¹³C‐urea breath test for Helicobacter pylori in young children: cut‐off point determination by finite mixture model

Abstract

SUMMARYThe 13 C-urea breath test (UBT) is currently regarded as one of the most important noninvasive diagnostic methods for detecting Helicobacter pylori (H. pylori) infection in adults and children. However, for infants and young children, the standard for UBT interpretation has not been validated, and its reliability has not been established for diagnosing H. pylori infection in this group. The primary outcome data from UBT consist of mixture data, which come from subjects whose H. pylori infection classiÿcations are unconÿrmed. In this paper, we propose the ÿnite mixture distribution method to identify a reliable UBT cut-o value in a large baseline sample in which gastric biopsy is not available to conÿrm the H. pylori infection in younger children. Maximum likelihood estimators of the parameters in the mixture model were obtained using an expectation maximization (EM) algorithm. The standard deviation of the cut-o point was estimated by bootstrap methods. We applied the same analytical methods to the UBT results yielded from the follow up, as well as the overall UBT results in the longitudinal cohort data. The cut-o points from those UBT data sets are similar. The advantage of the ÿnite mixture model is that it may be used to calculate sensitivity and speciÿcity in the absence of other diagnostic tests.

Determination of Urinary Cotinine Cut-Off Concentrations for Pregnant Women in the Japan Environment and Children’s Study (JECS)

“…The association between consumption of foods that might be a potential source of nicotine and urinary cotinine concentration was evaluated by Spearman's rank correlation coefficient, with no association found (see Figure S2), indicating that foods were a negligible source of urinary cotinine in subsequent analyses. Du et al's method [21] was employed to derive COVs for urinary cotinine concentrations distinguishing active smokers from others and passive smokers from non-smokers. Urinary cotinine concentrations were first log10-transformed and the EM-like algorithm was applied (R package 'mixtools, ver.…”

“…To the best of our knowledge, only one study to date used plasma cotinine concentrations as a gold-standard test and estimated the sensitivity and specificity of self-reported questionnaires for smoking status [20]. Du et al suggested the use of the expectation-maximization (EM) algorithm to find the best fit mixture model and then derivation of a COV from the mixture model when a gold-standard test is unavailable [21]. This method employs the EM algorithm to fit multiple univariate empirical distribution functions to continuous measurement data.…”

Evaluation of 13C‐Urea Breath Test and Fecal Antigen Immunoassay to Detect Helicobacter pylori Infection in Gambian Infants

“…[ 13 C]-UBT results are conventionally expressed as positive or negative, relative to empirically derived cutoffs (4), and high false-positivity rates have been reported in very young children (5)(6)(7). Enzyme immunoassays detecting bacterial antigens in stool offer an alternative noninvasive diagnostic test, which may be more accurate than [ 13 C]-UBT in this age group (8), although comparison with endoscopic diagnosis has suggested that sensitivity may be decreased in young children (9,10).…”

Cut-off optimization for 13C-urea breath test in a community-based trial by mathematic, histology and serology approach

“…Du et al . have established a cut-off point for 13 C-UBT in children 14 via this model. In our study, we chose a more conservative cut-off point (DOB = 3.8) to achieve a high specificity instead of a cut-off point (DOB = 3.1) with the highest Youden’s index after model fitting.…”

“…But this approach was not appropriate for such a large-scale community-based trial due to its invasiveness. The finite mixture model (FMM) has been applied in calculating the cut-off point of diagnostic tests including 13 C-UBT recently 14 , suggesting mathematical tools could serve as alternative measures for optimising the cut-off point of 13 C-UBT in our large trial. In addition, the recomLine H.pylori immunoglobulin G (IgG) assay, as a novel serological method for detecting H.pylori infection with high sensitivity (97.6%) and specificity (96.2%) 15 , might be useful for further optimizing a cut-off point and assessing H.pylori status in subjects within the “gray zone” of 13 C-UBT.…”