Amna Klich

Performance of creatinine-based equations compared in older patients.

BACKGROUND The current equations for estimating glomerular filtration rate (GFR) have limited precision in older people. The Berlin Initiative Study (BIS-1) equation has recently been developed to improve the precision and accuracy of GFR estimation in older people, over the previous simplified Modification of Diet in Renal Disease (MDRD) Study and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. METHODS The study included 224 white patients aged >70 years who had simultaneous measurements of plasma creatinine and renal clearance of inulin. Creatinine assays used an enzymatic method with calibrators defined by isotope dilution mass spectrometry. The performance of BIS-1, MDRD and CKD-EPI equations in estimating GFR were compared. RESULTS BIS-1 was the most accurate: the percentage of GFR estimates that fell within the range of measured GFR ± 30% (P30) was 75.56% vs. 70.67% with MDRD and 72% with CKD-EPI. BIS-1 had the lowest median bias: (interquartile range) (4.1 (11.4) vs 5.8 (12.7) and 5.4 (12.8) respectively) the highest precision (the SD of the estimated GFR minus measured GFR differences was 9.21 vs 12.78 and 10.83 mL/min/1.73 m² respectively) and the highest concordance correlation coefficient (CCC) (0.82 vs. 0.74 and 0.79 respectively, p<0.05). However, in chronic kidney disease (CKD) stages 4 and 5, the CKD-EPI equation had the highest P30, the lowest median bias and the highest CCC: it was more accurate than the BIS-1 equation. CONCLUSION Among the 3 creatinine-based equations compared, BIS-1 was the most reliable for assessing renal function in older white patients, especially in those with CKD stages 1 to 3.

Endoscopic treatment of severe duodenal polyposis as an alternative to surgery for patients with familial adenomatous polyposis

BACKGROUND Patients with familial adenomatous polyposis (FAP) and severe (stage IV) duodenal polyposis are candidates for pancreaticoduodenectomy, which has high morbidity. Little information is available about the feasibility of therapeutic endoscopy for these patients. OBJECTIVE To evaluate the long-term efficiency and risks of endoscopic therapy. DESIGN Retrospective study. SETTING A 2-referral center long-term cohort study. PATIENTS Thirty-five FAP patients (15 men, mean age 48 years) presenting with stage IV duodenal polyposis were included. Patients had a mean Spigelman classification score of 9.8 points (range 9-12 points) at their first examination. INTERVENTIONS Patients underwent a surveillance endoscopy, including lateral and axial viewing with chromoendoscopy while under sedation, along with 7 ± 4.8 therapeutic endoscopic sessions during a follow-up period of 9 ± 4.5 years (range 1-19 years) after their first endoscopy. MAIN OUTCOME MEASUREMENTS Treatment modalities, adverse events, and efficiency (evolution of the Spigelman score) were reviewed. RESULTS A total of 245 therapeutic endoscopies were performed and 15 adverse events (6%) occurred. During the follow-up period, Spigelman scores decreased in 95% of patients by 6 ± 2.2 points (P = .002). Modeling analysis showed that the mean Spigelman score decreased by 60% after 150 months. LIMITATIONS Retrospective study and the duration of the follow-up, even though this is the longest follow-up reported in medical literature. CONCLUSION Endoscopic treatment of severe duodenal polyposis in patients with FAP produces few adverse events and allows efficient downstaging of the polyposis. Long-term follow-up data did not reveal a high risk of invasive duodenal cancer in these patients.

A graphical method to assess distribution assumption in group-based trajectory models

Group-based trajectory models had a rapid development in the analysis of longitudinal data in clinical research. In these models, the assumption of homoscedasticity of the residuals is frequently made but this assumption is not always met. We developed here an easy-to-perform graphical method to assess the assumption of homoscedasticity of the residuals to apply especially in group-based trajectory models. The method is based on drawing an envelope to visualize the local dispersion of the residuals around each typical trajectory. Its efficiency is demonstrated using data on CD4 lymphocyte counts in patients with human immunodeficiency virus put on antiretroviral therapy. Four distinct distributions that take into account increasing parts of the variability of the observed data are presented. Significant differences in group structures and trajectory patterns were found according to the chosen distribution. These differences might have large impacts on the final trajectories and their characteristics; thus on potential medical decisions. With a single glance, the graphical criteria allow the choice of the distribution that best capture data variability and help dealing with a potential heteroscedasticity problem.

Unequal intra-group variance in trajectory classification

Classifying patients into groups according to longitudinal series of measurements (ie, trajectory classification) has become frequent in clinical research. Most classification models suppose an equal intra-group variance across groups. This assumption is sometimes inappropriate because measurements in diseased subjects are often more heterogeneous than in healthy ones. We developed a new classification model for trajectories that uses unequal intra-group variance across groups and evaluated its impact on classification using simulations and a clinical study. The classification and typical trajectories were estimated using the classification Expectation Maximization (EM) algorithm to maximize the classification likelihood, the log-likelihood being profiled during the Maximization (M) step of the algorithm. The simulations showed that assuming equal intra-group variance resulted in a high misclassification rate (up to 50%) when the real intra-group variances were different. This rate was greatly reduced by allowing intra-group variances to be different. Similar classification was obtained when the real intra-group variances were equal, except when the total sample size and the number of repeated measurements were small. In a randomized trial that compared the effect of low vs standard cyclosporine A dose on creatinine levels after cardiac transplantation, the classification model with unequal intra-group variance led to more meaningful groups than with equal intra-group variance and showed distinct benefits of low dose. In conclusion, we recommend the use of a classification model for trajectories that allows for unequal intra-group variance across groups except when the number of repeated measurements and total sample size are small.

Renal transplantation in children under 3 years of age: Experience from a single-center study

RTx remains challenging in children under 3 years of age. This single‐center study reviewed the medical records of children <3 years transplanted since 1987 (N = 32, Group 1). They were matched for donor type and RTx period with children aged 3‐13 years (N = 32, Group 2) and 13‐18 years (N = 32, Group 3). There were no between‐group significant differences regarding distributions of gender, primary renal disease, proportion of dialysis before RTx, and growth (SDS). Compared to Groups 2 and 3, Group 1 had more peritoneal dialyses (P < .001), more EBV mismatches (P = .04), and longer warm ischemia times (P < .001). The risk of graft loss was not significantly different among age groups (hazard ratio, 2.4 in Group 2 and 2.0 in Group 3 vs Group 1; P = .2). Death occurred in four patients (3 in Group 1 and 1 in Group 2) and graft loss occurred in 28 patients, mainly due to chronic allograft nephropathy. In recipients <3 years of age, the outcomes of RTx are close to those obtained in older pediatric age groups. Thus, young patients may be transplanted in experienced multidisciplinary teams without additional risks provided that particular attention is paid to donor selection and prevention/early diagnosis of comorbidities and complications.

Pediatric renal transplantation: A retrospective single-center study on epidemiology and morbidity due to EBV

Pediatric R‐Tx patients are at high risk of developing EBV primary infection. Although high DNA replication is a risk factor for PTLD, some patients develop PTLD with low viral load. In this retrospective single‐center study including all pediatric patients having received R‐Tx (2003‐2012 period), we aimed to identify risk factors for uncontrolled reactions to EBV (defined as the presence of a viral load >10 000 copies/mL or PTLD). A Cox proportional hazard model was performed. A total of 117 patients underwent R‐Tx at a mean age of 9.7 ± 5.3 years, 46 of them being seronegative for EBV at the time of R‐Tx. During follow‐up, 54 patients displayed positive EBV viral load, 22 of whom presenting with primary infection. An uncontrolled reaction to EBV was observed in 24 patients, whilst 4 patients developed PTLD. Univariate and multivariate analyses suggested the following risk factors for an uncontrolled reaction: age below 5 years, graft from a deceased donor, ≥5 HLA mismatches, EBV‐seronegative status at the time of R‐Tx, and a secondary post‐Tx loss of anti‐EBNA. Monitoring anti‐EBNA after R‐Tx may contribute to the early identification of patients at risk for uncontrolled reaction.

A Quadriparametric Model to Describe the Diversity of Waves Applied to Hormonal Data

BACKGROUND Even in normally cycling women, hormone level shapes may widely vary between cycles and between women. Over decades, finding ways to characterize and compare cycle hormone waves was difficult and most solutions, in particular polynomials or splines, do not correspond to physiologically meaningful parameters. OBJECTIVE We present an original concept to characterize most hormone waves with only two parameters. METHODS The modelling attempt considered pregnanediol-3-alpha-glucuronide (PDG) and luteinising hormone (LH) levels in 266 cycles (with ultrasound-identified ovulation day) in 99 normally fertile women aged 18 to 45. The study searched for a convenient wave description process and carried out an extended search for the best fitting density distribution. RESULTS The highly flexible beta-binomial distribution offered the best fit of most hormone waves and required only two readily available and understandable wave parameters: location and scale. In bell-shaped waves (e.g., PDG curves), early peaks may be fitted with a low location parameter and a low scale parameter; plateau shapes are obtained with higher scale parameters. I-shaped, J-shaped, and U-shaped waves (sometimes the shapes of LH curves) may be fitted with high scale parameter and, respectively, low, high, and medium location parameter. These location and scale parameters will be later correlated with feminine physiological events. CONCLUSION Our results demonstrate that, with unimodal waves, complex methods (e.g., functional mixed effects models using smoothing splines, second-order growth mixture models, or functional principal-component- based methods) may be avoided. The use, application, and, especially, result interpretation of four-parameter analyses might be advantageous within the context of feminine physiological events.

Variance component analysis to assess protein quantification in biomarker validation: application to selected reaction monitoring-mass spectrometry

BackgroundIn the field of biomarker validation with mass spectrometry, controlling the technical variability is a critical issue. In selected reaction monitoring (SRM) measurements, this issue provides the opportunity of using variance component analysis to distinguish various sources of variability. However, in case of unbalanced data (unequal number of observations in all factor combinations), the classical methods cannot correctly estimate the various sources of variability, particularly in presence of interaction. The present paper proposes an extension of the variance component analysis to estimate the various components of the variance, including an interaction component in case of unbalanced data.ResultsWe applied an experimental design that uses a serial dilution to generate known relative protein concentrations and estimated these concentrations by two processing algorithms, a classical and a more recent one. The extended method allowed estimating the variances explained by the dilution and the technical process by each algorithm in an experiment with 9 proteins: L-FABP, 14.3.3 sigma, Calgi, Def.A6, Villin, Calmo, I-FABP, Peroxi-5, and S100A14. Whereas, the recent algorithm gave a higher dilution variance and a lower technical variance than the classical one in two proteins with three peptides (L-FABP and Villin), there were no significant difference between the two algorithms on all proteins.ConclusionsThe extension of the variance component analysis was able to estimate correctly the variance components of protein concentration measurement in case of unbalanced design.