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Perez-Yarza E.G.,Hospital Universitario Donostia Instituto Biodonostia | Perez-Yarza E.G.,Research Center Biomedica En Red Of Enfermedades Respiratorias Ciberes | Perez-Yarza E.G.,University of the Basque Country | Castro-Rodriguez J.A.,University of Santiago de Chile | And 49 more authors.
Anales de Pediatria | Year: 2015

Objective: The Childhood Asthma Control Test (c-ACT) is a validated tool for determining pediatric asthma control. However, it is not validated in the Spanish language in Spain. We evaluated the psychometric properties of the Spanish version of the Childhood Asthma Control Test (Sc-ACT) for assessing asthma control in children ages 4 to11. Methods: This national, multicentre, prospective study was conducted in Spain with asthmatic children and their caregivers. Patients were assessed at 3 visits (Baseline, 2 Weeks, and 4 Months). Clinical variables included: symptoms, exacerbations, FEV1, asthma classification, PAQLQ and PACQLQ questionnaire scores, and asthma control as perceived by physicians, patients and caregivers. The Sc-ACT feasibility, validity, reliability, and sensitivity to change were assessed. Results: A total of 394 children were included; mean (SD) time to complete the Sc-ACT was 5.3 (4.4) minutes. Sc-ACT score was correlated with asthma control as perceived by physician (-0.52), patient (-0.53), and caregiver (-0.51) and with the PAQLQ (0.56) and PACQLQ (0.55) scores. Sc-ACT was found to be significantly related to intensity and frequency of asthma symptoms. Cronbach alpha coefficient α was 0.81 and intraclass correlation coefficient was ≥0.85 for all of the items. The global effect size of Sc-ACT was 0.55. The cutoff point scores of 21 or higher indicated a good asthma control and their MCID was 4 points. Conclusion: The Spanish version of the c-ACT was found to be a reliable and valid questionnaire for evaluating asthma control in Spanish-speaking children ages 4 to 11 in Spain. © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.


Hormigo-Pozo A.,Medicina Familiar y Comunitaria | Lopez-Simarro F.,Medicina Familiar y Comunitaria | Aguirre J.C.,Granada | Fernandez M.A.,University of Oviedo | And 32 more authors.
Semergen | Year: 2015

People with type 2 diabetes mellitus have a 2 to 4 times higher risk of developing cardiovascular diseases when compared to general population of similar age and sex. This risk remains after adjustment of other traditional cardiovascular risk factors. The dyslipidemia associated with type 2 diabetes mellitus is present in up to 60% of people with diabetes and contributes greatly to increased cardiovascular, morbidity and mortality risk in these patients. Diabetic dyslipidemia is a disorder of lipid metabolism characterized by an excess of triglycerides, a decrease in HDL-cholesterol and altered lipoprotein composition, consisting mainly in an excess of small, dense LDL particles. Multiple clinical trials have demonstrated the benefits of drug treatment of dyslipidemia (mainly statins) to prevent cardiovascular events and mortality in people with diabetes, both in primary and secondary prevention. This consensus document, developed by general practitioners, members of the Diabetes Group of the Spanish Society of Primary Care Physicians (SEMERGEN), aims to assist in the management of patients with diabetes and dyslipidemia in accordance with the most recent recommendations. © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN).


Zhao J.,University of California at Los Angeles | Giles B.M.,Aurora University | Taylor R.L.,University of Western Australia | Yette G.A.,Aurora University | And 114 more authors.
Annals of the Rheumatic Diseases | Year: 2016

Objectives Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association. Methods Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR. Results The strongest association signal was detected at rs1876453 in intron 1 of CR2 (pmeta=4.2×10-4, OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control pmeta=7.6×10-7, OR 0.71; case-only pmeta=1.9×10-4, OR 0.75). Although allele-specific effects on B cell CR2 mRNA or protein levels were not identified, levels of complement receptor 1 (CR1/CD35) mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR. Conclusions These data suggest that rs1876453 in CR2 has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications.


Zhao J.,University of California at Los Angeles | Wu H.,University of California at Los Angeles | Kaufman K.M.,Cincinnati Childrens Hospital Medical Center | Kelly J.A.,Oklahoma Medical Research Foundation | And 103 more authors.
Clinical Immunology | Year: 2015

Leptin is abnormally elevated in the plasma of patients with systemic lupus erythematosus (SLE), where it is thought to promote and/or sustain pro-inflammatory responses. Whether this association could reflect an increased genetic susceptibility to develop SLE is not known, and studies of genetic associations with leptin-related polymorphisms in SLE patients have been so far inconclusive. Here we genotyped DNA samples from 15,706 SLE patients and healthy matched controls from four different ancestral groups, to correlate polymorphisms of genes of the leptin pathway to risk for SLE. It was found that although several SNPs showed weak associations, those associations did not remain significant after correction for multiple testing. These data do not support associations between defined leptin-related polymorphisms and increased susceptibility to develop SLE. © 2015 Elsevier Inc.


Cara-Fuentes M.,University of Almeria | Machuca-Ariza J.,Malaga | Ruiz-Martos A.,Madrid | Martinez-Lara I.,University of Granada
Medicina Oral, Patologia Oral y Cirugia Bucal | Year: 2016

Background: This study aims to evaluate the technique of sinus bone reformation, which consists of elevating the sinus membrane and placement the implant without bone graft, compared with the widely-used technique involving raising the maxillary sinus and grafting, using animal hydroxyapatite as the filler, while simultaneously fixing the implants. Material and Methods: This is a retrospective study on two groups of patients who underwent elevation of the sinus membrane and simultaneous placement of the implant. The grafting technique was applied to one group, while the other had no graft. An alveolar ridge height of 4 to 7 mm was necessary. Radiological control was undertaken at 6 months and one year post-prosthetic loading. In each group 38 implants were placed. Results: No significant behavioural differences were observed in the implants according to the Albrektsson success criteria. Implant failure was observed in 2 implants from the bone grafting group (success rate 93%) and in 1 implant from the reformation group (success rate 97%). In this group, bone formation was observed on both sides of each implant, the bone gain was measured using image management software (2.7±0.9mm mesial and 2.6±0.9mm distal). There was no correlation between mesial and distal bone gain and implant´s length. Conclusions: The results indicate that bone reformation is a valid technique in cases involving atrophy of the posterior maxilla. Primary stability, maintenance of space by the implant, and the formation of a blood clot are crucial in this technique in order to achieve bone formation around the implant. It is an alternative to the conventional technique of sinus lift with filling material, and has several advantages over this procedure, including a lower infection risk, as it does not involve a biomaterial, reduced cost, a simpler technique, and better acceptance by the patient. © 2015, Medicina Oral, Patologia Oral y Cirugia Bucal. All rights reserved.


Valsesia A.,Merck Serono SA | Valsesia A.,Nestlé | Chatelain P.,University of Lyon | Stevens A.,Royal Manchester Childrens Hospital | And 62 more authors.
European Journal of Endocrinology | Year: 2015

Meta-analysis has shown a modest improvement in first-year growth response to recombinant human GH (r-hGH) for carriers of the exon 3-deleted GH receptor (GHRd3) polymorphism but with significant interstudy variability. The associations between GHRd3 and growth response to r-hGH over 3 years in relation to severity of GH deficiency (GHD) were investigated in patients from 14 countries. Treatment-naïve pre-pubertal children with GHD were enrolled from the PREDICT studies (NCT00256126 and NCT00699855), categorized by peak GH level (peak GH) during provocation test: ≤4 μg/l (severe GHD; n>45) and >4 to <10 μg/l mild GHD; n=49) and genotyped for the GHRd3 polymorphism (full length (fl/fl, fl/d3, d3/d3). Gene expression (GE) profiles were characterized at baseline. Changes in growth (height (cm) and SDS) over 3 years were measured. There was a dichotomous influence of GHRd3 polymorphism on response to r-hGH, dependent on peak GH level. GH peak level (higher vs lower) and GHRd3 (fl/fl vs d3 carriers) combined status was associated with height change over 3 years (P<0.05). GHRd3 carriers with lower peak GH had lower growth than subjects with fl/fl (median difference after 3 years K3.3 cm; K0.3 SDS). Conversely, GHRd3 carriers with higher peak GH had better growth (+2.7 cm; C0.2 SDS). Similar patterns were observed for GH-dependent biomarkers. GE profiles were significantly different between the groups, indicating that the interaction between GH status and GHRd3 carriage can be identified at a transcriptomic level. This study demonstrates that responses to r-hGH depend on the interaction between GHD severity and GHRd3 carriage. © 2015 The authors Published by Bioscientifica Ltd.


PubMed | University of Warsaw, Porto, Malaga, Houston and 11 more.
Type: | Journal: Alimentary pharmacology & therapeutics | Year: 2016

High-quality data on the management of autoimmune hepatitis (AIH) are scarce. Despite published guidelines, management of AIH is still expert based rather than evidence based.To survey expert hepatologists, asking each to describe their practices in the management of patients with AIH.A survey questionnaire was distributed to members of the International AIH Group. The questionnaire consisted of four clinical scenarios on different presentations of AIH.Sixty surveys were sent, out of which 37 were returned. None reported budesonide as a first line induction agent for the acute presentation of AIH. Five (14%) participants reported using thiopurine S-methyltransferase measurements before commencement of thiopurine maintenance therapy. Thirteen (35%) routinely perform liver biopsy at 2 years of biochemical remission. If histological inflammatory activity is absent, four (11%) participants reduced azathioprine, whereas 10 (27%) attempted withdrawal altogether. Regarding the management of difficult-to-treat patients, mycophenolate mofetil is the most widely used second-line agent (n = ~450 in 28 centres), whereas tacrolimus (n = ~115 in 21 centres) and ciclosporin (n = ~112 in 18 centres) are less often reported. One centre reported considerable experience with infliximab, while rescue therapy with rituximab has been tried in seven centres.There is a wide variation in the management of patients with autoimmune hepatitis even among the most expert in the field. Although good quality evidence is lacking, there is considerable experience with second-line therapies. Future prospective studies should address these issues, so that we move from an expert- to an evidence- and personalised-based care in autoimmune hepatitis.

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