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ROSE: decision trees, automatic learning and their applications in cardiac medicine.

Computerized information systems, especially decision support systems, have acquired an increasingly important role in medical applications, particularly in those where important decisions must be made effectively and reliably. But the possibility of using computers in medical decision making is limited by many difficulties, including the complexity of conventional computer languages, methodologies, and tools. Thus a conceptual simple decision making model with the possibility of automating learning should be used. In this paper, we introduce a cardiological knowledge-based system based on the decision tree approach supporting the mitral valve prolapse determination. Prolapse is defined as the displacement of a bodily part from its normal position. The term mitral valve prolapse (PMV), therefore, implies that the mitral leaflets are displaced relative to some structure, generally taken to be the mitral annulus. The implications of the PMV are: disturbed normal laminar blood flow, turbulence of the blood flow, injury of the chordae tendinae, the possibility of thrombus's composition, bacterial endocarditis, and, finally, hemodynamic changes defined as mitral insufficiency and mitral regurgitation. Uncertainty persists about how it should be diagnosed and about its clinical importance. It is our deep belief that the echocardiography enables properly trained expert armed with proper criteria to evaluate PMV almost 100%. But, unfortunately, there are some problems concerned with the use of echocardiography. With this in mind, we have decided to start a research project aimed at finding new criteria and enabling the general practitioner to evaluate the PMV using conventional methods and to select potential patients from the general population. To empower doctors to perform needed activities, we have developed a computer tool called ROSE (computeRized prOlaps Syndrome dEtermination) based on algorithms of automatic learning. This tool supports the definition of new criteria and the selection of potential PMV-patients. The ROSE is based on concepts of decision trees and automatic learning. The decisions and learning process can be presented with an easily visualized two dimensional model; thus decision trees are straightforward to build and interpret. Decision trees use different object attributes to classify different subsets of objects. (Their great advantage is that they don't use a fixed number of predetermined attributes.) In the decision tree approach, the members of a set of objects are classified as either positive or negative instances (in our case patients with PMV Syndrome or without it). Candidate attributes that may possibly describe the concept are then outlined. A decision tree construction tool uses outlined attributes to formulate the appropriate decision tree that identifies all positive instances of the underlying concept according to objects with known classification. (In our case the classification is done with the echo examination). The first set of objects used for the tree generation is usually called the training set. This decision tree characterization next becomes a basis: 1) forecasting whether an object previously unseen is a positive or negative instance of the concept being modeled, and 2) the hierarchical representation of the most important attributes of the concept being investigated. Our main interest and idea is to discover symptoms, syndromes, and illnesses related to PMV that can be distinguished by general practitioners in their everyday job and which should help them to identify possible PMV candidate patients. To this end, we constructed a computerized tool called ROSE. According to the principles presented above, we first taught ROSE using the sample of 400 examined volunteers. ROSE, considering that the clinical PMV diagnosis is practically not researched, is relatively successful. (abstract truncated)

Algorithms↗

The named nurse in Scotland: time for action runs short.

The implementation of the named-nurse standard for Scotland takes place in 1997. Scottish nurses therefore have the opportunity to learn from the successes and pitfalls experienced by their English colleagues. This article examines the change process in one Lanarkshire hospital which saw a marked change in the extent to which patients could identify their named nurse. At the start of the project 72% of 50 patients surveyed could identify who their named nurse was. After a structured change programme involving planning, training implementation and evaluation, 100% of patients in the first eight wards that took part in the project could identify their named nurse, with 75% saying that they spoke with their named nurse on a regular basis.

England↗

[Target population for hypertensive therapy].

The efficacy of treatment may be demonstrated globally but, in some patients, treatment can be either inappropriate or harmful because of undesirable secondary effects. Ideally, treatment should be limited to patients who respond, but this is impossible with the published data from clinical trials. This could become possible by creating a data base containing all published results and carrying out meta analyses on individual parameters. Using the most powerful methods of analysis this could allow identification of patients responding to treatment by taking into account not only the benefits but also the risks of a given treatment (the principle is to identify and estimate factors--demographical, sociological, generic, which interfere with the size of the effect). In order to identify responders to antihypertensive treatment, a meta analysis of individual data was started, the INDANA project. With a common data base of all the preventive trials of antihypertensive therapy, this study should contribute to improved identification of responders and therefore to individualization of treatment of hypertension.

Antihypertensive Agents↗

Pharmacodynamics of topoisomerase I inhibition: Western blot determination of topoisomerase I and cleavable complex in patients with upper gastrointestinal malignancies treated with topotecan.

Analogues of camptothecins are specific inhibitors of eukaryotic DNA topoisomerase I (topo I) that lead to DNA damage and, eventually, cellular cytotoxicity. Camptothecin analogues bind to this target enzyme in the course of its normal function and stabilize the DNA-enzyme adduct to form a "cleavable complex." Preclinical experiments using Western blot analyses have shown cleavable complex formation to be the key intermediate step in topo I inhibition. In this series of experiments, it was our goal to convert this laboratory technique into a useful clinical assay, allowing measurement of the target enzyme and detection of the key intermediate in clinical specimens taken from patients being treated with the topo I inhibitor topotecan. Because available antibodies were not sufficiently sensitive at the start of this project, we identified a highly specific human SCL-70 antibody from a patient with scleroderma, which allowed quantitative determination of topo I copy number in HeLa and HT-29 cell lines. Additional refinements of the Western blot technique were accomplished to improve signal:noise ratio. In surgical tumor specimens, we found the median topo I level to be 30.1 x 10(5) copies/cell for gastric adenocarcinomas, compared to 18.4 x 10(5) copies/cell for normal gastric mucosae in the same samples. For lung adenocarcinoma, the median protein level was 21.5 x 10(5) copies/cell, compared with the normal tissue counterpart protein level of 12.7 x 10(5) copies/cell. The median tumor:normal ratios from paired samples of these tumor types were 1.51 and 1.84, respectively. As part of a Phase II study evaluating the efficacy of topotecan (1.5-2.0 mg/m2 daily for 5 days) in upper gastrointestinal malignancies, we obtained tumor and normal mucosa biopsies in 11 patients with gastric or esophageal cancer, 30 min after administration on day 4 or 5. Three patients with gastric adenocarcinoma had stable disease as their best response, with the remainder of patients progressing. Improvement in Western blotting methodology allowed the quantitation of topo I levels in these gastric and esophageal cancer biopsies, which could be augmented by brief heating to release complexed topo I. We were also able to directly visualize high molecular weight topo I-containing bands, which were shown to be cleavable complexes by heat reversal, with restoration of the topo I Mr 100,000 band. Using this heat reversal technique, we determined the presence of cleavable complex in a total of 7 of 11 patient biopsy samples (5 tumors and 2 normal mucosae). In patients treated with topotecan on this dose and schedule, we determined that a median of 73% of the total tumor topo I was involved in cleavable complex (range, 18.3-91%). The intensity of the Mr 100,000 topo I band in biopsy specimens of patients receiving topotecan represented "free" or noncomplexed topo I. The median copy number for the residual, noncomplexed topo I (n = 11) was 7.36 x 10(5) copies/cell, significantly less than the median of 30.1 x 10(5) copies/cell for random tumor specimens from patients with gastric adenocarcinomas (P < 0.001). Pharmacodynamic analysis demonstrated a negative correlation between the noncomplexed topo I copy number and topotecan area under the curve (Spearman rank test: r(s) = -0.81, P = 0.003). Nonlinear regression analyses of these data were best fit with an inhibitory maximum effect model, yielding parameter estimates for Emax and EC50 of 29.3 x 10(5) copies/cell (coefficient of variation = 22%) and 43.1 ng x h/ml (coefficient of variation = 27%), respectively. Through a series of careful modifications and refinements, we have improved the Western blot assay for topo I for use in clinical monitoring. We have demonstrated the ability to directly visualize cleavable complex in patients being treated with topo I inhibitor therapy and have directly quantitated free topo I, as well as the key topo I intermediate (cleavable complex), in biopsy specimens obtained from pat

Adenoma, Islet Cell↗

Historical overview of the project "Sunshine" in Belgium.

The project "Sunshine" was originally focused on the study of strontium 90 from the world-wide radioactive fallout and its effects on man. It was one of the most important projects the USAEC had ever had. It was being conducted as a scientific study, the primary purpose of which was to discuss the scientific truth and present the facts publicly. The implementation of the Project in Belgium started in 1958 and developed into two main directions: a) Environmental survey and b) Experimental research in both natural and controlled conditions. The paper described the characteristics of the seven stations "Sunshine" distributed in the typical agricultural regions of the country, their sampling, the analytical procedures used and the results obtained (relationship rain/grass; milk/grass; the observed ratio etc.). Experimental researches performed in natural conditions aimed to investigate the influence of the yield of the grass/crops on the direct retention of the deposited fission products; other experiments watched the transfer of radiostrontium and radiocesium from soils to plants; several experiments on artificially contaminated pastures grazed by cows allowed to clarify the importance of such factors as the methods of feeding and types of pastures for the transfer of major radionuclides to milk. Experimental researches conducted in controlled conditions dealt with such topics as study on the retention of strontium 90 in soil, studies on foliar contamination by radiostrontium and radiocesium, absorption and distribution in plants of Sr and Ca, discrimination between Sr and Ca during the transfer from feed to cow milk, study on the contamination by the major fission products of the milk products. Finally tentative countermeasures were tested: application of significant amounts of stable strontium in contaminated soils and influence of alginate on radiostrontium absorption from contaminated milk to piglets.

Belgium↗

[Present situation and future subjects of N.SAS study--based on experience of managing data center].

The "National Surgical Adjuvant Study" (N-SAS) was established as a study group on carcinostatics on the market as part of the Ministry of Health and Welfare's 1995/1996 consignment project. Patient registration started in October 1996, and later it was restructured as a consignment study by Taiho Pharmaceutical Co., Ltd. in April 1997. It still continues to date. EPS Co., Ltd. has operated the "N.SAS Data Center" to conduct three clinical trials of N.SAS study. In the following, we analyse the current situation and subjects of N.SAS study from the viewpoint of the data center, recognising the necessity of infrastructure at medical institutions while complying with enforcement of newly GCP and GPMSP. First, the organization and function of N.SAS, and the role and position of data center on N.SAS study, are explained. Some notes are introduced from conducting In-house Monitoring on N.SAS, especially methods and formation of communicating information between N.SAS Data Center and institutions. We also propose an infrastructure which will be essential for smooth promotion of long-term and large-scale trials like the N.SAS study.

Clinical Trials as Topic↗

Two-year comparison of income, education, and depression among parents participating in regular Head Start or supplementary Family Service Center Services.

Changes after 2 years in a Head Start Family Service Center Demonstration Project were assessed through pre-implementation and post-implementation interviews with 80 parents of Head Start children to evaluate changes during the project noted for the children's parents. Compared with parents in regular Head Start, parents in the supplementary Family Service Center project reported more contact with staff, increased their functional literacy scores, and increased their family incomes. The percentage of these parents with high depression scores decreased. These changes encourage implementation of more intensive social services within Head Start programs as a means of effectively assisting Head Start parents.

Adult↗

[Health telematics projects in the perspective of the German federal states].

Starting in autumn 2005 with pilot projects, the new German electronic health card (EHC) and electronic health professional cards (HPC) will be implemented in the German health system. These cards are constituents of the full coverage networking of more than 120,000 doctor's practices, 22,000 pharmacies, 2,200 hospitals and 300 health insurance companies. The functions of the EHC, for example electronic prescriptions, the digital medication recording and the European emergency database, need both the interactions with the HPCs and with a complex network of IT systems and telecommunication services, i. e. with a comprehensive health telematics infrastructure. Model regions for the construction of a telematics infrastructure have been established in numerous federal states, e. g. Baden- Wurttemberg, Bavaria, Bremen, Lower Saxony, North Rhine-Westphalia, Rhineland-Palatinate, Saxony and Schleswig-Holstein, and also recently in Mecklenburg-Vorpommern and Brandenburg. These model regions are designed in a way that allows smooth integration of the specifications of the so-called solution architecture of the EHC and also of electronic HPCs as soon as these are available. The implementation of first pilot trials in the model regions, each with 10,000 insured, is planned for the second half of 2005. A project task force was founded by a group from the German federal states in December 2004. The objective of these implementations is to establish a fully networked health system providing patients various e-Health applications which can be used any place and any time.

Computer Communication Networks↗

[Teaching and counseling families with small children in an urban area about minor illnesses of childhood].

INTRODUCTION: Parents' knowledge of and experience with illness in their children are often limited. They find it difficult to take the responsibility when their children are ill. They seek help immediately from the health care system, although the symptoms are mild. We wanted to discover whether teaching parents about minor illness in children and counselling over the telephone during acute illness would mean that parents sought help less often from the health care system, when their children became ill. This article deals with the teaching of the parents. MATERIAL AND METHODS: The project had an intervention group of 91 children aged 12-35 months and a control group of 400 children aged 9-33 months. The intervention group was instructed for two hours twice in the local day nursery and telephone counselling from a nurse trained in children's acute illnesses was made available from 4 pm to 11 pm on weekdays and from 10 am to 11 pm at weekends during the period 20th October 1998 to 1st May 1999. RESULTS: No visible change was seen in the use of the health care system in either group, but there was a small change in favour of the intervention group in the use of a general practitioner instead of calling the emergency medical service. Eighty per cent of the counselling dealt with common acute illnesses; 75% ended without referral. DISCUSSION: There was no visible difference in the use of the health care system in either group. Parents were happy with the offer of teaching and telephone counselling, but it should have been given when the infants started at the nursery. They felt their children were too old at the time the project started. We suggest a continuation of antenatal classes in the form of "parent preparation classes", where one subject could be minor acute illnesses in children.

Adult↗

How to construct a research project.

A research proposal should start with defining its aims. A synopsis of the literature and observations that the hypothesis is grounded should be given together with relevant references. The significance of the project, expected contributions to the field should also be indicated. If available, preliminary data enhance the impact of the proposal. A detailed description of the methods and subjects to be used is an important part of the proposal. What data are to be collected, the method of collecting data, and selection criteria for subjects should be indicated. Variables and how the measurements will be taken, have to be defined precisely. Data processing and analysis tools should be described. Additionally, the expected time table, project cost, the ethical and legal issues should be included in the proposal. It should be kept in mind that a scientist's primary responsibility is to create conditions such that the hypothesis can be tested objectively rather than proving his hypothesis.

Clinical Trials as Topic↗

The application of chemical leasing business models in Mexico.

BACKGROUND, AIM AND SCOPE: To better address the requirements of the changing multilateral order, the United Nations Industrial Development Organization (UNIDO) Cleaner Production Programme, in 2004, developed the new Sustainable Industrial Resource Management (SIRM) approach. This approach is in accordance with the principles decided at the United Nations Conference on Environment and Development (UNCED) in Rio de Janeiro, Brazil in 1992. Unlike the traditional approaches to environmental management, the SIRM concept captures the idea of achieving sustainable industrial development through the implementation of circular material and energy flows in the entire production chain and reduction of the amount of material and energy used with greater efficiency solutions. The SIRM approach seeks to develop new models to encourage a shift from selling products to supplying services, modifying, in this manner, the supplier/user relationship and resulting in a win-win situation for the economy and the environment. Chemical Leasing represents such a new service-oriented business model and is currently being promoted by UNIDO's Cleaner Production Programme. MAIN FEATURES. One of the potential approaches to address the problems related to ineffective use and over-consumption of chemicals is the development and implementation of Chemical Leasing business models. These provide concrete solutions to the effective management of chemicals and on the ways negative releases to the environment can be reduced. The Chemical Leasing approach is a strategy that addresses the obligations of the changing international chemicals policy by focusing on a more service-oriented strategy. Mexico is one of the countries that were selected for the implementation of UNIDO's demonstration project to promote Chemical Leasing models in the country. The target sector of this project is the chemical industry, which is expected to shift their traditional business concept towards a more service and value-added approach. This is being achieved through the development of company specific business models that implement the above-indicated Chemical Leasing concept with the support from the Mexican National Cleaner Production Centre (NCPC). RESULTS AND CONCLUSIONS: The implementation of Chemical Leasing in Mexico has proven to be an efficient instrument in enhancing sustainable chemical management and significantly reducing emissions in Mexico. Several companies from the chemical industrial sector implement or agreed to implement chemical leasing business models. Based on the positive findings of the project, several Mexican companies started to negotiate contents of possible Chemical Leasing contracts with suitable business partners. The project further aimed at disseminating information on Chemical Leasing. It successfully attracted globally operating companies in the chemicals sector to explore possibilities to implement Chemical Leasing business models in Mexico. At the international level, the results of the UNIDO project were presented on 20th September 2005 during a side event of the Strategic Approach to International Chemicals Management (SAICM) Preparation Conference in Vienna. RECOMMENDATIONS AND OUTLOOK: To facilitate the promotion and application of Chemical Leasing project at international level, UNIDO is currently developing a number of tools to standardize Chemical Leasing projects. These include, among others, Chemical leasing contract models; Chemical Leasing data base to find partners for chemical leasing; and guidelines to implement Chemical Leasing projects and work programmes.

Chemical Industry↗

User requirements rating and knowledge-level of general practitioners at the start of CholGate - a lipid management decision support project.

In the CholGate project we performed a preliminary study evaluating user requirements and knowledge level on lipid management in 40 primary care practices in The Netherlands. Practitioners rated speed, usability and completeness as important. We hope to show that the knowledge level of physicians regarding lipid management can be passively increased from its current levels by an integrated decision support system.

Attitude to Computers↗

The UICC/WHO-CCCE Cancer Education project: a different approach.

The Union Internationale Contre le Cancer (UICC) and the WHO-Collaborating Centre for Cancer Education (WHO-CCCE) have started an international pilot project offering assistance to medical schools that want to implement in their curricula a two-week multidisciplinary cancer course aimed at cancer care in general practice. The approach will be bottom-up (based on the possibilities in individual medical schools) instead of top-down (based on general recommendations and rules established in published studies). In April 2000 one or more medical schools from each of four continents had registered. Registration is open to any medical school and to other schools that have satisfactory ongoing cancer courses. The aim is to develop a network among medical schools in order for them to learn from each other's cancer education strategies and experiences.

Americas↗

Forensic entomology in Germany.

Forensic entomology (FE) is increasingly gaining international recognition. In Germany, however, the development of FE has been stagnating, mainly because of the lack of cooperation between police, forensic medicine and entomology. In 1997 a co-operative research project 'Forensic Entomology' was started in Frankfurt/Main at the Center of Legal Medicine and the Research Institute Senckenberg. The aim of this project is to establish FE in Germany as a firmly integrated component of the securing of evidence from human cadavers in cases of suspected homicide. For this purpose we developed a forensic insect collecting kit, and policemen are educated for greater acceptance and better application of FE. The scientific programme focuses on the investigation of the insect succession on cadavers in urban and rural habitats. This also includes new indicator groups (e.g. parasitic wasps) for a more precise calculation of the late post mortem interval. Recently a DNA-based reliable and fast identification method especially for the immature stages of necrophagous insects became part of the project. Preliminary results are reported and two case studies presented.

Animals↗

Screening for neuroblastoma at 3 weeks of age: methods and preliminary results from the Quebec Neuroblastoma Screening Project.

A large neuroblastoma screening study was recently started in the province of Quebec, Canada. This project, a collaboration between the Quebec Network for Genetic Medicine and the University of Minnesota, is studying the impact of screening infants for the preclinical detection of neuroblastoma on the population-based mortality caused by this tumor. All infants born in Quebec during a 5-year period will be screened twice, at 3 weeks and at 6 months. Urinary homovanillic acid and vanillylmandelic acid determination from dried filter paper samples is used for screening. Initial qualitative screening is done by means of thin-layer chromatography with confirmatory quantitative screening by gas chromatography-mass spectrometry (GC-MS). During the initial 6 months of 3-week screening, 41,673 neonates (92% compliance rate) were screened and 10.6% of them were tested also by GC-MS. Nine of these neonates had positive results on two GC-MS tests and were referred for evaluation to rule out the presence of neuroblastoma. Four had the tumor, 1 had a calcified adrenal gland, and 4 had no tumor detected. Three additional neonates had clinical diagnosis of neuroblastoma before they reached the screening age of 3 weeks. A neuroblastoma that did not secrete homovanillic acid or vanillylmandelic acid was diagnosed clinically in 1 additional patient who tested negative by screening.

Chromatography, Gas↗