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Significant Covariates (significant + covariate)
Selected AbstractsChildren's Responses to Computer-Synthesized Speech in Educational Media: Gender Consistency and Gender Similarity EffectsHUMAN COMMUNICATION RESEARCH, Issue 3 2007Kwan Min Lee This study examines children's social responses to gender cues in synthesized speech in a computer-based instruction setting. Eighty 5th-grade elementary school children were randomly assigned to one of the conditions in a full-factorial 2 (participant gender) × 2 (voice gender) × 2 (content gender) experiment. Results show that children apply gender-based social rules to synthesized speech. More specifically, children evaluate synthesized speech more positively, trust the speech more, and learn more effectively when voice gender matches either content gender (consistency attraction) and/or their own gender (similarity attraction). Children's computer self-efficacy was a significant covariate for their social responses to synthesized speech. Theoretical and practical implications of the current study for the design of educational media are discussed. [source] The effects of obstructive jaundice on the pharmacodynamics of propofol: does the sensitivity of intravenous anesthetics change among icteric patients?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009J. C. SONG Background Some studies suggest that certain clinical symptoms of cholestasis, such as fatigue and pruritus, result from altered neurotransmission. Patients with obstructive jaundice also have labile blood pressure and heart rate. In the present study, the authors investigated whether obstructive jaundice affects a patient's sensitivity to hypnotics and the haemodynamic profile of propofol. Methods Thirty-six ASA physical status I/II/III patients with serum total bilirubin (TBL) from 7.8 to 362.7 ,mol/l scheduled for bile duct surgery were recruited. A computer-controlled propofol infusion programmed for effect site target was used to rapidly attain and maintain sequential increase of the compartment concentration (from 1 to 3 ,g/ml). Each target-controlled concentration was maintained for about 12 min, and arterial blood samples were drawn for propofol concentration determination. The bispectral index (BIS) and mean arterial pressures (MAP) were used as indices of the propofol effect. The relation between the concentration and the effects was described by the Hill equation. The pharmacodynamic parameters were optimized using a nonlinear mixed-effect model. Results TBL was not a significant covariate of EC50 for the pharmacodynamic model. For BIS and MAP, the parameters of the pharmacodynamic model were Emax=75.77%, EC50=2.34 ,g/ml, and ,=1.82, and Emax=47.83%, EC50=1.49 ,g/ml, and ,=1.88, respectively. Conclusions We demonstrated that obstructive jaundice with serum TBL from 7.8 to 362.7 ,mol/l had no effect on propofol pharmacodynamics observed by BIS and MAP. [source] Administration of enoxaparin by continuous infusion in a naturalistic setting: analysis of renal function and safety,JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2005S. L. Kane-Gill Pharm D MSc Summary Study objective:, To describe the clinical use and safety of continuous infusion (CI) enoxaparin in a naturalistic setting and to evaluate the influence of renal function on enoxaparin elimination. Design:, Retrospective medical record review. Setting:, 1000-bed tertiary care teaching centre. Patients:, Hospitalized patients that received enoxaparin by CI during a 2-year period. Interventions:, None. Measurements:, Specific details of dosage and monitoring were collected. Adverse drug reactions (ADR) were recorded. Creatinine clearance (CrCl) was calculated using Cockroft and Gault and Brater equations. A population pharmacokinetic analysis was performed using the non-linear mixed effect model (NONMEM). For patients located in the intensive care unit (ICU) and ward, POSTHOC pharmacokinetic parameter estimates were evaluated using the Wilcoxon rank-sum. Pearson correlation coefficient was calculated to determine the association between renal function and anti-Xa clearance. Main results:, Sixty-seven patients received enoxaparin by CI of which 61·2% were in the ward and 38·8% in the ICU. The average initial rate and duration of infusion were 5·2 mg/h and 5·6 days, respectively. The number of anti-Xa concentration measurements averaged five per patient. Nine patients experienced an ADR. The most frequent ADR was gastrointestinal bleeding (n = 4). Among the 67 patients, 48 had available anti-Xa concentrations and were included in the NONMEM model. The anti-Xa CL and volume of distribution for ICU and ward patients averaged 0·64 ± 0·34 L/h, 10·6 ± 1·55 L and 1·01 ± 0·39 L/h, 9·08 ± 1·17 L, respectively. CrCl was not a significant covariate when included in the NONMEM model, and the association between CrCl and anti-Xa clearance was not significant (R2 = 0·0005; P = 0·8916). Conclusions:, This study is the first to report the use and safety of prolonged CI enoxaparin. Pharmacokinetic parameters of enoxaparin differ in ICU vs. ward patients. Overall, we found the safety of CI to be comparable to subcutaneous administration. Also, we found no effect of renal function on enoxaparin elimination. [source] Effects of multimedia and schema induced analogical reasoning on science learningJOURNAL OF COMPUTER ASSISTED LEARNING, Issue 6 2008R.Z. Zheng Abstract The present study investigates the effects of multimedia and schema induced analogical reasoning on science learning. It involves 89 fourth grade elementary students in the north-east of the United States. Participants are randomly assigned into four conditions: (a) multimedia with analogy; (b) multimedia without analogy; (c) analogy without multimedia; and (d) non-multimedia and non-analogy. The multivariate analyses of covariance reveal significant main effects for multimedia and analogy learning as well as a significant interaction between multimedia and analogy. The findings show that schema induced analogical reasoning can significantly improve science learning and that multimedia becomes more effective when it is integrated with an instructional method such as analogy and less so when it is used only as a visual tool. The study also shows the field dependence/independence as a significant covariate that influences learners' schema induced analogical reasoning in learning. Discussions pertaining to the significance of the findings and their implications for teaching and learning are made. Suggestions for future research are included with an emphasis on developing multimedia supported analogical reasoning for science learning. [source] Quality of life in multiple sclerosis: a Kuwaiti MSQOL-54 experienceACTA NEUROLOGICA SCANDINAVICA, Issue 6 2008A. F. Alshubaili Objectives,,, We compared the quality of life (QOL) self-ratings of relapsing,remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (PMS) patients with those of the general population; and assessed the association of demographic, clinical, and caregiver variables with patients' QOL. Methods,,, Consecutive clinic attendees were assessed with MSQOL-54, Beck's Depression Inventory, and Expanded Disability Status Scale. Caregivers rated their impression of patients' QOL and attitudes to patients' illness. Results,,, Of 170 patients (35.5% M, 64.5% F), 85.3% had RRMS and 14.7% PMS. RRMS had higher QOL domain scores (P < 0.001). Patients had lower QOL than controls (P < 0.001). Depression was the commonest significant covariate of QOL domains. After controlling for depression and disability, differences between the MS groups were less significant. Predictors of overall QOL were caregiver impression of patient's QOL, depression, and treatment side effects. Conclusion,,, Programs that address depression, disability, the impact of treatment side effects, caregiver attitudes and education should enhance QOL outcomes. [source] Single Question about Drunkenness to Detect College Students at Risk for InjuryACADEMIC EMERGENCY MEDICINE, Issue 6 2006Mary Claire O'Brien MD Abstract Objectives: To examine the frequency of injuries reported by college students who replied affirmatively to the question, "In a typical week, how many days do you get drunk?" Methods: In Fall 2003, a Web-based survey was administered to a stratified random sample of 3,909 college students from ten North Carolina (NC) universities. Students answered questions regarding alcohol use and its consequences. Data were analyzed using multiple logistic regression, controlling for within-school clustering of drinking behaviors and adjusting for other significant covariates. Adjusted odds ratios (AORs) and 95% confidence intervals (CI) were calculated for significant predictors (p < 0.05). Results: Two thousand four hundred eighty-eight students reported that they are current drinkers; 1,353 (54.4%) reported getting drunk at least once in a typical week. Compared with students who did not report getting drunk at least once a week, these students had higher odds of being hurt or injured at least once as a result of their own drinking (AOR = 4.97; 95% CI = 3.47 to 7.09), experiencing a fall from a height that required medical treatment (AOR = 2.16; 95% CI = 1.36 to 3.43), and being taken advantage of sexually as a result of another's drinking (AOR = 2.59; 95% CI = 1.72 to 3.89). Students who reported getting drunk at least one day in a typical week also were more likely to cause an injury requiring medical treatment to someone else. They had higher odds of causing injury in an automobile crash (AOR = 1.84; 95% CI = 1.01 to 3.40), of causing a burn that required medical treatment (AOR = 2.85; 95% CI = 1.51 to 5.39), and of causing a fall from a height that required medical treatment (AOR = 2.02; 95% CI = 1.01 to 4.04). Getting drunk was a better indicator of "self-experienced injury" and of "injury caused to someone else" than was binge drinking, for all outcomes (p < 0.05). Conclusions: The single question, "In a typical week, how many days do you get drunk?" identifies college students who are at higher than normal risk of injury as a result of their own drinking and the drinking of others. Future research should assess this question's effectiveness as a screening tool in campus health centers and in emergency departments. [source] The Effect of Reminiscence Group Work on Life Satisfaction, Self-Esteem and Mood of Ageing People with Intellectual DisabilitiesJOURNAL OF APPLIED RESEARCH IN INTELLECTUAL DISABILITIES, Issue 1 2009Joris Van Puyenbroeck Background, This study evaluates the effects of reminiscence group work on the subjective well-being of ageing people with intellectual disabilities. Methods, The content of the successive group work sessions was manipulated as follows: a control-phase with three ,current topics' sessions, an experimental phase with six ,reminiscence' sessions and finally three ,current topics' sessions. Life satisfaction, perceived self-competence and mood were measured by questionnaires, filled in by the participants and direct support workers. Results, A quasi-experimental pre-test,post-test design (n = 41) did not detect any changes in life satisfaction and perceived self-competence. For mood, a quasi-experimental ABA-design (n = 41) did not yield an experimental treatment effect, but a significant increase in scores was observed over time. Personality characteristics ,extraversion' and ,emotional stability', but not memory specificity were found to be significant covariates for the mood scores. Conclusion, Although the study's design did not allow us to confirm the effect of reminiscence group work, the analysis nonetheless revealed some useful indications for further research. Also, interviews conducted before and after the programme resulted in positive appraisals of the programme as a worthwhile and meaningful activity for ageing people with intellectual disability. [source] Religious coping among jews: development and initial validation of the JCOPEJOURNAL OF CLINICAL PSYCHOLOGY, Issue 7 2009David H. Rosmarin Abstract Numerous studies have underscored the importance of religious coping in psychological health and illness; however, the majority of research in this area has been conducted with Christian samples and knowledge about other religious groups is lacking. Although recent investigations have developed scales to measure religious coping among Hindus and Muslims, the potential for future research in Jewish populations remains limited as no measures of religious coping have been validated in the general Jewish community. This two-part study reports on the development and validation of the 16-item Jewish Religious Coping Scale (JCOPE). In Study 1, an exploratory factor analysis identified two factors reflecting positive and negative religious coping strategies, and the concurrent validity for the measure was evaluated by examining correlations with indices of Jewish beliefs and practices. In Study 2, a confirmatory factor analysis (CFA) verified the JCOPE's 2-factor structure, and the scale's incremental validity was evaluated by examining Jewish religious coping as a predictor of psychological distress over and above significant covariates. Results suggest that the JCOPE has good psychometric properties, and that religious coping is a significant predictor of psychological distress among Jews. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65: 1,14, 2009. [source] Outcome of patients with hepatocellular carcinoma referred to a tertiary centre with availability of multiple treatment options including cadaveric liver transplantationLIVER INTERNATIONAL, Issue 9 2007John F. Perry Abstract Hepatocellular carcinoma (HCC) is a primary cancer of the liver with an established causal link to viral hepatitis and other forms of chronic liver disease. Aims: The aim of this study was to analyse the determinants of outcome in patients with HCC referred to a tertiary centre for management. Method: Two hundred and thirty-five prospective patients with HCC and minimum 12-month follow-up were studied. Results: The cohort was heterogeneous, with 52% Caucasian, 40% Asian and 5% of Middle-Eastern origin. Independent predictors of outcome included tumour size and number, the presence of ascites or portal vein thrombosis, ,-foetoprotein >50 U/L and an impaired performance status. Treatment was determined on an individual case basis by a multidisciplinary tumour team. Surgical resection was primary treatment in 43 patients, liver transplantation in 40 patients, local ablation (percutaneous radiofrequency ablation or alcohol injection) in 33 patients, transarterial chemoembolisation in 33 patients, chemotherapy or other systemic therapy in 30 patients and no treatment in 56 patients. After adjustment for significant covariates, both liver transplantation (P<0.001) and surgical resection (P=0.029) had a significant effect on patient survival compared with no treatment, but local ablation (P=0.410) and chemoembolisation (P=0.831) did not. Liver transplantation resulted in superior overall and, in particular, disease-free survival compared with surgical resection (disease-free survival 84 vs 15% at 5 years). Conclusion: In conclusion, both surgical resection and liver transplantation significantly improve the survival of patients with HCC, but improvements need to be made to the delivery of loco-regional therapy to enhance its effectiveness. [source] Variance components analyses of multiple asthma traits in a large sample of Australian families ascertained through a twin probandALLERGY, Issue 2 2006M. A. R. Ferreira Background:, Intermediate phenotypes are often measured as a proxy for asthma. It is largely unclear to what extent the same set of environmental or genetic factors regulate these traits. Objective:, Estimate the environmental and genetic correlations between self-reported and clinical asthma traits. Methods:, A total of 3073 subjects from 802 families were ascertained through a twin proband. Traits measured included self-reported asthma, airway histamine responsiveness (AHR), skin prick response to common allergens including house dust mite (Dermatophagoides pteronyssinus [D. pter]), baseline lung function, total serum immunoglobulin E (IgE) and eosinophilia. Bivariate and multivariate analyses of eight traits were performed with adjustment for ascertainment and significant covariates. Results:, Overall 2716 participants completed an asthma questionnaire and 2087 were clinically tested, including 1289 self-reported asthmatics (92% previously diagnosed by a doctor). Asthma, AHR, markers of allergic sensitization and eosinophilia had significant environmental correlations with each other (range: 0.23,0.89). Baseline forced expiratory volume in 1 s (FEV1) showed low environmental correlations with most traits. Fewer genetic correlations were significantly different from zero. Phenotypes with greatest genetic similarity were asthma and atopy (0.46), IgE and eosinophilia (0.44), AHR and D. pter (0.43) and AHR and airway obstruction (,0.43). Traits with greatest genetic dissimilarity were FEV1 and atopy (0.05), airway obstruction and IgE (0.07) and FEV1 and D. pter (0.11). Conclusion:, These results suggest that the same set of environmental factors regulates the variation of many asthma traits. In addition, although most traits are regulated to great extent by specific genetic factors, there is still some degree of genetic overlap that could be exploited by multivariate linkage approaches. [source] Noninvasive assessment of energy expenditure in childrenAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2006Isabelle Sarton-Miller This study establishes an affordable, simple, and noninvasive method to assess energy expenditure (EE) in children, an underrepresented group. The method is based on regression modeling, where prediction of oxygen consumption (VO2), a proxy of EE, was deduced from heart rate (HR) and several variables that adjusted for interindividual variability. Limb activities (arms vs. legs) and posture (sitting vs. standing) were represented in the regression as dichotomous covariates. The order of activities and intensities was randomized. Seventy-four children (aged 7,10 years), raised at sea-level (Seattle, WA), comprised the sample. Anthropometric measures were taken, and VO2 and HR were measured for activities using the arms in sitting and standing positions (mixing and punching), as well as walking at different velocities on a treadmill. Repeated measures and least square regression estimation were used. HR, body mass, number of hours of physical activity per week (HPA), an interaction term between sitting and standing resting HR, and the two dichotomous variables, sex and limbs, were significant covariates; posture was not. Several equations were developed for various field uses. The equations were built from sea-level data, but ultimately this method could serve as a baseline for developing a similar approach in other populations, where noninvasive estimation of EE is imperative in order to gain a better understanding of children's energetic issues. Am. J. Hum. Biol. 18:600,609, 2006. © 2006 Wiley-Liss, Inc. [source] Witnessing Community Violence and Health-Risk Behaviors Among Detained AdolescentsAMERICAN JOURNAL OF ORTHOPSYCHIATRY, Issue 4 2007Dexter R. Voisin PhD This study examines whether witnessing community violence, in the 12 months prior to juvenile detention, is related and health-related outcomes in the 2 months prior to being detained among 550 youth. Participants answered survey questions using audio-computer assisted self-interviewing procedures, which assessed demographic, problem, and drug and sexual risk behaviors. Multiple logistic regression analyses, controlling for significant covariates, indicated that adolescents, in the last 12 months, who reported witnessing community violence, relative to their peer witnessing no violence, were in the last 2 months prior to being detained, twice more likely to have suicidal threats, 2 times more likely to use marijuana and alcohol, 2 times more likely to get high on alcohol or other drugs during sexual intercourse, and 2 times more likely to have sex with a partner who was high on alcohol or other drugs. Finding suggest that detained youth, many of whom may not access traditional helath care, should be offered prevention and intervention services dring detention, which provides a critical window of opportunity for needed services. [source] On inference for a semiparametric partially linear regression model with serially correlated errorsTHE CANADIAN JOURNAL OF STATISTICS, Issue 4 2007Jinhong You Abstract The authors consider a semiparametric partially linear regression model with serially correlated errors. They propose a new way of estimating the error structure which has the advantage that it does not involve any nonparametric estimation. This allows them to develop an inference procedure consisting of a bandwidth selection method, an efficient semiparametric generalized least squares estimator of the parametric component, a goodness-of-fit test based on the bootstrap, and a technique for selecting significant covariates in the parametric component. They assess their approach through simulation studies and illustrate it with a concrete application. L'inférence dans le cadre d'un modèle de régression semiparamétrique partiellement linéaire à termes d'erreur corrélés en série Les auteurs s'intéressent à un modèle de régression semiparamétrique partiellement linéaire à termes d'erreur corrélés en série. Ils proposent une façon originale d'estimer la structure d'erreur qui a l'avantage de ne faire intervenir aucune estimation non paramétrique. Ceci leur permet de développer une procédure d'inférence comportant un choix de fen,tre, l'emploi de la méthode des moindres carrés généralisés pour l'estimation semiparamétrique efficace de la composante paramétrique, un test d'adéquation fondé sur le rééchantillonnage et une technique de sélection des covariables significatives de la composante paramétrique. Ils évaluent leur approche par voie de simulation et en donnent une illustration concrète. [source] A Validation Study of Type 2 Diabetes-related Variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ Genes in one Endogamous Ethnic Group of North IndiaANNALS OF HUMAN GENETICS, Issue 4 2010Vipin Gupta Summary The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal population, having 18-clans. This endogamous population model was heavily supported by recent land mark work and we also verified the homogeneity of this population by clan-based stratification analysis. Two SNPs (rs4506565; rs7903146) in TCF7L2 were found to be significant (p-value = 0.00191; p-value = 0.00179, respectively), and odds ratios of 2.1 (dominant-model) and 2.0 (recessive-model) respectively, were obtained for this population. The TTT haplotype in the TCF7L2 gene was significantly associated with T2D. Waist-Hip ratio (WHR), systolic blood pressure (SBP), and age were significant covariates for increasing risk of T2D. Single-SNP, combined-SNPs and haplotype analysis provides clear evidence that the causal mutation is near to or within the significant haplotype (TTT) of the TCF7L2 gene. In spite of a culturally-learned sedentary lifestyle and fat-enriched dietary habits, WHR rather than body-mass-index emerged as a robust predictor of risk for T2D in this population. [source] Co-administration of proton pump inhibitors delays elimination of plasma methotrexate in high-dose methotrexate therapyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2009Kunihiro Suzuki WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Co-administration of proton pump inhibitors (PPIs) increases plasma methotrexate (MTX) concentration in cancer patients receiving high-dose MTX (HDMTX) therapy. , There is controversy as to whether or not co-administration of PPIs affects plasma MTX elimination in HDMTX therapy. , Inhibitory activity of PPIs on breast cancer resistance protein (BCRP) is a possible mechanism for the drug interaction between MTX and PPIs. WHAT THIS STUDY ADDS , Co-administration of a PPI (omeprazole, lansoprazole, or rabeprazole) was more frequently observed in the delayed MTX elimination group than in the normal MTX elimination group. , Multiple logistic regression analysis with adjustment for significant covariates revealed that PPI co-administration was a significant risk factor for delayed plasma MTX elimination. , The half-maximal inhibitory concentration of each PPI in inhibiting BCRP function was much higher than the therapeutic unbound concentration in the plasma. AIM To assess whether or not co-administration of proton pump inhibitors (PPIs) is a risk factor for delayed elimination of plasma methotrexate (MTX) in high-dose MTX (HDMTX) therapy for malignant diseases. METHODS To assess the effects of PPI co-administration on elimination of plasma MTX, we examined plasma MTX concentration data on 171 cycles of HDMTX therapy performed in 74 patients. We performed multiple logistic regression analysis to evaluate PPI co-administration as a risk factor. Inhibitory potencies of omeprazole, lansoprazole, rabeprazole and pantoprazole on MTX transport via breast cancer resistance protein (BCRP, ABCG2) were also investigated in an in vitro study using membrane vesicles expressing human BCRP. RESULTS We identified co-administration of PPIs as a risk factor for delayed elimination (odds ratio 2.65, 95% confidence interval 1.03, 6.82) as well as renal and liver dysfunction. All four PPIs inhibited BCRP-mediated transport of MTX, with half-maximal inhibitory concentrations of 5.5,17.6 µM , considerably higher than the unbound plasma concentrations of the PPIs. CONCLUSIONS Our results support previous findings suggesting that PPI co-administration is associated with delayed elimination of plasma MTX in patients with HDMTX therapy. This drug interaction, however, cannot be explained solely by the inhibitory effects of PPIs on BCRP-mediated MTX transport. [source] Population pharmacokinetics and bioavailability of tacrolimus in kidney transplant patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2007Marie Antignac What is already known about this subject , ,In spite of its success in ensuring graft survival, therapeutic use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. , ,Some studies of population pharmacokinetics have already been conducted in liver transplant recipients and in paediatric patients. What this study adds , ,Our work determined population pharmacokinetic parameters, in particular bioavailability, in kidney transplant recipients and the relative importance of factors influencing the disposition of tacrolimus. , ,Clearance was modelled and days postoperation and corticosteroids dose were significant covariates. Aims The use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. Tacrolimus population pharmacokinetics, including bioavailability, were investigated in an adult kidney transplant cohort to identify patient characteristics that influence pharmacokinetics. Methods The database (drug monitoring data) included 83 adult kidney transplant recipients and analysis was performed by a population approach with NONMEM. Data were collected during the first months after transplantation. Patients were administered oral or intravenous tacrolimus as part of a triple immunosuppressive regimen that also included mycophenolate mofetil and corticosteroids. Subsequent doses were adjusted on the basis of clinical evidence of efficacy and toxicity as in routine therapeutic drug monitoring. Results A one compartment open model with linear absorption and elimination adequately described the data. The typical value of minimal clearance was 1.8 ± 0.2 l h,1. Clearance increased with time post transplantation to reach 50% of maximal value after 3.8 ± 0.5 days, with a maximal value of 5.6 l h,1. Moreover clearance increased by approximately 1.6 fold (range 0.5,1.6) if the dose of prednisone was >25 mg. The typical value for volume of distribution, V, (98 ± 13 l kg,1) was similar to reported values in kidney transplant patients. The oral bioavailability of tacrolimus was poor and ranged from 11.2 to 19.1%. No covariates significantly influenced V or F. Conclusions The number of days postoperation and corticosteroid dose were significant covariates influencing tacrolimus clearance. [source] Minimal effect of MDR1 and CYP3A5 genetic polymorphisms on the pharmacokinetics of indinavir in HIV-infected patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2007Caroline Solas What is already known about this subject ,,Before this study, few data were available on the potential effect of genetic variants of P-glycoprotein or the CYP3A5 enzyme on the pharmacokinetic variability of protease inhibitors (PI). ,,MDR1 C3435T polymorphism was often linked with the pharmacokinetic variability of nelfinavir. CYP3A5*3 polymorphism was linked with the pharmacokinetic variability of calcineurin inhibitors and was therefore strongly suspected of being one of the key factors in the pharmacokinetic variability of other CYP3A susbtrates. What this study adds ,,Our results showed that both MDR1 C3435T and CYP3A5*3 polymorphisms are involved in the pharmacokinetic variability of the absorption or elimination of indinavir, but probably jointly with other factors. ,,The potent CYP3A inhibitory effect of ritonavir may hide the variability linked to genetic differences in the CYP3A5 gene, thereby reducing the overall pharmacokinetic variability of the boosted protease inhibitor. ,,Genotyping MDR1 and/or CYP3A5 does not appear to be a clinically relevant factor in optimizing protease inhibitor boosted regimens. Aims The protease inhibitor indinavir is characterized by an important interindividual pharmacokinetic variability, which results from the actions of the metabolizing enzymes cytochrome P450 (CYP) 3A and the multidrug efflux pump P-glycoprotein (P-gp), encoded by MDR1. Using a population pharmacokinetic approach, we investigated the effect of several MDR1 and CYP3A5 polymorphisms on the pharmacokinetic parameters of indinavir in HIV-infected patients. Methods Twenty-eight patients receiving indinavir alone or together with ritonavir were included. Indinavir pharmacokinetics were studied over a 12 h interval. Genetic polymorphisms were assessed by real-time PCR assays and direct sequencing for MDR1 and by PCR-SSCP analysis for CYP3A5. Results The pharmacokinetics of indinavir were best described by a one-compartment model with first-order absorption. In the final model, the MDR1 C3435T genotype and ritonavir were identified as statistically significant covariates (P , 0.001) for the absorption rate constant (95% confidence interval on the difference between CC and CT genotype 0.37, 5.53) and for clearance (95% confidence interval on the difference 5.8, 26.2), respectively. Patients with the CYP3A5*3/*3 genotype receiving indinavir alone had a 31% decrease in the indinavir clearance rate compared with patients carrying the CYP3A5*1/*3 genotype. Conclusions The MDR1 C3435T genotype affects the absorption constant of indinavir suggesting that P-gp may be implicated in its pharmacokinetic variability. Through its inhibition of CYP3A and P-gp, ritonavir could attenuate the pharmacokinetic variability linked to genetic differences, reducing significantly the interindividual variability of indinavir. However, genotyping MDR1 and/or CYP3A5 to optimize protease inhibitor boosted regimens does not seem clinically relevant. [source] Effect of age on anterior chamber angle configuration in Asians determined by anterior segment optical coherence tomography; clinic-based studyACTA OPHTHALMOLOGICA, Issue 6 2010Mi Hyun Cheon Acta Ophthalmol. 2010: 88: e205,e210 Abstract. Purpose:, To evaluate the distribution of anterior chamber angle (ACA) parameters and to assess association of these parameters with age in Asian subjects. Methods:, Four hundred and thirty-nine consecutive Korean subjects aged from 30 to 89 were enrolled from a university clinic. All participants were scanned using anterior segment optical coherence tomography (AS-OCT, Visante, version 2.0). We measured ACA parameters such as anterior chamber depth (ACD), angle opening distance at 500 and 750 ,m (AOD500,750), angle recess area at 500 and 750 ,m (ARA500,750), trabecular iris space area at 500 and 750 ,m (TISA500,750), and determined age-related changes in these parameters with use of a linear mixed effect model that adjusted for gender, axial length, intraocular pressure, and keratometry data. Slopes of ACA parameters as a function of age were determined. For various AS-OCT parameters, the normalized slope was calculated by dividing the slope by the mean value. Results:, All analysed ACA parameters decreased with age in both nasal and temporal quadrants. Axial length and keratometry data were significant covariates for ACA changes. The slopes of ACD were ,0.02396 mm/year, AOD500, ARA500, and TISA500 measured at the temporal angle were ,0.00634 mm/year, ,0.0019 mm2/year, and ,0.00177 mm2/year, respectively. There was no age-dependent difference in central corneal thickness (p value; 0.4597) Based on the normalized slopes, the AOD showed the steepest slope at both temporal and nasal sectors. Conclusion:, All ACA parameters assessed by AS-OCT, which accounted for other ocular biometric parameters, showed significant negative slopes with increasing age. These results should be considered when assessing changes in the anterior chamber over time. [source] Self-esteem in a clinical sample of morbidly obese children and adolescentsACTA PAEDIATRICA, Issue 1 2009P Nowicka Abstract Aim: To study self-esteem in clinical sample of obese children and adolescents. Methods: Obese children and adolescents aged 8,19 years (n = 107, mean age 13.2 years, mean BMI 32.5 [range 22.3,50.6], mean BMI z-score 3.22 [range 2.19,4.79]; 50 boys and 57 girls) were referred for treatment of primary obesity. Self-esteem was measured with a validated psychological test with five subscales: physical characteristics, talents and skills, psychological well-being, relations with the family and relations with others. A linear mixed effect model used the factors gender and adolescence group, and the continuous covariates: BMI z-scores, and BMI for the parents as fixed effects and subjects as random effects. Results: Age and gender, but neither the child's BMI z-score nor the BMI of the parents were significant covariates. Self-esteem decreased (p < 0.01) with age on the global scale as well as on the subscales, and was below the normal level in higher ages in both genders. Girls had significantly lower self-esteem on the global scale (p = 0.04) and on the two subscales physical characteristics (p < 0.01) and psychological well-being (p < 0.01). Conclusion: Self-esteem is lower in girls and decreases with age. In treatment settings special attention should be paid to adolescent girls. [source] | ||||||||||||||||