Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia.

PURPOSE: To characterize the spectrum of germline mutations in BRCA1, BRCA2, and PALB2 in population-based unselected breast cancer cases in an Asian population. METHODS: Germline DNA from 467 breast cancer patients in Sarawak General Hospital, Malaysia, where 93% of the breast cancer patients in Sarawak are treated, was sequenced for the entire coding region of BRCA1; BRCA2; PALB2; Exons 6, 7, and 8 of TP53; and Exons 7 and 8 of PTEN. Pathogenic variants included known pathogenic variants in ClinVar, loss of function variants, and variants that disrupt splice site. RESULTS: We found 27 pathogenic variants (11 BRCA1, 10 BRCA2, 4 PALB2, and 2 TP53) in 34 patients, which gave a prevalence of germline mutations of 2.8, 3.23, and 0.86% for BRCA1, BRCA2, and PALB2, respectively. Compared to mutation non-carriers, BRCA1 mutation carriers were more likely to have an earlier age at onset, triple-negative subtype, and lower body mass index, whereas BRCA2 mutation carriers were more likely to have a positive family history. Mutation carrier cases had worse survival compared to non-carriers; however, the association was mostly driven by stage and tumor subtype. We also identified 19 variants of unknown significance, and some of them were predicted to alter splicing or transcription factor binding sites. CONCLUSION: Our data provide insight into the genetics of breast cancer in this understudied group and suggest the need for modifying genetic testing guidelines for this population with a much younger age at diagnosis and more limited resources compared with Caucasian populations.

Comparison of Hybribio-H13 and Hybrid Capture® 2 human papillomavirus tests for detection of CIN2+ and CIN3. / Comparación de las pruebas para el virus del papiloma humano Hybribio-H13 y Hybrid Capture® 2 para la detección de NIC2+ y NIC3+

INTRODUCTION: Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. OBJECTIVE: To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). MATERIALS AND METHODS: Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. RESULTS: The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT <0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. CONCLUSION: The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.

Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2 para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT <0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.

Predictors of physical activity in older adults 65 years and older: findings in health survey of the Valencian Community.

Background: Physical activity is part of a healthy lifestyle in the older adult and is related to multiple variables that promote this behavior. Objective: To identify the relationship and predictive power of sociodemographic variables, multimorbidity, severity index, risk of poor mental health, social support, affective support and confidential support with the time devoted to physical activity in the population over 65 years of age in the Valencian Community. Methods: Cross-sectional descriptive analytical study of the data collected in the Health Survey of the Valencian Community on a total of 3,199 people over 65 years of age. The study variables were age, sex, educational level, marital status, social class, multimorbidity, severity index collected with the EQ-5D-5L tool, risk of poor mental health collected with the Goldberg general health questionnaire (GHQ-12), and perceived social, affective and confidential support collected with the Duke-Unc social support scale (Duke-UNC-11). Results: All variables, except affective support, are significantly related to the time of physical activity performed by people older than 65 years. The severity index has a predictive capacity of 13.7% of physical activity performed and age is able to predict 1.2% of this variable. Conclusion: Sex, age, education, social class, marital status, multimorbidity, risk of poor mental health or social support and confidentiality are related to the physical activity time of the Valencian population over 65 years of age. On the other hand, the variables severity index and age have been identified as variables capable of predicting up to 14.8% of the variance of the physical activity time variable in our study population.

Does Self-Directed Learning with Simulation Improve Critical Thinking and Motivation of Nursing Students? A Pre-Post Intervention Study with the MAES© Methodology.

Motivation and critical thinking are fundamental for the development of adequate learning. The purpose of the present study was to assess the motivation for learning and critical thinking among nursing students before and after self-directed simulation-based training using the MAES© methodology. A cross-sectional and descriptive quantitative study was conducted with a sample of third-year nursing students. The instruments utilized were the Spanish-adapted version of the Motivated Strategies for Learning Questionnaire (MSLQ-44), and the Critical Thinking for Nursing Professionals Questionnaire (CuPCPE). The students improved their levels both of motivation components, (such as self-efficacy, strategy use, self-regulation) and critical thinking components (such as personal characteristics, intellectual and cognitive abilities, interpersonal abilities and self-management, and technical abilities). These improvements could be a result of the intrinsic characteristics of the MAES© methodology (as a team-based, self-directed, collaborative and peer-to-peer learning method).

[Parental anxiety and associated factors in pediatric hospital emergencies, a cross-sectional descriptive study.] / Ansiedad parental y factores asociados en Urgencias pediátricas hospitalarias, un estudio descriptivo transversal.

OBJECTIVE: Pediatric hospital emergencies have increased hardly in the recent years, product of the irrational use and the over-massification. The objective of this study was to evaluate the relationship between anxiety and sociodemographic factors of the parents and mothers. METHODS: Descriptive cross-sectional study on parental anxiety and associated factors in a pediatric hospital emergency service with sample n=200 fathers and mothers who demand care in a level 3 hospital in Valencia. (Spain), during march, april and may of 2019. It was estimated the reliability of the Anxiety Scale E-7 (STAI-E7). The data was obtained with a self-administrated and desired document for the purpose. Data related to the level of anxiety and possible predictive variables were collected. The analysis of the data obtained was performed with the Statistical Package for the Social Sciences program (SPSS, version 20.0 for Windows) and ordinal regression with the R commander program. RESULTS: The results show that 75.5% of the people who went to the hospital with their children were mothers and 24.5% were fathers. The mean score obtained regarding the level of anxiety in the sample is moderate (9.18±4.92). Mothers present higher levels of anxiety than fathers (9.7±4.8 and 7.5±5.1, respectively). The probability of experiencing a higher level of anxiety in mothers is multiplied by two (OR=2.286; 95% CI: 1.212-4.353; P=0.01) compared to parents. The STAI-E7 scale presents a good internal consistency (Cronbach's α=0.847). CONCLUSIONS: Mothers have higher levels of anxiety. It will be appreciated doing more studies to quantify the levels of parental anxiety, with the purpose of creating tools and programs to decrease it.

OBJETIVO: Las Urgencias hospitalarias pediátricas han aumentado notablemente en los últimos años, produciendo un uso irracional y la sobremasificación de las mismas. El objetivo de este estudio fue evaluar el nivel de ansiedad y los factores asociados en los padres y madres que acudían con sus hijos a Urgencias. METODOS: Se realizó un estudio descriptivo transversal con una muestra de 200 padres y madres que demandaban asistencia en un hospital de nivel 3 de Valencia (España), durante los meses de marzo, abril y mayo de 2019. También se estimó la fiabilidad de la escala State-Trait Anxiety E-7 (STAI-E7). Los datos se obtuvieron a partir de un documento autoadministrado y diseñado para tal fin. Se recogieron datos relacionados con el nivel de ansiedad y las posibles variables predictoras relacionadas con los padres y con los niños. El análisis de los datos obtenidos se realizó mediante el programa estadístico Statistical Package for the Social Sciences (SPSS, versión 20.0 para Windows) y la regresión ordinal con el programa estadístico R commander. RESULTADOS: Un 75,5% de las personas que acudieron con sus hijos a Urgencias hospitalarias eran madres y un 24,5% padres. La puntuación media obtenida respecto al nivel de ansiedad de la muestra fue moderada (9,18±4,92). Las madres presentaban cifras más elevadas que los padres (9,7±4,8 y 7,5±5,1, respectivamente). La probabilidad de sufrir un mayor nivel de ansiedad en las madres se multiplicaba por dos (OR=2,286; IC 95%: 1,212-4,353; P=0,01) respecto a los padres. La escala STAI-E7 presentó una buena consistencia interna (α de Cronbach=0,847). CONCLUSIONES: Las madres presentan cifras más elevadas de ansiedad. Se valora la necesidad de realizar más estudios para cuantificar los niveles de ansiedad parental en el ámbito de Urgencias, con el propósito de crear herramientas y programas para disminuirla.

Comparison of Hybribio-H13 and Hybrid Capture® 2 human papillomavirus tests for detection of CIN2+ and CIN3+ / Comparación de las pruebas para el virus del papiloma humano Hybribio-H13 y Hybrid Capture® 2 para la detección de NIC2+ y NIC3+

Abstract Introduction. Low-cost, accurate high-risk HPV tests are needed for cervical cancer screening in limited-resource settings. Objective. To compare the performance of the low-cost Hybribio-H13 test with the Hybrid Capture® 2 to detect cervical intraepithelial neoplasia grade 2 or 3 (CIN2 and CIN3). Materials and methods. Archived baseline samples tested by the Hybrid Capture® 2 from women of the ASCUS-COL trial, aged 20 to 69 years, with biopsy-colposcopy directed diagnosis of CIN2+ (n = 143), CIN3+ (n = 51), and < CIN2 (n = 632) were blindly tested by the Hybribio-H13 test. Results. The relative sensitivity of the Hybribio-H13 test versus the Hybrid Capture® 2 for detecting CIN2+ was 0.89 (90% CI = 0,80-0,98; NIT = 0,66), and for CIN3+ was 0,92 (90% CI = 0,85-0,98; NIT = 0,35). Relative specificity was 1.19 (90% CI = 1.05-1.33; NIT < 0.00001). In the analysis restricted to women older than 30 years, the relative sensitivity of the Hybribio-H13 for CIN3+ was marginally below unity (ratio = 0.97; 90% CI = 0.95-0.99), and the specificity remained higher than the Hybrid Capture® 2 test. Conclusion. The Hybribio-H13 test was as specific as the Hybrid Capture® 2 for detecting CIN2+ or CIN3+ but less sensitive. Considering these results and the young age of the population recruited for screening because of ASCUS cytology, we suggest our results warrant the evaluation of the Hybribio-H13 for screening cervical cancer, especially in the evaluated population.

Resumen Introducción. Se necesitan pruebas para detectar genotipos de VPH de alto riesgo, precisas y de bajo costo, para la tamización del cáncer de cuello uterino en entornos de recursos limitados. Objetivo. Comparar el desempeño de la prueba de bajo costo Hybrid-H13 con la de Hybrid Capture® 2 para detectar NIC2+ y NIC3+. Materiales y métodos. Se analizaron en ciego muestras de la línea base provenientes de mujeres del estudio ASCUS-COL, entre los 20 y los 69 años, con diagnóstico dirigido por biopsia-colposcopia de NIC2+ (n = 143), NIC3 + (n = 51) y < NIC2 (n = 632) con la prueba para detección de virus de papiloma humano Hybribio-H13. Estas muestras fueron previamente evaluadas con la prueba Hybrid Capture® 2. Resultados. La sensibilidad relativa de Hybribio-13 versus la de Hybrid Capture® 2 para detectar NIC2+ fue de 0,89 (IC90%: 0,80-0,98; NIT = 0,66) y para NIC3+ fue de 0,92 (IC90%: 0,85-0,98; NIT = 0,35). La especificidad relativa fue de 1,19 (IC90%: 1,05-1,33; NIT < 0,00001). En el análisis restringido a mujeres mayores de 30 años, la sensibilidad relativa de Hybribio-H13 para NIC3+ estuvo marginalmente por debajo de la unidad (proporción = 0,97; IC90%: 0,95-0,99) y la especificidad permaneció más alta que la de la prueba Hybrid Capture® 2. Conclusión. La prueba de Hybribio-H13 fue tan específica como la de Hybrid Capture® 2, pero menos sensible para detectar NIC2+ o NIC3+. Teniendo en cuenta estos resultados y la temprana edad de la población reclutada en la tamización por la presencia de ASCUS en la citología, se sugiere continuar con la evaluación de la prueba Hybribio-H13 para la detección de cáncer de cuello uterino en poblaciones con las mismas características que las de la aquí evaluada.

Addressing health disparities in Hispanic breast cancer: accurate and inexpensive sequencing of BRCA1 and BRCA2.

BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes account for 20-25 % of inherited breast cancers and about 10 % of all breast cancer cases. Detection of BRCA mutation carriers can lead to therapeutic interventions such as mastectomy, oophorectomy, hormonal prevention therapy, improved screening, and targeted therapies such as PARP-inhibition. We estimate that African Americans and Hispanics are 4-5 times less likely to receive BRCA screening, despite having similar mutation frequencies as non-Jewish Caucasians, who have higher breast cancer mortality. To begin addressing this health disparity, we initiated a nationwide trial of BRCA testing of Latin American women with breast cancer. Patients were recruited through community organizations, clinics, public events, and by mail and Internet. Subjects completed the consent process and questionnaire, and provided a saliva sample by mail or in person. DNA from 120 subjects was used to sequence the entirety of BRCA1 and BRCA2 coding regions and splice sites, and validate pathogenic mutations, with a total material cost of $85/subject. Subjects ranged in age from 23 to 81 years (mean age, 51 years), 6 % had bilateral disease, 57 % were ER/PR+, 23 % HER2+, and 17 % had triple-negative disease. RESULTS: A total of seven different predicted deleterious mutations were identified, one newly described and the rest rare. In addition, four variants of unknown effect were found. CONCLUSIONS: Application of this strategy on a larger scale could lead to improved cancer care of minority and underserved populations.

Genome Analysis of Latin American Cervical Cancer: Frequent Activation of the PIK3CA Pathway.

PURPOSE: Cervical cancer is one of the most common causes of cancer mortality for women living in poverty, causing more than 28,000 deaths annually in Latin America and 266,000 worldwide. To better understand the molecular basis of the disease, we ascertained blood and tumor samples from Guatemala and Venezuela and performed genomic characterization. EXPERIMENTAL DESIGN: We performed human papillomavirus (HPV) typing and identified somatically mutated genes using exome and ultra-deep targeted sequencing with confirmation in samples from Mexico. Copy number changes were also assessed in the exome sequence. RESULTS: Cervical cancer cases in Guatemala and Venezuela have an average age of diagnosis of 50 years and 5.6 children. Analysis of 675 tumors revealed activation of PIK3CA and other PI3K/AKT pathway genes in 31% of squamous carcinomas and 24% of adeno- and adenosquamous tumors, predominantly at two sites (E542K, E545K) in the helical domain of the PIK3CA gene. This distribution of PIK3CA mutations is distinct from most other cancer types and does not result in the in vitro phosphorylation of AKT. Somatic mutations were more frequent in squamous carcinomas diagnosed after the age of 50 years. Frequent gain of chromosome 3q was found, and low PIK3CA mutation fractions in many tumors suggest that PI3K mutation can be a late event in tumor progression. CONCLUSIONS: PI3K pathway mutation is important to cervical carcinogenesis in Latin America. Therapeutic agents that directly target PI3K could play a role in the therapy of this common malignancy.