Search

The occurrence of furan in commercial baby food samples from the Spanish market was evaluated using an automated headspace solid-phase microextraction method coupled to gas chromatography-mass spectrometry (HS-SPME-GC-MS). A total of 76 baby food samples including infant formula, baby cereals, fruit in cans and/or jars, vegetables, meat, and fish, were surveyed for furan content. The lowest concentration of this compound was found in infant formula (<0.02–0.33 ng ml−1), and cereal-based food (0.15–2.1 ng g−1) while baby food containing fish showed the highest concentrations (19–84 ng g−1). Following recommendation of the European Food Safety Authority (EFSA), the effect on furan content was evaluated of consumer home preparation of foods, heating and handling. Furan concentrations were reduced by up to 35% when samples were heated in a dish using microwave oven and by up to 53% when a hot water bath was used. Finally, we estimated the furan intake from baby food consumption (0.002–1.18 µg kg−1body weight day−1) and we calculated the margin of exposure (MOE) from samples as purchased and also after home preparation of the food. For infant formula and cereal baby foods, the MOEs (26,278–412,776) indicated no infant health concern or priority, while for meat and fish-based baby foods the values pointed to a potential public health risk, even considering the furan losses during preparation at home. [ABSTRACT FROM AUTHOR]

Abstract: The antiproliferative effect of everolimus provides a therapeutic option in the immunosuppression therapy of lung transplantation, by reducing both the risk of acute rejection and the process of progressive fibrosis that determines chronic graft rejection. However, few data on the use of everolimus in lung transplantation have been published to date, and the specific indications of the drug, along with the most adequate time for its introduction or dosing, have not been defined yet. The aim of this article is to propose recommendations for the use of everolimus in lung transplant recipients, including indications, dosing schedules and the use of concomitant immunosuppression. This consensus document has been developed by experts of all the Spanish lung transplant groups from the review of the existing literature and the clinical experience. [Copyright &y& Elsevier]

Background: Demand for home care services has increased considerably, along with the growing complexity of cases and variability among resources and providers. Designing services that guarantee co-ordination and integration for providers and levels of care is of paramount importance. The aim of this study is to determine the effectiveness of a new case-management based, home care delivery model which has been implemented in Andalusia (Spain). Methods: Quasi-experimental, controlled, non-randomised, multi-centre study on the population receiving home care services comparing the outcomes of the new model, which included nurse-led case management, versus the conventional one. Primary endpoints: functional status, satisfaction and use of healthcare resources. Secondary endpoints: recruitment and caregiver burden, mortality, institutionalisation, quality of life and family function. Analyses were performed at baseline, and at two, six and twelve months. A bivariate analysis was conducted with the Student's t-test, Mann-Whitney's U, and the chi squared test. Kaplan-Meier and log-rank tests were performed to compare survival and institutionalisation. A multivariate analysis was performed to pinpoint factors that impact on improvement of functional ability. Results: Base-line differences in functional capacity - significantly lower in the intervention group (RR: 1.52 95%CI: 1.05-2.21; p = 0.0016) - disappeared at six months (RR: 1.31 95%CI: 0.87-1.98; p = 0.178). At six months, caregiver burden showed a slight reduction in the intervention group, whereas it increased notably in the control group (base-line Zarit Test: 57.06 95%CI: 54.77-59.34 vs. 60.50 95%CI: 53.63-67.37; p = 0.264), (Zarit Test at six months: 53.79 95%CI: 49.67-57.92 vs. 66.26 95%CI: 60.66-71.86 p = 0.002). Patients in the intervention group received more physiotherapy (7.92 CI95%: 5.22-10.62 vs. 3.24 95%CI: 1.37-5.310; p = 0.0001) and, on average, required fewer home care visits (9.40 95%CI: 7.89-10.92 vs.11.30 95%CI: 9.10-14.54). No differences were found in terms of frequency of visits to A&E or hospital re-admissions. Furthermore, patients in the control group perceived higher levels of satisfaction (16.88; 95%CI: 16.32-17.43; range: 0-21, vs. 14.65 95%CI: 13.61-15.68; p = 0,001). Conclusion: A home care service model that includes nurse-led case management streamlines access to healthcare services and resources, while impacting positively on patients' functional ability and caregiver burden, with increased levels of satisfaction. [ABSTRACT FROM AUTHOR]

The objectives of this paper are two-fold. First, to elaborate a theoretical model that shows the characteristics of an entrepreneur of quality and the factors that influence them. Second, to apply the model to entrepreneurs in the province of Seville, one of the least developed areas in the European Union. The purpose is to show the importance of entrepreneurship for business success and, more importantly, in economic development. In summary, the model shows that entrepreneurs of quality possess an intrinsic motivation and, as consequence of this, they adopt some energizer behaviours, such as the capacity for innovation, ambition and co-operation with others. The model also takes into account factors that influence these characteristics, including the personal context of the entrepreneur, such as experience, education and family, and the global context, such as productive opportunities, socio-cultural factors and political-institutional factors. In the analysis of the entrepreneurs of Seville, the paper mainly focuses on the motivation and the energizer behaviours and their interdependence. The empirical findings indicate that the model is valid. [ABSTRACT FROM AUTHOR]

Investigates the occurrence of Pestalotia stevensonii on Pinus pinea in Spain. Effect of fungi of the genus Pestalotia on several coniferous tree species; Recovery of fungal isolates from necrotic needles of Pinus pinea; Detection of symptoms when a high concentration of spores is used on adult trees.

Background: Major depressive disorder (MDD) represents a sizable economic burden in Spain. Pharmacogenetic (PGx) screening to guide the choice of antidepressant medication (ADM) in MDD patients yields higher response and remission rates, which could reduce both healthcare and indirect costs., Methods: We built a cost-effectiveness probabilistic Markov model with microsimulation using Tree Age Pro 2022, simulating a patient cohort from the SNHS starting ADM for MDD, and comparing PGx screening before starting ADM versus no screening (No PGx). We carried out a probabilistic sensitivity analysis using the Monte Carlo simulation with microsimulation, set for 1000 iterations and 1000 microsimulation trials, both from societal and healthcare provider perspectives, for a time horizon of 3 years., Results: From a societal perspective, the model estimated a mean cost of 3172.85€ and effectiveness of 2.64 quality-adjusted life years (QALYs) for the No PGx strategy, and a mean cost of 1687.02€ and effectiveness of 2.84 QALYs for the PGx strategy. The mean ICER was -7820.56 €/QALY. From a healthcare provider perspective (no indirect costs considered), the mean cost was 662.62€ for the No PGx strategy, and 446.60€ for the PGx strategy. The mean ICER was -1130.16 €/QALY., Limitations: The heterogeneity of input data from the literature, the need for assumptions of homogeneous distribution of variables and events across population and time, and the inherent limitations of cost-effectiveness analysis should be considered. The model omits combined therapies (ADMs with mood stabilizers, antipsychotics, cognitive behavioral therapy…)., Conclusions: PGx screening in MDD prior to ADM start is a dominant strategy in the SNHS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: F.A.-S. has been consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Aptatargets, Chemo, Cinfa, FAES, Farmalíder, Ferrer, GlaxoSmithKline, Galenicum, Gilead, Italfarmaco, Janssen-Cilag, Kern, Moderna, MSD, Normon, Novartis, Servier, Silver Pharma, Teva, and Zambon. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Genetic variations impact drug response, driving the need for personalised medicine through pre-emptive pharmacogenetic testing. However, the adoption of pre-emptive pharmacogenetic testing for commonly prescribed drugs, such as statins, outside of tertiary hospitals is limited due to a lack of pharmacoeconomic evidence to support widespread implementation by healthcare policy-makers. The Spanish Consortium for the Implementation of Pharmacogenetics (iPHARMGx Consortium) addresses this by developing a clinical trial master protocol that will govern multiple nested adaptive clinical trials that compare genotype-guided treatments to standard care in specific drug-gene-population triads, asses their cost-efficacy and identify novel biomarkers through advanced sequencing techniques. The first of these studies aims to assess whether a pre-emptive statin therapy genotyping scheme reduces the incidence of statin-associated muscle symptoms (SAMS) in a population at risk of cardiovascular disease susceptible of receiving high-intensity or moderate-intensity doses of statins: The PREVESTATGx trial., Methods and Analysis: the PREVESTATGX trial is a multicentre, adaptive randomised controlled pragmatic phase IV clinical trial nested to the iPHARMGx master protocol with two parallel arms, aiming for superiority. Randomisation will be conducted on an individual basis with a centralised approach and stratification by centre. After inclusion in the trial and genotyping has been performed, subjects will be randomly allocated to experimental group (pharmacogenetic genotype-guided statin prescription) or standard-of-care statin prescription (as deemed by attending physician). The main objective is to assess the efficacy of a statin pre-emptive genotyping strategy in reducing the incidence of SAMS. A total of 225 subjects will be recruited among the 10 participating centres if no futility/efficacy boundary is reached in the prespecified interim analyses. Recruitment will be carried out during a 12-month period and subjects will be followed for a 9-month period., Ethics and Dissemination: The PREVESTATGx trial received ethical approval on 24 April 2024. Results will be disseminated via publication in peer-reviewed journals as well as presentation at international conferences. Trial results will be submitted for publication in an open-access peer-reviewed medical speciality-specific publication., Trial Registration Number: EU CT number: 2023-509418-12-00/Clinical trial Identifier (ClinicalTrials.gov): NCT06262685. Protocol version 1.2 12 April 2024 (includes non-substantial modification number 14 June 2024). Trial registration of this study can be located at both the EU Clinical Trials Register available from https:// euclinicaltrials.eu/search-for-clinical-trials/?lang=en and https://clinicaltrials.gov. Registration on both websites was done before the enrolment of the first patient complying with European regulations. EU Clinical Trials Register is a primary registry according to the WHO., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Clinical management of transplant patients abruptly changed during the first months of COVID-19 pandemic (March to May 2020). The new situation led to very significant challenges, such as new forms of relationship between healthcare providers and patients and other professionals, design of protocols to prevent disease transmission and treatment of infected patients, management of waiting lists and of transplant programs during state/city lockdown, relevant reduction of medical training and educational activities, halt or delays of ongoing research, etc. The two main objectives of the current report are: 1) to promote a project of best practices in transplantation taking advantage of the knowledge and experience acquired by professionals during the evolving situation of the COVID-19 pandemic, both in performing their usual care activity, as well as in the adjustments taken to adapt to the clinical context, and 2) to create a document that collects these best practices, thus allowing the creation of a useful compendium for the exchange of knowledge between different Transplant Units. The scientific committee and expert panel finally standardized 30 best practices, including for the pretransplant period (n = 9), peritransplant period (n = 7), postransplant period (n = 8) and training and communication (n = 6). Many aspects of hospitals and units networking, telematic approaches, patient care, value-based medicine, hospitalization, and outpatient visit strategies, training for novelties and communication skills were covered. Massive vaccination has greatly improved the outcomes of the pandemic, with a decrease in severe cases requiring intensive care and a reduction in mortality. However, suboptimal responses to vaccines have been observed in transplant recipients, and health care strategic plans are necessary in these vulnerable populations. The best practices contained in this expert panel report may aid to their broader implementation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Little evidence appears to exist for the use of anakinra, a recombinant interleukin-1 receptor antagonist, after non-response to treatment with corticosteroids alone or combined with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammatory state., Patients and Methods: A retrospective observational cohort study was carried out involving 143 patients with severe COVID-19 pneumonia and moderate hyperinflammation. They received standard therapy along with pulses of methylprednisolone (group 1) or methylprednisolone plus tocilizumab (group 2), with the possibility of receiving anakinra (group 3) according to protocol. The aim of this study was to assess the role of anakinra in the clinical course (death, admission to the intensive care ward) during the first 60 days after the first corticosteroid pulse. Clinical, laboratory, and imaging characteristics as well as infectious complications were also analyzed., Results: 74 patients (51.7%) in group 1, 59 (41.3%) patients in group 2, and 10 patients (7%) in group 3 were included. 8 patients (10.8%) in group 1 died, 6 (10.2%) in group 2, and 0 (0%) in group 3. After adjustment for age and clinical severity indices, treatment with anakinra was associated with a reduced risk of mortality (adjusted hazard ratio 0.518, 95% CI 0.265-0.910; p = 0.0437). Patients in group 3 had a lower mean CD4 count after 3 days of treatment. No patients in this group presented infectious complications., Conclusions: In patients with moderate hyperinflammatory state associated with severe COVID-19 pneumonia, treatment with anakinra after non-response to corticosteroids or corticosteroids plus tocilizumab therapy may be an option for the management of these patients and may improve their prognosis.

In this work, the performance of the atmospheric pressure chemical ionization (APCI) and photoionization (APPI) was assessed to develop a new selective and sensitive gas chromatography-high resolution mass spectrometry (GC-HRMS) method for the determination of polychlorinated naphthalenes (PCNs) in sediment samples. The capability of both APCI and APPI sources for the ionization of PCNs was investigated, showing the formation of the molecular ion and the [M‒Cl+O] ‒ ion in positive and negative ion modes, respectively. Positive ion APCI provided high responses using high corona ion current, while the use of high vapour pressure dopant-solvents, such as toluene in positive mode and diethyl ether in the negative mode, was required to achieve high ionization efficiencies in APPI. The performance of the two API sources in the PCN determination by GC-HRMS were compared and the best results were achieved using the GC-APPI(+)-HRMS (Orbitrap) system. The GC-APPI(+)-HRMS (Orbitrap) method was applied to the characterization of Halowax mixtures and the analysis of marine sediments collected near to the coastal area of Barcelona (NE, Spain), demonstrating a great detection capability with low method limits of detection (0.2-1.6 pg g -1 dry weight), good precision (RSD <15%) and trueness (relative error <13%). Total PCN concentrations ranged from 0.35 to 5.0 ng g -1 dry weight and the presence of related compounds, such as polychlorinated biphenyls (PCBs), was also detected by combining positive and negative ion modes, providing complementary information to better monitor of all PCN congener groups. The results presented here show the feasibility of the GC-APPI-HRMS method for the suitable determination of PCNs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Dabigatran is a direct oral anticoagulant (DOAC) used for the treatment of several thrombotic conditions. To date, very few pharmacogenetic studies on dabigatran were published. We aimed to investigate the influence of 59 polymorphisms in 15 genes (including CES1, UGT and CYP that encode enzymes and ABCB1 and SLC that encode transporters), concomitant treatment with pantoprazole and demographic characteristics (including sex or race) on dabigatran pharmacokinetics and safety., Methods: This was a candidate gene pharmacogenetic study. The study population comprised 107 volunteers enrolled in two dabigatran bioequivalence clinical trials; they were genotyped with a ThermoFisher QuantStudio 12K Flex OpenArray instrument. SPSS software v.21 was used for statistical analysis., Results: Women showed a higher exposure to dabigatran compared to men. The concomitant treatment with pantoprazole was associated with a decreased exposure to the drug. CYP2D6 poor metabolizers (PMs) were related to lower clearance (Cl/F) (p = 0.049) and a tendency was observed towards higher area under the curve (AUC), maximum concentration (C max ) and to lower volume of distribution (V d /F) (p < 0.10). SLC22A1 haplotype was related to pharmacokinetic variability (p < 0.05). The remaining genes (including CYP, UGT1A1 and ABCB1) had no effect on dabigatran pharmacokinetics (p > 0.10). Women showed more adverse drug reactions (ADR) compared to men (0.40 ± 0.68 vs 0.15 ± 0.41 ADR per person, p = 0.03) and SLC22A1 mutant haplotype was related to a lower risk of nausea (p = 0.02)., Conclusion: Sex, concomitant use of pantoprazole and SLC22A1, CYP2D6 and CYP3A5 polymorphism had an effect on dabigatran pharmacokinetics and safety. Previously published pharmacogenetic predictors, namely CES1 or ABCB1 polymorphisms, had no effect on pharmacokinetics and safety. This study is of interest as it increases the scarce pharmacogenetic information on dabigatran.

Introduction: Ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam and ceftolozane-tazobactam are novel antibiotics used to treat infections caused by multidrug-resistant pathogens (MDR). Their use should be supervised and monitored as part of an antimicrobial stewardship programme (ASP). Appropriate use of the new antibiotics will be improved by including consensual indications for their use in local antibiotic guidelines, together with educational interventions providing advice to prescribers to ensure that the recommendations are clearly understood., Methods and Analysis: This study will be implemented in two phases. First, a preliminary historical cohort (2017-2019) of patients from 13 Andalusian hospitals treated with novel antibiotics will be analysed. Second, a quasiexperimental intervention study will be developed with an interrupted time-series analysis (2020-2021). The intervention will consist of an educational interview between prescribers and ASP leaders at each hospital to reinforce the proper use of novel antibiotics. The educational intervention will be based on a consensus guideline designed and disseminated by leaders after the retrospective cohort data have been analysed. The outcomes will be acceptance of the intervention and appropriateness of prescription. Incidence of infection and colonisation with MDR organisms as well as incidence of Clostridioides difficile infection will also be analysed. Changes in prescription quality between periods and the safety profile of the antibiotics in terms of mortality rate and readmissions will also be measured., Ethics and Dissemination: Ethical approval will be obtained from the Andalusian Coordinating Institutional Review Board. The study is being conducted in compliance with the protocol and regulatory requirements consistent with International Council of Harmonisation E6 Good Clinical Practice and the ethical principles of the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and disseminated at national and international conferences., Trial Registration Number: NCT03941951; Pre-results., Competing Interests: Competing interests: ZRPB reports personal fees from Gilead for educational purposes outside the submitted work. PRG and JRB participated in accredited educational activities supported by Merck through unrestricted grants outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19., Methods: In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437., Findings: We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39·0%) were female and the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62-2·41) and risk factors (1·46, 1·23-1·73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77-1·15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64-1·00) or angiotensin-receptor blockers (1·10, 0·88-1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI 0·34-0·80). The adjusted ORs were similar across severity degrees of COVID-19., Interpretation: RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19., Funding: Instituto de Salud Carlos III., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To evaluate co-infection of Strongyloides stercoralis and Trypanosoma cruzi and to assess eosinophilia as a screening test for the detection of S. stercoralis infection in patients with Chagas disease (CD)., Methods: A retrospective diagnostic validation study was performed on serum samples from primary care patients diagnosed with CD in the southern Barcelona metropolitan area. All samples with eosinophilia (n = 87) and a random sample of non-eosinophilic sera (n = 180) were selected. Diagnosis of CD was based on positive serology by means of two tests: ORTHO® T. cruzi ELISA test, and BIO-FLASH® Chagas or Bioelisa CHAGAS. SCIMEDX ELISA STRONGY-96 was used to diagnose strongyloidiasis., Results: Strongyloides stercoralis serology was positive in 15% of patients of whom 95% showed eosinophilia, vs. 21% of those with negative serology (P < 0.001), with differences in the mean eosinophil count (0.49 vs. 0.27 × 10 9 /l). Only 1.1% of patients with CD but without eosinophilia presented positive serology for S. stercoralis, whereas 44% of patients with CD and eosinophilia did (P < 0.001). Sensitivity and specificity values for eosinophilia were thus 95% and 79%, respectively. PPV was 42.5% and NPV, 98.9%., Conclusions: The prevalence of co-infection by T. cruzi and S. stercoralis is not negligible and has probably been underestimated for years in many areas, due to frequently subclinical infections. Therefore, serology seems mandatory for these patients and the use of eosinophilia as initial screening could facilitate the task, decreasing the number of analyses to be performed., (© 2019 John Wiley & Sons Ltd.)

Peñahueca is an athalassohaline hypersaline inland ephemeral lake originated under semiarid conditions in the central Iberian Peninsula (Spain). Its chemical composition makes it extreme for microbial life as well as a terrestrial analogue of other planetary environments. To investigate the persistence of microbial life associated with sulfate-rich crusts, we applied cultivation-independent methods (optical and electron microscopy, 16S rRNA gene profiling and metagenomics) to describe the prokaryotic community and its associated viruses. The diversity for Bacteria was very low and was vastly dominated by endospore formers related to Pontibacillus marinus of the Firmicutes phylum. The archaeal assemblage was more diverse and included taxa related to those normally found in hypersaline environments. Several 'metagenome assembled genomes' were recovered, corresponding to new species of Pontibacillus, several species from the Halobacteria and one new member of the Nanohaloarchaeota. The viral assemblage, although composed of the morphotypes typical of high salt systems, showed little similarity to previously isolated/reconstructed halophages. Several putative prophages of Pontibacillus and haloarchaeal hosts were identified. Remarkably, the Peñahueca sulfate-rich metagenome contained CRISPR-associated proteins and repetitions which were over 10-fold higher than in most hypersaline systems analysed so far., (© 2019 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Individualisation of the therapeutic strategy for the oral antifungal agent voriconazole (VCZ) is extremely important for treatment optimisation. To date, regulatory agencies include CYP2C19 as the only major pharmacogenetic (PGx) biomarker in their dosing guidelines; however, the effect of other genes might be important for VCZ dosing prediction. We developed an exploratory PGx study to identify new biomarkers related to VCZ pharmacokinetics. We first designed a 'clinical practice VCZ-AUC prediction model' based on CYP2C19 to be used as a reference model in this study. We then designed a multifactorial polygenic prediction model and found that genetic variability in FMO3, NR1I2, POR, CYP2C9 and CYP3A4 partially contributes to VCZ total area under the concentration-time curve (AUC 0-∞ ) interindividual variability, and its inclusion in VCZ AUC 0-∞ prediction algorithms improves model precision. To our knowledge, there are no PGx studies specifically relating POR, FMO3 and NR1I2 polymorphisms to VCZ pharmacokinetic variability. Further research is needed in order to test the model proposed here., (Copyright © 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Introduction: Exogenous progesterone is prescribed for a variety of conditions with endogenous progesterone deficiency, e.g. menstrual alterations, primary or secondary infertility or premenopause. To the best of our knowledge, no pharmacogenetic studies have been published in relation to exogenous progesterone pharmacokinetic safety or progesterone metabolites so far., Methods: Candidate-gene study where we evaluated whether five single-nucleotide polymorphisms (CYP2C9*2, *3, CYP2C19*2, *3 and *17) were related to the pharmacokinetics, safety and metabolism of progesterone in 24 healthy volunteers who received a 200-mg progesterone formulation either orally or vaginally., Results: The vaginal formulation had an average AUCt value approximately 18 times greater than the oral formulation. CYP2C19 intermediate metabolizers (IM) consistently showed higher adjusted AUCt and adjusted C max than extensive metabolizers (EM) (P < 0.05); CYP2C9 EM incongruently exhibited higher adjusted C max and longer half-life than IM (p < 0.05)., Conclusion: This is the first study that reports variability in progesterone disposition according to the CYP2C19 and CYP2C9 phenotype. We suggest that CYP2C19 may condition progesterone disposition and that it may be more relevant than CYP2C9. This study lays the foundations for further in-depth research to evaluate the pharmacogenetics of progesterone., Trial Registration: EudraCT numbers are 2012-005105-43 and 2012-005011-10.

Background: the use of proton pump inhibitors (PPI) has increased substantially during the last years, possibly due to a significant proportion of prescriptions that do not follow the approved indications., Objective: to assess the prevalence of PPI prescription and the appropriateness of the prescription within the Emergency Department (ED) of a Spanish university hospital., Materials and Methods: a cross-sectional, retrospective prescription-indication drug-use study was performed, which selected 384 patients that presented to the ED over two days in January 2016., Results: of the total cohort, 23.2% were taking PPI before their hospital visit and only 20.2% had a correct indication and dosage; 2.9% of the patient cohort had an indication for PPI treatment but had not been prescribed them. A drug other than omeprazole was used in 25% of cases; 30.47% of the patients were discharged with a PPI and only 28.2% of them had the correct indication and dosage. Finally, 5.7% were not prescribed PPI even though it was warranted. PPI prescription increased with age whereas the indication for the prescription decreased. Furthermore, the use of these drugs was higher in hospitalized patients compared to discharged patients., Conclusions: these results are in line with similar studies, which demonstrate the existence of an over-prescription of PPI. PPI prescription needs to be improved, thereby reducing drug interactions, adverse effects and unnecessary economical expenses.

P-glycoprotein, encoded by ABCB1, is an ATP-dependent drug efflux pump which exports substances outside the cell. Some studies described connections between C3435T polymorphism T allele and lower P-glycoprotein expression; therefore, homozygous T/T could show higher plasma levels. Our aim was to evaluate the effect of C3435T on pharmacokinetics of 4 antipsychotics (olanzapine, quetiapine, risperidone and aripiprazole) and 4 antidepressants (trazodone, sertraline, agomelatine and citalopram). The study included 473 healthy volunteers receiving a single oral dose of one of these drugs, genotyped by real-time PCR. Multivariate analysis was performed to adjust the effect of sex and genotype of the main cytochrome P450 enzymes. C3435T polymorphism had an effect on olanzapine pharmacokinetics, as T/T individuals showed lower clearance and volume of distribution. T/T individuals showed lower T 1/2 of 9-OH-risperidone, but this difference disappeared after multivariate correction. T/T homozygous individuals showed lower dehydro-aripiprazole and trazodone area under the concentration-time curve, along with lower half-life and higher clearance of trazodone. C/T genotype was associated to higher citalopram maximum concentration. C3435T had no effect on quetiapine, sertraline or agomelatine pharmacokinetics. C3435T can affect the elimination of some drugs in different ways. Regarding risperidone, trazodone and dehydro-aripiprazole, we observed enhanced elimination while it was reduced in olanzapine and citalopram. However, in quetiapine, aripiprazole, sertraline and agomelatine, no changes were detected. These results suggest that P-glycoprotein polymorphisms could affect CNS drugs disposition, but the genetic factor that alters its activity is still unknown. This fact leads to consider the analysis of ABCB1 haplotypes instead of individual variants., (© 2018 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Objective: To assess if serum free 25-hydroxyvitamin D (25OHD) is a better indicator of vitamin D status than total 25OHD in healthy children., Methods: Cross-sectional prospective clinical study was designed. We measured serum free 25OHD concentrations and its correlation with calculated free 25OHD, total 25OHD, intact parathyroid hormone (PTH), and vitamin D binding protein (DBP) in children. The influence of age, sex, ethnicity, body mass index (BMI), season of the year, diet intake, vitamin supplements, time spent outdoors and albumin concentrations on free 25OHD was also analyzed. 241 children aged from 0 days to 14 years, and living in the northern Spain (latitude 43° N), were included., Results: Mean (SD) free 25OHD concentrations were 2.48 (1.39), 5.46 (3.12), 4.12 (1,72), 3.82 (1.43) pg/ml in children aged 0 days, 1 month-2 years, 2-6 years and >6 years, respectively. Correlation between directly measured and calculated free 25OHD was high and significant (r = 0.66) as well as the correlation between serum free and total 25OHD concentrations (r = 0.61). No significant correlation was found between PTH and free 25OHD (r = -0.08). The total 25OHD and PTH concentrations' correlation was inverse (r = -0.25) and significant. Neither free nor total 25OHD concentrations correlated with DBP concentrations. Among the analyzed variables, free 25OHD values were higher in spring/summer than in autumn/winter in children older than 6 years., Conclusions: : These findings do not support that free 25OHD is a better marker of vitamin D deficiency than total 25OHD in healthy pediatric population., Competing Interests: The authors have declared that no competing interests exist.

Background: Vitamin D and vitamin D dependent antimicrobial peptides such as Cathelicidin (LL-37) and β-defensin 2 have an important role in innate and adaptative immunity, but their role in pleural effusions has not been studied before., Methods: Serum and pleural fluid samples from 152 patients with pleural effusion were collected, corresponding to 45 transudates and 107 exudates, 51 infectious effusions (14 complicated and 37 non-complicated), 44 congestive heart failure effusions and 38 malignant effusions. The levels of 25 OH-vitamin D, 1,25-(OH)2-vitamin D, Vitamin D Binding Protein (VDBP), LL-37 and β-defensin 2, both in serum and pleural fluid were evaluated in this prospective study. Differences between groups were analysed using unpaired t tests or Mann-Whitney tests. Correlations between data sets were examined using Pearson correlation coefficient or Spearman rank correlation coefficient. Diagnostic accuracy was estimated using ROC curve analysis., Results: Low serum 25 OH vitamin D levels were found in all groups. Infectious effusions (IE) had higher serum and pleural fluid LL-37 levels compared to congestive heart failure or malignant effusions. Among IE, complicated had higher serum and pleural fluid LL-37 levels, and lower serum β-defensin-2 levels. Positive correlations were found between serum 25 OH-vitamin D levels and serum or pleural 1,25-(OH)2-vitamin D levels, and between 1,25-(OH)2-vitamin D and LL-37 serum. Diagnostic accuracy of the different molecules was moderate at best., Conclusions: Hypovitaminosis D is highly prevalent in pleural effusions. LL-37 is produced intrapleurally in IE. This production is higher in complicated IE. No evidence of pleural production of β-defensin 2 was found in any of the groups. Diagnostic accuracy of the different molecules is at the best moderate for discriminating different types of effusions.

Located on the Iberian Mediterranean coast, El Collado is an open-air site where a rescue excavation was conducted over two seasons in 1987 and 1988. The archaeological work excavated a surface area of 143 m2 where 14 burials were discovered, providing skeletal remains from 15 individuals. We have obtained AMS dates for 10 of the 15 individuals by means of the direct dating of human bones. The ranges of the probability distribution of the calibrated dates suggest that the cemetery was used during a long period of time (781-1020 years at a probability of 95.4%). The new dates consequently set back the chrono-cultural attribution of the cemetery from the initial proposal of Late Mesolithic to an older date in the Early Mesolithic. Therefore, El Collado becomes the oldest known cemetery in the Iberian Peninsula, earlier than the numerous Mesolithic funerary contexts documented on the Atlantic façade such as the Portuguese shell-middens in the Muge and Sado Estuaries or the funerary sites on the northern Iberian coast.

Wintertime trends in mixed layer depth (MLD) were calculated in the Bay of Biscay over the period 1975-2010 using the Simple Ocean Data Assimilation (SODA) package. The reliability of the SODA database was confirmed correlating its results with those obtained from the experimental Argo database over the period 2003-2010. An iso-thermal layer depth (TLD) and an iso-pycnal layer depth (PLD) were defined using the threshold difference method with ΔT = 0.5°C and Δσθ = 0.125 kg/m3. Wintertime trends of the MLD were calculated using winter extended (December-March) anomalies and annual maxima. Trends calculated for the whole Bay of Biscay using both parameters (TLD and PLD) showed to be dependent on the area. Thus, MLD became deeper in the southeastern corner and shallower in the rest of the area. Air temperature was shown to play a key role in regulating the different spatial behavior of the MLD. Negative air temperature trends localized in the southeastern corner coincide with MLD deepening in this area, while, positive air temperature trends are associated to MLD shoaling in the rest of the bay. Additionally, the temperature trend calculated along the first 700 m of the water column is in good agreement with the different spatial behavior revealed for the MLD trend.

In the present work, a simple and fast method for the analysis of linear and cyclic methylsiloxanes in ambient air based on active sampling combined with gas chromatography - mass spectrometry (GC-MS) was developed. The retention efficiency of five sampling sorbents (activated coconut charcoal, Carbopack B, Cromosorb 102, Cromosorb 106 and Isolute ENV+) was evaluated and Isolute ENV+ was found to be the most effective. A volume of 2700 L of air can be sampled without significant losses of the most volatile methylsiloxanes. To improve the sensitivity of the GC-MS method, concurrent solvent recondensation - large volume injection (CSR-LVI), using volumes up to 30 µl of sample extract, is proposed and limits of quantification down to 0.03-0.45 ng m(-3), good linearity (r>0.999) and precision (RSD %<9%) were obtained. The developed method was applied to the analysis of ambient air. Concentrations of linear and cyclic methylsiloxanes in indoor air ranging from 3.9 to 319 ng m(-3) and between 48 and 292668 ng m(-3), were obtained, respectively, while levels from 6 to 22 ng m(-3) for linear and between 2.2 and 439 ng m(-3) for cyclic methylsiloxanes in outdoor air from Barcelona (Spain), were found., (© 2013 Published by Elsevier B.V.)

Background & Objectives: Susceptibility to psoriasis has been associated with the HLA-C*0602 allele, although it may be affected by other polymorphisms., Materials & Methods: We genotyped 142 patients and 160 healthy volunteers to evaluate the possible relationship between susceptibility to psoriasis and the HLA-C*0602 allele and polymorphisms in the TNF, IL12B, and IL23R genes., Results: The frequency of the wild-type TNF-238, TNF-308, and TNF-1031 genotypes was greater in patients with psoriasis than in healthy volunteers, although that of the mutant TNF-857 genotype was higher. The only difference between psoriasis and psoriatic arthritis was TNF-857. The frequency of the HLAC*0602 allele was higher in psoriatic patients than in healthy volunteers. No differences were observed for IL12B and IL23R. Multivariate logistic regression analysis only confirmed these associations for TNF-238, TNF-857, and HLA-C*0602., Conclusion: Our results support an association between susceptibility to psoriasis and TNF polymorphisms in the Spanish population.

Unlabelled: The main purpose was to build a database while facilitating access to genotyping in order to improve the clinical and molecular knowledge of primary tubulopathies. Three tertiary referral centers of Spain collect clinical data through the site http://www.renaltube.com , while offering the analysis of 22 genes corresponding to 23 primary tubulopathies. There are three ways of collaboration: option 1 consists of adding patients to the database with clinical and biochemical information and requesting for genetic study, option 2 requires the payment of a fee for genetic analysis exclusively, and option 3 allows the enrollment of patients with a previously confirmed mutation. After 2 years of activity, RenalTube has collected data from 222 patients, the majority from Spain and Latin America (85.3 %). The most common tubulopathies are distal renal tubular acidosis (22.5 %) and classical Bartter syndrome (19.3 %) followed by familial hypomagnesemia with hypercalciuria and nephrocalcinosis (15.7 %) and Gitelman syndrome (15 %). Option 1 is the collaborating method preferred by doctors (62.3 %) followed by option 3 (36.3 %)., Conclusion: RenalTube is a network-based registry that can be easily reached and filled out worldwide. A web-based approach with a multilateral collaboration scheme enhances the recruitment of data and promotes the understanding of underlying mechanisms of rare inherited diseases, defines more accurate diagnostic and follow-up criteria, develops new molecular techniques and will improve the overall care of the patients.

Pompe disease is an uncommon autosomal recessive glycogen storage disorder caused by deficiency of acid α-glucosidase. Classic infantile form triggers severe cardiomyopathy, hypotonia, and respiratory failure, leading to death within the first two years of life. The majority of patients with Pompe disease have been reported to have point mutations in the GAA gene. We report the first complex deletion-insertion encompassing the complete structure of GAA gene and a large fragment of the gene CCDC40 in a patient with very severe form of Pompe disease. Sequencing analysis of breakpoints allowed us to determine the potential implication of an Alu repeat in the pathogenic mechanism. We suggest that molecular strategy of Pompe disease should include systematic analysis of large rearrangements., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The Spanish Lung Transplant Registry (SLTR) began its activities in 2006 with the participation of all the lung transplantation (LT) groups with active programs in Spain. This report presents for the first time an overall description and results of the patients who received lung transplants in Spain from 2006 to 2010. LT activity has grown progressively, and in this time period 951 adults and 31 children underwent lung transplantation. The mean age of the recipients was 48.2, while the mean age among the lung donors was 41.7. In adult LT, the most frequent cause for lung transplantation was emphysema/COPD, followed by idiopathic pulmonary fibrosis, both representing more than 60% the total number of indications. The probability for survival after adult LT to one and three years was 72% and 60%, respectively, although in patients who survived until the third month post-transplantation, these survival rates reached 89.7% and 75.2%. The factors that most clearly influenced patient survival were the age of the recipient and the diagnosis that indicated the transplantation. Among the pediatric transplantations, cystic fibrosis was the main cause for transplantation (68%), with a one-year survival of 80% and a three-year survival of 70%. In adult as well as pediatric transplantations, the most frequent cause of death was infection. These data confirm the consolidated situation of LT in Spain as a therapeutic option for advanced chronic respiratory disease, both in children as well as in adults., (Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.)

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is an autosomal recessive tubular disorder characterized by excessive renal magnesium and calcium excretion and chronic kidney failure. This rare disease is caused by mutations in the CLDN16 and CLDN19 genes. These genes encode the tight junction proteins claudin-16 and claudin-19, respectively, which regulate the paracellular ion reabsorption in the kidney. Patients with mutations in the CLDN19 gene also present severe visual impairment. Our goals in this study were to examine the clinical characteristics of a large cohort of Spanish patients with this disorder and to identify the disease causing mutations. We included a total of 31 patients belonging to 27 unrelated families and studied renal and ocular manifestations. We then analyzed by direct DNA sequencing the coding regions of CLDN16 and CLDN19 genes in these patients. Bioinformatic tools were used to predict the consequences of mutations. Clinical evaluation showed ocular defects in 87% of patients, including mainly myopia, nystagmus and macular colobomata. Twenty two percent of patients underwent renal transplantation and impaired renal function was observed in another 61% of patients. Results of the genetic analysis revealed CLDN19 mutations in all patients confirming the clinical diagnosis. The majority of patients exhibited the previously described p.G20D mutation. Haplotype analysis using three microsatellite markers showed a founder effect for this recurrent mutation in our cohort. We also identified four new pathogenic mutations in CLDN19, p.G122R, p.I41T, p.G75C and p.G75S. A strategy based on microsequencing was designed to facilitate the genetic diagnosis of this disease. Our data indicate that patients with CLDN19 mutations have a high risk of progression to chronic renal disease.

Background: Hemorrhagic events are frequent in patients on treatment with antivitamin-K oral anticoagulants due to their narrow therapeutic margin. Studies performed with acenocoumarol have shown the relationship between demographic, clinical and genotypic variants and the response to these drugs. Once the influence of these genetic and clinical factors on the dose of acenocoumarol needed to maintain a stable international normalized ratio (INR) has been demonstrated, new strategies need to be developed to predict the appropriate doses of this drug. Several pharmacogenetic algorithms have been developed for warfarin, but only three have been developed for acenocoumarol. After the development of a pharmacogenetic algorithm, the obvious next step is to demonstrate its effectiveness and utility by means of a randomized controlled trial. The aim of this study is to evaluate the effectiveness and efficiency of an acenocoumarol dosing algorithm developed by our group which includes demographic, clinical and pharmacogenetic variables (VKORC1, CYP2C9, CYP4F2 and ApoE) in patients with venous thromboembolism (VTE)., Methods and Design: This is a multicenter, single blind, randomized controlled clinical trial. The protocol has been approved by La Paz University Hospital Research Ethics Committee and by the Spanish Drug Agency. Two hundred and forty patients with VTE in which oral anticoagulant therapy is indicated will be included. Randomization (case/control 1:1) will be stratified by center. Acenocoumarol dose in the control group will be scheduled and adjusted following common clinical practice; in the experimental arm dosing will be following an individualized algorithm developed and validated by our group. Patients will be followed for three months. The main endpoints are: 1) Percentage of patients with INR within the therapeutic range on day seven after initiation of oral anticoagulant therapy; 2) Time from the start of oral anticoagulant treatment to achievement of a stable INR within the therapeutic range; 3) Number of INR determinations within the therapeutic range in the first six weeks of treatment., Discussion: To date, there are no clinical trials comparing pharmacogenetic acenocoumarol dosing algorithm versus routine clinical practice in VTE. Implementation of this pharmacogenetic algorithm in the clinical practice routine could reduce side effects and improve patient safety., Trial Registration: Eudra CT. Identifier: 2009-016643-18.

Background: Several studies have reported an association between tumor necrosis factor α (TNF-α) polymorphisms and inflammatory diseases such as psoriasis vulgaris and psoriatic arthritis, although the results vary according to the population studied. No studies have been performed in the Spanish population., Objective: To analyze the polymorphisms of the promoter region of the TNF-α gene in patients with moderate to severe psorasis and to identify potential differences in genotype compared to a group of healthy volunteers., Material and Methods: Eighty-nine patients with moderate to severe psoriasis and 76 healthy controls with no personal or family history of psoriasis were selected. Polymorphisms of the TNF-α promoter region of both groups were genotyped., Results: We observed a higher prevalence of the genotype with both wild-type alleles at positions -238 (GG genotype, 86.5% vs 70.4%, respectively) and -1031 (TT genotype, 80.2% vs 45.8%, respectively) in patients compared to the healthy control group. The differences at positions -308 and -857 were not significant., Conclusion: There are differences in polymorphisms at positions -238 and -1031 in patients with moderate to severe psoriasis compared to healthy volunteers. This observation provides further support for the importance of the part that TNF-α plays in the pathophysiology of this disease., (Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.)

This paper proposes a new method for the analysis of linear and cyclic methylsiloxanes in water samples based on headspace-solid phase microextraction (HS-SPME) coupled to gas chromatography-mass spectrometry (GC-MS). The extraction efficiency of four commercially available SPME-fibres was evaluated and it was found that a 65 μm polydimethylsiloxane/divinylbenzene (PDMS/DVB) coating was the most suitable for the extraction of siloxanes. The method provided good linearity (r>0.999) and precision (RSD % <17%), and low limits of quantification ranging from 0.01 to 0.74 ng L(-1) for linear siloxanes and between 18 and 34 ng L(-1) for cyclic siloxanes. The HS-SPME-GC-MS method was applied to the analysis of linear and cyclic siloxanes in river waters from Catalonia (NE, Spain) and the results showed concentrations of linear and cyclic siloxanes ranging from 0.09 to 3.94 ng L(-1) and 22.2 to 58.5 ng L(-1), respectively., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Everolimus has potent antifibrotic effects that may potentially affect the clinical course of bronchiolitis obliterans syndrome (BOS) or provide nephroprotective immunosuppressive regimens for lung transplantation., Methods: We retrospectively assessed the 12-month outcomes of the conversion to everolimus among lung recipients in six Spanish centers., Results: From March 2005 to December 2007, 65 lung recipients who were at a mean posttransplantation time of 10.2 ± 7.9 months were converted to everolimus, mainly because of BOS (64.6%) or renal insufficiency (RI; 12.3%). The initial dose of everolimus was 1.9 ± 0.6 mg/d and the mean blood trough levels were stable over time (6.4 ± 2.8 ng/mL at 12 months). Conversion to everolimus allowed us to eliminate the calcineurin inhibitor (CNI) in 21% of patients. Among the overall population, the forced expiratory volume at 1 second (FEV(1)) and renal function remained stable. Mean FEV(1) did not change among the 35 (81%) patients surviving BOS at 12 months: preconversion FEV(1): 1.449.5 ± 641.9 mL vs 12-month FEV(1): 1420.0 ± 734.6 mL (P = .866). There was a significant improvement in renal function among the RI patients with mean glomerular filtration rates of 42.2 ± 15.2 mL/min/1.73 m(2) (P = .043) at 6 and 44.4 ± 18.8 mL/min/1.73 m(2) at 12 months, (P = .063) and a decrease in the use of CNIs from 1% of RI patients preconversion to 57% at 6 and 75% at 12 months. With a mean of 8.1- months follow-up (range: 1-31.3) overall survival was 84.6% at 1 year and 50% at 22.3 months. Progressive BOS was the main cause of death. Reasons for everolimus discontinuation were patient death (n = 10), lack of efficacy (n = 4), gastrointestinal adverse events (n = 2), and edema (n = 2)., Conclusions: BOS and RI were the main indications for conversion to everolimus among lung recipients. Conversion to everolimus improved renal function among patients converted because of RI. The present results were inconclusive regarding effects of everolimus on BOS., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Three IL-10 gene promoter single nucleotide polymorphisms -1082G > A, -819C > T and -592C > A and the haplotypes they define in Caucasians, GCC, ACC, ATA, associated with different IL-10 production rates, have been linked to schizophrenia in some populations with conflicting results. On the basis of the evidence of the sex-dependent effect of certain genes in many complex diseases, we conducted a sex-stratified case-control association study to verify the linkage of the IL-10 gene promoter SNPs and haplotypes with schizophrenia and the possible sex-specific genetic effect in a Spanish schizophrenic population., Methods: 241 DSM-IV diagnosed Spanish schizophrenic patients and 435 ethnically matched controls were genotyped for -1082G > A and -592C > A SNPs. Chi squared tests were performed to assess for genetic association of alleles, genotypes and haplotypes with the disease., Results: The -1082A allele (p = 0.027), A/A (p = 0.008) and ATA/ATA (p = 0.003) genotypes were significantly associated with schizophrenia in females while neither allelic nor genotypic frequencies reached statistical significance in the male population., Conclusions: Our results highlight the hypothesis of an imbalance towards an inflammatory syndrome as the immune abnormality of schizophrenia. Anyway, a better understanding of the involvement of the immune system would imply the search of immune abnormalities in endophenotypes in whose sex and ethnicity might be differential factors. It also reinforces the need of performing complex gene studies based on multiple cytokine SNPs, including anti and pro-inflammatory, to clarify the immune system abnormalities direction in the etiology of schizophrenia.

This article seeks to provide an in depth review about one of the most revolutionary and influential methods used in understanding the variables and processes that explain human health. Based on a new vision in the analysis of the consequences of the Nazi Holocaust, a doctor-sociologist--Aaron Antonovsky--managed to influence medicine and behavioral science by facilitating the keys for the optimal development of public health today. Despite the fact that this theory began appearing in the 1970s in the 20th century, its real development and expansion have been seen in recent years. In fact, in Spain, there is little scientific literature that analyses the theoretic keys of the model in depth. This work seek to cover this gap; to achieve this objective, it first presents how the construct of salutogenesis arose, the social-cultural context that promoted it, as well as the importance public health acquires today. This is the aim of this work, which analyses the theoretical bases of the salutogenesis model, with specific emphasis on its background and precursors, as well as its inception, development and current expansion.

Aims: How genes affect the response in a patient to a given medication is still poorly understood; the validation of biomarkers and technologies need to be performed. This study aims to determine the analytical characteristics of PHARMAChip(®), a newly developed pharmacogenetic array, and the Spanish population allelic and genotypic frequencies of the genetic variants included in this chip., Materials & Methods: The analytical characteristics of PHARMAChip assessed were sensitivity and specificity (for CYP2D6 and SLC6A4), accuracy (for SLC6A4) and genotyping rate: frequencies of the 90 pharmacogenetic variants of 36 genes were included in PHARMAChip. These were compared in 449 Spanish subjects with data reported in Caucasians., Results & Conclusion: Sensitivity and specificity ranged from 96-100%, accuracy was 94.8% and genotyping success rate was 99.6%. PHARMAChip is an accurate, rapid and updatable tool, which may be especially useful for cytochrome P450 testing. The allelic and genotypic frequencies found in the Spanish subjects reinforce the need for establishing possible intraethnic differences among populations prior to performing this kind of study.

ALSFRS-R is a tool designed to measure disease progress in ALS patients. It consists of 12 items grouped into four functions designed to assess disabilities according to the Activities of daily living (ADL). Our objective was to validate the Spanish version of ALSFRS-R based on the original version. Four examiners assessed 73 ALS patients, applying the ALSFRS-R, ALSAQ-40 and the respiratory function variable assessed by the SRI scale, which measures respiratory insufficiency. Internal consistency and test-retest correlations were measured using Cronbach's alpha and Spearman's Rho tests. Factor analysis was performed by applying Varimax rotation and Kaiser standardization. Validity was analysed based on correlations between items in the ALSFRS-R scales and equivalents in the ALSAQ-40 and SRI questionnaires. The results showed high internal consistency (0.77-0.95) and a good test-retest correlation (0.80-0.95). Factor analysis showed a 73.3% principal component contribution; the weight of each item regarding their corresponding factors was 0.7-0.9. High correlations were observed (rs >0.60) between corresponding factors of ALSFRS-R/ALSAQ-40 and ALSFRS-R/SRI. We conclude that the version obtained from the ALSFRS-R maintains the internal consistency and validity of the construct of the original scale. The Spanish version of ALSFRS-R is available for readers at http://www.fundela.es/verOtras.php.

The number of patients awaiting lung transplantation has steadily increased over the past decade, but the number of donors has remained relatively stable. Owing to the increasing scarcity of donor lungs, especially for pediatric and small adult recipients, advanced operative strategies for the use of larger grafts for smaller recipients have been developed. Size matching between donors and recipients represents one of the organ distribution criteria widely accepted by lung transplantation teams. However, in some cases it is not possible to allocate a donor to the corresponding size-compatible recipient. To avoid possible complications derived from the implantation of oversized lungs into smaller recipients, various methods of downsizing are applied for cadaveric donor lungs, such as lobar transplantation. We review our experience in 6 patients undergoing volume reduction of the lung graft by lobar resection at the time of transplantation. Graft volume reduction by anatomic resection (lobar transplantation) is a reliable and safe procedure to overcome size disparities between the donor and the recipient of a lung transplant, and thus to maximize the number of donors., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Ruidera Pools Natural Park, Spain, constitutes one of the most representative systems of carbonate precipitation in Europe. The prokaryotic community of a dry modern stromatolite recovered from the park has been analyzed by molecular techniques that included denaturing gradient gel electrophoresis (DGGE) and 16S rRNA gene clone library analysis, together with microscopic observations from the sample and cultures. Ribosomal RNA was directly extracted to study the putatively active part of the microbial community present in the sample. A total of 295 16S rRNA gene sequences were analyzed. Libraries were dominated by sequences related to Cyanobacteria, most frequently to the genus Leptolyngbya. A diverse and abundant assemblage of non-cyanobacterial sequences was also found, including members of Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Acidobacteria,Planctomycetes and Chloroflexi groups. No amplification was obtained when using archaeal primers. The results showed that at the time of sampling, when the pool was dry, the bacterial community of the stromatolites was dominated by groups of highly related Cyanobacteria, including new groups that had not been previously reported, although a high diversity outside this phylogenetic group was also found. The results indicated that part of the Cyanobacteria assemblage was metabolically active and could thus play a role in the mineralization processes inside the stromatolites.

Unlabelled: Intravenous immunoglobulin (IVIG) use in non-approved indications, the increase in consumption and its high cost recommend rationalisation in its utilisation., Aims: To assess the use of IVIG in Spanish hospitals., Methods: An observational, prospective and multicentre drug utilisation study was conducted in 13 tertiary Spanish hospitals. Data were collected for 3 months in patients receiving any IVIG. Patient demographics, indication for IVIG use, dosage regimen and cost of treatment were collected., Results: Five hundred and fifty-four patients (mean age of 52 years) were included in the study. A total of 1,287 prescriptions were administered, and the average number of prescriptions per patient was 2.3. The mean daily dose was 24 g (range 0.6-90 g). Overall, IVIG was prescribed for authorised indications in 335 patients (60%) with 953 prescriptions (74%), for non-authorised indications with scientific evidentiary support in 86 patients (16%) with 137 prescriptions (11%), and non-authorised and non-accepted indications in 133 patients (24%) with 197 prescriptions (15%). The most frequent authorised indications were primary and secondary immunodeficiencies, and the most frequent non-authorised and non-accepted indications were multiple sclerosis and bullous dermatosis. The mean cost of IVIG per patient for authorised indications was 2,636.2 , non-authorised indications with scientific support 5,262.1 and non-accepted indications 3,555.8 ., Conclusions: IVIG is prescribed for a significant number of non-authorised and non-accepted indications with a notable cost. There is an important variability in IVIG prescriptions between hospitals, indicating room for improvement in IVIG use and the need for a consensus of protocol use.

Sex differences in body image, weight control and Body Mass Index of Spanish adolescents. This research paper studied the differences among 21,811 adolescents (between the ages of 11 and 18) in key variables in the development of eating disorders, including the Body Mass Index, the perception of and satisfaction with their body image, and the behaviours used to control weight. In spite of the fact that the girls had a better adjusted BMI and a lesser degree of overweight and obesity, we found that they perceived themselves as being fatter, were less satisfied with body image, and the ones who dieted the most to lose weight. On the other hand, we found that the main reason for boys and girls to diet in an effort to lose weight was not their real body weight, but rather their perception of their own bodies, followed by just how satisfied they were with their bodies. Therefore, important differences are revealed between boys and girls in this article, which must be taken into consideration in the design and development of the various programs that are aimed at the prevention of problems with body image and diet behaviour.

Hereditary hypophosphatemic rickets with hypercalciuria is a rare autosomal recessive disorder (OMIM #241530), characterized by decreased renal phosphate reabsorption that leads to hypophosphatemia, rickets, and bone pain; hypophosphatemia is believed to stimulate 1,25 dihydroxyvitamin D synthesis which, in turn, results in hypercalciuria. Hereditary hypophosphatemic rickets with hypercalciuria is caused by loss-of-function in the type 2c sodium phosphate cotransporter encoded by the SLC34A3 gene. This report shows a family with a non-previously identified mutation in the SLC34A3 gene and exhibiting mild and different manifestations of HHRH. The probandus had hypophosphatemia, elevated serum 1,25 dihydroxyvitamin D concentrations, high serum alkaline phosphatase levels, hypercalciuria and nephrocalcinosis. The other members of the family presented some of these alterations: the mother, hypercalciuria and high 1,25 dihydroxyvitamin D concentrations; the son, hypercalciuria, high 1,25 dihydroxyvitamin D values and elevated alkaline phosphatases; the father, high alkaline phosphatases. The genetic analysis revealed the existence of a single mutation (G78R) in heterozygosis in the SLC34A3 gene in the probandus, her mother and her brother, but not in the father. These findings suggest that he mutation in heterozygosis likely gave rise to a mild phenotype with different penetrance in the three relatives and also indicates that the elevation of 1,25 dihydroxyvitamin D does not result from hypophosphatemia. Thus, this family raises some issues on the transmission and pathophysiology of hereditary hypophosphatemic rickets with hypercalciuria.

Trifolium species are the most common legumes present in wild Spanish soils; however, there are no studies to date on the diversity of rhizobia nodulating clover in Spain. Twenty strains from different Spanish soils with acidic, neutral, and basic pH were selected to study their genotypic, phenotypic, and symbiotic features. The results showed that the isolates were genotypically diverse, displaying 12 different DNA fingerprint patterns and also 14 different plasmid profiles. Although they have 16S rRNA gene sequences that are nearly identical to that of the type strain of Rhizobium leguminosarum, their recA and atpD gene sequences were phylogenetically divergent from those of R. leguminosarum reference strains, and phenotypic divergence as well as different host ranges were also found. Although most of them nodulated both Trifolium and Phaseolus, only 5 strains were also able to nodulate Pisum. The results of the effectiveness analysis showed a high variability in the symbiotic characteristics of our strains and suggested that Pisum is the more restrictive host of this group. Interestingly, some of the Trifolium isolates showed an ability to promote growth of Pisum in the absence of nodulation.

Background: The information generated by nurses through standardised nursing languages is insufficiently evaluated and exploited, mainly in home care services, as is its potential impact on outcomes., Objectives: To find out how often nursing diagnoses are made during nursing home care visits, and to explore their relation with use of resources, mortality, institutionalisation and satisfaction., Design: Observational, longitudinal follow-up study., Settings: Home care services delivered by Primary Healthcare Districts in Málaga, Costa del Sol, Almería and Granada, in Spain., Participants: Patients and caregivers who initiated the Home Care Programme., Methods: The accumulated incidence of nursing diagnosis was analysed over 34 months of follow-up. Diagnoses were made by nurse case managers in their daily practice. Several regression models were devised to analyse their linkage with the use of resources, mortality, institutionalisation and satisfaction., Results: Two hundred and forty-seven subjects were included (129 patients and 118 caregivers). 93.8 had been diagnosed (2.8 diagnoses per subject). Risk of caregiver strain and mobility impairment accounted for 40% of total home visits (p=0.033). Significant differences were observed in the use of physiotherapy and rehabilitation services. The home visits for caregivers were, in 78% of cases, due to the recipient's baseline functional status. No relation was detected for institutionalisation or for patient satisfaction. There was a higher rate of anxiety diagnosed in the caregiver when the recipient was at greater risk for mortality (RR: 2.08 CI 95%: 1.26-3.42) (p=0.012)., Conclusions: These data confirm results from other studies which find nursing diagnoses to be sound predictors of resources use. Their synergy with other case-mix systems in home care should be investigated.