Toward harmonized interpretation of anticardiolipin and anti-ß2-glycoprotein I antibody detection for diagnosis of antiphospholipid syndrome using defined level intervals and likelihood ratios: communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

BACKGROUND: Improving harmonization of the clinical interpretation of anticardiolipin (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies immunoglobulin G (IgG)/immunoglobulin M (IgM) in the diagnosis of antiphospholipid syndrome (APS) is desirable. Likelihood ratios (LRs) with corresponding test-result intervals can identify the power of a test to discriminate between a diseased and nondiseased patient and may be useful for the semiquantitative interpretation of aCL/aß2GPI results. OBJECTIVES: To determine moderate and high thresholds for aCL and aß2GPI IgG/IgM measured with chemiluminescent immunoassay, enzyme-linked immunosorbent assay, fluorescence enzyme immunoassay, and multiplex flow immunoassay. METHODS: aCL and aß2GPI antibodies IgG/IgM were determined with 4 solid-phase systems in a case-control study population including 381 APS patients and 727 controls. Interval-specific LRs (IS-LR) were calculated for ranges determined by prespecified specificity and sensitivity levels. Three methods were used for determining thresholds that separated low, moderate, and high positive antibody levels. Interassay agreement was checked with Cohen's kappa statistics. RESULTS: Assay- and antibody-specific thresholds demonstrated increasing IS-LR, reflecting different clinical significance for low, moderate, and high levels, especially for IgG aCL and aß2GPI and in thrombotic APS. IS-LRs per antibody and unit range were comparable across solid-phase platforms resulting in enhanced harmonization of result interpretation. Agreement between assays for identifying high levels was improved by semiquantitative interpretation compared with that by quantitative reporting. CONCLUSION: aCL and aß2GPI IgG/IgM moderate and high thresholds were determined for 4 analytical platforms. Thresholds improve harmonized interpretation of aCL/aß2GPI levels across platforms. The proposed thresholds should be verified in an independent case-control study to check interlaboratory transferability.

SPECT Ventilation/Perfusion Imaging for Acute Pulmonary Embolism: Meta-analysis of Diagnostic Test Accuracy.

RATIONALE AND OBJECTIVES: This study aimed to evaluate the diagnostic accuracies of ventilation/perfusion-single photon emission computed tomography (V/Q-SPECT) imaging modalities for acute pulmonary embolism (PE). These included, in addition to V/Q-SPECT, V/Q-SPECT with low-dose computed tomography (CT; V/Q-SPECT-CT), Q-SPECT with low-dose CT (Q-SPECT-CT), and Q-SPECT. MATERIALS AND METHODS: PubMed, Embase, CINAHL, and Web of Science databases were searched, and studies included if they studied ≥10 adult participants with acute PE and reported data on the imaging tests' diagnostic performance. Data were meta-analyzed using bivariate random effects regression model. RESULTS: Data from participants totaling 4146 from 11 V/Q-SPECT studies, 785 from 7 V/Q-SPECT-CT studies, 1196 from 7 Q-SPECT-CT studies, and 728 from five Q-SPECT studies were separately meta-analyzed. The bivariate weighted mean sensitivity and specificity were 0.94 (95% confidence interval [CI]: 0.88-0.97) and 0.95 (95% CI: 0.87-0.98) for V/Q-SPECT, 0.95 (95% CI: 0.88-0.98) and 0.99 (95% CI: 0.92-1.00) for V/Q-SPECT-CT, 0.92 (95% CI: 0.79-0.97) and 0.92 (95% CI: 0.83-0.96) for Q-SPECT-CT, and 0.89 (95% CI: 0.76-0.95) and 0.86 (95% CI: 0.67-0.95) for Q-SPECT studies. The positive and negative likelihood ratios (+LRs and -LRs) were 17.4 (6.9-44.0) and 0.06 (0.03-0.13), 76.7 (11.8-498.0) and 0.06 (0.02-0.13), 11.0 (5.3-22.9) and 0.09 (0.04-0.23), and 6.4 (2.6-15.8) and 0.13 (0.07-0.27) for V/Q-SPECT, V/Q-SPECT-CT, Q-SPECT-CT, and Q-SPECTs, respectively. CONCLUSION: In the diagnosis of acute PE, this meta-analysis showed that V/Q-SPECT-CT had the highest specificity and +LR. Conversely, Q-SPECT showed the lowest specificity and an unfavorably high -LR.

Likelihood interval for nonlinear regression.

Wald confidence interval has been used as the conventional method of interval estimation for the parameters in nonlinear models. Because Wald confidence interval is symmetric around the point estimate, it does not reflect the asymmetry of the likelihood profile in nonlinear regression. In contrast, a likelihood interval is estimated directly from the likelihood profile and does reflect the shape of the likelihood profile. However, the lack of software for the estimation of likelihood intervals and visualization of likelihood profiles posed an obstacle to the use of likelihood intervals in nonlinear models. There was a need for software implementation to tackle these tasks. Likelihood interval estimation and likelihood profile plotting for nonlinear models had not been previously implemented in R software. This article describes the implementation of likelihood interval estimation and likelihood profile plotting in the wnl R software package. To demonstrate the usage of implemented functions, an example of fitting a nonlinear pharmacokinetic model to concentration-time data is presented.

Added value of PET Bayesian penalized likelihood reconstruction algorithm in the diagnosis of solitary pulmonary nodules/masses / 中华核医学与分子影像杂志

Objective:To investigate the effects of silicon photomutipliers (SiPM) detector and Bayesian penalized likelihood (BPL) reconstruction algorithm on semiquantitative parameters of 18F-FDG PET/CT and diagnostic efficiency for solitary pulmonary nodules/masses compared with traditional photomultiplier tube (PMT) and ordered subsets expectation maximization (OSEM). Methods:From March 2020 to January 2022, 118 patients (76 males, 42 females, age (63.0±10.1) years) newly diagnosed with solitary pulmonary nodules/masses in First Hospital of Shanxi Medical University were prospectively enrolled and underwent 18F-FDG PET/CT imaging with two different PET/CT scanners successively. The images were divided into PMT+ OSEM, SiPM+ OSEM and SiPM+ BPL groups according to PET detector and reconstruction algorithms. The SUV max, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of pulmonary nodules/masses were measured, then signal-to-noise ratio (SNR) and signal-to-background ratio (SBR) were calculated. One-way analysis of variance and Kruskal-Wallis rank sum test were performed to compare differences of above parameters among groups. ROC curve analysis was used to analyze the optimal threshold of SUV max for the differential diagnosis of pulmonary nodules/masses and AUCs were obtained. Results:There were 83 malignant nodules and 35 benign nodules. The image quality of SiPM+ BPL group (4.23±0.64) was better than that of SiPM+ OSEM group (3.57±0.50) or PMT+ OSEM group (3.58±0.51; F=54.85, P<0.001). There were significant differences in SUV max (7.57(3.86, 15.61) vs 4.95(2.22, 10.48)), SUV mean (4.43(2.28, 9.12) vs 2.84(1.21, 5.71)), MTV (3.54(1.57, 7.67) vs 5.09(2.83, 11.79)), SNR (28.12(12.55, 54.38) vs 20.16(8.29, 41.45)) and SBR (4.03(1.83, 7.75) vs 2.32(0.96, 5.03)) between SiPM+ BPL and SiPM+ OSEM groups ( H values: 16.63-37.05, all P<0.001). The optimal threshold values of SUV max in SiPM+ BPL, SiPM+ OSEM and PMT+ OSEM were 3.31, 2.21, 2.05 with AUCs of 0.686, 0.689, 0.615 for nodules < 2 cm, and were 10.29, 6.49, 4.33 with AUCs of 0.775, 0.782, 0.774 for nodules/masses ≥2 cm. Conclusions:Image quality and parameters of pulmonary nodules/masses are mainly affected by the reconstruction algorithms. BPL can improve SUV max, SUV mean, SBR and SNR, but reduce MTV without significant effect on liver parameters. SiPM+ BPL has a higher diagnostic threshold of SUV max than SiPM+ OSEM and PMT+ OSEM.

Heritability Analyses Uncover Shared Genetic Effects of Lung Function and Change over Time.

Genetic influence on lung functions has been identified in previous studies; however, the relative longitudinal effects of genetic factors and their interactions with smoking on lung function remain unclear. Here, we identified the longitudinal effects of genetic variants on lung function by determining single nucleotide polymorphism (SNP) heritability and genetic correlations, and by analyzing interactions with smoking. Subject-specific means and annual change rates were calculated for eight spirometric measures obtained from 6622 Korean adults aged 40−69 years every two years for 14 years, and their heritabilities were estimated separately. Statistically significant (p < 0.05) heritability for the subject-specific means of all spirometric measures (8~32%) and change rates of forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC; 16%) and post-bronchodilator FEV1/FVC (17%) were detected. Significant genetic correlations of the change rate with the subject-specific mean were observed for FEV1/FVC (ρg = 0.64) and post-bronchodilator FEV1/FVC (ρg = 0.47). Furthermore, post-bronchodilator FEV1/FVC showed significant heritability of SNP-by-smoking interaction (hGXS2 = 0.4) for the annual change rate. The GWAS also detected genome-wide significant SNPs for FEV1 (rs4793538), FEV1/FVC (rs2704589, rs62201158, and rs9391733), and post-bronchodilator FEV1/FVC (rs2445936). We found statistically significant evidence of heritability role on the change in lung function, and this was shared with the effects on cross-sectional measurements. We also found some evidence of interaction with smoking for the change of lung function.

Poisson Regression Modeling of Diarrhea Events in Pasuruan Regency with Maximum Likelihood Estimates and Generalized Method Moment.

CONTEXT: Diarrhea characterized by a frequency increased of defecation more than 3 times/ day accompanied by changes in consistency (becoming liquid). The causes of diarrhea can be divided into 2 parts, which are direct causes and indirect causes that can facilitate or accelerate the occurrence of diarrhea, including bacteria, nutritional conditions, hygiene and sanitation, social culture such as population density, economic status, low birth weight, and immunization. AIMS: The purpose of this study to examine the factors that influence the incidence of diarrhea. METHODS: This research used secondary data, the prevalence of diarrhea and risk factors in Pasuruan Regency Health Center. Poisson regression approach with maximum likelihood estimator (MLE) estimation and Generalized Method Moment (GMM) used in this study. RESULTS: The results showed that GMM estimation method in the Poisson regression model gave better performance in terms of significance parameters compared to the MLE method. CONCLUSIONS: Factors affecting the increase of diarrhea occurrences in area with an estimated MLE Percentage of non-exclusive breastfeeding and Percentage of normal nutritional status. Whereas the GMM estimation is the percentage of non-exclusive breastfeeding, the percentage of low birth weight, the percentage of population density, the percentage of smokers among family members in the house, the percentage of incomplete immunizations, the percentage of under-five years old children less than 2, the percentage of normal nutritional status, and the percentage of middle class socioeconomic status.

Choosing Interim Sample Sizes in Group Sequential Designs.

This manuscript investigates sample sizes for interim analyses in group sequential designs. Traditional group sequential designs (GSD) rely on "information fraction" arguments to define the interim sample sizes. Then, interim maximum likelihood estimators (MLEs) are used to decide whether to stop early or continue the data collection until the next interim analysis. The possibility of early stopping changes the distribution of interim and final MLEs: possible interim decisions on trial stopping excludes some sample space elements. At each interim analysis the distribution of an interim MLE is a mixture of truncated and untruncated distributions. The distributional form of an MLE becomes more and more complicated with each additional interim analysis. Test statistics that are asymptotically normal without a possibly of early stopping, become mixtures of truncated normal distributions under local alternatives. Stage-specific information ratios are equivalent to sample size ratios for independent and identically distributed data. This equivalence is used to justify interim sample sizes in GSDs. Because stage-specific information ratios derived from normally distributed data differ from those derived from non-normally distributed data, the former equivalence is invalid when there is a possibility of early stopping. Tarima and Flournoy [3] have proposed a new GSD where interim sample sizes are determined by a pre-defined sequence of ordered alternative hypotheses, and the calculation of information fractions is not needed. This innovation allows researchers to prescribe interim analyses based on desired power properties. This work compares interim power properties of a classical one-sided three stage Pocock design with a one-sided three stage design driven by three ordered alternatives.

Predictive Accuracy of a Polygenic Risk Score for Postoperative Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (PoAF) remains a significant risk factor for increased morbidity and mortality after cardiac surgery. The ability to accurately identify patients at risk through clinical risk factors is limited. There is growing evidence that polygenic risk contributes significantly to PoAF and incorporating measures of genetic risk could enhance prediction. METHODS: A retrospective cohort study of 1047 patients of White European ancestry who underwent either coronary artery bypass grafting or valve surgery at a tertiary academic center and were free from a history or persistent preoperative atrial fibrillation. The primary outcome was defined as PoAF based on postoperative ECG reports, medical record documentation, and changes in medication. The exposure was a polygenic risk score (PRS) comprising 2746 single-nucleotide polymorphisms previously associated with atrial fibrillation risk. The prediction of PoAF risk was assessed using measures of model discrimination, calibration, and net reclassification improvement. RESULTS: A total of 259 patients (24.7%) developed PoAF. The PRS was significantly associated with a higher risk for PoAF (odds ratio, 1.63 per SD increase in PRS [95% CI, 1.41-1.90]). Addition of PRS to patient- and procedure-related predictors of PoAF significantly increased the C statistic from 0.742 to 0.782 (change in C statistic, 0.040 [95% CI, 0.021-0.060]) while maintaining good calibration. The addition of the PRS to patient- and procedure-related predictors of PoAF improved model fit (likelihood ratio test, P=2.8×10-15) and significantly improved measures of reclassification (net reclassification improvement, 0.158 [95% CI, 0.066-0.274]). CONCLUSIONS: The PRS for PoAF was associated with improved discrimination, calibration, and risk reclassification compared with conventional clinical predictors suggesting that a PoAF PRS may enhance risk prediction of PoAF in patients undergoing coronary artery bypass grafting or valve surgery.

Multi-sensor data fusion based on soft likelihood functions and OWA aggregation and its application in target recognition system.

Multi-sensor data fusion plays an irreplaceable role in actual production and application. Dempster-Shafer theory (DST) is widely used in numerous fields of information modeling and information fusion due to the flexibility and effectiveness of processing uncertain information and dealing with uncertain information without prior probabilities. However, when highly contradictory evidence is combined, it may produce results that are inconsistent with human intuition. In order to solve this problem, a hybrid method for combining belief functions based on soft likelihood functions (SLFs) and ordered weighted averaging (OWA) operators is proposed. More specifically, a soft likelihood function based on OWA operators is used to provide the possibility to fuse uncertain information compatible with each other. It can characterize the degree to which the probability information of compatible propositions in the collected evidence is affected by unknown uncertain factors. This makes the results of using the Dempster's combination rule to fuse uncertain information from multiple sources more comprehensive and credible. Experimental results manifest that this method is reliable. Example and application show that this method has obvious advantages in solving the problem of conflict evidence fusion in multi-sensor. In particular, in target recognition, when three pieces of evidence are fused, the target recognition rate is 96.92%, etc.

Introduction to the LIVECAT web-based computerized adaptive testing platform.

This study introduces LIVECAT, a web-based computerized adaptive testing platform. This platform provides many functions, including writing item content, managing an item bank, creating and administering a test, reporting test results, and providing information about a test and examinees. The LIVECAT provides examination administrators with an easy and flexible environment for composing and managing examinations. It is available at http://www.thecatkorea.com/. Several tools were used to program LIVECAT, as follows: operating system, Amazon Linux; web server, nginx 1.18; WAS, Apache Tomcat 8.5; database, Amazon RDMS-Maria DB; and languages, JAVA8, HTML5/CSS, Javascript, and jQuery. The LIVECAT platform can be used to implement several item response theory (IRT) models such as the Rasch and 1-, 2-, 3-parameter logistic models. The administrator can choose a specific model of test construction in LIVECAT. Multimedia data such as images, audio files, and movies can be uploaded to items in LIVECAT. Two scoring methods (maximum likelihood estimation and expected a posteriori) are available in LIVECAT and the maximum Fisher information item selection method is applied to every IRT model in LIVECAT. The LIVECAT platform showed equal or better performance compared with a conventional test platform. The LIVECAT platform enables users without psychometric expertise to easily implement and perform computerized adaptive testing at their institutions. The most recent LIVECAT version only provides a dichotomous item response model and the basic components of CAT. Shortly, LIVECAT will include advanced functions, such as polytomous item response models, weighted likelihood estimation method, and content balancing method.

Aplicación de modelos paramétricos alternativos para el análisis de supervivencia de pacientes con cáncer / Application of alternative parametric models for the survival analysis of cancer patients

RESUMEN En el presente artículo se describe una metodología que permite tener un acercamiento a modelos probabilísticos alternativos para el análisis de supervivencia, con censura por la derecha, distintos a los que usualmente se estudian (distribución: exponencial, gamma, Weibull y log-normal), ya que es posible que los datos no se ajusten siempre con suficiente precisión por las distribuciones existentes. La metodología utilizada permite mayor flexibilidad de modelar observaciones extremas, ubicadas generalmente en la cola derecha de la distribución de los datos, lo cual admite que algunos eventos aún tengan la probabilidad de ocurrir, lo que no sucede con los modelos tradicionales y el estimador de Kaplan-Meier, el cual estima para los tiempos más prolongados, probabilidades de supervivencia aproximadamente iguales a cero. Para mostrar la utilidad de la propuesta metodológica, se consideró una aplicación con datos reales que relaciona tiempos de supervivencia de pacientes con cáncer de colon.

ABSTRACT This article describes a methodology that allows an approach to alternative right-censored probabilistic models for the analysis of survival, different to those usually studied (exponential, gamma, Weibull, and log-normal distribution) since it is possible that the data do not always fit with sufficient precision due to existing distributions. The methodology used allows for greater flexibility when modeling extreme observations, generally located in the right tail of data distribution, which admits that some events still have the probability of occurring, which is not the case with traditional models and the Kaplan-Meier estimator, which estimates for the longest times, survival probabilities approximately equal to zero. To show the usefulness of the methodological proposal, we considered an application with real data that relates survival times of patients with colon cancer (CC).

Low serum vitamin D is associated with an increased likelihood of acquired premature ejaculation

Abstract Purpose: To investigate the relationship between 25-hydroxyvitamin D (25 (OH) D) levels and acquired premature ejaculation (PE). Materials and Methods: A total of 97 patients with acquired PE and 64 healthy men as a control group selected from volunteers without PE attending our Andrology Outpatient Clinic between November 2016 and April 2017 were included the study. All patients were considered to have acquired PE if they fulfilled the criteria of the second Ad Hoc International Society for Sexual Medicine Committee. Premature ejaculation diagnostic tool questionnaires were used to assessment of PE and all participants were instructed to record intravaginal ejaculatory latency time. Vitamin D levels were evaluated in all participants using high performance liquid chromatography method included in the study. Results: Compared to men without PE, the patients with acquired PE had significantly lower 25 (OH) D levels (12.0 ± 4.5 ng/mL vs. 18.2 ± 7.4 ng/mL, p < 0.001). In the logistic regression analysis, 25 (OH) D was found to be an independent risk factor for acquired PE, with estimated odds ratios (95% CI) of 0.639 (0.460-0.887, p = 0.007) and the area under curve of the ROC curve of 25 (OH) D diagnosing acquired PE was 0.770 (95% CI: 0.695 to 0.844, p < 0.001). The best cut-off value was 16 ng/mL with a sensitivity of 60.9%, specificity of 83.5%, PPV of 70.9%, and NPV of 76.4% to indicate acquired PE. Conclusions: This study demonstrates that lower vitamin D levels are associated with the acquired PE. The result of our study showed that the role of serum vitamin D levels should be investigate in the etiology of acquired PE. Perhaps supplementation of vitamin D in men with acquired PE will ameliorate the sexual health of these patients.

Low serum vitamin D is associated with an increased likelihood of acquired premature ejaculation.

PURPOSE: To investigate the relationship between 25-hydroxyvitamin D (25 (OH) D) levels and acquired premature ejaculation (PE). MATERIALS AND METHODS: A total of 97 patients with acquired PE and 64 healthy men as a control group selected from volunteers without PE attending our Andrology Outpatient Clinic between November 2016 and April 2017 were included the study. All patients were considered to have acquired PE if they fulfilled the criteria of the second Ad Hoc International Society for Sexual Medicine Committee. Premature ejaculation diagnostic tool questionnaires were used to assessment of PE and all participants were instructed to record intravaginal ejaculatory latency time. Vitamin D levels were evaluated in all participants using high performance liquid chromatography method included in the study. RESULTS: Compared to men without PE, the patients with acquired PE had significantly lower 25 (OH) D levels (12.0 ± 4.5 ng/mL vs. 18.2 ± 7.4 ng/mL, p < 0.001). In the logistic regression analysis, 25 (OH) D was found to be an independent risk factor for acquired PE, with estimated odds ratios (95% CI) of 0.639 (0.460-0.887, p = 0.007) and the area under curve of the ROC curve of 25 (OH) D diagnosing acquired PE was 0.770 (95% CI: 0.695 to 0.844, p < 0.001). The best cut-off value was 16 ng/mL with a sensitivity of 60.9%, specificity of 83.5%, PPV of 70.9%, and NPV of 76.4% to indicate acquired PE. CONCLUSIONS: This study demonstrates that lower vitamin D levels are associated with the acquired PE. The result of our study showed that the role of serum vitamin D levels should be investigate in the etiology of acquired PE. Perhaps supplementation of vitamin D in men with acquired PE will ameliorate the sexual health of these patients.

Augmenting beta regression for periodontal proportion data via the SAS NLMIXED procedure.

Often in clinical dental research, clinical attachment level (CAL) is recorded at several sites throughout the mouth to assess the extent of periodontal disease (PD). One might be interested to quantify PD at the tooth-level via the proportion of diseased sites per tooth type (say, incisors, canines, pre-molars and molars) per subject. However, these studies might consist of relatively disease-free and highly diseased subjects leading to the proportion responses distributed in the interval [0, 1]. While beta regression (BR) is often the model of choice to assess covariate effects for proportion data, the presence (and/or abundance) of zeros and/or ones makes it inapplicable here because the beta support is defined in the interval (0, 1). Avoiding ad hoc data transformation, we explore the potential of the augmented BR framework which augments the beta density with non-zero masses at zero and one while accounting for the clustering induced. Our classical estimation framework using maximum likelihood utilizes the potential of the SAS® Proc NLMIXED procedure. We explore our methodology via simulation studies and application to a real cross-sectional dataset on PD, and we assess the gain in model fit and parameter estimation over other ad hoc alternatives. This reveals newer insights into risk quantification on clustered proportion responses. Our methods can be implemented using standard SAS software routines. The augmented BR model results in a better fit to clustered periodontal proportion data over the standard beta model. We recommend using it as a parametric alternative for fitting proportion data, and avoid ad hoc data transformation.

Prediction model for para-aortic lymph node metastasis in patients with locally advanced cervical cancer.

OBJECTIVE: Concurrent chemoradiotherapy is usually administered to patients with locally advanced cervical cancer (LACC). Extended-field chemoradiotherapy is required if para-aortic lymph node (PALN) metastasis is detected. This study aimed to construct a prediction model for PALN metastasis in patients with LACC before definitive treatment. METHODS: Between 2009 and 2016, all consecutive patients with LACC who underwent para-aortic lymphadenectomy at two tertiary centers were retrospectively analyzed. A multivariate logistic model was constructed, from which a prediction model for PALN metastasis was developed and internally validated. Before analysis, risk grouping was predefined based on the likelihood ratio. RESULTS: In total, 245 patients satisfied the eligibility criteria. Thirty-four patients (13.9%) had pathologically proven PALN metastases. Additionally, 16/222 (7.2%) patients with negative PALNs on positron emission tomography/computed tomography (PET/CT) had PALN metastasis. Moreover, 11/105 (10.5%) patients with both negative PALNs and positive pelvic lymph nodes on PET/CT had PALN metastasis. Tumor size on magnetic resonance imaging and PALN status on PET/CT were independent predictors of PALN metastasis. The model incorporating these two predictors displayed good discrimination and calibration (bootstrap-corrected concordance index=0.886; 95% confidence interval=0.825-0.947). The model categorized 169 (69%), 52 (22%), and 23 (9%) patients into low-, intermediate-, and high-risk groups, respectively. The predicted probabilities of PALN metastasis for these groups were 2.9, 20.8, and 76.2%, respectively. CONCLUSION: We constructed a robust model predicting PALN metastasis in patients with LACC that may improve clinical trial design and help clinicians determine whether nodal-staging surgery should be performed.

Importancia del cálculo de la sensibilidad, la especificidad y otros parámetros estadísticos en el uso de las pruebas de diagnóstico clínico y de laboratorio / Importance of calculation of sensitivity, specificity, and other statistical parameters in the use of clinical and laboratory diagnostic tests

Resumen: la elección de una prueba a realizar para un paciente, así como su interpretación, es un escenario diario al cual el médico se debe enfrentar y para el cual debe aplicar su juicio crítico basado en las evidencias informadas. Es común que cuando se habla de una prueba de diagnóstico clínico o de laboratorio se describan parámetros como la sensibilidad, la especificidad y los valores predictivos positivos y negativos. Estos reflejan las características de una prueba diagnóstica y sirven para decidir en qué momento se deben utilizar (sensibilidad y especificidad de una prueba) o qué significado tiene el resultado de una prueba en un paciente en particular. Cuando se trata de comparar estos parámetros en diferentes pruebas y optar por la que es de mayor utilidad en el diagnóstico de una enfermedad determinada, es indispensable que el médico conozca y aprenda cómo se obtienen estas medidas y cuál es su interpretación para decidir la conducta más apropiada para el paciente. El objetivo de la presente revisión es ofrecer los conceptos estadísticos básicos y simples para la comprensión y aplicación de las pruebas de diagnóstico clínico y de laboratorio. (AU)

Abstract: The selection of a test to request a patient as well as their interpretation is a daily scenario in which the physician must deal and apply his critical judgment based on the reported evidences. It is common that when talking about a clinical or laboratory diagnostic test, parameters such as sensitivity, specificity and positive and negative predictive values are described. These parameters reflect the characteristics of a diagnostic test and serve to decide when should be used (sensitivity and specificity of a test) or what is the meaning of a test result in a particular patient. When it is necessary to compare these parameters in different tests and opting for the most useful for the diagnosis of a particular disease, it is essential that the physician knows and learns how these measures are obtained and their interpretation to decide the most appropriate behavior for the patient. The objective of the present review is to provide basic and simple statistical concepts for the understanding and application of clinical and laboratory diagnostic tests. (AU)

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals / Imagem molecular pré-clínica: desenvolvimento de instrumentação para pesquisa translacional com pequenos animais

ABSTRACT Objective: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. Methods: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. Results: Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). Conclusion: This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others.

RESUMO Objetivo: Apresentar o resultado da adaptação de uma gama câmara clínica para uso dedicado na obtenção de imagens tomográficas in vivo de órgãos de pequenos animais de experimentação, e de sua aplicação na obtenção de imagens cardíacas, renais e neurológicas. Métodos: Foi construída uma versão atualizada do dispositivo de adaptação miniSPECT, composto por três subsistemas: mecânico, eletrônico e de software. O dispositivo foi montado em uma câmara Discovery VH da General Electric Healthcare, retirada do serviço clínico e instalada no Centro de Imagem Pré-Clínica do Hospital Israelita Albert Einstein. O sistema combinado foi caracterizado, determinando parâmetros de funcionamento como resolução espacial, magnificação, limites de tamanho dos alvos de estudo, número de projeções, tempo de registro e tempo de reconstrução das imagens tomográficas. Resultados: Foram obtidas imagens com resolução espacial de até 0,5mm, com tempos de registro e reconstrução de 30 a 45 minutos, utilizando reconstrução iterativa com 10 a 20 iterações e 4 subconjuntos de projeções. O sistema foi validado obtendo imagens tomográficas in vivo do coração, dos rins e do cérebro de animais normais (camundongos e ratos adultos), utilizando os radiofármacos hexaquis-2-metoxi-isobutil-isonitrila marcado com 99mTc (Sestamibi-99mTc), ácido dimercaptosuccínico marcado com 99mTc (DMSA-99mTc) e hexametil-propileno-amina-oxima marcada com 99mTc (HMPAO-99mTc). Conclusão: Este tipo de aplicação, que consiste na adaptação para um objetivo alternativo de instrumentação já existente, constituiu-se em uma opção de infraestrutura de baixo custo, que permite realizar estudos in vivo em larga escala, com qualidade aprimorada, em áreas diversas, como neurologia, nefrologia, cardiologia, entre outras.

Predictive performance of BI-RADS magnetic resonance imaging descriptors in the context of suspicious (category 4) findings.

OBJECTIVE: To determine the positive predictive value (PPV) and likelihood ratio for magnetic resonance imaging (MRI) characteristics of category 4 lesions, as described in the Breast Imaging Reporting and Data System (BI-RADS(®)) lexicon, as well as to test the predictive performance of the descriptors using multivariate analysis and the area under the curve derived from a receiver operating characteristic (ROC) curve. MATERIALS AND METHODS: This was a double-blind review study of 121 suspicious findings from 98 women examined between 2009 and 2013. The terminology was based on the 2013 edition of the BI-RADS. RESULTS: Of the 121 suspicious findings, 53 (43.8%) were proven to be malignant lesions, with no significant difference between mass and non-mass enhancement (p = 0.846). The PPVs were highest for masses with a spiculated margin (71%) and round shape (63%), whereas segmental distribution achieved a high PPV (80%) for non-mass enhancement. Kinetic analyses performed poorly, except for type 3 curves applied to masses (PPV of 73%). Logistic regression models were significant for both patterns, although the results were better for masses, particularly when kinetic assessments were included (p = 0.015; pseudo R(2) = 0.48; area under the curve = 90%). CONCLUSION: Some BI-RADS MRI descriptors have high PPV and good predictive performance-as demonstrated by ROC curve and multivariate analysis-when applied to BI-RADS category 4 findings. This may allow future stratification of this category.

OBJETIVO: Determinar o valor preditivo positivo (VPP) e a razão de verossimilhança positiva de características de ressonância magnética (RM) de lesões da categoria 4, como descritas no léxico do Breast Imaging Reporting and Data System (BI-RADS®), e testar o desempenho preditivo dos descritores por meio de análise multivariada e área sob a curva derivada da curva receiver operating characteristic (ROC). MATERIAIS E MÉTODOS: Foi realizado um estudo revisional duplo-cego de 121 achados suspeitos em 98 mulheres examinadas entre 2009 e 2013. A terminologia foi baseada na edição de 2013 do BI-RADS. RESULTADOS: Dos 121 achados suspeitos, 53 (43,8%) eram de fato lesões malignas, sem diferença significativa entre nódulos e realce não nodular (p = 0,846). Nódulos com margem espiculada (71%) e forma redonda (63%) apresentaram os maiores VPPs, ao passo que a distribuição segmentar teve alto VPP para realce não nodular (80%). Apenas a curva cinética do tipo 3 teve bom desempenho quando aplicada a nódulos (VPP = 73%). Modelos de regressão logística foram significantes para os dois padrões principais, embora os nódulos tenham apresentado resultados melhores, particularmente com a introdução da análise cinética (p = 0,015; pseudo-R2 = 0,48; área sob a curva = 90%). CONCLUSÃO: Alguns descritores de RM do BI-RADS têm alto VPP e bom desempenho preditivo - demonstrado por curva ROC e análise multivariada - quando aplicados a achados da categoria 4 segundo o BI-RADS. Isso pode permitir futura estratificação dessa categoria.

Predictive performance of BI-RADS magnetic resonance imaging descriptors in the context of suspicious (category 4) findings / Desempenho preditivo dos descritores de ressonância magnética do BI-RADS no contexto de achados suspeitos (categoria 4)

Abstract Objective: To determine the positive predictive value (PPV) and likelihood ratio for magnetic resonance imaging (MRI) characteristics of category 4 lesions, as described in the Breast Imaging Reporting and Data System (BI-RADS®) lexicon, as well as to test the predictive performance of the descriptors using multivariate analysis and the area under the curve derived from a receiver operating characteristic (ROC) curve. Materials and Methods: This was a double-blind review study of 121 suspicious findings from 98 women examined between 2009 and 2013. The terminology was based on the 2013 edition of the BI-RADS. Results: Of the 121 suspicious findings, 53 (43.8%) were proven to be malignant lesions, with no significant difference between mass and non-mass enhancement (p = 0.846). The PPVs were highest for masses with a spiculated margin (71%) and round shape (63%), whereas segmental distribution achieved a high PPV (80%) for non-mass enhancement. Kinetic analyses performed poorly, except for type 3 curves applied to masses (PPV of 73%). Logistic regression models were significant for both patterns, although the results were better for masses, particularly when kinetic assessments were included (p = 0.015; pseudo R2 = 0.48; area under the curve = 90%). Conclusion: Some BI-RADS MRI descriptors have high PPV and good predictive performance-as demonstrated by ROC curve and multivariate analysis-when applied to BI-RADS category 4 findings. This may allow future stratification of this category.

Resumo Objetivo: Determinar o valor preditivo positivo (VPP) e a razão de verossimilhança positiva de características de ressonância magnética (RM) de lesões da categoria 4, como descritas no léxico do Breast Imaging Reporting and Data System (BI-RADS®), e testar o desempenho preditivo dos descritores por meio de análise multivariada e área sob a curva derivada da curva receiver operating characteristic (ROC). Materiais e Métodos: Foi realizado um estudo revisional duplo-cego de 121 achados suspeitos em 98 mulheres examinadas entre 2009 e 2013. A terminologia foi baseada na edição de 2013 do BI-RADS. Resultados: Dos 121 achados suspeitos, 53 (43,8%) eram de fato lesões malignas, sem diferença significativa entre nódulos e realce não nodular (p = 0,846). Nódulos com margem espiculada (71%) e forma redonda (63%) apresentaram os maiores VPPs, ao passo que a distribuição segmentar teve alto VPP para realce não nodular (80%). Apenas a curva cinética do tipo 3 teve bom desempenho quando aplicada a nódulos (VPP = 73%). Modelos de regressão logística foram significantes para os dois padrões principais, embora os nódulos tenham apresentado resultados melhores, particularmente com a introdução da análise cinética (p = 0,015; pseudo-R2 = 0,48; área sob a curva = 90%). Conclusão: Alguns descritores de RM do BI-RADS têm alto VPP e bom desempenho preditivo - demonstrado por curva ROC e análise multivariada - quando aplicados a achados da categoria 4 segundo o BI-RADS. Isso pode permitir futura estratificação dessa categoria.