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Databases in genomic research.

Genome-related databases have already become an invaluable part of the scientific landscape. The role played by these databases will only increase as the volume and complexity of relevant biology data rapidly expand. We are far enough into the genome project and into the development of these databases to assess their attributes and to reexamine some of the conceptual organizations and approaches they are taking. It is clear that there are needs for both highly detailed and simplified database views, the latter being especially needed to make expert domain data more accessible to nonspecialists.

Animals↗

Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database.

Oxacillin-resistant Staphylococcus aureus (ORSA) is a virulent pathogen responsible for both health care-associated and community onset disease. We used SmaI-digested genomic DNA separated by pulsed-field gel electrophoresis (PFGE) to characterize 957 S. aureus isolates and establish a database of PFGE patterns. In addition to PFGE patterns of U.S. strains, the database contains patterns of representative epidemic-type strains from the United Kingdom, Canada, and Australia; previously described ORSA clonal-type isolates; 13 vancomycin-intermediate S. aureus (VISA) isolates, and two high-level vancomycin-resistant, vanA-positive strains (VRSA). Among the isolates from the United States, we identified eight lineages, designated as pulsed-field types (PFTs) USA100 through USA800, seven of which included both ORSA and oxacillin-susceptible S. aureus isolates. With the exception of the PFT pairs USA100 and USA800, and USA300 and USA500, each of the PFTs had a unique multilocus sequence type and spa type motif. The USA100 PFT, previously designated as the New York/Tokyo clone, was the most common PFT in the database, representing 44% of the ORSA isolates. USA100 isolates were typically multiresistant and included all but one of the U.S. VISA strains and both VRSA isolates. Multiresistant ORSA isolates from the USA200, -500, and -600 PFTs have PFGE patterns similar to those of previously described epidemic strains from Europe and Australia. The USA300 and -400 PFTs contained community isolates resistant only to beta-lactam drugs and erythromycin. Noticeably absent from the U.S. database were isolates with the previously described Brazilian and EMRSA15 PFGE patterns. These data suggest that there are a limited number of ORSA genotypes present in the United States.

Databases, Factual↗

Establishment of a universal size standard strain for use with the PulseNet standardized pulsed-field gel electrophoresis protocols: converting the national databases to the new size standard.

The PulseNet National Database, established by the Centers for Disease Control and Prevention in 1996, consists of pulsed-field gel electrophoresis (PFGE) patterns obtained from isolates of food-borne pathogens (currently Escherichia coli O157:H7, Salmonella, Shigella, and Listeria) and textual information about the isolates. Electronic images and accompanying text are submitted from over 60 U.S. public health and food regulatory agency laboratories. The PFGE patterns are generated according to highly standardized PFGE protocols. Normalization and accurate comparison of gel images require the use of a well-characterized size standard in at least three lanes of each gel. Originally, a well-characterized strain of each organism was chosen as the reference standard for that particular database. The increasing number of databases, difficulty in identifying an organism-specific standard for each database, the increased range of band sizes generated by the use of additional restriction endonucleases, and the maintenance of many different organism-specific strains encouraged us to search for a more versatile and universal DNA size marker. A Salmonella serotype Braenderup strain (H9812) was chosen as the universal size standard. This strain was subjected to rigorous testing in our laboratories to ensure that it met the desired criteria, including coverage of a wide range of DNA fragment sizes, even distribution of bands, and stability of the PFGE pattern. The strategy used to convert and compare data generated by the new and old reference standards is described.

Databases as Topic↗

Injury surveillance in children--usefulness of a centralised database of accident and emergency attendances.

OBJECTIVE: To assess the usefulness of a centralised injury database in monitoring progress towards nationally set health targets for the reduction of childhood injuries. SETTING: West Glamorgan County, Wales. METHODS: Analysis was undertaken of data held in the West Glamorgan injury database which amalgamates population data with data from the three hospital units covering a population of 370,000. All first attendances due to a new injury in children aged 0-14 occurring in 1993 were analysed, with subgroup analysis for injuries occurring in the home and injuries resulting in fractures. Standardised injury ratios were compared with the distance travelled, car ownership, and Townsend index of deprivation at the ward level, using multiple linear regression. RESULTS: A total of 10,117 first time visits due to injuries were recorded, representing a rate of 182 injuries/1000 children aged 0-14 in West Glamorgan County. Distance from home to the accident and emergency departments was inversely correlated with total injury attendances, and injuries occurring at home, but not with injuries resulting in fractures. Visit rates for any type of injury were not associated with local car ownership rates or deprivation indices. CONCLUSIONS: Proximity to accident and emergency departments is a strong determinant of the use of the service by children with overall injuries, and injuries occurring at home. The lack of a significant association between travel distance and injuries resulting in fractures suggests that it is more meaningful to use a centralised database of accident and emergency department attendances to monitor the more severe spectrum of childhood injuries in assessing progress towards national targets for their reduction. The absence of an association between severe injuries and local socioeconomic factors suggests that national targets for the reduction of socioeconomic differentials in childhood injuries may need to be reassessed. These databases are also useful in generating information to direct preventive strategies and to target resources to areas of greatest need.

Accident Prevention↗

Children dying in car trunks: how adequate are child death databases?

OBJECTIVE: To determine the frequency of and circumstances surrounding child deaths resulting from inadvertent entrapment in motor vehicle trunks in the US by querying child fatality review databases. METHOD: A telephone survey was conducted with the persons or offices identified as having primary responsibility for child fatality review programs in each state. The survey requested information on the number of child deaths resulting from trunk entrapments, the ages of the victims, the time period covered by the surveillance system, and variables concerning the circumstances surrounding each incident. RESULTS: All states reported that these deaths are exceedingly rare, with most reporting no such events in recent history. However, state databases could not be readily accessed to identify such deaths. There was enormous interstate variation in guidelines governing the population covered by the child fatality review process. The age range varied greatly from one jurisdiction to another, and often only children in the state's welfare system were included. Interstate differences in practices preclude meaningful compilation of data across jurisdictions. CONCLUSIONS: It was not possible to ascertain the incidence of inadvertent entrapment of children in vehicle trunks because there is no consistency in the available databases. A national database of child fatalities, based on standardized guidelines and definitions, is needed to identify causes and magnitude of specific child deaths, in order to design, implement, and evaluate interventions.

Adolescent↗

Evaluation of the quality of information retrieval of clinical findings from a computerized patient database using a semantic terminological model.

OBJECTIVES: To measure the strength of agreement between the concepts and records retrieved from a computerized patient database, in response to physician-derived questions, using a semantic terminological model for clinical findings with those concepts and records excerpted clinically by manual identification. The performance of the semantic terminological model is also compared with the more established retrieval methods of free-text search, ICD-10, and hierarchic retrieval. DESIGN: A clinical database (Diabeta) of 106,000 patient problem record entries containing 2,625 unique concepts in an clinical academic department was used to compare semantic, free-text, ICD-10, and hierarchic data retrieval against a gold standard in response to a battery of 47 clinical questions. MEASUREMENTS: The performance of concept and record retrieval expressed as mean detection rate, positive predictive value, Yates corrected and Mantel-Haenszel chi-squared values, and Cohen kappa value, with significance estimated using the Mann-Whitney test. RESULTS: The semantic terminological model used to retrieve clinically useful concepts from a patient database performed well and better than other methods, with a mean detection rate of 0.86, a positive predictive value of 0.96, a Yates corrected chi-squared value of 1,537, a Mantel-Haenszel chi-squared value of 19,302, and a Cohen kappa of 0.88. Results for record retrieval were even better, with a mean record detection rate of 0.94, a positive predictive value of 0.99, a Yates corrected chi-squared value of 94, 774, a Mantel-Haenszel chi-squared value of 1,550,356, and a Cohen kappa value of 0.94. The mean detection rate, Yates corrected chi-squared value, and Cohen kappa value for semantic retrieval were significantly better than for the other methods. CONCLUSION: The use of a semantic terminological model in this test scenario provides an effective framework for representing clinical finding concepts and their relationships. Although currently incomplete, the model supports improved information retrieval from a patient database in response to clinically relevant questions, when compared with alternative methods of analysis.

Data Interpretation, Statistical↗

Integration of a multimedia teaching and reference database in a PACS environment.

In one radiology department, a computerized authoring and editing environment was developed and integrated with the picture archiving and communication systems (PACS) for creation of image-based electronic teaching files to replace a collection of printed film images. This multimedia database and authoring environment allows physicians to create reference databases for teaching and research directly from clinical cases being reviewed on PACS diagnostic workstations. The database engine allows users to generate stand-alone CD-ROMs (compact disks, read-only memory) and World Wide Web-based teaching files. The system is fully compliant with the Digital Imaging and Communications in Medicine (DICOM) standard and supports a large number of standard multimedia image file formats. The focus of the development was on convenience and ease of use of a generic system adaptable to all users. The software was integrated on the PACS workstations to allow users to add new cases to the database at any time and anywhere in the department. A pilot system was implemented in clinical operation, with a central server and several client units.

CD-ROM↗

Genebanks: a comparison of eight proposed international genetic databases.

OBJECTIVE: To identify and compare population-based genetic databases, or "genebanks", that have been proposed in eight international locations between 1998 and 2002. A genebank can be defined as a stored collection of genetic samples in the form of blood or tissue, that can be linked with medical and genealogical or lifestyle information from a specific population, gathered using a process of generalized consent. METHODS: Genebanks were identified by searching Medline and internet search engines with key words such as "genetic database" and "biobank" and by reviewing literature on previously identified databases such as the deCode project. Collection of genebank characteristics was by an electronic and literature search, augmented by correspondence with informed individuals. The proposed genebanks are located in Iceland, the United Kingdom, Estonia, Latvia, Sweden, Singapore, the Kingdom of Tonga, and Quebec, Canada. Comparisons of the genebanks were based on the following criteria: genebank location and description of purpose, role of government, commercial involvement, consent and confidentiality procedures, opposition to the genebank, and current progress. RESULTS: All of the groups proposing the genebanks plan to search for susceptibility genes for complex diseases while attempting to improve public health and medical care in the region and, in some cases, stimulating the local economy through expansion of the biotechnology sector. While all of the identified plans share these purposes, they differ in many aspects, including funding, subject participation, and organization. The balance of government and commercial involvement in the development of each project varies. Genetic samples and health information will be collected from participants and coded in all of the genebanks, but consent procedures range from presumed consent of the entire eligible population to recruitment of volunteers with informed consent. Issues regarding confidentiality and consent have resulted in opposition to some of the more publicized projects. None of the proposed databases are currently operational and at least one project was terminated due to opposition. CONCLUSIONS: Ambitious genebank projects have been proposed in numerous countries and provinces. The characteristics of the projects vary, but all intend to map genes for common diseases and hope to improve the health of the populations involved. The impact of these projects on understanding genetic susceptibility to disease will be increasingly apparent if the projects become operational. The ethical, legal, and social implications of the projects should be carefully considered during their development.

Canada↗

Large medical databases, population-based research, and patient confidentiality.

OBJECTIVE: This article is a discussion of the use of large clinical databases in population-based research on psychiatric disorders. METHOD: The authors review uses of large clinical databases in research on the etiology, impact, and treatment of psychiatric disorders. They also describe existing privacy safeguards applicable to use of medical records data in research. RESULTS: The growth of large medical databases has prompted increasing concern about the confidentiality of patient records. Efforts to restrict access to computerized medical data, however, may preclude use of such data in important and legitimate research. Prior research using large medical databases has made important contributions across a broad range of topics, including epidemiology, genetics, treatment effectiveness, and health policy. Continued population-based research will be essential in order to preserve the accessibility and quality of treatment for people with psychiatric disorders. CONCLUSIONS: Public domain research should be distinguished from proprietary or commercial uses of health information, and existing privacy safeguards should be vigorously applied. In our efforts to protect patient privacy, however, we should take care not to endorse or reinforce prejudices against psychiatric treatment and people who suffer from psychiatric disorders. Neither should we ignore important opportunities to improve quality of care and influence public policy through population-based research.

Confidentiality↗

State-level treatment outcome studies using administrative databases.

State substance dependence administrative databases contain both administrative and clinical information on large numbers of patients collected over extended time periods. Access to other state databases--employment, criminal behavior, and Medicaid--has also been achieved in some instances. Such data could prove an important source for the evaluation of long-term treatment outcomes and their determinants. This selected review describes and evaluates the treatment outcome and cost-related findings of the most advanced studies using these databases. A number of these studies have shown that completion of substance dependence treatment is associated with reduced societal costs. Some of these studies have focused on significant subpopulations of patients, including pregnant women and adolescents. A shortcoming of the findings of most of these studies concerns their use of noncompleter or non-randomly collected comparison groups. The utility of these databases can be enhanced by coupling them with clinical research treatment outcome evaluation approaches.

Data Collection↗

Computer-assisted instruction in otolaryngology: the use of a database for examination review.

A database of questions and answers has been developed to assist residents in reviewing current topics in otolaryngology-head and neck surgery. Each question/item has an associated answer, general category, specific category, and reference that allows cross-referencing on the computer system. The user can search the database for categories of interest and obtain a specific subset of questions. This allows an efficient means of knowledge acquisition and review for Board examinations. Additional data entry is also facilitated to expand the database as desired. Currently there are more than 2300 items in the database.

Computer-Assisted Instruction↗

The need for a control animal pathology database: an international survey.

1. The sensitivity of long-term toxicity tests is impaired due to the 'background noise' of spontaneous lesions which are unrelated to treatment. 2. The need for a comprehensive source of computerized information concerning the occurrence and incidence of spontaneous lesions in control animals has been highlighted by initiatives in Europe and the USA. It is, however, essential to identify the potential users, and the type of information required for such a database to be of value. 3. This information has been acquired following an international survey of the pharmaceutical industry in Europe, Japan and the USA, including responses from 48 toxicologists and toxicopathologists representing 38 company groups. 4. Thirty-eight respondents indicated that they would use a historical control database that was regularly updated with the majority of respondents suggesting that they currently use external sources (Breeder's data, the literature, other companies) occasionally to acquire information on control animal pathology data. 5. The majority (94%) of the respondents indicated that a control animal database should contain information on both neoplastic and non-neoplastic lesions for use in evaluating long-term studies, in particular carcinogenicity studies. 6. The survey confirms the need for a historical control animal pathology database wider then those currently available.

Animals↗

Use of DRUGLINE--a question-and-answer database.

BACKGROUND: DRUGLINE is a full-text, question-and-answer database offering drug information that has been evaluated as a result of consultations in a drug information center. A problem-oriented database such as DRUGLINE can be an efficient way to meet the increasing need among healthcare professionals for timely and accurate drug information. OBJECTIVE: To investigate how DRUGLINE was used during the years 1988 and 1990 and to identify any changes in needs, expectations, satisfaction, and use that occurred during those two years. DESIGN: This study investigated the use of DRUGLINE during two separate years. Questionnaires relating to DRUGLINE use during 1988 and 1990 were sent on two occasions to all users having access to the database. The anonymous questionnaires contained 17 and 18 questions, respectively. SETTING: The setting included MEDLINE/DRUGLINE use in healthcare institutions, pharmacies, medical libraries, and the pharmaceutical industry. PARTICIPANTS: The questionnaires were sent to all customers of the database host Medical Information Centre at the Karolinska Institute Library and Information Centre having access to DRUGLINE during 1988 and 1990.

Databases, Factual↗

Combining state administrative databases and provider records to assess the quality of care for children enrolled in Medicaid.

Our objective was to assess the capability of state administrative health care databases to evaluate the quality of immunization rates for a Medicaid managed care population. Data on 5599 2 year olds were obtained from a Medicaid claims database, a health department database, and the records of the children's assigned providers. The study was conducted on 1 managed care program in 1 state. Test performance ratio analyses were used to assess the relative accuracy and contribution of each source of administrative data. We found that of the 67,188 doses needed, 45,511 (68%) were documented as administered per at least 1 of the data sources. Medicaid claims data alone accounted for 18% of immunized children, while health department data used by itself accounted for 12%. Together, these 2 sources identified 34% of immunized children. Large administrative databases, such as Medicaid claims and data from a health department, while valuable sources of information on quality, may underestimate outcomes such as immunization rates. Assessments of the quality of health care should rely on a combination of administrative data and providers' records as sources of information.

Child Health Services↗

PEDro: a database of randomised controlled trials in physiotherapy.

PEDro is a database of clinical trials designed to assist the practice of evidence-based physiotherapy. When complete, it will contain bibliographic details, abstracts and quality assessment scores of all published randomised controlled trials in physiotherapy. Trials on the database will be rated on the basis of their methodological quality, so that users of the database can be guided to those trials which provide the most methodologically sound sources of evidence. The database has been made freely available on the world wide web, where it can be searched with a powerful and user-friendly search engine.

Australia↗

A format for databasing and comparison of AFLP fingerprint profiles.

BACKGROUND: Amplified fragment length polymorphism (AFLP) is a PCR-based technique that involves restriction of genomic DNA followed by ligation of adaptors to the fragments generated and selective PCR amplification of a subset of these fragments. The amplified fragments are separated on a sequencing gel and visualized by autoradiography or fluorescent sequencing equipment. AFLP allows high-resolution genotyping but the lack of a format for databasing and comparison of AFLP fingerprint profiles limits its wider applications in profiling large numbers of biological samples. RESULTS: A scheme is described to represent a DNA fingerprint profile with a nucleotide sequence-like format in which the information line contains the minimal necessary details to interpret an AFLP DNA fingerprint profile. They include technique used, information on restriction enzymes, primer combination, biological source for DNA materials, fragment sizing and annotation. The bodylines contain information on size and relative intensity of DNA fragments by a string of defined alphabets or symbols. Algorithms for normalizing raw data, binning of fragments and comparing AFLP DNA fingerprint profiles are described. Firstly, the peak heights are normalized against their average and then represented by five symbols according to their relative intensities. Secondly, a binning algorithm based loosely on common springs and rubber bands is applied, which positions sequence fragments into their best possible integer approximations. A BLAST-like reward-penalty concept is used to compare AFLP fingerprint profiles by matching peaks using two metrics: score and percentage of similarity. A software package was developed based on our scheme and proposed algorithms. Example of use this software is given in evaluating novelty of a new tropical orchid cultivar by comparing its AFLP fingerprint profile against those of related commercial cultivars in a database. CONCLUSIONS: AFLP DNA fingerprint profiles can be databased and compared effectively with software developed based on our scheme and algorithms. It will facilitate wider use of this DNA fingerprinting technique in areas such as forensic study, intellectual property protection for biological materials and biodiversity management. Moreover, the same concepts can be applied to databasing and comparing DNA fingerprint profiles obtained with other DNA fingerprint techniques.

Algorithms↗

cuticleDB: a relational database of Arthropod cuticular proteins.

BACKGROUND: The insect exoskeleton or cuticle is a bi-partite composite of proteins and chitin that provides protective, skeletal and structural functions. Little information is available about the molecular structure of this important complex that exhibits a helicoidal architecture. Scores of sequences of cuticular proteins have been obtained from direct protein sequencing, from cDNAs, and from genomic analyses. Most of these cuticular protein sequences contain motifs found only in arthropod proteins. DESCRIPTION: cuticleDB is a relational database containing all structural proteins of Arthropod cuticle identified to date. Many come from direct sequencing of proteins isolated from cuticle and from sequences from cDNAs that share common features with these authentic cuticular proteins. It also includes proteins from the Drosophila melanogaster and the Anopheles gambiae genomes, that have been predicted to be cuticular proteins, based on a Pfam motif (PF00379) responsible for chitin binding in Arthropod cuticle. The total number of the database entries is 445: 370 derive from insects, 60 from Crustacea and 15 from Chelicerata. The database can be accessed from our web server at http://bioinformatics.biol.uoa.gr/cuticleDB. CONCLUSIONS: CuticleDB was primarily designed to contain correct and full annotation of cuticular protein data. The database will be of help to future genome annotators. Users will be able to test hypotheses for the existence of known and also of yet unknown motifs in cuticular proteins. An analysis of motifs may contribute to understanding how proteins contribute to the physical properties of cuticle as well as to the precise nature of their interaction with chitin.

Amino Acid Motifs↗

A SNP-centric database for the investigation of the human genome.

BACKGROUND: Single Nucleotide Polymorphisms (SNPs) are an increasingly important tool for genetic and biomedical research. Although current genomic databases contain information on several million SNPs and are growing at a very fast rate, the true value of a SNP in this context is a function of the quality of the annotations that characterize it. Retrieving and analyzing such data for a large number of SNPs often represents a major bottleneck in the design of large-scale association studies. DESCRIPTION: SNPper is a web-based application designed to facilitate the retrieval and use of human SNPs for high-throughput research purposes. It provides a rich local database generated by combining SNP data with the Human Genome sequence and with several other data sources, and offers the user a variety of querying, visualization and data export tools. In this paper we describe the structure and organization of the SNPper database, we review the available data export and visualization options, and we describe how the architecture of SNPper and its specialized data structures support high-volume SNP analysis. CONCLUSIONS: The rich annotation database and the powerful data manipulation and presentation facilities it offers make SNPper a very useful online resource for SNP research. Its success proves the great need for integrated and interoperable resources in the field of computational biology, and shows how such systems may play a critical role in supporting the large-scale computational analysis of our genome.

Databases, Genetic↗