CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions.

BACKGROUND: CDH1 and CTNNA1 remain as the main genes for hereditary gastric cancer. However, they only explain a small fraction of gastric cancer cases with suspected inherited basis. In this study, we aimed to identify new hereditary genes for early-onset gastric cancer patients (EOGC; < 50 years old). METHODS: After germline exome sequencing in 20 EOGC patients and replication of relevant findings by gene-panel sequencing in an independent cohort of 152 patients, CTNND1 stood out as an interesting candidate gene, since its protein product (p120ctn) directly interacts with E-cadherin. We proceeded with functional characterization by generating two knockout CTNND1 cellular models by gene editing and introducing the detected genetic variants using a lentiviral delivery system. We assessed ß-catenin and E-cadherin levels, cell detachment, as well as E-cadherin localization and cell-to-cell interaction by spheroid modeling. RESULTS: Three CTNND1 germline variants [c.28_29delinsCT, p.(Ala10Leu); c.1105C > T, p.(Pro369Ser); c.1537A > G, p.(Asn513Asp)] were identified in our EOGC cohorts. Cells encoding CTNND1 variants displayed altered E-cadherin levels and intercellular interactions. In addition, the p.(Pro369Ser) variant, located in a key region in the E-cadherin/p120ctn binding domain, showed E-cadherin mislocalization. CONCLUSIONS: Defects in CTNND1 could be involved in germline predisposition to gastric cancer by altering E-cadherin and, consequently, cell-to-cell interactions. In the present study, CTNND1 germline variants explained 2% (3/172) of the cases, although further studies in larger external cohorts are needed.

[From face-to-face consultation to teleconsultation: Primary health care professionals' experiences in the Basque Country during the pandemic]. / De la consulta presencial a la teleconsulta: experiencias de profesionales de atención primaria del País Vasco durante la pandemia.

OBJECTIVE: To explore the perceptions of Primary Health Care (PHC) professionals on changes in consultation modalities and their impact on PHC fundamentals during the pandemic. DESIGN: Qualitative exploratory research conducted between October and November, 2021. LOCATION: Four urban and one rural primary health care centers with different socioeconomic profiles in the threeterritories of the Basque Country. PARTICIPANTS: Forty-six professionals from different categories of the PHC team and health centre directors. METHOD: Purposive sampling. Five focus groups and fourin-depth interviews. Thematic analysis with the support of the Atlas.ti programme. Triangulation of results among the research team. RESULTS: Experiences with the development of teleconsultation appear to be directly conditioned by the pandemic context in its different phases and by the PC situation. The professionals identified communication barriers, as well as potentialities of its use that require adequate training and evaluation. Risks of inequity were perceived in the use of teleconsultations that could be affecting the quality of care. Longitudinality was assessed as a facilitating factor and problems of coordination and communication through teleconsultation between care levels were identified. CONCLUSIONS: The replacement of face-to-face consultation by teleconsultation had an impact on fundamental aspects of PHC such as quality, accessibility, equity, coordination and longitudinality. Teleconsultation in PHC should always be evaluated considering the specific circumstances and contexts of its implementation.

Predictive Value of Genetic Risk Scores in the Development of Colorectal Adenomas.

INTRODUCTION: Unlike colorectal cancer (CRC), few studies have explored the predictive value of genetic risk scores (GRS) in the development of colorectal adenomas (CRA), either alone or in combination with other demographic and clinical factors. METHODS: In this study, genomic DNA from 613 Spanish Caucasian patients with CRA and 829 polyp-free individuals was genotyped for 88 single-nucleotide polymorphisms (SNPs) associated with CRC risk using the MassArray™ (Sequenom) platform. After applying a multivariate logistic regression model, five SNPs were selected to calculate the GRS. Regression models adjusted by sex, age, family history of CRC, chronic use of NSAIDs, low-dose ASA, and consumption of tobacco were built in order to study the association between GRS and CRA risk. We evaluated the discriminatory capacity using the area under the receiver operating characteristic curve (AUC). The interactions between demographic information and GRS were also analyzed. RESULTS: Significant associations between high GRS values and risk of CRA for analyzed models were observed. In particular, patients with higher GRS values had 2.3-2.6-fold increase in risk of CRA compared to patients with middle values. Combining sex and age with the GRS significantly increased the discriminatory accuracy of the univariate model with GRS alone. The best model achieved an AUC value of 0.665 (95% CI: 0.63-0.69). The GRS showed a different behavior depending on sex and age. CONCLUSION: Our findings showed that, besides sex and age, GRS is an important risk factor for development of CRA and may be useful for CRC risk stratification and adaptation of screening programs.

[Gender inequality and mental health medicalization: Sociocultural determining factors from the analysis of expert perceptions]. / Desigualdad de género y medicalización de la salud mental: factores socioculturales determinantes desde el análisis de percepciones expertas.

To identify the sociocultural roots that explain the higher frequency of diagnoses of depression and/or anxiety and the prescription of psychotropic drugs in women, in order to propose a preliminary explanatory framework for the investigation of gender inequalities in mental health and its medicalization. Qualitative study with a descriptive-interpretive design, through in-depth interviews conducted in January and February 2021. Interviews were held in various cities of the Basque Country, Barcelona and Madrid. 12 experts in gender and mental health from the clinical (Primary Care and Mental Health), academic and associative fields. Intentional sampling, following the snowball technique, until covering the diversity of previously identified profiles and the saturation of the discourse. An analysis of thematic content was carried out starting from a critical-realistic epistemological perspective. The main dimensions to explain gender inequalities in diagnoses of depression or anxiety and prescription of psychoactive drugs were: 1) the material and symbolic subordination of women, 2) the role of «psi¼ sciences in the pathologization of the feminine identity, 3) the epistemological and androcentric biases of biomedicine, and 4) the active agency of women in medicalization processes. The reduction of gender inequalities in the diagnoses and prescription of psychotropic drugs will require joint intervention at the clinical, community and structural levels that, from a feminist perspective, manage to reverse the socioeconomic, symbolic and epistemic vulnerability of women.

[Population's perceptions and experiences of the changing pattern of primary care consultations during the pandemic]. / Percepciones y experiencias de la población ante la transformación de la modalidad de las consultas en atención primaria durante la pandemia.

AIM: To explore the perceptions and experiences of the general population regarding the impact of the implementation of teleconsultation in primary health care during the pandemic. DESIGN: methodology with a descriptive-interpretative approach, whose fieldwork was carried out between May and November 2020. PLACE: Study conducted in Navarra and Euskadi. Population groups with different profiles of associated and non-associated citizenship in both Autonomous Communities. A total of 62 primary health care users have participated and 10 focus groups were carried out. METHOD: The focus groups followed a semi-structured script based on the variables of analysis and dimensions of interest according to the different participant profiles and objectives. The sessions were recorded and transcribed. An inductive content analysis was performed. Data triangulation was realized in order to ensure validity. RESULTS: The perception of teleconsultation by the population has varied throughout the pandemic and has been heterogeneous. The participants consider that the non-face-to-face modality may have repercussions on the quality of care, as well as amplifying inequalities in access to primary health care. CONCLUSIONS: It is essential to carry out analyses and evaluations from a health equity perspective in order to make decisions related to the use of technology in general and teleconsultation in particular, in the post-pandemic future of primary health care.

[Does the Electronic Health Record reflect the social determinants of health from Primary Health Care?] / ¿Refleja la historia clínica electrónica los determinantes sociales de la salud desde Atención Primaria?

OBJECTIVE: Analyze whether the use of Z codes in the Electronic Health Record (EHR) correlates with the socioeconomic reality of the population attended. DESIGN: Observational, descriptive, cross-sectional, ecological study. LOCATION: 90 health centres of two Primary Health Care (PHC) Departments of the Community of Madrid. PARTICIPANTS: The total number of patients treated during 2016: 1,920,124 (54.33% women, 45.67% men). The 7.15% received some Z code (67.29% women, 32.71% men). MAIN MEASUREMENTS: As a dependent variable, the proportion of patients with Z code records in their EHRs was established. As independent variable, two socioeconomic indicators were selected that objectively reflect the differences between Basic Health Areas: Average Income Available per capita and Proportion of Economic Immigrants. To evaluate the correlation between dependent and independent variables, a multivariate correlation-regression analysis was used. RESULTS: It was observed that the higher the disposable income, the lower the proportion of Z code records in the EHRs (Pearson correlation coefficient: -0.56). However, there is a great variability in the registration of Z codes and the coding fails to make visible the socio-economic realities of the populations covered (Diagnostic Odds Ratio: 0.12. CI: 0.05-0.32). CONCLUSIONS: The use of different tools that facilitate the visualization of the health impact of social inequalities, as well as their evaluation through various research methodologies, is relevant for a community orientation of the PHC. The Z codes do not make visible in the studied area the social determinants of health of the population attended.

Comprehensive primary health care and non-communicable diseases management: a case study of El Salvador.

BACKGROUND: One of today's greatest challenges in public health worldwide - and especially its key management from Primary Health Care (PHC) - is the growing burden of non-communicable diseases (NCDs). In El Salvador, since 2009 the Minister of Health (MoH) has scaled up a national public health system based on a comprehensive PHC approach. A national multi-sectorial strategic plan for a comprehensive approach to NCDs has also been developed. This analysis explores stakeholders' perceptions related to the management of NCDs in PHC and, in particular, the role of social participation. METHODS: A case-study was developed consisting of semi structured interviews and official document reviews. Semi-structured interviews were developed with chronic patients (14) and PHC professionals working in different levels within PHC (12). Purposive sampling was used to recruit participants. A non-pure, deductive approach was implemented for coding. After grouping codes into potential themes, a thematic framework was elaborated through a reflexive approach and the triangulation of the data. The research was conducted between March and August of 2018 in three different departments of El Salvador. RESULTS: The structure and the functioning of the Salvadoran PHC system and its intersectoral approach is firstly described. The interdisciplinary PHC-team brings holistic health care closer to the communities in which health promoters play a key role. The findings reflect the generally positive perception of the PHC system in terms of accessibility, quality and continuity of care by chronic patients. Community engagement and the National Health Forum are ensuring accountability through social controllership mechanisms. However, certain challenges were also noted during the interviews related to the shortage of medication and workforce; coordination between the levels of care and the importance of prevention and health promotion programmes for NCDs. CONCLUSIONS: The Salvadoran PHC and its comprehensive approach to NCDs with an emphasis on intersectoral participation has been positively perceived by the range of stakeholders interviewed. Social engagement and the NHF works as a driving force to ensure accountability as well as in the promotion of a preventive culture. The challenges identified provide keys to amplify knowledge for addressing inequalities in health by strengthening PHC and its NCDs management.

Predictive factors of clinical response to treatment with anti-TNF agents in ulcerative colitis: what have we learned from our patients?

INTRODUCTION: inhibitors of tumor necrosis factor alpha (anti-TNFs) are effective drugs for the treatment of moderate-to-severe ulcerative colitis (UC). However, many patients do not respond or lose therapeutic response during follow-up. OBJECTIVES: to analyze the determining factors of clinical response to anti-TNFs in UC. METHODS: a multicenter retrospective study was performed in 79 patients with UC who started treatment with anti-TNFs between 2009 and 2015. The primary endpoint was clinical remission (pMayo index ≤ 1) at 12 months. Furthermore, remission and clinical response (final pMayo score ≤ 3) and corticoids discontinuation were assessed at three, six and 12 months. An analysis was performed to identify variables predictive of clinical response. RESULTS: at 12 months, remission and clinical response were seen in 59.2 % and 77.8 % of patients, respectively. Corticoids could be discontinued in 82.4 % of patients. At 12 months, corticoids discontinuation (< 3 months) (OR 0.06; 95 % CI: 0.01-0.24) and clinical response at six months (OR 0.008; 95 % CI: 0.001-0.053) were independent factors predictive of clinical remission. CONCLUSION: in patients with active UC on anti-TNFs, corticoid discontinuation within three months and clinical response at six months after treatment onset are predictive of clinical disease remission.

Genetic susceptibility in the development of colorectal adenomas according to family history of colorectal cancer.

Our study aimed to evaluate the relevance of genetic susceptibility in the development of colorectal adenomas (CRA) and its relationship with the presence of family history of colorectal cancer (CRC). Genomic DNA from 750 cases (first degree relatives of patients with CRC) and 750 controls (subjects with no family history of CRC) was genotyped for 99 single nucleotide polymorphisms (SNPs) previously associated with CRC/CRA risk by GWAS and candidate gene studies by using the MassArray™ (Sequenom) platform. Cases and controls were matched by gender, age and histological lesion. Eight hundred and fifty-eight patients showed no neoplastic lesions, whereas 288 patients showed low-risk adenomas, and 354 patients presented high-risk adenomas. Two SNPs (rs10505477, rs6983267) in the CASC8 gene were associated with a reduced risk of CRA in controls (log-additive models, OR: 0.67, 95%CI:0.54-0.83, and OR:0.66, 95%CI:0.54-0.84, respectively). Stratified analysis by histological lesion revealed the association of rs10505477 and rs6983267 variants with reduced risk of low- and high-risk adenomas in controls, being this effect stronger in low-risk adenomas (log-additive models, OR:0.63, 95%CI:0.47-0.84 and OR:0.64, 95%CI:0.47-0.86, respectively). Moreover, 2 SNPs (rs10795668, rs11255841) in the noncoding LINC00709 gene were significantly associated with a reduced risk of low-risk adenomas in cases (recessive models, OR:0.22, 95%CI:0.06-0.72, and OR:0.08, 95%CI:0.03-0.61) and controls (dominant models, OR:0.50, 95%CI:0.34-0.75, and OR:0.52, 95%CI:0.35-0.78, respectively). In conclusion, some variants associated with CRC risk (rs10505477, rs6983267, rs10795668 and rs11255841) are also involved in the susceptibility to CRA and specific subtypes. These associations are influenced by the presence of family history of CRC.

Comparison of Two Intensive Bowel Cleansing Regimens in Patients With Previous Poor Bowel Preparation: A Randomized Controlled Study.

OBJECTIVES: Inadequate bowel cleansing is a major burden for endoscopy units. The aim of this study was to compare two intensive bowel cleansing regimens in patients with previous colonoscopy with inadequate bowel preparation. METHODS: Patients with inadequate cleansing at index colonoscopy were randomized to 4-L split-dose polyethylene-glycol (PEG) regimen vs. 2-L split-dose PEG plus ascorbic acid (PEG+Asc) regimen. All individuals underwent a 3-day low-residue diet and received 10 mg of bisacodyl, the day before colonoscopy. Cleansing was considered to be adequate if the Boston Bowel Preparation Scale scored ≥2 at each colonic segment. A non-inferiority analysis was performed to demonstrate that colonic cleansing with 2-L PEG+Asc was not inferior to 4-l PEG, considering a non-inferiority margin of 10%. RESULTS: Adequate bowel cleansing was significantly higher in patients assigned to 4-L PEG regimen (n=127) vs. those randomized to 2-L PEG+Asc regimen (n=129) by intention-to-treat analysis (81.1 vs. 67.4%, odds ratio (OR) 2.07, 95% confidence interval (CI) (1.163-3.689)) and by per-protocol analysis (86.6 vs. 71.7%, OR: 2.55, 95% CI: (1.316-4.922)). The study was terminated for futility after the interim analysis, because the 95% CI of the difference of proportions was 3.13-24.27% in the intention-to-treat analysis and 3.33-26.47% in the per-protocol analysis, confirming the superiority of 4-L PEG preparation. CONCLUSIONS: After 3-day low-residue diet and oral bisacodyl before colonoscopy, colon cleansing with 4-L split-dose PEG was superior to 2-L split-dose PEG+Asc in patients with previous inadequate cleansing. (EUDRACT: 2013-002506-31, NCT02073552).

Risk factors for inadequate bowel preparation: a validated predictive score.

Background and study aim Inadequate bowel cleansing negatively affects the efficiency of colonoscopy in routine clinical practice. The aim of this study was to design and validate a predictive model for inadequate bowel cleanliness. Patients and methods The model was built from 667 consecutive outpatients (development cohort) who were prospectively scheduled for colonoscopy between June and September 2014. The validation cohort included 409 outpatients who underwent colonoscopy between October and December 2014. Cleansing was evaluated using the Boston Bowel Preparation Scale (BBPS). Bowel preparation was administered on the same day as the examination. Results In the development cohort, BBPS was adequate in 541 patients (81.1 %). At multivariate analysis, antidepressants (odds ratio [OR] 4.25, 95 % confidence interval [CI] 1.91 - 9.47), co-morbidity (OR 3.35, 95 %CI 2.16 - 5.18), constipation (OR 2.09, 95 %CI 1.29 - 3.40), and abdominal/pelvic surgery (OR 1.60, 95 %CI 1.03 - 2.47) were independent predictors for inadequate cleansing. The model built with these variables showed an area under the curve of 0.72 in the development cohort and 0.70 in the validation cohort. A cutoff of 1.225 predicted inadequate bowel preparation with a sensitivity, specificity, positive predictive value, and negative predictive value of 60.3 % (95 %CI 51.6 - 68.4), 75.4 % (95 %CI 71.6 - 78.9), 36.4 % (95 %CI 30.1 - 43.1), and 89.1 % (95 %CI 85.9 - 91.6) in the development cohort, and 50.0 % (95 %CI 38.1 - 61.9), 80.0 % (95 %CI 75.3 - 84.2), 35.7 % (95 %CI 26.4 - 45.6), and 87.9 % (95 %CI 83.7 - 91.3) in the validation cohort. Conclusion A simple score may assist the clinician in predicting which patients are at high risk of inadequate bowel cleanliness. This may guide changes in bowel preparation strategy accordingly.

Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study.

BACKGROUND: First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). METHODS AND FINDINGS: This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer ("familial-risk group") and 3,038 as asymptomatic with average-risk for colorectal cancer ("average-risk group"). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36-2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83-1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90-1.58, p = 0.20). After the age of 50 y, men developed advanced neoplasia over two times more frequently than women and advanced neoplasia appeared at least ten y earlier. Fewer colonoscopies by 2-fold were required to detect one advanced neoplasia in men than in women. Major limitations of this study were first that although average-risk individuals were consecutively included in a randomized control trial, this was not the case for all individuals in the familial-risk cohort; and second, the difference in age between the average-risk and familial-risk cohorts. CONCLUSIONS: Individuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population.

Colorectal cancer screening in the familial risk population: Is colonoscopy still the strategy of choice?

First-degree relatives of patients with colorectal cancer (CRC) are at high risk of this disease. For this reason, medical organizations and clinical guidelines recommend more intensive screening and surveillance for such first-degree relatives than for the average-risk population. Colonoscopy has been the cornerstone of CRC screening in this setting. Although colonoscopy is the most sensitive technique for the detection of neoplastic lesions (especially non-advanced adenomas), its role is less clear for CRC. In addition, screening colonoscopy has several limitations that may affect the success of a screening campaign, such as poor participant acceptance, the need for skilled endoscopists, participant access to screening colonoscopy, overburdened endoscopy units, potential complications, and procedure-related costs. In addition, recent evidence has cast doubt on the advantage of colonoscopy over other strategies for the detection of advanced neoplastic lesions. Despite being less sensitive in general, other screening methods frequently recommended in the average-risk population may be more acceptable and thus help increase CRC screening uptake. This review discusses recent evidence on the risk of CRC in first-degree relatives, the advantages and disadvantages of each screening technique, participation rates depending on the technique, patient preferences, and barriers to screening.

Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia.

INTRODUCTION: Matrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia. OBJECTIVE: To assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels. METHODS: We analysed blood and tissue samples from patients with non-advanced adenomas (n=25), advanced adenomas (n=25), colorectal cancer (n=25) and healthy controls (n=75). Plasma and tissue gelatinase levels were determined by Luminex XMAP technology and gelatin zymography. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimum cut-off for the detection of advanced colorectal neoplasia. RESULTS: Plasma MMP2 levels were similar between groups whatever the type of lesion. Plasma MMP9 levels were significantly higher in patients with neoplastic lesions than in healthy controls (median 292.3ng/ml vs. 139.08ng/ml, P<0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6ng/ml vs. 274.3ng/ml, P=0.03). There was a significant correlation between plasma and tissue levels of MMP9 (r=0.5, P<0.001). The plasma MMP9 cut-off range with the highest diagnostic accuracy was between 173ng/ml and 204ng/ml (AUC=0.80 [95% CI: 0.72-0.86], P<0.001; sensitivity, 80-86% and specificity, 57-67%). CONCLUSION: Plasma MMP9 could be a surrogate biomarker for the early detection of advanced colorectal neoplasia, although its diagnostic performance could be increased by combination with other biomarkers.

Uptake of Colon Capsule Endoscopy vs Colonoscopy for Screening Relatives of Patients With Colorectal Cancer.

BACKGROUND & AIMS: The efficacy of screening colonoscopy in first-degree relatives (FDRs) of patients with colorectal cancer (CRC) is limited by suboptimal uptake. We compared screening uptake of colon capsule endoscopy (CCE) vs colonoscopy in this population. METHODS: We performed a prospective study of 329 asymptomatic FDRs of patients with CRC who were randomly assigned to groups examined by CCE (PillCam, second generation; n = 165) or colonoscopy (n = 164) at a tertiary hospital in Spain from July 2012 through December 2013. Crossover was permitted for patients who did not wish to undergo the assigned procedure. Subjects assigned to CCE who had a significant lesion (polyp ≥ 10 mm, >2 polyps of any size, or CRC) were invited to undergo colonoscopy. RESULTS: One hundred twenty subjects in the CCE group and 113 in the colonoscopy group were eligible for inclusion. In the intention-to-screen analysis, uptake was similar between groups (55.8% CCE vs 52.2% colonoscopy; odds ratio [OR], 0.86; 95% confidence interval [CI], 0.51-1.44; P = .57); 57.4% of subjects crossed over from the CCE group, and 30.2% crossed over from the colonoscopy group (OR, 3.11; 95% CI, 1.51-6.41; P = .002). Unwillingness to repeat bowel preparation in the case of a positive result was the main reason that subjects assigned to the CCE group crossed over; fear of colonoscopy was the reason that most patients in this group crossed over. A significant lesion was detected in 14 subjects (11.7%) in the CCE group and 13 subjects (11.5%) in the colonoscopy group (OR, 1.02; 95% CI, 0.45-2.26; P = .96). CONCLUSIONS: In a prospective study, similar numbers of FDRs of patients with CRC assigned to undergo CCE or colonoscopy agreed to participate, but most preferred to undergo colonoscopy. CCE was as effective as colonoscopy in detecting significant lesions; it could be a valid rescue strategy for subjects who reject screening colonoscopy. ClinicalTrials.gov number: NCT01557101.

Equivalency of fecal immunochemical tests and colonoscopy in familial colorectal cancer screening.

BACKGROUND & AIMS: Colonoscopy is the recommended screening procedure for first-degree relatives of patients with colorectal cancer (CRC), but few studies have compared its efficacy for CRC detection with that of other screening strategies. We conducted a controlled randomized trial to compare the efficacy of repeated fecal immunochemical tests (FITs) and colonoscopy in detecting advanced neoplasia (advanced adenoma or CRC) in family members of patients with CRC. METHODS: In a prospective study, 1918 first-degree relatives of patients with CRC were randomly assigned (1:1 ratio) to receive a single colonoscopy examination or 3 FITs (1/year for 3 years; OC-Sensor; cutoff ≥10 µg hemoglobin/g feces, corresponding to 50 ng hemoglobin/mL buffer). The strategies were considered to be equivalent if the 95% confidence interval of the difference for the detection of advanced neoplasia was ±3%. Follow-up analyses were performed to identify false-negative FIT results and interval CRCs. RESULTS: Of all eligible asymptomatic first-degree relatives, 782 were included in the colonoscopy group and 784 in the FIT group. In the intention-to-screen analysis, advanced neoplasia was detected in 33 (4.2%) and 44 (5.6%) first-degree relatives in the FIT and colonoscopy groups, respectively (odds ratio = 1.41; 95% confidence interval: 0.88-2.26; P = .14). In the per-protocol analysis, 28 first-degree relatives (3.9%) in the FIT group and 43 (5.8%) in the colonoscopy group had advanced neoplasia (odds ratio = 1.56; 95% confidence interval: 0.95-2.56; P = .08). FIT missed 16 of 41 advanced adenomas but no CRCs. The FIT strategy required endoscopic evaluation of 4-fold fewer individuals to detect 1 advanced neoplasia than the colonoscopy strategy. CONCLUSIONS: Repeated FIT screening (1/year for 3 years) detected all CRCs and proved equivalent to colonoscopy in detecting advanced neoplasia in first-degree relatives of patients with CRC. This strategy should be considered for populations where compliance with FITs is higher than with colonoscopy. ClinicalTrials.gov number: NCT01075633 (COLONFAM Study).

Gender Inequalities in Publications about COVID-19 in Spain: Authorship and Sex-Disaggregated Data.

Gender inequalities in biomedical literature have been widely reported in authorship as well as the scarcity of results that are stratified by sex in the studies. We conducted a bibliometric review of articles on COVID-19 published in the main Spanish medical journals between April 2020 and May 2021. The purpose of this study was to analyse differences in authorship order and composition by sex and their evolution over time, as well as the frequency of sex-disaggregated empirical results and its relationship with the author sex in articles on COVID-19 in the main Spanish biomedical journals. We identified 914 articles and 4921 authors, 57.5% men and 42.5% women. Women accounted for 36.7% of first authors and for 33.7% of last authors. Monthly variation in authorship over the course of the pandemic indicates that women were always less likely to publish as first authors. Only 1.0% of the articles broke down empirical results by sex. Disaggregation of results by sex was significantly more frequent when women were first authors and when women were the majority in the authorship. It is important to make gender inequalities visible in scientific dissemination and to promote gender-sensitive research, which can help to reduce gender bias in clinical studies as well as to design public policies for post-pandemic recovery that are more gender-equitable.

[Monitoring COVID-19 in Spain: is a gender analysis possible?] / Monitorización de la COVID-19 en España: ¿es posible un análisis con perspectiva de género?

OBJECTIVE: To analyse the sex disaggregation and availability of gender indicators in the reports of the National Epidemiological Surveillance Network (RENAVE) and the National Study of Sero-Epidemiology (ENE-COVID-19). METHOD: Peer review of indicators available in 72 RENAVE reports and 4 rounds of the ENE-COVID-19 study to calculate the percentage of those disaggregated by sex and their variation over time. RESULTS: In March 2021, 52.4% of RENAVE indicators were disaggregated by sex. From July 2020, 54% of disaggregated indicators ceased to be published and 23% lost their disaggregation. In the ENE-COVID-19 study, the 1st round 88,23% of the indicators are disaggregated and the 4th round 94,74%. The 2nd and 3rd round do not disaggregated by sex. CONCLUSIONS: The RENAVE reports do not allow for a gender-sensitive analysis while the ENE-COVID-19 study provides the most information on social determinants.

[Gender invisibility in the COVID-19 management: who are the policy decision-makers during the pandemic?] / Invisibilidad de género en la gestión de la COVID-19: ¿quién toma las decisiones políticas durante la pandemia?

OBJECTIVE: To analyse the gender composition of the advisory boards created for the management and policy decision-making during the COVID-19 pandemic in Spain. METHOD: A peer review was carried out to identify the advisory boards involved in the management of COVID-19 in the autonomous regions and in Spain. Name, number of members, sex and sources of information were collected, and the percentage of women was calculated. RESULTS: At the regional level, the composition of eleven advisory boards was identified, with a mean representation of women of 39.2%; 42.9% at the national level. 75% of all boards represented women below the parity threshold. CONCLUSIONS: There is a significant under-representation of women in the advisory boards for the COVID-19 management, which may limit a necessary feminist perspective for the crisis recovery.

[COVID-19 and gender: certainties and uncertainties in monitoring the pandemic.] / COVID-19 y género: certezas e incertidumbres en la monitori-zación de la pandemia.

OBJECTIVE: Highlighting gender inequalities during the pandemic and its relationship with other axes of social inequality will be decisive for its adequate monitoring. The aim of this study was to assess the differences between men and women in the main measures of infection and mortality by COVID-19, considering its temporal evolution, raising awareness about the weaknesses and contradictions between sources of information. METHODS: Cross-sectional analysis based on the microdata on COVID cases notified by the National Epidemiological Surveillance Network (RENAVE), the Death Statistics of the National Statistical Institute (INE) and the estimates of excess mortality from the INE and the Daily Mortality Monitoring System (MoMo) microdata. Standardized rates, prevalences and and ratios by sex were calculated for each indicator. The percentage of excess mortality without COVID-19 diagnosis in each sex was calculated. Male/female ratios for symptoms and risk factors of COVID-19 were also calculated. RESULTS: The rate of infection by COVID-19 was higher in women in the three waves of the pandemic, reaching 65% of infections during April and May 2020. Complications were between 1.5 and 2.5 times higher in men, especially in ICU admissions, which were 2.5 times more frequent than in women. Although mortality rates and excess mortality were also higher in men (around 1.8 times), the percentage of excess mortality without COVID-19 diagnosis was higher in women (44% in men vs. 52% in women the first wave). With regard to the symptoms of COVID-19, fever, cough, and dyspnoea were more frequent in men (20%, 10% and 19% more, respectively) compared to sore throat, vomiting or diarrhea that were more prevalent in women (90%, 40% and 10% more, respectively). CONCLUSIONS: The analysis disaggregated by sex has made it possible to identify differences between men and women in the diagnosis, presentation and severity of the COVID-19 that can help a better clinical and epidemiological approach to the disease. However, official sources present important gaps when presenting information disaggregated by sex. It is therefore necessary to advance in the inclusion of a gender perspective in the statistics on COVID-19, starting with a necessary but not sufficient condition such as the disaggregation by sex of the data.

OBJETIVO: Visibilizar las desigualdades de género durante la pandemia y su relación con otros ejes de desigualdad social resultará decisivo para su adecuada monitorización. El objetivo de este estudio fue analizar las diferencias entre hombres y mujeres en las principales medidas de contagio, complicaciones y mortalidad por la COVID-19 teniendo en cuenta la evolución temporal de las mismas a lo largo de la pandemia en el estado español, visibilizando las aportaciones y carencias entre fuentes de información. METODOS: Análisis transversal en base a los casos COVID notificados por la Red Nacional de Vigilancia Epidemiológica (RENAVE); las estimaciones de mortalidad del Instituto Nacional de Estadística (INE) y las estimaciones de exceso de mortalidad del INE y los microdatos del Sistema de Monitorización de la Mortalidad diaria (MoMo). Se calcularon tasas, prevalencias y ratios por sexo de cada indicador. Se calculó el porcentaje de exceso de mortalidad sin diagnóstico COVID-19 en cada sexo. Se calcularon, así mismo, las ratios hombres/mujeres para los síntomas y factores de riesgo de la COVID-19 recogidos. RESULTADOS: La tasa de infección por la COVID-19 fue superior en mujeres en las tres olas de la pandemia, llegando a constituir un 65% de las infecciones durante abril y mayo de 2020. Las complicaciones por coronavirus fueron entre 1,5 y 2,5 veces mayores en hombres de manera constante especialmente en las admisiones en UCI que llegaron a ser 2,5 veces más frecuentes que en mujeres. Si bien las tasas de mortalidad y el exceso de mortalidad fueron también superiores en hombres (en torno a 1,8 veces), el porcentaje de exceso de mortalidad sin diagnóstico COVID-19 fue superior en mujeres (44% en hombres frente a 52% en mujeres en la primera ola). Con respecto a los síntomas de la COVID-19, la fiebre, la tos y la disnea fueron más frecuentes en hombres (un 20%, 10% y 19% más, respectivamente) frente al dolor de garganta, vómitos o diarrea que se presentó más en mujeres (90%, 40% y 10% más, respectivamente). CONCLUSIONES: El análisis desagregado por sexo ha permitido identificar diferencias entre hombres y mujeres en el diagnóstico, presentación y gravedad de la COVID-19 que ayudarán a un mejor abordaje clínico y epidemiológico de la enfermedad. Sin embargo, las fuentes oficiales presentan importantes lagunas a la hora de presentar la información desagregada por sexo. Es por ello necesario avanzar en la inclusión de la perspectiva de género en la estadística sobre el COVID-19, empezando por una condición necesaria, pero no suficiente, como la desagregación por sexo de los datos.