Rate Of False-positive Results Research Articles

Incidence of Inborn Errors of Metabolism and Endocrine Disorders Among 40965 Newborn Infants at Riyadh Second Health Cluster of the Ministry of Health Saudi Arabia.

Inborn errors of metabolism (IEM) and endocrine disorders are common genetic conditions in the Saudi population with the incidence rate often underestimated. Newborn screening (NBS) using various disease panels provides the first line in the early detection and intervention among infants with a high risk of IEM. Here we aim to assess the incidence of screening disorders and provide an overview of the NBS program at the Ministry of Health Tertiary Care King Fahad Medical City. Dried blood spots (DBS) from 40,965 newborn infants collected on the second day after birth were analyzed for 20 disorders. The total number of positive screen ("repeat") samples over 10 years was about 1% (n = 382/40,965). The true positive result rate was 15.3% (n = 46/301) with the recall rates of individual disorders ranging from 0.26% (95% CI, 0.17-0.69) to 2.6% (95% CI, 2.19-3.05). The false positive result rate was 84.7% (n = 255/301) with biotinidase activity found to be the most common cause of the second sample repeat. The overall incidence of the screened diseases was 1:891 (95% CI, 11.61-12.47). CH and CAH are the most prevalent among endocrine disorders with an incidence of 1:4097 (95% CI, 2.19-3.05), and PA and ASA among the IEM with an incidence of 1:10,241 (95% CI, 0.09-0.95). In summary, we provide updated data and our experience on the incidence of various IEM and endocrine disorders among the Saudi population, highlight the role of false positive results of biotinidase activity that can increase the recall rate and lead to overestimation of the incidence data, and recommend multicenter studies to achieve a successful national NBS program.

Synovial calprotectin in prosthetic joint infection. A systematic review and meta-analysis of the literature.

Calprotectin is a protein endowed with antimicrobial properties, rendering it a distinctive marker for infection. Two methods are currently available for the assay of calprotectin: the enzyme-linked immunosorbent assay (ELISA) and the lateral flow test (LFT). We aimed to assess the diagnostic accuracy of synovial fluid calprotectin and to compare the accuracy of the laboratory-based test and the qualitative assessment for the diagnosis of hip and knee prosthetic infection. We searched (from inception to November 2023) MEDLINE, Scopus, EMBASE, Web of Science, and Cochrane for studies on calprotectin in the diagnosis of periprosthetic joint infection (PJI). Sensitivity, specificity, positive and negative likelihood ratio (LR), and diagnostic odds ratio were analyzed. The receiver-operating curve for each method was calculated. We included 14 articles in our meta-analysis, including 902 patients who underwent total hip and knee arthroplasties revision; 331 (37%) had a joint infection according to MSIS, MSIS-modified criteria, ICM 2018 and EBJIS 2021. Considering the false-positive result rate of 6% and false-negative result rate of 7%, pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.93 (0.91-0.95), respectively. The area under the curve (AUC) was 0.93 (95% CI 0.91-0.94). No statistical differences in terms of sensitivity and specificity were found between ELISA and LFT. The pooled sensitivity and specificity of the two calprotectin assessment methods were: LFT 0.90 (95% CI 0.869-0.935) and 0.92 (95% CI 0.894-0.941), respectively; ELISA 0.96 (95% CI 0.914-0.986) and 0.97 (95% CI 0.934-0.988), respectively. The diagnostic odds ratio of the ELISA was superior to that of the LFT (906.6667, 95% CI 271.2686-3030.3712 versus 113.8886, 95% CI 70.4001-184.2414; p < 0.001). The AUC for ELISA and LFT was 0.968 (95% CI 0.944-0.984) and 0.915 (95% CI 0.895-0.933), respectively. Detection of synovial calprotectin is an accurate test for diagnosis of hip and knee prosthetic infections. The diagnostic accuracy of the two calprotectin assessment methods is almost comparable. The LFT is a valid, rapid, and more available diagnostic tool, particularly to rule out PJI.

Herd-level true seroprevalence of caseous lymphadenitis and paratuberculosis in the goat population of Poland

A large-scale study was carried out in the Polish goat population in 2014–2021 to determine the herd-level true seroprevalence (HTP) of caseous lymphadenitis (CLA) caused by Corynebacterium pseudotuberculosis (Cp) and paratuberculosis (PTB) caused by Mycobacterium avium ssp. paratuberculosis (Map). Two-stage cluster sampling was applied to herds counting at least 20 adult goats (aged >1 year) and in each herd all males and 10–13 females were tested. At least one seropositive goat regardless of its sex was necessary to consider the herd as infected. HTP was estimated using the Bayesian approach with the Gibbs sampler in the EpiTools and reported as the median and 95 % credibility interval (95 % CrI). A total of 1282 adult goats from 86 herds were serologically tested using two commercial ELISAs (Cp-ELISA and Map-ELISA). At least 1 seropositive result of Cp-ELISA and Map-ELISA was obtained in 73/86 herds (84.9 %) and 40/86 herds (46.5 %), respectively. HTP of CLA was estimated at 73.3 % (95 % CrI: 65.0 %, 80.4 %) and HTP of PTB was estimated at 42.9 % (95 % CrI: 25.8 %, 58.0 %). There was a significant positive association between the occurrence of CLA and PTB in the herds (odds ratio 6.0, 95 % confidence interval: 1.2, 28.8; p = 0.010). Probability of the seropositive result for PTB was also significantly higher in Cp-seropositive goats than in Cp-seronegative goats (odds ratio 3.9, 95 % confidence interval: 2.4, 6.3; p < 0.001) which could indicate either a higher risk of co-infection or a higher rate of false positive results for PTB in Cp-positive goats. To investigate this issue, optical densities obtained in Map-ELISA were compared between Cp-positive and Cp-negative goats and results of Map-ELISA were adjusted accordingly. Map-negative sera from Cp-positive goats turned out to have significantly higher optical densities than Map-negative sera from Cp-negative goats (p < 0.001). After the adjustment, the herd-level apparent seroprevalence of PTB was 41.9 % (36/86 herds) so it still fell within the 95 % CrI of HTP of PTB calculated before the adjustment. Concluding, CLA appears to be widespread in the Polish goat population. In many of them it may be subclinical at the moment, however will likely emerge in the future as the disease follows cyclic pattern in Poland. On the other hand, given the total lack of clinical PTB in Polish goats, an explanation for a high HTP of PTB remains unclear and warrants further studies using tests of higher analytical specificity than ELISA.

Evaluation of cost-effective multiple cancer early detection with extremely low coverage whole genome sequencing from plasma.

10538 Background: Cancer continues to be a significant global health concern, with approximately 19.3 million new cases diagnosed and 10.0 million cancer-related deaths reported in 2020. Multi-cancer early detection (MCED) test using the peripheral blood offers a great opportunity to improve the current cancer screening tests with better performance and benefit-to-harm balance. Methods: Here we introduce a novel MCED test called HIFI-PROF, which utilizes extremely low pass whole-genome sequencing (median coverage of 0.6X) to create a multi-dimensional fragmentation signatures model through machine learning approach. HIFI-PROF was developed to detect and localize six types of cancer (colorectal, pancreas, liver, lung, esophagus and gastric cancer). Results: The study included a total of 1,487 participants, comprising 235 colorectal cancers, 227 pancreatic cancers, 150 liver cancers, 125 lung cancers, 107 esophageal cancers, 106 gastric cancers and 537 healthy volunteers. Most of the cancer cases were I/II stage patients (stage I: 38%, stage II: 35%, stage III: 23%, stage IV: 4%). The participants, stratified by age and clinical status, were divided into two sets: a training set (n=1,079) and a validation set (n=408).HIFI-PROF exhibited an excellent performance in the early detection of multiple cancer types, achieving a sensitivity of 87.58% at a specificity of 99.09% and identifying the tissue of origin (TOO) with an accuracy of 81.99%. The sensitivity rates for detecting cancer at different stages were also promising, with a sensitivity of 84.62% for stage I, 85.59% for stage II, 89.61% for stage III and 92.86% for stage IV. Conclusions: These results highlight the high sensitivity and specificity of HIFI-PROF in identifying cancer cases while maintaining a low rate of false-positive results. The use of HIFI-PROF offers a cost-effective MCED test with excellent performance. Such advancements will contribute to improve strategies for multi-cancer early detection, leading to more effective clinical interventions and better outcomes.

Effect of polygenic risk score for clinically significant prostate cancer in a screening program: The BARCODE 1 study results.

10500 Background: Incidence of prostate cancer (PCa) is increasing, but there is no internationally agreed population screening program. Studies using an age-based PSA approach show a high rate of false-positive results as well as over-diagnosis of indolent PCa. Genome wide association studies identify common germline variants to calculate a polygenic risk score (PRS) associated with PCa risk. The BARCODE1 study used PRS to target PCa screening to those at higher risk based on genotype. Methods: European men aged 55-69yrs were recruited via Primary Care in the UK. PRS was constructed by summing weighted risk alleles for 130 PCa risk variants using germline DNA from saliva samples via mailed kits. Men with a PRS &gt; 90th centile were invited for PCa screening using MRI and 12-core transperineal biopsy (including MRI fusion to target additional lesions where identified) irrespective of PSA result. Results: Invitation letters were sent to 40,292 men. 8,953 (22%) expressed an interest; 8,014 were eligible and sent a saliva kit. 6,644 consented; 6,393 were genotyped; 251 failed QC. A total of 6,142 participants had PRS calculated: 745 (12.1%) had a PRS &gt; 90th centile and were invited to screening. 558/745 participants attended screening (121 declined, 66 excluded on health grounds). 551 underwent MRI and 468 had prostate biopsy resulting in 187 (40.0%) diagnoses of PCa, overall PCa detection rate 2.8%. Mean age at diagnosis 64.1yrs (range 57-73; median 64). Using NCCN criteria (2023) 103/187 (55.1%) of cancers were Intermediate or High Risk; 40/187 (21.4%) were Intermediate Unfavourable/High/Very High Risk. 119/187 (63.6%) men had a PSA &lt;3.0ug/L; PPV of biopsy for PSA &gt; 3.0ug/L was 49.6%. PPV of MRI (presence of PI-RADS 3-5 lesion) 60.4%. PPV of PRS alone 40%. 103/187 (55.1%) had Gleason &gt;7; compared with 360/1014 (35.5%) p &lt; 0.001 in the PSA directed ERSPC study. Conclusions: A population PCa screening program using PRS risk-stratification enriches for clinically significant PCa requiring treatment. It detects a high proportion of clinically significant disease compared with PSA or MRI based screening programs and MRI missed a significant proportion (17-67%) of cancers found on biopsy. This is the first study to assess if this approach will be useful in population screening programs. Clinical trial information: NCT03857477 . [Table: see text]

School urinary screening program in Japan: history, outcomes, perspectives.

In Japan, pediatric urinary screening in schools for asymptomatic hematuria and proteinuria began in 1974 and has been very successful in detecting asymptomatic kidney diseases at an early stage. While the American Academy of Pediatrics recommended discontinuing urinalysis as a public health service in 2007, urinary screening in Japan has proven extremely successful in reducing the incidence of kidney failure with replacement therapy in children and young adults, especially through the early treatment of glomerulonephritis, such as immunoglobulin A nephropathy. Furthermore, the positivity rate on urinary screening in Japan is significantly lower than in the United States where the rate of false positive results is typically very high. Japan's seamless and efficient pediatric urinary screening may be a helpful example for other countries as well. However, the present investigation revealed several, unresolved problems with the system. For example, the methods used varied in terms of their cutoff point, additional examinations, and types of detailed testing. In Japan, various urinary screening methods are being tested to optimize the system for national use. Recently, the authors also recommended a system of detailed examinations, including beta-2 microglobulin testing and ultrasonography, to detect congenital anomalies of the kidney and urinary tract, the most common, underlying disease in kidney failure with replacement therapy, which is often overlooked until the symptoms have become grave. While school urinary screening has been ongoing for about 50 years and should be continued, improvements should also be made to it as needed.

The Common Carotid Artery in the Ultrasound Evaluation of Giant Cell Arteritis.

Vascular ultrasound is commonly used to diagnose giant cell arteritis (GCA). Most protocols include the temporal arteries and axillary arteries, but it is unclear which other arteries should be included. This study investigated whether inclusion of intima media thickness (IMT) of the common carotid artery (CCA) in the ultrasound evaluation of GCA improves the accuracy of the examination. We formed a fast-track clinic to use ultrasound to rapidly evaluate patients with suspected GCA. In this cohort study, patients referred for new concern for GCA received a vascular ultrasound for GCA with the temporal arteries and branches, the axillary artery, and CCA. We compared 57 patients with GCA and 86 patients without GCA. Three patients with GCA had isolated positive CCA between 1 and 1.49 mm, and 21 patients without GCA had isolated positive CCA IMT. At the 1.5-mm CCA cutoff, 4 patients without GCA had positive isolated CCA, and 1 patient with GCA had a positive isolated CCA. The sensitivity of ultrasound when adding carotid arteries to temporal and axillary arteries was 84.21% and specificity 65.12% at an intima media thickness (IMT) cutoff of ≥1 mm and 80.70% and 87.21%, respectively, at a cutoff of ≥1.5 mm. Measurement of the CCA IMT rarely contributed to the diagnosis of GCA and increased the rate of false-positive results. Our data suggest that the CCA should be excluded in the initial vascular artery ultrasound protocol for diagnosing GCA. If included, an IMT cutoff of higher than 1.0 mm should be used.

Comparison of plasma and blood cell samples in metagenomic next-generation sequencing for identification of the causative pathogens of fever

BackgroundMetagenomic next-generation sequencing (mNGS) of plasma DNA has become an attractive diagnostic method for infectious diseases; however, the rate of false-positive results is high. This study aims to evaluate the diagnostic accuracy of mNGS in plasma versus blood cell samples for immunocompromised children with febrile diseases. MethodsThe results of conventional microbiological test (CMT) and mNGS using plasma and blood cells in 106 patients with 128 episodes of febrile diseases from the Department of Hematology/Oncology were analyzed and described. ResultsThe positivity rates for CMT and mNGS of plasma and blood cells were 35.9 %, 84.4 % and 46.9 %, respectively (P < 0.001). Notably, mNGS identified multiple pathogens in a single specimen in 68.5 % of plasma samples and 38.3 % of blood cell samples (P < 0.001). Furthermore, plasma and blood cell mNGS identified causative pathogens in 58 and 46 cases, accounting for 53.7 % and 76.7 % of the mNGS-positive cases for each sample type, respectively (P = 0.002). By integrating results from both plasma and blood cell samples, causative pathogens were identified in 77 cases (60.2 %), enhancing sensitivity to 87.5 % but reducing specificity to 15.0 %, compared to plasma (65.9 % sensitivity and 20.0 % specificity) and blood cell samples (52.3 % sensitivity and 80.0 % specificity). ConclusionsmNGS of plasma is sensitive but has a high false-positive rate, while mNGS of blood cells has low sensitivity but higher specificity.

Categorization of continuous covariates and complex regression models—friends or foes in intersectionality research

ObjectivesTo reduce health inequities, it is important to identify intersections in characteristics of individuals subject to privilege or disadvantage. Different proposals for that have recently been published. One approach (1) considers models specified with first- and all second-order effects and another (2) the stratification based on multiple covariates; both categorize continuous covariates. A simulation study was conducted in order to review both methods with regard to identification of intersections showing true differences, rate of false-positive results, and generalizability to independent data compared to an established approach (3) of backward variable elimination according to Bayesian information criterion (BE-BIC) combined with splines. Study Design and SettingR software has been used to simulate the covariates age, sex, body mass index, education, and diabetes to examine their association with a continuous frailty score for osteoporosis using multiple linear regression. In setting 1, none of the covariates was associated with the frailty score, that is, only noise is present in the data. In setting 2, the covariates age, sex, and their interaction were associated with the frailty score, such that only females above 55 years formed an intersection associated with an increased frailty score. All approaches were compared under varying sample sizes (N = 200–3000) and signal-to-noise ratios (SNRs, 0.5–4) in 1000 replications. For model evaluation, bootstrap resampling was used. The models were fitted in internal learning data and then used to predict outcomes in the internal validation data. The mean squared error (MSE) was used for comparison and the frequency of false-positive findings calculated. ResultsIn setting 1, approaches 1 and 2 generated spurious effects in more than 90% of simulations across all sample sizes. In a smaller sample size, approach 3 (BE-BIC) selected 36.5% of the correct model, in larger sample size in 89.8% and always had a lower number of spurious effects. MSE in independent data was generally higher for approaches 1 and 2 when compared to 3. In setting 2, approach 1 selected most frequently the correct interaction but frequently showed spurious effects (>75%). Across all sample sizes and SNR, approach 3 generated least often spurious results and had lowest MSE in independent data. ConclusionCategorization of continuous covariates is detrimental to studies on intersectionality. Due to high and unrestricted model complexity, such approaches are prone to spurious effects and often lack interpretability. Approach 3 (BE-BIC) is considerably more robust against spurious findings, showed better generalizability to independent data, and can be used with most statistical software. For intersectionality research, we consider it most important to describe relevant differences between intersections and to avoid nonreproducible and spurious findings.

Colposcopic findings to study cervical changes in reproductive age group women using various contraceptives.

Colposcopy has a key role to play in see-and-treat programs for premalignant cervical lesions. The aim of the study/was to observe cervical changes with a colposcope using the Swede scoring system in fertile age group women using various contraceptives: conventional methods (barrier methods, coitus interruptus), oral contraceptives (OCPs), copper-T and bilateral tubectomy. The aim of the study was to observe and evaluate the colposcopic findings using the Swede scoring system for the diagnosis of premalignant/malignant lesions in reproductive age group women using various contraceptives. This was a prospective observational study, conducted among 200 women of reproductive age group using various contraceptives in a tertiary care institute in North India. PAP smear, direct visual examination, VIA (Visual Inspection with Acetic Acid) examination, colposcopic examination, and (biopsy if indicated) were done. The data were collected, and analysis was done using Microsoft Excel Office Software 2019 version 19.11 and epi info (CDC Atlanta) 7.23.1. Statistical analysis was done using percentages, mean, mode, median, standard deviation, Chi-square, Fisher's Test, and Anova Test. We found positive PAP (Papanicolaou test) smears in 61.50%, positive VIA examination in 9%, and positive findings in colposcopic examination in 28.50%, Swede score of 0-3 in 100% (0-91%, 1-2%, 2-6%, and 3-1%) and positive biopsy in 9% subjects. Malignant findings were observed in 1.00% of PAP smears. Colposcopic findings were CIN 1 (cervical intraepithelial neoplasia 1) in 8.5% and CIN 2 in 0.5% subjects. Swede score was zero in 91%, 1 in 2%, 2 in 6%, and 3 in 1% of subjects. HPE (histopathological examination) was chronic cervicitis in 8.50% and mild dysplasia/CIN 1 in 0.5%. No significant statistical associations between contraceptive choice and false-positive test results or disease prevalence was found in any group except Cu-T users p = 0.0184 (especially for CIN 2; p = 0.0109 and CIN 1 more in all groups than Cu-T users). Colposcopy had sensitivity 100%, specificity 91.46% (0/0 = 0%) PPV = 5.56%, NPV = 100%, Accuracy = 91.5% for detecting mild dysplasia/CIN-non-significant (p = 0.055). Our study had mainly low-grade lesions with 100% NPV. With increase in Swede Score, sensitivity increases but at the expense of specificity but it was statistically non-significant (p = 0.055). Our study may guide the rational use of colposcopy with Swede scoring for see-and-treat lesions, which is easy and with a low learning curve, as a tool for diagnosis but only in cases where indicated like unhealthy cervix because of the high rate of false-positive results. In low-grade lesions, it is highly useful to rule out the disease.

The best anti-HCV S/Co values for reflecting HCV infection in a university hospital in the eastern part of Turkey.

The measurement of hepatitis C virus (HCV) RNA is a test that requires high cost, advanced technique, and qualified personnel. Diagnosis and treatment of patients may be delayed due to the high rate of false-positive results. This study aims to predict true antibody positivity and viremia by determining the most appropriate anti-HCV signal-to-cutoff (S/Co) value reflecting HCV infection. The presence of anti-HCV antibodies and HCV RNA levels were examined in 72341 people who applied to the Mengücek Gazi Training and Research Hospital between January 2018 and December 2020. The anti-HCV levels were determined by using the Abbot Architect i2000 SR device (Abbot Diagnostics, Chicago, IL, USA). The levels of HCV RNA were determined in the COBAS AmpliPrep/COBAS, TaqMan 48 (Roche, Diagnostics, Pleasanton, USA) devices using serum samples from patients. Our study is a retrospective and methodological study. Of the 150 patients with anti-HCV antibodies, 50 (33.3%) were HCV RNA positive, and 100 (66.7%) were HCV RNA negative. Anti-HCV levels of HCV RNA-positive patients were statistically higher than HCV RNA-negative patients. The most appropriate anti-HCV S/Co value for diagnosing hepatitis C patients was 15.4. The sensitivity of this value was 72%, specificity 88%, positive predictive value (PPV) 73.5%, and negative predictive value (NPV) 86.1%. Receiver operating characteristic (ROC) curve was significantly higher than 0.5 (95% confidence interval 0.938-0.827). Correct approaches can be applied in the diagnosis of HCV infection using the anti-HCV S/Co value found in our study.

Clinical Impact of a Local Triage System Using the Emergent Large Vessel Occlusion Screen with a Rotation System of Thrombectomy-Capable Hospitals.

Early intervention with mechanical thrombectomy (MT) is expected to improve the functional outcome in patients with large vessel occlusion (LVO); however, a method for the effective detection of these patients in a prehospital setting and early transport to MT-capable hospitals has not been established. This study aimed to analyze the clinical impact and diagnostic performance of the emergent large vessel occlusion (ELVO) screen and its influence on the transportation time. The emergency medical services (EMS) in one of the secondary medical areas in Akita, Japan, introduced a prehospital triage system employing an ELVO screen and a rotation system of three MT-capable hospitals on December 1, 2021. Patients who were transferred to each of the three hospitals involved in the rotation system according to a predefined priority list from December 2021 to November 2022 were included in the triage group. Patients who underwent MT in the three hospitals before the introduction of the triage system were assigned to the pre-triage group. We compared the transportation time parameters between the two groups and analyzed the performance of the ELVO screen for the diagnosis of LVOs. This study was approved by the institutional review boards of all three hospitals. Time parameters were compared between the 37 and 42 patients who underwent MT and had detailed data in the triage (n = 351) and pre-triage (n = 43) groups, respectively. The time from door to puncture tended to decrease in the triage group in all hospitals, with one hospital showing a statistically significant shortening of 14 min (p = 0.018). In the triage group, 209 ELVO screen-positive patients were present, with 60 (28.7%) of these having LVO. The sensitivity, specificity, positive and negative predictive values, and area under the curve of the ELVO screen to detect LVO under the present triage system were 87.0%, 47.2%, 28.7%, 93.7%, and 0.671, respectively. The present study demonstrated that the introduction of a triage system may have shortened the time required for MT. ELVO screen may be considered a useful marker for screening LVO in prehospital settings in terms of the sensitivity and negative predictive value; however, further improvement may be necessary to reduce the rate of false positive results.

Using signal-to-cutoff ratios of HIV screening assay to predict HIV infection

BackgroundThe sensitivity of HIV screening assays often leads to a high rate of false-positive results, requiring retests and confirmatory tests. This study aimed to analyze the capability of signal-to-cutoff (S/CO) ratios of HIV screening assay to predict HIV infection.MethodsA retrospective study on the HIV screening-positive population was performed at Zhongshan Hospital, Xiamen University, the correlation between HIV screening assay S/CO ratios and HIV infection was assessed, and plotted Receiver Operating Characteristic (ROC) curves were generated to establish the optimal cutoff value for predicting HIV infection.ResultsOut of 396,679 patients, 836 were confirmed to be HIV-infected, with an HIV prevalence of 0.21%. The median S/CO ratios in HIV infection were significantly higher than that in non-HIV infection (296.9 vs. 2.41, P < 0.001). The rate of confirmed HIV infection was increased with higher S/CO ratios in the screening assay. The ROC curve based on the HIV screening assay S/CO ratio achieved a sensitivity of 93.78% and a specificity of 93.12% with an optimal cutoff value of 14.09. The area under the ROC curve was 0.9612. Further analysis of the ROC curve indicated that the S/CO ratio thresholds yielding positive predictive values of 99%, 99.5%, and 100% for HIV infection were 26.25, 285.7, and 354.5, respectively.ConclusionUsing HIV screening assay S/CO ratio to predict HIV infection can largely reduce necessitating retests and confirmatory tests. Incorporating the S/CO ratio into HIV testing algorithms can have significant implications for medical and public health practices.

External quality control program in infectious diseases screening at laboratories and blood banks in Latin America: an analysis of the past 5 years.

To evaluate the screening of blood samples for infectious disease markers at laboratories and blood banks in Latin America per the findings of an External Quality Assessment Program (EQAP). This qualitative analysis used data from the EQAP coordinated by the Fundação Pro Sangue Hemocentro de São Paulo with the support of the Pan American Health Organization to assess the performance of blood screening for infectious diseases from 2014 to 2018 in Latin America. Each participating laboratory or blood bank received an identical blind panel with 24 blood samples with variable reactivity for all the screening parameters. Panels were processed at each participating facility and results were returned to the Fundação Pro Sangue Hemocentro de São Paulo for individual and joint analyses. Two types of discrepant results were potential failures: false positive results (FPRs) and false nonreactive results (FNRRs). A total of 23 136 samples were evaluated. Global rates of FPR, FNRR, and concordant results were 0.3%, 1.0% and 98.7%, respectively. Seven FNRRs were found for HBsAg (1.0%), 12 for syphilis (2.6%), and 21 for Chagas disease (2.9%). No FNRRs were found for the HIV, HCV, and HTLV viruses. The average accuracy of all the laboratories and blood banks participating in the EQAP during the study period was 99.5% (standard deviation, 0.5%). The findings of this qualitative analysis are positive for blood safety in Latin America, with an average accuracy of 99.5% among the participating laboratories and blood banks. This report reflects an important improvement in blood bank serological screening EQAP-PAHO report since the 2003.

Comparative Diagnostic Accuracy of VistaCam IX Proxi and Bitewing Radiography for Detection of Interproximal Caries.

Early detection of caries and the extent of carious lesions for appropriate treatment planning are very important and lead to introduction of new diagnostic tools. This study aimed to compare the diagnostic accuracy of VistaCam IX Proxi and bitewing radiography for detection of posterior interproximal caries. This in vitro study was performed on 40 extracted posterior teeth without cavitated carious lesions. Bitewing radiographs were obtained, infrared (IR) examination was performed, and the teeth were sectioned for histopathological analysis under a stereomicroscope as the gold standard for detection of caries and determination of the extent of carious lesions. Data were analyzed with Cohen's kappa statistic, and Wilcoxon rank sum test. The specificity of VistaCam IX Proxi and bitewing radiography was 71.4% and 87.7%, respectively. Their sensitivity was 100% and 40% for enamel caries, 72.8% and 54.5% for external half dentin caries, and 82.3% and 58.8% for internal half dentin caries, respectively (p= 0.048). Bitewing radiography had a higher specificity and lower rate of false positive results. However, VistaCam IX Proxi had higher sensitivity for caries detection with lower rate of false negative results. Considering the higher sensitivity and significantly lower frequency of false negative results by VistaCam IX Proxi, it may be reliably used for caries detection specially enamel caries, and can serve as an adjunct to bitewing radiography.

A-315 Pregnant Women Showed Lower Incidence Rates of False-positive Treponemal Antibody Screening Results When Compared with Nonpregnant Women and Men at an Appalachian Academic Medical Center

Abstract Background Screening for syphilis infection is recommended for all pregnant women and any adult or adolescent with increased risk for infection. Many clinical labs have adopted the reverse syphilis serology testing algorithm, that employs an automated and high-throughput treponemal antibody test as the initial screen followed by a non-treponemal antibody test to confirm all reactive samples. For specimens with discordant results, a second treponemal antibody test is used as the adjudicator. Syphilis serological tests can have false-positive results, causing discordant results between screening test and confirmatory test and complicating result interpretation. It is controversial from the literature whether pregnancy is a cause of false-positive results. This study is to determine the incidence rate of false-positive treponemal screening results among pregnant and nonpregnant patients, and to assess whether false-positivity is associated with pregnancy and age. Methods This is a retrospective study of sequential results from two treponemal antibody screening tests, including BioPlex 2200 Syphilis Total immunoassay between May 2020 and Jan 2022, and Alinity i Syphilis TP assay between Feb 2022 and Nov 2022. For each screening test, the incidence rates of false-positive results were calculated based on the reverse algorithm criteria and compared among pregnant women, nonpregnant women and men. The age differences between patients with false-positive results and patients with nonreactive results were also evaluated. Results Overall, 0.32% of 9 575 samples tested by Alinity assay showed false-positive results not confirmed by RPR or TP-PA. This is significantly lower (P &amp;lt; 0.01) than 0.60% of 14 983 samples observed for BioPlex assay. However, the lower incidence rate of false-positive results for Alinity assay relative to the Bioplex assay is only observed in pregnant women (0.18% vs 0.44%, P &amp;lt; 0.01) and nonpregnant women (0.32% vs 0.71%, P = 0.06), but not in men (0.68% vs 0.63%, P = 0.81). For both assays, male patients with false-positive results had an older median age than those with nonreactive results, and female patients showed the opposite trend, although statistical significance was only observed in nonpregnant women for Bioplex assay (median [IQR], 25 [19–35] vs 30 [22–43], P = 0.047). For both assays, pregnant women had lower incidence rates of false-positive results than nonpregnant women, although the differences did not reach statistical significance without age adjustment (Bioplex assay: 0.44% vs 0.71%, P = 0.07; Alinity assay: 0.18% vs 0.32%, P = 0.26). When age is adjusted, binary logistic regression analysis showed that pregnant women had significantly lower incidence rates of false-positive results relative to nonpregnant women for both assays (BioPlex assay: P = 0.049; Alinity assay: P &amp;lt; 0.01). Conclusion Although the incidence rates of false-positive results in BioPlex and Alinity treponemal antibody screening tests were overall within a low range, a significantly lower rate was observed for Alinity assay in pregnant women but not in men. For both assays, pregnant women showed a significantly lower incidence rate of false-positive results in comparison with nonpregnant women after age adjustment.

Liver function tests in patients with hypertension in primary care: a prospective cohort study.

Liver function tests (LFTs) are frequently used to monitor patients with hypertension in UK primary care. Evidence is lacking on whether testing improves outcomes. To estimate the diagnostic accuracy of LFTs in patients with hypertension and determine downstream consequences of testing. Prospective study using the Clinical Practice Research Datalink (CPRD). In total, 30 000 patients with hypertension who had LFTs in 2015 were randomly selected from CPRD. The diagnostic accuracy measures for eight LFT analytes and an overall LFT panel were calculated against the reference standard of liver disease. Rates of consultations, blood tests, and referrals within 6 months following testing were measured. The 1-year incidence of liver disease in patients with hypertension was 0.5% (95% confidence interval [CI] = 0.4% to 0.6%). Sensitivity and specificity of an LFT panel were modest: 61.3% (95% CI = 53.1% to 69.0%) and 73.8% (95% CI = 73.1% to 74.3%), respectively. The positive predictive value (PPV) of the eight individual LFT analytes were low ranging from 0.2% to 8.9%. Among patients who did not develop liver disease, mean number of consultations, referrals, and tests were higher in the 6 months following false-positives at 10.5, 0.7 and 29.8, respectively, compared with true-negatives: 8.6, 0.6, and 19.8. PPVs of LFTs in primary care were low, with high rates of false-positive results and increased rates of subsequent consultations, referrals, and blood testing. Avoiding LFTs for routine monitoring could potentially reduce patients' anxiety, GP workload, and healthcare costs.

Resistance patterns and transmission of mono- and polyresistant TB: clinical impact of WGS.

Rapidly diagnosing drug-resistant TB is crucial for improving treatment and transmission control. WGS is becoming increasingly accessible and has added value to the diagnosis and treatment of TB. The aim of the study was to perform WGS to determine the rate of false-positive results of phenotypic drug susceptibility testing (pDST) and characterize the molecular mechanisms of resistance and transmission of mono- and polyresistant Mycobacterium (M.) tuberculosis. WGS was performed on 53 monoresistant and 25 polyresistant M. tuberculosis isolates characterized by pDST. Sequencing data were bioinformatically processed to infer mutations encoding resistance and determine the origin of resistance and phylogenetic relationship between isolates studied. The data showed the variable sensitivity and specificity of WGS in comparison with pDST as the gold standard: isoniazid 92.7% and 92.3%; streptomycin 41.9% and 100.0%; pyrazinamide 15% and 94.8%; and ethambutol 75.0% and 98.6%, respectively. We found novel mutations encoding resistance to streptomycin (in gidB) and pyrazinamide (in kefB). Most isolates belonged to lineage 4 (80.1%) and the overall clustering rate was 11.5%. We observed lineage-specific gene variations encoding resistance to streptomycin and pyrazinamide. This study highlights the clinical potential of WGS in ruling out false-positive drug resistance following phenotypic or genetic drug testing, and recommend this technology together with the WHO catalogue in designing an optimal individualized treatment regimen and preventing the development of MDR TB. Our results suggest that resistance is primarily developed through spontaneous mutations or selective pressure.

Estimating the false discovery risk of (randomized) clinical trials in medical journals based on published p-values.

The influential claim that most published results are false raised concerns about the trustworthiness and integrity of science. Since then, there have been numerous attempts to examine the rate of false-positive results that have failed to settle this question empirically. Here we propose a new way to estimate the false positive risk and apply the method to the results of (randomized) clinical trials in top medical journals. Contrary to claims that most published results are false, we find that the traditional significance criterion of α = .05 produces a false positive risk of 13%. Adjusting α to.01 lowers the false positive risk to less than 5%. However, our method does provide clear evidence of publication bias that leads to inflated effect size estimates. These results provide a solid empirical foundation for evaluations of the trustworthiness of medical research.

O06 Novel multispectral imaging vs. clinical assessment to assess disease activity in paediatric morphoea

Abstract The assessment of disease activity in paediatric morphoea is challenging. Clinical examination and the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT) are subjective. Thermography is the monitoring tool of choice but has a high rate of false-positive results, with low specificity. Multispectral imaging (measuring depth, volume, haemoglobin and melanin) may provide a noninvasive objective assessment of disease activity. The aim of this study was to compare activity assessment with multispectral imaging vs. clinical assessment in children with morphoea. 3D images of site-matched affected and unaffected skin were obtained using a handheld portable Antera 3D camera (Miravex Ltd). Analysis of depth, volume, haemoglobin and melanin was performed using the Antera Clinical Studies software. Objective and subjective clinical assessment was performed using LoSCAT and Children's Dermatology Life Quality Index (CDLQI). To date, 17 children (age range 7–18 years) have been recruited. Two-thirds (65%) had linear morphoea and 58% were treated with systemic agents (pulsed methylprednisolone, methotrexate, mycophenolate mofetil, abatacept). Average LoSCAT scores were 20.6 (range 5–73), and average CDLQI scores were 3.7 (range 0–14). The average haemoglobin gradient between affected and unaffected skin was 0.3 in children with active disease and 0.08 in those who had persistent disease remission (P &amp;lt; 0.0001). The sensitivity of multispectral imaging in paediatric morphoea is 90% with specificity of 100%, giving a positive predictive value of 100%, and a negative predictive value of 95%. Multispectral imaging of affected skin may aid activity detection in paediatric morphoea and is particularly useful in darkly pigmented skin.