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1.
Heliyon ; 10(12): e32476, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-39021944

RESUMEN

Throughout the COVID-19 pandemic, China effectively contained the virus, resulting in increased public trust in the government. Mobile government (mGovernment) applications (apps) played a critical role in this improvement. This study aims to examine how mGovernment apps build citizens' trust in governments during public crises. The DeLone and McLean Information Systems Success Model (ISSM) is used to evaluate the quality of these apps. Public satisfaction serves as an intermediary variable, while public awareness of epidemic risks in sudden public relations crises acts as a moderating variable to explore the impact of mGovernment apps on government trust. Data analysis is conducted using SPSS Statistics 22.0 and AMOS 21.0. The study's results show that the system quality, information quality, and service quality of mobile government apps influence citizens' trust in governments through the mediating effect of public satisfaction. All three factors positively correlate with public satisfaction, with service quality having the greatest impact. Similarly, system quality, information quality, and service quality are positively correlated with public trust in governments, with system quality having the most noticeable influence. There is a strong correlation between public satisfaction and trust in governments, and the mediating effect of public satisfaction is significant. In addition, epidemic risk perception moderates the relationship between public satisfaction and citizens' trust in governments.

2.
Ann Surg Open ; 5(1): e363, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38883942

RESUMEN

Objective: The aim of this study is to identify risk factors for readmission after elective esophagogastric cancer surgery and characterize the impact of readmission on long-term survival. The study will also identify whether the location of readmission to either the hospital that performed the primary surgery (index hospital) or another institution (nonindex hospital) has an impact on postoperative mortality. Background: Over the past decade, the center-volume relationship has driven the centralization of major cancer surgery, which has led to improvements in perioperative mortality. However, the impact of readmission, especially to nonindex centers, on long-term mortality remains unclear. Methods: This was a national population-based cohort study using Hospital Episode Statistics of adult patients undergoing esophagectomy and gastrectomy in England between January 2008 and December 2019. Results: This study included 27,592 patients, of which overall readmission rates were 25.1% (index 15.3% and nonindex 9.8%). The primary cause of readmission to an index hospital was surgical in 45.2% and 23.7% in nonindex readmissions. Patients with no readmissions had significantly longer survival than those with readmissions (median: 4.5 vs 3.8 years; P < 0.001). Patients readmitted to their index hospital had significantly improved survival as compared to nonindex readmissions (median: 3.3 vs 4.7 years; P < 0.001). Minimally invasive surgery and surgery performed in high-volume centers had improved 90-day mortality (odds ratio, 0.75; P < 0.001; odds ratio, 0.60; P < 0.001). Conclusion: Patients requiring readmission to the hospital after surgery have an increased risk of mortality, which is worsened by readmission to a nonindex institution. Patients requiring readmission to the hospital should be assessed and admitted, if required, to their index institution.

3.
Ann Surg ; 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38904105

RESUMEN

OBJECTIVE: To evaluate prognostic differences between minimally invasive esophagectomy (MIE) and open esophagectomy (OE) in patients with surgery after a prolonged interval (>12 wk) following chemoradiotherapy (CRT). BACKGROUND: Previously, we established that a prolonged interval after CRT prior to esophagectomy was associated with poorer long-term survival. METHODS: This was an international multi-center cohort study involving seventeen tertiary centers, including patients who received CRT followed by surgery between 2010-2020. Patients undergoing MIE were defined as thoracoscopic and laparoscopic approach. RESULTS: 428 patients (145 MIE and 283 OE) had surgery between 12 weeks and two years after CRT. Significant differences were observed in ASA grade, radiation dose, clinical T stage, and histological subtype. There were no significant differences between the groups in age, sex, BMI, pathological T or N stage, resection margin status, tumor location, surgical technique, or 90-day mortality. Survival analysis showed MIE was associated with improved survival in univariate (P=0.014), multivariate analysis after adjustment for smoking, T and N stage, and histology (HR=1.69; 95% CI 1.14 to 2.5) and propensity matched analysis (P=0.02). Further subgroup analyses by radiation dose and interval after CRT showed survival advantage for MIE, in 40-50Gy dose groups (HR=1.9; 95% CI 1.2 to 3.0), and in patients having surgery within six months of CRT (HR=1.6; 95% CI 1.1 to 2.2). CONCLUSION: MIE was associated with an improved overall survival compared to OE in patients with a prolonged interval from CRT to surgery. The mechanism for this observed improvement in survival remains unknown, with potential hypotheses including a reduction in complications and improved functional recovery after MIE.

4.
Nat Commun ; 15(1): 4958, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862508

RESUMEN

An antiferromagnet emits spin currents when time-reversal symmetry is broken. This is typically achieved by applying an external magnetic field below and above the spin-flop transition or by optical pumping. In this work we apply optical pump-THz emission spectroscopy to study picosecond spin pumping from metallic FeRh as a function of temperature. Intriguingly we find that in the low-temperature antiferromagnetic phase the laser pulse induces a large and coherent spin pumping, while not crossing into the ferromagnetic phase. With temperature and magnetic field dependent measurements combined with atomistic spin dynamics simulations we show that the antiferromagnetic spin-lattice is destabilised by the combined action of optical pumping and picosecond spin-biasing by the conduction electron population, which results in spin accumulation. We propose that the amplitude of the effect is inherent to the nature of FeRh, particularly the Rh atoms and their high spin susceptibility. We believe that the principles shown here could be used to produce more effective spin current emitters. Our results also corroborate the work of others showing that the magnetic phase transition begins on a very fast picosecond timescale, but this timescale is often hidden by measurements which are confounded by the slower domain dynamics.

5.
Soft Matter ; 20(26): 5153-5163, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38895763

RESUMEN

Polymers of intrinsic microporosity exhibit a combination of high gas permeability and reasonable permselectivity, which makes them attractive candidates for gas separation membrane materials. The diffusional selective gas transport properties are connected to the molecular mobility of these polymers in the condensed state. Incoherent quasielastic neutron scattering was carried out on two polymers of intrinsic microporosity, PIM-EA-TB(CH3) and its demethylated counterpart PIM-EA-TB(H2), which have high Brunauer-Emmett-Teller surface area values of 1030 m2 g-1 and 836 m2 g-1, respectively. As these two polymers only differ in the presence of two methyl groups at the ethanoanthracene unit, the effect of methyl group rotation can be investigated solely. To cover a broad dynamic range, neutron time-of-flight was combined with neutron backscattering. The demethylated PIM-EA-TB(H2) exhibits a relaxation process with a weak intensity at short times. As the backbone is rigid and stiff this process was assigned to bend-and-flex fluctuations. This process was also observed for the PIM-EA-TB(CH3). A further relaxation process is found for PIM-EA-TB(CH3), which is the methyl group rotation. It was analyzed by a jump-diffusion in a three-fold potential considering also the fact that only a fraction of the present hydrogens in PIM-EA-TB(CH3) participate in the methyl group rotation. This analysis can quantitatively describe the q dependence of the elastic incoherent structure factor. Furthermore, a relaxation time for the methyl group rotation can be extracted. A high activation energy of 35 kJ mol-1 was deduced. This high activation energy evidences a strong hindrance of the methyl group rotation in the bridged PIM-EA-TB(CH3) structure.

6.
Mar Environ Res ; 199: 106607, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38879902

RESUMEN

The extent to which juvenile abundance can predict future populations of lethrinids at Ningaloo Reef was assessed using size frequency data collected over 13 consecutive years. Annual abundance of juvenile lethrinids (<5 cm TL) was highest in northern Ningaloo during La Niña years, when seawater is warmer and oceanic currents stronger. Juvenile lethrinid abundance explained 35% of the variance in 1-2 year-old Lethrinus nebulosus abundance the following year, a steeper relationship in the north suggesting greater survival of juveniles. Juvenile lethrinid abundance was also positively correlated to abundance of 1-2 year-old L. atkinsoni in the southern region of Ningaloo. Abundance of juvenile lethrinids were however poor predictors of L. nebulosus and L. atkinsoni older than 2 years of age. Post settlement processes likely weaken the link between juvenile supply and abundance of lethrinids >2 years old making it difficult to accurately quantify the overall size of future lethrinid populations.


Asunto(s)
Arrecifes de Coral , Animales , Peces/fisiología , Peces/crecimiento & desarrollo , Dinámica Poblacional , Monitoreo del Ambiente , Densidad de Población , El Niño Oscilación del Sur
7.
Digit Health ; 10: 20552076241260507, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38868368

RESUMEN

Background: Wearable technology is used in healthcare to monitor the health of individuals. This study presents an updated systematic literature review of the use of wearable technology in promoting child and adolescent health, accompanied by recommendations for future research. Methods: This review focuses on studies involving children and adolescents aged between 2 and 18 years, regardless of their health condition or disabilities. Studies that were published from 2016 to 2024, and which met the inclusion criteria, were extracted from four academic databases (i.e. PubMed, Cochrane, Embase, and Web of Science) using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) protocol. Data on intervention purposes, interventions deployed, intervention duration, measurements, and the main outcomes of the studies were collected. Results: A total of 53 studies involving 14,852 participants were reviewed. They focused on various aspects, including the ownership and use of wearable devices (n = 3), the feasibility (n = 22), effectiveness (n = 4), and adherence (n = 2) of intervention strategies, or a combination of multiple aspects (n = 22). Among the interventions deployed, Fitbit was the most frequently used, featuring in 26 studies, followed by ActiGraph (n = 11). In intervention studies, the majority of studies focused on pre-morbidity prevention (n = 26) and the treatment of illnesses (n = 20), with limited attention given to postoperative monitoring (n = 4). Conclusions: The use of wearable technology by children and adolescents has proven to be both feasible and effective for health promotion. This systematic review summarizes existing research by exploring the use of wearable technology in promoting health across diverse youth populations, including healthy and unhealthy individuals. It examines health promotion at various stages of the disease continuum, including pre-disease prevention, in-disease treatment, and postoperative monitoring. Additionally, the review provides directions for future research.

8.
Chemistry ; : e202401728, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888459

RESUMEN

Transitioning towards a circular economy, extensive research has focused on dynamic covalent bonds (DCBs) to pave the way for more sustainable materials. These bonds enable debonding and rebonding on demand, as well as facilitating end-of-life recycling. Acylhydrazone/hydrazone chemistry offers a material with high stability under neutral and basic conditions making it a promising candidate for materials research, though the material is susceptible to acid degradation. However, this degradation under acidic conditions can be exploited, making it widely applicable in self-healing and biomedical fields, with potential for reprocessing and recycling. This review highlights studies exploring the reversibility of acylhydrazone/hydrazone bonds in various polymers, altering their properties, and utilizing them in applications such as self-healing, reprocessing, and recycling. The review also focuses on how the mechanical properties are affected by the presence of dynamic linkages, and methods to improve the mechanical performance.

10.
Open Heart ; 11(1)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724266

RESUMEN

OBJECTIVES: Myocardial revascularisation and cardiopulmonary bypass (CPB) can cause ischaemia-reperfusion injury, leading to myocardial and other end-organ damage. Volatile anaesthetics protect the myocardium in experimental studies. However, there is uncertainty about whether this translates into clinical benefits because of the coadministration of propofol and its detrimental effects, restricting myocardial protective processes. METHODS: In this single-blinded, parallel-group randomised controlled feasibility trial, higher-risk patients undergoing elective coronary artery bypass graft (CABG) surgery with an additive European System for Cardiac Operative Risk Evaluation ≥5 were randomised to receive either propofol or total inhalational anaesthesia as single agents for maintenance of anaesthesia. The primary outcome was the feasibility of recruiting and randomising 50 patients across two cardiac surgical centres, and secondary outcomes included the feasibility of collecting the planned perioperative data, clinically relevant outcomes and assessments of effective patient identification, screening and recruitment. RESULTS: All 50 patients were recruited within 11 months in two centres, allowing for a 13-month hiatus in recruitment due to the COVID-19 pandemic. Overall, 50/108 (46%) of eligible patients were recruited. One patient withdrew before surgery and one patient did not undergo surgery. All but one completed in-hospital and 30-day follow-up. CONCLUSIONS: It is feasible to recruit and randomise higher-risk patients undergoing CABG surgery to a study comparing total inhalational and propofol anaesthesia in a timely manner and with high acceptance and completion rates. TRIAL REGISTRATION NUMBER: NCT04039854.


Asunto(s)
Anestésicos Intravenosos , Puente de Arteria Coronaria , Estudios de Factibilidad , Propofol , Humanos , Propofol/administración & dosificación , Propofol/efectos adversos , Masculino , Femenino , Proyectos Piloto , Anciano , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Persona de Mediana Edad , Método Simple Ciego , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Anestesia por Inhalación/métodos , Anestesia por Inhalación/efectos adversos , Resultado del Tratamiento , Medición de Riesgo/métodos , Factores de Riesgo , COVID-19/epidemiología , COVID-19/prevención & control , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/efectos adversos , Puente Cardiopulmonar/efectos adversos , Puente Cardiopulmonar/métodos
11.
Nature ; 630(8016): 493-500, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38718835

RESUMEN

The introduction of AlphaFold 21 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design2-6. Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein-ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein-nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody-antigen prediction accuracy compared with AlphaFold-Multimer v.2.37,8. Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework.


Asunto(s)
Aprendizaje Profundo , Ligandos , Modelos Moleculares , Proteínas , Programas Informáticos , Humanos , Anticuerpos/química , Anticuerpos/metabolismo , Antígenos/metabolismo , Antígenos/química , Aprendizaje Profundo/normas , Iones/química , Iones/metabolismo , Simulación del Acoplamiento Molecular , Ácidos Nucleicos/química , Ácidos Nucleicos/metabolismo , Unión Proteica , Conformación Proteica , Proteínas/química , Proteínas/metabolismo , Reproducibilidad de los Resultados , Programas Informáticos/normas
12.
Front Public Health ; 12: 1364973, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38799685

RESUMEN

Introduction: Village clinics (VCs) are the foundation of the three-tiered health service system in China, delivering basic and routine outpatient services to citizens in rural China. VC technical efficiency and its convergence play a critical role in policy decisions regarding the distribution of health service resources in rural China. Methods: This study measured VC technical efficiency (using the slacks-based measure model), its convergence (using the convergence model), and the factors that influence the convergence in Shanxi Province, China. Data were obtained from the Shanxi Rural Health Institute 2014-2018 Health Statistics Report, which involved 3,543 VCs. Results: The results showed that VC technical efficiency was low and differed by region. There was no α convergence in VC technical efficiency, but evidence of ß convergence was found in Shanxi. The main factors that influence convergence were the building area of each VC (BA), proportion of government subsidies (PGS), and ratio of total expenditure to total income of each VC (RTETI). Conclusion: The government should increase investments in VCs and improve VC technical efficiency. Meanwhile, the government should be aware of and take measures to curb the inequity in VC technical efficiency among different regions and take suitable measures to curb this disparity.


Asunto(s)
Servicios de Salud Rural , China , Humanos , Servicios de Salud Rural/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Eficiencia Organizacional/estadística & datos numéricos
15.
PLoS One ; 19(3): e0296525, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38478488

RESUMEN

BACKGROUND: Atrial Fibrillation After Cardiac Surgery (AFACS) occurs in about one in three patients following Coronary Artery Bypass Grafting (CABG). It is associated with increased short- and long-term morbidity, mortality and costs. To reduce AFACS incidence, efforts are often made to maintain serum potassium in the high-normal range (≥ 4.5mEq/L). However, there is no evidence that this strategy is efficacious. Furthermore, the approach is costly, often unpleasant for patients, and risks causing harm. We describe the protocol of a planned randomized non-inferiority trial to investigate the impact of intervening to maintain serum potassium ≥ 3.6 mEq/L vs ≥ 4.5 mEq/L on incidence of new-onset AFACS after isolated elective CABG. METHODS: Patients undergoing isolated CABG at sites in the UK and Germany will be recruited, randomized 1:1 and stratified by site to protocols maintaining serum potassium at either ≥ 3.6 mEq/L or ≥ 4.5 mEq/L. Participants will not be blind to treatment allocation. The primary endpoint is AFACS, defined as an episode of atrial fibrillation, flutter or tachycardia lasting ≥ 30 seconds until hour 120 after surgery, which is both clinically detected and electrocardiographically confirmed. Assuming a 35% incidence of AFACS in the 'tight control group', and allowing for a 10% loss to follow-up, 1684 participants are required to provide 90% certainty that the upper limit of a one-sided 97.5% confidence interval (CI) will exclude a > 10% difference in favour of tight potassium control. Secondary endpoints include mortality, use of hospital resources and incidence of dysrhythmias not meeting the primary endpoint (detected using continuous heart rhythm monitoring). DISCUSSION: The Tight K Trial will assess whether a protocol to maintain serum potassium ≥ 3.6 mEq/L is non inferior to maintaining serum potassium ≥ 4.5 mEq/L in preventing new-onset AFACS after isolated CABG. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04053816. Registered on 13 August 2019. Last update 7 January 2021.


Asunto(s)
Fibrilación Atrial , Potasio , Humanos , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Fibrilación Atrial/prevención & control , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Alemania , Incidencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios de Equivalencia como Asunto
16.
Am J Vet Res ; 85(6)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38513345

RESUMEN

OBJECTIVE: Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. ANIMALS: 8 healthy horses. METHODS: In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed. RESULTS: There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240. CLINICAL RELEVANCE: Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects.


Asunto(s)
Resinas Acrílicas , Biomarcadores , Líquido Sinovial , Animales , Caballos , Líquido Sinovial/efectos de los fármacos , Líquido Sinovial/química , Resinas Acrílicas/administración & dosificación , Inyecciones Intraarticulares/veterinaria , Femenino , Masculino , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/inducido químicamente , Enfermedades de los Caballos/patología , Cojera Animal/inducido químicamente , Membrana Sinovial/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Osteoartritis/veterinaria , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Articulaciones/efectos de los fármacos , Articulaciones/patología
17.
Adv Mater ; 36(21): e2311643, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38407359

RESUMEN

Ultrafast manipulation of magnetic order has challenged the understanding of the fundamental and dynamic properties of magnetic materials. So far single-shot magnetic switching has been limited to ferrimagnetic alloys, multilayers, and designed ferromagnetic (FM) heterostructures. In FM/antiferromagnetic (AFM) bilayers, exchange bias (He) arises from the interfacial exchange coupling between the two layers and reflects the microscopic orientation of the antiferromagnet. Here the possibility of single-shot switching of the antiferromagnet (change of the sign and amplitude of He) with a single femtosecond laser pulse in IrMn/CoGd bilayers is demonstrated. The manipulation is demonstrated in a wide range of fluences for different layer thicknesses and compositions. Atomistic simulations predict ultrafast switching and recovery of the AFM magnetization on a timescale of 2 ps. The results provide the fastest and the most energy-efficient method to set the exchange bias and pave the way to potential applications for ultrafast spintronic devices.

18.
J Phys Condens Matter ; 36(30)2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38354418

RESUMEN

We present an experimental and computational investigation the Neodymium thickness dependence of the effective damping constant (αeff) inNi80Fe20/Neodymium (Py/Nd) bilayers. The computational results show that the magnetic damping is strongly dependent on the thickness of Nd, which is in agreement with experimental data. Self consistent solutions of the spin accumulation model and the local magnetisation were used in the simulations. It was not possible to obtain agreement with experiment under the assumption of an enhanced damping in a single Py monolayer. Instead, it was found that the enhanced damping due to spin pumping needed to be spread across two monolayers of Py. This is suggested to arise from interface mixing. Subsequently, the temperature dependence of the effective damping was investigated. It is found that, with increasing temperature, the influence of thermally-induced spin fluctuations on magnetic damping becomes stronger with increasing Nd thickness.

19.
Circ Cardiovasc Interv ; 17(3): e013367, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38410944

RESUMEN

INTRODUCTION: Percutaneous coronary intervention for complex coronary disease is associated with a high risk of cardiogenic shock. This can cause harm and limit the quality of revascularization achieved, especially when left ventricular function is impaired at the outset. Elective percutaneous left ventricular unloading is increasingly used to mitigate adverse events in patients undergoing high-risk percutaneous coronary intervention, but this strategy has fiscal and clinical costs and is not supported by robust evidence. METHODS: CHIP-BCIS3 (Controlled Trial of High-Risk Coronary Intervention With Percutaneous Left Ventricular Unloading) is a prospective, multicenter, open-label randomized controlled trial that aims to determine whether a strategy of elective percutaneous left ventricular unloading is superior to standard care (no planned mechanical circulatory support) in patients undergoing nonemergent high-risk percutaneous coronary intervention. Patients are eligible for recruitment if they have severe left ventricular systolic dysfunction, extensive coronary artery disease, and are due to undergo complex percutaneous coronary intervention (to the left main stem with calcium modification or to a chronic total occlusion with a retrograde approach). Cardiogenic shock and acute ST-segment-elevation myocardial infarction are exclusions. The primary outcome is a hierarchical composite of all-cause death, stroke, spontaneous myocardial infarction, cardiovascular hospitalization, and periprocedural myocardial infarction, analyzed using the win ratio. Secondary outcomes include completeness of revascularization, major bleeding, vascular complications, health economic analyses, and health-related quality of life. A sample size of 250 patients will have in excess of 80% power to detect a hazard ratio of 0.62 at a minimum of 12 months, assuming 150 patients experience an event across all follow-up. CONCLUSIONS: To date, 169 patients have been recruited from 21 National Health Service hospitals in the United Kingdom, with recruitment expected to complete in 2024. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05003817.


Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Estudios Prospectivos , Calidad de Vida , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/terapia , Choque Cardiogénico/etiología , Medicina Estatal , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
20.
Clin Proteomics ; 21(1): 1, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172678

RESUMEN

BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy in women, and high-grade serous ovarian cancer (HGSOC) is the most common subtype. Currently, no clinical test has been approved by the FDA to screen the general population for ovarian cancer. This underscores the critical need for the development of a robust methodology combined with novel technology to detect diagnostic biomarkers for HGSOC in the sera of women. Targeted mass spectrometry (MS) can be used to identify and quantify specific peptides/proteins in complex biological samples with high accuracy, sensitivity, and reproducibility. In this study, we sought to develop and conduct analytical validation of a multiplexed Tier 2 targeted MS parallel reaction monitoring (PRM) assay for the relative quantification of 23 putative ovarian cancer protein biomarkers in sera. METHODS: To develop a PRM method for our target peptides in sera, we followed nationally recognized consensus guidelines for validating fit-for-purpose Tier 2 targeted MS assays. The endogenous target peptide concentrations were calculated using the calibration curves in serum for each target peptide. Receiver operating characteristic (ROC) curves were analyzed to evaluate the diagnostic performance of the biomarker candidates. RESULTS: We describe an effort to develop and analytically validate a multiplexed Tier 2 targeted PRM MS assay to quantify candidate ovarian cancer protein biomarkers in sera. Among the 64 peptides corresponding to 23 proteins in our PRM assay, 24 peptides corresponding to 16 proteins passed the assay validation acceptability criteria. A total of 6 of these peptides from insulin-like growth factor-binding protein 2 (IBP2), sex hormone-binding globulin (SHBG), and TIMP metalloproteinase inhibitor 1 (TIMP1) were quantified in sera from a cohort of 69 patients with early-stage HGSOC, late-stage HGSOC, benign ovarian conditions, and healthy (non-cancer) controls. Confirming the results from previously published studies using orthogonal analytical approaches, IBP2 was identified as a diagnostic biomarker candidate based on its significantly increased abundance in the late-stage HGSOC patient sera compared to the healthy controls and patients with benign ovarian conditions. CONCLUSIONS: A multiplexed targeted PRM MS assay was applied to detect candidate diagnostic biomarkers in HGSOC sera. To evaluate the clinical utility of the IBP2 PRM assay for HGSOC detection, further studies need to be performed using a larger patient cohort.

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