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Towards precise classification of cancers based on robust gene functional expression profiles.

BACKGROUND: Development of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level. RESULTS: Inspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s) for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles. CONCLUSION: This modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge has facilitated the interpretation of the underlying molecular mechanisms for complex human diseases at the modular level.

Algorithms↗

Classification and knowledge discovery in protein databases.

We consider the problem of classification in noisy, high-dimensional, and class-imbalanced protein datasets. In order to design a complete classification system, we use a three-stage machine learning framework consisting of a feature selection stage, a method addressing noise and class-imbalance, and a method for combining biologically related tasks through a prior-knowledge based clustering. In the first stage, we employ Fisher's permutation test as a feature selection filter. Comparisons with the alternative criteria show that it may be favorable for typical protein datasets. In the second stage, noise and class imbalance are addressed by using minority class over-sampling, majority class under-sampling, and ensemble learning. The performance of logistic regression models, decision trees, and neural networks is systematically evaluated. The experimental results show that in many cases ensembles of logistic regression classifiers may outperform more expressive models due to their robustness to noise and low sample density in a high-dimensional feature space. However, ensembles of neural networks may be the best solution for large datasets. In the third stage, we use prior knowledge to partition unlabeled data such that the class distributions among non-overlapping clusters significantly differ. In our experiments, training classifiers specialized to the class distributions of each cluster resulted in a further decrease in classification error.

Algorithms↗

Building a bioinformatics ontology using OIL.

This paper describes the initial stages of building an ontology of bioinformatics and molecular biology. The conceptualization is encoded using the ontology inference layer (OIL), a knowledge representation language that combines the modeling style of frame-based systems with the expressiveness and reasoning power of description logics (DLs). This paper is the second of a pair in this special issue. The first described the core of the OIL language and the need to use ontologies to deliver semantic bioinformatics resources. In this paper, the early stages of building an ontology component of a bioinformatics resource querying application are described. This ontology (TaO) holds the information about molecular biology represented in bioinformatics resources and the bioinformatics tasks performed over these resources. It, therefore, represents the metadata of the resources the application can query. It also manages the terminologies used in constructing the query plans used to retrieve instances from those external resources. The methodology used in this task capitalizes upon features of OIL-The conceptualization afforded by the frame-based view of OIL's syntax; the expressive power and reasoning of the logical formalism; and the ability to encode both handcrafted, hierarchies of concepts, as well as defining concepts in terms of their properties, which can then be used to establish a classification and infer relationships not encoded by the ontologist. This ability forms the basis of the methodology described here: For each portion of the TaO, a basic framework of concepts is asserted by the ontologist. Then, the properties of these concepts are defined by the ontologist and the logic's reasoning power used to reclassify and infer further relationships. This cycle of elaboration and refinement is iterated on each portion of the ontology until a satisfactory ontology has been created.

Algorithms↗

The cohesive metaschema: a higher-level abstraction of the UMLS Semantic Network.

The Unified Medical Language System (UMLS) joins together a group of established medical terminologies in a unified knowledge representation framework. Two major resources of the UMLS are its Metathesaurus, containing a large number of concepts, and the Semantic Network (SN), containing semantic types and forming an abstraction of the Metathesaurus. However, the SN itself is large and complex and may still be difficult to view and comprehend. Our structural partitioning technique partitions the SN into structurally uniform sets of semantic types based on the distribution of the relationships within the SN. An enhancement of the structural partition results in cohesive, singly rooted sets of semantic types. Each such set is named after its root which represents the common nature of the group. These sets of semantic types are represented by higher-level components called metasemantic types. A network, called a metaschema, which consists of the meta-semantic types connected by hierarchical and semantic relationships is obtained and provides an abstract view supporting orientation to the SN. The metaschema is utilized to audit the UMLS classifications. We present a set of graphical views of the SN based on the metaschema to help in user orientation to the SN. A study compares the cohesive metaschema to metaschemas derived semantically by UMLS experts.

Algorithms↗

The Rat Genome Database (RGD): developments towards a phenome database.

The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms.

Animals↗

Nursing constraint models for electronic health records: a vision for domain knowledge governance.

Various forms of electronic health records (EHRs) are currently being introduced in several countries. Nurses are primary stakeholders and need to ensure that their information and knowledge needs are being met by such systems information sharing between health care providers to enable them to improve the quality and efficiency of health care service delivery for all subjects of care. The latest international EHR standards have adopted the openEHR approach of two-level modelling. The first level is a stable information model determining structure, while the second level consists of constraint models or 'archetypes' that reflect the specifications or clinician rules for how clinical information needs to be represented to enable unambiguous data sharing. The current state of play in terms of international health informatics standards development activities is providing the nursing profession with a unique opportunity and challenge. Much work has been undertaken internationally in the area of nursing terminologies and evidence-based practice. This paper argues that to make the most of these emerging technologies and EHRs we must now concentrate on developing a process to identify, document, implement, manage and govern our nursing domain knowledge as well as contribute to the development of relevant international standards. It is argued that one comprehensive nursing terminology, such as the ICNP or SNOMED CT is simply too complex and too difficult to maintain. As the openEHR archetype approach does not rely heavily on big standardised terminologies, it offers more flexibility during standardisation of clinical concepts and it ensures open, future-proof electronic health records. We conclude that it is highly desirable for the nursing profession to adopt this openEHR approach as a means of documenting and governing the nursing profession's domain knowledge. It is essential for the nursing profession to develop its domain knowledge constraint models (archetypes) collaboratively in an international context.

Artificial Intelligence↗

springScape: visualisation of microarray and contextual bioinformatic data using spring embedding and an 'information landscape'.

The interpretation of microarray and other high-throughput data is highly dependent on the biological context of experiments. However, standard analysis packages are poor at simultaneously presenting both the array and related bioinformatic data. We have addressed this challenge by developing a system springScape based on 'spring embedding' and an 'information landscape' allowing several related data sources to be dynamically combined while highlighting one particular feature. Each data source is represented as a network of nodes connected by weighted edges. The networks are combined and embedded in the 2-D plane by spring embedding such that nodes with a high similarity are drawn close together. Complex relationships can be discovered by varying the weight of each data source and observing the dynamic response of the spring network. By modifying Procrustes analysis, we find that the visualizations have an acceptable degree of reproducibility. The 'information landscape' highlights one particular data source, displaying it as a smooth surface whose height is proportional to both the information being viewed and the density of nodes. The algorithm is demonstrated using several microarray data sets in combination with protein-protein interaction data and GO annotations. Among the features revealed are the spatio-temporal profile of gene expression and the identification of GO terms correlated with gene expression and protein interactions. The power of this combined display lies in its interactive feedback and exploitation of human visual pattern recognition. Overall, springScape shows promise as a tool for the interpretation of microarray data in the context of relevant bioinformatic information.

Algorithms↗

Computerised vascular data management: a flexible modular registry suitable for the evaluation of long-term results in patients subjected to multiple interventions.

We have designed a computerised vascular registry (CVR) combining storage of complete patient histories in minute detail, including reoperations and long-term follow-up, with clinical applicability. The basic concept of this registry is the storage of data in a structure of cycles (one cycle per treatment episode), modules (clusters of logistically correlated data) and data-chapters (clusters of clinically correlated data). The registry was designed to minimally interfere with routine clinical practice, for instance by collecting the data step-by-step at the wards and out-patient clinics, quite similar to traditional record keeping. The CVR enables production of inventories of all stored data. More importantly, and in addition to other registries, the structure of our registry adequately enables analyses of data of patients with multiple interventions and patients with long-term follow-up. A microcomputer was used for the input of data, which were stored in a structure enabling effortless transportation of the data to a mainframe computer. Standard software programs were used. Simple inventories and analyses were performed on a microcomputer, and a mainframe computer was used for more complex analyses. The performance and applicability of the newly designed CVR was thoroughly tested in comprehensive retrospective studies. On the basis of these experiences several adjustments were carried out after which the CVR was introduced into clinical practice.

Computer Systems↗

Project IMPACT: results from a pilot validity study of a new observational database.

OBJECTIVE: The objective of this study was to evaluate the accuracy of the information contained in the Project IMPACT database. Project IMPACT is a comprehensive database system developed to measure and describe the care of intensive care patients. This database is being used by a large group of hospitals to help clinicians improve the care of these patients. Data on patient demographics, diagnoses, treatment, and outcomes are entered into the Project IMPACT database by staff at participating hospitals. This pilot study was a first step in assessing the accuracy of these data to determine the usefulness of the Project IMPACT database for measuring intensive care unit (ICU) performance and patient outcomes. DESIGN: The design of the pilot study was the independent abstraction of selected data items from a random sample of ICU patient records from two hospitals participating in Project IMPACT. The abstracted data were compared with the data existing in the Project IMPACT database for agreement. SETTING: Abstraction was performed onsite at the two pilot hospitals by a trained abstractor who was not affiliated with either hospital. PATIENTS: Patients whose records were abstracted included 45 randomly selected ICU patients at each of the two pilot hospitals. MEASUREMENTS AND MAIN RESULTS: Comparison of the Project IMPACT data with the independently abstracted data indicated good agreement (80% or above) on discrete items, such as type of ICU patient. Poorer agreement (under 80%) was seen for continuous items (e.g., 24-hr urine output) and coded items requiring judgment (e.g., reason for ICU admission). CONCLUSIONS: The pilot study showed good internal validity for most of the abstracted variables. High agreement rates were observed, regardless of method of original data capture (electronic download or manual entry), although agreement was higher for some data items that had been electronically downloaded into the Project IMPACT database. The results suggest that Project IMPACT is a valuable resource for ICUs to collect and evaluate information about treatment and patient outcomes.

Database Management Systems↗

Advanced and secure architectural EHR approaches.

OBJECTIVES: Electronic Health Records (EHRs) provided as a lifelong patient record advance towards core applications of distributed and co-operating health information systems and health networks. For meeting the challenge of scalable, flexible, portable, secure EHR systems, the underlying EHR architecture must be based on the component paradigm and model driven, separating platform-independent and platform-specific models. METHODS: Allowing manageable models, real systems must be decomposed and simplified. The resulting modelling approach has to follow the ISO Reference Model - Open Distributing Processing (RM-ODP). The ISO RM-ODP describes any system component from different perspectives. Platform-independent perspectives contain the enterprise view (business process, policies, scenarios, use cases), the information view (classes and associations) and the computational view (composition and decomposition), whereas platform-specific perspectives concern the engineering view (physical distribution and realisation) and the technology view (implementation details from protocols up to education and training) on system components. Those views have to be established for components reflecting aspects of all domains involved in healthcare environments including administrative, legal, medical, technical, etc. Thus, security-related component models reflecting all view mentioned have to be established for enabling both application and communication security services as integral part of the system's architecture. Beside decomposition and simplification of system regarding the different viewpoint on their components, different levels of systems' granularity can be defined hiding internals or focusing on properties of basic components to form a more complex structure. The resulting models describe both structure and behaviour of component-based systems. RESULTS: The described approach has been deployed in different projects defining EHR systems and their underlying architectural principles. In that context, the Australian GEHR project, the openEHR initiative, the revision of CEN ENV 13606 "Electronic Health Record communication", all based on Archetypes, but also the HL7 version 3 activities are discussed in some detail. The latter include the HL7 RIM, the HL7 Development Framework, the HL7's clinical document architecture (CDA) as well as the set of models from use cases, activity diagrams, sequence diagrams up to Domain Information Models (DMIMs) and their building blocks Common Message Element Types (CMET) Constraining Models to their underlying concepts. CONCLUSION: The future-proof EHR architecture as open, user-centric, user-friendly, flexible, scalable, portable core application in health information systems and health networks has to follow advanced architectural paradigms.

Computer Security↗

GOLEM: an interactive graph-based gene-ontology navigation and analysis tool.

BACKGROUND: The Gene Ontology has become an extremely useful tool for the analysis of genomic data and structuring of biological knowledge. Several excellent software tools for navigating the gene ontology have been developed. However, no existing system provides an interactively expandable graph-based view of the gene ontology hierarchy. Furthermore, most existing tools are web-based or require an Internet connection, will not load local annotations files, and provide either analysis or visualization functionality, but not both. RESULTS: To address the above limitations, we have developed GOLEM (Gene Ontology Local Exploration Map), a visualization and analysis tool for focused exploration of the gene ontology graph. GOLEM allows the user to dynamically expand and focus the local graph structure of the gene ontology hierarchy in the neighborhood of any chosen term. It also supports rapid analysis of an input list of genes to find enriched gene ontology terms. The GOLEM application permits the user either to utilize local gene ontology and annotations files in the absence of an Internet connection, or to access the most recent ontology and annotation information from the gene ontology webpage. GOLEM supports global and organism-specific searches by gene ontology term name, gene ontology id and gene name. CONCLUSION: GOLEM is a useful software tool for biologists interested in visualizing the local directed acyclic graph structure of the gene ontology hierarchy and searching for gene ontology terms enriched in genes of interest. It is freely available both as an application and as an applet at http://function.princeton.edu/GOLEM.

Computer Graphics↗

[Drinking water data collection and information system in North Rhine-Westphalia. Integration of water supply zones].

To comply with the drinking water regulation act of 2001 and as basis for reports to the European Community, North Rhine-Westphalia has defined water supply zones and collected the necessary data from local health authorities. The software used for drinking water surveillance by the local health authorities and on state level has been adapted to the new requirements. In principle, a supply zone in NRW means a region where the water comes from one water-works. Under certain conditions exceptions are possible. 53 out of 54 local health authorities supplied data about water supply zones up to summer 2006. There are 410 water supply zones which get their water from around 550 water-works. The number of people per supply zone varies between a few hundred and nearly 900,000. Most of the supply zones fall within the responsibility of one health authority. Only 37 supply zones out of 410 contain regions of more than one local health authority. 27 % of the supply zones get water from three or more water-works, 73% get water from one or two water-works. Looking at the other side of the medal, the structure is also relatively simple. More than 80% of the water-works deliver water into only one supply zone. The definition of water supply zones as chosen in NRW has proved to be a good basis for a clear description of the drinking water supply. Besides, the definition enables the state to produce reports which can link water quality, regions and the supplied persons.

Database Management Systems↗

WEBnm@: a web application for normal mode analyses of proteins.

BACKGROUND: Normal mode analysis (NMA) has become the method of choice to investigate the slowest motions in macromolecular systems. NMA is especially useful for large biomolecular assemblies, such as transmembrane channels or virus capsids. NMA relies on the hypothesis that the vibrational normal modes having the lowest frequencies (also named soft modes) describe the largest movements in a protein and are the ones that are functionally relevant. RESULTS: We developed a web-based server to perform normal modes calculations and different types of analyses. Starting from a structure file provided by the user in the PDB format, the server calculates the normal modes and subsequently offers the user a series of automated calculations; normalized squared atomic displacements, vector field representation and animation of the first six vibrational modes. Each analysis is performed independently from the others and results can be visualized using only a web browser. No additional plug-in or software is required. For users who would like to analyze the results with their favorite software, raw results can also be downloaded. The application is available on http://www.bioinfo.no/tools/normalmodes. We present here the underlying theory, the application architecture and an illustration of its features using a large transmembrane protein as an example. CONCLUSION: We built an efficient and modular web application for normal mode analysis of proteins. Non specialists can easily and rapidly evaluate the degree of flexibility of multi-domain protein assemblies and characterize the large amplitude movements of their domains.

Algorithms↗

Hum-PLoc: a novel ensemble classifier for predicting human protein subcellular localization.

Predicting subcellular localization of human proteins is a challenging problem, especially when unknown query proteins do not have significant homology to proteins of known subcellular locations and when more locations need to be covered. To tackle the challenge, protein samples are expressed by hybridizing the gene ontology (GO) database and amphiphilic pseudo amino acid composition (PseAA). Based on such a representation frame, a novel ensemble classifier, called "Hum-PLoc", was developed by fusing many basic individual classifiers through a voting system. The "engine" of these basic classifiers was operated by the KNN (K-nearest neighbor) rule. As a demonstration, tests were performed with the ensemble classifier for human proteins among the following 12 locations: (1) centriole; (2) cytoplasm; (3) cytoskeleton; (4) endoplasmic reticulum; (5) extracell; (6) Golgi apparatus; (7) lysosome; (8) microsome; (9) mitochondrion; (10) nucleus; (11) peroxisome; (12) plasma membrane. To get rid of redundancy and homology bias, none of the proteins investigated here had > or = 25% sequence identity to any other in a same subcellular location. The overall success rates thus obtained via the jackknife cross-validation test and independent dataset test were 81.1% and 85.0%, respectively, which are more than 50% higher than those obtained by the other existing methods on the same stringent datasets. Furthermore, an incisive and compelling analysis was given to elucidate that the overwhelmingly high success rate obtained by the new predictor is by no means due to a trivial utilization of the GO annotations. This is because, for those proteins with "subcellular location unknown" annotation in Swiss-Prot database, most (more than 99%) of their corresponding GO numbers in GO database are also annotated with "cellular component unknown". The information and clues for predicting subcellular locations of proteins are actually buried into a series of tedious GO numbers, just like they are buried into a pile of complicated amino acid sequences although with a different manner and "depth". To dig out the knowledge about their locations, a sophisticated operation engine is needed. And the current predictor is one of these kinds, and has proved to be a very powerful one. The Hum-PLoc classifier is available as a web-server at http://202.120.37.186/bioinf/hum.

Algorithms↗

[Speech recognition: impact on workflow and report availability].

With ongoing technical refinements speech recognition systems (SRS) are becoming an increasingly attractive alternative to traditional methods of preparing and transcribing medical reports. The two main components of any SRS are the acoustic model and the language model. Features of modern SRS with continuous speech recognition are macros with individually definable texts and report templates as well as the option to navigate in a text or to control SRS or RIS functions by speech recognition. The best benefit from SRS can be obtained if it is integrated into a RIS/RIS-PACS installation. Report availability and time efficiency of the reporting process (related to recognition rate, time expenditure for editing and correcting a report) are the principal determinants of the clinical performance of any SRS. For practical purposes the recognition rate is estimated by the error rate (unit "word"). Error rates range from 4 to 28%. Roughly 20% of them are errors in the vocabulary which may result in clinically relevant misinterpretation. It is thus mandatory to thoroughly correct any transcribed text as well as to continuously train and adapt the SRS vocabulary. The implementation of SRS dramatically improves report availability. This is most pronounced for CT and CR. However, the individual time expenditure for (SRS-based) reporting increased by 20-25% (CR) and according to literature data there is an increase by 30% for CT and MRI. The extent to which the transcription staff profits from SRS depends largely on its qualification. Online dictation implies a workload shift from the transcription staff to the reporting radiologist.

Database Management Systems↗

Consistency across the hierarchies of the UMLS Semantic Network and Metathesaurus.

OBJECTIVE: To develop and test a method for automatically detecting inconsistencies between the parent-child is-a relationships in the Metathesaurus and the ancestor-descendant relationships in the Semantic Network of the Unified Medical Language System (UMLS). METHODS: We exploited the fact that each Metathesaurus concept is assigned one or more semantic types from the UMLS Semantic Network and that the semantic types are arranged in a hierarchy. We compared the semantic types of each pair of parent and child concepts to determine if the types "explained" the Metathesaurus is-a relationships. We considered cases where the semantic type of the parent was neither the same as, nor an ancestor of, the semantic type of the child to be "unexplained." We applied this method to the January 2002 release of the UMLS and examined the unexplained cases we discovered to determine their causes. RESULTS: We found that 17022 (24.3%) of the parent-child is-a relationships in the UMLS Metathesaurus could not be explained based on the semantic types of the concepts. Causes for these discrepancies included cases where the parent or child was missing a semantic type, cases where the semantic type of the child was too general or the semantic type of the parent was too specific, cases where the parent-child relationship was incorrect, and cases where an ancestor-descendant relationship should be added to the UMLS Semantic network. In many cases, the specific cause of the discrepancy cannot be resolved without authoritative judgment by the UMLS developers. CONCLUSIONS: Our method successfully detects inconsistencies between the hierarchies of the UMLS Metathesaurus and Semantic Network. We believe that our method should be added to the set of tools that the UMLS developers use to maintain and audit the UMLS knowledge sources.

Abstracting and Indexing↗

GenoLink: a graph-based querying and browsing system for investigating the function of genes and proteins.

BACKGROUND: A large variety of biological data can be represented by graphs. These graphs can be constructed from heterogeneous data coming from genomic and post-genomic technologies, but there is still need for tools aiming at exploring and analysing such graphs. This paper describes GenoLink, a software platform for the graphical querying and exploration of graphs. RESULTS: GenoLink provides a generic framework for representing and querying data graphs. This framework provides a graph data structure, a graph query engine, allowing to retrieve sub-graphs from the entire data graph, and several graphical interfaces to express such queries and to further explore their results. A query consists in a graph pattern with constraints attached to the vertices and edges. A query result is the set of all sub-graphs of the entire data graph that are isomorphic to the pattern and satisfy the constraints. The graph data structure does not rely upon any particular data model but can dynamically accommodate for any user-supplied data model. However, for genomic and post-genomic applications, we provide a default data model and several parsers for the most popular data sources. GenoLink does not require any programming skill since all operations on graphs and the analysis of the results can be carried out graphically through several dedicated graphical interfaces. CONCLUSION: GenoLink is a generic and interactive tool allowing biologists to graphically explore various sources of information. GenoLink is distributed either as a standalone application or as a component of the Genostar/Iogma platform. Both distributions are free for academic research and teaching purposes and can be requested at academy@genostar.com. A commercial licence form can be obtained for profit company at info@genostar.com. See also http://www.genostar.org.

Computer Graphics↗

Identification of serious drug-drug interactions: results of the partnership to prevent drug-drug interactions.

OBJECTIVE: To develop a list of clinically important drug-drug interactions (DDIs) likely to be encountered in community and ambulatory pharmacy settings and detected by a computerized pharmacy system. DESIGN: Cross-sectional, one-time evaluation. SETTING: United States in fall 2001. PARTICIPANTS: An expert panel comprising two physicians, two clinical pharmacists, and an expert on DDIs. INTERVENTIONS: Systematic review of drug interaction compendia and published literature, ratings (on a 1 to 10 scale) of various clinical aspects of DDIs (e.g., clinical importance, quality and quantity of evidence, causal relationship, risk of morbidity and mortality), and a modified Delphi consensus-building process. MAIN OUTCOME MEASURE: Panelists' opinions about clinical importance of DDIs. RESULTS: The expert panel considered 56 DDIs. Of these, 28 had a mean clinical importance score of 8.0 or more. The ratings for clinical importance ranged from 3.2 to 9.6, with a mean +/- SD of 7.5 +/- 1.5 across the combinations examined. The mean score for the quality of literature suggesting the interaction exists ranged from 1.0 to 9.6, with a mean +/- SD of 5.8 +/- 2.5. In terms of substantiation of the interactions evaluated, the mean +/- SD rating was 6.3 +/- 2.2, with a range from 1.4 to 9.2. Through the modified Delphi process, the panel determined that 25 interactions were clinically important. CONCLUSION: Using an expert panel and a standard evaluation tool, 25 clinically important drug interactions that are likely to occur in the community and ambulatory pharmacy settings were identified. Pharmacists should take steps to prevent patients from receiving these interacting medications, and computer software vendors should focus interaction alerts on these and similarly important DDIs.

Community Pharmacy Services↗