Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico.

PURPOSE: Genetic cancer risk assessment (GCRA) provides pathogenic variant (PV) carriers with the invaluable opportunity to undertake timely cancer risk-reducing (RR) measures and initiate cascade testing (CT). This study describes the uptake of these strategies and the related barriers among breast cancer-associated germline PV carriers in Mexico. METHODS: Carriers who were at least 6 months after disclosure of genetic test results at two GCRA referral centers were invited to answer a survey assessing sociodemographic characteristics, awareness of their carrier status and its implications, uptake of RR measures according to international guidelines by PV, CT initiation, and associated challenges. RESULTS: Of the eligible carriers, 246/384 (64%) answered the survey (median age: 44 years). Most were female (88%), married/in domestic partnership (66%), and had personal breast/ovarian cancer history (61%). PVs included BRCA1/2 (75%), CHEK2 (10%), PALB2 (5%), ATM (5%), NF1 (2%), RAD51C (2%), PTEN (1%), and TP53 (1%). Most (87%) participants were aware of their carrier status. When recommended, 37% underwent RR bilateral mastectomy, 48% RR oophorectomy, 70% annual mammogram, and 20% breast magnetic resonance imaging. Challenges hindering the uptake of RR measures included financial limitations (67%), lack of recommendation by their physician (35%), and fear (24%). Nearly all (98%) claimed sharing their results with their relatives. CT was initiated in 63% of families and was associated with carriers being married/in domestic partnership (P = .04) and believing GCRA was useful (P < .001). CONCLUSION: Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.

Comparison of the Diagnostic Performance of Five Clinical Questionnaires for Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) remains one of the most prevalent pathologies in the world and is among the leading causes of mortality and morbidity, partially due to underdiagnosis. The use of clinical questionnaires to identify high-risk individuals to take them to further diagnostic procedures has emerged as a strategy to address this problem. Objective: To compare the performance of the COULD IT BE COPD, CDQ, COPD-PS, LFQ, and PUMA questionnaires for COPD diagnosis. Methods: A cross-sectional study was carried out on subjects who underwent spirometry in the third-level center. Data were collected between January 2015 and March 2020. Bivariate analysis was performed between the study variables and the presence of COPD. The area under the receiver operating characteristics curve (AUC-ROC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) for each questionnaire were calculated. The AUC-ROCs were compared with the DeLong test, considering a p value <0.05 statistically significant. Results: 681 subjects met the inclusion criteria and were taken to the final analysis. The prevalence of COPD was 27.5% (187/681). The mean age of the subjects was 65.9 years (SD ± 11.79); 46.3% (315/681) were female, and 83.6% (569/681) reported respiratory symptoms. Statistically significant relationship was found for COPD diagnosis with male sex, older age, respiratory symptoms, and exposure to wood smoke (p value <0.05). The AUC-ROCs of the questionnaires were between 0.581 and 0.681. The COULD IT BE COPD questionnaire had a lower discriminatory capacity AUC-ROC of 0.581, concerning the other scores (DeLong test, p = 0.0002). Conclusion: The CDQ, COPD-PS, LFQ, PUMA, and COULD IT BE COPD questionnaires have acceptable performance for the diagnosis of COPD together with low sensitivity and specificity. Therefore, its use must be complemented with other diagnostic tests or techniques such as pulmonary function tests.

Germline DNA Repair Genes Pathogenic Variants Among Mexican Patients With Prostate Cancer.

BACKGROUND: Early identification of germline mutation carriers may be relevant for the optimal management of prostate cancer and to inform cancer risk in relatives. However, population minorities have limited access to genetic testing. The aim of this study was to describe the frequency of DNA repair gene pathogenic variants (PVs) among Mexican men with prostate cancer referred for Genomic Cancer Risk Assessment and testing. METHODS: Patients diagnosed with prostate cancer who meet criteria for genetic testing and enrolled in the Clinical Cancer Genomics Community Research Network at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City were included. Descriptive statistics were performed using frequency and proportions for categorical variables and median and range for quantitative variables. X2 and t test were used for group comparisons. RESULTS: A total of 199 men were enrolled, median age at diagnosis was 66 (range 44-88) years; 45% were de novo metastatic and 44% were high- very high and 10% were intermediate risk group. Four (2%) had a pathogenic germline variant; one each of the following genes: ATM, CHEK2, BRIP1, and MUTYH (all monoallelic). Younger men at diagnosis were more likely to carry a PV than older age at diagnosis (56.7 vs. 66.4 years, P = .01). CONCLUSION: Our results showed a low prevalence of known prostate cancer associated PVs and no BRCA PVs in Mexican men with prostate cancer. This suggests that the genetic and/or epidemiologic risk factors for prostate cancer are not well characterized in this specific population.

Sobrevida en una cohorte con diagnóstico de tuberculosis en Colombia / Survival at cohort diagnosed with tuberculosis in Colombia

Introducción: La tuberculosis es una patología infecciosa crónica cuya incidencia es elevada en países en vía de desarrollo, sin embargo, es limitada la información y los estudios que analizan la mortalidad y sobrevida a largo plazo. Metodología: estudio de cohorte retrospectivo, en pacientes con diagnóstico de tuberculosis mayores de 18 años, el ingreso fue de manera consecutiva hasta completar el periodo de estudio. Se analizó la sobrevida y mortalidad a través del estimador Kaplan ­ Meier por la prueba de log Rank. Resultados: ingresaron 329 sujetos, la mortalidad a los 30 días fue de 11,9% y al año del 24,6%, la tuberculosis pulmonar fue el tipo más frecuente con en el 70,2%. Los hallazgos al examen físico relacionados con mortalidad fueron la caquexia (p<0,001) y el edema en extremidades (p<0,001). La sobrevida general fue del 87,2% a los 30 días y del 72,9% al año. En los pacientes con tuberculosis pulmonar la sobrevida fue del 85,8% a los 30 días y del 72,8% al año. Conclusión: La tasa de sobrevida a un año en pacientes hospitalizados por tuberculosis es baja, la edad avanzada, desnutrición, PaO2/FiO2 menor de 300, proteína c reactiva mayor de 45 mg/dL, enfermedad cerebrovascular y enfermedad vascular periférica fueron variables que se asociaron con una mayor mortalidad(AU)

Background: Tuberculosis is a chronic infectious pathology whose incidence is high in developing countries, however, information and studies that analyze mortality and long-term survival are limited. Methodology: retrospective cohort study, in patients with a diagnosis of tuberculosis older than 18 years, admission was consecutive until completing the study period. Survival and mortality were analyzed using the Kaplan-Meier estimator by the log Rank test. Results: 329 subjects were admitted, mortality at 30 days was 11.9% and at one year 24.6%, pulmonary tuberculosis was the most frequent type with 70.2%. Physical examination findings related to mortality were cachexia (p<0.001) and extremity edema (p<0.001). Overall survival was 87.2% at 30 days and 72.9% at one year. In patients with pulmonary tuberculosis, survival was 85.8% at 30 days and 72.8% at one year. Conclusion: The one-year survival rate in patients hospitalized for tuberculosis is low, advanced age, malnutrition, PaO2/FiO2 less than 300, c-reactive protein greater than 45 mg/dL, cerebrovascular disease and peripheral vascular disease were variables that were associated with higher mortality(AU)