Perceptions and attitudes of clinicians in Spain toward clinical practice guidelines and grading systems: a protocol for a qualitative study and a national survey

BACKGROUND: Clinical practice guidelines (CPGs) have become a very popular tool for decision making in healthcare. While there is some evidence that CPGs improve outcomes, there are numerous factors that influence their acceptability and use by healthcare providers. While evidence of clinicians' knowledge, perceptions and attitudes toward CPGs is extensive, results are still disperse and not conclusive. Our study will evaluate these issues in a large and representative sample of clinicians in Spain. METHODS/DESIGN: A mixed-method design combining qualitative and quantitative research techniques will evaluate general practitioners (GPs) and hospital-based specialists in Spain with the objective of exploring attitudes and perceptions about CPGs and evidence grading systems. The project will consist of two phases: during the first phase, group discussions will be carried out to gain insight into perceptions and attitudes of the participants, and during the second phase, this information will be completed by means of a survey, reaching a greater number of clinicians. We will explore these issues in GPs and hospital-based practitioners, with or without previous experience in guideline development. DISCUSSION: Our study will identify and gain insight into the perceived problems and barriers of Spanish practitioners in relation to guideline knowledge and use. The study will also explore beliefs and attitudes of clinicians towards CPGs and evidence grading systems used to rate the quality of the evidence and the strength of recommendations. Our results will provide guidance to healthcare researchers and healthcare decision makers to improve the use of guidelines in Spain and elsewhere

Perceptions and attitudes of clinicians in Spain toward clinical practice guidelines and grading systems : A protocol for a qualitative study and a national survey

FADQThis project has been funded by the Instituto de Salud Carlos III, co-financed by the European Regional Development Fund (PI08 90647). The publication of this document has been funded within the framework of collaboration designed for the Quality Plan of the Spanish National Health System, under the agreement signed by the Carlos III Health Institute and the Aragon Health Science Institute as GuiaSalud secretariat. Pablo Alonso-Coello is funded by a Miguel Servet contract by the Instituto de Salud Carlos III (CP09/00137).Background: Clinical practice guidelines (CPGs) have become a very popular tool for decision making in healthcare. While there is some evidence that CPGs improve outcomes, there are numerous factors that influence their acceptability and use by healthcare providers. While evidence of clinicians' knowledge, perceptions and attitudes toward CPGs is extensive, results are still disperse and not conclusive. Our study will evaluate these issues in a large and representative sample of clinicians in Spain. Methods/Design. A mixed-method design combining qualitative and quantitative research techniques will evaluate general practitioners (GPs) and hospital-based specialists in Spain with the objective of exploring attitudes and perceptions about CPGs and evidence grading systems. The project will consist of two phases: during the first phase, group discussions will be carried out to gain insight into perceptions and attitudes of the participants, and during the second phase, this information will be completed by means of a survey, reaching a greater number of clinicians. We will explore these issues in GPs and hospital-based practitioners, with or without previous experience in guideline development. Discussion. Our study will identify and gain insight into the perceived problems and barriers of Spanish practitioners in relation to guideline knowledge and use. The study will also explore beliefs and attitudes of clinicians towards CPGs and evidence grading systems used to rate the quality of the evidence and the strength of recommendations. Our results will provide guidance to healthcare researchers and healthcare decision makers to improve the use of guidelines in Spain and elsewhere. © 2010 Kotzeva et al; licensee BioMed Central Lt

A model based on the quantification of complement C4c, CYFRA 21-1 and CRP exhibits high specificity for the early diagnosis of lung cancer

Lung cancer screening detects early-stage cancers, but also a large number of benign nodules. Molecular markers can help in the lung cancer screening process by refining inclusion criteria or guiding the management of indeterminate pulmonary nodules. In this study, we developed a diagnostic model based on the quantification in plasma of complement-derived fragment C4c, cytokeratin fragment 21-1 (CYFRA 21-1) and C-reactive protein (CRP). The model was first validated in two independent cohorts, and showed a good diagnostic performance across a range of lung tumor types, emphasizing its high specificity and positive predictive value. We next tested its utility in two clinically relevant contexts: assessment of lung cancer risk and nodule malignancy. The scores derived from the model were associated with a significantly higher risk of having lung cancer in asymptomatic individuals enrolled in a computed tomography (CT)-screening program (OR = 1.89; 95% CI = 1.20–2.97). Our model also served to discriminate between benign and malignant pulmonary nodules (AUC: 0.86; 95% CI = 0.80–0.92) with very good specificity (92%). Moreover, the model performed better in combination with clinical factors, and may be used to reclassify patients with intermediate-risk indeterminate pulmonary nodules into patients who require a more aggressive work-up. In conclusion, we propose a new diagnostic biomarker panel that may dictate which incidental or screening-detected pulmonary nodules require a more active work-up

Heterogenous presence of neutrophil extracellular traps in human solid tumours is partially dependent on IL-8

Neutrophil extracellular traps (NETs) are webs of extracellular nuclear DNA extruded by dying neutrophils infiltrating tissue. NETs constitute a defence mechanism to entrap and kill fungi and bacteria. Tumours induce the formation of NETs to the advantage of the malignancy via a variety of mechanisms shown in mouse models. Here, we investigated the presence of NETs in a variety of human solid tumours and their association with IL-8 (CXCL8) protein expression and CD8+ T-cell density in the tumour microenvironment. Multiplex immunofluorescence panels were developed to identify NETs in human cancer tissues by co-staining with the granulocyte marker CD15, the neutrophil marker myeloperoxidase and citrullinated histone H3 (H3Cit), as well as IL-8 protein and CD8+ T cells. Three ELISA methods to detect and quantify circulating NETs in serum were optimised and utilised. Whole tumour sections and tissue microarrays from patients with non-small cell lung cancer (NSCLC; n = 14), bladder cancer (n = 14), melanoma (n = 11), breast cancer (n = 31), colorectal cancer (n = 20) and mesothelioma (n = 61) were studied. Also, serum samples collected retrospectively from patients with metastatic melanoma (n = 12) and NSCLC (n = 34) were ELISA assayed to quantify circulating NETs and IL-8. NETs were detected in six different human cancer types with wide individual variation in terms of tissue density and distribution. At least in NSCLC, bladder cancer and metastatic melanoma, NET density positively correlated with IL-8 protein expression and inversely correlated with CD8+ T-cell densities. In a series of serum samples from melanoma and NSCLC patients, a positive correlation between circulating NETs and IL-8 was found. In conclusion, NETs are detectable in formalin-fixed human biopsy samples from solid tumours and in the circulation of cancer patients with a considerable degree of individual variation. NETs show a positive association with IL-8 and a trend towards a negative association with CD8+ tumour-infiltrating lymphocytes

Large enhancement of deuteron polarization with frequency modulated microwaves

We report a large enhancement of 1.7 in deuteron polarization up to values of 0.6 due to frequency modulation of the polarizing microwaves in a two liters polarized target using the method of dynamic nuclear polarization. This target was used during a deep inelastic polarized muon-deuteron scattering experiment at CERN. Measurements of the electron paramagnetic resonance absorption spectra show that frequency modulation gives rise to additional microwave absorption in the spectral wings. Although these results are not understood theoretically, they may provide a useful testing ground for the deeper understanding of dynamic nuclear polarization.Comment: 10 pages, including the figures coming in uuencoded compressed tar files in poltar.uu, which also brings cernart.sty and crna12.sty files neede

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC

Early life risk factors and their cumulative effects as predictors of overweight in Spanish children

Objectives: To explore early life risk factors of overweight/obesity at age 6 years and their cumulative effects on overweight/obesity at ages 2, 4 and 6 years. Methods: Altogether 1031 Spanish children were evaluated at birth and during a 6-year follow-up. Early life risk factors included: parental overweight/obesity, parental origin/ethnicity, maternal smoking during pregnancy, gestational weight gain, gestational age, birth weight, caesarean section, breastfeeding practices and rapid infant weight gain collected via hospital records. Cumulative effects were assessed by adding up those early risk factors that significantly increased the risk of overweight/obesity. We conducted binary logistic regression models. Results: Rapid infant weight gain (OR 2.29, 99% CI 1.54–3.42), maternal overweight/obesity (OR 1.93, 99% CI 1.27–2.92), paternal overweight/obesity (OR 2.17, 99% CI 1.44–3.28), Latin American/Roma origin (OR 3.20, 99% CI 1.60–6.39) and smoking during pregnancy (OR 1.61, 99% CI 1.01–2.59) remained significant after adjusting for confounders. A higher number of early life risk factors accumulated was associated with overweight/obesity at age 6 years but not at age 2 and 4 years. Conclusions: Rapid infant weight gain, parental overweight/obesity, maternal smoking and origin/ethnicity predict childhood overweight/obesity and present cumulative effects. Monitoring children with rapid weight gain and supporting a healthy parental weight are important for childhood obesity prevention