Timing of P2Y12 Inhibitor Administration in Patients With STEMI Undergoing Primary PCI.

BACKGROUND: The optimal timing of P2Y12 inhibitor administration in patients with ST-segment elevation myocardial infarction (STEMI) has not been completely elucidating. OBJECTIVES: This analysis from a prospective multicenter registry sought to assess the safety and effectiveness of P2Y12 inhibitor pretreatment in patients transferred for primary percutaneous coronary intervention (PCI) within a regional STEMI network. METHODS: Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography. Endpoints were major adverse cardiac events (MACE), major bleeding, and net adverse clinical events, a composite of MACE or major bleeding, within 30 days of index admission. Association of P2Y12 inhibitor pretreatment with outcomes was modeled using doubly robust weighted estimators based on propensity score analysis. RESULTS: Of 1,624 patients included, 1,033 received P2Y12 inhibitors before angiography and 591 in the catheterization laboratory (cath lab). The non-pretreated cohort more often had history of coronary artery disease and were more likely to receive antiplatelet therapy before the index admission. After adjustment for confounding and dependent censoring, pretreatment with P2Y12 inhibitors predicted lower risk of MACE (adjusted HR: 0.53; 95% CI: 0.37-0.76), without increasing bleeding risk (adjusted HR: 0.62; 95% CI: 0.36-1.05), resulting in superior net clinical benefit (adjusted HR: 0.47; 95% CI: 0.26-0.86) compared with in-cath lab administration of P2Y12 inhibitors. There was a significant treatment-by-time interaction for MACE risk, whereby the observed benefits of pretreatment only became apparent when time between P2Y12 inhibitor administration and PCI was longer than 80 minutes. CONCLUSIONS: In contemporary patients with STEMI transferred for primary PCI, pretreatment with P2Y12 inhibitors was associated with a significant time-dependent reduction of 30-day MACE without increasing bleeding risk.

AI-driven remote sensing enhances Mediterranean seagrass monitoring and conservation to combat climate change and anthropogenic impacts.

Seagrasses are undergoing widespread loss due to anthropogenic pressure and climate change. Since 1960, the Mediterranean seascape lost 13-50% of the areal extent of its dominant and endemic seagrass-Posidonia oceanica, which regulates its ecosystem. Many conservation and restoration projects failed due to poor site selection and lack of long-term monitoring. Here, we present a fast and efficient operational approach based on a deep-learning artificial intelligence model using Sentinel-2 data to map the spatial extent of the meadows, enabling short and long-term monitoring, and identifying the impacts of natural and human-induced stressors and changes at different timescales. We apply ACOLITE atmospheric correction to the satellite data and use the output to train the model along with the ancillary data and therefore, map the extent of the meadows. We apply noise-removing filters to enhance the map quality. We obtain 74-92% of overall accuracy, 72-91% of user's accuracy, and 81-92% of producer's accuracy, where high accuracies are observed at 0-25 m depth. Our model is easily adaptable to other regions and can produce maps in in-situ data-scarce regions, providing a first-hand overview. Our approach can be a support to the Mediterranean Posidonia Network, which brings together different stakeholders such as authorities, scientists, international environmental organizations, professionals including yachting agents and marinas from the Mediterranean countries to protect all P. oceanica meadows in the Mediterranean Sea by 2030 and increase each country's capability to protect these meadows by providing accurate and up-to-date maps to prevent its future degradation.

Nonadherence to ticagrelor versus clopidogrel and clinical outcomes in patients with ACS. Results from the CREA-ARIAM registry.

INTRODUCTION AND OBJECTIVES: Prior studies have not determined whether the effect of dual antiplatelet therapy (DAPT) cessation on the subsequent risk of major adverse cardiac events (MACE) varies by the choice of P2Y12-inhibitor after acute coronary syndrome (ACS). METHODS: We performed a prespecified subanalysis of a multicenter, prospective registry of ACS patients discharged on ticagrelor or clopidogrel between 2015 and2019. Nonadherence to DAPT was categorized as physician-guided discontinuation and disruption due to adverse effects, nonadherence, or bleeding. The association between DAPT cessation and 1-year MACE was analyzed using multivariate time-updated Cox models with inverse probability of censoring weighted estimators. RESULTS: Out of 2180 patients, 174 (8.3%) prematurely discontinued DAPT (physician-guided, n=126; disruption, n=48). Nonadherent patients were older and had more comorbidities than those on DAPT. Compared with physician-guided discontinuation, disruption occurred earlier after discharge and was more frequent with ticagrelor than with clopidogrel. In time-varying analysis, DAPT cessation was associated with an increased risk of MACE (adjusted HR, 1.32, 95%CI, 1.10-1.76), largely driven by disruption (adjusted HR, 1.47, 95%CI, 1.22-1.73). There was an exponential increase in MACE risk after DAPT cessation within 90 days after ACS, especially after disruption of ticagrelor compared with clopidogrel (Pinteraction<.001). After adjustment for DAPT duration, this interaction was not statistically significant on the additive scale (relative excess risk due to interaction 0.12, 95%CI,-0.99-1.24). CONCLUSIONS: In this all-comers registry, 1 in 12 patients prematurely discontinued DAPT within 1 year after ACS. Compared with physician-recommended discontinuation, disruption resulted in a significantly higher risk of MACE. After adjustment for DAPT duration, this association was not moderated by the choice of P2Y12-inhibitor. Clinical trial registered at ClinicalTrials.gov (Identifier: NCT02500290).

Occurrence of Aliarcobacter spp. in fresh and pre-cut vegetables of common use in San José, Costa Rica.

Aliarcobacter is a Gram-negative rod that can cause disease in both animals and humans. Several studies have evidenced its presence in a wide variety of foods. Given that the number of foodborne illness outbreaks linked to the consumption of vegetables has increased worldwide and that there is a lack of information about the occurrence of Aliarcobacter spp. in these, the aim of this study was to evaluate its presence and the occurrence of virulence factors in both fresh and ready-to-eat vegetable samples. 180 vegetable samples from Costa Rica were analyzed for the presence of Aliarcobacter spp., including 90 pre-cut vegetable packages and 90 fresh vegetables. Two (2.2%) of the isolates from pre-cut vegetables and 19 (21.1%) of the isolates obtained from fresh vegetables were confirmed as Aliarcobacter spp. One of the isolates from the pre-cut vegetable samples was identified as A. butzleri. For the fresh vegetables, 11 isolates were identified as A. skirrowii, one as A. butzleri, and the 7 remaining isolates could not be identified at a species level. There is an 87.5% positivity for hecA and 93.8% for pldA, virulence genes in strains isolated from fresh produce, contrasting with an absolute absence from pre-cut vegetable-isolated strains. These results evidence the presence of Aliarcobacter on fresh and pre-cut vegetables from Costa Rica and the potential hazard it might represent for public health.

Comparative Safety and Effectiveness of Ticagrelor versus Clopidogrel in Patients With Acute Coronary Syndrome: An On-Treatment Analysis From a Multicenter Registry.

Background: The net clinical benefit of ticagrelor over clopidogrel in acute coronary syndrome (ACS) has recently been questioned by observational studies which did not account for time-dependent confounders. We aimed to assess the comparative safety and effectiveness of ticagrelor vs. clopidogrel accounting for non-adherence in a real-life setting. Methods: This is a prospective, multicenter cohort study of patients with ACS discharged on ticagrelor or clopidogrel between 2015 and 2019. Major exclusions were previous intracranial bleeding, and the use of prasugrel or oral anticoagulation. Association of P2Y12 inhibitor therapy with 1-year risk of Bleeding Academic Research Consortium Type 3 or 5 bleeding; major adverse cardiac events (MACEs), a composite endpoint of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, or urgent target lesion revascularization; definite/probable stent thrombosis; vascular death; and net adverse clinical event (a composite endpoint of major bleeding and MACE) were analyzed according to the "on-treatment" principle, using fully adjusted Cox and Fine-Gray regression models with doubly robust inverse probability of censoring weighted estimators. Results: Among 2,070 patients (mean age 63 years, 27% women, 62.5% ST-elevation MI), 1,035 were discharged on ticagrelor and clopidogrel, respectively. Ticagrelor-treated patients were younger and had few comorbidities, but high rates of medication non-compliance, compared with clopidogrel users. After comprehensive multivariate adjustments, ticagrelor did not increase the risk of major bleeding compared with clopidogrel [subhazard ratio, 1.40; 95% confidence interval (CI), 0.96-2.05], while proved superior in reducing MACE (hazard ratio 0.62; 95% CI, 0.43-0.90), vascular death (subhazard ratio, 0.71; 95% CI, 0.52-0.97) and definite/probable stent thrombosis (subhazard ratio, 0.54; 95% CI, 0.30-0.79); thereby resulting in a favorable net clinical benefit (hazard ratio 0.78; 95% CI, 0.60-0.98) compared with clopidogrel. Results from sensitivity analyses were consistent with those from the primary analysis, whereas those from the intention-to-treat (ITT) analysis went in the opposite direction. Conclusion: Among all-comers with ACS, ticagrelor did not significantly increase the risk of major bleeding, while resulting in a net clinical benefit compared with clopidogrel. Further research is warranted to confirm these findings in high bleeding risk populations. CREA-ARIAM Andalucía: (ClinicalTrials.gov Identifier: NCT02500290); Current pre-specified analysis (ClinicalTrials.gov Identifier: NCT04630288).

Fondaparinux versus enoxaparin in the contemporary management of non-ST-elevation acute coronary syndromes. Insights from a multicenter registry.

BACKGROUND: Fondaparinux is thought to have the most favorable risk-benefit profile among all anticoagulants in non-ST-elevation acute coronary syndrome (NSTE-ACS). However, conflicting findings exist whether this holds true in current clinical practice. We aimed to assess the net clinical benefit of fondaparinux versus enoxaparin in the contemporary management of NSTE-ACS. METHODS: Analysis of prospective multicenter registry data of NSTE-ACS patients who received fondaparinux or enoxaparin from February 2015, through December 2017. Survival models within a competing risks framework including site-specific random effects, were used to assess the composite of clinically relevant bleedings and major adverse cardiovascular events at 30 days. RESULTS: Of 2094 patients, 1724 (82%) received enoxaparin and 370 (18%) fondaparinux. Both groups were comparable except for a lower prevalence of diabetes and renal impairment, and greater use of transradial approach in the fondaparinux group. Multivariate analysis revealed a net clinical benefit in favour of fondaparinux versus enoxaparin (Subhazard Ratio [SHR] 0.59; 95%CI 0.37-0.92), mainly driven by a reduction in bleeding (SHR 0.57; 95%CI 0.37-0.89). Exploratory analysis suggested greater reductions in bleeding with fondaparinux among patients undergoing transradial approach, revealing a significant interaction between treatment and vascular access on the multiplicative scale (Pinteraction = 0.0056), but not on an additive scale (P = 0.457). Propensity-score-matching analysis yielded similar results. CONCLUSIONS: In contemporary management of NSTE-ACS, fondaparinux seems to provide a favorable net clinical benefit compared with enoxaparin, primarily driven by a bleeding reduction. Effect modification on the safety profile of fondaparinux by the vascular access approach warrants further investigation.

Searching for the erosion of empathy in medical undergraduate students: a longitudinal study.

OBJECTIVE: To analyse the trajectory of empathy throughout the degree programme of medicine in a Spanish school of medicine. DESIGN: Longitudinal, prospective 5-year study, between October 2014 and June 2019. SETTING: Students from a Spanish university of medicine. PARTICIPANTS: Two voluntary cohorts of undergraduate medical students from two different school years were invited to participate (n=135 (cohort 1, C1) and 106 (cohort 2, C2) per school year). Finally, a total number of 174 students (102 (C1, 71.6% women) and 72 (C2, 70.8% women) students, respectively) were monitored for 5 years. Each cohort was divided in two subcohorts of paired and unpaired students that were analysed to check possible social desirability bias. PRIMARY OUTCOME MEASURE: The Jefferson Scale of Empathy (JSE). RESULTS: The cohort of 102 students (C1) monitored between their first and fifth years of study (71.6% women) showed an improvement among paired women of 2.15 points in total JSE score (p=0.01) and 2.39 points in cognitive empathy (p=0.01); in the unpaired female cohort the increase was of 2.32 points (cognitive empathy) (p=0.02). The cohort of 72 students (C2) monitored between their second and sixth years of study (70.8% women) displayed a cognitive empathy increase of 2.32 points (p=0.04) in the paired group of women. There were no significant differences between paired and unpaired results for either cohort. Empathy scores among men did not decrease. CONCLUSIONS: The empathy of medical students at our school did not decline along grade years. In fact, it improved slightly, particularly cognitive empathy, among women. This paper contributes to enlarge data from Europe, where longitudinal studies are scarce. It supports the idea that there may be global geo-sociocultural differences; however, more studies comparing different school settings are needed.

Rate of detection of advanced neoplasms in proximal colon by simulated sigmoidoscopy vs fecal immunochemical tests.

BACKGROUND & AIMS: We compared the ability of biennial fecal immunochemical testing (FIT) and one-time sigmoidoscopy to detect colon side-specific advanced neoplasms in a population-based, multicenter, nationwide, randomized controlled trial. METHODS: We identified asymptomatic men and women, 50-69 years old, through community health registries and randomly assigned them to groups that received a single colonoscopy examination or biennial FIT. Sigmoidoscopy yield was simulated from results obtained from the colonoscopy group, according to the criteria proposed in the UK Flexible Sigmoidoscopy Trial for colonoscopy referral. Patients who underwent FIT and were found to have ≥75 ng hemoglobin/mL were referred for colonoscopy. Data were analyzed from 5059 subjects in the colonoscopy group and 10,507 in the FIT group. The main outcome was rate of detection of any advanced neoplasm proximal to the splenic flexure. RESULTS: Advanced neoplasms were detected in 317 subjects (6.3%) in the sigmoidoscopy simulation group compared with 288 (2.7%) in the FIT group (odds ratio for sigmoidoscopy, 2.29; 95% confidence interval, 1.93-2.70; P = .0001). Sigmoidoscopy also detected advanced distal neoplasia in a higher percentage of patients than FIT (odds ratio, 2.61; 95% confidence interval, 2.20-3.10; P = .0001). The methods did not differ significantly in identifying patients with advanced proximal neoplasms (odds ratio, 1.17; 95% confidence interval, 0.78-1.76; P = .44). This was probably due to the lower performance of both strategies in detecting patients with proximal lesions (sigmoidoscopy detected these in 19.1% of patients and FIT in 14.9% of patients) vs distal ones (sigmoidoscopy detected these in 86.8% of patients and FIT in 33.5% of patients). Sigmoidoscopy, but not FIT, detected proximal lesions in lower percentages of women (especially those 50-59 years old) than men. CONCLUSIONS: Sigmoidoscopy and FIT have similar limitations in detecting advanced proximal neoplasms, which depend on patients' characteristics; sigmoidoscopy underperforms for women 50-59 years old. Screening strategies should be designed on the basis of target population to increase effectiveness and cost-effectiveness. ClinicalTrials.gov number: NCT00906997.

Risk of advanced proximal neoplasms according to distal colorectal findings: comparison of sigmoidoscopy-based strategies.

BACKGROUND: Screening for colorectal cancer with sigmoidoscopy benefits from the fact that distal findings predict the risk of advanced proximal neoplasms (APNs). This study was aimed at comparing the existing strategies of postsigmoidoscopy referral to colonoscopy in terms of accuracy and resources needed. METHODS: Asymptomatic individuals aged 50-69 years were eligible for a randomized controlled trial designed to compare colonoscopy and fecal immunochemical test. Sigmoidoscopy yield was estimated from results obtained in the colonoscopy arm according to three sets of criteria of colonoscopy referral (from those proposed in the UK Flexible Sigmoidoscopy, Screening for COlon REctum [SCORE], and Norwegian Colorectal Cancer Prevention [NORCCAP] trials). Advanced neoplasm detection rate, sensitivity, specificity, and number of individuals needed to refer for colonoscopy to detect one APN were calculated. Logistic regression analysis was performed to identify distal findings associated with APN. All statistical tests were two-sided. RESULTS: APN was found in 255 of 5059 (5.0%) individuals. Fulfillment of UK (6.2%), SCORE (12.0%), and NORCCAP (17.9%) criteria varied statistically significantly (P < .001). The NORCCAP strategy obtained the highest sensitivity for APN detection (36.9%), and the UK approach reached the highest specificity (94.6%). The number of individuals needed to refer for colonoscopy to detect one APN was 6 (95% confidence interval [CI] = 4 to 7), 8 (95% CI = 6 to 9), and 10 (95% CI = 8 to 12) when the UK, SCORE, and NORCCAP criteria were used, respectively. The logistic regression analysis identified distal adenoma ≥10 mm (odds ratio = 3.77; 95% CI = 2.52 to 5.65) as the strongest independent predictor of APN. CONCLUSIONS: Whereas the NORCCAP criteria achieved the highest sensitivity for APN detection, the UK recommendations benefited from the lowest number of individuals needed to refer for colonoscopy.

[Acute coronary syndrome in women. Gender differences]. / Síndrome coronario agudo en la mujer. Diferencias de género.

BACKGROUND AND OBJECTIVE: Our aims was to investigate possible gender differences in the diagnostic assessment, treatment and prognosis of patients admitted with acute coronary syndrome (ACS). PATIENTS AND METHODS: Prospective study of a cohort of 396 patients consecutively admitted to the coronary unit in the period of 18 months with the diagnoses of ACS. We divided the sample into two groups based on gender: 294 men and 102 women. We analysed the diagnostic assessment, hospital treatment, coronary revascularization (ICP), appearance of heart failure (HF) and in-hospital and 1-year mortality. We analyzed predictors of mortality in a multivariate model. RESULTS: Women were older (70.9±11.9 versus 64.4±12.0; P<.001) and had more comorbidities such as hypertension (70.5% versus 53.7%; P=.003), diabetes (51.0% versus 33.3%; P<.01) and HF (20.5% versus 9.1%; P<.01) than men, while men had greater frequency of smoking (54.42% versus 13.73%; P<.001). Women had higher incidence of cardiogenic shock on admission. There were no differences in thrombolysis and women did not have a different pattern of access to coronary angiography, but men had greater frequency of ICP (50.8% versus 34.6%; P<.01). Women were more likely to develop a higher in-hospital HF (32.6% versus 25.9%; P<.05) and in-hospital mortality (17.6% versus 4.7%; P<.001). In the multivariate analyses, HF on admission OR 8.98 (3.29-24.47), older age OR 1.07 (1.01-1.13) and female gender OR 3.14 (1.27-7.74), were independent predictors of in-hospital mortality. CONCLUSIONS: In our study, female gender was an independent predictor of in-hospital mortality in patients with ACS.

Supported p-toluenesulfonic acid as a highly robust and eco-friendly isocyanide scavenger.

We document here the use of polymer-supported p-toluenesulfonic acid as a highly effective, robust, economical and eco-friendly isocyanide scavenger. The herein described strategy circumvent the intense and repulsive odor of volatile isocyanides, enabling simplified and odorless workup and purifications. The usefulness of the new scavengers has been validated in a set of diverse isocyanide-based organic transformations and this approach is also amenable to parallel synthesis techniques.

[Factors related to refuse antiretroviral therapy in prison]. / Factores relacionados con rehusar el tratamiento antirretroviral en prisión.

INTRODUCTION: Despite the benefits of highly-active antiretroviral therapy (HAART) on morbidity and mortality, some seropositive patients refuse to accept this treatment. Prisons provide easier access to this population. OBJECTIVE: To determine the psychosocial characteristics of prisoners who refuse HAART. METHODS: We performed a cross-sectional study in 580 seropositive prisoners in 3 hospitals in Andalusia (Spain). The dependent variable was being under treatment or refusal to be so. The independent variables were sociodemographic and psychosocial factors related to the prison environment and clinical factors related to health status and drug addiction. A logistic regression analysis was performed to determine which factors were related with refusal to accept HAART. RESULTS: HAART was recommended to 73.1% of seropositive prisoners. This treatment was refused by 23.1% of these prisoners and was accepted by 76.9%. The factors related to refusal to accept HAART were high viral load, worse self-perceived health status, a greater number of stays in prison, and being visited by persons other than relatives. CONCLUSIONS: There is a group of prisoners with specific characteristics that refuse HAART. Specific interventions should be performed in these prisoners to make them aware of the effects of their decision on the course of their disease.

Adherence to antiretroviral treatment in prisons.

The effectiveness of antiretroviral drugs is closely linked to the degree of adherence. The prison environment has specific characteristics that may affect adherence in HIV-positive patients, so that it may not be possible to extrapolate factors associated with nonadherence in HIV+ patients outside prison. The objective was to analyze the prevalence of nonadherence to antiretroviral treatment in three Spanish prisons, and to examine the relation between a large group of factors and nonadherence to the medication. A cross-sectional study of all patients receiving antiretroviral treatment was done. Adherence was evaluated using a validated questionnaire (SMAQ). The prevalence of nonadherence was 54.8%, and the factors independently associated with nonadherence were having difficulties in taking the medication, feeling completely or largely unable to follow the medication, classifying the food as "bad", mentioning not having anyone concerned for them outside prison, suffering anxiety or depression in the last week, and having the flexibility of the prison staff opening their cell in the event of them forgetting their medication.

Carbocyclic analogues of nucleosides from bis-(Hydroxymethyl)-cyclopentane: synthesis, antiviral and cytostatic activities of adenosine, inosine and uridine analogues.

Six new carbocyclic nucleosides were prepared by constructing a purine base (in compounds 9-11) or pyrimidine base (in 6-8) on the amino groups of (+/-)-(1 beta,2 alpha,4 beta)-4-amino-1,2-cyclopentanedimethanol (4) and (+/-)-(1 beta,3 alpha,4 beta)-4-amino-1,3-cyclopentanedimethanol (5), and their activities against a variety of viruses and tumour cell lines were determined.

Técnica para la conservación del semen congelado / Technique for the preservation of frozen semen

Se realiza un análisis de las dificultades que presentan las inseminaciones artificiales tanto homólogas como heterólogas, con semen fresco, y los beneficios de la creación de un banco de semen. Se analiza la técnica empleada para la conservación de semen congelado en nitrógeno líquido. Se realiza un ánalisis de los resultados obtenidos con la inseminación por este método. Se hacen conclusiones

Nacimiento por inseminación artificial heteróloga y por semen congelado: presentación de 3 casos / Birth by heterologous artificial insemination and frozen semen

Se realiza un esbozo histórico de la inseminación artificial, desde su surgimiento hasta llegar a la técnica de la inseminación artificial heteróloga con semen congelado. Se analizan los resultados obtenidos con la aplicación de este método de inseminación. Se presentan los 3 primeros casos de recién nacidos engendrados por esta técnica en este centro docente. Se hacen conclusiones

Técnica de la inseminación artificial / Artificial insemination technique

Se describe un esbozo histórico del comienzo de la inseminación artificial. Se dan a conocer distintos métodos para la realización de la misma a la mujer. Se analiza el método para la inseminación artificial homóloga y heteróloga, con semen fresco o congelado. Se hace un análisis de los resultados obtenidos. Se realizan conclusiones

Prueba poscoital: correlación de la misma con los resultados del cultivo del moco cervical, del espermocultivo, del cultivo del líquido prostático y del espermograma / Postcoital test: its correlation with results from the culture of cervical mucus, spermoculture, culture of prostatic fluid and spermogram

Se hace un recuento histórico donde se pone de manifiesto el origen de la prueba poscoital o de Sims-Hünner, así como la importancia que el mismo ha tenido y aún tiene en el estudio de la pareja infértil. Se realiza un estudio de los resultados de los test poscoitales realizados a 50 parejas. Se correlacionan dichos resultados con los obtenidos del cultivo del moco cervical, del espermocultivo, del cultivo del líquido prostático y del espermograma

Recién nacido producto de inseminación artificial / Newborn from artificial insemination

En el Hospital Docente Materno Infantil "10 de Octubre", se realizó inseminación artificial a 21 mujeres, en un período de 4 años (l980-l983), donde este procedimiento predominó con semen homológo. Se señala que en más de la mitad de los casos los resultados fueron satisfactorios y que los recien nacidos fueron considerados como sanos y no presentaron durante su período neonatal ningún factor de riesgo que pudiera interferir a largo plazo su desarrollo intelectual y somático. Se indica que en todos nuestros casos el cociente de desarrollo estuvo igual o por encima de la edad cronológica