Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

The predictive validity of grade point average scores in a partial lottery medical school admission system

PURPOSE To ascertain whether the grade point average (GPA) of school-leaving examinations is related to study success, career development and scientific performance. The problem of restriction of range was expected to be partially reduced due to the use of a national lottery system weighted in favour of students with higher GPAs. METHOD We studied the students (n = 398) admitted to the Faculty of Medicine, University of Groningen, the Netherlands in 1982 and 1983. Data concerning drop-out and study progress were derived from the student administration. Data about career development were obtained from annual interviews with graduates (n = 318) between 1993 and 2000. Literature searches yielded data concerning scientific performance. Multiple linear regression and logistic regression were used to analyse the data. The variables 'gender' and 'cohort' and their interaction were included in the analyses to account for variation in the general level of the dependent variable and the effect of GPA on the dependent variable. RESULTS GPA scores had no effect on drop-out rate. High GPA scores were associated with significantly less time to graduation, more chance of a preferred placement for specialist training and higher scientific output. GPA was not related to income. Gender differences were found for study duration and scientific output. Women graduated earlier and published less. CONCLUSION The GPA of school-leaving examinations was found to be related to study success, career development and scientific performance. In this study the usual problem of restriction of range was shown to be absent. The weighted lottery procedure even resulted in an over-dispersion of candidates relative to the applicants. The resulting effect sizes were in agreement with those reported in other studies

Variance components of two-dimensional strain parameters in the left-ventricular heart wall obtained by magnetic resonance tagging

This study quantifies variance components of two-dimensional strains in the left-ventricular heart wall assessed by magnetic resonance (MR) tagging in 18 healthy xxvolunteers. For a 7-mm tagging grid and homogeneous strain analysis, the intersubject variability and measurement error were estimated, as well as the intra- and interobserver variability. The variance components were calculated for the mean strain of a circumferential sector. The results show that the measurement error was almost equal to the intra-observer variability. With four circumferential sectors of 90° each, approximately 65% of the total variance in ε r and ε c was due to intersubject variability, the remaining 35% was due to measurement error. With 12 sectors of 30° each, the intersubject variability and measurement error both contributed 50% to the total variance. With 18 sectors of 20° each, only 40% of the total variance was due to intersubject variability. The total variability increased with the number of sectors and therefore the number of sectors used in a study will be a trade-off between segment size (defining spatial resolution) and variability

Trafikbullerskärmar nära bebyggelse /

In this article, an alternative for Tinto's integration theory of student persistence is proposed and tested. In the proposed theory, time available for individual study is considered a major determinant of both study duration and graduation rate of students in a particular curriculum. In this view, other activities in the curriculum, in particular lectures, constrain self-study time and therefore must have a negative impact on persistence. To test this theory, we collected study duration and graduation rate information of all-almost 14,000 students-enrolling in eight Dutch medical schools between 1989 and 1998. In addition, information was gathered regarding the timetables of each of these curricula in the particular period: lectures hours, hours spent in small-group tutorials, practicals, and time available for self-study. Structural equation modeling was used to study relations among these variables. In line with our predictions, time available for self-study was the only determinant of graduation rate and study duration. Lectures were negatively related to self-study time, negatively related to graduation rate, and positively related to study duration. The results suggest that extensive lecturing may be detrimental in higher education. However, in the curricula employing limited lecturing considerable energy was spent in supporting self-study activities of students and preventing postponement of learning. Given our findings, both activities will likely have large pay offs, in particular in curricula with low graduation rates