心律失常发病机制研究进展

  目的  了解金昌队列职业人群心律失常发病危险因素,为心律失常病因学研究及防治提供参考依据。  方法  采用巢式病例对照研究方法,于2011年6月 — 2013年12月在金昌队列职业人群中按年龄分层抽样获得5 758名研究对象,随访2年后将随访期内459例新发心律失常者和3 090名心电图正常者分别作为病例组和对照组,应用多因素非条件logistic回归模型分析金昌队列职业人群心律失常的主要危险因素。  结果  金昌队列病例组心率失常患者收缩压 > 140 mm Hg、有高血压家族史、肌酸激酶偏高和尿酸偏高的比例分别为18.30 %、45.32 %、8.06 %和18.30 %,均高于对照组心电图正常人群的13.37 %、40.13 %、5.66 %和13.69 %,差异均有统计学意义（均P < 0.05）。多因素非条件logistic回归分析结果显示,年龄 < 45岁和 ≥ 65岁、有高血压家族史、尿酸偏高是金昌队列职业人群心律失常发病的危险因素。  结论  年龄较高或较低、有高血压家族史和尿酸较高的金昌队列职业人群更易发生心律失常。     

Occupational case-control studies: I. Collecting information on work histories and work-related exposures

The strength and credibility of evidence from occupational case-control studies largely depend on the validity and precision with which the work history is reported and the exposure is assessed. We discuss the two steps which ultimately lead to an exposure decision. The first step involves the exchange between the respondent and an interviewer. The latter is usually naïve to occupations and workplace exposures and, as such, is limited to asking generic and open-ended questions about the workplace. Often, this type of information is too nonspecific to assess exposure. In the second step, an expert reviews the information reported on each occupation and decides on exposure status without contacting either the interviewer or respondent. Exposure assessment is not, therefore, integrated with data collection and, in fact, is usually not initiated until after all the interviews are completed. As such, the exposure expert does not have an opportunity to resolve questions before making the exposure decision. To improve the quality and specificity of data collected, we have developed over 40 sets of close-ended questions (branch questions) which are specific to defined occupations. These branch questions, incorporated into a computer-assisted telephone interview, are asked if selected occupations or their synonyms are reported. Second, to link the data collection process with the assessment process, we have developed a procedure called SCORE (Subject Corrected Occupational Report) which provides the industrial hygienist with a cost efficient method to ask questions directly of respondents. Shortly after each interview is completed, a computerized version of the work history is reviewed by the industrial hygienist who develops questions when more information is needed. Subsequently, respondents are mailed a form listing their reported work history along with the questions. After two mailings, 73% of participants in a pilot study returned the SCORE form.     

Occupational case-control studies: II. Recommendations for exposure assessment

Obtaining valid and reliable quantitative exposure estimates is a significant challenge in community-based case-control studies in part, because industrial hygiene monitoring data are usually not available and detailed information on the job and work environment is usually not systematically obtained or assessed. To improve the quality and credibility of disease risk information obtained from occupational case-control studies, we recommend that standardized exposure assessment methods be used to derive quantitative exposure estimates. We identify sources of variation inherent to the assessment process, including: the quality of the information reported on the job, industry, activities, and materials; the industrial hygienist's familiarity with the reported job/industry; the probability that the job/industry was exposed, which depends on plant preferences for particular substances, on process technology, and on customer specifications; and variability in workplace characteristics. To improve the reliability of estimating job-related exposures both within and between studies, we recommend that the epidemiologic analyses be conducted with and without data rated to be of poor quality; that contact be made with experts when the study industrial hygienist is unfamiliar with the manufacturing process in question; that existing data bases be used to estimate the probability of exposure; that a data base be developed that describes manufacturing processes; and that explicit criteria based on industrial hygiene principles be used to evaluate workplace characteristics. In addition, a procedure is described for deriving quantitative exposure estimates by using a reference scale of frequently monitored jobs with their associated mean exposure levels. Areas of research are identified to improve exposure assessment in community-based case-control studies.     

Comparability of different methods of retrospective exposure assessment of metals in manufacturing industries

Many occupational case-control studies have relied on either self-report or exposure assessment based on job titles linked to a job exposure matrix (JEM) as opposed to the generally considered more accurate, but labor intensive, method of expert review of job histories. Our study examined the comparability of these different methods in assessing occupational exposure to the metals copper (Cu), lead (Pb), and iron (Fe) in manufacturing industries. Subjects were older people from a case-control study of a neurologic disease, and consisted of 188 individuals (72% male, 85% white) who had worked an average of 22.4 years in the manufacturing industry. An industrial hygienist review (IHR) of occupational history data from a comprehensive questionnaire was used as the reference method. The percent agreement (%A), sensitivity (SE), and specificity (SP) for direct self-report of metal exposures were: Cu, %A = 94.6, SE = 83.6, SP = 96.1; Pb, %A = 91.9, SE = 72.5, SP = 93.5; and Fe, %A = 82.7, SE = 64.5, SP = 88.1. Using the National Institute for Occupational Safety and Health (NIOSH) JEM, we analyzed the jobs of 115 of the 188 study subjects who had all their jobs listed in the JEM. Exposure assessment based on the NIOSH JEM compared with the IHR resulted in greater misclassification relative to direct self-report: Cu, %A = 81.5, SE = 21.2, SP = 89.2; Pb, %A = 86.0, SE = 0.0, SP = 92.6; and Fe, %A = 69.2, SE = 15.5, SP = 86.4. For all three study metals, combining the information from both direct self-report and the JEM did not improve upon the results compared with direct self-report alone. Due to the complex nature of metal exposure assessment, we suggest using an expert review of job histories whenever possible to minimize potential misclassification. Am. J. Ind. Med. 31:36–43 © 1997 Wiley-Liss, Inc.     

Wood dust exposure and the association with lung cancer risk

BACKGROUND: Wood dust was designated as a human carcinogen based on increased sinus and nasal cancer rates among exposed workers. However, data on an association with lung cancer have been inconclusive. METHODS: Self-reported wood dust exposure was compared between 1,368 lung cancer patients and 1,192 cancer-free adults, in a lung cancer case-control study. Epidemiological information was collected through a detailed personal interview. RESULTS: Using several definitions of wood dust exposure we consistently observed statistically significant elevated adjusted risk estimates; for example, the adjusted odds ratio (OR) for combined wood dust related occupations and industries was 3.15 (95% confidence intervals (CI) 1.45-6.86) and for an overall summary exposure measure it was 1.60 (95% CI 1.19-2.14). The association was maintained when stratified by histopathological type. Among those exposed to cigarette smoke and wood dust, 21% of the cases were attributable to biologic interaction. CONCLUSIONS: Wood dust exposure is a potential risk factor for lung cancer.     

Analysis of secondary outcomes in nested case‐control study designs

One of the main perceived advantages of using a case‐cohort design compared with a nested case‐control design in an epidemiologic study is the ability to evaluate with the same subcohort outcomes other than the primary outcome of interest. In this paper, we show that valid inferences about secondary outcomes can also be achieved in nested case‐control studies by using the inclusion probability weighting method in combination with an approximate jackknife standard error that can be computed using existing software. Simulation studies demonstrate that when the sample size is sufficient, this approach yields valid type 1 error and coverage rates for the analysis of secondary outcomes in nested case‐control designs. Interestingly, the statistical power of the nested case‐control design was comparable with that of the case‐cohort design when the primary and secondary outcomes were positively correlated. The proposed method is illustrated with the data from a cohort in Cardiovascular Health Study to study the association of C‐reactive protein levels and the incidence of congestive heart failure. Copyright © 2014 John Wiley & Sons, Ltd.     

Leukemia mortality and occupational exposure to rubber: a nested case-control study

OBJECTIVE: The excess risk of leukemia in rubber industry was considered to be real and attributed to the exposure to solvents, particularly benzene. METHODS: Following a nested case-control study, we used the data of 7 leukemia deaths in 1973-1997 and 28 controls matched for sex and age from the same cohort of a rubber plant. Leukemia risks due to exposure to rubber were assessed, unadjusted and adjusted for non-occupational factors by conditional logistic regression. RESULTS: OR for leukemia was found to be 7.81 (95% CI = 0.77-78) in grouped analysis for one or more years of work in the inner tire tube department. The models for continuous exposure variables indicated that working for one year in the inner tire tube department was associated with a 10 percent increment in the OR (95% CI = 1.00-1.24; score test for linear trend: chi 1(2) = 6.27, P = 0.012). The confounding effects studied could not be ruled out for the excess risks. No excess risk was found in the remaining four departments. CONCLUSIONS: Because of widespread exposure to various carcinogens in the process of making inner tire tubes, removal of a single agent (benzene) may not eliminate the risk of leukemia in the entire industry.     

Allocation designs in cohort and case-control studies

Four unequal allocation designs for cohort and case-control studies that incorporate cost and power are considered and compared with the equal allocation design, with the aim of providing researchers some flexibility in planning their studies. It is found that the type of design to be adopted depends on available resources and projected needs. In the case of tight expenditure, the minimized cost design is the optimal, whereas the maximized power design may be sought if the researcher intends to ensure a high chance of detecting any clinically significant relative risk of disease.     

自组织神经网络在长寿基因研究设计中的应用：巢式病例对照研究样本选择

目的应用自组织神经网络为长寿研究选择对照组, 以改进长寿基因研究设计。方法本研究基于2013年中国慢性病及其危险因素监测与全国死因监测数据融合形成的自然人群队列, 纳入年龄≥90岁的老年人或年龄<80岁且已死亡的汉族人群(对照组), 排除死于伤害、传染病、寄生虫病和恶性肿瘤的个案, 利用自组织神经网络方法, 通过多次迭代和自组织聚类, 选取人口学特征、患病、生活习惯、社会行为、精神心理等多方面因素相似的≥90岁老年人和对照组, 开展全基因组测序。研究采用PLINK 1.9软件评估测序数据质量, 开展常染色体上的单核苷酸多态性(SNPs)和长寿的logistic回归, 用Q-Q图可视化SNPs与长寿关联的P值。结果研究从基线177 099例调查对象中筛选出1 019例人群基因组样本开展全基因组测序, 其中长寿组517例、对照组502例。长寿组和对照组在吸烟、饮酒、饮食、睡眠时长、血脂水平和自评口腔健康状况总体相似, 在社会经济状况、身体活动时间、BMI和自评健康状况差异较大。全基因组测序结果经质控, 4 618 216个SNPs进入关联分析。长寿组相关SNPs分析结果P值的Q-Q图...     

Variation in female breast cancer risk by occupation

Data from a population-based case control study were used to estimate occupation-specific relative risks for female breast cancer, adjusted for established breast cancer risk factors. Breast cancer cases under age 75 were identified from tumor registries in four states. Controls were randomly selected from driver's license and Medicare beneficiary lists. Information on usual occupation and risk factors was obtained by telephone interview. Odds ratios from logistic regression adjusted for age, state, body mass index, benign breast disease, family history of breast cancer, menopausal status, age at menarche, parity, age at first birth, lactation history, education, and alcohol consumption were calculated for each of 26 occupational groups. Complete occupational information was obtained for 6,835 cases and 9,453 controls. Of 26 occupational groups, only “administrative support occupations” had a statistically significantly increased risk of breast cancer (OR = 1.15, 95% Cl 1.06–1.24). In these data, no specific occupational group had an unusual risk of breast cancer. Increased risks reported elsewhere for nurses and teachers were not corroborated. © 1996 Wiley-Liss, Inc.     

Development of an asthma specific job exposure matrix and its application in the epidemiological study of genetics and environment in asthma (EGEA)

OBJECTIVES—To develop a method suitable for estimating exposure risks in population studies of asthma from job titles and international codes, by combining a new job exposure matrix (JEM) with the expert judgement approach. The method was applied in the French epidemiological study of the genetics and environment in asthma (EGEA).METHODS—The JEM contains 22 exposure groups including 18 high risk groups based on known risk factors for occupational asthma, divided into high molecular weight agents, low molecular weight agents, and mixed environments. After applying the JEM to job codes, exposure estimates for each subject were re-evaluated by examining job title texts. Three high risk exposure estimates for asthma were compared: firstly, applying the JEM to original codes (from different coders in each study centre); secondly, applying the JEM to revised codes (from one experienced coder); and thirdly, after reviewing JEM exposure estimates in the light of job title texts.RESULTS—The study comprised 173 cases with asthma and 285 controls (age 18-65). Odds ratios (ORs) for asthma for high risk jobs were 1.0 (95% confidence interval (95% CI) 0.6 to 1.7), applying the JEM to original codes; 1.4 (95% CI 0.8 to 2.3), applying the JEM to revised codes; and 1.7 (95% CI 1.1 to 2.7), applying the JEM and subsequently re-evaluating exposure estimates from job title texts. Asthma ORs were 1.4 (95% CI 0.6 to 2.9) for high molecular weight agents, 2.3 (95% CI 1.2 to 4.4) for low molecular weight agents, and 2.1 (95% CI 0.9 to 5.2) for mixed environments.CONCLUSIONS—This asthma JEM, when enhanced by expert re-evaluation of exposure estimates from job title texts, may be a useful tool in general population studies of asthma. In this study, a 1.7-fold increase in prevalence odds of high risk exposures was found among asthmatic workers compared with controls, with risk magnitude varying for different classes of exposure.     

Risks of biliary tract cancer and occupational exposures among Shanghai women textile workers: a case-cohort study

BACKGROUND: Biliary tract cancer (BTC) is a relatively rare malignancy worldwide. Little is known about potential etiologic contributions of occupational exposures. METHODS: The associations between occupational exposures to textile dusts and chemicals and BTC are investigated in a cohort of 267,400 women textile workers in Shanghai, China. A nested case-cohort analysis of 162 BTC cases diagnosed during 1989-1998 was conducted with a reference subcohort of 3,188 workers. Exposures to workplace dusts and chemicals were reconstructed by linking complete work history data with a job-exposure matrix (JEM). Hazard ratios (HR) and dose-response trends were estimated by Cox proportional hazards modeling modified for case-cohort design. RESULTS: An elevated risk of > or = 1-year employment in maintenance jobs (HR 2.92, 95% CI: 1.48, 5.73) with a significant trend by duration is observed. Excess risk was also found for > or = 20 years exposure to metals (HR 2.50, 95% CI: 1.09, 5.72). CONCLUSIONS: Long-term exposure to maintenance work and metals in the textile industry may have increased BTC risk in this population.     

Design and conduct of occupational epidemiology studies: III. Design aspects of case-control studies

Currently available approaches for the design of occupational case-control studies are reviewed. An accompanying paper reviews methods of analysis. We commence by drawing a distinction between cohort-based and registry-based studies. Methods for selecting cases and controls are then reviewed, including cumulative incidence and incidence density sampling, matching, sources of controls, and issues in control selection. Finally, the advantages and disadvantages of the case-control approach are summarized.     

Interval estimation of the attributable risk in case-control studies with matched pairs

OBJECTIVE: The attributable risk (AR), which represents the proportion of cases who can be preventable when we completely eliminate a risk factor in a population, is the most commonly used epidemiological index to assess the impact of controlling a selected risk factor on community health. The goal of this paper is to develop and search for good interval estimators of the AR for case-control studies with matched pairs. METHODS: This paper considers five asymptotic interval estimators of the AR, including the interval estimator using Wald's statistic suggested elsewhere, the two interval estimators using the logarithmic transformations: log(x) and log(1-x), the interval estimator using the logit transformation log(x/(1-x)), and the interval estimator derived from a simple quadratic equation developed in this paper. This paper compares the finite sample performance of these five interval estimators by calculation of their coverage probability and average length in a variety of situations. RESULTS: This paper demonstrates that the interval estimator derived from the quadratic equation proposed here can not only consistently perform well with respect to the coverage probability, but also be more efficient than the interval estimator using Wald's statistic in almost all the situations considered here. This paper notes that although the interval estimator using the logarithmic transformation log(1-x) may also perform well with respect to the coverage probability, using this estimator is likely to be less efficient than the interval estimator using Wald's statistic. Finally, this paper notes that when both the underlying odds ratio (OR) and the prevalence of exposure (PE) in the case group are not large (OR < or =2 and PE < or =0.10), the application of the two interval estimators using the transformations log(x) and log(x/(1-x)) can be misleading. However, when both the underlying OR and PE in the case group are large (OR > or =4 and PE > or =0.50), the interval estimator using the logit transformation can actually outperform all the other estimators considered here in terms of efficiency. CONCLUSIONS: When there is no prior knowledge of the possible range for the underlying OR and PE, the interval estimator derived from the quadratic equation developed here for general use is recommended. When it is known that both the OR and PE in the case group are large (OR > or =4 and PE > or =0.50), it is recommended that the interval estimator using the logit transformation is used.     

Design and conduct of occupational epidemiology studies: IV. The analysis of case-control data

This paper reviews the basic methods of analysis of data from case-control studies. The standard analytic methods are outlined first for a single stratum. The discussion is then extended to stratified analysis, multiple exposure levels, and analyses allowing for disease induction and latency periods. Finally, logistic regression is discussed as an extension of the more basic forms of analysis. The methods are illustrated with data from a study of lung cancer among asbestos textile plant workers.     

铁矿工人尘肺发病及影响因素分析

目的 分析铁矿接尘工人尘肺的发病规律及影响因素,为铁矿工人尘肺防制提供依据.方法 以某铁矿1960年至1974年在册且工作1年以上的所有接尘工人建立队列,随访至2003年底.尘肺诊断由职业病诊断小组确定.采用Cox比例风险模型分析危险因素.结果 队列接尘工人3647名,累积接尘132 574.4人年.诊断尘肺316例,人年发病率为0.24％.1960年前开始接尘者中发现尘肺274例(86.7％),人年发病率为0.40％,明显高于1960年后开始接尘工人尘肺人年发病率(43例,0.07‰).尘肺发病平均潜伏期是(26.0±7.3)年.尘肺晋级年限分别为0+晋Ⅰ期(5.3士3.2)年,Ⅰ晋Ⅱ期为(6.6±5.2)年,Ⅱ晋Ⅲ期为(1 1.3±5.0)年,随诊断年代的推后,各期晋级年限均有延长趋势.164例尘肺为脱尘后诊断,平均脱尘8.3年.铁矿工尘肺发病危险度随累积接尘量增加而上升,呈明显的接触剂量-反应关系.尘肺患者年平均累积接尘量为(173.7±91.6)mg/m3,远高于非尘肺接尘工人(112.1±64.8)mg/m3.除累积接尘量外,影响尘肺发病风险因素包括肺结核(HR=5.9,P＜0.01)、吸烟(HR=1.7,P＜0.01).结论 累积接尘量与尘肺发病之间存在明显的剂量-反应关系,并发结核、吸烟是影响尘肺发病的危险因素.     

Using tensor product splines in modeling exposure-time-response relationships: application to the Colorado Plateau Uranium Miners cohort

An adequate depiction of exposure-time-response relationships is important in assessing public health implications of an occupational or environmental exposure. Recent advances have focused on flexible modeling of the overall shape of latency. Methods are needed to allow for varying shapes of latency under different exposure profiles. A tensor product spline model is proposed for describing exposure-response relationships for protracted time-dependent occupational exposure histories in epidemiologic studies. The methods use flexible multi-dimensional techniques to jointly model age, latency and exposure-response effects. In analyzing data from the Colorado Plateau Uranium Miners cohort, a model that allows for varying exposure-dependent latency shapes is found to be superior to models that only allowed for an overall latency curve. Specifically, the model suggests that, at low exposure levels risk increased at short latencies followed by a slow decline for longer latency periods. On the other hand, risk was higher but did not change much by latency for higher exposure levels. The proposed methodology has the advantage of allowing for latency functions that vary by exposure levels and, conversely, exposure-response relationships that are influenced by the latency structure.     

Probabilistic assessment of acute health symptoms related to pesticide use under intensified Nepalese agriculture

Agriculture intensification has pushed farmers to use pesticides for maintaining agricultural productivity and to increase income. However, pesticide use has a significant negative impact on farmers' health. In Nepal, uses of pesticides have been already documented in agriculturally intensified areas, however, little is known on health impacts. Weekly interviews were conducted during 2005 to assess the emerging pesticide problems, estimate the magnitude of pesticide-related acute illness, and identify associated risk factors. The study showed that very few farmers have adopted safety gear during pesticide spraying. The safety measures regression shows that warm temperature and drinking habits significantly reduced adoption of safety gear, whereas, integrated pest management (IPM) training and farm experience increased its adoption. The dose-response analyses showed that use of insecticides or fungicides, spray duration and mixing pesticides significantly affect farmer's health, which could be reduced either by educating farmers, increasing the use of safety gear, or reducing mixtures applications.     

Use of city directories as a source of occupational data in a case-cotnrol study

The association between occupational factors and male breast cancer was investigated in a population-based case-control study conducted in Western New York state. Since 9% of cases and controls were missing occupational information in the tumor registry (usual occupation) and screening clinic (type of work done) files, supplemental occupational data were collected from commercial city directories. Occupational data were located for 69% of participants via the city directory thereby reducing the missing occupational data to 3%. For individuals with occupational listings in both the original source document and the city directories, similar titles were found for 94% of cases. Factors to be considered in assessing the feasiblty of directory usage include purpose of study, degree of directory coverage within the geographic area, gender of participants, and availability of personnel and resources. City directories are a valuable supplemental source of occupational data for hypothesis generating case-control studies or registry-based studies of men conducted in urban areas. © 1993 Wiley-Liss, Inc.