Tumor necrosis-like weak inducer of apoptosis as a proinflammatory cytokine in human adipocyte cells: up-regulation in severe obesity is mediated by inflammation but not hypoxia.

CONTEXT Adipose tissue hypoxia and endoplasmic reticulum (ER) stress may link the presence of chronic inflammation and macrophage infiltration in severely obese subjects. We previously reported the up-regulation of TNF-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in adipose tissue of severely obese type 2 diabetic subjects. OBJECTIVES The objective of the study was to examine TWEAK and Fn14 adipose tissue expression in obesity, severe obesity, and type 2 diabetes in relation to hypoxia and ER stress. DESIGN In the obesity study, 19 lean, 28 overweight, and 15 obese nondiabetic subjects were studied. In the severe obesity study, 23 severely obese and 35 control subjects were studied. In the type 2 diabetes study, 11 type 2 diabetic and 36 control subjects were studied. The expression levels of the following genes were analyzed in paired samples of sc and visceral adipose tissue: Fn14, TWEAK, VISFATIN, HYOU1, FIAF, HIF-1a, VEGF, GLUT-1, GRP78, and XBP-1. The effect of hypoxia, inflammation, and ER stress on the expression of TWEAK and Fn14 was examined in human adipocyte and macrophage cell lines. RESULTS Up-regulation of TWEAK/Fn14 and hypoxia and ER stress surrogate gene expression was observed in sc and visceral adipose tissue only in our severely obese cohort. Hypoxia modulates TWEAK or Fn14 expression in neither adipocytes nor macrophages. On the contrary, inflammation up-regulated TWEAK in macrophages and Fn14 expression in adipocytes. Moreover, TWEAK had a proinflammatory effect in adipocytes mediated by the nuclear factor-kappaB and ERK but not JNK signaling pathways. CONCLUSIONS Our data suggest that TWEAK acts as a pro-inflammatory cytokine in the adipose tissue and that inflammation, but not hypoxia, may be behind its up-regulation in severe obesity.

Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias.

Background: Mortality from invasive meningococcal disease (IMD) has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias. Methods: A retrospective analysis was made of clinical reports of all patients (n = 848) diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and prehospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables. Results: Data were recorded on 848 patients, 49 (5.72%) of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93). Conclusion: Pre-hospital oral antibiotherapy appears to reduce IMD mortality.

Preanalytical mistakes in samples from primary care patients.

BACKGROUND Preanalytical mistakes (PAMs) in samples usually led to rejection upon arrival to the clinical laboratory. However, PAMs might not always be detected and result in clinical problems. Thus, PAMs should be minimized. We detected PAMs in samples from Primary Health Care Centres (PHCC) served by our central laboratory. Thus, the goal of this study was to describe the number and types of PAMs, and to suggest some strategies for improvement. METHODS The presence of PAMs, as sample rejection criteria, in samples submitted from PHCC to our laboratory during October and November 2007 was retrospectively analysed. RESULTS Overall, 3885 PAMs (7.4%) were detected from 52,669 samples for blood analyses. This included missed samples (n=1763; 45.4% of all PAMs, 3.3% of all samples), haemolysed samples (n=1408; 36.2% and 2.7%, respectively), coagulated samples (n=391; 10% and 0.7%, respectively), incorrect sample volume (n=110; 2.8% and 0.2%, respectively), and others (n=213; 5.5% and 0.4%, respectively). For urine samples (n=18,852), 1567 of the samples were missing (8.3%). CONCLUSIONS We found the proportion of PAMs in blood and urine samples to be 3-fold higher than that reported in the literature. Therefore, strategies for improvement directed towards the staff involved, as well as an exhaustive audit of preanalytical process are needed. To attain this goal, we first implemented a continued education programme, financed by our Regional Health Service and focused in Primary Care Nurses.

Estudio bibliométrico de la revista Nutrición Hospitalaria en el periodo 2001 a 2005: parte 2, análisis de consumo; las referencias bibliográficas.

OBJECTIVE To describe and assess the consumption of the information consulted and cited in the articles published in the journal Nutrición Hospitalaria for the period 2001--2005 by means of bibliometric analysis. METHOD Cross-sectional descriptive analysis of the results obtained from the analysis of the lists of bibliographic references of the articles published at Nutrición Hospitalaria. We studied the most cited journals, the signatures index, the type of document referred, the publication language, the distribution of geographical origin, and obsolescence and readiness index. We took into account all types of documents with the exception of Communications to Congresses. RESULTS 345 articles were published at Nutr Hosp, containing 8,113 bibliographic references, with a median of 18, a maximum of 136 and minimum of 0 BR per article. The mean (rate of publications per published article during the specified period) is 23.52 (95% IC 20.93-26.10) and the mean at 5% is 20.66 per article. The 25th and 75th percentiles are 6 and 32, respectively, the interquartile interval being 26 BR per document. The semi-period of Burton and Kebler is 7 years and the Price Index is 38.18%. CONCLUSION The bibliographic references, the consumption of information, of the articles published at Nutrición Hospitalaria present parameters similar to other journals on health science. However, good data on obsolescence are observed, which reveal the good validity of most of the references studied.

Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study.

INTRODUCTION Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. METHODS Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. RESULTS For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors.

Sources of pre-analytical variations in yield of DNA extracted from blood samples: analysis of 50,000 DNA samples in EPIC.

The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies.

Use of palliative radiotherapy in brain and bone metastases (VARA II study).

INTRODUCTION Metastases are detected in 20% of patients with solid tumours at diagnosis and a further 30% after diagnosis. Radiation therapy (RT) has proven effective in bone (BM) and brain (BrM) metastases. The objective of this study was to analyze the variability of RT utilization rates in clinical practice and the accessibility to medical technology in our region. PATIENTS AND METHODS We reviewed the clinical records and RT treatment sheets of all patients undergoing RT for BM and/or BrM during 2007 in the 12 public hospitals in an autonomous region of Spain. Data were gathered on hospital type, patient type and RT treatment characteristics. Calculation of the rate of RT use was based on the cancer incidence and the number of RT treatments for BM, BrM and all cancer sites. RESULTS Out of the 9319 patients undergoing RT during 2007 for cancer at any site, 1242 (13.3%; inter-hospital range, 26.3%) received RT for BM (n = 744) or BrM (n = 498). These 1242 patients represented 79% of all RT treatments with palliative intent, and the most frequent primary tumours were in lung, breast, prostate or digestive system. No significant difference between BM and BrM groups were observed in: mean age (62 vs. 59 yrs, respectively); gender (approximately 64% male and 36% female in both); performance status (ECOG 0-1 in 70 vs. 71%); or mean distance from hospital (36 vs. 28.6 km) or time from consultation to RT treatment (13 vs. 14.3 days). RT regimens differed among hospitals and between patient groups: 10 × 300 cGy, 5 × 400 cGy and 1x800cGy were applied in 32, 27 and 25%, respectively, of BM patients, whereas 10 × 300cGy was used in 49% of BrM patients. CONCLUSIONS Palliative RT use in BM and BrM is high and close to the expected rate, unlike the global rate of RT application for all cancers in our setting. Differences in RT schedules among hospitals may reflect variability in clinical practice among the medical teams.

Compliance with dietary and nutrient recommendations in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Granada cohort at recruitment

BACKGROUND: The overall intake of energy and nutrients in the Granada EPIC-cohort (European Prospective Investigation into Cancer and Nutrition) is examined in order to assess compliance with the Spanish Nutritional Objectives (NO) and the Recommended Intakes (RI). METHODS: During recruitment (1992-1996), 7,789 participants, aged 35-69, were asked about diet through a validated diet history questionnaire. Nutrient intake is compared to the NO and RI that were valid at that time. Risk of inadequate intake is estimated as the percentage of the sample with intakes: ≤ 1/3 RI (high risk), ≤ 2/3 RI- > 1/3 RI (moderate risk), ≤ RI- > 2/3 RI, > RI. Differences in intakes have been analyzed by sex and age, and by smoking status and BMI. RESULTS: The daily intake of nutrients did not meet the NO as the total contribution of energy from proteins and fats exceeded these guidelines. Whilst intake of most nutrients was above the RI, the amount of iron, magnesium and vitamins D and E provided by the diet was not enough to meet the RI: in women aged 20-49 years, about 55% were at moderate risk for iron inadequacy, and a 20% of women for magnesium. Both sexes were at high risk of inadequacy for vitamin D, although sunlight exposure may supply adequate amounts. Never smokers showed a higher compliance to the NO. CONCLUSION: At recruitment, the nutrient profile of the diet was unbalanced. The observed nutrient inadequacy for iron, magnesium and vitamin E might be attributed to inappropriate dietary habits, and may have implications for future disease risk.

Modelo de estadios de cambio: compatibilidad con relatos biográficos de mujeres que sufren violencia doméstica

This study aims to analyze the adjustment of women, victims of intimate partner violence, by applying the Prochaska and Di Clemente Stages of Change Model. An interpretative qualitative study was made in 35 domestic violence victims women detected in primary care, women who recognized their relationship as abusive (perceived maltreatment). This is a multicentric study, with participation of six health centers of Malaga city. Biographical Narration technique by audio-recorded and transcribed interview was used; about this, thematic analysis adjustment to Transtheoretic Model phases was applied. ATLAS-TI 5.0 program was used for codification. Precontemplative, maintenance and ending stages were more represented while action phases were poorly mentioned. Main phases characteristics were: "blindness" and inexplicability in precontemplative stage; pros / cons analysis in contemplative phase; making decisions difficulty in action phases; suffering and going ahead purpose in maintenance stage, and determination and analysis capacity in the ending stage. Keys for intervention according to the phase of the process were offered.

El lavado de manos: ¿una recomendación atendida?

Objective: to determine the incidence of hand washing in parents as a preventive factor in the spread of viral respiratory infections in children under two years assigned to an urban pediatric basic health area affected by catarrhal symptoms during the influenza vaccination campaign. Material and methods: from 230 children under two years included in the basic health area attending the Well Child program, 51 consulted during the influenza vaccination campaign (October 2011) by catarrhal symptoms. Results: fifty-one children were included, 23 male and 28 female. From the clinical point of view, 33 cases were afebrile and only 18 had fever, runny nose 100%. The clinic diagnosis in 44 cases was nasopharyngitis, acute bronchitis in 5 cases and obstructive bronchiolitis in 2 cases. No family history in 19, however 32 cases had a family member with catarrhal symptoms. As for the performance of hand washing as a preventive measure, 34 cases said they did not comply with this measure, only 17 cases did, despite the recommendations. Conclusions: while recognizing the importance of hand washing as a preventive measure for respiratory infections and being included among the recommendations offered in the well child program, only 33% of the population of our study reported washing hands. This recommendation should also be included in consultations on demand during the influenza season to encourage compliance.

Long-term assessment of didanosine, lamivudine, and efavirenz in antiretroviral-naive patients: 3-year follow-up.

The aim of this study was to evaluate the long-term efficacy and safety of didadosine (ddI), lamivudine (3TC), and efavirenz (EFV). This was a follow-up to the VESD study, a 12-month open-label, observational, multicenter study of adult patients with HIV infection who started antiretroviral treatment with the ddI-3TC-EFV once-daily regimen. Of the 167 patients originally included, 106 patients remained on the same triple therapy at the end of the study (1 year), and they were offered an extra 24 months of follow-up; 96 were enrolled in this study (VESD-2). Seventy patients out of the initial cohort were still on the same regimen at month 36, with 97% of them with plasma viral load <50 copies /ml. An intention-to-treat analysis showed that the percentage of patients with plasma viral load <50 copies/ml was 73% at 36 months. CD4 cell counts increased 344 cells/microl over the 36 months. Safety and tolerance were good with no unexpected long-term toxicity. After 3 years of treatment with ddI-3TC-EFV, more than 40% of the patients were still receiving the initial antiretroviral therapy with sustained, durable immunovirological benefit and good acceptance. Long-term toxicity and virological failure were low.

A cohort study of routinely used sepsis biomarkers and 28-day mortality.

The evaluation of sepsis severity is complicated by the highly variable and nonspecific nature of clinical signs and symptoms. We studied routinely used biomarkers together with clinical parameters to compare their prognostic value for severe sepsis and evaluate their usefulness.

Prescripción enfermera en el entorno de las urgencias y emergencias. Marco conceptual vs entorno legislado en España

The prescription, widely discussed and defined conceptually in recent years in an environment of widening the spectrum of responsibilities nurse, has capacity for integration and definition in the area of accident and emergency care and carried out over the patient urgently, about emergencies and life-long commitment. Be necessary to frame throughout the legal framework, following the amendment of the Twelfth Additional Provision of Law 29/2006 of guarantees and rational use of drugs and medical devices, can be waived and implementation required, provided under model and through the nursing process and method and as an exponent and endorsementn of science and advanced clinical practice, to join the idea of interdisciplinary professional consensus that the law posed by the preparation and implementation of standardized protocols, algorithms and / or clinical practice guidelines in the context of what has come to be called "collaborative standard prescription": Prescription to the nurse in certain clinical situations in terms of a performance protocol, agreed with multidisciplinary team care health of the population (Group Protocols), which can be considered an intermediate step in the evolution towards independent nurse prescribing, providing nurses experience of a prescription under these protocols and demonstrating their capabilities.