Development of RSV Vaccines

Respiratory syncytial virus (RSV) is one of the most im portant viral pathogens that cause infections of lower res piratory tract in infants and young children. Evidence ofinfection with RSV has been found in every geographicarea in the world. Its inci…     

The performance of Luminex ARIES® Flu A/B & RSV and Cepheid Xpert® Flu/RSV XC for the detection of influenza A,influenza B,and respiratory syncytial virus in prospective patient samples

BackgroundThe demand for rapid, accurate viral testing has increased the number of assays available for the detection of viral pathogens. One of the newest FDA cleared platforms is the Luminex ARIES^® Flu A/B & RSV, which is a fully automated, real-time PCR-based assay used for detection of influenza A, influenza B, and respiratory syncytial virus (RSV).ObjectivesWe sought to compare the performance of Luminex ARIES^® Flu A/B & RSV assay to the Cepheid Xpert^® Flu/RSV XC assay for rapid Flu and RSV testing.Study designA series of consecutive nasopharyngeal specimens received in the clinical microbiology laboratory during peak influenza season at a major academic center in Chicago, IL, were prospectively tested, using both the ARIES^® Flu A/B & RSV and Xpert^® Flu/RSV XC assays, side by side. Discrepant results were tested on the BioFire FilmArray^® Respiratory Panel for resolution.ResultsA total of 143 consecutive nasopharyngeal specimens, obtained from patients ranging from six months to ninety-three years in age were received between January 1st, 2017 and March 21st, 2017. There was 96.6% agreement between the two assays for detection influenza A, 100% agreement for detection influenza B and RSV, and 98.9% agreement for negative results. The Xpert^® Flu/RSV XC performed with an average turn-around time of approximately 60 min, compared to the ARIES^® Flu A/B & RSV of approximately 120 min. Both assays were equally easy to perform, with a similar amount of hands-on technologist time for each platform.ConclusionsOverall, these results indicate that both tests are comparable in terms of result agreement and technical ease-of-use. The Xpert^® Flu/RSV XC assay did produce results with less turn-around-time, approximately 60 min quicker than the ARIES^® Flu A/B & RSV.     

A prospective study to assess the diagnostic performance of the Sofia® Immunoassay for Influenza and RSV detection.

BackgroundRespiratory viruses RSV and influenza A and B viruses are responsible for important disease outbreaks during the winter season in temperate climate regions. Rapid diagnostic tests (RDTs) are assays designed to yield a rapid diagnosis, which facilitates patient management. The Sofia Influenza A + B Fluorescence Immunoassay and Sofia RSV Fluorescence Immunoassay are RDTs for Influenza and RSV detection that employ a new technology to enhance their sensitivity.ObjectivesSensitivity, specificity and positive and negative predictive values of the assays were calculated compared with the reference diagnostic method: real-time RT-PCR.Study designA prospective evaluation was carried out on 1065 respiratory samples for Sofia Influenza A + B FIA and on 261 samples for Sofia RSV FIA from November 2013 to April 2014.ResultsThe sensitivities of the Sofia Influenza A + B FIA for influenza A and influenza B detection were, respectively, 75.3% (244/324) and 50.0% (8/16). The sensitivity of the Sofia RSV FIA was 92.1% (128/139). There were no differences in Sofia FIA performance depending on the virus subtype.ConclusionsThe results showed high sensitivity and specificity values for influenza A and RSV detection, but values were lower for influenza B. More information is needed regarding the performance for influenza B given the small number of positive samples assessed.     

Performance of Cepheid® Xpert MTB/RIF® and TB-Biochip® MDR in two regions of Russia with a high prevalence of drug-resistant tuberculosis

The purpose of this study was to assess the performance of Cepheid® Xpert MTB/RIF® (“Xpert”) and TB-Biochip® MDR (“TB-Biochip”). Sputum specimens from adults with presumptive tuberculosis (TB) were homogenized and split for: (1) direct Xpert and microscopy, and (2) concentration for Xpert, microscopy, culture [Lowenstein–Jensen (LJ) solid media and Mycobacteria Growth Indicator Tube® (MGIT)], indirect drug susceptibility testing (DST) using the absolute concentration method and MGIT, and TB-Biochip. In total, 109 of 238 (45.8 %) specimens were culture-positive for Mycobacterium tuberculosis complex (MTBC), and, of these, 67 isolates were rifampicin resistant (RIF-R) by phenotypic DST and 64/67 (95.5 %) were isoniazid resistant (INH-R). Compared to culture of the same specimen, a single direct Xpert was more sensitive for detecting MTBC [95.3 %, 95 % confidence interval (CI), 90.0–98.3 %] than direct (59.6 %, 95 % CI, 50.2–68.5 %) or concentrated smear (85.3 %, 95 % CI, 77.7–91.1 %) or LJ culture (80.8 %, 95 % CI, 72.4–87.5 %); the specificity was 86.0 % (95 % CI, 78.9–91.3 %). Compared with MGIT DST, Xpert correctly identified 98.2 % (95 % CI, 91.5–99.9 %) of RIF-R and 95.5 % (95 % CI, 85.8–99.2 %) of RIF-susceptible (RIF-S) specimens. In a subset of 104 specimens, the sensitivity of TB-Biochip for MTBC detection compared to culture was 97.3 % (95 % CI, 91.0–99.5 %); the specificity was 78.1 % (95 % CI, 61.5–89.9 %). TB-Biochip correctly identified 100 % (95 % CI, 94.2–100 %) of RIF-R, 94.7 % (95 % CI, 76.7–99.7 %) of RIF-S, 98.2 % (95 % CI, 91.4–99.9 %) of INH-R, and 78.6 % (95 % CI, 52.1–94.2 %) of INH-S specimens compared to MGIT DST. Xpert and Biochip were similar in accuracy for detecting MTBC and RIF resistance compared to conventional culture methods.     

Performance of a rapid antigen test (Binax NOW® RSV) for diagnosis of respiratory syncytial virus compared with real-time polymerase chain reaction in a pediatric population

BackgroundInfants from Alaska's Yukon–Kuskokwim Delta (YKD) have a high respiratory syncytial virus (RSV) hospitalization rate (104/1000/yr). Appropriate patient management requires rapid and accurate RSV diagnosis. Antigen-based methods are often used in clinical settings, but these tests can lack sensitivity.ObjectiveWe compared Binax NOW^® RSV (BN) used for RSV diagnosis in the YKD hospital with a real-time polymerase chain reaction assay (RT-qPCR) used for viral surveillance.Study designBetween October 2005 and September 2007 we obtained nasopharyngeal washes (NPW) from children <3 years hospitalized with a lower respiratory tract infection. The NPW were tested using BN and RT-qPCR.Results79/311 (25%) children had RSV infection as determined by RT-qPCR. As compared with RT-qPCR, sensitivity and specificity of BN were 72% and 97%, respectively. The sensitivity of BN was higher in children <1 year compared with children ≥1 year (79% vs. 52%; p = 0.025), children with bronchiolitis compared with children without bronchiolitis (89% vs. 38%; p < 0.001), and children with a shorter duration of symptoms before testing (0–1 (92%) vs. 2–4 (78%) vs. 5+ (65%) days; p = 0.04). The median RSV viral load in NPW positive by BN and RT-qPCR was 1.01 × 10⁹ copies/mL vs. a median of 5.25 × 10⁷ copies/mL for NPW positive by RT-qPCR only (p < 0.001).ConclusionRT-qPCR is more sensitive than BN in detecting RSV infection. BN sensitivity is high in children with bronchiolitis, but the sensitivity is low when children present with a non-bronchiolitis illness, especially after a longer duration of symptoms before testing.     

Inter-rater reliability of the GNRB® knee arthrometer

BackgroundIn clinical settings, where arthrometers are mainly used by different clinicians, knowing the inter-rater reliability of the instrument is crucial in order for the results from different examiners to be accurately interpreted and limitations fully understood. The aim of this study was to evaluate the inter-rater reliability of the GNRB® knee arthrometer.MethodsKnee anterior laxity in both knees was tested in a group of young, uninjured subjects (N = 27, 13 females) by two examiners. Knee anterior laxity was calculated at test forces of 134 N and 250 N with values presented for the unstandardised and standardised conditions (relative to patellar stabilisation force).ResultsThe ICCs ranged from 0.220 to 0.424.ConclusionsThe inter-rater reliability of the GNRB® knee arthrometer is low.     

Development of the nursing problem list subset of SNOMED CT®

ObjectiveTo create an interoperable set of nursing diagnoses for use in the patient problem list in the EHR to support interoperability.DesignQueries for nursing diagnostic concepts were executed against the UMLS Metathesaurus to retrieve all nursing diagnoses across four nursing terminologies where the concept was also represented in SNOMED CT. A candidate data set was retrieved and included the nursing diagnoses and corresponding SNOMED CT concepts from the UMLS Metathesaurus. The team members identified the concepts that met the semantic selection criteria for inclusion in the nursing problem list.Results1320 concepts were returned in the initial UMLS Metathesaurus query of nursing diagnostic concepts. Further analysis was conducted to identify those nursing diagnostic concepts mapped to SNOMED CT and duplicate concepts were removed resulting in 591 unique UMLS Metathesaurus concepts. The query extracted all concepts from two of the nursing terminologies that contained interventions and outcomes. After cleaning the dataset, the final count of SNOMED CT concepts in the nursing problem list subset is 369.ConclusionsThe problem list is a key component of the patient care and has been acknowledged as critical by the EHR Meaningful Use criteria. Nursing diagnoses on the problem list are foundational for constructing a nursing care plan. A multidisciplinary patient problem list will facilitate communication and evaluation of the contribution of nursing care to the patient’s clinical care experiences and outcomes.     

The experience of Flebogammadif® in primary immune thrombocytopenia

Primary immune thrombocytopenia (ITP) is a common autoimmune disease characterized by autoantibody-induced platelet destruction, suboptimal megakaryocytic production of platelets and consequent bleeding. Numerous controlled trials have proved that the administration of high-dose intravenous immunoglobulins (IVIG) results in rapid increases in the platelet numbers. Therefore, they are indicated in emergency settings or in patients needing surgical procedures. Here, the efficacy and safety of Flebogammadif?, a new high-purity IVIG, was assessed by an open, multi-centre, non-controlled, prospective study in 20 adult patients diagnosed with ITP for at least 6 months before recruitment and with a platelet count ≤ 20,000/μl before treatment. Patients received 0·4 g/kg/body weight of Flebogammadif? for 5 consecutive days and were followed-up for 3 months. There were three efficacy end-points: proportion of patients who reached a platelet count ≥ 50 000/μl; time for the platelet count to reach that level; and duration of response. Safety parameters [adverse events (AE), laboratory determinations and vital signs] and viral markers were monitored regularly. A total of 14 patients achieved a platelet count of ≥ 50,000/μl. The median time to platelet response was ≤ 2·5 days and the median number of days in which the platelet count remained ≥ 50,000/μl was ≥ 7·0 days. A regression of haemorrhages was reported for 17 patients on day 14. Eight patients presented 20 AEs (mainly mild) related potentially to the study drug. Neither abnormalities in laboratory values nor in viral markers were registered during the follow-up period. In conclusion, Flebogammadif? was well tolerated and succeeded in providing a haemostatic platelet count in ITP patients.     

The effect of lubrication on the friction and wear of Biolox®delta

The performance of total hip-joint replacements depends strongly on the state of lubrication in vivo. In order to test candidate prosthetic materials, in vitro wear testing requires a lubricant that behaves in the same manner as synovial fluid. The current study investigated three lubricants and looked in detail at the lubrication conditions and the consequent effect on ball-on-flat reciprocating wear mechanisms of Biolox®delta against alumina. Biolox®delta, the latest commercial material for artificial hip-joint replacements, is an alumina-matrix composite with improved mechanical properties through the addition of zirconia and other mixed oxides. Three commonly used laboratory lubricants, ultra pure water, 25 vol.% new-born calf serum solution and 1 wt.% carboxymethyl cellulose sodium salt (CMC-Na) solution, were used for the investigation. The lubrication regimes were defined by constructing Stribeck curves. Full fluid-film lubrication was observed for the serum solution whereas full fluid-film and mixed lubrications were observed in both water and the CMC-Na solution. The wear rates in the CMC-Na and new-born calf serum were similar, but were an order of magnitude higher in water. The worn surfaces all exhibited pitting, which is consistent with the transition from mild wear to severe or “stripe” wear. The extent of pitting was greatest in the serum solution, but least in the water. On all worn surfaces, the zirconia appeared to have fully transformed from tetragonal to monoclinic symmetry. However, there was no evidence of microcracking associated with the transformed zirconia. Nevertheless, AFM indicated that zirconia was lost preferentially to the alumina grains during sliding. Thus, the current study has shown conclusively that the wear mechanisms for Biolox®delta clearly depend on the lubricant used, even where wear rates were similar.     

The use of FTA® filter papers for diagnosis of avian influenza virus

Avian influenza viruses (AIVs) infect a wide range of host species including domestic poultry and wild birds; also, AIVs may infect humans in whom some highly pathogenic viruses (HPAIV) may cause acute fatal disease. Accurate laboratory diagnosis of AIV infections requires time-consuming and logistically complex precautionary measures for shipment of specimens or viruses to avoid biohazard exposure. The feasibility was investigated of the Flinders Technology Associates filter paper (FTA? card) for infectivity of AIVs and to preserve viral RNA for detection by RT-qPCR, sequencing and by DNA microarray assay. The infectivity of AIV subtype H6N2 and HPAIV subtype H5N1 was inactivated completely within one hour after adsorption to the FTA card at room temperature. FTA-adsorbed viral RNA remained stable for five months. Swab samples obtained from chickens infected experimentally with H5N1 virus and spotted directly onto the FTA? cards allowed a sensitive and straightforward diagnosis by RT-qPCR. FTA? cards were also suitable for examination of field samples, although AIV RNA was detected with reduced sensitivity in comparison to direct examination of swab fluids. The use of FTA? cards will facilitate safe transport of samples for molecular diagnosis of AIV avoiding the need for an uninterrupted cold storage.     

Effects of PerClot® on the healing of full-thickness skin wounds in rats

PerClot^® is a hemostatic material made of polysaccharide from modified starch and has been shown to assist in topical hemostasis. The principal goal in treating surgical and non-surgical wounds is the need for rapid closure of the lesion. This study investigated whether topical application of PerClot^® could improve impaired wound healing in Sprague-Dawley (SD) rats. Full-thickness skin wounds were created on the back of the rats. Immediately, PerClot^® was introduced into the wound bed, while wounds receiving starch or nothing served as controls. Wound closure was monitored using well-recognized wound-healing parameters: histological examination for inflammatory cells and fibroblast infiltration, newly formed capillaries, and collagen deposition. Meanwhile, transforming growth factor (TGF-β1) was measured by immunochemistry. Wound closure was significantly accelerated by local application of PerClot^®. Furthermore, PerClot^®-treated wounds showed significantly increased fibroblast numbers at 5 days post-wounding, and newly formed capillaries at 7 days post-wounding, and collagen regeneration at 7 and 14 days post-wounding. The number of infiltrating fibroblasts expressing TGF-β1 was significantly higher than that in the controls at 7 and 14 days post-wounding. PerClot^® can improve the wound healing and this effect might involve an increase in the activity of fibroblasts and increased release of TGF-β1.     

Usefulness of Sofia Pneumococcal FIA® test in comparison with BinaxNOW® Pneumococcal test in urine samples for the diagnosis of pneumococcal pneumonia

The Sofia Pneumococcal FIA® test is a recently introduced immunofluorescent assay automatically read aimed to detect Streptococcus pneumoniae antigen in urine. The aim of this study was to evaluate the usefulness of SofiaFIA® urinary antigen test (UAT) in comparison with classical immunochromatographic BinaxNOW® test for the diagnosis of pneumococcal pneumonia (PP). Observational study was conducted in the Hospital Universitari Vall d’Hebron from December 2015 to August 2016. Consecutive adult patients diagnosed of pneumonia and admitted to the emergency department in whom UAT was requested were prospectively enrolled. Paired pneumococcal UAT was performed (BinaxNOW® and SofiaFIA®) in urine samples. To assess the performance of both tests, patients were categorized into proven PP (isolation of S. pneumoniae in sterile fluid) or probable PP (isolation of S. pneumoniae in respiratory secretion). Sensitivity, specificity, and concordance were calculated. A total of 219 patients with pneumonia were enrolled, of whom 14% had a proven or probable PP, 22% a non-pneumococcal etiology, and 64% an unidentified pathogen. Concordance between tests was good (κ?=?0.81). Sensitivity of SofiaFIA® and BinaxNOW® UAT was 78.6 and 50% for proven PP (p?=?0.124), and 74.2 and 58% for proven/probable PP (p?=?0.063). Specificity for both tests was 83.3 and 85.5% for proven and proven/probable PP. In patients without an identified pathogen, SofiaFIA® test was positive in 33 (23.6%) cases and BinaxNOW® in 25 (17.8%), so Sofia Pneumococcal FIA® detected 32.6% more cases than BinaxNOW® (p?=?0.001). Sofia Pneumococcal FIA® test showed an improved sensitivity over visual reading of BinaxNOW® test without a noticeable loss of specificity.     

Evaluation of two VIDAS ®prototypes for detecting anti-HEV IgG

BackgroundHigh performance anti-hepatitis E virus (HEV) IgG assays are crucial for epidemiology.ObjectiveTo evaluate the performance of 2 prototypes developed for the VIDAS^® automatic system for detecting anti-HEV IgG, one based on the ORF2 antigen (ORF2 prototype) and the other on the ORF2 and ORF3 antigens (ORF2/3 prototype), with reference to the Wantai anti-HEV IgG assay.Study designThe sensitivity of each assay was determined by testing 113 blood samples, 63 from immunocompetent and 50 from immunocompromised patients, with a proven HEV infection defined by detecting HEV RNA. Their specificity was assessed with 103 blood samples that the Wantai assay indicated was negative for anti-HEV IgM and IgG, and negative for HEV-RNA. Cross reactivity was assessed using samples that were positive for hepatitis A virus IgG (n = 16), hepatitis C virus antibodies (n = 15), hepatitis B virus antigen and anti-HBc antibodies (n = 16), rheumatoid factor (n = 14), and negative for anti-HEV IgG with the Wantai assay.ResultsThe sensitivities in immunocompetent patients were: 95.2% (ORF2), 96.8% (ORF2/3), and 93.6% (Wantai); in immunocompromised patients they were: 66% (ORF2), 72% (ORF2/3), and 68% (Wantai). Both VIDAS prototypes detected low concentrations of anti-HEV IgG. The overall specificity was 100% (ORF2 prototype) and 98.1% (ORF2/3 prototype). Both VIDAS prototypes cross-reacted in five samples (9.6%), mainly those containing HCV antibodies or rheumatoid factor.ConclusionBoth VIDAS^® prototypes performed very well and appear to be suitable for routine detection of anti-HEV IgG.     

Evaluation of the Virus Counter® for rapid baculovirus quantitation

The utility of a new instrument for rapid virus quantitation, the Virus Counter, was evaluated in a blind study conducted at three sites. This instrument is a substantially improved version of the original academic research instrument described previously by Stoffel and Rowlen (2005a). The addition of hydrodynamic focusing, a self-contained fluidics system and customized software for system control and data analysis has resulted in a commercially viable and available design. Baculovirus samples were provided by Protein Sciences Corporation and blinded to InDevR and Baylor College of Medicine. Protein Sciences Corporation and Baylor College of Medicine analyzed the samples by plaque assay and InDevR analyzed the samples using the Virus Counter. Serial dilution of stock viruses into growth media and buffer allowed for comparison of measured versus intended concentrations. Direct log-scale comparison between pooled Virus Counter results and pooled plaque assay results indicated a linear relationship (slope = 1.1 ± 0.2, R² = 0.86) with statistically significant Pearson correlation (r = 0.93, p < 0.001).     

Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population

BackgroundMeningitis causes significant mortality in sub-Saharan Africa and limited diagnostics exist. We evaluated the utility of the BioFire® FilmArray® Meningitis/Encephalitis multiplex PCR panel (BioFire ME) in HIV-infected adults and HIV-infected and uninfected children presenting with suspected meningitis in Uganda.MethodsWe tested cerebrospinal fluid (CSF) using a stepwise meningitis diagnostic algorithm including BioFire ME. We determined the diagnostic performance of BioFire ME for cryptococcal meningitis, using cryptococcal antigen (CrAg) and CSF culture as reference standards, and assessed other central nervous system (CNS) pathogens identified by the panel.ResultsWe evaluated 328 adult and 42 pediatric CSF specimens using BioFire ME. Of the adult CSF samples tested, 258 were obtained at baseline, and 70 were obtained from repeat lumbar punctures in cryptococcal meningitis. For Cryptococcus, sensitivity was 82%, specificity was 98%, PPV was 98%, and NPV was 79% in baseline specimens using CSF CrAg as the reference standard. Among follow-up specimens, a negative BioFire ME for Cryptococcus predicted CSF culture sterility with 84% NPV. Overall sensitivity was decreased at low fungal burdens: 29% for 0–99 Cryptococcus CFU/mL compared to 94% for ≥100 CFU/mL in baseline specimens. Other pathogens detected included E. Coli, H. influenzae, S. pneumoniae, CMV, enterovirus, HSV, HHV-6, and VZV. Two specimens tested positive for S. pneumoniae and one for Cryptococcus in the pediatric population.ConclusionsMultiplex PCR is a promising rapid diagnostic test for meningitis in adults and children in resource-limited settings. Cryptococcus at low fungal burdens in CSF may be missed by BioFire ME.     

Evaluation of the combination of the NucliSENS easyMAG® and the EasyQ® applications for the detection of Mycoplasma pneumoniae and Chlamydia pneumoniae in respiratory tract specimens

Mycoplasma pneumoniae and Chlamydia pneumoniae are respiratory tract pathogens frequently involved in community-acquired pneumonia, but are fastidious microorganisms. Their direct detection mainly requires molecular amplification techniques. A nucleic acid extraction system, NucliSENS easyMAG®, and a real-time nucleic acid sequence-based amplification (NASBA) technique, NucliSENS EasyQ®, were recently developed by bioMérieux to detect both bacteria. The aim of our study was to compare the easyMAG/EasyQ combination with our in-house combination, MagNA Pure extraction (Roche) and real-time polymerase chain reaction (PCR), to detect both bacteria in respiratory tract specimens. The analytical specificities of both combinations were similar. A higher analytical sensitivity was found for C. pneumoniae using the easyMAG/EasyQ combination, since the easyMAG/EasyQ system detected nucleic acid extracts 10⁶ times more diluted than the in-house combination. Both combinations were equivalent when detecting M. pneumoniae in positive respiratory tract samples. Finally, the easyMAG/EasyQ combination is a potential useful tool for the detection of both bacteria regarding sensitivity, specificity, monitoring, and standardization of the procedure.     

Diagnostic test accuracy of the BioFire® FilmArray® meningitis/encephalitis panel: a systematic review and meta-analysis

BackgroundThe FilmArray® meningitis/encephalitis (ME) panel is a multiplex PCR assay which can detect the most commonly identified pathogens in central nervous system infections. It significantly decreases the time to diagnosis of ME and data has yielded several positive outcomes. However, in part, reports of both false positive and false negative detections have resulted in concerns about adoption.ObjectivesThe aim was to evaluate the ME panel in a diagnostic test accuracy review.Data sourcesThe PubMed and EMBASE databases were systematically searched through May 2019.Study eligibility criteriaEligible studies were those providing sensitivity and specificity data for the ME panel compared with a reference standard. Studies providing details on false positive and false negative results of the panel as well as further investigation (adjudication) of the discordant results between the panel and comparator assays were included and assessed separately.ParticipantsPatients with suspected ME for whom a panel was ordered were included.MethodsThe ME panel was compared to reference standard methods for diagnosing community-acquired ME. We performed a meta-analysis and calculated the summary sensitivity and specificity of the ME panel. Moreover, we evaluated the false positive and false negative results of the panel.ResultsThirteen studies (3764 patients) were included in the review and 8 of them (3059 patients) were pooled in a meta-analysis. The summary estimates of sensitivity and specificity with 95% confidence intervals (CI) was 90% (95% CI 86–93%) and 97% (95% CI 94–99%), respectively. When we looked specifically at studies that assessed further the false positive and false negative results, false positive detections were 11.4% and 4% before and after adjudication, respectively. The highest proportion of false positive was observed for Streptococcus pneumoniae followed by Streptococcus agalactiae. False negative isolates were 2.2% and 1.5% before and after adjudication, respectively. Herpes simplex virus 1 and 2, enterovirus and Cryptococcus neoformans/gattii had the highest proportions of false negative determinations. False negative C. neoformans/gattii were mostly patients with positive antigen titres, on treatment or cleared disease.ConclusionsThe currently available literature suggests that the ME panel has high diagnostic accuracy. However, the decision for implementation should be individualized based on the needs of the patient population, the capabilities of the laboratory, and the knowledge of the healthcare providers that will utilize the test.