Impact of the implementation of best practice guidelines on nurse's evidence-based practice and on nurses' work environment: Research protocol.

AIM: To determine the impact of the Best Practice Spotlight Organization® initiative on nurses' perception of their work environment and their attitudes to evidence-based practice. DESIGN: Quasi-experimental, multicentre study. The intervention is the participation in Best Prectice Spotilight Organizations to implement Best Practice Guidelines. METHODS: The study will include seven centres in the interventional group and 10 in the non-equivalent control group, all of them belonging to the Spanish national health system. The Practice Environment Scale of the Nursing Work Index, and the Health Sciences Evidence-Based Practice Questionnaire will be administered to a sample of 1,572 nurses at the beginning of the programme and at 1 year. This 3-year study started in April 2018 and will continue until December 2021. Statistical analyses will be carried out using the SPSS 25.0. This project was approved by the Drug Research Ethics Committee of the Parc de Salut Mar and registered in Clinical Trials. DISCUSSION: The study findings will show the current state of nurses' perception of their work environment and attitudes to evidence-based practice, and possible changes in these parameters due to the programme. IMPACT: The findings could provide a strong argument for health policymakers to scale up the Best Practice Spotlight Organization® initiative in the Spanish national health system.

Content validity of a health science evidence-based practice questionnaire (HS-EBP) with a web-based modified Delphi approach.

OBJECTIVE: To develop a tool for measuring evidence-based practice (EBP) and to evaluate its content validity by Delphi technique. A five-factor/dimensions latent structure for the EBP construct was defined a priori and operationalized. DESIGN: Online Delphi technique. SETTING AND PARTICIPANTS: A group of 32 national EBP experts from different health professions. INTERVENTION: The experts rated the initial questionnaire items according to adequacy and relevance criteria using four-point Likert scales and including open fields for suggestions, with basic and supplementary criteria consensus established a priori. MAIN OUTCOME MEASURE: Level of consensus in the Content Validity Index Item. RESULTS: An EBP construct solution was designed with the elements that constitute the operationalization proposal of the EBP. This initial version consisted of 76 items, whereas the version arising from the Delphi study was made up of 73 items. In the first round, 13 items did not reach the minimum level of consensus, and 12 of these were reformulated. Three additional items were removed in the second round. CONCLUSIONS: A new psychometric tool forms measuring EBP with a five-factor structure, and 73 items obtained adequate content validity evidence based on expert opinion.

A multisample model validation of the evidence-based practice questionnaire.

Evidence-based practice may be implemented more successfully if the barriers to its implementation have been previously identified. Many of the available instruments to measure these barriers have been validated in single samples or without confirmatory analyses. The objective of the study was to contrast the goodness of fit of two measurement models (24 items and 19 items) for the Spanish version of the Evidence-Based Practice Questionnaire (EBPQ) in a sample of 1,673 full-time registered nurses in 10 hospitals and 57 primary health care centers in the Spanish Public Health Service. The 19-item model performed better in all four subsamples. A hypothesis of strict invariance, with equal factor loadings, intercepts, and error variance in all contexts in which it was evaluated, was supported. Goodness-of-fit indices provided strong evidence of good fit according to standard cut-off criteria in a multisample confirmatory factor analysis.

Innovations therapy: mammalian target of rapamycin (mTOR) inhibitors for the treatment of neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms that require a multidisciplinary approach for an optimal management. The lack of effectiveness of traditional DNA-damaging agents has led to the exploration of new targeted drugs in order to exploit phenotypical features of GEP-NET therapy. However, due to the orphan setting of these tumors, deeper characterization of molecular features and pathways that characterize cell growth, apoptosis, angiogenesis, and invasion are lacking, particularly genetic mutations or epigenetic alterations that generate oncogenic dependency or even addiction. The PI3K-AKT-mTOR pathway has been implicated as having a crucial role in GEP-NETs not only due to the overexpression of several growth factors and their receptors that finally activate this axis but also hereditary syndromes with constitutive activation of the mTOR pathway with high incidence of GEP-NETs. In this article, we aim to review the recent development of the main molecules that target mTOR complex and have showed promising activity in the treatment of GEPNETs.

Circulating tumor cell count is a prognostic factor in metastatic colorectal cancer patients receiving first-line chemotherapy plus bevacizumab: a Spanish Cooperative Group for the Treatment of Digestive Tumors study.

BACKGROUND: The Maintenance in Colorectal Cancer trial was a phase III study to assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus chemotherapy in patients with metastatic colorectal cancer. An ancillary study was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic and/or predictive marker for efficacy endpoints. PATIENTS AND METHODS: One hundred eighty patients were included. Blood samples were obtained at baseline and after three cycles. CTC enumeration was carried out using the CellSearch® System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment. RESULTS: The median progression-free survival (PFS) interval for patients with a CTC count ≥3 at baseline was 7.8 months, versus the 12.0 months achieved by patients with a CTC count <3 (p = .0002). The median overall survival (OS) time was 17.7 months for patients with a CTC count ≥3, compared with 25.1 months for patients with a lower count (p = .0059). After three cycles, the median PFS interval for patients with a low CTC count was 10.8 months, significantly longer than the 7.5 months for patients with a high CTC count (p = .005). The median OS time for patients with a CTC count <3 was significantly longer than for patients with a CTC count ≥3, 25.1 months versus 16.2 months, respectively (p = .0095). CONCLUSIONS: The CTC count is a strong prognostic factor for PFS and OS outcomes in metastatic colorectal cancer patients.

First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TTD study.

PURPOSE: The aim of this phase III trial was to compare the efficacy and safety of bevacizumab alone with those of bevacizumab and capecitabine plus oxaliplatin (XELOX) as maintenance treatment following induction chemotherapy with XELOX plus bevacizumab in the first-line treatment of patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety. RESULTS: The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n = 239; bevacizumab, n = 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0-53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand-foot syndrome, and neuropathy. CONCLUSION: Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with single-agent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients.

Psychometric testing of the Spanish version of the practice environment scale of the nursing work index in a primary healthcare context.

AIM: This paper is a report of psychometric testing of the Spanish version of the Practice Environment Scale of the Nursing Work Index for use in a primary health care. BACKGROUND: The Practice Environment Scale of the Nursing Work Index has been widely used in different studies and contexts. However, there is no validated version for primary care nursing staff in Spain. METHODS: A descriptive, multicentre, cross-sectional study for transcultural adaptation and psychometric validation purposes. Data were collected from October 2009 to January 2010. To test the reliability of the factors in the measurement model, Cronbach's alpha was used. To study the measurement model, different structural models were tested, using exploratory and confirmatory factor analyses. 377 completed questionnaires were obtained from a total of 553 nurses working for the Public Health Service in the Balearic Islands (Spain). This represents a response rate of 68·2%. RESULTS: For overall reliability, a Cronbach alpha of 0·91 was obtained. The confirmatory analysis upholds the original five-factor structure. CONCLUSION: The excellent goodness of fit of the confirmatory analysis corroborates the validity of this adapted version in primary healthcare contexts.

Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD).

INTRODUCTION: Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy. PATIENTS AND METHODS: Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling. RESULTS: Of 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15-1.48; p < 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13-1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00-1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05-1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21-1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13-1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08-1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS. CONCLUSION: Considering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.

Physiotherapists' Evidence-Based Practice profiles by HS-EBP questionnaire in Spain: A cross-sectional normative study.

Evidence-Based Practice (EBP) is a cost-effective approach for improving the quality of clinical care and implementing only well-tested evidence. Health professions, especially physiotherapy, must embrace EBP principles. This paper presents normative data from the Spanish physiotherapist population using the Health-Sciences Evidence-Based Practice questionnaire and explores EBP clusters/profiles of professionals in practice. An intentional sample of 419 practicing physiotherapists was recruited from the Spanish Professional Council of Physiotherapy. Participants completed a cross-sectional online survey with 60 Likert items (scale 1-10) measuring 5 dimensions: 1) Beliefs and attitudes, 2) Results from literature, 3) Professional practice, 4) Assessment of results, and 5) Barriers and Facilitators. The protocol also included sociodemographic, training, and practice-related contrast variables. Normative data were estimated and tabulated for each dimension and then a K-means clustering procedure was implemented using the contrast variables. Results for normative data showed, in descending order, the following 50th percentile values for the five EBP factors: Beliefs and attitudes (8.25), Professional practice (8.00), Assessment of results (7.42), Results from literature (6.71), and EBP Barriers and Facilitators (5.17); all expressed on a scale of 1 to 10. Academic degree, EBP training level, and work time shared in healthcare activity, research, or teaching activity were all statistically significant for discriminating EBP dimension scores. Finally, six different clusters showed that when EBP level is low, the scores in all dimensions are equally low, and vice-versa. The EBP dimensions "Beliefs and attitudes", "Professional practice", and "Evaluation of results" obtained better normative scores overall than "Search for bibliographic evidence and its inclusion in practice" and especially "Perception of EBP barriers", which had the worst score. Normative data are useful for comparing individual scores and the reference population, and information about clusters will enable appropriate global EBP intervention programs to be designed and implemented.

Cross-cultural Adaptation of the Health Sciences Evidence-based Practice Questionnaire into Japanese and Its Test-Retest Reliability in Undergraduate Students.

OBJECTIVES: The Health Sciences Evidence-Based Practice (HS-EBP) questionnaire was recently developed for measuring five constructs of evidence-based clinical practice among Spanish health professionals by applying content and construct validity investigation. The current study aims to undertake a cross-cultural adaptation of the HS-EBP into Japanese and to investigate the internal consistency and test-retest reliability of the Japanese HS-EBP among undergraduate students of nursing and physical and occupational therapies. METHODS: Cross-cultural adaptation was undertaken by following Beaton's five-step process. Subsequently, the Japanese HS-EBP test-retest reliability was assessed with a 2-week interval. Participants were recruited from among third and fourth grade undergraduate students of nursing and physical and occupational therapies with clinical training experience. RESULTS: Pilot testing included 30 participants (11 nursing students, 11 physical therapy students, 8 occupational therapy students). Consequently, we developed the Japanese HS-EBP to be understandable for undergraduate students of nursing and physical and occupational therapies. Data from 52 participants who completed test-retest reliability questionnaires demonstrated adequate test-retest reliability in the total scores of Domains 1, 3, 4, and 5 [intraclass correlation coefficients were (ICC)=0.74, 0.70, 0.75, and 0.74, respectively]; the exception was Domain 2, which had an ICC of 0.66. Internal consistency (Cronbach's α) was adequate for Domains 1-5, for which α was 0.87, 0.94, 0.86, 0.93, and 0.95, respectively. CONCLUSIONS: This study developed the Japanese version of HS-EBP and provided preliminary evidence of adequate internal consistency and test-retest reliability in most domains for undergraduate students of nursing and physical and occupational therapies.

First-Line Biological Agents Plus Chemotherapy in Older Patients with Metastatic Colorectal Cancer: A Retrospective Pooled Analysis.

BACKGROUND: Biologicals, in combination with chemotherapy, are recommended as first-line treatment of metastatic colorectal cancer (mCRC); however, evidence guiding the appropriate management of older patients with mCRC is limited. OBJECTIVE: This study was undertaken to compare the efficacy and safety outcomes in older versus younger patients with mCRC who received first-line biological therapy. METHODS: This retrospective analysis used pooled data from five trials undertaken by the Spanish Cooperative Group for the Treatment of Digestive Tumours. All were studies of adults with advanced CRC who received first-line treatment with chemotherapy plus bevacizumab, cetuximab or panitumumab, stratified by age (≥ 65 vs. < 65 years). Endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and safety. RESULTS: In total, 999 patients from five studies were included in the analysis: 480 (48%) were aged ≥ 65 years, and 519 (52%) were aged < 65 years. Median PFS did not differ significantly between patients aged ≥ 65 and < 65 years (9.9 vs. 9.4 months; hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.88-1.17). Median OS was significantly shorter in older than in younger patients (21.3 vs. 25.0 months; HR 1.21; 95% CI 1.04-1.41). There was no significant difference between older and younger patients in ORR (59 vs. 62%). Patients aged ≥ 65 years experienced significantly more treatment-related grade 3 or higher adverse events (61.67%) than did patients aged < 65 years (45.86%). CONCLUSIONS: Biologicals plus chemotherapy is an effective first-line treatment option for selected patients aged ≥ 65 years with mCRC and has a manageable safety profile and efficacy comparable to that observed in younger patients.

A proteomic approach links decreased pyruvate kinase M2 expression to oxaliplatin resistance in patients with colorectal cancer and in human cell lines.

We aimed to gain further understanding of the molecular mechanisms involved in oxaliplatin resistance in colorectal cancer by using a proteomic approach. A 5-fold oxaliplatin-resistant cell line, HTOXAR3, was compared with its parental cell line, HT29, using two-dimensional PAGE. Mass spectrometry, Western blot, and real-time quantitative PCR confirmed the down-regulation of pyruvate kinase M2 (PK-M2) in HTOXAR3 cells. In a panel of eight colorectal cancer cell lines, we found a negative correlation between oxaliplatin resistance and PK-M2 mRNA levels (Spearman r=-0.846, P=0.008). Oxaliplatin exposure in both HT29 and HTOXAR3 led to PK-M2 mRNA up-regulation. PK-M2 mRNA levels were measured by real-time quantitative PCR in 41 tumors treated with oxaliplatin/5-fluorouracil. Tumors with the lowest PK-M2 levels attained the lowest response rates (20% versus 64.5%, P=0.026). High PK-M2 levels were associated with high p53 levels (P=0.032). In conclusion, the data provided clearly link PK-M2 expression and oxaliplatin resistance mechanisms and further implicate PK-M2 as a predictive marker of response in patients with oxaliplatin-treated colorectal cancer.

Pharmacogenomic approach for the identification of novel determinants of acquired resistance to oxaliplatin in colorectal cancer.

Oxaliplatin is a third-generation platinum agent used in colorectal cancer treatment. Oxaliplatin resistance acquisition is a complex process mainly based on alteration of genes and pathways involved in its mechanism of action. Therefore, our purpose was to perform a gene expression screening in an in vitro model to identify genes that could play a role in oxaliplatin resistance acquisition processes. Four colorectal cancer cell lines and their oxaliplatin-resistant derived sublines were compared. Microarray analysis was done using Human 19K Oligo Array Slides. RNA from cells were hybridized with a commercial RNA reference sample and labeled with both fluorochromes Cy3 and Cy5. Data were analyzed by hierarchical clustering method. Subsequently, quantitative real-time PCR (qRT-PCR) was used to corroborate microarray data, considering as positively validated those genes that showed significant differences in expression levels between groups and a correlation between microarray and qRT-PCR data. By microarray analysis, 32 candidate genes were identified. After validation process by qRT-PCR, the genes AKT1, CDK5, TRIP, GARP, RGS11, and UGCGL1 were positively validated. The 3 first genes proved to be involved in regulation of nuclear factor-kappabeta antiapoptotic transcription factor previously related to drug resistance, and the other 3 genes are novel finds. We have identified 6 genes related to oxaliplatin resistance acquisition. These findings are of paramount importance to understand these processes better and open new lines of study to elucidate the relevance of this pharmacogenomic approach into the clinic.

Latent structure and factor invariance of somatic symptoms in the patient health questionnaire (PHQ-15).

BACKGROUND: Somatic symptoms are highly prevalent in primary care although insufficiently understood. The Patient Health Questionnaire (PHQ-15) is a valuable screening test but it has not yet been possible to unequivocally demonstrate its latent structure and measurement invariance. METHODS: A total of 1,255 patients from 28 primary care centres suffering symptoms of anxiety, depression or somatisation participated in a clinical trial. They completed the PHQ-15 at baseline and 374 retook it at three months. Exploratory structural equation modelling (ESEM) was used to compare three models: 1) a single global factor for somatisation, 2) four specific correlated factors, and 3) a bifactor model integrating the first two models. RESULTS: A multi-group invariance analysis of the best-fit model was performed: the bifactor model (χ2=25.17, df=23, p = 0.34, RMSEA=0.009, CFI=1.00, TLI=0.999). Strict invariance was good for both gender (RMSEA = 0.046, CFI = 0.973, TLI = 0.963) and age (RMSEA = 0.048, CFI = 0.964, TLI = 0.962). Configural and metric invariance were confirmed for moment of assessment, but scalar invariance was not. LIMITATIONS: The two main limitations were the sample (primary care patients with emotional disorders), which was not representative of the general population, and the utilisation of ESEM (vs. confirmatory factor analysis), which did not allow a second-order factor model to be tested. CONCLUSIONS: PHQ-15 showed a bifactor structure, providing both a single global measure of somatisation and specific measures of pain, gastrointestinal, cardiopulmonary and fatigue factors. Its factor invariance with regard to both gender and age was confirmed.

Health Sciences-Evidence Based Practice Questionnaire (HS-EBP): Normative Data and Differential Profiles in Spanish Osteopathic Professionals.

The main goal of this study was to obtain normative data of the scores of the Health-Sciences Evidence Based Practice (HS-EBP) questionnaire, and to analyse evidence-based practice (EBP) among potential clusters of osteopathy professionals in Spain. An online descriptive cross-sectional study has been applied. A total number of 443 Spanish practicing osteopaths answered a survey including the 5 dimensions of the HS-EBP questionnaire and sociodemographic, training, and practice variables using the "LimeSurvey" online platform. Results point out that the median scores for each five HS-EBP questionnaire dimensions were 95.00, 86.00, 78.00, 84.00 and 62.00 considering that the range of possible scores in each of the dimensions was: from 12 to 120 in dimensions 1, 4 and 5; from 14-140 in dimension 2; and from 10-100 in dimension 3. A clustering algorithm extracted 6 different profiles across the five HS-EBP latent dimensions: low scores in all dimensions (cluster 1); low scores in all dimensions but with medium scores in dimension 1 (cluster 2); mixed pattern of scores, low in dimensions 2 and 5 and medium in the rest of the dimensions; medium scores in all dimensions (cluster 4); high scores in all dimensions and low scores in dimension 5 (cluster 5); and high scores in all dimensions (cluster 6). Significant relationship was found among the response patterns in the clusters and: academic degree level, EBP training and training level, and work time invested in healthcare activity, research and teaching activity. These results allow a description of the actual level of EBP and differential profiles of Osteopathy care practice in Spain. Knowledge of normative scores of the HS-EBP questionnaire and identification of different predictors of Spanish osteopaths' EBP, e.g., academic degree, EBP training and training level, work time invested in healthcare activity, research, and teaching activity, and having a working relationship with an accredited educational centre, enable a comprehensive evaluation of the EBP of osteopathic professionals and can also be useful for developing and implementing formative intervention programs for improving EBP practice in osteopathic practice.

Increased levels of copper efflux transporter ATP7B are associated with poor outcome in colorectal cancer patients receiving oxaliplatin-based chemotherapy.

Recently, the copper efflux transporters ATP7B and ATP7A have been implicated in the transport of and resistance to platinum drugs in breast and ovarian cancers. Because of the extensive use of oxaliplatin in colorectal cancer (CRC), we examined the expression of both transporters in tumors from CRC patients treated with oxaliplatin/5FU and sought to determine whether their expression can predict clinical outcome in these patients. ATP7B and ATP7A levels were determined by quantitative real-time PCR in 50 primary tumors of previously untreated patients with advanced colorectal adenocarcinoma who were subsequently treated with oxaliplatin/5FU. Additionally, ATP7B protein expression was assessed by immunohistochemical staining using a tissue microarray. Patients with the lowest mRNA expression levels of ATP7B had a significantly longer time to progression (TTP) (p = 0.0009) than patients with the highest levels (12.14 months vs. 6.43 months) who also had an increased risk of progression (HR = 3.56; 95% CI, 1.6-7.9; p = 0.002). Furthermore, patients with low levels of both protein and mRNA of ATP7B derived the maximum benefit from oxaliplatin/5FU with the longest TTP as compared with patients with high levels of ATP7B protein and mRNA (14.64 months vs. 4.63 months, respectively, p = 0.01) and showed a nonsignificant trend toward a lower response rate (37.5% and 75%, respectively). In conclusion, ATP7B mRNA and protein expression in colorectal tumors is associated with clinical outcome to oxaliplatin/5FU. Prospective studies are required to evaluate the role of this marker in tailoring chemotherapy.

[Validation of the Spanish version of the Evidence Based Practice Questionnaire in Nurses]. / Validación de la versión española del cuestionario sobre la práctica basada en la evidencia en enfermería.

BACKGROUND: The lack of adequate instruments prevents the possibility of assessing the competence of health care staff in evidence-based decision making and further, the identification of areas for improvement with tailored strategies. The aim of this study is to report about the validation process in the Spanish context of the Evidence-Based Practice Questionnaire (EBPQ) from Upton y Upton. METHODS: A multicentre, cross-sectional, descriptive psychometric validation study was carried out. For cultural adaptation, a bidirectional translation was developed, accordingly to usual standards. The measuring model from the questionnaire was undergone to contrast, reproducing the original structure by Exploratory Factorial Analysis (EFA) and Confirmatory Factorial Analysis (CFA), including the reliability of factors. RESULTS: Both EFA (57.545% of total variance explained) and CFA (chi(2)=2359,9555; gl=252; p < 0.0001; RMSEA=0,1844; SRMR=0,1081), detected problems with items 7, 16, 22, 23 and 24, regarding to the original trifactorial version of EBPQ. After deleting some questions, a reduced version containing 19 items obtained an adequate factorial structure (62.29% of total variance explained), but the CFA did not fit well. Nevertheless, it was significantly better than the original version (chi(2)=673.1261; gl=149; p < 0.0001; RMSEA=0.1196; SRMR=0.0648). CONCLUSIONS: The trifactorial model obtained good empiric evidence and could be used in our context, but the results invite to advance with further refinements into the factor "attitude", testing it in more contexts and with more diverse professional profiles.

The methodology of Data Mining. An application to alcohol consumption in teenagers.

This paper is aimed mainly at making researchers in the field of drug addictions aware of a methodology of data analysis aimed at knowledge discovery in databases (KDD). KDD is a process consisting of a series of phases, the most characteristic of which is called data mining (DM), whereby different modelling techniques are applied in order to detect patterns and relationships among the data. Common and differentiating factors between the most widely used DM techniques are analysed, mainly from a methodological viewpoint, and their use is exemplified using data related to alcohol consumption in teenagers and its possible relationship with personality variables (N=7030). Although the overall accuracy obtained (% correct predictions) is very similar in the three models analyzed, the Artificial Neural Network (ANN) technique generates the most accurate model (64.1%), followed by Decision Trees (DT) (62.3%) and Naïve Bayes (NB) (59.9%).

Tumour location and efficacy of first-line EGFR inhibitors in KRAS/RAS wild-type metastatic colorectal cancer: retrospective analyses of two phase II randomised Spanish TTD trials.

Purpose: Metastatic colorectal cancer (mCRC) is a group of distinct diseases, with clinical and molecular differences between right-sided and left-sided tumours driving varying prognosis. Methods: Patients with KRAS/RAS-wild type (wt) mCRC treated in first line with epidermal growth factor receptor inhibitors (EGFR-Is) (cetuximab or panitumumab) plus oxaliplatin or irinotecan-based chemotherapy from two phase II randomised trials conducted by the Spanish Cooperative for the Treatment of Digestive Tumours group were included in this retrospective study. The main objective was to analyse the prognostic effect of primary tumour location on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: Patients with KRAS-wt right-sided tumours (n=52) had significantly lower efficacy as compared with patients with KRAS-wt left-sided tumours (n=209); confirmed ORR (25% vs 47%, respectively; OR 0.4, 95% CI 0.2 to 0.8, p=0.004); and shorter median PFS (7.2 vs 9.9 months; HR 0.6, 95% CI 0.4 to 0.9, p=0.0157) and OS (13.6 vs 27.7 months; HR 0.5, 95% CI 0.3 to 0.7, p<0.0001). Similar results were observed in the RAS-wt populations. The further classification of left-sided tumours as colon or rectum delivered similar survival outcomes, as well as a tendency to diminished ORR in patients with rectum tumours. Conclusion: We observed significantly improved efficacy outcomes in patients with KRAS/RAS-wt mCRC treated with first-line EGFR-I plus chemotherapy in left-sided primary tumours as compared with right-sided primary tumours. Trial registration numbers: NCT01161316 and NCT00885885.

Pharmacogenetic approach for capecitabine or 5-fluorouracil selection to be combined with oxaliplatin as first-line chemotherapy in advanced colorectal cancer.

We studied the role of TS (5'VNTR, 5'SNP and 3'UTR), XRCC1-399, XPD-751, ERCC1-118 and XRCC3-241 genetic polymorphisms in tailoring fluroropyrimidine/oxaliplatin treatment. For this purpose, 110 XELOX (capecitabine/oxaliplatin)- or FUOX (fluorouracil/oxaliplatin)-treated metastatic colorectal cancer patients were selected prospectively for genotyping. In the FUOX group, TS-3'UTR +6bp/+6bp (hazards ratio, HR=2.62, p=0.007) and ERCC1-118C/T or C/C (HR=1.96, p=0.050) genotypes correlated with a shorter progression-free survival (PFS). When analysed jointly, the higher the number of favourable genotypes (FG) the longer the PFS (6.8m, 9.6m and 25.8m for 0, 1 or 2 FG; p=0.005). Disease-control rate was 100% in patients with 2 FG (87% and 38.5% for 1 or 0 FG; p=0.001). In the multivariate analysis, ERCC1-118 (HR=2.12, p=0.0037) and TS-3'UTR (HR=2.68, p=0.006) were strong independent prognostic factors. According to this, patients harbouring TS-3'UTR +6bp/+6bp and ERCC1-118C/T or C/C genotypes may better receive capecitabine instead of 5FU in an oxaliplatin-based first-line treatment.