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PubMed1998

The perfect C. elegans project: an initial report.

The soil nematode Caenorhabditis Elegans (C. elegans) is the most investigated of all multicellular organisms. Since the proposal to use it as a model organism, a series of research projects have been undertaken, investigating various aspects of this organism. As a result, the complete cell lineage, neural circuitry, and various genes and their functions have been identified. The complete C. elegans DNA sequencing and gene expression mapping for each cell at different times during embryogenesis will be identified in a few years. Given the abundance of collected data, we believe that the time is ripe to introduce synthetic models of C. elegans to further enhance our understanding of the underlying principles of its development and behavior. For this reason, we have started the Perfect C. elegans Project, which aims to produce ultimately a complete synthetic model of C. elegans' cellular structure and function. This article describes the goal, the approach, and the initial results of the project.

Animals↗
PubMed2002

Long-term survival of children with neuroblastoma prior to the neuroblastoma screening project in Germany.

BACKGROUND: In the last decades, prognosis of children with neuroblastoma has improved only slightly. Traditional estimates of survival reflect the survival experience of children diagnosed many years ago, and may thus not capture more recent progress in prognosis. We applied a new method of survival analysis, denoted period analysis, to provide more up-to-date estimates of long-term prognosis. We selected the cases diagnosed before the German neuroblastoma screening project in 1995, allowing to assess the method by comparing the 1994 projected survival estimates with the observations made today (2000). PROCEDURE: The data comes from the population based German Childhood Cancer Registry. We included all 1,353 children diagnosed with neuroblastoma below age 15 between 1980 and 1994. We derived 5-, 10-, and 15-year survival estimates using traditional analysis or period analysis as needed. Where possible we compared the period analysis estimates with the later obtained actual estimates. We showed trends in survival for the sample as a whole and for prognostic subgroups. RESULTS: Survival probabilities increased over time especially in the subgroups with poor prognosis. Short-term survival probabilities improved more than long-term survival probabilities. Evaluation of the period-analysis estimates showed them to provide accurate and timely projections of prognosis of newly diagnosed patients. CONCLUSIONS: The results suggest major improvements in prognosis of children with neuroblastoma, even prior to the start of the German neuroblastoma screening project, especially in advanced disease. This could have been disclosed with the application of the period analysis method in 1995 even then with considerable accuracy. We recommend a more widespread application of this method especially in population-based cancer registries.

Adolescent↗
PubMed2005

[Project on disease-related proteomics and a proteome factory for drug innovation].

The proteome is expected to be thoroughly researched in Post Genome Projects following the completion of the Human Genome Sequencing Project. Many research projects to investigate disease-related proteins are being undertaken worldwide. Analysis of the proteome, which has an intimate involvement in biogenics, should provide a breakthrough in vital activity and provide substantial clues for new treatments, diagnoses and new target of drugs. In the 2003 fiscal year, The Ministry of Health, Labour and Welfare (MHLW) started the Health, Labour and Welfare Scientific Research Founding Program "Disease Related Proteomics". At the time, the Japan Health Sciences Foundation was delegated the project from MHLW, along with the Japan Pharmaceutical Manufactures Association, and established a consortium with 22 pharmaceutical companies for this project, collaborating with the National Institute of Health Science to start the Project on Disease Related Proteomics and a Proteome Factory for Drug Innovation. In this report, the project overview and its facilities will be introduced.

Databases, Protein↗
PubMed2005

Flexible information storage in MUDR(II) EHR.

An important research task of the EuroMISE Centre is the applied research in the field of electronic health record (EHR) design including electronic medical guidelines and intelligent systems for data mining and decision support. The research in this field was inspired by several European projects. We have proposed a mathematical meta-description of a flexible information storage model based on the experience gathered in cooperation in those projects. In this model, we use two basic structures called a knowledge base and data files. We describe those two structures using the graph theory concepts. Furthermore, we use logical formulas to express conditions that should be valid. Additionally, we present a description of a global system architecture of a 3-tier EHR application with interfaces based on the latest technologies; predominately on Web Services, SOAP, XML, HTTP, CORBA, etc. According to our experience and test results gained from the MUDR EHR usage, we describe an open universal solution, which can be applied as the EHR kernel of hospital information systems. To realize this approach in a daily practice for health professionals we have started a co-operative project with clinical information systems developers. Within that project we are developing a new system for continual shared health care.

Biomedical Research↗
PubMed1996

US experiences for quality assurance in Swiss health care settings.

This report illustrates the first step of a research project at the Institute of Business Research, University of Zurich, concerning quality improvement techniques in Swiss health care institutions. It endeavors to provide a forecast of further research activities. Apart from the analysis provided by the most recent follow-up on the National Demonstration Project for Quality Improvement in Health Care (NDP), this also shows the lessons learned from the perspective of the initial NDP participants. Additionally, the results are adapted for application to European circumstances for quality improvement activities in health care institutions. US experience shows that physician involvement along with a good database are key success factors for quality improvement. Strategically important processes must be selected early on for quality improvement projects. It is important to start with intensive training of process leaders instead of a broad-based training. Furthermore, the new Swiss law regarding quality assurance and its results are explained. The formation of the National Committee for Quality Assurance (NAQ) means that first-time Swiss health care providers, as well as health insurance-companies and cantonal representatives, are discussing quality measures and clinical standards on a national level.

Forecasting↗
PubMed1994

Digital image communication using a public digital telephone network.

At the University Hospital in Malmö, a project concerning image communication has been started during 1992. At the hospital, the departments principally involved are the Departments of Radiation Physics, Diagnostic Radiology, Medical Technology and Clinical Physiology. The project goal is to develop a system for sending images--with little or no degradation of diagnostic information--during nights and weekends from the X-ray department to the home of an experienced radiologist on duty. The purpose is to shorten the time needed for diagnosis and decisions in acute situations. Up to now this has sometimes required that this radiologist has to turn up at the hospital, which can delay the diagnosis up to 0.5 h.

Computer Communication Networks↗
PubMed1996

The ganglionic eminence may be an intermediate target for corticofugal and thalamocortical axons.

In the nervous system of many species, growing axons associate transiently with cellular groupings along their path. Whether this mechanism applies to the development of corticothalamic and thalamocortical projections is unknown. Using carbocyanine dyes, we studied the early growth of both corticofugal and thalamocortical fibers in hamster embryos. At embryonic day 11.5 (E11.5), corticofugal fibers invade the lateral ganglionic eminence (LGE), and thalamocortical fibers invade the medial ganglionic eminence (MGE). At this age, both sets of fibers are not yet in contact with each other. At the same time, neurons in each subdivision of the GE grow toward the cortex and thalamus. During the next 24 hr, corticofugal and thalamocortical fibers remain within the confines of the GE, where they course at different radial levels and bear large and complex growth cones. In the LGE, corticofugal fibers are often found in close association with cells that are likely to be neuronal. Starting on E13.5, both early projections from the GE decrease, and corticothalamic and thalamocortical fibers invade their definitive target regions. To test whether the GE specifically orients the growth and trajectories of cortical fibers even in the absence of the reciprocal thalamic projection, we cocultured explants of cortex and GE from either hamster or mouse embryos. These experiments showed that the GE, but not other tested brain regions, is able specifically to orient the growth of cortical axons. We therefore suggest that the GE may be an intermediate target in the pathfinding of axons between the cortex and the thalamus.

Animals↗
PubMed1990

Mapping the human genome: current status.

The human genome has already been the subject of extensive research activity even though the Human Genome Project is only just officially starting. This review and the accompanying wall chart attempt to provide an integrated, quantitative, and detailed summary of the status of knowledge on the human genome in mid-1990. The analysis has highlighted the rudimentary nature of many of the information links needed for the task. While this overview could not be fully comprehensive and required simplifying assumptions, the results have provided estimates of relative progress on a region-by-region basis throughout the genome.

Chromosome Banding↗
PubMed2006

Risk assessment of chemicals in foundries: the International Chemical Toolkit pilot-project.

In Brazil, problems regarding protection from hazardous substances in small-sized enterprises are similar to those observed in many other countries. Looking for a simple tool to assess and control such exposures, FUNDACENTRO has started in 2005 a pilot-project to implement the International Chemical Control Toolkit. During the series of visits to foundries, it was observed that although many changes have occurred in foundry technology, occupational exposures to silica dust and metal fumes continue to occur, due to a lack of perception of occupational exposure in the work environment. After introducing the Chemical Toolkit concept to the foundry work group, it was possible to show that the activities undertaken to improve the management of chemicals, according to its concept, will support companies in fulfilling government legislations related to chemical management, occupational health and safety, and environmental impact. In the following meetings, the foundry work group and FUNDACENTRO research team will identify "inadequate work situations". Based on the Chemical Toolkit, improvement measures will be proposed. Afterwards, a survey will verify the efficiency of those measures in the control of hazards and consequently on the management of chemicals. This step is now in course.

Brazil↗
PubMed2003

Identification and verification of critical performance dimensions. Phase 1 of the systematic process redesign of drug distribution.

BACKGROUND: Worldwide patient safety has become a major social policy problem for healthcare organisations. As in other organisations, the patients in our hospital also suffer from an inadequate distribution process, as becomes clear from incident reports involving medication errors. Medisch Spectrum Twente is a top primary-care, clinical, teaching hospital. The hospital pharmacy takes care of 1070 internal beds and 1120 beds in an affiliated psychiatric hospital and nursing homes. OBJECTIVE: In the beginning of 1999, our pharmacy group started a large interdisciplinary research project to develop a safe, effective and efficient drug distribution system by using systematic process redesign. The process redesign includes both organisational and technological components. This article describes the identification and verification of critical performance dimensions for the design of drug distribution processes in hospitals (phase 1 of the systematic process redesign of drug distribution). METHODS: Based on reported errors and related causes, we suggested six generic performance domains. To assess the role of the performance dimensions, we used three approaches: flowcharts, interviews with stakeholders and review of the existing performance using time studies and medication error studies. CONCLUSIONS: We were able to set targets for costs, quality of information, responsiveness, employee satisfaction, and degree of innovation. We still have to establish what drug distribution system, in respect of quality and cost-effectiveness, represents the best and most cost-effective way of preventing medication errors. We intend to develop an evaluation model, using the critical performance dimensions as a starting point. This model can be used as a simulation template to compare different drug distribution concepts in order to define the differences in quality and cost-effectiveness.

Attitude of Health Personnel↗
PubMed2006

Benefit or burden: introducing paraprofessional support staff to health visiting teams: the case of Starting Well.

With increased public-sector funding to expand and improve frontline services, pre-existing skill shortages within key professional workforces have become more acute. One response to this has been to encourage the development of skill-mix approaches which allow tasks previously undertaken by professional staff groupings to be assumed by new paraprofessional employees. Within the UK National Health Service, one group of professionals who are being challenged to change their way of working in this way are health visitors. Starting Well, one of Scotland's four health demonstration projects, which was established in 2000 to bring about a step-change in child health within deprived communities in Glasgow, operated as a pilot for such a skill-mix model of health visiting. The project was evaluated using a multimethod approach that encompassed the study of both processes and outcomes. The present paper reports on a process evaluation of the project's implementation that addressed the rationale underlying the development of Starting Well's skill-mix approach and the challenges which this model faced in practice. The perceptions of both managerial staff (n=18) and those working in practice (n=33) were gathered using semistructured interviews which sought to elicit and test Starting Well's theory of change in relation to the use of paraprofessional staff. Two sets of interviews were conducted with each group of staff between 2001 and 2003. Two main types of challenge were identified: deploying potentially vulnerable members of staff; and co-management of paraprofessionals by the health service and a voluntary-sector organisation. A potential challenge identified from the literature, i.e. that of implementing a new role within an existing team, proved to be less problematic within Starting Well. These issues are discussed in relation to current policy and practice debates.

Child↗
PubMed2005

Cost-effectiveness projections of oxaliplatin and infusional fluorouracil versus irinotecan and bolus fluorouracil in first-line therapy for metastatic colorectal carcinoma.

BACKGROUND: The results of a randomized comparison study (N9741) showed that oxaliplatin and infusional fluorouracil (FU) (FOLFOX) was superior to the previous standard of care in the United States, irinotecan and bolus FU (IFL), as first-line therapy for patients with metastatic colon carcinoma. The trade-offs between costs and survival for these two regimens have not been explored. METHODS: A post-hoc, incremental cost-effectiveness (ICE) projection using simulated cohorts of patients starting FOLFOX or IFL was tracked for major clinical events, toxicities, and survival. Recurrence and survival risks were based on clinical trial data. Resource use was projected using observed dose intensity, duration of therapy, delays in therapy, and toxicities Grade > 2 in N9741. The frequency, costs, and consequences of second-line therapy were examined. The time frame was 5 years, and the perspective was that of Medicare as a third-party payer. RESULTS: Initial treatment with FOLFOX versus IFL had an average incremental cost of dollars 29,523, a survival benefit of 4.4 months, and an ICE of dollars 80,410 per life year (LY), dollars 111,890 per quality-adjusted LY, and dollars 89,080 per progression-free year. By using the 95% confidence interval for the time to progression observed in N9741, the ICE associated with FOLFOX ranged from dollars 121,220 to dollars 59,250 per LY. In the clinical trial, dose delays and skipped doses were frequent. If progression-free patients were treated without delay for the first year or lifetime, then the ICE for FOLFOX increased to dollars 117,910 and dollars 222,200 per LY, respectively. The ICE increased to dollars 84,780 per LY when the model incorporated a revised IFL schedule with lower early toxicity and similar rates of treatment with second-line regimens. CONCLUSIONS: FOLFOX provided substantial benefits that incurred substantial additional costs. The ICE for FOLFOX fell into the upper range of commonly accepted oncology interventions in the context of the United States healthcare system.

Age Factors↗
PubMed1996

Tuberculosis in the community: 1. Evaluation of a volunteer health worker programme to enhance adherence to anti-tuberculosis treatment.

SETTING: A voluntary health worker project (Operation Elsies River) was started in a high incidence tuberculosis (TB) area in the Western Cape of South Africa, in order to assist the local TB Control programme with case-holding. OBJECTIVE: To evaluate the effectiveness of this group of volunteers in enhancing adherence of notified TB patients to tuberculosis treatment. DESIGN: A cohort study was conducted with 351 TB patients (203 children and 148 adults). RESULTS: The data from the child and the adult groups were analysed separately. The child group was more adherent to TB treatment than adults. The supervision option with staff dedicated to the treatment of TB, such as the clinic and the SANTA crèche, achieved better adherence results for pre-school children. The supervision modalities for adults did not differ in their adherence performance even following adjustment for confounders. CONCLUSION: The supervision option provided by the volunteers did not significantly improve the adherence of adult patients to antituberculosis treatment.

Adolescent↗
PubMedDate not supplied

[Endocrinologic after-care of brain tumor patients: initial retrospective analysis of HIT-study documented auxologic and endocrine parameters].

BACKGROUND: In 1987, a pilot trial (HIT 88/89) was initiated by GPOH to investigate the effectivity and toxicity of intense preradiation chemotherapy. The aim of this study was to improve the treatment of children with malignant brain tumors, but provided no standardized recording of auxological and/or endocrinological parameters. In 1993 a sub-project, "Endocrinological late effects", was started during the ongoing study to examine the late effects of treatment, and a retrospective evaluation was performed in order to standardize parameters. PATIENTS: We considered auxological and hormonal data from those patients (n = 133; 78 m, 55 f) who were alive at the time of the survey, and had completed tumor therapy. RESULTS: Analysis of the growth pattern of the children after the end of therapy indicate impaired growth. Group 1 (n = 77, CA < 10 yrs): Mean height SDS at tumor diagnosis was +0.32 (n = 77), and fell constantly after completion of therapy to -0.75 (n = 16) after 3-4.5 yrs. Group 2 (n = 56, CA > 10 yr): Height SDS-CA fell from +0.24 (n = 45) at the time of diagnosis to -0.62 (n = 14) after 3-4.5 yrs. Unfortunately, only body height and weight were recorded regularly, data on sitting height, pubertal stage and bone age were incomplete. Endocrine evaluation after end of therapy was insufficient. CONCLUSIONS: A standardization of endocrinological follow up is necessary as soon as possible, for an adequate description of the endocrinological late effects.

Adolescent↗
PubMed2004

Preschool hearing screening: pass/refer rates for children enrolled in a head start program in eastern North Carolina.

This 4-year project investigated the pass/refer rates of preschool children in a hearing screening program. Three- and 4-year-old children who attended Head Start centers in rural, traditionally medically underserved, eastern North Carolina participated (n = 1,462). Screening procedures and pass/refer criteria were based on the Guidelines for Audiologic Screening (American Speech-Language-Hearing Association [ASHA], Panel on Audiologic Assessment, 1997). Only 54% (n = 787) of children passed the initial screening (i.e., passed all three of the screening components, which included pure-tone audiometry, tympanometry, and otoscopy), and an additional 22% (n = 323) passed the rescreening, for an overall pass rate of 76%. The initial pass rate was 90%, 71%, and 71% for otoscopy, tympanometry, and pure-tone audiometry, respectively. After the initial screening, 675 children were referred (i.e., 83%, 2%, and 15% for audiologic rescreening, medical evaluation, or both, respectively). About 71% (n = 478) received the recommended evaluation. Follow-up assessment compliance after the rescreening was poor. Slightly more than 10% of children were evaluated. The hearing status of 267 (i.e., 18.3%) children was never determined. Six (i.e., 0.5%) of the 1,195 children who completed the audiologic screening and/or received diagnostic audiologic assessment were confirmed to have hearing loss. Methodological factors that may have contributed to this high refer rate include the use of all screening techniques (pure tones, tympanometry, and otoscopy), procedural considerations in testing protocol and pass/refer criteria, and the demographic characteristics of the children screened.

Acoustic Impedance Tests↗
PubMed1993

Medical need for quality specifications--a NORDKEM project for selecting the appropriate quality in clinical laboratories.

The Nordic Clinical Chemistry Project (NORDKEM) has during its existence run several projects dealing with analytical quality requirements and the specifications of such requirements. The latest project-"Medical Need for Quality Specifications in Laboratory Medicine"-started three years ago and is now to be reported. The project consists of three main subprojects and a large number of associated projects. The main subprojects deal with: *External quality assurance for proteins (Per Hyltoft Petersen et al.) *Transferability of clinical laboratory data (Torgny Groth & C-H de Verdier) *Terminology (René Dybkaer) "Clinical goals" are assessed using different kinds of procedures. Comparison with the characteristics of "the analytical procedures" and "the quality assurance programs" gives the Management of the clinical laboratory a background for determining the "analytical quality specifications" of the laboratory. Procedures for setting up clinical goals and analytical quality specifications are given and they are further exemplified in the associated projects. Clinical goals and the analytical quality specifications are expressed and calculated in similar ways as total allowable error (TEa), as a coefficient of variation or an absolute error within defined concentration intervals.

Chemistry, Clinical↗
PubMed1999

Physicians vs. MCOs: can they cooperate to improve care quality?

The notion persists that quality improvement efforts cause more contention than cooperation between health care plans/payers and physicians. Some plans are overcoming this by investing a variety of resources in physician quality improvement projects--and involving physicians from the start. Aetna U.S. Healthcare Research takes a collaborative approach to physician quality improvement. Detroit's Health Alliance Plan has awarded +3.9 million in grants to fund physician quality improvement projects--as drawn up by its physician groups.

Cooperative Behavior↗
PubMed2003

Analysis of quantitative trait loci that influence animal behavior.

Behavioral differences between inbred strains of mice and rats have a genetic basis that can now be dissected using quantitative trait locus (QTL) analysis. Over the last 10 years, a large number of genetic loci that influence behavior have been mapped. In this article I review what that information has revealed about the genetic architecture of behavior. I show that most behaviors are influenced by QTL of small effect, each contributing to less than 10% of the variance of a behavioral trait. The small effect of each QTL on behavioral variation suggests that the mutational spectrum is different from that which results in Mendelian disorders. Regions of DNA should be appropriately prioritized to find the molecular variants, for instance by looking at sequences that control the level of gene expression rather than variants in coding regions. While the number of allelic loci that can contribute to a trait is large, this is not necessarily the case: the analysis of selected strains shows that a remarkably small number of QTL can explain the bulk of the genetic variation in behavior. I conclude by arguing that genetic mapping has more to offer than a starting point for positional cloning projects. With advances in multivariate analyses, mapping can also test hypotheses about the psychological processes that give rise to behavioral variation.

Animals↗