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Core Set (core + set)

Distribution by Scientific Domains

Medical Sciences	55%
Life Sciences	27%
Engineering	6%
Business, Economics, Finance and Accounting	6%

Selected Abstracts

Core Set of Data Elements for Reporting Water Quality Results

GROUND WATER MONITORING & REMEDIATION, Issue 2 2001
Charles Job
First page of article [source]

Development of a Core Set from a Large Rice Collection using a Modified Heuristic Algorithm to Retain Maximum Diversity

JOURNAL OF INTEGRATIVE PLANT BIOLOGY, Issue 12 2009
Hun-Ki Chung
Abstract A new heuristic approach was undertaken for the establishment of a core set for the diversity research of rice. As a result, 107 entries were selected from the 10 368 characterized accessions. The core set derived using this new approach provided a good representation of the characterized accessions present in the entire collection. No significant differences for the mean, range, standard deviation and coefficient of variation of each trait were observed between the core and existing collections. We also compared the diversity of core sets established using this Heuristic Core Collection (HCC) approach with those of core sets established using the conventional clustering methods. This modified heuristic algorithm can also be used to select genotype data with allelic richness and reduced redundancy, and to facilitate management and use of large collections of plant genetic resources in a more efficient way. [source]

The use of the comprehensive International Classification of Functioning, Disability and Health Core Set for low back pain in clinical practice: a reliability study

PHYSIOTHERAPY RESEARCH INTERNATIONAL, Issue 3 2009
Roger Hilfiker
Abstract Background and Purpose.,The comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for low back pain (LBP) can be used to describe functioning and the influence of the environment of patients with LBP with a selection of 78 categories, from the ICF components ,body functions', ,body structures', ,activities and participation' and ,environmental factors'. The reliability of the qualifiers' scale of the ICF Core Set for LBP has not yet been studied.,Methods.,Reliability study was conducted in three study centres in the German-speaking part of Switzerland. In the first step, two physiotherapists independently assessed 31 patients with LBP with the original qualifier scale of the 78 ICF categories from the comprehensive ICF Core Set for LBP. After the first 31 patients, inter-rater reliability was assessed and the response options were reduced based on a Rasch analysis. The second sample (n = 30) was assessed by the physiotherapists with the modified qualifier scale and inter-rater reliability was calculated again.,Results.,The percentage agreement for the ICF categories ranged from 19% to 87%, mean 44% (nominal kappa from ,0.73 to 0.54, median 0.22; weighted kappa ,0.2 to 0.69, median 0.38) in the first round with the original qualifier scale. In the second round with the reduced response options, the percentage agreement ranged from 23% to 90%, mean 49% (nominal kappa from ,0.15 to 0.71, median 0.24; weighted kappa ,0.16 to 0.81, median 0.25). The overall percentage agreement was 44% in the first round and 49% with the reduced response categories. The overall kappa value in the first round was 0.29 and in the second round 0.32. There was a small but statistically significant improvement in the agreement.,Conclusion.,The low-to-moderate reliability found in this study requires an improved operationalization (e.g. the definition and description of each response category) and improved instructions for the ICF Core Set for LBP. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Health care resource utilization in patients with active epilepsy

EPILEPSIA, Issue 5 2010
Tobias Kurth
Summary Purpose:, To evaluate health care resource utilization (HRU) in active epilepsy. Methods:, Thomson-Reuters insurance databases included 14 million persons in 2005,2007. We extracted information for individuals with insurance claims suggestive of epilepsy. Using iterative expert classification, we sorted patients by type of epilepsy. For each type we calculated prevalence and HRU. A distance analysis identified closely similar types, and a principal components analysis revealed dimensions of variation in HRU. Results:, The prevalence of active epilepsy was 3.4 per 1,000. Most common diagnoses among 46,847 patients were generalized convulsive epilepsy (33.3%) and complex partial seizures (24.8%). Patients averaged 10 physician visits per year, 24 diagnostic tests/procedures per year, >30 drug dispensings per year, and <1 emergency room (ER) visit per year, the minority of each of these being related to epilepsy. Female patients generally had more HRU, and HRU increased with age. Patients were hospitalized most frequently for disorders other than epilepsy. HRU was similar for most epilepsy types, excepting grand mal status, epilepsia partialis continua, and infantile spasms. The first principal components of HRU variation was nonepilepsy HRU, followed by components of epilepsy-related medications, other epilepsy/emergency care, and epilepsy visits/diagnostic procedures. Discussion:, The prevalence of active epilepsy in the United States is substantially less than the prevalence of any history of recurrent seizure. Nonepilepsy-related HRU dominated HRU in epilepsy patients and was the principal source of variation. There is a core set of epilepsy diagnoses, the HRU patterns of which are indistinguishable, whereas patients with grand mal status, epilepsia partialis continua, and infantile spasms all have distinct patterns. To provide more specific insights into the economic impact of the condition, studies of HRU in epilepsy should make a distinction about epilepsy-related and unrelated care. [source]

Explanatory models in the interpretations of clinical features of dental patients within a university dental education setting

EUROPEAN JOURNAL OF DENTAL EDUCATION, Issue 1 2002
Gerardo Maupome
Clinicians may acquire biased perceptions during their dental education that can affect decisions about treatment/management of dental decay. This study established explanatory models used by students to interpret clinical features of patients. It employed a stereotypical dental patient under standardised consultation conditions to identify the interpretation of oral health/disease features in the eyes of student clinicians. The study aimed to establish the perceptions of the patient as a client of the university dental clinic, as seen through the ideological lens of a formal Dental Education system. The discourse during simulated clinical consultations was qualitatively analysed to interpret values and concepts relevant to the assessment of restorative treatment needs and oral health status. Three constructs during the consultation were identified: the Dual Therapeutic Realms, the Choices Underlying Treatment Options, and the High-Risk Triad. Comparing these discourse components, the Patient Factors of the Bader and Shugars model for treatment decisions supported the existence of a core set of themes. It was concluded that certain consultation circumstances influenced the adequacy of diagnostic strategies, mainly by introducing loosely defined but highly specific socio-cultural biases ingrained in the Dental Education concepts and diagnostic/treatment needs systems. [source]

Measuring and managing engagement in a cross-cultural workforce: New insights for global companies

GLOBAL BUSINESS AND ORGANIZATIONAL EXCELLENCE, Issue 1 2006
Paul Sanchez
Should a company take a global or local approach to building engagement in its worldwide workforce? Research by Mercer Human Resource Consulting finds that country norms for drivers of engagement, as well as for other employee perceptions about their work and their employers, differ noticeably from region to region,and not in ways that might be expected. But a core set of drivers is emerging globally. This should help multinational companies distinguish between global and local engagement issues, design a manageable global engagement strategy and initiatives, and tailor implementation to meet the needs and preferences of the local workforce. © 2006 Wiley Periodicals, Inc. [source]

Assessing functional health status in adults with haemophilia: towards a preliminary core set of clinimetric instruments based on a literature search in Rheumatoid Arthritis and Osteoarthritis

HAEMOPHILIA, Issue 4 2005
P. De Kleijn
Summary., People with haemophilia experience a progressive deterioration of their functional health status. Regular clinical assessment of functional health status provides insight into their process of disablement. As such, the development of a core-set of measurement tools is warranted. The aim of this study was to gather data to prepare a (preliminary) core set of clinically relevant and feasible instruments to assess the functional health status of adults with haemophilia, and to indicate their psychometric qualities. Therefore, clinimetric instruments frequently used in two haemophilia-resembling diseases (Rheumatoid Arthritis and Osteoarthritis) were reviewed from the literature. An extensive search in Medline yielded 13 relevant review articles, incorporating a total of 182 instruments, of which 40 were appropriate for haemophilia. Of these 40 instruments 3 measure body structures, 13 body functions, 19 activities (of which 5 are performance based and 14 self-report based), and 3 measure participation. This classification is based on the International Classification of Functioning, Disability and Health. Detailed information regarding the psychometrics (reliability, validity and responsiveness) of four instruments is described fully in the literature, whereas the psychometrics of the majority of the other instruments are only partly described. The results of this literature study may contribute to the formation of a (preliminary) core set of clinimetric instruments to assess the functional health status of adults with haemophilia. Decisions on the final core set should be held within the Musculoskeletal Committee of the World Federation of Haemophilia. [source]

Measuring Hospital Care from the Patients' Perspective: An Overview of the CAHPS® Hospital Survey Development Process

HEALTH SERVICES RESEARCH, Issue 6p2 2005
Elizabeth Goldstein
Objective. To describe the developmental process for the CAHPS® Hospital Survey. Study Design. A pilot was conducted in three states with 19,720 hospital discharges. Methods of Analysis. A rigorous, multi-step process was used to develop the CAHPS Hospital Survey. It included a public call for measures, multiple Federal Register notices soliciting public input, a review of the relevant literature, meetings with hospitals, consumers and survey vendors, cognitive interviews with consumer, a large-scale pilot test in three states and consumer testing and numerous small-scale field tests. Findings. The current version of the CAHPS Hospital Survey has survey items in seven domains, two overall ratings of the hospital and five items used for adjusting for the mix of patients across hospitals and for analytical purposes. Conclusions. The CAHPS Hospital Survey is a core set of questions that can be administered as a stand-alone questionnaire or combined with a broader set of hospital specific items. [source]

Use of Nursing Diagnoses and Interventions in Public Health Nursing Practice

INTERNATIONAL JOURNAL OF NURSING TERMINOLOGIES AND CLASSIFICATION, Issue 1 2002
Jennifer C. Rivera MSN
PURPOSE. To determine the frequency of use of NANDA diagnoses and the Nursing Interventions Classification in care plans written by public health nurses (PHNs) in Orange County, CA. METHODS.Retrospective chart review. FINDINGS. The frequency pattern of nursing diagnoses and nursing interventions used in care plans is consistent with the scope of practice of the PHN, whose emphasis is on health promotion and disease prevention. CONCLUSIONS. The most commonly used diagnoses and interventions provide evidence of a core set of interventions useful for PHN practice. IMPLICATIONS FOR PRACTICE.Linking diagnoses and interventions allow PHNs to build a body of knowledge based on patient care and improve clinical decision-making process. Search terms:Interventions, nursing diagnosis, public health nursing Utilisation des diagnostics infirmiers et interventions en santé publique BUT.Déterminer la fréquence des diagnostics infirmiers (ANADI) et des interventions (NIC) dans les plans de soins rédigés par les infirmières de santé publique dans le Comté d'Orange, CA. METHODE.Étude rétrospective des dossiers. RÉSULTATS.La répartition des diagnostics infirmiers et des interventions utilisés dans les plans de soin est cohérente avec la pratique des infirmières en santé publique, c'est-à-dire qu'elle souligne l'importance de la promotion de la santé et la prévention de la maladie. CONCLUSIONS.Les diagnostics et interventions les plus fréquemment utilisés permettent d'identifier le groupe d'interventions au centre de la pratique des soins en santé publique. IMPLICATIONS POUR LA PRATIQUE.L'articulation des diagnostics et interventions de soins permet de construire un corpus de connaissances en santé publique basée sur le soin des patients et d'améliorer le processus de décision clinique. Mots-clés:Diagnostics infirmiers, interventions, soins infirmiers en santé publique Utilización de los diagnósticos e intervenciones de enfermería en la práctica de enfermería de salud pública PROPÓSITO.Determinar la frecuencia del uso de los diagnósticos de la NANDA y de la clasificación de las intervenciones enfermeras (NIC), en planes del cuidados escritos por enfermeras de salud pública en el Condado de Orange, California. MÉTODOS.Revisión retrospectiva de gráficos. RESULTADOS. El patrón de frecuencia de diagnósticos de enfermería y de intervenciones enfermeras utilizados en los planes del cuidados, es consistente con el ámbito asistencial de las enfermeras de salud pública, cuyo énfasis está en la promoción de salud y la prevención de la enfermedad. CONCLUSIÓN.Los diagnósticos e intervenciones más comúnmente utilizados, proporcionan evidencia de un grupo nuclear de intervenciones útiles a la práctica de enfermería de salud pública. IMPLICACIONES PARA LA PRÁCTICA.Conectar los diagnósticos y las intervenciones permite a las Enfermeras de Salud Pública construir un cuerpo de conocimientos basado en el cuidado de los pacientes y mejorar el proceso de toma de decisiones en la práctica clínica. Términos de búsqueda:Diagnóstico enfermero, enfermería de salud pública, intervenciones Uso de diagnósticos e intervenções de enfermagem na prótica de enfermagem em Saúde Pública OBJETIVO.Determinar a freqüência de uso dos diagnósticos da NANDA e da Classificação de Intervenções de Enfermagem (NIC) em planos de cuidados escritos por enfermeiras da área de Saúde Pública no Condado de Orange, Califórnia. MÉTODO.Revisão retrospectiva de fichas. ACHADOS.O padrão de freqüência de diagnósticos de enfermagem e intervenções de enfermagem utilizados em planos de cuidados é compatível com o escopo da prática das enfermeiras da área de Saúde Pública, cuja ênfase está na promoção da saúde e prevenção de doenças. CONCLUSãO.Os diagnósticos e intervenções mais comumente utilizados evidenciam a existência de um conjunto de intervenções principais, que éútil para a prática destas enfermeiras. IMPLICAÇõES PARA A PRÁTICA. A ligação entre diagnósticos e intervenções permite às enfermeiras da área de saúde pública construírem um corpo de conhecimentos baseado no cuidado do paciente e melhora o processo de tomada de decisão. Palavras para busca:Diagnóstico de enfermagem, enfermagem em saúde publica, intervenções [source]

Development of a Core Set from a Large Rice Collection using a Modified Heuristic Algorithm to Retain Maximum Diversity

THE MESOZOIC RADIATION OF EUKARYOTIC ALGAE: THE PORTABLE PLASTID HYPOTHESIS,

JOURNAL OF PHYCOLOGY, Issue 2 2003
Daniel Grzebyk
Although all chloroplasts appear to have been derived from a common ancestor, a major schism occurred early in the evolution of eukaryotic algae that gave rise to red and green photoautotrophic lineages. In Paleozoic and earlier times, the fossil record suggests that oceanic eukaryotic phytoplankton were dominated by the green (chl b -containing) algal line. However, following the end-Permian extinction, a diverse group of eukaryotic phytoplankton evolved from secondary symbiotic associations in the red (chl c -containing) line and subsequently rose to ecological prominence. In the contemporary oceans, red eukaryotic phytoplankton taxa continue to dominate marine pelagic food webs, whereas the green line is relegated to comparatively minor ecological and biogeochemical roles. To help elucidate why the oceans are not dominated by green taxa, we analyzed and compared whole plastid genomes in both the red and green lineages. Our results suggest that whereas all algal plastids retain a core set of genes, red plastids retain a complementary set of genes that potentially confer more capacity to autonomously express proteins regulating oxygenic photosynthetic and energy transduction pathways. We hypothesize that specific gene losses in the primary endosymbiotic green plastid reduced its portability for subsequent symbiotic associations. This corollary of the plastid "enslavement" hypothesis may have limited subsequent evolutionary advances in the green lineage while simultaneously providing a competitive advantage to the red lineage. [source]

Total Cost of Ownership Models: An Exploratory Study

JOURNAL OF SUPPLY CHAIN MANAGEMENT, Issue 3 2002
Bruce G. Ferrin
SUMMARY This research examines organizational purchasing models focusing on the use of total cost of ownership (TCO) to value purchase opportunities. The research presents evidence that leading-edge companies actually use such models. This exploratory study provides, for the first time, data on the nature, and use, of the cost drivers on which organizations base their TCO computations. The study suggests a generic model of total cost of ownership is not appropriate. However, the findings of this research suggest a TCO model based on a core set of cost drivers, along with an auxiliary set of cost drivers, is appropriate. The core cost drivers would be present in all, or most, TCO computations. Purchasing managers could use different, specific cost drivers from the auxiliary set to tailor the TCO computation for a particular purchase situation. The authors also suggest that a value-based, multi-firm, or supply chain, TCO computation model is needed. Such a TCO model should be similar to a single-firm TCO model. [source]

The Mga virulence regulon: infection where the grass is greener

MOLECULAR MICROBIOLOGY, Issue 5 2007
Elise R. Hondorp
Summary Co-ordinate regulation of virulence gene expression in response to different host environments is central to the success of the group A streptococcus (GAS, Streptococcus pyogenes) as an important human pathogen. Mga represents a ubiquitous stand-alone virulence regulator that controls genes (Mga regulon) whose products are necessary for adherence, internalization and host immune evasion. Mga highly activates a core set of virulence genes, including its own gene, by directly binding to their promoters. Yet, Mga also influences expression of over 10% of the GAS genome, primarily genes and operons involved in metabolism and sugar utilization. Expression of the Mga regulon is influenced by conditions that signify favourable growth conditions, presumably allowing GAS to take advantage of promising new niches in the host. The ability of Mga to respond to growth signals clearly involves regulation of mga expression via global regulatory networks such as RALPs, Rgg/RopB and the catabolite control protein CcpA. However, the presence of predicted PTS regulatory domains (PRDs) within Mga suggests an intriguing model whereby phosphorylation of Mga by the PTS phosphorelay might link growth and sugar utilization with virulence in GAS. As Mga homologues have been found in several important Gram-positive pathogens, the Mga regulon could provide a valuable paradigm for increasing our understanding of global virulence networks in bacteria. [source]

Transcriptome analysis of Listeria monocytogenes identifies three groups of genes differently regulated by PrfA

MOLECULAR MICROBIOLOGY, Issue 6 2003
Eliane Milohanic
Summary PrfA is the major regulator of Listeria virulence gene expression. This protein is a member of the Crp/Fnr family of transcription regulators. To gain a deeper understanding of the PrfA regulon, we constructed a whole-genome array based on the complete genome sequence of Listeria monocytogenes strain EGDe and evaluated the expression profiles of the wild-type EGDe and a prfA -deleted mutant (EGDe ,prfA). Both strains were grown at 37°C in brain,heart infusion broth (BHI) and BHI supplemented with either activated charcoal, a compound known to enhance virulence gene expression, or cellobiose, a sugar reported to downregulate virulence gene expression in spite of full expression of PrfA. We identified three groups of genes that are regulated differently. Group I comprises, in addition to the 10 already known genes, two new genes, lmo2219 and lmo0788, both positively regulated and preceded by a putative PrfA box. Group II comprises eight negatively regulated genes: lmo0278 is preceded by a putative PrfA box, and the remaining seven genes (lmo0178,lmo0184) are organized in an operon. Group III comprises 53 genes, of which only two (lmo0596 and lmo2067) are preceded by a putative PrfA box. Charcoal addition induced upregulation of group I genes but abolished regulation by PrfA of most group III genes. In the presence of cellobiose, all the group I genes were downregulated, whereas group III genes remained fully activated. Group II genes were repressed in all conditions tested. A comparison of the expression profiles between a second L. monocytogenes strain (P14), its spontaneous mutant expressing a constitutively active PrfA variant (P14prfA*) and its corresponding prfA -deleted mutant (P14,prfA) and the EGDe strain revealed interesting strain-specific differences. Sequences strongly similar to a sigma B-dependent promoter were identified upstream of 22 group III genes. These results suggest that PrfA positively regulates a core set of 12 genes preceded by a PrfA box and probably expressed from a sigma A-dependent promoter. In contrast, a second set of PrfA-regulated genes lack a PrfA box and are expressed from a sigma B-dependent promoter. This study reveals that PrfA can act as an activator or a repressor and suggests that PrfA may directly or indirectly activate different sets of genes in association with different sigma factors. [source]

Mining for robust transcriptional and metabolic responses to long-term salt stress: a case study on the model legume Lotus japonicus

PLANT CELL & ENVIRONMENT, Issue 4 2010
DIEGO H. SANCHEZ
ABSTRACT Translational genomics, the use of model species to generate knowledge about biological processes and the functions of genes, offers great promise to biotechnologists. Few studies have sought robust responses of model plants to environmental stresses, such as salinity, by altering the stress dosage or by repeating experiments in consecutive years and/or different seasons. We mined our published and unpublished data on legume salt acclimation for robust system features at the ionomic, transcriptomic and metabolomic levels. We analysed data from the model legume Lotus japonicus, obtained through six independent, long-term, non-lethal salt stress experiments which were carried out over two consecutive years. Best possible controlled greenhouse conditions were applied and two main questions asked: how reproducible are results obtained from physiologically meaningful salinity experiments, and what degree of bias may be expected if conclusions are drawn from less well-repeated sampling? A surprisingly large fraction of the transcriptional and metabolic responses to salt stress were not reproducible between experiments. A core set of robust changes was found that was shared between experiments. Many of these robust responses were qualitatively and quantitatively conserved between different accessions of the same species, indicating that the robust responses may be a sound starting point for translational genomics. [source]

MULTIPLE RATERS IN SURVEY-BASED OPERATIONS MANAGEMENT RESEARCH: A REVIEW AND TUTORIAL

PRODUCTION AND OPERATIONS MANAGEMENT, Issue 2 2000
Kenneth K. Boyer
Research in the area of operations strategy has made significant progress during the past decade in terms of quantity of articles published, as well as the quality of these articles. Recent studies have examined the published literature base and determined that, in general, the field has progressed beyond an exploratory stage to a point where there is a core set of basic terminology and models. Concurrent with the formation and solidification of a core terminology, there is an increasing emphasis on developing and employing a set of reliable, valid, and reproducible methods for conducting research on operations strategy. We provide a review of common methods for assessing the degree of reliability and agreement of the responses provided by multiple raters within a given organization to a set of qualitative questions. In particular, we examine four methods of determining whether there is evidence of disagreement or bias between multiple raters within a single organization in a mail survey. [source]

Practitioner Review: The assessment of language pragmatics

THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 8 2002
Catherine Adams
Background: The assessment of pragmatics expressed in spoken language is a central issue in the evaluation of children with communication impairments and related disorders. A developmental approach to assessment has remained problematic due to the complex interaction of social, linguistic, cognitive and cultural influences on pragmatics. Method: A selective review and critique of current formal and informal testing methods and pragmatic analytic procedures. Results: Formal testing of pragmatics has limited potential to reveal the typical pragmatic abnormalities in interaction but has a significant role to play in the assessment of comprehension of pragmatic intent. Clinical assessment of pragmatics with the pre-school child should focus on elicitation of communicative intent via naturalistic methods as part of an overall assessment of social communication skills. Assessments for older children should include a comprehensive investigation of speech acts, conversational and narrative abilities, the understanding of implicature and intent as well as the child's ability to employ contextual cues to understanding. Practical recommendations are made regarding the choice of a core set of pragmatic assessments and elicitation techniques. The practitioner's attention is drawn to the lack of the usual safeguards of reliability and validity that have persisted in some language pragmatics assessments. Conclusions: A core set of pragmatic assessment tools can be identified from the proliferation of instruments in current use. Further research is required to establish clearer norms and ranges in the development of pragmatic ability, particularly with respect to the understanding of inference, topic management and coherence. [source]

Validation of 15 microsatellites for parentage testing in North American bison, Bison bison and domestic cattle

ANIMAL GENETICS, Issue 6 2000
R D Schnabel
Fifteen bovine microsatellites were evaluated for use in parentage testing in 725 bison from 14 public populations, 178 bison from two private ranches and 107 domestic cattle from five different breeds. The number of alleles per locus ranged from five to 16 in bison and from five to 13 in cattle. On average, expected heterozygosity, polymorphism information content (PIC) and probability of exclusion values were slightly lower in bison than in cattle. A core set of 12 loci was further refined to produce a set of multiplexed markers suitable for routine parentage testing. Assuming one known parent, the core set of markers provides exclusion probabilities in bison of 0·9955 and in cattle of 0·9995 averaged across all populations or breeds tested. Tests of Hardy-Weinberg and linkage equilibrium showed only minor deviations. This core set of 12 loci represent a powerful and efficient method for determining parentage in North American bison and domestic cattle. [source]

LY2439821, a humanized anti,interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis: A phase I randomized, double-blind, placebo-controlled, proof-of-concept study

ARTHRITIS & RHEUMATISM, Issue 4 2010
M. C. Genovese
Objective We undertook this study to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of LY2439821, a humanized anti,interleukin-17 (anti,IL-17) monoclonal antibody, in a first in-human trial in rheumatoid arthritis (RA) patients taking oral disease-modifying antirheumatic drugs (DMARDs). Methods This randomized, double-blind, placebo-controlled study consisted of 2 parts. In part A, 20 patients received 1 intravenous (IV) dose of LY2439821 (0.06, 0.2, 0.6, or 2.0 mg/kg, escalating) or placebo followed by 8 weeks of evaluation. End points included safety, tolerability, and pharmacokinetics. In part B, 77 patients received 1 IV dose of LY2439821 (0.2, 0.6, or 2.0 mg/kg) or placebo every 2 weeks for a total of 5 doses, with a total evaluation period of 16 weeks. End points included safety, tolerability, pharmacokinetics/pharmacodynamics, and efficacy (Disease Activity Score in 28 joints [DAS28] and percentages of patients meeting American College of Rheumatology 20%, 50%, or 70% improvement criteria [achieving an ACR20, ACR50, or ACR70 response]). The primary efficacy end point was the DAS28 at week 10. Results Baseline characteristics were similar across all groups. Changes in the DAS28 were significantly greater in the 0.2 mg/kg, 2.0 mg/kg, and all-LY2439821,combined groups (,2.3, ,2.4, and ,2.3, respectively) than in the placebo group (,1.7) at week 10 (P , 0.05), and these differences were significant as early as week 1. Percentages of ACR20, ACR50, and ACR70 responses as well as improvements in the ACR core set of measures were greater in LY2439821-treated patients than in placebo-treated patients at multiple time points. There was no apparent dose-response relationship in treatment-emergent adverse events. Conclusion LY2439821 added to oral DMARDs improved signs and symptoms of RA, with no strong adverse safety signal noted. This first evaluation of LY2439821 supports neutralization of IL-17 as a potential novel goal for the treatment of RA. [source]

Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a double-blind, methotrexate-controlled study of patients with active rheumatoid arthritis,

ARTHRITIS & RHEUMATISM, Issue 2 2009
Stanley B. Cohen
Objective To determine the efficacy and safety of pamapimod (a selective inhibitor of the ,-isoform of p38 MAP kinase) as monotherapy in comparison with methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis (RA). Methods Patients were randomly assigned to 1 of 4 treatment groups and received 12 weeks of double-blind treatment. One group received MTX (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received pamapimod (50, 150, or 300 mg) once daily. The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end points included ACR50 and ACR70 responses, change from baseline in the Disease Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European League Against Rheumatism response, and change from baseline in each parameter of the ACR core set of measures. Safety monitoring included recording of adverse events (AEs), laboratory testing, immunology assessments, administration of electrocardiograms, and assessment of vital signs. Results Patients assigned to receive MTX and pamapimod had similar demographics and baseline characteristics. At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 31% in the 50-, 150-, and 300-mg groups, respectively) compared with patients taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs were typically characterized as mild and included infections, skin disorders, and dizziness. Pamapimod was generally well tolerated, but the 300-mg dose appeared to be more toxic than either the 2 lower doses or MTX. Conclusion The present results showed that pamapimod was not as effective as MTX in the treatment of active RA. [source]

Clinical responses to tumor necrosis factor , antagonists do not show a bimodal distribution: Data from the Stockholm Tumor Necrosis Factor , Followup Registry

ARTHRITIS & RHEUMATISM, Issue 6 2003
Ronald F. van Vollenhoven
Objective To study the distribution of clinical responses to treatment with the tumor necrosis factor , (TNF,) antagonists etanercept and infliximab, and in particular, to determine whether there is a biologically meaningful distinction between responders and nonresponders. Methods Among patients in the Stockholm TNF, Followup Registry, we analyzed the clinical responses to etanercept and infliximab, using the American College of Rheumatology (ACR) core set of outcome measures. For each parameter, the absolute change (value at baseline , current value) and the percentage change ([absolute change]/[value at baseline] × 100) from baseline were calculated. The results were plotted as histograms and inspected visually, and the distributions were statistically compared with computer-generated normal distributions. Results Absolute and relative changes in outcomes on the ACR core set of measures in 406 patients receiving etanercept or infliximab were studied. All but a few of these analyses yielded normal or somewhat skewed distributions. The statistical analyses did not detect any non-normal distributions, and visually, the distributions did not appear to be bimodal. Conclusion The clinical response to TNF, blockade displays a normal or skewed, but not bimodal, distribution. The frequently encountered perception that a clear distinction can be made between responders and nonresponders is not borne out. These relatively straightforward findings imply that the biologic mechanisms determining responsiveness to TNF, blockade are multifactorial and may also have important implications for regulatory guidelines pertaining to treatment with these biologic agents. [source]

Measuring disease activity and functional status in patients with scleroderma and Raynaud's phenomenon

ARTHRITIS & RHEUMATISM, Issue 9 2002
Peter A. Merkel
Objective To document disease activity and functional status in patients with scleroderma (systemic sclerosis [SSc]) and Raynaud's phenomenon (RP) and to determine the sensitivity to change, reliability, ease of use, and validity of various outcome measures in these patients. Methods Patients with SSc and moderate-to-severe RP participating in a multicenter RP treatment trial completed daily diaries documenting the frequency and duration of RP attacks and recorded a daily Raynaud's Condition Score (RCS). Mean scores for the 2-week periods prior to baseline (week 0), end of trial (week 6), and posttrial followup (week 12) were calculated. At weeks 0, 6, and 12, physicians completed 3 global assessment scales and performed clinical assessments of digital ulcers and infarcts; patients completed the Health Assessment Questionnaire (HAQ), the Arthritis Impact Measurement Scales 2 (AIMS2) mood and tension subscales, 5 specific SSc/RP-related visual analog scales (VAS), and 3 other VAS global assessments. We used these measures to document baseline disease activity and to assess their construct validity, sensitivity to change, and reliability in trial data. Results Two hundred eighty-one patients (248 women, 33 men; mean age 50.4 years [range 18,82 years]) from 14 centers participated. Forty-eight percent had limited cutaneous SSc; 52% had diffuse cutaneous SSc. Fifty-nine patients (21%) had digital ulcers at baseline. Patients had 3.89 ± 2.33 (mean ± SD) daily RP attacks (range 0.8,14.6), with a duration of 82.1 ± 91.6 minutes/attack. RCS for RP activity (possible range 0,10) was 4.30 ± 1.92. HAQ scores (0,3 scale) indicated substantial disability at baseline (total disability 0.86, pain 1.19), especially among the subscales pertaining to hand function (grip, eating, dressing). AIMS2 mood and tension scores were fairly high, as were many of the VAS scores. Patients with digital ulcers had worse RCS, pain, HAQ disability (overall, grip, eating, and dressing), physician's global assessment, and tension, but no significant difference in the frequency of RP, duration of RP, patient's global assessment, or mood, compared with patients without digital ulcers. VAS scores for digital ulcers as rated by the patients were not consistent with the physician's ratings. Factor analysis of the 18 measures showed strong associations among variables in 4 distinct domains: disease activity, RP measures, digital ulcer measures, and mood/tension. Reliability of the RCS, HAQ pain and disability scales, and AIMS2 mood and tension subscales was high. The RP measures demonstrated good sensitivity to change (effect sizes 0.33,0.76). Conclusion Our findings demonstrate that the significant activity, disability, pain, and psychological impact of RP and digital ulcers in SSc can be measured by a small set of valid and reliable outcome measures. These outcome measures provide information beyond the quantitative metrics of RP attacks. We propose a core set of measures for use in clinical trials of RP in SSc patients that includes the RCS, patient and physician VAS ratings of RP activity, a digital ulcer/infarct measure, measures of disability and pain (HAQ), and measures of psychological function (AIMS2). [source]

The myeloid differentiation factor 88 is dispensable for the development of a delayed host response to Pseudomonas aeruginosa lung infection in mice

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2006
M. R. Power
Summary Because MyD88 transduces a core set of Toll-like receptor (TLR)-induced signals, microbial-induced host responses can be divided broadly into the MyD88-dependent and MyD88-independent pathways. A specific pathogen induces a distinct pattern of host response dependent upon the signalling pathways employed. Recently, we demonstrated that a MyD88-dependent pathway is essential for the development of early (4,8 h) host response to Pseudomonas aeruginosa lung infection. Here, we show that the development of a delayed (24,48 h) host response to P. aeruginosa is independent of MyD88. Using MyD88-deficient mice, the production of macrophage inflammatory protein 2, tumour necrosis factor and interleukin 1, in the airway was observed following P. aeruginosa lung infection for 24 or 48 h. Moreover, the MyD88-deficient mice recruited sufficient neutrophils in the lung and cleared the bacteria efficiently from the lung after 48 h. Thus, the full development of host responses to P. aeruginosa lung infection involves, in a sequential, stepwise fashion, a MyD88-dependent early response and a MyD88-independent delayed mechanism. [source]