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BACKGROUND: PLAnning Treatment For Oesophago-gastric Cancer: a Randomised Maintenance Therapy Trial (PLATFORM) is an adaptive phase II study assessing the role of maintenance therapies in advanced oesophago-gastric (OG) adenocarcinoma. We evaluated the role of the anti-programmed death-ligand 1 (PD-L1) inhibitor durvalumab in these patients. PATIENTS AND METHODS: Patients with human epidermal growth factor receptor 2-negative locally advanced or metastatic OG adenocarcinoma with disease control or response to 18 weeks of platinum-based first-line chemotherapy were randomised to active surveillance or maintenance durvalumab. The primary endpoint was progression-free survival (PFS). Safety was assessed in all patients who had commenced surveillance visits or received at least one dose of durvalumab. Exploratory survival analyses according to PD-L1 Combined Positive Score (CPS) and immune (biomarker-positive) or angiogenesis dominant (biomarker-negative) tumour microenvironment (TME) phenotypes were conducted. RESULTS: Between March 2015 and April 2020, 205 patients were randomised to surveillance (n = 100) and durvalumab (n = 105). No significant differences were seen in PFS [hazard ratio (HR) 0.84, P = 0.13] and overall survival (OS; HR 0.98, P = 0.45) between surveillance and durvalumab. Five patients randomised to durvalumab demonstrated incremental radiological responses compared with none with surveillance. Treatment-related adverse events occurred in 77 (76.2%) durvalumab-assigned patients. A favourable effect in OS with durvalumab over surveillance in CPS ≥5 and immune biomarker-positive patients was observed compared with CPS <5 and biomarker-negative subgroups, respectively: CPS ≥5 versus <5: HR 0.63, 95% confidence interval (CI) 0.32-1.22 versus HR 0.93, 95% CI 0.44-1.96; biomarker-positive versus negative: HR 0.60, 95% CI 0.29-1.23 versus HR 0.84, 95% CI 0.42-1.65. CONCLUSION: Maintenance durvalumab does not improve PFS in patients with OG adenocarcinoma who respond to first-line chemotherapy but induced incremental radiological responses in a subset of patients. TME characterisation could refine patient selection for anti-PD-L1 therapy above PD-L1 CPS alone.
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Adenocarcinoma , Anticuerpos Monoclonales , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Gástricas/tratamiento farmacológico , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacología , Adenocarcinoma/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Receptor ErbB-2/metabolismo , Anciano de 80 o más Años , Supervivencia sin ProgresiónRESUMEN
It is often assumed that future coastal cliff retreat rates will accelerate as global sea level rises, but few studies have investigated how SLR (sea level rise) might change cliff-front wave dynamics. Using a new simple numerical model, this study simulates the number and type (breaking, broken, or unbroken) of cliff-front waves under future SLR scenarios. Previous research shows breaking waves deliver more energy to cliffs than broken waves, and unbroken waves generate minimal impact. Here, we investigated six cliff-platform profiles from three regions (USA, New Zealand, and UK) with varied tidal ranges and wave climates. Model inputs included 2013-2100 hindcast/forecast incident wave height and tidal water level, and three future SLR scenarios. Results show the number of both cliff-front breaking and broken waves generally increase for a high-elevation (relative to tide) cliff-platform junction. In contrast, breaking/broken wave occurrence decrease by 38-92% for a near-horizontal shore platform with a low-elevation cliff-platform junction under a high SRL scenario, leading to high (96-97%) unbroken wave occurrence. Overall, results suggest the response of cliff-front waves to future SLR is complex and depends on shore platform geometries and SLR scenarios, indicating that future cliff retreat rates may not homogeneously accelerate under SLR.
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BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.
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COVID-19 , Angiografía por Tomografía Computarizada , Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores , Angiografía por Tomografía Computarizada/métodos , COVID-19/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Pronóstico , Estudios Prospectivos , SARS-CoV-2 , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
Disability awareness and competency trainings are an important component of addressing ableism and health equity in the health promotion context. This commentary describes our process of developing, implementing, and refining a disability competency training, the Inclusive Community Exercise Training, for community-based group exercise instructors. The training originated from a partnership between academic researchers, community organizations, and individuals with disabilities. After initial pilot testing, we used feedback from participants to enhance the training. To optimize successful dissemination of this training, we utilized the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, which is widely used in public health. The revision process focused on generalizing content to suit a wider audience, utilizing an eLearning platform for dissemination, and optimizing interactivity to improve learning effectiveness. The commentary emphasizes the lessons learned and the significance of systematic program revision, considering diverse expertise, content tailoring, and the benefits of accessible eLearning platforms.
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Concienciación , Personas con Discapacidad , Promoción de la Salud , Humanos , Personas con Discapacidad/educación , Proyectos Piloto , Promoción de la Salud/métodos , Evaluación de Programas y Proyectos de Salud/métodos , Ejercicio Físico , Conocimientos, Actitudes y Práctica en SaludRESUMEN
We collected blank non-specialist anaesthetic records from 71 National Health Service Trusts in England. A data set was established by collating all data items found in an initial tranche of 28 records. All 71 records were subsequently analysed for each data item in this data set. We found significant variation: the most populated record included 216 data items and the least included 38 data items: a greater than five-fold variation. There was significant variation in the inclusion of data items commonly considered important to patient safety; 42% of records omitted documentation of fasting status, 72% omitted documentation of a discussion around the risk of accidental awareness during general anaesthesia, 92% omitted documentation of quantitative neuromuscular blockade monitoring and 63% omitted documentation for 'Stop Before You Block' when performing regional anaesthesia. The study highlights significant variability in the composition of anaesthetic records across England which may impact on its value as a data repository, an action trigger, a medicolegal account, and a tool to facilitate safe handover. Standardisation of the anaesthetic record or the establishment of standards of recording would help to allay potential risks to patient safety and assist in guiding future procurement of electronic solutions for anaesthetic records.
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Coupons of a medical grade PLDL polymer matrix uniaxially reinforced with a 15% volume fraction of Mg wires have been manufactured by fused filament fabrication for the first time. Two different types of Mg wires, without and with a surface treatment by plasma electrolytic oxidation were used. Both composite materials were subjected to degradation in phosphate buffer solution over a 3-week period, and their degradation and deformation micromechanisms were analysed in detail. Additionally, the materials were subjected to extensive mechanical testing under various loading conditions, and the interface strength was also analysed. It was found that the presence of the Mg wires improves the mechanical behaviour and accelerates the corrosion rate of the composite with respect that of the polymer matrix and these properties can be further tailored through the surface-modification of Mg wires by plasma electrolytic oxidation. The additive manufacturing strategy presented opens the path to fabricate multimaterial implants and scaffolds with complex shape and tailored properties provided by biodegradable polymers reinforced with either Mg and Zn particles and/or wires.
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Polímeros , Prótesis e Implantes , Andamios del TejidoRESUMEN
Objective.Deformable image registration (DIR) is a widely used technique in radiotherapy. Complex deformations, resulting from large anatomical changes, are a regular challenge. DIR algorithms generally seek a balance between capturing large deformations and preserving a smooth deformation vector field (DVF). We propose a novel structure-based term that can enhance the registration efficacy while ensuring a smooth DVF.Approach.The proposed novel similarity metric for controlling structures was introduced as a new term into a commercially available algorithm. Its performance was compared to the original algorithm using a dataset of 46 patients who received pelvic re-irradiation, many of which exhibited complex deformations.Main results.The mean Dice Similarity Coefficient (DSC) under the improved algorithm was 0.96, 0.94, 0.76, and 0.91 for bladder, rectum, colon, and bone respectively, compared to 0.69, 0.89, 0.62, and 0.88 for the original algorithm. The improvement was more pronounced for complex deformations.Significance.With this work, we have demonstrated that the proposed term is able to improve registration accuracy for complex cases while maintaining realistic deformations.
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Procesamiento de Imagen Asistido por Computador , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Vejiga Urinaria , Pelvis , Algoritmos , Planificación de la Radioterapia Asistida por Computador/métodosRESUMEN
Saltmarsh restoration such as managed realignment (MR) projects often include excavation of simplified tidal creek networks to improve drainage and marsh functioning, but their design is based on limited evidence. This paper compares the morphological evolution of creek networks in current MR projects in the UK with creek networks in natural saltmarshes, in order to provide improved guidance. The evolution of creek networks was monitored for 2-20 years post-breach at 10 MR sites across the UK by semi-automatically extracting 12 morphological creek parameters from lidar. The rates of creek evolution in MR sites are linked to the initial tidal, morphological and sedimentological conditions using principal component analysis, then compared with power law relationships of morphological equilibrium defined from 13 mature natural saltmarshes. MR creeks evolved into larger, more complex, better distributed systems, with a total creek length and volume statistically similar to their natural counterparts. However, the creek volume remains poorly distributed, with a mean distance between creeks ranging from 33 to 101 m versus 5-15 m for natural mature saltmarshes. MR creeks are also clustered around the breach area, leaving the marsh interior poorly drained. MR creek network morphologies remain strongly influenced by the initial creek template, as evidenced by unnaturally straight creeks inherited from former drainage ditches. A combination of external conditions (i.e., tidal range, sediment concentration in the wider estuary) and local conditions (i.e., site elevation, topographical heterogeneity, soil compaction) controls how easily creeks can form within MR sites. This in turn determines the amount of engineering effort required to help achieve reference site conditions. The end goal of creek design is to create MR sites that closely resemble reference site conditions, however the final design is also likely to be affected by a range of practical factors (e.g. engineering/cost) unique to each site and project.
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Objective Patients admitted from the emergency department may be co-located on the treating team's 'home ward'. If no bed is available, patients may be sent to another ward, where they may remain under the admitting team as an 'outlier'. Conversely, care may be handed over to the team on whose home ward they are located. We conducted a retrospective analysis to understand the impact of outlier status and handovers of care on outcomes for General Medicine inpatients. Methods General Medicine admissions at the Royal Adelaide Hospital between September 2020 and November 2021 were analysed. We examined the rate of hospital-acquired complications, inpatient mortality rate, mortality within 48 h of admission, Relative Stay Index, time of discharge from hospital and rate of adverse events within 28 days of discharge. Results A total of 3109 admissions were analysed. Handovers within 24 h of admission were associated with a longer length of stay. There was a trend towards higher rates of adverse events within 28 days of discharge with handovers of care. Outlier status did not affect any outcome measures. Conclusions Handovers within the first 24 h of admission are associated with longer than expected length of stay.
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Insuficiencia Cardíaca , Medicina , Humanos , Insuficiencia Cardíaca/terapia , HospitalizaciónRESUMEN
Pyrocumulonimbus (pyroCb) are wildfire-generated convective clouds that can inject smoke directly into the stratosphere. PyroCb have been tracked for years, yet their apparent rarity and episodic nature lead to highly uncertain climate impacts. In situ measurements of pyroCb smoke reveal its distinctive and exceptionally stable aerosol properties and define the long-term influence of pyroCb activity on the stratospheric aerosol budget. Analysis of 13 years of airborne observations shows that pyroCb are responsible for 10 to 25% of the black carbon and organic aerosols in the "present-day" lower stratosphere, with similar impacts in both the North and South Hemispheres. These results suggest that, should pyroCb increase in frequency and/or magnitude in future climates, they could generate dominant trends in stratospheric aerosol.
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Cannabidiol (CBD) and Tetrahydrocannabinol (THC) have become easily available to athletes over the years. Using these substances may inadvertently expose an athlete to the possibility of an adverse analytical finding (a "positive" test) and a sanction. Athletes need to understand the risk of an anti-doping rule violation or adverse analytical finding should these products be used, especially if no therapeutic use exemption exists. This position statement attempts to clarify the use of CBD and THC and their associated risks with Anti-Doping Rule Violations (ADRV) in the athletic population. The South African Sports Medicine Association supports this position statement.
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AIMS: Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Epidemiological studies suggest serum Osteoprotegrin (OPG)/Tumour-necrosis-factor-related-apoptosis-inducing- ligand (TRAIL) ratio may be a useful marker of cardiovascular risk. This study aimed to compare serum levels of TRAIL, OPG and OPG/TRAIL ratio in people with T2DM, with and without a history of CVD, and controls; and to determine which of these indices, if any, predict cardiovascular risk. METHODS: In this single centre observational study of 133 participants, people with T2DM, with and without a history of a cardiovascular event in the last 5 years, were recruited along with a control cohort without T2DM or CVD. Demographic information and anthropometric measurements were recorded. Blood samples were taken and OPG and TRAIL were measured using ELISA. RESULTS: People with T2DM and CVD had higher OPG/TRAIL ratios compared to controls or those with a new diagnosis of T2DM. After adjustment for potential confounding factors, OPG/TRAIL ratio was significantly associated with the presence of CVD in people with T2DM and an OPG/TRAIL ratio cut-off > 38.6 predicted the presence of CVD in this cohort with a sensitivity of 80% and specificity of 82%. CONCLUSION: This study suggests that OPG/TRAIL ratio may have a role as a biomarker of CVD in people with T2DM.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Biomarcadores , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Osteoprotegerina , Ligando Inductor de Apoptosis Relacionado con TNFRESUMEN
In 2016, the 21st Century Cures Act included ONC's 10 functionality recommendations for voluntary testing and certification of pediatric EHRs. Since 2019, Drummond has been developing a new pediatric EHR testing and certification program with pediatric and industry experts. The testing criteria are based upon AAP's 47 requirements that include ONC's 10 recommendations. It is anticipated the program will be operationalized and ready for EHR vendors in 1Q2022.
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Certificación , Registros Electrónicos de Salud , Niño , Comercio , Humanos , Industrias , Estados UnidosRESUMEN
The feasibility to manufacture scaffolds of poly-lactic acid reinforced with Zn particles by fused filament fabrication is demonstrated for the first time. Filaments of 2.85 mm in diameter of PLA reinforced with different weight fractions of µm-sized Zn - 1 wt.% Mg alloy particles (in the range 3.5 to 17.5 wt.%) were manufactured by a double extrusion method in which standard extrusion is followed by precision extrusion in a filament-maker machine. Filaments with constant diameter, negligible porosity and a homogeneous reinforcement distribution were obtained for Zn weight fractions of up to 10.5%. It was found that the presence of Zn particles led to limited changes in the physico-chemical properties of the PLA that did not affect the window temperature for 3D printing nor the melt flow index. Thus, porous scaffolds could be manufactured by fused filament fabrication at 190 °C with poly-lactic acid/Zn composites containing 3.5 and 7 wt.% of Zn and at 170 °C when the Zn content was 10.5 wt.% with excellent dimensional accuracy and mechanical properties.
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Poliésteres , Andamios del Tejido , Ácido Láctico , Poliésteres/química , Porosidad , Impresión Tridimensional , Andamios del Tejido/química , ZincRESUMEN
Coastal wetlands provide crucial ecosystem services including flood protection and carbon storage, but are being lost rapidly worldwide to the combined effects of sea-level rise, erosion and coastal urbanisation. Managed Realignment (MR) aims to mitigate for these losses by restoring reclaimed land to tidal influence. Data of creek evolution is critical to assess the performance of design strategies and improve design and implementation practices. This data descriptor provides a dataset of the horizontal morphological evolution of creek systems from various initial conditions in 10 MR schemes across the UK. Using a semi-automated workflow, morphological creek parameters were extracted from 52 lidar datasets at 1 m horizontal resolution spanning 2 to 20 years post-breach. This constitutes the most comprehensive systematic monitoring of MR creek morphology to date. The dataset will assist future MR design and provide baseline morphological information for ecological and biogeochemical surveying.
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AIM: To determine the diagnostic accuracy of an automated artificial intelligence derived right ventricle/left ventricle diameter ratio (RV/LV) computed tomography pulmonary angiography (CTPA) analysis tool to detect pulmonary hypertension (PH) in patients with suspected PH referred to a specialist centre. MATERIALS AND METHODS: The present study was a retrospective analysis of a prospectively maintained database of 202 consecutive patients with suspected PH, who underwent CTPA within 12 months of right heart catheterisation (RHC). Automated ventricular segmentation and RV/LV calculation (Imbio LLC, Minneapolis, MN, USA) was undertaken on the CTPA images. PH diagnosis was made using the RHC reference standard. RESULTS: The automated RV/LV correlated more strongly with RHC metrics than main pulmonary artery (MPA) diameter and MPA to ascending aorta diameter ratio (MPA/AA) measured manually (mean pulmonary arterial pressure [mPAP] r=0.535, R2 = 0.287 p<0.001; pulmonary vascular resistance [PVR] r=0.607, R2 = 0.369 p<0.001). In the derivation cohort (n=100), the area under the receiver-operating curve for automated RV/LV discriminating PH was 0.752 (95% confidence interval [CI] 0.677-0.827, p<0.001). Using an optimised Youden's Index of ≥1.12 classified from derivation, automated RV/LV ratio analysis was more sensitive for the detection of PH with higher positive predictive value (PPV) when compared with manual MPA and MPA/AA in the validation cohort (n=102). Automated RV/LV compromise (1.12) and specific (1.335) thresholds were strongly predictive of mortality (log-rank 7.401, p=0.007 and log-rank 16.075, p<0.001 respectively). CONCLUSION: In suspected PH, automated RV/LV diameter thresholds have high sensitivity for PH, outperform manual MPA and MPA/AA and can predict survival.
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Hipertensión Pulmonar , Angiografía/métodos , Inteligencia Artificial , Cateterismo Cardíaco , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Hipertensión Pulmonar/diagnóstico por imagen , Arteria Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Previous studies have reported differing clinical outcomes among hospitalized heart failure (HF) patients admitted under cardiology and general medicine (GM) without consideration of patients' frailty. AIMS: To explore outcomes in patients admitted under the two specialities after taking into account their frailty and other characteristics. METHODS: This retrospective study included all HF patients ≥18 years admitted between 1 January 2013 and 31 December 2019 at two Australian tertiary hospitals. Frailty was determined by use of the Hospital Frailty Risk Score (HFRS) and patients with HFRS ≥ 5 were classified as frail. Propensity score matching (PSM) was used to match 11 variables between the two specialities. The primary outcomes included the days-alive-and-out-of-hospital (DAOH90) at 90 days of discharge, 30-day mortality and readmissions. RESULTS: Of 4913 HF patients, mean age 76.2 (14.1) years, 51% males, 2653 (54%) were admitted under cardiology compared to 2260 (46%) under GM. Patients admitted under GM were more likely to be older females, with a higher Charlson index and poor renal function than those admitted under cardiology. Overall, 23.8% patients were frail and frail patients were more likely to be admitted under GM than cardiology (33.6% vs. 15.3%, P < 0.001). PSM created 1532 well-matched patients in each group. After PSM, the DAOH90 was not significantly different among patients admitted in GM when compared to cardiology (coefficient -5.36, 95% confidence interval -11.73 to 1.01, P = 0.099). Other clinical outcomes were also similar between the two specialities. CONCLUSIONS: Clinical characteristics of HF patients differ between GM and cardiology; however, clinical outcomes were not significantly different after taking into account frailty and other variables.
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Fragilidad , Insuficiencia Cardíaca , Anciano , Femenino , Humanos , Masculino , Australia/epidemiología , Anciano Frágil , Fragilidad/epidemiología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Tiempo de Internación , Alta del Paciente , Estudios RetrospectivosRESUMEN
Innovative nursing education methods became essential due to the COVID-19 pandemic. Immersive Virtual Reality (VR) education offers nursing students authentic patient encounters in a realistic simulated environment. A pilot study was conducted to identify nursing education clinical scenarios that should be developed for immersive VR and to assess students' perception of immersive VR in education. We formed a focus group composed of nursing faculty (N=10) with expertise in the clinical setting and simulation. Faculty participants identified important topics and aspects of immersive VR scenarios during focus group discussions. We assessed nursing student participants' (N=11) perception of immersive VR in nursing education using a VR game (Anatomy Explorer 2020). Most student participants indicated that a VR game was immersive and realistic and recommended using immersive VR to learn clinical nursing skills. Realistic immersive VR clinical education scenarios could result in effective clinical nursing education.