Assessing Quality Control Strategies for HbA1c Measurements From a Patient Risk Perspective.

Background: Current laboratory risk management principles emphasize the importance of assessing laboratory quality control (QC) practices in terms of the risk of patient harm. Limited practical guidance or examples on how to do this are available.

Methods: The patient risk model described in a published laboratory risk management guideline was combined with a recently reported approach to computing the predicted probability of patient harm to produce a risk management index (RMI) that compares the predicted probability of patient harm for a QC strategy to the acceptable probability of patient harm based on the expected severity of harm caused by an erroneously reported patient result.

Utilization of assay performance characteristics to estimate hemoglobin A1c result reliability.

Background: Allowable total error (TE(a)) goals for hemoglobin (Hb) A(1c) require minimal assay imprecision and bias and implementation of a robust QC monitoring program. Here, we compare the combined influence on the risk of reporting unreliable results of TE(a) goals, a routine QC practice, and assay performance characteristics of 6 Hb A(1c) instruments across 4 academic medical centers.

Methods: The CLSI protocols EP-5 and EP-9 were applied to investigate Hb A(1c) result imprecision and bias on the Variant II Turbo and Variant II (Bio-Rad), G8 (Tosoh), Capillarys 2 Flex Piercing (Sebia), COBAS Integra 800 (Roche), and DCA Vantage (Siemens).

Comparing analytic performance criteria: evaluation of HbA1c certification criteria as an example.

Background: Direct comparison of analytical performance criteria that utilize different statistical approaches can be problematic. We describe a mathematical approach to compare performance criteria for hemoglobin A1c (HbA1c) analysis used by the NGSP standardization program and the College of American Pathologists (CAP) to enhance consistency between the schemes.

Methods: The imprecision (CV) and bias combinations required to pass each criterion at probabilities of 0.

Validating the performance of QC procedures.

A methodology for computing the maximum expected number of unreliable patient results produced because of an out-of-control condition for a given quality control strategy is presented along with strategies for changing the expected number of unreliable results produced and reported. The expected number of unreliable patient results reported before and after the last accepted quality control evaluation before the detection of an out-of-control condition are discussed and used as design criteria for quality control strategies that meet a laboratory's risk criteria.

Should I repeat my 1:2s QC rejection?

Background: Repeating a QC that is outside 2SD from the mean (1:2s rule) appears to be a common practice. Although this form of repeat sampling is frowned on by many, the comparative power of the approach has not been formally evaluated.

Methods: We computed power functions mathematically and by computer simulation for 4 different 1:2s repeat-sampling strategies, as well as the 1:2s rule, the 1:3s rule, and 2 common QC multirules.

HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome.

Human papilloma virus (HPV) is an etiologic agent in a subset of oropharyngeal squamous cell carcinomas (SCCs). The aim of this study was to sub-classify SCC of the oropharynx based upon histologic features into nonkeratinizing (NK) SCC, keratinizing (K) SCC, and hybrid SCC, and determine the frequency of HPV and patient survival in each group. Patients with oropharyngeal SCC with a minimum of 2 years of clinical follow-up were identified from radiation oncology databases from 1997 to 2004.

Synaptic ultrastructural alterations anticipate the development of neuroaxonal dystrophy in sympathetic ganglia of aged and diabetic mice.

Neuroaxonal dystrophy, a distinctive axonopathy characterized by marked enlargement of distal axons, is the hallmark pathologic alteration in aged and diabetic human prevertebral sympathetic ganglia and in corresponding rodent models. Neuroaxonal dystrophy is thought to represent the abnormal outcome of cycles of synaptic degeneration and regeneration; a systematic study of identified axon terminals in aged and diabetic prevertebral ganglia, however, has not previously been performed. We examined the initial changes that develop in presynaptic and postsynaptic elements in sympathetic ganglia of aged and diabetic mice and found numerous synaptic changes involving both presynaptic and postsynaptic elements.

Assessing the impact of the frequency of quality control testing on the quality of reported patient results.

Background: The traditional measure used to evaluate QC performance is the probability of rejecting an analytical run that contains a critical out-of-control error condition. The probability of rejecting an analytical run, however, is not affected by changes in QC-testing frequency. A different performance measure is necessary to assess the impact of the frequency of QC testing.

The impact of QC frequency on patient results.

The expected number of unacceptable patient results due to an undetected, malfunction--E(Nu)--can be set as a patient-based quality goal. Using the number of patients tested between QC specimens as a design parameter allows one to design QC strategies that meet specified patient-based quality goals. The QC utilization rate can be minimized in a QC design for a given E(Nu).

Statistical topics in the laboratory sciences.

This chapter concerns statistical concepts and procedures that are applicable to diagnostic testing performed in the clinical laboratory. Three important laboratory issues are addressed: the estimation of analytical imprecision, the design of an effective laboratory quality control strategy, and the establishment of population reference ranges. These three topics were selected because each demonstrates a valuable statistical principle.

Clinical and economic impact of falsely decreased calcium values caused by gadoversetamide interference.

Objective: Gadolinium is administered as a contrast agent in MRI procedures. Two gadolinium-based contrast agents, gadodiamide and gadoversetamide, interfere with colorimetric total serum calcium methods. The purpose of this prospective observational study was to examine the incidence of calcium interference after gadoversetamide procedures, associated clinical outcomes, and costs 20 months after implementation of quality assurance and physician education programs.

Use of serum FSH to identify perimenopausal women with pituitary hCG.

Background: Human chorionic gonadotropin (hCG) tests are performed on many female patients before performing medical procedures or administering medications that may harm a fetus. hCG of pituitary origin has been shown to increase with age. Therefore, mild increases in serum hCG in an older patient can be of pituitary origin and does not necessarily indicate pregnancy.

Erythropoietin and its carbamylated derivative prevent the development of experimental diabetic autonomic neuropathy in STZ-induced diabetic NOD-SCID mice.

Autonomic neuropathy is a significant diabetic complication resulting in increased morbidity and mortality. Studies of autopsied diabetic patients and several rodent models demonstrate that the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in prevertebral ganglia is the occurrence of synaptic pathology resulting in distinctive dystrophic neurites ("neuritic dystrophy"). Our prior studies show that neuritic dystrophy is reversed by exogenous IGF-I administration without altering the metabolic severity of diabetes, i.

Impact of a multidisciplinary intervention for diabetes in Eritrea.

Background: When hemoglobin A1c (HbA1c) testing was made available to diabetic patients in the nation of Eritrea, the majority of values were markedly increased. As a result, a multidisciplinary clinical education program was instituted in Eritrea and the rate of HbA1c testing was increased to monitor progress.

Methods: In February 2003, a cooperative diabetes project was initiated in Eritrea to train diabetes educators, enhance physician education, create patient-teaching materials, and promote glucose monitoring.

Evaluation of the performance of randomized versus fixed time schedules for quality control procedures.

Background: Although minimum regulatory standards exist for determining QC testing frequency, decisions regarding when and how to run QC samples are not standardized. Most QC testing strategies test control samples at fixed time intervals, often placing the samples in the same position on an instrument during subsequent QC events and leaving large gaps of time when control samples are never run, yet patient samples are being tested.

Methods: Mathematical derivations and computer simulation were used to determine the expected waiting time between an out-of-control condition and the next scheduled QC test for various QC testing strategies that use fixed or random intervals between QC tests.

A direct comparison between lamellar body counts and fluorescent polarization methods for predicting respiratory distress syndrome.

Our objective was to directly compare the diagnostic usefulness of lamellar body counting (LBC) and the TDx-FLM II assay (Abbott Laboratories, Abbott Park, IL) for predicting respiratory distress syndrome (RDS). This was a 5-year, retrospective, cohort study. A diagnosis of RDS was given to infants who received surfactant treatment and/or required ventilator support and/or continuous positive airway pressure for more than 24 hours.

Evaluation of polymerase chain reaction for group B streptococcus detection using an improved culture method.

Objective: The administration of antibiotic prophylaxis to laboring women who harbor Group B streptococci (GBS) depends on identification of carriers. We sought to evaluate the diagnostic accuracy of real-time polymerase chain reaction (PCR) for detection of GBS using a more stringent culture method.

Methods: Two swabs were used simultaneously to obtain rectovaginal GBS samples from consenting women.

Ischemia-modified albumin increases after skeletal muscle ischemia during arthroscopic knee surgery.

Background: Ischemia can alter the ability of albumin to bind free metal atoms. Based on these biochemical changes, methods to quantify ischemia modified albumin (IMA) were developed to assist in the evaluation of patients with symptoms of cardiac ischemia. Since ischemia can occur in any vascular bed, the specificity of IMA for cardiac muscle ischemia is unclear and requires further investigation.

Sympathetic neuroaxonal dystrophy in the aged rat pineal gland.

Dysfunction of circadian melatonin production by the pineal gland in aged humans and rats is thought to reflect the functional loss of its sympathetic innervation. Our ultrastructural neuropathologic studies of the sympathetic innervation of the pineal gland of aged (24 months old) Fischer-344 and Sprague-Dawley rats showed loss of nerve terminals as well as the development of neuroaxonal dystrophy (NAD), an ultrastructurally distinctive distal axonopathy, far in excess of that in young control rats. Immunolocalization of tyrosine hydroxylase confirmed the age-related loss of normal noradrenergic innervation and development of NAD.

Diagnostic considerations in the measurement of human chorionic gonadotropin in aging women.

Background: Human chorionic gondadotropin (hCG) screening tests are performed on nearly all female patients of childbearing age before any medical intervention. Although older women usually have negative hCG test results, positive results do occur and may cause clinical confusion. We examined changes with age in serum hCG concentrations in nonpregnant women and investigated the use of serum follicle-stimulating hormone (FSH) measurements as an aid to interpreting higher than expected ("positive") hCG results.