Commercial Laboratory Tests Research Articles

Direct-to-consumer testing as consumer initiated testing: compromises to the testing process and opportunities for quality improvement.

Direct-to-consumer testing (DTCT) refers to commercial laboratory tests initiated by laypersons without the involvement of healthcare professionals. As this market grows in size and variety of products, a clear definition of DTCT to ground the conceptualization of their harms and benefits is needed. We describe how three different modalities of DTCT (home self-testing, self-sampled tests, and direct access tests) present caveats to the traditional testing process ('brain-to-brain loop'), and how this might differ between medical vs. non-medical laboratories. We make recommendations for ways to improve quality and reduce errors with respect to DTCT. The potential benefits and harms of DTCT will invariably depend on the context and situation of individual consumers and the types of tests involved. Importantly, implications for both consumers and the healthcare system should be considered, such as the effects on improving health outcomes and reducing unnecessary testing and use of clinical resources. 'Consumer initiation' must be a central defining characteristic of DTCT, to clearly demarcate the key drawbacks as well as opportunities of this type of testing from a laboratory specialists' perspective. The concept of 'consumer initiated testing' should also help define DTCT regulation, and provide a locus of efforts to support consumers as the main decision-makers in the purchasing and conducting of these tests in the absence of clinician gatekeeping.

PD-BAT: A novel approach of pooling basophil donors for expansion of commercial laboratory testing of Chronic Spontaneous Urticaria

The type II autoimmune subtype of Chronic Spontaneous Urticaria (CSU) is characterized by the presence of IgG autoantibodies targeting IgE or the IgE high-affinity receptor (FcεRI) on mast cells and basophils. In evaluation of CSU patients, indirect basophil activation testing (BAT), has been utilized, involving the mixing of patient serum with heterologous peripheral blood donors, followed by flow cytometric assessment of basophil markers. However, the reliability of the indirect BAT results hinges on the quality of the donor basophils utilized. In this study, we introduce an innovative approach where multiple potential basophil donors undergo rigorous BAT characterization alongside control samples. By selecting and pooling donors with optimal performance, we significantly enhance the inter-assay reproducibility of the indirect BAT test.

Implications of Measles Inclusion by Commercial Syndromic Polymerase Chain Reaction Panels - United States, May 2022-April 2023.

Syndromic polymerase chain reaction (PCR) panels are used to test for pathogens that can cause rash illnesses, including measles. Rash illnesses have infectious and noninfectious causes, and approximately 5% of persons experience a rash 7-10 days after receipt of a measles, mumps, and rubella (MMR) vaccine. MMR vaccine includes live attenuated measles virus, which is detectable by PCR tests. No evidence exists of person-to-person transmission of measles vaccine virus, and illness does not typically result among immunocompetent persons. During September 2022-January 2023, the Tennessee Department of Health received two reports of measles detected by syndromic PCR panels. Both reports involved children (aged 1 and 6 years) without known risk factors for measles, who were evaluated for rash that occurred 11-13 days after routine MMR vaccination. After public health responses in Tennessee determined that both PCR panels had detected measles vaccine virus, six state health departments collaborated to assess the frequency and characteristics of persons receiving a positive measles PCR panel test result in the United States. Information was retrospectively collected from a commercial laboratory testing for measles in syndromic multiplex PCR panels. During May 2022-April 2023, among 1,548 syndromic PCR panels, 17 (1.1%) returned positive test results for measles virus. Among 14 persons who received a positive test result and for whom vaccination and case investigation information were available, all had received MMR vaccine a median of 12 days before specimen collection, and none had known risk factors for acquiring measles. All positive PCR results were attributed to detection of measles vaccine virus. Increased awareness among health care providers about potential measles detection by PCR after vaccination is needed. Any detection of measles virus by syndromic PCR testing should be immediately reported to public health agencies, which can use measles vaccination history and assessment of risk factors to determine the appropriate public health response. If a person recently received MMR vaccine and has no risk factors for acquiring measles, additional public health response is likely unnecessary.

812 FOLATES-RELATED ERYTHROCYTE DIVERSION LEAD TO ATRIAL CARDIOMYOPATHY/FIBRILLATION THROUGH EPCS DYSFUNCTION

Abstract Background Recent advances support the concept that pre-persistent Atrial Fibrillation (AF) and paradoxical embolism do not explain the wholeness of embolic strokes, thus suggesting a broad Atrial Cardiomyopathy (AC). Pathogenic mechanisms underlying AC are still largely unknown. Folate cycle disorders are a yet underrated dysmetabolism. MTHFR-inherited defects could hinder both endothelial and circulating endothelial progenitor cell (EPCs) functioning, therefore providing one-shot explanation to both atrial stasis (increasing atrial fibrosis and generating atrial hypocontractility even in sinus rhythm) and endothelial dysfunction (ED). Purpose This study aims to enquire for the hypothesis that: 1) atrial fibrosis (AFib – intended as a relative percentage of low voltage area in the context of left atrial endocavitary voltage mapping) would relate to folate cycle disorders (intended as both: a)MTHFR C677T inherited mutations and b)bone-marrow function disorders, here referring to erythropoiesis diversions) and 2) AF patients would show dysfunctional EPCs. Methods We studied 59 consecutive patients admitted to the cardiology Unit of the General Hospital “F.Miulli”, with preserved EF, subjected to AF ablation. AFib was quantified by bipolar peak-to-peak voltage areas (<0,5 mV) with respect to the wholeness of the picked voltage points. Blood count cell was evaluated by a commercial laboratory test. EPCs isolation and characterization were performed by Ficoll-Hypaque gradient and following flow cytometry analysis for cell surface antigens: CD45, CD34, CD133, VEGFR2 and KDR. EPCs functional wound healing assay was performed to determine the number of EPCs migrated to the “wound”, measuring the percentage of relative wound closure compared with matched-controls. Results Baseline characteristics did not differ between Sample and Control groups. % of Afib significantly differs between C677T MTHFR homozigosis patients (n=15) with respect to non-C&//T MTHFR homozygosis patients (n=44 p < 0,02). Once univariate analysis was performed, subsequent multivariate analysis highlights highest fit once merged RBC, RDW-SD and folates values were inputed: Goodness of fit was proper, modelling good (Low figure - R2=0,39; p=0,0001). Either RBC, RDW-SD and folates coefficient reached significance (p < 0,0001; p < 0,01; p < 0,05 respectively). Number of EPCs significantly differs between AF patients and matched controls (p < 0,001). Conclusions Our findings support the hypothesis that genetically determined folates dysmetabolism (MTHFR dysfunction) promotes AFib via a complex cardiac-bone marrow networking involving circulating EPCs and unraveled by erythropoiesis diversions. Such results suggest a pathogenic role of folate cycle disorders in the AC development

Assessing the Content Quality of Online Parental Resources about Newborn Metabolic Disease Screening: A Content Analysis.

Parents increasingly utilise the internet to obtain information on health practices, but the quality of online information about screening for inherited metabolic diseases (IMD) needs to be improved. A content analysis examined how IMD blood and urine tests were described online in local healthcare sectors between May and June 2021. Among the nine resources, four were blood test providers and five were urine test providers. All mentioned the test benefits and procedures. Other information, such as false-positive/negative or risk of pain, was infrequently mentioned. The descriptions of urine tests are advertised as outperforming blood tests and can be purchased from commercial laboratory sites without medical guidance. Two urine test providers claimed no false results were reported. A few commercial advertisements highlighted the simplicity of the urine test and potentially overstated the invasiveness of the blood test. We found that some advertisements described IMD as "silent killers" and emphasised the advantage of getting "reassurance" in controlling the child's developmental health and well-being. To better protect the parents, or broadly, the public interest, regulatory and oversight measures on the urine tests should be implemented to promote the proper use of genetic tests. Without timely regulation and oversight, the incorrect descriptions might create a public misconception about utilising these commercial laboratory tests to inform health decisions.

Analysis of serological surveys of antibodies to SARS-CoV-2 in the United States to estimate parameters needed for transmission modeling and to evaluate and improve the accuracy of predictions

Seroprevalence studies can estimate proportions of the population that have been infected or vaccinated, including infections that were not reported because of the lack of symptoms or testing. Based on information from studies in the United States from mid-summer 2020 through the end of 2021, we describe proportions of the population with antibodies to SARS-CoV-2 as functions of age and time. Slices through these surfaces at arbitrary times provide initial and target conditions for simulation modeling. They also provide the information needed to calculate age-specific forces of infection, attack rates, and – together with contact rates – age-specific probabilities of infection on contact between susceptible and infectious people.We modified the familiar Susceptible-Exposed-Infectious-Removed (SEIR) model to include features of the biology of COVID-19 that might affect transmission of SARS-CoV-2 and stratified by age and location. We consulted the primary literature or subject matter experts for contact rates and other parameter values. Using time-varying Oxford COVID-19 Government Response Tracker assessments of US state and DC efforts to mitigate the pandemic and compliance with non-pharmaceutical interventions (NPIs) from a YouGov survey fielded in the US during 2020, we estimate that the efficacy of social-distancing when possible and mask-wearing otherwise at reducing susceptibility or infectiousness was 31% during the fall of 2020. Initialized from seroprevalence among people having commercial laboratory tests for purposes other than SARS-CoV-2 infection assessments on 7 September 2020, our age- and location-stratified SEIR population model reproduces seroprevalence among members of the same population on 25 December 2020 quite well.Introducing vaccination mid-December 2020, first of healthcare and other essential workers, followed by older adults, people who were otherwise immunocompromised, and then progressively younger people, our metapopulation model reproduces seroprevalence among blood donors on 4 April 2021 less well, but we believe that the discrepancy is due to vaccinations being under-reported or blood donors being disproportionately vaccinated, if not both. As experimenting with reliable transmission models is the best way to assess the indirect effects of mitigation measures, we determined the impact of vaccination, conditional on NPIs. Results indicate that, during this period, vaccination substantially reduced infections, hospitalizations and deaths.This manuscript was submitted as part of a theme issue on “Modelling COVID-19 and Preparedness for Future Pandemics.”

Intratumoral heterogeneity of c-KIT mutations in a feline splenic mast cell tumor and their functional effects on cell proliferation

A cat was presented with mast cell tumors (MCTs) of the skin and spleen. During the initial diagnosis, the exon 8 mutation of c-KIT was detected in the masses from skin and spleen by a commercial laboratory test. Consequently, treatment with toceranib was started. After complete remission, because of recurrence on day 117, the spleen and skin tumors were removed, but the cat eventually died on day 191. The analysis of ten cDNA clones of the c-KIT gene cloned from the surgically removed spleen revealed that seven different cDNA patterns were included, indicating the heterogeneity of this gene in the splenic MCT. The seven cDNA nucleotide patterns can be classified into four protein sequence patterns. In addition to the previously known mutations in exon 8, we identified novel mutations in exons 9, 10, and 18; four amino acids deletion in exon 9, and a point mutation in exons 10 and 18. Mouse IL-3-dependent cell line, Ba/F3, was transduced with these mutant clones, and c-KIT phosphorylation and proliferation assays were performed. We found that certain mutations affected the c-KIT phosphorylation status and cell proliferation. This suggests that heterogeneity among the population of tumor cells exists in MCTs, and that the dominant clones of this heterogeneity may contribute to the subsequent tumor cell growth.

Bayesian Approach To Improve The Confidence Of The Estimation Of The Shear Strength Of Coarse Mine Waste Using Barton’s Empirical Criterion

The evaluation of the shear strength of waste rock is required for the verification of the stability of high waste dumps, especially those that reach hundreds of meters in height. Mine waste rock material in open pit mining contains particles of metric scale which precludes the utilisation of commercial laboratory testing equipment. To overcome testing limitations, the shear strength of waste rock is frequently estimated using the empirical criterion of Barton-Kjærnsli. This criterion takes into consideration the nonlinearity of the shear strength envelope, characterising the behaviour of very coarse granular materials submitted to high loads. In the criterion, a stress-dependent structural component of the shear strength is parametrised with the equivalent roughness (R) and equivalent strength (S) and the structural component is added to the basic friction angle (φb) of the parental rock to determine the shear strength of the waste rock material. This paper demonstrates the use of Bayesian inference to determine the best set of parameters φb, R and S that satisfied both: large-scale laboratory testing results characterising a waste rock material, and reconciliation data from observations of stability of the waste dumps. The methodology allows the estimation of project-specific model parameters that honour both, laboratory data and site performance information. This objective is achieved through the estimation of correction factors to downgrade the strength from laboratory to field scale.

Folates dysmetabolism promotes atrial cardiomyopathy/fibrillation through a cardiac-bone marrow networking involving endothelial progenitor cell dysfunction and erythropoiesis diversion

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): dedicated cardiovascular research foud Background Recent advances support the concept that pre-persistent Atrial Fibrillation (AF) does not explain the wholeness of embolic strokes, suggesting the recently postulated hypothesis of a broad Atrial Cardiomyopathy (AC). In contrast to its worldwide distribution and its very inclusive definition, pathogenic mechanisms underlying AC are still largely unknown. Folate cycle disorders (FCD) are a yet underrated dysmetabolism only partly explained by methylene tetrahydrofolate reductase (MTHFR)-inherited defects. On a translational basis, FCD could hinder both endothelial and circulating endothelial progenitor cell (EPCs) functioning, therefore providing one-shot explanation to both atrial stasis (increasing atrial fibrosis and generating atrial hypocontractility) and endothelial dysfunction (ED). If such cardiac-bone marrow networking would be verified, a fundamental pathogenic mechanism of AC and subsequent AF would be unraveled. Purpose This study aims to enquire for the hypothesis that: 1) atrial fibrosis (AFib) would relate to FCD (intended as both: a)MTHFR C677T inherited mutations and b)bone-marrow function disorders, here referring to erythropoiesis diversions) and 2) AF patients would show dysfunctional EPCs. Methods We studied 59 consecutive patients admitted to the Cardiology Unit of the General Hospital "F.Miulli", with preserved EF, subjected to AF ablation. AFib was quantified by relative % of low-voltage (<0,5 mV) bipolar peak-to-peak points, with respect to the wholeness of the endocavitary mapping. Blood count cell was evaluated. MTHFR C677T genotypes were elucidated by RT-PCR. Folate were measured by a commercial laboratory test. EPCs isolation and characterization were performed by Ficoll-Hypaque gradient and flow cytometry analysis for cell surface antigens: CD45, CD34, CD133, VEGFR2 and KDR. EPCs functional wound healing assay was performed. Results Baseline characteristics did not differ between Sample and Control groups (Fig. 1 – Left Table). % of Afib significantly differs between C677T MTHFR homozigosis patients (n=15) with respect to non-C677T MTHFR homozygosis patients (n=44) (Fig.1 – Right graph. - p < 0,02). Once univariate analysis was performed, subsequent multivariate analysis highlights highest fit once merged RBC, RDW-SD and folates values were inputed: Goodness of fit was proper, modelling good (Fig.2 – superior graph. - R2=0,39; p=0,0001). Either RBC, RDW-SD and folates coefficient reached significance (p < 0,0001; p < 0,01; p < 0,05 respectively). Number of EPCs significantly differs between AF patients and matched controls (Fig 2 – inferior graph. – p < 0,001). Conclusions Our findings support the hypothesis that genetically determined folates dysmetabolism (MTHFR dysfunction) promotes AFib via a complex cardiac-bone marrow networking involving circulating EPCs and unraveled by erythropoiesis diversions. Such results suggest a pathogenic role of folate cycle disorders in the AC development.

Clinical and genetic analysis of children with hearing loss and bilateral enlarged vestibular aqueducts

ObjectivesTo evaluate the clinical and genetic features of children with hearing loss associated with one of the most common malformations of the inner ear: bilateral enlargement of vestibular aqueducts (EVA). MethodsClinical and genetic features were investigated in 28 children with hearing loss diagnosed with bilateral EVA by computed tomography from January 2008 to September 2019. ResultsFourteen subjects had undergone newborn hearing screening (NHS). Nine subjects (64.3%) were referred in both ears, 4 subjects (28.6%) were referred in one ear, and one subject (7.1%) passed in both ears. Nineteen of 26 subjects (73.1%) who were followed for more than 3 years had hearing fluctuations, while 17 (65.4%) had hearing loss progression. Eleven of 28 subjects (39.2%) had vertigo attacks. Pathogenic variants were identified in two alleles of the SLC26A4 gene in 24 of 27 subjects (88.9%) by sequencing of all exons and flanking introns, leading to genetic diagnosis of Pendred syndrome/DFNB4. Our results indicate that genetic screening for specific SLC26A4 variants using a commercial clinical laboratory test in Japan would have achieved genetic diagnoses in 13 of the 27 subjects (54.2%). Although there was no statistically significance in the frequency of hearing fluctuation or progression depending on the presence or absence of the gene variant, mean hearing level was severe in subjects with two pathogenic variants in SLC26A4 gene. The most common variant detected in our subjects was p.His723Arg (13 alleles, 27.1%), followed by c. 919-2A > G (four alleles, 8.3%). Two novel variants were detected in this study: c.1544+1G > T and c.1614+5G > A. ConclusionsOur data suggest that some subjects may present with bilateral EVA that cannot be detected by NHS. We estimated that genetic diagnosis for SLC264 gene would not have been made in almost half subjects with the commercial genetic screening approach used in the present study in Japan. Although there were some limitations in this study, the subjects with pathogenic variants in two alleles of the SLC26A4 gene could have more severe hearing loss.

Physical and Numerical Modeling of the Slag Splashing Process.

The influence of technological factors on the process of slag splashing was analyzed in the paper. The problems were solved in several stages using our own and commercial calculation programs and laboratory tests. Based on the performed calculations and simulations, factors affecting the slag splashing were determined. It was observed that the high efficiency of the process can be achieved by optimizing numerous technological parameters, e.g., flow parameters, pressure, and temperature of the nitrogen stream, height and angle of the lance position, as well as slag height into which the gas stream enters and MgO consumption. In addition, the chemical and mineralogical composition of the slag and its physicochemical parameters should be also considered. The obtained results of numerical simulations of slag splashing in the oxygen converter coincide with the results of experiments carried out using the physical model of oxygen converter. This means that the simulations well represent the real course of the slag splashing process for the studied variants.

MPL exon 10 mutations other than canonical MPL W515L/K mutations identified by in-house MPL exon 10 direct sequencing in essential thrombocythemia.

MPL exon 10 mutations are one of the driver mutations in essential thrombocythemia (ET) or myelofibrosis (MF). We have established an in-house MPL mutation analysis system, covering the entire region of MPL exon 10 by direct sequencing. Since 2009, MPL exon 10 mutation analysis has been performed for diagnosis of myeloproliferative neoplasms (MPN) without JAK2 V617F or CALR exon 9 mutations. So far, 11 cases of MPL exon 10 mutation have been found in 51 patients with suspected MPN. In patients with ET, we detected five non-canonical MPL mutations including one novel mutation, MPL R514_P518delinsK, and one canonical MPL W515L mutation. Notably, three ET patients without canonical MPL mutations had thrombotic events. Meanwhile, in primary or secondary MF, only canonical MPL W515L/K mutations were found. Further cases need to be examined to elucidate the full MPL mutation profile in MPN. However, our data indicate that analysis of the whole of MPL exon 10 is warranted for the diagnosis of MPL mutations, especially in ET, and that the use of Japanese commercial laboratory tests that only detect canonical MPL W515L/K mutations may miss a significant percentage of MPL exon 10 mutations, which could delay the administration of anti-thrombotic therapy.

Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection

Understanding the effect of serum antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on susceptibility to infection is important for identifying at-risk populations and could have implications for vaccine deployment. The study purpose was to evaluate evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test (NAAT) among patients with positive vs negative test results for antibodies in an observational descriptive cohort study of clinical laboratory and linked claims data. The study created cohorts from a deidentified data set composed of commercial laboratory tests, medical and pharmacy claims, electronic health records, and hospital chargemaster data. Patients were categorized as antibody-positive or antibody-negative according to their first SARS-CoV-2 antibody test in the database. Primary end points were post-index diagnostic NAAT results, with infection defined as a positive diagnostic test post-index, measured in 30-day intervals (0-30, 31-60, 61-90, >90 days). Additional measures included demographic, geographic, and clinical characteristics at the time of the index antibody test, including recorded signs and symptoms or prior evidence of coronavirus 2019 (COVID) diagnoses or positive NAAT results and recorded comorbidities. The cohort included 3 257 478 unique patients with an index antibody test; 56% were female with a median (SD) age of 48 (20) years. Of these, 2 876 773 (88.3%) had a negative index antibody result, and 378 606 (11.6%) had a positive index antibody result. Patients with a negative antibody test result were older than those with a positive result (mean age 48 vs 44 years). Of index-positive patients, 18.4% converted to seronegative over the follow-up period. During the follow-up periods, the ratio (95% CI) of positive NAAT results among individuals who had a positive antibody test at index vs those with a negative antibody test at index was 2.85 (95% CI, 2.73-2.97) at 0 to 30 days, 0.67 (95% CI, 0.6-0.74) at 31 to 60 days, 0.29 (95% CI, 0.24-0.35) at 61 to 90 days, and 0.10 (95% CI, 0.05-0.19) at more than 90 days. In this cohort study, patients with positive antibody test results were initially more likely to have positive NAAT results, consistent with prolonged RNA shedding, but became markedly less likely to have positive NAAT results over time, suggesting that seropositivity is associated with protection from infection. The duration of protection is unknown, and protection may wane over time.

Warsaw Glacial Quartz Sand with Different Grain-Size Characteristics and Its Shear Wave Velocity from Various Interpretation Methods of BET.

After obtaining the value of shear wave velocity (VS) from the bender elements test (BET), the shear modulus of soils at small strains (Gmax) can be estimated. Shear wave velocity is an important parameter in the design of geo-structures subjected to static and dynamic loading. While bender elements are increasingly used in both academic and commercial laboratory test systems, there remains a lack of agreement when interpreting the shear wave travel time from these tests. Based on the test data of 12 Warsaw glacial quartz samples of sand, primarily two different approaches were examined for determining VS. They are both related to the observation of the source and received BE signal, namely, the first time of arrival and the peak-to-peak method. These methods were performed through visual analysis of BET data by the authors, so that subjective travel time estimates were produced. Subsequently, automated analysis methods from the GDS Bender Element Analysis Tool (BEAT) were applied. Here, three techniques in the time-domain (TD) were selected, namely, the peak-to-peak, the zero-crossing, and the cross-correlation function. Additionally, a cross-power spectrum calculation of the signals was completed, viewed as a frequency-domain (FD) method. Final comparisons between subjective observational analyses and automated interpretations of BET results showed good agreement. There is compatibility especially between the two methods: the first time of arrival and the cross-correlation, which the authors considered the best interpreting techniques for their soils. Moreover, the laboratory tests were performed on compact, medium, and well-grained sand samples with different curvature coefficient and mean grain size. Investigation of the influence of the grain-size characteristics of quartz sand on shear wave velocity demonstrated that VS is larger for higher values of the uniformity coefficient, while it is rather independent of the curvature coefficient and the mean grain size.

A new laboratory test to help diagnose a specific type of pemphigoid

An autoimmune disease is a condition where the body sees one of its own proteins as foreign and will try to destroy it. There are various types of autoimmune diseases and one rare form is anti-laminin-332 mucous membrane pemphigoid, a severe chronic disease which causes blistering of the mucous membranes in the mouth, eyes, nose and airways, the oesophagus and the genital region. The disease is characterized by IgG (antibodies) which attack a protein called laminin-332 that is essential for an intact skin. Binding of IgG to laminin-332 results in inflammation, forming erosions and blisters. There are other forms of mucous membrane pemphigoid that look similar and diagnosis is therefore difficult. A commercial laboratory test that can find the antibodies in the blood is not available. In this study from the Netherlands, the authors developed a simple and specific method to detect the IgG against laminin-332, called keratinocyte footprint assay. They cultured (meaning grew in a lab) keratinocytes, which are the main cells of skin, on small glass disks. In culture, cells move over the glass and thereby, like slugs, leave behind a trail. These trails contain laminin-332. After culture the glass disks are air dried and stored in a freezer. When a diagnosis of anti-laminin-332 is suspected a disk is taken out and serum (part of the blood) of the patient is brought onto the disk. If IgG to laminin-332 is present this will bind to the trails. After an hour the disks are rinsed and a fluorescent substance that binds to IgG is put onto the disk. The disks are then investigated under a fluorescent microscope and if the trails are fluorescent, that is proof that the patient has anti-laminin-332 antibodies. Comparing blood samples of healthy persons and patients with other autoimmune diseases showed that this method is very specific and sensitive, meaning it is accurate. This summary relates to the study: Keratinocyte footprint assay discriminates antilaminin-332 pemphigoid from all other forms of pemphigoid diseases

Evaluation of serological diagnostic tests of human brucellosis for prevention and control in Mexico.

Brucellosis is a zoonosis mainly present in developing countries. The WHO reports 500,000 new cases every year. From 2012 to 2016, 13,677 cases were reported in Mexico, with 2.00 to 2.64 rate per 100,000 inhabitants. To analyze the diagnostic algorithm of brucellosis in Mexico, we compared the commercial laboratory tests ELISA, Brucellacapt®, and lateral flow test (LFT) in a study of 473 individuals from two endemic Mexican populations. All patients were treated in first-level medical units for presenting brucellosis compatible symptoms and without a history of the disease. Clinical-epidemiological information was gathered and initial serum samples were obtained to react with anti-Brucella antibodies; subsequent samples were collected at follow-up treatment visits. Using the Rose Bengal screening, we found 165 negative samples and 308 positive reactive samples, of which 222 cases were confirmed and 234 were positive on at least one marker (IgG or IgM) or LFT. When Brucellacapt® was used, similar results to those observed with the conventional algorithm were found as judged by the Cohen's kappa coefficient (κ) (0.813, 95% CI 0.7788-0.8472). Similar κ indices between conventional algorithm and ELISA pair were found, 0.7038 (95% CI 0.6555-0.7521), representing high similarity between both groups of diagnosis. We conclude that conventional serodiagnoses, Brucellacapt® and LFT, presented inconclusive results and poor correlation between them. By contrast, ELISA test pair (IgG + IgM) presented high correlation with the conventional algorithm and greater capacity for correct positive and negative classification.

P.377Myasthenia gravis (MG) anti-musk in Argentina: demographic, clinical findings and therapeutic response in a cohort of 56 patients

MuSK antibody positive Myasthenia Gravis (MuSK-MG) is diagnosed between 0-49% cases with generalized seronegative MG in different populations. Segmental muscular atrophy, frequent bulbar symptoms and a high incidence of myasthenic crisis characterize the disease. The aim of this study is to present a large cohort of MuSK-MG patients from Argentina. We performed a retrospective chart review on 56 muscle-specific kinase antibody (MuSK-Ab)-positive myasthenia gravis (MG) patients in nine neuromuscular centers in Argentina. All of them were identified to have MuSK-Ab on commercial laboratory testing. MG severity and response to treatment were assessed according to MGFA classification. We identified 56 patients with diagnosis of Musk-MG. Of them, 66% were female. Mean age at diagnosis was 45,6 and 44,9 years-old in women and men respectively. Initial symptoms were: oculo-bulbar (34,3%), pure ocular (21,8%), pure bulbar (21,8%). 2 patients initiated with ocular and limb weakness, 2 with only limb weakness, 2 showed respiratory symptoms an 1 presented with dropped head. Initial MGFA status was: IIB (62%), I (13,7 %), IIIB (7%), IIA 6,9 % and 27,5% had myasthenic crisis at diagnosis. Peak MGFA was: IIb (20%), IIIB 26,6%, IVB 30 %. 6 (20%) patients had myasthenic crisis Three clinical phenotypes were found: the oculo-bulbar, the respiratory and the pseudo-myopathic. We did not find a clearly female predominance as described in previous reports. The presence of thymoma or thymic pathology was not detected by CT scan or MRI. Most patients respond favorably to immunotherapy. The best clinical response was to rituximab ,corticosteroids and plasma exchange, and the poorest response was to IVIG and anticholinesterase. Long-term outcome is favorable in about 80% of cases. This is the first series of patients with MuSK-MG described in South America and one of the largest worldwide.

442. The Results of a Primary Care-based Screening Program for Trypanosoma cruzi in East Boston, Massachusetts

BackgroundThis study reports the outcomes of the Strong Hearts pilot project to integrate screening for Trypanosoma cruzi into a primary care setting and facilitate referral for treatment at East Boston Neighborhood Health Center.MethodsContinuing education about Chagas disease was offered to healthcare providers, and community-based outreach was provided. One-time screening for all patients ≤50 years old who lived in Mexico, South or Central America for ≥6 months was recommended. The initial screening test was an ELISA performed by a commercial laboratory and confirmatory testing was performed at the US CDC. Confirmed positives were defined as positive on both the screening and confirmatory tests. Confirmed positive patients were referred to the Pediatric and Adult Infectious Disease clinics at Boston Medical Center for further evaluation and treatment. We compared the proportion of confirmed positives by sex, age, and self-reported national origin using chi-squared tests. We then used multivariable logistic regression to examine predictors of (1) confirmed positive or (2) discordant screening and confirmatory testing.ResultsA total of 2,183 screening tests were sent; 84 (3.8%) were positive, 2,082 (95.4%) negative, and 17 (0.8%) indeterminate. Among 73 tests with confirmatory results available, 19 (26%) were positive and 54 (74%) negative. All indeterminate tests were confirmed negative. The proportion of confirmed positives increased with increasing age (P = 0.014) (Table 1), but there were no significant differences by sex (M: 8/757, F: 11/1,413, P = 0.51) or national origin (P = 0.79). Nineteen confirmed positives have been evaluated and six initiated benznidazole to date. Three confirmed positives were pregnant. In multivariable models, there were no significant predictors of confirmed positive or discordant testing.ConclusionThis pilot shows that integration of screening for Chagas disease is feasible in primary care. Although the prevalence of T. cruzi infection was higher in older age groups, there were no clear demographic predictors of a confirmed positive or discordant test. We also found a high false-positive rate of the screening test, highlighting the need for improved serologic testing options.Table 1.Age Group (Years)Positive Cases (#)*Total Screened (#)Prevalence (%)≤1901010.020–2937420.430–3978200.940–4953921.3≥5041153.5Disclosures All authors: No reported disclosures.

The Impact of Disruption of the Care Delivery System by Commercial Laboratory Testing in a Children's Health Care System.

Disruption of outpatient laboratory services by routing the samples to commercial reference laboratories may seem like a cost-saving measure by the payers, but results in hidden costs in quality and resources to support this paradigm. To identify differences when outpatient tests are performed at the Children's Healthcare of Atlanta (Children's) Hospital lab compared to a commercial reference lab, and the financial costs to support the reference laboratory testing. Outpatient testing was sent to 3 different laboratories specified by the payer. Orders were placed in the Children's electronic health record, blood samples were drawn by the Children's phlebotomists, samples were sent to the testing laboratory, and results appeared in the electronic health record. Data comparing the time to result, cancelled samples, and cost to sustain the system of ordering and reporting were drawn from multiple sources, both electronic and manual. The median time from phlebotomy to result was 0.7 hours for testing at the Children's lab and 20.72 hours for the commercial lab. The median time from result posting to caregiver acknowledgment was 5.4 hours for the Children's lab and 18 hours for the commercial lab. The commercial lab cancelled 2.7% of the tests; the Children's lab cancelled 0.8%. The financial cost to support online ordering and reporting for testing performed at commercial labs was approximately $640,000 per year. Tangible monetary costs, plus intangible costs related to delayed results, occur when the laboratory testing system is disrupted.

Point-of-care testing for Toxoplasma gondii IgG/IgM using Toxoplasma ICT IgG-IgM test with sera from the United States and implications for developing countries.

BackgroundCongenital toxoplasmosis is a serious but preventable and treatable disease. Gestational screening facilitates early detection and treatment of primary acquisition. Thus, fetal infection can be promptly diagnosed and treated and outcomes can be improved.MethodsWe tested 180 sera with the Toxoplasma ICT IgG-IgM point-of-care (POC) test. Sera were from 116 chronically infected persons (48 serotype II; 14 serotype I-III; 25 serotype I-IIIa; 28 serotype Atypical, haplogroup 12; 1 not typed). These represent strains of parasites infecting mothers of congenitally infected children in the U.S. 51 seronegative samples and 13 samples from recently infected persons known to be IgG/IgM positive within the prior 2.7 months also were tested. Interpretation was confirmed by two blinded observers. A comparison of costs for POC vs. commercial laboratory testing methods was performed.ResultsWe found that this new Toxoplasma ICT IgG-IgM POC test was highly sensitive (100%) and specific (100%) for distinguishing IgG/IgM-positive from negative sera. Use of such reliable POC tests can be cost-saving and benefit patients.ConclusionsOur work demonstrates that the Toxoplasma ICT IgG-IgM test can function reliably as a point-of-care test to diagnose Toxoplasma gondii infection in the U.S. This provides an opportunity to improve maternal-fetal care by using approaches, diagnostic tools, and medicines already available. This infection has serious, lifelong consequences for infected persons and their families. From the present study, it appears a simple, low-cost POC test is now available to help prevent morbidity/disability, decrease cost, and make gestational screening feasible. It also offers new options for improved prenatal care in low- and middle-income countries.