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.

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.

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.

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.

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.

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.

Comparison of clinician diagnosis of COVID-19 with real time polymerase chain reaction in an adult-representative population in Sweden.

BACKGROUND: Due to the high transmissibility of SARS-CoV-2, accurate diagnosis is essential for effective infection control, but the gold standard, real-time reverse transcriptase-polymerase chain reaction (RT-PCR), is costly, slow, and test capacity has at times been insufficient. We compared the accuracy of clinician diagnosis of COVID-19 against RT-PCR in a general adult population. METHODS: COVID-19 diagnosis data by 30th September 2021 for participants in an ongoing population-based cohort study of adults in Western Sweden were retrieved from registers, based on positive RT-PCR and clinician diagnosis using recommended ICD-10 codes. We calculated accuracy measures of clinician diagnosis using RT-PCR as reference for all subjects and stratified by age, gender, BMI, and comorbidity collected pre-COVID-19. RESULTS: Of 42,621 subjects, 3,936 (9.2%) and 5705 (13.4%) had had COVID-19 identified by RT-PCR and clinician diagnosis, respectively. Sensitivity and specificity of clinician diagnosis against RT-PCR were 78% (95%CI 77-80%) and 93% (95%CI 93-93%), respectively. Positive predictive value (PPV) was 54% (95%CI 53-55%), while negative predictive value (NPV) was 98% (95%CI 98-98%) and Youden's index 71% (95%CI 70-72%). These estimates were similar between men and women, across age groups, BMI categories, and between patients with and without asthma. However, while specificity, NPV, and Youden's index were similar between patients with and without chronic obstructive pulmonary disease (COPD), sensitivity was slightly higher in patients with (84% [95%CI 74-90%]) than those without (78% [95%CI 77-79%]) COPD. CONCLUSIONS: The accuracy of clinician diagnosis for COVID-19 is adequate, regardless of gender, age, BMI, and asthma, and thus can be used for screening purposes to supplement RT-PCR.

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.

Hepatocellular Carcinoma Risk Scores Predict Patients Under Surveillance at Low Risk of Benefit and High Risk of Harm.

AIMS: Surveillance for hepatocellular carcinoma (HCC) is recommended for patients with cirrhosis. Multiple risk scores aim to stratify HCC risk, potentially allowing individualized surveillance strategies. We sought to validate four risk scores and quantify the consequences of surveillance via the calculation of numbers needed to benefit (NNB) and harm (NNH) according to classification by risk score strata. METHODS: Data were collected on 482 patients with cirrhosis during 2013-2014, with follow-up until 31/12/2019. Risk scores (aMAP, Toronto risk index, ADRESS HCC, HCC risk score) were derived from index clinic results. The area under the receiving operating characteristic curve (AUC) was calculated for each. Additionally, per-risk strata, NNB was calculated as total surveillance ultrasounds per surveillance diagnosed early HCC (stage 0/A) and NNH as total ultrasounds performed per false positive (abnormal surveillance with normal follow-up imaging). RESULTS: 22 (4.6%) patients developed HCC. 77% (17/22) were diagnosed through surveillance, of which 13/17 (76%) were early stage. There were 88 false positives and no false negatives (normal surveillance result however subsequent HCC detection). Overall NNB and NNH were 241 and 36, respectively. No score was significantly superior using AUC. Patients classified as low risk demonstrated no surveillance benefit (AMAP, THRI) or had a high NNB of > 300/900 (ADRESS HCC, HCC risk score), with low NNH (24-38). CONCLUSION: Given the lack of benefit and increased harm through false positives in low-risk groups, a risk-based surveillance strategy may have the potential to reduce patient harm and increase benefit from HCC surveillance. CLINICAL TRIALS REGISTRATION: This was not a clinical trial and the study was not pre-registered.

Viremia as a predictor of absence of serious bacterial infection in children with fever without source.

Most children with fever without source (FWS) require diagnostic laboratory tests to exclude a serious bacterial infection (SBI), often followed by admission and empirical antibiotics. As febrile children with a viral infection are less likely to have a SBI, identifying patients with systemic viral infection could contribute to exclude SBI. We evaluated whether the presence of virus in the blood could be used as a biomarker to rule out SBI. Children < 3 years old with FWS were prospectively enrolled and had real-time (reverse-transcription) PCR performed on the blood for adenovirus, enterovirus, parechovirus, and HHV6. 20/135 patients had SBI, and in 47/135, at least one virus was detected in the blood. Viremia had a higher sensitivity and negative predictive value (90% and 96%) to rule out SBI compared to CRP (65% and 93%) and PCT (55% and 90%). The odds ratio (OR) for the presence of SBI among non-viremic patients was 5.8 (p = 0.0225), compared to 5.5 for CRP ≥ 40 mg/l (p = 0.0009) and 3.7 for PCT ≥ 0.5 ng/mL (0.0093). This remained significant after adjusting for CRP and PCT (OR 5.6 and 5.9, respectively; p = 0.03 for both). Area under the ROC curve for CRP and PCT were 0.754 and 0.779, respectively, but increased to 0.803 and 0.832, respectively, when combined with viremia. CONCLUSION: The presence of viremia had a better performance than commonly used biomarkers to rule-out SBI and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS. Larger studies should evaluate the role of point-of-care testing of viruses by (revere-transcription) PCR in the plasma in management algorithms of children with FWS. WHAT IS KNOWN: • Most children with FWS have a viral infection, but up to 15% have a SBI; most require laboratory tests, and many admission and empirical antibiotics. • Children with a viral infection are less likely to have a SBI. WHAT IS NEW: • Children with a systemic viral infection are less likely to have an SBI. • Viremia is a better predictor of absence of SBI than commonly used biomarkers and could potentially be used in conjunction with CRP and/or PCT in the evaluation of children with FWS.

Poor Accuracy of Manually Derived Head Computed Tomography Parameters in Predicting Intracranial Hypertension After Nontraumatic Intracranial Hemorrhage.

BACKGROUND: The utility of head computed tomography (CT) in predicting elevated intracranial pressure (ICP) is known to be limited in traumatic brain injury; however, few data exist in patients with spontaneous intracranial hemorrhage. METHODS: We conducted a retrospective review of prospectively collected data in patients with nontraumatic intracranial hemorrhage (subarachnoid hemorrhage [SAH] or intraparenchymal hemorrhage [IPH]) who underwent external ventricular drain (EVD) placement. Head CT scans performed immediately prior to EVD placement were quantitatively reviewed for features suggestive of elevated ICP, including temporal horn diameter, bicaudate index, basal cistern effacement, midline shift, and global cerebral edema. The modified Fisher score (mFS), intraventricular hemorrhage score, and IPH volume were also measured, as applicable. We calculated the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these radiographic features for the coprimary outcomes of elevated ICP (> 20 mm Hg) at the time of EVD placement and at any time during the hospital stay. Multivariable backward stepwise logistic regression analysis was performed to identify significant radiographic factors associated with elevated ICP. RESULTS: Of 608 patients with intracranial hemorrhages enrolled during the study time frame, 243 (40%) received an EVD and 165 (n = 107 SAH, n = 58 IPH) had a preplacement head CT scan available for rating. Elevated opening pressure and elevated ICP during hospitalization were recorded in 48 of 152 (29%) and 103 of 165 (62%), respectively. The presence of ≥ 1 radiographic feature had only 32% accuracy for identifying elevated opening pressure (PPV 30%, NPV 58%, area under the curve [AUC] 0.537, 95% asymptotic confidence interval [CI] 0.436-0.637, P = 0.466) and 59% accuracy for predicting elevated ICP during hospitalization (PPV 63%, NPV 40%, AUC 0.514, 95% asymptotic CI 0.391-0.638, P = 0.820). There was no significant association between the number of radiographic features and ICP elevation. Head CT scans without any features suggestive of elevated ICP occurred in 25 of 165 (15%) patients. However, 10 of 25 (40%) of these patients had elevated opening pressure, and 15 of 25 (60%) had elevated ICP during their hospital stay. In multivariable models, mFS (adjusted odds ratio [aOR] 1.36, 95% CI 1.10-1.68) and global cerebral edema (aOR 2.93, 95% CI 1.27-6.75) were significantly associated with elevated ICP; however, their accuracies were only 69% and 60%, respectively. All other individual radiographic features had accuracies between 38 and 58% for identifying intracranial hypertension. CONCLUSIONS: More than 50% of patients with spontaneous intracranial hemorrhage without radiographic features suggestive of elevated ICP actually had ICP > 20 mm Hg during EVD placement or their hospital stay. Morphological head CT findings were only 32% and 59% accurate in identifying elevated opening pressure and ICP elevation during hospitalization, respectively.

Principled leveraging of external data in the evaluation of diagnostic devices via the propensity score-integrated composite likelihood approach.

In the area of diagnostics, it is common practice to leverage external data to augment a traditional study of diagnostic accuracy consisting of prospectively enrolled subjects to potentially reduce the time and/or cost needed for the performance evaluation of an investigational diagnostic device. However, the statistical methods currently being used for such leveraging may not clearly separate study design and outcome data analysis, and they may not adequately address possible bias due to differences in clinically relevant characteristics between the subjects constituting the traditional study and those constituting the external data. This paper is intended to draw attention in the field of diagnostics to the recently developed propensity score-integrated composite likelihood approach, which originally focused on therapeutic medical products. This approach applies the outcome-free principle to separate study design and outcome data analysis and can mitigate bias due to imbalance in covariates, thereby increasing the interpretability of study results. While this approach was conceived as a statistical tool for the design and analysis of clinical studies for therapeutic medical products, here, we will show how it can also be applied to the evaluation of sensitivity and specificity of an investigational diagnostic device leveraging external data. We consider two common scenarios for the design of a traditional diagnostic device study consisting of prospectively enrolled subjects, which is to be augmented by external data. The reader will be taken through the process of implementing this approach step-by-step following the outcome-free principle that preserves study integrity.

Digital tomosynthesis spot view in architectural distortions: outcomes in management and radiation dose.

PURPOSE: To evaluate if digital breast tomosynthesis spot compression view (DBT-SCV) could be an additional projection to confirm or deny architectural distortions (ADs) detected by digital breast tomosynthesis (DBT) while assessing the average glandular radiation dose. METHODS: This is a retrospective cohort study enrolling 8864 DBT exams, of which only cases detecting primary AD and with BI-RADS 2-5 score were considered. Seventy-one AD cases examined with DBT-SCV, US and MRI were evaluated for correlation in terms of BI-RADS score; variables among exams were assessed for inter-relationships. RESULTS: Of all ADs identified at DBT, biopsy yielded malignancy in only 38%. PPV in identifying malignancy of ADs was higher for DBT-SCV than DBT (p < 0.05); the NPV of DBT-SCV was 94%. The difference between DBT and DBT-SCV in the detection of benign ADs was statistically significant (p < 0.05). AD without US or MRI confirmation was less likely to represent malignancy (p < 0.05). In detecting malignant cases of ADs, both DBT and DBT-SCV were strongly correlated with US and RM (Kappa > 0.90). In identifying benign cases of ADs, DBT-SCV was poorly/moderately correlated with US and RM (Kappa 0.25 and 0.66); DBT was negatively correlated with US and MRI. CONCLUSION: DBT-SCV could be useful to better characterize AD firstly identified by DBT, keeping dose levels within the reference limits. If AD is detected by DBT without an US or MRI correlate, that is not confirmed by DBT-SCV, a "wait and see" approach can be applied to reduce unnecessary biopsy.

Performance of Methicillin-Resistant Staphylococcus aureus Polymerase Chain Reaction Nasal Screening for Ruling Out MRSA Pneumonia in Hospitalized, Immunocompromised Patients.

Background: Recent literature demonstrates support for using methicillin-resistant Staphylococcus aureus (MRSA) nasal swab polymerase chain reaction (NaPCR) screening as an antimicrobial stewardship tool aiding early de-escalation of anti-MRSA antimicrobials. However, immunocompromised patients have been underrepresented in previous studies despite increased risk of morbidity and mortality from multidrug-resistant organisms (MDRO). Objective: The purpose of this study was to determine the negative predictive value (NPV) of the MRSA NaPCR in hospitalized, immunocompromised adult patients with suspected pneumonia. Methods: A single-center, retrospective, observational review was conducted of hospitalized, immunocompromised adult patients that had an MRSA NaPCR obtained between March 1, 2020 and January 10, 2021. For inclusion, bacterial cultures must have been collected within 2 weeks after MRSA NaPCR. The primary outcome was the NPV of MRSA NaPCR in hospitalized, immunocompromised patients with suspected pneumonia. Secondary outcomes include NPV in other infections. Results: Between March 1, 2020 and January 10, 2021, 59 patients with 78 unique cultures, including 28 respiratory cultures, were included in the study. The NPV of the MRSA NaPCR for pneumonia was 91.7%. The NPV for bloodstream infections was 100% and for urinary tract infections was 100%, but interpretation of these results should be cautioned due to the small sample sizes. Conclusion: The NPV of MRSA NaPCR in pneumonia remains high in this study. The MRSA NaPCR has utility as a de-escalation tool in hospitalized, immunocompromised adult patients, but larger studies are warranted to evaluate all immunocompromised patient populations.

The triglyceride glucose-body mass index: a non-invasive index that identifies non-alcoholic fatty liver disease in the general Japanese population.

BACKGROUND: By identifying individuals at high risk for non-alcoholic fatty liver disease (NAFLD), interventional programs could be targeted more effectively. Some studies have demonstrated that triglyceride glucose-body mass index (TyG-BMI) showed an independent positive association with NAFLD. However, research on its diagnostic value in patients with suspected NAFLD is limited. In this study, we aimed to evaluate whether TyG-BMI was accurate in detecting NAFLD in the general Japanese population. METHODS: A cross-sectional study of 14,280 individuals who underwent a comprehensive health examination was conducted. Standard protocols were followed to collect anthropometric measurements, lab data, and ultrasonography features. All participants were randomly stratified into the development group (n = 7118) and validation group (n = 7162). The TyG-BMI was calculated. Following this, the diagnostic value of the TyG-BMI was evaluated based on the area under the receiver-operating characteristic curve (AUROC). Two cutoff points were selected and used to rule out or rule in the NALFD, and the specificity, sensitivity, negative predictive value, and positive predictive value were explored, respectively. In order to verify the stability of the results, external verification was performed. RESULTS: There were 1272 and 1243 NAFLD participants in the development and validation groups, respectively. The area under the ROC curve (AUC) of TyG-BMI was 0.888 (95% CI 0.876-0.896) and 0.884 (95% CI 0.875-0.894) for the training and validation group, respectively. Using the low TyG-BMI (182.2) cutoff, NAFLD could be excluded with high accuracy (negative predictive value: 96.9% in estimation and 96.9% in validation). The presence of NAFLD could effectively be determined by applying the high cutoff of TyG-BMI (224.0), as the positive predictive value of the estimation and validation groups is 70.7% and 70.1%, respectively. As a result of applying this model, 9996 (70%) of the 14,280 participants would not have undergone ultrasonography, with an accurate prediction of 9308 (93.1%). AUC was 0.874 for external validation using 183,730 Chinese non-obese participants. TyG-BMI was demonstrated to be an excellent diagnostic tool by both internal and external validation. CONCLUSIONS: In conclusion, the present study developed and validated a simple, non-invasive, and cost-effective tool to accurately separate participants with and without NAFLD in the Japanese population, rendering ultrasonography for identifying NAFLD unnecessary in a substantial proportion of people.

On the probability of lymph node negativity in pN0-staged prostate cancer-a theoretically derived rule of thumb for adjuvant needs.

PURPOSE: The extent of lymphadenectomy and clinical features influence the risk of occult nodes in node-negative prostate cancer. We derived a simple estimation model for the negative predictive value (npv) of histopathologically node-negative prostate cancer patients (pN0) to guide adjuvant treatment. METHODS: Approximations of sensitivities in detecting lymph node metastasis from current publications depending on the number of removed lymph nodes were used for a theoretical deduction of a simplified formulation of npv assuming a false node positivity of 0. RESULTS: A theoretical formula of npv = p(N0IpN0) = (100 - prevalence) / (100 - sensitivityâ€¯× prevalence) was calculated (sensitivity and preoperative prevalence in %). Depending on the number of removed lymph nodes (nLN), the sensitivity of pN0-staged prostate cancer was derived for three sensitivity levels accordingly: sensitivity = f(nLN) = 9â€¯× nLN /100 for 0 ≤ nLN ≤ 8 and f(nLN) = (nLN + 70) /100 for 9 ≤ nLN ≤ 29 and f(nLN) = 1 for nLN ≥ 30. CONCLUSION: We developed a theoretical formula for estimation of the npv in pN0-staged prostate cancer patients. It is a sine qua non to use the formula in a clinically experienced context before deciding to electively irradiate pelvic lymph nodes or to intensify adjuvant systemic treatment.

Reappraisal of CSF-specific oligoclonal bands in Asia.

The prevalence of cerebrospinal fluid-specific oligoclonal bands (CSF-OCBs) was reported to be low in Asian people with multiple sclerosis (pwMS) compared to that in Western pwMS. It is yet to be determined whether it is a genuine feature of Asian pwMS or a misapprehension owing to past mis-classification of MS-mimicking diseases as MS. We aimed to reappraise the prevalence of CSF-OCBs in Korean pwMS after carefully excluding other central nervous system-inflammatory demyelinating diseases since 2017. Among 88 subjects, 78 (88.6%) were positive for CSF-OCBs, which suggests the prevalence of CSF-OCBs is not different between Korean and Western pwMS.

Nomogram predicting prostate cancer in patients with negative prebiopsy multiparametric magnetic resonance.

Aim: To build two nomograms for predicting the possibilities of prostate cancer (PCa) and clinically significant PCa (csPCa) in patients with negative prebiopsy multiparametric MRI (mpMRI). Methods: The independent predictors associated with PCa or csPCa in patients with negative mpMRI were determined and served in the construction of the two nomograms. Results: The nomogram predicting PCa consisted of age, positive digital rectal examination, free/total prostate-specific antigen (PSA) ratio and PSA density, while age, positive digital rectal examination and PSA density comprised the nomogram predicting csPCa. The negative predictive value of mpMRI for PCa and csPCa improved from 77.1 and 87.5% to 90.4 and 96.1%, respectively, in the training cohort (n = 376) and from 81.9 and 89.0% to 91.8 and 96.5%, respectively, in the validation cohort (n = 127) when combined with the two nomograms. Conclusion: The negative predictive value of negative mpMRI for the detection of PCa or csPCa was improved with the results of the nomograms.

When a patient has an elevated PSA level, a prostate biopsy is frequently required to diagnose prostate cancer (PCa). However, many men are not diagnosed with PCa or have indolent PCa, which means they are subjected to unnecessary biopsies that may lead to bleeding, pain and infection. With the development of multiparametric MRI (mpMRI), more biopsy-naive patients will undergo mpMRI to minimize unnecessary biopsies. Nonetheless, some patients with negative mpMRI findings but elevated levels of prostate-specific antigen still undergo prostate biopsies to rule out the possibility of MRI-invisible cancer, driving a potential for unnecessary biopsies. Therefore we developed two prediction models to estimate the likelihood of PCa and clinically significant PCa in patients with negative mpMRI, which may help to select optimal strategies to avoid unnecessary biopsies.

Critical Care Randomized Trials Demonstrate Power Failure: A Low Positive Predictive Value of Findings in the Critical Care Research Field.

BACKGROUND: We aimed to determine the post-hoc power of randomized controlled trials (RCTs) in critical care, and describe the implications for long-term positive (PPV) and negative predictive value (NPV) of statistically significant and non-significant findings respectively in the research field. METHODS: We reviewed three cohorts of RCTs. "Adult-RCTs" were 216 multicenter RCTs with a mortality outcome from a published systematic review. "Pediatric-RCTs" were 120 RCTs with a mortality outcome, obtained by search of picutrials.net. "Consecutive-RCTs" were 90 recent RCTs obtained by screening publications in 6 journals. Post-hoc power for each study was calculated at α 0.05 and 0.005, for measures of small, medium, and large effect-size, using G*Power software. Long-run expected PPV and NPV of critical care research field findings were then calculated. RESULTS: With α 0.05, post-hoc power for small effect-size was very low in all RCT-cohorts (eg, median 24% in Adult-RCTs). For medium effect-size, post-hoc power was low, except for Adult-RCTs (eg, median 9% in Pediatric-RCTs). For large effect-size, post-hoc power for non-human-animal Consecutive-RCTs was low (median 32%). With α 0.005, post-hoc power was even lower. The corollary was that both PPV and NPV were poor for small effect-size, unless α 0.005 was used. Even with α 0.005, with realistic (vs. optimistic) prior probability of the alternative hypothesis, the PPV was low (eg, in Adult-RCTs 57.1% vs. 92.3%). Adding mild bias (0.1) reduced the PPV even further. For medium effect-size both PPV and NPV were better; nevertheless, with α 0.05 and realistic prior probability of the alternative hypothesis the PPV was poor, and with α 0.005 and mild bias (0.1) the PPV was very low (eg, Adult-RCTs median 44.1%). CONCLUSIONS: To improve the predictive value of findings in the critical care research field, RCTs should be designed to have 80% power for realistic effect-size at α 0.005.

The Paris System for reporting urinary cytology improves the negative predictive value of high-grade urothelial carcinoma.

BACKGROUND: The Paris System (TPS) for reporting urinary cytology differs from conventional systems (CS) in that it focuses on the diagnosis of high-grade urothelial carcinoma (HGUC). This study investigated the impact of TPS implementation on the diagnostic accuracy of HGUC by comparing it with our institutional CS. METHODS: A total of 649 patients who underwent transurethral resection of bladder tumor (TURBT) between January 2009 and December 2020 were included in this study. Our institution adopted TPS to report urinary cytology in February 2020. The diagnostic accuracy of HGUC in preoperative urinary cytology was compared with the presence or absence of HGUC in resected specimens of TURBT before and after TPS implementation. RESULTS: After implementing TPS in urinary cytology, 89 patients were reviewed and compared with 560 patients whose urinary cytology was diagnosed by CS. TPS and CS for detecting HGUC had 56.0% and 58.2% sensitivity, 97.8% and 91.2% specificity, and 93.3% and 87.9% positive predictive values, respectively. There were no significant differences between TPS and CS in terms of sensitivity, specificity, and positive predictive value for HGUC (P = 0.83, 0.21, 1.00). On the other hand, the negative predictive value for HGUC using TPS was 80.0%, which was significantly higher than that of CS (66.4%, P = 0.04) The multivariate logistic regression analysis indicated that not using TPS was one of the independent predictive factors associated with false-negative results for HGUC (odds ratio, 2.26; 95% confidence interval, 1.08-4.77; P = 0.03). CONCLUSION: In instances where urinary cytology is reported as negative for HGUC by TPS, there is a low probability of HGUC, indicating that TPS has a potential diagnostic benefit.