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1.  Collection-based analysis of selected medical libraries in the Philippines using Doody’s Core Titles 
This study assessed the book collection of five selected medical libraries in the Philippines, based on Doodys’ Essential Purchase List for basic sciences and clinical medicine, to compare the match and non-match titles among libraries, to determine the strong and weak disciplines of each library, and to explore the factors that contributed to the percentage of match and non-match titles.
List checking was employed as the method of research.
Among the medical libraries, De La Salle Health Sciences Institute and University of Santo Tomas had the highest percentage of match titles, whereas Ateneo School of Medicine and Public Health had the lowest percentage of match titles. University of the Philippines Manila had the highest percentage of near-match titles.
De La Salle Health Sciences Institute and University of Santo Tomas had sound medical collections based on Doody’s Core Titles. Collectively, the medical libraries shared common collection development priorities, as evidenced by similarities in strong areas. Library budget and the role of the library director in book selection were among the factors that could contribute to a high percentage of match titles.
PMCID: PMC5234441  PMID: 28096742
2.  Developing a virtual community for health sciences library book selection: Doody's Core Titles 
Purpose: The purpose of this article is to describe Doody's Core Titles in the Health Sciences as a new selection guide and a virtual community based on an effective use of online systems and to describe its potential impact on library collection development.
Setting/Participants/Resources: The setting is the availability of health sciences selection guides. Participants include Doody Enterprise staff, Doody's Library Board of Advisors, content specialists, and library selectors. Resources include the online system used to create Doody's Core Titles along with references to complementary databases.
Brief Description: Doody's Core Titles is described and discussed in relation to the literature of selection guides, especially in comparison to the Brandon/Hill selected lists that were published from 1965 to 2003. Doody's Core Titles seeks to fill the vacuum created when the Brandon/Hill lists ceased publication. Doody's Core Titles is a unique selection guide based on its method of creating an online community of experts to identify and score a core list of titles in 119 health sciences specialties and disciplines.
Results/Outcome: The result is a new selection guide, now available annually, that will aid health sciences librarians in identifying core titles for local collections.
Evaluation Method: Doody's Core Titles organizes the evaluation of core titles that are identified and recommended by content specialists associated with Doody's Book Review Service and library selectors. A scoring mechanism is used to create the selection of core titles, similar to the star rating system employed in other Doody Enterprise products and services.
PMCID: PMC1324773  PMID: 16404471
6.  What Is eHealth (3): A Systematic Review of Published Definitions 
The term eHealth is widely used by many individuals, academic institutions, professional bodies, and funding organizations. It has become an accepted neologism despite the lack of an agreed-upon clear or precise definition. We believe that communication among the many individuals and organizations that use the term could be improved by comprehensive data about the range of meanings encompassed by the term.
To report the results of a systematic review of published, suggested, or proposed definitions of eHealth.
Data Sources
Using the search query string “eHealth” OR “e-Health” OR “electronic health”, we searched the following databases: Medline and Premedline (1966-June 2004), EMBASE (1980-May 2004), International Pharmaceutical Abstracts (1970-May 2004), Web of Science (all years), Information Sciences Abstracts (1966-May 2004), Library Information Sciences Abstracts (1969-May 2004), and Wilson Business Abstracts (1982-March 2004). In addition, we searched dictionaries and an Internet search engine.
Study Selection
We included any source published in either print format or on the Internet, available in English, and containing text that defines or attempts to define eHealth in explicit terms. Two of us independently reviewed titles and abstracts of citations identified in the bibliographic databases and Internet search, reaching consensus on relevance by discussion.
Data Extraction
We retrieved relevant reports, articles, references, letters, and websites containing definitions of eHealth. Two of us qualitatively analyzed the definitions and coded them for content, emerging themes, patterns, and novel ideas.
Data Synthesis
The 51 unique definitions that we retrieved showed a wide range of themes, but no clear consensus about the meaning of the term eHealth. We identified 2 universal themes (health and technology) and 6 less general (commerce, activities, stakeholders, outcomes, place, and perspectives).
The widespread use of the term eHealth suggests that it is an important concept, and that there is a tacit understanding of its meaning. This compendium of proposed definitions may improve communication among the many individuals and organizations that use the term.
PMCID: PMC1550636  PMID: 15829471
eHealth; Internet; medical informatics; systematic review; information services; telemedicine
7.  Online medical books: their availability and an assessment of how health sciences libraries provide access on their public Websites 
Objective: The objective of this study was to determine the number and topical range of available online medical books and to assess how health sciences libraries were providing access to these resources on their public Websites.
Method: The collection-based evaluative technique of list checking was used to assess the number and topical range of online medical books of the six largest publishers. Publisher inventory lists were downloaded over a two-day period (May 16–17, 2004). Titles were counted and compared with the 2003 Brandon/Hill list. A sample of health sciences libraries was subsequently derived by consulting the 2004 “Top Medical Schools-Research” in U.S. News & World Report. Bibliographic and bibliothecal access methods were evaluated based on an inspection of the publicly available Websites of the sample libraries.
Results: Of 318 currently published online medical books, 151 (47%) were Brandon/Hill titles covering 42 of 59 Brandon/Hill topics (71%). These 151 titles represented 22% (N = 672) of the Brandon/Hill list, which further broke down as 52 minimal core, 41 initial purchase, and 58 other recommended Brandon/Hill titles. These numbers represented 50%, 28%, and 12%, respectively, of all Brandon/Hill titles corresponding to those categories. In terms of bibliographic access, 20 of 21 of sampled libraries created catalog records for their online medical books, 1 of which also provided analytical access at the chapter level, and none provided access at the chapter section level. Of the 21 libraries, 19 had library Website search engines that provided title-level access and 4 provided access at the chapter level and none that at the chapter section level. For bibliothecal access, 19 of 21 libraries provided title-level access to medical books, 8 of which provided classified and alphabetic arrangements, 1 provided a classified arrangement only, and 10 provided an alphabetic arrangement only. No library provided a bibliothecal arrangement for medical book chapters or chapter sections.
Conclusions: This study shows that the number and topical range of online medical books is reaching a point where collection-level consideration is warranted to facilitate efficient use and to prevent the problem of split files. However, the results also show that few efforts are underway on the publicly available Websites of the surveyed health sciences libraries to provide the analytical access necessary to meet the structural needs of clinical information seekers.
PMCID: PMC1324775  PMID: 16404473
8.  A systematic review of implementation frameworks of innovations in healthcare and resulting generic implementation framework 
Implementation science and knowledge translation have developed across multiple disciplines with the common aim of bringing innovations to practice. Numerous implementation frameworks, models, and theories have been developed to target a diverse array of innovations. As such, it is plausible that not all frameworks include the full range of concepts now thought to be involved in implementation. Users face the decision of selecting a single or combining multiple implementation frameworks. To aid this decision, the aim of this review was to assess the comprehensiveness of existing frameworks.
A systematic search was undertaken in PubMed to identify implementation frameworks of innovations in healthcare published from 2004 to May 2013. Additionally, titles and abstracts from Implementation Science journal and references from identified papers were reviewed. The orientation, type, and presence of stages and domains, along with the degree of inclusion and depth of analysis of factors, strategies, and evaluations of implementation of included frameworks were analysed.
Frameworks were assessed individually and grouped according to their targeted innovation. Frameworks for particular innovations had similar settings, end-users, and ‘type’ (descriptive, prescriptive, explanatory, or predictive). On the whole, frameworks were descriptive and explanatory more often than prescriptive and predictive. A small number of the reviewed frameworks covered an implementation concept(s) in detail, however, overall, there was limited degree and depth of analysis of implementation concepts. The core implementation concepts across the frameworks were collated to form a Generic Implementation Framework, which includes the process of implementation (often portrayed as a series of stages and/or steps), the innovation to be implemented, the context in which the implementation is to occur (divided into a range of domains), and influencing factors, strategies, and evaluations.
The selection of implementation framework(s) should be based not solely on the healthcare innovation to be implemented, but include other aspects of the framework’s orientation, e.g., the setting and end-user, as well as the degree of inclusion and depth of analysis of the implementation concepts. The resulting generic structure provides researchers, policy-makers, health administrators, and practitioners a base that can be used as guidance for their implementation efforts.
Electronic supplementary material
The online version of this article (doi:10.1186/s12961-015-0005-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4364490  PMID: 25885055
Diffusion; Framework; Implementation; Knowledge translation; Model; Systematic literature review; Theory
9.  Mapping the literature of health care management 
Objectives: The research provides an overview of the health care management literature and the indexing coverage of core journal literature.
Method: Citations from five source journals for the years 2002 through 2004 were studied using the protocols of the Mapping the Literature of Allied Health Project and Mapping the Literature of Nursing Project. The productivity of cited journals was analyzed by applying Bradford's Law of Scattering.
Results: Journals were the most frequently cited format, followed by books. Only 3.2% of the cited journal titles from all 5 source journals generated two-thirds of the cited titles. When only the health care management practitioner–oriented source journals were considered, two-thirds of the output of cited journal titles came from 10.8% of the titles. Science Citation Index and PubMed provided the best overall coverage of the titles cited by all 5 source journals, while the cited titles from the 2 practitioner-oriented journals were covered most completely by Social Sciences Citation Index and Business Source Complete.
Conclusions: Health care management is a multidisciplinary field. Librarians must consider the needs of their users and assist them by providing the necessary materials and combination of indexes to access this field adequately.
PMCID: PMC1852631  PMID: 17443238
10.  The Increasing Use of Theory in Social Gerontology: 1990–2004 
To determine how often theory is used in published research in social gerontology, compare theory use over a 10-year period (1990–1994 to 2000–2004), and identify the theories most frequently used in social gerontology research.
Systematic review of articles published in eight leading journals from 2000 to 2004 (N = 1,046) and comparison with a review conducted 10 years earlier.
Theory was mentioned in 39% of articles published from 2000 to 2004, representing a 12% increase in the use of theory over 10 years. This increase was driven by theories outside the core sociology of aging theories identified by Bengtson, V. L., Burgess, E. O., and Parrott, T. M. (1997). Theory, explanation, and a third generation of theoretical development in social gerontology. Journal of Gerontology: Social Sciences, 52B, S72–S88. The five most frequently used theories included the life course perspective, life-span developmental theories, role theory, exchange theory, and person–environment theory/ecological theories of aging. Commonly used models included stress process/stress and coping models, successful aging models, the Andersen behavioral model of health services use, models of control/self-efficacy/mastery, and disablement process models.
Theory use in social gerontology increased between 1990 and 2004, with a shift toward theories that cross disciplines. However, the majority of research in social gerontology continues to be atheoretical. Models are widely used as a supplement to or substitute for theory. Many of these models are currently being debated and elaborated, and over time, they may emerge as important theoretical contributions to social gerontology.
PMCID: PMC2920947  PMID: 20675614
Models; Science of gerontology; Theories of aging
11.  Roles of DctA and DctB in Signal Detection by the Dicarboxylic Acid Transport System of Rhizobium leguminosarum 
Journal of Bacteriology  1998;180(10):2660-2669.
The dctA gene, coding for the dicarboxylate transport protein, has an inducible promoter dependent on activation by the two-component sensor-regulator pair DctB and DctD. LacZ fusion analysis indicates that there is a single promoter for dctB and dctD. The dctA promoter is also induced by nitrogen limitation, an effect that requires DctB-DctD and NtrC. DctB alone is able to detect dicarboxylates in the absence of DctA and initiate transcription via DctD. However, DctA modifies signal detection by DctB such that in the absence of DctA, the ligand specificity of DctB is broader. dctAp also responds to heterologous induction by osmotic stress in the absence of DctA. This effect requires both DctB and DctD. A transposon insertion in the dctA-dctB intergenic region (dctA101) which locks transcription of dctA at a constitutive level independent of DctB-DctD results in improper signalling by DctB-DctD. Strain RU150, which carries this insertion, is defective in nitrogen fixation (Fix−) and grows very poorly on ammonia as a nitrogen source whenever the DctB-DctD signalling circuit is activated by the presence of a dicarboxylate ligand. Mutation of dctB or dctD in strain RU150 reinstates normal growth on dicarboxylates. This suggests that DctD-P improperly regulates a heterologous nitrogen-sensing operon. Increased expression of DctA, either via a plasmid or by chromosomal duplication, restores control of DctB-DctD and allows strain RU150 to grow on ammonia in the presence of a dicarboxylate. Thus, while DctB is a sensor for dicarboxylates in its own right, it is regulated by DctA. The absence of DctA allows DctB and DctD to become promiscuous with regard to signal detection and cross talk with other operons. This indicates that DctA contributes significantly to the signalling specificity of DctB-DctD and attenuates cross talk with other operons.
PMCID: PMC107217  PMID: 9573150
12.  Comparison of internal target volumes defined on 3-dimensional, 4-dimensonal, and cone-beam CT images of non-small-cell lung cancer 
OncoTargets and therapy  2016;9:6945-6951.
The purpose of this study was to compare the positional and volumetric differences of internal target volumes defined on three-dimensional computed tomography (3DCT), four-dimensional CT (4DCT), and cone-beam CT (CBCT) images of non-small-cell lung cancer (NSCLC).
Materials and methods
Thirty-one patients with NSCLC sequentially underwent 3DCT and 4DCT simulation scans of the thorax during free breathing. The first CBCT was performed and registered to the planning CT using the bony anatomy registration during radiotherapy. The gross tumor volumes were contoured on the basis of 3DCT, maximum intensity projection (MIP) of 4DCT, and CBCT. CTV3D (clinical target volume), internal target volumes, ITVMIP and ITVCBCT, were defined with a 7 mm margin accounting for microscopic disease. ITV10 mm and ITV5 mm were defined on the basis of CTV3D: ITV10 mm with a 5 mm margin in left–right (LR), anterior–posterior (AP) directions and 10 mm in cranial–caudal (CC) direction; ITV5 mm with an isotropic internal margin (IM) of 5 mm. The differences in the position, size, Dice’s similarity coefficient (DSC) and inclusion relation of different volumes were evaluated.
The median size ratios of ITV10 mm, ITV5 mm, and ITVMIP to ITVCBCT were 2.33, 1.88, and 1.03, respectively, for tumors in the upper lobe and 2.13, 1.76, and 1.1, respectively, for tumors in the middle-lower lobe. The median DSCs of ITV10 mm, ITV5 mm, ITVMIP, and ITVCBCT were 0.6, 0.66, and 0.83 for all patients. The median percentages of ITVCBCT not included in ITV10 mm, ITV5 mm, and ITVMIP were 0.1%, 1.63%, and 15.21%, respectively, while the median percentages of ITV10 mm, ITV5 mm, and ITVMIP not included in ITVCBCT were 57.08%, 48.89%, and 20.04%, respectively.
The use of the individual ITV derived from 4DCT merely based on bony registration in radiotherapy may result in a target miss. The ITVs derived from 3DCT with isotropic margins have a good coverage of the ITV from CBCT, but the use of those would result in a high proportion of normal tissue being irradiated unnecessarily.
PMCID: PMC5119621  PMID: 27895491
non-small-cell lung cancer; cone-beam CT; four-dimensional CT; three-dimensional CT; internal target volume; volume comparison
13.  The Chilling Effect: How Do Researchers React to Controversy? 
PLoS Medicine  2008;5(11):e222.
Can political controversy have a “chilling effect” on the production of new science? This is a timely concern, given how often American politicians are accused of undermining science for political purposes. Yet little is known about how scientists react to these kinds of controversies.
Methods and Findings
Drawing on interview (n = 30) and survey data (n = 82), this study examines the reactions of scientists whose National Institutes of Health (NIH)-funded grants were implicated in a highly publicized political controversy. Critics charged that these grants were “a waste of taxpayer money.” The NIH defended each grant and no funding was rescinded. Nevertheless, this study finds that many of the scientists whose grants were criticized now engage in self-censorship. About half of the sample said that they now remove potentially controversial words from their grant and a quarter reported eliminating entire topics from their research agendas. Four researchers reportedly chose to move into more secure positions entirely, either outside academia or in jobs that guaranteed salaries. About 10% of the group reported that this controversy strengthened their commitment to complete their research and disseminate it widely.
These findings provide evidence that political controversies can shape what scientists choose to study. Debates about the politics of science usually focus on the direct suppression, distortion, and manipulation of scientific results. This study suggests that scholars must also examine how scientists may self-censor in response to political events.
Drawing on interview and survey data, Joanna Kempner's study finds that political controversies shape what many scientists choose not to study.
Editors' Summary
Scientific research is an expensive business and, inevitably, the organizations that fund this research—governments, charities, and industry—play an important role in determining the directions that this research takes. Funding bodies can have both positive and negative effects on the acquisition of scientific knowledge. They can pump money into topical areas such as the human genome project. Alternatively, by withholding funding, they can discourage some types of research. So, for example, US federal funds cannot be used to support many aspects of human stem cell research. “Self-censoring” by scientists can also have a negative effect on scientific progress. That is, some scientists may decide to avoid areas of research in which there are many regulatory requirements, political pressure, or in which there is substantial pressure from advocacy groups. A good example of this last type of self-censoring is the withdrawal of many scientists from research that involves certain animal models, like primates, because of animal rights activists.
Why Was This Study Done?
Some people think that political controversy might also encourage scientists to avoid some areas of scientific inquiry, but no studies have formally investigated this possibility. Could political arguments about the value of certain types of research influence the questions that scientists pursue? An argument of this sort occurred in the US in 2003 when Patrick Toomey, who was then a Republican Congressional Representative, argued that National Institutes of Health (NIH) grants supporting research into certain aspects of sexual behavior were “much less worthy of taxpayer funding” than research on “devastating diseases,” and proposed an amendment to the 2004 NIH appropriations bill (which regulates the research funded by NIH). The Amendment was rejected, but more than 200 NIH-funded grants, most of which examined behaviors that affect the spread of HIV/AIDS, were internally reviewed later that year; NIH defended each grant, so none were curtailed. In this study, Joanna Kempner investigates how the scientists whose US federal grants were targeted in this clash between politics and science responded to the political controversy.
What Did the Researchers Do and Find?
Kempner interviewed 30 of the 162 principal investigators (PIs) whose grants were reviewed. She asked them to describe their research, the grants that were reviewed, and their experience with NIH before, during, and after the controversy. She also asked them whether this experience had changed their research practice. She then used the information from these interviews to design a survey that she sent to all the PIs whose grants had been reviewed; 82 responded. About half of the scientists interviewed and/or surveyed reported that they now remove “red flag” words (for example, “AIDS” and “homosexual”) from the titles and abstracts of their grant applications. About one-fourth of the respondents no longer included controversial topics (for example, “abortion” and “emergency contraception”) in their research agendas, and four researchers had made major career changes as a result of the controversy. Finally, about 10% of respondents said that their experience had strengthened their commitment to see their research completed and its results published although even many of these scientists also engaged in some self-censorship.
What Do These Findings Mean?
These findings show that, even though no funding was withdrawn, self-censoring is now common among the scientists whose grants were targeted during this particular political controversy. Because this study included researchers in only one area of health research, its findings may not be generalizable to other areas of research. Furthermore, because only half of the PIs involved in the controversy responded to the survey, these findings may be affected by selection bias. That is, the scientists most anxious about the effects of political controversy on their research funding (and thus more likely to engage in self-censorship) may not have responded. Nevertheless, these findings suggest that the political environment might have a powerful effect on self-censorship by scientists and might dissuade some scientists from embarking on research projects that they would otherwise have pursued. Further research into what Kempner calls the “chilling effect” of political controversy on scientific research is now needed to ensure that a healthy balance can be struck between political involvement in scientific decision making and scientific progress.
Additional Information.
Please access these Web sites via the online version of this summary at
The Consortium of Social Science Associations, an advocacy organization that provides a bridge between the academic research community and Washington policymakers, has more information about the political controversy initiated by Patrick Toomey
Some of Kempner's previous research on self-censorship by scientists is described in a 2005 National Geographic news article
PMCID: PMC2586361  PMID: 19018657
14.  The Sensor Kinase DctS Forms a Tripartite Sensor Unit with DctB and DctA for Sensing C4-Dicarboxylates in Bacillus subtilis 
Journal of Bacteriology  2014;196(5):1084-1093.
The DctSR two-component system of Bacillus subtilis controls the expression of the aerobic C4-dicarboxylate transporter DctA. Deletion of DctA leads to an increased dctA expression. The inactivation of DctB, an extracellular binding protein, is known to inhibit the expression of dctA. Here, interaction between the sensor kinase DctS and the transporter DctA as well as the binding protein DctB was demonstrated in vivo using streptavidin (Strep) or His protein interaction experiments (mSPINE or mHPINE), and the data suggest that DctA and DctB act as cosensors for DctS. The interaction between DctS and DctB was also confirmed by the bacterial two-hybrid system (BACTH). In contrast, no indication was obtained for a direct interaction between the transporter DctA and the binding protein DctB. Activity levels of uptake of [14C]succinate by bacteria that expressed DctA from a plasmid were similar in the absence and the presence of DctB, demonstrating that the binding protein DctB is not required for transport. Thus, DctB is involved not in transport but in cosensing with DctS, highlighting DctB as the first example of a TRAP-type binding protein that acts as a cosensor. The simultaneous presence of DctS/DctB and DctS/DctA sensor pairs and the lack of direct interaction between the cosensors DctA and DctB indicate the formation of a tripartite complex via DctS. It is suggested that the DctS/DctA/DctB complex forms the functional unit for C4-dicarboxylate sensing in B. subtilis.
PMCID: PMC3957698  PMID: 24375102
15.  Imaging methods for quantifying glenoid and Hill-Sachs bone loss in traumatic instability of the shoulder: a scoping review 
Glenohumeral instability is a common problem following traumatic anterior shoulder dislocation. Two major risk factors of recurrent instability are glenoid and Hill-Sachs bone loss. Higher failure rates of arthroscopic Bankart repairs are associated with larger degrees of bone loss; therefore it is important to accurately and reliably quantify glenohumeral bone loss pre-operatively. This may be done with radiography, CT, or MRI; however no gold standard modality or method has been determined. A scoping review of the literature was performed to identify imaging methods for quantifying glenohumeral bone loss.
The scoping review was systematic in approach using a comprehensive search strategy and standardized study selection and evaluation. MEDLINE, EMBASE, Scopus, and Web of Science were searched. Initial selection included articles from January 2000 until July 2013, and was based on the review of titles and abstracts. Articles were carried forward if either reviewer thought that the study was appropriate. Final study selection was based on full text review based on pre-specified criteria. Consensus was reached for final article inclusion through discussion amongst the investigators. One reviewer extracted data while a second reviewer independently assessed data extraction for discrepancies.
Forty-one studies evaluating glenoid and/or Hill-Sachs bone loss were included: 32 studies evaluated glenoid bone loss while 11 studies evaluated humeral head bone loss. Radiography was useful as a screening tool but not to quantify glenoid bone loss. CT was most accurate but necessitates radiation exposure. The Pico Method and Glenoid Index method were the most accurate and reliable methods for quantifying glenoid bone loss, particularly when using three-dimensional CT (3DCT). Radiography and CT have been used to quantify Hill-Sachs bone loss, but have not been studied as extensively as glenoid bone loss.
Radiography can be used for screening patients for significant glenoid bone loss. CT imaging, using the Glenoid Index or Pico Method, has good evidence for accurate quantification of glenoid bone loss. There is limited evidence to guide imaging of Hill-Sachs bone loss. As a consensus has not been reached, further study will help to clarify the best imaging modality and method for quantifying glenohumeral bone loss.
Electronic supplementary material
The online version of this article (doi:10.1186/s12891-015-0607-1) contains supplementary material, which is available to authorized users.
PMCID: PMC4506419  PMID: 26187270
Shoulder instability; Diagnostic imaging; Specificity; Sensitivity
16.  Trends in reference usage statistics in an academic health sciences library 
Purpose: To examine reference questions asked through traditional means at an academic health sciences library and place this data within the context of larger trends in reference services.
Methodology: Detailed data on the types of reference questions asked were collected during two one-month periods in 2003 and 2004. General statistics documenting broad categories of questions were compiled over a fifteen-year period.
Results: Administrative data show a steady increase in questions from 1990 to 1997/98 (23,848 to 48,037, followed by a decline through 2004/05 to 10,031. The distribution of reference questions asked over the years has changed—including a reduction in mediated searches 2,157 in 1990/91 to 18 in 2004/05, an increase in instruction 1,284 in 1993/94 to 1,897 in 2004/05 and an increase in digital reference interactions 0 in 1999/2000 to 581 in 2004/05. The most commonly asked questions at the current reference desk are about journal holdings 19%, book holdings 12%, and directional issues 12%.
Conclusions: This study provides a unique snapshot of reference services in the contemporary library, where both online and offline services are commonplace. Changes in questions have impacted the way the library provides services, but traditional reference remains the core of information services in this health sciences library.
PMCID: PMC1773032  PMID: 17252063
17.  Application of statistical process control in healthcare improvement: systematic review 
Quality & Safety in Health Care  2007;16(5):387-399.
To systematically review the literature regarding how statistical process control—with control charts as a core tool—has been applied to healthcare quality improvement, and to examine the benefits, limitations, barriers and facilitating factors related to such application.
Data sources
Original articles found in relevant databases, including Web of Science and Medline, covering the period 1966 to June 2004.
Study selection
From 311 articles, 57 empirical studies, published between 1990 and 2004, met the inclusion criteria.
A standardised data abstraction form was used for extracting data relevant to the review questions, and the data were analysed thematically.
Statistical process control was applied in a wide range of settings and specialties, at diverse levels of organisation and directly by patients, using 97 different variables. The review revealed 12 categories of benefits, 6 categories of limitations, 10 categories of barriers, and 23 factors that facilitate its application and all are fully referenced in this report. Statistical process control helped different actors manage change and improve healthcare processes. It also enabled patients with, for example asthma or diabetes mellitus, to manage their own health, and thus has therapeutic qualities. Its power hinges on correct and smart application, which is not necessarily a trivial task. This review catalogues 11 approaches to such smart application, including risk adjustment and data stratification.
Statistical process control is a versatile tool which can help diverse stakeholders to manage change in healthcare and improve patients' health.
PMCID: PMC2464970  PMID: 17913782
18.  Polysomnography in Patients With Obstructive Sleep Apnea 
Executive Summary
The objective of this health technology policy assessment was to evaluate the clinical utility and cost-effectiveness of sleep studies in Ontario.
Clinical Need: Target Population and Condition
Sleep disorders are common and obstructive sleep apnea (OSA) is the predominant type. Obstructive sleep apnea is the repetitive complete obstruction (apnea) or partial obstruction (hypopnea) of the collapsible part of the upper airway during sleep. The syndrome is associated with excessive daytime sleepiness or chronic fatigue. Several studies have shown that OSA is associated with hypertension, stroke, and other cardiovascular disorders; many researchers believe that these cardiovascular disorders are consequences of OSA. This has generated increasing interest in recent years in sleep studies.
The Technology Being Reviewed
There is no ‘gold standard’ for the diagnosis of OSA, which makes it difficult to calibrate any test for diagnosis. Traditionally, polysomnography (PSG) in an attended setting (sleep laboratory) has been used as a reference standard for the diagnosis of OSA. Polysomnography measures several sleep variables, one of which is the apnea-hypopnea index (AHI) or respiratory disturbance index (RDI). The AHI is defined as the sum of apneas and hypopneas per hour of sleep; apnea is defined as the absence of airflow for ≥ 10 seconds; and hypopnea is defined as reduction in respiratory effort with ≥ 4% oxygen desaturation. The RDI is defined as the sum of apneas, hypopneas, and abnormal respiratory events per hour of sleep. Often the two terms are used interchangeably. The AHI has been widely used to diagnose OSA, although with different cut-off levels, the basis for which are often unclear or arbitrarily determined. Generally, an AHI of more than five events per hour of sleep is considered abnormal and the patient is considered to have a sleep disorder. An abnormal AHI accompanied by excessive daytime sleepiness is the hallmark for OSA diagnosis. For patients diagnosed with OSA, continuous positive airway pressure (CPAP) therapy is the treatment of choice. Polysomnography may also used for titrating CPAP to individual needs.
In January 2005, the College of Physicians and Surgeons of Ontario published the second edition of Independent Health Facilities: Clinical Practice Parameters and Facility Standards: Sleep Medicine, commonly known as “The Sleep Book.” The Sleep Book states that OSA is the most common primary respiratory sleep disorder and a full overnight sleep study is considered the current standard test for individuals in whom OSA is suspected (based on clinical signs and symptoms), particularly if CPAP or surgical therapy is being considered.
Polysomnography in a sleep laboratory is time-consuming and expensive. With the evolution of technology, portable devices have emerged that measure more or less the same sleep variables in sleep laboratories as in the home. Newer CPAP devices also have auto-titration features and can record sleep variables including AHI. These devices, if equally accurate, may reduce the dependency on sleep laboratories for the diagnosis of OSA and the titration of CPAP, and thus may be more cost-effective.
Difficulties arise, however, when trying to assess and compare the diagnostic efficacy of in-home PSG versus in-lab. The AHI measured from portable devices in-home is the sum of apneas and hypopneas per hour of time in bed, rather than of sleep, and the absolute diagnostic efficacy of in-lab PSG is unknown. To compare in-home PSG with in-lab PSG, several researchers have used correlation coefficients or sensitivity and specificity, while others have used Bland-Altman plots or receiver operating characteristics (ROC) curves. All these approaches, however, have potential pitfalls. Correlation coefficients do not measure agreement; sensitivity and specificity are not helpful when the true disease status is unknown; and Bland-Altman plots measure agreement (but are helpful when the range of clinical equivalence is known). Lastly, receiver operating characteristics curves are generated using logistic regression with the true disease status as the dependent variable and test values as the independent variable. Thus, each value of the test is used as a cut-point to measure sensitivity and specificity, which are then plotted on an x-y plane. The cut-point that maximizes both sensitivity and specificity is chosen as the cut-off level to discriminate between disease and no-disease states. In the absence of a gold standard to determine the true disease status, ROC curves are of minimal value.
At the request of the Ontario Health Technology Advisory Committee (OHTAC), MAS has thus reviewed the literature on PSG published over the last two years to examine new developments.
Review Strategy
There is a large body of literature on sleep studies and several reviews have been conducted. Two large cohort studies, the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study, are the main sources of evidence on sleep literature.
To examine new developments on PSG published in the past two years, MEDLINE, EMBASE, MEDLINE In-Process & Other Non-Indexed Citations, the Cochrane Database of Systematic Reviews and Cochrane CENTRAL, INAHTA, and websites of other health technology assessment agencies were searched. Any study that reported results of in-home or in-lab PSG was included. All articles that reported findings from the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study were also reviewed.
Diffusion of Sleep Laboratories
To estimate the diffusion of sleep laboratories, a list of sleep laboratories licensed under the Independent Health Facility Act was obtained. The annual number of sleep studies per 100,000 individuals in Ontario from 2000 to 2004 was also estimated using administrative databases.
Summary of Findings
Literature Review
A total of 315 articles were identified that were published in the past two years; 227 were excluded after reviewing titles and abstracts. A total of 59 articles were identified that reported findings of the Sleep Heart Health Study and the Wisconsin Sleep Cohort Study.
Based on cross-sectional data from the Wisconsin Sleep Cohort Study of 602 men and women aged 30 to 60 years, it is estimated that the prevalence of sleep-disordered breathing is 9% in women and 24% in men, on the basis of more than five AHI events per hour of sleep. Among the women with sleep disorder breathing, 22.6% had daytime sleepiness and among the men, 15.5% had daytime sleepiness. Based on this, the prevalence of OSA in the middle-aged adult population is estimated to be 2% in women and 4% in men.
Snoring is present in 94% of OSA patients, but not all snorers have OSA. Women report daytime sleepiness less often compared with their male counterparts (of similar age, body mass index [BMI], and AHI). Prevalence of OSA tends to be higher in older age groups compared with younger age groups.
Diagnostic Value of Polysomnography
It is believed that PSG in the sleep laboratory is more accurate than in-home PSG. In the absence of a gold standard, however, claims of accuracy cannot be substantiated. In general, there is poor correlation between PSG variables and clinical variables. A variety of cut-off points of AHI (> 5, > 10, and > 15) are arbitrarily used to diagnose and categorize severity of OSA, though the clinical importance of these cut-off points has not been determined.
Recently, a study of the use of a therapeutic trial of CPAP to diagnose OSA was reported. The authors studied habitual snorers with daytime sleepiness in the absence of other medical or psychiatric disorders. Using PSG as the reference standard, the authors calculated the sensitivity of this test to be 80% and its specificity to be 97%. Further, they concluded that PSG could be avoided in 46% of this population.
Obstructive Sleep Apnea and Obesity
Obstructive sleep apnea is strongly associated with obesity. Obese individuals (BMI >30 kg/m2) are at higher risk for OSA compared with non-obese individuals and up to 75% of OSA patients are obese. It is hypothesized that obese individuals have large deposits of fat in the neck that cause the upper airway to collapse in the supine position during sleep. The observations reported from several studies support the hypothesis that AHIs (or RDIs) are significantly reduced with weight loss in obese individuals.
Obstructive Sleep Apnea and Cardiovascular Diseases
Associations have been shown between OSA and comorbidities such as diabetes mellitus and hypertension, which are known risk factors for myocardial infarction and stroke. Patients with more severe forms of OSA (based on AHI) report poorer quality of life and increased health care utilization compared with patients with milder forms of OSA. From animal models, it is hypothesized that sleep fragmentation results in glucose intolerance and hypertension. There is, however, no evidence from prospective studies in humans to establish a causal link between OSA and hypertension or diabetes mellitus. It is also not clear that the associations between OSA and other diseases are independent of obesity; in most of these studies, patients with higher values of AHI had higher values of BMI compared with patients with lower AHI values.
A recent meta-analysis of bariatric surgery has shown that weight loss in obese individuals (mean BMI = 46.8 kg/m2; range = 32.30–68.80) significantly improved their health profile. Diabetes was resolved in 76.8% of patients, hypertension was resolved in 61.7% of patients, hyperlipidemia improved in 70% of patients, and OSA resolved in 85.7% of patients. This suggests that obesity leads to OSA, diabetes, and hypertension, rather than OSA independently causing diabetes and hypertension.
Health Technology Assessments, Guidelines, and Recommendations
In April 2005, the Centers for Medicare and Medicaid Services (CMS) in the United States published its decision and review regarding in-home and in-lab sleep studies for the diagnosis and treatment of OSA with CPAP. In order to cover CPAP, CMS requires that a diagnosis of OSA be established using PSG in a sleep laboratory. After reviewing the literature, CMS concluded that the evidence was not adequate to determine that unattended portable sleep study was reasonable and necessary in the diagnosis of OSA.
In May 2005, the Canadian Coordinating Office of Health Technology Assessment (CCOHTA) published a review of guidelines for referral of patients to sleep laboratories. The review included 37 guidelines and associated reviews that covered 18 applications of sleep laboratory studies. The CCOHTA reported that the level of evidence for many applications was of limited quality, that some cited studies were not relevant to the recommendations made, that many recommendations reflect consensus positions only, and that there was a need for more good quality studies of many sleep laboratory applications.
As of the time of writing, there are 97 licensed sleep laboratories in Ontario. In 2000, the number of sleep studies performed in Ontario was 376/100,000 people. There was a steady rise in sleep studies in the following years such that in 2004, 769 sleep studies per 100,000 people were performed, for a total of 96,134 sleep studies. Based on prevalence estimates of the Wisconsin Sleep Cohort Study, it was estimated that 927,105 people aged 30 to 60 years have sleep-disordered breathing. Thus, there may be a 10-fold rise in the rate of sleep tests in the next few years.
Economic Analysis
In 2004, approximately 96,000 sleep studies were conducted in Ontario at a total cost of ~$47 million (Cdn). Since obesity is associated with sleep disordered breathing, MAS compared the costs of sleep studies to the cost of bariatric surgery. The cost of bariatric surgery is $17,350 per patient. In 2004, Ontario spent $4.7 million per year for 270 patients to undergo bariatric surgery in the province, and $8.2 million for 225 patients to seek out-of-country treatment. Using a Markov model, it was concluded that shifting costs from sleep studies to bariatric surgery would benefit more patients with OSA and may also prevent health consequences related to diabetes, hypertension, and hyperlipidemia. It is estimated that the annual cost of treating comorbid conditions in morbidly obese patients often exceeds $10,000 per patient. Thus, the downstream cost savings could be substantial.
Considerations for Policy Development
Weight loss is associated with a decrease in OSA severity. Treating and preventing obesity would also substantially reduce the economic burden associated with diabetes, hypertension, hyperlipidemia, and OSA. Promotion of healthy weights may be achieved by a multisectorial approach as recommended by the Chief Medical Officer of Health for Ontario. Bariatric surgery has the potential to help morbidly obese individuals (BMI > 35 kg/m2 with an accompanying comorbid condition, or BMI > 40 kg/m2) lose weight. In January 2005, MAS completed an assessment of bariatric surgery, based on which OHTAC recommended an improvement in access to these surgeries for morbidly obese patients in Ontario.
Habitual snorers with excessive daytime sleepiness have a high pretest probability of having OSA. These patients could be offered a therapeutic trial of CPAP to diagnose OSA, rather than a PSG. A majority of these patients are also obese and may benefit from weight loss. Individualized weight loss programs should, therefore, be offered and patients who are morbidly obese should be offered bariatric surgery.
That said, and in view of the still evolving understanding of the causes, consequences and optimal treatment of OSA, further research is warranted to identify which patients should be screened for OSA.
PMCID: PMC3379160  PMID: 23074483
19.  Lifestyle and Outcomes of Assisted Reproductive Techniques: A Narrative Review 
Studies reveal that lifestyles such as physical activity patterns, obesity, nutrition, and smoking, are factors that affect laboratory test results and pregnancy outcomes induced by assisted fertility techniques in infertile couples. The present study is a narrative review of studies in this area.
In this study, researchers conducted their computer search in public databases Google Scholar general search engine, and then more specific: Science Direct, ProQuest, SID, Magiran, Irandoc, Pubmed, Scopus, cochrane library, and Psych info; Cumulative Index to Nursing and Allied Health Literature (CINAHL), using Medical Subject Headings (MeSH) keywords: infertility (sterility, infertility), lifestyle (life behavior, lifestyle), Assisted Reproductive Techniques (ART), antioxidant and infertility, social health, spiritual health, mental health, Alcohol and drug abuse, preventive factors, and instruments., and selected relevant articles to the study subject from 2004 to 2013. Firstly, a list of 150 papers generated from the initial search. Then reviewers studied titles and abstracts. Secondly, 111 papers were included. Finally, quality assessment of full text studies was performed by two independent reviewers. Researchers reviewed summary of all articles sought, ultimately used data from 62 full articles to compile this review paper.
Review of literature led to arrangement of 9 general categories of ART results’ relationship with weight watch and diet, exercise and physical activity, psychological health, avoiding medications, alcohol and drugs, preventing diseases, environmental health, spiritual health, social health, and physical health.
The following was obtained from review of studies: since lifestyle is among important, changeable, and influential factors in fertility, success of these methods can be greatly helped through assessment of lifestyle patterns of infertile couples, and design and implementation of healthy lifestyle counseling programs, before and during implementing assisted fertility techniques.
PMCID: PMC4803851  PMID: 26156898
lifestyle; assisted reproductive techniques; narrative review
20.  Quantity, Design, and Scope of the Palliative Oncology Literature 
The Oncologist  2011;16(5):694-703.
The quantity, research design, and research topics of palliative oncology publications in the first 6 months of 2004 and 2009 were reviewed, and significant deficiencies were identified.
The current state of the palliative oncology literature is unclear. We examined and compared the quantity, research design, and research topics of palliative oncology publications in the first 6 months of 2004 with the first 6 months of 2009. We systematically searched MEDLINE, PsychInfo, EMBASE, ISI Web of Science, and CINAHL for original studies, review articles, and systematic reviews related to “palliative care” and “cancer” during the first 6 months of 2004 and 2009. Two physicians reviewed the literature independently and coded the study characteristics with high inter-rater reliability. We found a consistent decrease in the proportion of oncology studies related to palliative care between 2004 and 2009, despite an absolute increase in the total number of palliative oncology studies. Combining the two time periods, the most common original study designs were case report/series, cross-sectional studies, and qualitative studies. Randomized controlled trials comprised 6% of all original studies. The most common topics were physical symptoms, health services research, and psychosocial issues. Communication, decision making, spirituality, education, and research methodologies all represented <5% of the literature. Comparing 2004 with 2009, we found an increase in the proportion of original studies among all palliative oncology publications but no significant difference in study design or research topic. We identified significant deficiencies in the quantity, design, and scope of the palliative oncology literature. Further effort and resources are necessary to improve the evidence base for this important field.
PMCID: PMC3228194  PMID: 21471275
Literature; Neoplasms; Palliative care; Research design
21.  Differential Access to Digital Communication Technology: Association with Health and Health Survey Recruitment within an African-American Underserviced Urban Population 
Digital communication technologies (DCT), such as cell phones and the internet, have begun to replace more traditional technologies even in technology-poor communities. We characterized access to DCT in an underserved urban population and whether access is associated with health and study participation. A general probability community sample and a purposive high-turnover housing sample were recruited and re-interviewed after 3 months. Selected characteristics were compared by sample type and retention. Associations between DCT access and self-reported health were examined using multivariable logistic regression. Of 363 eligible individuals, 184 (general community = 119; high-turnover housing = 65) completed the baseline survey. Eighty-four percent of respondents had a cell phone and 62% had ever texted. Ever use of the internet was high (69%) overall, but frequency and years of internet use were higher in the general community sample. Self-reported fair or poor health was more common for residents of cell phone–only households and those with less frequent internet use. Technology use was similar for those retained and not retained. Overall, access to DCT was high in this underserved urban population but varied by sample type. Health varied significantly by DCT use, but study retention did not. These data have implications for incorporating DCT into health-related research in urban populations.
PMCID: PMC3126929  PMID: 21279451
Technology and health; Recruitment and retention; Health survey research
22.  Negative regulation of sigma 54-dependent dctA expression by the transcriptional activator DctD. 
Journal of Bacteriology  1993;175(9):2674-2681.
In Rhizobium meliloti, the presence of the C4-dicarboxylate transport protein DctA is required for symbiotic N2 fixation in alfalfa root nodules. Expression of dctA is inducible and is mediated by a sensor and activator gene pair encoded by dctB and dctD. In the presence of C4-dicarboxylates, the DCTB sensor protein is believed to phosphorylate and activate DCTD, which in turn activates transcription at the sigma 54-dependent dctA promoter. Here, we present evidence that in addition to activating dctA transcription, DCTD can also repress expression of dctA. By employing an ntrC allele, ntrC283, whose product appears to activate dctA transcription independently of DCTD, we found that while ntrC283 leads to constitutive dctA expression in the absence of dctB and dctD, in a dctB+ dctD+ ntrC283 background high-level expression of dctA occurred in succinate but not in glucose-grown cells. This result suggested that in uninduced cells, inactive DCTD binds to the dctA promoter and prevents its activation by NTRC283. Consistent with the latter interpretation was the observation that overexpression of DCTD from a plasmid promoter prevents dctA expression and results in a Dct- phenotype. Moreover the Dct- phenotype resulting from the overexpression of dctD was dominant to ntrC283. Results from studies of the ability of ntrC283 to suppress the Dct- phenotype of dctB alleles, together with the finding that the Fix- phenotype of a particular dctB allele was dctD dependent, suggest that in particular dctB alleles, sufficient dctD transcription occurs such that the resulting inactive DCTD prevents activation of dctA transcription by NtrC283 or alternate symbiotic regulators. The latter suggestion is supported by the observation that in symbiosis, R. meliloti strains in which DCTD was overexpressed formed nodules which failed to fix nitrogen.
PMCID: PMC204570  PMID: 8478332
23.  64-Slice Computed Tomographic Angiography for the Diagnosis of Intermediate Risk Coronary Artery Disease 
Executive Summary
In July 2009, the Medical Advisory Secretariat (MAS) began work on Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease (CAD), an evidence-based review of the literature surrounding different cardiac imaging modalities to ensure that appropriate technologies are accessed by patients suspected of having CAD. This project came about when the Health Services Branch at the Ministry of Health and Long-Term Care asked MAS to provide an evidentiary platform on effectiveness and cost-effectiveness of non-invasive cardiac imaging modalities.
After an initial review of the strategy and consultation with experts, MAS identified five key non-invasive cardiac imaging technologies for the diagnosis of CAD. Evidence-based analyses have been prepared for each of these five imaging modalities: cardiac magnetic resonance imaging, single photon emission computed tomography, 64-slice computed tomographic angiography, stress echocardiography, and stress echocardiography with contrast. For each technology, an economic analysis was also completed (where appropriate). A summary decision analytic model was then developed to encapsulate the data from each of these reports (available on the OHTAC and MAS website).
The Non-Invasive Cardiac Imaging Technologies for the Diagnosis of Coronary Artery Disease series is made up of the following reports, which can be publicly accessed at the MAS website at: or at
Single Photon Emission Computed Tomography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Stress Echocardiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Stress Echocardiography with Contrast for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
64-Slice Computed Tomographic Angiography for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Cardiac Magnetic Resonance Imaging for the Diagnosis of Coronary Artery Disease: An Evidence-Based Analysis
Pease note that two related evidence-based analyses of non-invasive cardiac imaging technologies for the assessment of myocardial viability are also available on the MAS website:
Positron Emission Tomography for the Assessment of Myocardial Viability: An Evidence-Based Analysis
Magnetic Resonance Imaging for the Assessment of Myocardial Viability: an Evidence-Based Analysis
The Toronto Health Economics and Technology Assessment Collaborative has also produced an associated economic report entitled:
The Relative Cost-effectiveness of Five Non-invasive Cardiac Imaging Technologies for Diagnosing Coronary Artery Disease in Ontario [Internet]. Available from:
The objective of this report is to determine the accuracy of computed tomographic angiography (CTA) compared to the more invasive option of coronary angiography (CA) in the detection of coronary artery disease (CAD) in stable (non-emergent) symptomatic patients.
CT Angiography
CTA is a cardiac imaging test that assesses the presence or absence, as well as the extent, of coronary artery stenosis for the diagnosis of CAD. As such, it is a test of cardiac structure and anatomy, in contrast to the other cardiac imaging modalities that assess cardiac function. It is, however, unclear as to whether cardiac structural features alone, in the absence cardiac function information, are sufficient to determine the presence or absence of intermediate pretest risk of CAD.
CTA technology is changing rapidly with increasing scan speeds and anticipated reductions in radiation exposure. Initial scanners based on 4, 8, 16, 32, and 64 slice machines have been available since the end of 2004. Although 320-slice machines are now available, these are not widely diffused and the existing published evidence is specific to 64-slice scanners. In general, CTA allows for 3-dimensional (3D) viewing of the coronary arteries derived from software algorithms of 2-dimensional (2D) images.
The advantage of CTA over CA, the gold standard for the diagnosis of CAD, is that it is relatively less invasive and may serve as a test in determining which patients are best suited for a CA. CA requires insertion of a catheter through an artery in the arm or leg up to the area being studied, yet both tests involve contrast agents and radiation exposure. Therefore, the identification of patients for whom CTA or CA is more appropriate may help to avoid more invasive tests, treatment delays, and unnecessary radiation exposure. The main advantage of CA, however, is that treatment can be administered in the same session as the test procedure and as such, it’s recommended for patients with a pre-test probability of CAD of ≥80%. The progression to the more invasive CA allows for the diagnosis and treatment in one session without the added radiation exposure from a previous CTA.
The visibility of arteries in CTA images is best in populations with a disease prevalence, or pre-test probabilities of CAD, of 40% to 80%, beyond which patients are considered at high pre-test probability. Visibility decreases with increasing prevalence as arteries become increasingly calcified (coronary artery calcification is based on the Agaston score). Such higher risk patients are not candidates for the less invasive diagnostic procedures and should proceed directly to CA, where treatment can be administered in conjunction with the test itself, while bypassing the radiation exposure from CTA.
CTA requires the addition of an ionated contrast, which can be administered only in patients with sufficient renal function (creatinine levels >30 micromoles/litre) to allow for the clearing of the contrast from the body. In some cases, the contrast is administered in patients with creatinine levels less than 30 micromoles/litre.
A second important criterion for the administration of the CTA is patient heart rate, which should be less than 65 beats/min for the single source CTA machines and less than 80 beats/min for the dual source machines. To decrease heart rates to these levels, beta-blockers are often required. Although the accuracy of these two machines does not differ, the dual source machines can be utilized in a higher proportion of patients than the single source machines for patients with heart beats of up to 80 beats/min. Approximately 10% of patients are considered ineligible for CTA because of this inability to decrease heart rates to the required levels. Additional contra-indications include renal insufficiency as described above and atrial fibrillation, with approximately 10% of intermediate risk patients ineligible for CTA due these contraindications. The duration of the procedure may be between 1 and 1.5 hours, with about 15 minutes for the CTA and the remaining time for the preparation of the patient.
CTA is licensed by Health Canada as a Class III device. Currently, two companies have licenses for 64-slice CT scanners, Toshiba Medical Systems Corporation (License 67604) and Philips Medical Systems (License 67599 and 73260).
Research Questions
How does the accuracy of CTA compare to the more invasive CA in the diagnosis of CAD in symptomatic patients at intermediate risk of the disease?
How does the accuracy for CTA compare to other modalities in the detection of CAD?
Research Methods
Literature Search
A literature search was performed on July 20, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 until July 20, 2009. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any relevant studies not identified through the search. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology.
Inclusion Criteria
English language articles and English or French-language HTAs published from January 1, 2004 to July 20, 2009.
Randomized controlled trials (RCTs), non-randomized clinical trials, systematic reviews and meta-analyses.
Studies of symptomatic patients at intermediate pre-test probability of CAD.
Studies of single source CTA compared to CA for the diagnosis of CAD.
Studies in which sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) could be established. HTAs, SRs, clinical trials, observational studies.
Exclusion Criteria
Non-English studies.
Pediatric populations.
Studies of patients at low or high pre-test probability of CAD.
Studies of unstable patients, e.g., emergency room visits, or a prior diagnosis of CAD.
Studies in patients with non-ischemic heart disease.
Studies in which outcomes were not specific to those of interest in this report.
Studies in which CTA was not compared to CA in a stable population.
Outcomes of Interest)
CAD defined as ≥50% stenosis.
Coronary angiography.
Measures of Interest
Sensitivity, specificity;
Negative predictive value (NPV), positive predictive value (PPV);
Area under the curve (AUC) and diagnostic odds ratios (DOR).
Results of Literature Search and Evidence-Based Analysis
The literature search yielded two HTAs, the first published by MAS in April 2005, the other from the Belgian Health Care Knowledge Centre published in 2008, as well as three recent non-randomized clinical studies. The three most significant studies concerning the accuracy of CTA versus CA are the CORE-64 study, the ACCURACY trial, and a prospective, multicenter, multivendor study conducted in the Netherlands. Five additional non-randomized studies were extracted from the Belgian Health Technology Assessment (2008).
To provide summary estimates of sensitivity, specificity, area under the SROC curve (AUC) and diagnostic odds rations (DORs), a meta-analysis of the above-mentioned studies was conducted. Pooled estimates of sensitivity and specificity were 97.7% (95%CI: 95.5% - 99.9%) and 78.8% (95%CI: 70.8% - 86.8%), respectively. These results indicate that the sensitivity of CTA is almost as good as CA, while its specificity is poorer. The diagnostic odds ratio (DOR) was estimated at 157.0 (95%CI: 11.2 - 302.7) and the AUC was found to be 0.94; however, the inability to provide confidence estimates for this estimate decreased its utility as an adequate outcome measure in this review.
This meta-analysis was limited by the significant heterogeneity between studies for both the pooled sensitivity and specificity (heterogeneity Chi-square p=0.000). To minimize these statistical concerns, the analysis was restricted to studies of intermediate risk patients with no previous history of cardiac events. Nevertheless, the underlying prevalence of CAD ranged from 24.8% to 78% between studies, indicating that there was still some variability in the pre-test probabilities of disease within this stable population. The variation in the prevalence of CAD, accompanied with differences in the proportion of calcification, likely affected the specificity directly and the sensitivity indirectly across studies.
In February 2010, the results of the Ontario Multi-detector Computed Tomography Coronary Angiography Study (OMCAS) became available and were thus included in a second meta-analysis of the above studies. The OMCAS was a non-randomized double-blind study conducted in 3 centers in Ontario that was conducted as a result of a MAS review from 2005 requesting an evaluation of the accuracy of 64-slice CTA for CAD detection. Within 10 days of their scheduled CA, all patients received an additional evaluation with CTA. Included in the meta-analysis with the above-mentioned studies are 117 symptomatic patients with intermediate probability of CAD (10% - 90% probability), resulting in a pooled sensitivity of 96.1% (95%CI: 94.0%-98.3%) and pooled specificity of 81.5% (95%CI: 73.0% - 89.9%).
Summary of Findings
CTA is almost as good as CA in detecting true positives but poorer in the rate of false positives. The main value of CTA may be in ruling out significant CAD.
Increased prevalence of CAD decreases study specificity, whereas specificity is increased in the presence of increased arterial calcification even in lower prevalence studies.
Positive CT angiograms may require additional tests such as stress tests or the more invasive CA, partly to identify false positives.
Radiation exposure is an important safety concern that needs to be considered, particularly the cumulative exposures from repeat CTAs.
PMCID: PMC3377576  PMID: 23074388
24.  WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity 
BMC Public Health  2006;6:177.
Health care planning for chronic pelvic pain (CPP), an important cause of morbidity amongst women is hampered due to lack of clear collated summaries of its basic epidemiological data. We systematically reviewed worldwide literature on the prevalence of different types of CPP to assess the geographical distribution of data, and to explore sources of variation in its estimates.
We identified data available from Medline (1966 to 2004), Embase (1980 to 2004), PsycINFO (1887 to 2003), LILACS (1982 to 2004), Science Citation index, CINAHL (January 1980 to 2004) and hand searching of reference lists. Two reviewers extracted data independently, using a piloted form, on participants' characteristics, study quality and rates of CPP. We considered a study to be of high quality (valid) if had at least three of the following features: prospective design, validated measurement tool, adequate sampling method, sample size estimation and response rate >80%. We performed both univariate and multivariate meta-regression analysis to explore heterogeneity of results across studies.
There were 178 studies (459975 participants) in 148 articles. Of these, 106 studies were (124259 participants) on dysmenorrhoea, 54 (35973 participants) on dyspareunia and 18 (301756 participants) on noncyclical pain. There were only 19/95 (20%) less developed and 1/45 (2.2%) least developed countries with relevant data in contrast to 22/43 (51.2%) developed countries. Meta-regression analysis showed that rates of pain varied according to study quality features. There were 40 (22.5%) high quality studies with representative samples. Amongst them, the rate of dysmenorrhoea was 16.8 to 81%, that of dyspareunia was 8 to 21.8%, and that for noncyclical pain was 2.1 to 24%.
There were few valid population based estimates of disease burden due to CPP from less developed countries. The variation in rates of CPP worldwide was due to variable study quality. Where valid data were available, a high disease burden of all types of pelvic pain was found.
PMCID: PMC1550236  PMID: 16824213
25.  Alterations within the activation domain of the sigma 54-dependent activator DctD that prevent transcriptional activation. 
Journal of Bacteriology  1997;179(18):5812-5819.
Rhizobium meliloti DctD (C4-dicarboxylate transport protein D) is a transcriptional activator that catalyzes the ATP-dependent isomerization of closed complexes between sigma 54-RNA polymerase holoenzyme and the dctA promoter to open complexes. Following random mutagenesis of dctD, 55 independent mutant forms of DctD that failed to activate transcription from a dctA'-'lacZ reporter gene in Escherichia coli were selected, and the amino acid substitutions were determined for these mutant proteins. Amino acid substitutions were distributed throughout the central domain of the protein, the domain responsible for transcription activation, but most of the substitutions occurred within three highly conserved regions of the protein. Selected mutant proteins were purified, and their activities were studied in vitro. All of the purified mutant proteins appeared to have normal DNA-binding activity and interacted with sigma 54 and core RNA polymerase, as determined from protein crosslinking assays. Proteins with amino acid substitutions in a region spanning amino acid positions 222 to 225 retained their ATPase activities, whereas proteins with substitutions in other regions had little or no ATPase activity. Taken together, these data suggest that the region that encompasses amino acid residues 222 through 225 probably functions in coupling the energy released from ATP hydrolysis to open complex formation rather than as a major determinant for binding to RNA polymerase.
PMCID: PMC179471  PMID: 9294439

Results 1-25 (529294)