Clinical Laboratory Community Research Articles

A New Easy-to-Perform Flow Cytometry Assay for Determining Bacterial- and Viral-Infection-Induced Polymorphonuclear Neutrophil and Monocyte Membrane Marker Modulation in Febrile Patients.

We developed a flow cytometry (FC) assay enabling the rapid and accurate identification of bacterial and viral infections using whole blood samples. The streamlined flow cytometry assay is designed to be user-friendly, making it accessible even for operators with limited experience in FC techniques. The key components of the assay focus on the expression levels of specific surface markers-CD64 on polymorphonuclear neutrophils (PMN) as a marker for bacterial infection, and CD169 on monocytes (MO) for viral infection. The strong performance indicated by an area under the receiver operating characteristic (ROC) curve of 0.94 for both PMN CD64 positive predictive value (PPV) 97.96% and negative predictive value (NPV) 76.67%, and MO CD169 PPV 82.6% and NPV 86.9%, highlight the assay's robustness in differentiating between bacterial and viral infections accurately. The FC assay includes the assessment of immune system status through HLA-DR and IL-1R2 modulation in MO, providing a useful insight into the patients' immune response. The significant increase in the frequency of MO exhibiting reduced HLA-DR expression and elevated IL-1R2 levels in infected patients (compared to healthy controls) underscores the potential of these markers as indicators of infection severity. Although the overall correlation between HLA-DR and IL-1R2 expression levels was not significant across all patients, there was a trend in patients with more severe disease suggesting that these markers may have the potential to assist in stratifying patient risk. The present FC assay has the potential to become routine in the clinical microbiology laboratory community and to be helpful in guiding clinical decision making.

ARTIFICIAL INTELLIGENCE APPLICATIONS IN CLINICAL MICROBIOLOGY LABORATORY

Artificial intelligence is becoming an increasingly important component of clinical microbiology informatics. Researchers, microbiologists, laboratorians, and diagnosticians are interested in AI-based testing because these applications have the potential to improve the turnaround time, quality, and cost of a test. Artificial intelligence which has gained importance in the laboratory, is used to support decision-making, identification and antimicrobial susceptibility testing with various technologies, image analyses, and MALDI-TOF-MS in medical microbiology and in infectious disease testing. Treatment of infections requires rapid and accurate identification and antimicrobial susceptibility testing. Modern artificial intelligence (AI) and machine-learning (ML) methods can now complete tasks with performance characteristic comparable to those of expert human operators. As a result, many healthcare fields combine these technologies, including in vitro diagnostics and, more broadly laboratory medicine, incorporate these technologies. These technologies are rapidly being developed and disclosed, but by comparison, their application so far has been limited. We need to further establish best practices and improve our information system and communications infrastructure to promote the implementation of reliable and advanced machine learning-based technologies. İnvolvement of the clinical microbiology laboratory community is essential to ensure that laboratory data is adequately accessible and thoughtfully incorporated into robust, safe and clinically effective ML-supported clinical diagnoses. This has been made possible by advances in modern computing and the widespread digitalization of health information. In this review, it is aimed to give information about to AI and its subfield of ML application areas in clinical microbiology laboratory.

Mass Spectrometry in Clinical Laboratory: Applications in Therapeutic Drug Monitoring and Toxicology.

Mass spectrometry (MS) coupled with liquid chromatography (LC) or gas chromatography (GC) has been proven to be a powerful platform in research and specialized clinical laboratories for decades. In clinical laboratories, it is used for compound identification and quantification. Due to the ability to provide specific identification, high sensitivity, and simultaneous analysis of multiple analytes (>100) in recent years, application of MS in routine clinical laboratories has increased significantly. Although MS is used in many laboratory areas, therapeutic drug monitoring, drugs of abuse, and clinical toxicology remain the primary focuses of the field. Due to rapid increase in the number of prescription drugs and drugs of abuse (e.g., novel psychoactive substances), clinical laboratories are challenged with developing new MS assays to meet the clinical needs of the patients. We are here to present "off-the-shelf" and "ready-to-use" protocols of recent developments in new assays to help the clinical laboratory community adopt the technology and analysis for the betterment of patient care.

FRI485 High Interlaboratory Variability In Free Thyroxine Measurement Indicates Need For Method Standardization

Abstract Disclosure: A. Ribera: None. U. Danilenko: None. O. Sugahara: None. L. Collins: None. T. Buchannan: None. N. Vazquez: None. F. Pokuah: None. D. Wirtz: None. L. Zhang: None. A.N. Lyle: None. H.W. Vesper: None. Thyroid function tests are critical to diagnose diseases of the thyroid. Concerns about the accuracy and reliability of thyroid function tests, especially free thyroxine (FT4), have been stated by the clinical laboratory community for many years. In response to these concerns, the CDC Clinical Standardization Program (CSP) has created a standardization program for FT4 based on the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference system and is partnering with IFCC to standardize FT4 and harmonize TSH testing globally. As part of this program, CDC developed an accurate and sensitive reference measurement procedure (RMP) to assign reference values to individual donor sera. Assay manufacturers and research and clinical laboratories can use these sera to assess the analytical performance of their measurements, and monitor analytical performance over time. To obtain initial information about the analytical performance of FT4 and TSH measurements, an interlaboratory study among commercial assays and laboratory developed test was conducted. A panel of 40 blinded, fresh-frozen single donor patient serum samples with FT4 concentration ranging between 11-32 pmol/L concentrations was measured by participants and compared to the results obtained by CDC RMP for FT4. In addition, commercial assay manufacturers were asked to measure thyroid-stimulating hormone (TSH). Results from sixteen commercial assays and four laboratory developed test (LDT) participated. Preliminary results indicate a negative mean bias for all commercial FT4 assays ranging from -34.46% to -5.08%. Some of the assays agreed more closely to the RMP than others (four assays had mean bias over -25%). An equilibrium dialysis mass spectrometry-based assays had mean biases ranging from -8.86% to - 1.72% agreeing well with RMP. The data suggest that the observed bias can be effectively minimized through recalibration to the RMPs operated by the CDC CSP and the IFCC reference laboratory network. The mean TSH concentrations ranged from 0.34 to 21.56 uIU/mL with mean %CV of 11.42% (95%CI 8.07%-14.76%) suggesting good agreement between various platforms. Findings from this study will be used to customize CDC’s protocols and procedures for standardizing FT4 measurements. Presentation: Friday, June 16, 2023

A-080 Overcoming Challenges of Equilibrium Dialysis-Based Free Thyroxine Measurements

Abstract Background Thyroid function tests are widely used to detect diseases of the thyroid. Concerns about the accuracy and reliability of free thyroxine (FT4) measurements have been stated by the clinical laboratory community. To address these concerns, CDC established a reference measurement procedure (RMP) for FT4 based on equilibrium dialysis (ED). ED-based methods have advantages over traditional direct immunoassays. As with all analytical methods, factors affecting accuracy and reliability of ED-based methods need identification and understanding. To investigate potential sources of error, the CDC FT4 RMP was used to evaluate T4 stability at different of storage conditions, adsorption of FT4 to common labware surfaces, and the effect of dialysis membrane materials on the measured FT4 in serum. Methods FT4 was measured in serum using the IFCC RMP (1). FT4 was separated from the protein-bound form during the equilibrium dialysis step of the RMP. Dialysates were spiked with internal standard (13C6-T4) and the analyte was further isolated by C18 solid phase extraction (SPE) and liquid-liquid extraction (LLE) in ethyl acetate prior to injection on an UHPLC system coupled with a triple quadrupole mass spectrometer. Bracketed calibration and primary reference materials were used to determine FT4 concentration in serum. This procedure was used to evaluate stability of serum FT4 during storage at −70 to 5 °C. Short- and long-term T4 stability of calibrator solutions at −70 °C to ambient temperature and the extent of adsorption of T4 calibrator solutions to the commonly used labware surfaces were evaluated. Furthermore, the suitability of 4 different dialysis membranes was assessed. In addition, three alternatives to the currently used SPE and LLE extraction steps were tested: LLE using cyclohexane and ethyl acetate, LLE with ethyl acetate, and supported liquid extraction with cyclohexane and ethyl acetate. Results T4 calibrator solution was stable in 1.7% ammonium hydroxide in ethanol for at least 2.9 years at −70 °C and up to 7 days at ambient temperature. Exposure of various calibrator solutions such as T4 in ethanol, ethanol with 1.7% ammonium hydroxide, 10% acetonitrile with 0.1% formic acid to common labware resulted in up to 10.1% loss of the analyte. FT4 in serum and T4 in dialysates and extracts were stable at −70 to 5 °C. Use of alternative dialysis membranes resulted in up to −8.8% mean bias to the reference membranes. Recoveries of the analyte using four extraction methods were 85.4%–95.0%. None of the tested extraction conditions significantly changed the results obtained with the original FT4 RMPs. Conclusion Although FT4 RMP must strictly adhere to the ED conditions described for the RMP, other parts of the sample preparation procedures can deviate from the originally published procedure. Careful selection of procedure for calibrator solvents, dialysis membranes, labware, and storage conditions is required to ensure accurate and reproducible FT4 measurements.

Robust Response of the Clinical Laboratory to the COVID-19 Pandemic despite Significant Challenges.

Clinical laboratories immediately provided rapid, reliable, and high-throughout diagnostic testing for COVID-19, which was an essential component in combating the pandemic. As the pandemic evolved, the clinical laboratory was faced with additional challenges. However, there are limited studies on the impact of the pandemic on the clinical laboratory over the past 3 years. The American Association for Clinical Chemistry (AACC) sent 8 surveys over a 32-month time period to international clinical laboratory leadership asking questions about COVID-19 testing, supplies, staffing, and lessons learned. There were a total of 191 unique respondents: 133 laboratories in the US and 58 laboratories from 37 other countries participated. By May 2020, more than 70% of laboratories offered COVID-19 diagnostic testing with average turnaround times ranging from 1 to 24 h. Daily COVID-19 testing volumes peaked in January of 2022 at a median of 775 tests per day. Throughout the pandemic, supplies and staffing concerns increased. In most of the 8 surveys, 55% to 65% of laboratories reported they were unable to obtain supplies. Obtaining reagents and test kits was the most problematic. Staffing challenges continue to be a significant concern and most laboratories have struggled hiring testing personnel. Survey results were utilized to demonstrate the impact of the pandemic on the clinical laboratory community, and importantly, findings were presented to the White House Coronavirus Taskforce. Overall, the clinical laboratories had a robust response to the COVID-19 pandemic, and despite ongoing and evolving challenges, continue to provide rapid diagnostic testing.

ODP479 Equilibrium Dialysis ID-LC/MS/MS Procedure for Routine Measurement of Free Thyroxine in Serum

Abstract Free thyroxine (FT4) test is essential for diagnosis of thyroid diseases. Most FT4 tests used in patient care are immunoassays (IAs). However, concerns about the accuracy of FT4 IAs have been raised in the clinical laboratory community. Reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established and are well recognized. While FT4 RMP is highly accurate and precise, it is not intended for routine clinical use. Our aim is to develop an ED-based FT4 assay that is traceable to the RMP and suitable for routine measurements such as investigations in epidemiologic studies. The described assay is based on ED-LC-MS/MS. FT4 in serum was isolated from protein-bound T4 in serum according to the CLSI C45-A guideline. FT4 levels achieved equilibrium in a commercially available micro-ED plate after 18 hours. The dialysate was collected and spiked with internal standard (13 C 6 -T4). The IRMM-468 certified primary reference material (JRC, Belgium) of T4 was used for assay calibration. FT4 in dialysate was extracted with ISOLUTE-96-well C18 SPE plates (Biotage) before LC-MS/MS analysis. T4 could be resolved from Triiodothyronine (T3), reverse triiodothyronine (rT3), and other interferences in the dialysate on a C18 UPLC column with an elution time of less than 8 min. Selective reaction monitoring in positive electrospray ionization mode was used for detection. The measuring range covered 1-100 pg/mL of FT4. The assay sensitivity allowed detection of 0.5 pg/mL FT4, which is sufficient for detection of FT4 in normal and hypothyroid patient samples. The difference of this method to the CDC FT4 RMP was within ±5%. The imprecision of the routine assay, evaluated over four different days, was less than 10% CV. The slopes of calibration curves in dialysate matrix and water were comparable with each other indicating no significant matrix effect on FT4 quantification. The use of micro-ED plates in combination with an automated liquid handling system allows for effective automation of the procedure. The stability of T4 calibrator stock and working solutions were confirmed at various conditions. Currently, a comprehensive comparison study is underway between the newly developed routine method and the CDC FT4 RMP. The described routine FT4 assay can significantly improve throughput. The sensitivity, precision, and accuracy are suitable for routine FT4 measurements in clinical laboratories and conducting large epidemiologic studies. Applying this FT4 routine method to generate population data will support the use of standardized FT4 measurements and to address data needs on FT4 in general population. Presentation: No date and time listed

ODP467 CDC Clinical Standardization Programs (CSP) for Free Thyroxine (FT4) to improve the accuracy and reliability of FT4 measurements in patient care and clinical research

Abstract Concerns about the accuracy and reliability of thyroid function tests, especially free thyroxine (FT4), have been stated by the clinical laboratory community for many years. Thyroid function tests are the most used tests in the U. S. and are the only means to detect and treat diseases of the thyroid. The consequences of inadequate thyroid hormone levels can be severe and are easily preventable and treatable with early detection. In response to these concerns, the CDC CSP has partnered with the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and created a standardization program for FT4 based on the IFCC reference system. The CDC program aims to improve the accuracy, reliability, and comparability of current methods and, thus, improve the diagnosis, treatment, and prevention of thyroidal illnesses. There were no commutable, certified serum-based FT4 reference materials (RMs) available to assess the accuracy and reliability of FT4 assays. CDC has developed an accurate and sensitive reference measurement procedure (RMP) to assign reference values to individual donor sera. Assay manufacturers and research and clinical laboratories can use these sera to assess the analytical performance of their measurements, and monitor performance over time. In addition, the CDC's FT4 RMP is used to assign reference values to materials used in EQA/PT programs to verify that standardization efforts at the developer level translate to the end-user level. The CDC FT4 RMP uses equilibrium dialysis (ED), based on an internationally recognized ED procedure, followed by solid-phase and solvent extractions before analysis by LC-MS/MS. Certified primary RM IRMM468 is used as calibrators. The intra- and inter-day imprecision of the CDC RMP are 3. 0% and 1.1%, respectively. The CDC RMP measurement range is 3. 02–258 pmol/L, which is suitable for analysis of hypo- and hyperthyroid patients. Based on an IFCC comparison study between four FT4 RMPs, the CDC RMP's bias was within 2.5% of the all-labs mean. CDC CSP is currently conducting a comparison to further define the differences among various types of commercially available FT4 assays. A set of 40 serum RMs value assigned with the FT4 RMP are now available via the Phase 1 of the Hormone Standardization (HoSt) Program. These materials can be used for calibration and verification by assay developers. CDC CSP is currently working to develop a Phase 2 of the HoSt Program for FT4 to assist developers with certification of FT4 assays. Based on the needs and requests from the clinical community, programs for new biomarkers, such as thyroid-stimulating hormone, are also being developed. Presentation: No date and time listed

Artificial Intelligence and Mapping a New Direction in Laboratory Medicine: A Review.

Modern artificial intelligence (AI) and machine learning (ML) methods are now capable of completing tasks with performance characteristics that are comparable to those of expert human operators. As a result, many areas throughout healthcare are incorporating these technologies, including in vitro diagnostics and, more broadly, laboratory medicine. However, there are limited literature reviews of the landscape, likely future, and challenges of the application of AI/ML in laboratory medicine. In this review, we begin with a brief introduction to AI and its subfield of ML. The ensuing sections describe ML systems that are currently in clinical laboratory practice or are being proposed for such use in recent literature, ML systems that use laboratory data outside the clinical laboratory, challenges to the adoption of ML, and future opportunities for ML in laboratory medicine. AI and ML have and will continue to influence the practice and scope of laboratory medicine dramatically. This has been made possible by advancements in modern computing and the widespread digitization of health information. These technologies are being rapidly developed and described, but in comparison, their implementation thus far has been modest. To spur the implementation of reliable and sophisticated ML-based technologies, we need to establish best practices further and improve our information system and communication infrastructure. The participation of the clinical laboratory community is essential to ensure that laboratory data are sufficiently available and incorporated conscientiously into robust, safe, and clinically effective ML-supported clinical diagnostics.

The Lab Must Go On.

ObjectivesThe clinical laboratory community has faced unprecedented challenges in responding to the coronavirus disease 2019 (COVID-19) pandemic. Long-held assumptions about laboratory management have been reconsidered in light of these new circumstances.MethodsExperience during the first 6 months of the COVID-19 pandemic at a clinical reference laboratory was reviewed in the context of several commonly held management principles to assess their relevance to clinical laboratory operations during a crisis.ResultsManagement and operational ideas regarding different modes of communication, physical proximity and interaction, operating under a fixed budget, and maintaining a breadth of laboratory service offerings have been challenged during the COVID-19 pandemic. The importance of putting people first, maintaining collaboration, and providing effective leadership and communication throughout an organization have been highlighted.ConclusionsThe collaborative activities of highly interdependent teams and individuals have helped the clinical laboratory community respond to society’s needs in the COVID-19 crisis. Not all laboratory management principles apply equally well in the course of an international respiratory pandemic. When navigating crises, leaders need to distinguish situational management principles from those that are universal.

Building a Public-Private Partnership to Enhance Laboratory Preparedness and Response in the United States.

The public health community has recognized that it cannot handle responses to all possible public health emergencies on its own. The public health sector has deep scientific expertise and excels at initial identification, complex characterization, and test development. The private sector has many resources and capabilities that can complement and augment the public health response. This is especially true in the clinical laboratory sector. Many commercial laboratories are designed for high-volume, high-throughput diagnostic testing in a way that public health laboratories are not. Significant steps have been taken since 2017 to improve the communication and coordination between public health and the private clinical laboratory community, especially during a response to a public health emergency. This paper describes the strong foundation that has been built for an improved clinical and public health laboratory response to the next public health emergency.

Assessment of antinuclear antibodies by indirect immunofluorescence assay: report from a survey by the American Association of Medical Laboratory Immunologists.

The indirect immunofluorescence assay (IFA) using HEp-2 cell substrates is the preferred method by some for detecting antinuclear antibodies (ANA) as it demonstrates a number of characteristic staining patterns that reflect the cellular components bound as well as semi-quantitative results. Lack of harmonized nomenclature for HEp-2 IFA patterns, subjectivity in interpretation and variability in the number of patterns reported by different laboratories pose significant harmonization challenges. The main objectives of this study were to assess current practice in laboratory assessment of HEp-2 IFA, identify gaps and define strategies to improve reading, interpretation and reporting. We developed and administered a 24-item survey based on four domains: educational and professional background of participants, current practice of HEp-2 IFA testing and training, gap assessment and the perceived value of International Consensus on Antinuclear Antibody Patterns (ICAP) and other factors in HEp-2 IFA assessment. The Association of Medical Laboratory Immunologists (AMLI) and American Society for Clinical Pathology administered the survey from April 1 to June 30, 2018, to members involved in ANA testing. This report summarizes the survey results and discussion from a dry workshop held during the 2019 AMLI annual meeting. One hundred and seventy-nine (n = 179) responses were obtained where a significant number were clinical laboratory scientists (46%), laboratory directors (24%), supervisors (13%) or others (17%). A majority of respondents agreed on the need to standardize nomenclature and reporting of HEp-2 IFA results. About 55% were aware of the ICAP initiative; however, among those aware, a significant majority thought its guidance on HEp-2 IFA nomenclature and reporting is of value to clinical laboratories. To improve ICAP awareness and further enhance HEp-2 IFA assessment, increased collaboration between ICAP and the clinical laboratory community was suggested with emphasis on education and availability of reference materials. Based on these suggestions, future efforts to optimize HEp-2 IFA reading, interpretation and reporting would benefit from more hands-on training of laboratory personnel as well as continuous collaboration between professional organizations, in vitro diagnostic manufacturers and clinical laboratories.

Clinical Laboratory Personnel Workforce Survey in Montana

<h3>ABSTRACT</h3> <h3>INTRODUCTION:</h3> The medical laboratory professional workforce shortage in the United States has been documented through several national survey reports that also describe the use of temporary staffing to fill vacancies. The primary study objectives were to determine the extent of the workforce shortage in Montana and describe the usage of temporary staffing to fill vacancies. <h3>STUDY OBJECTIVES:</h3> The study objectives were as follows: (1) identify Montana Clinical Laboratory Improvement Amendments laboratories by geographical area classification, (2) identify usage of temporary medical laboratory professionals based on laboratory type, (3) determine wage differences between full-time/part-time permanent employees versus temporary medical laboratory professionals, (4) determine the usage rates of temporary medical laboratory professionals, (5) identify the cause(s) for usage of temporary staffing, and (6) determine the length of time to fill vacancies. <h3>METHOD:</h3> An electronic survey composed of multiple-choice, dichotomous, short-answer, and open-ended questions was developed to collect qualitative and quantitative data and was distributed via email. <h3>RESULTS:</h3> The survey was sent to 83 facilities, with a 54% (<i>n</i> = 45) response rate. Of respondents, 49% (<i>n</i> = 22) reported employing temporary staffing, and 51% (<i>n</i> = 23) do not employ temporary staffing. The reasons for hiring temporary staffing included being unable to fill the position (62%), medical leave (13%), vacation (10%), and other reasons, such as deployment, maternity leave, being short-staffed, and administrative projects (15%). Of the 22 facilities employing temporary staffing, 45% (<i>n</i> = 10) have a temporary staffing budget line item. <h3>CONCLUSION:</h3> The survey results indicated there is a medical laboratory professional shortage in Montana, and compared with the national rate, the usage of temporary staffing is higher, and vacancies take longer to fill by up to 2 years. The usage of temporary staffing is more than twice as high compared with national survey rates. The state-specific data obtained from this study provided vital information to the Montana clinical laboratory community and could serve as an impetus to work collaboratively to explore solutions to the shortage based on state-specific needs. The survey design can also serve as an example for other states to conduct similar studies to gather state-specific information versus national survey aggregate data.

Interventions to Improve Follow-Up of Laboratory Test Results Pending at Discharge: A Systematic Review.

Failure to follow up test results pending at discharge (TPAD) from hospitals or emergency departments is a major patient safety concern. The purpose of this review is to systematically evaluate the effectiveness of interventions to improve follow-up of laboratory TPAD. We conducted literature searches in PubMed, CINAHL, Cochrane, and EMBASE using search terms for relevant health care settings, transition of patient care, laboratory tests, communication, and pending or missed tests. We solicited unpublished studies from the clinical laboratory community and excluded articles that did not address transitions between settings, did not include an intervention, or were not related to laboratory TPAD. We also excluded letters, editorials, commentaries, abstracts, case reports, and case series. Of the 9,592 abstracts retrieved, eight met the inclusion criteria and reported the successful communication of TPAD. A team member abstracted predetermined data elements from each study, and a senior scientist reviewed the abstraction. Two experienced reviewers independently appraised the quality of each study using published Laboratory Medicine Best Practices (LMBP™) A-6 scoring criteria. We assessed the body of evidence using the A-6 methodology, and the evidence suggested that electronic tools or one-on-one education increased documentation of pending tests in discharge summaries. We also found that automated notifications improved awareness of TPAD. The interventions were supported by suggestive evidence; this type of evidence is below the level of evidence required for LMBP™ recommendations. We encourage additional research into the impact of these interventions on key processes and health outcomes.

Pharmacists in the Laboratory Space: Friends or Foes?

As they have been in the past, pharmacists are ranked among the most trusted professionals, according to the results of an annual Gallup poll. These trusted healthcare professionals are easily accessible to most Americans, with nearly 60 000 community pharmacies in the US. Approximately 18% of these pharmacies have CLIA-waived status and can perform any of the approximately 120 CLIA-waived tests. In addition, many pharmacists are now helping patients make drug dosage decisions in specialized Coumadin and diabetes clinics, among others. With healthcare dollars and physician time stretching thin, the easy access to pharmacists is an attractive way for many patients to receive medical care. But what does this mean for the clinical laboratory community? Do pharmacists receive the proper training to perform and interpret laboratory tests, and how do we ensure the quality of testing? Here we talk to 4 experts, 2 pharmacists and 2 laboratorians, to discuss this rapidly changing space. Additionally, a list of suggested reading materials is provided in a Supplemental file that accompanies the online version of this article at http://www.clinchem.org/content/vol62/issue5. What kinds of testing are pharmacists now involved with? Are they all CLIA waived or do they also order non–CLIA-waived tests? Alex Adams: In a recent study, more than 10 800 pharmacies in the US were reported to hold a CLIA waiver. Thus, pharmacies are currently the fourth leading CLIA-waived facility in the country. Of these pharmacies, 99.85% held only a CLIA waiver, and thus very few pharmacies are currently providing non–CLIA-waived tests. Interestingly, the number of CLIA waivers varies by pharmacy format. More than 43% of supermarkets with pharmacies hold a CLIA waiver; by contrast, only 24% of traditional chain pharmacies, 5% of independent pharmacies, and 4% of mass merchant pharmacies hold a CLIA waiver. Recent publications have documented the growth of …

Effectiveness of Practices To Increase Timeliness of Providing Targeted Therapy for Inpatients with Bloodstream Infections: a Laboratory Medicine Best Practices Systematic Review and Meta-analysis.

SUMMARYBackground.Bloodstream infection (BSI) is a major cause of morbidity and mortality throughout the world. Rapid identification of bloodstream pathogens is a laboratory practice that supports strategies for rapid transition to direct targeted therapy by providing for timely and effective patient care. In fact, the more rapidly that appropriate antimicrobials are prescribed, the lower the mortality for patients with sepsis. Rapid identification methods may have multiple positive impacts on patient outcomes, including reductions in mortality, morbidity, hospital lengths of stay, and antibiotic use. In addition, the strategy can reduce the cost of care for patients with BSIs.Objectives.The purpose of this review is to evaluate the evidence for the effectiveness of three rapid diagnostic practices in decreasing the time to targeted therapy for hospitalized patients with BSIs. The review was performed by applying the Centers for Disease Control and Prevention's (CDC's) Laboratory Medicine Best Practices Initiative (LMBP) systematic review methods for quality improvement (QI) practices and translating the results into evidence-based guidance (R. H. Christenson et al., Clin Chem 57:816–825, 2011, http://dx.doi.org/10.1373/clinchem.2010.157131).Search strategy.A comprehensive literature search was conducted to identify studies with measurable outcomes. A search of three electronic bibliographic databases (PubMed, Embase, and CINAHL), databases containing “gray” literature (unpublished academic, government, or industry evidence not governed by commercial publishing) (CIHI, NIHR, SIGN, and other databases), and the Cochrane database for English-language articles published between 1990 and 2011 was conducted in July 2011.Dates of search.The dates of our search were from 1990 to July 2011.Selection criteria.Animal studies and non-English publications were excluded. The search contained the following medical subject headings: bacteremia; bloodstream infection; time factors; health care costs; length of stay; morbidity; mortality; antimicrobial therapy; rapid molecular techniques, polymerase chain reaction (PCR); in situ hybridization, fluorescence; treatment outcome; drug therapy; patient care team; pharmacy service, hospital; hospital information systems; Gram stain; pharmacy service; and spectrometry, mass, matrix-assisted laser desorption-ionization. Phenotypic as well as the following key words were searched: targeted therapy; rapid identification; rapid; Gram positive; Gram negative; reduce(ed); cost(s); pneumoslide; PBP2; tube coagulase; matrix-assisted laser desorption/ionization time of flight; MALDI TOF; blood culture; EMR; electronic reporting; call to provider; collaboration; pharmacy; laboratory; bacteria; yeast; ICU; and others. In addition to the electronic search being performed, a request for unpublished quality improvement data was made to the clinical laboratory community.Main results.Rapid molecular testing with direct communication significantly improves timeliness compared to standard testing. Rapid phenotypic techniques with direct communication likely improve the timeliness of targeted therapy. Studies show a significant and homogeneous reduction in mortality associated with rapid molecular testing combined with direct communication.Authors' conclusions.No recommendation is made for or against the use of the three assessed practices of this review due to insufficient evidence. The overall strength of evidence is suggestive; the data suggest that each of these three practices has the potential to improve the time required to initiate targeted therapy and possibly improve other patient outcomes, such as mortality. The meta-analysis results suggest that the implementation of any of the three practices may be more effective at increasing timeliness to targeted therapy than routine microbiology techniques for identification of the microorganisms causing BSIs. Based on the included studies, results for all three practices appear applicable across multiple microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-sensitive S. aureus (MSSA), Candida species, and Enterococcus species.

Genomic Test Validation for Incidental Findings

In March of 2013, the American College of Medical Genetics and Genomics (ACMG) issued recommendations for the reporting of incidental findings produced by clinical exome and genome sequencing (1, 2). This guideline on incidental findings has been controversial, because the recommendations are a departure from previous ethical concepts of patient autonomy and the reporting of adult-onset disease in children (3–5). One aspect of the incidental-findings guideline that has not been discussed is the lack of required analytical validation for the reporting of a subset of pathogenic variants known to cause severe disease. Analytical validation of any clinical test is critical before its implementation. In the case of genetic testing, clinical laboratories should neither interpret nor report sequence changes that have not been previously validated. More importantly, test results that do not meet the minimum requirements of analytical performance should not be used for clinical decision-making. The ethical concerns raised by the general clinical community in response to the incidental-findings guideline are justified. The clinical laboratory community must specifically consider the ethical and regulatory implications of returning life-changing results from tests that have not been analytically validated or have not met the minimal quality standards established by the laboratory. The incidental-findings guideline was based on a working group appointed by the ACMG. The guideline is for clinical exome/genome laboratories to report a limited number of pathogenic DNA variants; there are 57 genes in the current guideline. The criteria on which the selection of genes was based include only “unequivocally pathogenic mutations in genes where pathogenic variants lead to disease with very high probability and …

Harmonization of laboratory testing — Current achievements and future strategies

Harmonization in laboratory testing is more far-reaching than merely analytical harmonization. It includes all aspects of the total testing process from the “pre-pre-analytical” phase through analysis to the “post-post-analytical” phase. Harmonizing the pre-analytical phase requires use of standardized operating procedures for correct test selection, sample collection and handling, while standardized test terminology, and units and traceability to ISO standard 17511 are required to ensure equivalency of measurement results. Use of harmonized reference intervals and decision limits for analytes where platforms share allowable bias requirements will reduce inaccurate clinical interpretation and unnecessary laboratory testing. In the post-analytical phase, harmonized procedures for the management of critical laboratory test results are required to improve service quality and ensure patient safety. Monitoring of the outcomes of harmonization activities is through surveillance by external quality assessment schemes that use commutable materials and auditing of the “pre-pre-analytical” and “post-post-analytical” phases. Successful implementation of harmonization in laboratory testing requires input by all stakeholders, including the clinical laboratory community, diagnostics industry, clinicians, professional societies, IT providers, consumer advocate groups and governmental bodies.

Vitamin B12 and folate tests: the ongoing need to determine appropriate use and public funding

[Extract] It's not as simple as new for old: we need to follow a process for “disinvestment” in existing medical procedures, services and technologies Criteria have been developed for assessing the safety, effectiveness and cost‐effectiveness of new and emerging health interventions, but additional challenges exist in identifying opportunities for reducing the use of existing health technologies or procedures that are potentially overused, (cost‐)ineffective or unsafe.1 Criteria have been proposed to flag technologies that might warrant further investigation under quality improvement programs.1 These criteria are: new evidence becomes available; there is geographical variation in use; variation in care between providers is present; the technology has evolved and differs markedly from the original; there exists a temporal trend in the volume of use; public interest or controversy is present; consultation with health care workers and funders raises concerns; new technology has displaced old technology; there is evidence of leakage (use beyond the restriction or indication); the technology or intervention is a “legacy item” that has never been assessed for cost‐effectiveness; use is not in accordance with clinical guidelines; or the technology is nominated by clinical groups. After such a nomination was made by members of the clinical laboratory community regarding vitamin B12 and folate tests, we sought to determine whether these tests met other criteria. We hope that this article will encourage debate and discussion about the appropriate use of these tests.

New Technologies in Clinical Microbiology

ABSTRACT Rapid identification of microorganisms in the clinical microbiology laboratory can be of great value for selection of optimal patient management strategies for infections caused by bacteria, viruses, fungi, mycobacteria, and parasites. Rapid identification of microorganisms in clinical samples enables expedient de-escalation from broad-spectrum agents to targeted antimicrobial therapy. The switch to tailored therapy minimizes risks of antibiotics, namely, disruption of normal flora, toxic side effects, and selective pressure. There is a critical need for new technologies in clinical microbiology, particularly for bloodstream infections, in which associated mortality is among the highest of all infections. Just as importantly, there is a need for the clinical laboratory community to embrace the practices of evidence-based interventional laboratory medicine and collaborate in translational research projects to establish the clinical utility, cost benefit, and impact of new technologies.