Buenas prácticas organizativas en Atención Primaria : una organización facilitadora de la seguridad clínica

En este capítulo se describen dos experiencias concretas de organización del trabajo en seguridad del paciente en dos áreas sanitarias de dos comunidades autónomas. Cada una tiene ventajas e inconvenientes en el despliegue de la estrategia de seguridad del paciente si bien, cada una tiene la virtud de adaptarse lo mejor posible a las circunstancias organizativas del medio en el que trabaja. La finalidad de ambas experiencias es poner sobre la mesa que la incorporación de la cultura de seguridad del paciente de una manera efectiva no se fundamenta creando estructuras nuevas sino consiguiendo adaptar la realidad existente para que se priorice mejorar la seguridad del paciente en el sistema sanitario

Nonuniversality due to inhomogeneous stress in semiconductor surface nanopatterning by low-energy ion-beam irradiation

A lack of universality with respect to ion species has been recently established in nanostructuring of semiconductor surfaces by low-energy ion-beam bombardment. This variability affects basic properties of the pattern formation process, like the critical incidence angle for pattern formation, and has remained unaccounted for. Here, we show that nonuniform generation of stress across the damaged amorphous layer induced by the irradiation is a key factor behind the range of experimental observations, as the form of the stress field is controlled by the ion/target combination. This effect acts in synergy with the nontrivial evolution of the amorphous-crystalline interface. We reach these conclusions by contrasting a multiscale theoretical approach, which combines molecular dynamics and a continuum viscous flow model, with experiments using Xe+ and Ar+ ions on a Si(100) target. Our general approach can apply to a variety of semiconductor systems and conditions.This work has been partially supported by MICINN (Spain) Grant MAT2011-13333-E, and MINECO (Spain) Grants FIS2012-38866-C05-01, FIS2012-38866-C05-05, FIS2013-47949-C2-2-P and FIS2012-32349. TEM work has been conducted at LABMET laboratory, associated with Red de Laboratorios of CAM, Spain. A.M.-B. acknowledges support from MINECO, through FPI scolarship BES-2010-036179. A.R.C. acknowledges funding from Juan de la Cierva program (Spain) under Contract No. JCI-2012-14509.Publicad

A 3’-UTR polymorphism in soluble epoxide hydrolase gene Is associated with acute rejection in renal transplant recipients

Antecedentes y finalidad: Los ácidos epoxyeicosatrienoic (EETs) son metabolitos del ácido araquidónico que desempeñan una función protectora contra procesos perjudiciales que pueden ocurrir después de re-oxigenación del injerto. Decidimos investigar si la presencia de polimorfismos funcionales en el gen que codifica el epóxido hidrolasa soluble (EPHX2), que metaboliza EETs a menos compuestos activos, pueden jugar un papel importante en el resultado del trasplante renal. Métodos En un grupo de 259 receptores caucásicos de trasplante renal y 183 donantes fallecidos, se determinó la presencia de tres EPHX2 común, a saber, los SNPs rs41507953 (K55R), rs751141 (R287Q) y rs1042032 A/G. Las asociaciones con los parámetros de la función del injerto y la incidencia de rechazo agudo fueron investigados retrospectivamente durante el primer año después del injerto mediante regresión logística, ajustándose a las variables clínicas y demográficas. Resultados Los portadores del genotipo rs1042032 GG muestran significativamente menor tasa de filtración glomerular estimada (eGFR) (38.15 ± 15.57 vs. 45.99 ± 16.05; p = 0,04) y mayores valores de creatinina sérica (1,57 ± 0,58 vs. 1,30 ± 0,47 g/dL; p=0.02) un año después del injerto, en comparación con los pacientes portadores del alelo A wildtype. El mismo genotipo GG también se asoció a un mayor riesgo de rechazo agudo. Curiosamente, esta asociación fue observada por el genotipo de ambos destinatarios [o =6.34 (1.35-29.90); p = 0,015] y donantes [OR = 5.53 (1.10 - 27.80); p=0,042]. Un modelo estadístico incluyendo ambos genotipos junto con otras variables demográficas y clínicas significativas se tradujo en un aumento de la importancia de la asociación con los receptores del genotipo [OR=8,28 (1.21-74.27); p=0,031]. Conclusiones Nuestros resultados indican que la variabilidad genética en el gen metabolizante de EETs, EPHX2, pueden tener un impacto significativo en los resultados del trasplante renal de donante fallecido.Background and Purpose: Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites that play a protective role against damaging processes that may occur after re-oxygenation of the graft. We aimed to investigate whether the presence of functional polymorphisms in the gene encoding soluble epoxy hydrolase (EPHX2), which metabolizes EETs to less active compounds, may play a role in the outcome of renal transplantation. Methods In a group of 259 Caucasian renal transplant recipients and 183 deceased donors, we determined the presence of three common EPHX2 SNPs, namely rs41507953 (K55R), rs751141 (R287Q) and rs1042032 A/G. Associations with parameters of graft function and the incidence of acute rejection were retrospectively investigated throughout the first year after grafting by logistic regression adjusting for clinical and demographic variables. Results Carriers of the rs1042032 GG genotype displayed significantly lower estimated glomerular filtration rate (eGFR) (38.15 ± 15.57 vs. 45.99 ± 16.05; p = 0.04) and higher serum creatinine values (1.57 ± 0.58 vs. 1.30 ± 0.47 g/dL; p=0.02) one year after grafting, compared to patients carrying the wildtype A-allele. The same GG genotype was also associated to increased risk of acute rejection. Interestingly, this association was observed for the genotype of both recipients [OR =6.34 (1.35-29.90); p = 0.015] and donors [OR = 5.53 (1.10- 27.80); p=0.042]. A statistical model including both genotypes along with other meaningful demographic and clinical variables resulted in an increased significance for the association with the recipients’ genotype [OR=8.28 (1.21-74.27); p=0.031]. Conclusions Our results suggest that genetic variability in the EETs-metabolizing gene, EPHX2, may have a significant impact on the outcome of deceased-donor renal transplantation.• Asociación para el Estudio y la Prevención de las Enfermedades Renales (ASEPER), Badajoz • Junta de Extremadura, Consejería de Economía, Comercio e Innovación: Proyecto GR10022 • Red de Investigación Renal - REDINREN (Instituto de Salud Carlos III – Fondo Europeo de Desarrollo Regional – FEDER) : Ayudas a Eliecer Coto García, Carmen Díaz Corte y Carlos López LarreapeerReviewe

Heme oxygenase 1 and 2 common genetic variants and risk for essential tremor

Varios informes sugirieren que una función hemo oxigenasa 1 y 2 de los genes HMOX HMOX1 y 2 modifican el riesgo de desarrollar la enfermedad de Parkinson (EP). Porque el temblor esencial (ET) y PD comparten fenotipo y, probablemente, unos factores etiológicos semejantes, analizamos si tales genes están relacionados con el riesgo de desarrollar ET. Se analizó la distribución de las frecuencias genotípicas y alélicas de los HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363 y rs1051308 HMOX2 polimorfismos de nucleótido único, así como la presencia de variaciones de número de copias de estos genes en 202 sujetos con ET familiar y 747 controles sanos. Las frecuencias alélicas de rs2071746T y R1051308G ET fueron significativamente menores en los pacientes que en los controles. Ninguno de los polimorfismos estudiados influyeron en el comienzo de la enfermedad. El presente estudio sugiere una débil asociación entre HMOX1 rs2071746 y rs1051308 HMOX2 polimorfismo y el riesgo de desarrollar ET en la población española.Several reports suggested a role of heme oxygenase genes 1 and 2 (HMOX1 and HMOX2) in modifying the risk to develop Parkinson disease (PD). Because essential tremor (ET) and PD share phenotypical and, probably, etiologic factors of the similarities, we analyzed whether such genes are related with the risk to develop ET. We analyzed the distribution of allelic and genotype frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 single nucleotide polymorphisms, as well as the presence of copy number variations of these genes in 202 subjects with familial ET and 747 healthy controls. Allelic frequencies of rs2071746T and rs1051308G were significantly lower in ET patients than in controls. None of the studied polymorphisms influenced the disease onset. The present study suggests a weak association between HMOX1 rs2071746 and HMOX2 rs1051308 polymorphisms and the risk to develop ET in the Spanish population.T• Instituto de Salud Carlos III, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324 y RETICS RD12/0013/0002 • Junta de Extremadura: Ayuda GR10068 • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011–2013) • Parcialmente financiado Fondos FEDER – Fondo Europeo de Desarrollo RegionalpeerReviewe

Overview of pneumococcal serotypes and genotypes causing diseases in patients with chronic obstructive pulmonary disease in a Spanish hospital between 2013 and 2016

Background: Streptococcus pneumoniae is an important pathogen in chronic obstructive pulmonary disease (COPD). We aimed at showing the recent changes in the epidemiology of pneumococcal diseases in patients with COPD, especially after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods: From 2013 to 2016, strains causing invasive pneumococcal disease (IPD), non-bacteremic pneumococcal pneumonia (non-BPP), and acute exacerbation of COPD (AE-COPD) were prospectively included. Antimicrobial susceptibility testing, serotyping, and genotyping were analyzed. Results: We collected 345 pneumococci from 286 COPD patients (57 IPD, 78 non-BPP, and 210 AE-COPD). The most frequent serotypes were serotypes 3 (14.0%), 8 (14.0%), and 12F (8.8%) in IPD; serotypes 3 (16.7%), 11A (9%), 9L/N (7.7%), and 23A (7.7%) in non-BPP; and serotypes 11A (11%), nontypeable (11%), and 6C (10%) in AE-COPD. Resistance rates were highest among AE-COPD strains. Penicillin resistance was associated with serotypes 11A (CC156) and 19A (CC320 and CC230). Compared with previous studies, fluoroquinolone resistance in AE-COPD increased (9.5%), PCV13 serotypes decreased (31.6%, 26.9%, and 16.7% for IPD, non-BPP, and AE-COPD, respectively), and serotype 11A-CC156 in AE-COPD and serotype 8 in IPD increased. Conclusion: The epidemiology of pneumococcal disease in COPD changed after the introduction of PCV13 in children. Increases in the highly invasive serotype 8 among patients with IPD and in serotype 11A-CC156 among patients with AE-COPD could compromise the ability of current PCVs to prevent diseases. Vaccines with a greater coverage could improve the benefits of adult vaccination

Heme oxygenase-1 and 2 common genetic variants and risk for restless legs syndrome

Varios neurotransmisores, neuropatológicos, neuroimagen, y los datos experimentales, sugieren que la deficiencia de hierro juega un papel importante en la fisiopatología del síndrome de piernas inquietas (RLS). HMOX (Hemeoxygenases) es un importante mecanismo de defensa contra el estrés oxidativo, principalmente a través de la degradación del hemo a biliverdin, libre de hierro, y monóxido de carbono. Hemos analizado si los genes HMOX1 y HMOX2 están relacionados con el riesgo de desarrollar el síndrome de piernas inquietas. Se analizó la distribución de genotipos y las frecuencias alélicas de los HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363 y rs1051308 HMOX2 SNPs, así como la presencia de variaciones de número de copia (CNVs) de estos genes en 205 sujetos RLS y 445 controles sanos. Las frecuencias de rs2071746 genotipo TT y R2071746T variante alélica fueron significativamente inferiores en los pacientes de SPI que en controles, aunque los otros 3 SNPs estudiados RLS no difirió entre pacientes y controles. Ninguno de los polimorfismos estudiados influyeron en el inicio de la enfermedad, la gravedad de la RLS, historia familiar de SPI, la ferritina sérica, o respuesta a agonistas dopaminérgicos, clonazepam o GABAergic drogas. El presente estudio sugiere una débil asociación entre el polimorfismo rs2071746 HMOX1 y el riesgo de desarrollar el SPI en la población española.Several neurochemical, neuropathological, neuroimaging, and experimental data, suggest that iron deficiency plays an important role in the pathophysiology of restless legs syndrome (RLS). Hemeoxygenases (HMOX) are an important defensive mechanism against oxidative stress, mainly through the degradation of heme to biliverdin, free iron, and carbon monoxide. We analyzed whether HMOX1 and HMOX2 genes are related with the risk to develop RLS. We analyzed the distribution of genotypes and allelic frequencies of the HMOX1 rs2071746, HMOX1 rs2071747, HMOX2 rs2270363, and HMOX2 rs1051308 SNPs, as well as the presence of Copy number variations (CNVs) of these genes in 205 subjects RLS and 445 healthy controls. The frequencies of rs2071746TT genotype and rs2071746T allelic variant were significantly lower in RLS patients than that in controls, although the other 3 studied SNPs did not differ between RLS patients and controls. None of the studied polymorphisms influenced the disease onset, severity of RLS, family history of RLS, serum ferritin levels, or response to dopaminergic agonist, clonazepam or GABAergic drugs. The present study suggests a weak association between HMOX1 rs2071746 polymorphism and the risk to develop RLS in the Spanish population.• Instituto de Salud Carlos III, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324 y RETICS RD12/0013/0002 • Junta de Extremadura: Ayuda GR10068 GR10068 y PRIS10016 (Fundesalud,Mérida, Spain) • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011–2013) • Parcialmente financiado Fondos FEDER – Fondo Europeo de Desarrollo RegionalpeerReviewe

Association between vitamin D receptor rs731236 (Taq1) polymorphism and risk for restless legs syndrome in the Spanish caucasian population

Varios trabajos recientes sugieren un posible papel de la deficiencia de vitamina D en la etiología o el síndrome de las piernas inquietas (RLS). Hemos analizado la posible relación de 2 polimorfismos de un solo nucleótido (SNP) en el receptor de la vitamina D3 (GEN VDR) con el riesgo de SPI. Hemos estudiado la variante alélica genotipo y frecuencias de VDR rs2228570 y rs731236 VDR SNPs en 205 RLS pacientes y 445 controles sanos mediante un ensayo TaqMan. Las frecuencias de los rs731236AAgenotype y la variante alélica rs731236un SPI fue significativamente inferior en los pacientes que en los controles (P<0,005 y 0,01, respectivamente). El síndrome de las piernas inquietas pacientes portadoras de la variante alélica rs731236G había una edad temprana en el inicio, y los portadores del genotipo GG731236rs tuvieron mayor severidad de RLS, aunque estos datos desaparecieron después de los análisis multivariados. Ninguno de los SNPs estudiados estaba relacionada con la positividad de la historia familiar de SPI. Estos resultados sugieren una modesta, pero significativa asociación entre rs731236 VDR SNP y el riesgo de síndrome de piernas inquietas.Several recent works suggest a possible role of vitamin D deficiency in the etiology or restless legs syndrome (RLS). We analyzed the possible relationship of 2 common single nucleotide polymorphisms (SNPs) in the vitamin D3 receptor (VDR) gene with the risk for RLS. We studied the genotype and allelic variant frequencies of VDR rs2228570 and VDR rs731236 SNPs in 205 RLS patients and 445 healthy controls using a TaqMan essay. The frequencies of the rs731236AAgenotype and the allelic variant rs731236A were significantly lower in RLS patients than in controls (P<0.005 and<0.01, respectively). Restless legs syndrome patients carrying the allelic variant rs731236G had an earlier age at onset, and those carrying the rs731236GG genotype had higher severity of RLS, although these data disappeared after multivariate analyses. None of the SNPs studied was related with the positivity of family history of RLS. These results suggest a modest, but significant association between VDR rs731236 SNP and the risk for RLS.• Instituto de Salud Carlos III, Madrid, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324, y RETICS RD12/0013/0002 • Junta de Extremadura: GR15026 y PRIS10016 • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011-2013) • Parciamente financiado con Fondos FEDERpeerReviewe

Association between vitamin D receptor rs731236 (Taq1) polymorphism and risk for restless legs syndrome in the Spanish caucasian population

Varios trabajos recientes sugieren un posible papel de la deficiencia de vitamina D en la etiología o el síndrome de las piernas inquietas (RLS). Hemos analizado la posible relación de 2 polimorfismos de un solo nucleótido (SNP) en el receptor de la vitamina D3 (GEN VDR) con el riesgo de SPI. Hemos estudiado la variante alélica genotipo y frecuencias de VDR rs2228570 y rs731236 VDR SNPs en 205 RLS pacientes y 445 controles sanos mediante un ensayo TaqMan. Las frecuencias de los rs731236AAgenotype y la variante alélica rs731236un SPI fue significativamente inferior en los pacientes que en los controles (P<0,005 y 0,01, respectivamente). El síndrome de las piernas inquietas pacientes portadoras de la variante alélica rs731236G había una edad temprana en el inicio, y los portadores del genotipo GG731236rs tuvieron mayor severidad de RLS, aunque estos datos desaparecieron después de los análisis multivariados. Ninguno de los SNPs estudiados estaba relacionada con la positividad de la historia familiar de SPI. Estos resultados sugieren una modesta, pero significativa asociación entre rs731236 VDR SNP y el riesgo de síndrome de piernas inquietas.Several recent works suggest a possible role of vitamin D deficiency in the etiology or restless legs syndrome (RLS). We analyzed the possible relationship of 2 common single nucleotide polymorphisms (SNPs) in the vitamin D3 receptor (VDR) gene with the risk for RLS. We studied the genotype and allelic variant frequencies of VDR rs2228570 and VDR rs731236 SNPs in 205 RLS patients and 445 healthy controls using a TaqMan essay. The frequencies of the rs731236AAgenotype and the allelic variant rs731236A were significantly lower in RLS patients than in controls (P<0.005 and<0.01, respectively). Restless legs syndrome patients carrying the allelic variant rs731236G had an earlier age at onset, and those carrying the rs731236GG genotype had higher severity of RLS, although these data disappeared after multivariate analyses. None of the SNPs studied was related with the positivity of family history of RLS. These results suggest a modest, but significant association between VDR rs731236 SNP and the risk for RLS.• Instituto de Salud Carlos III, Madrid, Fondo de Investigación Sanitaria: Ayudas PI12/00241, PI12/00324, y RETICS RD12/0013/0002 • Junta de Extremadura: GR15026 y PRIS10016 • Ministerio de Ciencia e Innovación: Ayudas SAF2006-10126 (2006–2009) y SAF2010-22329-C02-01 (2011-2013) • Parciamente financiado con Fondos FEDERpeerReviewe

PREDIRCAM eHealth platform for individualized telemedical assistance for lifestyle modification in the treatment of obesity, diabetes, and cardiometabolic risk prevention: a pilot study (PREDIRCAM 1)

Background: Healthy diet and regular physical activity are powerful tools in reducing diabetes and cardiometabolic risk. Various international scientific and health organizations have advocated the use of new technologies to solve these problems. The PREDIRCAM project explores the contribution that a technological system could offer for the continuous monitoring of lifestyle habits and individualized treatment of obesity as well as cardiometabolic risk prevention. Methods: PREDIRCAM is a technological platform for patients and professionals designed to improve the effectiveness of lifestyle behavior modifications through the intensive use of the latest information and communication technologies. The platform consists of a web-based application providing communication interface with monitoring devices of physiological variables, application for monitoring dietary intake, ad hoc electronic medical records, different communication channels, and an intelligent notification system. A 2-week feasibility study was conducted in 15 volunteers to assess the viability of the platform. Results: The website received 244 visits (average time/session: 17 min 45 s). A total of 435 dietary intakes were recorded (average time for each intake registration, 4 min 42 s ± 2 min 30 s), 59 exercises were recorded in 20 heart rate monitor downloads, 43 topics were discussed through a forum, and 11 of the 15 volunteers expressed a favorable opinion toward the platform. Food intake recording was reported as the most laborious task. Ten of the volunteers considered long-term use of the platform to be feasible. Conclusions: The PREDIRCAM platform is technically ready for clinical evaluation. Training is required to use the platform and, in particular, for registration of dietary food intake

Inhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury

Acetaminophen (APAP)-induced liver injury is one of the most prevalent causes of acute liver failure (ALF). We assessed the role of the bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 in APAP-induced hepatotoxicity. The molecular mechanisms that regulate the balance between cell death and survival and the response to oxidative stress induced by APAP was assessed in cultured human hepatocyte-derived (Huh7) cells treated with pharmacological inhibitors of ALK receptors and with modulated expression of ALK2 or ALK3 by lentiviral infection, and in a mouse model of APAP-induced hepatotoxicity. Inhibition of ALK3 signalling with the pharmacological inhibitor DMH2, or by silencing of ALK3, showed a decreased cell death both by necrosis and apoptosis after APAP treatment. Also, upon APAP challenge, ROS generation was ameliorated and, thus, ROS-mediated JNK and P38 MAPK phosphorylation was reduced in ALK3-inhibited cells compared to control cells. These results were also observed in an experimental model of APAP-induced ALF in which post-treatment with DMH2 after APAP administration significantly reduced liver tissue damage, apoptosis and oxidative stress. This study shows the protective effect of ALK3 receptor inhibition against APAP-induced hepatotoxicity. Furthermore, findings obtained from the animal model suggest that BMP signalling might be a new pharmacological target for the treatment of ALF.This study was supported by grants RTI2018-094203-B-I00 (to AMR), PID2020-11794RB-IOO (to FJC), PID2021-124688OB-I00 (to AMR) and PID2021-122766OB-100 (to AMV) and funded by MCIN/AEI/10.13039/501100011033 (Spain) and “ERDF A way of making Europe” by the European Union; the European Horizon's research and innovation programme HORIZON-HLTH-2022-STAYHLTH-02 under agreement No 101095679, funded by the European Union, and COST Action CA17112, supported by COST (European Cooperation in Science and Technology), to FJC, and contract CP19/00032, and grants PI16/00853 and PI19/00123 from Instituto de Salud Carlos III (ISCIII, Spain), partially funded by FEDER, and CIBERDEM (ISCIII, Spain) to AGR. FJC belongs to the validated Research Groups Ref. 970935 "Liver Pathophysiologÿ, 920631 "Lymphocyte immunobiologÿ, 920361 “Inmunogenética e inmunología de las mucosas” and IBL-6 (imas12-associated). CCF is supported by grant FPU18/03475 from the Ministerio de Universidades (Spain), partially funded by FEDER. PMB is supported by a research contracts (PEJD-2018-PRE/BMD-9500PEJ-2020-AI/BMD-19491) funded by Comunidad de Madrid (Spain). SCI is supported by a predoctoral contract (FI20-00296) from ISCIII/FEDER (Spain).Peer reviewe