Analysis of the Financial Impact of Using Cangrelor on the Safety and Efficacy Outcomes in Patients Undergoing Percutaneous Coronary Intervention in Whom Oral Therapy with P2Y12 Inhibitors is Not Feasible or Desirable, in Spain

Purpose: Cangrelor is an intravenous, direct-acting, reversible P2Y12 inhibitor indicated for the reduction of thrombotic cardiovascular events in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) in whom oral P2Y12 inhibitors are not feasible or desirable. The objective was to assess the financial impact of introducing cangrelor into the hospital formulary in Spain. Patients and Methods: A budget impact model was developed to calculate the cost difference between two scenarios (without and with cangrelor) to treat CAD patients undergoing PCI in whom oral P2Y12 inhibitors are not feasible or desirable, over 3 years. Intravenous P2Y12 inhibitor (cangrelor), oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor), and glycoprotein IIb-IIIa inhibitors (GPIs) for bail-out use were considered. Epidemiological, efficacy (thrombotic events including cardiac death), safety (bleeding events), and costs (¿, 2019) data were based on Spanish registries, clinical trials, and meta-analyses. One-way sensitivity analysis established the effect of uncertainty on results. Results: For years 1, 2, and 3, the target population to receive cangrelor was 607, 1,822, and 3,340 patients, and cangrelor uptake was 23.70%, 58.30%, and 51.30%, respectively. The 3-year budget impact was 1,021,717¿ varying from 50,245¿ in year 1 to 599,272¿ in year 3. The results were sensitive to the number of patients treated with GPIs in Spanish hospitals. Conclusion: Based on our results, the financial effort needed to introduce the use of cangrelor in patients undergoing PCI in whom antiplatelet therapy with oral P2Y12 inhibitors is not feasible or desirable barely exceeds one million ¿ over three years, in Spain

Do People with Type 2 Diabetes Think They are Unhealthy? A Cross-Sectional Study in Celaya, Mexico

Background: Type 2 diabetes is a chronic disease that presents a significant burden on health care systems in many countries. With the rise of obesity, the incidence of Type 2 diabetes has also been steadily increasing. A healthy lifestyle and understanding of diabetes management are important factors for delaying the onset of comorbidities associated with Type 2 diabetes. The objective of this study was to evaluate the self-perception of health in individuals with Type 2 diabetes as it relates to BMI status, which has important implications for the implementation of preventive programs. Methods: A cross-sectional lifestyle survey was implemented in the region of Celaya, Guanajuato, Mexico, targeting 100 participants diagnosed with Type 2 diabetes. Anthropometric measurements and participant characteristics were also obtained. Fisher’s exact test was used to determine if the proportions of lifestyles perceptions differed by BMI status. Results:  Participants had a mean age of 56.12 ± 10.26, a mean BMI of 29.13 ± 5.48 kg/m2, were mostly married (67.0%), and female (70.0%). None of the normal weight participants perceived themselves as unhealthy. 95% of overweight/obese participants perceived themselves to be healthy, despite a diagnosis of diabetes and being overweight/obese, while only 5% perceived themselves to be unhealthy. However, these differences in the perceptions of health classified by BMI status were not statistically significant (p = 0.42).Conclusion: Our findings indicate that overweight and obese persons with Type 2 diabetes in Celaya, Mexico may have misperceptions about their own health, even though these findings were not statistically significant. These preliminary data highlight the importance of implementing prevention and educational programs among those with diabetes, in order to combat health misperceptions and raise awareness about the dangers of diabetes and obesity. Furthermore, more research with larger sample sizes is needed  in order to fully understand the effects of perception of health on actual health.

What Is the Capacity of Individuals with Schizophrenia and Bipolar Disorder to Make Healthcare Decisions? An Exploratory Study of the Views of Patients, Psychiatrists, and Family Caregivers—A Survey on Decisional Capacity in Mental Health

Background: Research on the decisional capacity of schizophrenia and bipolar disorder patients mostly reflects the hospital context. Aim: To describe the views of patients, psychiatrists, and caregivers on the capacity of individuals with schizophrenia and bipolar disorder to make everyday decisions on their care related to their illness. Methods: A survey was conducted among schizophrenia and bipolar disorder patients, psychiatrists, and caregivers (June 2019 to January 2020; seven countries). A questionnaire was emailed to members of the Global Alliance of Mental Illness of Advocacy Network—Europe (GAMIAN; patients) and the European Federation of Families of People with Mental Illness (EUFAMI; caregivers) and to psychiatrists who voluntarily agreed to participate. Questions referred to patients’ involvement and capacity for healthcare decision making, and to barriers to and opportunities for autonomous decision making. Frequency, agreement, and importance were rated on Likert scales. Descriptive statistics were conducted. Results: 21 schizophrenia or bipolar disorder patients (52.3% female; mean age (years) ± SD: 50.71 ± 12.02), 11 psychiatrists (18.2% female), and 15 caregivers (86.6% female; 100% family related) participated in the survey. In total, 86% of patients felt frequently involved in decisions about everyday care and medications, and 91% of psychiatrists and 40% of caregivers perceived the same; 38% of patients felt frequently involved in decisions about the use of acute symptom medications, and 57% on care planning, and 55% and 82% of psychiatrists, and 40% and 53% of caregivers, respectively, believed the same; and 86% of patients, 91% of psychiatrists, and 47% of caregivers agreed on the capacity of schizophrenia or bipolar disorder patients to value the implications of taking medicines to prevent acute psychotic crises. Poor understanding and training are barriers, while advocacy and increasing interest in patients’ needs are opportunities for increasing autonomous decision making. Conclusions: Stakeholders concur that schizophrenia and bipolar disorder patients have the capacity to make everyday decisions around their care related to their illness, including acute symptom management. Barriers and opportunities exist to foster autonomous decisions among mental illness individuals

Isolation of Ovicidal Fungi from Fecal Samples of Captive Animals Maintained in a Zoological Park

There are certain saprophytic fungi in the soil able to develop an antagonistic effect against eggs of parasites. Some of these fungal species are ingested by animals during grazing, and survive in their feces after passing through the digestive tract. To identify and isolate ovicidal fungi in the feces of wild captive animals, a total of 60 fecal samples were taken from different wild animals kept captive in the Marcelle Natureza Zoological Park (Lugo, Spain). After the serial culture of the feces onto Petri dishes with different media, their parasicitide activity was assayed against eggs of trematodes (Calicophoron daubneyi) and ascarids (Parascaris equorum). Seven fungal genera were identified in the feces. Isolates from Fusarium, Lecanicillium, Mucor, Trichoderma, and Verticillium showed an ovicidal effect classified as type 3, because of their ability to adhere to the eggshell, penetrate, and damage permanently the inner embryo. Penicillium and Gliocladium developed a type 1 effect (hyphae attach to the eggshell but morphological damage was not provoked). These results provide very interesting and useful information about fungi susceptible for being used in biological control procedures against parasitesThis research was partly supported by the Research Projects AGL2012-34355 and CTM2015-65954-R (Ministerio de Economía y Competitividad, Spain; FEDER). María S. Arias is recipient of a “Parga Pondal” postdoctoral research fellowship (Xunta de Galicia, Spain)S

A non-replicative antibiotic resistance-free DNA vaccine delivered by the intranasal route protects against canine leishmaniasis

Leishmania infantum is the etiological agent of zoonotic visceral leishmaniasis (ZVL). The disease is endemic in Central and South America, Central and South East Asia, and the Mediterranean basin. Dogs are the main reservoir, with an estimated prevalence of approximately 2.5 million dogs in Southern Europe. Current treatments cause side effects, disease recurrence, and drug resistance. Therefore, the development of vaccines against canine leishmaniasis is necessary. We have generated a DNA vaccine based on the non-replicative antibiotic resistance marker-free plasmid vector pPAL that contains the encoding gene for the L. infantum activated protein kinase C receptor analog (LACK). Homologous pPAL-LACK prime-boost intranasal administration confers efficacious protection in Beagle dogs with a reduction of clinical signs and a statistically significant reduction of the parasite burden in the bone marrow of more than 90% of dogs after experimental infection with highly infective promastigotes. This DNA vaccine elicits a robust cellular immune response skewed towards the Th1 profile

Effectiveness hyperoxygenated fatt y acid with silicone in lo wer extremities with and without ulcerations

Introducción: Existen evidencias científicas sobre los beneficios del uso de ácidos grasos para la regeneración epidérmica y la prevención de las úlceras crónicas. Los ácidos grasos hiperoxigenados (AGHO) son productos compuestos por ácidos grasos esenciales (AGE) a los que se añade oxigeno a la molécula inicial a través de un proceso llamado hiperoxidación. La formula a estudio presenta además ciclometicona (silicona). El objetivo de este estudio es comprobar la eficacia de los AGHO con silicona en extremidades inferiores, con y sin ulceraciones. Metodología: Estudio observacional, longitudinal, por cohortes de carácter prospectivo y multicéntrico realizado desde octubre de 2010 hasta septiembre de 2011. En una muestra de pacientes se aplicó AGHO con silicona en formato aceite, en extremidades inferiores con alteraciones vasculares venosas y AGHO con silicona en formato leche en extremidades inferiores isquémicas y/o neuropáticas. Se efectúo un seguimiento de 8 semanas, valorando a través de la escala Fedpalla la evolución del grado de deterioro de la integridad cutánea. Resultados: En general la muestra evolucionó tras 8 semanas de aplicación de AGHO, desde un grado II (mal pronóstico de epitelización) a un grado IV (muy buen pronóstico) de la escala Fedpalla. En 9 pacientes se midió la presión transcutánea de oxígeno, al inicio y al final del estudio, elevándose un 11.1%. Conclusión: Los AGHO con silicona utilizados han permitido la restauración de la integridad cutánea en la mayoría de los pacientes en un periodo de 56 días.Introduction: There is scientific evidence on the benefits of the use of fatty acids for epidermal regeneration and prevention of chronic ulcers. The hyperoxygenated fatty acids (HOFAs) are products composed for essential fatty acids (EFA) to which oxygen is added to molecule through a process called hyperoxidation. The formula to study presents addition cyclomethicone (silicone). The objective of this study is to test the efficacy of the HOFA with silicone in lower extremities, with or without ulcerations. Methodology: An observational study, longitudinal, cohort of character and prospective multicenter from October 2010 to September 2011. In a sample of patients were applied HOFA with silicone in oil format, in the lower extremities with vascular alterations venous and HOFA in milk format with silicone in lower extremities ischemic and/or neuropathic. There was a followup to 8 weeks, valuing through Fedpalla scale the evolution of the degree of deterioration of the skin integrity. Results: In general the sample evolved after 8 weeks of implementation of HOFA, since a grade II (poor prognosis of epithelization) to a grade IV (very good prognosis) of the scale Fedpalla. In 9 patients was measured the transcutaneous oxygen pressure at the beginning and the end of the study, rising 11.1 %. Conclusion: The HOFAs with silicone used have allowed the restoration of skin integrity in the majority of patients in a period of 56 days.Enfermerí

The Latin American experience of allografting patients with severe aplastic anaemia: real-world data on the impact of stem cell source and ATG administration in HLA-identical sibling transplants

We studied 298 patients with severe aplastic anaemia (SAA) allografted in four Latin American countries. The source of cells was bone marrow (BM) in 94 patients and PBSCs in 204 patients. Engraftment failed in 8.1% of recipients with no difference between BM and PBSCs (P = 0.08). Incidence of acute GvHD (aGvHD) for BM and PBSCs was 30% vs 32% (P = 0.18), and for grades III–IV was 2.6% vs 11.6% (P = 0.01). Chronic GvHD (cGvHD) between BM and PBSCs was 37% vs 59% (P = 0.002) and extensive 5% vs 23.6% (P = 0.01). OS was 74% vs 76% for BM vs PBSCs (P = 0.95). Event-free survival was superior in patients conditioned with anti-thymocyte globulin (ATG)-based regimens compared with other regimens (79% vs 61%, P = 0.001) as excessive secondary graft failure was seen with other regimens (10% vs 26%, P = 0.005) respectively. In multivariate analysis, aGvHD II–IV (hazard ratio (HR) 2.50, confidence interval (CI) 1.1–5.6, P = 0.02) and aGvHD III–IV (HR 8.3 CI 3.4–20.2, Po0.001) proved to be independent negative predictors of survival. In conclusion, BM as a source of cells and ATG-based regimens should be standard because of higher GvHD incidence with PBSCs, although the latter combining with ATG in the conditioning regimen could be an option in selected high-risk patient

A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19

Background: current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. Methods: we conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. Results: the analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. Conclusions: postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.)

Molecular Characterization of Spontaneous Mesenchymal Stem Cell Transformation

Background. We previously reported the in vitro spontaneous transformation of human mesenchymal stem cells (MSC) generating a population with tumorigenic potential, that we termed transformed mesenchymal cells (TMC). Methodology/Principal Findings. Here we have characterized the molecular changes associated with TMC generation. Using microarrays techniques we identified a set of altered pathways and a greater number of downregulated than upregulated genes during MSC transformation, in part due to the expression of many untranslated RNAs in MSC. Microarray results were validated by qRT-PCR and protein detection. Conclusions/Significance. In our model, the transformation process takes place through two sequential steps; first MSC bypass senescence by upregulating c-myc and repressing p16 levels. The cells then bypass cell crisis with acquisition of telomerase activity, Ink4a/Arf locus deletion and Rb hyperphosphorylation. Other transformation-associated changes include modulation of mitochondrial metabolism, DNA damage-repair proteins and cell cycle regulators. In this work we have characterized the molecular mechanisms implicated in TMC generation and we propose a two-stage model by which a human MSC becomes a tumor cell

Epigenetic clocks in relapse after a first episode of schizophrenia

The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (p = 0.030). Shorter telomere length was associated with cognitive performance (working memory, r = 0.31 p = 0.015; verbal fluency, r = 0.28 p = 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages