特定转移Cox模型在阿尔茨海默病进程研究中的应用

目的 将特定转移Cox模型应用于老年人阿尔茨海默病（alzheimer's disease,AD）进程研究中,探讨AD不同阶段转归的影响因素。方法 利用太原市三个社区2010年10月~2014年10月的9次随访数据,根据AD进程中的五个状态结构,包括轻度认知损害（mild cognitive impairment,MCI）、AD、失访或删失、死于AD（DEATH）和死于其他原因,拟合特定转移Cox模型,分析AD进程中各状态向其他状态转移的影响因素。结果 按照α=0.05水准,年龄（HR=0.68,95% CI:0.52～0.90）、性别（HR=2.13,95% CI:1.32～3.43）、吸烟（HR=1.93,95% CI:1.25～2.98）、高血压（HR=2.51,95% CI:1.55～4.08）、高血脂（HR=2.03,95% CI:1.25～3.30）、糖尿病（HR=1.71,95% CI:1.10～2.67）对MCI→AD转移有统计学意义;亲属痴呆情况（HR=4.11,95% CI:1.33～12.69）对MCI→DEATH转移有统计学意义;亲属痴呆情况（HR=5.88,95% CI:1.91～18.06）、高血压（HR=7.06,95% CI:1.60～31.26）对AD→DEATH转移有统计学意义。结论 根据AD进程中各状态间转移的主要影响因素,采取疾病分状态的重点防治措施,延缓疾病进展。     

基于分段常数强度Markov模型的阿尔茨海默病进程研究

目的将分段常数强度Markov模型应用于轻度认知损害(mild cognitive impairment,MCI)向阿尔茨海默病(Alzheimer's disease,AD)转归过程中,深入研究影响转归过程的因素,为制定不同发展阶段的预防措施提供理论依据,为其他多状态慢性病不同发展阶段影响因素的探讨提供方法学借鉴。方法应用太原市600名社区老年人的4次随访资料,以MCI为状态1,中重度认知损害为状态2,AD为状态3,拟合分段常数强度Markov模型,分析MCI向AD转归不同发展阶段的影响因素,并根据模型计算3年转移概率矩阵。结果经假设检验,数据满足Markov性(P=0.89),不满足时齐性(P0.001),应用分段常数强度Markov模型拟合,经多因素筛选,女性、年龄、吸烟、高血压和糖尿病是MCI向AD转归的危险因素,高文化程度和从事脑力劳动是MCI向AD转归的保护因素。由中重度认知损害向AD的转移概率随着随访时间的增加而增加。结论在数据满足Markov性,不满足时齐性时,分段常数强度Markov模型是对疾病转归过程的相关影响因素及其变化规律的有效分析方法。     

时间转换Markov模型在阿尔茨海默病进程研究中的应用

目的建立轻度认知损害(mild cognitive impairment,MCI)向阿尔茨海默病(Alzheimer's disease,AD)状态转归的时间转换Markov模型,探讨MCI状态向AD状态转归的影响因素并进行转归预测,同时对模型进行评价。方法截止到2012年对太原市518名社区老年人共进行5次随访调查,将MCI到AD的过程分为MCI(状态1),中重度认知损害状态(状态2)和AD(状态3)3个状态。对随访数据拟合3状态的时间转换Markov模型,评价模型拟合情况并分析AD进程不同阶段的影响因素,依据拟合的时间转换Markov模型计算转移强度矩阵,并预测3年转移概率。结果通过假设检验,数据不满足时齐性(P0.01),但是满足马氏性(P=0.468),可对数据采用时间转换Markov模型进行拟合,模型拟合优度较好(P0.05)。采用时间转换Markov模型,经多因素筛选,发现性别、年龄、教育水平、工作类型、吸烟和高血压对状态1到状态2的转移有统计学意义,年龄、教育水平、工作类型、糖尿病和高血压对状态1到状态3的转移有统计学意义,年龄、教育水平、吸烟、糖尿病和高血压对状态2到状态3的转移有统计学意义。结论在AD发展进程的不同阶段,主要影响因素不同。与齐次Markov模型相比,时间转换Markov模型能更全面地分析相关的影响因素与探讨疾病进程的变化规律。     

基于竞争风险模型的老年人轻度认知损害转归研究

目的 将竞争风险模型应用于老年人轻度认知损害(MCI)转归研究,探讨MCI向阿尔茨海默病(AD)转归的影响因素并进行转归预测。方法 利用太原市600例社区老年人2010年10月至2013年5月每6个月随访1次的共6次随访数据,以MCI作为暂态,AD与发生AD前死亡分别作为两个吸收态,发生AD前死亡为AD的竞争风险事件,构建竞争风险模型,获得模型参数,分析MCI向AD转归的影响因素,同时根据多状态模型估计3年转移概率。结果 经过多因素竞争风险模型筛选,高年龄(HR=1.56,95%CI:1.01～2.39)、女性(HR=1.72,95%CI:1.02～2.92)、高文化程度(HR=0.64,95%CI:0.41～1.00)、经常读书看报(HR=0.57,95%CI:0.32～0.99)、有高血压(HR=3.43,95%CI:1.08～10.85)和高SBP(HR=1.67,95%CI:1.04～2.66)是MCI转移为AD的影响因素。MCI 3年后转移为AD的概率为10.7%(95%CI:8.6%～13.2%)。结论 年龄、性别、文化程度、高血压,读书看报和SBP对MCI状态向AD状态的转归过程有影响。竞争风险模型对具有多种潜在结局的纵向资料分析有一定的优势。     

基于多状态Markov模型的老年人认知损害转归研究

目的将多状态Markov模型应用于轻度认知损害(mild cognitive impairment,MCI)转归研究,为慢性病转归研究提供方法学借鉴。方法通过MCI患者IQ变化反映随访人群认知功能的变化趋势,构建一个四状态模型。根据多状态Markov模型分析原理,获得各状态转移影响因素、逗留时间、生存曲线,并进行模型拟合优度评价。结果 MCI病人处于认知功能稳定、认知轻度恶化和认知好转的时间大约分别为6.4年、3.6年和5.2年;生存曲线显示预后由好到差为认知功能好转、认知功能稳定、认知功能轻度恶化;多状态Markov模型拟合结果较好。结论多状态Markov模型是多状态、多阶段慢性病转归研究的有效分析方法。     

天津市社区老年人轻度认知功能障碍人口学特征分析

目的 了解天津市社区老年人轻度认知功能障碍(mild cognitive impairment,MCI)患病率及人群分布特征.方法 采用多阶段整群随机抽样方法,利用Petersen等诊断标准对天津市塘沽区60岁以上老年人进行筛查,对筛选出的MCI患者进行问卷调查,对其人口学特征进行Pearson检验和多因素非条件Logistic回归分析.结果 MCI患病率为10.89％,MCI患病率在不同性别、年龄、经济收入、文化程度、婚姻状况的差异均有统计学意义(均有P ＜0.05).多因素Logistic回归分析结果显示:危险因素包括:高龄(OR =3.12,95％ CI:1.46～6.55)、离婚(OR=1.61,95％ CI:1.55～1.67),保护因素包括:文化程度(OR =0.16,95％ CI:0.08～0.35).结论 天津市社区60岁以上老年人群MCI患病率较高(10.89％),高龄、低文化程度、离婚可能是MCI的高危因素,应及早采取有效措施,延缓患者病情进展.     

太原市社区老年人轻度认知功能障碍向阿尔茨海默病转归三年随访研究

目的 探讨太原市社区轻度认知功能障碍(MCI)老年人向阿尔茨海默病(AD)的转归率,并分析影响因素.方法 从太原市9个社区6152名≥65岁老年人中筛查出600例MCI,实际随访557例,从认知正常(NC)中选择557名与MCI相匹配的老年人进行配对,对MCI组和NC组进行3年随访研究.采用自制问卷面对面调查MCI组的一般人口学资料、生活行为方式、慢性病史、主观感受等,采用16PF调查MCI的人格特征,静脉血采样进行实验室遗传基因学分析,对NC组老年人进行电话访问以得到疾病结局和发病时间.用SPSS 13.0软件进行数据录入及分析,统计学方法采用log-rank检验和Cox回归.结果 MCI组老年人向AD的平均年转归率为6.53%人年.NC组老年人向AD的平均年转归率为1.24%人年,MCI组发生AD的危险性是NC组的5.27倍(95%CI:3.01～9.82).Cox回归分析结果显示,高龄(RR=3.14,95%CI:2.98～7.46)、患高血压(RR=3.28,95%CI:3.02～8.48)、高血脂(RR=2.22,95%CI:1.29～3.82)、糖尿病(RR=4.87,95%CI:2.56～9.25)、较少运动(RR=2.02,95%CI:1.29～3.14)、焦虑(RR=4.46,95%CI:3.07～8.14)、害怕(RR=4.08,95%CI:3.52～5.25)、非乐群型(RR=1.89,95%CI:1.13～3.16)、焦虑人格(RR=5.07,95%CI:2.56～10.04)、性格内向(RR=2.05,95%CI:1.33～3.15)、携带ApoE4(RR=1.73,95%CI:1.15～2.63)是MCI转归为AD的危险因素,文化程度高(RR=0.29,95%CI:0.07～0.43)、脑力劳动(RR=0.14,95%CI:0.05～0.32)、常读书看报(RR=0.30,95%CI:0.15～0.58)、常参加活动(RR=0.41,95%CI:0.23～0.75)是MCI转归为AD的保护因素.结论 患有MCI的老年人更易发展为AD,应长期监测.

Abstract：

Objective To explore the incidence rate of people with mild cognitive impairment (MCI) which transferred to Alzheimer's disease (AD) and to study the related influencing factors. Methods 600 MCI aged people were experienced screening test which was conducted by WHO-BCA, MMSE and DCR. A three-year follow-up study was conducted to get the information on the aged people with MCI. Data related to demography, behavior, chronic diseases and perception of the elderly with MCI were collected through face to face interview. Characteristics of the elderly with MCI aged people were tested by 16PF. The content of Apoe was tested by PCR.People with NC were investigated by telephone to get the progression and the time to AD.Methodologies on statistics were log-rank test and Cox proportional hazards regression model.Results The incidence rate of MCI to AD was 6.53% person-years. The incidence rate of the normal people to AD was 1.24% person-years. The hazard of MCI to AD was 5.27 times (95%CI: 3.01-9.82)of the normal people to AD. The result of Cox proportional hazards regression model displayed that: older age (RR=3.14, 95% CI: 2.98-7.46) , hypertension (RR=3.28, 95% CI: 3.02-8.48) ,hyperlipermia (RR = 2.22,95%CI: 1.29-3.82), diabetes (RR=4.87,95%CI: 2.56-9.25), lack of sports (RR=2.02, 95%CI: 1.29-3.14), anxiety (RR=4.46, 95%CI: 3.07-8.14), dread fulness (RR=4.08,95% CI: 3.52-5.25), loneliness (RR= 1.89,95% CI: 1.13-3.16), characteristics of anxiety (RR= 5.07,95%CI: 2.56-10.04, introvert characteristics (RR=2.05,95%CI: 1.33-3.15) and ApoE4 (RR= 1.73,95% CI: 1.15-2.63) were the risk factors of MCI to AD. Higher education (RR=0.29, 95% CI:0.07-0.43), intellectual work(RR=0.14,95%CI: 0.05-0.32), often reading books(RR=0.30,95%CI:0.15-0.58), often taking part in recreational activities (RR=0.41,95%CI: 0.23-0.75) seemed to be the protective of MCI to AD. Conclusion The rate of the elderly with MCI that developing to AD was high, suggesting further study on the cognitive situation among the MCI aged people should be carried out.     

南昌市社区老年人轻度认知功能障碍向阿尔茨海默病转归研究

  目的   探讨南昌市社区老年人轻度认知功能障碍(mild cognitive impairment, MCI)向阿尔茨海默病(Alzheimer disease, AD)的转归率, 并分析其影响因素。   方法   采用分层整群抽样方法选取南昌市10个社区作为研究现场, 从抽取年龄≥60岁的1 942名老年人中筛查出361名MCI患者, 采用问卷调查和实验室检测收集研究对象一般人口学特征、生活习惯信息、疾病既往史、阿尔茨海默病相关神经丝蛋白(Alzheimer-associated neuronal thread protein, AD7c-NTP)、β淀粉样蛋白42(amyloidβ-protein 42, Aβ42)、β淀粉样蛋白40(amyloidβ-protein 40, Aβ40)等信息, 对MCI患者随访三年判断是否进展为AD。   结果   361例MCI患者共有121例转归为AD, 年均转归率为9.49%, Logistic回归分析模型分析结果显示, 高龄(80~98岁)(OR=3.651, 95% CI:1.295~10.297, P < 0.001)、女性(OR=2.603, 95% CI:1.136~5.966, P < 0.001)、大量饮酒(OR=1.479, 95% CI:1.343~1.627, P < 0.001)、ADL分值升高(OR=1.790, 95% CI:1.443~2.220, P=0.031)、吸烟(OR=1.157, 95% CI:1.091~1.224, P < 0.001)是危险因素, 而Moca分值升高(OR=0.766, 95% CI:0.681~0.861, P < 0.001)则是保护因素。   结论   加强对高龄女性的MCI患者监控, 并提倡老年人拥有健康生活方式, 积极参加体育锻炼、多读书和看报, 以延缓MCI患者向AD转归。     

轻度认知障碍转化为阿尔茨海默病的生存分析

目的 分析轻度认知障碍（mild cognitive impairment,MCI）患者的生存率以及MCI转化为阿尔茨海默病（alzheimer’s disease,AD）的影响因素。方法 对113名MCI患者的影响因素采用非参数检验进行单因素分析,进一步采用Cox回归进行多因素分析。结果 在2005 - 2014年的10年内MCI患者在3、6、24、36、48、96、120个月生存率依次为99.1%、98.2%、97.3%、87.1%、64.1%、33.4%、0.9%,其中位生存时间为72个月;单因素分析得到MCI患者的生存率在年龄、性别、APOEε4、FAQ、CDRSB、MMSE中有统计学差异（P＜0.05）;多因素分析显示高龄(HR = 1.007, 95%CI:1.020～1.138)、女性(HR = 1.849, 95%CI:1.101～3.105)、高CDRSB得分(HR = 1.171, 95%CI:1.045,1.312)为MCI转化为AD的危险因素。结论 MCI患者的生存率较低,且年龄、性别和CDRSB得分对MCI进展为AD具有重要意义。     

发热伴血小板减少综合征重症及死亡危险因素的Logistic回归分析

目的 分析发热伴血小板减少综合征(SFTS)患者的临床特征和危险因素.方法 收集2011年5月至2012年7月解放军第一五四医院就诊的273例SFTS患者的相关信息,采用RT-PCR检测新布尼亚病毒(SFTSV),通过ELISA检测SFTSV-IgM和IgG抗体,采用Human BioPlex ProTM Assays 17-Plex Panel方法测定细胞因子.对确诊病例采用单因素、多因素Logistic回归模型分析SFTS病例重症和死亡发生的危险因素.结果 273例SFTS患者中180例SFTSV核酸阳性.主要临床表现为发热、乏力、肌肉酸痛和胃肠道症状.多因素Logistic分析显示,年龄≥60岁(OR=1.08,95％CI:1.03～1.13)、淋巴结肿大(OR =3.75,95％CI:1.45～9.66)、下呼吸道感染(OR=3.57,95％CI:1.40～9.11)、肌酐(Cr)＞97 mmol/L(OR=4.10,95％CI:1.55～10.82)及意识障碍(OR=3.35,95％CI:1.21～9.29)与重症病例发生显著相关.年龄≥60岁(OR=1.06,95％CI:1.00～1.12),下呼吸道感染(OR=4.33,95％CI:1.35～13.93),Cr＞97 mmol/L (OR=10.14,95％CI:3.19～32.21)及意识障碍(OR=3.47,95％CI:1.03～11.72)与死亡病例发生显著相关.结论 年龄≥60岁、合并下呼吸道感染、Cr＞97 mmol/L、意识障碍是SFTS患者预后不良的危险因素,应予重点治疗.     

Calcium intake in the elderly: validation of a dietary questionnaire

Epidemiological studies of calcium and osteoporosis have been hampered by the lack of a suitable tool for assessing calcium intake. This report describes a new frequency and amount questionnaire for measuring present and past calcium intake in the elderly. The validity of the questionnaire was tested against two commonly used standards of dietary assessment, five-day duplicate diets and seven-day weighed dietary inventories. The resulting correlation coefficients were, respectively, r = 0.76 and r = 0.69, while that for repeatability was r = 0.84. Furthermore, the questionnaire categorized subjects into thirds of the distribution of intake with almost no gross misclassification. It is suggested that the present findings may be extended to the majority of normal, healthy elderly subjects, implying wide application for the questionnaire in the assessment of calcium intake in the elderly.     

The occurrence of antimicrobial substances in toilet,sink and shower drainpipes of clinical units: A neglected source of antibiotic residues

Antibiotics represent one of the most important drug groups used in the management of bacterial infections in humans and animals. Due to the increasing problem of antibiotic resistance, assurance of the antibacterial effectiveness of these substances has moved into the focus of public health. The reduction in antibiotic residues in wastewater and the environment may play a decisive role in the development of increasing rates of antibiotic resistance. The present study examines the wastewater of 31 patient rooms of various German clinics for possible residues of antibiotics, as well as the wastewater of five private households as a reference.To the best of our knowledge, this study shows for the first time that in hospitals with high antibiotic consumption rates, residues of these drugs can be regularly detected in toilets, sink siphons and shower drains at concentrations ranging from 0.02?μg·L^?1 to a maximum of 79?mg·L^?1. After complete flushing of the wastewater siphons, antibiotics are no longer detectable, but after temporal stagnation, the concentration of the active substances in the water phases of respective siphons increases again, suggesting that antibiotics persist through the washing process in biofilms. This study demonstrates that clinical wastewater systems offer further possibilities for the optimization of antibiotic resistance surveillance.     

Self-reported health problems among Swedish miners one year after unemployment

Unemployment is considered to be a public health concern sincedeterioration in the health of the unemployed is often anticipated.However, for some groups, such as miners, unemployment mightimprove health due to a cessation of potentially harmful occupationalexposures. This study evaluates the health of 79 miners in oneSwedish iron-ore mine, and 226 age-matched controls from thegeneral population, during one year after the closure of themine. The participants received a questionnaire regarding medicalhistory and subjective symptoms at the beginning of the studyperiod, and after one year. Statistically significant negativeeffects on self-reported health attributable to unemploymentwere not found, although neuropsychiatric symptoms were morecommon among the unemployed miners. The miners reported a statisticallysignificant improvement in grip force (p=0.031). They had asignificantly higher prevalence of symptoms associated withmining related exposures when compared with the population controls;pain in the upper extremities [relative risk (RR)=2.27, 95%confidence interval (Cl)=1.44–3.59), back pain (RR=1.84;Cl=1.237–2.75), vasospastic disease of the fingers (RR=2.05;Cl=1.18–3.57) and obstructive respiratory symptoms (attacksof dyspnea and wheezing: RR=3.67; Cl=1.167–11.6).     

Excès de cas humains et animaux de tularémie en France au cours de l’hiver 2007–2008 : émergence ou phénomène isolé ?

Context

Tularemia is a zoonosis affecting humans and hares in France. We describe the results of surveillance in both species, in 2007 and 2008.

Methods

Human tularemia cases are mandatorily notifiable in France since 2003. In hares, surveillance relies on volunteer hunter associations in all districts of the country. Data from mandatory reports and volunteer surveillance in 2007/2008 were analyzed and compared with previous results.

Results

In 2007/2008, 144 cases were reported in humans and 117 cases in hares. This was a 100% increase compared to previous years. Human cases differed from those of previous years only by the frequency of contact with breeding animals. Human cases without any documented risk exposure were also more frequent.

Conclusion

An increase of tularemia cases occurred in 2007/2008 in both species. Complementary studies are needed to identify the species reservoir in France to understand the causes of this peak of cases.     

Occupational health hazards in mining: an overview

This review article outlines the physical, chemical, biological, ergonomic and psychosocial occupational health hazards of mining and associated metallurgical processes. Mining remains an important industrial sector in many parts of the world and although substantial progress has been made in the control of occupational health hazards, there remains room for further risk reduction. This applies particularly to traumatic injury hazards, ergonomic hazards and noise. Vigilance is also required to ensure exposures to coal dust and crystalline silica remain effectively controlled.     

Manufacture and use of nanomaterials: current status in the UK and global trends

This paper provides an overview of the production and use of nanomaterials (NMs), particularly in the UK. Currently, relatively few companies in the UK are identifiable as NM manufacturers, the main emphasis being the bulk markets in metals and metal oxides, and some niche markets such as carbon nanotubes and quantum dots. NM manufacturing in the UK does not reflect the global emphasis on fullerenes, nanotubes and fibres. Some assumptions have been made about the types of NM that are likely to be imported into the UK, which currently include fullerenes, modified fullerenes and other carbon-based NMs including nanotubes. Many university departments, spin-offs and private companies have developed processes for the manufacture of NMs but may only be producing small quantities for research and development (R&D) purposes. However, some have the potential to scale up to produce large quantities. The nanotechnology industry in the UK has strong R&D backup from universities and related institutions. This review has covered R&D trends at such institutions, and appropriate information has been added to a searchable database. While several companies are including NMs in their products, only a few (e.g. manufacturers of paints, coatings, cosmetics, catalysts, polymer composites) are using nanoparticles (NPs) in any significant quantities. However, this situation is likely to change rapidly. There is a need to collect more information about exposure to NPs in both manufacturing and user scenarios. As the market grows, and as manufacturers switch from the micro- to the nanoscale, the potential for exposure will increase. More research is required to quantify any risks to workers and consumers.     

深圳公立医院管理体制改革制度设计

深圳公立医院管理体制改革实行政事分开、管办分开,在理事会架构下按法定机构模式组建市医管中心,落实公立医院运营管理自主权.作者从当前公立医院管理体制的弊端入手,介绍了深圳市进行公立医院管理体制改革的基本思路及改革方案设计的主要举措,深入剖析了的改革方案的特点,并对改革效果进行了预测.     

Effects of nitrogen dioxide on red blood cells of rats: Changes in components of red cell membranes during in vivo exposure to NO2

Red cell membranes, prepared from red blood cells of rats exposed to 4, 10, or 20 ppm nitrogen dioxide (NO₂) for 1 to 10 days, were examined for evidence of changes in membrane components. Appreciable changes were not found in contents of phospholipid and cholesterol during exposure to 10 ppm NO₂. By contrast, protein content altered with the time of exposure. Moreover, changes in protein composition were observed by employing sodium dodecyl sulfate — polyacrylamide gel electrophoresis. Twenty-four-hour exposure to NO₂ at the concentration above 10 ppm resulted in a marked increase in the percentage of lysophosphatidylethanolamine (LysoPE) to the total phospholipids. The prolonged exposure to 10 ppm NO₂ gave rise to a further increase in LysoPE, whereas the percentage of phosphatidylethanolamine (PE) showed a gradual decrease. A 1-day exposure to 4.0 ppm NO₂ also caused an increase in sialic acid content and decreases in those of PE and hexose. In addition to contents of these components the percentage of LysoPE increased 5 days after exposure and the elevated values were maintained up to the end of exposure period. These results demonstrate that red blood cells in circulation exhibit different membrane properties in terms of lipid and carbohydrate composition during 10 days of exposure to 4.0 ppm NO₂.     

Investigating clusters in the workplace and beyond

Clusters of disease are common and occur in the workplace and in the general community. They often arouse considerable concern among the population. Investigations have sometimes lead to exciting new knowledge, but in general the investigation of clusters is difficult and often unrewarding, especially for community clusters. In the workplace, investigations are more likely to find associations and even new causes, but still many clusters remain enigmatic. Despite this, there are many reasons for investigating clusters, including allaying community concern and identifying uncontrolled exposures. A structure for investigating clusters in the workplace is suggested.