A thorough investigation of the switching dynamics of TiN/Ti/10 nm-HfO2/W resistive memories

Producción CientíficaThe switching dynamics of TiN/Ti/HfO2/W-based resistive memories is investigated. The analysis consisted in the systematic application of voltage sweeps with different ramp rates and temperatures. The obtained results give clear insight into the role played by transient and thermal effects on the device operation. Both kinetic Monte Carlo simulations and a compact modeling approach based on the Dynamic Memdiode Model are considered in this work with the aim of assessing, in terms of their respective scopes, the nature of the physical processes that characterize the formation and rupture of the filamentary conducting channel spanning the oxide film. As a result of this study, a better understanding of the different facets of the resistive switching dynamics is achieved. It is shown that the temperature and, mainly, the applied electric field, control the switching mechanism of our devices. The Dynamic Memdiode Model, being a behavioral analytic approach, is shown to be particularly suitable for reproducing the conduction characteristics of our devices using a single set of parameters for the different operation regimes.Ministerio de Ciencia e Innovación de España - FEDER [PID2022-139586NB-C41, PID2022-139586NB-C42, PID2022-139586NB-C43, PID2022-139586NB-C44]Consejería de Conocimiento, Investigación y Universidad, Junta de Andalucía [B-TIC-624-UGR20]Consejo Superior de Investigaciones Científicas (CSIC)- FEDER [20225AT012]Ramón y Cajal grant number RYC2020-030150-IEuropean project MEMQuD (code 20FUN06) which has received funding from the EMPIR programme co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation programme

Clinical and Ecological Impact of an Educational Program to Optimize Antibiotic Treatments in Nursing Homes (PROA-SENIOR): A Cluster, Randomized, Controlled Trial and Interrupted Time-Series Analysis

[Background] Antimicrobial stewardship programs (ASPs) are recommended in nursing homes (NHs), although data are limited. We aimed to determine the clinical and ecological impact of an ASP for NHs.[Methods] We performed a cluster, randomized, controlled trial and a before–after study with interrupted time-series analyses in 14 NHs for 30 consecutive months from July 2018 to December 2020 in Andalusia, Spain. Seven facilities implemented an ASP with a bundle of 5 educational measures (general ASP) and 7 added 1-to-1 educational interviews (experimental ASP). The primary outcome was the overall use of antimicrobials, calculated monthly as defined daily doses (DDD) per 1000 resident days (DRD).[Results] The total mean antimicrobial consumption decreased by 31.2% (−16.72 DRD; P = .045) with respect to the preintervention period; the overall use of quinolones and amoxicillin–clavulanic acid dropped by 52.2% (P = .001) and 42.5% (P = .006), respectively; and the overall prevalence of multidrug-resistant organisms (MDROs) decreased from 24.7% to 17.4% (P = .012). During the intervention period, 12.5 educational interviews per doctor were performed in the experimental ASP group; no differences were found in the total mean antimicrobial use between groups (−14.62 DRD; P = .25). Two unexpected coronavirus disease 2019 waves affected the centers increasing the overall mean use of antimicrobials by 40% (51.56 DRD; P < .0001).[Conclusions] This study suggests that an ASP for NHs appears to be associated with a decrease in total consumption of antimicrobials and prevalence of MDROs. This trial did not find benefits associated with educational interviews, probably due to the coronavirus disease 2019 pandemic.[Clinical Trials Registration] NCT03543605.Peer reviewe

Adecuación de ranelato de estroncio tras alertas de farmacovigilancia en un área de gestión sanitaria

Objetivo: Analizar el impacto de una estrategia de adecuación de ranelato de estroncio tras la emisión de recomendaciones, en base a las notas de farmacovigilancia emitidas por la Agencia Española de Medicamentos y Productos Sanitarios, así como el grado de aceptación. Diseño: Estudio prospectivo de intervención desde abril de 2012 a noviembre de 2014. Emplazamiento: Área de Gestión Sanitaria Sur de Sevilla. Participantes: Pacientes con prescripción activa de ranelato de estroncio. Intervenciones: Se realizó en cuatro fases, ligada a la emisión de notas de farmacovigilancia sobre ranelato de estroncio por la Agencia Española de Medicamentos y Productos Sanitarios, listados de pacientes y recomendaciones de adecuación. Mediciones principales: Adecuación del tratamiento con ranelato de estroncio y grado de aceptación de las recomendaciones por los facultativos. Resultados: Desde el inicio del estudio, con 182 pacientes incluidos, hasta el comienzo de la revisión de la adecuación por farmacia, se produjo una reducción del 87,9%. La prescripción de ranelato de estroncio era inadecuada en 16 pacientes de los 22; 11 por no cumplir criterios de tratamiento, tres por no haber tenido tratamiento previo con otros medicamentos para prevención de fracturas y dos por contraindicación. El grado de aceptación de las recomendaciones fue del 87,5%, produciéndose en diez pacientes la suspensión de ranelato de estroncio y en cuatro, el cambio a alendrónico o alendrónico/colecalciferol. Conclusiones: El número de pacientes con prescripción de ranelato de estroncio ha disminuido considerablemente. Las intervenciones dirigidas a la revisión de la adecuación del tratamiento, en base a las alertas de farmacovigilancia han sido efectivas

Drug–drug interactions between treatment specific pharmacotherapy and concomitant medication in patients with COVID-19 in the first wave in Spain

Abstract Primary aim was to assess prevalence and severity of potential and real drug–drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) (‘potential interactions’) and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02–1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12–1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development

Design and synthesis of water-soluble and potent MMP-13 inhibitors with activity in human osteosarcoma cells

Osteoarthritis is a degenerative disease, often resulting in chronic joint pain and commonly affecting elderly people. Current treatments with anti-inflammatory drugs are palliative, making the discovery of new treatments necessary. The inhibition of matrix metalloproteinase MMP-13 is a validated strategy to prevent the progression of this common joint disorder. We recently described polybrominated benzotriazole derivatives with nanomolar inhibitory activity and a promising selectivity profile against this collagenase. In this work, we have extended the study in order to explore the influence of bromine atoms and the nature of the S1 ' heterocyclic interacting moiety on the solubility/selectivity balance of this type of compound. Drug target interactions have been assessed through a combination of molecular modeling studies and NMR experiments. Compound 9a has been identified as a water-soluble and highly potent inhibitor with activity in MG-63 human osteosarcoma cells

Prospective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections

BACKGROUND: Few previous retrospective studies suggest that Plasmodium ovale wallikeri seems to have a longer latency period and produces deeper thrombocytopaenia than Plasmodium ovale curtisi. Prospective studies were warranted to better assess interspecies differences. METHODS: Patients with imported P. ovale spp. infection diagnosed by thick or thin film, rapid diagnostic test (RDT) or polymerase chain reaction (PCR) were recruited between March 2014 and May 2017. All were confirmed by DNA isolation and classified as P. o. curtisi or P. o. wallikeri using partial sequencing of the ssrRNA gene. Epidemiological, analytical and clinical differences were analysed by statistical methods. RESULTS: A total of 79 samples (35 P. o. curtisi and 44 P. o. wallikeri) were correctly genotyped. Males predominate in wallikeri group (72.7%), whereas were 48.6% in curtisi group. Conversely, 74.3% of curtisi group were from patients of African ethnicity, whilst 52.3% of Caucasians were infected by P. o. wallikeri. After performing a multivariate analysis, more thrombocytopaenic patients (p = 0.022), a lower number of platelets (p = 0.015), a higher INR value (p = 0.041), and shorter latency in Caucasians (p = 0.034) were significantly seen in P. o. wallikeri. RDT sensitivity was 26.1% in P. o. curtisi and 42.4% in P. o. wallikeri. Nearly 20% of both species were diagnosed only by PCR. Total bilirubin over 3 mg/dL was found in three wallikeri cases. Two patients with curtisi infection had haemoglobin under 7 g/dL, one of them also with icterus. A wallikeri patient suffered from haemophagocytosis. Chemoprophylaxis failed in 14.8% and 35% of curtisi and wallikeri patients, respectively. All treated patients with various anti-malarials which included artesunate recovered. Diabetes mellitus was described in 5 patients (6.32%), 4 patients of wallikeri group and 1 curtisi. CONCLUSIONS: Imported P. o. wallikeri infection may be more frequent in males and Caucasians. Malaria caused by P. o. wallikeri produces more thrombocytopaenia, a higher INR and shorter latency in Caucasians and suggests a more pathogenic species. Severe cases can be seen in both species. Chemoprophylaxis seems less effective in P. ovale spp. infection than in P. falciparum, but any anti-malarial drug is effective as initial treatment. Diabetes mellitus could be a risk factor for P. ovale spp. infection