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.

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.

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.

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.

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.

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.

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.

First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD).

BACKGROUND: In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations. METHODS: Multicentre, open-label study in untreated patients ≥ 18 years with (WT)-KRAS mCRC and multiple or unresectable liver-limited disease (LLD) randomised to either Pmab-FOLFOX4 or Pmab-FOLFIRI. The primary end-point was objective response rate (ORR). Secondary end-points included liver metastases resection rate (R0 + R1), progression-free survival (PFS), overall survival (OS), adverse events and perioperative safety. Exploratory end-points were: response by RAS status, early tumour shrinkage (ETS) and depth of response (DpR) in WT-RAS patients. RESULTS: Data on 77 patients were analysed (38 Pmab-FOLFOX4; 39 Pmab-FOLFIRI; WT-RAS: 27/26, respectively). ORR was 74% with Pmab-FOLFOX4 and 67% with Pmab-FOLFIRI (WT-RAS: 78%/73%). Out of the above, 45% and 59% underwent surgical resection, respectively (WT-RAS: 37%/69%). The R0-R1 resection rate was 34%/46% (WT-RAS:26%/54%). Median PFS was 13/14 months (hazard ratio [HR] Pmab-FOLFIRI versus Pmab-FOLFOX4: 0.9; 95% confidence interval: [0.6-1.5]; WT-RAS:13/15; HR: 0.7 [0.4-1.3]). Median OS was 37/41 months (HR:1.0 [0.6-1.8]; WT-RAS: 39/49; HR:0.9 [0.4-1.9]). In WT-RAS patients with confirmed response, median DpR was 71%/66%, and 65%/77% of patients showed ETS ≥ 30%/ ≥ 20% at week 8, without significant differences between arms; these patients had longer median PFS and OS and higher resectability rates. Surgery was associated with longer survival. Perioperative and overall safety were similar, except for higher grade 3/4 neutropenia (40%/10%; p = 0.003) and neuropathy (13%/0%; p = 0.025) in the Pmab-FOLFOX4 arm. CONCLUSIONS: In patients with WT-KRAS mCRC and LLD, both first-line Pmab-FOLFOX4 and Pmab-FOLFIRI resulted in high ORR and ETS, allowing potentially curative resection. No significant differences in efficacy were observed between the two regimens. (clinicaltrials.gov:NCT00885885).

Health Sciences-Evidence Based Practice questionnaire (HS-EBP) for measuring transprofessional evidence-based practice: Creation, development and psychometric validation.

INTRODUCTION: Most of the EBP measuring instruments available to date present limitations both in the operationalisation of the construct and also in the rigour of their psychometric development, as revealed in the literature review performed. The aim of this paper is to provide rigorous and adequate reliability and validity evidence of the scores of a new transdisciplinary psychometric tool, the Health Sciences Evidence-Based Practice (HS-EBP), for measuring the construct EBP in Health Sciences professionals. METHODS: A pilot study and a subsequent two-stage validation test sample were conducted to progressively refine the instrument until a reduced 60-item version with a five-factor latent structure. Reliability was analysed through both Cronbach's alpha coefficient and intraclass correlations (ICC). Latent structure was contrasted using confirmatory factor analysis (CFA) following a model comparison aproach. Evidence of criterion validity of the scores obtained was achieved by considering attitudinal resistance to change, burnout, and quality of professional life as criterion variables; while convergent validity was assessed using the Spanish version of the Evidence-Based Practice Questionnaire (EBPQ-19). RESULTS: Adequate evidence of both reliability and ICC was obtained for the five dimensions of the questionnaire. According to the CFA model comparison, the best fit corresponded to the five-factor model (RMSEA = 0.049; CI 90% RMSEA = [0.047; 0.050]; CFI = 0.99). Adequate criterion and convergent validity evidence was also provided. Finally, the HS-EBP showed the capability to find differences between EBP training levels as an important evidence of decision validity. CONCLUSIONS: Reliability and validity evidence obtained regarding the HS-EBP confirm the adequate operationalisation of the EBP construct as a process put into practice to respond to every clinical situation arising in the daily practice of professionals in health sciences (transprofessional). The tool could be useful for EBP individual assessment and for evaluating the impact of specific interventions to improve EBP.

Advanced Practice Nursing Competency Assessment Instrument (APNCAI): clinimetric validation.

OBJECTIVE: To describe the development and clinimetric validation of the Advanced Practice Nursing Competency Assessment Instrument (APNCAI) through several evidence sources about reliability and validity in the Spanish context. DESIGN AND SETTING: APNCAI development was based on a multisequential and systematic process: literature review, instrument content consensus through qualitative Delphi method approach (a panel of 51 Advanced Practice in Nursing -APN- experts was selected) and the clinimetric validation process based on a sample of 600 nurses from the Balearic Islands public healthcare setting. METHODS: An initial step for tool's content development process based on Delphi method approach of expert consensus was implemented. A subsequent phase of tool validation started from the analysis of APN core competencies latent measurement model, including exploratory and confirmatory techniques. Reliability evidence for each latent factor was also obtained. Items' scores were submitted to descriptive analysis, plus univariate and multivariate normality tests. RESULTS: An eight-factor competency assessment latent model obtained adequate fit, and it was composed by 'Research and Evidence-Based Practice', 'Clinical and Professional Leadership', 'Interprofessional Relationship and Mentoring', 'Professional Autonomy', 'Quality Management', 'Care Management', 'Professional Teaching and Education' and 'Health Promotion'. CONCLUSIONS: Adequate empirical evidence of reliability and validity for APNCAI makes it useful for application in healthcare policy programmes for APN competency assessment in Spain.

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.

Curcumin mediates oxaliplatin-acquired resistance reversion in colorectal cancer cell lines through modulation of CXC-Chemokine/NF-κB signalling pathway.

Resistance to oxaliplatin (OXA) is a complex process affecting the outcomes of metastatic colorectal cancer (CRC) patients treated with this drug. De-regulation of the NF-κB signalling pathway has been proposed as an important mechanism involved in this phenomenon. Here, we show that NF-κB was hyperactivated in in vitro models of OXA-acquired resistance but was attenuated by the addition of Curcumin, a non-toxic NF-κB inhibitor. The concomitant combination of Curcumin + OXA was more effective and synergistic in cell lines with acquired resistance to OXA, leading to the reversion of their resistant phenotype, through the inhibition of the NF-κB signalling cascade. Transcriptomic profiling revealed the up-regulation of three NF-κB-regulated CXC-chemokines, CXCL8, CXCL1 and CXCL2, in the resistant cells that were more efficiently down-regulated after OXA + Curcumin treatment as compared to the sensitive cells. Moreover, CXCL8 and CXCL1 gene silencing made resistant cells more sensitive to OXA through the inhibition of the Akt/NF-κB pathway. High expression of CXCL1 in FFPE samples from explant cultures of CRC patients-derived liver metastases was associated with response to OXA + Curcumin. In conclusion, we suggest that combination of OXA + Curcumin could be an effective treatment, for which CXCL1 could be used as a predictive marker, in CRC patients.

[Consensus on competencies for advanced nursing practice in Spain]. / Consenso sobre competencias para la enfermería de práctica avanzada en España.

INTRODUCTION: There is a lack of international consensus on the exact definition and core competencies of advanced practice nursing (APN) roles, a problem particularly acute in our national context due to the lack of APN role development, which has a significantly short history in our country. The main objective of this paper was the delineation of the competence framework for Advanced Practice Nurses in our national context based on expert consensus through the Delphi method METHOD: Based on a preliminary literature review process, a conglomerate of 17 domains of competence (clusters of related competencies) were identified. This initial set was revised, refined and validated by a group of expert panellists on the subject (clinicians, researchers, managers, and teachers) through successive rounds in search of a suitable consensus on each of the various proposed items RESULTS: The results helped to establish a solid foundation in the form of a skills map that could identify those sets of more specific competencies for advanced practice roles, regardless of regulatory and professional practice context, identifying domains such as Research and Evidence Based Practice, Clinical and Professional Leadership, or Care Management DISCUSSION: This set of skills related to advanced practice roles in our environment can delineate competency standards common to this level of nursing practice, and serve as a reference for policy development, a review of roles, or the establishment of academic profiles.

Tumor-Related Molecular Mechanisms of Oxaliplatin Resistance.

Oxaliplatin was the first platinum drug with proven activity against colorectal tumors, becoming a standard in the management of this malignancy. It is also considered for the treatment of pancreatic and gastric cancers. However, a major reason for treatment failure still is the existence of tumor intrinsic or acquired resistance. Consequently, it is important to understand the molecular mechanisms underlying the appearance of this phenomenon to find ways of circumventing it and to improve and optimize treatments. This review will be focused on recent discoveries about oxaliplatin tumor-related resistance mechanisms, including alterations in transport, detoxification, DNA damage response and repair, cell death (apoptotic and nonapoptotic), and epigenetic mechanisms.

PKM2 Subcellular Localization Is Involved in Oxaliplatin Resistance Acquisition in HT29 Human Colorectal Cancer Cell Lines.

Chemoresistance is the main cause of treatment failure in advanced colorectal cancer (CRC). However, molecular mechanisms underlying this phenomenon remain to be elucidated. In a previous work we identified low levels of PKM2 as a putative oxaliplatin-resistance marker in HT29 CRC cell lines and also in patients. In order to assess how PKM2 influences oxaliplatin response in CRC cells, we silenced PKM2 using specific siRNAs in HT29, SW480 and HCT116 cells. MTT test demonstrated that PKM2 silencing induced resistance in HT29 and SW480 cells and sensitivity in HCT116 cells. Same experiments in isogenic HCT116 p53 null cells and double silencing of p53 and PKM2 in HT29 cells failed to show an influence of p53. By using trypan blue stain and FITC-Annexin V/PI tests we detected that PKM2 knockdown was associated with an increase in cell viability but not with a decrease in apoptosis activation in HT29 cells. Fluorescence microscopy revealed PKM2 nuclear translocation in response to oxaliplatin in HCT116 and HT29 cells but not in OXA-resistant HTOXAR3 cells. Finally, by using a qPCR Array we demonstrated that oxaliplatin and PKM2 silencing altered cell death gene expression patterns including those of BMF, which was significantly increased in HT29 cells in response to oxaliplatin, in a dose and time-dependent manner, but not in siPKM2-HT29 and HTOXAR3 cells. BMF gene silencing in HT29 cells lead to a decrease in oxaliplatin-induced cell death. In conclusion, our data report new non-glycolytic roles of PKM2 in response to genotoxic damage and proposes BMF as a possible target gene of PKM2 to be involved in oxaliplatin response and resistance in CRC cells.

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.

Validity and reliability of instruments aimed at measuring Evidence-Based Practice in Physical Therapy: a systematic review of the literature.

RATIONALE, AIMS AND OBJECTIVES: Our goal is to compile and analyse the characteristics - especially validity and reliability - of all the existing international tools that have been used to measure evidence-based clinical practice in physiotherapy. METHODS: A systematic review conducted with data from exclusively quantitative-type studies synthesized in narrative format. An in-depth search of the literature was conducted in two phases: initial, structured, electronic search of databases and also journals with summarized evidence; followed by a residual-directed search in the bibliographical references of the main articles found in the primary search procedure. The studies included were assigned to members of the research team who acted as peer reviewers. Relevant information was extracted from each of the selected articles using a template that included the general characteristics of the instrument as well as an analysis of the quality of the validation processes carried out, by following the criteria of Terwee. RESULTS: Twenty-four instruments were found to comply with the review screening criteria; however, in all cases, they were found to be limited as regards the 'constructs' included. Besides, they can all be seen to be lacking as regards comprehensiveness associated to the validation process of the psychometric tests used. CONCLUSION: It seems that what constitutes a rigorously developed assessment instrument for EBP in physical therapy continues to be a challenge.

Epigenetic inactivation of the BRCA1 interactor SRBC and resistance to oxaliplatin in colorectal cancer.

BACKGROUND: A major problem in cancer chemotherapy is the existence of primary resistance and/or the acquisition of secondary resistance. Many cellular defects contribute to chemoresistance, but epigenetic changes can also be a cause. METHODS: A DNA methylation microarray was used to identify epigenetic differences in oxaliplatin-sensitive and -resistant colorectal cancer cells. The candidate gene SRBC was validated by single-locus DNA methylation and expression techniques. Transfection and short hairpin experiments were used to assess oxaliplatin sensitivity. Progression-free survival (PFS) and overall survival (OS) in metastasic colorectal cancer patients were explored with Kaplan-Meier and Cox regression analyses. All statistical tests were two-sided. RESULTS: We found that oxaliplatin resistance in colorectal cancer cells depends on the DNA methylation-associated inactivation of the BRCA1 interactor SRBC gene. SRBC overexpression or depletion gives rise to sensitivity or resistance to oxaliplatin, respectively. SRBC epigenetic inactivation occurred in primary tumors from a discovery cohort of colorectal cancer patients (29.8%; n = 39 of 131), where it predicted shorter PFS (hazard ratio [HR] = 1.83; 95% confidence interval [CI] = 1.15 to 2.92; log-rank P = .01), particularly in oxaliplatin-treated case subjects for which metastasis surgery was not indicated (HR = 1.96; 95% CI = 1.13 to 3.40; log-rank P = .01). In a validation cohort of unresectable colorectal tumors treated with oxaliplatin (n = 58), SRBC hypermethylation was also associated with shorter PFS (HR = 1.90; 95% CI = 1.01 to 3.60; log-rank P = .045). CONCLUSIONS: These results provide a basis for future clinical studies to validate SRBC hypermethylation as a predictive marker for oxaliplatin resistance in colorectal cancer.

Using the R-MAPE index as a resistant measure of forecast accuracy.

BACKGROUND: The mean absolute percentage error (MAPE) is probably the most widely used goodness-of-fit measure. However, it does not meet the validity criterion due to the fact that the distribution of the absolute percentage errors is usually skewed to the right, with the presence of outlier values. In these cases, MAPE overstates the corresponding population parameter. In this study, we propose an alternative index, called Resistant MAPE or R-MAPE based on the calculation of the Huber M-estimator, which allows overcoming the aforementioned limitation. METHOD: The results derived from the application of Artificial Neural Network (ANN) and Autoregressive Integrated Moving Average (ARIMA) models are used to forecast a time series. RESULTS: The arithmetic mean, MAPE, overstates the corresponding population parameter, unlike R-MAPE, on a set of error distributions with a statistically significant right skew, as well as outlier values. CONCLUSIONS: Our results suggest that R-MAPE represents a suitable alternative measure of forecast accuracy, due to the fact that it provides a valid assessment of forecast accuracy compared to MAPE.