False-positive Test Results Research Articles

Value of soluble fms-like tyrosine kinase-1/placental growth factor test in third trimester of pregnancy for predicting preeclampsia in asymptomatic women.

To estimate the value of screening maternal serum soluble fms-like tyrosine kinase/placental growth factor (sFlt-1/PlGF) ratio in asymptomatic women during 3rd trimester to predict preeclampsia (PE) development. The investigated group comprised of 178 pregnant women. During this gestation, 24 cases had developed PE and 12 isolated gestational hypertension (GH); whereas 142 remained normotensive. Blood samples were collected between 180 and 259 gestational days (g.d.) when the participants were asymptomatic. Serums were analyzed using the BRAHMS sFlt-1 Kryptor/BRAHMS PlGF plus Kryptor PE ratio test (Thermo Fisher Scientific, Henningdorf, Germany). High-risk pregnancies for the PE development were defined as sFlt-1/PlGF>38. The detection rate (DR) for manifestation of PE≤30days after sampling was 83.3% and overall DR during pregnancy 58.3%. Ten of 15 women having false positive prediction of PE suffered from GH, preterm birth and/or delivery of a small-for-gestational-age-newborn. False positive rate was significantly higher at 239-253 g.d. compared to sampling at 210-224 g.d. and 225-238 g.d. (21.9% vs. 7.8% and 5.3%; p < 0.05). The sFlt-1/PlGF test during 180-259 g.d. detected approximately half of subsequent PE cases. An optimal time to use the test for screening purposes was estimated 225-238 g.d. (DR 66.7%). False positive test results were more common to cases with other adverse pregnancy outcomes and samples drawn at higher gestational age.

Convalescent serum-derived exosomes: Attractive niche as COVID-19 diagnostic tool and vehicle for mRNA delivery.

The spread of SARS-CoV-2 over the entire world is more commonly known as COVID-19. COVID-19 has impacted society in every aspect of routine life. SARS-CoV-2 infection is often misdiagnosed as influenza or seasonal upper respiratory tract viral infections. General diagnostic tools can detect the viral antigen or isotypes of antibodies. However, inter- and intraindividual variations in antibody levels can cause false negatives in antibody immunoassays. On the contrary, the false-positive test results can also occur due to either cross-reactivity of the viral antigens or some other patient-related autoimmune factors. There is need for a cogent diagnostic tool with more specificity, selectivity, and reliability. Here, we have described the potential of convalescent serum-derived exosome as a diagnostic tool for the detection of SARS-CoV-2, even in asymptomatic patients, which is a limitation for currently practiced diagnostic tests throughout the globe. In addition, its potential as a vehicle for messenger RNA (mRNA) delivery is also emphasized.

A serology conundrum – HIV infection in acute babesiosis infection could merely be a false positive result

Babesiosis is a tick-borne disease caused by Babesia microti. We present a case of false positive HIV in the setting of confirmed babesiosis infection. An understanding that patients with babesiosis can have a false positive HIV test result is important in management decisions.

Case Series of False-Positive HIV Test Results in Pediatric Acute Lymphoblastic Leukemia Patients Following Chimeric Antigen Receptor T-Cell Therapy: Guidance on How to Avoid and Resolve Diagnostic Dilemmas.

Chimeric antigen receptor T-cell (CAR-T) Cell Therapy is approved for the treatment of pediatric patients with relapsed/refractory acute lymphoblastic leukemia B-ALL. Lentiviral vector technology, highly modified from HIV-1, is used to induce stable, long-term transgene expression by integration into the host genome. This integration may interfere with HIV-1 NAAT producing false-positive results. Guidance for HIV diagnostic testing in pediatric B-ALL undergoing this type of therapy is lacking. Herein, we report case series with presented scenarios in which HIV-1 NAAT testing among CAR-T cell patients produced false-positive results, highlighting the importance careful assay selection and performance among this patient population.

MP11-03 FALSE POSITIVE PREGNANCY TESTS AMONG PEDIATRIC PATIENTS WITH AUGMENTATION ENTEROCYSTOPLASTIES

You have accessJournal of UrologyCME1 May 2022MP11-03 FALSE POSITIVE PREGNANCY TESTS AMONG PEDIATRIC PATIENTS WITH AUGMENTATION ENTEROCYSTOPLASTIES Zoë Baker, Arthi Hannallah, Hannah Dillon, Yuding Wang, and Evalynn Vasquez Zoë BakerZoë Baker More articles by this author , Arthi HannallahArthi Hannallah More articles by this author , Hannah DillonHannah Dillon More articles by this author , Yuding WangYuding Wang More articles by this author , and Evalynn VasquezEvalynn Vasquez More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002533.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A high number of false positive pregnancy test results have been self-reported among patients with augmentation enterocystoplasties using over-the-counter (OTC) urine pregnancy tests. We sought to determine the accuracy of OTC pregnancy tests among pediatric patients who had previously undergone augmentation enterocystoplasties. METHODS: Patients at a tertiary care pediatric hospital who had previously undergone augmentation enterocystoplasties or Mitrofanoff appendicovesicostomies only were prospectively recruited. Urine samples were obtained and two OTC pregnancy tests, one point of care testing (POCT) urine pregnancy test, and urinalysis (UA) were completed. All pregnancy tests qualitatively assessed human chorionic gonadotropin (hCG). OTC Test A was a sandwich immunoassay employing monoclonal anti-β-hCG, goat anti-rabbit, anti-α-hCG, and rabbit Immunoglobulin G (IgG) antibodies and using chromatography to separate bound and free colored label. OTC Test B was a lateral flow immunoassay dipstick containing mouse monoclonal anti-β-hCG antibody colloidal gold conjugate pre-dried on a pad, mouse monocolonal anti-α-hCG antibodies, and goat anti-mouse IgG. The POCT test employed mouse monoclonal anti-hCG antibodies and goat polyclonal anti-hCG antibodies. RESULTS: Among 14 pediatric patients who had undergone augmentation cystoplasty, 12 (85.7%) had positive pregnancy test results on OTC Test A, including all 9 females and 60% of males (n = 3/5; Table 1). No patients had positive pregnancy test results on OTC Test B or the POCT pregnancy test (Table 1). No false positive OTC pregnancy test results occurred among 4 patients with Mitrofanoff appendicovesicostomies only. Among patients with enterocystoplasties, UA results indicated that the majority had at least trace levels of protein, blood, and leukocytes, most tested positive for nitrite, and mean urine pH was 6.7 (±0.5; Table 1). CONCLUSIONS: Preliminary findings indicate that certain OTC pregnancy tests qualitatively assessing hCG in urine may be inaccurate among patients who have previously undergone augmentation enterocystoplasties. Female patients of reproductive age should be counseled regarding appropriate pregnancy testing options to avoid unplanned pregnancy scares or concerns about ectopic pregnancies. Source of Funding: The Long Road Foundation © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e157 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Zoë Baker More articles by this author Arthi Hannallah More articles by this author Hannah Dillon More articles by this author Yuding Wang More articles by this author Evalynn Vasquez More articles by this author Expand All Advertisement PDF DownloadLoading ...

PRAME Expression Correlates With Genomic Aberration and Malignant Diagnosis of Spitzoid Melanocytic Neoplasms.

Spitzoid melanocytic neoplasms are a diagnostically challenging class of lesions in dermatopathology. Recently, molecular assays and immunohistochemical markers have been explored as ancillary methods to assist in the diagnostic workup. Specifically, preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is a nuclear stain commonly positive in melanomas, but not in nevi. This study investigates PRAME immunoreactivity (≥75% positive nuclear staining in tumor cells) in a set of 59 spitzoid melanocytic neoplasms with known clinical outcomes. We compared PRAME status with (1) the clinical outcomes, (2) the morphologic diagnoses, and (3) the status of TERT promoter mutation. Regarding clinical outcomes, 3 cases developed metastatic disease, of which 2 expressed diffusely positive PRAME staining. Of the 56 cases that did not show evidence of metastasis, 6 expressed diffusely positive PRAME staining. Morphologically, diffusely positive PRAME staining was seen in 7 of 21 cases (33.3%) diagnosed as melanoma and only 1 benign tumor 1 of 38 (2.6%). There were 4 of 8 cases with a TERT promoter mutation which were diffusely PRAME-positive compared with 4 of 51 cases without TERT promoter mutation ( P = 0.001). Our results show a statistically significant correlation between PRAME expression and the diagnosis, outcome, and TERT promoter mutation status of atypical spitzoid melanocytic neoplasms, suggesting immunohistochemistry for PRAME can help support a suspected diagnosis. However, because of occasional false-positive and negative test results, correlation with the clinical and histologic findings as well as results from other tests is needed for the interpretation of diagnostically challenging spitzoid melanocytic neoplasms.

The CCAS-scale in hereditary ataxias: helpful on the group level, particularly in SCA3, but limited in individual patients

BackgroundA brief bedside test has recently been introduced by Hoche et al. (Brain, 2018) to screen for the Cerebellar Cognitive Affective Syndrome (CCAS) in patients with cerebellar disease.ObjectiveThis multicenter study tested the ability of the CCAS-Scale to diagnose CCAS in individual patients with common forms of hereditary ataxia.MethodsA German version of the CCAS-Scale was applied in 30 SCA3, 14 SCA6 and 20 FRDA patients, and 64 healthy participants matched for age, sex, and level of education. Based on original cut-off values, the number of failed test items was assessed, and CCAS was considered possible (one failed item), probable (two failed items) or definite (three failed items). In addition a total sum raw score was calculated.ResultsOn a group level, failed items were significantly higher and total sum scores were significantly lower in SCA3 patients compared to matched controls. SCA6 and FRDA patients performed numerically below controls, but respective group differences failed to reach significance. The ability of the CCAS-Scale to diagnose CCAS in individual patients was limited to severe cases failing three or more items. Milder cases failing one or two items showed a great overlap with the performance of controls exhibiting a substantial number of false-positive test results. The word fluency test items differentiated best between patients and controls.ConclusionsAs a group, SCA3 patients performed below the level of SCA6 and FRDA patients, possibly reflecting additional cerebral involvement. Moreover, the application of the CCAS-Scale in its present form results in a high number of false-positive test results, that is identifying controls as patients, reducing its usefulness as a screening tool for CCAS in individual patients.

Patient-reported outcomes associated with cancer screening: a systematic review

BackgroundMulti-cancer early detection tests have been developed to enable earlier detection of multiple cancer types through screening. As reflected by patient-reported outcomes (PROs), the psychosocial impact of cancer screening is not yet clear. Our aim is to evaluate the impact of cancer screening through PRO assessment.MethodsA systematic review was conducted using MEDLINE, EMBASE, and reference lists of articles from January 2000 to August 2020 for relevant publications assessing the psychosocial impact of cancer screening before and within 1 year after screening in the general asymptomatic population, including following receipt of results. Studies focused on diagnostic evaluation or involving patients previously diagnosed with cancer were excluded.ResultsIn total, 31 studies (12 randomized controlled trials; 19 observational studies) were included, reflecting PRO assessments associated with lung, breast, colorectal, anal, ovarian, cervical, and prostate cancer screening procedures. The most commonly assessed construct was symptoms of anxiety, using the State-Trait Anxiety Inventory. Cancer-specific distress and worry were also assessed using a broad range of measures. Overall, individuals tolerated screening procedures well with no major psychosocial effects. Of note, increases in symptoms of anxiety and levels of distress and worry were generally found prior to communication of screening results and following communication of indeterminate or positive results that required further testing. These negative psychosocial effects were, however, not long-lasting and returned to baseline relatively soon after screening. Furthermore, individuals with higher cancer risk, such as current smokers and those with a family history of cancer, tended to have higher levels of anxiety and distress throughout the screening process, including following negative or indeterminate results.ConclusionsThe psychosocial impact of cancer screening is relatively low overall and short-lived, even following false-positive test results. Individuals with a higher risk of cancer tend to experience more symptoms of anxiety and distress during the screening process; thus, more attention to this group is recommended.

Amenorrhea and pituitary human chorionic gonadotrophin production in a 38-year-old presenting as pregnancy of unknown location: case report and review of literature

Background: Amenorrhea and extraplacental production of serum human chorionic gonadotropin (hCG), particularly in young women, can mimic a pregnancy of unknown location. Elevated serum hCG in the absence of pregnancy can pose a diagnostic dilemma and has led to potentially harmful and unwarranted interventions including chemotherapeutic agents like methotrexate or have led to delay in necessary medical interventions in women. We report a case to demonstrate that amenorrhea and extraplacental human chorionic gonadotropin (hCG) production in young women can mimic a pregnancy of unknown location. Furthermore, we performed a critical review of literature on pituitary hCG production. Case: A 38-year-old woman with a diagnosis of Silver-Russell syndrome, a unicornuate uterus, history of right oophorectomy for a benign serous cystadenoma and a desire for pregnancy presenting with a provisional diagnosis of pregnancy of unknown location.After performing a thorough review of history, physical examination, ultrasound exams, and a review of hormone analysis [including hCG, Tumor markers, Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Anti-Mullerian Hormone (AMH), Estradiol (E2) levels], we confirmed the diagnosis of premature ovarian insufficiency and pituitary hCG production. Conclusions: In women, serum levels of hCG may increase with age, and are not always an indicator of pregnancy. Therefore, it is imperative to interpret false-positive test results and rule out the extraplacental production of hCG. This will help prevent unnecessary surgical procedures and treatment, including chemotherapy.

Analysis of the characteristics of patients with false-positive HIV screening assay results

ObjectiveTo investigate the clinical characteristics of patients with false-positive human immunodeficiency virus (HIV) screening test results and provide a theoretical basis to interpret the results of HIV screening tests. MethodsThis retrospective study evaluated the incidence of false-positive results for HIV screening tests and characterized false-positive reactions during HIV screening in a large-scale study at Zhongshan Hospital, Xiamen University. ResultsFalse-positive HIV test results occurred for 264 of 275,263 (0.10%) serum samples. Although the incidence of a false-positive HIV screening result did not differ between male and female patients (screening χ2 = 1.194; P = 0.275), it increased with age (χ2 = 25.759; P < 0.01). False-positive reactions were associated with 16 disease categories, including 101 diseases, some of which have never been reported previously to be associated with false-positive HIV screening results. ConclusionsThe occurrence of false-positive HIV screening test results may indicate underlying serious disorders. Characterization of patients with false-positive HIV screening test results can help identify potential diseases unrelated to HIV.

Analysis of nucleic acids extracted from rapid diagnostic tests reveals a significant proportion of false positive test results associated with recent malaria treatment

BackgroundSurveillance programmes often use malaria rapid diagnostic tests (RDTs) to determine the proportion of the population carrying parasites in their peripheral blood to assess the malaria transmission intensity. Despite an increasing number of reports on false-negative and false-positive RDT results, there is a lack of systematic quality control activities for RDTs deployed in malaria surveillance programmes.MethodsThe diagnostic performance of field-deployed RDTs used for malaria surveys was assessed by retrospective molecular analysis of the blood retained on the tests.ResultsOf the 2865 RDTs that were collected in 2018 on Bioko Island and analysed in this study, 4.7% had a false-negative result. These false-negative RDTs were associated with low parasite density infections. In 16.6% of analysed samples, masked pfhrp2 and pfhrp3 gene deletions were identified, in which at least one Plasmodium falciparum strain carried a gene deletion. Among all positive RDTs analysed, 28.4% were tested negative by qPCR and therefore considered to be false-positive. Analysing the questionnaire data collected from the participants, this high proportion of false-positive RDTs could be explained by P. falciparum histidine rich protein 2 (PfHRP2) antigen persistence after recent malaria treatment.ConclusionMalaria surveillance depending solely on RDTs needs well-integrated quality control procedures to assess the extent and impact of reduced sensitivity and specificity of RDTs on malaria control programmes.

Suitability of Different Diagnostic Platforms for Virological Testing of Blood Samples from Cornea Donors

Background: To minimize the risk of disease transmission in cornea transplantation, donor screening for blood-derived viral infections is mandatory. Ideally, pre-mortem blood samples are used, but based on availability, cadaveric blood samples of cornea donors may also be used. However, serological and nucleic acid amplification tests (NATs) need to be validated for the use of cadaveric specimens. Methods: Hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) 1/2, and Treponema pallidum (syphilis)-specific serological and/or NAT assays were validated on different platforms (Abbott Alinity i, Alinity m, Roche Cobas 6800, and Roche Cobas AmpliPrep/Cobas TaqMan (CAP/CTM)) using (un)spiked paired pre- and post-mortem cornea donor blood samples from the same individual (up to 23.83 h after death) of 28 individuals in accordance with the specifications of the German Federal Institute for Vaccines and Biomedicines (Paul-Ehrlich-Institut [PEI]). In addition, routinely HBV-, HCV- and HIV-PCR-negative tested post-mortem blood samples of 24 individuals were used to assess NAT specificity. Results: For the majority of serological parameters on the Abbott Alinity i (HBsAg, anti-HBc, anti-HBs, anti-HCV, anti-HIV, anti-HTLV 1/2, and anti-Treponema pallidum), ratios of generated test results of (un)spiked paired pre- and post-mortem blood samples differed ≤25%, with an agreement of qualitative pre- and post-mortem test results ranging from 91.2 to 100%. For NAT parameters (HBV, HCV, and HIV) on the Cobas 6800, Alinity m, and CAP/CTM, no significant deviation in virus concentrations (factor >5) of spiked pre- and post-mortem blood samples could be observed. Ct-values of corresponding internal controls did also not differ significantly (>1.5 Ct-values). In addition, no false-positive test results were generated when specificity was assessed. Conclusion: Overall, fluctuations of test results for serological and NAT parameters in pre- and post-mortem blood samples examined in this study, were only limited and within the range of what is also observed when routinely testing fresh patient specimens. We conclude that all examined assays are eligible for the screening of blood samples taken up to about 24 h after the occurrence of death.

Budget impact of the Oncotype DX® test compared to other gene expression tests in patients with early breast cancer in Germany

PurposeGene expression tests can inform decisions on whether to recommend chemotherapy for patients with HR+, HER2- early breast cancer. The goal of this analysis was to compare treatment costs by an expanded budget impact model of reimbursed gene expression tests in Germany. MethodsA cost comparison was constructed as an expanded budget impact model to calculate average total costs per patient covered by public health insurance. Based on the strong clinical evidence from the prospective randomized controlled trial TAILORx including more than 10,000 patients with HR+ and node negative breast cancer, the assumption was made that the Oncotype DX® test accurately predicts chemotherapy benefit and clinical outcomes. For the further reimbursed tests (EndoPredict®, MammaPrint®, Prosigna®), results from comparative studies – aligned with prognosis studies – as analyzed in IQWiG Rapid Report D19–01 were applied. ResultsThe use of the Oncotype DX test led to estimated average savings per patient of 2,500 € vs. EndoPredict, 1,936 € vs. MammaPrint, and 649 € vs. Prosigna. Savings were achieved by reduction of unnecessary chemotherapy use, a consequence of false-positive test results (EndoPredict 73%, MammaPrint 42%, Prosigna 20%). False-negative test results (EndoPredict 5%, MammaPrint 22%, Prosigna 49%) reduced necessary chemotherapies, which initially results in cost savings, but may lead to increased long-term costs associated with management of progressive disease. ConclusionThe results from this model suggest that the use of the Oncotype DX test reduces the cost of health care in Germany making it the most cost effective test compared to the further tests.

The role of first-trimester ultrasound screening for women with positive noninvasive prenatal testing results.

This study aimed to assess the utility of ultrasound screening for pregnancies with positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. We performed a retrospective analysis of positive noninvasive prenatal testing results and first-trimester ultrasound screening at our department between 2013 and 2019. Invasive genetic testing was performed if the patient had positive noninvasive prenatal testing results. Fetal ultrasound and cytogenetic data were collected. Noninvasive prenatal testing was performed in the women for advanced maternal age, nuchal translucency thickness, or history of abnormality in the previous child or relative. Forty-one pregnant women had positive noninvasive prenatal testing results for trisomy 21, trisomy 18, and trisomy 13. Twenty-three women had positive results for trisomy 21, 13 had positive results for trisomy 18, and 5 had positive results for trisomy 13 at 11 to 14 weeks of gestation. The positive predictive value of noninvasive prenatal testing was 100% for trisomy 21, 84.6% for trisomy 18, and 100% for trisomy 13. The positive predictive value of positive noninvasive prenatal testing results and fetal morphological abnormalities was 100% for trisomy 21, trisomy 18, and trisomy 13. Combining an ultrasound examination with noninvasive prenatal testing resulted in a higher positive predictive value for trisomy 18. Normal ultrasound examination results can help alleviate stress caused by false-positive noninvasive prenatal testing results. In contrast, the positive predictive value and negative predictive value for trisomy 21 were not altered by adding an ultrasound examination to noninvasive prenatal testing.

Evolving Interpretation of Screening and Diagnostic Tests in Allergy

Diagnostic tests for allergy usually are performed to confirm a diagnosis of an allergic disease. If a food allergy suspected, a test can help to determine whether it is present, to monitor its activity over time, and to determine whether the allergy is resolving. In this way, tests are used for diagnosis, monitoring, screening, and prognosis. There are 2 schools of thought for using tests: Frequentist and Bayesian approaches. The Frequentist approach defines probability in terms of the frequency of an event if it were to be repeated numerous times and uses parameters such as sensitivity, specificity, and predictive values to make a diagnosis. In contrast, the Bayesian approach defines probability as the degree of belief or disbelief regarding the diagnosis and asserts that only data are real and that test parameters are to be inferred from the data. There are strengths and limitations to each approach; however, the Bayesian approach provides an algorithm leading to a disease probability. To use the Bayesian approach, test results need to be expressed as a likelihood ratio. This helps to determine how much the result of a test changes the probability of a particular diagnosis. Once a probability of disease is determined, decision thresholds need to be defined so that a treatment decision can be made. Using this Bayesian approach, the concept of a false-positive or false-negative test result becomes obsolete.

Mexiletine and False Positive Urine Drug Screen for Amphetamine: A Case Review

Advanced heart failure patients commonly suffer from ventricular arrhythmias which can be managed by antiarrhythmic drugs like mexiletine. These ventricular arrhythmias can be complicated by illicit drug use which alter outcomes and can potentially impact the patient-physician relationship through countertransference. However, mexiletine can lead to false positive urine drug screen testing for amphetamine, and these false-positive urine drug screen test results can affect the decision-making process. Health care providers should be aware of this fact and should either use confirmatory testing or look for confounding compounds in patients who deny using illicit substances and have a positive urine drug screen. Our patient is 64 years old who arrived at the emergency department after experiencing a shock by his intracardiac defibrillator. The patient tested positive for amphetamine on his urine drug screen and was later ruled out by confirmatory quantitative testing.

A Membrane-Modulated Centrifugal Microdevice for Enzyme-Linked Immunosorbent Assay-Based Detection of Illicit and Misused Drugs.

Increased opioid use and misuse have imposed large analytical demands across clinical and forensic sectors. Due to the absence of affordable, accurate, and simple on-site tests (e.g., point of interdiction and bedside), analysis is primarily conducted in centralized laboratories via time-consuming, labor-intensive methods. Many healthcare facilities do not have such analytical capabilities and must send samples to commercial laboratories, increasing turnaround time and care costs, as well as delaying public health warnings regarding the emergence of specific substances. Enzyme-linked immunosorbent assays (ELISAs) are used ubiquitously, despite lengthy workflows that require substantial manual intervention. Faster, reliable analytics are desperately needed to mitigate the mortality and morbidity associated with the current substance use epidemic. We describe one such alternative─a portable centrifugal microfluidic ELISA system that supplants repetitive pipetting with rotationally controlled fluidics. Embedded cellulosic membranes act as microvalves, permitting flow only when centrifugally generated hydraulic pressure exceeds their liquid entry pressure. These features enable stepwise reagent introduction, incubation, and removal simply by tuning rotational frequency. We demonstrate the success of this platform through sensitive, specific colorimetric detection of opiates, a subclass of opioids naturally derived from the opium poppy. Objective image analysis eliminated subjectivity in human color perception and permitted reliable detection of opiates in buffer and artificial urine at the ng/μL range. Opiates were clearly differentiated from other drug classes without interference from common adulterants known to cause false positive results in current colorimetric field tests. Eight samples were simultaneously analyzed in under 1 h, a marked reduction from the traditional multiday timeline. This approach could permit rapid, automatable ELISA-based drug detection outside of traditional laboratories by nontechnical personnel.

Deleting Unreported Innovation

AbstractThe absence of observable innovation data for a firm often leads us to exclude or classify these firms as non-innovators. We assess the reliability of six methods for dealing with unreported innovation using several different counterfactuals for firms without reported R&amp;D or patents. These tests reveal that excluding firms without observable innovation or imputing them as zero innovators and including a dummy variable can lead to biased parameter estimates for observed innovation and other explanatory variables. Excluding firms without patents is especially problematic, leading to false-positive results in empirical tests. Our tests suggest using multiple imputation to handle unreported innovation.

Diagnostics to support elimination of lymphatic filariasis-Development of two target product profiles.

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools.

Qualitative Evaluation of Causes for Routine Salmonella Monitoring False-Positive Test Results in Dutch Poultry Breeding Flocks.

The Salmonella monitoring program, as outlined in the EU Commission regulation 200/2010, asks for repeated sampling in order to ascertain progress in achievement of the EU target. According to Article 2.2.2.2.c of this regulation, the competent authority may decide to do a resample and retest when it has reasons to question the results of initial testing. In the Netherlands, the competent authorities have been resampling and retesting all initial positive samplings for several years because of doubts about false positive initial test results. An analysis of population data in the period 2015–2019 indicates that 48% of initial samplings at the farm were classified as false positive after resampling and retesting by the competent authorities. A qualitative analysis, assessing factors that could be associated with the occurrence of false positives, indicates that cross-contamination during the sampling process by the poultry farmer is probably the most likely source. Cross-contamination of samples during transport from the farm to the laboratory and/or cross-contamination at the laboratory are also considered possible sources. Given the slightly non-optimal system-specificity of the Salmonella monitoring program, there is good reason to make, or consider, standard resampling and retesting of initial positive results by the competent veterinary authorities possible within the EU.