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Several controlled clinical trials have studied the efficacy of topiramate in the treatment of alcoholism. In this paper, we have performed a meta-analysis of those trials in which topiramate was compared with placebo and then we reviewed its efficacy in trials in which it was compared with other drugs.A quantitative synthesis of data was per-formed using inverse variance weighting in a random effects model.Based on three placebo-controlled trials, topiramate is more efficacious than placebo in reducing the percentage of heavy drinking days (23.2%, 95% confidence interval [CI]: 15.7 to 34.4), increasing the number of days of abstinence (mean difference: 2.9 days, 95% CI: 2.5 to 3.3),and lowering the logarithm of g-GT levels (mean difference:0.075 95% CI: 0.048 to 0.118). Two trials suggested that topiramate is also more efficacious than naltrexone, and one open-label study reported better results for disulfiram than for topiramate.Topiramate can be used in alcohol dependence. Adverse effects such as paresthesia or insomnia should be taken into account when prescribing topiramate.Its optimal dosage requires further research.

— A numerical study of the influence of crack surface roughness on fatigue crack closure is presented. Calculations are performed with a research oriented finite difference code suitably modified to study fatigue crack propagation and closure. A powerful algorithm of contact detection is used to ascertain the interaction between the crack surfaces and a penalty forces method is employed to avoid node-to-node and node-to-face penetration. The results indicate that the key controlling factor of roughness-induced fatigue crack closure is the tilt angle between crack branches and the average direction of crack propagation. Crack opening and closure loads increase with the tilt angle, and when plasticity effects are negligible, they are not affected by the crack branch length. Numerical results are also able to explain the large closure levels measured experimentally in 2124 Al alloy fatigue cracks.

To validate the "Risk Quantification of Early Outcome After Lung Transplantation" (RQLT) scale in a cohort of lung transplantation patients.The parameters included in the RQLT scale were recorded prospectively.A total of 74 lung transplant patients in the University Hospital Marquis of Valdecilla (Santander) were analyzed between September 2004 and March 2008.This was the association of the score on the RQLT scale with mortality at 30 days and prolonged ICU stay. The dependent variable of mortality at 30 days was adjustment of scale using the logistic regression model. Diagnostic efficacy was evaluated using the ROC curve and calibration of the system on the sample with the Hosmer and Lemeshow goodness of fit test.The 30-day mortality in lung transplant patients increases significantly as the RQLT score increases, with an odds ratio (OR) of 2.20 (1.24-3.93) for each point increase on the RQLT scale. The area under the ROC curve for 30-day mortality was 0.79 (0.68-0.88; P=0.01). The Hosmer and Lemeshow goodness of fit test described a value p=0.58.The RQLT scale is a useful tool as an indicator of 30-day mortality in transplant patients.

TNF-alpha increases expression of inducible nitric oxide synthase (iNOS) in macrophages and vascular endothelial cells. Under normal conditions, iNOS activity is very low. However, iNOS activity is stimulated during inflammation by cytokines such as TNF-alpha and the amount of NO produced by iNOS may be a 1,000-fold greater than that produced by endothelial NOS. Since functional iNOS gene polymorphisms have been associated with susceptibility to rheumatoid arthritis (RA), drugs blocking TNF-alpha might decrease production of cytotoxic concentrations of NO leading to beneficial effect on RA or its complications. In the present study we investigated whether the infusion of the anti-TNF-alpha-infliximab may yield a short-term effect altering circulating NO oxidation products in patients with severe RA.We investigated 33 RA patients on periodical treatment with infliximab. Serum levels of nitrates, nitrites and NOx (nitrites+nitrates) were determined immediately prior to and after infliximab infusion. Correlation with clinical variables, laboratory markers of inflammation, metabolic syndrome features, adipokines and adhesion molecules was also assessed.Upon infliximab administration, serum NOx concentrations (microM) decreased significantly ([mean+/-SD: 15.0+/-8.8; median: 11.9; interquartile range: 9.2-18.5] before infliximab-time 0 (baseline) and [12.9+/-6.3; 10.9; 7.8-17.2] after infliximab infusion-time 120 minutes; p=0.03). It was also the case for nitrates (9.8+/- 8.3; 7.6; 5.5-10.2] before infliximab and [7.5+/-4.0; 6.6; 5.2-10.0] after infliximab infusion; p=0.008). There was a positive correlation between basal levels of nitrites and leptin concentration prior to infliximab administration. However, no significant correlations between NO oxidation products and clinical or other laboratory variables were found.Our results show, for the first time, a short-term effect of anti-TNF-alpha therapy on the levels of nitric oxide production.

The adipocytokine leptin regulates weight centrally and participates in the regulation of the immune and inflammatory responses. Chronic systemic inflammation is of major importance in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study we investigated whether inflammation, obesity or both of these characteristics are potential determinants of circulating leptin concentrations in a group of RA patients on periodical treatment with the TNF-alpha-blocker-infliximab due to severe disease. We also assessed whether the infusion of infliximab may alter circulating leptin concentrations in patients with severe RA.We investigated 33 patients with RA on periodical treatment with infliximab. Serum leptin levels were determined immediately prior to and after infliximab infusion.There was a positive correlation between body mass index of RA patients and baseline serum level of leptin (rho=0.665, p0.001). Apart from a significant correlation with VCAM-1 (rho=0.349, p=0.04), no significant correlations between baseline leptin levels and the age at the time of the study or at the onset of the disease, disease duration, ESR and CRP levels, DAS28, lipids, insulin sensitivity, adhesion molecules, resistin, adiponectin, ghrelin or the cumulative prednisone dose at the time of the study were found. Leptin levels did not change upon infliximab infusion (p=0.48).In RA patients on TNF-alpha blocker treatment, circulating leptin levels are unrelated to disease activity but constitute a manifestation of adiposity. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by reduction in serum levels of leptin.

To analyze the prevalence and frequency spectrum of the most relevant diseases found in the autopsies of patients who underwent a lung transplant and died in the first month after transplantation. To evaluate the consistency of the pre-and post-mortem diagnoses, comparing them with the Goldman et al. scale modified by Battle et al.Retrospective and longitudinal analysis, comparison of the medical records and records of autopsies of patients who received a lung transplant in our center (University Hospital Marques de Valdecilla) from 1997 to 2007, who died in the early postoperative period (first month post-transplant). The discordance between clinical and pathological diagnosis was classified according to the classification of Goldman et al. and Battle et al. The Student t test for quantitative variables and chi-square for qualitative variables were used for the comparison of the groups.The five class I errors are limited to respiratory diseases: 2 undiagnosed acute rejection, 1 bilateral pulmonary thromboembolism, 1 fat embolism and 1 hemorrhagic infarction of the lung graft. We found a significant difference (p=0.05) between days of survival of patients with group Class I errors (6+/-4.52 days) and patients from the group with no discrepancy (15.42+/-8.99).The short time between transplant and death of the patient reduces the possibility of reaching a correct diagnosis. Because of this information, diagnostic possibilities must be maximized in life-threatening diseases during this period. Therefore, the rate of autopsy studies in this period should be 100%.

Complex interactions between environmental and genetic determinants in both the host immune system and the vasculature may operate modifying the vascular risk in rheumatoid arthritis (RA). An increased incidence of cardiovascular (CV) events in RA patients carrying HLA-DRB1 shared epitope alleles, in particular HLA-DRB1*0404, has recently been found. In the present study we have assessed the potential contribution of inducible and endothelial nitric oxide synthase (NOS2A and NOS3) gene polymorphisms to CV events in a cohort of patients with rheumatoid arthritis (RA). Also, interactions between NOS2A or NOS3 gene polymorphisms and HLA-DRB1 alleles for the risk of developing CV events were assessed.One hundred and eighty-two consecutive patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the Rheumatology outpatient clinic of Hospital Xeral Calde, Lugo, Northwest Spain, between March and September 1996 were included. Patients were genotyped by PCR based techniques for a multiallelic (CCTTT)n repeat in the promoter region of the NOS2A gene and for a T/C polymorphism at position -786 in the promoter region and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the NOS3 gene. They were prospectively followed and clinical records were examined until patient's death or September 1, 2005. At the end of the study 39 (21%) patients had experienced CV events.No significant differences in allele or genotype frequencies for the NOS2A promoter CCTTT repeat microsatellite and NOS3 gene polymorphisms between RA patients with or without CV events were found. However, an increased frequency of CV events was observed in RA patients who carried the HLA-DRB1*0404 allele and were homozygous for the NOS3 (-786) TT genotype (OR: 9.06 [95% CI: 1.29-63.37]; p= 0.03) or for the presence of long NOS2A alleles (OR: 11.7 [95% CI: 1.53-88.4]); p= 0.02).Our results show that NOS2A or NOS3 gene polymorphisms do not infer a direct risk for CV events in RA. However, some interactions between NOS gene polymorphisms and HLA-DRB1 alleles confer and increased risk of developing CV events in patients with RA.

In this paper the 23 longest temperature series on Earth are analyzed: 19 from Europe, 3 from the United Sates and one from India (unique in the intertropical zone). The study is made from a climatological point of view, e. g. for 30-years’ periods: climatological normal (CLINO) and shifted (up to the last one 1978-2007). It is to point out that considering the shifted periods most of the risings in temperature average, maxima and minima highlighted in the CLINO series show no statistical significance, weakening the “global warming” theory.Dans ce travail on analyse les séries thermométriques les plus anciennes de la surface de la Terre : 19 de l’Europe, 3 des Estats Uniés et une de l’ Inde (unique dans la zone intertropicale). L’ étude a eté faite du point de vue de la climatologie, c’ est à dire, pour des périodes de treinte ans, les séries CLINO (climatique normales) et déplacées (finissant en 1978-2007). Les montées des temperatures moyennes, des maxima et des minima aux périodes CLINO n’ ont pas de signification statistique quand on travaille avec des séries déplacées, et la théorie du « réchauffement global » s’ affaiblie. En el presente trabajo se estudia las 23 series termométricas más antiguas de La Tierra, 19 europeas, 3 estadounidenses y 1a índia (única de la zona intertropical), desde un punto de vista climático, esto es considerando los sucesivos treintenios, CLINO y desplazados (hasta el 1978-2007). Destaca el hecho de que en estos últimos la mayor parte de las subidas que en las series CLINO afectan a las medias y a los valores mínimos y máximos de éstas, ya pierden su significación estadística, poniendo en tela de juicio el llamado “calentamiento global”.

The Cali meteorite fall occurred on 6 July 2007 at 21h33m±1m UTC. Some specimens were recovered just after their fall so they are extremely fresh materials. Mineral analysis and bulk chemistry revealed that the measured abundances for most elements closely match the values recorded for other ordinary chondrites classified as H/L. We present here thermoluminescence studies of this recently fallen meteorite in order to get additional information on the radiation environment, and the thermal history of this meteorite. Such information is revealed to be complementary with the range of orbital elements deduced from eyewitness reports of the fireball.

To assess the potential influence of the age in the clinical spectrum of giant cell arteritis (GCA).The case records of all patients diagnosed with biopsy-proven GCA at the Department of Medicine of the Hospital Xeral-Calde (Lugo, Northwest Spain) between 1981 and 2006 were reviewed.During the period of study, 273 Lugo residents were diagnosed with biopsy-proven GCA. The mean age +/- standard deviation at the time of disease diagnosis was 75.1+/-6.8 years (median: 75 years; interquartile range 71-80 years). A longer delay to the diagnosis was observed in patients younger than 70 years of age (13.2+/-12.8 weeks) compared to those 70 years and older (9.4+/-10.2 weeks) (p=0.03). Patients younger than 70 years presented more frequently polymyalgia rheumatica (p=0.02), cerebrovascular accidents (p=0.004), peripheral arteriopathy of recent onset due to large artery stenosis (p=0.03) and high alkaline phosphatase values (p=0.001) than those 70 years and older. Individuals 70-79 years of age at the time of disease diagnosis had ESR values (90.2+/-22.8 mm/1st hour) lower than those observed in patients younger than 70 years (98.3+/-22.2 mm/1st hour) or 80 years and older (99.5+/-20.6 mm/1st hour) (p=0.005). However, no significant differences in the frequency of visual ischemic complications according to the age at the time of disease diagnosis were observed.The results from this study display differences in the clinical spectrum of the disease according to the age of disease onset.

Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study, we investigated whether anti-TNF-alpha antagonist-monoclonal antibody-infliximab administration alters circulating levels of resistin, a proinflammatory adipokine. We further assessed associations of circulating resistin concentrations with CRP and ESR levels, platelet counts and metabolic syndrome and demographic characteristics in RA patients on periodical treatment with infliximab.We investigated 33 patients with RA on periodical treatment with infliximab. Serum resistin levels were determined immediately prior to and after infliximab infusion.Upon infliximab administration, mean (SD) serum resistin concentrations (ng/ml) decreased from 21.9 (9.9) to 17.4 (8.9) (p=0.005). Also, a significant association between the mean ESR (r=0.405; p=0.03) and CRP (r=0.571; p=0.0005) from disease diagnosis and ESR (r=0.486; p=0.004), CRP (r=0.599; p=0.0005) and platelet count (r=0.559; p=0.0007) at the time of the study and baseline resistin levels was found.The present study shows that anti-TNF-alpha therapy results in a rapid reduction of serum resistin levels in patients with RA. It also confirms a close association between laboratory markers of inflammation, particularly CRP and resistin levels. These observations support a potential role of resistin in the inflammatory cascade in RA.

To make an independent evaluation of the capacity for exercise as a predictive factor in lung transplant recipients.Retrospective study.Lung transplant unit of the Intensive Care Unit (ICU) of a university hospital.We analyzed 132 lung transplants in a total of 130 patients. The patients were monitorized up to June 18, 2005 or their death.An evaluation was made of their pre-operative exercise capacity with the 6-minute walking test (6MWT). Long-term survival in relationship with the walking test value was also assessed. The survival curves were estimated using the Kaplan-Meier method. Comparison between curves was made with the Log-Rank methods and the hazard ratios were estimated by Cox regression.The association between mortality and the walking test value showed a hazard ratio of 0.99 (95% CI: 0.99-1.00) per metric unit (meter), (p = 0.282). The patients were classified according to the distance covered in the 4 groups: group 1 (distance covered less than 100 meters), group II (distance covered between 101-200 meters), group III (distance covered between 201 and 300 meters) and group IV (distance greater than 301 meters). No significant differences were found when comparing the survival curves of the four groups (p = 0.709). The multivariant analysis also did not show any statistical significance.We do not believe that the distance covered in the 6MWT conducted in the study protocol in the lung transplant candidates is useful as a marker to predict long-term mortality in patients undergoing lung transplant.

A numerical analysis of plasticity-induced fatigue crack closure based upon the finite difference method is presented. This new method permits modelling easily fatigue crack growth as well as contacts between fracture faces, without requiring sophisticated algorithms. The model is applied to a wide analysis on the influence of mechanical properties of the material (yield stress, strain hardening capacity) and testing conditions (plane stress or strain, stress ratio, maximum load) on plasticity-induced fatigue crack closure. The agreement with other numerical or experimental results when possible is excellent. It is concluded that plasticity-induced crack closure is determined by compressive residual stresses induced behind the crack tip. These residual stresses depend on plastic strains produced in the material as well as on its strain hardening capacity.

A simplified model to study crack growth resistance in cohesive materials has been developed. The model relies on the assumption that the crack displacements are known a priori for different crack lengths. The load-displacement curves are obtained for three point bend specimens and compared with experimental results and numerical calculations performed using the finite element method. The range of validity of the model is discussed.

Objectives To establish the cardiovascular (CV) morbidity and associated risk factors for CV disease (CVD) in Spanish patients with chronic inflammatory rheumatic diseases (CIRD) and unexposed individuals attending rheumatology clinics Methods Analysis of data from the baseline visit of a 10-year prospective study (CARdiovascular in rheuMAtology-CARMA-project) that includes a cohort of patients with CIRD [rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA)] and another cohort of matched individuals without CIRD attending outpatient rheumatology clinics from sixty-seven hospitals in Spain. Prevalence of CV morbidity, CV risk factors and systematic coronary risk evaluation (SCORE) assessment were analyzed Results 2,234 patients (775 RA, 738 AS and 721 PsA) and 677 unexposed subjects were included. A high percentage of patients had low disease activity at the time of recruitment. PsA patients had more commonly classic CV risk factors and metabolic syndrome features than did the remaining individuals. Prevalence of CVD was higher in RA (10.5%) than in AS (7.6%), PsA (7.2%) and unexposed individuals (6.4%). A multivariate analysis adjusted for the presence of classic CV risk factors and disease duration revealed a positive trend for CVD in RA (OR=1.58; 95%CI=0.90-2.76; p=0.10) and AS (OR=1.77; 95%CI=0.96-3.27; p=0.07). Disease duration in all CIRD groups (RA: OR=1.06; 95%CI=1.01-1.11; AS: OR=1.06; 95%CI=1.01-1.06; PsA: OR=1.15; 95%CI=1.07-1.23) and functional capacity (HAQ) in RA (OR=2.15; 95%CI=1.29-3.56; p=0.003) were associated with an increased risk of CVD. Most patients had a moderate CV risk according to the SCORE charts. Conclusions Despite recent advances in the management of CIRD, prevalence of CVD remains increased in Spanish subjects with CIRD attending outpatient rheumatology clinics. Disclosure of Interest S. Castaneda: None declared, M. A. Martin Martinez: None declared, C. Gonzalez Juanatey: None declared, J. Llorca: None declared, M. J. Garcia Yebenes: None declared, S. Perez Vicente: None declared, J. T. Sanchez Costa: None declared, F. Diaz Gonzalez: None declared, M. A. Gonzalez Gay Grant/research support from: This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results and preparation of the manuscript has been done independently of Abbvie. Dr. Gonzalez-Gay9s studies have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748 and PI12/00060, and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain).

Chronic systemic inflammation plays a pivotal role in the development of atherosclerosis in rheumatoid arthritis (RA). Soluble (s) adhesion molecules were found significantly increased in RA patients with active disease. Since increased levels of some adhesion molecules were closely linked to the development of endothelial dysfunction and atherosclerosis and administration of anti-TNF-alpha-infliximab resulted in a rapid and dramatic improvement of endothelial function in long-term infliximab treated RA patients, we assessed whether infusion of the chimeric anti-TNF-alpha infliximab might also yield a rapid and favorable effect on serum levels of soluble adhesion molecules in RA patients periodically treated with this drug because of severe disease.We recruited patients with RA refractory to conventional therapy seen over a period of 2 months at Hospital Xeral-Calde, Lugo, Spain, who were on periodical treatment with infliximab for at least 14 weeks. Blood samples for determination of sICAM-1, sICAM-3, sVCAM-1, sE-selectin, and sP-selectin levels by ELISA were taken immediately before and after infliximab infusion.Thirty-four RA patients (25 women; mean age: 55.4 years; mean DAS28: 4.27) fulfilled the inclusion criteria. Following infliximab infusion a reduction of the overall mean values of the five adhesion molecules was observed. However, when a Wilcoxon signed-rank test was used, only significant differences for sICAM-3 and sP-selectin were observed. In this regard, sICAM-3 and sP-selectin levels fell in 26 (77%) and 28 (82%) of the 34 patients.Our study confirms a rapid and beneficial effect of infliximab infusion on expression of some adhesion molecules in RA patients treated periodically with this anti-TNF-alpha monoclonal antibody because of severe disease.

Endothelial dysfunction has been found in patients with rheumatoid arthritis (RA). In this study we aimed to assess whether adalimumab, a fully human monoclonal antibody directed against TNF-alpha, was able to improve endothelial function in RA patients with long-standing disease refractory to infliximab.Eight RA patients (7 women; range: 24- 74 years) were studied. They had been treated with the chimeric monoclonal anti-TNF-alpha antibody-infliximab for at least 1 year and were switched to adalimumab therapy because of loss of efficacy following periodical treatment with infliximab. Endothelial dependent (EDV) and independent vasodilatation (EIV) were measured by brachial ultrasonography. Patients were assessed prior to (day 0) and at day 2, and weeks 2 and 12 after the onset of adalimumab therapy.Following adalimumab administration a rapid increase in the percentage (%) of EDV was found in all patients (mean +/- SD: 10.1 +/- 5.1% at day 2 compared to 5.8 +/- 4.1% at day 0). At weeks 2 and 12 the %EDV was also significantly increased compared to day 0. All patients showed decrease in the disease activity score 28 and C-reactive protein levels (P = 0.012). Moreover, at week 12 the atherogenic index was reduced in all patients (P = 0.012).Our study confirms that short-term adalimumab therapy yields an active and positive effect on endothelial function in long-standing RA patients with severe disease. This observation emphasizes the potential role of the TNF-alpha blockade in the mechanisms implicated in the development of atherogenesis in RA.

The biodiversity and concentration of environmental fungi in the hospital surgical area was monitored for 36 months. A total of 120 measures were made, 70% of which had fungal growth, a single genus being identified in 62%. Nine different genus were isolated (Penicillium, Aspergillus, Acremonium, Dactylaria, Fusarium, Cladophialophora, Alternaria, Candida and Rodothorula) with a clear predominance of Cladophialophora. Aspects that still must be resolved are discussed. These are: periodicity of the sample obtention, definition of the area of risk, interpretation of the counts and species considered pathogenic. At present, in spite of the large gaps in knowledge, the maintenance of continuous registry system of the environmental biosafety levels is fundamental, since the cause cannot be identified in most of the times when elevated fungal count is detected.

Systemic inflammation, insulin resistance, and endothelial dysfunction have been implicated in the development of cardiovascular disease in rheumatoid arthritis (RA). Since insulin resistance can promote endothelial dysfunction and anti-TNF-alpha blockade yield a rapid improvement of endothelial function, we have sought to assess whether TNF-alpha blockade may also result in a reduction of insulin serum levels and improvement of insulin resistance in RA patients who require this therapy because of severe and refractory disease.We recruited patients with RA seen over a period of 1 month at Hospital Xeral-Calde, Lugo, Spain, that were on treatment with anti-TNF-alpha monoclonal antibody-infliximab. Patients with diabetes mellitus or plasma glucose110 mg/dl were excluded. Fasting blood samples were taken for determination of plasma glucose and serum insulin levels immediately prior to and after infliximab infusion.Twenty-seven RA patients (21 women; mean age: 57.1 years; mean DAS28: 4.43) fulfilled the inclusion criteria. Dramatic reduction in the serum insulin levels and insulin/glucose index was observed following infliximab infusion. Also, a significant improvement of insulin resistance and insulin sensitivity was found.Our study confirms a rapid beneficial effect of infliximab on insulin resistance and insulin sensitivity in RA patients treated periodically with this drug. It may support the long-term use of drugs that act blocking TNF-alpha function to reduce the mechanisms implicated in the development of atherosclerosis in patients with RA.

Aim: to investigate whether flow cytometry could help to define the optimal therapeutic strategy of primary gastric lymphomas. Material and method: retrospective study of 46 patients having primary gastric lymphoma -according to Dawson criteria- in Ann Arbor stage I E and II E, who were surgically treated. From selected paraffin-embedded tissue blocks of the tumor, DNA content was studied by flow cytometry (FC). Other pathological tumor features were analysed by hematoxiline-eosine and Giemsa stains as well as immunohistochemical study; any possible influence on postoperative survival was investigated through statistical analysis. Results: the DNA ploidy pattern was diploid in 40 cases (87%) and aneuploid (hyperdiploid) in 6 (13%). Postoperative survival probability (PSP) was 62.7% at 5 years. Statistical analysis showed significant prognostic value for Ann Arbor classification -with higher PSP for stage I E (p = 0.009)- and FC parameters: diploid tumors had higher PSP than aneuploid tumors. Also tumors having S-phase (p = 0.044) or G2-M phase values (p = 0.023) under the respective mean values had higher PSP. No influence on PSP was found for wall invasion, Helicobacter pylori infection, Isaacson's histologic type or resection margin involvement. No significant relationship was appreciated between Isaacson's histologic type and DNA ploidy patterns. Conclusion: FC could be useful in assessing gastric lymphoma prognosis.

To examine the frequency and predictors of cerebrovascular accidents (CVA) in giant cell arteritis (GCA) patients from a defined population.Retrospective study of biopsy-proven GCA patients diagnosed from 1981 through 2001 at the single hospital for the population of Lugo (Northwest Spain).Thirty (14.3%) of the 210 biopsy-proven GCA patients had CVA, 5 of them (16.7%) involving the vertebrobasilar territory. Five patients (4 of them involving the carotid territory) had CVA within the 2 years prior to the onset of GCA symptoms. Four patients had CVA within the first month after the diagnosis of the disease. Of these, 3 involved the vertebrobasilar territory. Another 5 patients suffered carotid stroke between the 4th and the 12th month after the disease diagnosis. The remaining 16 GCA patients had CVA (all but one involving the carotid territory) at least 1 year after the diagnosis of vasculitis. No differences in the clinical and laboratory features at the time of diagnosis between patients who had CVA and the rest of the biopsy-proven GCA patients were observed. However, hypertension and hyperlipidemia at the time of diagnosis of GCA were associated with the development of CVA (p0.05 for both). Also, anemia at the time of diagnosis (hemoglobin12 g/dL) [hazard ratio = 0.34 (95% CI 0.12 - 1.00; p = 0.05)] was negatively associated with CVA within the first 10 years after the diagnosis of the disease. Mortality in GCA patients with CVA was not significantly higher than that in patients without CVA (hazard ratio = 1.53; p = 0.14).The present study confirms that CVA may occur in GCA. Vertebrobasilar accidents are more common than carotid accidents at the time of diagnosis of the disease. Vascular risk factors should be carefully controlled in the follow-up of GCA patients.

To compare the quality of clinical trials on glaucoma between those evaluating the effectiveness of medical treatments and those evaluating surgical treatments.Clinical trials on glaucoma published in seven international journals between January 1980 and December 1999 were selected. The papers were revised by researchers with a background in epidemiology using a standard qualitative questionnaire. Proportions were compared using Fisher's exact test.Sample size was pre-estimated in 19% of medical treatment trials and 2% of surgical trials (p=0.005); masking (72% vs. 9%; p0.001) and intention-to-treat analysis (17 vs. 0 papers; p0.001) were also more frequent in medical trials. Only 50% of the trials correctly described the patient flow.Quality in clinical trials on glaucoma medical treatment was higher than in surgical trials regarding sample size pre-estimation, masking and intention-to-treat analysis. However, both medical and surgical trials should improve in these aspects and in the patient flow description

One of the main features of Friedreich's ataxia (FA) is phenotypic variability that can now be explained by the molecular mechanism (GAA expansion) underlying the disease.We have analyzed genotype-phenotype correlations in a group of 40 patients homozygous for the GAA expansion.The smaller GAA expansion (GAA1 allele) size correlated with age at onset and progression disease rate, but we found no correlation between the larger GAA expansion (GAA2 allele) size and these clinical parameters. The frequency of pes cavus, scoliosis, axonal sensory neuropathy and areflexia increased with the size of GAA1, whereas some signs such as sphincter disturbances, cerebellar atrophy on MRI, amyotrophy, dysarthria and decreased vibration sense were associated with increased duration of the disease.GAA1 size is the main determinant of FA phenotype and GAA2 size is a poor predictor of clinical variation. Some clinical features are independent of GAA1 and GAA2 sizes and are determined by the duration of the disease.

The main objective was to analyze the influence of social factors on the interval from diagnosis to treatment in a cohort of 217 patients with digestive tract cancer. From the clinical charts data were obtained for: date of the beginning of illness, dates of medical attendance, type and date of diagnostic tests, characteristics of the disease (symptoms, stage), and date of treatment. From the personal interview we gathered information lacking in the clinical charts such as socio-demographic factors, other underlying diseases, and variables related to life style. The information on hospital admission, diagnosis, and treatment was prospectively gathered, whereas data before hospitalization were retrospectively assessed. In statistical analysis the Kruskal-Wallis test and Cox regression were used. The predictors associated with a shorter diagnosis - treatment period were: low social class, lymphatic involvement at diagnosis, first visit at secondary/ tertiary level of health care, no car availability, two or more symptoms at the beginning of disease, sex (male), age (less than 74 years), and diagnosis out of vacation periods. In conclusion, several socio-demographic variables (age, gender, social class, and car availability) influence the interval diagnosis - treatment.

To evaluate the quality of clinical trials on asthma published in Spanish journals in comparison with those published in European or North American English-language journals.Clinical trials were identified by searching MEDLINE and the Spanish Medical Index (Indice Médico Español), and by manual searches for trials mentioned in the bibliographies of the previously identified trials. Quality was assessed by the method proposed by Detsky and colleagues in their 1992 article in Journal of Clinical Epidemiology.The articles published in Spanish journals had lower mean quality scores than those in European or North American English-language journals. Trials published in Spain were less likely to give certain details of methodology, including ethics committee approval, details of randomization or patient enrollment and blinding. Among trials published in Spain, those with non-Spanish authors had lower mean quality scores.Clinical trials published in Spain on asthma treatments are of poorer quality than those published in English-language journals. Editors should consider using clinical trial quality checklists during the peer review process to raise the standards for published articles.

A study was designed to determine significant variables that could be used to predict survival in patients with ruptured abdominal aortic aneurysm.Data of 106 unselected consecutive patients with ruptured abdominal aortic aneurysm undergoing operation between 1989 and 1998 were identified from a prospective hospital-based registry. A total of 32 variables were analyzed including demographic characteristics, vascular risk factors, coexisting conditions, preoperative findings, intraoperative variables, and postoperative complications. Preoperative and intraoperative variables related to vital status (alive, death) in the univariate analysis were subjected to stepwise linear regression analysis to determine whether a combination of variables would predict death. Of 99 evaluable patients, 48 died (mortality rate 48.5%).At univariate analysis, age, serum creatinine, hemoglobin, electrocardiographic ischemia, loss of consciousness on admission, preoperative shock, supra-renal rupture, and transfusion requirements were significantly associated with 30-day operative mortality. Postoperative complications except sepsis, mesenteric ischemia, and neurologic events were significantly associated with mortality. Electrocardiographic ischemia, shock, and supra-renal rupture appeared to be independent predictors of mortality in the multivariate analysis. The cumulative effect of 0, 1, andor = 2 risk factors on mortality was 29%, 39%, and 90%, respectively.Electrocardiographic ischemia, preoperative shock, and supra-renal rupture were predictors of death in patients with ruptured abdominal aortic aneurysm.

Fibre fracture is modelled using either an atomistic approach or a continuum approach. In the first case, three different levels were considered; one-dimensional models applied to polymer fibres, two-dimensional models for nanotube fibres, and three-dimensional models for whiskers. Tensile stresses in commercial fibres are, in general, one order of magnitude below theoretical estimates. This discrepancy is due to the presence of defects, and realistic atomistic modelling should take account of these imperfections. Modelling fibre fracture from a continuum point of view deals first with homogeneous fibres and next with the more involved subject of heterogeneous fibres, stressing the relevance of interfaces, where neither strong nor very weak interfaces give optimum fracture results. Quantitative predictions are mostly based on linear elastic fracture mechanics so they are valid only inside the frame of this theory. The paper ends with some comments on the fracture of biological fibres with a complex hierarchical structure.

The mechanical response of particle-reinforced metal-matrix composites is dictated by the competition between two mechanisms. On the one hand, the composite hardens during deformation as a result of the matrix plastic deformation and of the load transfer from the matrix to the reinforcements. On the other hand, the increase in particle stresses leads to the nucleation of damage in the form of particle fracture, interface decohesion or matrix voiding, which reduce the load bearing capability of the composite. Evidently, the progress of damage during deformation depends on the matrix, reinforcement and interface properties as well as on the external stresses applied on the material.

Background Neoplasms may cause joint symptoms by local compression of the primary tumor or metastases, or paraneoplastic syndrome. In some cases, they appear before thetumor diagnosis and would be helpful to have warning signs or symptoms. Objectives Describe the presence of articular manifestations in later diagnosed cancer patients and their characteristics. Methods Review of medical records of patients seen in outpatient oncology all along 3 years, which in the previous five years were assessed by locomotor symptoms related to subsequent cancer diagnosis. Results 120 patients who met the inclusion criteria were identified. 73% were male and 27% female. 5% were under 30 years old, 30% 30-45 years, 45% 45-60 years, 15% between 60-75 years and 10% over 75 years. 10% of patients had more than 3 months of symptoms before being referred to a specialist, 60% between 3-6 months, 6-12 months 20% and 10% over 12 months. 100% of those under 35 years had more than 6 months of symptoms evolution. In 85% the primary tumor was detected and 15% were diagnosed of unknown primary cancer. Of these 45% had hematologic and 55% non- hematologic malignancies. Of the hematologic neoplasm, 20% were multiple myeloma, 15% leukemias and 5% lymphomas. In the group of solid tumors: 25% prostate, 15% breast, 15% renal, 12% lung, 8% colon, 5% gastric, 3% thyroid and 2% other tumors. Articular symptoms were due to bone metastasis in 100% of solid tumors. None primary bone tumor was descriibed. Generalized arthralgias without arthritis were observed exclusively in hematologic diseases. 45% had low back pain, 20% hip pain, 15% flank pain, 15% polyarthritis and 5% monoarthritis (90% knee). The locations most frequently affected by bone leisons were spine (50%), pelvis (25%), ribs (20%), skull (15%) and long bones (5%), femur and humerus. 96% of patients had multiple metastatic disease. The most frequently accompanying symptoms were weight loss of in 45% of cases, severe asthenia in 60% and fever in 35%. None was significantly related to a particular neoplasia, although 90% of patients which presented with fever were diagnosed of hematologic malignancy; in the remaining 5% fever was due to liver disease or infectious process companion. The most frequent causes of monoarthritis were breast and lung cancer, which together account for 60%. In the case of polyarthritis, leukemias and lymphomas were frecuently detected. For routine analytical performed, the 3 most commonly altered parameters were: anemia 65% in men and women 100%, being 75% lower 10g/dL HB; elevated ESR in 100% of cases, being greater than 80mm/1st h in 80% ( Conclusions The presence of persistent joint clinic over 3 months of unknown cause at any age accompanied by one or more of the following signs: ESR >80, Hb 500 seems to be highly suggestive of occult cancer. A prospective study with more patients is necessary to confirm this hypothesis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5953

The main objective of this cohort study was to analyze the influence of social factors on the interval from the onset of symptoms to diagnosis in the 217 patients with digestive tract cancer. From the clinical charts, the following information was extracted: date of the beginning of illness, dates of medical attendance, type and date of diagnostic tests, characteristics of the disease (symptoms, stage), and date of treatment. From personal interviews we gathered the data not present in the clinical chart: sociodemographic data, information about other underlying diseases, and variables related to lifestyle. The time periods considered were from onset of symptoms to initial consultation (S-C); from initial consultation to hospital admission (C-H); and from hospital admission to diagnosis (H-D). The information on hospital admission, diagnosis, and treatment was prospectively gathered, whereas data before hospitalization were assessed retrospectively. For statistical analysis, we used Kruskal-Wallis test and Cox regression. Pain was the only predictor associated with a shorter S-C period. Hemorrhage, number of symptoms, and hospital consultation significantly shortened the interval C-H. Both hemorrhage and pain, and an initial visit at private primary care were the independent predictors that decreased the period H-D. In conclusion, sociodemographic factors did not influence healthcare attendance.

The objective of this study was to identify the risk factors associated with the nosocomial sepsis syndrome according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference.A 1-year prospective case-control study matched for sex, age (+/- 5 years), and pre-infection hospital stay (+/- 1 day) was performed in a 1,200-bed university hospital. Cases were selected according to the above criteria. Controls were randomly selected from the daily list of hospitalized patients. Crude and adjusted odds ratios (OR) were determined.346 cases and 346 controls were included. Multivariate analysis identified the following intrinsic risk factors: coma in the 48 hours before sepsis (OR: 15.1; CI 95%, 5.6-41.2), renal failure (OR: 3.4; CI 95%; 1.5-10.8), neoplasm (OR: 2.4; CI 95%, 1.1-5.1), prosthesis material (OR: 2.7; CI 95%, 1.0-7.8), and serum albumin concentration at admission lower than 3.1 g/dl (OR: 5.3; CI 95%, 2.3-12.4). Main extrinsic risk factors were: previous nosocomial infection (OR: 12.5; CI 95%, 1.61-96.3), intensive care unit (ICU) stay (OR: 10.6; CI 95%, 3.1-36.2), naso-gastric tube (OR: 8.4; CI 95%, 2.3-31.3), indwelling urinary catheter (OR: 5.0; CI 95%, 1.4-18.9), H2 blockers treatment (OR: 5.0; CI 95%, 1.6-15.2), and IV central line (OR: 4.1; CI 95%, 1.2-14.0).In our study, main risk factors for development of nosocomial sepsis were presence of coma in the 48 hours before sepsis, ICU stay, and prior cross infection during hospitalization.

To examine the outcome and risk factors for renal sequelae in an unselected population of adults with Henoch-Schonlein Purpura (HSP).Retrospective study of adult patients (20 years) with biopsy proved cutaneous vasculitis diagnosed as having HSP seen at a single center between 1984 and 1998. Patients were classified as having HSP according to proposed criteria. Only those patients with a followup of at least 1 year were included in this study of renal sequelae.Twenty-eight patients with a mean followup of 5.5 years fulfilled the inclusion criteria. When the study was concluded, 10 patients (36%) had renal sequelae and 2 (7%) had renal insufficiency. Men outnumbered women. However, neither a previous history of drugs, gender, nor age at disease onset was associated with a higher risk of permanent renal involvement. Patients with hematuria at disease onset or renal involvement during the course of the disease more commonly developed renal sequelae (p0.001). The presence of anemia (p = 0.05) at the time of diagnosis and the onset in summer (p0.05) were also more common in those with permanent renal involvement (renal sequelae). Patients with relapses had also a higher trend to develop renal sequelae (p = 0.07). All patients who fulfilled more than 2 of these 5 risk factors developed permanent renal involvement. With this model we were able to predict renal sequelae in 8 of the 10 patients who had this complication. The Goodman-Kruskal gamma test value was 0.92 (95% CI 0.78-1.00).In unselected adults with HSP, permanent renal involvement (renal sequelae) is not uncommon. Hematuria at disease onset and persistence of renal manifestations during the course of the disease are significant indicators of possible development of renal sequelae. These manifestations plus other features such as onset in summer, anemia at disease onset, or relapses of the disease may predict the development of renal sequelae in most patients.

The goal of this paper is to revise the concept, estimation methods, and interpretations of the population attributable fraction. From the usual formula of the population attributable fraction: (Ip ­ I₀) / Ip, where Ip is the cumulative incidence in the overall population, and I₀ is the cumulative incidence in the non-exposed group, other formulae are presented for use in exposures with more than two levels, and in the presence of confounding factors. Differences in estimation methods between cohort and case-control studies are discussed, and equations to estimate confidence intervals are displayed. Finally, some interpretations -­including the concepts of «etiologic case» and «case in excess», suggested by Greenland and Robbins-­, and some habitual errors are discussed.

To compare two methods in the estimation of the uncertainty in laboratory quality control.A computerized simulation is performed to compare the delta method (suggested by the International Organization for Standardization and the Entidad Nacional de Acreditación) and a bootstrap-based method. The simulation includes several situations with different environmental conditions and different relationships between the analyzed variables.The mean in the coverage obtained by the estimated confidence intervals is higher and closer to the nominal using the bootstrap than using the delta method. The most important differences are observed in the coverage percent distribution: while using the bootstrap, a great number of simulations obtain coverage near the nominal of 95%; using the delta method the coverage are more dispersed, including coverage of 100% in some occasions and lesser than 80% in others. The bootstrap offers very similar results under different conditions, including in the presence of unknown and unmeasured variables or when the analyzed variables are correlated. The delta method shows poorer results in both situations.The uncertainty in the laboratory quality control can be estimated more accurately with bootstrapping than with the delta method.

To examine the clinical spectrum of hypersensitivity vasculitis (HV) in an unselected population of adults and establish differences between patients with HV limited to the skin and those with systemic involvement.Retrospective study of adult patients (20 years) with biopsy-proven cutaneous leukocytoclastic vasculitis diagnosed as having HV, who were seen at the single hospital serving a well defined population between 1984 and 1998. Patients were classified as having HV according to the criteria of Michel et al. (9). To examine outcome and relapses of the disease only those patients with a follow-up of at least 1 year were included in this study.64 patients with a mean follow-up of 4.9 +/- 3.5 (range: 1.1-13.6) years were studied. Ten (15.6%) had visceral involvement (3 gastrointestinal and 7 renal manifestations) during the course of the disease. The remaining patients had a leukocytoclastic vasculitis limited to the skin. When the study was concluded persistent hematuria and proteinuria was only observed in 1 patient and none developed renal insufficiency. Patients with a history of drug treatment and elevated ESR had more systemic complications but the difference was not statistically significant. The outcome was excellent in both patients with HV limited to the skin and in those with systemic complications during the course of the disease.In unselected adults HV is generally a benign disease confined exclusively to the skin. In those patients with systemic manifestations, visceral involvement is generally mild and transient.

The standard anti-HBV vaccination elicits protective anti-HBs levels (above 10 UI/l) in most people. However, the effective duration of immunologic memory is not well-known. Consequently, the recommendations on the postvaccination follow-up are not uniform: from vaccination with no follow-up blood test (anti-HBs levels) to regular follow-up blood tests for all vaccines. In unresponsive subjects a booster dose has been demonstrated to be effective. However, the optimal procedure for management depending anti-HBs levels has not been well established. Postvaccination antibody testing and regular testing for antibodies is recommended only to high-risk subjects, especially to health care workers and subjects with immunodeficiency. In these cases, the booster dose should be administered in nonresponders, and might include double doses. Unanimous consensus does not exist about to the appropriate timing for booster dose administration.

Recent reports indicate that the K variant of the butyrylcholinesterase (BCHE) gene may act in synergism with the epsilon4 allele of apolipoprotein E (APOE) to increase the risk of Alzheimer's disease (AD), but this is controversial.We genotyped for the BCHE-K and APOE epsilon4 alleles in a sample of 249 AD patients and 250 controls derived from the same region in a Spanish population.A protective effect of the K variant of BCHE with an odds ratio of 0.41 (95% confidence interval 0.19-0.86, P=0.02) was observed among non-APOE epsilon4 carriers, but it was limited to women.Our study is the first to demonstrate that lower susceptibility to AD determined by the K variant of BCHE is dependent on gender.