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1.  Optimum Methadone Compliance Testing 
Executive Summary
Objective
The objective of this analysis was to determine the diagnostic utility of oral fluid testing collected with the Intercept oral fluid collection device.
Clinical Need: Target Population and Condition
Opioids (opiates or narcotics) are a class of drugs derived from the opium poppy plant that typically relieve pain and produce a euphoric feeling. Methadone is a long-acting synthetic opioid used to treat opioid dependence and chronic pain. It prevents symptoms of opioid withdrawal, reduces opioid cravings and blocks the euphoric effects of short-acting opioids such as heroin and morphine. Opioid dependence is associated with harms including an increased risk of exposure to Human Immunodeficiency Virus and Hepatitis C as well as other health, social and psychological crises. The goal of methadone treatment is harm reduction. Treatment with methadone for opioid dependence is often a long-term therapy. The Ontario College of Physicians and Surgeons estimates that there are currently 250 physicians qualified to prescribe methadone, and 15,500 people in methadone maintenance programs across Ontario.
Drug testing is a clinical tool whose purpose is to provide objective meaningful information, which will reinforce positive behavioral changes in patients and guide further treatment needs. Such information includes knowledge of whether the patient is taking their methadone as prescribed and reducing or abstaining from using opioid and other drugs of abuse use. The results of drug testing can be used with behavior modification techniques (contingency management techniques) where positive reinforcements such as increased methadone take-home privileges, sustained employment or parole are granted for drug screens negative for opioid use, and negative reinforcement including loss of these privileges for drug screens positive for opioid used.
Body fluids including blood, oral fluid, often referred to as saliva, and urine may contain metabolites and the parent drug of both methadone and drugs of abuse and provide a means for drug testing. Compared with blood which has a widow of detection of several hours, urine has a wider window of detection, approximately 1 to 3 days, and is therefore considered more useful than blood for drug testing. Because of this, and the fact that obtaining a urine specimen is relatively easy, urine drug screening is considered the criterion measure (gold standard) for methadone maintenance monitoring. However, 2 main concerns exist with urine specimens: the possibility of sample tampering by the patient and the necessity for observed urine collection. Urine specimens may be tampered with in 3 ways: dilution, adulteration (contamination) with chemicals, and substitution (patient submits another persons urine specimen). To circumvent sample tampering the supervised collection of urine specimens is a common and recommended practice. However, it has been suggested that this practice may have negative effects including humiliation experienced by patient and staff, and may discourage patients from staying in treatment. Supervised urine specimen collection may also present an operational problem as staff must be available to provide same-sex supervision. Oral fluid testing has been proposed as a replacement for urine because it can be collected easily under direct supervision without infringement of privacy and reduces the likelihood of sample tampering. Generally, the results of oral fluid drug testing are similar to urine drug testing but there are some differences, such as lower concentrations of substances in oral fluid than urine, and some drugs remain detectable for longer periods of time in urine than oral fluid.
The Technology Being Reviewed
The Intercept Oral Specimen Collection Device (Ora-Sure Technologies, Bethlehem, PA) consists of an absorbent pad mounted on a plastic stick. The pad is coated with common salts. The absorbent pad is inserted into the mouth and placed between the cheek and gums for 3 minutes on average. The pad absorbs the oral fluid. After 3 minutes (range 2min-5 min) the collection device is removed from the mouth and the absorbent pad is placed in a small vial which contains 0.8mL of pH-balanced preservative, for transportation to a laboratory for analysis. It is recommended that the person undergoing oral fluid drug testing have nothing to eat or drink for a 10- minute period before the oral fluid specimen is collected. This will remove opportunity for adulteration. Likewise, it is recommended that the person be observed for the duration of the collection period to prevent adulteration of the specimen. An average of 0.4 mL of saliva can be collected. The specimen may be stored at 4C to 37C and tested within 21 days of collection (or within 6 weeks if frozen).
The oral fluid specimen must be analyzed in a laboratory setting. There is no point-of-care (POC) oral fluid test kit for drugs of abuse (other than for alcohol). In the laboratory the oral fluid is extracted from the vial after centrifugation and a screening test is completed to eliminate negative specimens. Similar to urinalysis, oral fluid specimens are analyzed first by enzyme immunoassay with positive specimens sent for confirmatory testing. Comparable cut-off values to urinalysis by enzyme immunoassay have been developed for oral fluids
Review Strategy
 
Research Question
What is the diagnostic utility of the Intercept oral specimen device?
Inclusion criteria:
Studies evaluating paired urine and oral fluid specimens from the same individual with the Intercept oral fluid collection device.
The population studied includes drug users.
Exclusion criteria:
Studies testing for marijuana (THC) only.
Outcomes:
Sensitivity and Specificity of oral fluid testing compared to urinalysis for methadone (methadone metabolite), opiates, cocaine, benzodiazepines, and alcohol.
Quality of the Body of Evidence
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of the body of evidence (defined as 1 or more studies) supporting the research questions explored in this systematic review. A description of the GRADE system is reported in Appendix 1.
Summary of Findings
A total of 854 potential citations were retrieved. After reviewing titles and abstracts, 2 met the inclusion and exclusion criteria. Two other relevant studies were found after corresponding with the author of the 2 studies retrieved from the literature search. Therefore a total of 4 published studies are included in this analysis. All 4 studies carried out by the same investigator meet the definition of Medical Advisory Secretariat level III (not a-randomized controlled trial with contemporaneous controls) study design. In each of the studies, paired urine and oral fluid specimens where obtained from drug users. Urine collection was not observed in the studies however, laboratory tests for pH and creatinine were used to determine the reliability of the specimen. Urine specimens thought to be diluted and unreliable were removed from the evaluation. Urinalysis was used as the criterion measurement for which to determine the sensitivity and specificity of oral fluid testing by the Intercept oral fluid device for opiates, benzodiazepines, cocaine and marijuana. Alcohol was not tested in any of the 4 studies. From these 4 studies, the following conclusions were drawn:
The evidence indicates that oral fluid testing with the Intercept oral fluid device has better specificity than sensitivity for opiates, benzodiazepines, cocaine and marijuana.
The sensitivity of oral fluids testing with the Intercept oral fluid device seems to be from best to worst: cocaine > benzodiazepines >opiates> marijuana.
The sensitivity and specificity for opiates of the Intercept oral fluid device ranges from 75 to 90% and 97- 100% respectively.
The consequences of opiate false-negatives by oral fluid testing with the Intercept oral fluid device need to be weighed against the disadvantages of urine testing, including invasion of privacy issues and adulteration and substitution of the urine specimen.
The window of detection is narrower for oral fluid drug testing than urinalysis and because of this oral fluid testing may best be applied in situations where there is suspected frequent drug use. When drug use is thought to be less frequent or remote, urinalysis may offer a wider (24-48 hours more than oral fluids) window of detection.
The narrow window of detection for oral fluid testing may mean more frequent testing is needed compared to urinalysis. This may increase the expense for drug testing in general.
POC oral fluid testing is not yet available and may limit the practical utility of this drug testing methodology. POC urinalysis by immunoassay is available.
The possible applications of oral fluid testing may include:
Because of its narrow window of detection compared to urinalysis oral fluid testing may best be used during periods of suspected frequent or recent drug use (within 24 hours of drug testing). This is not to say that oral fluid testing is superior to urinalysis during these time periods.
In situations where an observed urine specimen is difficult to obtain. This may include persons with “shy bladder syndrome” or with other urinary conditions limiting their ability to provide an observed urine specimen.
When the health of the patient would make urine testing unreliable (e,g., renal disease)
As an alternative drug testing method when urine specimen tampering practices are suspected to be affecting the reliability of the urinalysis test.
Possible limiting Factors to Diffusion of Oral Fluid Technology
No oral fluid POC test equivalent to onsite urine dips or POC analyzer reducing immediacy of results for patient care.
Currently, physicians get reimbursed directly for POC urinalysis. Oral fluid must be analyzed in a lab setting removing physician reimbursement, which is a source of program funding for many methadone clinics.
Small amount of oral fluid specimen obtained; repeat testing on same sample will be difficult.
Reliability of positive oral fluid methadone (parent drug) results may decrease because of possible contamination of oral cavity after ingestion of dose. Therefore high methadone levels may not be indicative of compliance with treatment. Oral fluid does not as yet test for methadone metabolite.
There currently is no licensed provincial laboratory that analyses oral fluid specimens.
Abbreviations
2-ethylidene- 1,5-dimethyl-3,3-diphenylpyrrolidine
enzyme immunoassay
Enzyme Linked Immunosorbent Assay (ELISA),
Enzyme Multiplied Immunoassay Test (EMIT)
Gas chromatography
gas chromatography/mass spectrometry
High-performance liquid chromatography
Limit of Detection
Mass spectrometry
Methadone Maintenance Treatment
Oral fluid testing
Phencyclidine
Point of Care Testing
tetrahydrocannabinol
11-nor-delta-9-tetrhydrocannabinol-9-carboxylic acid
urine drug testing
PMCID: PMC3379523  PMID: 23074492
2.  An Evaluation of Multiple Query Representations for the Relevance Judgments used to Build a Biomedical Test Collection 
Objectives
The purpose of this study is to validate a method that uses multiple queries to create a set of relevance judgments used to indicate which documents are pertinent to each query when forming a biomedical test collection.
Methods
The aspect query is the major concept of this research; it can represent every aspect of the original query with the same informational need. Manually generated aspect queries created by 15 recruited participants where run using the BM25 retrieval model in order to create aspect query based relevance sets (QRELS). In order to demonstrate the feasibility of these QRELSs, The results from a 2004 genomics track run supported by the National Institute of Standards and Technology (NIST) were used to compute the mean average precision (MAP) based on Text Retrieval Conference (TREC) QRELSs and aspect-QRELSs. The rank correlation was calculated using both Kendall's and Spearman's rank correlation methods.
Results
We experimentally verified the utility of the aspect query method by combining the top ranked documents retrieved by a number of multiple queries which ranked the order of the information. The retrieval system correlated highly with rankings based on human relevance judgments.
Conclusions
Substantial results were shown with high correlations of up to 0.863 (p < 0.01) between the judgment-free gold standard based on the aspect queries and the human-judged gold standard supported by NIST. The results also demonstrate that the aspect query method can contribute in building test collections used for medical literature retrieval.
doi:10.4258/hir.2012.18.1.65
PMCID: PMC3324757  PMID: 22509475
Information Storage and Retrieval; Evaluation Studies; MEDLINE; Correlation Studies; Gold Standard
3.  MScanner: a classifier for retrieving Medline citations 
BMC Bioinformatics  2008;9:108.
Background
Keyword searching through PubMed and other systems is the standard means of retrieving information from Medline. However, ad-hoc retrieval systems do not meet all of the needs of databases that curate information from literature, or of text miners developing a corpus on a topic that has many terms indicative of relevance. Several databases have developed supervised learning methods that operate on a filtered subset of Medline, to classify Medline records so that fewer articles have to be manually reviewed for relevance. A few studies have considered generalisation of Medline classification to operate on the entire Medline database in a non-domain-specific manner, but existing applications lack speed, available implementations, or a means to measure performance in new domains.
Results
MScanner is an implementation of a Bayesian classifier that provides a simple web interface for submitting a corpus of relevant training examples in the form of PubMed IDs and returning results ranked by decreasing probability of relevance. For maximum speed it uses the Medical Subject Headings (MeSH) and journal of publication as a concise document representation, and takes roughly 90 seconds to return results against the 16 million records in Medline. The web interface provides interactive exploration of the results, and cross validated performance evaluation on the relevant input against a random subset of Medline. We describe the classifier implementation, cross validate it on three domain-specific topics, and compare its performance to that of an expert PubMed query for a complex topic. In cross validation on the three sample topics against 100,000 random articles, the classifier achieved excellent separation of relevant and irrelevant article score distributions, ROC areas between 0.97 and 0.99, and averaged precision between 0.69 and 0.92.
Conclusion
MScanner is an effective non-domain-specific classifier that operates on the entire Medline database, and is suited to retrieving topics for which many features may indicate relevance. Its web interface simplifies the task of classifying Medline citations, compared to building a pre-filter and classifier specific to the topic. The data sets and open source code used to obtain the results in this paper are available on-line and as supplementary material, and the web interface may be accessed at .
doi:10.1186/1471-2105-9-108
PMCID: PMC2263023  PMID: 18284683
4.  Towards Automatic Recognition of Scientifically Rigorous Clinical Research Evidence 
The growing numbers of topically relevant biomedical publications readily available due to advances in document retrieval methods pose a challenge to clinicians practicing evidence-based medicine. It is increasingly time consuming to acquire and critically appraise the available evidence. This problem could be addressed in part if methods were available to automatically recognize rigorous studies immediately applicable in a specific clinical situation. We approach the problem of recognizing studies containing useable clinical advice from retrieved topically relevant articles as a binary classification problem. The gold standard used in the development of PubMed clinical query filters forms the basis of our approach. We identify scientifically rigorous studies using supervised machine learning techniques (Naïve Bayes, support vector machine (SVM), and boosting) trained on high-level semantic features. We combine these methods using an ensemble learning method (stacking). The performance of learning methods is evaluated using precision, recall and F1 score, in addition to area under the receiver operating characteristic (ROC) curve (AUC). Using a training set of 10,000 manually annotated MEDLINE citations, and a test set of an additional 2,000 citations, we achieve 73.7% precision and 61.5% recall in identifying rigorous, clinically relevant studies, with stacking over five feature-classifier combinations and 82.5% precision and 84.3% recall in recognizing rigorous studies with treatment focus using stacking over word + metadata feature vector. Our results demonstrate that a high quality gold standard and advanced classification methods can help clinicians acquire best evidence from the medical literature.
doi:10.1197/jamia.M2996
PMCID: PMC2605595  PMID: 18952929
5.  MedEval — A Swedish medical test collection with doctors and patients user groups 
Journal of Biomedical Semantics  2011;2(Suppl 3):S4.
Background
Test collections for information retrieval are scarce. Domain specific test collections even more so, and medical test collections in the Swedish language non-existent prior to the making of the MedEval test collection. Most research in information retrieval has been performed in the English language, thus most test collections contain English documents. However, English is morphologically poor compared to many other European languages and a number of interesting and important aspects have not been investigated. Building a medical test collection in Swedish opens new research opportunities.
Methods
This article describes the making of and potential uses of MedEval, a Swedish medical test collection with assessments, not only for topical relevance, but also for target reader group: Doctors or Patients. A user of the test collection may choose if she wishes to search in the Doctors or the Patients scenario where the topical relevance assessments have been adjusted with consideration to user group, or to search in a scenario which regards only topical relevance.
In addition to having three user groups, MedEval, in its present form, has two indexes, one where the terms are lemmatized and one where the terms are lemmatized and the compounds split and the constituents indexed together with the whole compound.
Results
Differences discovered between the documents written for medical professionals and documents written for laypersons are presented. These differences may be utilized in further studies of retrieval of documents aimed at certain groups of readers. Differences between the groups of documents are, for example, that professional documents have a higher ratio of compounds, have a greater average word length and contain more multi-word expressions.
An experiment is described where the user scenarios have been utilized, searching with expert terms and lay terms, separately and in combination in the different scenarios. The tendency discovered is that the medical expert gets best results using expert terms and the lay person best results using lay terms, but also quite good results using expert terms or lay and expert terms in combination.
Conclusions
The many features of MedEval gives a variety of research possibilities, such as comparing the effectiveness of search terms when it comes to retrieving documents aimed at the different user groups or to study the effect of compound decomposition in retrieval of documents. As Swedish, the language of MedEval, is a morphologically more complex language than English, it is possible to study additional aspects of the effect of natural language processing in information retrieval, for example utilizing different inflectional word forms in the retrieval of expert vs lay documents. MedEval is the first Swedish test collection of the medical domain.
Availability
The Department of Swedish at the University of Gothenburg is in the process of making the MedEval test collection available to academic researchers.
doi:10.1186/2041-1480-2-S3-S4
PMCID: PMC3194176  PMID: 21992659
6.  Search strategies to identify reports on “off-label” drug use in EMBASE 
Background
Medications are frequently prescribed outside their regulatory approval (off-label) by physicians particularly where appropriate therapies are not available. However, the risk/benefit ratio of drugs in off-label use needs to be critically appraised because it may differ from approved on-label usage. Therefore, an extensive exploration of current evidence on clinical data is well-advised. The objective of this study was to develop a search strategy that facilitates detection of the off-label drug use documents in EMBASE via OvidSP.
Methods
We constructed two sets of gold standards from relevant records to off-label drug use by a sensitive search of MEDLINE and EMBASE. Search queries, including search words and strings, were conceived based on definition of off-label use of medications as well as text analysis of 500 randomly selected relevant documents. The selected terms were searched in EMBASE (from 1988 to 2011) and their retrieval performance was compared with the gold standards. We developed a sensitivity-maximizing, and a sensitivity- and precision-maximizing search strategy.
Results
From 4067 records relevant to off-label drug use in our full gold standard set, 3846 records were retrievable from EMBASE. “off label*.af.” was the most sensitive single term (overall sensitivity 77.5%, sensitivity within EMBASE 81.9%, precision 88.1%). The highest sensitive search strategy was achieved by combining 36 search queries with overall sensitivity of 94.0% and precision of 69.5%. An optimal sensitive and precise search strategy was yielded precision 87.4% at the expense of decreasing overall sensitivity to 89.4%.
Conclusion
We developed highly sensitive search strategies to enhance the retrieval of studies on off-label drug use in OvidSP EMBASE.
doi:10.1186/1471-2288-12-190
PMCID: PMC3543848  PMID: 23272771
Off-label use; Information retrieval; EMBASE; MEDLINE; Sensitivity
7.  Barriers to Retrieving Patient Information from Electronic Health Record Data: Failure Analysis from the TREC Medical Records Track 
Objective:
Secondary use of electronic health record (EHR) data relies on the ability to retrieve accurate and complete information about desired patient populations. The Text Retrieval Conference (TREC) 2011 Medical Records Track was a challenge evaluation allowing comparison of systems and algorithms to retrieve patients eligible for clinical studies from a corpus of de-identified medical records, grouped by patient visit. Participants retrieved cohorts of patients relevant to 35 different clinical topics, and visits were judged for relevance to each topic. This study identified the most common barriers to identifying specific clinic populations in the test collection.
Methods:
Using the runs from track participants and judged visits, we analyzed the five non-relevant visits most often retrieved and the five relevant visits most often overlooked. Categories were developed iteratively to group the reasons for incorrect retrieval for each of the 35 topics.
Results:
Reasons fell into nine categories for non-relevant visits and five categories for relevant visits. Non-relevant visits were most often retrieved because they contained a non-relevant reference to the topic terms. Relevant visits were most often infrequently retrieved because they used a synonym for a topic term.
Conclusions:
This failure analysis provides insight into areas for future improvement in EHR-based retrieval with techniques such as more widespread and complete use of standardized terminology in retrieval and data entry systems.
PMCID: PMC3540501  PMID: 23304287
8.  Acupuncture for glaucoma 
Background
Glaucoma is a multifactorial optic neuropathy characterized by an acquired loss of retinal ganglion cells at levels beyond normal age-related loss and corresponding atrophy of the optic nerve. Although many treatments are available to manage glaucoma, glaucoma is a chronic condition. Some patients may seek complementary or alternative medicine approaches such as acupuncture to supplement their regular treatment. The underlying plausibility of acupuncture is that disorders related to the flow of Chi (the traditional Chinese concept translated as vital force or energy) can be prevented or treated by stimulating relevant points on the body surface.
Objectives
The objective of this review was to assess the effectiveness and safety of acupuncture in people with glaucoma.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to January 2013), ZETOC (January 1993 to January 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to January 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (IC-TRP) (www.who.int/ictrp/search/en) and the National Center for Complementary and Alternative Medicine web site (NCCAM) (http://nccam.nih.gov). We did not use any language or date restrictions in the search for trials. We last searched the electronic databases on 8 January 2013 with the exception of NCCAM which was last searched on 14 July 2010. We also handsearched Chinese medical journals at Peking Union Medical College Library in April 2007.
We searched the Chinese Acupuncture Trials Register, the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), and the Chinese Biological Database (CBM) for the original review; we did not search these databases for the 2013 review update.
Selection criteria
We included randomized controlled trials (RCTs) in which one arm of the study involved acupuncture treatment.
Data collection and analysis
Two authors independently evaluated the search results and then full text articles against the eligibility criteria. We resolved discrepancies by discussion.
Main results
We included one completed and one ongoing trial, and recorded seven trials awaiting assessment for eligibility. These seven trials were written in Chinese and were identified from a systematic review on the same topic published in a Chinese journal. The completed trial compared auricular acupressure- a nonstandard acupuncture technique- with the sham procedure for glaucoma. This trial is rated at high risk of bias for masking of outcome assessors, unclear risk of bias for selective outcome reporting, and low risk of bias for other domains. The difference in intraocular pressure (measured in mm Hg) in the acupressure group was significantly less than that in the sham group at four weeks (−3.70, 95% confidence interval [CI] −7.11 to −0.29 for the right eye; −4.90, 95% CI −8.08 to −1.72 for the left eye), but was not statistically different at any other follow-up time points, including the longest follow-up time at eight weeks. No statistically significant difference in visual acuity was noted at any follow-up time points. The ongoing trial was registered with the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization. To date this trial has not recruited any participants.
Authors’ conclusions
At this time, it is impossible to draw reliable conclusions from available data to support the use of acupuncture for the treatment of glaucoma. Because of ethical considerations, RCTs comparing acupuncture alone with standard glaucoma treatment or placebo are unlikely to be justified in countries where the standard of care has already been established. Because most glaucoma patients currently cared for by ophthalmologists do not use nontraditional therapy, clinical practice decisions will have to be based on physician judgments and patient preferences, given this lack of data in the literature. Inclusion of the seven Chinese trials in future updates of this review may change our conclusions.
doi:10.1002/14651858.CD006030.pub3
PMCID: PMC4260653  PMID: 23728656
Acupuncture Therapy [*methods]; Acupuncture, Ear; Glaucoma [*therapy]; Randomized Controlled Trials as Topic; Humans
9.  A Document Clustering and Ranking System for Exploring MEDLINE Citations 
Objective
A major problem faced in biomedical informatics involves how best to present information retrieval results. When a single query retrieves many results, simply showing them as a long list often provides poor overview. With a goal of presenting users with reduced sets of relevant citations, this study developed an approach that retrieved and organized MEDLINE citations into different topical groups and prioritized important citations in each group.
Design
A text mining system framework for automatic document clustering and ranking organized MEDLINE citations following simple PubMed queries. The system grouped the retrieved citations, ranked the citations in each cluster, and generated a set of keywords and MeSH terms to describe the common theme of each cluster.
Measurements
Several possible ranking functions were compared, including citation count per year (CCPY), citation count (CC), and journal impact factor (JIF). We evaluated this framework by identifying as “important” those articles selected by the Surgical Oncology Society.
Results
Our results showed that CCPY outperforms CC and JIF, i.e., CCPY better ranked important articles than did the others. Furthermore, our text clustering and knowledge extraction strategy grouped the retrieval results into informative clusters as revealed by the keywords and MeSH terms extracted from the documents in each cluster.
Conclusions
The text mining system studied effectively integrated text clustering, text summarization, and text ranking and organized MEDLINE retrieval results into different topical groups.
doi:10.1197/jamia.M2215
PMCID: PMC1975797  PMID: 17600104
10.  Finding biomarkers in non-model species: literature mining of transcription factors involved in bovine embryo development 
BioData Mining  2012;5:12.
Background
Since processes in well-known model organisms have specific features different from those in Bos taurus, the organism under study, a good way to describe gene regulation in ruminant embryos would be a species-specific consideration of closely related species to cattle, sheep and pig. However, as highlighted by a recent report, gene dictionaries in pig are smaller than in cattle, bringing a risk to reduce the gene resources to be mined (and so for sheep dictionaries). Bioinformatics approaches that allow an integration of available information on gene function in model organisms, taking into account their specificity, are thus needed. Besides these closely related and biologically relevant species, there is indeed much more knowledge of (i) trophoblast proliferation and differentiation or (ii) embryogenesis in human and mouse species, which provides opportunities for reconstructing proliferation and/or differentiation processes in other mammalian embryos, including ruminants. The necessary knowledge can be obtained partly from (i) stem cell or cancer research to supply useful information on molecular agents or molecular interactions at work in cell proliferation and (ii) mouse embryogenesis to supply useful information on embryo differentiation. However, the total number of publications for all these topics and species is great and their manual processing would be tedious and time consuming. This is why we used text mining for automated text analysis and automated knowledge extraction. To evaluate the quality of this “mining”, we took advantage of studies that reported gene expression profiles during the elongation of bovine embryos and defined a list of transcription factors (or TF, n = 64) that we used as biological “gold standard”. When successful, the “mining” approach would identify them all, as well as novel ones.
Methods
To gain knowledge on molecular-genetic regulations in a non model organism, we offer an approach based on literature-mining and score arrangement of data from model organisms. This approach was applied to identify novel transcription factors during bovine blastocyst elongation, a process that is not observed in rodents and primates. As a result, searching through human and mouse corpuses, we identified numerous bovine homologs, among which 11 to 14% of transcription factors including the gold standard TF as well as novel TF potentially important to gene regulation in ruminant embryo development. The scripts of the workflow are written in Perl and available on demand. They require data input coming from all various databases for any kind of biological issue once the data has been prepared according to keywords for the studied topic and species; we can provide data sample to illustrate the use and functionality of the workflow.
Results
To do so, we created a workflow that allowed the pipeline processing of literature data and biological data, extracted from Web of Science (WoS) or PubMed but also from Gene Expression Omnibus (GEO), Gene Ontology (GO), Uniprot, HomoloGene, TcoF-DB and TFe (TF encyclopedia). First, the human and mouse homologs of the bovine proteins were selected, filtered by text corpora and arranged by score functions. The score functions were based on the gene name frequencies in corpora. Then, transcription factors were identified using TcoF-DB and double-checked using TFe to characterise TF groups and families. Thus, among a search space of 18,670 bovine homologs, 489 were identified as transcription factors. Among them, 243 were absent from the high-throughput data available at the time of the study. They thus stand so far for putative TF acting during bovine embryo elongation, but might be retrieved from a recent RNA sequencing dataset (Mamo et al. , 2012). Beyond the 246 TF that appeared expressed in bovine elongating tissues, we restricted our interpretation to those occurring within a list of 50 top-ranked genes. Among the transcription factors identified therein, half belonged to the gold standard (ASCL2, c-FOS, ETS2, GATA3, HAND1) and half did not (ESR1, HES1, ID2, NANOG, PHB2, TP53, STAT3).
Conclusions
A workflow providing search for transcription factors acting in bovine elongation was developed. The model assumed that proteins sharing the same protein domains in closely related species had the same protein functionalities, even if they were differently regulated among species or involved in somewhat different pathways. Under this assumption, we merged the information on different mammalian species from different databases (literature and biology) and proposed 489 TF as potential participants of embryo proliferation and differentiation, with (i) a recall of 95% with regard to a biological gold standard defined in 2011 and (ii) an extension of more than 3 times the gold standard of TF detected so far in elongating tissues. The working capacity of the workflow was supported by the manual expertise of the biologists on the results. The workflow can serve as a new kind of bioinformatics tool to work on fused data sources and can thus be useful in studies of a wide range of biological processes.
doi:10.1186/1756-0381-5-12
PMCID: PMC3563503  PMID: 22931563
11.  Retrieval feedback in MEDLINE. 
OBJECTIVE: To investigate a new approach for query expansion based on retrieval feedback. The first objective in this study was to examine alternative query-expansion methods within the same retrieval-feedback framework. The three alternatives proposed are: expansion on the MeSH query field alone, expansion on the free-text field alone, and expansion on both the MeSH and the free-text fields. The second objective was to gain further understanding of retrieval feedback by examining possible dependencies on relevant documents during the feedback cycle. DESIGN: Comparative study of retrieval effectiveness using the original unexpanded and the alternative expanded user queries on a MEDLINE test collection of 75 queries and 2,334 MEDLINE citations. MEASUREMENTS: Retrieval effectivenesses of the original unexpanded and the alternative expanded queries were compared using 11-point-average precision scores (11-AvgP). These are averages of precision scores obtained at 11 standard recall points. RESULTS: All three expansion strategies significantly improved the original queries in terms of retrieval effectiveness. Expansion on MeSH alone was equivalent to expansion on both MeSH and the free-text fields. Expansion on the free-text field alone improved the queries significantly less than did the other two strategies. The second part of the study indicated that retrieval-feedback-based expansion yields significant performance improvements independent of the availability of relevant documents for feedback information. CONCLUSIONS: Retrieval feedback offers a robust procedure for query expansion that is most effective for MEDLINE when applied to the MeSH field.
PMCID: PMC116298  PMID: 8653452
12.  A LDA-based approach to promoting ranking diversity for genomics information retrieval 
BMC Genomics  2012;13(Suppl 3):S2.
Background
In the biomedical domain, there are immense data and tremendous increase of genomics and biomedical relevant publications. The wealth of information has led to an increasing amount of interest in and need for applying information retrieval techniques to access the scientific literature in genomics and related biomedical disciplines. In many cases, the desired information of a query asked by biologists is a list of a certain type of entities covering different aspects that are related to the question, such as cells, genes, diseases, proteins, mutations, etc. Hence, it is important of a biomedical IR system to be able to provide relevant and diverse answers to fulfill biologists' information needs. However traditional IR model only concerns with the relevance between retrieved documents and user query, but does not take redundancy between retrieved documents into account. This will lead to high redundancy and low diversity in the retrieval ranked lists.
Results
In this paper, we propose an approach which employs a topic generative model called Latent Dirichlet Allocation (LDA) to promoting ranking diversity for biomedical information retrieval. Different from other approaches or models which consider aspects on word level, our approach assumes that aspects should be identified by the topics of retrieved documents. We present LDA model to discover topic distribution of retrieval passages and word distribution of each topic dimension, and then re-rank retrieval results with topic distribution similarity between passages based on N-size slide window. We perform our approach on TREC 2007 Genomics collection and two distinctive IR baseline runs, which can achieve 8% improvement over the highest Aspect MAP reported in TREC 2007 Genomics track.
Conclusions
The proposed method is the first study of adopting topic model to genomics information retrieval, and demonstrates its effectiveness in promoting ranking diversity as well as in improving relevance of ranked lists of genomics search. Moreover, we proposes a distance measure to quantify how much a passage can increase topical diversity by considering both topical importance and topical coefficient by LDA, and the distance measure is a modified Euclidean distance.
doi:10.1186/1471-2164-13-S3-S2
PMCID: PMC3394425  PMID: 22759611
13.  Discovering biomedical semantic relations in PubMed queries for information retrieval and database curation 
Identifying relevant papers from the literature is a common task in biocuration. Most current biomedical literature search systems primarily rely on matching user keywords. Semantic search, on the other hand, seeks to improve search accuracy by understanding the entities and contextual relations in user keywords. However, past research has mostly focused on semantically identifying biological entities (e.g. chemicals, diseases and genes) with little effort on discovering semantic relations. In this work, we aim to discover biomedical semantic relations in PubMed queries in an automated and unsupervised fashion. Specifically, we focus on extracting and understanding the contextual information (or context patterns) that is used by PubMed users to represent semantic relations between entities such as ‘CHEMICAL-1 compared to CHEMICAL-2.’ With the advances in automatic named entity recognition, we first tag entities in PubMed queries and then use tagged entities as knowledge to recognize pattern semantics. More specifically, we transform PubMed queries into context patterns involving participating entities, which are subsequently projected to latent topics via latent semantic analysis (LSA) to avoid the data sparseness and specificity issues. Finally, we mine semantically similar contextual patterns or semantic relations based on LSA topic distributions. Our two separate evaluation experiments of chemical-chemical (CC) and chemical–disease (CD) relations show that the proposed approach significantly outperforms a baseline method, which simply measures pattern semantics by similarity in participating entities. The highest performance achieved by our approach is nearly 0.9 and 0.85 respectively for the CC and CD task when compared against the ground truth in terms of normalized discounted cumulative gain (nDCG), a standard measure of ranking quality. These results suggest that our approach can effectively identify and return related semantic patterns in a ranked order covering diverse bio-entity relations. To assess the potential utility of our automated top-ranked patterns of a given relation in semantic search, we performed a pilot study on frequently sought semantic relations in PubMed and observed improved literature retrieval effectiveness based on post-hoc human relevance evaluation. Further investigation in larger tests and in real-world scenarios is warranted.
doi:10.1093/database/baw025
PMCID: PMC4808250  PMID: 27016698
14.  CDAPubMed: a browser extension to retrieve EHR-based biomedical literature 
Background
Over the last few decades, the ever-increasing output of scientific publications has led to new challenges to keep up to date with the literature. In the biomedical area, this growth has introduced new requirements for professionals, e.g., physicians, who have to locate the exact papers that they need for their clinical and research work amongst a huge number of publications. Against this backdrop, novel information retrieval methods are even more necessary. While web search engines are widespread in many areas, facilitating access to all kinds of information, additional tools are required to automatically link information retrieved from these engines to specific biomedical applications. In the case of clinical environments, this also means considering aspects such as patient data security and confidentiality or structured contents, e.g., electronic health records (EHRs). In this scenario, we have developed a new tool to facilitate query building to retrieve scientific literature related to EHRs.
Results
We have developed CDAPubMed, an open-source web browser extension to integrate EHR features in biomedical literature retrieval approaches. Clinical users can use CDAPubMed to: (i) load patient clinical documents, i.e., EHRs based on the Health Level 7-Clinical Document Architecture Standard (HL7-CDA), (ii) identify relevant terms for scientific literature search in these documents, i.e., Medical Subject Headings (MeSH), automatically driven by the CDAPubMed configuration, which advanced users can optimize to adapt to each specific situation, and (iii) generate and launch literature search queries to a major search engine, i.e., PubMed, to retrieve citations related to the EHR under examination.
Conclusions
CDAPubMed is a platform-independent tool designed to facilitate literature searching using keywords contained in specific EHRs. CDAPubMed is visually integrated, as an extension of a widespread web browser, within the standard PubMed interface. It has been tested on a public dataset of HL7-CDA documents, returning significantly fewer citations since queries are focused on characteristics identified within the EHR. For instance, compared with more than 200,000 citations retrieved by breast neoplasm, fewer than ten citations were retrieved when ten patient features were added using CDAPubMed. This is an open source tool that can be freely used for non-profit purposes and integrated with other existing systems.
doi:10.1186/1472-6947-12-29
PMCID: PMC3366875  PMID: 22480327
15.  COM3/369: Knowledge-based Information Systems: A new approach for the representation and retrieval of medical information 
Introduction
Present solutions for the representation and retrieval of medical information from online sources are not very satisfying. Either the retrieval process lacks of precision and completeness the representation does not support the update and maintenance of the represented information. Most efforts are currently put into improving the combination of search engines and HTML based documents. However, due to the current shortcomings of methods for natural language understanding there are clear limitations to this approach. Furthermore, this approach does not solve the maintenance problem. At least medical information exceeding a certain complexity seems to afford approaches that rely on structured knowledge representation and corresponding retrieval mechanisms.
Methods
Knowledge-based information systems are based on the following fundamental ideas. The representation of information is based on ontologies that define the structure of the domain's concepts and their relations. Views on domain models are defined and represented as retrieval schemata. Retrieval schemata can be interpreted as canonical query types focussing on specific aspects of the provided information (e.g. diagnosis or therapy centred views). Based on these retrieval schemata it can be decided which parts of the information in the domain model must be represented explicitly and formalised to support the retrieval process. As representation language propositional logic is used. All other information can be represented in a structured but informal way using text, images etc. Layout schemata are used to assign layout information to retrieved domain concepts. Depending on the target environment HTML or XML can be used.
Results
Based on this approach two knowledge-based information systems have been developed. The 'Ophthalmologic Knowledge-based Information System for Diabetic Retinopathy' (OKIS-DR) provides information on diagnoses, findings, examinations, guidelines, and reference images related to diabetic retinopathy. OKIS-DR uses combinations of findings to specify the information that must be retrieved. The second system focuses on nutrition related allergies and intolerances. Information on allergies and intolerances of a patient are used to retrieve general information on the specified combination of allergies and intolerances. As a special feature the system generates tables showing food types and products that are tolerated or not tolerated by patients. Evaluation by external experts and user groups showed that the described approach of knowledge-based information systems increases the precision and completeness of knowledge retrieval. Due to the structured and non-redundant representation of information the maintenance and update of the information can be simplified. Both systems are available as WWW based online knowledge bases and CD-ROMs (cf. http://mta.gsf.de topic: products).
doi:10.2196/jmir.1.suppl1.e16
PMCID: PMC1761778
Knowledge-based Information Systems; Knowledge-based Systems; Information Retrieval
16.  Advancing Biomedical Image Retrieval: Development and Analysis of a Test Collection 
Objective
Develop and analyze results from an image retrieval test collection.
Methods
After participating research groups obtained and assessed results from their systems in the image retrieval task of Cross-Language Evaluation Forum, we assessed the results for common themes and trends. In addition to overall performance, results were analyzed on the basis of topic categories (those most amenable to visual, textual, or mixed approaches) and run categories (those employing queries entered by automated or manual means as well as those using visual, textual, or mixed indexing and retrieval methods). We also assessed results on the different topics and compared the impact of duplicate relevance judgments.
Results
A total of 13 research groups participated. Analysis was limited to the best run submitted by each group in each run category. The best results were obtained by systems that combined visual and textual methods. There was substantial variation in performance across topics. Systems employing textual methods were more resilient to visually oriented topics than those using visual methods were to textually oriented topics. The primary performance measure of mean average precision (MAP) was not necessarily associated with other measures, including those possibly more pertinent to real users, such as precision at 10 or 30 images.
Conclusions
We developed a test collection amenable to assessing visual and textual methods for image retrieval. Future work must focus on how varying topic and run types affect retrieval performance. Users' studies also are necessary to determine the best measures for evaluating the efficacy of image retrieval systems.
doi:10.1197/jamia.M2082
PMCID: PMC1561788  PMID: 16799124
17.  Evaluation of the Educational Value of YouTube Videos About Physical Examination of the Cardiovascular and Respiratory Systems 
Background
A number of studies have evaluated the educational contents of videos on YouTube. However, little analysis has been done on videos about physical examination.
Objective
This study aimed to analyze YouTube videos about physical examination of the cardiovascular and respiratory systems. It was hypothesized that the educational standards of videos on YouTube would vary significantly.
Methods
During the period from November 2, 2011 to December 2, 2011, YouTube was searched by three assessors for videos covering the clinical examination of the cardiovascular and respiratory systems. For each video, the following information was collected: title, authors, duration, number of viewers, and total number of days on YouTube. Using criteria comprising content, technical authority, and pedagogy parameters, videos were rated independently by three assessors and grouped into educationally useful and non-useful videos.
Results
A total of 1920 videos were screened. Only relevant videos covering the examination of adults in the English language were identified (n=56). Of these, 20 were found to be relevant to cardiovascular examinations and 36 to respiratory examinations. Further analysis revealed that 9 provided useful information on cardiovascular examinations and 7 on respiratory examinations: scoring mean 14.9 (SD 0.33) and mean 15.0 (SD 0.00), respectively. The other videos, 11 covering cardiovascular and 29 on respiratory examinations, were not useful educationally, scoring mean 11.1 (SD 1.08) and mean 11.2 (SD 1.29), respectively. The differences between these two categories were significant (P<.001 for both body systems). The concordance between the assessors on applying the criteria was 0.89, with a kappa score >.86.
Conclusions
A small number of videos about physical examination of the cardiovascular and respiratory systems were identified as educationally useful; these videos can be used by medical students for independent learning and by clinical teachers as learning resources. The scoring system utilized by this study is simple, easy to apply, and could be used by other researchers on similar topics.
doi:10.2196/jmir.2728
PMCID: PMC3841366  PMID: 24225171
YouTube; learning resources; medical education; cardiovascular system physical examination; respiratory system physical examination; medical curriculum; clinical skills; self-directed learning; competency
18.  Design and development of a content-based medical image retrieval system for spine vertebrae irregularity 
Background
Content-based medical image retrieval (CBMIR) system enables medical practitioners to perform fast diagnosis through quantitative assessment of the visual information of various modalities.
Methods
In this paper, a more robust CBMIR system that deals with both cervical and lumbar vertebrae irregularity is afforded. It comprises three main phases, namely modelling, indexing and retrieval of the vertebrae image. The main tasks in the modelling phase are to improve and enhance the visibility of the x-ray image for better segmentation results using active shape model (ASM). The segmented vertebral fractures are then characterized in the indexing phase using region-based fracture characterization (RB-FC) and contour-based fracture characterization (CB-FC). Upon a query, the characterized features are compared to the query image. Effectiveness of the retrieval phase is determined by its retrieval, thus, we propose an integration of the predictor model based cross validation neural network (PMCVNN) and similarity matching (SM) in this stage. The PMCVNN task is to identify the correct vertebral irregularity class through classification allowing the SM process to be more efficient. Retrieval performance between the proposed and the standard retrieval architectures are then compared using retrieval precision (Pr@M) and average group score (AGS) measures.
Results
Experimental results show that the new integrated retrieval architecture performs better than those of the standard CBMIR architecture with retrieval results of cervical (AGS > 87%) and lumbar (AGS > 82%) datasets.
Conclusions
The proposed CBMIR architecture shows encouraging results with high Pr@M accuracy. As a result, images from the same visualization class are returned for further used by the medical personnel.
doi:10.1186/1475-925X-14-6
PMCID: PMC4349791  PMID: 25595511
X-ray images; Vertebrae irregularity; Modelling; Indexing; Retrieval; CBMIR
19.  Boolean versus ranked querying for biomedical systematic reviews 
Background
The process of constructing a systematic review, a document that compiles the published evidence pertaining to a specified medical topic, is intensely time-consuming, often taking a team of researchers over a year, with the identification of relevant published research comprising a substantial portion of the effort. The standard paradigm for this information-seeking task is to use Boolean search; however, this leaves the user(s) the requirement of examining every returned result. Further, our experience is that effective Boolean queries for this specific task are extremely difficult to formulate and typically require multiple iterations of refinement before being finalized.
Methods
We explore the effectiveness of using ranked retrieval as compared to Boolean querying for the purpose of constructing a systematic review. We conduct a series of experiments involving ranked retrieval, using queries defined methodologically, in an effort to understand the practicalities of incorporating ranked retrieval into the systematic search task.
Results
Our results show that ranked retrieval by itself is not viable for this search task requiring high recall. However, we describe a refinement of the standard Boolean search process and show that ranking within a Boolean result set can improve the overall search performance by providing early indication of the quality of the results, thereby speeding up the iterative query-refinement process.
Conclusions
Outcomes of experiments suggest that an interactive query-development process using a hybrid ranked and Boolean retrieval system has the potential for significant time-savings over the current search process in the systematic reviewing.
doi:10.1186/1472-6947-10-58
PMCID: PMC2966450  PMID: 20937152
20.  GLAD4U: deriving and prioritizing gene lists from PubMed literature 
BMC Genomics  2012;13(Suppl 8):S20.
Background
Answering questions such as "Which genes are related to breast cancer?" usually requires retrieving relevant publications through the PubMed search engine, reading these publications, and creating gene lists. This process is not only time-consuming, but also prone to errors.
Results
We report GLAD4U (Gene List Automatically Derived For You), a new, free web-based gene retrieval and prioritization tool. GLAD4U takes advantage of existing resources of the NCBI to ensure computational efficiency. The quality of gene lists created by GLAD4U for three Gene Ontology (GO) terms and three disease terms was assessed using corresponding "gold standard" lists curated in public databases. For all queries, GLAD4U gene lists showed very high recall but low precision, leading to low F-measure. As a comparison, EBIMed's recall was consistently lower than GLAD4U, but its precision was higher. To present the most relevant genes at the top of a list, we studied two prioritization methods based on publication count and the hypergeometric test, and compared the ranked lists and those generated by EBIMed to the gold standards. Both GLAD4U methods outperformed EBIMed for all queries based on a variety of quality metrics. Moreover, the hypergeometric method allowed for a better performance by thresholding genes with low scores. In addition, manual examination suggests that many false-positives could be explained by the incompleteness of the gold standards. The GLAD4U user interface accepts any valid queries for PubMed, and its output page displays the ranked gene list and information associated with each gene, chronologically-ordered supporting publications, along with a summary of the run and links for file export and functional enrichment and protein interaction network analysis.
Conclusions
GLAD4U has a high overall recall. Although precision is generally low, the prioritization methods successfully rank truly relevant genes at the top of the lists to facilitate efficient browsing. GLAD4U is simple to use, and its interface can be found at: http://bioinfo.vanderbilt.edu/glad4u.
doi:10.1186/1471-2164-13-S8-S20
PMCID: PMC3535723  PMID: 23282288
21.  Objective and automated protocols for the evaluation of biomedical search engines using No Title Evaluation protocols 
BMC Bioinformatics  2008;9:132.
Background
The evaluation of information retrieval techniques has traditionally relied on human judges to determine which documents are relevant to a query and which are not. This protocol is used in the Text Retrieval Evaluation Conference (TREC), organized annually for the past 15 years, to support the unbiased evaluation of novel information retrieval approaches. The TREC Genomics Track has recently been introduced to measure the performance of information retrieval for biomedical applications.
Results
We describe two protocols for evaluating biomedical information retrieval techniques without human relevance judgments. We call these protocols No Title Evaluation (NT Evaluation). The first protocol measures performance for focused searches, where only one relevant document exists for each query. The second protocol measures performance for queries expected to have potentially many relevant documents per query (high-recall searches). Both protocols take advantage of the clear separation of titles and abstracts found in Medline. We compare the performance obtained with these evaluation protocols to results obtained by reusing the relevance judgments produced in the 2004 and 2005 TREC Genomics Track and observe significant correlations between performance rankings generated by our approach and TREC. Spearman's correlation coefficients in the range of 0.79–0.92 are observed comparing bpref measured with NT Evaluation or with TREC evaluations. For comparison, coefficients in the range 0.86–0.94 can be observed when evaluating the same set of methods with data from two independent TREC Genomics Track evaluations. We discuss the advantages of NT Evaluation over the TRels and the data fusion evaluation protocols introduced recently.
Conclusion
Our results suggest that the NT Evaluation protocols described here could be used to optimize some search engine parameters before human evaluation. Further research is needed to determine if NT Evaluation or variants of these protocols can fully substitute for human evaluations.
doi:10.1186/1471-2105-9-132
PMCID: PMC2292696  PMID: 18312673
22.  TopFed: TCGA tailored federated query processing and linking to LOD 
Backgroud
The Cancer Genome Atlas (TCGA) is a multidisciplinary, multi-institutional effort to catalogue genetic mutations responsible for cancer using genome analysis techniques. One of the aims of this project is to create a comprehensive and open repository of cancer related molecular analysis, to be exploited by bioinformaticians towards advancing cancer knowledge. However, devising bioinformatics applications to analyse such large dataset is still challenging, as it often requires downloading large archives and parsing the relevant text files. Therefore, it is making it difficult to enable virtual data integration in order to collect the critical co-variates necessary for analysis.
Methods
We address these issues by transforming the TCGA data into the Semantic Web standard Resource Description Format (RDF), link it to relevant datasets in the Linked Open Data (LOD) cloud and further propose an efficient data distribution strategy to host the resulting 20.4 billion triples data via several SPARQL endpoints. Having the TCGA data distributed across multiple SPARQL endpoints, we enable biomedical scientists to query and retrieve information from these SPARQL endpoints by proposing a TCGA tailored federated SPARQL query processing engine named TopFed.
Results
We compare TopFed with a well established federation engine FedX in terms of source selection and query execution time by using 10 different federated SPARQL queries with varying requirements. Our evaluation results show that TopFed selects on average less than half of the sources (with 100% recall) with query execution time equal to one third to that of FedX.
Conclusion
With TopFed, we aim to offer biomedical scientists a single-point-of-access through which distributed TCGA data can be accessed in unison. We believe the proposed system can greatly help researchers in the biomedical domain to carry out their research effectively with TCGA as the amount and diversity of data exceeds the ability of local resources to handle its retrieval and parsing.
doi:10.1186/2041-1480-5-47
PMCID: PMC4417511  PMID: 25937882
Federated queries; SPARQL; TCGA; RDF
23.  Utilization of the PICO framework to improve searching PubMed for clinical questions 
Background
Supporting 21st century health care and the practice of evidence-based medicine (EBM) requires ubiquitous access to clinical information and to knowledge-based resources to answer clinical questions. Many questions go unanswered, however, due to lack of skills in formulating questions, crafting effective search strategies, and accessing databases to identify best levels of evidence.
Methods
This randomized trial was designed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system. Two of the search interfaces utilized a specific framework called PICO, which was designed to focus clinical questions and to prompt for publication type or type of question asked. The third interface was the standard PubMed interface readily available on the Web. Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US. Thirty-one subjects were randomized to one of the three interfaces, given 3 clinical questions, and asked to search PubMed for a set of relevant articles that would provide an answer for each question. The success of the search results was determined by a precision score, which compared the number of relevant or gold standard articles retrieved in a result set to the total number of articles retrieved in that set.
Results
Participants using the PICO templates (Protocol A or Protocol B) had higher precision scores for each question than the participants who used Protocol C, the standard PubMed Web interface. (Question 1: A = 35%, B = 28%, C = 20%; Question 2: A = 5%, B = 6%, C = 4%; Question 3: A = 1%, B = 0%, C = 0%) 95% confidence intervals were calculated for the precision for each question using a lower boundary of zero. However, the 95% confidence limits were overlapping, suggesting no statistical difference between the groups.
Conclusion
Due to the small number of searches for each arm, this pilot study could not demonstrate a statistically significant difference between the search protocols. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results.
doi:10.1186/1472-6947-7-16
PMCID: PMC1904193  PMID: 17573961
24.  Diet and Physical Activity for the Prevention of Noncommunicable Diseases in Low- and Middle-Income Countries: A Systematic Policy Review 
PLoS Medicine  2013;10(6):e1001465.
Carl Lachat and colleagues evaluate policies in low- and middle-income countries addressing salt and fat consumption, fruit and vegetable intake, and physical activity, key risk factors for non-communicable diseases.
Please see later in the article for the Editors' Summary
Background
Diet-related noncommunicable diseases (NCDs) are increasing rapidly in low- and middle-income countries (LMICs) and constitute a leading cause of mortality. Although a call for global action has been resonating for years, the progress in national policy development in LMICs has not been assessed. This review of strategies to prevent NCDs in LMICs provides a benchmark against which policy response can be tracked over time.
Methods and Findings
We reviewed how government policies in LMICs outline actions that address salt consumption, fat consumption, fruit and vegetable intake, or physical activity. A structured content analysis of national nutrition, NCDs, and health policies published between 1 January 2004 and 1 January 2013 by 140 LMIC members of the World Health Organization (WHO) was carried out. We assessed availability of policies in 83% (116/140) of the countries. NCD strategies were found in 47% (54/116) of LMICs reviewed, but only a minority proposed actions to promote healthier diets and physical activity. The coverage of policies that specifically targeted at least one of the risk factors reviewed was lower in Africa, Europe, the Americas, and the Eastern Mediterranean compared to the other two World Health Organization regions, South-East Asia and Western Pacific. Of the countries reviewed, only 12% (14/116) proposed a policy that addressed all four risk factors, and 25% (29/116) addressed only one of the risk factors reviewed. Strategies targeting the private sector were less frequently encountered than strategies targeting the general public or policy makers.
Conclusions
This review indicates the disconnection between the burden of NCDs and national policy responses in LMICs. Policy makers urgently need to develop comprehensive and multi-stakeholder policies to improve dietary quality and physical activity.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Noncommunicable diseases (NCDs)—chronic medical conditions including cardiovascular diseases (heart disease and stroke), diabetes, cancer, and chronic respiratory diseases (chronic obstructive pulmonary disease and asthma)—are responsible for two-thirds of the world's deaths. Nearly 80% of NCD deaths, close to 30 million per year, occur in low- and middle-income countries (LMICs), where they are also rising most rapidly. Diet and lifestyle (including smoking, lack of exercise, and harmful alcohol consumption) influence a person's risk of developing an NCD and of dying from it. Because they can be modified, these risk factors have been at the center of strategies to combat NCDs. In 2004, the World Health Organization (WHO) adopted the Global Strategy on Diet, Physical Activity and Health. For diet, it recommended that individuals achieve energy balance and a healthy weight; limit energy intake from total fats and shift fat consumption away from saturated fats to unsaturated fats and towards the elimination of trans-fatty acids; increase consumption of fruits, vegetables, legumes, whole grains, and nuts; limit the intake of free sugars; and limit salt consumption from all sources and ensure that salt is iodized. For physical activity, it recommended at least 30 minutes of regular, moderate-intensity physical activity on most days throughout a person's life.
Why Was This Study Done?
By signing onto the Global Strategy in 2004, WHO member countries agreed to implement it with high priority. A first step of implementation is usually the development of local policies. Consequently, one of the four objectives of the WHO Global Strategy is “to encourage the development, strengthening and implementation of global, regional, national and community policies and action plans to improve diets and increase physical activity.” Along the same lines, in 2011 the United Nations held a high-level meeting in which the need to accelerate the policy response to the NCD epidemic was emphasized. This study was done to assess the existing national policies on NCD prevention in LMICs. Specifically, the researchers examined how well those policies matched the WHO recommendations for intake of salt, fat, and fruits and vegetables, as well as the recommendations for physical activity.
What Did the Researchers Do and Find?
The researchers searched the Internet (including websites of relevant ministries and departments) for all publicly available national policies related to diet, nutrition, NCDs, and health from all 140 WHO member countries classified as LMICs by the World Bank in 2011. For countries for which the search did not turn up policies, the researchers sent e-mail requests to the relevant national authorities, to the regional WHO offices, and to personal contacts. All documents dated from 1 January 2004 to 1 January 2013 that included national objectives and guidelines for action regarding diet, physical exercise, NCD prevention, or a combination of the three, were analyzed in detail.
Most of the policies obtained were not easy to find and access. For 24 countries, particularly in the Eastern Mediterranean, the researchers eventually gave up, unable to establish whether relevant national policies existed. Of the remaining 116 countries, 29 countries had no relevant policies, and another 30 had policies that failed to mention specifically any of the diet-related risk factors included in the analysis. Fifty-four of the 116 countries had NCD policies that addressed at least one of the risk factors. Thirty-six national policy documents contained strategies to increase fruit and vegetable intake, 20 addressed dietary fat consumption, 23 aimed to limit salt intake, and 35 had specific actions to promote physical activity. Only 14 countries, including Jamaica, the Philippines, Iran, and Mongolia, had policies that addressed all four risk factors. The policies of 27 countries mentioned only one of the four risk factors.
Policies primarily targeted consumers and government agencies and failed to address the roles of the business community or civil society. Consistent with this, most were missing plans, mechanisms, and incentives to drive collaborations between the different stakeholders.
What Do These Findings Mean?
More than eight years after the WHO Global Strategy was agreed upon, only a minority of the LMICs included in this analysis have comprehensive policies in place. Developing policies and making them widely accessible is a likely early step toward specific implementation and actions to prevent NCDs. These results therefore suggest that not enough emphasis is placed on NCD prevention in these countries through actions that have been proven to reduce known risk factors. That said, the more important question is what countries are actually doing to combat NCDs, something not directly addressed by this analysis.
In richer countries, NCDs have for decades been the leading cause of sickness and death, and the fact that public health strategies need to emphasize NCD prevention is now widely recognized. LMICs not only have more limited resources, they also continue to carry a large burden from infectious diseases. It is therefore not surprising that shifting resources towards NCD prevention is a difficult process, even if the human cost of these diseases is massive and increasing. That only about 3% of global health aid is aimed at NCD prevention does not help the situation.
The authors argue that one step toward improving the situation is better sharing of best practices and what works and what doesn't in policy development. They suggest that an open-access repository like one that exists for Europe could improve the situation. They offer to organize, host, and curate such a resource under the auspices of WHO, starting with the policies retrieved for this study, and they invite submission of additional policies and updates.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001465.
This study is further discussed in a PLOS Medicine Perspective by Stuckler and Basu
The WHO website on diet and physical activity contains links to various documents, including a diet and physical activity implementation toolbox that contains links to the 2004 Global Strategy document and a Framework to Monitor and Evaluate Implementation
There is a 2011 WHO primer on NCDs entitled Prioritizing a Preventable Epidemic
A recent PLOS Medicine editorial and call for papers addressing the global disparities in the burden from NCDs
A PLOS Blogs post entitled Politics and Global HealthAre We Missing the Obvious? and associated comments discuss the state of the fight against NCDs in early 2013
The NCD Alliance was founded by the Union for International Cancer Control, the International Diabetes Federation, the World Heart Federation, and the International Union Against Tuberculosis and Lung Disease; its mission is to combat the NCD epidemic by putting health at the center of all policies
The WHO European Database on Nutrition, Obesity and Physical Activity (NOPA) contains national and subnational surveillance data, policy documents, actions to implement policy, and examples of good practice in programs and interventions for the WHO European member states
doi:10.1371/journal.pmed.1001465
PMCID: PMC3679005  PMID: 23776415
25.  Total disc replacement surgery for symptomatic degenerative lumbar disc disease: a systematic review of the literature 
European Spine Journal  2010;19(8):1262-1280.
The objective of this study is to evaluate the effectiveness and safety of total disc replacement surgery compared with spinal fusion in patients with symptomatic lumbar disc degeneration. Low back pain (LBP), a major health problem in Western countries, can be caused by a variety of pathologies, one of which is degenerative disc disease (DDD). When conservative treatment fails, surgery might be considered. For a long time, lumbar fusion has been the “gold standard” of surgical treatment for DDD. Total disc replacement (TDR) has increased in popularity as an alternative for lumbar fusion. A comprehensive systematic literature search was performed up to October 2008. Two reviewers independently checked all retrieved titles and abstracts, and relevant full text articles for inclusion. Two reviewers independently assessed the risk of bias of included studies and extracted relevant data and outcomes. Three randomized controlled trials and 16 prospective cohort studies were identified. In all three trials, the total disc replacement was compared with lumbar fusion techniques. The Charité trial (designed as a non-inferiority trail) was considered to have a low risk of bias for the 2-year follow up, but a high risk of bias for the 5-year follow up. The Charité artificial disc was non-inferior to the BAK® Interbody Fusion System on a composite outcome of “clinical success” (57.1 vs. 46.5%, for the 2-year follow up; 57.8 vs. 51.2% for the 5-year follow up). There were no statistically significant differences in mean pain and physical function scores. The Prodisc artificial disc (also designed as a non-inferiority trail) was found to be statistically significant more effective when compared with the lumbar circumferential fusion on the composite outcome of “clinical success” (53.4 vs. 40.8%), but the risk of bias of this study was high. Moreover, there were no statistically significant differences in mean pain and physical function scores. The Flexicore trial, with a high risk of bias, found no clinical relevant differences on pain and physical function when compared with circumferential spinal fusion at 2-year follow up. Because these are preliminary results, in addition to the high risk of bias, no conclusions can be drawn based on this study. In general, these results suggest that no clinical relevant differences between the total disc replacement and fusion techniques. The overall success rates in both treatment groups were small. Complications related to the surgical approach ranged from 2.1 to 18.7%, prosthesis related complications from 2.0 to 39.3%, treatment related complications from 1.9 to 62.0% and general complications from 1.0 to 14.0%. Reoperation at the index level was reported in 1.0 to 28.6% of the patients. In the three trials published, overall complication rates ranged from 7.3 to 29.1% in the TDR group and from 6.3 to 50.2% in the fusion group. The overall reoperation rate at index-level ranged from 3.7 to 11.4% in the TDR group and from 5.4 to 26.1% in the fusion group. In conclusion, there is low quality evidence that the Charité is non-inferior to the BAK cage at the 2-year follow up on the primary outcome measures. For the 5-year follow up, the same conclusion is supported only by very low quality evidence. For the ProDisc, there is very low quality evidence for contradictory results on the primary outcome measures when compared with anterior lumbar circumferential fusion. High quality randomized controlled trials with relevant control group and long-term follow-up is needed to evaluate the effectiveness and safety of TDR.
doi:10.1007/s00586-010-1445-3
PMCID: PMC2989191  PMID: 20508954
Degenerative disc degeneration; Low back pain; Total disc replacement; Systematic review

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