Cost-Effectiveness Analysis of Apixaban Versus Edoxaban in Patients with Atrial Fibrillation for Stroke Prevention

OBJECTIVE: Our objective was to assess the cost effectiveness of apixaban versus edoxaban in the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF) in Spain. METHODS: We customized a Markov model with ten health states to estimate the lifetime economic and clinical outcomes in 6-week cycles. The efficacy (clinical event rates per 100 patient-years) and safety data were derived from a pairwise indirect treatment comparison. The analysis was conducted from both the national health service (NHS) and societal perspectives, and included pharmaceutical costs (retail price plus value-added tax (VAT) and applicable national deductions) according to daily dosages (apixaban 10 mg (5 mg twice daily (bid)) and edoxaban 60 or 30 mg) and complications and disease-management costs, obtained from national databases. Utilities for quality-adjusted life-year (QALY) calculations reflected EuroQoL 5-Dimension scores in patients with AF. An annual discount rate of 3% was applied for costs (euro, year 2019 values) and outcomes. RESULTS: In a 1000-patient cohort, apixaban 5 mg bid versus edoxaban 60 mg could avoid five strokes, six major bleedings and 29 clinically relevant non-major bleedings (CRNMBs). Compared with edoxaban 30 mg, apixaban could avoid 21 strokes and two SEs. An increase in bleedings was observed with apixaban (seven haemorrhagic strokes, 48 major bleedings and 17 CRNMBs). Apixaban yielded 0.04 additional QALYs compared with edoxaban 60 mg or 30 mg. Incremental costs/QALY were euro9639.33 and euro354.22 for apixaban versus edoxaban 60 mg and edoxaban 30 mg, respectively, from the NHS perspective and euro7756.62 for apixaban versus edoxaban 60 mg from the societal perspective. Apixaban was dominant versus edoxaban 30 mg from the societal perspective. Sensitivity analyses confirmed the robustness of the model. CONCLUSIONS: This study suggests that apixaban 5 mg bid is a cost-effective alternative to edoxaban for stroke prevention in the AF population in Spain

Ultrafast laser-scanning optical resolution photoacoustic microscopy at up to 2 million A-lines per second

The imaging speed of optical resolution photoacoustic microscopy (OR-PAM) using pulsed excitation is fundamentally limited by the range ambiguity condition, which defines the maximum laser pulse repetition frequency (PRF). To operate at this theoretical upper limit and maximize acquisition speed, a custom-built fiber laser capable of operating at a PRF of up to 2 MHz was combined with a fast laser scanning optical OR-PAM system based on a stationary fiber-optic ultrasound sensor. A large area (10 mm × 10 mm) of the mouse ear was imaged within 8 s, when acquiring 16 million A-lines and operating the laser at a PRF of 2 MHz. This corresponds to a factor of four improvement in imaging speed compared to the fastest OR-PAM system previously reported. The ability to operate at high-imaging frame rates also allows the capture of hemodynamic events such as blood flow. It is considered that this system offers opportunities for high throughput imaging and visualizing dynamic physiological events using OR-PAM

Factores que inhiben la compra de entradas al cine a trav?s de aplicaciones m?viles : caso Cineplanet

El uso de dispositivos m?viles y el comercio electr?nico se ha incrementado en el Per? en la ?ltima d?cada. Sin embargo, el comercio m?vil a?n no se ha desarrollado a comparaci?n de otros pa?ses de la regi?n. Adem?s, a pesar de existir aplicaciones m?viles para la compra de entradas al cine existen algunos factores que no facilitan la compra de entradas mediante esta plataforma. Para identificar estos factores se realiz? la presente investigaci?n, tomando el caso de Cineplanet, l?der en el mercado de exhibici?n en el Per?. Como resultado, se identificaron cinco factores que inhiben el tema investigado: la expectativa de desempe?o, la expectativa de esfuerzo, la percepci?n de confianza, la orientaci?n al ahorro y la calidad de informaci?n. Algunos de estos factores est?n relacionados con la usabilidad y experiencia al usuario. Adem?s, se pudo identificar que las personas entre 21 y 35 a?os s? est?n dispuestas a realizar compras de entradas al cine mediante la aplicaci?n m?vil de Cineplanet y las redes sociales como Facebook y YouTube son importantes para el proceso de decisi?n de compra de los clientes

Pleomorphic adenoma of the vulva, clinical reminder of a rare occurrence

Pleomorphic adenoma, also known as mixed tumor, is a benign tumor which typically presents as a painless and persistent mass. The majority of pleomorphic adenomas involve the salivary glands, most commonly the parotid gland. Other sites include breast and skin. It is a rare tumor in the vulva. In this article we are reporting a case of pleomorphic adenoma of labia with characteristic pathologic and clinical findings, as reminder of a common benign neoplasm occurring with rare locality

AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients

[Abstract] Introduction. One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR. Methods. Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR. Results. We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients. Conclusion. We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.Instituto de Salud Carlos III; PI13/0217

Impact of cardiovascular risk factors on the clinical presentation and survival of pulmonary embolism without identifiable risk factor

Background: The nature of pulmonary embolism (PE) without identifiable risk factor (IRF) remains unclear. The objective of this study is to investigate the potential relationship between cardiovascular risk factors (CVRFs) and PE without IRF (unprovoked) and assess their role as markers of disease severity and prognosis. Methods: A case-control study was performed of patients with PE admitted to our hospital [2010-2019]. Subjects with PE without IRF were included in the cohort of cases, whereas patients with PE with IRF were allocated to the control group. Variables of interest included age, active smoking, obesity, and diagnosis of arterial hypertension, dyslipidemia or diabetes mellitus. Results: A total of 1,166 patients were included in the study, of whom 64.2% had PE without IRF. The risk for PE without IRF increased with age [odds ratio (OR): 2.68; 95% confidence interval (CI): 1.95-3.68], arterial hypertension (OR: 1.63; 95% CI: 1.27-2.07), and dyslipidemia (OR: 1.63; 95% CI: 1.24-2.15). The risk for PE without IRF was higher as the number of CVRF increased, being 3.99 (95% CI: 2.02-7.90) for subjects with >/=3 CVRF. The percentage of high-risk unprovoked PE increased significantly as the number of CVRF rose [0.6% for no CVRF; 23.8% for a CRF, P/=3, P<0.001 (OR: 14.1; 95% CI: 4.06-49.4)]. No significant differences were observed in 1-month survival between cases and controls, whereas differences in 24-month survival reached significance. Conclusions: A relationship was observed between CVRF and PE without IRF, as the risk for unprovoked PE increased with the number of CVRF. In addition, the number of CVRF was associated with PE without IRF severity, but not with prognosis

Biogeographical origin and timing of the founder ichthyosis TGM1 c.1187G > A mutation in an isolated Ecuadorian population

An unusually high frequency of the lamellar ichthyosis TGM1 mutation, c.1187G > A, has been observed in the Ecuadorian province of Manabi. Recently, the same mutation has been detected in a Galician patient (Northwest of Spain). By analyzing patterns of genetic variation around this mutation in Ecuadorian patients and population matched controls, we were able to estimate the age of c.1187G > A and the time to their most recent common ancestor (TMRCA) of c.1187G > A Ecuadorian carriers. While the estimated mutation age is 41 generations ago (~1,025 years ago [ya]), the TMRCA of Ecuadorian c.1187G > A carrier haplotypes dates to just 17 generations (~425 ya). Probabilistic-based inferences of local ancestry allowed us to infer a most likely European origin of a few (16% to 30%) Ecuadorian haplotypes carrying this mutation. In addition, inferences on demographic historical changes based on c.1187G > A Ecuadorian carrier haplotypes estimated an exponential population growth starting ~20 generations, compatible with a recent founder effect occurring in Manabi. Two main hypotheses can be considered for the origin of c.1187G > A: (i) the mutation could have arisen in Spain >1,000 ya (being Galicia the possible homeland) and then carried to Ecuador by Spaniards in colonial times ~400 ya, and (ii) two independent mutational events originated this mutation in Ecuador and Galicia. The geographic and cultural characteristics of Manabi could have favored a founder effect that explains the high prevalence of TGM1 c.1187G > A in this region

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Structural determinants of the SINE B2 element embedded in the long non-coding RNA activator of translation AS Uchl1

Pervasive transcription of mammalian genomes leads to a previously underestimated level of complexity in gene regulatory networks. Recently, we have identified a new functional class of natural and synthetic antisense long non-coding RNAs (lncRNA) that increases translation of partially overlapping sense mRNAs. These molecules were named SINEUPs, as they require an embedded inverted SINE B2 element for their UP-regulation of translation. Mouse AS Uchl1 is the representative member of natural SINEUPs. It was originally discovered for its role in increasing translation of Uchl1 mRNA, a gene associated with neurodegenerative diseases. Here we present the secondary structure of the SINE B2 Transposable Element (TE) embedded in AS Uchl1. We find that specific structural regions, containing a short hairpin, are required for the ability of AS Uchl1 RNA to increase translation of its target mRNA. We also provide a high-resolution structure of the relevant hairpin, based on NMR observables. Our results highlight the importance of structural determinants in embedded TEs for their activity as functional domains in lncRNAs