Cost-of-illness studies: concepts,scopes, and methods

Liver diseases are one of the main causes of death, and their ever-increasing prevalence is threatening to cause significant damage both to individuals and society as a whole. This damage is especially serious for the economically active population in Korea. From the societal perspective, it is therefore necessary to consider the economic impacts associated with liver diseases, and identify interventions that can reduce the burden of these diseases. The cost-of-illness study is considered to be an essential evaluation technique in health care. By measuring and comparing the economic burdens of diseases to society, such studies can help health-care decision-makers to set up and prioritize health-care policies and interventions. Using economic theories, this paper introduces various study methods that are generally applicable to most disease cases for estimating the costs of illness associated with mortality, morbidity, disability, and other disease characteristics. It also presents concepts and scopes of costs along with different cost categories from different research perspectives in cost estimations. By discussing the epidemiological and economic grounds of the cost-of-illness study, the reported results represent useful information about several evaluation techniques at an advanced level, such as cost-benefit analysis, cost-effectiveness analysis, and cost-utility analysis.     

Transplant tolerance: models, concepts and facts

Despite extensive research, our understanding of immunological tolerance to self-antigens is incomplete, and the goal of achieving tolerance to allogeneic transplanted tissue remains elusive. Currently, it is generally believed that the blockade of T cell co-stimulation offers considerable potential for achieving tolerance in the clinical setting. However, the recent finding that CD154-specific antibody may act through the depletion of activated T cells rather than co-stimulation blockade alone highlights the need for a re-evaluation of published data and the role of co-stimulation blockade in transplant tolerance. Activated T cells are programmed to die unless they receive sufficient survival signals in the form of inflammatory and lymphotropic cytokines produced by activated antigen-presenting cells or the T cells themselves. In conditions where the threshold for surviving activation is not reached, for example when a small number of responder T cells are activated in the absence of substantial injury or inflammation, the ensuing death of all activated T cells can result in deletional tolerance. Therefore, we propose that tolerance represents a failure of T cells to survive activation and develop into memory cells. This concept is likely to apply in the transplant setting, where the strength of the alloresponse depends on both the number/phenotype of the recipients’ alloreactive T cells and immunogenicity of the transplanted tissue. Hence, in some rodent donor–recipient strain combinations that instigate a weak alloresponse, many treatments that only modestly decrease the alloresponse can achieve tolerance. In contrast, clinical transplantation is characterised by a strong alloresponse and highly immunogenic allografts, and thus, most treatments fail to control allograft rejection, and tolerance is difficult to achieve.     

Glucose, exercise and insulin: emerging concepts

Physical exercise induces a rapid increase in the rate of glucose uptake in the contracting skeletal muscles. The enhanced membrane glucose transport capacity is caused by a recruitment of glucose transporters (GLUT4) to the sarcolemma and t-tubules. This review summarises the recent progress in the understanding of signals that trigger GLUT4 translocation in contracting muscle. The possible involvement of calcium, protein kinase C (PKC), nitric oxide (NO), glycogen and AMP-activated protein kinase (AMPK) are discussed. Furthermore, the possible mechanisms behind the well-described improvement of insulin action on glucose uptake and glycogen synthase activity in the post-exercise period is discussed. It is concluded that both during and following muscle contractions, glycogen emerges as an important modulator of signalling events in glucose metabolism.     

Menopause, estrogens, and endothelial dysfunction: current concepts

Menopause is defined as the permanent cessation of menses. Cardiovascular disease is the leading cause of death among postmenopausal women in developed countries. The disparity between the incidence of cardiovascular disease among women in pre- and postmenopause has been ascribed to the actions of endogenous estrogen on the cardiovascular system and, particularly, on the vascular endothelium. The endothelium plays an important role in cardiovascular homeostasis, either through the vascular tonus and its regulation, or through coagulation and the inflammatory response. Endothelial dysfunction is implicated in the genesis of atherosclerosis and other chronic disorders, such as diabetes mellitus and hypertension. The pharmacological use of estrogen exerts influence on the circulating levels of markers of vascular tonus, and inflammation, as well as prothrombotic, and fibrinolytic markers, but the impact of these changes on the atherosclerotic disease is still uncertain.     

Tissue polarimetry: concepts, challenges, applications, and outlook

Polarimetry has a long and successful history in various forms of clear media. Driven by their biomedical potential, the use of the polarimetric approaches for biological tissue assessment has also recently received considerable attention. Specifically, polarization can be used as an effective tool to discriminate against multiply scattered light (acting as a gating mechanism) in order to enhance contrast and to improve tissue imaging resolution. Moreover, the intrinsic tissue polarimetry characteristics contain a wealth of morphological and functional information of potential biomedical importance. However, in a complex random medium-like tissue, numerous complexities due to multiple scattering and simultaneous occurrences of many scattering and polarization events present formidable challenges both in terms of accurate measurements and in terms of analysis of the tissue polarimetry signal. In order to realize the potential of the polarimetric approaches for tissue imaging and characterization/diagnosis, a number of researchers are thus pursuing innovative solutions to these challenges. In this review paper, we summarize these and other issues pertinent to the polarized light methodologies in tissues. Specifically, we discuss polarized light basics, Stokes-Muller formalism, methods of polarization measurements, polarized light modeling in turbid media, applications to tissue imaging, inverse analysis for polarimetric results quantification, applications to quantitative tissue assessment, etc.     

Meiosis-activating sterols: background, discovery, and possible use

Several years ago we discovered that spent media from cultured human and bull testes contain components that initiate meiosis in germ cells from fetal mouse testes which have been cultured for 6 days in the spent medium. The active substance(s) was termed meiosis-inducing substance. We later found that human follicular fluid harvested after stimulation with gonadotropins has a similar effect. These meiosis-activating substances have now been identified and characterized in extracts from bull testes and human preovulatory follicular fluid as naturally occurring sterols (meiosis-activating sterols, MAS). MAS are intermediates in the cholesterol biosynthetic pathway and are thus present in all cells which produce cholesterol de novo and from lanosterol. However, MAS accumulate only in the gonads. We discuss the possible physiological role of these sterols in initiating meiosis and in oocyte resumption of meiosis, and their potential use in promoting and preventing fertility. Received: 2 December 1997*Accepted: 6 April 1998     

The Herbal Alternatives for Menopause (HALT) Study: background and study design

We designed a randomized double-blind randomized trial to examine the short and long-term effects of alternative approaches commonly used to manage menopause symptoms. Women were randomly assigned to: (1) black cohosh 160 mg daily; (2) multibotanical (50 mg black cohosh, alfalfa, chaste tree, dong quai, false unicorn, licorice, oats, pomegranate, Siberian ginseng, boron) four capsules daily; (3) multibotanical plus telephone counseling to increase dietary soy; (4) conjugated equine estrogen 0.625 mg +/- 2.5 mg medroxyprogesterone acetate; or (5) placebo. Working with a skilled CAM provider helped us choose interventions that reflected naturopathic practices worthy of study. Mass mailing, with careful tracking and rapid responses to recruitment rates, was an effective and cost-effective recruitment strategy. Creativity was necessary to construct methods for blinding capsules and the dietary soy intervention. Independent testing of herbal products was vital to confirming their constituents. The Data and Safety and Monitoring Committee, and project officers at the funding agency, were critical partners in designing responses to unanticipated Women's Health Initiative findings published during the HALT trial. Careful monitoring of adverse events may provide much needed information about side effects of herbal products and supplements. Despite inherent challenges, the study of alternative therapies for menopause symptoms is a rewarding and important area deserving of further inquiry.     

Oligodendroglial neoplasms: current concepts, misconceptions, and folklore.

Given current prognostic and therapeutic implications, the accurate classification and grading of oligodendroglial neoplasms has become critical. However, the prevalence of morphologically ambiguous gliomas, subjective histologic criteria, personal biases, oligodendroglioma mimics, and the lack of specific oligodendroglioma markers has led to high interobserver variability and created a contentious problem encountered daily in active surgical neuropathology practices. Since histologic assessment is still a powerful prognosticator, it appropriately remains the diagnostic gold standard. However, recent efforts have focused on identifying the most reproducible and clinically relevant criteria, standardizing classification and grading schemes, and searching for useful ancillary biologic and genetic markers capable of further stratifying an otherwise heterogeneous patient population. This paper reviews the morphologic and genetic spectrum of oligodendroglial neoplasms, recent diagnostic and prognostic developments, and potential future directions.     

Hematopoietic stem cells: concepts, assays, and controversies.

Mature cells of the hematopoietic system, including B and T lymphocytes, have a limited life span and must be continuously replenished by differentiation from immature precursors. The stability of the hematopoietic system depends on the maintenance of a pool of pluripotent hematopoietic stem cells. During the past 30 years, the development of quantitative assays for stem cells and their progeny has led to an explosion of information concerning the stages of differentiation, regulatory factors and receptors, and characterization of surface markers. Nevertheless, there remain many controversies about the properties of cells in the stem cell compartment. The degree of heterogeneity within the stem cell compartment is unknown. The detailed mechanisms for regulation of stem cells are uncertain. Finally, the factors which control the recruitment of quiescent stem cells are unknown and controversial.     

New concepts in the design and use of biological prosthetic valves

The natural aortic valve is a structure that has thus far eluded all attempts at duplication with synthetic materials. Real success in the replacement of the aortic valve has come about primarily through the use of biological devices, such as the porcine aortic valve xenograft. In the future, bioprostheses based more closely on the natural aortic valve may ultimately succeed where synthetic approaches have failed. Some recent advances in the design and development of bioprosthetic heart valves, such as the absence of a stent and the better preservation of the valve's natural biomechanical properties, show considerable promise in improving the long term durability of these devices. With a greater understanding of the structure/function relationship of the aortic valve at the micromechanical level, the future of bioprostheses may be even more biologically oriented than it is today.     

循证运动医学的定义、基础、实践与发展

背景：随着传统运动医学的发展,运动医学研究与实践越来越多的采用“循证医学”的思想和方法。循证运动医学是循证医学与运动医学相结合的一门学科,也是一种新的运动医学实践模式。 目的：分析并总结循证运动医学的定义、基础、发展与实践。 方法：以电子检索方式检索The Cochrane Library(2015年第12期)、EMbase、PubMed 、SPORTDiscus、CNKI、WanFang Data和VIP数据库的研究文献,检索时间为从建库至2015年8月,英文检索词为：sports medicine和evidence-based;中文检索词为：运动医学和循证,排除重复性研究。 结果与结论：共纳入156篇文献,检索结果表明,循证运动人体科学、循证运动预防医学、循证运动创伤学和循证运动康复学发表文章数量均衡,说明这4个领域的学术研究进展的相对良好,而循证运动营养学和循证体育保健学,发表文章数量相对较少,说明这两个领域的学术研究进展相对缓慢。科学的循证运动医学实践与循证体育决策,不但能够系统指导运动员科学训练、有效防治运动员伤病以及高效提高运动员成绩,而且也能够系统指导大众科学健身、增强人民体质,增进人民健康。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程      

Patients' and physicians' understanding of health and biomedical concepts: relationship to the design of EMR systems

OBJECTIVE: The aim of this paper is to examine knowledge organization and reasoning strategies involved in physician-patient communication and to consider how these are affected by the use of computer tools, in particular, electronic medical record (EMR) systems. DESIGN: In the first part of the paper, we summarize results from a study in which patients were interviewed before their interactions with physicians and where physician-patient interactions were recorded and analyzed to evaluate patients' and physicians' understanding of the patient problem. We give a detailed presentation of one of such interaction, with characterizations of physician and patient models. In a second set of studies, the contents of both paper and EMRs were compared and in addition, physician-patient interactions (involving the use of EMR technology) were video recorded and analyzed to assess physicians' information gathering and knowledge organization for medical decision-making. RESULTS: Physicians explained the patient problems in terms of causal pathophysiological knowledge underlying the disease (disease model), whereas patients explained them in terms of narrative structures of illness (illness model). The data-driven nature of the traditional physician-patient interaction allows physicians to capture the temporal flow of events and to document key aspects of the patients' narratives. Use of electronic medical records was found to influence the way patient data were gathered, resulting in information loss and disruption of temporal sequence of events in assessing patient problem. CONCLUSIONS: The physician-patient interview allows physicians to capture crucial aspects of the patient's illness model, which are necessary for understanding the problem from the patients' perspective. Use of computer-based patient record technology may lead to a loss of this relevant information. As a consequence, designers of such systems should take into account information relevant to the patient comprehension of medical problems, which will influence their compliance.     

Men and therapy: critical concepts, theoretical frameworks, and research recommendations

Scholars are increasingly recognizing the existence of multiple evolving conceptions of masculinity and the need for psychologists to better attend to masculinity-related constructs and their implications for men's lives. This article seeks to respond to this need by (a) reviewing research linking masculinity-related constructs to clinically relevant issues, (b) providing suggestions for building effective therapeutic relationships with male clients, (c) describing the role that culture and racism may play in male clients' lives, and (d) offering recommendations for future research.     

Interleukin-6: historical background, genetics and biological significance

Interleukin-6 (IL-6) is a pleiotropic cytokine previously known as B cell stimulatory factor (BSF-2), interferon-beta 2 (IFN-beta 2), 26-kDa protein, and hepatocyte stimulating factor (HSF). The name IL-6 was proposed when the nucleotide sequences of the cDNAs for these proteins had been determined and the molecules were found to be identical. IL-6 production can be induced by a wide variety of agents in a wide range of cells, although IL-6 gene expression seems to be regulated in a tissue and stimulus specific manner. At least 3 different signal pathways regulate IL-6 gene expression, emphasizing its multiply inducible nature. The currently known activities of IL-6 include regulatory functions in hematopoiesis, immune reactions and acute phase responses. IL-6 appears to be a key member of the IL family; however, it is still poorly understood how IL-6 interacts with other lymphokines within the network. The anti-viral activity of IL-6 seems to be negligible. Elevated IL-6 levels have been found in diseases like rheumatoid arthritis, multiple myeloma and systemic lupus erythematosus. The abnormal expression and dysregulation of IL-6 in certain disorders may be a typical feature of this cytokine, making it the first cytokine that may be directly related to pathogenesis.