Factors related to inter-observer reproducibility of conventional Pap smear cytology: a multilevel analysis of smear and laboratory characteristics.

OBJECTIVE: To identify factors that influence the inter-observer reproducibility of the routine, conventional Pap smear cytology (Pap smear test) in a network of certificated laboratories in a middle-income Latin American country. METHODS: Twenty-six laboratories provided each an average of 26 negative for malignancy (NILM) and high-grade squamous intraepithelial lesion (HSIL) Pap smears. An external panel reviewed the slides. The kappa index and multilevel logistic regression were used to estimate the reproducibility and odds ratios (OR) of a false result with 95% confidence intervals (95% CI), respectively. Results are presented for laboratories that collect (collector laboratories) and do not collect (non-collector laboratories) samples. RESULTS: The agreements ranged widely (median kappa 0.51, range 0.16-0.70). The overall false-positive (FP) and false-negative (FN) rates were 31% (95% CI 27-35) and 11% (95% CI 7-17). Among collector laboratories (N = 14), a bigger sample collection volume decreased the probability of a FP (OR-adjusted 0.05, 95% CI 0.02-0.1) whereas the number of quality defects (OR-adjusted 1.67, 95% CI 1.25-2.24), high workload (OR-adjusted 5.52, 95% CI 3.85-7.92) and collection by cytotechnologists (OR-adjusted 1.28, 95% CI 1.15-1.42) or health professionals (OR-adjusted 2.26, 95% CI 2.04-2.49) instead of nursing assistants increased it. Among non-collector laboratories (N = 9), the FP rate increased with the number of quality defects (OR-adjusted 1.86, 95% CI 1.06-3.26) but decreased if the samples were collected by health professionals instead of nursing assistants (OR-adjusted 0.37, 95%CI 0.17-0.80). No significant associations were observed for FN. CONCLUSIONS: Staff in charge of cervical sampling significantly determined the reproducibility of the Pap smear test, but this depended on whether the laboratory collects samples or read samples collected elsewhere.

Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.

We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0 ± 5.2 years compared with 41.1 ± 7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy.

The MAPP Room Memory Test: Examining Contextual Memory Using a Novel Computerized Test in Cognitively-Unimpaired Individuals with Autosomal Dominant Alzheimer's Disease.

Contextual memory, the ability to remember spatial or temporal features related to an event, is affected in Alzheimer's disease (AD). There is a shortfall of tests that measure contextual memory. To evaluate visuospatial contextual memory, we developed a computerized cognitive test, the MAPP Room Memory Test, which requires participants to identify in which visual scene target items were previously presented. We hypothesized that cognitively-unimpaired carriers of an autosomal dominant AD mutation (Presenilin-1 E280A, n=15) would perform more poorly on this test than non-carrier family members (n=31). Compared to non-carriers, the carriers had significantly worse delayed room recognition. The results indicate that the MAPP Room Memory Test may be sensitive to subtle cognitive changes associated with risk of AD. Future studies with larger samples using the MAPP Room Memory Test and biomarkers are needed to examine whether this test may also be sensitive to the earliest pathological changes in preclinical AD.

The objective structured clinical examination (OSCE): Main aspects and the role of imaging.

The objective structured clinical examination (OSCE) is a format of examination that enables students to be evaluated in a uniform, standardized, reliable, and objective way. It is carried out in different clinical stations that simulate real clinical situations and scenarios. Numerous universities in Spain and other countries employ this approach for the final examination for medical school students. This update describes the organization, design, and fundamentals for the OSCE, proposing that radiology should form part of multidisciplinary OSCEs to the extent that it forms part of clinical practice. Moreover, it is interesting and opportune to introduce the OSCE in undergraduate and postgraduate training in radiology. Online platforms enable bidimensional OSCEs that are cost-effective in terms of staff, resources, and physical space, although this approach has certain limitations. Virtual world technologies make it possible to reproduce OSCE stations in three-dimensional scenarios; recent experiences in radiology have shown that this approach interests and motivates students and is widely accepted by them.

Memory for Semantically Related Objects Differentiates Cognitively Unimpaired Autosomal Dominant Mutation Carriers from Non-Carrier Family Members.

Early cognitive changes due to Alzheimer's disease (AD) include difficulties in semantic access and working memory. Using a computerized cognitive test developed by our group, called the Memory for Semantically Related Objects test (MESERO), we evaluated if cognitively unimpaired carriers of an autosomal dominant AD (ADAD) mutation performed worse on this test than non-carrier family members. 35 cognitively unimpaired ADAD mutation carriers and 26 non-carrier family members from a Colombian ADAD cohort took the MESERO on a laptop computer. Cognitively unimpaired ADAD carriers had significantly worse MESERO total scores than non-carrier family members, driven by worse performance in semantically-related object sets; group performances did not differ on semantically unrelated object sets. Findings suggest that MESERO performance may be sensitive to subtle cognitive changes associated with AD. Future MESERO research should examine performances between healthy older adults and people at risk for sporadic AD.

APOE3 Christchurch modulates tau phosphorylation and ß-catenin/Wnt/Cadherin signaling in induced pluripotent stem cell-derived cerebral organoids from Alzheimer's cases.

Alzheimer's disease (AD) is the most common cause of dementia among older adults. APOE3 Christchurch (R136S, APOE3Ch ) variant homozygosity was reported in an individual with extreme resistance to autosomal dominant AD due to the PSEN1 E280A mutation. This subject had a delayed clinical age at onset and resistance to tauopathy and neurodegeneration despite extremely high amyloid plaque burden. We established induced pluripotent stem (iPS) cell-derived cerebral organoids from this resistant case and from a non-protected kindred control (with PSEN1 E280A and APOE3/3 ). We used CRISPR/Cas9 gene editing to successfully remove the APOE3Ch to wild type in iPS cells from the protected case and to introduce the APOE3Ch as homozygote in iPS cells from the non-protected case to examine causality. We found significant reduction of tau phosphorylation (pTau 202/205 and pTau396) in cerebral organoids with the APOE3Ch variant, consistent with the strikingly reduced tau pathology found in the resistant case. We identified Cadherin and Wnt pathways as signaling mechanisms regulated by the APOE3Ch variant through single cell RNA sequencing in cerebral organoids. We also identified elevated ß-catenin protein, a regulator of tau phosphorylation, as a candidate mediator of APOE3Ch resistance to tauopathy. Our findings show that APOE3Ch is necessary and sufficient to confer resistance to tauopathy in an experimental ex-vivo model establishing a foundation for the development of novel, protected case-inspired therapeutics for tauopathies, including Alzheimer's.

Baseline 18F-FDG PET/CT quantitative parameters as prognostic factors in esophageal squamous cell cancer.

AIM: To determine the utility of [18F]FDG PET/CT quantitative parameters as prognostic factors for the response to neoadjuvant treatment, progression-free survival (PFS) and cancer-specific survival (CSS) in patients with esophageal squamous cell carcinoma (SCC). MATERIAL AND METHODS: Thirty patients (29 men) diagnosed with SCC were retrospectively evaluated over a 6-year interval. Metabolic parameters were determined: maximum SUV (SUVmax), mean SUV (SUVmed), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from baseline PET/CT study. After treatment with chemotherapy and/or radiotherapy, response to treatment and patient survival were assessed. The comparison of parameters between groups of responders and non-responders was carried out using a Mann-Whitney U test ROC curves and the Kaplan-Meier method were used for analysis of prognostic factors and survival curves. RESULTS: The average follow-up was 22.4 months, with 22 recurrence-progressions and 25 deaths. Significant differences were demonstrated between responders and non-responders with respect to tumor size, MTV and TLG. Survival analysis found significant differences for SCE and CSS depending on these three parameters. CONCLUSION: Metabolic parameters MTV and TLG, and tumor size were prognostic factors for neoadjuvant treatment response, PFS, and CSS in patients diagnosed with SCC. Neither SUVmax nor SUVmed were predictive for any of the evaluation criteria. Results could help to personalize patient treatment.

Utility of gastrointestinal transit scintigraphy in the evaluation of chronic constipation.

AIM: Chronic constipation is a common pathology in clinical practice. In the absence of response to treatment, assessment of gastrointestinal function is recommended. This can be performed by scintigraphy, although its use is not widespread. The aim of this paper was to assess the utility of gastrointestinal transits scintigraphy in patients with chronic constipation. MATERIAL AND METHODS: Twenty patients (13 children) sent for scintigraphy for chronic constipation refractory to treatment, syringomyelia, rectocele or abdominal migraine were evaluated. All underwent clinical assessment, analytical determination, radiological imaging and/or rectal biopsy. A complete study protocol was performed, including gastric emptying, small bowel and colonic transits scintigraphy. For this, a dose of [111In]In-DTPA diluted in water (37MBq) was administered together with standardized food. Following international guidelines, regions of interest were defined in the stomach, terminal ileum and different regions of the large intestine to calculate the geometric center as a measure of progression. RESULTS: Of the 13 pediatric patients, 10 had abnormal gammagraphic patterns, with treatment being modified in 8 of them. Most of the children showed no alterations on radiological explorations. In adult patients, the results of the test changed the therapeutic management in all of them. CONCLUSIONS: Scintigraphic study provided useful information in the study of chronic constipation, influencing the diagnosis and therapeutic management of the patient. The physiological and quantitative information it provides allows both global and regional of gastrointestinal transit time determination.

Prognostic value of PERCIST and PET/CT metabolic parameters after neoadjuvant treatment in patients with esophageal cancer.

AIM: To assess the clinical utility of PERCIST criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival and cancer-specific survival (CSS) in patients with esophageal cancer treated by chemoradiotherapy. MATERIAL AND METHODS: Fifty patients (48 men) diagnosed with esophageal cancer were retrospectively evaluated over a 7.5-year interval. PERCIST criteria were used to assess response to neoadjuvant therapy. Variations in the metabolic parameters maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) between pre- and post-treatment PET/CT studies were also determined. ROC curves, Kaplan-Meier method and Cox regression model were used for the analysis of prognostic factors and survival curves. RESULTS: The average follow-up was 26.8 months, with 40 recurrences-progressions and 41 deaths. Survival analysis showed statistically significant differences in CSS curves for PERCIST criteria and variation of MTV and TLG. PERCIST criteria were the only independent predictor in the multivariate analysis. Neither SUVmax nor tumor size were predictors for any of the assessment criteria. CONCLUSION: Application of PERCIST criteria as well as change in MTV and TLG from PET/CT studies proved to be prognostic factors for CSS in patients in our setting treated for esophageal cancer. The results could help to personalize treatment.

Baseline 18F-FDG PET/CT quantitative parameters as prognostic factors in esophageal squamous cell cancer. / Parámetros cuantitativos de la PET/TC basal con 18F-FDG como factores pronósticos en el carcinoma de células escamosas de esófago.

AIM: To determine the utility of 18F-FDG PET/CT quantitative parameters as prognostic factors for the response to neoadjuvant treatment, progression-free survival (PFS) and cancer-specific survival (CSS) in patients with esophageal squamous cell carcinoma (SCC). MATERIAL AND METHODS: Thirty patients (29 men) diagnosed with SCC were retrospectively evaluated over a 6-year interval. Metabolic parameters were determined: maximum SUV (SUVmax), mean SUV (SUVmed), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from baseline PET/CT study. After treatment with chemotherapy and/or radiotherapy, response to treatment and patient survival were assessed. The comparison of parameters between groups of responders and non-responders was carried out using a Mann-Whitney U test. ROC curves and the Kaplan-Meier method were used for analysis of prognostic factors and survival curves. RESULTS: The average follow-up was 22.4months, with 22 recurrence-progressions and 25 deads. Significant differences were demonstrated between responders and non-responders with respect to tumor size, MTV and TLG. Survival analysis found significant differences for SCE and CSS depending on these three parameters. CONCLUSION: Metabolic parameters MTV and TLG, and tumor size were prognostic factors for neoadjuvant treatment response, PFS, and CSS in patients diagnosed with SCC. Neither SUVmax nor SUVmed were predictive for any of the evaluation criteria. Results could help to personalize patient treatment.

Long-Term Results of ACL Reconstruction Using a Nonanatomic Double-Bundle Technique with Extra-Articular Reinforcement.

Extra-articular procedures for the improvement in rotational stability after anterior cruciate ligament (ACL) reconstruction have gained popularity in the last decade. This surgical gesture hoped to improve resistance to the high tensional forces affecting the ACL graft during cutting and pivoting movements of the lower extremity and eventually prevent ACL reconstruction failure. We performed this study to analyze the long-term results of patients undergoing ACL reconstruction using a nonanatomic double-bundle technique with an additional extra-articular augmentation. All the cases that underwent an ACL reconstruction using a nonanatomic double-bundle technique with an extra-articular reinforcement during the period between 1992 and 1997 were reviewed. The inclusion criteria for this study included a minimum follow-up of 10 years and age between 14 and 45 years at the time of the surgery. Forty patients were included in this series (34 males and 6 females). The mean Lysholm score after a minimum follow-up period of 10 years was 92.3 (standard deviation [SD], 9.4). The average preoperative Tegner score of the participants was 7.0 (SD, 1.1). This score decreased to 5.7 (SD, 1.2) at the end of follow-up. Follow-up X-rays were reviewed to assess the degenerative changes in the three knee compartments. Degenerative changes ≥ Kellgren-Lawrence grade 2 were observed in our six (15%) patients, all of them in the medial knee compartment. With these results, we conclude that double-bundle nonanatomic ACL reconstruction combined with an extra-articular reinforcement resembling the anterolateral ligament offers good overall long-term results, with relatively low rates of osteoarthritis.

Visual working memory for semantically related objects in healthy adults. / Memoria de trabajo visual para objetos relacionados semánticamente en adultos sanos.

INTRODUCTION: Few studies have examined how manipulating the semantic relationship between objects impacts visual working memory accuracy or reaction time. AIM: To characterize how the semantic relatedness of visual objects impacts working memory accuracy and reaction time in healthy adults using a newly developed mobile-tablet cognitive task. SUBJECTS AND METHODS: A delayed matching to sample paradigm on the tablet task was studied in a sample of 76 community-dwelling adult participants from Spain and Colombia. The tablet task included 80 unique sets of either four or six semantically related or semantically unrelated objects. The accuracy and reaction time of the participants on the task were recorded for analysis. RESULTS: When objects were semantically related, reaction time was greater in the six object sets relative to the four object sets. Age was positively associated with reaction time, but not accuracy across all four task conditions. Participants with fewer years of formal education than the sample median (16 years) exhibited worse response accuracy and slower reaction time on both the four and six semantically related conditions relative to participants with 16 or more years of formal education. CONCLUSIONS: Findings from this study suggest that when objects are semantically related (versus unrelated) and object load is increased, more processing time is needed to determine whether an object was or was not in the encoded set. The results also suggest that greater educational attainment -which likely relates with greater exposure to more technologies- is related with faster and more accurate responses on some task conditions.

TITLE: Memoria de trabajo visual para objetos relacionados semánticamente en adultos sanos.Introducción. Pocos estudios han examinado cómo la manipulación de la relación semántica entre objetos puede influir en el desempeño o el tiempo de reacción en tareas de memoria de trabajo visual. Objetivo. Caracterizar cómo la relación semántica de los objetos afecta el desempeño o el tiempo de reacción en una tarea de memoria de trabajo en adultos sanos utilizando una tarea cognitiva diseñada para el uso con tableta. Sujetos y métodos. Se usó una tarea de emparejamiento demorado (delayed matching to sample) con una muestra de 76 participantes adultos de España y Colombia. La tarea incluyó 80 conjuntos únicos de cuatro o seis objetos relacionados/no relacionados semánticamente. Se registraron las respuestas y el tiempo de reacción de los participantes. Resultados. Cuando los objetos estaban semánticamente relacionados, el tiempo de reacción fue mayor en la condición de seis objetos con respecto a la condición de cuatro objetos. La edad se asoció positivamente con el tiempo de reacción, pero no con la precisión de las respuestas. Los participantes con menos años de educación formal tuvieron un peor de­sempeño y un tiempo de reacción más lento en las condiciones somáticamente relacionadas en relación con los participantes con 16 años o más de educación formal. Conclusión. Los resultados sugieren que, cuando los objetos están semánticamente relacionados y aumenta su número, se necesita más tiempo de procesamiento para determinar si un objeto está o no en el grupo de objetos codificado. Además, un mayor nivel educativo se relaciona con respuestas más rápidas y un mejor desempeño en ciertas condiciones de la tarea.

Epidemiology of human papillomavirus-related oropharyngeal cancer in a classically low-burden region of southern Europe.

The incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing in some regions. Nevertheless, the epidemiology of this disease has not been extensively investigated in southern Europe. We conducted a retrospective cohort study of patients diagnosed with primary oropharyngeal cancer from 1991 to 2016. Cancer tissues underwent histopathological evaluation, DNA quality control, HPV-DNA detection and p16INK4a immunohistochemistry. Data were collected from medical records. Factors associated with HPV positivity and time trends were evaluated with multivariable Bayesian models. The adjusted prevalence of HPV-related cases in 864 patients with a valid HPV-DNA result was 9.7%, with HPV-DNA/p16INK4a double positivity being considered. HPV-related oropharyngeal cancer was likely to occur in non-smokers and non-drinkers, to be located in the tonsil or diagnosed at advanced stages. Time-trend analysis showed an increasing risk of HPV-related oropharyngeal cancer in the most recent periods (5-year period increase of 30%). This increase was highest and with a clear increasing trend only in the most recent years (2012-2016). The prevalence of HPV-related oropharyngeal cancer started to sharply increase in the most recent years in our setting, as occurred two decades ago in areas where most oropharyngeal cancer cases are currently HPV-related. Our results provide a comprehensive assessment of the epidemiological landscape of HPV-related oropharyngeal cancer in a region of southern Europe.

Evasion and subversion of antigen presentation by Mycobacterium tuberculosis.

Mycobacterium tuberculosis is one of the most successful of human pathogens and has acquired the ability to establish latent or progressive infection and persist even in the presence of a fully functioning immune system. The ability of M. tuberculosis to avoid immune-mediated clearance is likely to reflect a highly evolved and coordinated program of immune evasion strategies, including some that interfere with antigen presentation to prevent or alter the quality of T-cell responses. Here, we review an extensive array of published studies supporting the view that antigen presentation pathways are targeted at many points by pathogenic mycobacteria. These studies show the multiple potential mechanisms by which M. tuberculosis may actively inhibit, subvert or otherwise modulate antigen presentation by major histocompatibility complex class I, class II and CD1 molecules. Unraveling the mechanisms by which M. tuberculosis evades or modulates antigen presentation is of critical importance for the development of more effective new vaccines based on live attenuated mycobacterial strains.

Biological and Cognitive Markers of Presenilin1 E280A Autosomal Dominant Alzheimer's Disease: A Comprehensive Review of the Colombian Kindred.

The study of individuals with autosomal dominant Alzheimer's disease affords one of the best opportunities to characterize the biological and cognitive changes of Alzheimer's disease that occur over the course of the preclinical and symptomatic stages. Unifying the knowledge gained from the past three decades of research in the world's largest single-mutation autosomal dominant Alzheimer's disease kindred - a family in Antioquia, Colombia with the E280A mutation in the Presenilin1 gene - will provide new directions for Alzheimer's research and a framework for generalizing the findings from this cohort to the more common sporadic form of Alzheimer's disease. As this specific mutation is virtually 100% penetrant for the development of the disease by midlife, we use a previously defined median age of onset for mild cognitive impairment for this cohort to examine the trajectory of the biological and cognitive markers of the disease as a function of the carriers' estimated years to clinical onset. Studies from this cohort suggest that structural and functional brain abnormalities - such as cortical thinning and hyperactivation in memory networks - as well as differences in biofluid and in vivo measurements of Alzheimer's-related pathological proteins distinguish Presenilin1 E280A mutation carriers from non-carriers as early as childhood, or approximately three decades before the median age of onset of clinical symptoms. We conclude our review with discussion on future directions for Alzheimer's disease research, with specific emphasis on ways to design studies that compare the generalizability of research in autosomal dominant Alzheimer's disease to the larger sporadic Alzheimer's disease population.

Knowledge of Pap screening and human papillomavirus among women attending clinics in Medellín, Colombia.

This study evaluated Pap screening and human papillomavirus (HPV) knowledge in a population of Colombian women as a possible contributing factor of low cervical cancer screening success. This is a descriptive, cross-sectional analysis of 454 women who were approached in five different hospitals and clinics throughout Medellín, Colombia. Of them, 449 females agreed to participate and answered a standardized face-to-face questionnaire regarding Pap screening and HPV knowledge. Using logistic regression, predictors of both Pap and HPV knowledge were examined. Overall, 76.3% of the participants exhibited a high level of Pap screening knowledge, while only 7.8% showed high level of HPV knowledge. Of the 449 women, 71.5% reported that it had been 1 year or less since their last Pap test, while 7.8% reported never having had a Pap test or not having had a recent test. Factors influencing Pap screening knowledge included education level and insurance; factors influencing HPV knowledge included education level and age. The high level of Pap screening knowledge and use do not explain the high cervical cancer rates in Colombia. The results of this study suggest that educational efforts should be focused on increasing women's knowledge and awareness of HPV in anticipation of the availability of HPV vaccines and HPV tests for screening.

Study of paracetamol 1-g oral solution bioavailability.

The aim of this work was to assess paracetamol bioavailability after administering 1 g in oral solution. Eighteen healthy volunteers were selected for this open-label study. A total of 15.4 ml of Gelocatil Oral Solution (Laboratorios Gelos, S.L.), corresponding to 1 g of paracetamol, were administered to fasting subjects. Blood samples were collected at 0 min, 10 min, 20 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h and 12 h. Paracetamol plasma concentrations were determined by reverse-phase high-performance liquid chromatography. The study was conducted without deviations from protocol. Pharmacokinetic data from 18 subjects were allowed for estimating fast and high-paracetamol bioavailability: t(max) 20 min (10-45) [median (range)], C(max) 24. 3 mg/l (6.5) [mean (standard deviation)], AUC(0-t) 64.0 mg h/l (16.1) and AUC(0-00) 68.1 mg h/l (17.9). These results are comparable to those described for Gelocatil Oral Solution given at a 650 mg dose and for immediate release Gelocatil 650 mg tablets. Absorption speed was very fast, similar to that described for other oral-solution formulations, which provides an immediate onset of pain and fever relief. The results of this study show suitable bioavailability for 1 g Gelocatil Oral Solution, with fast-absorption speed that provides an immediate onset of pain and fever relief.

Factors associated with implementation of the 5A's smoking cessation model.

BACKGROUND: Several health organizations have adopted the 5A's brief intervention model (Ask, Advise, Assess, Assist, Arrange), based on evidence-based guidelines for smoking cessation. We examine individual, cognitive, behavioral, and organizational factors associated with the 5A's performance among clinical healthcare workers in Catalonia. We also investigate how these factors interact and potentially predict the implementation of each component of the 5A's. METHODS: A cross-sectional survey was conducted among clinical health workers enrolled in an online smoking cessation training course (n = 580). The survey included questions about individual characteristics as well as cognitive, behavioral, and organizational factors previously identified in research. We assessed self-reported performance of the 5A's, assessed on a scale from 0 to 10, and used Multivariate regression to examine factors associated with its performance. RESULTS: The performance means (standard deviation) were moderate for the first 3A's [Ask: 6.4 (3.1); Advise: 7.1 (2.7); Assess: 6.3 (2.8)] and low for the last 2A's [Assist: 4.4 (2.9); Arrange: 3.2 (3.3)]. We observed a high correlation between Assist and Arrange (r = 0.704, p < 0.001). Having positive experiences and feeling competent were positively associated with performing the 5A's model and having organizational support with Assist and Arrange. Personal tobacco use among healthcare workers was negatively associated with Advice and Arrange. CONCLUSIONS: Our study found that clinical healthcare workers do not perform the 5A's completely. The main barriers identified suggest the need of training and making available practical guidelines in healthcare services. Organizational support is essential for moving towards the implementation of Assist and Arrange.

[Intranasal opioids for acute pain]. / Opioides por vía intranasal en el tratamiento del dolor agudo.

Intranasal drug administration is an easy, well-tolerated, noninvasive transmucosal route that avoids first-pass metabolism in the liver. The nasal mucosa provides an extensive, highly vascularized surface of pseudostratified ciliated epithelium. It secretes mucus that is subjected to mucociliary movement that can affect the time of contact between the drug and the surface. Absorption is influenced by anatomical and physiological factors as well as by properties of the drug and the delivery system. We review the literature on intranasal administration of fentanyl, meperidine, diamorphine, and butorphanol to treat acute pain. The adverse systemic effects are similar to those described for intravenous administration, the most common being drowsiness, nausea, and vomiting. Local effects reported are a burning sensation with meperidine and a bad taste.

Influence of demographic and tumour variables on prostate cancer treatment with curative intent in Spain. Results of the 2010 national prostate cancer registry. / Influencia de las variables demográficas y tumorales en el tratamiento del cáncer de próstata con fines curativos en España. Resultados del Registro nacional de cáncer de próstata 2010.

OBJECTIVE: The aim of this study is to determine which cancer and demographic criteria influence the indication for surgery (radical prostatectomy) or radiation therapy (external or brachytherapy) in the treatment of prostate cancer. MATERIAL AND METHODS: An analysis of the 2714 patients of the 2010 National Prostate Cancer Registry treated with curative intent. The analysed variables were age, prostate-specific antigen (PSA), prostate volume, the number of biopsy cores, the percentage of positive cores, the stage, Gleason score, the type of pathologist, the presence of perineural invasion and the study centre. We analysed the association among these variables and the type of treatment (surgery vs. radiation therapy/brachytherapy), using a univariate analysis (Student's t test and chi-squared) and a binary multiple logistic regression. RESULTS: The 48.12% of the patients (1306/2714) were treated with surgery, and 51.88% (1,408/2,714) underwent radiation therapy/brachytherapy. Differences were observed between the patients treated with prostatectomy and those treated with radiation therapy/brachytherapy (p<.05) in age (63.50±6.5 vs. 69.0±6.7), PSA (8.76±16.97 vs. 13.21±15.88), biopsied cores, percentage of positives cores (30.0±22 vs. 38.7±29), Gleason score (G6: 53.9% vs. 46.1%; G7: 45% vs. 55% G8-10: 26.6%, 73.4%), stage (localised: 50% vs. 50%; locally advanced: 14.6% vs. 85.4%), perineural invasion and hospital centre. In the multivariate analysis, the selected independent variables were age, PSA, percentage of positives cores, stage, Gleason score and hospital centre. CONCLUSION: According to our study, age, tumour aggressiveness and stage and the centre where the patient will be treated affect the selection of curative treatment for prostate cancer.