Construction of miRNA–mRNA networks for the identification of lung cancer biomarkers in liquid biopsies

Lung cancer (LC) is the most common cause of cancer death worldwide mostly due to the low survival rate: 75% of cases are identified in advanced stages. In this study, the list of useful biomarkers to make an early diagnosis using liquid biopsies was expanded. A total of 30 samples of LC were analyzed to define potential miRNA biomarkers in liquid biopsies for LC. The biomarkers have been identified in interaction networks miRNA–mRNA. The potential biomarkers have been then validated in large cohorts. A total of 15 candidate miRNAs, that regulate the repression of 30 mRNAs, have been identified as a specific functional interaction network for squamous carcinoma, while the specific functional interaction network of adenocarcinoma consists of four candidate miRNAs that seem to handle the repression of five mRNA. Inspection of expression levels in larger cohorts validates the usefulness of the 11 candidates as biomarkers in liquid biopsies. The 11 candidate miRNAs found could be utilized to form diagnostic predictive biomarkers for LC in liquid biopsies (AU)

Construction of miRNA-mRNA networks for the identification of lung cancer biomarkers in liquid biopsies.

Lung cancer (LC) is the most common cause of cancer death worldwide mostly due to the low survival rate: 75% of cases are identified in advanced stages. In this study, the list of useful biomarkers to make an early diagnosis using liquid biopsies was expanded. A total of 30 samples of LC were analyzed to define potential miRNA biomarkers in liquid biopsies for LC. The biomarkers have been identified in interaction networks miRNA-mRNA. The potential biomarkers have been then validated in large cohorts. A total of 15 candidate miRNAs, that regulate the repression of 30 mRNAs, have been identified as a specific functional interaction network for squamous carcinoma, while the specific functional interaction network of adenocarcinoma consists of four candidate miRNAs that seem to handle the repression of five mRNA. Inspection of expression levels in larger cohorts validates the usefulness of the 11 candidates as biomarkers in liquid biopsies. The 11 candidate miRNAs found could be utilized to form diagnostic predictive biomarkers for LC in liquid biopsies.

Seasonal variability in clinical care of COPD outpatients: results from the Andalusian COPD audit.

OBJECTIVES: Clinical practice in chronic obstructive pulmonary disease (COPD) can be influenced by weather variability throughout the year. To explore the hypothesis of seasonal variability in clinical practice, the present study analyzes the results of the 2013-2014 Andalusian COPD audit with regard to changes in clinical practice according to the different seasons. METHODS: The Andalusian COPD audit was a pilot clinical project conducted from October 2013 to September 2014 in outpatient respiratory clinics of hospitals in Andalusia, Spain (8 provinces with more than 8 million inhabitants) with retrospective data gathering. For the present analysis, astronomical seasons in the Northern Hemisphere were used as reference. Bivariate associations between the different COPD guidelines and the clinical practice changes over the seasons were explored by using binomial multivariate logistic regression analysis with age, sex, Charlson comorbidity index, type of hospital, and COPD severity by forced expiratory volume in 1 second as covariates, and were expressed as odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: The Andalusian COPD audit included 621 clinical records from 9 hospitals. After adjusting for covariates, only inhaler device satisfaction evaluation was found to significantly differ according to the seasons with an increase in winter (OR, 3.460; 95% CI, 1.469-8.151), spring (OR, 4.215; 95% CI, 1.814-9.793), and summer (OR, 3.371; 95% CI, 1.391-8.169) compared to that in autumn. The rest of the observed differences were not significant after adjusting for covariates. However, compliance with evaluating inhaler satisfaction was low. CONCLUSION: The various aspects of clinical practice for COPD care were found to be quite homogeneous throughout the year for the variables evaluated. Inhaler satisfaction evaluation, however, presented some significant variation during the year. Inhaler device satisfaction should be evaluated during all clinical visits throughout the year for improved COPD management.

Determinants for changing the treatment of COPD: a regression analysis from a clinical audit.

INTRODUCTION: This study is an analysis of a pilot COPD clinical audit that evaluated adherence to guidelines for patients with COPD in a stable disease phase during a routine visit in specialized secondary care outpatient clinics in order to identify the variables associated with the decision to step-up or step-down pharmacological treatment. METHODS: This study was a pilot clinical audit performed at hospital outpatient respiratory clinics in the region of Andalusia, Spain (eight provinces with over eight million inhabitants), in which 20% of centers in the area (catchment population 3,143,086 inhabitants) were invited to participate. Treatment changes were evaluated in terms of the number of prescribed medications and were classified as step-up, step-down, or no change. Three backward stepwise binominal multivariate logistic regression analyses were conducted to evaluate variables associated with stepping up, stepping down, and inhaled corticosteroids discontinuation. RESULTS: The present analysis evaluated 565 clinical records (91%) of the complete audit. Of those records, 366 (64.8%) cases saw no change in pharmacological treatment, while 99 patients (17.5%) had an increase in the number of drugs, 55 (9.7%) had a decrease in the number of drugs, and 45 (8.0%) noted a change to other medication for a similar therapeutic scheme. Exacerbations were the main factor in stepping up treatment, as were the symptoms themselves. In contrast, rather than symptoms, doctors used forced expiratory volume in 1 second and previous treatment with long-term antibiotics or inhaled corticosteroids as the key determinants to stepping down treatment. CONCLUSION: The majority of doctors did not change the prescription. When changes were made, a number of related factors were noted. Future trials must evaluate whether these therapeutic changes impact clinically relevant outcomes at follow-up.

Guideline Adherence in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Results from a Clinical Audit.

OBJECTIVES: Previous clinical audits of COPD have provided relevant information about medical intervention in exacerbation admissions. The present study aims to evaluate adherence to current guidelines in COPD through a clinical audit. METHODS: This is a pilot clinical audit performed in hospital outpatient respiratory clinics in Andalusia, Spain (eight provinces with more than 8 million inhabitants), including 9 centers (20% of the public centers in the area) between 2013 and 2014. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The performance of the outpatient clinics was benchmarked against three guidance documents available at the time of the audit. The appropriateness of the performance was categorized as excellent (>80%), good (60-80%), adequate (40-59%), inadequate (20-39%), and highly inadequate (<20%). RESULTS: During the audit, 621 clinical records were audited. Adherence to the different guidelines presented a considerable variability among the different participating hospitals, with an excellent or good adherence for symptom recording, MRC or CAT use, smoking status evaluation, spirometry, or bronchodilation therapy. The most outstanding areas for improvement were the use of the BODE index, the monitoring of treatments, the determination of alpha1-antitrypsin, the performance of exercise testing, and vaccination recommendations. CONCLUSIONS: The present study reflects the situation of clinical care for COPD patients in specialized secondary care outpatient clinics. Adherence to clinical guidelines shows considerable variability in outpatient clinics managing COPD patients, and some aspects of the clinical care can clearly be improved.

Clinical Audits in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Methodological Considerations and Workflow.

OBJECTIVES: Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations. However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available. Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow. METHODS: A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed. The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The usefulness of formally scheduled regular follow-up visits was assessed. Two different databases (resources and clinical database) were constructed. Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes. Exacerbations and survival served as the main endpoints. CONCLUSIONS: This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting. Results from such audits can guide health information systems development and implementation in real-world settings.