From human genome epidemiology to systems epidemiology: current progress and future perspective

The recent progress in human genome epidemiology (HuGE) is already having a profound impact on the practice of medicine and public health. First, the success of genome-wide association studies has greatly expanded the direction and content of epidemiological researches, including revealing new genetic mechanisms of complex diseases, identifying new targets for therapeutic interventions, and improving application in early screening of high-risk populations. At the same time, large-scale genomic studies make it possible to efficiently explore the gene-environment interactions, which will help better understand the biological pathways of complex diseases and identify individuals who may be more susceptible to diseases. Additionally, the emergence of systems epidemiology aims to integrate multi-omics together with epidemiological data to create a systems network that can comprehensively characterize the diverse range of factors contributing to disease development. These progress will help to apply HuGE findings into practice to improve the health of individuals and populations.     

Molecular epidemiology of tuberculosis in the Tula area,Central Russia,before the introduction of the Directly Observed Therapy Strategy

Tuberculosis remains a major public health concern in Russia and worldwide. Given the great geographical, ethnic, and socio-economic heterogeneities between Russian regions, epidemiological data cannot be generalized from a regional to a country-wide level. We present data on the epidemiology of tuberculosis in Central Russia. We report a high level of resistance to major antitubercular drugs in both new and previously treated patients in the region. The level of drug resistance in new cases was almost twice as high as the estimated average national level. The Mycobacterium tuberculosis strains that circulated in the region were predominantly represented by LAM-RUS and Beijing genotypes. These two lineages were strongly associated with drug resistance and clustering. Using molecular epidemiology techniques, we showed a high interpenetration by M. tuberculosis strains between the prison and civilian populations. A limited number of identical strains were responsible for the majority of drug-resistant tuberculosis cases in both settings.     

Molecular epidemiology of tuberculosis: Objectives,methods, and prospects

During the last decade, the role of molecular epidemiology in tuberculosis research has become unquestionable. Methods such as the IS6110-based RFLP analysis, spoligotyping, and VNTR genotyping, as well as genomic deletion analysis and single nucleotide polymorphism analysis, are used for epidemiological and phylogenetic studies of Mycobacterium tuberculosis. The results of these methods are used to study the mechanisms of the origin and transmission of tuberculosis, as well as the resistance of M. tuberculosis strains to anti-tuberculosis drugs. This review considers the main molecular and genetic methods for studying tuberculosis epidemiology, as well as their prospective applications in the Russian Federation taking into consideration the epidemiological situation in the country and the available laboratory infrastructure.     

External validation of bloodstream infection mortality risk score in a population-based cohort

A risk score was recently derived to predict mortality in adult patients with Gram-negative bloodstream infection (BSI). The aim of this study was to provide external validation of the BSI mortality risk score (BSIMRS) in a population-based cohort. All residents of Olmsted County, Minnesota, with Escherichia coli and Pseudomonas aeruginosa BSI from 1 January 1998 to 31 December 2007 were identified. Logistic regression was used to examine the association between BSIMRS and mortality. Area under receiver operating characteristic curve (AUC) was calculated to quantify the discriminative ability of the BSIMRS to predict a variety of short-term and long-term outcomes. Overall, 424 unique Olmsted County residents with first episodes of E. coli and P. aeruginosa BSI were included in the study. Median age was 68 (range 0–99) years, 280 (66%) were women, 61 (14%) had cancer and 9 (2%) had liver cirrhosis. The BSIMRS was associated with 28-day mortality (p <0.001) with an AUC of 0.86. There was an almost 56% increase in 28-day mortality for each point increase in BSIMRS (OR 1.56, 95% CI 1.40–1.78). A BSIMRS ≥5 had a sensitivity of 74% and a specificity of 87% to predict 28-day mortality with a negative predictive value of 97%. The BSIMRS had AUC of 0.85, 0.85 and 0.81 for 7-, 14- and 365-day mortality, respectively. BSIMRS stratified mortality with high discrimination in a population-based cohort that included patients of all age groups who had a relatively low prevalence of cancer and liver cirrhosis.     

The autopsy and vital statistics

Vital statistics in the United States are collected through a decentralized, cooperative system of various levels of government administrated by the National Center for Health Statistics. Although registration of all deaths is virtually complete and demographic items are accurate, the reliability of cause of death data is hampered by the current state of medical knowledge, the incompleteness of information available at the time of death, the way in which physicians complete death certificates, and the system of classification of underlying cause. The need for quality assurance in national cause of death statistics can be met in large part by connecting the autopsy to the mainstream of vital statistics. Through case by case individual linkage of death certificates and autopsies in designated demographic and/or geographic areas, a representative, continuously collected, population-based system of aggregated autopsy data would be created. Demographic and clinical selection bias should be checked and adjusted through traditional methods of epidemiologic standardization. Such a use of autopsy information could further pathology's goals of understanding disease and improving the public health.     

Sources, uses, strengths and limitations of data collected in primary care in England

In the UK, general practitioners are responsible for both providing primary care services and for organising referrals for specialist care. Consequently, the medical records held by general practitioners include details of all diagnoses and prescribed drugs, in many cases extending from birth. In an increasing number of general practices, these records are held in electronic format and are potentially available for extraction and analysis. Electronic data from general practice therefore offer unique opportunities to plan and monitor health services, measure the quality of care provided by the National Health Service, and undertake population-based research.     

Social determinants and epidemiology of cardiovascular diseases

Recent approaches to studies of social determinants and social epidemiology of cardiovascular diseases are reviewed. This approach originating in some industrialized countries has so far been neglected in Croatia in spite of previous experiences and existence of sociomedical tradition. The possible explanations are considered. Obvious health problems related to the standard of living, poverty, high unemployment, work insecurity, unjustified inequality of income, and other forms of discrimination in health are not tackled. The social determinants important for health are defined and at least five categories identified, i. e. broad cultural and economic circumstances, structural determinants and social position, intermediate determinants reflected in lifestyles, available social network and social capital, and finally discrimination in health care are recommended to include in epidemiological research and design of health interventions. The following measures are proposed as necessary in the current situation: 1) changes in scope and orientation of epidemiological and clinical research; 2) intensification of information for the public, experts and politicians on the role of social determinants; and 3) amplification of health interventions avoiding patterns of the predominant neoliberal approaches (blaming the victim), as well as administrative egalitarian approaches (teaching people to become victims waiting for elderly brother to provide solutions).     

Epidemiology of human rabies in South Africa, 1983-2007

Rabies remains a global public health problem but increasingly so in the developing world. Given a lack of awareness, priority and diagnostic capability, very few developing countries, especially in Africa, report on laboratory confirmed human rabies cases. Here we present a retrospective study on the epidemiology of human rabies in Republic of South Africa for a 25-year period, 1983-2007, based on laboratory confirmed cases. The study highlights the role of the domestic dog as a reservoir and vector of rabies and contrasts this to the almost negligible contribution of wildlife vectors to the overall burden of human rabies in dog rabies endemic areas. From the collective data set, epidemiological aspects that include various features of these human rabies cases as well as failures in or towards the treatment of exposures are reported. Molecular analysis of virus isolates did not identify any additional cases of rabies attributed to infection with the Duvenhage, Lagos bat or Mokola or any other rabies-related viruses.     

Sad, glad, or mad hearts? Epidemiological evidence for a causal relationship between mood disorders and coronary artery disease.

OBJECTIVE: To examine the epidemiological evidence to determine if there is sufficient support for the hypothesis that mood disorders convey a risk factor in the pathogenesis of coronary artery disease (CAD). METHOD: Based on a review of the related research on Type A behavioral pattern (TABP) and other variables such as anger and hostility and their relationship to coronary artery disease (CAD), the findings were analyzed to ascertain any clinical patterns or similarities between behaviors of Type A and those in mood disorders. Using the given epidemiological criteria for a causal relationship, the association between the mood and coronary artery disease was explored. RESULTS: There are similar symptoms and behaviors noted among Type A, manic, cyclothymic and hyperthymic individuals. There is sufficient historical and contemporaneous epidemiological evidence to support the notion that mood disorders confer risk for CAD, but it is premature to describe it as a causative factor. Depressive symptoms and general mood disorders emerged as toxic risk factors for CAD. LIMITATION: This article presents only a selective literature review, and it is limited by an epidemiological analyses of secondary sources. The impact of this limitation on the interpretation of the analyses is discussed. CLINICAL RELEVANCE: Patients require scrupulous clinical assessment for the presence of mood disorders including subtype; the stakes are high, since their cardiac health status may depend upon it. Pathophysiological pathways may play a covariate role in both mood and coronary disease, and some tentative hypotheses regarding the role of catchecholamines and cortisol are explored. CONCLUSIONS: There is evidence to justify studying the role of mood as a covariate risk factor in the pathogenesis of CAD. Implications for mental health, public health, primary care practice, and psychometric measurement are discussed. The hypothesis that mood disorders are a cause of CAD requires further research.     

The necessary role of the autopsy in cardiovascular epidemiology

The autopsy rate in the United States today is remarkably low, with proportionally fewer autopsies for natural causes of death. Consequently, most cardiovascular epidemiology studies do not use autopsy data and rely on death certificates, medical records, questionnaires, and family interviews as sources of mortality information. These practices introduce a high degree of variability and uncertainty regarding cause of death. This review illustrates the necessity for increased use of autopsies in cardiovascular epidemiology by critically evaluating other measures of cardiovascular disease (CVD) incidence. We evaluated the literature regarding CVD as cause of death and conducted discussions with cardiologists, pathologists, and epidemiologists. No attempt was made for meta-analysis. This review shows the limited reliability of death certificates, medical records, and interviews as sources of mortality statistics. In addition, the autopsy's role in clearly indicating the presence of CVD is illustrated. The autopsy used in conjunction with medical records is the only reliable means for establishing cause of death from CVD. There is an urgent need to reassess the current dependence of statistical mortality data on death certificates and other inadequate sources of CVD incidence. Death certificates, in general, are inadequately monitored for quality control and appropriate administrative oversight. With an increase in the number of hospitals performing no autopsies to investigate cause of death, a uniform national autopsy database is needed.     

Stages and results of Epidemiology Department activities

The paper sums up the activities of Department of Epidemiology of Medical Prophylaxis Faculty, I. M. Setchenov Moscow Medical Academy, in the 70 years of its existence. The Department plays the leading role in training specialists for sanitary and epidemiological service of the country. The main research, training, and methodological works in this speciality were prepared by the Department staff members, who prepared curricula for pre- and postgraduate training. For many years the department has been the methodological center in epidemiology training. Trends of research at the Department are concentrated on the pressing problems of general and special epidemiology. Due to activities of the department staff, epidemiological aspects have been studied and fundamentals of prevention and liquidation of many infectious diseases in the country have been formulated: enteric and streptococcal infections, typhus, tularemia, diphtheria, etc. Problems of epidemiological geography, including nosogeography, territorial and republican epidemiology have been investigated. Functioning of parasitic systems and mechanisms of epidemic process in some infections have been characterized with due regard for modern theoretical, methodological, and organization base of epidemiology. The data were used for developing new basis and organization forms of epidemiological surveillance of infectious diseases.     

New data on ecological analysis of possible relationship between magnesium in drinking water and liver cancer.

Based on extensive ecological data and conducted Bayesian modeling, this paper reports on epidemiological findings concerning a possible relationship between magnesium in drinking water and carcinogenesis in human liver. Relative contributions of water quality to endemic waterborne disease for particular categories of magnesium concentration and for age groups of patients were ascertained, i.e. the smaller liver cancer morbidity is referred with a greater magnesium concentration in drinking water, both in males and females. The achieved outcomes provide statistically significant evidence of positive health effects of magnesium water supplies on this lethal disease.     

Molecular epidemiology and population dynamics of hepatitis B virus in Dianjiang County, Chongqing, China

Hepatitis B virus infection is highly endemic in China, especially in rural areas such as Dianjiang County with poor-quality health care and little local HBV information. Therefore, for the first time, the present study was carried out to investigate the molecular epidemiology, phylogeny and population dynamics of HBV based on 146 HBV-infected patients. A 435-bp portion of the HBV S region was sequenced, and the phylogeny was reconstructed, indicating that three genotypes, B, C and D of HBV were distributed in Dianjiang County. The predominant genotype is B (67.12 %), followed by C (32.19 %) and D (0.68 %). Patient demographic information and clinical outcomes were examined by genotypes, and no significant association was found. Population dynamics analysis suggested that both genotype B and C have experienced a tenfold expansion during the last five years for reasons that are unclear. Thus, a thorough molecular epidemiology investigation is strongly recommended in the future.     

基于HTML5 的结直肠癌流行病学数据采集系统

结直肠癌是危害人类生命健康的重大疾病。获取结直肠癌高危人群的流行病学数据,能及时掌握他们的生活习惯、个人和家族疾病史等信息,对结直肠癌的早诊早治有重要意义。本研究构建了一个基于B/S架构且能离线运行的结直肠癌流行病学数据采集系统。该系统采用ASP.NET结合HTML5的离线运行技术,利用jQuery异步调用Web Service实现数据在线提交,利用Web SQL Database实现数据离线存储。测试结果表明,该系统不仅能在iOS,Android等移动平台加载,并且能在没有网络或网络不稳定的场所正常运行,满足使用移动终端在缺乏网络的场所,进行流行病学数据采集和归档的实际需求。目前已利用该系统采集了178份结直肠癌流行病学数据,这些数据已作为数据源存储于前期工作开发的转化医学平台。本研究表明,利用HTML5可同时有效解决流行病学数据采集系统的平台依赖性和网络依赖性两大问题。     

Gene diversity and estimation of genetic admixture among Mexican-Americans of Starr County, Texas.

The Mexican-Americans of Starr County, Texas, classified by sex and birthplace, were studied to determine the extent of genetic variation and contributions from ancestral populations such as Spanish, Amerindian and West African. Using 21 genetic marker systems, genetic distance and diversity analyses indicate that subpopulations of Mexican-Americans in Starr County are similar, and that more than 99% of the total gene diversity (HT) can be attributed to individual variation within the population. Genetic admixture analysis shows the predominant influence comes from the Spanish, a lesser contribution from Amerindians and a slight one from the West Africans. The contribution of the ancestral population to various subpopulations of the Mexican-Americans of Starr County is similar. The Mexican-Americans of Starr County are similar to the Mexican population from northeastern Mexico. The history of admixture is apparently old enough to have brought the entire Mexican-American gene pool to Hardy-Weinberg equilibrium. There is no non-random association of alleles among the genetic marker systems considered in the present study, in spite of the fact that this population is of admixed origin. These results, in aggregate, suggest genetic homogeneity of the Mexican-Americans of Starr County, Texas, and point towards the utility of this population for genetic and epidemiological studies.     

Quality assurance of autopsy face sheet reporting,final autopsy report turnaround time,and autopsy rates: a College of American Pathologists Q-Probes study of 10003 autopsies from 418 institutions

OBJECTIVE: To develop a multi-institutional reference database of autopsy practice and performance for quality improvement purposes. DESIGN: In 1990, participants in the Q-Probes quality improvement program of the College of American Pathologists (CAP) each retrospectively evaluated the 25 most recently completed consecutive autopsy reports and determined the number of deaths and autopsies that occurred in their institutions during 1989. SETTING: Hospital-based autopsies excluding forensic cases and stillborn infants. PARTICIPANTS: Four hundred ten institutions in the United States and eight institutions in Canada. MAIN OUTCOME MEASURES: Completeness of face sheet information contained in final autopsy reports, turnaround time for completion of final reports, and institutional autopsy rates. RESULTS: In the aggregate database of 10003 autopsies, the following six data items (from a total of 21) were present in 95% to 100% of the final autopsy reports in at least 85% of the participating institutions: institution where autopsy was performed, patient's name, patient's sex, autopsy number, autopsy date, and prosecter's name. The turnaround times for the final autopsy reports were as follows: 30 days or less in 47.6% of the cases, 31 to 60 days in 28.8%, and more than 60 days in 23.7%. A higher median percentage of autopsy final reports were completed in 30 days or less in institutions with the following characteristics: nonteaching (P < .004), no pathology residency program (P < .002), and rural location (P < .027). A lower number of autopsies performed in 1989 was associated with a higher median percentage of final reports completed in 30 days or less (P < .007). The aggregate autopsy rate for all participating institutions was 12.4%, and the median rate was 8.3%. Median autopsy rates for teaching institutions and institutions with pathology residency training programs were 15% and 19%, respectively. CONCLUSIONS: This multi-institutional study identified a core group of face sheet data items that were consistently present on final autopsy reports. However, the majority of the face sheet data items examined were inconsistently recorded. Approximately 75% of final autopsy report turnaround times were within the standard established by the Joint Commission on Accreditation of Healthcare Organizations. Nearly two thirds of the institutions reported autopsy rates for 1989 of 0% to 10%.     

The pleiotropic vasoprotective functions of high density lipoproteins (HDL)

The pleiotropic functions of circulating high density lipoprotein (HDL) on peripheral vascular health are well established. HDL plays a pivotal role in reverse cholesterol transport and is also known to suppress inflammation, endothelial activation and apoptosis in peripheral vessels. Although not expressed in the central nervous system, HDL has nevertheless emerged as a potential resilience factor for dementia in multiple epidemiological studies. Animal model data specifically support a role for HDL in attenuating the accumulation of β-amyloid within cerebral vessels concomitant with reduced neuroinflammation and improved cognitive performance. As the vascular contributions to dementia are increasingly appreciated, this review seeks to summarize recent literature focused on the vasoprotective properties of HDL that may extend to cerebral vessels, discuss potential roles of HDL in dementia relative to brainderived lipoproteins, identify gaps in current knowledge, and highlight new opportunities for research and discovery.