On-demand Testing Research Articles

Monitoring and Treatment of Paroxysmal Nocturnal Hemoglobinuria in Patients with Aplastic Anemia in Asia: An Expert Consensus.

Paroxysmal nocturnal hemoglobinuria (PNH) clones can be identified in a significant proportion of patients with aplastic anemia (AA). Screening for PNH clones at the time of an AA diagnosis is recommended by national and international guidelines. In this report, an expert panel of physicians discusses current best practices and provides recommendations for managing PNH in patients with AA in the Asia-Pacific region. Plasma/serum lactate dehydrogenase (LDH) levels and reticulocyte count should be measured with every blood test. PNH clone size should be monitored regularly by flow cytometry, with on-demand testing in the event of a rise in LDH level ± reticulocyte count or development of symptoms such as thrombosis. Monitoring for PNH clones can guide the choice of initial AA treatment, although flow cytometry has resource implications which may present a challenge in some Asia-Pacific countries. The treatment of patients with both PNH and AA depends on which condition predominates; following PNH treatment guidelines if hemolysis is the main symptom and AA treatment guidelines if bone marrow failure is severe (regardless of whether hemolysis is mild or moderate). The expert panel's recommendations on the monitoring and treatment of PNH in patients with AA are practical for healthcare systems in the Asia-Pacific region.

Evaluation of the rapid Quidel Sofia Lyme fluorescent immunoassay as a first-tier test in a modified 2-tier testing algorithm for Lyme disease: A comparison with the Zeus ELISA Borrelia VlsE1/pepC10 lgG/IgM assay followed by the Zeus monovalent IgM/IgG confirmatory assay.

Recently modified 2-tier testing (MTTT) algorithms using 2 enzyme immunoassays (EIAs) as opposed to an EIA followed by immunoblot have been approved by the US Food and Drug Administration (FDA) for the screening and confirmation of Lyme disease. The Quidel Sofia Lyme fluorescent immunoassay is a rapid lateral-flow method that can be performed in real time, permitting on-demand testing. We evaluated the performance of the Sofia assay as a first-tier test in an MTTT algorithm. We compared the Sofia Lyme test with the Zeus ELISA Borrelia VlsE1/pepC10 lgG/IgM test, followed by the Zeus monovalent IgM/IgG EIA as the confirmatory test. When used as a first-tier test compared with a standard Zeus MTTT assay, the positive percentage agreement was 91.4%% (95% CI, 77.6%-97.0%). The negative percentage agreement was 100% (95% CI, 94.0%-100%). The overall agreement was 98.3% (95% CI, 94.2%-99.4%). κ = 0.945, indicating "almost perfect agreement." The Sofia Lyme test performs well compared with an FDA-approved MTTT.

Utilization and Impact of Symptomatic and Exposure SARS-CoV-2 Testing in K-12 Schools.

The Centers for Disease Control and Prevention recommend that schools can offer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic (on-demand) testing for students and staff with coronavirus disease 2019 symptoms or exposures. Data related to the uptake, implementation, and effect of school-associated on-demand diagnostic testing have not been described. The Rapid Acceleration of Diagnostics Underserved Populations Return to School program provided resources to researchers to implement on-demand SARS-CoV-2 testing in schools. This study describes the strategies used and uptake among the different testing programs. Risk of positivity was compared for symptomatic and exposure testing during the δ and ο variant periods. We estimated the number of school absence days saved with school-based diagnostic testing. Of the 16 eligible programs, 7 provided school-based on-demand testing. The number of persons that participated in these testing programs is 8281, with 4134 (49.9%) receiving >1 test during the school year. Risk of positivity was higher for symptomatic testing compared with exposure testing and higher during the ο variant predominant period compared with the δ variant predominant period. Overall, access to testing saved an estimated 13 806 absent school days. School-based on-demand SARS-CoV-2 testing was used throughout the school year, and nearly half the participants accessed testing on more than 1 occasion. Future studies should work to understand participant preferences around school-based testing and how these strategies can be used both during and outside of pandemics.

Synthesis of an Anti-CD7 Recombinant Immunotoxin Based on PE24 in CHO and E. coli Cell-Free Systems.

Recombinant immunotoxins (RITs) are an effective class of agents for targeted therapy in cancer treatment. In this article, we demonstrate the straight-forward production and testing of an anti-CD7 RIT based on PE24 in a prokaryotic and a eukaryotic cell-free system. The prokaryotic cell-free system was derived from Escherichia coli BL21 StarTM (DE3) cells transformed with a plasmid encoding the chaperones groEL/groES. The eukaryotic cell-free system was prepared from Chinese hamster ovary (CHO) cells that leave intact endoplasmic reticulum-derived microsomes in the cell-free reaction mix from which the RIT was extracted. The investigated RIT was built by fusing an anti-CD7 single-chain variable fragment (scFv) with the toxin domain PE24, a shortened variant of Pseudomonas Exotoxin A. The RIT was produced in both cell-free systems and tested for antigen binding against CD7 and cell killing on CD7-positive Jurkat, HSB-2, and ALL-SIL cells. CD7-positive cells were effectively killed by the anti-CD7 scFv-PE24 RIT with an IC50 value of 15 pM to 40 pM for CHO and 42 pM to 156 pM for E. coli cell-free-produced RIT. CD7-negative Raji cells were unaffected by the RIT. Toxin and antibody domain alone did not show cytotoxic effects on either CD7-positive or CD7-negative cells. To our knowledge, this report describes the production of an active RIT in E. coli and CHO cell-free systems for the first time. We provide the proof-of-concept that cell-free protein synthesis allows for on-demand testing of antibody-toxin conjugate activity in a time-efficient workflow without cell lysis or purification required.

Feasibility of SARS-CoV-2 Surveillance Testing Among Children and Childcare Workers at German Day Care Centers

Closure of day care centers has been implemented globally to contain the COVID-19 pandemic but has negative effects on children's health and psychosocial well-being. To investigate the feasibility of surveillance among children and childcare workers and to model the efficacy of surveillance on viral spread prevention. This nonrandomized controlled trial was conducted at 9 day care centers in Wuerzburg, Germany, from October 2020 to March 2021. Participants included children attending day care, childcare workers, and household members. Participating day care centers were assigned to different surveillance modules in a nonrandomized feasibility study. A mathematical model for SARS-CoV-2 spread in day care centers was developed to identify optimal surveillance. Modules 1, 2, and 3 involved continuous surveillance of asymptomatic children and childcare workers by SARS-CoV-2 polymerase chain reaction testing of either midturbinate nasal swabs twice weekly (module 1) or once weekly (module 2) or self-sampled saliva samples twice weekly (module 3). Module 4 involved symptom-based, on-demand testing of children, childcare workers, and their household members by oropharyngeal swabs. All participants underwent SARS-CoV-2 antibody status testing before and after the sampling period. Questionnaires on attitudes and perception of the pandemic were administered in weeks 1, 6, and 12. Mathematical modeling was used to estimate SARS-CoV-2 spread in day care centers. The primary outcomes were acceptance of the respective surveillance protocols (feasibility study) and the estimated number of secondary infections (mathematical modeling). Of 954 eligible individuals (772 children and 182 childcare workers), 592 (62%), including 442 children (median [IQR] age, 3 [2-4] years; 214 [48.6%] female) and 150 childcare workers (median [IQR] age, 29 [25-44] years; 129 [90.8%] female) participated in the surveillance. In total, 4755 tests for SARS-CoV-2 detected 2 infections (1 childcare worker and 1 adult household member). Acceptance for continuous surveillance was highest for biweekly saliva testing (150 of 221 eligible individuals [67.9%; 95% CI, 61.5%-73.7%]) compared with biweekly (51 of 117 individuals [43.6%; 95% CI, 35.0%-52.6%]) and weekly (44 of 128 individuals [34.4%; 95% CI, 26.7%-43.0%]) midturbinate swabbing (P < .001). Dropout rates were higher for midturbinate swabbing (biweekly, 11 of 62 participants [18%]; once weekly, 11 of 55 participants [20%]) than for saliva testing (6 of 156 participants [4%]). Mathematical modeling based on study and literature data identified biweekly testing of at least 50% of children and childcare workers as minimal requirements to limit secondary infections. In this nonrandomized controlled trial, surveillance for SARS-CoV-2 in 9 German day care centers was feasible and well accepted. Mathematical modeling estimated that testing can minimize the spread of SARS-CoV-2 in day care centers. These findings enable setup of surveillance programs to maintain institutional childcare. German Registry for Clinical Trials Identifier: DRKS00023721.

Association of COVID-19 mortality with politics and on-demand testing in 217\u2009U.S. counties

BackgroundPrevious research found increased COVID-19 spread associated with politics and on-demand testing but not in the same study. The objective of this study is to estimate the contribution of each corrected for the other and a variety of known risk factors.MethodsUsing data from 217 U.S. counties of more than 50,000 population where testing data were available in April, 2021, the associations of COVID-19 deaths with politics, testing and other risk factors were examined by Poisson and least squares regression.ResultsStatistical controls for 15 risk factors failed to eliminate the association of COVID mortality risk with percent of vote for Donald Trump in 2016 or negative tests per population. Each is independently predictive of increased mortality.ConclusionApparently, many people who test negative for the SARS-CoV-2 virus engage in activities that increase their risk, a problem likely to increase with the availability of home tests. There is no association of negative tests with the Trump vote but, according to polling data, Trump voters’ past resistance to public health recommendations has been extended to resistance to being vaccinated, threatening the goal of herd immunity.

Verification of analytical bacterial spectrum of QIAstat-Dx® GI V2 and Novodiag® Bacterial GE+ V2-0 diagnostic panels.

BackgroundImplementing multiplex PCR or syndromic panel-based testing platforms to detect microbial species that cause acute diarrhoea may guide patient management more effectively and efficiently.ObjectivesTo assess and compare the performance of two syndromic panel-based testing systems, QIAstat-Dx® Gastrointestinal Panel V2 (QGI) and the Novodiag® Bacterial GE+ V2-0 (NGE).MethodsThe QGI and NGE panels include 16 and 14 bacterial gastrointestinal pathogens, respectively. The performance of the panels was tested retrospectively using 141 positive clinical stool specimens, External Quality Assessment (EQA) panels and spiked faecal specimens.ResultsFor Campylobacter jejuni and coli (n = 20), Salmonella (n = 24), Shigella (n = 13), Yersinia enterocolitica (non-1A biotypes) (n = 8), Clostridioides difficile (n = 24) and Vibrio parahaemolyticus (n = 2), QGI correctly verified 19/20, 20/24, 13/13, 8/8, 23/24 and 2/2, whereas NGE correctly verified 20/20, 17/24, 13/13, 8/8, 14/24 and 1/2. Among diarrhoeagenic Escherichia coli (n = 29), QGI reported one Shiga toxin-producing E. coli (STEC) stx1a O26:H11 as STEC serotype O157:H7 and NGE failed on one enteropathogenic E. coli, one enteroaggregative E. coli and one STEC (stx2e). Y. enterocolitica biotype 1A (non-pathogenic) (n = 6) were all positive in QGI, but negative in NGE.ConclusionsBoth QGI and NGE testing panels can improve laboratory workflow and patient management by providing user-friendly platforms that can rapidly detect a number of targets with one specimen. QGI was significantly more sensitive in identifying C. difficile. Both methods had suboptimal detection of Salmonella and this needs to be examined further. The short hands-on time and turnaround time are of value for on-demand testing and use in a high-throughput setting.

Evaluation of a Prototype of a Novel Galactomannan Sandwich Assay Using the VIDAS® Technology for the Diagnosis of Invasive Aspergillosis.

ObjectivesTo evaluate the analytical and clinical performance of a prototype of a VIDAS® Galactomannan (GM) unitary test (bioMérieux, Marcy l’Etoile, France) and compare to that of the Platelia™ Aspergillus Ag assay (Bio-Rad, CA, USA).MethodsRepeatability, reproducibility, and freeze-thaw stability of VIDAS®GM were evaluated. Sera from patients at risk of IA were concurrently tested with both the VIDAS®GM and Platelia™ Aspergillus Ag assays. Correlations between the two assays were assessed by Passing Bablok (PB) regression and performance by ROC analysis.ResultsThe correlations between the VIDAS®GM indexes after one and two cycles of freezing/thawing were r=1.00 and r=0.989, respectively. The coefficients of variation for negative, low-positive, and positive sera were 13%, 6%, and 5% for repeatability and 14.4%, 7.2%, and 5.5% for reproducibility. Overall, 126 sera were tested with both assays (44 fresh and 82 frozen). The correlation between VIDAS®GM and Platelia™ Aspergillus Ag was r=0.798. The areas under the curve of the ROC analyses were 0.892 and 0.894, for VIDAS®GM and Platelia™ Aspergillus Ag, respectively.ConclusionsThis new VIDAS®GM prototype assay showed adequate analytical and clinical performance and a good correlation with that of Platelia™ Aspergillus Ag with 126 sera, although these results need to be confirmed in a larger prospective and multicentric study. As for the other VIDAS® assays, VIDAS®GM is a single-sample automated test using a solid reagent strip and receptacle. It is easy to use and suitable for rapid on-demand test results.

Optogenetic manipulation of an ascending arousal system tunes cortical broadband gamma power and reveals functional deficits relevant to schizophrenia.

Increases in broadband cortical electroencephalogram (EEG) power in the gamma band (30–80 Hz) range have been observed in schizophrenia patients and in mouse models of schizophrenia. They are also seen in humans and animals treated with the psychotomimetic agent ketamine. However, the mechanisms which can result in increased broadband gamma power and the pathophysiological implications for cognition and behavior are poorly understood. Here we report that tonic optogenetic manipulation of an ascending arousal system bi-directionally tunes cortical broadband gamma power, allowing on-demand tests of the effect on cortical processing and behavior. Constant, low wattage optogenetic stimulation of basal forebrain (BF) neurons containing the calcium-binding protein parvalbumin (PV) increased broadband gamma frequency power, increased locomotor activity, and impaired novel object recognition. Concomitantly, task-associated gamma band oscillations induced by trains of auditory stimuli, or exposure to novel objects, were impaired, reminiscent of findings in schizophrenia patients. Conversely, tonic optogenetic inhibition of BF-PV neurons partially rescued the elevated broadband gamma power elicited by subanesthetic doses of ketamine. These results support the idea that increased cortical broadband gamma activity leads to impairments in cognition and behavior and identify BF-PV activity as a modulator of this activity. As such, BF-PV neurons may represent a novel target for pharmacotherapy in disorders such as schizophrenia which involve aberrant increases in cortical broadband gamma activity.

Current state and future directions of the National Board of Chiropractic Examiners

The objective of this paper is to describe changes made to chiropractic national board examinations in the United States, including methodologies in test scoring, and to discuss future directions in test development and administration being considered by the National Board of Chiropractic Examiners (NBCE). Additionally, this paper serves as an introduction to the articles written by the NBCE staff and published in this issue of the journal. Statistical perspective on the properties of a test are presented, and reasons for the NBCE moving to item response theory for test scoring are described. NBCE consideration of on-demand testing and changes implemented in the Part IV practical examination are also discussed.

The Natural History of Adrenal Insufficiency in X-Linked Adrenoleukodystrophy: An International Collaboration

Context: Primary adrenal insufficiency is an important clinical manifestation of X-linked adrenoleukodystrophy (ALD). Other manifestations include spinal cord disease and/or inflammatory demyelinating cerebral disease. Implementation of newborn screening requires natural history data to develop follow-up recommendations. Objective: To delineate the natural history of adrenal insufficiency in male patients with ALD and to assess associations between the risk for developing adrenal insufficiency, spinal cord disease, or cerebral disease and plasma C26:0/C22:0 and C24:0/C22:0 ratios, which are diagnostic biomarkers for ALD. Design: Retrospective review of medical records. Setting: Two international tertiary referral centers of expertise for ALD. Patients: Male patients with ALD followed at the centers between 2002 and 2016. Main Outcome Measures: The primary endpoint was adrenal insufficiency; secondary endpoints were spinal cord and cerebral disease. Results: Data on 159 male patients was available. The probability of developing adrenal insufficiency was described with survival analysis. Median time until adrenal insufficiency was 14 years (95% CI, 9.70 to 18.30 years). The cumulative proportion of patients who developed adrenal insufficiency was age-dependent and highest in early childhood [0 to 10 years, 46.8% (SEM 0.041%); 11 to 40 years, 28.6% (SEM, 0.037%); >40 years, 5.6% (SEM, 0.038%)]. No association between clinical manifestations and plasma ratios was detected with Cox model or Spearman correlation. Conclusions: Lifetime prevalence of adrenal insufficiency in male patients with ALD is ~80%. Adrenal insufficiency risk is time-dependent and warrants age-dependent follow-up. Besides ondemand testing if symptoms manifest, we suggest a minimum of adrenal testing every 4 to 6 months for patients age ≤10 years, annual testing for those age 11 to 40 years, and solely on-demand testing for those age >40 years.

Building On-Demand Test Forms in R

Automated Test Assembly (ATA) plays important role in test development, especially in large scale test administrations. However, there is a lack of tutorials showing how to solve ATA problems. This tutorial aims to show to how build on-demand test forms easily for researchers and practitioners, and share the R codes for their use. The study presents the annotated R codes for thirty-nine unique examples. The examples include building one form, multiple forms and more complex ones under different constraint conditions across equal or different form lengths. All examples were solved by using “xxIRT” R package. The graphical depictions of the form-level information functions for all examples were also provided. Some important notes about the codes were also provided at the end of the paper in case one did not find a solution. The thirty-six examples were provided in the main body of the paper, the other three complex examples were given in the Supplementary material.

A Comparison of Methods for Detecting Examinee Preknowledge of Items

In an on-demand testing program, some items are repeatedly used across test administrations. This poses a risk to test security. In this study, we considered a scenario wherein a test was divided into two subsets: one consisting of secure items and the other consisting of possibly compromised items. In a simulation study of multistage adaptive testing, we used three methods to detect item preknowledge: a predictive checking method (PCM), a likelihood ratio test (LRT), and an adapted Kullback–Leibler divergence (KLD-A) test. We manipulated four factors: the proportion of compromised items, the stage of adaptive testing at which preknowledge was present, item-parameter estimation error, and the information contained in secure items. The type I error results indicated that the LRT and PCM methods are favored over the KLD-A method because the KLD-A can experience large inflated type I error in many conditions. In regard to power, the LRT and PCM methods displayed a wide range of results, generally from 0.2 to 0.8, depending on the amount of preknowledge and the stage of adaptive testing at which the preknowledge was present.

The Natural History of Adrenal Insufficiency in X-Linked Adrenoleukodystrophy: An International Collaboration.

Primary adrenal insufficiency is an important clinical manifestation of X-linked adrenoleukodystrophy (ALD). Other manifestations include spinal cord disease and/or inflammatory demyelinating cerebral disease. Implementation of newborn screening requires natural history data to develop follow-up recommendations. To delineate the natural history of adrenal insufficiency in male patients with ALD and to assess associations between the risk for developing adrenal insufficiency, spinal cord disease, or cerebral disease and plasma C26:0/C22:0 and C24:0/C22:0 ratios, which are diagnostic biomarkers for ALD. Retrospective review of medical records. Two international tertiary referral centers of expertise for ALD. Male patients with ALD followed at the centers between 2002 and 2016. The primary endpoint was adrenal insufficiency; secondary endpoints were spinal cord and cerebral disease. Data on 159 male patients was available. The probability of developing adrenal insufficiency was described with survival analysis. Median time until adrenal insufficiency was 14 years (95% CI, 9.70 to 18.30 years). The cumulative proportion of patients who developed adrenal insufficiency was age-dependent and highest in early childhood [0 to 10 years, 46.8% (SEM 0.041%); 11 to 40 years, 28.6% (SEM, 0.037%); >40 years, 5.6% (SEM, 0.038%)]. No association between clinical manifestations and plasma ratios was detected with Cox model or Spearman correlation. Lifetime prevalence of adrenal insufficiency in male patients with ALD is ~80%. Adrenal insufficiency risk is time-dependent and warrants age-dependent follow-up. Besides on-demand testing if symptoms manifest, we suggest a minimum of adrenal testing every 4 to 6 months for patients age ≤10 years, annual testing for those age 11 to 40 years, and solely on-demand testing for those age >40 years.

Creating Parallel Forms to Support On-Demand Testing for Undergraduate Students in Psychology

On-demanding testing requires that multiple forms of an exam be administered to students in each testing session. But the use of multiple forms raises test security concern because of item exposure. One way to limit exposure is with parallel forms construction. Parallel forms are different versions of a test that measure the same content areas and have the same difficulty level but contain different sets of items. The purpose of our study is to describe and demonstrate how parallel forms can be created even from small test banks. We present three unique yet plausible test assembly problems. We also provide a solution for each problem using the results from a free, open-source, software add-in for Microsoft Excel called the Opensolver. Implications for test design and item development are discussed.

Rapid Molecular Panels: What Is in the Best Interest of the Patient? A Review of Patient Outcome Studies for Multiplex Panels Used in Bloodstream, Respiratory, and Neurological Infections

In the clinical microbiology laboratory, the focus when choosing new tests is often on performance, turnaround time, and labor needs. This review examines available rapid, multiplexed tests from a different perspective: that of the patient. It considers whether published evidence supports the notion that use of rapid, on-demand tests (as opposed to batched testing) leads to better patient outcomes and whether broad, syndrome-based, multiplexed panels translate into better patient care than narrower monoplex or duplex assays. Finally, we examine how synergy between the clinical microbiology and antimicrobial stewardship programs is necessary to ensure that rapid tests, if implemented, impact the patients they are designed to support.

Abstract LB-046: Evaluation of an assay for on-demand and easy assessment of MGMT gene promoter methylation in glioblastoma patients

Abstract Background: Epigenetic silencing of the O6-methylguanine DNA methyltransferase (MGMT) gene by promoter methylation is observed in 40 to 50% of glioblastomas and is associated with improved overall survival on radiation and/or temozolamide therapy. Currently, pyrosequencing is commonly used to assess the methylation status of the MGMT gene in formalin-fixed, paraffin-embedded (FFPE) samples. We examined the concordance of the recently developed GeneXpert (GX) MGMT Methylation RUO Assay with pyrosequencing in three independent glioblastoma cohorts. Patients and methods: The GX MGMT Methylation RUO Assay is a research use only, cartridge-based methylation specific PCR assay performed on the GeneXpert® Instrument (Cepheid) that automates DNA purification, bisulfite conversion, and methylation-specific PCR after sample preparation. Cartridge results are reported in less than 4 hours as delta cycle threshold (dCt) measurements (dCt = beta-actin/ACTB Ct - MGMT Ct). The MGMT methylation status was assessed on FFPE tumor blocks from 262 glioblastoma patients obtained from OHSU (n=63), MUV (n=96), and KUL (n=103). Two adjacent sections from each block were prepared, one 4 µm section for H&amp;E staining to determine the % tumor cell content/tumor area and one 4 µm section for lysate preparation and GX testing. Both GX MGMT Methylation testing and pyrosequencing results were correlated with overall survival of the patients in the MUV cohort. Results: All of the 262 (100%) glioblastoma samples tested yielded valid results for both GX MGMT Methylation testing and pyrosequencing. The cut-offs were set at dCt -6.2 for the GX MGMT Methylation RUO Assay and 8% methylation for pyrosequencing. The concordance rate between GX MGMT Methylation testing and pyrosequencing was 92% (58/63 OHSU samples, 92% (88/96 MUV samples) and 83% (85/103 KUL samples). The overall concordance rate was 88% (231/262 samples). Sensitivity and specificity was 84% (27/32) and 100% (31/31) for OHSU samples, 89% (33/37) and 93% (55/59) for MUV samples, and 70% (31/44/) and 92% (54/59) for KUL samples, respectively. Overall sensitivity was 81% (91/113) and overall specificity was 94% (140/149). Overall survival data were available for 95 MUV patients. Patients with MGMT promoter hypermethylation based on pyrosequencing had a significantly longer overall survival compared to patients without hypermethylation (median 16 vs. 11 months, p = 0.001). Similar results were observed with the GX MGMT Methylation RUO Assay (median 15 vs. 11 months, p = 0.005). Conclusion: GX MGMT Methylation testing is highly reproducible and shows good concordance with pyrosequencing in three independent cohorts of glioblastoma patients. Our results suggest that standardized, simplified, and on-demand testing of MGMT promoter methylation by the GX MGMT Methylation RUO Assay is feasible. Citation Format: Martin Filipits, Anita Brandstetter, Matthias Preusser, Johannes Hainfellner, Sabine Spiegl-Kreinecker, Edwin W. Lai, Kriszten Kocmond, Andrew Kohlway, Jodi Weidler, Michael Bates, Christopher Corless. Evaluation of an assay for on-demand and easy assessment of MGMT gene promoter methylation in glioblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-046. doi:10.1158/1538-7445.AM2017-LB-046

Assessing the clinical and cost impact of on-demand immunoassay testing for the diagnosis of heparin induced thrombocytopenia

BackgroundThe diagnostic work-up for heparin induced thrombocytopenia (HIT) can take several days. Consequently patients may be speculatively switched onto replacement anticoagulant therapy before a diagnosis is confirmed. On-demand immunoassay diagnostic testing enables timely treatment decisions, based on test results. ObjectiveTo estimate the clinical and cost impact of the use of on-demand versus batched diagnostic tests for HIT. MethodsLiterature was reviewed to identify test performance, clinical and cost data. Semi-structured interviews (n=4) and a survey (n=90) provided insights into current practice and challenges. Flow diagram models were developed to estimate the potential impact of on-demand testing. ResultsModelling estimated more HIT-related outcomes for patients maintained on heparin whilst awaiting test results and patients switched onto replacement anticoagulant therapy awaiting test results, compared with on-demand testing and treatment based on the results. The budget impact model estimated that on-demand testing reduced replacement anticoagulant therapy costs from $39,616 to $12,799 per patient. There are limitations to the data available to inform modelling and the estimates should be treated with caution. ConclusionsUsing on-demand testing may drive positive effects on clinical and cost outcomes.

Assessing The Clinical And Economic Impact Of An Automated, On-Demand Immunoassay For The Diagnosis Of Heparin Induced Thrombocytopenia

To understand and quantify the clinical and economic impact of an automated, on-demand diagnostic test versus current diagnostic tests, for heparin-induced thrombocytopenia (HIT). A mixed methods study combining a literature review with primary research. The literature review searched multiple databases to identify data on test performance, clinical and economic data. Semi-structured interviews (n=4) provided insight into current practice and challenges faced, validated by a larger survey (n=90). Two flow diagrams modelling a hypothetical cohort of 1000 patients were used to calculate the clinical and cost impact of automated, on-demand testing. The automated, on-demand test had comparable or lower sensitivity, and a higher specificity than other available tests. Clinical data and survey findings indicate that the specificity of the most widely used antibody tests (ELISA) is suboptimal. The survey revealed that half of patients are speculatively switched off of heparin and onto replacement therapy based on clinical assessment alone, rather than based on clinical assessment and diagnostic test results as per guideline recommendations. Speculative treatment is driven by test turnaround time of >24 hours for >50% of respondents. The cost model indicated that the cost of replacement therapy whilst awaiting tests results of >24 hours’ turnaround time was between $7215 and $31268. Automated, on-demand antibody testing and switching patients off heparin based on test results reduced this cost to between $2737 and $13092. Automated, on-demand HIT antibody testing could enable physicians to use timely diagnostic test results with better specificity than current tests to make treatment decisions. This could potentially enable earlier treatment of HIT to reduce complications such as extended hospitalisation and death, thus improving clinical outcomes and reducing costs. Also, earlier informed treatment decisions could yield pathway cost reductions through reducing the use of replacement therapies in non-confirmed and false positive cases.

Benefits of Rapid Molecular Diagnosis of Chlamydia Trachomatis and Neisseria Gonorrhoeae Infections in Women Attending Family Planning Clinics

We evaluated the benefits of on-demand systematic screening for Chlamydia trachomatis and Neisseria gonorrhoeae using the Xpert CT/NG assay in 589 women attending family planning clinics. The sexually transmitted infection prevalence was 16.5% with 15.1% C. trachomatis and 3.1% N. gonorrhoeae infections. The on-demand test allowed for a quicker management of patients at high risk for sexually transmitted infections.