Anticoagulation Control with Acenocoumarol or Warfarin in Non-Valvular Atrial Fibrillation in Primary Care (Fantas-TIC Study)

Introduction: The use of vitamin K antagonists (VKAs) in non-valvular atrial fibrillation (NVAF) is complicated due to the narrow therapeutic margin they present and their unpredictable dose-response relationship. Most studies are based on warfarin, with the results being extrapolated to acenocoumarol. However, studies comparing the two treatments in terms of the degree of anticoagulation control are scarce, justifying the present study. Main factors associated with poor control of time in therapeutic range (TTR) of anticoagulated patients are also studied. Methods: Cross-sectional study, with real-world data from patients treated in primary care (PC). Data were obtained from the System for the Improvement of Research in PC (SIDIAP) database, covering 60,978 NVAF-anticoagulated patients from 287 PC centres in 2018. Descriptive statistics were derived, and odds ratios were estimated by multivariate logistic regression. Results: 41,430 patients were considered: 93% were being treated with acenocoumarol and 7% with warfarin. There was no difference in poor control of TTR between the two types of VKA treatment, acenocoumarol and warfarin (38.9 vs. 38.4; p = 0.610). Poor anticoagulation control was mainly associated with advanced alcoholism (OR = 1.38), liver failure (OR = 1.37) and intracranial haemorrhage (OR = 1.35) as well as female sex, age < 60 years, cardiovascular history, diabetes mellitus and other variables. Conclusions: There is no association between poor anticoagulation control and the type of VKA treatment administered. Factors associated with poor control of TTR must be considered in clinical practice to improve control and decision-making

A new clinical decision support tool for improving the adequacy of anticoagulant therapy and reducing the incidence of stroke in nonvalvular atrial fibrillation

Altres ajuts: Pla estratègic de recerca i innovació en salut (PERIS) - Subvencions per a projectes de recerca orientats a l'atenció primària), grant number SLT002/16/00146.Atrial fibrillation (AF) is the most common cardiac arrhythmia and increases the risk of ischemic stroke 4 to 5-fold. The first choice of anticoagulant therapy (AT) is the vitamin K antagonist (VKA). Contraindication to VKA or poor control of the International Normalized Ratio leads to the administration of direct-acting oral anticoagulants. There is a trend toward inadequate AT in nonvalvular AF (NVAF) patients. Aim: To evaluate the impact of the implementation of a decision support tool linked to the digital clinical history on the adequacy of AT, the incidence of complications, and the mortality in patients with NVAF in primary care centers (PCCs) of the Catalan Institute of Health (ICS). Randomized clinical trial in 287 PCCs, formed by 2 groups (intervention and control). Population: patients controlled in PCCs, diagnosed with NVAF 1 year before the implementation of the decision support tool and with VKA treatment over a minimum of 1 year. A simple randomization method will be performed at a sector level. The decision support tool will be available for 1 year. The time in therapeutic range (TTR) will be available in the digital clinical history only to professionals of the intervention group. The information system for primary care research development database will be used for the data extraction. Statistical analysis will be done at 3 time points: before the implementation of the tool, at 1 year, and at 2 years after the beginning of the intervention. Multilevel (patient and professional levels) logistic regression models will be used to estimate the effect of the intervention. This study protocol was approved by the Ethical Committee of Clinical Investigation of the Institut Universitari d'Investigació en Atenció Primària Jordi Gol (code P17/091). Articles will be published in scientific journals. Clinical-Trials.gov: NCT03367325

Force spectroscopy-based simultaneous topographical and mechanical characterization to study polymer-to-polymer interactions in coated alginate microspheres

Cell-laden hydrogel microspheres have shown encouraging outcomes in the fields of drug delivery, tissue engineering or regenerative medicine. Beyond the classical single coating with polycations, many other different coating designs have been reported with the aim of improving mechanical properties and in vivo performance of the microspheres. Among the most common strategies are the inclusion of additional polycation coatings and the covalent bonding of the semi-permeable membranes with biocompatible crosslinkers such as genipin. However, it remains challenging to characterize the effects of the interactions between the polycations and the hydrogel microspheres over time in vitro. Here we use a force spectroscopy-based simultaneous topographical and mechanical characterization to study polymer-to-polymer interactions in alginate microspheres with different coating designs, maintaining the hydrogels in liquid. In addition to classical topography parameters, we explored, for the first time, the evolution of peak/valley features along the z axis via thresholding analysis and the cross-correlation between topography and stiffness profiles with resolution down to tens of nanometers. Thus, we demonstrated the importance of genipin crosslinking to avoid membrane detachment in alginate microspheres with double polycation coatings. Overall, this methodology could improve hydrogel design rationale and expedite in vitro characterization, therefore facilitating clinical translation of hydrogel-based technologies

Oral Anticoagulant Adequacy in Non-Valvular Atrial Fibrillation in Primary Care: A Cross-Sectional Study Using Real-World Data (Fantas-TIC Study)

Background: Oral anticoagulants (OAs) are the treatment to prevent stroke in atrial fibrillation (AF). Anticoagulant treatment choice in non-valvular atrial fibrillation (NVAF) must be individualized, taking current guidelines into account. Adequacy of anticoagulant therapy under the current criteria for NVAF in real-world primary care is presented. Methods: Cross-sectional study, with real-world data from patients treated in primary care (PC). Data were obtained from the System for the Improvement of Research in Primary Care (SIDIAP) database, covering 60,978 NVAF-anticoagulated patients from 287 PC centers in 2018. Results: In total, 41,430 (68%) were treated with vitamin K antagonists (VKAs) and 19,548 (32%) NVAF with direct-acting oral anticoagulants (DOACs). Inadequate prescription was estimated to be 36.0% and 67.6%, respectively. Most DOAC inadequacy (77.3%) was due to it being prescribed as a first-line anticoagulant when there was no history of thromboembolic events or intracranial hemorrhage (ICH). A total of 22.1% had missing estimated glomerular filtration rate (eGFR) values. Common causes of inadequate VKA prescription were poor control of time in therapeutic range (TTR) (98.8%) and ICH (2.2%). Conclusions: Poor adequacy to current criteria was observed, being inadequacy higher in DOACs than in VKAs. TTR and GFR should be routinely calculated in electronic health records (EHR) to facilitate decision-making and patient safety

Frequency and Clinicopathological Profile Associated with Braf Mutations in Patients with Advanced Melanoma in Spain

Real-world data on BRAF mutation frequency in advanced melanoma are lacking in Spain. Moreover, data available on clinicopathological profile of patients with advanced BRAF-mutant melanoma are currently limited. This study aimed to assess the frequency of BRAF V600 mutations in Spanish patients with advanced or metastatic melanoma and to identify clinical and histopathological features associated with BRAF-mutated tumors. A multicenter, cross-sectional epidemiological study was conducted in 33 Spanish hospitals in adult patients with stage IIIc/IV melanoma. A total of 264 patients were included. The median age was 68 years and 57% were male. Melanoma mainly involved skin with intermittent (40.4%) and low or no sun exposure (43.5%). Most patients (85.6%) had stage IV disease (M1a: 19.3%; M1b: 13.3%; M1c: 22.7%). Serum lactate dehydrogenase levels were elevated in 20% of patients. Superficial spreading melanoma was the most frequent histological type (29.9%). Samples were predominantly obtained from metastases (62.7%), mostly from skin and soft tissues (80%). BRAF mutation analysis was primarily performed using the Cobas 4800 BRAF V600 Mutation Test (92.8%) on formalin-fixed, paraffin-embedded tissue (95.8%). BRAF mutations were detected in 41.3% of samples. Multivariate analysis identified age (odd ratio [OR] 0.975) and stage IV M1a (OR 2.716) as independent factors associated with BRAF mutation. The frequency of BRAF mutations in tumor samples from patients with advanced or metastatic melanoma in Spain was 41.3%. BRAF mutations seem to be more frequent in younger patients and stage M1a patients. This study provides the basis for further investigation regarding BRAF-mutated advanced melanoma in larger cohorts.This study was sponsored by Roche Farma S.A

Pay-per-use from the car

[EN] Cities evolution, and in particular the struggle against pollution and congestion, has led in recent years to develop new pay per use models. These models are using as tools for the implementation of new models of mobility. The ¿Pay-per-use SIM¿ project proposes a solution that enables real-time interaction between vehicle and infrastructure and, especially, with the user, in order to give space for new services such as smart parking or congestion charges.[ES] La evolución de las ciudades y en particular la lucha contra la contaminación y la saturación del tráfico, ha llevado en los últimos años a diseñar nuevos modelos de pago por uso que están siendo utilizados como herramientas para la puesta en marcha de nuevos modelos de movilidad. El proyecto ¿Pay-per-use SIM¿ propone una solución que permite la interacción en tiempo real de la infraestructura con el vehículo y especialmente con el usuario, para dar cabida a nuevos servicios como el aparcamiento inteligente o los peajes urbanos.El proyecto Pay-Per-Use SIM está cofinanciado, dentro del programa de Unidades Estratégicas de Cooperación, por el Instituto Valenciano de Competitividad empresarial (IVACE) y el Fondo Europeo de Desarrollo Regional (FEDER), dentro del Programa Operativo FEDER de la Comunidad Valenciana 2007-2013.Soler Valero, A.; Castellanos Hernández, WE.; Vivas Vivas, JA.; Solaz Sanahuja, JS.; Signes Pérez, E.; Moliner Fernandez, C.; Solves Camallonga, C.... (2013). Pagar desde el automóvil. Revista de biomecánica. 60:7-10. http://hdl.handle.net/10251/38686S7106

Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia

For PETHEMA Programa para el Estudio de la Terapéutica en Hemopatías Malignas Cooperative Study Group.The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥0.1%; ≥0.01-0.1%; and <0.01), with a 5-year RFS of 38%, 50% and 71%, respectively (p = 0.002). Cytogenetics is the most relevant prognosis factor in AML, however intermediate risk cytogenetics represent a grey zone that require other biomarkers for risk stratification, and we show that MRD evaluation discriminate three prognostic subgroups (p = 0.03). Also, MRD assessments yielded relevant information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics.This work was supported in part by Spanish grants from Fondo de Investigación Sanitaria-ISCIII (FIS 00/0023-03, PI12/02321), DGCYT (SAF 94- 0308, SAF2001-1687), Conserjería de Educación de Castilla y León (HUS416A12), and Red Temática de Investigación Cooperativa en Cáncer (RTICC-ISCIII) (RD12/0036/0069).Peer Reviewe

Evolution of Quality of Life and Treatment Adherence after One Year of Intermittent Bladder Catheterisation in Functional Urology Unit Patients

Objective: To determine patient difficulties and concerns when performing IBC (Intermittent Bladder Catheterisation), as well as the evolution of adherence, quality of life, and emotional state of patients one year after starting IBC. Method: A prospective, observational, multicentre study conducted in 20 Spanish hospitals with a one-year follow-up. Data sources were patient records and the King's Health Questionnaire on quality of life, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale (HADS). Perceived adherence was measured using the ICAS (Intermittent Catheterization Adherence Scale) and perceived difficulties with IBC were assessed using the ICDQ (Intermittent Catheterization Difficulty Questionnaire). For data analysis, descriptive and bivariate statistics were performed for paired data at three points in time (T1: one month, T2: three months, T3: one year). Results: A total of 134 subjects initially participated in the study (T0), becoming 104 subjects at T1, 91 at T2, and 88 at T3, with a mean age of 39 years (standard deviation = 22.16 years). Actual IBC adherence ranged from 84.8% at T1 to 84.1% at T3. After one year of follow-up, a statistically significant improvement in quality of life (p <= 0.05) was observed in all dimensions with the exception of personal relationships. However, there were no changes in the levels of anxiety (p = 0.190) or depression (p = 0.682) at T3 compared to T0. Conclusions: Patients requiring IBC exhibit good treatment adherence, with a significant proportion of them performing self-catheterisation. After one year of IBC, a significant improvement in quality of life was noted, albeit with a significant impact on their daily lives and their personal and social relationships. Patient support programmes could be implemented to improve their ability to cope with difficulties and thus enhance both their quality of life and the maintenance of their adherence

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study

Background: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. Aim: To assess the daily clinical practice approach to LyP and the response to first-line treatments. Methods: This was a retrospective study enrolling 252 patients with LyP. Results: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. Conclusions: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse