Using the new technologies in claudication patients: CReTe: Claudication patients and telematic register

Objetivo: Presentamos una aplicación informática para teléfonos móviles ideada para el control de sesiones de ejercicio domiciliario en claudicantes. Exponemos también nuestros resultados preliminares. Material y métodos: La aplicación está dise˜nada para teléfonos móviles con sistema operativo Android, tecnología de geolocalización y conexión de datos. Está conectada a una base de datos codificada que preserva el secreto médico. Los datos que se recogen de las sesiones de ejercicio son la fecha, la hora de inicio y de fin, el tiempo dedicado, el número de las paradas realizadas y la velocidad máxima, la velocidad media global y la velocidad entre paradas. Durante el mes de enero de 2014 se reclutó a aquellos pacientes que aceptaran el estudio, poseyeran y entendieran un dispositivo móvil Android con geolocalización y conexión de datos. Los criterios de exclusión del estudio una vez comenzado fueron progresión hacia isquemia arterial crítica, enfermedad intercurrente grave, fallecimiento y ausencia de comunicación con el paciente. Se recogieron las principales morbilidades y los resultados de los cuestionarios de calidad de vida SF36 y EuroQol 5D. Se midió el tiempo de primera consulta y el tiempo dedicado por semana y paciente durante un seguimiento de 28 días. Se calculó el cumplimiento de las sesiones con respecto a las sesiones pactadas con cada paciente, con un mínimo de 2 semanales. Resultados: Un total de 5 pacientes fueron incluidos, con edad media de 59,3 a˜nos (mediana 52; rango 40-80). De ellos 2 se excluyeron, uno por progresión a isquemia crítica y otro por ausencia de comunicación. El tiempo medio dedicado por consulta nueva fue de 29,1 min (mediana 27,5; rango 45-20). El cumplimiento de las sesiones fue del 100% en 2 pacientes y del 63% en otro. El tiempo dedicado en el seguimiento semanal por paciente fue de 1,68 min. Conclusiones: CReTe es una herramienta aplicable a nuestro medio que precisa de estudios mayores para demostrar su utilidad.Objective: The preliminary results are presented on the use of a new application for mobile phones designed to control home exercise sessions in claudication.Materials and methods: The application is designed for Android systems with geolocation tech-nology and Internet connection. It is connected to a database encoded to ensure medical confidentiality. The data collected from the exercise sessions were the date, start time and end time, the time spent, the number of stops made, and the maximum speed, average speed and overall speed between stops. During the month of January 2014 patients who accepted and understood the study, and possessed an Android mobile device with geolocation and data connection, were enrolled. The exclusion criteria, 11 the study started, were progression to arterial ischemia, severe intercurrent illness, non-communication with the patient, and death. Major morbidities and results of quality of life questionnaires SF36 and EuroQol 5 D were collec-ted. Time of first consultation and time spent per week per patient during a 28-day follow-up was recorded. Compliance as regards the agreed sessions was calculated for each patient, with a minimum of 2 weeks.Results: The study included 5 patients with a mean age 59.3 years (median 52; range 40-80). Of these, 2 were excluded, one for progression to critical ischemia and another for non-communication. The average time spent in a new consultation was 29.1 minutes (median 27.5, range 45-20). The compliance with the sessions was 100% in 2 patients, and 63% in another. Time spent in the weekly monitoring per patient was 1.68 minutes.Conclusions: CReTe is an applicable tool in our environment that requires further study to demonstrate its usefulness

Drug Repurposing for Cancers With Limited Survival: Protocol for a Retrospective Cohort Study

Only 5% of the molecules tested in oncology phase 1 trials reach the market after an average of 7.5 years of waiting and at a cost of tens of millions of dollars. To reduce the cost and shorten the time of discovery of new treatments, drug repurposing (research with molecules already approved for another indication) and the use of secondary data (not collected for the purpose of research) have been proposed. Due to advances in informatics in clinical care, secondary data can, in some cases, be of equal quality to primary data generated through prospective studies.Objective: The objective of this study is to identify drugs currently marketed for other indications that may have an effect on the prognosis of patients with cancer.Methods: We plan to monitor a cohort of patients with high-lethality cancers treated in the public health system of Catalonia between 2006 and 2012, retrospectively, for survival for 5 years after diagnosis or until death. A control cohort, comprising people without cancer, will also be retrospectively monitored for 5 years. The following study variables will be extracted from different population databases: type of cancer (patients with cancer cohort), date and cause of death, pharmacological treatment, sex, age, and place of residence. During the first stage of statistical analysis of the patients with cancer cohort, the drugs consumed by the long-term survivors (alive at 5 years) will be compared with those consumed by nonsurvivors. In the second stage, the survival associated with the consumption of each relevant drug will be analyzed. For the analyses, groups will be matched for potentially confounding variables, and multivariate analyses will be performed to adjust for residual confounding variables if necessary. The control cohort will be used to verify whether the associations found are exclusive to patients with cancer or whether they also occur in patients without cancer.Results: We anticipate discovering multiple significant associations between commonly used drugs and the survival outcomes of patients with cancer. We expect to publish the initial results in the first half of 2024.Conclusions: This retrospective study may identify several commonly used drugs as candidates for repurposing in the treatment of various cancers. All analyses are considered exploratory; therefore, the results will have to be confirmed in subsequent clinical trials. However, the results of this study may accelerate drug discovery in oncology

Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis.

BACKGROUND: Chagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population. METHODS: Six databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model. RESULTS: Forty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants. CONCLUSIONS: This systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease

Genome-Wide Analysis of Factors Affecting Transcription Elongation and DNA Repair: A New Role for PAF and Ccr4-Not in Transcription-Coupled Repair

RNA polymerases frequently deal with a number of obstacles during transcription elongation that need to be removed for transcription resumption. One important type of hindrance consists of DNA lesions, which are removed by transcription-coupled repair (TC-NER), a specific sub-pathway of nucleotide excision repair. To improve our knowledge of transcription elongation and its coupling to TC-NER, we used the yeast library of non-essential knock-out mutations to screen for genes conferring resistance to the transcription-elongation inhibitor mycophenolic acid and the DNA-damaging agent 4-nitroquinoline-N-oxide. Our data provide evidence that subunits of the SAGA and Ccr4-Not complexes, Mediator, Bre1, Bur2, and Fun12 affect transcription elongation to different extents. Given the dependency of TC-NER on RNA Polymerase II transcription and the fact that the few proteins known to be involved in TC-NER are related to transcription, we performed an in-depth TC-NER analysis of a selection of mutants. We found that mutants of the PAF and Ccr4-Not complexes are impaired in TC-NER. This study provides evidence that PAF and Ccr4-Not are required for efficient TC-NER in yeast, unraveling a novel function for these transcription complexes and opening new perspectives for the understanding of TC-NER and its functional interconnection with transcription elongation

Cyclooxygenase-2 and prostaglandin E<inf>2</inf> signaling through prostaglandin receptor EP- 2 favor the development of myocarditis during acute trypanosoma cruzi infection

Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68+ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2- dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.This work was supported by (NG) grants from “Fondo de Investigaciones Sanitarias” (PS09/00538 and PI12/00289); “Universidad Autónoma de Madrid” and “Comunidad de Madrid” (CC08-UAM/SAL-4440/08); by (MF) grants from “Ministerio de Ciencia e Innovación” (SAF2010-17833); “Red de Investigación de Centros de Enfermedades Tropicales” (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD- 2332) and “Fundación Ramón Areces”. NAG was recipient of a ISCIII Ph.D. fellowship financed by the Spanish “Ministerio de Sanidad”. CCM and HC were recipients of contracts from SAF2010-17833 and PI060388, respectively.Peer Reviewe

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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