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[European guideline for the quality of non-commercial clinical trials: elegant implementation in the Netherlands via the amended Dutch Medical Research Involving Human Subjects Act].

As of May 2004, the new European directive 2001/20/EC will require European member states to follow Good Clinical Practice rules for non-commercial academic clinical investigations. For several member states this poses a serious threat to such investigations. In the Netherlands however, most items of the new directive can be incorporated in the Dutch Medical Research Involving Human Subjects Act. In fact, many of the items are already covered by this Act, notably with respect to data integrity and patient safety. However, an extra effort is needed to implement the quality control standards to which the registration research already complies. The Dutch Medical Research Involving Human Subjects Act is currently being amended to comply with the new European directive. This is also an ideal opportunity for enhancing the national climate of clinical research and ensuring an improved translation of local research ideas into clinical trial protocols.

Clinical Protocols↗

Topographic mapping of brain electromagnetic signals: a review of current technology.

Topographic mapping of brain electromagnetic signals has become increasingly popular in recent years both as a clinical tool and as an area of research in its own right. The capabilities of existing computerized systems for displaying such maps and for performing localization of current sources in the brain have continued to expand. In this paper we review some of the methodological and technological issues concerning topographic mapping. These include issues of choice of interpolation algorithm, what to map, head geometry, EEG reference location, and scaling. We also discuss characteristics of clinical databases for patient comparison and the usefulness of quantitative EEG (which includes mapping) for the diagnosis of nervous system disorders. Finally, we compare five representative systems in terms of their topographic mapping capabilities. The overall conclusion is that future developments must make use of integrated data from other neuroimaging technologies such as MRI, PET, and SPECT, and determination of the normal limits of topographic parameters must be more carefully examined.

Brain Mapping↗

Rapid analysis of protein structure and dynamics by hydrogen/deuterium exchange mass spectrometry.

An automated approach for the rapid analysis of protein structure has been developed and used to study acid-induced conformational changes in human growth hormone. The labeling approach involves hydrogen/deuterium exchange (H/D-Ex) of protein backbone amide hydrogens with rapid and sensitive detection by mass spectrometry (MS). Briefly, the protein is incubated for defined intervals in a deuterated environment. After rapid quenching of the exchange reaction, the partially deuterated protein is enzymatically digested and the resulting peptide fragments are analyzed by liquid chromatography mass spectrometry (LC-MS). The deuterium buildup curve measured for each fragment yields an average amide exchange rate that reflects the environment of the peptide in the intact protein. Additional analyses allow mapping of the free energy of folding on localized segments along the protein sequence affording unique dynamic and structural information. While amide H/D-Ex coupled with MS is recognized as a powerful technique for studying protein structure and protein-ligand interactions, it has remained a labor-intensive task. The improvements in the amide H/D-Ex methodology described here include solid phase proteolysis, automated liquid handling and sample preparation, and integrated data reduction software that together improve sequence coverage and resolution, while achieving a sample throughput nearly 10-fold higher than the commonly used manual methods.

Amides↗

Nutrient intakes of 2- to 10-year-old American children: 10-year trends.

Nutrient intakes of American children aged 2 to 10 years were compared for the years 1978 and 1988 using a unique nutrient assessment system designed and developed by the Nutrition Department at General Mills. This system integrated data from three sources: 14-day food consumption diaries collected from 4,000 households in the Market Research Corporation of America Menu Census panel surveys; serving-size data from the spring 1977 Nationwide Food Consumption Survey; and nutrient data from the Michigan State University Nutrient Data Bank. The results indicate that energy and macronutrient intakes remained fairly constant over the 10-year period. Average daily vitamin and mineral intakes were lower in 1988 than in 1978 for the majority of those studied; however, most nutrient levels remained over 100% of the Recommended Dietary Allowances (RDAs). For more than 50% of the population, the intakes of calcium, vitamin B-6, and zinc were below the RDAs. Our findings indicate the need for continued monitoring of the impact of changing food consumption patterns on the diets of American children.

Child↗

Using clinical outcomes to explore the theory of expert practice in physical therapy.

BACKGROUND AND PURPOSE: Theoretical models of physical therapist expertise have been developed through research on physical therapists sampled solely on the basis of years of experience or reputation. Expert clinicians, selected on the basis of their patients' outcomes, have not been previously studied, nor have the patient outcomes of peer-nominated experts been analyzed. The purpose of our study was to describe characteristics of therapists who were classified as expert or average therapists based on the outcomes of their patients. SUBJECTS: Subjects were 6 therapists classified as expert and 6 therapists classified as average through retrospective analysis of an outcomes database. METHODS: The study was guided by grounded theory method, using a multiple case study design. Analysis integrated data from quantitative and qualitative sources and developed a grounded theory. RESULTS: All therapists expressed a commitment to professional growth and an ethic of caring. Therapists classified as expert were not distinguished by years of experience, but they differed in academic and work experience, utilization of colleagues, use of reflection, view of primary role, and pattern of delegation of care to support staff. Therapists classified as expert had a patient-centered approach to care, characterized by collaborative clinical reasoning and promotion of patient empowerment. DISCUSSION AND CONCLUSION: These findings add to the understanding of factors related to patient outcomes and build upon grounded theory for elucidating expert practice in physical therapy.

Adult↗

A methodology for multi-source Record Linkage.

As patient's medical data is disseminated in different health structures, building a data-warehousing system at a regional level, for healthcare co-operation, has some specific requirements compared to intra healthcare structure data-warehousing projects. In particular, there is no common patient electronic record's identifier among all the sources. Hence, data integration and Record Linkage is the most important issue in such projects. In this paper, we present Background on Information integration with the two main approaches of the problem: Schema Integration approach and Entity reconciliation approach. We show the limits of each of the two approaches and propose an approach based on theory of a set partitioning and instance identification.

Computer Systems↗

Automated integration of external databases: a knowledge-based approach to enhancing rule-based expert systems.

Expert system applications in the biomedical domain have long been hampered by the difficulty inherent in maintaining and extending large knowledge bases. We have developed a knowledge-based method for automatically augmenting such knowledge bases. The method consists of automatically integrating data contained in commercially available, external, on-line databases with data contained in an expert system's knowledge base. We have built a prototype system, named DBX, using this technique to augment an expert system's knowledge base as a decision support aid and as a bibliographic retrieval tool. In this paper, we describe this prototype system in detail, illustrate its use and discuss the lessons we have learned in its implementation.

Asthma↗

Towards clinical bioinformatics: advancing genomic medicine with informatics methods and tools.

OBJECTIVES: To summarize the challenges facing clinical applications in the light of growing research results in genomic medicine and bioinformatics. METHODS: Analysis of the contents of the Yearbook of Medical Informatics 2004 of the International Medical Informatics Association (IMIA). RESULTS: The Yearbook of Medical Informatics 2004 includes 32 articles selected from 22 peer-reviewed scientific journals. A special section on clinical bioinformatics highlights recent developments in this field. Several guest editors review the promises and limitations of available methods and resources from biomedical informatics that are relevant to clinical medicine. Integrated data and knowledge resources are generally regarded to be central and key issues for clinical bioinformatics. Further review papers deal with public health implications of bioinformatics, knowledge management and trends in health care education. The Yearbook includes for the first time a section on the history of medical informatics, where the significant impact of the Reisensburg protocol 1973 on international health and medical informatics education is examined. CONCLUSIONS: Close collaboration between bioinformatics and medical informatics researchers can contribute to new insights in genomic medicine and contribute towards the more efficient and effective use of genomic data to advance clinical care.

Computational Biology↗

Splicing factors are differentially expressed in tumors.

Although alternative splicing of many genes has been found associated with different stages of tumorigenesis and splicing variants have been characterized as tumor markers, it is still not known whether these examples are sporadic or whether there is a broader association between the two phenomena. In this report we evaluated, through a bioinformatics approach, the expression of splicing factors in both normal and tumor tissues. This was possible by integrating data produced by proteomics, serial analysis of gene expression (SAGE) and microarray experiments. We observed a significant shift in the expression of splicing factors in tumors in both SAGE and microarray data, resulting from a large amount of experiments. We discuss that this supports the notion of a broader association between alternative splicing and cell transformation, and that splicing factors may be involved in oncogenic pathways.

Alternative Splicing↗

National Provider Identifier (NPI) planning and implementation fundamentals for providers and payers.

Federal HIPAA legislation mandates that the National Provider Identifier (NPI) be fully implemented across all healthcare entities between May 2005 and May 2007, or 2008 for small payers. Starting May 2005, healthcare providers will be eligible to obtain an NPI and use these numbers to submit claims or conduct other transactions specified by HIPAA. By 2007, the NPI must be used in connection with the electronic transactions identified in HIPAA. Today, individual payers assign unique identification numbers to healthcare providers, and, in most cases, payers assign multiple identification numbers to healthcare providers and their "subparts." As a result, providers have multiple payer-specific identification numbers. The NPI is a unique, 10-digit federal healthcare provider identification number that will be used by all healthcare providers and payers and other healthcare entities involved in administrative and financial transactions associated with health service events and related activities. This article will use software and data experts' knowledge as well as the authors' NPI implementation readiness assessment work to review the impact to both payers and providers, including hospitals, clinics, and other service entities. The authors will suggest planning, budgeting, architecting, and data management solutions for payers and providers to achieve the optimal administrative simplification goals intended by the NPI, without compromising data integrity and interoperability objectives across the service spectrum of the healthcare enterprise.

Guideline Adherence↗

Biochip platforms as functional genomics tools for drug discovery.

Improvements in DNA microarray technology have resulted in the generation of data on a scale that, for the first time, permits detailed scrutiny of the human genome. These data provide the foundation for understanding not only the connections between genes and the purpose of genes in the human genome, but also the molecular basis of genetic defects. These advances have the potential to significantly improve healthcare management by improving disease diagnosis and specifically targeting molecular therapy. Herein, the current state of the technology is reviewed, the commercial platforms used by the biopharmaceutical industry are compared and contrasted, and recent efforts in cross-platform data integration are explored.

Animals↗

Origins and clinical relevance of child death review teams.

Interagency child death review teams have emerged in response to the increasing awareness of severe violence against children in the United States. Since 1978, when the first team originated in Los Angeles, Calif, child death review teams have been established across the nation. Approximately 100 million Americans or 40% of the nation's population now live in counties or states served by such teams; most have been formed since 1988. Multiagency child death review involves a systematic, multidisciplinary, and multiagency process to coordinate and integrate data and resources from coroners, law enforcement, courts, child protective services, and health care providers. This article provides an introduction to the unique factors and magnitude of suspicious child deaths, and to the concept and process of interagency child death review. Future expansion of this process should lead to more effective multiagency case management and prevention of future deaths and serious injuries to children from child abuse and neglect.

Adolescent↗

[Benzene exposure in Modena: historical trend and health risk assessment].

OBJECTIVE: The present paper estimates the 1980-2000 trend in exposure to benzene of the population living within the urban area of Modena. An assessment of leukaemia risk is also presented. DESIGN: The 2000 annual means of benzene atmospheric concentrations in 73 sites has been derived using a procedure which integrated data from fixed site stations and passive samplers: on this basis, an annual mean for the whole urban area has been calculated. The population exposure trend for the period 1980-2000 has been estimated using the information on traffic emission changes. The expected annual number of leukaemia cases attributable to benzene has been calculated by using two different approaches. SETTING: Residents in the urban area of Modena. MAIN OUTCOME MEASURES: Annual incidence of leukaemia attributable to benzene. RESULTS: In 2000, the mean urban concentration was about 7 microg/m3 and in average the population was exposed to about 9 microg/m3. In the eighties, the population exposure was 5 times higher than the 2000 value, with a maximum of 51 microg/m3 in 1988. The leukaemia risk assessment procedures gave a value of about 4 x 10(-1) with the method based on cumulative exposure and of about 4 x 10(-2) with the method based on weighted exposure. DISCUSSION AND CONCLUSION: This study is one of the few examples of evaluation of both the trend in benzene exposure for a population and assessment of leukaemia risk. Uncertainties in the assessment of health impact derive from inconsistencies in the underlyng methods.

Benzene↗

Safety and efficacy of alefacept in elderly patients and other special populations.

BACKGROUND: The safety of biologic agents for psoriasis treatment is of particular importance in patient groups at higher risk for adverse events. We assessed the safety and efficacy of alefacept in elderly, obese, and diabetic patients with moderate to severe chronic plaque psoriasis by integrating data from phase 2 and 3 clinical studies and their extensions. OBSERVATIONS: Ninety-nine elderly, 652 obese, and 122 diabetic patients received at least 1 course of alefacept. In each cohort, accidental injury, headache, and pharyngitis were among the most common adverse events; infections were primarily common colds; and malignancies were mostly skin carcinomas. No opportunistic infections were reported. Safety was maintained over repeated courses. The safety profile of alefacept in each cohort was consistent with that of the overall population; however, additional data are needed to confirm our findings in the elderly and diabetic subgroups in the later courses due to the limited sample sizes. In course 1, 24% to 33% of patients achieved 75% or greater improvement in Psoriasis Area and Severity Index (PASI) at any time, with further enhancement of benefit with subsequent courses (eg, course 3, 41% to 58%). CONCLUSIONS: Alefacept was well-tolerated and effective in elderly, obese, and diabetic patients with psoriasis.

Age Factors↗

Fueling global fishing fleets.

Over the course of the 20th century, fossil fuels became the dominant energy input to most of the world's fisheries. Although various analyses have quantified fuel inputs to individual fisheries, to date, no attempt has been made to quantify the global scale and to map the distribution of fuel consumed by fisheries. By integrating data representing more than 250 fisheries from around the world with spatially resolved catch statistics for 2000, we calculate that globally, fisheries burned almost 50 billion L of fuel in the process of landing just over 80 million t of marine fish and invertebrates for an average rate of 620 L t(-1). Consequently, fisheries account for about 1.2% of global oil consumption, an amount equivalent to that burned by the Netherlands, the 18th-ranked oil consuming country globally, and directly emit more than 130 million t of CO2 into the atmosphere. From an efficiency perspective, the energy content of the fuel burned by global fisheries is 12.5 times greater than the edible-protein energy content of the resulting catch.

Air Pollutants↗

INFOBIOMED: European Network of Excellence on Biomedical Informatics to support individualised healthcare.

INFOBIOMED is an European Network of Excellence (NoE) funded by the Information Society Directorate-General of the European Commission (EC). A consortium of European organizations from ten different countries is involved within the network. Four pilots, all related to linking clinical and genomic information, are being carried out. From an informatics perspective, various challenges, related to data integration and mining, are included.

Biomedical Research↗

[Requisite muscle relaxation using vecuronium for tracheobronchial suction in neurosurgical intensive care patients].

Coordination of respiratory care with protection of the brain is critical in neurosurgical intensive care. Therefore, in addition to hyperventilation, adequate sedation and muscle relaxation are applied to mitigate the difficulties with control of intracranial pressure (ICP) during routine tracheobronchial suctioning (TBS). Although hypnotics have been shown to be effective in mitigating increases in ICP in response to endotracheal suctioning in paralyzed patients, brisk bucking and coughing with further increases in ICP may occur without muscle relaxation. Long-term neuromuscular (nm) paralysis may be undesirable in neurosurgical critical care because clinical evaluation with early detection of neurological deterioration will be impossible in the paralyzed patient. Therefore, the effects of TBS without and after nm blockade with an intermediate-acting nondepolarizing muscle relaxant on ICP were studied. PATIENTS AND METHODS. Nine patients with moderate increases in mean ICP of 19.2 +/- 8 mmHg due to head injuries and spontaneous subarachnoid hemorrhage were investigated. All patients were on-line sedated with midazolam and sufentanil and controlled ventilation was adjusted to maintain a paCO2 of 30 +/- 2 mmHg. Respiratory and hemodynamic parameters and ICP (epidural probe) were continuously monitored and recorded on an integrated data bank. After a bolus dose of propofol, routine TBS was performed without the use of muscle relaxants. Before the next TBS, nm monitoring was initiated and train-of-four (TOF) stimulation was imposed at the ulnar nerve using supramaximal pulses. The response of the adductor pollicis muscle was recorded by accelerometry. After supramaximal stimulation had been achieved, a bolus dose of 2 times the ED95 of vecuronium (0.12 mg/kg) was given. Depth of nm blockade was quantified by the posttetanic count (PTC). ICP and CPP were measured before, during, and after TBS. Diaphragmatic movement, bucking, and coughing were registered by visual observation and graded as absent, slight, moderate, or severe. STATISTICS. Student's t-test and the Wilcoxon test for paired data (P less than 0.05; values as mean +/- SD) were used. RESULTS. (see Table and Figure). Despite adequate sedation, moderate to severe diaphragmatic movements in response to carinal stimulation with significant increases in ICP (18.2 +/-7 to 24 +/- 8 mmHg) an d subsequent decreases in cerebral perfusion pressure (CPP) (68.9 +/- 2 to 62.4 +/- 8 mmHg) could be observed without muscle relaxation. After a bolus of vecuronium, profound nm paralysis quantified by a PTC of 5 was observed after an onset time of 4.2 +/- 1 min. ICP (20.2 +/- 8 vs. 20.1 +/- 8 mmHg) and CPP (64.0 +/- 13 vs. 64.8 +/- 13 mmHg) remained unchanged. Slight diaphragmatic movements could be elicited in only two patients during TBS. DISCUSSION. TBS is a potent trigger of diaphragmatic movement, bucking, and coughing by reflex activation of the phrenic nerve. A major determinant of the magnitude of ICP increase during TBS is the transmission of the cough-induced increase in intrathoracic pressure to the cerebral venous system. Vecuronium was utilized for nm blockade because of its proven lack of cerebral and cardiovascular side effects, its relatively short onset, and its intermediate duration of action. Despite the postulated faster onset of nm blockade in the diaphragm, suppression of thumb-twitch response to TOF stimulation does not necessarily predict absence of diaphragmatic movement elicited by excessive tracheal stimulation. As demonstrated, intense nm blockade quantified by a PTC of 5 is necessary to rule out any bucking and coughing, i.e., to ensure total diaphragmatic paralysis in response to tracheal stimulation. On-line neurological evaluation, one of the essentials in the approach to the neurosurgical patient, will not be prevented by the intermittent bolus regime utilized in this study.

Adult↗

[An introduction of the principle for the middleware based on HL7].

This article introduces the development of a middleware based on HL7, which solves the problem of data integration and sharing effectively and successfully, among the hospital internal subsystems and different hospitals' information systems.

Computer Communication Networks↗