During infectious disease outbreaks such as the COVID-19 pandemic, nurses are crucial in patient care and public health safety; however, they face challenges such as inadequate training and high stress in isolation wards. Virtual reality (VR) technology offers innovative training solutions to enhance nurses' clinical skills and preparedness. However, extensive studies on its effectiveness in isolation ward environments are still limited. This study aims to develop a nonimmersive VR (NIVR) simulation training program for isolation wards and further validate its feasibility and training effectiveness in aiding nurses in adapting to isolation ward settings. This study was a prospective, parallel, open-label, randomized controlled trial. A total of 90 nurses from 3 hospitals in China were randomly assigned to either the control or intervention group, with 45 (50%) individuals in each group. Both groups received training on isolation ward layout and nursing procedures. The control group underwent a 4-hour conventional training session consisting of 2 hours of face-to-face lectures and 2 hours of ward visits. The intervention group received a 4-hour NIVR simulation training session. Subsequently, both groups completed approximately 4 hours of emergency drills and assessments. After the intervention, there were no significant differences in theoretical test or performance assessment scores between the 2 groups (t88=-0.30, P=.75; Cohen d=-0.06; z score=0.00, P>.99), using a 2-tailed t test. However, the intervention group completed 6 tasks faster than the control group (t88=5.10, P<.001; Cohen d=1.08), with an average reduction of about 3 minutes (control group: mean 43.91, SD 2.99 min; intervention group: mean 40.77, SD 2.85 min). Notably, they completed task 3 (patient reception inward) and task 6 (exiting the isolation area) significantly quicker (t88=3.22, P=.002; Cohen d=0.68; t88=3.03, P=.003; Cohen d=0.64, respectively), with no significant differences for the other tasks. This study highlights the potential of NIVR simulation training for nurses working in isolation wards. Although NIVR simulation training does not significantly surpass traditional methods in imparting theoretical knowledge, it does reduce task completion time for specific activities. Its capacity for safe, repetitive practice and realistic scenario simulation makes NIVR a valuable tool in medical education. Further research and optimization of VR simulation training programs are recommended to enhance nurses' practical skills and pandemic preparedness. Chinese Clinical Trial Registry ChiCTR240083155; https://www.chictr.org.cn/hvshowproject.html?id=250356&v=1.0.
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