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BACKGROUND: Darbepoetin alfa is the second erythropoietic protein to be approved for the treatment of chemotherapy-induced anemia (CIA). In the clinical setting, darbepoetin alfa can be administered less frequently than epoetin alfa with similar efficacy. Practice patterns and outcomes associated with the use of darbepoetin alfa and epoetin alfa in the clinical setting have not been reported. OBJECTIVE: This study compared practice patterns and clinical outcomes of the use of darbepoetin alfa and epoetin alfa for CIA at oncology practices in the United States. METHODS: This was a multicenter retrospective cohort study. Data were abstracted from the medical charts of consecutive patients who began darbepoetin alfa treatment between August 1 and October 4, 2002, or epoetin alfa treatment between April 1 and July 31, 2002, and were receiving concurrent chemotherapy. These data were used to determine the initial dose and dosing schedule, dose changes, and changes in hemoglobin concentrations after 4, 8, and 12 weeks of treatment, adjusted for red blood cell (RBC) transfusions, and the incidence of RBC transfusions over time. To minimize potential bias, the study protocol defined specific end points and prespecified analytic techniques for assessing clinical outcomes with the 2 agents. RESULTS: The records of 1391 patients from 16 community and hospital outpatient oncology clinics were abstracted. Of these, 1293 patients (93.0%) received only 1 erythropoietic agent (darbepoetin alfa, 735 [56.8%]; epoetin alfa, 558 [43.2%]); the remainder received both agents. In the patients who received darbepoetin alfa, most (553 [75.2%]) received an initial dosage of 200 microg q2wk. A similar proportion (414 [74.2%]) received epoetin alfa at an initial dosage of 40,000 U qwk. As these were the regimens for the majority of patients whose records were abstracted, the results reported here are for these patients. The dose was increased in 63 darbepoetin alfa recipients (11.4%) and 58 epoetin alfa recipients (14.0%) at a median of 7 weeks. After 12 weeks, the 2 groups had an identical mean imputed change from baseline in hemoglobin concentration (1.0 g/dL), and the incidence of RBC transfusions during treatment was also similar between groups (darbepoetin alfa, 44553 [8.0%]; epoetin alfa, 39414 [9.4%]). CONCLUSIONS: Darbepoetin alfa 200 microg q2wk was used as a standard regimen for CIA at the 16 US oncology practices participating in this study. It appeared to be as effective as epoetin alfa 40,000 U qwk, with a reduced frequency of dosing. [ABSTRACT FROM AUTHOR]

Abstract Background Clinical practice guidelines are not uniformly successful in influencing clinicians' behaviour toward best practices. Implementability refers to a set of characteristics that predict ease of (and obstacles to) guideline implementation. Our objective is to develop and validate a tool for appraisal of implementability of clinical guidelines. Methods Indicators of implementability were identified from the literature and used to create items and dimensions of the GuideLine Implementability Appraisal (GLIA). GLIA consists of 31 items, arranged into 10 dimensions. Questions from 9 of the 10 dimensions are applied individually to each recommendation of the guideline. Decidability and Executability are critical dimensions. Other dimensions are Global, Presentation and Formatting, Measurable Outcomes, Apparent Validity, Flexibility, Effect on Process of Care, Novelty/Innovation, and Computability. We conducted a series of validation activities, including validation of the construct of implementability, expert review of content for clarity, relevance, and comprehensiveness, and assessment of construct validity of the instrument. Finally, GLIA was applied to a draft guideline under development by national professional societies. Results Evidence of content validity and preliminary support for construct validity were obtained. The GLIA proved to be useful in identifying barriers to implementation in the draft guideline and the guideline was revised accordingly. Conclusion GLIA may be useful to guideline developers who can apply the results to remedy defects in their guidelines. Likewise, guideline implementers may use GLIA to select implementable recommendations and to devise implementation strategies that address identified barriers. By aiding the design and operationalization of highly implementable guidelines, our goal is that application of GLIA may help to improve health outcomes, but further evaluation will be required to support this potential benefit.

Abstract Background American public policy makers recently established the goal of providing the majority of Americans with electronic health records by 2014. This will require a National Health Information Infrastructure (NHII) that is far more complete than the one that is currently in its formative stage of development. We describe a conceptual framework to help measure progress toward that goal. Discussion The NHII comprises a set of clusters, such as Regional Health Information Organizations (RHIOs), which, in turn, are composed of smaller clusters and nodes such as private physician practices, individual hospitals, and large academic medical centers. We assess progress in terms of the availability and use of information and communications technology and the resulting effectiveness of these implementations. These three attributes can be studied in a phased approach because the system must be available before it can be used, and it must be used to have an effect. As the NHII expands, it can become a tool for evaluating itself. Summary The NHII has the potential to transform health care in America – improving health care quality, reducing health care costs, preventing medical errors, improving administrative efficiencies, reducing paperwork, and increasing access to affordable health care. While the President has set an ambitious goal of assuring that most Americans have electronic health records within the next 10 years, a significant question remains "How will we know if we are making progress toward that goal?" Using the definitions for "nodes" and "clusters" developed in this article along with the resulting measurement framework, we believe that we can begin a discussion that will enable us to define and then begin making the kinds of measurements necessary to answer this important question.

In 2011, the Institute of Medicine (IOM) (now the National Academy of Medicine) published standards for trustworthy guidelines and recommended that the National Guideline Clearinghouse (NGC) of the Agency for Healthcare Research and Quality clearly indicate the extent to which guidelines adhere to these standards. To accomplish this, the authors developed and tested the NGC Extent of Adherence to Trustworthy Standards (NEATS) instrument. The standards were operationalized as an instrument containing 15 items that cover disclosure of the funding source; disclosure and management of conflicts of interest; multidisciplinary input; incorporation of patient perspectives; rigorous systematic review; recommendations accompanied by rationale, assessment of benefits and harms, clear linkage to the evidence, and assessment of strength of evidence and strength of recommendation; clear articulation of recommendations; external review by diverse stakeholders; and plans for updating. After multiple rounds of feedback from experts on clinical practice guideline development, the external validity and interrater reliability of the instrument were evaluated. For each item, 80% to 100% of survey respondents judged it to be a good measure of the IOM standards. All external stakeholders stated that NEATS was suitable for its intended goal. Interrater reliability for the final NEATS instrument had a weighted κ of 0.73. The NEATS instrument is a focused tool that provides a concise evaluation of a guideline's adherence to the IOM standards for trustworthy guidelines. It has good external validity among guideline developers and good interrater reliability across trained reviewers.

Background: Clinical decision support (CDS) is a key tool for enabling evidence-based medicine and improving the quality of healthcare. However, effective CDS faces a variety of challenges, including those relating to knowledge synthesis, capture, transformation, localization and maintenance. If not properly addressed, these challenges can limit the effectiveness of CDS, and potentially risk inaccurate or inappropriate interventions to clinicians., Objectives: (1) To describe an approach to CDS development using evidence as a basis for clinical decision support systems that promote effective care; (2) To review recent evidence regarding the effectiveness of selected clinical decision support systems., Method: Review and analysis of recent literature with identification of trends and best practices., Results: The state-of-the-art in CDS has advanced significantly, and many recent trials have shown CDS to be effective, although the results are mixed overall. Issues related to knowledge capture and synthesis, problems in knowledge transformation at the interface between knowledge authors and CDS developers, and problems specific to local CDS design and implementation can interfere with CDS development. Best practices, tools and techniques to manage them are described., Conclusions: CDS, when used well, can be effective, but further research is needed for it to reach its full potential.

Objective: To evaluate whether National Institute of Child Health and Human Health and Development (NICHD) fetal heart rate categories were predictive of neonatal survival in periviable pregnancies., Methods: We reviewed the charts of 57 infants delivered at 23 and 24 weeks' gestation. Fetal heart rate tracings were evaluated following the NICHD 2008 criteria, using the acceleration height of 10 bpm and duration of 10 s. Multiple logistic regression analyses were performed using survival, fetal morbidities, and cord pH <7.1 as dependent variables. Independent variables included fetal heart rate category, mode of delivery, resuscitation, and histological chorioamnionitis. Outcomes of infants delivered at 23 and 24 weeks were also compared., Results: In 23-week pregnancies, fetal heart rate category 2 was associated with improved short-term survival compared to category 3 (OR 1.3, 95% CI 0.11-15.7). Cesarean delivery and histological chorioamnionitis were not predictive of survival [(OR 0.5, 95% CI 0.04-7.1, and OR 0.4, 95% CI 0.02-6.85), respectively]. Long-term survival for infants born at 23 and 24 weeks was 8% and 56%, respectively., Conclusions: The NICHD fetal heart rate category during labor may be associated with survival for infants born at 23 and 24 weeks of gestation. Cesarean delivery was not associated with improved survival.

There are numerous known benefits associated with the use of an electronic medical record (EMR). In October of 2004, a pediatric respiratory medicine practice at a major academic institution began the process of implementing an EMR system. Through this process, another benefit was realized, improved coordination between out-patient and in-patient care in relation to asthma education. The process began with the formation of an implementation team. The team consisted of technical as well as clinical experts from various disciplines. Together the team developed templates, decision support tools and standardized patient care letters. The team also determined workflow and provided training on the EMR system. A major benefit associated with EMR implementation was the increase in the number of children who were hospitalized with an asthma exacerbation and received an asthma action plan upon discharge. Prior to the EMR system, 4% received an asthma action plan upon discharge. After implementation of the EMR system, 58% received an asthma action plan upon discharge.

Recent research indicates that inpatients with hyperglycemia suffer poor outcomes. Efforts to improve glycemic control need measures of performance. We proposed candidate measures, but these require analysis of large glucose datasets, a cumbersome task for individual institutions. We developed an application accessible over the internet that facilitates computation of these performance measures.

Core binding factor (CBF) participates in specification of the hematopoietic stem cell and functions as a critical regulator of hematopoiesis. Translocation or point mutation of acute myeloid leukemia 1 (AML1)/RUNX1, which encodes the DNA-binding subunit of CBF, plays a central role in the pathogenesis of acute myeloid leukemia and myelodysplasia. We characterized the t(X;21)(p22.3;q22.1) in a patient with myelodysplasia that fuses AML1 in-frame to the novel partner gene FOG2/ZFPM2. The reciprocal gene fusions AML1-FOG2 and FOG2-AML1 are both expressed. AML1-FOG2, which fuses the DNA-binding domain of AML1 to most of FOG2, represses the transcriptional activity of both CBF and GATA1. AML1-FOG2 retains a motif that recruits the corepressor C-terminal binding protein (CtBP) and these proteins associate in a protein complex. These results suggest a central role for CtBP in AML1-FOG2 transcriptional repression and implicate coordinated disruption of the AML1 and GATAdevelopmental programs in the pathogenesis of myelodysplasia.

Mitochondrial DNA depletion syndrome is a clinically heterogeneous group of disorders characterized by a reduction in mitochondrial DNA copy number. The recent discovery of mutations in the deoxyguanosine kinase (dGK) gene in patients with the hepatocerebral form of mitochondrial DNA depletion syndrome prompted us to screen 21 patients to determine the frequency of dGK mutations, further characterize the clinical spectrum, and correlate genotypes with phenotypes. We detected mutations in three patients (14%). One patient had a homozygous GATT duplication (nucleotides 763-766), and another had a homozygous GT deletion (nucleotides 609-610); both mutations lead to truncated proteins. The third patient was a compound heterozygote for two missense mutations (R142K and E227K) that affect critical residues of the protein. These mutations were associated with variable phenotypes, and their low frequencies suggests that dGK is not the only gene responsible for mitochondrial DNA depletion in liver. The patient with the missense mutations had isolated liver failure and responded well to liver transplantation, which may be a therapeutic option in selected cases.

Among the most effective strategies for changing the process and outcomes of clinical care are those that make use of computer-mediated decision support. A variety of representation models that facilitate computer-based implementation of medical knowledge have been published, including the Guideline Elements Model (GEM) and the Arden Syntax for Medical Logic Modules (MLMs). We describe an XML-based application that facilitates automated generation of partially populated MLMs from GEM-encoded guidelines. These MLMs can be further edited and shared among Arden-compliant information systems to provide decision support. Our work required three steps: (a) Knowledge extraction from published guideline documents using GEM, (b) Mapping GEM elements to the MLM slots, and (c) XSL transformation of the GEM-encoded guideline. Processing of a sample guideline generated 15 MLMs, each corresponding to a conditional or imperative element in the GEM structure. Mechanisms for linking various MLMs are necessary to represent the complexity of logic typical of a guideline.

Access to timely decision support information is critical for delivery of high-quality medical care. Transformation of clinical knowledge that is originally expressed in the form of a guideline to a computable format is one of the main obstacles to the integration of knowledge sharing functionality into computerized clinical systems. The Guideline Element Model (GEM) provides a methodology for such a transformation. Although the model has been used to store heterogeneous guideline knowledge, it is important to demonstrate that GEM markup facilitates guideline implementation. This report demonstrates the feasibility of implementation of GEM-encoded guideline recommendations using Apache Group s Cocoon Web Publishing Framework. We further demonstrate how XML-based programming allows for maintaining the separation of guideline content from processing logic and from presentation format. Finally, we analyze whether the guideline authors original intent has been sufficiently captured and conveyed to the end user.

Implementation of practice guidelines refers to the creation of strategies and systems to operationalize the knowledge and recommendations set forth by guideline developers. We describe an approach to guideline implementation that makes direct use of the guideline document as a knowledge base. The Guideline Elements Model (GEM) provides an XML-based guideline document model that facilitates implementation of guidelines. Knowledge extraction using GEM requires document markup rather than programming and can promote authenticity and consistent knowledge encoding. Knowledge customization for the local enterprise requires addition of meta-information to pertinent components of the GEM hierarchy in a design database. GEM provides an audit trail to track local adaptation. Knowledge integration with patient data can be promoted using information management services. A design goal is to devise a system that can be applied by local clinical domain experts, quality assurance experts, and information systems programmers without requiring trained informaticians and knowledge engineers to serve as intermediaries

A variety of rating instruments that evaluate the quality of practice guidelines have been published. Application of these instruments can be difficult and time-consuming. In a literature review, we identified two evaluation instruments that are comprehensive, have clearly defined constructs, and have undergone validation/testing-the Guidelines Quality Assessment Questionnaire (GQAQ) and the Appraisal Instrument for Clinical Guidelines (AICG). Overall, the AICG is more comprehensive. The AICG addresses the implementability of a guideline, which is not evaluated by the GQAQ. However, the GQAQ is more amenable to computerization. GEM-Q is a Guideline Elements Model (GEM)-derived application intended to facilitate automated evaluation of guideline quality using one of the published instruments. To develop GEM-Q, various items in the GQAQ were mapped to corresponding elements in the GEM hierarchy and a customized XSL stylesheet was designed based on this mapping. GEM-Q selectively extracts text components of the guideline relevant to quality evaluation and displays the results in HTML format. GEM-Q was applied to a set of six guidelines to test its reliability. It ranked two guidelines as of "good" quality, two as "intermediate", and two as "poor". In all six instances, GEM-Q ranked guidelines in the same order of quality as the experts who validated the GQAQ. This work demonstrates the feasibility of developing an application to facilitate automated guideline quality evaluation.