Improve Turnaround Time Research Articles

236 Trends from over 85,000 genome-wide cell-free DNA tests

Genome-wide cell-free DNA (cfDNA) screening has been clinically-available since 2015. Since that time, over 85,000 samples have been submitted for testing, spanning various versions of the laboratory assay. The current study analyzes testing trends from one assay version (AV) to the next. Maternal blood samples submitted for genome-wide cfDNA testing were subjected to DNA extraction, library preparation, and genome-wide massively parallel sequencing as previously described by Jensen et al. Sequencing data were analyzed using a novel algorithm to detect aneuploidies and other subchromosomal events as described by Lefkowitz et al. Retrospective analysis of 86,902 genome-wide cfDNA samples (47,981 samples from AV4 and 38,921 from AV5) was performed. The gestational age of samples stayed relatively consistent over time, with the majority (59%) of samples submitted during the first trimester, and only 4% during the third trimester. The indication for testing shifted from AV4 to AV5, with significantly fewer advanced maternal age (AMA) cases, and significantly more cases with “no known high risk indication”. The average maternal age decreased significantly between assay versions from 34.3 to 32.9 years. Turn-around time decreased significantly from 5.7 calendar days with AV4 to 3.4 calendar days with AV5. The overall positivity rate of the test was 4.8%, with a statistically significant decrease from AV4 to AV5 (4.9% to 4.6%). No significant difference in positive findings was seen over time, with 25% of abnormalities detected being unique to genome-wide screening, consistent from AV4 to AV5. Over 5 years of genome-wide cfDNA screening has seen a significant decrease in the average maternal age of patients tested, and an increase in testing of patients with no known high-risk indication. As the number of presumably average risk patients has increased, the positivity rate of testing has decreased, though the frequency of genome-specific findings has remained constant. Significant improvements in turnaround time have been seen from one assay version to the next.

Automated molecular testing of saliva for SARS-CoV-2 detection

With surging global demand for SARS-CoV-2 testing capacity, laboratories seek automated, high-throughput molecular solutions, particularly for specimens not requiring specialized collection devices or viral transport media. Saliva specimens submitted from patients under investigation for COVID-19 from March to July 2020 were processed in the laboratory with sterile phosphate-buffered saline in a 1:2 dilution and tested using manual extraction and a commercial assay for detection of the SARS-CoV-2 E gene (LightMix®) in comparison to the Roche cobas® SARS-CoV-2 Test on the cobas® 6800 instrument. 34.4% (22/64) of saliva samples were positive for SARS-CoV-2. Positive and negative concordance between the LightMix® and cobas® assays were 100%. The overall invalid rate for saliva on the cobas® 6800 (1/128, 0.78%) was similar to the baseline invalid rate observed for nasopharyngeal swabs/viral transport media. Saliva is a feasible specimen type for SARS-CoV-2 testing on the cobas® 6800 platform, with potential to improve turnaround time and enhance testing capacity.

Rapid and Simple Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC) Method for Simultaneous Quantifications of Triazole Antifungals in Human Serum.

To develop and validate a one-step, rapid and simple reversed-phase high-performance liquid chromatography (HPLC)-based protocol for the simultaneous measurement of voriconazole (VCZ), posaconazole (POSA), itraconazole (ITC) in serum/plasma. Calibration standards (CS) and quality control samples were prepared in drug-free serum by spiking with the triazoles at different concentrations. HPLC was performed with C18 column, isocratic mobile phase after extraction with cold acetonitrile. The standardized method was tested in 2693 patients' serum/plasma samples. Linearity of CS for ITC, VCZ and POSA was proportional to the nominal concentration (correlation coefficient > 0.999). Limit of detection (mg/L) for ITC, VCZ and POSA was 0.25, 0.25 and 0.125, respectively. The lower limit of quantification (mg/L) for ITC, VCZ and POSA was 0.5, 0.5 and 0.25, respectively. Precision and accuracy were in acceptable range with 100% average percentage recovery. No interferences from endogenous substances and other antimicrobial compounds were noted. In clinical samples, the therapeutic range achieved for VCZ was 39.9%. Whereas, 61.1% and 44% of samples with ITC and POSA, respectively, were in the sub-therapeutic range. We developed a rapid and simple HPLC method to quantify common triazoles in a single chromatographic run allowing simultaneous measurement of different antifungals in a small volume of serum/plasma. Thus, therapeutic drug monitoring requests can be processed in one run without changing the protocol parameters, column or column conditioning thereby improving turnaround time.

Electronic application to improve management of infections in low-income neonatal units: pilot implementation of the NeoTree beta app in a public sector hospital in Zimbabwe

There are 2. 4 million annual neonatal deaths worldwide. Simple, evidence-based interventions such as temperature control could prevent approximately two-thirds of these deaths. However, key problems in implementing these interventions...

A rapid response vaccine development strategy for newcastle disease in poultry

Poultry is a major source of protein in sub-Saharan Africa and many other lower-income regions. Newcastle disease virus (NCDV) comprises a significant threat toward poultry production. While NCDV vaccines are routinely used in developed countries, those used in sub-Saharan Africa are mostly imported and are not specific to locally circulating strains. Indeed, the lack of rapid, field-based NCDV detection and the absence of cost-effective production methods for pure, strain-specific vaccines hampers efficient poultry production throughout these regions. This remains a major problem for both subsistence and commercial farming.The aim for this study was firstly, to develop a field-based isothermal PCR assay for NCDV detection that employed a portable instrument and real-time data transfer application. Secondly,to use the nucleic acid sequence data obtained from field isolates to develop a protocol compatible with rapid emergency vaccine production for NCDV.To achieve this, the isothermal PCR detection assay was applied to field isolates from suspected NCDV outbreaks on commercial poultry farms in KwaZulu-Natal, South Africa, while for the vaccine development, the NCDV matrix gene of one of the isolates was sequenced and used to design primers for the recombinant cloning of this antigen into an adenoviral vector.This‘vaccine vector’ and a control adenoviral vector were each amplified in 293T cells and then used to infect both 293T cells as a production cell line and chicken embryo fibroblasts (CEF) as a preliminary model of the target host. Western blotting confirmed the successful expression of the V5epitopetagby the control vector in both cell lines, which established the compatibility of the adenovirus vector as an appropriate carrier of the target antigen. Mass spectrometry confirmed expression of the NCDV matrix protein by the vaccine vector in both cell lines. In conclusion, the improved turnaround time from detection to the production of the vaccine antigen was under6weeks.The approach described here provides a rapid and cost-effective protocol for both the pathogen detection on-site and the production of pure vaccine antigens specific to an emerging field strain of NCDV within lower-income regions.

Analytical validity of nanopore sequencing for rapid SARS-CoV-2 genome analysis

Viral whole-genome sequencing (WGS) provides critical insight into the transmission and evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Long-read sequencing devices from Oxford Nanopore Technologies (ONT) promise significant improvements in turnaround time, portability and cost, compared to established short-read sequencing platforms for viral WGS (e.g., Illumina). However, adoption of ONT sequencing for SARS-CoV-2 surveillance has been limited due to common concerns around sequencing accuracy. To address this, here we perform viral WGS with ONT and Illumina platforms on 157 matched SARS-CoV-2-positive patient specimens and synthetic RNA controls, enabling rigorous evaluation of analytical performance. We report that, despite the elevated error rates observed in ONT sequencing reads, highly accurate consensus-level sequence determination was achieved, with single nucleotide variants (SNVs) detected at >99% sensitivity and >99% precision above a minimum ~60-fold coverage depth, thereby ensuring suitability for SARS-CoV-2 genome analysis. ONT sequencing also identified a surprising diversity of structural variation within SARS-CoV-2 specimens that were supported by evidence from short-read sequencing on matched samples. However, ONT sequencing failed to accurately detect short indels and variants at low read-count frequencies. This systematic evaluation of analytical performance for SARS-CoV-2 WGS will facilitate widespread adoption of ONT sequencing within local, national and international COVID-19 public health initiatives.

Verification and Implementation of HIV Antibody Differentiation Testing to Improve Turnaround Time for the HIV Diagnostic Algorithm.

Relying on reference laboratories for HIV confirmation testing may lead to delays in treatment and can cause stress for patients who have positive HIV screening results. To internalize HIV-1/HIV-2 antibody differentiation testing within the hospital laboratory. We analytically verified an HIV antibody differentiation immunoassay and subsequently compared result turnaround times (TATs) for HIV antibody differentiation and HIV-1 qualitative RNA in the months before and after the test internalization. HIV antibody differentiation was successfully verified. TATs for HIV antibody differentiation and HIV-1 RNA significantly improved, from medians of 40.4 hours and 156.5 hours to medians of 17.7 hours and 56.5 hours, respectively, after the internalization. The 90th-percentile turnaround times declined by 72% and 44%, respectively. It is feasible for a hospital laboratory to verify HIV antibody-differentiation testing. Its implementation may considerably improve result TATs for the HIV diagnostic algorithm.

Augmented Human Intelligence and Automated Diagnosis in Flow Cytometry for Hematologic Malignancies.

Clinical flow cytometry is laborious, time-consuming, and expensive given the need for data review by highly trained personnel such as technologists and pathologists as well as the significant number of normal cases. Given these issues, automation in analysis and diagnosis holds the key to major efficiency gains. The objective was to design an automated pipeline for the diagnosis of B-cell malignancies in flow cytometry and evaluate its performance against our standard clinical diagnostic flow cytometry process. Using 3,417 cases of peripheral blood data over 6 months from our 10-color B-cell screening tube, we used a newly described method for feature extraction and dimensionality reduction called UMAP on the raw flow cytometry data followed by random forest classification to classify cases without gating on specific population. Our automated classifier was able to achieve greater than 95% accuracy in diagnosing all B-cell malignancies, and even better performance for specific malignancies for which the panel was designed, such as chronic lymphocytic leukemia. By adjusting classifier cutoffs, 100% sensitivity could be achieved with an albeit low 14% specificity. Hypothetically, this would allow 11% of the cases to be autoverified without human intervention. These results suggest that a clinical implementation of this pipeline can greatly assist in quality control, improve turnaround time, and decrease staff workloads.

Evaluation of the performance of sysmex XN-3100 automated hematology analyzer regarding the sysmex XE-2100 and microscopic examination

Abstract Objectives We performed a verification study of the Sysmex XN-3100 hematology analyzer in comparison with the XE-2100 according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) and the International Council for Standardization in Hematology (ICSH). Materials and methods Blood samples and quality control materials were used for precision. For comparison, we used the current XE-2100 as the comparative method and analyzed 540 blood samples. The Passing-Bablok and Bland-Altman tests were performed according to the CLSI EP09-A3 and a carryover study was performed according to the CLSI H26-A2 guidelines. The flagging performance of the two analyzers was compared, using two experienced laboratory technicians as the reference method. Results The Sysmex XN-3100 demonstrated high levels of precision for most parameters. For the comparison analysis, all parameters, except for MCHC, monocytes and basophils were within the systematic error limits of desirable biological variability criterion (SeDBV). The carryover was less than 0.4% for all parameters. The flagging performance of the XN-3100 was satisfactory and the overall efficiency was high. Conclusions The XN-3100 not only showed a strong correlation and agreement with the XE-2100 but also displayed a comparable analytical sensitivity, and increased specificity, which may result in an improved turnaround time and throughpu.

Artificial Intelligence Substantially Supports Chromosome Banding Analysis Maintaining Its Strengths in Hematologic Diagnostics Even in the Era of Newer Technologies

Background: Chromosome banding analysis (CBA) is one of the most important techniques in diagnostics and prognostication in hematologic neoplasms. CBA is still a challenging method with very labor-intensive wet lab processes and karyotyping that requires highly skilled and experienced specialists for tumor cytogenetics. Short turnaround times (TAT) are becoming increasingly important to enable genetics-based treatment stratification at diagnosis. Aim: Improve TAT and quality of CBA by automated wet lab processes and AI-based algorithms for automatic karyotyping. Methods: In the last 15 years the CBA workflow has gradually been automated with focus on the wet lab and metaphase capturing processes. Now, a retrospective unselected digital data set of 100,000 manually arranged karyograms (KG) with normal karyotype (NKG) from routine diagnostics was used to train a deep neural network (DNN) classifier to automatically determine the class/number and orientation of the respective chromosomes (AI based classifier normal, AI-CN). With a total of 6 Mio parameters, the DNN uses two distinct output layers to simultaneously predict the chromosome number (24 classes) and the angle that is required to rotate the chromosome in its correct, vertical position (360 classes). Training of the DNN took 16 days on a Nvidia RTX 2080 Ti graphic card with 4352 cores. AI-CN was implemented into the routine workflow (including ISO 15189) after 7 months of development and intensive testing. Results: The AI-CN was tested by highly experienced staff in an independent prospective validation set of 500 NKG: 22,675/23,000 chromosomes (98.6%) were correctly assigned by AI-CN. In 369/500 (73.8%) of cells all chromosomes were correctly assigned, in an additional 20% only 2 chromosomes were interchanged. The chromosomes accounting for the majority of misclassifications were chromosomes 14 and 15 as well as 4 and 5, which are difficult to distinguish in poor quality metaphases also for humans. The 1st AI-CN was implemented into routine diagnostics in August 2019 and the 2nd AI-CN - optimized for chromosome orientation - was used since November 2019. Since then more than 17,500 cases have been processed with AI-CN (>350,000 metaphases) in routine diagnostics resulting in the following benefits: 1) Reduced working time: an experienced cytogeneticist needs - depending on chromosome quality - between 1 and 3 minutes to arrange a KG, while AI-CN needs only 1 second and the cytogeneticist about 30 seconds to review the KG. 2) Shorter TAT: The proportion of cases reported within 5 days increased from 30% before AI-CN (2019) to 36% with AI-CN1 (2019) and 45% with AI-CN2 (2019/2020), while the proportion of cases reported >7 days was reduced to 28%, 21%, and 17%, respectively (figure). Using AI-CN for aberrant karyotypes results in correct assignment of normal chromosomes and thus also correct KG in cases with solely numerical chromosome abnormalities. Derivative chromosomes derived from structural abnormalities (SA) that differ clearly from any normal chromosome are not automatically assigned but are left out for manual classification. Thus, even in cases with SA, using AI-CN saves time. To allow AI based SA assignment, two additional classifiers normal/aberrant (CNA) were built: AI-CNA1 was trained on 54,634 KG encompassing 10 different SA (AKG) and 100,000 NKG and AI-CNA2 was trained on all AKG and an equal number of NKG. First validation tests are promising and optimization is ongoing. Once the CNA has been optimized, a standardized high quality of chromosome aberration detection is feasible. A fully automated separation of chromosomes is currently in progress and will reduce the TAT by another 12-24 hours. In a fully automated workflow the detection of small subclones can be further optimized by increasing today's standard of 20 metaphases to several hundred, even without any delay in TAT and need for additional personnel. Conclusions: Implementation of AI in CBA substantially improves the quality of results and shortens turnaround times even in comparison to highly trained and experienced cytogeneticists. In the majority of cases a complete karyotype analysis can be guaranteed within 3 to 7 days, allowing CBA based treatment strategies at diagnosis. This fully automated workflow can be implemented worldwide, is rapidly scalable, can be performed cloud based and requires in the near future fewer experienced tumor cytogeneticists. Figure Disclosures Hänselmann: MetaSystems: Current Employment. Lörch:MetaSystems: Current equity holder in private company.

Optimizing the Handling of Invasive Fungal Sinusitis Surgical Specimens

Abstract Introduction/Objective Invasive fungal sinusitis (IFS) is an aggressive disease characterized by invasion of fungal hyphae into tissue/neurovascular bundles. This project assessed the handling of IFS specimens and implemented protocols to improve turnaround time (TAT). Methods A retrospective review of cases accessioned with a clinical concern for IFS from 2014-2019 was performed. TAT for each step in the specimen processing was recorded. A flowchart was created using stakeholder interviews and a revised protocol was developed after assessing critical needs. Assessment of interventions was performed following implementation of the new protocol. The protocol will be evaluated by prospective direct case-by-case feedback and after a 6-month interval (projected August/2020). At 6-months, goals are a 24 hours median time between frozen section and sign-out and elimination of outliers (greater than 2 working days). Results We identified 53 specimens from 32 patients in the pre-intervention period (36 cases positive for IFS). Median time from frozen section to final sign-out was 28 (5-312) hours. Four areas for improvements were identified: (1) triaging specimens to different protocols according to arrival time, (2) optimized triaging for available histology processors, (3) standardized GMS ordering, and (4) standardized case delivery/communication with sign-out staff. Interventions include: protocol for processing specimens based on time of day, new histology protocols to expedite GMS performance, an email group for rapid communication with staff pathologists and histology, and a worksheet/checklist to track each case. After implementation of the protocol, 8 cases from 7 patients were received. Median time from frozen section to final sign-out was reduced to 20 (2 – 50) hours. Conclusion The protocol for handling IFS specimens became live on 2/1/2020. It has reduced TAT of suspected IFS cases, from a median of 28 hours to 20 hours. The longest interval to sign-out went from312 hours to 50 hours.

Making Book Rights, Right

In 2017, the Book Industry Study Group (BISG), a U.S.-based trade association dedicated to improving the efficiency and effectiveness of the book industry supply chain, published Publishing Rights: An Untapped Opportunity. The white paper outlined six findings from an industry survey. Since then, BISG’s rights committee extended that initial research by updating a draft taxonomy for rights transactions. The new taxonomy defines rights data, transactions requests, transactions licenses, and royalty data. The taxonomy is being tested now in a set of pilot agreements between trading partners. Benefits of the proposed taxonomy are expected to include lower transaction costs, fewer errors in rights tracking and sale, and improved turnaround times for rights inquiries. Information about the work may be obtained by writing to info@bisg.org.

Streamlining the Quantitative Metrics Workflow at a Comprehensive Cancer Center

The objective of the project was to describe an efficient workflow for quantifying and disseminating tumor imaging metrics essential for assessing tumor response in clinical therapeutic trials. The clinical research utility of integration of the workflow into the electronic health record for radiology reporting was measured before and after the intervention. A search of institutional clinical trial databases was performed to identify trials with radiology department collaborators. Investigator initiated trials, or those which lacked a standardized or automated system of collaboration with the research team were selected for the study. A web based application integrated in the electronic health record platform, the Quantitative Imaging Analysis Core (QIAC) initiative was established as a divisional resource with institutional support to provide standardized and reproducible imaging metrics across the institution. The turnaround time for radiology reports before (phase 1) and after web based application workflow (phase 2) was measured. During our test period (November 2014 to June 2015), a total of 68 requests with 37 from phase 1 and 31 from phase 2 were analyzed for patients who were enrolled in prospective clinical therapeutic interventional trials. The mean turnaround time for generation of quantitative tumor metric results after implementation of the web based QIAC workflow (phase 2) was significantly lower than prior (phase 1) (15.9 ± 21.3 vs 31.7 ± 35.4 hours, p= 0.0005). The mean time from the scan to the preliminary assessment was 19.6 ± 25.6 hours before and significantly reduced to 8.0 ± 9.9 hours with implementation of web based QIAC workflow. Implementation of a web based QIAC workflow platform enabled significantly improved turnaround time for quantitative tumor metrics reports and enabled faster access to the reports.

Evaluation of Matrix Assisted Laser Desorption Ionisation-Time of Flight Mass Spectrometry in Direct Identification of Bacteriuria from Urine samples

AbstractObjective: The use of matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI) directly on urine can significantly improve turnaround time for diagnosing urinary tract infection (UTI). The present study was planned to compare the performance of MALDI directly on urine samples with conventional urine culture and evaluate an algorithm using a combination of significant pyuria and MALDI directly on urine samples as a screening method for diagnosing UTI. Materials and Methods: A total of 1000 urine samples from patients with symptoms suggestive of UTIs were analysed. Urine microscopy, urine culture and MALDI were performed simultaneously on all the samples. Results: MALDI correctly identified the microorganisms in 73.83% monomicrobial samples. In culture showing a mixed growth of two and more than three organisms, MALDI was able to identify one microorganism in 27.58% and 15.78% of samples, respectively. There were no peaks by MALDI in 93.53% of 464 sterile samples. The sequential algorithm using urine microscopy and MALDI could correctly identify UTI in 66.23% cases. Conclusion: MALDI can be utilised to rule out bacteriuria in >93% of sterile urine samples. The combination of significant pyuria and direct MALDI as screening method to diagnose UTI (whether monomicrobial or polymicrobial) was not found to be superior than using direct MALDI on urine samples alone.

Reducing Point-of-care Blood Gas Testing in the Intensive Care Unit through Diagnostic Stewardship: A Value Improvement Project.

Overutilization of point-of-care (POC) testing may reduce the overall value of care due to high-cost cartridges, need for staff training, and quality assurance requirements. The Diagnostic Stewardship group at Cincinnati Children's Hospital Medical Center assembled a multidisciplinary team to reduce the use of POC blood gas testing by 20% in the pediatric intensive care unit (PICU). Key drivers of test overutilization included poor knowledge of cost, concern with testing turnaround time, and a lack of a standard definition of when a POC test was appropriate. We calculated weekly the outcome measure of POC blood gas tests per PICU patient-day and a balancing measure of blood gas result turnaround time using data extracted from the electronic medical record. Interventions focused on staff education, the establishment of a standard practice guideline for the use of POC testing, and improving turnaround time for laboratory blood gas testing. Over the baseline period starting July 2016, a median of 0.94 POC blood gas tests per PICU patient-day was ordered. After initial staff training, the rate was reduced to 0.60 tests per PICU patient-day and further reduced to 0.41 tests per PICU patient-day after a formal policy change was adopted. We have sustained this rate for 15 months through June 2018. Institutional direct cost savings were estimated to be $19,000 per year. Our improvement initiative was associated with a significant and rapid reduction in the use of POC testing in the PICU. Interventions focused on cost awareness, and a formal guideline helped establish a consensus around appropriate utilization.

The Future of Concurrent Automated Coronary Artery Calcium Scoring on Screening Low-Dose Computed Tomography.

Low-dose computed tomography (LDCT) has been extensively validated for lung cancer screening in selected patient populations. Additionally, the use of gated cardiac CT to assess coronary artery calcium (CAC) burden has been validated to determine a patient's risk for major cardiovascular adverse events. This is typically performed by calculating an Agatston score based on density and overall burden of calcified plaque within the coronary arteries. Patients that qualify for LDCT for lung cancer screening commonly share major risk factors for coronary artery disease and would frequently benefit from an additional gated cardiac CT for the assessment of CAC. Given the widespread use of LDCT for lung cancer screening, we evaluated current literature regarding the use of non-gated chest CT, specifically LDCT, for the detection and grading of coronary artery calcifications. Additionally, given the evolving and increasing use of artificial intelligence (AI) in the interpretation of radiologic studies, current literature for the use of AI in CAC assessment was reviewed. We reviewed primary scientific literature dating up to April 2020 using Pubmed and Google Scholar, with the search terms low dose CT, lung cancer screening, coronary artery calcium, EKG/cardiac gated CT, deep learning, machine learning, and AI. These publications were then independently evaluated by each member of our team. Overall, there was a consensus within these papers that LDCT for lung cancer screening plays a role in the evaluation of CAC. Most studies note the inherent problems with the evaluation of the density of coronary calcifications on LDCT to give an accurate numeric calcium or Agatston score. The current method of evaluating CAC on LDCT involves using a qualitative categorical system (none, mild, moderate, or severe). When performed by cardiac imaging experts, this method broadly correlates with traditional CAC score groups (0, 1 to 100, 101 to 400, and > 400). Furthermore, given the high sensitivity of a properly protocolled LDCT for coronary calcium, a negative study for CAC precludes the need for a dedicated gated CT assessment. However, qualitative methods are not as accurate or reproducible when performed by general radiologists. The implementation of AI in the LDCT screening process has the potential to give a quantifiable and reproducible numeric value to the calcium score, based on whole heart volume scoring of calcium. This more closely aligns with the Agatston score and serves as a better guide for treatment and risk assessment using current guidelines.We conclude that CAC should be assessed on all LDCT performed for lung cancer screening and that a qualitative categorical scoring system should be provided in the impression for each patient. Early studies involving AI for the assessment of CAC are promising, but more extensive studies are needed before a final recommendation for its use can be given. The implementation of an accurate, automated AI CAC assessment tool would improve radiologist compliance and ease of overall workflow. Ultimately, the potential end result would be improved turnaround time, better patient outcomes, and reduced healthcare costs by maximizing preventative care in this high-risk population.

Group A Streptococcus Testing in Pediatrics: the Move to Point-of-Care Molecular Testing.

Each year, there are an estimated 11 million visits to ambulatory care centers for pharyngitis in children between the ages of 3 and 18 years. While there are many causes of pediatric pharyngitis, group A streptococcal pharyngitis represents 15 to 30% of infections and is the only cause for which treatment is recommended. Unfortunately, clinical suspicion is insufficient for the accurate diagnosis of group A streptococcal pharyngitis, and laboratory testing for confirmation of Streptococcus pyogenes infection is required to prevent complications of infection. Traditionally, throat swabs are inoculated onto agar plates for isolation of the large-zone beta-hemolytic streptococcus. However, traditional culture methods present a potential delay in treatment due to turnaround times of 18 to 48 h. In order to improve turnaround times and enhance antimicrobial stewardship, multiple point-of-care assays have been developed. This review describes current point-of-care testing for group A streptococcal pharyngitis, including rapid antigen detection tests and more recent molecular methods. Additional attention is given to the diagnostic considerations when choosing a method for group A streptococcal point-of-care testing, implementation of molecular group A streptococcal testing, and the institutional cost of immunoassays compared to those of newer molecular methods.

Utility of circulating tumor DNA (ctDNA) versus tumor tissue genotyping for enrollment of patients with metastatic colorectal cancer (mCRC) to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA combined analysis.

4071 Background: We recently reported that ctDNA genotyping had advantages compared with tumor tissue testing in terms of enrollment to matched clinical trials across a wide range of GI cancers (Nakamura Y, et al. ASCO-GI 2020). Here, we investigated the utility of ctDNA genotyping in mCRC in a SCRUM-Japan GI-SCREEN and GOZILA combined analysis. Methods: In GI-SCREEN, tumor tissue genotyping was performed using a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay since Feb 2015. In GOZILA, NGS-based ctDNA genotyping was performed using Guardant360 since Feb 2018. All tests were conducted centrally in a CLIA-certified and CAP-accredited laboratory. Patients with actionable alterations were enrolled into matched company-sponsored or investigator-initiated interventional clinical trials. Results: As of Apr 2019, 2,791 mCRC patients (2,754 eligible for analysis) in GI-SCREEN and 470 (464 eligible for analysis) in GOZILA were enrolled. There were no significant differences in baseline patient characteristics between GI-SCREEN and GOZILA. Most of trials affiliated with GI-SCREEN (81%) or GOZILA (78%) targeted the RTK/RAS/RAF pathway. Compared with tumor testing, ctDNA genotyping significantly improved turnaround time (median, 12 vs. 34 days, P < 0.0001), sequencing success rate (96.1 vs. 92.3%, P = 0.002), and detection rate of actionable alterations (73.3 vs. 62.2%, P = 0.02). Among patients with actionable alterations, enrollment to matched clinical trials was achieved in 5.0% in GI-SCREEN and 12.1% in GOZILA ( P < 0.0001). Median time from enrollment in the respective screening study to enrollment in a matched clinical trial was 6.5 months in GI-SCREEN and 0.9 months in GOZILA, respectively ( P < 0.0001). Objective response rate and progression-free survival were similar in both groups (tissue vs. ctDNA; ORR: 18.8 vs. 17.1%, P = 1.00; median PFS: 2.2 vs. 2.2 months, HR=1.05 [95% CI, 0.71–1.55], P = 0.79). Conclusions: For patients with mCRC, ctDNA genotyping had advantages over tissue genotyping with shorter turnaround time and higher sequencing success and actionable alteration detection rate, which were associated with improved clinical trial enrollment without compromising the efficacy. Funding: SCRUM-Japan Funds. Clinical trial information: UMIN000029315 .

Architect i2000 SR has improved turnaround time for infectious disease serology testing over Vitros ECiQ

BackgroundVitros ECiQ and Architect i2000 SR are two automated instruments used to detect serology biomarkers of hepatitis A, B and C viruses, and HIV infections. We compared performance of the Architect to the Vitro EciQ after implementation at our institution. MethodsA retrospective review was performed to compare patient samples tested on the Vitros ECiQ or Architect for hepatitis and HIV serological assays. The positivity rate, frequency of equivocal results, turnaround times (TAT), and hands-on time (HOT) were analyzed. ResultsThere was no statistical difference in the positivity rate between the two instruments, with the exception of two assays. An increase in equivocal results was observed for the Architect (0.2% vs 0.5%). Notably, the TAT for the Architect i2000 was shorter for all except one assay (31.6 vs 33.7 hours) and demonstrated improved workflow. ConclusionsOverall, both instruments performed comparably. Architect had shorter TAT over Vitros.

Impact of BD Kiestra InoqulA streaking patterns on colony isolation and turnaround time of methicillin-resistant Staphylococcus aureus and carbapenem-resistant Enterobacterale surveillance samples

ObjectivesTo determine if using alternative streaking patterns on the BD Kiestra InoqulA can impact colony isolation and improve turnaround time (TAT) of methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacterales (CRE) screening samples. MethodsA total of 1571 positive MRSA screening samples were studied, of which 755 screening plates were streaked by the standard pattern (4-Quadrant uniform S200) and 816 plates were streaked by an alternative pattern (Zigzag 3.5–1 S200). A total of 424 CRE-positive screening samples were studied, of which 211 screening plates were streaked by the standard pattern (Zigzag 2.5–1 inoc S200) and 213 plates were streaked by an alternative customized pattern (Zigzag 3.5–1 vertstreak s200). ResultsThere was a reduction in the number of MRSA screening plates with insufficient isolated colonies for confirmatory testing from 75 plates (9.9%) when using the standard pattern to 18 plates (2.2%) when using the alternative streaking pattern. MRSA cases with a TAT above 36 hours also reduced significantly from 144 (19.1%) to 20 (2.4%). The number of CRE screening plates with insufficient colonies for same-day confirmatory testing reduced from 16 (7.6%) when using the standard pattern to two plates (1.1%) when using the alternative customized pattern. CRE cases with a TAT above 36 hours also reduced from 16 (7.6%) to seven (3.3%). ConclusionsThe change in streaking patterns resulted in more plates with sufficient isolated colonies as well as reduced man-hours and materials required to perform subculture of mixed colonies and overall improvements in TAT.