Negative Predictive Value of Single-Day Drug Provocation Test for Immediate and Non-Immediate Beta-Lactam Hypersensitivity Reactions in Children.

INTRODUCTION: Beta-lactam antibiotics (BLAs) commonly cause hypersensitivity reactions in children. These reactions are categorized into immediate reactions, which include urticaria, angioedema, bronchospasm, and anaphylaxis, and non-immediate reactions, such as maculopapular rashes and delayed-onset urticaria/angioedema. Rashes in children, often caused by infections, may be misdiagnosed as BLA allergy. However, over 90% tolerate the medication following an allergic evaluation. METHODS: We aimed to evaluate patients with negative single-day drug provocation test (sdDPT) results for subsequent reactions and to determine the negative predictive value (NPV) of sdDPT for immediate (less than 1 h) and non-immediate (more than 1 h) suspected BLA allergy. In addition, non-immediate reactions were assessed by classifying them as occurring within 1-6 h or after 6 h. Patients who underwent sdDPT for suspected BLA allergy and tested negative between 2019 and 2023 were included in the study. They were questioned via telephone interviews about their reuse of the tested drug. RESULTS: 404 patients who underwent sdDPT for suspected BLA allergy were evaluated. The NPV of BLA sdDPT was determined to be 97.3%. When patients were categorized based on the time interval between the last dose and the reaction, the NPV was 97% for those experiencing a reaction within the first hour of drug use and 96.7% for reactions occurring after more than 1 h. Non-immediate reactions were further evaluated, revealing an NPV of 98.7% for reactions occurring between 1 and 6 h, and 92.5% for reactions occurring after 6 h. CONCLUSION: Our findings demonstrate that sdDPT has a high NPV for both immediate and non-immediate reactions. However, the NPV of sdDPT was lower for reactions occurring more than 6 h after the last dose.

Comparison of measles plaque reduction neutralization test (PRNT) and measles virus-specific IgG ELISA for assessment of immunogenicity of measles-mumps-rubella vaccination at 5-7 months of age and maternal measles antibodies.

Background: Assessing the risk of measles outbreaks and identifying the susceptible parts of the population is essential to timely intervention. Infants between 6-12 months are increasingly susceptible to measles but evaluating the performance of high throughput enzyme immunoassays (ELISAs) in infants < 9 months of age is lacking. Methods: A commercially available ELISA kit (Creative Diagnostics, DEIA359) for estimating measles seroprotection was evaluated in infants 5-7 months of age. In an immunogenicity substudy in the Danish MMR trial conducted between 2019-2021, infants (and mothers at baseline) were sampled before and one month after measles-mumps-rubella vaccination (MMR) or placebo as well as one month after routine MMR at 15 months. Measles IgG ELISA was compared to the gold standard but labor-intensive measles plaque reduction neutralization test (PRNT) by Pearson and Spearman correlations and by estimating sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Findings: Measles IgG levels compared to PRNT antibodies had a Pearson's correlation coefficient between 0.10-0.24. Seroprotection rates measured by ELISA in young infants were 10-14% lower than measured by PRNT. The sensitivity of the ELISA to detect serological protection compared to PRNT in the infant population differed markedly across sampling time points and was 14%, 40%, and 92% at baseline, post-intervention, and post-routine MMR, whereas the specificity was 99%, 93%, and 43%, respectively. The PPV and NPV were 68% and 87% in infants at baseline. Interpretation: The correlation between measles IgG and PRNT antibodies was low. Seroprotection was underestimated using ELISA. High-accuracy tests are needed to avoid misclassifications and practices that lead to primary or secondary vaccine failure or retention of vaccination in outbreak settings. Baseline PPV and NPV suggested some applicability of ELISA in predicting serological protection in this age group. However, PRNT may be the only accurate estimator of serological protection in young infants.

Enhancing Cervical Cancer Screening with 7-Type HPV mRNA E6/E7 Testing on Self-Collected Samples: Multicentric Insights from Mexico.

Cervical cancer remains a significant public health issue, particularly in regions with low screening uptake. This study evaluates the effectiveness of self-sampling and the 7-type HPV mRNA E6/E7 test in improving cervical cancer screening outcomes among a referral population in Mexico. A cohort of 418 Mexican women aged 25 to 65, referred for colposcopy and biopsy due to abnormal cytology results (ASC-US+), participated in this study. Self-samples were analyzed using both the 14-type HPV DNA test and the 7-type HPV mRNA E6/E7 test. The study assessed the sensitivity, specificity, positive predictive value (PPV), and the necessity of colposcopies to detect CIN3+ lesions. Participant acceptability of self-sampling was also evaluated through a questionnaire. The 7-type HPV mRNA E6/E7 test demonstrated equivalent sensitivity but significantly higher specificity (77.0%) and PPV for CIN3+ detection compared to the 14-type HPV DNA test (specificity: 45.8%, p < 0.001). The use of the HPV mRNA test as a triage tool reduced the number of colposcopies needed per CIN3+ case detected from 16.6 to 7.6 (p < 0.001). Self-sampling was highly accepted among participants, with the majority reporting confidence in performing the procedure, minimal discomfort, and willingness to undertake self-sampling at home. Self-sampling combined with the 7-type HPV mRNA E6/E7 testing offers a promising strategy to enhance cervical cancer screening by improving accessibility and ensuring precise diagnostics. Implementing these app roaches could lead to a significant reduction in cervical cancer morbidity and mortality, especially in underserved populations. Future research should focus on the long-term impact of integrating these methods into national screening programs and explore the cost-effectiveness of widespread implementation.

Preoperative factors associated with lateral lymph node metastasis in lower rectal cancer and the evaluation of the middle rectal artery.

PURPOSE: This study aimed to identify cases in which lateral lymph node (LLN) dissection (LLND) can be excluded by clarifying preoperative factors, including an evaluation of the middle rectal artery (MRA), associated with LLN metastasis. METHODS: Fifty-five consecutive patients who underwent preoperative positron emission tomography-computed tomography (PET/CT) and total mesorectal excision with LLND for rectal cancer were included. We retrospectively investigated the preoperative clinical factors associated with pathological LLN (pLLN) metastasis. We analyzed the regions of pLLN metastasis using MRA. RESULTS: pLLN metastasis occurred in 13 (23.6%) patients. According to a multivariate analysis, clinical LLN (cLLN) metastasis based on short-axis size and LLN status based on PET/CT were independent preoperative factors of pLLN metastasis. The negative predictive value (NPV) was high (97.1%) in patients evaluated as negative based on PET/CT and cLLN short-axis size. MRA was detected in 24 patients (43.6%) using contrast-enhanced CT, and there was a significant relationship between pLLN metastasis and the presence of MRA. pLLN metastasis in the internal iliac region but not in the obturator region was significantly correlated with the presence of MRA. CONCLUSION: Combined cLLN metastasis based on short-axis size and PET/CT showed a higher NPV, suggesting this to be a useful method for identifying cases in which LLND can be excluded.

Acu-URO17 is a highly sensitive and specific bladder cancer biomarker.

Objective: This study evaluates the efficacy of Acu-URO17, a highly sensitive and specific immunocytochemistry (ICC) test targeting Keratin 17, in comparison to urine cytology and UroVysion™ fluorescence in situ hybridization (FISH) for detecting bladder cancer cells in voided urine specimens. Methods: Acupath conducted a large-scale comparison study using 2378 voided urine specimens. Acu-URO17, urine cytology and UroVysion™ FISH were performed on these specimens according to standardized protocols. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for Acu-URO17 in comparison to urine cytology and UroVysion™ FISH. Results: In cases diagnosed with high-grade urothelial cancer via urine cytology, Acu-URO17 demonstrated a sensitivity of 96% and a specificity of 82%. When compared to UroVysion™ FISH results, Acu-URO17 exhibited a sensitivity of 97.1% and a specificity of 77.8%, surpassing the sensitivity of UroVysion™ FISH (57.1%). Notably, Acu-URO17 showed a high NPV of 99.9%, indicating its reliability in confirming negative urine cytology results and risk-stratifying atypical and suspicious cytology results. Conclusion: The results of this large-scale prospective study support Acu-URO17 as a clinically relevant, non-invasive and cost-effective tool for detecting bladder cancer cells in voided urine specimens. Its high sensitivity, specificity and NPV make it a valuable adjunct to urine cytology and UroVysion™ FISH in the diagnosis and management of urothelial carcinoma (UC).

Quantification of Metamorphopsia in Resolved Idiopathic Central Serous Chorioretinopathy: An Analysis Using M-CHARTS, Amsler Grid, and Optical Coherence Tomography.

Purpose: To quantify metamorphopsia in patients with resolved idiopathic Central Serous Chorioretinopathy (CSCR) using M-CHARTS and compare the results with the traditional Amsler grid and optical coherence tomography (OCT). Patients and Methods: For the purpose of this study, all consecutive cases of patients with resolved CSCR were evaluated for metamorphopsia (using the standard Amsler grid and M-CHARTS) and spectral domain OCT. The OCT images were analyzed for the following five parameters: central macular thickness, pigment epithelial detachment, retinal pigment epithelial bumps, discontinuation in the inner segment/outer segment junction or the external limiting membrane, fibrinous exudates in the subretinal space, and hyperreflective dots in the intraretinal and/or subretinal layer. Binary logistic regression was used to find the association between metamorphopsia and foveal morphology. Cohen's Kappa was used to determine the agreement between the M-CHARTS and Amsler grid for diagnosing metamorphopsia. The sensitivity, specificity, and accuracy in the diagnosis of metamorphopsia were calculated against the Amsler grid. Results: Of 41 eyes, Amsler Grid detected metamorphopsia in 39.02%, and M-CHARTS detected metamorphopsia in 53.66%. The agreement rate of detection between the two tests was moderate (Kappa=0.52). M-CHARTS had a sensitivity of 87.50%, a specificity of 68.00%, a positive predictive value of 63.64%; and a negative predictive value of 89.47% for the diagnosis of metamorphopsia compared to the Amsler grid. The presence of PED in OCT was significantly associated with metamorphopsia. Conclusion: M-CHARTS can be a useful ancillary test to detect and quantify metamorphopsia even after fluid resolution in CSCR. Structural changes in macular morphology as observed with OCT can predict the likelihood of metamorphopsia.

Medical diagnostic accuracy measures: an innovative approach based on the area under predictive values curves.

Positive and negative estimates are commonly used by clinicians to evaluate the likelihood of a disease stage being present based on test results. The predicted values are dependent on the prevalence of the underlying illness. However, for certain diseases or clinical conditions, the prevalence is unknown or different from one region to another or from one population to another, leading to an erroneous diagnosis. This article introduces innovative post-test diagnostic precision measures for continuous tests or biomarkers based on the combined areas under the predictive value curves for all possible prevalence values. The proposed measures do not vary as a function of the prevalence of the disease. They can be used to compare different diagnostic tests and/or biomarkers' abilities for rule-in, rule-out, and overall accuracy based on the combined areas under the predictive value curves. The relationship of the proposed measures to other diagnostic accuracy measures is discussed. We illustrate the proposed measures numerically and use a real data example on breast cancer.

CRP under 130 mg/L rules out the diagnosis of Legionella pneumophila serogroup 1 (URINELLA Study).

INTRODUCTION: In case of pneumonia, some biological findings are suggestive for Legionnaire's disease (LD) including C-reactive protein (CRP). A low level of CRP is predictive for negative Legionella Urinary-Antigen-Test (L-UAT). METHOD: Observational retrospective study in Nord-Franche-Comté Hospital with external validation in Besançon University Hospital, France which included all adults with L-UAT performed during January 2018 to December 2022. The objective was to determine CRP optimal threshold to predict a L-UAT negative result. RESULTS: URINELLA included 5051 patients (83 with positive L-UAT). CRP optimal threshold was 131.9 mg/L, with a negative predictive value (NPV) at 100%, sensitivity at 100% and specificity at 58.0%. The AUC of the ROC-Curve was at 88.7% (95% CI, 86.3-91.1). External validation in Besançon Hospital patients showed an AUC at 89.8% (95% CI, 85.5-94.1) and NPV, sensitivity and specificity was respectively 99.9%, 97.6% and 59.1% for a CRP threshold at 131.9 mg/L; after exclusion of immunosuppressed patients, index sensitivity and NPV reached also 100%. CONCLUSION: In case of pneumonia suspicion with a CRP level under 130 mg/L (independently of the severity) L-UAT is useless in immunocompetent patients with a NPV at 100%. We must remain cautious in patients with symptoms onset less than 48 h before CRP dosage.

Colorectal Cancer Screening by Fecal Immunochemical Tests (FIT): Considerations on Sampling and Markers (Hb and Hb/Hp Complex) of Fecal Occult Blood (FOB).

BACKGROUND/AIM: Formal demonstration of the efficacy of colorectal cancer (CRC) screening by fecal immunochemical tests (FITs) in reducing CRC incidence and mortality is still missing. The aim of this study was to analyze the impact of sampling and FIT marker in the recently implemented CRC screening program in Finland. PATIENTS AND METHODS: Because only the index test [FIT hemoglobin (Hb)]-positive subjects are verified by the reference test (colonoscopy), the new screening program is subject to verification bias that precludes estimating the diagnostic accuracy (DA) indicators. A previously published study (5) with 100% biopsy verification of colonoscopy referral subjects (called validation cohort, n=300) was used to derive these missing DA estimates. Two points of concern were addressed: i) only one-day sample tested, and ii) only the Hb component (but not Hb/Hp complex) was analyzed by FIT. RESULTS: The estimated DA of one-sample testing for Hb in the screening setting had a very low sensitivity (SE) (12.5%; 95%CI=12.3-12.7) for adenomas, with AUC=0.560 (for CRC, AUC=0.950). Testing three samples for Hb improved SE to 19.4% (95%CI=19.1-19.7%) but had little effect on overall DA (AUC=0.590). For adenomas, one-sample testing for Hb and Hb/Hp complex provided higher SE than three-sample testing for Hb (SE 20.6%; 95%CI=20.3-21.0), and the best SE was reached when two samples were tested for Hb and Hb/Hp complex (SE 47.5%; 95%CI=46.9-48.1%) (AUC=0.730). CONCLUSION: The strategy of the current CRC screening could be significantly improved by testing two consecutive samples by Hb and Hb/Hp complex, instead of stand-alone Hb testing of one sample.

The Utility of Quantitative D-Dimer Assay as a Biomarker in the Diagnosis and Exclusion of Cerebral Venous Sinus Thrombosis.

The utility and sensitivity of quantitative D-Dimer assay to rule out the diagnosis of deep vein thrombosis is well established. We extrapolated this principle to evaluate the utility of D-Dimer assay in exclusion of cerebral venous sinus thrombosis (CVST). As advanced imaging modalities required for the diagnosis of CVST might not be available everywhere, it is important to have a sensitive biomarker and a clinical decision rule which can assist in the diagnosis. Patients undergoing CT/MR Venography of the brain with the suspicion of CVST were enrolled. Quantitative D-Dimer assay was performed in those who had CVST on CT/MR Venography and was compared with those who did not. A Clinical decision rule for the diagnosis of CVST was formulated using logistic regression analysis. Receiver operating characteristic analysis evaluating the diagnostic accuracy of D Dimer for patients with CVST as compared to those who did not revealed an AUROC of 0.694. D-Dimer levels of < 300 ng/mL had a sensitivity of 90% for the exclusion of CVST. After logistic regression analysis, a clinical decision rule with a total score of 16 and individual components of Female gender (2 points), Headache (7 points), D-Dimer levels of ≥ 792 ng/mL (7 points) was proposed. D-Dimer had a poor diagnostic accuracy for differentiation of patients who had CVST from those who did not, however, had a high sensitivity at values < 300 ng/mL. The proposed clinical decision rule with a score of ≥ 9 had a good diagnostic accuracy in prediction of CVST (AUROC = 0.809).

Utility of self-report antiretroviral adherence for predicting HIV viral load among persons who inject drugs in Hai Phong Vietnam: assessing differences by methamphetamine use.

ABSTRACTIn resource-limited settings, alternatives to HIV viral load testing may be necessary to monitor the health of people living with HIV. We assessed the utility of self-report antiretroviral therapy (ART) to screen for HIV viral load among persons who inject drugs in Hai Phong Vietnam, and consider differences by recent methamphetamine use. From 2016 to 2018 we recruited PWID through cross sectional surveys and collected self-report ART adherence and HIV viral load to estimate sensitivity, specificity, positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR-) for self-reported ART adherence as a screening test for HIV viral load. We used three HIV viral load thresholds: < 1000, 500 and 250 copies/mL; laboratory-confirmed HIV viral load was the gold standard. Among 792 PWID recruited, PPV remained above 90% regardless of recent methamphetamine use with slightly higher PPV among those not reporting recent methamphetamine use. The results remained consistent across all three HIV viral load thresholds. Our findings suggest that when HIV viral load testing is not possible, self-reported ART adherence may inform decisions about how to prioritize HIV viral load testing among PWID. The high PPV values suggest self-reported high ART adherence indicates likely HIV viral suppression, irrespective of methamphetamine use.

Predictive value of methicillin-resistant staphylococcus aureus nasal swab in patients with COVID-19 pneumonia and secondary bacterial pneumonia.

OBJECTIVE: To determine the performance measures of admission methicillin-resistant Staphylococcus aureus (MRSA) nasal swabs for MRSA bacterial pneumonia in patients co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The study included patients admitted with SARS-CoV-2-positive nasopharyngeal specimens, MRSA nasal screens, and bacterial cultures to assess secondary MRSA pneumonia. RESULTS: 293 patients and 662 microbiological cultures evaluated. Overall, the specificity (91.8% [95% CI 88.6% to 95%]) and negative predictive value (NPV 97.4% [95% CI 95.4% - 99.3%]) of MRSA nasal swabs was high. However, the sensitivity (46.2%; 95% CI 19.1% to 73.3%) and positive predictive value (PPV 20.7%; 95% CI 59.5 - 35.4%) were low. Those patients in the MRSA nasal swab negative group had a shorter median duration of linezolid therapy. CONCLUSIONS: SARS-CoV-2 infection doesn't reduce the specificity or negative predictive value of MRSA nasal swabs for secondary MRSA pneumonia.

A study on diagnostic performance of different immunohematological diagnostic tests in assessing the prevalence of ABO Hemolytic Disease of Newborn in the antenatal O group mothers and their neonatal outcome in a tertiary care hospital in Northern India.

BACKGROUND: Hemolytic disease of the newborn (HDN) results in the decreased lifespan of the red cells. HDN related to ABO incompatibility is mostly unnoticed because routine screening is not being done. This study was done to assess the prevalence of ABO-HDN and to compare different immunohematological tests. Methods-In this study 213 O group mothers and the 122 ABO-incompatible newborns born to them were included. Quantifying the maternal IgG anti-A/anti-B antibody titer was done by Conventional Tube Technique (CTT) using Dithiothreitol (DTT) pretreated maternal serum. Hemolysin test was performed on the mothers having titer > 256. These cases were followed up and, after delivery, were monitored for ABO HDN, along with direct antiglobulin testing and elution studies. The prevalence of ABO-HDN was calculated, and the different diagnostic parameters of the tests were calculated. Results- The prevalence of ABO-HDN in our population was estimated to be 1.7%, 6.1% & 10.6% in our population, O group mothers, and O group mothers with ABOincompatible newborns, respectively. Maternal titer≥ 512 strongly correlated with ABOHDN. DAT positivity is a good predictor of ABO-HDN, especially using sensitive techniques. Maternal IgG titers have the highest sensitivity & Negative Predictive Value, while DAT has the highest specificity & Positive Predictive Value. Conclusion - Maternal ABO antibody titration may be advocated in the centers to identify high-risk groups. It can advocate institutional delivery and dedicated follow-up of newborns with ABO-HDN. Blood grouping & DAT may be performed in all newborns born to O blood group to identify high-risk cases.

Identificación con azul patente de ganglio centinela en cáncer de mama / Patent blue for identification of sentinel nodes in breast cancer

Resumen OBJETIVO: Describir las características sociodemográficas, clínicas y patológicas y los resultados obtenidos con la técnica de ganglio centinela con azul patente en la cirugía de cáncer de mama temprano. Además, reportar la experiencia en la identificación del ganglio centinela en cáncer de mama temprano con la técnica con azul patente al 2.5%. MATERIALES Y MÉTODOS: Estudio retrospectivo y analítico consistente en la evaluación de los expedientes clínicos de pacientes diagnosticadas con cáncer de mama temprano, sin sospecha clínica o radiológica de afectación axilar, atendidas entre junio de 2022 y junio de 2023 en el servicio de Ginecología Oncológica de la UMAE Hospital de Ginecoobstetricia, Centro Médico Nacional de Occidente del IMSS. El sitio de inyección del colorante fue subdérmico periareolar, los ganglios identificados se estudiaron en el transoperatorio. Se analizaron el porcentaje de identificación, las tasas de falsos negativos y el valor predictivo negativo del método. RESULTADOS: Se analizaron 95 procedimientos de biopsia de ganglio centinela. Solo se practicó la linfadenectomía axilar en las pacientes con metástasis en el ganglio centinela comprobada en el estudio transoperatorio y en las que no se identificaron ganglios teñidos por no migración del colorante. La edad promedio de las pacientes fue de 57.1 años límites 25 y 78 años. El tamaño del tumor fue menor a 3 cm. A 64 67% pacientes se les hizo la mastectomía en comparación con 31 a quienes se efectuó cirugía conservadora de mama 33%. Se estadificaron como IA 57 de las 95 pacientes; el subtipo molecular más frecuente fue compatible con luminal A en 49%. CONCLUSIONES: La biopsia del ganglio centinela, con azul patente, es una técnica rápida, sencilla, precisa y de bajo costo para identificar daño axilar en etapas tempranas del cáncer de mama. Lo aquí reportado son resultados que corresponden a una primera evaluación de la técnica en nuestro servicio.

Abstract OBJECTIVE: To describe the sociodemographic, clinical and pathological characteristics and results of the patent blue sentinel lymph node technique in early breast cancer surgery. And to report the experience in identifying the sentinel lymph node in early breast cancer using the 2.5% patent blue technique. MATERIALS AND METHODS: Retrospective and analytical study consisting of the evaluation of the clinical records of patients diagnosed with early breast cancer, without clinical or radiological suspicion of axillary involvement, seen between June 2022 and June 2023 at the Oncological Gynaecology Service of the UMAE Hospital de Ginecoobstetricia, Centro Médico Nacional de Occidente of the IMSS. The dye injection site was subdermal periareolar, and the identified lumps were examined in the transoperative period. The percentage of identification, false negative rates and negative predictive value of the method were analysed. RESULTS: Ninety-five sentinel node biopsies were analysed. Axillary lymphadenectomy was performed only in patients with sentinel lymph node metastasis confirmed at surgery and in those in whom no stained nodes were identified due to non-migration of the dye. The mean age of the patients was 57.1 years range 25 to 78 years. The tumour size was less than 3 cm. Sixty-four patients 67% underwent mastectomy, compared with 31 who underwent breast-conserving surgery 33%. Fifty-seven of the 95 patients were staged as AI; the most common molecular subtype was compatible with luminal A in 49%. CONCLUSIONS: Sentinel lymph node biopsy with patent blue is a rapid, simple, accurate and inexpensive technique for identifying axillary disease in early breast cancer. The results reported here represent an initial evaluation of the technique in our service.

Predictive Value of the International Classification of Diseases, 9th Revision Codes for Identifying Ocular Oncology Diagnoses.

Introduction: The aim of this study was to determine the predictive value of International Classification of Diseases, 9th Revision (ICD-9) billing codes for identifying ocular oncology diagnoses. Methods: Population-based retrospective cohort study of all Olmsted County, Minnesota residents with any ocular neoplasm-related ICD-9 code from January 1, 2006 to October 1, 2015. All medical records were reviewed for confirmation of ocular neoplasm. Diagnoses with ≥5 cases confirmed via a medical record review were compared to corresponding ICD-9 codes. Main outcome measures included positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of ICD-9 codes. Results: Among 3,932 subjects with ≥1 ocular neoplasm-related ICD-9 code, 21 diagnoses met study criteria. The most frequent intraocular, extraocular/orbital, and ocular surface diagnoses were choroidal nevus (n = 824), epidermal inclusion cyst (n = 263), and conjunctival nevus (n = 74), respectively. PPVs ranged from 1.2% to 73.8%, NPVs from 96.9% to 100%, sensitivity from 0% to 100%, and specificity from 85.7% to 100%. Among malignant neoplasms, PPV ranged from 0% to 73.8%: ocular surface squamous neoplasia (PPV: 0%), choroidal melanoma (PPV: 25.0%), eyelid squamous cell carcinoma (PPV: 46.7%), and eyelid basal cell carcinoma (PPV: 73.8%). Among benign neoplasms, PPV ranged from 1.2% (dermoid cyst) to 61.6% (choroidal nevus). Conclusion: There was a wide variation in a predictive value of ocular neoplasm-related ICD-9 billing codes, which suggests that ocular oncology-related claims data alone may overestimate the true number of ocular oncology diagnoses.

Enhancing Cervical Cancer Prevention in South African Women: Primary HPV mRNA Screening with Different Genotype Combinations.

BACKGROUND: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population. METHODS: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed. RESULTS: The HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) (p < 0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women. CONCLUSION: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.

Accuracy of Ultrasound and Computed Tomography in Diagnosing Acute Cholecystitis Patients in a Tertiary Care Center in Saudi Arabia.

Background Acute cholecystitis (AC) is a gallbladder inflammatory disease often associated with gallbladder stones. It accounts for up to 5% of emergency department visits. The majority of patients present with pain in the right upper quadrant, Murphy's sign, and fever. Furthermore, Saudi Arabia has been noted to have a significant prevalence of AC. According to the 2018 Tokyo Guidelines, imaging is an essential element, combined with local and systemic evidence of inflammation, for a confirmed diagnosis of AC. The definitive therapy is conducted surgically by cholecystectomy either urgently or electively. However, there are insufficient studies that focus on the accuracy of imaging in diagnosing AC patients in Saudi Arabia. Objective The aim of this study is to assess the accuracy of ultrasound (US) versus computed tomography (CT) in diagnosing AC patients at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. Methods and material A retrospective record review was conducted at KAUH during the period of June to July 2022. The study included 192 patients diagnosed with AC in the emergency department or outpatient department by US or CT or both and confirmed by laparoscopic cholecystectomy and histopathology between 2016 and 2022. Results The most common modality used was US (79.7%), followed by both US and contrast CT (10.9%). For CT, sensitivity was 81.3%, specificity was 62.5%, positive predictive value (PPV) was 59.1%, and negative predictive value (NPV) was 83.3%. For US, sensitivity was 37.9%, specificity was 81.7%, PPV was 50%, and NPV was 73.1%. A significant relationship was observed between both genders and high use of US (P = 0.0001). Conclusion We found that CT is more sensitive than US, while US is more specific in diagnosing AC.

The Effects of Human Papillomavirus Status and Treatment on the Positive Predictive Value of Post-radiotherapy 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Advanced Head and Neck Squamous Cell Carcinoma.

AIMS: The high negative predictive value of post-chemoradiation (CRT) positron emission tomography-computed tomography (PET-CT) is well established in head and neck squamous cell cancers (HNSCC). The positive predictive value (PPV) remains under scrutiny, with increasing evidence that it is affected by several factors. The aim of this study was to assess the PPV of post-treatment PET-CT for residual nodal disease when stratified by treatment modality and tumour human papillomavirus (HPV) status. MATERIALS AND METHODS: This was a retrospective cohort study in a tertiary oncology centre carried out between January 2013 and December 2019. Patients were radically treated with radiotherapy only/CRT for node-positive HNSCC. PET-CT nodal responses were categorised as complete, equivocal (EQR) or incomplete (ICR), and outcomes extracted from electronic records. RESULTS: In total, 480 patients were evaluated, all had a minimum potential follow-up of 2 years, with a median of 39.2 months. The PPV of 12-week PET-CT was significantly different between HPV-positive (22.5%) and HPV-unrelated (52.7%) disease, P < 0.001. It was also significantly different between the CRT (24.8%) and radiotherapy-only (51.1%) groups, P = 0.001. The PPV of an EQR was significantly less than an ICR, irrespective of HPV status and primary treatment modality. In HPV-positive disease, the PPV of an EQR was 9.0% for the CRT group compared with 21.4% for radiotherapy only, P = 0.278. The PPV in those who achieved an ICR was 34.2% in the CRT group, significantly lower than 70.0% in the radiotherapy-only group, P = 0.03. CONCLUSION: The PPV of 12-week PET-CT is significantly lower for HPV-positive compared with HPV-unrelated HNSCC. It is poorer in patients with HPV-positive disease treated with CRT compared with radiotherapy alone.

Post-test diagnostic accuracy measures under tree ordering of disease classes.

The medical field commonly employs post-test measures such as predictive values and likelihood ratios to assess diagnostic accuracy. Predictive values, including positive and negative values (PPV and NPV), indicate the probability that individuals have a target health condition based on test results. On the other hand, likelihood ratios, including positive and negative ratios (LR+ and LR- respectively), compare the probability of a particular test result between the diseased and non-diseased groups. While predictive values are useful in evaluating diagnostic test accuracy in populations with varying disease prevalence, likelihood ratios provide a direct link between pre-test and post-test probabilities in specific patients. In this study, we introduce and analyze a new approach called generalized predictive values and likelihood ratios, using a tree ordering of disease classes. We evaluate the effectiveness of these methods through simulation studies and illustrate their use with real data on lung cancer.

Whole-Genome Sequencing to Predict Mycobacterium tuberculosis Drug Resistance: A Retrospective Observational Study in Eastern China.

Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB). Whole-genome sequencing (WGS) holds great promise as an advanced technology for accurately predicting anti-TB drug resistance. The development of a reliable method for detecting drug resistance is crucial in order to standardize anti-TB treatments, enhance patient prognosis, and effectively reduce the risk of transmission. In this study, our primary objective was to explore and determine the potential of WGS for assessing drug resistance based on genetic variants recommended by the World Health Organization (WHO). A total of 1105 MTB strains were selected from samples collected from 2014-2018 in Zhejiang Province, China. Phenotypic drug sensitivity tests (DST) of the anti-TB drugs were conducted for isoniazid (INH), rifampicin (RFP), streptomycin, ethambutol, fluoroquinolones (levofloxacin and moxifloxacin), amikacin, kanamycin, and capreomycin, and the drug-resistance rates were calculated. The clean WGS data of the 1105 strains were acquired and analyzed. The predictive performance of WGS was evaluated by the comparison between genotypic and phenotypic DST results. For all anti-TB drugs, WGS achieved good specificity values (>90%). The sensitivity values for INH and RFP were 91.78% and 82.26%, respectively; however, they were ≤60% for other drugs. The positive predictive values for anti-TB drugs were >80%, except for ethambutol and moxifloxacin, and the negative predictive values were >90% for all drugs. In light of the findings from our study, we draw the conclusion that WGS is a valuable tool for identifying genome-wide variants. Leveraging the genetic variants recommended by the WHO, WGS proves to be effective in detecting resistance to RFP and INH, enabling the identification of multi-drug resistant TB patients. However, it is evident that the genetic variants recommended for predicting resistance to other anti-TB drugs require further optimization and improvement.