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

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

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)

Factors that influence treatment delay in patients with colorectal cancer

A prospective study was performed of patients diagnosed with colorectal cancer (CRC), distinguishing between colonic and rectal location, to determine the factors that may provoke a delay in the first treatment (DFT) provided.2749 patients diagnosed with CRC were studied. The study population was recruited between June 2010 and December 2012. DFT is defined as time elapsed between diagnosis and first treatment exceeding 30 days.Excessive treatment delay was recorded in 65.5% of the cases, and was more prevalent among rectal cancer patients. Independent predictor variables of DFT in colon cancer patients were a low level of education, small tumour, ex-smoker, asymptomatic at diagnosis and following the application of screening. Among rectal cancer patients, the corresponding factors were primary school education and being asymptomatic.We conclude that treatment delay in CRC patients is affected not only by clinicopathological factors, but also by sociocultural ones. Greater attention should be paid by the healthcare provider to social groups with less formal education, in order to optimise treatment attentio

Influence of Diagnostic Delay on Survival Rates for Patients with Colorectal Cancer

Colorectal cancer affects men and women alike. Sometimes, due to clinical-pathological factors, the absence of symptoms or the failure to conduct screening tests, its diagnosis may be delayed. However, it has not been conclusively shown that such a delay, especially when attributable to the health system, affects survival. The aim of the present study is to evaluate the overall survival rate of patients with a delayed diagnosis of colorectal cancer. This observational, prospective, multicenter study was conducted at 22 public hospitals located in nine Spanish provinces. For this analysis, 1688 patients with complete information in essential variables were included. The association between diagnostic delay and overall survival at five years, stratified according to tumor location, was estimated by the Kaplan-Meier method. Hazard ratios for this association were estimated using multivariable Cox regression models. The diagnostic delay ≥ 30 days was presented in 944 patients. The presence of a diagnostic delay of more than 30 days was not associated with a worse prognosis, contrary to a delay of less than 30 days (HR: 0.76, 0.64-0.90). In the multivariate analysis, a short delay maintained its predictive value (HR: 0.80, 0.66-0.98) regardless of age, BMI, Charlson index or TNM stage. A diagnostic delay of less than 30 days is an independent factor for short survival in patients with CRC. This association may arise because the clinical management of tumors with severe clinical characteristics and with a poorer prognosis are generally conducted more quickly.This study was supported by public grants from Instituto de Salud Carlos III (PI09/90397, PS09/00314, PS09/00746, PI09/90453, PI09/00910, PI09/90460, PI09/90490, PI13/01692, PI13/00013, PI18/01181, PI18/01589, PS0900805 & PI0900441) and was co-funded by the European Regional Development Fund.S

Predictors of one and two years' mortality in patients with colon cancer: A prospective cohort study

BACKGROUND: Tools to aid in the prognosis assessment of colon cancer patients in terms of risk of mortality are needed. Goals of this study are to develop and validate clinical prediction rules for 1- and 2-year mortality in these patients. METHODS: This is a prospective cohort study of patients diagnosed with colon cancer who underwent surgery at 22 hospitals. The main outcomes were mortality at 1 and 2 years after surgery. Background, clinical parameters, and diagnostic tests findings were evaluated as possible predictors. Multivariable multilevel logistic regression and survival models were used in the analyses to create the clinical prediction rules. Models developed in the derivation sample were validated in another sample of the study. RESULTS: American Society of Anesthesiologists Physical Status Classification System (ASA), Charlson comorbidity index (> = 4), age (>75 years), residual tumor (R2), TNM stage IV and log of lymph nodes ratio (> = -0.53) were predictors of 1-year mortality (C-index (95% CI): 0.865 (0.792-0.938)). Adjuvant chemotherapy was an additional predictor. Again ASA, Charlson Index (> = 4), age (>75 years), log of lymph nodes ratio (> = -0.53), TNM, and residual tumor were predictors of 2-year mortality (C-index:0.821 (0.766-0.876). Chemotherapy was also an additional predictor. CONCLUSIONS: These clinical prediction rules show very good predictive abilities of one and two years survival and provide clinicians and patients with an easy and quick-to-use decision tool for use in the clinical decision process while the patient is still in the index admission.This work was supported in part by grants from the Instituto de Salud Carlos III and by the European Regional Development Funds-ERDF (PS09/00314, PS09/00910, PS09/00746, PS09/00805, PI09/90460, PI09/90490, PI09/90453, PI09/90441, PI09/90397); Department of Health of the Basque Country (2010111098); the Research Committee of the Hospital Galdakao; and the thematic networks REDISSEC (Red de Investigación en Servicios de Salud en Enfermedades Crónicas)-of the Instituto de Salud Carlos III RD12/0001/0001 and Education, Politic Linguistic and Culture of the Basque Government IT620-13. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

A different gut microbiome linked to inflammation found in cirrhotic patients with and without hepatocellular carcinoma

Introduction and aim: A pro-oncogenic intestinal microbiome was observed in murine models; however, no specific microbiome in patients with hepatocellular carcinoma (HCC) has been reported. We aimed to compare the gut microbiome found in cirrhotic patients with or without HCC. Materials and methods: From 407 patients with Child Pugh A/B cirrhosis prospectively followed, 25 with HCC (cases) were matched with 25 without HCC (wo-HCC) in a 1:1 ratio according to age, gender, etiology, Child Pugh and severity of portal hypertension. In addition, results were also compared with 25 healthy subjects. Fecal stool samples were sequenced for the V3?V4 region of the microbial 16S rRNA (Illumina MiSeq Platform). Plasma cytokines were quantified including interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Results: We found a differential abundance in family members of Firmicutes with a 3-fold increase of Erysipelotrichaceae and a 5-fold decrease in family Leuconostocaceae in HCC when compared to wo-HCC controls. Genus Fusobacterium was found to be 5-fold decreased in HCC vs wo-HCC. The ratio bacteriodes/prevotella was increased in HCC. Three operational taxonomic units (OTUs), genus Odoribacter and Butyricimonas were more abundant in HCC, whereas a decreased abundance in Lachnospiraceae family genus Dorea was observed in HCC patients. A Random Forest model trained with differential abundant taxa correctly classified HCC individuals. This pattern was associated with an inflammatory milieu with a putative increased activation of NOD-like receptor pathways. Conclusion: We found a pattern of microbiome linked to inflammation that could be potentially useful as HCC biomarker after follow-up validation studies.Fil: Piñero, Federico. Red Latinoamericana de Investigación, Educación y Conciencia del Hígado; Argentina. Universidad Austral; ArgentinaFil: Vazquez, Martín. Heritas; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rohr, Cristian Oscar. Heritas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mendizabal, Manuel. Universidad Austral; Argentina. Red Latinoamericana de Investigación, Educación y Conciencia del Hígado; ArgentinaFil: Sciara, Mariela Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Heritas; ArgentinaFil: Alonso, Cristina. Universidad Austral; Argentina. Red Latinoamericana de Investigación, Educación y Conciencia del Hígado; ArgentinaFil: Fay, Fabián. Heritas; ArgentinaFil: Silva, Marcelo. Universidad Austral; Argentina. Red Latinoamericana de Investigación, Educación y Conciencia del Hígado; Argentin