Kazem Nasserinejad

No evidence for an association of osteopontin plasma levels with disease activity in multiple sclerosis

1. UK Multiple Sclerosis Specialist Nurse Association (UKMSSNA). Multiple sclerosis specialist nurses: Adding value and delivering targets. UKMSSNA, 2006; Ledbury, UK. 2. Nuffield Trust. Trends in emergency admission 2004–9: Is greater efficiency breeding inefficiency? Nuffield Trust, 2010; London, UK. 3. Health and Social Care Information Centre. Hospital episode statistics, www.hesonline.nhs.uk/Ease/servlet/ContentServ er?siteID=1937&categoryID=202 (2012, accessed August 2012).

Pregnancy, thrombophilia, and the risk of a first venous thrombosis : Systematic review and bayesian meta-analysis

Objective To provide evidence to support updated guidelines for the management of pregnant women with hereditary thrombophilia in order to reduce the risk of a first venous thromboembolism (VTE) in pregnancy. Design Systematic review and bayesian meta-analysis. Data sources Embase, Medline, Web of Science, Cochrane Library, and Google Scholar from inception through 14 November 2016. Review methods Observational studies that reported on pregnancies without the use of anticoagulants and the outcome of first VTE for women with thrombophilia were eligible for inclusion. VTE was considered established if it was confirmed by objective means, or when the patient had received a full course of a full dose anticoagulant treatment without objective testing. Results 36 studies were included in the meta-analysis. All thrombophilias increased the risk for pregnancy associated VTE (probabilities ≥91%). Regarding absolute risks of pregnancy associated VTE, high risk thrombophilias were antithrombin deficiency (antepartum: 7.3%, 95% credible interval 1.8% to 15.6%; post partum: 11.1%, 3.7% to 21.0%), protein C deficiency (antepartum: 3.2%, 0.6% to 8.2%; post partum: 5.4%, 0.9% to 13.8%), protein S deficiency (antepartum: 0.9%, 0.0% to 3.7%; post partum: 4.2%; 0.7% to 9.4%), and homozygous factor V Leiden (antepartum: 2.8%, 0.0% to 8.6%; post partum: 2.8%, 0.0% to 8.8%). Absolute combined antepartum and postpartum risks for women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutations, or compound heterozygous factor V Leiden and prothrombin G20210A mutations were all below 3%. Conclusions Women with antithrombin, protein C, or protein S deficiency or with homozygous factor V Leiden should be considered for antepartum or postpartum thrombosis prophylaxis, or both. Women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutation, or compound heterozygous factor V Leiden and prothrombin G20210A mutation should generally not be prescribed thrombosis prophylaxis on the basis of thrombophilia and family history alone. These data should be considered in future guidelines on pregnancy associated VTE risk.

Prevalence and determinants of declining versus stable hemoglobin levels in whole blood donors

A too short recovery time after blood donation results in a gradual depletion of iron stores and a subsequent decline in hemoglobin (Hb) levels over time. This decline in Hb levels may depend on individual, unobserved characteristics of the donor.

Predicting hemoglobin levels in whole blood donors using transition models and mixed effects models

BackgroundTo optimize the planning of blood donations but also to continue motivating the volunteers it is important to streamline the practical organization of the timing of donations. While donors are asked to return for donation after a suitable period, still a relevant proportion of blood donors is deferred from donation each year due to a too low hemoglobin level. Rejection of donation may demotivate the candidate donor and implies an inefficient planning of the donation process. Hence, it is important to predict the future hemoglobin level to improve the planning of donors’ visits to the blood bank.MethodsThe development of the hemoglobin prediction rule is based on longitudinal (panel) data from blood donations collected by Sanquin (the only blood product collecting and supplying organization in the Netherlands). We explored and contrasted two popular statistical models, i.e. the transition (autoregressive) model and the mixed effects model as plausible models to account for the dependence among subsequent hemoglobin levels within a donor.ResultsThe predictors of the future hemoglobin level are age, season, hemoglobin levels at the previous visits, and a binary variable indicating whether a donation was made at the previous visit. Based on cross-validation, the areas under the receiver operating characteristic curve (AUCs) for male donors are 0.83 and 0.81 for the transition model and the mixed effects model, respectively; for female donors we obtained AUC values of 0.73 and 0.72 for the transition model and the mixed effects model, respectively.ConclusionWe showed that the transition models and the mixed effects models provide a much better prediction compared to a multiple linear regression model. In general, the transition model provides a somewhat better prediction than the mixed effects model, especially at high visit numbers. In addition, the transition model offers a better trade-off between sensitivity and specificity when varying the cut-off values for eligibility in predicted values. Hence transition models make the prediction of hemoglobin level more precise and may lead to less deferral from donation in the future.

Effects of nongenetic factors on immune cell dynamics in early childhood: The Generation R Study

Background Numbers of blood leukocyte subsets are highly dynamic in childhood and differ greatly between subjects. Interindividual variation is only partly accounted for by genetic factors. Objective We sought to determine which nongenetic factors affect the dynamics of innate leukocytes and naive and memory lymphocyte subsets. Methods We performed 6‐color flow cytometry and linear mixed‐effects modeling to define the dynamics of 62 leukocyte subsets from birth to 6 years of age in 1182 children, with 1 to 5 measurements per subject. Subsequently, we defined the effect of prenatal maternal lifestyle‐related or immune‐mediated determinants, birth characteristics, and bacterial/viral exposure–related determinants on leukocyte subset dynamics. Results Functionally similar leukocyte populations were grouped by using unbiased hierarchical clustering of patterns of age‐related leukocyte dynamics. Innate leukocyte numbers were high at birth and predominantly affected by maternal low education level. Naive lymphocyte counts peaked around 1 year, whereas most memory lymphocyte subsets more gradually increased during the first 4 years of life. Dynamics of CD4+ T cells were predominantly associated with sex, birth characteristics, and persistent infections with cytomegalovirus (CMV) or EBV. CD8+ T cells were predominantly associated with CMV and EBV infections, and T‐cell receptor &ggr;&dgr;+ T cells were predominantly associated with premature rupture of membranes and CMV infection. B‐cell subsets were predominantly associated with sex, breast‐feeding, and Helicobacter pylori carriership. Conclusions Our study identifies specific dynamic patterns of leukocyte subset numbers, as well as nongenetic determinants that affect these patterns, thereby providing new insights into the shaping of the childhood immune system. Graphical abstract Figure. No caption available.

Diagnosis of bronchiectasis and airway wall thickening in children with cystic fibrosis: Objective airway-artery quantification

ObjectivesTo quantify airway and artery (AA)-dimensions in cystic fibrosis (CF) and control patients for objective CT diagnosis of bronchiectasis and airway wall thickness (AWT).MethodsSpirometer-guided inspiratory and expiratory CTs of 11 CF and 12 control patients were collected retrospectively. Airway pathways were annotated semi-automatically to reconstruct three-dimensional bronchial trees. All visible AA-pairs were measured perpendicular to the airway axis. Inner, outer and AWT (outer−inner) diameter were divided by the adjacent artery diameter to compute AinA-, AoutA- and AWTA-ratios. AA-ratios were predicted using mixed-effects models including disease status, lung volume, gender, height and age as covariates.ResultsDemographics did not differ significantly between cohorts. Mean AA-pairs CF: 299 inspiratory; 82 expiratory. Controls: 131 inspiratory; 58 expiratory. All ratios were significantly larger in inspiratory compared to expiratory CTs for both groups (p<0.001). AoutA- and AWTA-ratios were larger in CF than in controls, independent of lung volume (p<0.01). Difference of AoutA- and AWTA-ratios between patients with CF and controls increased significantly for every following airway generation (p<0.001).ConclusionDiagnosis of bronchiectasis is highly dependent on lung volume and more reliably diagnosed using outer airway diameter. Difference in bronchiectasis and AWT severity between the two cohorts increased with each airway generation.Key points• More peripheral airways are visible in CF patients compared to controls.• Structural lung changes in CF patients are greater with each airway generation.• Number of airways visualized on CT could quantify CF lung disease.• For objective airway disease quantification on CT, lung volume standardization is required.

Calibrating Doppler imaging of preterm intracerebral circulation using a microvessel flow phantom

Introduction: Preterm infants are born during critical stages of brain development, in which the adaptive capacity of the fetus to extra-uterine environment is limited. Inadequate brain perfusion has been directly linked to preterm brain damage. Advanced high-frequency ultrasound probes and processing algorithms allow visualization of microvessels and depiction of regional variation. To assess whether visualization and flow velocity estimates of preterm cerebral perfusion using Doppler techniques are accurate, we conducted an in vitro experiment using a microvessel flow phantom. Materials and Methods: An in-house developed flow phantom containing two microvessels (inner diameter 200 and 700 μm) with attached syringe pumps, filled with blood-mimicking fluid, was used to generate non-pulsatile perfusion of variable flow. Measurements were performed using an Esaote MyLab70 scanner. Results: Microvessel mimicking catheters with velocities as low as 1 cm/s were adequately visualized with a linear ultrasound probe. With a convex probe, velocities <2 cm/s could not be depicted. Within settings, velocity and diameter measurements were highly reproducible [intra-class correlation 0.997 (95% CI 0.996–0.998) and 0.914 (0.864–0.946)]. Overall, mean velocity was overestimated up to threefold, especially in high velocity ranges. Significant differences were seen in velocity measurements when using steer angle correction and in vessel diameter estimation (p < 0.05). Conclusion: Visualization of microvessel-size catheters mimicking small brain vessels is feasible. Reproducible velocity and diameter results can be obtained, although important overestimation of the values is observed. Before velocity estimates of microcirculation can find its use in clinical practice, calibration of the ultrasound machine for any specific Doppler purpose is essential. The ultimate goal is to develop a sonographic tool that can be used for objective study of regional perfusion in routine practice.

Prediction of hemoglobin in blood donors using a latent class mixed-effects transition model.

Blood donors experience a temporary reduction in their hemoglobin (Hb) value after donation. At each visit, the Hb value is measured, and a too low Hb value leads to a deferral for donation. Because of the recovery process after each donation as well as state dependence and unobserved heterogeneity, longitudinal data of Hb values of blood donors provide unique statistical challenges. To estimate the shape and duration of the recovery process and to predict future Hb values, we employed three models for the Hb value: (i) a mixed-effects models; (ii) a latent-class mixed-effects model; and (iii) a latent-class mixed-effects transition model. In each model, a flexible function was used to model the recovery process after donation. The latent classes identify groups of donors with fast or slow recovery times and donors whose recovery time increases with the number of donations. The transition effect accounts for possible state dependence in the observed data. All models were estimated in a Bayesian way, using data of new entrant donors from the Donor InSight study. Informative priors were used for parameters of the recovery process that were not identified using the observed data, based on results from the clinical literature. The results show that the latent-class mixed-effects transition model fits the data best, which illustrates the importance of modeling state dependence, unobserved heterogeneity, and the recovery process after donation. The estimated recovery time is much longer than the current minimum interval between donations, suggesting that an increase of this interval may be warranted.

Risk of Venous Thrombosis in Antithrombin Deficiency: A Systematic Review and Bayesian Meta-analysis

Abstract Antithrombin deficiency is a strong risk factor for venous thromboembolism (VTE), but the absolute risk of the first and recurrent VTE is unclear. The objective of this paper is to establish the absolute risks of the first and recurrent VTE and mortality in individuals with antithrombin deficiency. The databases Embase, Medline Ovid, Web of Science, the Cochrane Library, and Google Scholar were systematically searched for case‐control and cohort studies. Bayesian random‐effects meta‐analysis was used to calculate odds ratios (ORs), absolute risks, and probabilities of ORs being above thresholds. Thirty‐five publications were included in the systematic review and meta‐analysis. Based on 19 studies, OR estimates for the first VTE showed a strongly increased risk for antithrombin deficient individuals, OR 14.0; 95% credible interval (CrI), 5.5 to 29.0. Based on 10 studies, meta‐analysis showed that the annual VTE risk was significantly higher in antithrombin‐deficient than in non‐antithrombin‐deficient individuals: 1.2% (95% CrI, 0.8‐1.7) versus 0.07% (95% CrI, 0.01‐0.14). In prospective studies, the annual VTE risk in antithrombin deficient individuals was as high as 2.3%; 95% CrI, 0.2‐6.5%. Data on antithrombin deficiency subtypes are very limited for reliable risk‐differentiation. The OR for recurrent VTE based on 10 studies was 2.1; 95% CrI, 0.2 to 4.0. The annual recurrence risk without long‐term anticoagulant therapy based on 4 studies was 8.8% (95% CrI, 4.6‐14.1) for antithrombin‐deficient and 4.3% (95% CrI, 1.5‐7.9) for non‐antithrombin‐deficient VTE patients. The probability of the recurrence risk being higher in antithrombin‐deficient patients was 95%. The authors conclude that antithrombin deficient individuals have a high annual VTE risk, and a high annual recurrence risk. Antithrombin deficient patients with VTE require long‐term anticoagulant therapy.

Comparison of criteria for choosing the number of classes in Bayesian finite mixture models

Identifying the number of classes in Bayesian finite mixture models is a challenging problem. Several criteria have been proposed, such as adaptations of the deviance information criterion, marginal likelihoods, Bayes factors, and reversible jump MCMC techniques. It was recently shown that in overfitted mixture models, the overfitted latent classes will asymptotically become empty under specific conditions for the prior of the class proportions. This result may be used to construct a criterion for finding the true number of latent classes, based on the removal of latent classes that have negligible proportions. Unlike some alternative criteria, this criterion can easily be implemented in complex statistical models such as latent class mixed-effects models and multivariate mixture models using standard Bayesian software. We performed an extensive simulation study to develop practical guidelines to determine the appropriate number of latent classes based on the posterior distribution of the class proportions, and to compare this criterion with alternative criteria. The performance of the proposed criterion is illustrated using a data set of repeatedly measured hemoglobin values of blood donors.