Resolution of age-dependent reference intervals: Polynomial regression methodology with applicability to plasma zinc levels in a childhood population

Background: Acute Lower Respiratory Tract Infection (ALRI) is an important cause of morbidity and mortality in the developing world. Pneumonia is a severe form of ALRI that cause over 2 million deaths annually among children younger than 5 years of age. About 19% of all deaths, pneumonia is the leading cause of child mortality. Malnutrition is known to be associated with greater intensity of lower respiratory tract infections, higher the frequency of complications, longer episodes of infections. This study is to assess the plasma zinc levels in normal and malnourished children with LRI aged 2 months to 5 years.Methods: This is a case control study, which was carried out in the Department of Paediatrics, Sree Balaji Medical College and Hospital, the study period is one year from July 2016 to July 2017. 100 children between 2 months to 5 years of age with LRI was included in the study and children less than 2 months and more than 5 years. 50 Children with normal nutrition were taken as controls and 50 children with moderate and severe malnutrition were taken as cases. Age and sex were matched among cases and controls. Blood samples were collected for zinc estimation in both the cases and controls. All children were investigated and treated as per the department protocol for the particular condition. All statistical procedures were performed using SPSS v 21.0.Results: In present study, 66% of children had normal zinc levels, 34% of children had low zinc levels. The mean zinc level in our cases was 54.84±18.31 and in controls was 76.84±15.2, which was statistically significant (p = 0.000). Mean plasma zinc levels with respect to age and sex were not significant.Conclusions: Total 34% of children with LRI had low plasma zinc levels. Plasma zinc level were significantly low in malnourished children than normally nourished children with LRI, which is one of the most important cause of high childhood mortality in developing countries.

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Role and effects of zinc supplementation in HIV-infected patients with immunovirological discordance: A randomized, double blind, case control study

PLoS ONE ◽

10.1371/journal.pone.0244823 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0244823

Author(s):

Macarena Silva ◽

Carmen G. Montes ◽

Andrea Canals ◽

Maria J. Mackenna ◽

Marcelo Wolff

Keyword(s):

Zinc Supplementation ◽

Group Versus ◽

Cd4 Count ◽

Control Group ◽

Immune Recovery ◽

Plasma Zinc ◽

Absolute Increase ◽

Number Of Patients ◽

Significant Difference ◽

Zinc Levels

Introduction It has been estimated that between 15% and 18% of patients who start antiretroviral therapy (ART) do not achieve a successful immune recovery despite complete virological suppression. In the literature this phenomenom is known as poor immune recovery or immunovirological discordance (IVD). Zinc has an immunomodulatory role associated with T lymphocytes and its supplementation could enhance immune recovery. Objective To determine if zinc supplementation on IVD patients prevents immune failure after 12 months of supplementation. Secondary objectives were to determine serum zinc levels in HIV patients with and without IVD and the frequency of hypozincemia in discordant patients. Method We reviewed the historical record of patients under care at Arriarán Foundation. Following inclusion criteria were defined: 1) age ≥ 18 years, 2) standard ART (three effective drugs) for at least 18 months, 3) virologically suppressed for 12 months, 3) persistence of CD4 count ≤200 cells/mm3 and/or increase ≤ 80 cells/mm3 after one year of viral undetectability. A control group was assigned paired 1:1 by sex, age (± 2 years) that did achieved an increase of CD4> 350 cells/ mm3. In both groups plasma zinc levels were determined. In a later phase, patients with IVD were randomized to receive zinc (15 mg daily) versus placebo. Patients were followed for 12 months with CD4 count, viral load and zinc levels determinations every 4–6 months. Results A total of 80 patients, 40 patients with IVD criteria and 40 controls were included. 92.5% were men, and age average was 47.5 years. The median baseline CD4 was 189 cells/mm3 (71–258) in the cases vs. 552.5 cells/ mm3 (317–400) in the control group with a median increase at the end of the study of 39 cell/mm3 and 19 cell/mm3 respectively. There was no difference in baseline plasma zinc levels between both groups (81.7 + 18.1 in cases versus 86.2 + 11.0 in controls). In the 40 patients with IVD, the median absolute increase in CD4 after annual zinc supplementation was 31.5 cells/mm3 in the treated group versus 50 cells/mm3 in the placebo group, this difference being statistically not significant (p = 0.382). Conclusions Patients with IVD have plasma zinc levels similar to those who achieve adequate immune recovery. Zinc supplementation in IVD patients showed a statistically non-significant difference in in CD4 levels between cases and controls. The results warrant a comparative study with a larger number of patients.

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Comparison of Statistical Methods for Estimating Continuous Paediatric Reference Intervals: A Simulation Study

10.21203/rs.3.rs-144805/v1 ◽

2021 ◽

Author(s):

Monsurul Hoq ◽

Susan Donath ◽

Paul Monagle ◽

John Carlin

Keyword(s):

Statistical Methods ◽

Simulation Study ◽

Assessment Tool ◽

Polynomial Regression ◽

Reference Intervals ◽

Performance Measure ◽

Parametric Models ◽

New Method ◽

Sample Sizes ◽

Generalised Additive Model

Abstract Background: Reference intervals (RIs), which are used as an assessment tool in laboratory medicine, change with age for most biomarkers in children. Addressing this, RIs that vary continuously with age have been developed using a range of curve-fitting approaches. The choice of statistical method may be important as different methods may produce substantially different RIs. Hence, we developed a simulation study to investigate the performance of statistical methods for estimating continuous paediatric RIs.Methods: We compared four methods for estimating age-varying RIs. These were Cole’s LMS, the Generalised Additive Model for Location Scale and Shape (GAMLSS), Royston’s method based on fractional polynomials and exponential transformation, and a new method applying quantile regression using power variables in age selected by fractional polynomial regression for the mean. Data were generated using hypothetical true curves based on five biomarkers with varying complexity of association with age, i.e. linear or nonlinear, constant or nonconstant variation across age, and for four sample sizes (100, 200, 400 and 1000). Root mean square error (RMSE) was used as the primary performance measure for comparison. Results: Regression-based parametric methods performed better in most scenarios. Royston’s and the new method performed consistently well in all scenarios for sample sizes of at least 400, while the new method had the smallest average RMSE in scenarios with nonconstant variation across age. Conclusions: We recommend methods based on flexible parametric models for estimating continuous paediatric RIs, irrespective of the complexity of the association between biomarkers and age, for at least 400 samples.

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Reference Intervals for Serum Alpha-Fetoprotein and Carcinoembryonic Antigen in Chinese Han Ethnic Males from the Fangchenggang Area Male Health and Examination Survey

The International Journal of Biological Markers ◽

10.5301/jbm.2011.6364 ◽

2011 ◽

Vol 26 (1) ◽

pp. 65-71 ◽

Cited By ~ 10

Author(s):

Xue Qin ◽

Liwen Lin ◽

Zengnan Mo ◽

Hui Lv ◽

Yong Gao ◽

...

Keyword(s):

Carcinoembryonic Antigen ◽

Reference Intervals ◽

Alpha Fetoprotein ◽

Male Health ◽

Significant Difference ◽

Reference Limits ◽

Age Dependent ◽

Serum Alpha Fetoprotein ◽

Serum Cea ◽

Normally Distributed

Objectives We calculated upper 95% reference limits for serum alpha-fetoprotein (AFP)and carcinoembryonic antigen (CEA) according to the CLSI/NCCLS C28-A3 guideline. Material and methods Serum samples from 1400 healthy male subjects were collected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). Serum AFP and CEA values were measured by electrochemiluminescence immunoassay on COBAS 6000 system E601 (Elecsys module) immunoassay analyzers. Results Serum AFP and CEA values were not normally distributed but log normally distributed. The upper 95% reference limits of the reference intervals were ≤4.76 IU/mL (nonparametric) or ≤4.56 IU/mL (parametric) for AFP and ≤5.57 ng/mL (nonparametric) or ≤5.82 ng/mL (parametric) for CEA. The distribution of AFP levels was found to be consistent between the non-smoking and smoking (p=0.740) and non-drinking and drinking groups (p=0.698). The distribution of serum CEA levels was significantly higher in the smoking than the non-smoking group (p<105), whereas there was no significant difference in this respect between the non-drinking and drinking groups (p=0.147). A significant increase with age was found both for serum AFP and CEA levels, and the age-dependent reference intervals were calculated. Conclusions The reference intervals for serum AFP and CEA show a slight deviation compared to previously reported reference levels. Distinct reference intervals of serum CEA must be established for smoking and non-smoking populations. In addition, age-dependent reference intervals should be implemented in clinical laboratories.

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PLASMA-ZINC LEVELS

The Lancet ◽

10.1016/s0140-6736(74)90545-5 ◽

1974 ◽

Vol 303 (7862) ◽

pp. 879 ◽

Cited By ~ 3

Author(s):

R.G Burr

Keyword(s):

Plasma Zinc ◽

Zinc Levels

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Measurement of Hypozincaemia in Mice: A Sensitive Test for Detection of Pyrogens

Clinical Science ◽

10.1042/cs0610445 ◽

1981 ◽

Vol 61 (4) ◽

pp. 445-449 ◽

Cited By ~ 4

Author(s):

Susan Boobis ◽

Rose E. Hartley

Keyword(s):

Escherichia Coli ◽

Zinc Concentration ◽

Shigella Dysenteriae ◽

Metabolic Inhibitor ◽

Repeated Treatment ◽

Plasma Zinc ◽

Sensitive Test ◽

Zinc Concentrations ◽

Zinc Levels ◽

Dose Dependent

1. The effect of bacterial pyrogens on plasma zinc concentration in mice was studied as a method of bioassay for these substances. 2. A dose-related depression of plasma zinc concentrations was observed 4 h after intravenous injection of doses of 0.05-500 ng of purified endotoxins of Salmonella abortus equi, Shigella dysenteriae and Escherichia coli. Responses were dose-dependent and reproducible for each endotoxin in five strains of mice. 3. Tolerance to endotoxin could be induced in mice by injection of doses of 500 ng but was not seen with doses of <5 ng, even after repeated treatment. 4. Dinitrophenol, a metabolic inhibitor, and amphetamine, a metabolic enhancer, did not affect plasma zinc levels, indicating that changes in basal metabolic rate do not affect the outcome of this assay. The effects of pyrogenic materials other than endotoxin on plasma zinc levels were also tested and the results suggest that measurement of hypozincaemia in mice provides the basis for a simple, practical and inexpensive test for endotoxins and other pyrogens.

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Effect of age and gender on reference intervals of red blood cell distribution width (RDW) and mean red cell volume (MCV)

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-0155 ◽

2015 ◽

Vol 53 (12) ◽

Cited By ~ 29

Author(s):

Johannes J.M.L. Hoffmann ◽

Karin C.A.M. Nabbe ◽

Nicole M.A. van den Broek

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

Reference Intervals ◽

Cell Distribution ◽

Age Dependency ◽

Distribution Width ◽

Age Related ◽

Age Dependent ◽

Red Blood Cell Distribution ◽

Related Increase

AbstractRed blood cell distribution width (RDW) was recently shown to be age-dependent when using Sysmex XE-2100 hematology analyzers. As measuring RDW is subject to technology, we have investigated if this relation also exists when using a different hematology analyzer, Abbott CELL-DYN Sapphire. In addition, as RDW is generally expressed relative to mean red blood cell volume (MCV), we have explored how MCV influences the age-dependency of RDW.We measured RDW and MCV in a large cohort and calculated RDW-SD (the “absolute” RDW), which does not contain MCV. For establishing reference intervals we used Bhattacharya statistics.In our study cohort of 8089 individuals we found a strong association between RDW and age, but not with gender. Also MCV showed an age-related increase over the entire age range. The conventional RDW increased by 6% from the youngest to oldest age class, whereas RDW-SD increased by nearly 15%. This difference was caused by a mean age-related increase in MCV of 6.6%. Age-dependent reference intervals were established for RDW, RDW-SD and MCV.The age-dependency of RDW seems to be a universal biological feature rather than related with a single type of hematology analyzer. As not only RDW, but also MCV increases with age, we propose that future studies on the prognostic significance of RDW take its age-dependency into account and focus on RDW-SD as a potential marker of adverse events in many clinical conditions.

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