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Biomedical technology, socioeconomics, and biomedical computing: implications for change.

Pathology and laboratory medicine have changed rapidly since 1945. Three forces can be recognized as major vectors for change: rapid application of the biotechnology evolving from research in molecular biology, radically changing medical socioeconomics, and the evolving field of medical information science. While these apparently disparate elements affect all of medicine and health care, at the present time they appear to be changing pathology and laboratory medicine to a far greater extent than many other medical specialties. If pathologists fail to make the necessary changes, obsolescence may well overtake the specialty. Planning for the innovative educational and training programs that will be required to meet the future demands of the specialty is essential, not only for those now in practice but for those who will follow us.

Computers↗

A MEDLINE categorization algorithm.

BACKGROUND: Categorization is designed to enhance resource description by organizing content description so as to enable the reader to grasp quickly and easily what are the main topics discussed in it. The objective of this work is to propose a categorization algorithm to classify a set of scientific articles indexed with the MeSH thesaurus, and in particular those of the MEDLINE bibliographic database. In a large bibliographic database such as MEDLINE, finding materials of particular interest to a specialty group, or relevant to a particular audience, can be difficult. The categorization refines the retrieval of indexed material. In the CISMeF terminology, metaterms can be considered as super-concepts. They were primarily conceived to improve recall in the CISMeF quality-controlled health gateway. METHODS: The MEDLINE categorization algorithm (MCA) is based on semantic links existing between MeSH terms and metaterms on the one hand and between MeSH subheadings and metaterms on the other hand. These links are used to automatically infer a list of metaterms from any MeSH term/subheading indexing. Medical librarians manually select the semantic links. RESULTS: The MEDLINE categorization algorithm lists the medical specialties relevant to a MEDLINE file by decreasing order of their importance. The MEDLINE categorization algorithm is available on a Web site. It can run on any MEDLINE file in a batch mode. As an example, the top 3 medical specialties for the set of 60 articles published in BioMed Central Medical Informatics & Decision Making, which are currently indexed in MEDLINE are: information science, organization and administration and medical informatics. CONCLUSION: We have presented a MEDLINE categorization algorithm in order to classify the medical specialties addressed in any MEDLINE file in the form of a ranked list of relevant specialties. The categorization method introduced in this paper is based on the manual indexing of resources with MeSH (terms/subheadings) pairs by NLM indexers. This algorithm may be used as a new bibliometric tool.

Abstracting and Indexing↗

Depot versus daily administration of GnRH agonist protocols for pituitary desensitization in assisted reproduction cycles: a Cochrane Review.

UNLABELLED: This paper is based on a Cochrane review published in The Cochrane Library, issue 4, 2002 (see www.CochraneLibrary.net for information) with permission from The Cochrane Collaboration. Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the review. BACKGROUND: GnRH agonists have been widely used in cycles of IVF. There are two types of GnRH agonist administration that can be used to lead to hypophysis desensitization in IVF cycles in the long protocol: one consisting of daily low doses of GnRH agonist and the other the administration of analogues in higher, long-acting doses (depot). The objective of this study is to compare the use of a single long-acting depot dose with that of daily GnRH agonist doses in IVF cycles. METHODS: Relevant randomized controlled trials were identified by electronic search of the following databases: MEDLINE, EMBASE, LILACS (Latin American and Caribbean Center on Health Sciences Information) and the Cochrane Controlled Trials Register. Six studies, with a total of 552 women, were included and analysed. RESULTS: The studies do not indicate that there is a statistically significant difference between the use of depot GnRH agonist and of daily GnRH agonist in the primary outcome, clinical pregnancy rates per woman [odds ratio (OR) 0.94, 95% confidence interval (CI) 0.65-1.37]. However, there was sufficient evidence showing that the use of depot GnRH agonist for pituitary desensitization in IVF cycles increased the number of gonadotrophin ampoules [weighted mean difference (WMD) 3.30, 95% CI 1.27-5.34] and the duration of the ovarian stimulation (WMD 0.56, 95% CI 0.31-0.81), as compared with the use of daily GnRH agonist. CONCLUSIONS: Although we recognize that the clinical pregnancy rates per woman are not the ideal primary outcome, we found no evidence of differences between the long protocols using depot or daily GnRH agonist for IVF cycles. However, the use of depot GnRH agonist is associated with increased requirements for gonadotrophins and a longer time needed for ovarian stimulation. If these differences could be shown to translate into economic benefit, depot GnRH agonist would increase the overall costs of IVF treatment.

Delayed-Action Preparations↗

A database for evaluating the toxicological risk of pesticides.

This study of Overtox-DB, a computerized database for managing chemical toxicity data, is a product of the application of typical methodologies regarding information science and computer technology. The methodology applied can be reduced to three-basic elements: the collection of requirements, design, and achievement. Overtox-DB was developed by defining technological elements for managing data and its structure and by identifing the procedures and methodologies for data storage, retrieval, distribution, and standardization of many kinds of test data stored in the same format. The program stores data about chemical identification, physical and chemical properties, toxicological tests, mutagenicity, teratogenicity, carcinogenicity, and a bibliography of chemical compounds. Overtox-DB consists of five modules: experimental and bibliographic, data collection, molecular data collection, data search, and data report. The Overtox-DB user responds to a simplified set of query commands and boolean operators that interact with the system to retrieve different toxicological data (the majority of fields are defined as search fields and identify the test system, results of the assays, administration route, dose, etc.). The collected information provides an analytical characterization of biological activities for many compounds and identifies evidence possibly lacking in experimental approaches. Indeed, this database could permit a comparative evaluation with other substances and can be used for structure-activity relationship studies.

Database Management Systems↗

The Bioperl toolkit: Perl modules for the life sciences.

The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.

Algorithms↗

[Toward a model of communications in public health in Latin America and the Caribbean].

OBJECTIVE: So far, there have been no bibliometric or scientometric studies that make it possible to examine, with quantitative, retrospective, and comprehensive criteria, the scientific output on public health in Latin America and the Caribbean (LAC). Further, the weakness of the existing information systems makes it impossible to examine the relevance, quality, and impact of this scientific output, with a view to evaluating it in terms of societal needs and existing patterns of scientific communication. This article presents the results of a bibliographic analysis of the scientific output in the area of public health in Latin America and the Caribbean. The ultimate goal of the analysis is to build a model of scientific communication in this field, to help researchers, managers, and others working in the area of public health to make decisions and choose actions to take. METHODS: We conducted a literature review in order to identify the distribution of publications on public health that were produced by LAC researchers and published in each of the LAC countries from 1980 through 2002. The review used the Literatura Latino-Americana e do Caribe em Saúde Pública (LILACS-SP) (Latin American and Caribbean Literature on Public Health) bibliographic database. That database is operated by the Latin American and Caribbean Center on Health Sciences Information (BIREME), which is in São Paulo, Brazil. We processed the LILACS-SP data using two software packages, Microsoft Excel and Bibexcel, to obtain indicators of the scientific output, the type of document, the language, the number of authors for each publication, the thematic content, and the participating institutions. For the 1980-2002 period, there were 97,605 publications registered, from a total of 37 LAC countries. RESULTS: For the analysis presented in this article, we limited the sample to the 8 countries in Latin America and the Caribbean that had at least 3,000 documents each registered in the LILACS-SP database over the 1980-2002 study period. In descending order of the number of publications registered, the 8 nations were: Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Peru, and Venezuela. Those 8 countries were responsible for 83,054 publications (85.10% of the total of 97,605 registered documents produced by the 37 LAC countries). Of those 83,054 publications from the 8 countries, 56,253 of them (67.73%) were articles published in scientific journals and 24,488 were monographs (29.48%). The proportion of works produced by two or more coauthors was relatively high (56.48%). The 56,253 articles appeared in a total of 929 different journals. Of the 929 journals, 91 of them published at least 150 articles over the study period. In descending order, LAC journals with the largest number of articles on public health were: Revista de Saúde Pública (Brazil); Cadernos de Saúde Pública (Brazil); Revista Médica de Chile; Archivos Latinoamericanos de Nutrición (Venezuela); and Salud Pública de México. The 91 journals that published at least 150 articles represented 29 different specialties. The most common of the specialties for the 91 journals were general medicine (18 journals) and pediatrics (10 journals). In descending order, the populations that the publications dealt with primarily were human beings in general, females, males, and adults; and, in descending order, a relatively small number of publications dealt with pregnant women and middle-aged or elderly persons. The topics most often covered in the publications were risk factors, health policy, and primary health care, as well as family doctors in the case of Cuba. CONCLUSIONS: This research produced a preliminary model of communications in public health in LAC countries that will hopefully help lay the groundwork for further research to develop a model of scientific communication in LAC nations.

Argentina↗

Utilizing data grid architecture for the backup and recovery of clinical image data.

Grid Computing represents the latest and most exciting technology to evolve from the familiar realm of parallel, peer-to-peer and client-server models. However, there has been limited investigation into the impact of this emerging technology in medical imaging and informatics. In particular, PACS technology, an established clinical image repository system, while having matured significantly during the past ten years, still remains weak in the area of clinical image data backup. Current solutions are expensive or time consuming and the technology is far from foolproof. Many large-scale PACS archive systems still encounter downtime for hours or days, which has the critical effect of crippling daily clinical operations. In this paper, a review of current backup solutions will be presented along with a brief introduction to grid technology. Finally, research and development utilizing the grid architecture for the recovery of clinical image data, in particular, PACS image data, will be presented. The focus of this paper is centered on applying a grid computing architecture to a DICOM environment since DICOM has become the standard for clinical image data and PACS utilizes this standard. A federation of PACS can be created allowing a failed PACS archive to recover its image data from others in the federation in a seamless fashion. The design reflects the five-layer architecture of grid computing: Fabric, Resource, Connectivity, Collective, and Application Layers. The testbed Data Grid is composed of one research laboratory and two clinical sites. The Globus 3.0 Toolkit (Co-developed by the Argonne National Laboratory and Information Sciences Institute, USC) for developing the core and user level middleware is utilized to achieve grid connectivity. The successful implementation and evaluation of utilizing data grid architecture for clinical PACS data backup and recovery will provide an understanding of the methodology for using Data Grid in clinical image data backup for PACS, as well as establishment of benchmarks for performance from future grid technology improvements. In addition, the testbed can serve as a road map for expanded research into large enterprise and federation level data grids to guarantee CA (Continuous Availability, 99.999% up time) in a variety of medical data archiving, retrieval, and distribution scenarios.

Diagnostic Imaging↗

Insulin sensitizers in treatment of nonalcoholic fatty liver disease: Systematic review.

AIM: To summarize the evidence available for the clinical effectiveness of insulin sensitizers in the treatment of nonalcoholic fatty liver disease (NAFLD) systematically. METHODS: Relevant articles were located using computer-assisted searches of Medline (1966-March 2006), EMBASE (1988-March 2006), CINAHL (1982-March 2003), Educational Resource Information Center (1966-March 2006), Library, Information Science and Technology Abstracts (1967-March 2006), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (1994-2006), dissertations in ProQuest and FirstSearch databases. Manual searches were made in the abstracts from meetings of the American Gastroenterological Association (1999-2006), and the American Association for the Study of Liver Diseases (2003-2005). Studies were retrieved using the following selection criteria: (1) clinical trials using insulin sensitizers in subjects with NAFLD, (2) adult patients, (3) published as full manuscripts or abstracts, and (4) English, Spanish, German, and French languages only. Data were abstracted independently by two reviewers following standardized procedures. A face-to-face comparison of data was conducted to ensure the completeness and reliability of the abstraction process. RESULTS: Nine studies were included, six using metformin and three using thiazolidinediones. Only two studies were placebo-controlled trials. The median sample size for all studies was 18 subjects. In the placebo-controlled trials, metformin improved insulin resistance markers and liver function tests, but not histological scores. In the single-arm trials, metformin and thiazolidinediones improved insulin resistance markers and liver function tests, and beneficial histological changes were reported. There is limited high-quality information available from which to draw categorical conclusions about the clinical use of insulin sensitizers in NAFLD. CONCLUSION: Current information indicates that the use of insulin sensitizers in NAFLD improves insulin resistance and liver function. Histological changes must be corroborated in randomized controlled trials.

Controlled Clinical Trials as Topic↗

Observation of strong coupling between one atom and a monolithic microresonator.

Over the past decade, strong interactions of light and matter at the single-photon level have enabled a wide set of scientific advances in quantum optics and quantum information science. This work has been performed principally within the setting of cavity quantum electrodynamics with diverse physical systems, including single atoms in Fabry-Perot resonators, quantum dots coupled to micropillars and photonic bandgap cavities and Cooper pairs interacting with superconducting resonators. Experiments with single, localized atoms have been at the forefront of these advances with the use of optical resonators in high-finesse Fabry-Perot configurations. As a result of the extreme technical challenges involved in further improving the multilayer dielectric mirror coatings of these resonators and in scaling to large numbers of devices, there has been increased interest in the development of alternative microcavity systems. Here we show strong coupling between individual caesium atoms and the fields of a high-quality toroidal microresonator. From observations of transit events for single atoms falling through the resonator's evanescent field, we determine the coherent coupling rate for interactions near the surface of the resonator. We develop a theoretical model to quantify our observations, demonstrating that strong coupling is achieved, with the rate of coherent coupling exceeding the dissipative rates of the atom and the cavity. Our work opens the way for investigations of optical processes with single atoms and photons in lithographically fabricated microresonators. Applications include the implementation of quantum networks, scalable quantum logic with photons, and quantum information processing on atom chips.

Journal Article↗

Issues in applied statistics for public health bioterrorism surveillance using multiple data streams: research needs.

The objective of this report is to provide a basis to inform decisions about priorities for developing statistical research initiatives in the field of public health surveillance for emerging threats. Rapid information system advances have created a vast opportunity of secondary data sources for information to enhance the situational and health status awareness of populations. While the field of medical informatics and initiatives to standardize healthcare-seeking encounter records continue accelerating, it is necessary to adapt analytic and statistical methodologies to mature in sync with sibling information science technologies. One major right-of-passage for statistical inference is to advance the optimal application of analytic methodologies for using multiple data streams in detecting and characterizing public health population events of importance. This report first describes the problem in general and the data context, then delineates more specifically the practical nature of the problem and the related issues. Approaches currently applied to data with time-series, statistical process control and traditional inference concepts are described with examples in the section on Statistics and the Role of the Analytic Surveillance Data Monitor. These are the techniques that are providing substance to surveillance professionals and enabling use of multiple data streams. The next section describes use of a more complex approach that takes temporal as well as spatial dimensions into consideration for detection and situational awareness regarding event distributions. The space-time statistic has successfully been used to detect and track public health events of interest. Important research questions which are summarized at the end of this report are described in more detail with respect to the methodological application in the respective sections. This was thought to help elucidate the research requirements as summarized later in the report. Following the description of the space-time scan statistical application; this report extends to a less traditional area of promise given what has been observed in recent application of analytic methods. Bayesian networks (BNs) represent a conceptual step with advantages of flexibility for the public health surveillance community. Progression from traditional to the more extending statistical concepts in the context of the dynamic status quo of responsibility and challenge, leads to a conclusion consisting of categorical research needs. The report is structured by design to inform judgment about how to build on practical systems to achieve better analytic outcomes for public health surveillance. There are references to research issues throughout the sections with a summarization at the end, which also includes items previously unmentioned in the report.

Algorithms↗

Formal ontology for natural language processing and the integration of biomedical databases.

The central hypothesis underlying this communication is that the methodology and conceptual rigor of a philosophically inspired formal ontology can bring significant benefits in the development and maintenance of application ontologies [A. Flett, M. Dos Santos, W. Ceusters, Some Ontology Engineering Procedures and their Supporting Technologies, EKAW2002, 2003]. This hypothesis has been tested in the collaboration between Language and Computing (L&C), a company specializing in software for supporting natural language processing especially in the medical field, and the Institute for Formal Ontology and Medical Information Science (IFOMIS), an academic research institution concerned with the theoretical foundations of ontology. In the course of this collaboration L&C's ontology, LinKBase, which is designed to integrate and support reasoning across a plurality of external databases, has been subjected to a thorough auditing on the basis of the principles underlying IFOMIS's Basic Formal Ontology (BFO) [B. Smith, Basic Formal Ontology, 2002. http://ontology.buffalo.edu/bfo]. The goal is to transform a large terminology-based ontology into one with the ability to support reasoning applications. Our general procedure has been the implementation of a meta-ontological definition space in which the definitions of all the concepts and relations in LinKBase are standardized in the framework of first-order logic. In this paper we describe how this principles-based standardization has led to a greater degree of internal coherence of the LinKBase structure, and how it has facilitated the construction of mappings between external databases using LinKBase as translation hub. We argue that the collaboration here described represents a new phase in the quest to solve the so-called "Tower of Babel" problem of ontology integration [F. Montayne, J. Flanagan, Formal Ontology: The Foundation for Natural Language Processing, 2003. http://www.landcglobal.com/].

Artificial Intelligence↗

A preliminary analysis of the dental informatics literature.

Dental informatics is an emerging discipline applying computer and information science to dental practice, research, education, and management. To date, the dental informatics research literature has not been comprehensively reviewed. This study reports an initial analysis of the dental informatics literature. We developed an initial, comprehensive retrieval strategy to locate dental informatics citations in MEDLINE (1966-April 2003), including three concepts: dentistry, computers, and research. After refinement of the search, we manually classified the final set into four categories: (1) non-dental; (2) dental, but neither dental informatics nor IT-related; (3) dental informatics; and (4) IT in dentistry. We analyzed informatics and IT-related citations regarding their distribution across journals, growth rate, the number of authors and their publication frequency, and content as expressed by Medical Subject Headings (MeSH). The final set of citations (n = 3872) consisted of: 12% non-dental articles; 59% dental, but not informatics- or IT-related articles; 16% informatics-related articles; and 13% IT-related articles. Informatics-related citations appeared in 176 journals, and IT-related citations in 206 journals. Approximately 50 papers are currently published in both categories yearly. While a great many authors have contributed to this literature, very few have published more than three papers. Main topics of articles included "Imaging and Image Processing", "Computer-aided Diagnosis and Therapy", "Computer-aided Instruction", and "Other". The dental informatics literature is small, but growing. Imaging and image processing predominate as research topics.

Bibliographies as Topic↗

How well do physicians use electronic information retrieval systems? A framework for investigation and systematic review.

OBJECTIVE: Despite the proliferation of electronic information retrieval (IR) systems for physicians, their effectiveness has not been well assessed. The purpose of this review is to provide a conceptual framework and to apply the results of previous studies to this framework. DATA SOURCES: All sources of medical informatics and information science literature, including MEDLINE, along with bibliographies of textbooks in these areas, were searched from 1966 to January 1998. STUDY SELECTION: All articles presenting either classifications of evaluation studies or their results, with an emphasis on those studying use by physicians. DATA EXTRACTION: A framework for evaluation was developed, consisting of frequency of use, purpose of use, user satisfaction, searching utility, search failure, and outcomes. All studies were then assessed based on the framework. DATA SYNTHESIS: Due to the heterogeneity and simplistic study designs, no meta-analysis of studies could be done. General conclusions were drawn from data where appropriate. A total of 47 articles were found to include an evaluation component and were used to develop the framework. Of these, 21 articles met the inclusion criteria for 1 or more of the categories in the framework. Most use of IR systems by physicians still occurs with bibliographic rather than full-text databases. Overall use of IR systems occurs just 0.3 to 9 times per physician per month, whereas physicians have 2 unanswered questions for every 3 patients. CONCLUSIONS: Studies comparing IR systems with different searching features have not shown that advanced searching methods are significantly more effective than simple text word methods. Most searches retrieve only one fourth to one half of the relevant articles on a given topic and, once retrieved, little is known about how these articles are interpreted or applied. These studies imply that further research and development are needed to improve system utility and performance.

Evaluation Studies as Topic↗

Gene name identification and normalization using a model organism database.

Biology has now become an information science, and researchers are increasingly dependent on expert-curated biological databases to organize the findings from the published literature. We report here on a series of experiments related to the application of natural language processing to aid in the curation process for FlyBase. We focused on listing the normalized form of genes and gene products discussed in an article. We broke this into two steps: gene mention tagging in text, followed by normalization of gene names. For gene mention tagging, we adopted a statistical approach. To provide training data, we were able to reverse engineer the gene lists from the associated articles and abstracts, to generate text labeled (imperfectly) with gene mentions. We then evaluated the quality of the noisy training data (precision of 78%, recall 88%) and the quality of the HMM tagger output trained on this noisy data (precision 78%, recall 71%). In order to generate normalized gene lists, we explored two approaches. First, we explored simple pattern matching based on synonym lists to obtain a high recall/low precision system (recall 95%, precision 2%). Using a series of filters, we were able to improve precision to 50% with a recall of 72% (balanced F-measure of 0.59). Our second approach combined the HMM gene mention tagger with various filters to remove ambiguous mentions; this approach achieved an F-measure of 0.72 (precision 88%, recall 61%). These experiments indicate that the lexical resources provided by FlyBase are complete enough to achieve high recall on the gene list task, and that normalization requires accurate disambiguation; different strategies for tagging and normalization trade off recall for precision.

Abstracting and Indexing↗

Youth access laws: in the dark at the tanning parlor?

OBJECTIVE: To compare laws governing youth access to UV irradiation at indoor tanning facilities with laws governing youth access to tobacco. DESIGN: Tobacco and UV irradiation youth access laws were assessed via correspondence with public health offices and computerized legal searches of 6 industrialized nations with widely differing skin cancer incidence rates. SETTING: National, provincial, and state legal systems in Australia, Canada, France, New Zealand, the United Kingdom, and the United States. PARTICIPANTS: Public health, legal, information science, and medical professionals and government and tanning industry representatives. MAIN OUTCOME MEASURES: Statutes specifying age restrictions for the purchase of indoor tanning services or tobacco products. RESULTS: The 5 English-speaking countries with common law-based legal systems unilaterally prohibit youth access to tobacco but rarely limit youth access to UV irradiation from tanning salons. Only very limited regions in the United States and Canada prohibit youth access to indoor tanning facilities: Texas, Illinois, Wisconsin, and New Brunswick prohibit tanning salon use by minors younger than 13, 14, 16, and 18 years, respectively. In contrast, French law allows minors to purchase tobacco but prohibits those younger than 18 years from patronizing tanning salons. CONCLUSIONS: Youth access laws governing indoor tanning display remarkable variety. Uniform indoor tanning youth access laws modeled on the example of tobacco youth access laws merit consideration.

Adolescent↗

Reproductive and teratologic effects of low-frequency electromagnetic fields: a review of in vivo and in vitro studies using animal models.

In order to evaluate the reproductive risks of low-frequency electromagnetic fields (EMF), it is important to include epidemiological and animal studies in the evaluation, as well as the appropriate basic science information in developmental biology and teratology. This review presents a critical review of in vivo animal studies and in vitro tests, as well as the biological plausibility of the allegations of reproductive risks. In vitro or in vivo studies in nonhuman species can be used to study mechanisms and the effects that have been suggested by human investigations. Only well designed whole-animal teratology studies are appropriate when the epidemiologists and clinical teratologists are uncertain about the environmental risks. Even the inference of teratogenesis cannot be drawn from culture experiments, because the investigator is not in a position to know whether any of his observations will be manifested in living organisms at term. Other aspects of reproductive failure such as abortion, infertility, stillbirth, and prematurity, cannot be addressed by in vitro or culture experiments. In fact, they are very difficult to design and interpret in nonprimate in vivo models. The biological plausibility some of the basic mechanisms involved in reproductive pathology were evaluated, concentrating primarily on the mechanisms involved in the production of birth defects. The studies dealing with mutagenesis, cell death and cell proliferation using in vitro systems do not indicate that EMFs have the potential for deleteriously affecting proliferating and differentiating embryonic cells at the exposures to which populations are usually exposed. Of course, there is no environmental agent that has no effect, deleterious or not, at very high exposures. The animal and in vitro studies dealing with the reproductive effects of EMF exposure are extensive. There are >70 EMF research projects that deal with some aspect of reproduction and growth. Unfortunately, a large proportion of the embryology studies used the chick embryo and evaluated the presence or absence of teratogenesis after 48-52 h of development. This is not a stage of development at which an investigator could determine whether teratogenesis occurred. The presence of clinically relevant teratogenesis can only be determined at the end of the gestational period. The chick embryo studies are also of little assistance to the epidemiologist or clinician in determining whether EMF represents a hazard to the human embryo, and the results are, in any event, inconsistent. On the other hand, the studies involving nonhuman mammalian organisms dealing with fetal growth, congenital malformations, embryonic loss, and neurobehavioral development were predominantly negative and are therefore not supportive of the hypothesis that low-frequency EMF exposures result in reproductive toxicity.

Abnormalities, Radiation-Induced↗

Informatics and education in the health professions.

Informatics, the applied use of information science, is undergoing definition and development in the health professions with the encouragement of the National Library of Medicine and other professional organizations. Medical informatics and disciplinary subsets such as nursing and dental informatics look to optimize a growing range of applications ranging from video-disks to expert systems. Recommendations call for the integration of informatics into the education of health care professionals. Academic health sciences centers are developing informatics programs; the University of Maryland Campus for the Professions has convened a task force and a national advisory board on informatics.

Health Occupations↗

Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles.

BACKGROUND: Gonadotrophin-releasing hormone agonist (GnRHa) has been widely used in cycles of in vitro fertilization (IVF). Among the various types of GnRHa ovarian stimulation protocols, the long protocol presents the best clinical pregnancy rates per cycle initiated (GnRHa administration until the suppression of ovarian activity is evident, within approximately 14 days). There are two types of GnRHa administration that can be used to lead to hypophysis desensitization in the IVF cycle in the long protocol: one consisting of daily GnRHa low doses, and another with the administration of analogues in higher long-acting doses (depot). There are controversies in the data as far as the number of ampoules to be used in the cycles with the depot GnRHa treatment, as well as regarding the number of follicles made available, the number of oocytes, fertilization, implantation and pregnancy rates. OBJECTIVES: The objective of this study is to compare the use of a single long-acting depot dose to that of daily GnRHa doses in in vitro fertilization cycles. SEARCH STRATEGY: Relevant RCTs were identified by electronic search of the following databases: MEDLINE, EMBASE, LILACS (Latin American and Caribbean Center on Health Sciences Information) and the Cochrane Controlled Trials Register. SELECTION CRITERIA: Types of studies: The study analyses RCTs comparing depot and daily administration of GnRHa for long protocols in IVF treatment cycles. TYPES OF PARTICIPANTS: Couples with any cause of infertility. Types of interventions: Ovarian stimulation with human follicle stimulating hormone (hFSH) and/or human menopausal gonadotropin (hMG) and/or recombinant follicle stimulating hormone (rFSH) in IVF treatment cycles. Types of outcome measures: Clinical pregnancy rates per woman, per oocyte retrieval procedure, per embryo transfer, number of oocytes retrieved, oocyte fertilization rates, ongoing/delivered pregnancy rates per cycle started, abortion rates, multiple pregnancy rates, number of ampoules of gonadotropin employed, ovarian hyperstimulation syndrome (OHSS) incidence rates, cost analysis and patient convenience. DATA COLLECTION AND ANALYSIS: The reviewers evaluated allocation concealment, classified as adequate, uncertain or inadequate. Two reviewers extracted the data independently. All analyses were performed according to the intention-to-treat method. MAIN RESULTS: Six studies, with a total of 552 women, were included and analysed. The studies do not indicate that there is statistically significant difference between the use of depot GnRHa or daily GnRHa in the primary outcome, clinical pregnancy rates per woman (OR 0.94, 95% CI 0.65 to 1.37). However, there was sufficient evidence that the use of depot GnRHa for pituitary desensitization in IVF cycles increased the number of gonadotrophins ampoules (WMD 3.30, 95% CI 1.27 to 5.34) and the duration of the ovarian stimulation (WMD 0.56, 95% CI 0.31 to 0.81), as compared with daily GnRHa. REVIEWER'S CONCLUSIONS: Although we recognise that the clinical pregnancy rates per woman are not the ideal primary outcome, we found no evidence of differences between the long protocol using depot or daily GnRHa for IVF cycles. However, the use of depot GnRHa is associated with increased requirements for gonadotrophins and a longer time required for ovarian stimulation. If these differences could be shown to translate into economic benefit, depot GnRHa should increase the overall costs of IVF treatment.

Delayed-Action Preparations↗