良反应发生率相仿,均较轻微,患者耐受性好。     

多重耐药不动杆菌属血流感染74例临床分析

目的研究多重耐药不动杆菌血流感染的菌种分布特点、临床特征、抗菌治疗及其与预后的关系。方法回顾性分析复旦大学附属华山医院2005年1月—2011年12月不动杆菌血流感染患者的临床及微生物学资料。结果 74例不动杆菌血流感染患者入选,其中73例为医院感染,1例为社区获得性感染;原发性血流感染占51.4%（38/74）;继发性血流感染占48.6%（36/74）,继发于肺部感染最常见,占23.0%（17/74）。基础疾病以实体肿瘤最多见,占24.3%（18/74）,糖皮质激素应用、深静脉导管留置、手术及侵袭性操作是常见的诱发因素。发生血流感染后患者外周血白细胞总数及中性粒细胞比例较前升高,血清白蛋白水平下降,APACHEⅡ评分升高。74例血流感染患者中鲍曼不动杆菌感染65例,洛菲不动杆菌7例,琼氏不动杆菌1例,鲍曼不动杆菌和洛菲不动杆菌混合感染者1例;全因病死率为27.0%（20/74）。不动杆菌对头孢哌酮-舒巴坦耐药率最低,为20.0%（15/75）,对碳青霉烯类抗生素耐药率为40.0%～42.7%。患者预后与不动杆菌对抗菌药物的敏感性相关。对碳青霉烯类和含舒巴坦制剂不敏感菌株感染患者的病死率分别为46.9%（15/32）和40.0%（12/30）,显著高于敏感菌株感染患者的11.9%（5/42）和18.2%（8/44）。32例对碳青霉烯类不敏感菌株感染的患者中,20例接受了含舒巴坦制剂的抗菌药物,病死率为20.0%（4/20）,明显低于未使用含舒巴坦制剂药物患者的66.7%（8/,12）。结论不动杆菌血流感染绝大多数为医院感染,多发生于术后及重症患者。不动杆菌属对常用抗菌药物高度耐药,对碳青霉烯类和含舒巴坦制剂不敏感菌株感染患者病死率高,预后极差,应重视医院感染的防控。     

城市社区全科医生培训现状及需求调查：专题小组访谈

目的了解我国城市社区全科医生培训现况及需求,为下一步制定相关政策提供参考依据。方法2011年9—12月,对辽宁、福建、宁夏3个省的19名全科医学师资实施了专题小组访谈。访谈在各地培训基地会议室实施。访谈时间平均为2h左右。借助计算机对资料进行编码、归类、精简,总结出访谈主题。结果①集中授课及临床轮转是培训的主要方式;②培训内容多以基本知识和基本技能为主,大纲修订应侧重于这些方面;③作为师资对自身业务水平也有提高和帮助;④工学矛盾、师资水平不高是培训中的主要问题,受访者提出了解决建议。结论培训内容贴近实际需求、多手段解决工学矛盾、加强师资培训l是未来进一步提高全科医学培训质量所需解决的关键问题。     

2003-2012年吉林省新农合住院患者就诊及费用流向调查分析

目的：分析近10年来吉林省农村住院患者就诊与医疗费用的流向,探讨存在的主要问题并提出相应的对策。方法：通过2003-2012年吉林省新型农村合作医疗(新农合)信息系统中的统计报表收集资料,同时采用整群抽样方法,对2003-2012年参加新农合(简称参合)的住院患者进行调查,分析各级医院的住院人次、住院费用、住院补偿金额和次均住院补偿比等。结果：2003-2012年分流到县级以上和县级医疗机构的住院人次、住院费用和住院补偿费用逐年增加。2009年参合农民住院人次分流到县级以上、县级、乡级医疗机构的构成比分别为26.7%、46.3%和27.0%,2012年分别为30.4%54.2%和15.4%。2009年住院费用分流到县级以上、县级、乡级医疗机构的构成比分别为57.0%、34.0%和9.0%,2012年分别为56.3%、37.9%和5.8%。2009年住院补偿费用分流到县级以上、县级、乡级医疗机构的构成比分别为49.2%、38.1%和12.7%,2012年分别为46.3%、45.6%和8.1%。2009年县级以上、县级、乡级医疗机构的次均住院补偿比例分别为32.2%、41.5%和52.6%,2012年分别为43.2%、63.1%和73.4%。结论：近10年来,吉林省参合农民的住院人次、住院费用和住院补偿费用分流到县级以上和县级医疗机构的比例均明显增多,分流到乡级医疗机构则逐年减少。次均住院补偿比在省内各级医院均逐年升高,乡级医疗机构的次均住院补偿比最高。     

Safety,Tolerability, and Pharmacokinetics of Intravenous Nemonoxacin in Healthy Chinese Volunteers

Nemonoxacin (TG-873870) is a novel nonfluorinated quinolone with potent broad-spectrum activity against Gram-positive, Gram-negative, and atypical pathogens, including vancomycin-nonsusceptible methicillin-resistant Staphylococcus aureus (MRSA), quinolone-resistant MRSA, quinolone-resistant Streptococcus pneumoniae, penicillin-resistant S. pneumoniae, and erythromycin-resistant S. pneumoniae. This first-in-human study was aimed at assessing the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin in healthy Chinese volunteers. The study comprised a randomized, double-blind, placebo-controlled, dose escalating safety and tolerability study in 92 subjects and a randomized, single-dose, open-label, 3-period Latin-square crossover pharmacokinetic study in 12 subjects. The study revealed that nemonoxacin infusion was well tolerated up to the maximum dose of 1,250 mg, and the acceptable infusion rates ranged from 0.42 to 5.56 mg/min. Drug-related adverse events (AEs) were mild, transient, and confined to local irritation at the injection site. The pharmacokinetic study revealed that after the administration of 250, 500, and 750 mg of intravenous nemonoxacin, the maximum plasma drug concentration (C_max) values were 4.826 μg/ml, 7.152 μg/ml, and 11.029 μg/ml, respectively. The corresponding values for the area under the concentration-time curve from 0 to 72 hours (AUC_{0–72 h}) were 17.05 μg · h/ml, 39.30 μg · h/ml, and 61.98 μg · h/ml. The mean elimination half-life (t_1/2) was 11 h, and the mean cumulative drug excretion rate within 72 h ranged from 64.93% to 77.17%. Volunteers treated with 250 to 750 mg nemonoxacin exhibited a linear dose-response relationship between the AUC_{0–72 h} and AUC_0–∞. These findings provide further support for the safety, tolerability, and pharmacokinetic properties of intravenous nemonoxacin. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01944774","term_id":"NCT01944774"}}NCT01944774.)     

Pituitary adenomas in patients with multiple endocrine neoplasia type 1: a single-center experience in China

Purpose

To explore the clinical characteristics of pituitary adenomas in patients with MEN1 and to summarize treatment strategies for MEN1 in a Chinese population.

Methods

We retrospectively analyzed 54 MEN1 patients with pituitary adenomas diagnosed at Peking Union Medical College Hospital from March 2003 to January 2017. Clinical data, laboratory testing results, treatments of involved glands and treatment responses were collected and analyzed.

Results

The mean age at pituitary adenoma diagnosis was 53.9?±?17.8. The patients initially consulted the Endocrinology, General Surgery and Neurosurgery departments, in descending frequency. The nonfunctioning adenoma, prolactinoma, GH-secreting adenoma, cosecreting adenoma, and ACTH-secreting adenoma subtypes accounted for 48.1%, 27.8%, 9.3%, 9.3% and 5.6% of the cases, respectively. The remission rate for prolactinomas was 46.2% (6/13) treated with bromocriptine. And the remission rates were 87.5% (7/8) and 100% (3/3) for GH-secreting adenomas and ACTH-secreting adenomas respectively achieved by transsphenoidal surgery. Nineteen (35.2%) patients with asymptomatic nonfunctioning pituitary adenomas showed no progression after a 35-month follow-up with close observation. Regarding treatment priority, patients with thymic carcinoid tumors received first-line surgery, 54% of the patients with enteropancreatic tumors had these tumors treated first, and 26% of all patients had their pituitary adenomas treated first. In acromegalic patients, pituitary lesions tended to be treated first (75%, p?=?0.002). PHPT and adrenocortical adenomas can be managed with elective surgery.

Conclusions

The treatment of MEN1 requires cooperation between multidisciplinary teams. Individualized treatment according to the severity of glandular involvement is needed. GH-secreting and ACTH-secreting pituitary adenomas require active treatment, while nonfunctioning pituitary adenomas can be observed closely.

     

Lanostane triterpenoids and ergostane-type steroids from the cultured mycelia of Ganoderma capense

Abstract

Two new lanostane triterpenoids (1 and 2), two new ergostane-type steroids (3 and 4) together with two known lanostane triterpenoids (5 and 6) and one known steroid (7) were isolated from the cultured mycelia of Ganoderma capense (CGMCC 5.71). Their structures were determined on the basis of extensive spectroscopic (HRESIMS, 1D NMR, 2D NMR) data analyses. Compound 1 exhibited moderate cytotoxic activity against the human cancer cell line NCI-H1650 with an IC₅₀ value of 22.3 μM, and 7 displayed cytotoxic activity against the human cancer cell line HCT116 with an IC₅₀ value of 17.4 μM. In addition, compounds 2, 3, 5, and 6 displayed weak anti-HIV activity with IC₅₀ values of 23.5, 46.7, 21.6, and 30.1 μM, respectively.