Positive predictive value of myositis antibody line blot testing in patients with suspected idiopathic inflammatory myopathy.

INTRODUCTION/AIMS: Line blot (LB) is in widespread use for myositis antibody detection. Yet, studies of its positive predictive value (PPV) in patients with suspected idiopathic inflammatory myopathy (IIM), which would be of particular relevance to neuromuscular clinicians, are lacking. We aimed to determine the PPV of myositis antibody LB testing in patients with suspected IIM, and examine whether PPV was significantly impacted by intensity of antibody positivity. METHODS: This was a retrospective study of patients who underwent myositis antibody LB testing for suspected IIM between March 2019 and August 2022. RESULTS: Of 70 patients who underwent testing for suspected IIM and had positive myositis antibody LB results, 43 (61%) were female and the median age was 61 years (range: 10-83 years). Forty-four were classified as true-positives, yielding a PPV of 63%. The PPV of patients with weak-positive myositis antibody results (14/30, 47%) was significantly lower than the PPV of patients with moderate-positive or strong-positive myositis antibody results (30/40, 75%) (p = .02). DISCUSSION: Our study found that myositis antibody LB testing in patients with suspected IIM had a modest PPV, underscoring the need for antibody interpretation in the context of all available clinical and ancillary test data to avoid misdiagnosis. The significantly lower PPV in patients with weak-positive results emphasizes the particular importance of clinical correlation in such patients. Further study into the diagnostic performance of various LBs for myositis antibody detection is needed to inform their interpretation in clinical practice.

Comparative methods for quantifying plasma biomarkers in Alzheimer's disease: Implications for the next frontier in cerebral amyloid angiopathy diagnostics.

Plasma amyloid beta (Aß) and tau are emerging as accessible biomarkers for Alzheimer's disease (AD). However, many assays exist with variable test performances, highlighting the need for a comparative assessment to identify the most valid assays for future use in AD and to apply to other settings in which the same biomarkers may be useful, namely, cerebral amyloid angiopathy (CAA). CAA is a progressive cerebrovascular disease characterized by deposition of Aß40 and Aß42 in cortical and leptomeningeal vessels. Novel immunotherapies for AD can induce amyloid-related imaging abnormalities resembling CAA-related inflammation. Few studies have evaluated plasma biomarkers in CAA. Identifying a CAA signature could facilitate diagnosis, prognosis, and a safer selection of patients with AD for emerging immunotherapies. This review evaluates studies that compare the diagnostic test performance of plasma biomarker techniques in AD and cerebrovascular and plasma biomarker profiles of CAA; it also discusses novel hypotheses and future avenues for plasma biomarker research in CAA.

Concordance between the BD Onclarity and Roche cobas assays for detection of HPV DNA in a Chinese population.

As cervical cancer screening shifts from cytology to human papillomavirus (HPV) testing, a major issue involves validating more HPV tests. In recent years, some HPV tests are used for clinical performance verification in China. The purpose of this study was to explore whether the BD Onclarity (Becton, Dickinson and Company)HPV assay differs from the Roche cobas (Roche Molecular Systems)HPV assay, as determined using 944 cervical samples, including 588 with sequencing results. In the nucleic acid assay accuracy verification, the assays showed excellent concordance for detection of HPV16 (κ = 0.93, 95% confidence interval [CI]: 0.89-0.97) and HPV18 (κ = 0.90, 95% CI: 0.83-0.97), and very good concordance for the 12 other high-risk types (HPV31/33/35/39/45/51/52/56/58/59/66/68, κ = 0.79, 95% CI: 0.75-0.83). The overall agreement for HPV DNA detection between Onclarity and cobas was very good (κ = 0.7755). No difference for ≥CIN2 sensitivity was observed between Onclarity and cobas (both 96.5%), whereas the ≥CIN2 specificity for detection of Onclarity (16.6%, 95% CI: 13.7-19.9) was higher than that of cobas (11.5%, 95% CI: 9.1-14.5). Onclarity exhibited comparable screening performance and triage efficiency compared to cobas in the detection of cervical disease in Chinese women.

Thyroglobulin doubling time offers a better threshold than thyroglobulin level for selecting optimal candidates to undergo localizing [18F]FDG PET/CT in non-iodine avid differentiated thyroid carcinoma.

PURPOSE: To investigate the potential role of serum thyroglobulin doubling time (TgDT) in predicting 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT results in patients affected by differentiated thyroid carcinoma (DTC) who demonstrated a combination of positive Tg but a negative [131I] whole-body scan ([131I]-WBS). MATERIALS AND METHODS: Inclusion criteria were (1) prior [131I] treatment for DTC, (2) negative subsequent [131I]-WBS, (3) no interfering anti-Tg antibodies, (4) three consecutive Tg measurements under the thyroid hormone replacement therapy to calculate TgDT before 2-[18F]FDG PET/CT, and (5) at least 6 months of clinical and/or imaging follow-up to ascertain the diagnosis. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to identify the optimal cutoff point for the last stimulated Tg and TgDT prior to [18F]FDG PET/CT. RESULTS: One hundred and thirteen patients were included. Seventy-four (65%) patients had positive [18F]FDG PET/CT for DTC recurrence, while the remaining 39 (35%) negative. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of [18F]FDG PET/CT were 92%, 94%, 97%, 87%, and 93%. Patients with positive [18F]FDG PET/CT had higher Tg and TgDT than those with negative PET/CT. ROC curve analysis revealed an optimal Tg cutoff of 19 ng/mL (sensitivity 78%, specificity 85%, AUC = 0.844) and TgDT of 2.5 years (sensitivity 93%, specificity 87%, AUC = 0.911). TgDT threshold of 2.5 years predicted significantly (p = 0.023) better than Tg level PET/CT results. CONCLUSIONS: The diagnostic performance of [18F]FDG PET/CT could be significantly improved when TgDT is less than or equal to 2.5 years, as compared with using the absolute Tg level.

Clinical performance of Onclarity HPV assay and Cobas HPV test in detection of cervical precancer and cancer in Chinese women.

OBJECTIVE: The Roche Cobas (Cobas) and BD Onclarity (Onclarity) human papillomavirus (HPV) assays are convenient, PCR-based, HPV DNA tests; currently, data on performance of Onclarity in Chinese women is limited. We aimed to evaluate the clinical performance of Onclarity for detecting cervical lesions in Chinese women. METHODS: In total, 1122 women were enrolled into this study. Exfoliated cervical cells were collected in PreservCyt medium and were tested using Cobas and Onclarity. Cytology and histology were interpreted by senior cytologists and a panel of pathologists, respectively, at Cancer Hospital, Chinese Academy of Medical Sciences. RESULTS: The assays showed excellent concordance for HPV16 (kappa = 0.91, 95% CI: 0.85-0.97) and for 12 other high-risk types (HPV31/33/35/39/45/51/52/56/58/59/66/68, kappa = 0.84, 95% CI: 0.78-0.90), and very good concordance for HPV18 (kappa = 0.75, 95% CI: 0.69-0.81). No difference for ≥CIN2 sensitivity was observed between Onclarity and Cobas (both 90.5%); and the

Clinical Usefulness of Self-Rated Olfactory Performance-A Data Science-Based Assessment of 6000 Patients.

In clinical practice, with its time constraints, a frequent conclusion is that asking about the ability to smell may suffice to detect olfactory problems. To address this question systematically, 6049 subjects were asked about how well they can perceive odors, with 5 possible responses. Participants presented at a University Department of Otorhinolaryngology, where olfactory testing was part of the routine investigation performed in patients receiving surgery at the clinic (for various reasons). According to an odor identification test, 1227 subjects had functional anosmia and 3113 were labeled with normosmia. Measures of laboratory test performance were used to assess the success of self-estimates to capture the olfactory diagnosis. Ratings of the olfactory function as absent or impaired provided the diagnosis of anosmia at a balanced accuracy of 79%, whereas ratings of good or excellent indicated normosmia at a balanced accuracy of 64.6%. The number of incorrect judgments of anosmia increased with age, whereas false negative self-estimates of normosmia became rarer with increasing age. The subject's sex was irrelevant in this context. Thus, when asking the question "How well can you smell odors?" and querying standardized responses, fairly accurate information can be obtained about whether or not the subject can smell. However, this has to be completed with the almost 30% (355 subjects) of anosmic patients who judged their ability to smell as at least "average." Thus, olfactory testing using reliable and validated tests appears indispensable.

Assessing the performance of a Fasciola gigantica serum antibody ELISA to estimate prevalence in cattle in Cameroon.

BACKGROUND: Cattle rearing in Cameroon is both economically and culturally important, however parasitic diseases detrimentally impact cattle productivity. In sub-Saharan Africa bovine fasciolosis is generally attributed to F. gigantica, although understanding of Fasciola species present and local epidemiology in individual countries is patchy. Partly limited by the lack of representative surveys and understanding of diagnostic test perfromance in local cattle populations. The aims of this paper were to determine the Fasciola species infecting cattle, develop a species specific serum antibody ELISA, assess the performance of the ELISA and use it to assess the prevalence of F. gigantica exposure in two important cattle-rearing areas of Cameroon. RESULTS: A random sample of Fasciola parasites were collected and were all identified as F. gigantica (100%, CI:94.0-100%, n = 60) using RAPD-PCR analysis. A F. gigantica antibody ELISA was developed and initially a diagnostic cut-off was determined using a sample of known positive and negative cattle. The initial cut-off was used as starting point to estimate an optimal cut-off to estimate the best combination of sensitivity and specificity. This was achieved through sampling a naturally infected population with known infection status (cattle slaughtered at Bamenda abattoir, North West Region (n = 1112) and Ngaoundere abattoir, Vina Division, Adamawa Region (n = 776) in Cameroon). These cattle were tested and results analysed using a Bayesian non-gold standard method. The optimal cut-off was 23.5, which gave a sensitivity of 65.3% and a specificity of 65.2%. The prevalence of exposure to F. gigantica was higher in cattle in Ngaoundere (56.4% CI: 50.2-60.0%) than Bamenda (0.6% CI: 0.0-1.4%). CONCLUSION: Fasciola gigantica was identified as the predominant Fasciola species in Cameroon. Although the sensitivity and specificity F. gigantica antibody ELISA requires improvement, the test has shown to be a potentially useful tool in epidemiological studies. Highlighting the need for better understanding of the impact of F. gigantica infections on cattle production in Cameroon to improve cattle production in the pastoral systems of Central-West Africa. This paper also highlights that non-gold standard latent class methods are useful for assessing diagnostic test performance in naturally-infected animal populations in resource limited settings.

Why being an expert - despite xpert -remains crucial for children in high TB burden settings.

BACKGROUND: As access to Xpert expands in high TB-burden settings, its performance against clinically diagnosed TB as a reference standard provides important insight as the majority of childhood TB is bacteriologically unconfirmed. We aim to describe the characteristics and outcomes of children with presumptive TB and TB disease, and assess performance of Xpert under programmatic conditions against a clinical diagnosis of TB as a reference standard. METHODS: Retrospective review of children evaluated for presumptive TB in Mbeya, Tanzania. Baseline characteristics were compared by TB disease status and, for patients diagnosed with TB, by TB confirmation status using Wilcoxon rank sum test for continuous variables and the Chi-square test for categorical variables. Sensitivity and specificity were calculated to assess the performance of Xpert, smear, and culture against clinical TB. Kappa statistics were calculated to assess agreement between Xpert and smear to culture. RESULTS: Among children (N = 455) evaluated for presumptive TB, 70.3% (320/455) had Xpert and 62.8% (286/455) had culture performed on sputa. 34.5% (157/455) were diagnosed with TB: 80.3% (126/157) pulmonary TB, 13.4% (21/157) bacteriologically confirmed, 53.5% (84/157) HIV positive, and 48.4% (76/157) inpatients. Compared to the reference standard of clinical diagnosis, sensitivity of Xpert was 8% (95% CI 4-15), smear 6% (95% CI 3-12) and culture 16% (95% CI 9-24), and did not differ based on patient disposition, nutrition or HIV status. CONCLUSION: Despite access to Xpert, the majority of children with presumptive TB were treated based on clinical diagnosis. Reflecting the reality of clinical practice in resource limited settings, new diagnostics such as Xpert serve as important adjunctive tests but will not obviate the need for astute clinicians and comprehensive diagnostic algorithms.

A meta-analysis of diagnostic test performance of peripheral arterial tonometry studies.

STUDY OBJECTIVES: The objective of this meta-analysis was to analyze agreement in apnea-hypopnea index (AHI) determination between peripheral arterial tonometry (PAT) and polysomnography (PSG) studies. METHODS: Mean AHI bias and standard deviation extracted from Bland-Altman plots reported in studies were pooled in a meta-analysis, which was then used to calculate percentage errors of limit agreement in AHI determination by PAT using PSG AHI as the reference. Individual participant data (where reported in studies) were used to compute Cohen's kappa to assess agreement between PSG and PAT on sleep apnea severity and for computing the sensitivity and specificity of PAT at different AHI thresholds using PSG AHI as the reference. RESULTS: From 17 studies and 1,318 participants (all underwent simultaneous PSG and use of the WatchPAT device), a pooled mean AHI bias of 0.30 (standard error [SE], 0.74) and a WatchPAT AHI percentage error of 230% was calculated. The meta-analysis of Cohen's kappa for agreement between PSG and WatchPAT studies for classifying patients with no sleep apnea, mild, moderate, or severe sleep apnea severity was 0.45 (SE, 0.06), 0.29 (SE, 0.05), 0.25 (SE, 0.07), and 0.64 (SE, 0.05), respectively. At AHI thresholds of 5, 15 and 30 events/h, WatchPAT studies showed pooled sensitivities and specificities of 94.11% and 43.47%, 92.21% and 72.39%, and 74.11% and 87.10%, respectively. Likelihood ratios were not significant at any AHI threshold. CONCLUSIONS: The results of this meta-analysis suggest clinically significant discordance between WatchPAT and PSG measurements of AHI, significant sleep apnea severity misclassification by PAT studies, and poor diagnostic test performance. CITATION: Iftikhar IH, Finch CE, Shah AS, Augunstein CA, Ioachimescu OC. A meta-analysis of diagnostic test performance of peripheral arterial tonometry studies. J Clin Sleep Med. 2022;18(4):1093-1102.

Bovine Tuberculosis Antemortem Diagnostic Test Agreement and Disagreement in a Naturally Infected African Cattle Population.

The interferon-gamma (IFN-γ) assay and single comparative cervical skin test (SCITT) are used to estimate bovine tuberculosis (bTB) prevalence globally. Prevalence estimates of bTB, caused by Mycobacterium bovis, are poorly quantified in many Sub-Saharan African (SSA) cattle populations. Furthermore, antemortem diagnostic performance can vary at different stages of bTB pathogenesis and in different cattle populations. In this study, we aim to explore the level of agreement and disagreement between the IFN-γ assay and SCITT test, along with the drivers for disagreement, in a naturally infected African cattle population. In, 2013, a pastoral cattle population was sampled using a stratified clustered cross-sectional study in Cameroon. A total of 100 pastoral cattle herds in the North West Region (NWR) and the Vina Division (VIN) were sampled totalling 1,448 cattle. Individual animal data and herd-level data were collected, and animals were screened using both the IFN-γ assay and SCITT. Serological ELISAs were used to detect exposure to immunosuppressing co-infections. Agreement analyses were used to compare the performance between the two bTB diagnostic tests, and multivariable mixed-effects logistic regression models (MLR) were developed to investigate the two forms of IFN-γ assay and SCITT binary disagreement. Best agreement using the Cohen's κ statistic, between the SCITT (>2 mm) and the IFN-γ assay implied a 'fair-moderate' agreement for the NWR [κ = 0.42 (95%CI: 0.31-0.53)] and 'poor-moderate' for the VIN [κ = 0.33 (95% CI: 0.18-0.47)]. The main test disagreement was the animals testing positive on the IFN-γ assay and negative by the SCITT. From MLR modeling, adults (adults OR: 7.57; older adults OR = 7.21), females (OR = 0.50), bovine leucosis (OR = 2.30), and paratuberculosis positivity (OR = 6.54) were associated with IFN-γ-positive/SCITT-negative disagreement. Subsets to investigate diagnostic test disagreement for being SCITT-positive and IFN-γ-negative also identified that adults (adults OR = 15.74; older adults OR = 9.18) were associated with IFN-γ-negative/SCITT-positive disagreement. We demonstrate that individual or combined use of the IFN-γ assay and SCITT can lead to a large variation in bTB prevalence estimates. Considering that animal level factors were associated with disagreement between the IFN-γ assay and SCITT in this study, future work should further investigate their impact on diagnostic test performance to develop the approaches to improve SSA prevalence estimates.

Fifty years of Shannon information theory in assessing the accuracy and agreement of diagnostic tests.

Since 1948, Shannon theoretic methods for modeling information have found a wide range of applications in several areas where information plays a key role, which goes well beyond the original scopes for which they have been conceived, namely data compression and error correction over a noisy channel. Among other uses, these methods have been applied in the broad field of medical diagnostics since the 1970s, to quantify diagnostic information, to evaluate diagnostic test performance, but also to be used as technical tools in image processing and registration. This review illustrates the main contributions in assessing the accuracy of diagnostic tests and the agreement between raters, focusing on diagnostic test performance measurements and paired agreement evaluation. This work also presents a recent unified, coherent, and hopefully, final information-theoretical approach to deal with the flows of information involved among the patient, the diagnostic test performed to appraise the state of disease, and the raters who are checking the test results. The approach is assessed by considering two case studies: the first one is related to evaluating extra-prostatic cancers; the second concerns the quality of rapid tests for COVID-19 detection.

Anorectal manometry to diagnose dyssynergic defecation: Systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: Chronic constipation is a common condition, and dyssynergic defecation underlies up to 40% of cases. Anorectal manometry is recommended to assess for dyssynergic defecation among chronically constipated patients but remains poorly standardized. We aimed to evaluate the diagnostic accuracy of anorectal manometry and determine optimal testing parameters. METHODS: We performed a systematic review with meta-analysis of diagnostic test accuracy including cohort studies of chronically constipated patients and case-control studies of patients with dyssynergic defecation or healthy controls. Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI). KEY RESULTS: A total of 15 studies comprising 2140 patients were included. Including all studies (estimating optimal diagnostic accuracy), the AUC was 0.78 [95% CI 0.72-0.82], summary sensitivity was 79% [61%-90%], and summary specificity was 64% [44%-79%] to diagnose dyssynergic defecation. In cohort studies only (estimating real-world diagnostic accuracy), the AUC was 0.72 [0.66-0.77], summary sensitivity was 86% [64%-95%], and summary specificity was 49% [30%-68%]. Employing three consecutive simulated defecation attempts improved sensitivity to 94%. A fourth simulated defecation maneuver with air insufflation may improve accuracy. Measuring anorectal pressures to identify complex dyssynergic patterns did not improve real-world diagnostic accuracy estimates over anal pressure measurement alone. Choice of manometry system did not impact diagnostic accuracy. CONCLUSIONS & INFERENCES: Following the current iteration of the London consensus protocol (three simulated defecation attempts measuring anal relaxation), the role of anorectal manometry in evaluating dyssynergic defecation appears limited. Future iterations of this protocol may improve diagnostic accuracy.

Development, deployment and in-field demonstration of mobile coronavirus SARS-CoV-2 Nucleic acid amplification test.

Introduction. The evolving SARS-CoV-2 coronavirus pandemic presents a series of challenges to clinical diagnostic services. Many proprietary PCR platforms deployed outside centralised laboratories have limited capacity to upscale when public health demands increase. We set out to develop and validate an open-platform mobile laboratory for remote area COVID-19 diagnosis, with a subsequent field trial.Gap Statement. In regional Western Australia, molecular diagnostic support is limited to near point-of-care devices. We therefore aimed to demonstrate open-platform capability in a rapidly deployable format within the context of the COVID-19 pandemic.Methodology. We compared, selected and validated components of a SARS-CoV-2 RT-PCR assay in order to establish a portable molecular diagnostics laboratory. The optimal combination of PCR assay equipment, reagents and consumables required for operation to national standards in regional laboratories was identified. This comprised RNA extraction and purification (QuickGene-480, Kurabo, Japan), a duplex RT-PCR assay (Logix Smart COVID-19, Co-Diagnostics, USA), a Myra liquid handling robot (Biomolecular Systems, Australia) and a magnetic induction thermal cycler (MIC, Biomolecular Systems).Results The 95 and 99% limits of detection were 1.01 copies µl-1 (5.05 copies per reaction) and 2.80 copies µl-1 (14.00 copies per reaction) respectively. The Co-Diagnostics assay amplified both SARS-CoV-1 and -2 RNA but showed no other cross reactivity. Qualitative results aligned with the reference laboratory SARS-CoV-2 assay (sensitivity 100% [95 % CI 96.48-100%], specificity 100% [95% CI 96.52-100%]). In field trials, the laboratory was operational within an hour of arrival on-site, can process up to 36 samples simultaneously, produces results in two and a half hours from specimen reception, and performed well during six consecutive runs during a 1 week deployment.Conclusion. Our mobile laboratory enables an adaptive response to increased test demand, and unlike many proprietary point-of-care PCR systems, rapid substitution with an alternative assay if gene targets change or reagent supply chains fail. We envisage operation of this RT-PCR assay as a standby capability to meet varying regional test demands under public health emergency operations guidance.

Correlation study of thyroid nodule cytopathology and histopathology at two institutions in Jordan.

BACKGROUND: Fine-needle aspiration (FNA) plays a fundamental role in determining the appropriate management for patients presenting with thyroid nodules. AIMS: The aims of this study are to evaluate thyroid FNA test performance parameters through a cytohistological correlation. MATERIALS AND METHODS: A retrospective analysis of all thyroid FNAs received over a period of 18 months was carried out. The findings were compared to their subsequent definite diagnoses on surgical specimens as well as to their follow-up repeat FNA results. A total of 499 thyroid FNAs were collected and reviewed against The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The percentage of each diagnostic category was calculated, and the implied risk of malignancy was determined by comparing the cytology results to their definite diagnoses obtained on the resection specimens. Analytical procedures were performed using Microsoft Excel. RESULTS: Out of 499 thyroid FNAs, a benign interpretation was found in 273 patients (54.7%), atypia of undetermined significance in 81 (16.2%), follicular neoplasm in 20 (4%), suspicious for malignancy in 36 (7.2%), malignant in 32 (6.4%) and were nondiagnostic in 57 patients (11.4%). Only 101 patients (20.2%) underwent surgical resection and 47 (9.4%) underwent a follow-up FNA. After cytohistological correlation, FNA test performance, calculated by excluding the inadequate and undetermined categories revealed test sensitivity, specificity, and diagnostic accuracy of 95.6%, 54.8%, and 78.9%, respectively. The positive predictive value was 75.4%, and the negative predictive value was 89.5%. CONCLUSIONS: Our results are comparable to those previously published figures. The rate of atypia of undetermined significance/follicular lesion of undetermined significance is higher than what is currently recommended in TBSRTC.

Designing Radiology Outcomes Studies-Essential Principles.

Health outcomes research is essential to align radiology with current standards of high-value patient care, through the assessment of end results of diagnostic tests, interventions, or policy on patient health. To bridge studies of diagnostic test accuracy and health outcomes research, key considerations include: (1) how to determine when a diagnostic test merits evaluation of impact on outcomes, (2) when study of intermediate/surrogate outcomes can be useful, (3) how to consider the possible harms as well as potential benefits of a test, and (4) how to integrate evidence of an imaging test's efficacy/effectiveness with clinical data to assess outcomes. Due to challenges in conducting studies of long-term outcomes consequent to imaging use, intermediate health outcomes may capture a test's impact on successful diagnosis and therapy, and can provide readily measurable, incremental insights into the role of imaging in health-care delivery and efficiency. In an era marked by recognition of quality and value of care, outcomes research will provide essential evidence to inform radiologists' guidance of imaging use toward improved patient care, creation of clinical guidelines, and policy decisions.

Field application of immunoassays for the detection of Mycobacterium bovis infection in the African buffalo (Syncerus caffer).

The African buffalo (Syncerus caffer) is considered the most important maintenance host of bovine tuberculosis (BTB) in wildlife in Southern Africa. The diagnosis of Mycobacterium bovis infection in this species mostly relies on the single intradermal comparative tuberculin test (SICTT). As an alternative, the BOVIGAM® 1G, an interferon-gamma (IFN-γ) release assay, is frequently used. The test performance of cell-mediated immunity (CMI-) and humoral immunity (HI-) based assays for the detection of M. bovis infections in buffaloes was compared to identify the test or test combination that provided the highest sensitivity in the study. Buffaloes were sampled during the annual BTB SICTT testing in the Hluhluwe-iMfolozi-Park (KwaZulu-Natal, South Africa) during June 2013. A total of 35 animals were subjected to the SICTT, 13 of these tested positive and one showed an inconclusive reaction. CMI-based assays (BOVIGAM® 1G (B1G) and BOVIGAM® 2G (B2G)) as well as a serological assay (IDEXX TB ELISA) were used to further investigate and compare immune responsiveness. Thirteen SICTT positive buffaloes and one inconclusive reactor were slaughtered and a post-mortem (PM) examination was conducted to confirm BTB. Lesions characteristic of BTB were found in 8/14 animals (57.1%). Test results of individual assays were compared with serial and parallel test interpretation and the sensitivity was calculated as a percentage of test positives out of the number of SICTT positive animals with granulomatous lesions (relative sensitivity). The B1G assay showed the highest individual sensitivity (100%; 8/8) followed by the B2G assay (75%; 6/8) and the IDEXX TB ELISA (37.5%; 3/8). Therefore, using in parallel interpretation, any combination with the B1G showed a sensitivity of 100% (8/8), whereas combinations with the B2G showed a 75% sensitivity (6/8). Out of the 21 SICTT negative animals, 7 animals showed responsiveness in the B2G or IDEXX TB ELISA. In conclusion, this study has shown that the BOVIGAM® IFN-γ assay had the highest test performance.

Multiplex PCR testing for nine different sexually transmitted infections.

Current sexually transmitted infection (STI) testing is not optimal due to delays in reporting or missed diagnoses due to a lack of comprehensive testing. The FilmArray® (BioFire Diagnostics, LLC, Salt Lake City, Utah) is a user-friendly, fully automated, multiplex PCR system that is being developed for rapid point-of-care use. A research-use-only STI panel including multiple PCR primer sets for each organism was designed to detect Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Trichomonas vaginalis, Mycoplasma genitalium, Ureaplasma urealyticum, Haemophilus ducreyi, and herpes simplex virus (HSV) types 1 and 2. Standard clinical testing included Gram stain, nucleic acid amplification, wet mount examination, herpes simplex virus culture, and syphilis IgG. Standard clinical tests were not available for all the organisms tested by the FilmArray STI panel. Two hundred and ninety-five clinical specimens from 190 subjects were directly compared to standard testing. Urine (n = 146), urethral/cervical swabs (31), oral swabs (60), rectal swabs (43), and ulcer swabs (15) were tested. Among the tested samples, FilmArray detected C. trachomatis in 39 (13%), N. gonorrhoeae in 20 (7%), T. vaginalis in nine (3%), HSV 1 in five (2%), HSV 2 in five (2%), U. urealyticum in 36 (12%), M. genitalium in eight (3%), and T. pallidum in 11 (4%). Concordance between the FilmArray STI panel and standard nucleic acid amplification testing for C. trachomatis was 98% and for N. gonorrhoeae was 97%. Multiplex PCR STI testing has the potential to improve public health by providing rapid, sensitive, and reliable results within the clinic or nearby laboratory.

Informational analysis: a Shannon theoretic approach to measure the performance of a diagnostic test.

Diagnostic test accuracy, based on sensitivity, specificity, positive/negative predictive values (dichotomous case), and on ROC analysis (continuous case), should be expressed with a single, coherent index. We propose to modelize the diagnostic test as a flow of information between the disease, that is, a hidden state of the patient, and the physicians. We assume that (1) sensitivity, specificity, and false-positive/false-negative rates are the probabilities of a binary asymmetric channel; (2) the diagnostic channel information is measured by mutual information. We introduce two summary measures of accuracy, namely the information ratio (IR) for the dichotomous case, and the global information ratio (GIR) for the continuous case. We apply our model to a study by Pisano et al. (N Engl J Med 353(17):1773-1783, 2005), who compared digital versus film mammography, in diagnosing breast cancer in a screening population of 42,760 women. In film mammography, the maximum IR (0.178) corresponds to the standard cutoff of sensitivity and specificity provided by the ROC analysis (GIR 0.200). Maximum IR and GIR for digital mammography are higher (0.201 and 0.229, respectively), but IR corresponds to a cutoff with higher sensitivity but lower specificity, thus suggesting that larger information provided by digital mammography carries the risk of more false-positive cases.