Cancer mortality among Colombian and foreign populations over a 15-year period.

Purpose: We aimed to compare cancer mortality among foreign- and Colombian populations in Colombia during the period of 2006-2020. Methods: This retrospective study utilized vital statistics from the Colombian National Department of Statistics (DANE). The dataset included variables such as age group, sex, country of permanent residency, insurance, education level, marital status, ethnicity, and cause of death. The population data to calculate rates was obtained from the Colombian census and the United Nations. Crude and adjusted rates as well as proportional mortality rates were calculated. Results: A total of 561,932 cancer deaths occurred in Colombia from 2006 to 2020. The foreign population (country of permanent residency different to Colombia) had a lower crude cancer mortality rate (31.1 per 100,000 inhabitants) than the Colombian population (81.9 per 100,000 inhabitants). However, the age-adjusted cancer mortality rate among the foreign population was 253.6 per 100,000, compared to 86.1 per 100,000 among the Colombian population. The proportional cancer mortality was 10.4 % among foreign population compared to 17.4 % among Colombian population. Conclusions: The proportional cancer mortality shows that the proportion of cancer-related deaths is greater among the Colombian population compared to the immigrant population. However, immigrants in Colombia have a higher age-adjusted cancer mortality rate than Colombians, indicating that immigrants have worse cancer outcomes than the Colombians even though the immigrant population is younger. This is likely due to the frequent barriers that immigrants encounter in accessing health care in Colombia. Future research needs to focus on access to care for the immigrant population by investigating cancer-related risk factors among immigrants and addressing their barriers to cancer prevention and treatment.

Impact of the universal health insurance benefits on cervical cancer mortality in Colombia.

BACKGROUND: Cervical cancer patients in Colombia have a lower likelihood of survival compared to breast cancer patients. In 1993, Colombia enrolled citizens in one of two health insurance regimes (contributory-private insurance and subsidized- public insurance) with fewer benefits in the subsidized regime. In 2008, the Constitutional Court required the Colombian government to unify services of both regimes by 2012. This study evaluated the impact of this insurance change on cervical cancer mortality before and after 2012. METHODS: We accessed 24,491 cervical cancer mortality records for 2006-2020 from the vital statistics of Colombia's National Administrative Department of Statistics (DANE). We calculated crude mortality rates by health insurance type and departments (geopolitical division). Changes by department were analyzed by rate differences between 2006 and 2012 and 2013-2020, for each health insurance type. We analyzed trends using join-point regressions by health insurance and the two time-periods. RESULTS: The contributory regime (private insurance) exhibited a significant decline in cervical cancer mortality from 2006 to 2012, characterized by a noteworthy average annual percentage change (AAPC) of -3.27% (P = 0.02; 95% CI [-5.81, -0.65]), followed by a marginal non-significant increase from 2013 to 2020 (AAPC 0.08%; P = 0.92; 95% CI [-1.63, 1.82]). In the subsidized regime (public insurance), there is a non-significant decrease in mortality between 2006 and 2012 (AAPC - 0.29%; P = 0.76; 95% CI [-2.17, 1.62]), followed by a significant increase from 2013 to 2020 (AAPC of 2.28%; P < 0.001; 95% CI [1.21, 3.36]). Examining departments from 2013 to 2020 versus 2006 to 2012, the subsidized regime showed fewer cervical cancer-related deaths in 5 out of 32 departments, while 6 departments had higher mortality. In 21 departments, mortality rates remained similar between both regimes. CONCLUSION: Improvement of health benefits of the subsidized regime did not show a positive impact on cervical cancer mortality in women enrolled in this health insurance scheme, possibly due to unresolved administrative and socioeconomic barriers that hinder access to quality cancer screening and treatment.

Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain).

The singular BRCA1/2 mutational landscape of Asturias is updated 10 years after the first study. We analyzed BRCA1 and BRCA2 pathogenic variants in 1653 index cases. In total, 238 families were identified to carry a pathogenic variant, 163 families in BRCA1 and 75 families in BRCA2. This yielded a prevalence rate of 14.4%. Seven recurrent variants were found accounting for 55% of the cases. Among them, three are widely distributed (BRCA1 c.211A>G, c.470_471del and c.3331_3334del) and four had been reported as novel in Asturias: two in BRCA1 (c.1674del and c.2901_2902dup) and two in BRCA2 (c.2095C>T and c.4040_4035delinsC). A common haplotype was established for all recurrent variants indicating a shared ancestral origin. Three splicing analyses are shown: BRCA1:c.5152+3A>C and BRCA1:c.5333-3T>G that lead to skipping of exon 18, and 22 respectively, and BRCA1:c.5278-1G>T giving rise to two transcripts, one lacking exon 21 (p.Ille1760Glyfs*60) and one lacking the first 8 nucleotides of exon 21 (p.Phe1761Asnfs*14), supporting pathogenicity for these variants.

Perspectivas comunitarias e institucionales acerca del cáncer cervicouterino en indígenas del Amazonas colombiano / Community and Institutional Perspectives on Cervical Cancer in Indigenous People of the Colombian Amazon / Perspectivas comunitárias e institucionais sobre o câncer de colo de útero em indígenas da Amazônia colombiana

Introducción: la información en cáncer en poblaciones indígenas colombianas es escasa; de ahí que el objetivo de este estudio sea conocer las perspectivas comunitarias y de los prestadores de servicios de salud acerca del cáncer de cuello uterino (CaCU) en mujeres indígenas del Amazonas colombiano. Materiales y métodos: estudio cualitativo, derivado de una investigación de métodos mixtos de triangula-ción convergente. Se realizaron 40 entrevistas semiestructuradas que incluían profesionales de la salud y actores clave comunitarios representados en curacas, médicos tradicionales o chamanes, parteras, pro-motores de salud, auxiliares de salud pública, líderes y lideresas, abuelos, abuelas y mujeres indígenas en general. Para el análisis se utilizó la técnica de análisis de contenido. Resultados: emergieron cuatro categorías:1) concepciones y factores de riesgo alrededor del cáncer en general y el CaCU, 2) prácticas de cuidado y de atención occidentales y ancestrales para el CaCU, 3) dificultades socioculturales y del sistema de salud para la prevención y atención del CaCU y 4) recomendaciones para el fortalecimiento de la de prevención del CaCU. Conclusión: los participantes reconocen la citología cervicouterina como una forma de prevenir el cáncer y aunque los participantes mencionaron algunos aspectos culturales y personales que podrían constituirse en una barrera para la prevención y control del CaCU, se hizo hinca-pié en los problemas estructurales del sistema de salud, la falta de integración cultural y las dificultades de acceso al tamizaje, diagnóstico y tratamiento.

Introduction: Information on cancer in Colombian indigenous populations is scarce, the objective of this study was to know the community and health care providers' perspectives on cervical cancer (CaCU) in indigenous women of the Colombian Amazon. Materials and methods: Qualitative study, derived from a mixed methods research of convergent triangulation, 40 semi-structured interviews were conducted, including health professionals and key community actors represented by curacas, traditional doctors or shamans, midwives, health promoters, public health assistants, leaders, grandfathers, grandmothers, and indigenous women in general. The content analysis technique was used for the analysis. Results:Four categories emerged: (a) conceptions and risk factors surrounding cancer in general and CaCU; (b) western and ancestral care and attention practices for CaCU; (c) sociocultural and health system diffi-culties for the prevention and attention of CaCU, and (d) recommendations for strengthening CaCU pre-vention. Conclusion: Participants recognize cervical cytology as a way to prevent cancer and although participants mentioned some cultural and personal aspects that could constitute a barrier to cervical cancer prevention and control, the greatest emphasis was given to structural problems of the health system, lack of cultural integration and difficulties of access to screening, diagnosis and treatment.

Introdução: a informação sobre o câncer nas populações indígenas colombianas são escassas, o objetivo deste estudo foi conhecer as perspectivas da comunidade e dos prestadores de serviços de saúde sobre o câncer do colo do útero (CaCU), em mulheres indígenas da Amazônia colombiana. Materiais e méto-dos: estudo qualitativo, derivado de uma investigação de métodos mistos de triangulação convergente. Foram realizadas 40 entrevistas semiestruturadas que incluíram profissionais de saúde e principais atores comunitários representados em curacas, médicos tradicionais ou xamãs, parteiras, promotores de saúde, assistentes de saúde pública, lideranças, avôs, avós e mulheres indígenas em geral. Para a análise foi uti-lizada a técnica de análise de conteúdo. Resultados: emergiram quatro categorias, a) concepções e fatores de risco em torno do câncer em geral e do CaCU; b) cuidados e práticas de cuidado ocidentais e ancestrais para CaCU; c) dificuldades socioculturais e do sistema de saúde para a prevenção e cuidado do CaCU, e d) recomendações para fortalecer a prevenção de CaCU. Conclusão: as participantes reconhecem a citolo-gia cervical como forma de prevenção do câncer e embora as participantes tenham mencionado alguns aspectos culturais e pessoais que poderiam constituir uma barreira para a prevenção e controle do câncer do colo do útero, a maior ênfase foi dada aos problemas estruturais do sistema de saúde, a falta de integra-ção cultural e as dificuldades de acesso ao rastreio, ao diagnóstico e ao tratamento

Folate deficiency modifies the risk of CIN3+ associated with DNA methylation levels: a nested case-control study from the ASCUS-COL trial.

PURPOSE: To our knowledge, there are very few studies evaluating if the levels of folate modify the risk of cervical intraepithelial neoplasia grade 2 and higher (CIN2+ and CIN3+) associated with the levels of HPV genome methylation, two cofactors related to single carbon metabolism and independently associated with cervical cancer in previous studies. We conducted a case-control study nested in a three-arm randomized clinical pragmatic trial (ASCUS-COL trial) to evaluate the risk of CIN3+ associated with methylation levels according to serum folate concentrations. METHODS: Cases (n = 155) were women with histologically confirmed CIN2+ (113 CIN2, 38 CIN3, and 4 SCC) and controls were age and follow-up time at diagnosis-matched women with histologically confirmed ≤ CIN1 (n = 155), selected from the 1122 hrHPV + women of this trial. The concentrations of serum folate were determined by the radioimmunoassay SimulTRAC-SNB-VitaminB12/Folate-RIAKit and the methylation levels by the S5 classifier. Stepwise logistic regression models were used to estimate the association between folate or methylation levels and CIN2+ or CIN3+. The joint effect of folate levels and methylation on the risk of CIN3+ was estimated using combinations of categorical stratifications. RESULTS: Folate levels were significantly lower in women with CIN3+ than in other diagnostic groups (p = 0.019). The risk of CIN3+ was eight times higher (OR 8.9, 95% CI 3.4-24.9) in women with folate deficiency and high methylation levels than in women with normal folate and high methylation levels (OR 1.4, 95% CI 0.4-4.6). CONCLUSION: High methylation and deficient folate independently increased the risk of CIN3+ while deficient folate combined with high methylation was associated with a substantially elevated risk of CIN3+.

Latin America and the Caribbean Code Against Cancer 1st edition: Building capacity on cancer prevention to primary healthcare professionals.

INTRODUCTION: Every year 1.5 million new cancer cases are diagnosed in Latin America and the Caribbean (LAC). Of these, about 40 % could be prevented. Health illiteracy has been identified as a main barrier for cancer prevention. Primary healthcare professionals (HCP) are key in cancer prevention as they are the first entry point of the population into the healthcare system. The LAC Code Against Cancer 1st edition aims to improve health literacy and awareness of cancer prevention in the LAC population, through building capacity of primary HCP. METHODS: The definition and development of the learning objectives, curriculum, structure, and evaluation of an online learning program for primary HCP was led by a dedicated group of experts from the LAC Code Against Cancer project. A pedagogical guideline and a template to ensure harmonization across topics were produced to guide the program development. Two rounds of internal revisions and an editorial process were performed. RESULTS: An online competency-based microlearning program for primary HCP was produced, taking the LAC Code Against Cancer as a basis. The competences addressed in the curriculum are core knowledge, communication skills, decision-making and applying knowledge to real-world situations. A comprehensive evaluation to assess acquisition of these competences, based on the Miller's Pyramid, was designed with three data collection points: a) immediately before, to assess baseline knowledge and skills; b) immediately after, to determine acquired competences; and c) at 3-6 months follow-up, to assess performance in daily practice. The e-learning will be freely available in the Virtual Campus for Public Health of the Pan American Health Organization in Spanish, English, and Portuguese. CONCLUSION: Primary HCP, perceived as trustworthy sources of information, are key actors to increase the population's awareness and literacy on cancer prevention. Building capacity of these professionals has the potential to increase dissemination and impact of the LAC Code Against Cancer by prompting communication with the public and offering personalized actionable preventive messages through counselling.

Latin America and the Caribbean Code Against Cancer 1st edition: Formative research on the comprehension and persuasiveness of the recommendations by the general population.

BACKGROUND: Cancer prevention is the most efficient and cost-effective strategy in cancer control. One prevention strategy is giving credible, clear, and evidence-based recommendations to the individual; however, it is key that these messages are accepted and understood properly by the public. This study aimed to pilot the draft recommendations developed as part of the Latin America and the Caribbean (LAC) Code Against Cancer 1st edition, in terms of comprehension and persuasion of each message. METHODS: A mixed method two-wave study, in which two versions of the messages were presented to the general population in five LAC countries. We used an ad-hoc questionnaire and interviews that followed the cognitive-pretesting methodology. RESULTS: Findings suggest that the messages were generally well understood, especially in Spanish speaking countries, and that the messages were generally more understandable than persuasive. We adapted and revised the recommendations based on the findings of the first Wave and held a second iteration in the Spanish speaking countries. We observed a better understanding of most messages in Wave 2. CONCLUSION: The LAC Code Against Cancer is a valuable tool of well understood messages for the public, with concrete actions everyone can take to prevent cancer. Further research should assess particularities of the region for further efficient dissemination of these important health messages, identify key messages for certain population groups and future interventions that strengthen health literacy in rural and less educated populations to increase behavior change.

The Scarface Score: Deciphering Response to DNA Damage Agents in High-Grade Serous Ovarian Cancer-A GEICO Study.

Genomic Instability (GI) is a transversal phenomenon shared by several tumor types that provide both prognostic and predictive information. In the context of high-grade serous ovarian cancer (HGSOC), response to DNA-damaging agents such as platinum-based and poly(ADP-ribose) polymerase inhibitors (PARPi) has been closely linked to deficiencies in the DNA repair machinery by homologous recombination repair (HRR) and GI. In this study, we have developed the Scarface score, an integrative algorithm based on genomic and transcriptomic data obtained from the NGS analysis of a prospective GEICO cohort of 190 formalin-fixed paraffin-embedded (FFPE) tumor samples from patients diagnosed with HGSOC with a median follow up of 31.03 months (5.87-159.27 months). In the first step, three single-source models, including the SNP-based model (accuracy = 0.8077), analyzing 8 SNPs distributed along the genome; the GI-based model (accuracy = 0.9038) interrogating 28 parameters of GI; and the HTG-based model (accuracy = 0.8077), evaluating the expression of 7 genes related with tumor biology; were proved to predict response. Then, an ensemble model called the Scarface score was found to predict response to DNA-damaging agents with an accuracy of 0.9615 and a kappa index of 0.9128 (p < 0.0001). The Scarface Score approaches the routine establishment of GI in the clinical setting, enabling its incorporation as a predictive and prognostic tool in the management of HGSOC.

Salud sexual y reproductiva en exguerrilleras colombianas antes del Acuerdo de Paz y después de este / Sexual and Reproductive Health of Former Colombian Female Guerrillas before and after the Peace Agreement / Saúde sexual e reprodutiva em ex-guerrilheiras colombianas antes e depois do Acordo de Paz

El objetivo de este artículo es describir las experiencias en salud sexual y reproductiva de exguerrilleras de las Fuerzas Armadas Revolucionarias de Colombia-Ejército del Pueblo (fARC-EP) durante el conflicto armado y después de la firma del Acuerdo de Paz. A lo largo de 2018 se realizó un estudio de caso interpretativo a través de observación participante, once entrevistas y dos grupos focales. En las fARC-EP no hubo un enfoque de salud sexual y reproductiva integral ni con perspectiva de género; se privilegió la prevención del embarazo con métodos y sanciones para las mujeres. Debido a su carácter de ejército clandestino, las decisiones no eran tomadas de manera individual, y la autoridad del superior implicaba las relaciones erótico-afectivas, aunque se garantizaba una atención expedita para casos de urgencias. Posterior a la firma del acuerdo, con su consiguiente inserción en el sistema de salud colombiano, se amplían las posibilidades de atención para casos no urgentes, pero persisten las barreras de atención del sistema de salud.

This study examined the sexual and reproductive health statuses of former female guerrillas of the Revolutionary Armed Forces of Colombia-People's Army (fARC-EP) during the armed conflict and after the signing of the peace agreement. During 2018, an interpretive case study was conducted through the participant observation, 11 interviews, and 2 focus groups. In the fARC-EP group, no comprehensive approach to sexual and reproductive health was noted from a gender perspective, but pregnancy prevention using methods and sanctions for women was found to be privileged. Owing to its characteristic as a clandestine army, decisions were not made individually, and the authority of the superior involved erotic-affective relationships, although expedited attention was guaranteed for emergency cases. After the signing of the agreement, with its consequent insertion into the Colombian health system, the possibilities of care for non-urgent cases have been expanded, with the barriers to healthcare being emphasized

O objetivo deste artigo é descrever as experiências em saúde sexual e reprodutiva de ex-guerrilheiras das Forças Armadas Revolucionárias da Colômbia - Exército Popular (fARC-EP) durante o conflito armado e após a assinatura do acordo de paz. Durante o ano de 2018, foi realizado um estudo de caso interpretativo através da observação participante, 11 entrevistas e dois grupos focais. Nas fARC-EP não havia abordagem integral da saúde sexual e reprodutiva ou perspectiva de gênero; privilegiou-se a prevenção da gravidez com métodos e sanções para as mulheres. Por ser um exército clandestino, as decisões não eram tomadas individualmente, e a autoridade do superior implicava relações erótico-afetivas, embora garantisse atendimento ágil em casos de emergência. Após a assinatura do convênio, com sua consequente inserção no sistema de saúde colombiano, ampliam-se as possibilidades de atendimento aos casos não urgentes, mas enfatizam-se as barreiras para o atendimento no sistema de saúde.

Real-world safety and effectiveness of maintenance niraparib for platinum-sensitive recurrent ovarian cancer: A GEICO retrospective observational study within the Spanish expanded-access programme.

AIM: To describe patient characteristics, effectiveness and safety in a real-world population treated with niraparib in the Spanish expanded-access programme. PATIENTS AND METHODS: This retrospective observational study included women with platinum-sensitive recurrent high-grade serous ovarian cancer who received maintenance niraparib within the Spanish niraparib expanded-access programme. Eligible patients had received ≥2 previous lines of platinum-containing therapy, remained platinum-sensitive after the penultimate line of platinum and had responded to the most recent platinum-containing therapy. Niraparib dosing was at the treating physician's discretion (300 mg/day fixed starting dose or individualised starting dose [ISD] according to baseline body weight and platelet count). Safety, impact of dose adjustments, patient characteristics and effectiveness were analysed using data extracted from medical records. RESULTS: Among 316 eligible patients, 80% had BRCA wild-type tumours and 66% received an ISD. Median niraparib duration was 7.8 months. The most common adverse events typically occurred within 3 months of starting niraparib. Median progression-free survival was 8.6 (95% confidence interval [CI] 7.6-10.0) months. One- and 2-year overall survival rates were 86% (95% CI 81-89%) and 65% (95% CI 59-70%), respectively. Dose interruptions, dose reductions, haematological toxicities and asthenia/fatigue were less common with ISD than fixed starting dose niraparib, but progression-free survival was similar irrespective of dosing strategy. Subsequent therapy included platinum in 71% of patients who received further treatment. CONCLUSION: Outcomes in this large real-world dataset of niraparib-treated patients are consistent with phase III trials, providing reassuring evidence of the tolerability and activity of niraparib maintenance therapy for platinum-sensitive recurrent ovarian cancer. GOV REGISTRATION: NCT04546373.

Open-label phase II clinical trial of ketoconazole as CYP17 inhibitor in metastatic or advanced non-resectable granulosa cell ovarian tumors: the GREKO (GRanulosa Et KetOconazole) trial, GETHI 2011-03.

BACKGROUND: Granulosa cell ovarian tumor (GCT) is characterized by a pathognomonic mutation in the FOXL2 gene (402 C > G) that leads to an overactivation of steroidogenesis. CYP17 is a key enzyme in such process and can be inhibited by ketoconazole. METHODS: We designed a phase II clinical trial to assess the efficacy of ketoconazole in advanced GCT and conducted several in vitro studies to support the clinical findings. RESULTS: From October 1st 2012 to January 31st 2014, six evaluable patients were recruited in ten hospitals of the Spanish Group for Transversal Oncology and Research in Orphan and Infrequent Tumors" (GETTHI). FOXL2 (402C > G) mutation was confirmed in three; two cases were wild type and it could not be assessed in one. No objective response by RECIST was observed, but five cases achieved stable disease longer than 12 months. Median progression-free survival was 14.06 months (CI 95% 5.43-22.69) for the whole study population (3.38 and 13.47 months for wild-type cases and 14.06, 20.67 and 26.51 for those with confirmed FOXL2 mutation). Median overall survival was 22·99 months (CI 95% 8.99-36.99). In vitro assays confirmed the activity of ketoconazole in this tumor and suggested potential synergisms with other hormone therapies. CONCLUSION: Ketoconazole has shown activity in advanced GCT in clinical and in vitro studies. Based on these data, an orphan designation was granted by the European Medicines Agency for ketoconazole in GCT (EU/3/17/1857). GOV IDENTIFIER: NCT01584297.

Sistema de Monitoreo a la equidad territorial y avances en los Objetivos de Desarrollo Sostenible en Colombia

Aunque el cumplimiento de los Objetivos de Desarrollo del Milenio tuvo un balance positivo, con promedios nacionales que en general mejoraron, las desigualdades dentro de los países aumentaron. La agenda de los Objetivos de Desarrollo Sostenible (ODS) busca promover avances en términos de equidad territorial, por esto la incorporación del espacio geográfico en su monitoreo a escalas subnacionales ofrece ventajas importantes. Este artículo tuvo como objetivo describir el Sistema de Monitoreo Territorial a los ODS3 (MOT-ODS3), una herramienta digital diseñada para incrementar la disponibilidad de información a nivel municipal sobre las desigualdades e inequidades territoriales relacionadas con la salud y el bienestar en Colombia. Para demostrar su funcionalidad se describen los componentes del Sistema, indicadores, mapas, gráficos y métricas de desigualdad utilizados, así como también los perfiles de país y departamento, diseñados para reportar los resultados del monitoreo. Como ejemplo práctico de la utilización del Sistema se analizan los indicadores de Colombia entre 2015 y 2017. Según el monitoreo, Colombia mostró mejoras en la salud y el bienestar de la población; sin embargo, se apreciaron diferencias notables intermunicipales en casi todos los indicadores y brechas territoriales en la mortalidad entre municipios ricos y pobres y entre la zona rural y la urbana. Puede decirse que el MOT-ODS3 incrementó la disponibilidad de información para estimular y apoyar el avance del país hacia el logro de los Objetivos de Desarrollo Sostenible.

Although compliance with the Millennium Development Goals had a positive balance, with national averages that generally improved, inequalities within countries increased. The Sustainable Development Goals (SDGs) agenda seeks to promote progress in terms of territorial equity, which is why the incorporation of geographic space in its monitoring at subnational scales offers important advantages. This article aimed to describe the Territorial Monitoring System for the SDGs3 (MOT-ODS3), a digital tool designed to increase the availability of information at the municipal level on territorial inequalities and inequities related to health and well-being in Colombia. To demonstrate its functionality, the components of the System, indicators, maps, graphs and inequality metrics used are described, as well as the country and departmental profiles designed to report monitoring results. As a practical example of the use of the System, the indicators for Colombia between 2015 and 2017 are analyzed. According to the monitoring, Colombia showed improvements in the health and well-being of the population; however, notable inter-municipal differences were seen in almost all indicators and territorial gaps in mortality between rich and poor municipalities and between rural and urban areas. It can be said that the MOT-ODS3 increased the availability of information to stimulate and support the country's progress towards the achievement of the Sustainable Development Goals.

Laboratory Cross-Comparison and Ring Test Trial for Tumor BRCA Testing in a Multicenter Epithelial Ovarian Cancer Series: The BORNEO GEICO 60-0 Study.

Germline and tumor BRCA testing constitutes a valuable tool for clinical decision-making in the management of epithelial ovarian cancer (EOC) patients. Tissue testing is able to identify both germline (g) and somatic (s) BRCA variants, but tissue preservation methods and the widespread implementation of NGS represent pre-analytical and analytical challenges that need to be managed. This study was carried out on a multicenter prospective GEICO cohort of EOC patients with known gBRCA status in order to determine the inter-laboratory reproducibility of tissue sBRCA testing. The study consisted of two independent experimental approaches, a bilateral comparison between two reference laboratories (RLs) testing 82 formalin-paraffin-embedded (FFPE) EOC samples each, and a Ring Test Trial (RTT) with five participating clinical laboratories (CLs) evaluating the performance of tissue BRCA testing in a total of nine samples. Importantly, labs employed their own locally adopted next-generation sequencing (NGS) analytical approach. BRCA mutation frequency in the RL sub-study cohort was 23.17%: 12 (63.1%) germline and 6 (31.6%) somatic. Concordance between the two RLs with respect to BRCA status was 84.2% (gBRCA 100%). The RTT study distributed a total of nine samples (three commercial synthetic human FFPE references, three FFPE, and three OC DNA) among five CLs. The median concordance detection rate among them was 64.7% (range: 35.3-70.6%). Analytical discrepancies were mainly due to the minimum variant allele frequency thresholds, bioinformatic pipeline filters, and downstream variant interpretation, some of them with consequences of clinical relevance. Our study demonstrates a wide range of concordance in the identification and interpretation of BRCA sequencing data, highlighting the relevance of establishing standard criteria for detecting, interpreting, and reporting BRCA variants.

Safety of combining dabrafenib plus trametinib in elderly BRAF V600 mutation-positive advanced melanoma patients: real-world data analysis of Spanish patients (ELDERLYMEL).

Efficacy and safety of dabrafenib and trametinib in metastatic melanoma have been demonstrated in two-phase III and one-phase I/II clinical trials. However, patients at least 75 years old (y.o.) were largely underrepresented. Additionally, the safety profile of dabrafenib and trametinib based on age is unknown. ELDERLYMEL is a retrospective noninterventional multicenter study, describing the effectiveness and safety of at least 75 y.o. patients compared with less than 75 y.o. patients with advanced BRAF V600-mutated melanoma treated with dabrafenib plus trametinib or dabrafenib monotherapy. A total of 159 patients were included, 130 less than 75 y.o. and 29 at least 75 y.o. Clinical features were similar between the groups, except in the number of comorbidities, number of metastatic sites, Eastern Cooperative Oncology Group (ECOG) performance status, and BRAF V600-mutation type. Five patients per group received dabrafenib monotherapy. There were no differences in adverse events (AEs) rate or grade between the groups. However, AE profiles were different between the groups, being pyrexia infrequent in patients at least 75 y.o. (13.8% vs. 42.3%; P = 0.005). Dabrafenib and trametinib dose intensities were lower in at least 75 y.o. patients ( P = 0.018 and P = 0.020), but there were no differences in effectiveness between the groups. Finally, in a multivariate analysis, sex (female) was the only variable independently associated with an increased risk of AE grade ≥3. Data from the ELDERLYMEL study demonstrate that dabrafenib plus trametinib is safe and effective in at least 75 y.o. patients with advanced BRAF V600-mutated melanoma without increasing toxicity. Additionally, we describe a different safety profile depending on age and sex.

Gender Gap in Self-Rated Health: A Cohort Perspective in Eastern European Countries.

BACKGROUND: The relationship between self-rated health and gender differs across countries and generations. The aim of this study is to analyze the effect of socioeconomic conditions on self-rated health from a generational perspective, its differential effect on gender, and its influence on the gender gap in order to explore health diversity using a multidisciplinary approach and considering policy implications in Eastern European countries. METHODS: We used data drawn from the European Health Interview Survey for eight Eastern European countries and EUROSTAT from 2006 through to 2009. We conducted multilevel analyses to understand the individual and national health determinants of self-rated health by gender and to determine whether national differences remain after controlling for micro variables. In order to analyze the role of equity (Gini quartile) in gender differences, Oaxaca analyses were used. RESULTS: The self-rated health gender gap increases with age. Individual characteristics, such as educational level or smoking, influence citizens' perceived health, and have a stronger effect on women than on men. Knowing both the characteristics (endowment effects) and the effects of individual characteristics (coefficient effects) on health is important in order to understand gender gaps among people from the silent generation. CONCLUSIONS: Our research indicates that random effects are greater for men than for women. Moreover, random effects might be explained to a certain extent by economic equity (Gini index). The combined effects of gender, cohort, and geographical differences on self-rated health have to be taken into account to develop public health policies.

Consumo de productos de tabaco y factores asociados en mujeres en Antioquia, Colombia / Tobacco product use and associated factors among women in Antioquia, Colombia

Resumen Introducción: El uso del tabaco en mujeres está aumentando significativamente a pesar de los alarmantes peligros para la salud. Objetivo: Determinar la prevalencia y factores asociados al consumo de tabaco en mujeres del departamento de Antioquia, Colombia. Materiales y métodos: Estudio descriptivo transversal, con una muestra representativa de mujeres mayores de 18 años en las nueve subregiones del departamento, se utilizó un muestreo probabilístico multietápico, estratificado por región. Resultados: De 4377 mujeres, 10,8% eran fumadoras, 13,1% exfumadoras, y 75,9% nunca habían fumado. Variables relacionadas con mayor reporte de tabaquismo: tener más de 45 años (OR=3,2, IC 2,6-3,9); no tener educación o primaria incompleta (OR=2,2, IC 1,5-3,1), secundaria incompleta (OR=1,5, IC 1,1-2,2), consumir licor (OR=2,3, IC 1,9-2,7), no consumir verduras (OR=1,4, IC 1,02,0), no consumir frutas (OR=1,6, IC 1,2-2,1). Variables relacionadas con menor reporte de tabaquismo: estar casada (OR=0,6, IC 0,5-0,8), y vivir en algunas de las subregiones. Conclusiones: Se evidencia la importancia de programas enfocados a prevenir el consumo de productos nuevos como el cigarrillo electrónico, especialmente en población joven.

Abstract Introduction: Tobacco use among women is increasing significantly despite alarming health hazards. Objective: To determine the prevalence and factors associated with tobacco consumption in women from the department of Antioquia, Colombia. Material and methods: Cross-sectional descriptive study, with a representative sample of women over 18 years of age in the nine subregions of the department, using multistage probabilistic sampling, stratified by region. Results: Of the 4,377 women, 10.8% were smokers, 13.1% were ex-smokers, and 75.9% were women who had never smoked. Variables related to the highest reported smokers: having more than 45 years of age (OR=3.2, CI 2.6-3.9); not having an education or an incomplete primary education (OR=2.2, IC 1.5-3.1), incomplete secondary education (OR=1.5, CI 1.1-2.2), consuming liquor (OR=2.3, CI 1.9-2.7), not consuming vegetables (OR=1.4, IC 1.0-2.0), not consuming fruit (OR=1,6, CI 1,2-2,1). Variables related to less reported smoking: being married (OR=0.6, CI 0.5-0.8) and living in some of the subregions. Conclusions: The importance of programs focused on preventing the consumption of new products such as e-cigarettes is evident, especially in young people.

Type 2 Diabetes Mellitus and Cancer: Epidemiology, Physiopathology and Prevention.

Individuals with type 2 diabetes mellitus are at greater risk of developing cancer and of dying from it. Both diseases are age-related, contributing to the impact of population aging on the long-term sustainability of health care systems in European Union countries. The purpose of this narrative review was to describe, from epidemiological, pathophysiological and preventive perspectives, the links between type 2 diabetes mellitus and the most prevalent cancers in these patients. Multiple metabolic abnormalities that may occur in type 2 diabetes mellitus, particularly obesity, could explain the increased cancer risk. In addition, the effectiveness of drugs commonly used to treat type 2 diabetes mellitus (e.g., metformin and thiazolidinediones) has been broadly evaluated in cancer prevention. Thus, a better understanding of the links between type 2 diabetes mellitus and cancer will help to identify the contributing factors and the pathophysiological pathways and to design personalized preventive strategies. The final goal is to facilitate healthy aging and the prevention of cancer and other diseases related with type 2 diabetes mellitus, which are among the main sources of disability and death in the European Union and worldwide.

Experiencias en la atención en salud de mujeres con anormalidades citológicas o cáncer de cuello uterino en dos departamentos fronterizos: una lucha entre la vida y el sistema de salud colombiano / Experiences in the Health Care of Women with Cytological Abnormalities or Cervix Cancer in Two Border Departments: A Struggle between Life and the Colombian Health System / Experiências na atenção em saúde de mulheres com anormalidades citológicas ou câncer de colo de útero em dois estados da fronteira: uma luta entre a vida e o sistema de saúde colombiano

Resumen Objetivo: Describir la experiencia en la atención en salud de mujeres con anormalidades citológicas con biopsia negativa para malignidad o cáncer de cuello uterino invasor no mayor a 2 meses, en los departamentos de La Guajira y Nariño, en Colombia, entre 2016 y 2017. Metodología: Se presenta el componente cualitativo de un estudio de métodos mixtos de triangulación convergente, a través de 10 entrevistas y 3 grupos focales. Participaron 9 mujeres con cáncer y 6 con anormalidades citológicas entre los 43 y 65 años de edad, 6 de ellas indígenas y 14 pertenecientes al régimen subsidiado. Resultados: Las participantes mencionaron experiencias negativas frente a la atención en salud, pues enfrentan múltiples barreras para acceder al diagnóstico y al tratamiento, como demora en la asignación y la autorización de citas, exámenes y procedimientos; el gasto de bolsillo para traslados a ciudades capitales donde se brinda el servicio; dificultades para encontrar acompañamiento familiar fuera de sus comunidades de origen y barreras idiomáticas en mujeres de comunidades indígenas. También se presentaron dificultades de comunicación efectiva con el personal de salud, lo que llevó a algunas participantes a no entender su diagnóstico tratamiento, y a no sentirse escuchadas. La vivencia del cáncer generó sufrimiento, rechazo de personas de su entorno social y despersonalización. Conclusiones: Las barreras de diversa índole para el acceso oportuno al tratamiento se agudizan por características de base como la pobreza y la pertenencia a grupos étnicos, convirtiéndose la supervivencia en una lucha diaria, que va más allá de las características propias de la enfermedad.

Abstract Objective: To describe the health care experience of women with cytological abnormalities with negative biopsy for malignancy or invasive cervix cancer within two months after diagnosis, in La Guajira and Nariño departments, Colombia, between 2016 and 2017. Methodology: The qualitative component of a mixed methods study of convergent triangulation is presented, through ten interviews and three focus groups. Nine women with cancer and six women with cytological abnormalities between 43 and 65 years of age participated; six of them were indigenous, and fourteen are enrolled to the subsidized health regime. Results: Participants referred negative experiences in the health care system as they face numerous barriers for the diagnosis and access to treatment. Such as, delay in the assignment and authorization of medical appointments, tests, and procedures; the out-of-pocket expenses for transportation to capital cities where the health service is provided; difficulties to find family support outside their communities of origin, and language barriers among women from indigenous communities. Besides, effective communication problems with health personnel were also presented, which lead some participants to misunderstanding their diagnosis or treatment and feeling that they were not being heard. The experience of having cancer led to suffering, rejection from people in their social environment, and depersonalization. Conclusions: Barriers of various kinds for the timely access to treatment are exacerbated by baseline characteristics such as poverty and belonging to ethnic groups, turning survival into a daily struggle, which goes beyond the specific characteristics of the disease itself.

Resumo Objetivo: Descrever a experiência na atenção em saúde de mulheres com anormalidades citológicas com biopsia negativa para malignidade ou câncer de colo de útero invasivo não maior a 2 meses nos estados de La Guajira e Nariño, na Colômbia, entre 2016 e 2017. Metodologia: Foi apresentado o componente qualitativo de um estudo de métodos mistos de triangulação convergente, através de 10 entrevistas e 3 grupos de foco. Participaram 9 mulheres com câncer e 6 com anormalidades citológicas entre 43 e 65 anos da idade, 6 delas indígenas e 14 pertencentes ao sistema subsidiado. Resultados: As participantes mencionaram experiências negativas na atenção em saúde, pois enfrentaram múltiplos obstáculos para ter acesso ao diagnóstico e ao tratamento, como demora na marcação e autorização de consultas, exames e procedimentos; despesas com transporte para cidades capitais onde se oferece o serviço; dificuldades para ter acompanhamento familiar fora das suas comunidades de origem e barreiras idiomáticas para mulheres de comunidades indígenas. Apresentaram-se também, dificuldades de comunicação efetiva com o pessoal de saúde, o que levou a algumas participantes a não entender seu diagnóstico ou tratamento e a não se sentirem escutadas. A experiência do câncer gerou sofrimento, rejeição de pessoas do entorno social e despersonalização. Conclusões: As barreiras de diversas índoles para o acesso oportuno ao tratamento foram agudizadas por características de base como a pobreza e ao fato de pertencer a grupos étnicos, transformando a sobrevivência numa luta diária, que vai além das características próprias da enfermidade.

Identifying Clusters of Adherence to Cardiovascular Risk Reduction Behaviors and Persistence with Medication in New Lipid-Lowering Drug Users. Impact on Healthcare Utilization.

We sought to identify specific profiles of new lipid-lowering drug users based on adherence to a healthy lifestyle and persistence with medication, and to characterize co-morbidities, co-treatments, and healthcare utilization for each of the profiles identified. Observational study in 517 participants in the Aragon Workers' Health Study (AWHS) without previous cardiovascular disease (CVD) and who initiated lipid-lowering therapy. Data were collected from workplace medical examinations and administrative health databases (2010-2018). Using cluster analysis, we identified distinct patient profiles based on persistence with therapy and lifestyle. We then compared characteristics, morbidity, and healthcare utilization across clusters. Participants were aggregated into four clusters based on persistence with therapy, smoking status, adherence to Mediterranean diet, and physical activity. In cluster 1 (n = 113), comprising those with a healthiest lifestyle (14.2% smokers, 84.0% with medium-high adherence to Mediterranean diet, high physical activity), 16.8% were persistent. In cluster 3 (n = 108), comprising patients with the least healthy lifestyle (100% smokers, poor adherence to the Mediterranean diet, low level of physical activity), all were non-persistent. Clusters 2 (n = 150) and 4 (n = 146) both comprised patients with intermediate lifestyle behaviors, but differed in terms of persistence (100 and 0%, respectively). Compared with other clusters, the burden of morbidity, cardiovascular score, and healthcare utilization were lower in cluster 1. The healthy adherer effect was only observed in new lipid-lowering drug users of certain profiles. Furthermore, we found that differences in adherence to lifestyle and medication recommendations for CVD prevention influenced morbidity burden and healthcare utilization.

Prospective Association of Maternal Educational Level with Child's Physical Activity, Screen Time, and Diet Quality.

Evidence has identified unhealthy lifestyle behaviors as the main contributors to obesity in children, so it is essential to identify factors that could influence children's lifestyles. The objective of the present study was to analyze the association of baseline maternal educational level with child's physical activity, screen time, and dietary habits at follow-up. This community-based cohort study was carried out between 2012 and 2014 and included 1405 children aged 8 to 10 years old. Maternal educational level was used as an indicator of child's socioeconomic status. Physical activity, screen time, and dietary habits were assessed by validated questionnaires. The odds of having commercially baked goods for breakfast [OR 1.47 (95% CI 1.03 to 2.10)], going more than once a week to a fast-food restaurant [OR 1.64 (95% CI 1.20 to 2.26)], and taking sweets and candys several times a day [OR 3.23 (95% CI 2.14 to 4.87) were significantly higher among children whose mothers had a lower educational level compared to their peers whose mothers had a higher level. These associations held for taking sweets and candy several times a day after additional adjustment for the corresponding dietary behavior at baseline. Maternal educational level was inversely associated (p < 0.001) with child's screen time at follow up and being in the lowest maternal educational category was associated with an increased odds of surpassing the maximum recommended time of screen time of 120 min per day (OR (95% CI) 1.43 (1.07 to 1.90), p = 0.016). Maternal education is a predictor for unhealthy dietary habits and high screen time in children.