Human endogenous retrovirus HERV-Fc1 association with multiple sclerosis susceptibility: a meta-analysis.

BACKGROUND Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. METHODS A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. RESULTS Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11-1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14-1.53)]. CONCLUSION Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.

BACKGROUND Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). METHODS Treatment: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. RESULTS Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7). CONCLUSION First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.

Efectividad de una estrategia de intervención preventiva, basada en entrevistas telefónicas estructuradas, en una población laboral con riesgo cardiovascular moderado/alto.

OBJECTIVE This study assesses the effectiveness of a structured telephone survey on cardiovascular prevention, in modifying lifestyle, on cardiovascular risk parameters, percentage of smoking cessation and overall cardiovascular risk (CVR). DESIGN Quasi-experimental study of preventive intervention. SETTING Ibermutuamur (Spanish Accident and Health Insurance Company). Centres established throughout Spain. PARTICIPANTS A total of 4,792 workers with moderate/high cardiovascular risk who had agreed to be contacted by phone. Subjects with a previous diagnosis of cardiovascular disease and those receiving treatment for hypertension, hypercholesterolemia or diabetes were excluded. INTERVENTION A final total of 3,085 workers were contacted and were followed up by telephone surveys on the first, fourth and eighth month after the initial check up (CU) in order to emphasise cardiovascular health advice (Group A); we failed to contact 1,707 workers, who only attended the baseline and one year CUs (Group B). PRINCIPAL OUTCOMES: CUs included medical records and physical examination, with two blood pressure measurements, Body Mass Index (BMI), and biochemical parameters. Cardiovascular risk was stratified following the European cardiovascular SCORE. Individuals with a relative risk higher than 4 were also considered as high-risk. All workers were informed about their cardiovascular risk profile (CVRF) and healthy cardiovascular lifestyle measures. They were also given a letter for their General Practitioner (GP) to inform them on the worker's cardiovascular risk level. RESULTS A total of 71.5% of the workers were over 45 years, 95.0% males, 76.6% manual workers ("Blue Collar") and 69.7% smokers. Both groups showed improvement in lipid parameters, blood pressure, smoking cessation and overall cardiovascular risk in the second CU. There were significant differences in favour of Group A as regards blood pressure, lipids (except HDL cholesterol), BMI, glycaemia, smoking cessation (A: 23.5%/B: 19.44%, P=0.001) and CVR stratum improvement (A: 46.6%/B: 37.7%, P=0.0001). The large majority (85%) of workers read preventive recommendations; 33% knew their risk level and 73% knew their CVRF. 52.9% gave the letter to the GP, which led them to start therapies on diet (47%), hypertension (19.5%), dyslipidaemia (16.7%), diabetes (4.4%) and smoking (2.9%) and no changes were made in 36.5% of cases. CONCLUSIONS The results of this study suggests that cardiovascular prevention strategy based on structured telephone surveys on high/moderate CVR subjects to promote lifestyle changes could be effective at reducing CVR. A clinical trial is required for confirmation. Sending information on CVRF following routine medial CUs and Primary Care involvement, could contribute to the positive changes observed.

Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease.

II Plan Integral de Diabetes de Andalucía : 2009-2013

Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Igualdad, Salud y Políticas Sociales / Ciudadanía / Quiénes somos / Planes y Estrategias)

Nuevos datos sobre fibrilación auricular, observaciones al estudio OFRECE. Respuesta

We appreciate the interest shown by Vidal-Pérez et al. in our article published recently in Revista Española de Cardiología,1 which provides us with an opportunity to present some interesting additional information not included in the article itself. We agree on the importance of knowing the thromboembolic risk of the population included in the OFRECE study, both for patients with a diagnosis of atrial fibrillation and for the general population. In our study, the mean (standard deviation) CHADS2 and CHAD2DS2-VASc of patients with atrial fibrillation was 2.3 (1.3) and 3.8 (1.6), respectively. In the general population, the mean (standard deviation) CHADS2 and CHAD2DS2-VASc of patients with atrial fibrillation was 0.8 (1) and 1.8 (1.5), respectively. The distribution of both scales is in agreement with that of the Val-FAAP and AFABE studies,2, 3 although the similarity is greater in the 2 population-based studies (Figure). These data are, we believe, relevant because they show that the level of risk in the population with atrial fibrillation is very similar to that of the populations included in clinical trials with new oral anticoagulants. In addition, an increasing body of evidence suggests that thromboembolic risk, as measured with these scales in the population without a diagnosis of atrial fibrillation, is associated with the onset of events.

Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING Transnational registry in Spain. SUBJECTS We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES All-cause death. RESULTS Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.

Salvage radiosurgery for selected patients with recurrent malignant gliomas.

Purpose. To analyse the survival after salvage radiosurgery and to identify prognostic factors. Methods. We retrospectively reviewed 87 consecutive patients, with recurrent high-grade glioma, that underwent stereotactic radiosurgery between 1997 and 2010. We evaluated the survival after initial diagnosis and after reirradiation. The prognostic factors were analysed by bivariate and multivariate Cox regression model. Results. The median age was 48 years old. The primary histology included anaplastic astrocytoma (47%) and glioblastoma (53%). A margin dose of 18 Gy was administered in the majority of cases (74%). The median survival after initial diagnosis was 21 months (39 months for anaplastic astrocytoma and 18.5 months for glioblastoma) and after reirradiation it was 10 months (17 months for anaplastic astrocytoma and 7.5 months for glioblastoma). In the bivariate analyses, the prognostic factors significantly associated with survival after reirradiation were age, tumour and treatment volume at recurrence, recursive partitioning analyses classification, Karnofsky performance score, histology, and margin to the planning target volume. Only the last four showed significant association in the multivariate analyses. Conclusion. stereotactic radiosurgery is a safe and may be an effective treatment option for selected patients diagnosed with recurrent high-grade glioma. The identified prognostic factors could help individualise the treatment.

Nutrición parenteral domiciliaria en España 2011 y 2012: informe del grupo de nutrición artificial domiciliaria y ambulatoria NADYA

OBJETIVE: To report the data of the Home Parenteral Nutrition (HPN) registry of the NADYA-SENPE working group for the years 2011 and 2012. METHODOLOGY: We compiled the data from the on-line registry introduced by reviewers of NADYA group responsible for monitoring of NPD introduced by since January 1, 2011 to december 31, 2012. Included fields were: age, sex, diagnosis and reason for HPN, access path, complications, beginning and end dates, complementary oral or enteral nutrition, activity level, autonomy degree, product and fungible material supply, withdrawal reason and intestinal transplant indication. RESULTS: Year 2010: 184 patients from 29 hospitals , representing a rate of 3.98 patients/million inhabitants/ year 2011, with 186 episodes were recorded NPD . During 2012, 203 patients from 29 hospitals , representing a rate of 4.39 patients/million inhabitants/year 2012 , a total of 211 episodes were recorded NPD . CONCLUSIONS: We observe an increase in registered patients with respect to previous years.Neoplasia remains as the main pathology since 2003. Although NADYA is consolidated registry and has been indispensable source of information relevant to the understanding of the progress of Home Artificial Nutrition in our country, there is ample room for improvement. Especially that refers to the registration of pediatric patients and the registration of complications.

Plasmapheresis as treatment for hyperlipidemic pancreatitis.

BACKGROUND Severe hypertriglyceridemia with an accumulation of chylomicrons and triglyceride figures >1000 mg/dL can cause acute pancreatitis, a potentially fatal complication. The option of rapid reduction in triglyceride concentrations is attractive and possible with plasmapheresis. METHODS We present the results of an analysis of 11 patients admitted to the intensive care unit with severe hypertriglyceridemic pancreatitis and treated with plasmapheresis. The procedure was repeated until serum triglycerides were below 1000 mg/dL. We recorded anthropometric, clinical data as well as final outcome. RESULTS In eight patients a single plasma exchange was sufficient to reduce triglyceride figures <1000 mg/dL. Only three patients died, all with the worst severity indexes and who experienced the longest delay before the procedure. CONCLUSIONS Our results, together with a review of the literature, confirm the need for a randomized clinical trial to compare conventional treatment vs. plasmapheresis in patients with severe hypertriglyceridemic pancreatitis.

Protocolo de tratamiento de la deficiencia de vitamina D.

Vitamin D deficiency is highly prevalent worldwide and in our country estimated un 60% in the adult population and closer to 80% in the elderly population and the fractured hip.

Association of 25-hydroxyvitamin D with metabolic syndrome in patients with psoriasis: a case-control study.

Vitamin D deficiency is associated with higher cardiovascular risk and metabolic syndrome (MeS) criteria. The main objective of this study was to analyse the association of 25-hydroxyvitamin D (25-OHD) serum levels with MeS (National Cholesterol Education Program-Adult Treatment Panel-III criteria) in 46 Spanish patients with psoriasis, but without arthritis and systemic treatment, and 46 control subjects, matched by sex and age. The patients with psoriasis showed significantly lower level of 25-OHD than controls (30.5 vs. 38.3 ng/ml; p = 0.0001). Patients with MeS had significantly lower serum levels of 25-OHD than those without MeS (24.1 ± 7.5 vs. 32.8 ± 8.9, p = 0.007), and a negative correlation was found between 25-OHD and waist circumference, diastolic blood pressure, fasting glucose, and triglyceridaemia. In the control group no significant correlation between 25-OHD and MeS was found. Al-though the sample was small, our results suggest a potential protective role for 25-OHD in the metabolic profile of patients with psoriasis without arthritis.

Effectiveness of olive oil for the prevention of pressure ulcers caused in immobilized patients within the scope of primary health care: study protocol for a randomized controlled trial.

BACKGROUND Pressure ulcers are considered an important issue, mainly affecting immobilized older patients. These pressure ulcers increase the care burden for the professional health service staff as well as pharmaceutical expenditure. There are a number of studies on the effectiveness of different products used for the prevention of pressure ulcers; however, most of these studies were carried out at a hospital level, basically using hyperoxygenated fatty acids (HOFA). There are no studies focused specifically on the use of olive-oil-based products and therefore this research is intended to find the most cost-effective treatment and achieve an alternative treatment. METHODS/DESIGN The main objective is to assess the effectiveness of olive oil, comparing it with HOFA, to treat immobilized patients at home who are at risk of pressure ulcers. As a secondary objective, the cost-effectiveness balance of this new application with regard to the HOFA will be assessed. The study is designed as a noninferiority, triple-blinded, parallel, multi-center, randomized clinical trial. The scope of the study is the population attending primary health centers in Andalucía (Spain) in the regional areas of Malaga, Granada, Seville, and Cadiz. Immobilized patients at risk of pressure ulcers will be targeted. The target group will be treated by application of an olive-oil-based formula whereas the control group will be treated by application of HOFA to the control group. The follow-up period will be 16 weeks. The main variable will be the presence of pressure ulcers in the patient. Secondary variables include sociodemographic and clinical information, caregiver information, and whether technical support exists. Statistical analysis will include the Kolmogorov-Smirnov test, symmetry and kurtosis analysis, bivariate analysis using the Student's t and chi-squared tests as well as the Wilcoxon and the Man-Whitney U tests, ANOVA and multivariate logistic regression analysis. DISCUSSION The regular use of olive-oil-based formulas should be effective in preventing pressure ulcers in immobilized patients, thus leading to a more cost-effective product and an alternative treatment. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01595347.

Atención al paciente quirúrgico : proceso asistencial integrado

Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Salud / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

Complicated intra-abdominal infections worldwide: the definitive data of the CIAOW Study.

The CIAOW study (Complicated intra-abdominal infections worldwide observational study) is a multicenter observational study underwent in 68 medical institutions worldwide during a six-month study period (October 2012-March 2013). The study included patients older than 18 years undergoing surgery or interventional drainage to address complicated intra-abdominal infections (IAIs). 1898 patients with a mean age of 51.6 years (range 18-99) were enrolled in the study. 777 patients (41%) were women and 1,121 (59%) were men. Among these patients, 1,645 (86.7%) were affected by community-acquired IAIs while the remaining 253 (13.3%) suffered from healthcare-associated infections. Intraperitoneal specimens were collected from 1,190 (62.7%) of the enrolled patients. 827 patients (43.6%) were affected by generalized peritonitis while 1071 (56.4%) suffered from localized peritonitis or abscesses. The overall mortality rate was 10.5% (199/1898). According to stepwise multivariate analysis (PR = 0.005 and PE = 0.001), several criteria were found to be independent variables predictive of mortality, including patient age (OR = 1.1; 95%CI = 1.0-1.1; p < 0.0001), the presence of small bowel perforation (OR = 2.8; 95%CI = 1.5-5.3; p < 0.0001), a delayed initial intervention (a delay exceeding 24 hours) (OR = 1.8; 95%CI = 1.5-3.7; p < 0.0001), ICU admission (OR = 5.9; 95%CI = 3.6-9.5; p < 0.0001) and patient immunosuppression (OR = 3.8; 95%CI = 2.1-6.7; p < 0.0001).