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.

Optimizing strategies to identify high risk of developing type 2 diabetes.

Introduction: The success of diabetes prevention based on early treatment depends on high-quality screening. This study compared the diagnostic properties of currently recommended screening strategies against alternative score-based rules to identify those at high risk of developing diabetes. Methods: The study used data from ELSA-Brasil, a contemporary cohort followed up for a mean (standard deviation) of 7.4 (0.54) years, to develop risk functions with logistic regression to predict incident diabetes based on socioeconomic, lifestyle, clinical, and laboratory variables. We compared the predictive capacity of these functions against traditional pre-diabetes cutoffs of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), and glycated hemoglobin (HbA1c) alone or combined with recommended screening questionnaires. Results: Presenting FPG > 100 mg/dl predicted 76.6% of future cases of diabetes in the cohort at the cost of labeling 40.6% of the sample as high risk. If FPG testing was performed only in those with a positive American Diabetes Association (ADA) questionnaire, labeling was reduced to 12.2%, but only 33% of future cases were identified. Scores using continuously expressed clinical and laboratory variables produced a better balance between detecting more cases and labeling fewer false positives. They consistently outperformed strategies based on categorical cutoffs. For example, a score composed of both clinical and laboratory data, calibrated to detect a risk of future diabetes ≥20%, predicted 54% of future diabetes cases, labeled only 15.3% as high risk, and, compared to the FPG ≥ 100 mg/dl strategy, nearly doubled the probability of future diabetes among screen positives. Discussion: Currently recommended screening strategies are inferior to alternatives based on continuous clinical and laboratory variables.

Non-invasive prenatal testing for the diagnosis of congenital abnormalities: Insights from a large multicenter study in southern China

Although non-invasive prenatal testing (NIPT) is widely used to detect fetal abnormalities, the results of NIPT vary by population, and data for the screening efficiency of NIPT positive predictive value (PPV) from different populations is limited. Herein, we retrospectively analyzed the NIPT results in a large multicenter study involving 52,855 pregnant women. Depending on gestational age, amniotic fluid or umbilical cord blood was extracted for karyotype and/or chromosome microarray analysis (CMA) in NIPT-positive patients, and the PPV and follow-up data were evaluated to determine its clinical value. Among the 52,855 cases, 754 were NIPT-positive, with a positivity rate of 1.4%. Karyotype analysis and/or CMA confirmed 323 chromosomal abnormalities, with a PPV of 45.1%. PPV for trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), sex chromosomal aneuploidies (SCAs), and copy number variations (CNVs) were 78.9, 35.3, 22.2, 36.9, and 32.9%, respectively. The PPVs for T21, T18, and T13 increased with age, whereas the PPVs for SCAs and CNVs had little correlation with age. The PPV was significantly higher in patients with advanced age and abnormal ultrasound. The NIPT results are affected by population characteristics. NIPT had a high PPV for T21 and a low PPV for T13 and T18, and screening for SCAs and CNVs showed clinical significance in southern China.

Sensibilidad y especificidad de las escalas diagnósticas en la apendicitis aguda. Estudio prospectivo / Sensitivity and specificity of the diagnostic scales in acute appendicitis. Prospective study

La Apendicitis Aguda se manifiesta cuando existe inflamación del apéndice cecal, representando una de las más notables causas de abdomen agudo con pronóstico quirúrgico en el mundo. Existen sistemas de puntuaciones que se han generado para su comprobación, mediante técnicas no invasivas, de fácil aplicación y reproducción; destacando entre ellas las escalas de ALVARADO, RIPASA, AIR, entre otras. Objetivo: Comparar la sensibilidad y especificidad de las escalas AIR Vs. RIPASA para el diagnóstico de la Apendicitis Aguda en el Hospital General Nacional "Dr. Ángel Larralde", período enero 2020 ­ diciembre 2022. Materiales: Estudio observacional, descriptivo y evaluativo, prospectivo y de corte transversal. Muestra fue intencional no probabilística, cumpliendo con los criterios de inclusión. Para la recolección de datos, se empleó la observación directa como técnica y como instrumentos las escalas AIR y RIPASA. Resultados: Muestra conformada por 192 pacientes, sin predisposición de géneros. Sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y exactitud diagnóstica AIR: 70%; 58,33%; 73,68%; 53,84%; 65,62%; RIPASA: 88,88%; 42,85%; 66,66%; 75%; 68,75%. Conclusiones: La exactitud diagnóstica para la escala de RIPASA fue ligeramente mayor que para AIR (68,75% vs. 65,62%), permitiendo afirmar que, en el grupo de estudio, resultó más conveniente la aplicación de la escala de RIPASA en pacientes sanos para el diagnóstico correcto de Apendicitis Aguda(AU)

Acute Appendicitis manifests when there is inflammation of the cecal appendix, representing one of the most notable causes of acute abdomen with surgical prognosis in the world. There are scoring systems that have been generated for verification, using non-invasive techniques that are easy to apply and reproduce; highlighting among them the scales of ALVARADO, RIPASA, AIR, among others.Objective : To compare the sensitivity and specificity of the AIR Vs. RIPASA scales for the diagnosis of Acute Appendicitis at the National General Hospital "Dr. Ángel Larralde", period January 2020 ­ December 2022. Materials: Observational, descriptive and evaluative, prospective and cross-sectional study. Sample was intentional, non-probabilistic, meeting the inclusion criteria. For data collection, direct observation was used as a technique and the AIR and RIPASA scales as instruments.Results : Sample made up of 192 patients, with no gender predisposition. Sensitivity, specificity, positive predictive value, negative predictive value, and AIR diagnostic accuracy: 70%; 58.33%; 73.68%; 53.84%; 65.62%; RIPASE: 88.88%; 42.85%; 66.66%; 75%; 68.75%.Conclusions : The diagnostic accuracy for the RIPASA scale was slightly higher than for AIR (68.75% vs. 65.62%), allowing us to affirm that, in the study group, the application of the RIPASA scale was more convenient in healthy patients for the correct diagnosis of Acute Appendicitis(AU)

Procalcitonina y proteína C reactiva séricas como biomarcadores predictivos de dehiscencia de anastomosis intestinal en cirugía colorrectal.

BACKGROUND: There has been recent interest in the seric levels of procalcitonin (PCT) and C reactive protein (PCR) as a marker of intraabdominal infection after a colorrectal surgery, however, the actual literature remains inconclusive. OBJECTIVE: To test if C-Reactive Protein (PCR) and procalcitonin (PCT) as predictive factors of anastomotic leak after colorectal surgery. METHOD: Retrospective cohort, of patients with ileostomy or colostomy who had intestinal transit restitution by general surgeons in our center, from march 2018 to march 2020. RESULTS: We registered 4 (36.4%) anastomotic leaks. We compared median PCR and PCT between group 1 (without anastomotic leak) and group 2 (with anastomotic leak). Median PCT3PO was 4.86 ng/ml in group 1 vs 13.7 ng/ml in group 2, and PCT5PO was 1.3071 ng/ml vs 6.74 ng/ml (DS: 5.04 vs. 11.53 and 0.779 vs. 10.44). Median PCR3PO and PCR5PO was 194.7 mg/l in group 1 vs 100.97 mg/l in group 2, and 159.8 mg/l vs 65.67 mg/l, (DS: 88.78 vs. 82.01 and 94.77 vs. 58.009). CONCLUSIONS: Persistent higher levels of seric PCR and PCT at 3rd and 5th postoperative day could be an anastomotic leackage. This biomarkers might be added as additional criteria of discharge.

ANTECEDENTES: La medición sérica de procalcitonina (PCT) y proteína C reactiva (PCR) como marcadores de infección intraabdominal posterior a la cirugía colorrectal ha tomado interés en los recientes años, sin embargo, la literatura que existe en la actualidad no es concluyente. OBJETIVO: Evaluar los biomarcadores séricos de inflamación procalcitonina (PCT) y proteína C reactiva (PCR) como factores predictores para dehiscencia de anastomosis (DA) en cirugía colorrectal. MÉTODO: Cohorte retrospectiva de pacientes con cirugía abdominal, con ileostomía o colostomía, que fueron protocolizados para restitución del tránsito intestinal por el departamento de cirugía general en un hospital de tercer nivel, de marzo de 2018 a marzo de 2020. RESULTADOS: La DA ocurrió en 4 (36.4%) de 11 pacientes. Se comparó la media de dos grupos: el grupo 1 sin DA frente al grupo 2 que presentaron DA. Las concentraciones séricas de PCT3PO fueron de 4.86 ng/ml en el grupo 1 y 13.7 ng/ml en el grupo 2, y las de PCT5PO fueron de 1.3071 ng/ml y 6.74 ng/ml, respectivamente (desviación estándar [DE]: 5.04 vs. 11.53 y 0.779 vs. 10.44). Las concentraciones séricas de PCR3PO fueron de 194.7 mg/l en el grupo 1 y 100.97 mg/l en el grupo 2, y las de PCR5PO fueron de 159.8 mg/l y 65.67 mg/l, respectivamente (DE: 88.78 vs. 82.01 y 94.77 vs. 58.009). CONCLUSIONES: La persistencia de valores elevados den PCR y PCT séricas al tercer y quinto día posoperatorios pudieran demostrar DA. Estos marcadores podrían agregarse como criterio de egreso.

The importance of disease prevalence in clinical decision making: a real practice study on COVID-19 antigen test in Curacao.

The performance of a test can be suboptimal, but in appropriate setting such a test is still useful for clinical decision making. We investigated the role of Antigen Rapid Diagnostic Test (Ag-RDT) for clinical decision making in an Emergency Department (ED) in Curacao during peak of COVID-19 pandemic. Ag-RDT was performed in the naso- and oropharynx-swabs from patients with respiratory insufficiency presented to the ED. Ag-RDT was performed in 153 patients, of which 64 (41.8%) showed positive results. Comparing Ag-RDT results with molecular tests, its sensitivity was 68.8% (95% CI 57.4 to 78.7), and specificity of 94.6% (95% CI 84.9 to 98.9). The positive and negative predictive value were 95.1% (95% CI 86.5 to 98.3) and 66.3 (95% CI 58.6 to 73.3), respectively. All patients with Ag-RDT positive test were admitted to the cohorted COVD-19 department of the hospital. By using Ag-RDT, 35.9% of rapid PCR tests (that are more costly and laborious to perform) could be avoided at cost of 5.8% patients with false positive result. In conclusion, in real practice, disease prevalence is as important as test's performance for clinical decision making. The conclusion may also be applicable for other diagnostic tests than COVID-19 diagnostic.

Management of Non-Mass Enhancement at Breast Magnetic Resonance in Screening Settings Referred for Magnetic Resonance-Guided Biopsy.

Rationale and Objectives: According to the Breast Imaging and Reporting Data System (BI-RADS), one of the main limitations of MRI is diagnosing the non-mass enhancement (NME). The NME lesion is challenging since it is unique to the MRI lexicon. This study aims to report our experience with NME lesions diagnosed by MRI referred for MRI-guided biopsies and discuss the management and follow-up of these lesions. Materials and Methods: We retrospectively evaluated all MRI-guide breast biopsies. We included all patients referred for NME breast MRI-guided biopsy in screening settings. All patients had a negative second-look mammography or ultrasonography. We correlated the distribution and internal enhancement pattern (IEP) of the NME lesions with histology. Invasive ductal carcinomas (IDC) of no special type and ductal carcinoma in situ (DCIS) were considered malignant lesions. Results: From January-2018 to July-2021, we included 96 women with a total of 96 lesions in the study. There were 90 benign and 6 malignant lesions with DCIS prevalence (5/6 cancers). The most frequent benign lesion type was fibrocystic changes. There were no NME lesions with diffuse or multiple area distribution features referred to MRI-guided biopsy. The positive-predictive values (PPV) were respectively 0.0%, 2.5%, 9.0%, and 11.0% for linear, focal, regional, and segmental distribution describers, and 0.0, 3.0%, 7.9%, and 50% for homogenous, heterogeneous, clumped, and clustered-ring enhancement patterns. Conclusion: We observe the high potential risk for malignancy in the clustered-ring enhancement followed by the clumped pattern. Segmental distribution presented the highest predictive-positive values.

The importance of disease prevalence in clinical decision making: a real practice study on COVID-19 antigen test in Curacao

ABSTRACT The performance of a test can be suboptimal, but in appropriate setting such a test is still useful for clinical decision making. We investigated the role of Antigen Rapid Diagnostic Test (Ag-RDT) for clinical decision making in an Emergency Department (ED) in Curacao during peak of COVID-19 pandemic. Ag-RDT was performed in the naso- and oropharynxswabs from patients with respiratory insufficiency presented to the ED. Ag-RDT was performed in 153 patients, of which 64 (41.8%) showed positive results. Comparing Ag-RDT results with molecular tests, its sensitivity was 68.8% (95% CI 57.4 to 78.7), and specificity of 94.6% (95% CI 84.9 to 98.9). The positive and negative predictive value were 95.1% (95% CI 86.5 to 98.3) and 66.3 (95% CI 58.6 to 73.3), respectively. All patients with Ag-RDT positive test were admitted to the cohorted COVD-19 department of the hospital. By using Ag-RDT, 35.9% of rapid PCR tests (that are more costly and laborious to perform) could be avoided at cost of 5.8% patients with false positive result. In conclusion, in real practice, disease prevalence is as important as test's performance for clinical decision making. The conclusion may also be applicable for other diagnostic tests than COVID-19 diagnostic.

Non-invasive imaging criteria for the diagnosis of hepatocellular carcinoma in non-cirrhotic patients with chronic hepatitis B.

BACKGROUND & AIMS: Criteria defined by the European Association for the Study of the Liver (EASL) and Liver Imaging Reporting and Data System (LI-RADS) enable hepatocellular carcinoma (HCC) diagnosis based on imaging in cirrhosis. Non-cirrhotic patients require biopsy given the lower pre-test probability of HCC. The objective of our study was to assess the performance of EASL and LI-RADS criteria for the diagnosis of HCC in non-cirrhotic patients with chronic HBV infection. METHODS: This was a cross-sectional study performed at a referral center. We included all patients with HBV without cirrhosis with focal liver lesions who underwent contrast-enhanced CT or MRI at our clinic between 2005-2018. Studies were reviewed by 2 radiologists blinded to the diagnosis. RESULTS: We included 280 patients, median age was 56.8 (IQR 48.2-65.45) years and 223 (80%) were male. In 191 (79%) cases the lesion was found as a result of screening. Cirrhosis was excluded based on pathology in 252 (90%) cases. We assessed 338 nodules: 257 (76%) HCC, 40 (12%) non-HCC malignant lesions, and 41 (12%) benign lesions. EASL criteria and LR-5/LR-tumor-in-vein (TIV) categories had a 100% agreement in categorizing lesions as HCC, and 226 nodules (67%) were classified as HCCs. The sensitivity, specificity, positive predictive value, and negative predictive value were 82.1 (76.9-86.6), 81.5 (71.3-89.2), 93.4 (89.3-96.2), and 58.9 (49.2-68.1), respectively. When the pre-test probability of HCC is >70%, estimated as a PAGE-B score above 9, and EASL or LR-5/LR-TIV criteria are met, post-test probability would be >90%. CONCLUSIONS: EASL criteria and LR-5/LR-TIV categories show a positive predictive value in patients with HBV without cirrhosis that is comparable to that seen in patients with cirrhosis. These criteria can be used when the pre-test probability of HCC is >70%. LAY SUMMARY: Current guidelines recommend performing a biopsy to confirm the diagnosis of presumed hepatocellular carcinoma (HCC) in patients without cirrhosis. We showed that specific imaging criteria had a 100% agreement for categorizing lesions as HCC, with a positive predictive value of 93.4%. These imaging criteria could be used to diagnose HCC in HBV patients without cirrhosis with a pre-test probability of HCC of ≥70%, avoiding the need for a liver biopsy.

Magnetic resonance versus computed tomography for the detection of retroperitoneal lymph node metastasis due to testicular cancer: A systematic literature review.

INTRODUCTION: It is essential to see if MRI can be used as an alternative to CT for the detection of retroperitoneal lymphadenopathy in patients with testicular neoplasms. By doing so, the amount of radiation received by these young patients might be reduced. MATERIAL AND METHODS: A systematic literature review was carried out in 5 databases between January 1984 until December 2020. The articles included were randomized and non-randomized clinical trials, cross-sectional studies, cohort, case and control, and retrospective studies that compare the accuracy of MRI against CT to detect retroperitoneal lymph nodes in patients with testicular neoplasms. RESULTS: The search string initially retrieved 222 non duplicated papers from which a total of 3 studies of diagnostic accuracy were included for analysis. These articles evaluated a total of 127 patients with testicular neoplasm; the sample size per study ranged from 25 to 52 patients, with a mean age between 29-34 years. MRI presented a sensitivity ranging from 98-80% and specificity of 100 % when read by an experienced radiologist. However, when it was read by a radiologist with 1 year of experience, the sensitivity dropped to 78 % and specificity to 91%. CONCLUSION: This systematic literature review shows a knowledge gap since not much has been published regarding this topic; therefore, randomized clinical trials are mandatory. Research on when to use MRI over CT is necessary to reduce radiation exposure. The authors strongly suggest that readers start researching on this subject.

Electrocardiographic Recognition of Unprotected Left Main ST-Segment Elevation Myocardial Infarction: Looking Beyond aVR.

ST-segment elevation in aVR has traditionally been used for electrocardiographic identification of left main coronary artery (LM) myocardial infarction. We present two ST-segment elevation myocardial infarction (STEMI) cases with acute total occlusion of the LM without aVR ST-segment elevation. This report reviews the different electrocardiographic discriminators suggestive of unprotected LM STEMI. (Level of Difficulty: Intermediate.).

What is the role of ultrasonography in the early diagnosis of scaphoid fractures?

Scaphoid fractures are the most prevalent type of carpal bone fractures. High-spatial-resolution sonography detects direct signs of scaphoid fractures such as scaphoid cortical disruption; nevertheless, indirect signs such as radiocarpal effusion and scapho-trapezium-trapezoid effusion can also be visible. The diagnosis is performed when both direct and indirect signs of scaphoid fracture are presented. The presence of indirect signs alone is not enough to complete the diagnosis, for which more advanced imaging modalities are usually required. Here, we review the anatomy of the scaphoid, the clinical manifestations of scaphoid fractures, as well as ultrasonographic findings and differential diagnosis.

Diagnostic accuracy of symptoms as a diagnostic tool for SARS-CoV 2 infection: a cross-sectional study in a cohort of 2,173 patients.

BACKGROUND: The SARS-CoV-2 pandemic continues to be a priority health problem; According to the World Health Organization data from October 13, 2020, 37,704,153 confirmed COVID-19 cases have been reported, including 1,079,029 deaths, since the outbreak. The identification of potential symptoms has been reported to be a useful tool for clinical decision-making in emergency departments to avoid overload and improve the quality of care. The aim of this study was to evaluate the performances of symptoms as a diagnostic tool for SARS -CoV-2 infection. METHODS: An observational, cross-sectional, prospective and analytical study was carried out, during the period of time from April 14 to July 21, 2020. Data (demographic variables, medical history, respiratory and non-respiratory symptoms) were collected by emergency physicians. The diagnosis of COVID-19 was made using SARS-CoV-2 RT-PCR. The diagnostic accuracy of these characteristics for COVID-19 was evaluated by calculating the positive and negative likelihood ratios. A Mantel-Haenszel and multivariate logistic regression analysis was performed to assess the association of symptoms with COVID-19. RESULTS: A prevalence of 53.72% of SARS-CoV-2 infection was observed. The symptom with the highest sensitivity was cough 71%, and a specificity of 52.68%. The symptomatological scale, constructed from 6 symptoms, obtained a sensitivity of 83.45% and a specificity of 32.86%, taking ≥2 symptoms as a cut-off point. The symptoms with the greatest association with SARS-CoV-2 were: anosmia odds ratio (OR) 3.2 (95% CI; 2.52-4.17), fever OR 2.98 (95% CI; 2.47-3.58), dyspnea OR 2.9 (95% CI; 2.39-3.51]) and cough OR 2.73 (95% CI: 2.27-3.28). CONCLUSION: The combination of ≥2 symptoms / signs (fever, cough, anosmia, dyspnea and oxygen saturation < 93%, and headache) results in a highly sensitivity model for a quick and accurate diagnosis of COVID-19, and should be used in the absence of ancillary diagnostic studies. Symptomatology, alone and in combination, may be an appropriate strategy to use in the emergency department to guide the behaviors to respond to the disease. TRIAL REGISTRATION: Institutional registration R-2020-3601-145, Federal Commission for the Protection against Sanitary Risks 17 CI-09-015-034, National Bioethics Commission: 09 CEI-023-2017082 .

Reproducibility and validity of portable haemoglobinometer for the diagnosis of anaemia in children under the age of 5 years.

Portable haemoglobinometers have been used in order to estimate the prevalence of anaemia in diverse settings. However, few studies have been conducted to evaluate their performance in children of different age groups in distinct epidemiological contexts. To evaluate the reproducibility and reliability of a portable haemoglobinometer for the diagnosis of anaemia in children <5 years Hb was measured in the venous blood of 351 children <5 years by an automated system (standard method) and in three capillary blood samples, using a portable haemoglobinometer (HemoCue®; test method). The reproducibility of the device and of the test method was evaluated using the intraclass correlation coefficient (ICC) (Hb in its continuous form), κ and prevalence-adjusted bias-adjusted κ (PABAK) (categorised variable: anaemia: yes/no). For test method validation, Bland-Altman analyses were performed and sensitivity, specificity, accuracy rate, positive predictive value (PPV) and negative predictive values (NPV) were calculated. The haemoglobinometer presented good device reproducibility (ICC = 0·79) and reasonable method reproducibility (puncture, collection and reading) (ICC = 0·71). Superficial and fair agreement (κ) and good agreement (PABAK) were observed among the diagnoses obtained through the test method. The prevalence of anaemia was 19·1 and 19·7 % using the standard and the test method, respectively, with no statistically significant differences. The test method presented higher specificity (87·7 %) and NPV (88·3 %) than sensitivity (50·7 %) and PPV (49·3 %), and intermediary accuracy rate (57·8 %). HemoCue® showed good device reproducibility and reasonable method reproducibility, as well as good performance in estimating the prevalence of anaemia. Nevertheless, it showed a fair reliability and low individual diagnostic accuracy.

Positive Predictive Value Surfaces as a Complementary Tool to Assess the Performance of Virtual Screening Methods.

BACKGROUND: Since their introduction in the virtual screening field, Receiver Operating Characteristic (ROC) curve-derived metrics have been widely used for benchmarking of computational methods and algorithms intended for virtual screening applications. Whereas in classification problems, the ratio between sensitivity and specificity for a given score value is very informative, a practical concern in virtual screening campaigns is to predict the actual probability that a predicted hit will prove truly active when submitted to experimental testing (in other words, the Positive Predictive Value - PPV). Estimation of such probability is however, obstructed due to its dependency on the yield of actives of the screened library, which cannot be known a priori. OBJECTIVE: To explore the use of PPV surfaces derived from simulated ranking experiments (retrospective virtual screening) as a complementary tool to ROC curves, for both benchmarking and optimization of score cutoff values. METHODS: The utility of the proposed approach is assessed in retrospective virtual screening experiments with four datasets used to infer QSAR classifiers: inhibitors of Trypanosoma cruzi trypanothione synthetase; inhibitors of Trypanosoma brucei N-myristoyltransferase; inhibitors of GABA transaminase and anticonvulsant activity in the 6 Hz seizure model. RESULTS: Besides illustrating the utility of PPV surfaces to compare the performance of machine learning models for virtual screening applications and to select an adequate score threshold, our results also suggest that ensemble learning provides models with better predictivity and more robust behavior. CONCLUSION: PPV surfaces are valuable tools to assess virtual screening tools and choose score thresholds to be applied in prospective in silico screens. Ensemble learning approaches seem to consistently lead to improved predictivity and robustness.

IGF-1 assessed by pubertal status has the best positive predictive power for GH deficiency diagnosis in peripubertal children.

Background When evaluating peripubertal short stature patients, the interpretation of insulin-like growth factor 1 (IGF-1) levels based on chronological age (CA) can be inaccurate due to the influence of sex steroids and, presently, there is no evidence to support the assessment of IGF-1 values according to bone age (BA) and pubertal status (PS). Our objective was to assess the discriminatory performance of IGF-1 levels based on CA, BA and PS in the diagnosis of growth hormone (GH) deficiency. Methods We evaluated IGF-1 levels from 154 peripubertal short stature patients classified as GH deficient (GHD, n=23) or non-GHD (n=131). IGF-1 was assayed by a chemiluminescent immunometric assay and transformed into standard deviation scores (SDS) according to CA (IGF-1-SDS-CA), BA (IGF-1-SDS-BA) and PS (IGF-1-SDS-PS). Results The performances of IGF-1-SDS-CA, IGF-1-SDS-BA and IGF-1-SDS-PS in the receiver operator characteristics (ROC) curves were similar. There were greater accuracy and specificity of IGF-1-SDS-PS (98.4% and 93.3%, respectively) and IGF-1-SDS-BA (92.7% and 90.1%, respectively) when compared to IGF-1-SDS-CA (65.6% and 69.5%, respectively). The post-test probability of the IGF-1-SDS was also improved when compared to PS and BA - 44.8% (IGF-1-SDS-PS), 16.8% (IGF-1-SDS-BA) and 5.1% (IGF-1-SDS-CA), with similar negative predictive values. Conclusions The evaluation of IGF-1 levels based on CA has a higher sensitivity than those based on BA or PS, which justify its use as a screening tool. Additionally, IGF-1 assessed by PS has the best positive predictive power for GHD diagnosis in peripubertal age and could reduce the necessity of a second GH stimulation test.

Cascade Ligand- and Structure-Based Virtual Screening to Identify New Trypanocidal Compounds Inhibiting Putrescine Uptake.

Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001-0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.

Utilidad de una escala de riesgo para identificar pacientes con disglucemia / Utility of a risk scale to identify patients with dysglycemia

Introducción: la prevalencia de diabetes y prediabetes ha ido en aumento a nivel global y en Cuba. Para identificar individuos en riesgo de disglucemia se han desarrollado varias escalas. Objetivo: evaluar el desempeño de la escala de Bang y otros, para identificar individuos con disglucemia, en una población cubana laboralmente activa. Métodos: se realizó un estudio transversal en 2 902 pacientes, fueron clasificados en portadores o no de disglucemia, a través de las pruebas de glucemia en ayunas, de tolerancia a la glucosa y hemoglobina glucosilada. Se determinó la frecuencia de factores de riesgo de diabetes mellitus tipo 2 comprendidos en la escala de Bang y otros, y en el proceder enfocado en factores de riesgo de American Diabetes Association. Se determinó sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y Odds Ratio de ambas estrategias. En ambos se calculó el área bajo la curva operativa del receptor. Resultados: se encontró relación entre cada uno de los factores de riesgo previstos en ambos procederes con el diagnóstico de disglucemia. Se encontró sensibilidad de 96,5 por ciento y 79,9 por ciento; especificidad de 20,9 por ciento y 59,1 por ciento; valor predictivo positivo de 10,7 por ciento y 16,1 por ciento; valor predictivo negativo de 98,4 por ciento y 96,8 por ciento; OR de 7,33 y 6,76 y área bajo la curva 0,77 y 0,79 para la escala de Bang y otros, y el procedimiento enfocado en factores de riesgo, respectivamente. Conclusiones: ambos procederes identificaron de forma aceptable el grupo de pacientes con disglucemia(AU)

Introduction: The prevalence of diabetes and prediabetes has been increasing globally and also in Cuba. Several scales have been developed to identify individuals at risk for dysglycemia. Objective: To evaluate the performance of the Bang et al. scale to identify individuals with dysglycemia in a Cuban labor-active population. Methods: A cross-sectional study was carried out on 2 902 patients, classified as having or not suffering from dysglycemia, through fasting glycemia, glucose tolerance test and glycosylated hemoglobin. The frequencies of risk factors for type 2 diabetes mellitus included in the Bang et al. scale and in the risk factor approach of the American Diabetes Association were determined. Sensitivity, specificity, positive predictive value, negative predictive value and Odds Ratio of both strategies were determined. In both, the area under the receiver operating curve was calculated. Results: A relationship was found between each of the predicted risk factors in both procedures with the diagnosis of dysglycemia. Sensitivity was 96.5 percent and 79.9 percent; Specificity of 20.9 percent and 59.1 percent; Positive predictive value of 10.7 percent and 16.1 percent; Negative predictive value of 98.4 percent and 96.8 percent; OR of 7.33 and 6.76 and area under the curve 0.77 and 0.79 for the scale of Bang et al. and the procedure focused on risk factors respectively. Conclusions: Both procedures identified in an acceptable manner the group of patients with dysglycemia(AU)

Positive predictive value of the immunoassay for Clostridium difficile toxin A and B detection at a private hospital. / Valor predictivo positivo de la prueba de inmunoanálisis para detección de toxina A y B de Clostridium difficile en un hospital privado.

INTRODUCTION: Clostridium difficile (C. difficile) is a Gram-positive bacillus that is a common cause of diarrhea in the hospital environment, with a documented incidence of up to 10%. There are different methods to detect it, but a widely used test in our environment is the immunoassay for toxins A and B. AIMS: The aim of our study was to 1) estimate the positive predictive value of the immunoassay for the detection of the C. difficile toxins A and B, 2) to establish the incidence of C. difficile-associated diarrhea in the hospital, and 3) to know the most common associated factors. METHODS: A diagnostic test accuracy study was conducted within the time frame of January 2010 to August 2013 at the Hospital Christus Muguerza® Alta Especialidad on patients with symptoms suggestive of C. difficile-associated diarrhea that had a positive immunoassay test and confirmation of C. difficile through colon biopsy and stool culture. RESULTS: The immunoassay for toxins A and B was performed in 360 patients. Fifty-five of the cases had positive results, 35 of which showed the presence of C. difficile. Incidence was 10.2% and the positive predictive value of the test for C. difficile toxins A and B was 0.64 (95% CI, 0.51-0.76). Previous antibiotic therapy (n=29) and proton pump inhibitor use (n=19) were the most common associated factors. CONCLUSIONS: C. difficile incidence in our environment is similar to that found in the literature reviewed, but the positive predictive value of the test for toxin A and B detection was low.

Doctor, what does my positive test mean? From Bayesian textbook tasks to personalized risk communication.

Most of the research on Bayesian reasoning aims to answer theoretical questions about the extent to which people are able to update their beliefs according to Bayes' Theorem, about the evolutionary nature of Bayesian inference, or about the role of cognitive abilities in Bayesian inference. Few studies aim to answer practical, mainly health-related questions, such as, "What does it mean to have a positive test in a context of cancer screening?" or "What is the best way to communicate a medical test result so a patient will understand it?". This type of research aims to translate empirical findings into effective ways of providing risk information. In addition, the applied research often adopts the paradigms and methods of the theoretically-motivated research. But sometimes it works the other way around, and the theoretical research borrows the importance of the practical question in the medical context. The study of Bayesian reasoning is relevant to risk communication in that, to be as useful as possible, applied research should employ specifically tailored methods and contexts specific to the recipients of the risk information. In this paper, we concentrate on the communication of the result of medical tests and outline the epidemiological and test parameters that affect the predictive power of a test-whether it is correct or not. Building on this, we draw up recommendations for better practice to convey the results of medical tests that could inform health policy makers (What are the drawbacks of mass screenings?), be used by health practitioners and, in turn, help patients to make better and more informed decisions.