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Presence of pharmacoepidemiology in three bibliographic databases: Medline, IPA and SCI.

OBJECTIVE: The objective of this study is to make a comparative description of the evolution and distribution of international research into pharmacoepidemiology, using three bibliographic databases, in order to select the most appropriate for future bibliometric studies. METHODS: Bibliographic searches were performed using the following databases: Medline (1966-99), IPA (1970-99) and SCI (1990-99), using the term 'pharmacoepidemiology'. On the basis of these searches, the number of original articles per year and per journal title were noted. The growth of the output of scientific writing was found to fit Price's law. RESULTS: A total of 845 original articles were recovered: 467 from IPA, 219 from Medline and 159 from SCI. The highest mean number of original articles per year (33.4) was obtained with the IPA database. Price's exponential growth pattern was observed among all three databases. The total numbers of journals in which the original articles were published were 102 in Medline, 65 in IPA and 60 in SCI. The journals providing a single original article comprised 65% of the Medline titles and 61% of those in IPA and SCI. CONCLUSIONS: International research into pharmacoepidemiology presents an exponential growth pattern, in accordance with Price's law. There is a large degree of publishing dispersion. IPA was found to be the bibliographic database that recovered the greatest number of original articles, nearly half of which were published in Pharmacoepidemiology and Drug Safety. We therefore consider the latter database appropriate for bibliometric studies in the field of pharmacoepidemiology.

Bibliometrics↗

Practice databases and their uses in clinical research.

A few large clinical information databases have been established within larger medical information systems. Although they are smaller than claims databases, these clinical databases offer several advantages: accurate and timely data, rich clinical detail, and continuous parameters (for example, vital signs and laboratory results). However, the nature of the data vary considerably, which affects the kinds of secondary analyses that can be performed. These databases have been used to investigate clinical epidemiology, risk assessment, post-marketing surveillance of drugs, practice variation, resource use, quality assurance, and decision analysis. In addition, practice databases can be used to identify subjects for prospective studies. Further methodologic developments are necessary to deal with the prevalent problems of missing data and various forms of bias if such databases are to grow and contribute valuable clinical information.

Clinical Medicine↗

Database challenges and solutions in neuroscientific applications.

In the scientific community, the quality and progress of various endeavors depend in part on the ability of researchers to share and exchange large quantities of heterogeneous data with one another efficiently. This requires controlled sharing and exchange of information among autonomous, distributed, and heterogeneous databases. In this paper, we focus on a neuroscience application, Neuroanatomical Rat Brain Viewer (NeuART Viewer) to demonstrate alternative database concepts that allow neuroscientists to manage and exchange data. Requirements for the NeuART application, in combination with an underlying network-aware database, are described at a conceptual level. Emphasis is placed on functionality from the user's perspective and on requirements that the database must fulfill. The most important functionality required by neuroscientists is the ability to construct brain models using information from different repositories. To accomplish such a task, users need to browse remote and local sources and summaries of data and capture relevant information to be used in building and extending the brain models. Other functionalities are also required, including posing queries related to brain models, augmenting and customizing brain models, and sharing brain models in a collaborative environment. An extensible object-oriented data model is presented to capture the many data types expected in this application. After presenting conceptual level design issues, we describe several known database solutions that support these requirements and discuss requirements that demand further research. Data integration for heterogeneous databases is discussed in terms of reducing or eliminating semantic heterogeneity when translations are made from one system to another. Performance enhancement mechanisms such as materialized views and spatial indexing for three-dimensional objects are explained and evaluated in the context of browsing, incorporating, and sharing. Policies for providing the system with fault tolerance and avoiding possible intellectual property abuses are presented. Finally, two existing systems are evaluated and compared using the identified requirements.

Animals↗

Long-term ST database: a reference for the development and evaluation of automated ischaemia detectors and for the study of the dynamics of myocardial ischaemia.

The long-term ST database is the result of a multinational research effort. The goal was to develop a challenging and realistic research resource for development and evaluation of automated systems to detect transient ST segment changes in electrocardiograms and for supporting basic research into the mechanisms and dynamics of transient myocardial ischaemia. Twenty-four hour ambulatory ECG records were selected from routine clinical practice settings in the USA and Europe, between 1994 and 2000, on the basis of occurrence of ischaemic and non-ischaemic ST segment changes. Human expert annotators used newly developed annotation protocols and a specially developed interactive graphic editor tool (SEMIA) that supported paperless editing of annotations and facilitated international co-operation via the Internet. The database contains 86 two- and three-channel 24 h annotated ambulatory records from 80 patients and is stored on DVD-ROMs. The database annotation files contain ST segment annotations of transient ischaemic (1155) and heart-rate related ST episodes and annotations of non-ischaemic ST segment events related to postural changes and conduction abnormalities. The database is intended to complement the European Society of Cardiology ST-T database and the MIT-BIH and AHA arrhythmia databases. It provides a comprehensive representation of 'real-world' data, with numerous examples of transient ischaemic and non-ischaemic ST segment changes, arrhythmias, conduction abnormalities, axis shifts, noise and artifacts.

Adult↗

Bluetooth wireless database for scoliosis clinics.

A database system with Bluetooth wireless connectivity has been developed so that scoliosis clinics can be run more efficiently and data can be mined for research studies without significant increases in equipment cost. The wireless database system consists of a Bluetooth-enabled laptop or PC and a Bluetooth-enabled handheld personal data assistant (PDA). Each patient has a profile in the database, which has all of his or her clinical history. Immediately prior to the examination, the orthopaedic surgeon selects a patient's profile from the database and uploads that data to the PDA over a Bluetooth wireless connection. The surgeon can view the entire clinical history of the patient while in the examination room and, at the same time, enter in any new measurements and comments from the current examination. After seeing the patient, the surgeon synchronises the newly entered information with the database wirelessly and prints a record for the chart. This combination of the database and the PDA both improves efficiency and accuracy and can save significant time, as there is less duplication of work, and no dictation is required. The equipment required to implement this solution is a Bluetooth-enabled PDA and a Bluetooth wireless transceiver for the PC or laptop.

Computers, Handheld↗

A novel database of disulfide patterns and its application to the discovery of distantly related homologs.

Disulfide bonds are conserved strongly among proteins of related structure and function. Despite the explosive growth of protein sequence databases and the vast numbers of sequence search tools, no tool exists to draw relations between the disulfide patterns of homologous proteins. We present a comprehensive database of disulfide bonding patterns and a search method to find proteins with similar disulfide patterns. The disulfide database was constructed using disulfide annotations extracted from SwissProt, and was expanded significantly from 16,736 to 94,499 disulfide-containing domains by an inference method that combines SwissProt annotations with Pfam multiple alignments. To search the database, we define a disulfide description, called the disulfide signature, which encodes both spacings between cysteine residues and cysteine connectivity. A web tool was developed that allows users to search for related disulfide patterns and for subpatterns resulting from the removal of one or more disulfides from the pattern. We explore the possibility of using disulfide pattern conservation to identify protein homologs that are undetectable by PSI-BLAST. Examples include the homology between a sea anemone antihypertensive/antiviral protein and a sea anemone neurotoxin, and the homology between tick anticoagulant peptide and bovine trypsin inhibitor. In both examples, there is a clear structural similarity and a functional relationship. We used the database to find structural homologs for the Cripto CFC domain. The identification of a von Willebrand Factor C (VWFC)-like domain agrees with its functional role and explains mutation data. We believe that the rapid increase in structure determinations arising from structural genomics efforts and advances in mass spectrometry techniques will greatly increase the number of disulfide annotations. This information will become a valuable resource for structural and functional annotations of proteins. The availability of a searchable disulfide pattern database will thus provide a powerful new addition to existing homolog discovery methods.

Amino Acid Sequence↗

Molecular immunology databases and data repositories.

Over recent years databases have become an extremely important resource for biomedical research. Immunology research is increasingly dependent on access to extensive biological databases to extract existing information, plan experiments, and analyse experimental results. This review describes 15 immunological databases that have appeared over the last 30 years. In addition, important issues regarding database design and the potential for misuse of information contained within these databases are discussed. Access pointers are provided for the major immunological databases and also for a number of other immunological resources accessible over the World Wide Web (WWW).

Allergy and Immunology↗

Clinical databases of patients receiving antidepressants. The missing link between research and practice?

BACKGROUND: In the last 10 years the use of antidepressants has increased drastically. Unfortunately, the epidemiology of these compounds has shown significant gaps between recommendations derived from randomised controlled trials and current clinical practice. METHODS: We argue for the need to develop and maintain clinical databases of patients receiving antidepressants as a way of bridging this situation. RESULTS: In addition to experimental data generated in selected patients and settings, observational databases of large cohorts of typical patients, followed in typical settings, should be developed and maintained. Clinical databases could collect information on patient social and demographic characteristics, clinical symptoms, diagnosis and pharmacological and non-pharmacological treatments. In addition, they can provide accurate estimates of probabilities of different outcomes and on factors that affect outcome. CONCLUSION: Clinical databases should not be seen as another expensive administrative task for busy doctors. Clinical databases should be developed, organised and utilised only by clinicians who are interested in monitoring their clinical practice and want to provide patients, relatives and the public with information on prognosis and outcome in their specific context of care. Maintaining clinical databases is a routine process, nested in everyday clinical activity, which aims at constituting a permanent link between research and practice.

Antidepressive Agents↗

A database generator for human brain imaging.

Sharing scientific data containing complex information requires new concepts and new technology. NEUROGENERATOR is a database generator for the neuroimaging community. A database generator is a database that generates new databases. The scientists submit raw PET and fMRI data to NEUROGENERATOR, which then processes the data in a uniform way to create databases of homogeneous data suitable for data sharing, met-analysis and modelling the human brain at the systems level. These databases are then distributed to the scientists.

Brain↗

Searching fee and non-fee toxicology information resources: an overview of selected databases.

Toxicology profiles organize information by broad subjects, the first of which affirms identity of the agent studied. Studies here show two non-fee databases (ChemFinder and ChemIDplus) verify the identity of compounds with high efficiency (63% and 73% respectively) with the fee-based Chemical Abstracts Registry file serving well to fill data gaps (100%). Continued searching proceeds using knowledge of structure, scope and content to select databases. Valuable sources for information are factual databases that collect data and facts in special subject areas organized in formats available for analysis or use. Some sources representative of factual files are RTECS, CCRIS, HSDB, GENE-TOX and IRIS. Numerous factual databases offer a wealth of reliable information; however, exhaustive searches probe information published in journal articles and/or technical reports with records residing in bibliographic databases such as BIOSIS, EMBASE, MEDLINE, TOXLINE and Web of Science. Listed with descriptions are numerous factual and bibliographic databases supplied by 11 producers. Given the multitude of options and resources, it is often necessary to seek service desk assistance. Questions were posed by telephone and e-mail to service desks at DIALOG, ISI, MEDLARS, Micromedex and STN International. Results of the survey are reported.

Bibliographies as Topic↗

The use of databases to manage fertility.

Dairy farming now needs more records to be kept for quality assurance as well as for management. Herd fertility management is best brought about through the use of computerised records for each animal that integrate fertility, health and production. The development of dairy information systems over the last 25 years has allowed the creation of databases that give rise to "standards" of performance and "interference levels". These databases are of limited use for research unless the coding system has a structure and definition that works across herds. There is an increasing need to incorporate carefully coded disease records into these databases as there is increasing concern about welfare, zoonoses, assurance and the environment. Rules can be determined for satisfactory fertility so interference at an early stage is cost-effective. Integrated indices have been developed (using databases) that incorporate the costs of wastage caused by poor fertility, thus highlighting the priorities for management. Databases are best operated near to the farm, either in the veterinarian's office or on-line in the farm office. Databases can be made into expert systems that deliver high standards of fertility management. A checklist is included that can be followed to analyse the causes of poor fertility in a dairy herd.

Animals↗

Image matching algorithms for breech face marks and firing pins in a database of spent cartridge cases of firearms.

On the market several systems exist for collecting spent ammunition data for forensic investigation. These databases store images of cartridge cases and the marks on them. Image matching is used to create hit lists that show which marks on a cartridge case are most similar to another cartridge case. The research in this paper is focused on the different methods of feature selection and pattern recognition that can be used for optimizing the results of image matching. The images are acquired by side light images for the breech face marks and by ring light for the firing pin impression. For these images a standard way of digitizing the images used. For the side light images and ring light images this means that the user has to position the cartridge case in the same position according to a protocol. The positioning is important for the sidelight, since the image that is obtained of a striation mark depends heavily on the angle of incidence of the light. In practice, it appears that the user positions the cartridge case with +/-10 degrees accuracy. We tested our algorithms using 49 cartridge cases of 19 different firearms, where the examiner determined that they were shot with the same firearm. For testing, these images were mixed with a database consisting of approximately 4900 images that were available from the Drugfire database of different calibers.In cases where the registration and the light conditions among those matching pairs was good, a simple computation of the standard deviation of the subtracted gray levels, delivered the best-matched images. For images that were rotated and shifted, we have implemented a "brute force" way of registration. The images are translated and rotated until the minimum of the standard deviation of the difference is found. This method did not result in all relevant matches in the top position. This is caused by the effect that shadows and highlights are compared in intensity. Since the angle of incidence of the light will give a different intensity profile, this method is not optimal. For this reason a preprocessing of the images was required. It appeared that the third scale of the "à trous" wavelet transform gives the best results in combination with brute force. Matching the contents of the images is less sensitive to the variation of the lighting. The problem with the brute force method is however that the time for calculation for 49 cartridge cases to compare between them, takes over 1 month of computing time on a Pentium II-computer with 333MHz. For this reason a faster approach is implemented: correlation in log polar coordinates. This gave similar results as the brute force calculation, however it was computed in 24h for a complete database with 4900 images.A fast pre-selection method based on signatures is carried out that is based on the Kanade Lucas Tomasi (KLT) equation. The positions of the points computed with this method are compared. In this way, 11 of the 49 images were in the top position in combination with the third scale of the à trous equation. It depends however on the light conditions and the prominence of the marks if correct matches are found in the top ranked position. All images were retrieved in the top 5% of the database. This method takes only a few minutes for the complete database if, and can be optimized for comparison in seconds if the location of points are stored in files. For further improvement, it is useful to have the refinement in which the user selects the areas that are relevant on the cartridge case for their marks. This is necessary if this cartridge case is damaged and other marks that are not from the firearm appear on it.

Algorithms↗

A brief history of the formation of DNA databases in forensic science within Europe.

The introduction of DNA analysis to forensic science brought with it a number of choices for analysis, not all of which were compatible. As laboratories throughout Europe were eager to use the new technology different systems became routine in different laboratories and consequently, there was no basis for the exchange of results. A period of co-operation then started in which a nucleus of forensic scientists agreed on an uniform system. This collaboration spread to incorporate most of the established forensic science laboratories in Europe and continued through two major changes in the technology. At each step agreement was reached on which systems to use. From the beginning it was realised that DNA databases would provide the criminal justice systems with an efficient way of crime solving and consequently some local databases were created. It was not until the introduction of the amplification technology linked to the analysis of short tandem repeats that a sufficiently sensitive and robust system was available for the formation of efficient and effective DNA databases. Comprehensive legislation enacted in the UK in 1995 enabled forensic scientists to set up the first national DNA database which would hold both personal DNA profiles together with results obtained from crime scenes. Other countries quickly followed but in some the legislation has severely restricted the amount and type of data which can be retained and, therefore, effectiveness of the databases is limited. The widespread use of commercially produced multiplex kits has produced a situation in which nearly all European laboratories are using compatible systems and there is, therefore, the potential for the introduction of a pan-European DNA database. However, the exchange of results between countries is hampered by the various legislations which currently exist.

DNA Fingerprinting↗

Impact of different definitions on estimates of accuracy of the diagnosis data in a clinical database.

Computerized medical databases are increasingly used for research. The influence of different definitions of the accuracy of matching on the estimated accuracy of diagnosis data was assessed in a database of visits to a public pediatric clinic. Differences between definitions involved 1) unit of analysis, 2) number of diagnoses required to match per visit, and/or 3) whether database contents are required to match the medical record or medical record contents are required to be matched in the database. Overall, 90% of diagnoses in the database (391/435) were accurately coded relative to the medical record. Alternatively, 77% of diagnoses listed in the medical record (391/506) were accurately coded in the database. When individual visits were used as the unit of analysis, estimates of accuracy using six definitions ranged from 65% to 92%. The most appropriate definition to use for estimating accuracy of diagnosis data likely depends on the purpose of the study. Use of two or more such definitions may enhance portrayal of the accuracy of diagnosis data.

Algorithms↗

A new way of building a database of EEG findings.

Whereas computer-based electroencephalography (EEG) is widely applied, the EEG interpretations are usually not stored in a way that favours exploitation of modern computer technology. This paper reports an EEG description system facilitating categorization of EEG data in a computerized database. The system interactively communicates with the digital EEG system and also with the general patient administrative system. The main new quality of this system is the methods for data input and automatic data retrieval from several systems, rather than the establishment of a database of EEG data itself. The EEGs are visually analysed and categorized. Manually marked EEG events are automatically transferred to the database and such events as well as defined electrode positions within these epochs are directly linked to their corresponding descriptions. The database is updated without demand for filling in the events in the database in a second operation. Thereby, the EEG interpreter builds the database while analysing the EEG. This system provides an improved accessibility of EEG data for clinical, normative, educational and scientific use.

Brain↗

Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database.

A method to correlate uninterpreted tandem mass spectra of modified peptides, produced under low-energy (10-50 eV) collision conditions, with amino acid sequences in a protein database has been developed. The fragmentation patterns observed in the tandem mass spectra of peptides containing covalent modifications is used to directly search and fit linear amino acid sequences in the database. Specific information relevant to sites of modification is not contained in the character-based sequence information of the databases. The search method considers each putative modification site as both modified and unmodified in one pass through the database and simultaneously considers up to three different sites of modification. The search method will identify the correct sequence if the tandem mass spectrum did not represent a modified peptide. This approach is demonstrated with peptides containing modifications such as S-carboxymethylated cysteine, oxidized methionine, phosphoserine, phosphothreonine, or phosphotyrosine. In addition, a scanning approach is used in which neutral loss scans are used to initiate the acquisition of product ion MS/MS spectra of doubly charged phosphorylated peptides during a single chromatographic run for data analysis with the database-searching algorithm. The approach described in this paper provides a convenient method to match the nascent tandem mass spectra of modified peptides to sequences in a protein database and thereby identify previously unknown sites of modification.

Algorithms↗

Suitability of molecular descriptors for database mining. A comparative analysis.

Database mining methods rely on the molecular descriptors used to characterize a structural database. In the present investigation, five different types of descriptors (log P, UNITY fingerprints, ISIS keys, VolSurf, and GRIND) are applied to characterize various databases (n = 1007, 100, and 229) comprising drugs almost exclusively. The validity of the descriptors is comparatively analyzed via principal component analysis and its hierarchical variant, consensus principal component analysis. Both pharmacodynamic and pharmacokinetic aspects of database mining are treated. For pharmacodynamic aspects, clustering behavior achieved with the different descriptors is tested on the chemically homogeneous beta-blockers, benzodiazepines, and penicillins and on the chemically more diverse class I antiarrhythmics. The following ranking is observed: UNITY fingerprints > ISIS keys and GRIND > VolSurf > log P. Regarding information content, the CPCA superweight plot indicates similarity between fingerprints and ISIS keys as well as between VolSurf and log P, while GRIND differs from all the remaining descriptors. Solubility data and blood/brain barrier penetrating behavior serve as test cases for pharmacokinetic aspects. Comparison of the descriptors applied to these data reveals that VolSurf has the most realistic and consistent behavior, GRIND shows intermediate behavior, while UNITY fingerprints and ISIS keys are not well suited for pharmacokinetic profiling. From this comparative analysis, we conclude that VolSurf descriptors exhibit particular advantages in treating pharmacokinetic aspects; UNITY fingerprints, ISIS keys, and GRIND descriptors are of special value for tackling pharmacodynamic aspects of database mining. The parameter log P is of limited applicability in database mining because of rather poor reliability and lack of completeness of data.

Computing Methodologies↗

Database diversity assessment: new ideas, concepts, and tools.

We present some new ideas for characterizing and comparing large chemical databases. The comparison of the contents of large databases is not trivial since it implies pairwise comparison of hundreds of thousands of compounds. We have developed methods for categorizing compounds into groups or series based on their ring-system content, using precalculated structure-based hashcodes. Two large databases can then be compared by simply comparing their hashcode tables. Furthermore, the number of distinct ring-system combinations can be used as an indicator of database diversity. We also present an independent technique for diversity assessment called the saturation diversity approach. This method is based on picking as many mutually dissimilar compounds as possible from a database or a subset thereof. We show that both methods yield similar results. Since the two methods measure very different properties, this probably says more about the properties of the databases studied than about the methods.

Benzene Derivatives↗