Proton pump inhibitors decrease efficacy of palbociclib in patients with metastatic breast.

OBJECTIVES: The objective of this investigation was to assess the impact of concurrent proton pump inhibitors (PPIs) on progression-free survival (PFS) in patients with hormone receptor-positive and HER2-negative metastatic breast cancer (mBC) who received palbociclib as first-line or successives therapy. MATERIALS AND METHODS: A retrospective observational study was conducted, enrolling patients diagnosed with estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, and eligible for palbociclib treatment. Patients were categorized as "concurrent PPIs" if they received PPIs for at least two-thirds of the palbociclib therapy duration, and as "no concurrent PPIs" if they did not receive PPIs during the course of palbociclib treatment. RESULTS: A total of 165 patients were included in the study. Among first-line patients treated with palbociclib, those using concurrent PPIs exhibited a PFS of 8.88 months, while patients using palbociclib without concurrent PPIs had a PFS of 67.81 months (p < 0.0001). In second-line or subsequent treatments, patients on palbociclib with concurrent PPIs had a PFS of 7.46 months, whereas those using palbociclib without concurrent PPIs had a PFS of 17.29 months (p = 0.122). CONCLUSION: This study demonstrates that the concurrent use of PPIs in mBC patients receiving palbociclib negatively affects PFS, particularly in the first-line setting. Nevertheless, further investigation is warranted to explore the impact of PPIs on cycle-dependent kinase 4/6 inhibitors.

Ethanol Solvation of Polymer Residues in Graphene Solution-Gated Field Effect Transistors.

The persistence of photoresist residues from microfabrication procedures causes significant obstacles in the technological advancement of graphene-based electronic devices. These residues induce undesired chemical doping effects, diminish carrier mobility, and deteriorate the signal-to-noise ratio, making them critical in certain contexts, including sensing and electrical recording applications. In graphene solution-gated field-effect transistors (gSGFETs), the presence of polymer contaminants makes it difficult to perform precise electrical measurements, introducing response variability and calibration challenges. Given the absence of viable short to midterm alternatives to polymer-intensive microfabrication techniques, a postpatterning treatment involving THF and ethanol solvents was evaluated, with ethanol being the most effective, environmentally sustainable, and safe method for residue removal. Employing a comprehensive analysis with XPS, AFM, and Raman spectroscopy, together with electrical characterization, we investigated the influence of residual polymers on graphene surface properties and transistor functionality. Ethanol treatment exhibited a pronounced enhancement in gSGFET performance, as evidenced by a shift in the charge neutrality point and reduced dispersion. This systematic cleaning methodology holds the potential to improve the reproducibility and precision in the manufacturing of graphene devices. Particularly, by using ethanol for residue removal, we align our methodology with the principles of green chemistry, minimizing environmental impact while advancing diverse graphene technology applications.

Gender, smoking, and tobacco cessation with pharmacological treatment in a cluster randomized clinical trial.

INTRODUCTION: Whether men find it easier to quit smoking than women is still controversial. Different studies have reported that the efficacy of pharmacological treatments could be different between men and women. This study conducted a secondary analysis of 'Subsidized pharmacological treatment for smoking cessation by the Spanish public health system' (FTFT-AP study) to evaluate the effectiveness of a drug-funded intervention for smoking cessation by gender. METHODS: A pragmatic randomized clinical trial by clusters was used. The population included smokers aged ≥18 years, smoking >10 cigarettes per day, randomly assigned to an intervention group receiving regular practice and financed pharmacological treatment, or to a control group receiving only regular practice. The main outcome was continued abstinence at 12 months, self-reported and validated with CO-oximetry. The percentage, with 95% confidence intervals, of continued abstinence was compared between both groups at 12 months post-intervention, by gender and the pharmacological treatment used. Multilevel logistic regression analysis was performed. RESULTS: A total of 1154 patients from 29 healthcare centers were included. The average age was 46 years (SD=11.78) and 51.7% were men. Overall, the self-reported abstinence at 12 months was 11.1% (62) in women and 15.7% (93) in men (AOR=1.4; 95% CI: 1.0-2.0), and abstinence validated by CO-oximetry was 4.6% (26) and 5.9% (35) in women and men, respectively (OR=1.3; 95% CI: 0.7-2.2). In the group of smokers receiving nicotine replacement treatment, self-reported abstinence was higher in men compared to women (29.5% vs 13.5%, OR=2.7; 95% CI: 1.3-5.8). CONCLUSIONS: The effectiveness of a drug-financed intervention for smoking cessation was greater in men, who also showed better results in self-reported abstinence with nicotine replacement treatment.

Concurrent functional ultrasound imaging with graphene-based DC-coupled electrophysiology as a platform to study slow brain signals and cerebral blood flow under control and pathophysiological brain states.

Current methodology used to investigate how shifts in brain states associated with regional cerebral blood volume (CBV) change in deep brain areas, are limited by either the spatiotemporal resolution of the CBV techniques, and/or compatibility with electrophysiological recordings; particularly in relation to spontaneous brain activity and the study of individual events. Additionally, infraslow brain signals (<0.1 Hz), including spreading depolarisations, DC-shifts and infraslow oscillations (ISO), are poorly captured by traditional AC-coupled electrographic recordings; yet these very slow brain signals can profoundly change CBV. To gain an improved understanding of how infraslow brain signals couple to CBV we present a new method for concurrent CBV with wide bandwidth electrophysiological mapping using simultaneous functional ultrasound imaging (fUS) and graphene-based field effect transistor (gFET) DC-coupled electrophysiological acquisitions. To validate the feasibility of this methodology visually-evoked neurovascular coupling (NVC) responses were examined. gFET recordings are not affected by concurrent fUS imaging, and epidural placement of gFET arrays within the imaging window did not deteriorate fUS signal quality. To examine directly the impact of infra-slow potential shifts on CBV, cortical spreading depolarisations (CSDs) were induced. A biphasic pattern of decreased, followed by increased CBV, propagating throughout the ipsilateral cortex, and a delayed decrease in deeper subcortical brain regions was observed. In a model of acute seizures, CBV oscillations were observed prior to seizure initiation. Individual seizures occurred on the rising phase of both infraslow brain signal and CBV oscillations. When seizures co-occurred with CSDs, CBV responses were larger in amplitude, with delayed CBV decreases in subcortical structures. Overall, our data demonstrate that gFETs are highly compatible with fUS and allow concurrent examination of wide bandwidth electrophysiology and CBV. This graphene-enabled technological advance has the potential to improve our understanding of how infraslow brain signals relate to CBV changes in control and pathological brain states.

Single-Step Functionalization Strategy of Graphene Microtransistor Array with Chemically Modified Aptamers for Biosensing Applications.

Graphene solution-gated field-effect transistors (gSGFETs) offer high potential for chemical and biochemical sensing applications. Among the current trends to improve this technology, the functionalization processes are gaining relevance for its crucial impact on biosensing performance. Previous efforts are focused on simplifying the attachment procedure from standard multi-step to single-step strategies, but they still suffer from overreaction, and impurity issues and are limited to a particular ligand. Herein, a novel strategy for single-step immobilization of chemically modified aptamers with fluorenylmethyl and acridine moieties, based on a straightforward synthetic route to overcome the aforementioned limitations is presented. This approach is benchmarked versus a standard multi-step strategy using thrombin as detection model. In order to assess the reliability of the functionalization strategies 48-gSGFETs arrays are employed to acquire large datasets with multiple replicas. Graphene surface characterization demonstrates robust and higher efficiency in the chemical coupling of the aptamers with the single-step strategy, while the electrical response evaluation validates the sensing capability, allowing to implement different alternatives for data analysis and reduce the sensing variability. In this work, a new tool capable of overcome the functionalization challenges of graphene surfaces is provided, paving the way toward the standardization of gSGFETs for biosensing purposes.

Consenso de recomendaciones para la mejora de la coordinación asistencial inter e intra-centros en el abordaje de la hemofilia / Consensus recommendations for the improvement of inter- and intra-centre care coordination in the management of hemophilia

Objetivo: definir las recomendaciones consensuadas para mejorar la coordinación asistencial entre Farmacia Hospitalaria, Hematología y Enfermería, inter e intra-centros, en la atención a los pacientes con hemofilia. Método: se identificaron y valoraron las recomendaciones para la mejora de la coordinación asistencial en el abordaje de los pacientes con hemofilia, por parte de un panel multidisciplinar de profesionales con experiencia en este campo (Farmacia Hospitalaria, Hematología y Enfermería) y apoyado en la evidencia científica. La valoración de las recomendaciones identificadas se realizó por metodología de consenso Rand/UCLA (Delphi-adaptado) con base en su adecuación y, posteriormente, a su necesidad. En ambos casos, se empleó la escala ordinal de Likert. Los datos se analizaron estadísticamente a través de diferentes métricas. Resultados: se identificaron 53 recomendaciones para la mejora de la coordinación asistencial entre Farmacia Hospitalaria, Hematología y Enfermería en el manejo del paciente con hemofilia, agrupadas en 8 ámbitos de actuación: i) Unidades de Hemofilia, centros de referencia y abordaje multidisciplinar; ii) papel de Hematología, Farmacia Hospitalaria y Enfermería en el recorrido asistencial de los pacientes con hemofilia; iii) telefarmacia y telemedicina; iv) monitorización farmacocinética; v) transición al régimen de paciente adulto; vi) educación sanitaria al paciente; vii) cirugía, urgencias e ingreso hospitalario; y viii) evaluación de los resultados. Todas las recomendaciones fueron valoradas por el panel de expertos externos como adecuadas y necesarias. Conclusiones: el recorrido asistencial del paciente con hemofilia es complejo y depende de diversas variables. Además, requiere la implicación de distintos profesionales sanitarios que deben actuar de manera coordinada e integrada en todas las etapas de la vida del paciente, de manera adaptada a sus necesidades individuales. ... (AU)

Objective: Define consensus recommendations to improve care coordination between Hospital Pharmacy, Haematology and Nursing, inter- and intra-center, in the care of haemophilia patients.Method: Recommendations for the improvement of care coordination in the management of haemophilia patients were identified and assessed by a multidisciplinary panel of professionals with experience in this field (Hospital Pharmacy, Haematology and Nursing) and supported by scientific evidence. The identified recommendations were assessed by Rand/UCLA consensus methodology (Delphi-adapted) based on their appropriateness and, subsequently, on their necessity. In both cases, it was used ordinal Likert scale. Data were statistically analysed through different metrics. Results: Fifty-three recommendations for the improvement of care coordination between Hospital Pharmacy, Haematology and Nursing in the management of haemophilia patients were identified, grouped into eight areas of action: i) Haemophilia units, reference centers and multidisciplinary care; ii) Role of Haematology, Hospital Pharmacy and Nursing in the patient journey of haemophilia patients; iii) Telepharmacy and telemedicine; iv) Pharmacokinetic monitoring; v) Transition to adult patient regimen; vi) Patient health education; vii) Surgery, emergency room and hospital admission; and viii) Outcome evaluation. All recommendations were assessed as appropriate and necessary by the external expert panel. Conclusions: Haemophilia patient journey is complex and depends on different variables. It also requires the involvement of different healthcare professionals who must act in a coordinated and integrated manner at all stages of the patient's life, adapted to their individual needs. ... (AU)

[Translated article] Consensus recommendations for the improvement of inter- and intra-centre care coordination in the management of hemophilia.

OBJECTIVE: Define consensus recommendations to improve care coordination between Hospital Pharmacy, Hematology and Nursing, inter- and intra-center, in the care of hemophilia patients. METHOD: Recommendations for the improvement of care coordination in the management of hemophilia patients were identified and assessed by a multidisciplinary panel of professionals with experience in this field (Hospital Pharmacy, Hematology and Nursing) and supported by scientific evidence. The identified recommendations were assessed by Rand/UCLA consensus methodology (Delphi-adapted) based on their appropriateness and, subsequently, on their necessity. In both cases, it was used ordinal Likert scale. Data were statistically analyzed through different metrics. RESULTS: Fifty-three recommendations for the improvement of care coordination between Hospital Pharmacy, Hematology and Nursing in the management of hemophilia patients were identified, grouped into eight areas of action: i) Hemophilia units, reference centers and multidisciplinary care; ii) Role of Hematology, Hospital Pharmacy and Nursing in the patient journey of hemophilia patients; iii) Telepharmacy and telemedicine; iv) Pharmacokinetic monitoring; v) Transition to adult patient regimen; vi) Patient health education; vii) Surgery, emergency room and hospital admission; and viii) Outcome evaluation. All recommendations were assessed as appropriate and necessary by the external expert panel. CONCLUSIONS: Hemophilia patient journey is complex and depends on different variables. It also requires the involvement of different healthcare professionals who must act in a coordinated and integrated manner at all stages of the patient's life, adapted to their individual needs. On this matter, the identified and agreed recommendations may improve continuity and quality of care, as they facilitate the integration and coordination of the professionals involved in the management of this pathology, especially Hospital Pharmacy, Hematology and Nursing.

Physics-based bias-dependent compact modeling of 1/f noise in single- to few-layer 2D-FETs.

1/f noise is a critical figure of merit for the performance of transistors and circuits. For two-dimensional devices (2D-FETs), and especially for applications in the GHz range where short-channel FETs are required, the velocity saturation (VS) effect can result in the reduction of 1/f noise at high longitudinal electric fields. A new physics-based compact model has been for the first time introduced for single- to few-layer 2D-FETs in this study, precisely validating 1/f noise experiments for various types of devices. The proposed model mainly accounts for the measured 1/f noise bias dependence as the latter is defined by different physical mechanisms. Thus, analytical expressions are derived, valid in all regions of operation in contrast to conventional approaches available in the literature so far, accounting for carrier number fluctuation (ΔN), mobility fluctuation (Δµ) and contact resistance (ΔR) effects based on the underlying physics that rules these devices. The ΔN mechanism due to trapping/detrapping together with an intense Coulomb scattering effect dominates the 1/f noise from the medium to the strong accumulation region while Δµ has also been demonstrated to modestly contribute in the subthreshold region. ΔR can also be significant in a very high carrier density. The VS induced reduction of 1/f noise measurements at high electric fields was also remarkably captured by the model. The physical validity of the model can also assist in extracting credible conclusions when conducting comparisons between experimental data from devices with different materials or dielectrics.

Consensus recommendations for the improvement of inter- and intra-centre care coordination in the management of hemophilia. / Consenso de recomendaciones para la mejora de la coordinación asistencial inter e intra-centros en el abordaje de la hemofilia.

OBJECTIVE: Define consensus recommendations to improve care coordination between Hospital Pharmacy, Haematology and Nursing, inter- and intra-center, in the care of haemophilia patients. METHOD: Recommendations for the improvement of care coordination in the management of haemophilia patients were identified and assessed by a multidisciplinary panel of professionals with experience in this field (Hospital Pharmacy, Haematology and Nursing) and supported by scientific evidence. The identified recommendations were assessed by Rand/UCLA consensus methodology (Delphi-adapted) based on their appropriateness and, subsequently, on their necessity. In both cases, it was used ordinal Likert scale. Data were statistically analysed through different metrics. RESULTS: Fifty-three recommendations for the improvement of care coordination between Hospital Pharmacy, Haematology and Nursing in the management of haemophilia patients were identified, grouped into eight areas of action: i) Haemophilia units, reference centers and multidisciplinary care; ii) Role of Haematology, Hospital Pharmacy and Nursing in the patient journey of haemophilia patients; iii) Telepharmacy and telemedicine; iv) Pharmacokinetic monitoring; v) Transition to adult patient regimen; vi) Patient health education; vii) Surgery, emergency room and hospital admission; and viii) Outcome evaluation. All recommendations were assessed as appropriate and necessary by the external expert panel. CONCLUSIONS: Haemophilia patient journey is complex and depends on different variables. It also requires the involvement of different healthcare professionals who must act in a coordinated and integrated manner at all stages of the patient's life, adapted to their individual needs. On this matter, the identified and agreed recommendations may improve continuity and quality of care, as they facilitate the integration and coordination of the professionals involved in the management of this pathology, especially Hospital Pharmacy, Haematology and Nursing.

Real-world outcomes of abiraterone and enzalutamide in first-line treatment of metastatic castration-resistant prostate cancer: which patients benefit most?

OBJECTIVES: Abiraterone and enzalutamide are two oral novel androgen receptor axis-targeted agents approved for the treatment of castration-resistant prostate cancer (mCRPC). Despite the availability of multiple treatments, there is a need to improve the knowledge and management of these drugs in the real-world setting, especially in patient groups under-represented in clinical trials. Our aim was to review the outcome of patients with chemotherapy-naïve mCRPC treated with abiraterone or enzalutamide in routine clinical practice in order to identify factors that are predictive for response. METHODS: This observational retrospective study was performed in a Spanish tertiary hospital and included men with chemotherapy-naïve mCPRC who started treatment with abiraterone or enzalutamide between September 2012 and November 2018. The study end date was 30 October 2020. RESULTS: Ninety patients with mCRPC were included, 57 with abiraterone and 33 with enzalutamide. Median overall survival (OS) was 26.87 months (95% CI 19.68 to 34.05), with no difference found between the two treatment groups. Nine variables were related to increased OS in the univariate analysis: Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs 2), pain (need of opioids for cancer pain), visceral disease, ≥3 bone lesions, exclusively lymph node metastases, baseline prostate specific antigen (PSA) (<50 vs ≥50 ng/dL and <20 vs ≥20 ng/dL), haemoglobin (<12 vs ≥12 g/dL) and alkaline phosphatase (≤116 vs >116 IU/L). A PSA response >50% was observed in 65 patients (76.5%). In the multivariate analysis, ECOG performance status, pain, visceral disease and alkaline phosphatase provided independent prognostic information. Median OS by Kaplan-Meier analysis was significantly longer for patients with a PSA response (32.1 vs 17.9 months; HR 0.46, 95% CI 0.27 to 0.78; p=0.003). CONCLUSIONS: This study assessed the efficacy of abiraterone and enzalutamide in a real-world setting, including patients under-represented in pivotal studies. Some clinical factors were correlated with improved OS in chemotherapy-naïve men with mCPRC treated with these drugs.

Hospital pharmacy initiatives for improving the management of patients with congenital coagulopathies.

OBJECTIVE: To identify and promote initiatives aimed at improving the management by hospital pharmacists of patients with congenital  coagulopathies in the Spanish healthcare context. METHOD: A series of initiatives to improve the care of patients with congenital coagulopathies were identified, evaluated, and prioritized by a panel of hospital pharmacists. Prioritization was based on an assessment of each  initiative's impact and feasibility on a scale of 1 to 5. Once initiatives were  prioritized, those assigned the highest priority were grouped into three action  areas. RESULTS: Seven areas of activity were identified in which the role of hospital  pharmacists is key for the management of patients with congenital coagulopathies: coordination with the healthcare team; drug  evaluation and selection; dispensing; patient information and education;  pharmacotherapeutic follow-up; research and innovation in the field of  congenital coagulopathies; and capacity-building and training of hospital  pharmacists. Fifteen initiatives were considered a priority, with an average  impact score ≥ 3.8 and a feasibility score ≥ 3.2. A total of, 29.4% of the  prioritized initiatives corresponded to healthcare, 23.5% to patient information  and education, 11.8% to drug evaluation and selection, 11.8% to  phar macotherapeutic monitoring, 11.8% to cross-sectional initiatives, 5.9% to dispensing and 5.9% to research and innovation in the field of congenital coagulopathies: In contrast, initiatives related to capacity-building and training were not prioritized. CONCLUSIONS: Three main action areas were proposed based on the initiatives  identified as high priority for the management of patients with congenital  coagulopathies by a panel of 16 hospital pharmacists. Action areas revolved  around specific activities that hospital pharmacy departments can undertake to  contribute to improving the healthcare situation in Spain.

OBJETIVO: Identificar e impulsar iniciativas orientadas a la mejora del manejo  de los pacientes con coagulopatías congénitas por parte de farmacia hospitalaria en el contexto sanitario español.Método: Se identificaron, evaluaron y priorizaron, por parte de un panel de  farmacéuticos especialistas en farmacia hospitalaria, iniciativas para la mejora  de la atención a los pacientes con coagulopatías congénitas. La priorización se  realizó en base a la valoración de su impacto y factibilidad en una escala del 1  al 5. Una vez obtenida la priorización de las iniciativas, las de mayor  puntuación se agruparon en tres grandes líneas de actuación. RESULTADOS: Se identificaron siete áreas de actividad en las que el papel de  los farmacéuticos especialistas en farmacia hospitalaria resulta clave para el  manejo del paciente con coagulopatías congénitas: coordinación con el equipo  asistencial de pacientes con coagulopatías congénitas; evaluación y selección  de medicamentos; dispensación; información y formación al paciente;  seguimiento farmacoterapéutico; investigación e innovación en estas  patologías; formación y capacitación continuada del farmacéutico especialista  en farmacia hospitalaria. Se consideraron prioritarias 15 iniciativas por tener  una puntuación media de impacto ≥ 3,8 y factibilidad ≥ 3,2. Así, el 29,4% de  las iniciativas priorizadas pertenecen al ámbito asistencial, el 23,5% a  información y formación al paciente, el 11,8% a evaluación y selección de  medicamentos, el 11,8% al seguimiento farmacoterapéutico, el 11,8% a  iniciativas transversales, el 5,9% a dispensación y el 5,9% a investigación e  innovación en el campo de las coagulopatías congénitas, mientras que las  iniciativas referentes a la formación y capacitación a profesionales no  resultaron priorizadas. CONCLUSIONES: Se han propuesto tres grandes líneas de actuación basadas en  las iniciativas identificadas como altamente prioritarias por un panel de 16  expertos farmacéuticos especialistas en farmacia hospitalaria para el manejo  de pacientes con coagulopatías congénitas. Estas iniciativas se basan en  acciones concretas y pueden llevarse a cabo desde los servicios de farmacia  hospitalaria, por lo que se cree que podrán llegar a tener un impacto real en el  contexto sanitario español.

Iniciativas para la mejora del manejode los pacientes con coagulopatías congénitas por parte de farmacia hospitalaria / Hospital pharmacy initiatives for improving the management of patients with congenital coagulopathies

Objetivo: Identificar e impulsar iniciativas orientadas a la mejora delmanejo de los pacientes con coagulopatías congénitas por parte de farmaciahospitalaria en el contexto sanitario español.Método: Se identificaron, evaluaron y priorizaron, por parte de un panelde farmacéuticos especialistas en farmacia hospitalaria, iniciativas para lamejora de la atención a los pacientes con coagulopatías congénitas. Lapriorización se realizó en base a la valoración de su impacto y factibilidaden una escala del 1 al 5. Una vez obtenida la priorización de las iniciativas,las de mayor puntuación se agruparon en tres grandes líneas de actuación.Resultados: Se identificaron siete áreas de actividad en las que el papelde los farmacéuticos especialistas en farmacia hospitalaria resulta clavepara el manejo del paciente con coagulopatías congénitas: coordinacióncon el equipo asistencial de pacientes con coagulopatías congénitas;evaluación y selección de medicamentos; dispensación; información yformación al paciente; seguimiento farmacoterapéutico; investigacióne innovación en estas patologías; formación y capacitación continuadadel farmacéutico especialista en farmacia hospitalaria. Se consideraronprioritarias 15 iniciativas por tener una puntuación media de impacto≥ 3,8 y factibilidad ≥ 3,2. Así, el 29,4% de las iniciativas priorizadas pertenecen al ámbito asistencial, el 23,5% a información y formación alpaciente, el 11,8% a evaluación y selección de medicamentos, el 11,8%al seguimiento farmacoterapéutico, el 11,8% a iniciativas transversales, el5,9% a dispensación y el 5,9% a investigación e innovación en el campode las coagulopatías congénitas, mientras que las iniciativas referentesa la formación y capacitación a profesionales no resultaron priorizadas.

Objective: To identify and promote initiatives aimed at improving themanagement by hospital pharmacists of patients with congenital coagulopathiesin the Spanish healthcare context.Method: A series of initiatives to improve the care of patients with congenitalcoagulopathies were identified, evaluated, and prioritized by apanel of hospital pharmacists. Prioritization was based on an assessmentof each initiative’s impact and feasibility on a scale of 1 to 5. Once initiativeswere prioritized, those assigned the highest priority were groupedinto three action areas.Results: Seven areas of activity were identified in which the role ofhospital pharmacists is key for the management of patients with congenitalcoagulopathies: coordination with the healthcare team; drug evaluationand selection; dispensing; patient information and education; pharmacotherapeuticfollow-up; research and innovation in the field of congenitalcoagulopathies; and capacity-building and training of hospital pharmacists.Fifteen initiatives were considered a priority, with an average impactscore ≥ 3.8 and a feasibility score ≥ 3.2. A total of, 29.4% of the prioritizedinitiatives corresponded to healthcare, 23.5% to patient informationand education, 11.8% to drug evaluation and selection, 11.8% to pharmacotherapeutic monitoring, 11.8% to cross-sectional initiatives, 5.9% todispensing and 5.9% to research and innovation in the field of congenitalcoagulopathies: In contrast, initiatives related to capacity-building andtraining were not prioritized.Conclusions: Three main action areas were proposed based onthe initiatives identified as high priority for the management of patientswith congenital coagulopathies by a panel of 16 hospital pharmacists.Action areas revolved around specific activities that hospital pharmacydepartments can undertake to contribute to improving the healthcare situationin Spain.

Intervention by a clinical pharmacist carried out at discharge of elderly patients admitted to the internal medicine department: influence on readmissions and costs.

BACKGROUND: Patient education on pharmacological treatment could reduce readmissions. Our objective was to carry out a pharmacist intervention focused on providing information about high-risk medications to chronic patients and to analyse its influence on readmissions and costs. METHODS: A single-centre study with an intervention group and a retrospective control group was conducted. The intervention was carried out in all polymedicated patients ≥ 65 years who were admitted to internal medicine and signed the informed consent between June 2017 and February 2018. Patients discharged to nursing homes or long-term hospitals were excluded. The control group were all the patients who were admitted during the same months of 2014 who met the same inclusion criteria. The patients were classified according to the HOSPITAL score as having a low, intermediate, or high risk of potentially avoidable readmission. Outcome measures were 30-day readmission and cost data. To analyse the effect of the intervention on readmission, a logistic regression was performed. RESULTS: The study included 589 patients (286 intervention group; 303 control group). The readmission rate decreased from 20.13% to 16.43% in the intervention group [OR = 0.760 95% CI (0.495-1.166); p = 0.209)]. The incremental cost for the intervention to prevent one readmission was €3,091.19, and the net cost saving was €1,301.26. In the intermediate- and high-risk groups, readmissions were reduced 10.91% and 10.00%, and the net cost savings were €3,3143.15 and €3,248.71, respectively. CONCLUSIONS: The pharmacist intervention achieved savings in the number of readmissions, and the net cost savings were greater in patients with intermediate and high risks of potentially avoidable readmission according to the HOSPITAL score.

The Novel Phosphatase Domain Mutations Q171R and Y65S Switch PTEN from Tumor Suppressor to Oncogene.

Phosphatase and tensin homolog deleted on chromosome 10, or PTEN, is a well-characterized tumor suppressor with both lipid and protein phosphatase activities. PTEN is often downregulated by epigenetic mechanisms such as hypermethylation, which leads to constitutive activation of the PI3K-Akt pathway. Large datasets from next-generation sequencing, however, revealed that mutations in PTEN may not only hamper protein function but may also affect interactions with downstream effectors, leading to variable oncogenic readouts. Here, two novel PTEN mutations, Q171R and Y65S, identified in Filipino colorectal cancer patients, were phenotypically characterized in NIH3T3 and HCT116 cells, alongside the C124S canonical mutant and wild-type controls. The novel mutants increased cellular proliferation, resistance to apoptosis and migratory capacity. They induced gross morphological changes including cytoplasmic shrinkage, increased cellular protrusions and extensive cytoskeletal reorganization. The mutants also induced a modest increase in Akt phosphorylation. Further mechanistic studies will help determine the differential oncogenic potencies of these mutants, and resolve whether the structural constraints imposed by the mutations may have altered associations with downstream effectors.

Transverse Myelitis in Systemic Lupus Erythematosus: Clinical Features and Prognostic Factors in a Large Cohort of Latin American Patients.

BACKGROUND: Acute transverse myelitis (ATM) is an infrequent but severe complication of systemic lupus erythematosus (SLE). The purpose of study was to describe clinical features and prognostic factors of patients with SLE-related ATM. METHODS: In this medical records review study, data were collected from 60 patients from 16 centers seen between 1996 and 2017 who met diagnostic criteria for SLE and myelitis as defined by the American College of Rheumatology/Systemic International Collaborating Clinics and the Working Group of the Transverse Myelitis Consortium, respectively. Objective neurological impairment was measured with American Spinal Injury Association Impairment Scale (AIS) and European Database for Multiple Sclerosis Grade Scale (EGS). RESULTS: Among patients included, 95% (n = 57) were female, and the average age was 31.6 ± 9.6 years. Myelitis developed after diagnosis of SLE in 60% (n = 36). Symmetrical paraparesis with hypoesthesia, flaccidity, sphincter dysfunction, AIS = A/B, and EGS ≥ 8 was the most common presentation. Intravenous methylprednisolone was used in 95% (n = 57), and 78.3% (n = 47) received intravenous cyclophosphamide. Sensory/motor recovery at 6 months was observed in 75% (42 of 56), but only in 16.1% (9 of 56) was complete. Hypoglycorrhachia and EGS ≥ 7 in the nadir were associated with an unfavorable neurological outcome at 6 months (p < 0.05). A relapse rate during follow-up was observed in 30.4% (17 of 56). Hypoglycorrhachia and hypocomplementemia seem to be protective factors for relapse. Intravenous cyclophosphamide was associated with time delay to relapse. CONCLUSIONS: Systemic lupus erythematosus-related ATM may occur at any time of SLE course, leading to significant disability despite treatment. Relapses are infrequent and intravenous cyclophosphamide seems to delay it. Hypoglycorrhachia, hypocomplementemia, and EGS at nadir are the most important prognostic factors.

Safety and effectiveness of a four-factor prothrombin complex concentrate for vitamin K antagonist reversal following a fixed-dose strategy.

OBJECTIVES: Early reversal of anticoagulation improves outcomes in major bleeding and emergency surgery. To reverse vitamin K antagonists (VKA), vitamin K in addition to prothrombin complex concentrate (PCC) is recommended. Dosing recommendations for VKA reversal provided by the manufacturer are 25-50 IU/kg depending on the baseline international normalised ratio (INR). Nevertheless, we recommend an initial fixed dose of 1000 IU, and additional 500 IU doses evaluated on a case-by-case basis. As there is a paucity of clinical data demonstrating the efficacy and safety of this strategy, we designed this study to assess the effectiveness and safety of a four-factor (4F)-PCC for VKA reversal following a fixed-dose strategy. METHODS: This was a retrospective study of adult patients who received 4F-PCC for VKA reversal. The primary outcome was INR correction. INR correction was achieved if the first INR draw after 4F-PCC was ≤1.5. Safety outcome was any confirmed thromboembolic event within 3 months after 4F-PCC. Secondary outcomes included activated partial thromboplastin time (aPTT) correction, as well as haemostatic effectiveness for bleeding patients. RESULTS: A total of 145 patients were included: 106 (73.1%) in the bleeding group and 39 (26.9%) in the emergency surgery group. The INR target was reached in 102 (70.3%) patients (p<0.0001). In one case, a thromboembolic complication was possibly related to 4F-PCC. The aPTT ratio target was reached in 113 (77.9%) patients (p<0.0001), and 79 of the 106 (74.5%) patients reversed for bleeding achieved haemostatic effectiveness. CONCLUSIONS: After 4F-PCC, the majority of patients achieved the target INR, meaning 4F-PCC is a useful modality for rapid INR reduction. The safety profile may be considered acceptable. Fixed-dose 4F-PCC was able to restore haemostasis rapidly while minimising the risk of adverse events and optimising available resources.

Interpretation of OCT and OCTA images from a histological approach: Clinical and experimental implications.

Optical coherence tomography (OCT) and OCT angiography (OCTA) have been a technological breakthrough in the diagnosis, treatment, and follow-up of many retinal diseases, thanks to its resolution and its ability to inform of the retinal state in seconds, which gives relevant information about retinal degeneration. In this review, we present an immunohistochemical description of the human and mice retina and we correlate it with the OCT bands in health and pathological conditions. Here, we propose an interpretation of the four outer hyperreflective OCT bands with a correspondence to retinal histology: the first and innermost band as the external limiting membrane (ELM), the second band as the cone ellipsoid zone (EZ), the third band as the outer segment tips phagocytosed by the pigment epithelium (PhaZ), and the fourth band as the mitochondria in the basal portion of the RPE (RPEmitZ). The integrity of these bands would reflect the health of photoreceptors and retinal pigment epithelium. Moreover, we describe how the vascular plexuses vary in different regions of the healthy human and mice retina, using OCTA and immunohistochemistry. In humans, four, three, two or one plexuses can be observed depending on the distance from the fovea. Also, specific structures such as vascular loops in the intermediate capillary plexus, or spider-like structures of interconnected capillaries in the deep capillary plexus are found. In mice, three vascular plexuses occupy the whole retina, except in the most peripheral retina where only two plexuses are found. These morphological issues should be considered when assessing a pathology, as some retinal diseases are associated with structural changes in blood vessels. Therefore, the analysis of OCT bands and OCTA vascular plexuses may be complementary for the diagnosis and prognosis of retinal degenerative processes, useful to assess therapeutic approaches, and it is usually correlated to visual acuity.

Non-Redundant and Overlapping Oncogenic Readouts of Non-Canonical and Novel Colorectal Cancer KRAS and NRAS Mutants.

RAS oncogene family members are molecular switches of signaling pathways that control cell growth, proliferation, differentiation, and survival. In colorectal cancer, Kirsten-RAS (KRAS) and neuroblastoma-RAS (NRAS) are the commonly mutated isoforms. Activating mutations in RAS result in cellular transformation independent of upregulated epidermal growth factor receptor (EGFR)-initiated signaling. The present study characterized the functional consequences of non-canonical/novel KRAS and NRAS mutants identified in a targeted next-generation sequencing study of colorectal cancer specimens from Filipino patients. In vitro assays in NIH3T3 cells showed that similar to the canonical KRAS G12D mutant, overexpression of KRAS G12S, A59T, and Y137C, but not NRAS G12D and NRAS A11V, confer higher proliferation and migration rates. HCT116 cells transfected with the novel NRAS A11V and the canonical NRAS G12D, but not the KRAS mutants, display enhanced resistance to apoptosis. All four non-canonical/novel KRAS and NRAS mutants induce gross changes in F-actin cytoskeletal organization and cellular morphology of NIH3T3 cells. Only KRAS G12S and KRAS A59T appear to deregulate extracellular signal-regulated kinase (ERK) and its downstream target ETS transcription factor ELK1 (ELK1). Elucidation of differential effector engagement responsible for the variable phenotypic readouts of the mutants is warranted. If validated by mouse studies and clinical correlates, these can have wider implications in choosing treatment options.

Single-layer graphene modulates neuronal communication and augments membrane ion currents.

The use of graphene-based materials to engineer sophisticated biosensing interfaces that can adapt to the central nervous system requires a detailed understanding of how such materials behave in a biological context. Graphene's peculiar properties can cause various cellular changes, but the underlying mechanisms remain unclear. Here, we show that single-layer graphene increases neuronal firing by altering membrane-associated functions in cultured cells. Graphene tunes the distribution of extracellular ions at the interface with neurons, a key regulator of neuronal excitability. The resulting biophysical changes in the membrane include stronger potassium ion currents, with a shift in the fraction of neuronal firing phenotypes from adapting to tonically firing. By using experimental and theoretical approaches, we hypothesize that the graphene-ion interactions that are maximized when single-layer graphene is deposited on electrically insulating substrates are crucial to these effects.

Relación entre las concentraciones de la leptina y la actividad de la enfermedad en pacientes con artritis reumatoide / Relationship between leptin concentrations and disease activity in patients with rheumatoid arthritis

Introducción y objetivo: Múltiples estudios han encontrado una relación directa entre las concentraciones de leptina y la actividad de la enfermedad en artritis reumatoide. Pacientes y métodos: Se estudiaron 77 pacientes con artritis reumatoide, la determinación de la leptina fue a través de inmunoanálisis enzimático. Se evaluó la actividad de la enfermedad mediante el DAS-28 PCR. Se realizó un modelo de regresión logística multivariante para determinar la asociación entre las variables significativas y las concentraciones de leptina. Resultados: El 40,3% de los pacientes estaban en remisión, el 41,6% actividad leve, el 11,7% actividad moderada y el 6,5% actividad grave. Se encontró una relación independiente entre mayores concentraciones de leptina y la actividad de la enfermedad (RR 1,7; IC al 95%: 1,4-3,2; p = 0,03), el número de articulación tumefactas (RR 4,6; IC al 95%: 1,7-8,3; p = 0,000), el número de articulaciones dolorosas (RR 3,4; IC al 95%: 1,6-4,6; p = 0,000) y a presencia de síndrome metabólico (RR 1,3; IC al 95%: 1,2-1,9; p = 0,045). Conclusiones: Los datos obtenidos sugieren que la leptina sérica está elevada en pacientes con AR activa

Background and objective: Multiple studies have found a direct relationship between leptin concentrations and disease activity in rheumatoid arthritis. Patients and methods: We studied 77 patients with the diagnosis of rheumatoid arthritis; the leptin determination was through an enzyme immunoassay. Disease activity was assessed by the DAS-28 CRP. A multivariate logistic regression model was used to determine the association between significant variables and leptin concentrations. Results: 40.3% of the patients were in remission, 41.6% were mildly active, 11.7% were moderately active and 6.5% were severely active. The results show an independent association between higher concentrations of leptin and disease activity (OR 1.7; 95% CI 1.4-3.2; p .03), the number of swollen joints (OR 4.6; 95% CI 1.7-8.3; p .000), the number of painful joints (OR 3.4; 95% CI 1.6-4.6; p .000), and the presence of metabolic syndrome (OR 1.3; 95% IC 1.2-1,9; p .045). Conclusion: The data suggest that serum leptin is elevated in patients with active RA