US Clinical Laboratories Research Articles

Selecting a Risk-Based SQC Procedure for a HbA1c Total QC Plan.

Recent US practice guidelines and laboratory regulations for quality control (QC) emphasize the development of QC plans and the application of risk management principles. The US Clinical Laboratory Improvement Amendments (CLIA) now includes an option to comply with QC regulations by developing an individualized QC plan (IQCP) based on a risk assessment of the total testing process. The Clinical and Laboratory Standards Institute (CLSI) has provided new practice guidelines for application of risk management to QC plans and statistical QC (SQC). We describe an alternative approach for developing a total QC plan (TQCP) that includes a risk-based SQC procedure. CLIA compliance is maintained by analyzing at least 2 levels of controls per day. A Sigma-Metric SQC Run Size nomogram provides a graphical tool to simplify the selection of risk-based SQC procedures. Current HbA1c method performance, as demonstrated by published method validation studies, is estimated to be 4-Sigma quality at best. Optimal SQC strategies require more QC than the CLIA minimum requirement of 2 levels per day. More complex control algorithms, more control measurements, and a bracketed mode of operation are needed to assure the intended quality of results. A total QC plan with a risk-based SQC procedure provides a simpler alternative to an individualized QC plan. A Sigma-Metric SQC Run Size nomogram provides a practical tool for selecting appropriate control rules, numbers of control measurements, and run size (or frequency of SQC). Applications demonstrate the need for continued improvement of analytical performance of HbA1c laboratory methods.

Measurement Challenges at Low Blood Lead Levels.

In 2012, the Centers for Disease Control and Prevention (CDC) adopted its Advisory Committee on Childhood Lead Poisoning Prevention recommendation to use a population-based reference value to identify children and environments associated with lead hazards. The current reference value of 5 μg/dL is calculated as the 97.5th percentile of the distribution of blood lead levels (BLLs) in children 1 to 5 years old from 2007 to 2010 NHANES data. We calculated and updated selected percentiles, including the 97.5th percentile, by using NHANES 2011 to 2014 blood lead data and examined demographic characteristics of children whose blood lead was ≥90th percentile value. The 97.5th percentile BLL of 3.48 µg/dL highlighted analytical laboratory and clinical interpretation challenges of blood lead measurements ≤5 μg/dL. Review of 5 years of results for target blood lead values <11 µg/dL for US clinical laboratories participating in the CDC's voluntary Lead and Multi-Element Proficiency quality assurance program showed 40% unable to quantify and reported a nondetectable result at a target blood lead value of 1.48 µg/dL, compared with 5.5% at a target BLL of 4.60 µg/dL. We describe actions taken at the CDC's Environmental Health Laboratory in the National Center for Environmental Health, which measures blood lead for NHANES, to improve analytical accuracy and precision and to reduce external lead contamination during blood collection and analysis.

Comparison of point-of-care versus central laboratory measurement of hematocrit, hemoglobin, and electrolyte concentrations

ObjectivesWe aimed to investigate the accuracy of certain laboratory examinations obtained by the ABG analyzer (ROCHE AVL OMNI S) as compared to hospital central laboratory (CL). MethodsWe prospectively collected data obtained from the same arterial blood sample regarding hematocrit, hemoglobin, potassium, and sodium. ResultsABG analyzer results were significantly lower (p < 0.0001) compared to CL values thus values between the two methods are not interchangeable. The mean bias for Hb, Na+ and K+ were within accepted by US Clinical Laboratory Improvement Amendment (USCLIA) differences (cut-off points) but not for Ht. In 8.0%, 17.5%, 37.5% and 56.0% of Hb, Na+, K+ and Ht measurements respectively and 29.75% in sum the differences were over the USCLIA accepted limits. ABG analyzer significantly underestimate the values of Hb, Ht, Na+ and K+, compared to CL and almost 30% of all examined parameters were beyond USCLIA accepted biases. ConclusionsABG analyzer significantly underestimates the values of Hb, Ht, Na+ and K+ compared to CL and almost 30% for all examined parameters are beyond USCLIA accepted biases. These data do not support widespread or even careful use of POCT for making diagnostic and treatment decisions until technology improves and results in improved outcomes.

Frequencies of Mutations in 20 Genes Associated with Hereditary Ataxia: Experience from a US Clinical Laboratory (P2.135)

Frequencies of Mutations in 20 Genes Associated with Hereditary Ataxia: Experience from a US Clinical Laboratory (P2.135)

Estudios de sensibilidad en levaduras. Actualización y novedades

This text reviews and updates the uses of the reference procedures for antifungal susceptibility testing in yeasts, the reliability of the commercial methods and the guidelines for the use of these procedures for patient management and for epidemiological reasons to determine the susceptibility profile and the emergence of resistances. Novelties in the procedures of setting clinical breakpoints of antifungal agents by both the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the US Clinical Laboratory Standards Institute (CLSI) are also reviewed.

Comparison of different antimicrobial susceptibility testing methods for Stenotrophomonas maltophilia and results of synergy testing

Accurate determination of resistance is important to ensure appropriate antimicrobial therapy in Stenotrophomonas maltophilia infections. This study was undertaken to evaluate the susceptibility results obtained by disc diffusion, E-test, Phoenix system, and reference agar dilution method and also to evaluate the in vitro activity of various antimicrobial combinations against multidrug-resistant S. maltophilia. Susceptibilities to several antimicrobial agents were determined by agar dilution, disc diffusion, and E-test according to the US Clinical Laboratory and Standards Institute (CLSI) guidelines. Results were also evaluated in the in Phoenix system for available agents. Twelve different antibiotic combinations were tested for synergy by the E-test method. Most synergic combinations were confirmed by microdilution checkerboard assay. Tigecycline, trimethoprim/sulfamethoxazole (TMP-SMX) and doxycycline were the most effective drugs against S. maltophilia. Poorest agreement was determined by disc diffusion and E-test against ticarcillin/clavulanate and ciprofloxacin (κ<0.4), by disc diffusion against colistin (κ<0.4), and by the Phoenix system against piperacillin/tazobactam (κ<0.4). Based on these data, disc diffusion seems to be unreliable for ticarcillin/clavulanate, ciprofloxacin, and colistin; E-test for ticarcillin/clavulanate and ciprofloxacin; and the Phoenix system for piperacillin/tazobactam for S. maltophilia susceptibility testing. Synergistic activity was detected predominantly with TMP-SMX+ticarcillin/clavulanate and TMP-SMX+ceftazidime. TMP-SMX+ceftazidime synergy was also supported by the checkerboard method. However, TMP-SMX+ticarcillin/clavulanate combination revealed indifferent effect by the checkerboard assay. As ticarcillin/clavulanate and ciprofloxacin E-test results were beyond the acceptable correlation limits, synergy testing performed with these agents was considered as unreliable. Further studies are required to standardize susceptibility testing, especially for colistin, ticarcillin/clavulanate, and ciprofloxacin for S. maltophilia. TMP-SMX-containing drug combinations seemed to be more synergistic on multidrug-resistant S. maltophilia; however, these results merit further evaluation.

Prevalence of Estimated GFR Reporting Among US Clinical Laboratories

Routine laboratory reporting of estimated glomerular filtration rate (eGFR) may help clinicians detect kidney disease. The current national prevalence of eGFR reporting in clinical laboratories is unknown; thus, the extent of the situation of laboratories not routinely reporting eGFR with serum creatinine results is not quantified. Observational analysis. National Kidney Disease Education Program survey of clinical laboratories conducted in 2006 to 2007 by mail, web, and telephone follow-up. A national random sample, 6,350 clinical laboratories, drawn from the Federal Clinical Laboratory Improvement Amendments database and stratified by 6 major laboratory types/groupings. Laboratory reports serum creatinine results. Reporting eGFR values with serum creatinine results. Percentage of laboratories reporting eGFR along with reporting serum creatinine values, reporting protocol, eGFR formula used, and style of reporting cutoff values. Of laboratories reporting serum creatinine values, 38.4% report eGFR (physician offices, 25.8%; hospitals, 43.6%; independents, 38.9%; community clinics, 47.2%; health fair/insurance/public health, 45.5%; and others, 43.2%). Physician office laboratories have a reporting prevalence lower than other laboratory types (P < 0.001). Of laboratories reporting eGFR, 66.7% do so routinely with all adult serum creatinine determinations; 71.6% use the 4-variable Modification of Diet in Renal Disease Study equation; and 45.3% use the ">60 mL/min/1.73 m(2)" reporting convention. Independent laboratories are least likely to routinely report eGFR (50.6%; P < 0.05) and most likely to report only when specifically requested (45.4%; P < 0.05). High-volume laboratories across all strata are more likely to report eGFR (P < 0.001). Self-reporting by laboratories, federal database did not have names of laboratory directors/managers (intended respondents), assumed accuracy of federal database for sample purposes. Routine eGFR reporting with serum creatinine values is not yet universal, and laboratories vary in their reporting practices.

Research Highlights

Research Highlights

Has compliance with CLIA requirements really improved quality in US clinical laboratories?

Background: The Clinical Laboratory Improvement Amendments of 1988 (CLIA'88) mandate universal requirements for all U.S. clinical laboratory-testing sites. The intent of CLIA'88 is to ensure quality testing through a combination of minimum quality practices that incorporate total quality management concepts. These regulations do not contain established, objective indicators or measures to assess quality. However, there is an implicit assumption that compliance with traditionally accepted good laboratory practices—following manufacturers' directions, routinely analysing quality control materials, applying quality assurance principles, employing and assessing competent testing personnel, and participating in external quality assessment or proficiency testing (PT)—will result in improved test quality. Methods: The CLIA'88 regulations do include PT performance standards, which intentionally or unintentionally, define intra-laboratory performance. Passing PT has become a prime motivation for improving laboratory performance; it can also be used as an objective indicator to assess whether compliance to CLIA has improved intra-laboratory quality. Results: Data from 1994 through 2002 indicate that the percentage of laboratories passing PT has increased. In addition to PT performance, subjective indicators of improved quality—frequency of inspection deficiencies, the number of government sanctions for non-compliance, and customer satisfaction—were evaluated. Conclusions: The results from these subjective indicators are more difficult to interpret but also seem to show improved quality in US clinical laboratories eleven years post-CLIA'88.

Outbreak of Shiga toxin-producing Escherichia coli O111:H8 infections among attendees of a high school cheerleading camp.

Few US clinical laboratories screen stool specimens for Shiga toxin-producing Escherichia coli (STEC) other than E. coli O157. An outbreak of STEC O111:H8 infections indistinguishable from E. coli O157:H7 at a youth camp highlights the need to improve non-O157 STEC surveillance. Interviews of 521 (80%) of 650 attendees revealed 55 (11%) were ill; 2 developed hemolytic-uremic syndrome. Illness was associated with consuming salad during the camp's first lunch meal (hazard ratio [HR], 4.68; P<.01), consuming ice provided in barrels on the camp's final day (HR, 3.41; P<.01), eating cob corn (HR, 3.22; P<.01), and eating a dinner roll (HR, 2.82; P<.01). Cultures of 2 of 11 stools yielded E. coli O111:H8. Results of serologic testing and additional stool cultures demonstrated no evidence of infection with other bacterial pathogens, including E. coli O157, and supported infection with E. coli O111. Clinical laboratories should routinely screen suspect specimens for non-O157 STEC and should serotype and report Shiga-positive isolates.

Ceftriaxone activity against Gram-positive and Gram-negative pathogens isolated in US clinical microbiology laboratories from 1996 to 2000: results from The Surveillance Network® (TSN®) Database-USA

Ceftriaxone was introduced into clinical practice in the USA in 1985 and was the first extended-spectrum (third-generation) cephalosporin approved for once-daily treatment of patients with Gram-positive or Gram-negative infections. Review of ceftriaxone activity is important given its continued use since the mid-1980s and reports of emerging resistance among all antimicrobial agent classes. We reviewed the activity of ceftriaxone and relevant comparative agents against five Gram-positive and 11 Gram-negative species for a 5-year period, 1996–2000, using data from The Surveillance Network® (TSN®) Database-USA. All MIC results were interpreted using NCCLS breakpoint criteria. Ceftriaxone resistance among isolates of Streptococcus pneumoniae ( n=17 219) remained essentially unchanged over the 5 years studied and in fact was lower from 1998 to 2000 (5.0–5.1%) than in 1996 (6.3%) and 1997 (6.6%). Ceftriaxone resistance (range, 5.1–6.9%) among viridans group streptococci ( n=6621) varied by <2% from 1997 to 2000. Beta-lactam-resistant Streptococcus pyogenes ( n=935) and group B β-haemolytic streptococci ( n=2267) were not identified in any year. Among methicillin-susceptible Staphylococcus aureus ( n=39 284) ceftriaxone resistance was 0.1–0.3% per year from 1996 to 2000. Ceftriaxone resistance among Escherichia coli ( n=472 407; range, 0.2–0.4%), Klebsiella oxytoca ( n=16 231; range, 3.5–4.8%), Klebsiella pneumoniae ( n=117 754; range, 1.9–2.6%), Proteus mirabilis ( n=67 692; range, 0.2–0.3%), Morganella morganii ( n=11 251; range, 0.3–2.1%) and Serratia marcescens ( n=26 519; range, 1.6–3.8%) was low and consistent from 1996 to 2000. Resistance to ceftriaxone among Enterobacter cloacae ( n=48 114; range, 21.7–23.9%) was relatively high, compared with other Enterobacteriaceae, but unchanged from 1996 to 2000. Rates of resistance to ceftriaxone among Acinetobacter spp. ( n=20 813) increased from 24.8% in 1996 to 45.1% in 2000. All Haemophilus influenzae ( n=7911) and Neisseria gonorrhoeae ( n=218) were susceptible to ceftriaxone, as were 99.7% of Moraxella catarrhalis ( n=312) tested in 1996 and 1997. In summary, ceftriaxone has retained its potent activity against the most commonly encountered Gram-positive and Gram-negative human pathogens despite widespread and ongoing clinical use for more than 15 years.

Electronic “Quality Control” (EQC): is it just for unit use devices?

The US Clinical Laboratory Improvement Amendments of 1988 (CLIA'88) mandated daily quality control (QC) for all laboratory tests. CLIA'88 clearly envisioned traditional, matrix-based controls. However, recent interpretations allow routine use of “electronic” controls (EQC). These surrogate controls, reference cassettes, glass filters, electronic signals, etc., evaluate the photometric, electronic and computational components of the test system. EQC does not evaluate chemical reactions, sample and reagent manipulations, etc. When compared to traditional concepts, it represents a discontinuity in logic and subverts the fundamental purpose of QC. The advent of “unit-use” test systems (reagent packs, cassettes, cartridges, etc.) used primarily in decentralized testing locations opened the door to EQC. The rationale behind EQC is that if the test system is operating within specifications and the manufacturer reliably delivers consistent and uniform quality products, a simple electronic check will assure that the entire testing process is in control. Unrecognized test system failure is the most insidious problem facing today's instruments using EQC-based systems. We cite positive and negative examples. We also ask, “If EQC is accepted, from a regulatory perspective for some instruments, why not for all?” Is the next step universal EQC, for all systems, inevitable?