Disease Status (disease + status)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Disease Status

  • true disease status


  • Selected Abstracts


    Disease Status in Autosomal Dominant Osteopetrosis Type 2 Is Determined by Osteoclastic Properties,

    JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2006
    Kang Chu
    Abstract Asymptomatic gene carriers and clinically affected ADO2 subjects have the same ClCN7 mutation. We examined osteoclastic bone resorption in vitro as well as osteoclast formation, several markers, acid secretion, and cytoskeletal structure. We found that ADO2 expression results from osteoclast specific properties. Introduction: Autosomal dominant osteopetrosis type II (ADO2) is a heritable osteosclerotic disorder that results from heterozygous mutations in the ClCN7 gene. However, of those individuals with a ClCN7 mutation, one third are asymptomatic gene carriers who have no clinical, biochemical, or radiological manifestations. Disease severity in the remaining two thirds is highly variable. Materials and Methods: Human peripheral blood mononuclear cells were isolated and differentiated into osteoclasts by stimulation with hRANKL and human macrophage-colony stimulating factor (hM-CSF). Study subjects were clinically affected subjects, unaffected gene carriers, and normal controls (n = 6 in each group). Pit formation, TRACP staining, RANKL dose response, osteoclast markers, acid secretion, F-actin ring, and integrin ,v,3 expression and co-localization were studied. Results: Osteoclasts from clinically affected subjects had severely attenuated bone resorption compared with those from normal controls. However, osteoclasts from unaffected gene carriers displayed similar bone resorption to those from normal controls. In addition, the resorption lacunae from both unaffected gene carriers and normal controls appeared much earlier and spread much more rapidly than those from clinically affected subjects. As time progressed, the distinction between clinically affected subjects and the other two groups increased. No significant difference was found in acidic secretion or osteoclast formation between the three groups. Osteoclast cytoskeletal organization showed no difference between the three groups but there was low cellular motility in clinically affected subjects. Conclusions: Osteoclasts from the unaffected gene carriers, in contrast to those from the clinically affected subjects, functioned normally in cell culture. This finding supports the hypothesis that intrinsic osteoclast factors determine disease expression in ADO2. Further understanding of this mechanism is likely to lead to the development of new approaches to the treatment of clinically affected patients. [source]


    Electronic Medical Record Review as a Surrogate to Telephone Follow-up to Establish Outcome for Diagnostic Research Studies in the Emergency Department

    ACADEMIC EMERGENCY MEDICINE, Issue 11 2005
    Jeffrey A. Kline MD
    Abstract Background: Follow-up for diagnostic research studies might be facilitated if medical record review (MRR) could be used instead of telephone calls. Objectives: The authors hypothesized that MRR would yield similar accuracy to telephone follow-up. Methods: This was a secondary analysis of 2,178 initially disease-free patients who were followed after enrollment in a diagnostic study of either acute coronary syndrome (45 days) or pulmonary embolism (90 days) conducted in an urban teaching emergency department (ED). Disease status (positive or negative) was defined explicitly. Using structured data forms, trained researchers performed MRR using a comprehensive electronic database, and formulated an opinion about disease status. Trained researchers, blinded to the MRR, then dialed telephone numbers, asked questions from a script, and categorized disease status. The criterion standard was adjudication by consensus of two of three physicians who independently determined disease status based on explicit criteria and access to all follow-up data. Results: Adjudicators found that 13 of 2,178 patients developed disease during follow-up; all 13 true positives occurred among the 2,054 (94.3%) of patients who acknowledged intent to return to the study hospital. Telephone follow-up was successful in 81% of patients, and found all 13 true positives (sensitivity 100%) but with three additional false-positive cases. MRR disclosed 12 of 13 cases of disease (sensitivity 92%) with no false-positive cases. Further review of the one false-negative case from MRR revealed that it occurred after the prescribed time limit for follow-up. Conclusions: Under limited circumstances, accurate clinical follow-up for diagnostic studies conducted in the ED can be obtained by medical record review. [source]


    Flow cytometric measurement of circulating endothelial cells: The effect of age and peripheral arterial disease on baseline levels of mature and progenitor populations

    CYTOMETRY, Issue 2 2006
    Rebecca Gusic Shaffer
    Abstract Background: Age and cardiovascular disease status appear to alter numbers and function of circulating endothelial progenitor cells (EPCs). Despite no universal phenotypic definition, numerous studies have implicated progenitors with apparent endothelial potential in local responses to vascular injury and with cardiovascular disease in general. To further define the role of this lineage in peripheral artery disease (PAD), we developed a multiparameter flow cytometry assay to analyze multiple phenotypic definitions of progenitor cells (PCs), EPCs, and mature endothelial cells (ECs) and evaluate effects of age and PAD on baseline levels of each subset. Methods: Blood was collected from young healthy subjects (N = 9, mean age 33 ± 8 years), older healthy subjects (N = 13, mean age 66 ± 8 years), and older subjects with PAD (N = 15, mean age 69 ± 8 years). After ammonium chloride lysis, cells were stained and analyzed on a Becton-Dickinson LSR II with a 5-color antibody panel: FITC-anti-CD31, PE-anti-CD146, PE-anti-CD133, PerCP-Cy5.5-anti-CD3,-CD19,-CD33 (lineage panel), PE-Cy7-anti-CD34, and APC-anti-VEGF-R2. Viability was assessed by propidium iodide exclusion, and only viable, low to medium side scatter lineage-negative singlets were analyzed. In some studies, cells were sorted for morphological studies. Subsets were defined as indicated later. Results: Our results, using a comprehensive flow cytometric panel, indicate that CD133+, CD34+, and CD133+/CD34+ PCs are elevated in younger healthy individuals compared to older individuals, both healthy and with PAD. However, the number of EPCs and mature ECs did not significantly differ among the three groups. Assessment of endothelial colony forming units and dual acLDL-lectin staining supported the flow cytometric findings. Conclusions: We describe a comprehensive flow cytometric method to detect circulating mature and progenitor endothelial populations confirmed by conventional morphological and functional assays. Our findings suggest that aging may influence circulating levels of PCs, but not EPCs or ECs; PAD had no effect on baseline levels of any populations investigated. This study provides the basis for evaluating the potential effects of acute stress and therapeutic intervention on circulating progenitor and endothelial populations as a biomarker for cardiovascular status. © 2005 International Society for Analytical Cytology [source]


    Electronic Medical Record Review as a Surrogate to Telephone Follow-up to Establish Outcome for Diagnostic Research Studies in the Emergency Department

    ACADEMIC EMERGENCY MEDICINE, Issue 11 2005
    Jeffrey A. Kline MD
    Abstract Background: Follow-up for diagnostic research studies might be facilitated if medical record review (MRR) could be used instead of telephone calls. Objectives: The authors hypothesized that MRR would yield similar accuracy to telephone follow-up. Methods: This was a secondary analysis of 2,178 initially disease-free patients who were followed after enrollment in a diagnostic study of either acute coronary syndrome (45 days) or pulmonary embolism (90 days) conducted in an urban teaching emergency department (ED). Disease status (positive or negative) was defined explicitly. Using structured data forms, trained researchers performed MRR using a comprehensive electronic database, and formulated an opinion about disease status. Trained researchers, blinded to the MRR, then dialed telephone numbers, asked questions from a script, and categorized disease status. The criterion standard was adjudication by consensus of two of three physicians who independently determined disease status based on explicit criteria and access to all follow-up data. Results: Adjudicators found that 13 of 2,178 patients developed disease during follow-up; all 13 true positives occurred among the 2,054 (94.3%) of patients who acknowledged intent to return to the study hospital. Telephone follow-up was successful in 81% of patients, and found all 13 true positives (sensitivity 100%) but with three additional false-positive cases. MRR disclosed 12 of 13 cases of disease (sensitivity 92%) with no false-positive cases. Further review of the one false-negative case from MRR revealed that it occurred after the prescribed time limit for follow-up. Conclusions: Under limited circumstances, accurate clinical follow-up for diagnostic studies conducted in the ED can be obtained by medical record review. [source]


    Preliminary study of mucosal IgA in the equine small intestine: specific IgA in cases of acute grass sickness and controls

    EQUINE VETERINARY JOURNAL, Issue 5 2007
    F. G. NUNN
    Summary Reasons for performing study: There is much evidence to suggest that group III Clostridium botulinum (types C and D) are involved in the aetiology of equine grass sickness (EGS). Antibodies have been detected previously in the blood and high levels associated with resistance to disease. Specific mucosal antibodies in the gastrointestinal (GI) tract are likely to be important in protection, and this study was performed to ascertain if such antibodies could be detected and if their levels were related to disease state. Objectives: To develop a method for quantifying IgA antibodies to C. botulinum types C and D in the GI tract of horses and to relate antibody levels to disease status. Methods: Samples of tissue (n = 25: 6 duodenum, 7 jejunum and 12 ileum) were taken from acute grass sickness (AGS) cases and from control horses (n = 12; 4 samples from each site) at post mortem. They were extracted with the detergent saponin in the presence of protease inhibitors and assayed for total IgA, for specific IgA against botulinum neurotoxins types C and D (BoNT/C or BoNT/D), and against surface antigens of a BoNT/C negative strain of C. botulinum type C (SA) and of Clostridium tetani (TetSA), as a control. Specific IgA was expressed as percentage total IgA. Results: Compared to controls, significantly higher levels of specific IgA against BoNT/C were detected in the jejunum (P = 0.04) and ileum (P = 0.02) of AGS cases. Similarly, higher specific levels against BoNT/D were demonstrated in duodenum (P = 0.01) and jejunum (P = 0.02). Significantly higher levels of IgA against SA were demonstrated only in duodenal samples (P = 0.01). Conclusions: Levels of IgA antibody to BoNTs in control horses were at near undetectable levels, suggesting no recent exposure to toxins. In AGS cases, significantly higher levels of specific IgA were detected predominantly in jejunum and ileum. Potential relevance: If specific IgA is protective then any successful vaccine for EGS should induce a mucosal response. [source]


    Prostate cancer aggressiveness locus on chromosome segment 19q12,q13.1 identified by linkage and allelic imbalance studies

    GENES, CHROMOSOMES AND CANCER, Issue 4 2003
    Phillippa J. Neville
    Whole-genome scan studies recently identified a locus on chromosome segments 19q12,q13.11 linked to prostate tumor aggressiveness by use of the Gleason score as a quantitative trait. We have now completed finer-scale linkage mapping across this region that confirmed and narrowed the candidate region to 2 cM, with a peak between markers D19S875 and D19S433. We also performed allelic imbalance (AI) studies across this region in primary prostate tumors from 52 patients unselected for family history or disease status. A high level of AI was observed, with the highest rates at markers D19S875 (56%) and D19S433 (60%). Furthermore, these two markers defined a smallest common region of AI of 0.8 Mb, with 15 (29%) prostate tumors displaying interstitial AI involving one or both markers. In addition, we noted a positive association between AI at marker D19S875 and extension of tumor beyond the margin (P = 0.02) as well as a higher Gleason score (P = 0.06). These data provide strong evidence that we have mapped a prostate tumor aggressiveness locus to chromosome segments 19q12,q13.11 that may play a role in both familial and non-familial forms of prostate cancer. © 2003 Wiley-Liss, Inc. [source]


    Gene, region and pathway level analyses in whole-genome studies

    GENETIC EPIDEMIOLOGY, Issue 3 2010
    Omar De la Cruz
    Abstract In the setting of genome-wide association studies, we propose a method for assigning a measure of significance to pre-defined sets of markers in the genome. The sets can be genes, conserved regions, or groups of genes such as pathways. Using the proposed methods and algorithms, evidence for association between a particular functional unit and a disease status can be obtained not just by the presence of a strong signal from a SNP within it, but also by the combination of several simultaneous weaker signals that are not strongly correlated. This approach has several advantages. First, moderately strong signals from different SNPs are combined to obtain a much stronger signal for the set, therefore increasing power. Second, in combination with methods that provide information on untyped markers, it leads to results that can be readily combined across studies and platforms that might use different SNPs. Third, the results are easy to interpret, since they refer to functional sets of markers that are likely to behave as a unit in their phenotypic effect. Finally, the availability of gene-level P -values for association is the first step in developing methods that integrate information from pathways and networks with genome-wide association data, and these can lead to a better understanding of the complex traits genetic architecture. The power of the approach is investigated in simulated and real datasets. Novel Crohn's disease associations are found using the WTCCC data. Genet. Epidemiol. 34: 222,231, 2010. © 2009 Wiley-Liss, Inc. [source]


    PEL: an unbiased method for estimating age-dependent genetic disease risk from pedigree data unselected for family history

    GENETIC EPIDEMIOLOGY, Issue 5 2009
    F. Alarcon
    Abstract Providing valid risk estimates of a genetic disease with variable age of onset is a major challenge for prevention strategies. When data are obtained from pedigrees ascertained through affected individuals, an adjustment for ascertainment bias is necessary. This article focuses on ascertainment through at least one affected and presents an estimation method based on maximum likelihood, called the Proband's phenotype exclusion likelihood or PEL for estimating age-dependent penetrance using disease status and genotypic information of family members in pedigrees unselected for family history. We studied the properties of the PEL and compared with another method, the prospective likelihood, in terms of bias and efficiency in risk estimate. For that purpose, family samples were simulated under various disease risk models and under various ascertainment patterns. We showed that, whatever the genetic model and the ascertainment scheme, the PEL provided unbiased estimates, whereas the prospective likelihood exhibited some bias in a number of situations. As an illustration, we estimated the disease risk for transthyretin amyloid neuropathy from a French sample and a Portuguese sample and for BRCA1/2 associated breast cancer from a sample ascertained on early-onset breast cancer cases. Genet. Epidemiol. 33:379,385, 2009. © 2008 Wiley-Liss, Inc. [source]


    Measuring disability in older adults: The International Classification System of Functioning, Disability and Health (ICF) framework

    GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1 2008
    W Jack Rejeski
    Background: Despite the importance of disability to geriatric medicine, no large scale study has validated the activity and participation domains of the International Classification System of Functioning, Disability, and Health (ICF) in older adults. The current project was designed to conduct such as analysis, and then to examine the psychometric properties of a measure that is based on this conceptual structure. Methods: This was an archival analysis of older adults (n = 1388) who had participated in studies within our Claude D Pepper Older Americans Independence Center. Assessments included demographics and chronic disease status, a 23-item Pepper Assessment Tool for Disability (PAT-D) and 6-min walk performance. Results: Analysis of the PAT-D produced a three-factor structure that was consistent across several datasets: activities of daily living disability, mobility disability and instrumental activities of daily living disability. The first two factors are activities in the ICF framework, whereas the final factor falls into the participation domain. All factors had acceptable internal consistency reliability (>0.70) and test,retest (>0.70) reliability coefficients. Fast walkers self-reported better function on the PAT-D scales than slow walkers: effect sizes ranged from moderate to large (0.41,0.95); individuals with cardiovascular disease had poorer scores on all scales than those free of cardiovascular disease. In an 18-month randomized clinical trial, individuals who received a lifestyle intervention for weight loss had greater improvements in their mobility disability scores than those in a control condition. Conclusion: The ICF is a useful model for conceptualizing disability in aging research, and the PAT-D has acceptable psychometric properties as a measure for use in clinical research. [source]


    Determinants of adherence to highly active antiretroviral therapy (HAART) in Chinese HIV/AIDS patients

    HIV MEDICINE, Issue 2 2003
    OW Fong
    Objective Drug adherence is crucial to the success of highly active antiretroviral therapy (HAART) in the treatment of HIV disease. Adherence to HAART and its determinants may, however, differ across HIV/AIDS populations. Methods We retrospectively studied drug adherence by self-report in HIV-1 infected Chinese patients who have been on HAART for at least 1 year as at the end of year 2000. HAART is defined as three or more antiretrovirals with at least one protease inhibitor or non-nucleoside analogue reverse transcriptase inhibitor. Results The last drug adherence level assessed by self-report in 161 Chinese patients were: grade A (100%) , 130, 80.7%; grade B (95,99%) , 25, 15.5%; grade C (90,94%) , three, 1.9% and grade D (< 90%) , three, 1.9%. Patients with full adherence were more likely to have undetectable (< 500 copies/mL) plasma virus level (adjusted OR, 4.22; 95% CI, 1.75,12.33). Patients' demographics, HIV disease status and antiretroviral regimen did not affect adherence. Partial drug adherence was, however, independently associated with the psychosocial factors of missing clinic appointments (adjusted OR, 3.13; 95% CI, 1.23,8.33), forgetfulness (adjusted OR, 4.55; 95% CI, 1.64,12.5) and a busy work life (adjusted OR, 6.67; 95% CI, 1.75,25). Conclusion There were similarities and differences in determinants affecting HAART adherence in Chinese compared with other patients. Psychosocial factors rather than HIV disease or treatment were more important factors in our Chinese patients. The relevance of patient populations and care setting for adherence to HAART shall be further studied. [source]


    Genotype,phenotype correlations in hereditary familial retinoblastoma,

    HUMAN MUTATION, Issue 3 2007
    Melissa Taylor
    Abstract We studied 50 unrelated pedigrees with a family history of retinoblastoma (Rb) (165 carriers of a RB1 mutation) to delineate the spectrum of RB1 germline mutations in familial Rb and to identify genotype,phenotype correlations as well as putative modifiers. Patients were followed at Institut Curie and they were examined by an ophthalmologist, a pediatrician, and a geneticist. All cases of familial Rb were determined via genetic counseling. Clinical features included disease status, laterality, age at diagnosis, mutation type, follow-up, and disease,eye ratio (DER). To eliminate mosaic cases, first-generation carriers displaying low-penetrance (LP) Rb were excluded from the analysis. Complete penetrance was the rule for nonsense and frameshift mutations (25 families) and high penetrance was observed for large rearrangements (eight families). Promoter (two families) and missense (two families) mutations displayed heterogeneous phenotypes and LP. Variable penetrance was observed for splice abnormalities (13 families) and was explained by in/out of frame mutations or respect of functional domains. Surprisingly, two families with the LP g.45867G>T/IVS6+1G>T mutation presented data that conflicted with the data reported in previous publications, as unaffected carriers had paternally inherited mutant alleles. Moreover, RNA analyses suggested that the lack of penetrance in unaffected carriers could be explained by an increase in expression levels of the wild-type allele. This observation prompted us to define a new class "3" of LP alleles. We believe this is the first large-scale study of familial Rb with a high level of homogeneity in the clinical and genetic analysis of patients and their relatives, thereby allowing for reliable intrafamilial genotype,phenotype correlations. Our analysis suggests in some cases the influence of modifier factors probably involved in mRNA level regulation and/or pRB pathway regulation. Hum Mutat 28(3), 284,293, 2007. © 2006 Wiley-Liss, Inc. [source]


    Long-term reliability and observer comparisons in the radiographic diagnosis of periapical disease

    INTERNATIONAL ENDODONTIC JOURNAL, Issue 2 2002
    O. Molven
    Abstract Aim The aim of this study was to evaluate and compare the long-term diagnostic consistency of two examiners, an endodontist and a radiologist, and to make comparisons with findings recorded by an observer with more recent scientific and clinical experience in endodontics. Methodology Three groups, each consisting of 20 full mouth series of intraoral radiographs, with 79, 93 and 85 endodontically-treated roots, respectively, were successively evaluated for periapical disease. Evaluations were at first performed separately by the three observers. Disagreement and difficult, borderline cases were subjected to joint evaluation. Intra- and interexaminer comparisons were made. For two of the observers the observations were compared with findings recorded several years before for the same cases in the same radiographs. Results The intra- and interobserver long-term reliability of the two original examiners resulted in 83% overall agreement, the kappa values were 0.54, 0.57 and 0.53. Comparisons between all three observers disclosed 82%, 85% and 86% agreement and kappa values 0.55, 0.58 and 0.60. The joint evaluations and decisions did not indicate a dominating influence from any of the observers. Conclusions The long-term reliability of the two original observers was judged as being satisfactory. All three observers judged the overall disease status of the material in the same way. The joint discussions of selected cases might reduce observer variation to an acceptable level, avoid a number of false recordings and increase the reliability and validity of the findings. [source]


    Prognostic significance of HIF-1, polymorphisms in transitional cell carcinoma of the bladder

    INTERNATIONAL JOURNAL OF CANCER, Issue 6 2008
    Junichi Nadaoka
    Abstract Recently, two single nucleotide polymorphisms in the hypoxia-inducible factor-1, (HIF-1,) gene, P582S and A588T, were shown to cause significantly higher transcriptional activity than the wild type. We investigated the association between the HIF-1, polymorphisms and the incidence and progression of transitional cell carcinoma of the bladder, and the relationship between the polymorphisms and the tissue vascular endothelial growth factor (VEGF) level or microvessel density (MVD). A total of 219 patients with bladder cancer and 464 healthy native Japanese control subjects were enrolled. Tissue VEGF and HIF-1, expression levels and the mean MVD were evaluated in 73 radical cystectomy specimens by immunohistochemistry. The HIF-1, genotype did not significantly influence the incidence or disease status of bladder cancer. Among patients who underwent radical cystectomy, those with a variant allele had significantly worse disease-free survival (p = 0.001) and disease-specific survival (p = 0.006) than those without a variant allele. Multivariate analysis using a Cox proportional hazard model revealed that the presence of a variant allele was an independent predictor of disease-free survival (HR = 3.10, 95%CI = 1.38,6.99, p = 0.006). Although not statistically significant, the moderate/high expression levels of VEGF in tumor tissues were more frequently observed in patients with a HIF-1, variant allele (11/13, 84.6%) than in those without (33/60, 55%, p = 0.063). The HIF-1, polymorphisms may have a significant influence on the poor prognosis of the patients undergoing radical cystectomy for bladder cancer, while they seem to have no relation to the bladder cancer occurrence. © 2007 Wiley-Liss, Inc. [source]


    Parent,ETH;child agreement and prevalence estimates of diagnoses in childhood: Direct interview versus family history method

    INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 2 2009
    Stéphane Rothen
    Abstract Diagnostic information on children is typically elicited from both children and their parents. The aims of the present paper were to: (1) compare prevalence estimates according to maternal reports, paternal reports and direct interviews of children [major depressive disorder (MDD), anxiety and attention-deficit and disruptive behavioural disorders]; (2) assess mother,child, father,child and inter-parental agreement for these disorders; (3) determine the association between several child, parent and familial characteristics and the degree of diagnostic agreement or the likelihood of parental reporting; (4) determine the predictive validity of diagnostic information provided by parents and children. Analyses were based on 235 mother,offspring, 189 father,offspring and 128 mother,father pairs. Diagnostic assessment included the Kiddie-schedule for Affective Disorders and Schizophrenia (K-SADS) (offspring) and the Diagnostic Interview for Genetic Studies (DIGS) (parents and offspring at follow-up) interviews. Parental reports were collected using the Family History , Research Diagnostic Criteria (FH-RDC). Analyses revealed: (1) prevalence estimates for internalizing disorders were generally lower according to parental information than according to the K-SADS; (2) mother,child and father,child agreement was poor and within similar ranges; (3) parents with a history of MDD or attention deficit hyperactivity disorder (ADHD) reported these disorders in their children more frequently; (4) in a sub-sample followed-up into adulthood, diagnoses of MDD, separation anxiety and conduct disorder at baseline concurred with the corresponding lifetime diagnosis at age 19 according to the child rather than according to the parents. In conclusion, our findings support large discrepancies of diagnostic information provided by parents and children with generally lower reporting of internalizing disorders by parents, and differential reporting of depression and ADHD by parental disease status. Follow-up data also supports the validity of information provided by adolescent offspring. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Development, implementation and benefits of a rheumatology-specific electronic medical record application with automated display of outcome measures

    INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 4 2010
    Anand N. MALAVIYA
    Abstract Objectives:, To make a rheumatology-specific electronic medical record (EMR) application for easy clinical data entry, automated display of outcome measures in real-time that generates well laid-out print-outs; and provides an easily retrievable database for clinical analysis and research. Methods:, Highly labour-intensive ,MS-WORD®' template used earlier provided the basic framework for developing rheumatology-EMR applications. The authors, a rheumatologist and a soft tissue surgeon with expertise in developing medical software, successfully created a rheumatology-EMR application over a period of 2½ years using the same basic flow of work as used in the old ,MS-WORD®' template. Results:, The resulting EMR application form has a standard medical record documenting demographic data, complete diagnosis, appropriate dates, visit number, disease status, history, physical examination, investigations, follow-up and prescription page (with automatic updates wherever applicable). Mathematical calculations required for outcome measures (DAS, DAS28, CDAI, SDAI, AS-DAS, BASDAI, BASFI, BASMI, SLE-DAI and others) are embedded in the software, with automated updating as the examination of the musculoskeletal system proceeds in real time. Following implementation of this EMR application, more patients are being seen, patient waiting lists have been reduced; more time is available for academic and teaching work, without compromising the quality of notes, and print-outs for patients. Data retrieval has simplified clinical research with increased numbers of abstracts being presented and research papers being published. Conclusion:, Healthcare workers with understanding of the basic principles of computers and softwares should interact with software engineers who are either themselves medical doctors or are familiar with the workflow and clinical evaluation processes to create an efficient speciality-specific EMR application. [source]


    Do-Not-Resuscitate and Do-Not-Hospitalize Directives of Persons Admitted to Skilled Nursing Facilities Under the Medicare Benefit

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2005
    Cari R. Levy MD
    Objectives: To determine prevalence and factors associated with do-not-resuscitate (DNR) and do-not-hospitalize (DNH) directives of residents admitted under the Medicare benefit to a skilled nursing facility (SNF). To explore geographic variation in use of DNR and DNH orders. Design: Retrospective cohort study. Setting: Nursing homes in the United States. Participants: Medicare admissions to SNFs in 2001 (n=1,962,742). Measurements: Logistic regression was used to select factors associated with DNR and DNH directives and state variation in their use. Results: Thirty-two percent of residents had DNR directives, whereas less than 2% had DNH directives. Factors associated with having a DNR or DNH directive at the resident level included older age, cognitive impairment, functional dependence, and Caucasian ethnicity. African-American, Hispanic, Asian, and North American Native residents were all significantly less likely than Caucasian residents to have DNR (adjusted odds ratio (OR)=0.35, 0.51, 0.61, and 0.62, respectively) or DNH (adjusted OR=0.26, 0.41, 0.43, and 0.67, respectively) directives. In contrast, residents in rural and government facilities were more likely to have DNR or DNH directives. After controlling for resident and facility characteristics, significant variation between states existed in the use of DNR and DNH directives. Conclusion: Ethnic minorities are less likely to have DNR and DNH directives even after controlling for disease status, demographic, facility, and geographic characteristics. Wide variation in the likelihood of having DNR and DNH directives between states suggests a need for better-standardized methods for eliciting the care preferences of residents admitted to SNFs under the Medicare benefit. [source]


    Incidence of Loss of Ability to Walk 400 Meters in a Functionally Limited Older Population

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 12 2004
    Milan Chang PhD
    Objectives: To assess the incidence of and factors related to nondisabled but functionally limited older adults aged 75 to 85 years losing the ability to walk 400 m. Design: Observational study with average follow-up of 21 months. Setting: Community. Participants: At baseline, 101 persons with objective signs of functional limitations and intact cognitive function agreed to participate in the study. Of these, 81 were able to walk 400 m at baseline, and 62 participated in the follow-up examination. Measurements: Mobility disability was defined as an inability to complete a 400-m walk test. At baseline, eligible participants (n=81) had the ability to walk 400 m, scored between 4 and 9 on the Short Physical Performance Battery (SPPB; range 0,12), and scored 18 or more on the Mini-Mental State Examination. Demographics, difficulty in daily activities, disease status, behavioral risk factors, and muscle strength were assessed at baseline and follow-up. Results: Of 62 persons at follow-up, 21 (33.9%) developed incident mobility disability. The strongest predictors of loss of mobility were the time to complete the 400-m walk at baseline (odds ratio (OR)=1.6 per 1-minute difference, 95% confidence interval (CI)=1.04,2.45), and decline in SPPB score over the follow-up (OR=1.4 per 1-point difference, 95% CI=1.01,1.92). Conclusion: Older persons with functional limitations have a high rate of loss of ability to walk 400 m. The 400-m walk test is a highly relevant, discrete outcome that is an ideal target for testing preventive interventions in vulnerable older populations. [source]


    Plasma Hypertonicity: Another Marker of Frailty?

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2004
    Jodi D. Stookey PhD
    Objectives: To determine whether plasma hypertonicity might be a marker of early frailty, this study tested the associations between plasma hypertonicity, incident disability, and mortality in nondisabled older adults. Design: Longitudinal, observational study. Setting: Community-based. Participants: Older adults (,70), who reported no disability and gave blood in the 1992 Duke Established Populations for Epidemiologic Studies of the Elderly survey (n=705), were re-interviewed in 1996 for functional status (n=561) and followed for all deaths up to January 1, 2000. Measurements: Plasma tonicity was estimated from plasma glucose, sodium, and potassium measures and used to classify subjects as normo- (285,294 mOsm/L) or hypertonic (,300 mOsm/L). Disability was defined as any impairment on the Rosow-Breslau, activity of daily living (ADL), and instrumental activity of daily living (IADL) scales. The relative risk (RR) of any new disability and relative hazard of death associated with hypertonicity were estimated using logistic regression models and Cox proportional hazards models, respectively. All models were controlled for age, sex, race, weight status, current smoking, activity level, plasma blood urea nitrogen and creatinine, cognitive impairment, depression, and chronic disease status. To determine whether observed effects were attributable to plasma glucose alone, all models were repeated on a subsample of nondiabetic, normoglycemic subjects. Results: Plasma hypertonicity (observed in 15% of subjects) was associated with increased risk of new Rosow-Breslau (RR=2.1, 95% confidence interval (CI)=1.2,3.6), IADL (RR=2.3, 95% CI=1.2,4.3), and ADL (RR=2.7 95% CI=1.3,5.6) disability by 1996 and mortality by 2000 (RR=1.4, 95% CI=1.0,1.9). Results were similar for the normoglycemic subgroup (ADL: RR=2.9, 95% CI=1.0,8.0; IADL: RR=2.5, 95% CI=1.0,6.3; Rosow-Breslau: RR=1.8, 95% CI=0.8,3.9; mortality: RR=1.5, 95% CI=0.9,2.3). Conclusion: Plasma hypertonicity may be a marker of early frailty. It was prevalent in this sample of nondisabled community-dwelling older adults and predicted incident disability and mortality. Further research to identify its determinants and consequences may help inform interventions against frailty. [source]


    Periodontitis and perceived risk for periodontitis in elders with evidence of depression

    JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2003
    G. R. Persson
    Abstract Background: Depression and periodontitis are common conditions in older adults. There is some evidence that these two conditions may be related. Aims: To study a population of dentate elders and assess the prevalence of depression, self-assessment of risk for periodontitis and tooth loss, in relation to periodontal disease status. Material and methods: Data were obtained from 701 older subjects (mean age 67.2 years (SD±4.6), of whom 59.5% were women. Self-reports of a diagnosis of depression, scores of the Geriatric Depression Scale (GDS), and self-assessment of risk for future tooth loss and periodontitis were compared with a diagnosis of periodontitis based on probing depth, and bone loss assessed from panoramic radiographs. Other systemic diseases and smoking habits were also determined and studied in relation to depression. Results: A history of depression was reported by 20% of the subjects. GDS scores 8 were reported by 9.8% of the elders. Periodontitis was identified in 48.5% of the subjects. Depression was associated with heart attack (p<0.05), stroke (p<0.01), high blood pressure (p<0.02), all combined cardiovascular diseases (p<0.001), chronic pain (p<0.01), osteoarthritis (p<0.001), and osteoporosis (p< 0.001) but not with periodontitis (p=0.73). Subjects with depression had a higher self-reported risk score for future tooth loss (p<0.02). No group difference emerged for self-perceived risk for periodontitis. Logistic regression analysis demonstrated that a past history of tooth loss (p<0.001), self-perceived risk for periodontitis (p<0.02), the number of years with a smoking habit (p<0.02), and male gender (p<0.02) were associated with a diagnosis of periodontitis but neither measure of depression could be included in an explanatory model for periodontitis. Conclusions: Evidence of depression (self-report or by GDS) is not associated with risk for periodontitis in older subjects but is associated with tooth loss and chronic conditions associated with pain. Zusammenfassung Hintergrund: Depression und Parodontitis sind gewöhnliche Bedingungen bei älteren Erwachsenen. Es gibt einige Evidenz, dass diese zwei Bedingungen miteinander in Beziehung stehen könnten. Ziel: Studium einer älteren bezahnten Population und Feststellung der Prävalenz der Depression, Selbstbestimmung des Risikos für Parodontitis und Zahnverlust in Beziehung zum parodontalen Erkrankungsstatus. Material und Methoden: Die Daten wurden von 701 älteren Personen erhalten (mittleres Alter 67.2 Jahre, SD+4.6), von denen 59.5% Frauen waren. Die Selbstberichte zur Diagnose Depression, Scorewerte einer geriatrischen Depressionsskala (GDS) und Selbstbeobachtung des Risikos eines zukünftigen Zahnverlustes und der Parodontitis wurden mit der Diagnose Parodontitis verglichen, die auf der Sondierungstiefe und dem Knochenverlust, gemessen an Panoramaaufnahmen, beruhte. Andere systemische Erkrankungen und Rauchen wurden auch bestimmt und in Beziehung zur Depression studiert. Ergebnisse: Eine Depression wurde von 20% der Personen berichtet. GDS Werte 8 wurden bei 9.8% der Älteren berichtet. Parodontitis wurde bei 48.5% der Personen identifiziert. Depression war verbunden mit Herzattacken (p<0.05), Schlaganfall (p<0.01), Bluthochdruck (p<0.02), allen kombinierten kardiovaskulären Erkrankungen (p<0.001), aber nicht mit Parodontitis (p=0.73). Personen mit Depression hatten ein höheres selbst berichtetes Risiko für zukünftigen Zahnverlust (p<0.02). Keine Gruppendifferenzen tauchten für das selbst berichtetes Risiko für Parodontitis auf. Die logistische Regressionsanalyse demonstrierte, dass vergangener Zahnverlust (p<0.001), selbst erkanntes Risiko für Parodontitis (p<0.02), die Anzahl der Jahre mit Zigarettenrauchen (p<0.02) und das männliche Geschlecht (p<0.02) mit der Diagnose Parodontitis verbunden waren, aber keine Messung der Depression konnte in das erklärende Modell für Parodontitis eingebunden werden. Schlussfolgerungen: Die Evidenz für Depression (selbst berichtet oder mit Hilfe des GDS) ist nicht verbunden mit dem Risiko für Parodontitis bei älteren Personen, aber ist verbunden mit Zahnverlust und chronischen mit Schmerz verbundenen Bedingungen. Résumé Contexte: La dépression et la parodontite sont des conditions banales chez les adultes âgés. Il existe quelques preuves de la relation entre ces deux conditions. Buts: étudier une population de sujets âgés et dentés et mettre en évidence la prévalence de la dépression, l'évaluation personnelle de risque de développement d'une parodontite et de perte dentaire en relation avec l'état de maladie parodontale. Matériels et méthodes: Des données furent obtenues chez 701 sujets âgés (age moyen 67.2 ans (SD±4.6), dont 59.5%étaient des femmes. Le rapport personnel de diagnostique de dépression, les scores de l'échelle gériatrique de dépression (GDS), et l'évaluation personnelle de risque de future perte dentaire et de parodontite furent comparés avec un diagnostique de parodontite fondé sur la profondeur au sondage et la mise en évidence de perte osseuse sur des radiographies panoramiques. D'autres maladies systémiques et le tabagisme furent aussi déterminés et étudiés en relation avec la dépression. Résultats: Un historique de dépression fut reporté chez 20% des sujets. Des scores de GDS 8 furent reportés par 9.8% des personnes âgés. Une parodontite fut identifiée chez 48.5% des sujets. La dépression était associée avec une attaque cardiaque (p<0.05), congestion cérébrale (p<0.01), hypertension (p<0.02), toute maladie cardiaque confondue (p<0.001), douleur chronique (p<0.01), arthrite osseuse (p<0.001), et ostéoporose (p< 0.001) mais pas avec la parodontite (p=0.73). Les sujets atteints de dépression avait un score de risque auto-rapporté de future perte dentaire plus important (p<0.02). Aucune différence des groupes n'émergeait pour l'auto-perception d'un risque de parodontite. Une analyse de régression logistique démontrait qu'un historique préalable de perte dentaire (p<0.001), un risque auto-perçu de parodontite (p<0.02), la durée de tabagisme (p<0.02), et l'appartenance au sexe masculin (p<0.02) étaient associés avec un diagnostique de parodontite mais aucune mesure de dépression ne pouvait être incluse dans un modèle d'explication de parodontite. Conclusions: la mise en évidence de la dépression (auto-rapportée ou par GDS) n'est pas associée avec un risque de parodontite chez des personnes âgés mais avec la perte dentaire et des conditions chroniques associées avec la douleur. [source]


    Effects of specific nutrients on periodontal disease onset, progression and treatment

    JOURNAL OF CLINICAL PERIODONTOLOGY, Issue 7 2003
    Rodrigo F. Neiva
    Abstract Objectives: The aim of this paper is to review the available literature pertaining to the effects of specific nutritional elements (e.g. vitamin B-complex, vitamin C and dietary calcium) on general wound healing, periodontal disease status and response to periodontal therapy. Methods: Critical appraisal of various studies that have evaluated the effects of calcium, ascorbic acid and vitamin B-complex in wound healing and periodontal treatment. Results: Periodontal disease onset, progression and response to therapeutic interventions have been shown to be influenced by several systemic, local and environmental modifying factors. Nutritional supplementation has been suggested as a possible influencing factor on periodontal status and wound healing. Several studies have reported various degrees of association between nutritional elements/supplements and periodontal status, and others have reported possible positive influences of nutritional supplementation on periodontal therapeutic outcomes. Future research needs to more fully explore the presence and strength of association between nutrition and periodontal health. Conclusions: Data collected from the literature suggests that nutrient supplementation causes minimal or no side effects. However, the efficacy of prophylactic nutrient supplementation for the prevention of the onset and progression of periodontal disease, or for the enhancement of periodontal wound healing, remains to be determined. Zusammenfassung Es konnte gezeigt werden, dass der Beginn, der Verlauf und das Ansprechen auf therapeutische Intervention parodontaler Erkrankungen durch verschiedene modifizierende systemische, lokale und Umweltfaktoren beeinflusst werden. Ergänzungen zur Ernährung wurden als mögliche Einflussfaktoren für den parodontalen Status und die Wundheilung diskutiert. Diese Arbeit gibt eine Übersicht über die verfügbare Literatur zum Einfluss spezieller Elemente der Ernährung (z.B. Vitamin-B-Komplex, Vitamin C und Kalzium) auf die generelle Wundheilung, parodontale Erkrankungen sowie das Ansprechen auf parodontale Therapie. Verschiedene Studien haben über Zusammenhänge zwischen Elementen der Nahrung bzw. Ernährungsergänzungen und dem parodontalen Status berichtet. Andere berichten über mögliche positive Einflüsse von Ernährungsergänzungen auf das Ergebnis parodontaler Therapie. Besonderer Wert wird auf die kritische Bewertung der vorhandenen Studien gelegt und es werden Empfehlungen für zukünftigen Forschungsbedarf gegeben, um die Existenz und Ausprägung von Zusammenhängen zwischen Ernährung und parodontaler Gesundheit vollständig zu erfassen. Daten, die aus der Literatur gesammelt wurden, legen den Schluss nahe, dass eine Ergänzung der Ernährung minimale oder keine Nebenwirkungen hat. Allerdings die Wirksamkeit einer prophylaktischen Ernährungsergänzung für die Prävention der Entstehung und Progression von Parodontitis oder die Verbesserung der parodontalen Wundheilung muss noch bestimmt werden. Résumé L'apparition, la progression et la réponse de la maladie parodontale aux interventions thérapeutiques sont influencées par différents facteurs systémiques locaux et environnementaux. L'apport supplémentaire de substances nutritives a été suggéré comme facteur influençant l'état parodontal et la guérison. Cette étude revoit la littérature concernant les effets des éléments nutritionnels spécifiques comme le complexe vitaminique-B, le vitamine-C et le calcium diététique sur la guérison en général, l'état de la maladie parodontale et la réponse au traitement parodontal. Différentes études ont rapporté différents degrés d'association entre les éléments/suppléments nutritifs et l'état parodontal, et d'autres ont rapporté des influences positives possibles des suppléments nutritionnels sur la guérison thérapeutique parodontale. L'importance est axée sur l'appréciation critique d'études disponibles et sur une recommandation en recherches futures pour explorer davantage la présence et la force de l'association entre la nutrition et la santé parodontale. Des données collectées de la littérature suggèrent que l'apport de suppléments nutritifs n'est suivi que de peu ou pas d'effets secondaires. Cependant, l'efficacité d'un supplément nutritif prophylactique pour la prévention primaire et de la progression de la maladie parodontale, ou pour l'augmentation de la guérison parodontale reste à déterminer. [source]


    Demography of American chestnut populations: effects of a pathogen and a hyperparasite

    JOURNAL OF ECOLOGY, Issue 4 2004
    ANITA L. DAVELOS
    Summary 1Matrix models were used to evaluate the effect of chestnut blight infection on transition probabilities and population growth rates for American chestnuts. Disease-free, epidemic and recovering (i.e. pathogen infected with a double-stranded (ds) RNA hypovirus) populations were compared. 2Population growth rates (,) did not differ significantly over time or with disease status. However, predicted stable stage distributions differed between population types, with disease-free and recovering populations more similar to each other than either was to epidemic populations. 3Survival had the highest proportional contribution to population growth rates as revealed by elasticity analyses. However, reductions in stasis of the largest trees contributed most to reductions in population growth rate when comparing diseased with disease-free populations using LTRE. 4The presence of hypovirus reduces pathogen virulence, allowing individual American chestnut trees to increase in size. Where dsRNA has spread, chestnut populations in Michigan have attained population dynamics similar to those found in disease-free populations. 5Matrix models and life table response experiments can be used to detect important pathogen-mediated changes in the dynamics of host populations. [source]


    Sensitivity and specificity of current diagnostic tests for gill-associated virus in Penaeus monodon

    JOURNAL OF FISH DISEASES, Issue 11 2006
    J Munro
    Abstract This study reports the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy between a reverse transcriptase-nested polymerase chain reaction (RT-nPCR) and an enzyme-linked immunosorbent assay (ELISA) for the detection of gill-associated virus (GAV) from a sample of 120 Penaeus monodon. Subsequently, the same comparisons were applied to the ELISA and haemagglutination (HA) assays for detection of GAV from a second 120 prawns. The optical density (OD) or dilution cut-off point had a direct influence on the tested parameters. The cut-off OD of 0.5,0.6 with the ELISA produced a sensitivity of 98% compared with RT-nPCR. However, these OD produced the lowest accuracy (85.8% and 86.7%, respectively). The OD cut off of 0.75 resulted in the highest accuracy (91.7%) and NPV (81.3%) while it had the second highest sensitivity (97%) and PPV (93.3%). However, the OD cut off of 0.9 had the highest specificity (80%). With regards to HA, the titre cut off at 8 resulted in the highest sensitivity, specificity and NPV (94%, 100% and 100%, respectively) compared with the ELISA, while the HA titre of 16 gave the highest accuracy (73%) and the second highest specificity (75%). A HA titre of 64 gave the highest PPV (81%). Using the RT-nPCR as the gold standard, the ELISA had an accuracy of 91.7% when using a cut off >0.75 as a positive result. When compared with the ELISA, the HA had an accuracy of 73% when using an HA titre cut off greater than 16 as a positive result. These results indicate that alternative tests for GAV (ELISA and HA) can be used to explore multiple questions about the disease status of P. monodon stocks in a cost-effective manner. [source]


    High specificity of V3 serotyping among human immunodeficiency virus type-1 subtype C infected patients with varying disease status and viral phenotype

    JOURNAL OF MEDICAL VIROLOGY, Issue 10 2006
    Polly R. Walker
    Abstract V3 serotyping is a technique for determining HIV-1 genetic subtype based on the binding of antibodies from patient sera or plasma to synthetic V3 peptides derived from subtype consensus sequences. Variation in the performance of this assay has been attributed to V3 sequence heterogeneity, the degree of which varies with patient disease progression, virus co-receptor usage, and genetic subtype. This study assessed the performance of a competitive peptide enzyme immunoassay (cPEIA) in samples from HIV-1 subtype C infected patients with varying disease profiles, including those with syncytium (SI) and non-syncytium-inducing (NSI) viruses. Out of 90 sera tested, 94.4% reacted strongly against the subtype C peptide. There was no significant difference in assay sensitivity among samples from advanced AIDS patients in which humoral immune response may be lower, nor among SI viruses which carry changes in the V3 sequence. Four samples were found to be cross-reactive with other subtypes and one acutely infected patient sample was non-reactive due to low anti-gp120 antibody titers. A significantly higher number of samples showed secondary reactivity to subtype A, compared to other subtypes (P,<,0.005). In conclusion, the assay was able to identify HIV-1 subtype C infection with a high level of sensitivity (94%) irrespective of the stage of disease and therefore provides a valuable resource for the large-scale epidemiological monitoring of the spread of HIV-1 subtypes in South Africa. J. Med. Virol. 78:1262,1268, 2006. © 2006 Wiley-Liss, Inc. [source]


    Monitoring periodontal disease status in smokers and nonsmokers using a gingival crevicular fluid matrix metalloproteinase-8-specific chair-side test

    JOURNAL OF PERIODONTAL RESEARCH, Issue 6 2006
    P. Mäntylä
    Background and Objective:, With current periodontal diagnostic tools it is difficult to identify susceptible individuals or sites at risk. The aim of this study was to evaluate the efficacy of the matrix metalloproteinase (MMP)-8-specific chair-side dip-stick test in longitudinally monitoring the periodontal status of smoking (S) and nonsmoking (NS) patients with chronic periodontitis, using their gingival crevicular fluid (GCF) MMP-8 concentrations. Material and Methods:, Clinical parameters, MMP-8 test results and concentrations were monitored in 16 patients after initial treatment and in 15 patients after scaling and root planing (SRP), every other month, over a 12-mo time period. Progressing and stable sites, and sites with exceptionally high MMP-8 concentrations, were analysed in smokers and nonsmokers. Results:, SRP reduced the mean GCF MMP-8 levels, test scores, probing depth (PD), attachment loss (AL) and bleeding on probing (BOP). In sites of periodontal disease progression, the distribution of MMP-8 concentrations was broader than in stable sites, indicating a tendency for elevated concentrations in patients with periodontal disease. The mean MMP-8 concentrations in smokers were lower than in nonsmokers, but in smokers' and nonsmokers' sites with progressive disease, MMP-8 concentrations were similar. Sites with exceptionally elevated MMP-8 concentrations were clustered in smokers who also showed a poor response to SRP. In these sites, the MMP-8 concentration did not decrease with SRP and these sites were easily identified by the MMP-8 test. Conclusion:, Persistently elevated GCF MMP-8 concentrations may indicate sites at risk, as well as patients with poor response to conventional periodontal treatment (e.g. SRP). MMP-8 testing may be useful as an adjunct to traditional periodontal diagnostic methods during the maintenance phase. [source]


    Assessing accuracy of a continuous screening test in the presence of verification bias

    JOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 1 2005
    Todd A. Alonzo
    Summary., In studies to assess the accuracy of a screening test, often definitive disease assessment is too invasive or expensive to be ascertained on all the study subjects. Although it may be more ethical or cost effective to ascertain the true disease status with a higher rate in study subjects where the screening test or additional information is suggestive of disease, estimates of accuracy can be biased in a study with such a design. This bias is known as verification bias. Verification bias correction methods that accommodate screening tests with binary or ordinal responses have been developed; however, no verification bias correction methods exist for tests with continuous results. We propose and compare imputation and reweighting bias-corrected estimators of true and false positive rates, receiver operating characteristic curves and area under the receiver operating characteristic curve for continuous tests. Distribution theory and simulation studies are used to compare the proposed estimators with respect to bias, relative efficiency and robustness to model misspecification. The bias correction estimators proposed are applied to data from a study of screening tests for neonatal hearing loss. [source]


    The influence of common gene variants of the xenobiotic receptor (PXR) in genetic susceptibility to intrahepatic cholestasis of pregnancy

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010
    G. CASTAÑO
    Aliment Pharmacol Ther,31, 583,592 Summary Background, The xenobiotic nuclear pregnane X receptor is implicated in many physiological pathways and diseases, including bile acid detoxification and cholestasis. Aim, To estimate the contribution of common gene variants of the xenobiotic receptor (pregnane X receptor, PXR) to genetic susceptibility to intrahepatic cholestasis of pregnancy. Methods, A total of 101 intrahepatic cholestasis of pregnancy patients and 171 healthy pregnant women in the third trimester of their pregnancies were included. Four tag single nucleotide polymorphisms (SNPs) (rs12488820 C/T, rs2472671 C/T, rs2461823 A/G, and rs1054191 A/G) encompassing 36 kb in chromosome 3, with a minor allele frequency ,0.10 and representing 33 polymorphic sites were genotyped. Besides these, three additional SNPs (rs3814057, rs6785049, and rs7643645) were included because they showed previous evidence of functionality. Results, Genotypic test for single SNPs showed that rs2461823 genotypes were significantly associated with intrahepatic cholestasis of pregnancy (P < 0.0069), OR per G allele: 1.44, 95% CI: 1.01,2.05, P < 0.042. The Cochran-Armitage test for trend and the allelic test showed a significant association with disease status (P < 0.04 and 0.03 respectively), G being the risk allele. A positive association between rs2461823 and ALT, AST, and bilirubin concentrations was observed. Neonate birth weight adjusted by the Capurro index was significantly associated with rs2461823 (P < 0.05); the proportion of the total variation attributed to rs2461823 genotypes was 7.8%. Conclusion, Common PXR polymorphisms may contribute to the genetic susceptibility to intrahepatic cholestasis of pregnancy. [source]


    Evaluation of the meaningfulness of health-related quality of life improvements as assessed by the SF-36 and the EQ-5D VAS in patients with active Crohn's disease

    ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2009
    G. COTEUR
    Summary Background, Crohn's disease (CD) is a chronic inflammatory illness characterized by episodic abdominal pain, diarrhoea, fever, bleeding and obstruction. While the Crohn's Disease Activity Index (CDAI) remains the most commonly accepted measure for assessing the disease status in clinical trials, patient-reported outcome (PRO) instruments are being utilized more frequently to provide information about health-related quality of life (HRQOL). To facilitate interpretation of results, it is common to identify a meaningful unit of PRO score change, such as a minimal clinically important difference (MCID). Aim, To define and apply MCID estimates for the SF-36 and EuroQol-5D visual analogue scale (EQ-5D VAS) for use in CD treatment evaluation. Methods, Data from two phase III randomized controlled trials of certolizumab pegol were utilized. MCID estimates were computed from one trial using anchor-based and distribution-based methods. These estimates were applied to data from the other trial. Results, SF-36 PCS and MCS MCID estimates ranged from 1.6 to 7.0 and 2.3 to 8.7 respectively, depending on approach. EQ-5D VAS MCID estimates ranged from 4.2 to 14.8. Conclusions, For the first time, the MCID values provided interpretation guidelines for PRO results in CD. This research demonstrates that patients treated with certolizumab pegol benefit from meaningful and sustained HRQOL improvements. [source]


    Anti-Erythrocyte Antibodies and Disease Associations in Anemic and Nonanemic Dogs

    JOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 4 2008
    P. Morley
    Background: Flow cytometry has been used to detect anti-red blood cell (RBC) antibodies in dogs with immune-mediated hemolytic anemia (IMHA), but the prevalence of anti-RBC antibodies in anemic and nonanemic dogs with a variety of different diseases has not been assessed previously. Hypothesis: We hypothesized that anti-RBC antibodies would be more common in anemic dogs and in dogs with immune-mediated disorders and cancer. Animals: Blood samples from 292 dogs were analyzed prospectively by flow cytometry for anti-RBC antibodies. Methods: Blood samples from 147 anemic and 145 nonanemic dogs were evaluated by flow cytometry to detect surface-bound immunoglobulin (Ig) G and IgM antibodies on RBC. Disease associations with RBC antibodies were determined, as was the correlation between disease status and the percentage of Ig+ RBC. The specificity and sensitivity of flow cytometry and clinical variables for the diagnosis of IMHA were compared by Bayesian analysis. Results: Anemic dogs were significantly more likely to be positive for anti-RBC antibodies (IgG, IgM, or both) than nonanemic dogs. Anemic dogs also had significantly higher percentages of Ig+ RBC than nonanemic dogs, whereas dogs with IMHA had significantly higher percentages of Ig+ RBC than dogs with all other diseases. Dogs with IMHA, infectious diseases, and immune-mediated thrombocytopenia were significantly more likely to have anti-RBC antibodies than dogs with other medical or surgical diseases. Conclusions: Anemic dogs with immune-mediated diseases and infectious diseases were at the highest risk for the development of anti-RBC antibodies, and flow cytometry for the detection of IgG on RBC was highly sensitive and specific for the diagnosis of IMHA. [source]


    A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts

    LIVER TRANSPLANTATION, Issue 3 2009
    Edward Alabraba
    Previously, we have found that the absence of the colon after liver transplantation (LT) protects the patient from recurrent primary sclerosing cholangitis (rPSC). As our previous observation has not been confirmed in other series, we have reviewed our cohort of patients grafted for primary sclerosing cholangitis (PSC) with greater numbers and longer follow-up to reassess the rate, consequences, and risk factors for rPSC. We collected data on patients who underwent LT for PSC between January 1986 and April 2006. Data were collected for cytomegalovirus status, inflammatory bowel disease status, time of colectomy, type of colectomy, donor-recipient gender mismatch, recipient sex, extended donor criteria (EDC), and donor risk index. Accepted criteria were used to diagnose rPSC. Of a total of 230 consecutive adult patients, 61 (27%) underwent colectomy pre-/peri-LT, and 54 (23.5%) developed rPSC at a median of 4.6 (range, 0.5,12.9) years post-LT. A total of 263 deceased donor grafts were used, and 73 were EDC grafts. A diagnosis of rPSC was made in 61 of the 263 grafts (23%). The recurrence-free patient survival was significantly better (P < 0.05) in patients who underwent pre-/peri-LT colectomy and in those with non-EDC grafts. In conclusion, in this larger cohort of 230 patients and with longer follow-up of 82.5 (range, 0.0,238.6) months [in comparison with the previous report of 152 recipients with a follow-up of 52.8 (range, 1,146) months], we have shown that colectomy remains a significant risk factor for rPSC and that colectomy before and during initial LT for PSC confers a protective effect against rPSC in subsequent graft(s). Moreover, we have shown that EDC grafts are also a significant risk factor for rPSC. Liver Transpl 15:330,340, 2009. © 2009 AASLD. [source]


    Heterozygosity,fitness correlations and associative overdominance: new detection method and proof of principle in the Iberian wild boar

    MOLECULAR ECOLOGY, Issue 13 2009
    AURELIO F. MALO
    Heterozygosity-fitness correlations (HFC) may result from a genome-wide process , inbreeding , or local effects within the genome. The majority of empirical studies reporting HFCs have attributed correlations to inbreeding depression. However, HFCs are unlikely to be caused by inbreeding depression because heterozygosity measured at a small number of neutral markers is unlikely to accurately capture a genome-wide pattern. Testing the strengths of localized effects caused by associative overdominance has proven challenging. In their current paper, Amos and Acevedo-Whitehouse present a novel test for local HFCs. Using stochastic simulations, they determine the conditions under which single-locus HFCs arise, before testing the strength of the correlation between the neutral marker and a linked gene under selection in their simulations. They used insights gained from simulation to statistically investigate the likely cause of correlations between heterozygosity and disease status using data on bovine tuberculosis infections in a wild boar population. They discover that a single microsatellite marker is an excellent predictor of tuberculosis progression in infected individuals. The results are relevant for wild boar management but, more generally, they demonstrate how single-locus HFCs could be used to identify coding loci under selection in free-living populations. [source]