An assessment of existing models for individualized breast cancer risk estimation in a screening program in Spain

Background: The aim of this study was to evaluate the calibration and discriminatory power of three predictive models of breast cancer risk. Methods: We included 13,760 women who were first-time participants in the Sabadell-Cerdanyola Breast Cancer Screening Program, in Catalonia, Spain. Projections of risk were obtained at three and five years for invasive cancer using the Gail, Chen and Barlow models. Incidence and mortality data were obtained from the Catalan registries. The calibration and discrimination of the models were assessed using the Hosmer-Lemeshow C statistic, the area under the receiver operating characteristic curve (AUC) and the Harrell’s C statistic. Results: The Gail and Chen models showed good calibration while the Barlow model overestimated the number of cases: the ratio between estimated and observed values at 5 years ranged from 0.86 to 1.55 for the first two models and from 1.82 to 3.44 for the Barlow model. The 5-year projection for the Chen and Barlow models had the highest discrimination, with an AUC around 0.58. The Harrell’s C statistic showed very similar values in the 5-year projection for each of the models. Although they passed the calibration test, the Gail and Chen models overestimated the number of cases in some breast density categories. Conclusions: These models cannot be used as a measure of individual risk in early detection programs to customize screening strategies. The inclusion of longitudinal measures of breast density or other risk factors in joint models of survival and longitudinal data may be a step towards personalized early detection of BC.This study was funded by grant PS09/01340 and The Spanish Network on Chronic Diseases REDISSEC (RD12/0001/0007) from the Health Research Fund (Fondo de Investigación Sanitaria) of the Spanish Ministry of Health

Combining statistical techniques to predict postsurgical risk of 1-year mortality for patients with colon cancer

Introduction: Colorectal cancer is one of the most frequently diagnosed malignancies and a common cause of cancer-related mortality. The aim of this study was to develop and validate a clinical predictive model for 1-year mortality among patients with colon cancer who survive for at least 30 days after surgery. Methods: Patients diagnosed with colon cancer who had surgery for the first time and who survived 30 days after the surgery were selected prospectively. The outcome was mortality within 1 year. Random forest, genetic algorithms and classification and regression trees were combined in order to identify the variables and partition points that optimally classify patients by risk of mortality. The resulting decision tree was categorized into four risk categories. Split-sample and bootstrap validation were performed. ClinicalTrials.gov Identifier: NCT02488161. Results: A total of 1945 patients were enrolled in the study. The variables identified as the main predictors of 1-year mortality were presence of residual tumor, American Society of Anesthesiologists Physical Status Classification System risk score, pathologic tumor staging, Charlson Comorbidity Index, intraoperative complications, adjuvant chemotherapy and recurrence of tumor. The model was internally validated; area under the receiver operating characteristic curve (AUC) was 0.896 in the derivation sample and 0.835 in the validation sample. Risk categorization leads to AUC values of 0.875 and 0.832 in the derivation and validation samples, respectively. Optimal cut-off point of estimated risk had a sensitivity of 0.889 and a specificity of 0.758. Conclusion: The decision tree was a simple, interpretable, valid and accurate prediction rule of 1-year mortality among colon cancer patients who survived for at least 30 days after surgery.We are grateful for the support of the 22 participating hospitals, as well as the clinicians and staff members of the various services, research, quality units and medical records sections of these hospitals. We also gratefully acknowledge the patients who participated in the study. We would like to thank Editage (www.editage.com) for English language editing. We also wish to thank the anonymous referees for providing comments, which led to substantial improvement of the article. Financial support for this study was provided, in part, by grants from the Instituto de Salud Carlos III (PS09/00314, PS09/00910, PS09/00746, PS09/00805, PI09/90460, PI09/90490, PI09/90453, PI09/90441, PI09/90397 and the thematic network REDISSEC - Red de Investigacion en Servicios de Salud en Enfermedades Cronicas), co-funded by European Regional Development Fund/European Social Fund (ERDF/ESF "Investing in your future"); the Research Committee of the Hospital Galdakao; the Department of Health and the Department of Education, Language Policy and Culture from the Basque Government (2010111098, IT620-13 and BERC 2014-2017 program); the Spanish Ministry of Economy and Competitiveness MINECO and FEDER (MTM2013-40941-P, MTM2016-74931-P and BCAM Severo Ochoa excellence accreditation SEV-2013-0323). The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing and publishing the report

Conceptos básicos del metaanálisis en red

ResumenLas revisiones sistemáticas y los metaanálisis se han consolidado como una herramienta fundamental para la práctica clínica basada en la evidencia. Inicialmente, el metaanálisis fue propuesto como una técnica que podría mejorar la precisión y la potencia estadística de la investigación procedente de estudios individuales con pequeño tamaño muestral. Sin embargo, uno de sus principales inconvenientes es que suelen comparar no más de 2 intervenciones alternativas a la vez. Los «metaanálisis en red» utilizan técnicas novedosas de análisis que permiten incorporar la información procedente de comparaciones directas e indirectas a partir de una red de estudios que examina los efectos de diversos tratamientos de una manera más completa. Pese a sus potenciales limitaciones, su aplicación en epidemiología clínica podría ser potencialmente útil en situaciones en las que existen varios tratamientos que se han comparado frente a un comparador común.Además, estas técnicas pueden ser relevantes ante una pregunta clínica o de investigación cuando existen múltiples tratamientos que deben ser considerados, o cuando se dispone tanto de información directa como indirecta en el cuerpo de la evidencia.AbstractSystematic reviews and meta-analyses have long been fundamental tools for evidence-based clinical practice. Initially, meta-analyses were proposed as a technique that could improve the accuracy and the statistical power of previous research from individual studies with small sample size. However, one of its main limitations has been the fact of being able to compare no more than two treatments in an analysis, even when the clinical research question necessitates that we compare multiple interventions. Network meta-analysis (NMA) uses novel statistical methods that incorporate information from both direct and indirect treatment comparisons in a network of studies examining the effects of various competing treatments, estimating comparisons between many treatments in a single analysis. Despite its potential limitations, NMA applications in clinical epidemiology can be of great value in situations where there are several treatments that have been compared against a common comparator. Also, NMA can be relevant to a research or clinical question when many treatments must be considered or when there is a mix of both direct and indirect information in the body of evidence

COPD is a clear risk factor for increased use of resources and adverse outcomes in patients undergoing intervention for colorectal cancer : a nationwide study in Spain

We hypothesized that patients undergoing surgery for colorectal cancer (CRC) with COPD as a comorbidity would consume more resources and have worse in-hospital outcomes than similar patients without COPD. Therefore, we compared different aspects of the care process and short-term outcomes in patients undergoing surgery for CRC, with and without COPD. This was a prospective study and it included patients from 22 hospitals located in Spain - 472 patients with COPD and 2,276 patients without COPD undergoing surgery for CRC. Clinical variables, postintervention intensive care unit (ICU) admission, use of invasive mechanical ventilation, and postintervention antibiotic treatment or blood transfusion were compared between the two groups. The reintervention rate, presence and type of complications, length of stay, and in-hospital mortality were also estimated. Hazard ratio (HR) for hospital mortality was estimated by Cox regression models. COPD was associated with higher rates of in-hospital complications, ICU admission, antibiotic treatment, reinterventions, and mortality. Moreover, after adjusting for other factors, COPD remained clearly associated with higher and earlier in-hospital mortality. To reduce in-hospital morbidity and mortality in patients undergoing surgery for CRC and with COPD as a comorbidity, several aspects of perioperative management should be optimized and attention should be given to the usual comorbidities in these patients

Effect of a rehabilitation-based chronic disease management program targeting severe COPD exacerbations on readmission patterns

Pulmonary rehabilitation (PR) is recommended after a severe COPD exacerbation, but its short- and long-term effects on health care utilization have not been fully established. The aims of this study were to evaluate patient compliance with a chronic disease management (CDM) program incorporating home-based exercise training as the main component after a severe COPD exacerbation and to determine its effects on health care utilization in the following year. COPD patients with a severe exacerbation were included in a case-cohort study at admission. An intervention group participated in a nurse-supervised CDM program during the 2 months after discharge, comprising of home-based PR with exercise components directly supervised by a physiotherapist, while the remaining patients followed usual care. Nineteen of the twenty-one participants (90.5%) were compliant with the CDM program and were compared with 29 usual-care patients. Compliance with the program was associated with statistically significant reductions in admissions due to respiratory disease in the following year (median [interquartile range]: 0 [0-1] vs 1 [0-2.5]; P =0.022) and in days of admission (0 [0-7] vs 7 [0-12]; P =0.034), and multiple linear regression analysis confirmed the protective effect of the CDM program (β coefficient −0.785, P =0.014, and R 2 =0.219). A CDM program incorporating exercise training for COPD patients without limiting comorbidities after a severe exacerbation achieves high compliance and reduces admissions in the year following after the intervention

Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain

Introduction: Interval cancers are tumors arising after a negative screening episode and before the next screening invitation. They can be classified into true interval cancers, false-negatives, minimal-sign cancers, and occult tumors based on mammographic findings in screening and diagnostic mammograms. This study aimed to describe tumor-related characteristics and the association of breast density and tumor phenotype within four interval cancer categories. Methods: We included 2,245 invasive tumors (1,297 screening-detected and 948 interval cancers) diagnosed from 2000 to 2009 among 645,764 women aged 45 to 69 who underwent biennial screening in Spain. Interval cancers were classified by a semi-informed retrospective review into true interval cancers (n = 455), false-negatives (n = 224), minimal-sign (n = 166), and occult tumors (n = 103). Breast density was evaluated using Boyd’s scale and was conflated into: 75%. Tumor-related information was obtained from cancer registries and clinical records. Tumor phenotype was defined as follows: luminal A: ER+/HER2- or PR+/HER2-; luminal B: ER +/HER2+ or PR+/HER2+; HER2: ER-/PR-/HER2+; triple-negative: ER-/PR-/HER2-. The association of tumor phenotype and breast density was assessed using a multinomial logistic regression model. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. All statistical tests were two-sided. Results: Forty-eight percent of interval cancers were true interval cancers and 23.6% false-negatives. True interval cancers were associated with HER2 and triple-negative phenotypes (OR = 1.91 (95% CI:1.22-2.96), OR = 2.07 (95% CI:1.42-3.01), respectively) and extremely dense breasts (>75%) (OR = 1.67 (95% CI:1.08-2.56)). However, among true interval cancers a higher proportion of triple-negative tumors was observed in predominantly fatty breasts (<25%) than in denser breasts (28.7%, 21.4%, 11.3% and 14.3%, respectively; <0.001). False-negatives and occult tumors had similar phenotypic characteristics to screening-detected cancers, extreme breast density being strongly associated with occult tumors (OR = 6.23 (95% CI:2.65-14.66)). Minimal-sign cancers were biologically close to true interval cancers but showed no association with breast density. Conclusions: Our findings revealed that both the distribution of tumor phenotype and breast density play specific and independent roles in each category of interval cancer. Further research is needed to understand the biological basis of the overrepresentation of triple-negative phenotype among predominantly fatty breasts in true interval cancers

COPD is a clear risk factor for increased use of resources and adverse outcomes in patients undergoing intervention for colorectal cancer: a nationwide study in Spain

We hypothesized that patients undergoing surgery for colorectal cancer (CRC) with COPD as a comorbidity would consume more resources and have worse in-hospital outcomes than similar patients without COPD. Therefore, we compared different aspects of the care process and short-term outcomes in patients undergoing surgery for CRC, with and without COPD. This was a prospective study and it included patients from 22 hospitals located in Spain - 472 patients with COPD and 2,276 patients without COPD undergoing surgery for CRC. Clinical variables, postintervention intensive care unit (ICU) admission, use of invasive mechanical ventilation, and postintervention antibiotic treatment or blood transfusion were compared between the two groups. The reintervention rate, presence and type of complications, length of stay, and in-hospital mortality were also estimated. Hazard ratio (HR) for hospital mortality was estimated by Cox regression models. COPD was associated with higher rates of in-hospital complications, ICU admission, antibiotic treatment, reinterventions, and mortality. Moreover, after adjusting for other factors, COPD remained clearly associated with higher and earlier in-hospital mortality. To reduce in-hospital morbidity and mortality in patients undergoing surgery for CRC and with COPD as a comorbidity, several aspects of perioperative management should be optimized and attention should be given to the usual comorbidities in these patients

Trends in detection of invasive cancer and ductal carcinoma in situ at biennial screening mammography in Spain: a retrospective cohort study

Background: Breast cancer incidence has decreased in the last decade, while the incidence of ductal carcinoma in situ (DCIS) has increased substantially in the western world. The phenomenon has been attributed to the widespread adaption of screening mammography. The aim of the study was to evaluate the temporal trends in the rates of screen detected invasive cancers and DCIS, and to compare the observed trends with respect to hormone replacement therapy (HRT) use along the same study period. Methods: Retrospective cohort study of 1,564,080 women aged 45–69 years who underwent 4,705,681 screening mammograms from 1992 to 2006. Age-adjusted rates of screen detected invasive cancer, DCIS, and HRT use were calculated for first and subsequent screenings. Poisson regression was used to evaluate the existence of a change-point in trend, and to estimate the adjusted trends in screen detected invasive breast cancer and DCIS over the study period. Results: The rates of screen detected invasive cancer per 100.000 screened women were 394.0 at first screening, and 229.9 at subsequent screen. The rates of screen detected DCIS per 100.000 screened women were 66.8 at first screen and 43.9 at subsequent screens. No evidence of a change point in trend in the rates of DCIS and invasive cancers over the study period were found. Screen detected DCIS increased at a steady 2.5% per year (95% CI: 1.3; 3.8), while invasive cancers were stable. Conclusion: Despite the observed decrease in breast cancer incidence in the population, the rates of screen detected invasive cancer remained stable during the study period. The proportion of DCIS among screen detected breast malignancies increased from 13% to 17% throughout the study period. The rates of screen detected invasive cancer and DCIS were independent of the decreasing trend in HRT use observed among screened women after 2002

Multimorbidity patterns in COVID-19 patients and their relationship with infection severity : MRisk-COVID study

Several chronic conditions have been identified as risk factors for severe COVID-19 infection, yet the implications of multimorbidity need to be explored. The objective of this study was to establish multimorbidity clusters from a cohort of COVID-19 patients and assess their relationship with infection severity/mortality. The MRisk-COVID Big Data study included 14 286 COVID-19 patients of the first wave in a Spanish region. The cohort was stratified by age and sex. Multimorbid individuals were subjected to a fuzzy c-means cluster analysis in order to identify multimorbidity clusters within each stratum. Bivariate analyses were performed to assess the relationship between severity/mortality and age, sex, and multimorbidity clusters. Severe infection was reported in 9.5% (95% CI: 9.0-9.9) of the patients, and death occurred in 3.9% (95% CI: 3.6-4.2). We identified multimorbidity clusters related to severity/mortality in most age groups from 21 to 65 years. In males, the cluster with highest percentage of severity/mortality was Heart-liver-gastrointestinal (81-90 years, 34.1% severity, 29.5% mortality). In females, the clusters with the highest percentage of severity/mortality were Diabetes-cardiovascular (81-95 years, 22.5% severity) and Psychogeriatric (81-95 years, 16.0% mortality). This study characterized several multimorbidity clusters in COVID-19 patients based on sex and age, some of which were found to be associated with higher rates of infection severity/mortality, particularly in younger individuals. Further research is encouraged to ascertain the role of specific multimorbidity patterns on infection prognosis and identify the most vulnerable morbidity profiles in the community. Registered 4 August 2021 (retrospectively registered)

Anxiety, depression, health-related quality of life, and mortality among colorectal patients: 5-year follow-up

Purpose Health-related quality of life (HRQoL) measurement represents an important outcome in cancer patients. We describe the evolution of HRQoL over a 5-year period in colorectal cancer patients, identifying predictors of change and how they relate to mortality. Methods Prospective observational cohort study including colorectal cancer (CRC) patients having undergone surgery in nineteen public hospitals who were monitored from their diagnosis, intervention and at 1-, 2-, 3-, and 5-year periods thereafter by gathering HRQoL data using the EuroQol-5D-5L (EQ-5D-5L), European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30), and Hospital Anxiety and Depression Scale (HADS) questionnaires. Multivariable generalized linear mixed models were used. Results Predictors of Euroqol-5D-5L (EQ-5D-5L) changes were having worse baseline HRQoL; being female; higher Charlson index score (more comorbidities); complications during admission and 1 month after surgery; having a stoma after surgery; and needing or being in receipt of social support at baseline. For EORTC-QLQ-C30, predictors of changes were worse baseline EORTC-QLQ-C30 score; being female; higher Charlson score; complications during admission and 1 month after admission; receiving adjuvant chemotherapy; and having a family history of CRC. Predictors of changes in HADS anxiety were being female and having received adjuvant chemotherapy. Greater depression was associated with greater baseline depression; being female; higher Charlson score; having complications 1 month after intervention; and having a stoma. A deterioration in all HRQoL questionnaires in the previous year was related to death in the following year. Conclusions These findings should enable preventive follow-up programs to be established for such patients in order to reduce their psychological distress and improve their HRQoL to as great an extent as possible.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported in part by grants from the Instituto de Salud Carlos III and the European Regional Development Fund (PS09/00314, PS09/00910, PS09/00746, PS09/00805, PI09/90460, PI09/90490, PI09/90453, PI09/90441, PI09/90397); the Departments of Health (2010111098) and Education, Language Policy and Culture (IT620-13) of the Basque Government; the Research Committee of Hospital Galdakao; and the thematic network-REDISSEC (Red de Investigacion en Servicios de Salud en Enfermedades Cronicas)-of the Instituto de Salud Carlos III