Clinical profile and outcomes in very elderly patients with atrial fibrillation anticoagulated with rivaroxaban: data from the EMIR study.

Objectives: To analyze the clinical profile, adequacy of treatment with rivaroxaban and outcomes in octogenarians with atrial fibrillation (AF), taking rivaroxaban in clinical practice. Methods: Observational and non-interventional study that included AF adults recruited from 79 Spanish centers, anticoagulated with rivaroxaban ≥ 6 months before being included. Data were analyzed according to age (≥ 80 vs. < 80 years) at baseline. Results: Out of 1433 patients, 453 (31.6%) were octogenarians at baseline. Compared to younger patients, octogenarians had more comorbidities, higher CHA2DS2-VASc (4.5 ± 1.3 vs. 3.0 ± 1.4; P < 0.001) and HAS-BLED scores (2.0 ± 1.0 vs. 1.4 ± 1.0; P < 0.001). Overall, the dose of rivaroxaban was adequately prescribed in 83.4% of patients, but more frequently in the younger population (71.1% vs. 89.1%; P = 0.039). After a mean follow-up of 2.2 ± 0.6 years, annual rates of stroke + systemic embolism + transient ischemic attack, MACE, cardiovascular death and major bleeding were 1.03%, 1.24%, 1.03% and 1.75%, respectively, in octogenarian patients. Except for progressive heart failure death and major bleeding, rates of outcomes in octogenarians were similar compared to younger patients. In octogenarians, the concomitant use of antiplatelet agents and non-severe dementia were independently associated with the development of ischemic stroke, whereas previous coronary revascularization and heart failure with MACE, and higher HAS-BLED score with major bleeding. Conclusions: In clinical practice, around one third of patients taking rivaroxaban are octogenarians. These patients have many comorbidities and a high thromboembolic risk. Despite that, rates of adverse events remain low. Rivaroxaban is adequately prescribed in the majority of octogenarians.

Molecular Imaging of Melanoma VEGF-expressing Tumors through [99mTc]Tc-HYNIC-Fab(Bevacizumab).

BACKGROUND: Angiogenesis is a process that many tumors depend on for growth, development, and metastasis. Vascular endothelial growth factor (VEGF) is one of the major players in tumor angiogenesis in several tumor types, including melanoma. VEGF inhibition is achieved by bevacizumab, a humanized monoclonal antibody that binds with high affinity to VEGF and prevents its function. In order to successfully enable in vivo VEGF expression imaging in a murine melanoma model, we previously labeled bevacizumab with [99mTc]Tc. We observed that this was feasible, but it had prolonged blood circulation and delayed tumor uptake. OBJECTIVE: The aim of this study was to develop a radiolabeled Fab bevacizumab fragment, [99mTc]Tc-HYNICFab( bevacizumab), for non-invasive in vivo VEGF expression molecular imaging. METHODS: Flow cytometry was used to examine VEGF presence in the murine melanoma cell line (B16-F10). Bevacizumab was digested with papain for six hours at 37°C to produce Fab(bevacizumab), which was then conjugated to NHS-HYNIC-Tfa for radiolabeling with [99mTc]Tc. Stability and binding affinity assays were also evaluated. Biodistribution and single photon emission computed tomography/computed tomography (SPECT/CT) were performed at 1, 3, and 6 h (n = 4) after injection of [99mTc]Tc-HYNIC-Fab(Bevacizumab) in normal and B16-F10 tumor-bearing C57Bl/6J mice. RESULTS: Using flow cytometry, it was shown that the B16-F10 murine melanoma cell line has intracellular VEGF expression. Papain incubation resulted in the complete digestion of bevacizumab with good purity and homogeneity. The radiolabeling yield of [99mTc]Tc-HYNIC-Fab(bevacizumab) was 85.00 ± 6.06%, with a specific activity of 291.87 ± 18.84 MBq/mg (n=3), showing in vitro stability. Binding assays demonstrated significant intracellular in vitro VEGF expression. Fast blood clearance and high kidney and tumor uptake were observed in biodistribution and SPECT/CT studies. CONCLUSIONS: We present the development and evaluation of [99mTc]Tc-HYNIC-Fab(bevacizumab), a novel molecular VEGF expression imaging agent that may be used for precision medicine in melanoma and potentially in other VEGF-expressing tumors.

New Mediators in the Crosstalk between Different Adipose Tissues.

Adipose tissue is a multifunctional organ that regulates many physiological processes such as energy homeostasis, nutrition, the regulation of insulin sensitivity, body temperature, and immune response. In this review, we highlight the relevance of the different mediators that control adipose tissue activity through a systematic review of the main players present in white and brown adipose tissues. Among them, inflammatory mediators secreted by the adipose tissue, such as classical adipokines and more recent ones, elements of the immune system infiltrated into the adipose tissue (certain cell types and interleukins), as well as the role of intestinal microbiota and derived metabolites, have been reviewed. Furthermore, anti-obesity mediators that promote the activation of beige adipose tissue, e.g., myokines, thyroid hormones, amino acids, and both long and micro RNAs, are exhaustively examined. Finally, we also analyze therapeutic strategies based on those mediators that have been described to date. In conclusion, novel regulators of obesity, such as microRNAs or microbiota, are being characterized and are promising tools to treat obesity in the future.

Enhanced Tumor Targeting of Radiolabeled Mouse/Human Chimeric Anti-Tn Antibody in Losartan-Treated Mice Bearing Tn-Expressing Lung Tumors.

Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn- tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery.

Synergistic Effect of a Flavonoid-Rich Cocoa-Carob Blend and Metformin in Preserving Pancreatic Beta Cells in Zucker Diabetic Fatty Rats.

The loss of functional beta-cell mass in diabetes is directly linked to the development of diabetic complications. Although dietary flavonoids have demonstrated antidiabetic properties, their potential effects on pancreatic beta-cell preservation and their synergistic benefits with antidiabetic drugs remain underexplored. We have developed a potential functional food enriched in flavonoids by combining cocoa powder and carob flour (CCB), which has shown antidiabetic effects. Here, we investigated the ability of the CCB, alone or in combination with metformin, to preserve pancreatic beta cells in an established diabetic context and their potential synergistic effect. Zucker diabetic fatty rats (ZDF) were fed a CCB-rich diet or a control diet, with or without metformin, for 12 weeks. Markers of pancreatic oxidative stress and inflammation, as well as relative beta-cell mass and beta-cell apoptosis, were analyzed. Results demonstrated that CCB feeding counteracted pancreatic oxidative stress by enhancing the antioxidant defense and reducing reactive oxygen species. Moreover, the CCB suppressed islet inflammation by preventing macrophage infiltration into islets and overproduction of pro-inflammatory cytokines, along with the inactivation of nuclear factor kappa B (NFκB). As a result, the CCB supplementation prevented beta-cell apoptosis and the loss of beta cells in ZDF diabetic animals. The observed additive effect when combining the CCB with metformin underscores its potential as an adjuvant therapy to delay the progression of type 2 diabetes.

Natural Killer Repertoire Restoration in TB/HIV Co-Infected Individuals Experienced an Immune Reconstitution Syndrome (CAMELIA Trial, ANRS 12153).

IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. HIV+TB+ patients were followed for 32 weeks. The NK cell repertoire was assessed in whole blood at different time points. As CAMELIA has two arms (early and late cART initiation), we analysed them separately. At enrolment, individuals had low CD4 cell counts (27 cells/mm3) and high plasma viral loads (5.76 and 5.50 log/mL for IRIS and non-IRIS individuals, respectively). Thirty-seven people developed IRIS (in the early and late arms). In the early and late arms, we observed similar proportions of total NK and NK cell subsets in TB-IRIS and non-IRIS individuals during follow-up, except for the CD56dimCD16pos (both arms) and CD56dimCD16neg (late arm only) subsets, which were higher in TB-IRIS and non-IRIS individuals, respectively, after cART. Regarding the repertoire and markers of NK cells, significant differences (lower expression of NKp30, NKG2A (CD159a), NKG2D (CD314) were observed in TB-IRIS compared to non-IRIS individuals after the start of cART. In the late arm, some changes (increased expression of CD69, NKG2C, CD158i) were observed in TB-IRIS compared to non-IRIS individuals, but only before cART initiation (during TB treatment). KIR expression by NK cells (CD158a and CD158i) was similar in both groups. CD69 expression by NK cells decreased in all groups. Expression of the NCR repertoire (NKp30, NKp44, NKp46) has similar kinetics in TB-IRIS subjects compared to non-IRIS subjects regardless of the arm analysed. NK cell reconstitution appeared to be better in TB-IRIS subjects. Although NK cell reconstitution is impaired in HIV infection after cART, as previously reported, it does not appear to be affected by the development of IRIS in HIV and TB-infected individuals.

The current clinical practice for management of post-infarction ventricular septal rupture: a European survey.

Aims: Many historical and recent reports showed that post-infarction ventricular septal rupture (VSR) represents a life-threatening condition and the strategy to optimally manage it remains undefined. Therefore, disparate treatment policies among different centres with variable results are often described. We analysed data from European centres to capture the current clinical practice in VSR management. Methods and results: Thirty-nine centres belonging to eight European countries participated in a survey, filling a digital form of 38 questions from April to October 2022, to collect information about all the aspects of VSR treatment. Most centres encounter 1-5 VSR cases/year. Surgery remains the treatment of choice over percutaneous closure (71.8% vs. 28.2%). A delayed repair represents the preferred approach (87.2%). Haemodynamic conditions influence the management in almost all centres, although some try to achieve patients stabilization and delayed surgery even in cardiogenic shock. Although 33.3% of centres do not perform coronarography in unstable patients, revascularization approaches are widely variable. Most centres adopt mechanical circulatory support (MCS), mostly extracorporeal membrane oxygenation, especially pre-operatively to stabilize patients and achieve delayed repair. Post-operatively, such MCS are more often adopted in patients with ventricular dysfunction. Conclusion: In real-life, delayed surgery, regardless of the haemodynamic conditions, is the preferred strategy for VSR management in Europe. Extracorporeal membrane oxygenation is becoming the most frequently adopted MCS as bridge-to-operation. This survey provides a useful background to develop dedicated, prospective studies to strengthen the current evidence on VSR treatment and to help improving its currently unsatisfactory outcomes.

What are the predictive variables that increase the risk of developing a complex trauma? A meta-analysis.

In 2018, Complex Post Traumatic Stress Disorder (CPTSD) was officially recognized as a distinct syndrome in the International Classification of Diseases, 11th Revision (ICD-11). This recognition aimed to differentiate between neurotic disorders secondary to stressful situations and somatoform disorders, and disorders specifically associated with stress. The inclusion of CPTSD in the ICD-11 marked the culmination of two decades of research focused on understanding its symptoms, treatments, and risk factors. However, despite the progress made, a comprehensive meta-analysis to elucidate the specific risk factors and impact on the development of CPTSD is still lacking. The objective of this article is to conduct such a meta-analysis. A total of 24 studies were selected for analysis, and the findings revealed several key risk factors associated with the development of CPTSD. The main risk factor identified is having experienced sexual abuse in childhood (k = 12; OR = 2.880). In addition, childhood physical abuse (k = 11; OR = 2.841), experiencing emotional neglect during childhood (k = 5; OR = 2.510), physical abuse throughout life (k = 8; OR = 2.149) and being a woman (k = 13; OR = 1.726) were also significant risk factors.

Maternal Diet Determines Milk Microbiome Composition and Offspring Gut Colonization in Wistar Rats.

Mother's milk contains a unique microbiome that plays a relevant role in offspring health. We hypothesize that maternal malnutrition during lactation might impact the microbial composition of milk and affect adequate offspring gut colonization, increasing the risk for later onset diseases. Then, Wistar rats were fed ad libitum (Control, C) food restriction (Undernourished, U) during gestation and lactation. After birth, offspring feces and milk stomach content were collected at lactating day (L)4, L14 and L18. The V3-V4 region of the bacterial 16S rRNA gene was sequenced to characterize bacterial communities. An analysis of beta diversity revealed significant disparities in microbial composition between groups of diet at L4 and L18 in both milk, and fecal samples. In total, 24 phyla were identified in milk and 18 were identified in feces, with Firmicutes, Proteobacteria, Actinobacteroidota and Bacteroidota collectively representing 96.1% and 97.4% of those identified, respectively. A higher abundance of Pasteurellaceae and Porphyromonas at L4, and of Gemella and Enterococcus at L18 were registered in milk samples from the U group. Lactobacillus was also significantly more abundant in fecal samples of the U group at L4. These microbial changes compromised the number and variety of milk-feces or feces-feces bacterial correlations. Moreover, increased offspring gut permeability and an altered expression of goblet cell markers TFF3 and KLF3 were observed in U pups. Our results suggest that altered microbial communication between mother and offspring through breastfeeding may explain, in part, the detrimental consequences of maternal malnutrition on offspring programming.

A new tool for evaluating health equity in academic journals; the Diversity Factor.

Current methods to evaluate a journal's impact rely on the downstream citation mapping used to generate the Impact Factor. This approach is a fragile metric prone to being skewed by outlier values and does not speak to a researcher's contribution to furthering health outcomes for all populations. Therefore, we propose the implementation of a Diversity Factor to fulfill this need and supplement the current metrics. It is composed of four key elements: dataset properties, author country, author gender and departmental affiliation. Due to the significance of each individual element, they should be assessed independently of each other as opposed to being combined into a simplified score to be optimized. Herein, we discuss the necessity of such metrics, provide a framework to build upon, evaluate the current landscape through the lens of each key element and publish the findings on a freely available website that enables further evaluation. The OpenAlex database was used to extract the metadata of all papers published from 2000 until August 2022, and Natural language processing was used to identify individual elements. Features were then displayed individually on a static dashboard developed using TableauPublic, which is available at www.equitablescience.com. In total, 130,721 papers were identified from 7,462 journals where significant underrepresentation of LMIC and Female authors was demonstrated. These findings are pervasive and show no positive correlation with the Journal's Impact Factor. The systematic collection of the Diversity Factor concept would allow for more detailed analysis, highlight gaps in knowledge, and reflect confidence in the translation of related research. Conversion of this metric to an active pipeline would account for the fact that how we define those most at risk will change over time and quantify responses to particular initiatives. Therefore, continuous measurement of outcomes across groups and those investigating those outcomes will never lose importance. Moving forward, we encourage further revision and improvement by diverse author groups in order to better refine this concept.

Construcción de Perfiles de Usuario para el Modelo Integral de Salud Familiar y Comunitario en la Comuna de Alto Hospicio, Región de Tarapacá / User Profiles for the Integrated Family and Community Health Care Model in the Alto Hospicio, a commune of a northern region of Chile

INTRODUCCIÓN: El estudio presenta perfiles integrales para usuarios de los Centros de Salud primaria de la comuna de Alto Hospicio. OBJETIVO: Conocer los perfiles de usuarios inscritos en los Centros de Salud de la comuna de Alto Hospicio desde una perspectiva integral e incorporando indicadores de satisfacción y conocimiento acerca del Modelo de Atención Integral de Salud Familiar y Comunitaria (MAIS). MATERIAL Y MÉTODO: Se elaboró un instrumento conformado por ocho dimensiones y 73 ítems, el cual se aplicó en cuatro centros de Atención de Salud Primaria de la comuna. Se realizó un muestreo aleatorio simple por cada Centro. En total se encuestaron a 1.124 personas, se obtuvo una representatividad de entre 95% y 93% de confianza, con niveles de significación que van de 5% a 7%. RESULTADOS: La caracterización usuaria pone en relevancia la diversidad de perfiles atendidos en cada Centro de Salud y revela problemáticas generales como la escasa información recibida respecto del modelo de atención familiar, el desconocimiento de los servicios prestados por los Centros de Salud y la dificultad de enfrentar situaciones de salud mental en el contexto de la pandemia COVID-19. CONCLUSIONES: Aquellos Centros de Salud que transmiten mayor información del MAIS presentan mejores indicadores respecto al conocimiento de los servicios de salud y de satisfacción usuaria. En el marco de la implementación del Modelo de Salud Familiar, es relevante conocer los perfiles de usuarios según las características de cada Centro de Salud, su población y territorio, y compartir buenas prácticas entre los Centros.

BACKGROUND: The study presents comprehensive profiles of Primary Health Care Centers of the Alto Hospicio Commune users. OBJECTIVE: To characterize users registered in the Health Centers of Alto Hospicio Commune from a comprehensive perspective, including satisfaction indicators and knowledge about the Comprehensive Family and Community Health Care Model (MAIS). METHODS: A questionnaire of 8 dimensions and 73 items was designed and applied in 4 Primary Health Care Centers in the commune. Four simple random samplings were applied. In total, 1,124 users were surveyed. The confidence and significance levels were between 95%-93% and 5%-7%, respectively. RESULTS: The user profile highlights the diversity in each Health Care Center and reveals general problems such as the lack of information regarding the family care model and services provided by the Health Care Centers and the difficulty of facing mental health situations in the context of the COVID-19 pandemic. CONCLUSIONS: Those Health Centers that provide more information about MAIS show better indicators regarding knowledge of health services and user satisfaction. The changes in public health policies and the implementation of the Comprehensive Family and Community Health Care Model require clarifying user profiles according to the characteristics of each health center, its population, and the territory, as well as sharing best practices between health centers.

Adverse Clinical Outcomes and Associated Predictors in Rivaroxaban-Treated Atrial Fibrillation Patients With Renal Impairment.

Renal impairment confers worse prognosis in patients with atrial fibrillation (AF) but there is scarce evidence about the influence of direct-acting oral anticoagulants in routine clinical practice. Herein, we compared clinical outcomes between patients with AF with and without renal impairment on rivaroxaban and investigated predictors for clinical outcomes in patients with AF with renal impairment. This was a multicenter study including patients with AF on rivaroxaban for at least 6 months. During 2.5 years follow-up, ischemic strokes (IS)/transient ischemic attacks (TIA)/systemic embolisms (SE)/myocardial infarctions (MI), major bleeding, and major adverse cardiovascular events (MACE) were recorded. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation, renal impairment was defined as a CrCl <60 ml/min, and 1,433 patients (34.8% with CrCl <60 ml/min) were included. Patients with CrCl <60 ml/min showed higher event rates for major bleeding (1.87%/year vs 0.62%/year; p = 0.003) and MACE (1.97%/year vs 0.62%/year; p = 0.002) but similar event rates for IS/TIA/SE/MI (0.66%/year vs 0.67%/year; p = 0.955). In patients with renal impairment, CHA2DS2-VASc was associated with higher risk of IS/TIA/SE/MI; HAS-BLED and any dependency level were associated with higher risk of major bleeding; and male gender and heart failure were associated with higher risk of MACE. Antiplatelets were independently associated with increased risk of IS/TIA/SE/MI and MACE. In conclusion, in patients with AF on rivaroxaban, the incidence of IS/TIA/SE/MI did not increase in those with renal impairment, suggesting that rivaroxaban may be an effective option in this subgroup. In patients with AF, male gender, heart failure, dependency, antiplatelets, CHA2DS2-VASc, and HAS-BLED were associated with increased risk of adverse outcomes.

Early approach to LDL-related risk after acute coronary syndrome: the OPTA project.

INTRODUCTION: Hyperlipidemia is the main underlying cause of atherosclerotic cardiovascular disease. Reducing low-density lipoprotein (LDL) cholesterol to recommended targets after an acute coronary syndrome (ACS) is of utmost importance as it is associated with a reduction of mortality and further cardiovascular events. Unfortunately, there are considerable gaps between guideline recommendations and clinical practice. In addition, the approach to treatment of this population is very heterogeneous, even in specialized cardiovascular units. Some easy-to-implement strategies may help to optimize the management of these patients. AREAS COVERED: The OPTA Project was developed to identify these gaps and to provide recommendations to improve and harmonize the management of patients with ACS, with a specific focus on lipids. EXPERT OPINION: Five areas of interest were defined: 1) evaluation of cardiovascular risk at admission, 2) development of a strategy to effectively and rapidly reduce LDL cholesterol levels, 3) determining LDL cholesterol goals (<55 mg/dL or stricter) and follow-up, 4) data collection during hospitalization, and 5) standardized discharge report. Specific recommendations are given to reduce inequalities, following the targets 'the lower, the better' and 'the earlier, the better.'

Non-embolic outcomes in patients with cardiovascular disease and atrial fibrillation treated with rivaroxaban.

Aim: It is not well known how comorbidities may change the prognosis of atrial fibrillation (AF) patients. This study was aimed to analyze the impact of cardiovascular disease on this population. Materials & methods: EMIR was a multicenter, prospective study, including 1433 AF patients taking rivaroxaban for ≥6 months. Data were analyzed according to the presence of vascular disease. Results: Coronary artery disease was detected in 16.4%, peripheral artery disease/aortic plaque in 6.7%, vascular disease in 28.3%. Patients with coronary artery disease had higher rates (per 100 patient-years) of major adverse cardiovascular events (2.98 vs 0.71; p < 0.001) and cardiovascular death (1.79 vs 0.41; p = 0.004). Those with vascular disease had higher rates of thromboembolic events (1.47 vs 0.44; p = 0.007), major adverse cardiovascular events (2.03 vs 0.70; p = 0.004), and cardiovascular death (1.24 vs 0.39; p = 0.025). Patients with peripheral artery disease/aortic plaque had similar rates. Conclusion: AF patients with vascular disease have a higher risk of non-embolic outcomes.

Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis.

OBJECTIVE: There has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with atrial fibrillation (AF). This review identified and systematically evaluated literature on clinical and economic outcomes of inappropriate NOAC dosing and associated patient characteristics. METHODS: MEDLINE, Embase, Cochrane Library, International Pharmaceutical Abstracts, Econlit, PubMed and NHS EEDs databases were searched for English language observational studies from all geographies published between 2008 and 2020, examining outcomes of, or factors associated with, inappropriate NOAC dosing in adult patients with AF. RESULTS: One hundred and six studies were included in the analysis. Meta-analysis showed that compared with recommended NOAC dosing, off-label underdosing was associated with a null effect on stroke outcomes (ischaemic stroke and stroke/transient ischaemic attack (TIA), stroke/systemic embolism (SE) and stroke/SE/TIA). Meta-analysis of 15 studies examining clinical outcomes of inappropriate NOAC dosing found a null effect of underdosing on bleeding outcomes (major bleeding HR=1.04, 95% CI 0.90 to 1.19; p=0.625) but an increased risk of all-cause mortality (HR=1.28, 95% CI 1.10 to 1.49; p=0.006). Overdosing was associated with an increased risk of major bleeding (HR=1.41, 95% CI 1.07 to 1.85; p=0.013). No studies were found examining economic outcomes of inappropriate NOAC dosing. Narrative synthesis of 12 studies examining drivers of inappropriate NOAC dosing found that increased age, history of minor bleeds, hypertension, congestive heart failure and low creatine clearance (CrCl) were associated with an increased risk of underdosing. There was insufficient evidence to assess drivers of overdosing. CONCLUSIONS: Our analysis suggests that off-label underdosing of NOACs does not reduce bleeding outcomes. Patients prescribed off-label NOAC doses are at an increased risk of all-cause mortality. These data underscore the importance of prescriber adherence to NOAC dosing guidelines to achieve optimal clinical outcomes for patients with AF. PROSPERO REGISTRATION NUMBER: CRD42020219844.

[User Profiles for the Integrated Family and Community Health Care Model in the Alto Hospicio, a commune of a northern region of Chile]. / Construcción de Perfiles de Usuario para el Modelo Integral de Salud Familiar y Comunitario en la Comuna de Alto Hospicio, Región de Tarapacá.

BACKGROUND: The study presents comprehensive profiles of Primary Health Care Centers of the Alto Hospicio Commune users. OBJECTIVE: To characterize users registered in the Health Centers of Alto Hospicio Commune from a comprehensive perspective, including satisfaction indicators and knowledge about the Comprehensive Family and Community Health Care Model (MAIS). METHODS: A questionnaire of 8 dimensions and 73 items was designed and applied in 4 Primary Health Care Centers in the commune. Four simple random samplings were applied. In total, 1,124 users were surveyed. The confidence and significance levels were between 95%-93% and 5%-7%, respectively. RESULTS: The user profile highlights the diversity in each Health Care Center and reveals general problems such as the lack of information regarding the family care model and services provided by the Health Care Centers and the difficulty of facing mental health situations in the context of the COVID-19 pandemic. CONCLUSIONS: Those Health Centers that provide more information about MAIS show better indicators regarding knowledge of health services and user satisfaction. The changes in public health policies and the implementation of the Comprehensive Family and Community Health Care Model require clarifying user profiles according to the characteristics of each health center, its population, and the territory, as well as sharing best practices between health centers.

Components of event-related potentials and borderline personality disorder: a meta-analysis.

Background: Borderline personality disorder (BPD) is characterized by symptoms associated with difficulties in emotion regulation, altered self-image, impulsivity, and instability in personal relationships. A relationship has been found between BPD symptoms and altered neuropsychological processes. Studies of event-related potentials (ERP) measured with electroencephalogram (EEG) have found neural correlates related to BPD symptoms. Of note is the P300 component, considered a potential mental health biomarker for trauma-associated disorders. However, no meta-analysis has been found to demonstrate this relationship.Objectives: To evaluate the relationship between the P300 component and BPD symptoms. To evaluate the relationship of other ERP components with BPD symptoms.Methods: The method and procedure were adjusted to the PRISMA checklist. The search was performed in three databases: WOS, Scopus and PubMed. A Random Effects Model was used to perform the analysis of the studies. In addition, a meta-regression was performed with % women, Gini and GDP. Finally, a descriptive analysis of the main results found between P300, other ERP components (LPP, P100 and ERN/Ne) and BPD symptoms was performed.Results: From a review of 485 articles, a meta-analysis was performed with six articles that met the inclusion criteria. A moderate, positive relationship was found between the P300 component and BPD symptoms (REM = .489; p < .001). It was not possible to perform meta-analyses for other ERP components (LPP, P100 and ERN/Ne) due to the low number of articles found.Conclusion: The idea that P300 could be considered for use as a biomarker to identify altered neural correlates in BPD is reinforced. In addition, a moderating effect of inequality (Gini) was detected.

The P300 component of event-related potentials could be considered for use as a possible biomarker to identify altered neural correlates in Borderline Personality Disorder.There is support for the proposition that an altered P300 would be present in disorders related to exposure to traumatic events.P300 could be used to evaluate the therapeutic processes associated with the clinical symptoms of Borderline Personality Disorder.

A PRECEDE-PROCEED approach in the advocacy for computer-based education on correct medical certification of cause of death among physician-learners

Objective@#Mortality data is a critical input to public health decision-making and planning. Yet, about 36% of underlying causes of death reported by physicians in 2018 are considered garbage codes, not useful in analyzing public health and mortality (PSA, 2018). We used the PRECEDE-PROCEED approach to develop, implement, and report an advocacy and education Project to improve training on medical certification of cause of death (MCCOD) among senior medical students and interns. @*Methods@#An MCCOD Instructional Design and eLearning course was introduced and validated in 33 medical education institutions. Lessons enhanced these education materials and are proposed for nationwide adoption. In the middle of the COVID-19 pandemic, the Project fast-tracked the training of physician-learners on the correct cause of death reporting and certification.@*Results@#Awareness of correct MCCOD and its personal and public health value reached at least 4000 learners, over a hundred medical faculty, and all deans of medical colleges in the Philippines.@*Conclusion@#The PRECEDE-PROCEED Model provided a clear and practicable framework for the advocacy and education efforts to train senior medical students and interns on MCCOD. It can similarly guide other medical education innovations by defining predisposing, enabling, and reinforcing factors then considering these factors for intervention strategies, implementation, process evaluation, outcome evaluations, and impact evaluations.

Predicting performance of the HAS-BLED and ORBIT bleeding risk scores in patients with atrial fibrillation treated with Rivaroxaban: Observations from the prospective EMIR Registry.

BACKGROUND: Assessing bleeding risk during the decision-making process of starting oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients is essential. Several bleeding risk scores have been proposed for vitamin K antagonist users but, few studies have focused on validation of these bleeding risk scores in patients taking direct oral anticoagulants (DOACs). The aim was to compare the predictive ability of HAS-BLED and ORBIT bleeding risk scores in AF patients taking rivaroxaban in the EMIR ('Estudio observacional para la identificación de los factores de riesgo asociados a eventos cardiovasculares mayores en pacientes con fibrilación auricular no valvular tratados con un anticoagulante oral directo [Rivaroxaban]) Study. METHODS AND RESULTS: EMIR Study was an observational, multicenter, post-authorization, and prospective study that involved AF patients under OAC with rivaroxaban at least 6 months before enrolment. We analysed baseline clinical characteristics and adverse events after 2.5 years of follow-up and validated the predictive ability of HAS-BLED and ORBIT scores for major bleeding (MB) events.We analysed 1433 patients with mean age of 74.2 ± 9.7 (44.5% female). Mean HAS-BLED score was 1.6 ± 1.0 and ORBIT score was 1.1 ± 1.2. The ORBIT score categorised a higher proportion of patients as 'low-risk' (87.1%) compared with 53.5% using the HAS-BLED score. There were 33 MB events (1.04%/year) and 87 patients died (2.73%/year). Both HAS-BLED and ORBIT had a good predictive ability for MB{Area under the curve (AUC) 0.770, [95% confidence interval (CI) 0.693-0.847; P <0.001] and AUC 0.765 (95% CI 0.672-0.858; P <0.001), respectively}. There was a non-significant difference for discriminative ability of the two tested scores (P = 0.930) and risk reclassification in terms of net reclassification improvement (NRI) -5.7 (95% CI -42.4-31.1; P = 0.762). HAS-BLED score showed the best calibration and ORBIT score showed the largest mismatch in calibration, particularly in higher predicted risk patients. CONCLUSION: In a prospective real-world AF population under rivaroxaban from EMIR registry, the HAS-BLED score had good predictive performance and calibration compared with ORBIT score for MB events. ORBIT score presented worse calibration than HAS-BLED in this DOAC treated population.