Immunodeficiency Accelerates Vitamin A Deficiency.

BACKGROUND: Vitamin A deficiency increases susceptibility to infection caused by impaired immune function. OBJECTIVES: We investigated whether immunodeficiency could facilitate the development of vitamin A deficiency. METHODS: Vitamin A deficiency was followed in 2 mouse models of immunodeficiency: the athymic nude mouse (nu/nu) and the humoral immunodeficient SENCAR (SENsitive to CARcinogenesis) mouse. Vitamin A deficiency was also monitored in outbred Balb/c and in NIH mice. The monitoring of vitamin A deficiency was done after feeding the mice and their mothers a semisynthetic, vitamin A-deficient diet from birth of the experimental mice. These mice were weaned onto the same deficient diet at 3-4 wk of age, while control groups were fed the same diet containing 3 µg retinoic acid per gram of diet. RESULTS: The immunodeficient nu/nu and SENCAR mice developed vitamin A deficiency earlier than either the heterozygous nu/+ controls or the Balb/c and NIH strains. In female mice, symptoms included depletion of liver retinol and retinyl palmitate, squamous metaplasia of the uterus, and death. Male mice lost weight more frequently and sooner than female mice, in which mortality generally occurred in the absence of loss of body weight. Pairwise comparisons using Tukey's honest significant difference test of the nu/nu and SENCAR mice versus the Balb/c and NIH mice showed a faster loss of retinol and retinyl palmitate in all pairs (P ≤ 0.0001) except for retinol when comparing nu/nu and NIH strains (P = 0.3383). CONCLUSIONS: Our findings are consistent with an increased usage of liver retinol and retinyl palmitate in the immunocompromised nu/nu and in the immunodeficient SENCAR mice and suggest that compensatory mechanisms dependent on vitamin A utilization are called upon to rescue immunodeficiency both in the T-cell-deficient phenotype of the nu/nu mice and in the humoral immunodeficient SENCAR mice.

Using Sigma metrics to establish analytical product performance requirements and optimize analytical performance of an in vitro diagnostic assay using a theoretical total PSA assay as an example.

INTRODUCTION: Establishing analytical performance requirements for in vitro diagnostic (IVD) assays is a challenging process. Manufacturers try to optimize analytical performance by choosing amongst many combinations of different product performance characteristics. Sigma metrics and method decision charts can be helpful aids in choosing appropriate analytical performance requirements. The objective of this research was to demonstrate the use of Sigma metrics and method decision charts to help establish analytical performance requirements and to optimize analytical performance at medical decision concentrations for an IVD assay. MATERIALS AND METHODS: A range of possible Sigma metrics were determined using three sources for total allowable error (TEa) and hypothetical total PSA assay results. Method decision charts were created for each TEa source and used to identify the maximum precision and bias that the assay could have to maintain sigma level performance of at least 3. RESULTS: To achieve a sigma performance level of at least 3 for a hypothetical total PSA assay, the maximum allowable coefficient of variation ranged from 5.0% to 11.2% depending on the TEa source. To achieve a sigma performance level of at least 6, the maximum allowable coefficient of variation ranged from 2.5% to 5.6% depending on the TEa source. CONCLUSIONS: Using Sigma metrics and method decision charts when establishing analytical performance requirements can help manufacturers choose product requirements that will optimize IVD assay product performance.

Ensuring suitable quality of clinical measurements through design.

To design and deliver high quality, safe and effective products, manufacturers of in vitro diagnostic (IVD) products follow a structured, traceable process for controlling the uncertainty of results reported from their measurement systems. This process and its results however, are not often shared in detail with those outside of the manufacturing company. The objective of this paper is to facilitate discussion by describing some of the best practices used during the IVD design and development process, highlighting some design challenges manufacturers face, and to offer ideas for how IVD manufacturers and laboratories could work together to drive further improvement to public health.

Assessing precision, bias and sigma-metrics of 53 measurands of the Alinity ci system.

Assay performance is dependent on the accuracy and precision of a given method. These attributes can be combined into an analytical Sigma-metric, providing a simple value for laboratorians to use in evaluating a test method's capability to meet its analytical quality requirements. Sigma-metrics were determined for 37 clinical chemistry assays, 13 immunoassays, and 3 ICT methods on the Alinity ci system. METHODS: Analytical Performance Specifications were defined for the assays, following a rationale of using CLIA goals first, then Ricos Desirable goals when CLIA did not regulate the method, and then other sources if the Ricos Desirable goal was unrealistic. A precision study was conducted at Abbott on each assay using the Alinity ci system following the CLSI EP05-A2 protocol. Bias was estimated following the CLSI EP09-A3 protocol using samples with concentrations spanning the assay's measuring interval tested in duplicate on the Alinity ci system and ARCHITECT c8000 and i2000SR systems, where testing was also performed at Abbott. Using the regression model, the %bias was estimated at an important medical decisions point. Then the Sigma-metric was estimated for each assay and was plotted on a method decision chart. The Sigma-metric was calculated using the equation: Sigma-metric=(%TEa-|%bias|)/%CV. RESULTS: The Sigma-metrics and Normalized Method Decision charts demonstrate that a majority of the Alinity assays perform at least at five Sigma or higher, at or near critical medical decision levels. CONCLUSION: More than 90% of the assays performed at Five and Six Sigma. None performed below Three Sigma. Sigma-metrics plotted on Normalized Method Decision charts provide useful evaluations of performance. The majority of Alinity ci system assays had sigma values >5 and thus laboratories can expect excellent or world class performance. Laboratorians can use these tools as aids in choosing high-quality products, further contributing to the delivery of excellent quality healthcare for patients.