The use of pre-operative Virtual Reality to reduce anxiety in women undergoing gynecological surgeries: a prospective cohort study

The use of pre-operative Virtual Reality to reduce anxiety in women undergoing gynecological surgeries: a prospective cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Help Center Sign In Submit a Preprint Cite Share Download PDF Research article The use of pre-operative Virtual Reality to reduce anxiety in women undergoing gynecological surgeries: a prospective cohort study Jason Ju In Chan, Cheng Teng Yeam, Hwei Min Kee, Chin Wen Tan, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-20956/v4 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Oct, 2020 Read the published version in BMC Anesthesiology → Version 4 posted 2 You are reading this latest preprint version Show more versions Abstract Background: Pre-operative anxiety is common and is associated with negative surgical outcomes. Virtual reality (VR) is a promising new technology that offers opportunities to modulate patient experience and cognition and has been shown to be associated with lower levels of anxiety. In this study, we investigated changes in pre-operative anxiety levels before and after using VR in patients undergoing minor gynecological surgery. Methods: Patients who underwent elective minor gynecological surgeries in KK Women’s and Children’s hospital, Singapore were recruited. The VR intervention consisted of 10-minute exposure via a headset loaded with sceneries, background meditation music and breathing exercises. For the primary outcome of pre-operative anxiety, patients were assessed at pre- and post-intervention using the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes of self-reported satisfaction scores and EurQol 5-dimension 3-level (EQ-5D-3L) were also collected. Results: Data analysis from 108 patients revealed that HADS anxiety scores were significantly reduced from 7.2 ± 3.3 pre-intervention to 4.6 ± 3.0 post-intervention (p<0.0001). Furthermore, HADS depression scores were significantly reduced from 4.7 ± 3.3 pre-intervention to 2.9 ± 2.5 post-intervention (p<0.0001). Eighty-two percent of the patients self-reported VR intervention as ‘Good’ or ‘Excellent’. EQ-5D-3L showed significant changes in dimensions of ‘usual activities’ (p=0.025), ‘pain/discomfort’ (p=0.008) and ‘anxiety/ depression’ (p<0.0001). Conclusions: For patients undergoing minor gynecological procedures, the VR intervention brought about a significant reduction in pre-operative anxiety. This finding may be clinically important to benefit patients with high pre-operative anxiety without the use of anxiolytics. Trial registration: This study was registered on clinicaltrials.gov registry (NCT03685422) on 26 Sep 2018. Psychiatry Surgery Virtual reality preoperative anxiety patient satisfaction Figures Figure 1 Figure 2 Background Anxiety can be defined as emotions of fear, tension or unease and is often encountered before surgery [1, 2]. Pre-operative anxiety has been shown to be correlated with acute and chronic post-surgical pain, increased use of post-operative analgesia and post-operative nausea and vomiting [3-5]. It also has significant impact on recovery, including longer post-operative hospital stay and even cognitive and behavioral ramifications [2-5]. Furthermore, women often experiencing higher levels of pre-operative anxiety compared to men [2, 6, 7]. While pharmacological interventions for pre-operative anxiety are available, reservations such as safety profile and cost often hinder physicians to fully utilize them. Therefore, non-pharmacological methods such as music and Virtual Reality (VR) are gradually growing in popularity to improve the overall patient surgical experience [8-12]. The use of VR therapy in various clinical settings is well documented, such as physical rehabilitation, pain distraction, overcoming phobias, anxiety disorders, and post-traumatic stress disorder (PTSD) [13, 14]. It is reported that VR therapy results in significantly reduced anxiety, persistent pain intensity, faster wound healing, and improved neurorehabilitation outcomes in patients with burns and complex regional pain syndrome [15, 16]. The technology usually consists of an audio system (earphones or headphones), a visual system (head-mounted displays) and an integrated set up (motion tracking systems). By providing multiple stimuli to the human senses, VR systems are able to allow the user an immersive experience and presence in the virtual world [17-19]. In the gynecological population, limited evidence has been reported on the use of VR therapy for postoperative care and management. In a non-randomized controlled study recruiting patients undergoing colposcopy (cervical examination), Vasquez et al. showed that patients assigned to VR group reported reduced pain scores post-VR intervention [20]. Another prospective randomized controlled trial in an outpatient hysteroscopy setting showed that the use of VR during the procedure resulted in significantly decreased average pain score and anxiety when compared to controls [21]. Nevertheless, there are limited studies conducted in a gynecological population, and no formal sample size calculations were performed to study the expected clinical effect size related to pre-operative anxiety. In view of the potential clinical benefits of VR, our study aimed to assess pre-operative anxiety (primary outcome) and self-reported satisfaction of VR and health state (secondary outcomes) in women undergoing minor gynecological procedures. Methods This prospective cohort study was conducted between March 2019 and January 2020 at KK Women’s and Children’s Hospital, Singapore. The study protocol adhered to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines and was approved by the SingHealth Centralized Institutional Review Board, Singapore (SingHealth CIRB Ref: 2018/2200), and registered on Clinicaltrials.gov (ID: NCT03685422). Inclusion and Exclusion Criteria Women aged 21 – 70 years old, American Society of Anesthesiologist (ASA) physical status I or II, with no visual or mental impairment and undergoing gynecological surgery were included in this study. Patients with severe motion sickness, significant respiratory disease or obstructive sleep apnea, oncological gynecology and obstetrics patients were excluded. Women who were unable to communicate in English or unable to understand the administered questionnaires were also excluded from this study. Psychometric Assessment Tools Used The State-Trait Anxiety Inventory (STAI) designed by Spielberger et al. has been used extensively in research and clinical settings [22]. It has been used to measure the presence and severity of current symptoms of anxiety and a generalized propensity to be anxious. The tool consists of 40 items, 20 allocated each to state-anxiety and trait-anxiety. All items are rated on a 4-point Likert scale (e.g. from “Not at all” to “Very much so”; or from “Almost never” to “Almost always”).Test-retest reliability coefficients on initial development ranged from 0.31 to 0.86, with intervals ranging from 1 hour to 104 days [22]. The Hospital Anxiety and Depression Scale (HADS) is commonly used to assess the patients’ level of anxiety and depression during their hospitalization and is preferentially used as an indicator for global psychological distress [23]. Each item on the questionnaire is scored from 0 to 3, thus a patient may have a total score from 0 to 21 for the anxiety and depression subscales, respectively. A score of 0-7 indicates normal level of anxiety/depression while 8-10 indicates borderline abnormal and 11-21 indicates abnormal. Validity of the HADS was deemed “good” to “very good”, with comparable sensitivity and specificity of longer scales including the STAI and the Symptom Checklist-90 anxiety scales [24]. HADS has been validated in gynecological populations undergoing procedures, achieving good levels of internal consistency with Cronbach’s α of 0.78 and 0.84 for anxiety and depression subscales, respectively, and 0.88 for the whole instrument [25]. As compared with conventional instruments that measure anxiety (e.g. STAI), the shorter HADS provides increased convenience for patients and allows for multiple measurements at different time points pre and post intervention. The EuroQol 5-dimension 3-level (EQ-5D-3L) questionnaire [26] is one of the most widely used instruments for measuring health-related quality of life. It consists of a descriptive system on health state comprising five dimensions (5D) with three levels (3L) of self-reporting in each dimension: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; each dimension ranging from 1 to 3 to reflect level of impairment of “with no problem”, “with some problems” or “with severe problems”. The evaluation component involves a visual analog scale (VAS), asking to mark health state on the day of interview on a 20 cm vertical scale with end point of 0 and 100. Zero corresponds to "the worst health you can imagine" and hundred corresponds to "the best health you can imagine". For measuring patient satisfaction with regards to the VR intervention, a self-reported 4-point Likert scale with the following items: “Poor”, “Fair”, “Good” and “Excellent” was used. Pain score at rest was scored using a 0-10 Numerical Rating Scale (NRS). Patient Recruitment Patients presenting to the day surgery service for a variety of minor gynecological procedures were initially screened by study investigators using the operative room surgical listing schedule. The investigators then evaluated the patient’s medical records to determine her eligibility. Patients meeting inclusion criteria were approached in a pre-operative holding area. Risks and benefits of the study were explained, and informed consent was obtained. No patient remuneration was provided in this study. Pre-VR intervention assessments included demographic data, pain score and psychometric questionnaires (STAI, HADS and EQ-5D-3L; Figure 1). Patients were then given a Samsung Gear VR3 (Samsung Co. Ltd) headset and audio earpieces, fitted with a Samsung 8 smartphone (Figure 2A) running ‘Oculus Relax VR’ program (Figure 2C) [27]. Disposable sanitary covers and earbuds were provided, that were discarded and replaced between each user (Figure 2B). Patients were given 11 immersive scenarios to choose from, and the experience was integrated with background meditation music and breathing exercises. The 11 scenarios included sceneries from a tropical beach in the Philippines, a rice terrace in the Philippines, wine glass bay beach in Australia, 12 Apostles in Australia, Fern Bern in New Zealand, a forest creek in Germany, a daisy garden in Germany, the Grand Canyon in the (United States of America) USA, watching northern lights in the USA, floating in the sky in clouds and being on the moon in outer space. The VR intervention was conducted with patients lying in bed in the fowler’s position with knees straight, in a quiet pre-operative waiting area. Patients were able to move their body freely in bed while on the headsets and were also instructed to discontinue the VR intervention if they experienced any side effects such as motion sickness or dizziness. After the VR intervention, pain score, satisfaction score and psychometric assessments (HADS, EQ-5D-3L) were performed and collected. The VR intervention lasted for 10 minutes, with pre- and post-intervention surveys all done 1-2 hours before surgery. The patients subsequently underwent their intended surgical procedure under general anesthesia. Intra- and post-operative care provided adhered to standard hospital protocol. Data on intra- and post-operative analgesic use was also collected. Patients were all admitted to the day surgery unit in the hospital post-operatively before being further assessed to be discharged or for longer hospital stay. Data on analgesic use and pain score were also collected post-operatively in the recovery area. The primary outcome for this study was the change in pre-operative anxiety as quantified by the HADS scale. The HADS anxiety scores pre- and post-VR were compared for data analysis. For secondary outcomes, EQ-5D-3L and patient satisfaction of the VR intervention were targeted and used for data analysis of the patient’s health state and anxiety levels. Sample size calculation and statistical analysis Tan et al. [28] reported difference in mean (SD) HADs anxiety between pre- and post-intervention in music experiences as 4.61 (4.08). The calculated sample size of 70 was based on the following assumptions: considering a conservative mean (SD) HADS difference of 2.0 (8.0), level of significance as 5% and power as 90%. After adjusting for 40% loss to follow up, ineligibility and withdrawal, a recruitment goal of 110 patients was targeted. Categorical and continuous variables were summarized as frequency (proportion) and mean ± standard deviation (SD) respectively. Difference between pre- and post-VR experiences were compared using paired t – test and McNemar test for paired continuous and paired categorical data respectively. P-value < 0.05 was considered as statistical significance and all the tests were two – sided. Analyses were done using SAS version 9.4 software (SAS Institute; Cary, North Carolina, USA). Results A total of 110 patients aged 24– 59 years old were recruited but only 108 patients’ data were analyzed as 2 patients withdrew prior to the intervention. Table 1 shows the demographic data for the patients. Majority of the patients were of Chinese ethnicity (70.37%), ASA 1 status (72.22%) and underwent dilatation, curettage and hysteroscopy (82.41%) (Table 1). No adverse events were reported during and post VR intervention, and we observed no motion sickness nor dizziness in the recruited patients. Pre-operative HADS scores compared between types of surgery showed no significant difference (p = 0.4879). Eighty-eight patients (81.5%) were discharged on the same day of their surgery, whereas the rest (n=20 or 18.5%) were hospitalized overnight. Pre- and post-VR psychological outcomes are displayed in Table 2. Importantly, for our primary outcome, there were statistically significant reduction in anxiety and depression using HADS (p<0.0001). Furthermore, for our secondary outcome, anxiety/depression (p<0.0001), self-reported perception of pain and discomfort (p = 0.0073) and perceived health states (p<0.0001) in EQ-5D-3L also showed statistically significant improvements post-VR intervention pre-operatively. There was no significant association between STAI and change in HADS anxiety scores (p = 0.6352). Table 3 displays values of EQ-5D-3L for all five dimensions and three levels in detail, with the number of patients reporting each level within each dimension pre-VR and post-VR intervention. There was a statistically significant difference on EQ-5D-3L VAS health state (mean ± SD) of pre- and post-VR intervention (71.57 ± 17.75 vs 76.05 ± 15.07; p<0.001). Table 4 shows the pain and satisfaction scores collected. Notably, pain scores collected pre- and post-VR intervention did not reveal any significantly changes (p = 0.2178). Intra- and post-operative pharmacological information, including type, dosage and route of analgesia, are displayed in Table 4. Significantly, for the secondary outcome of patient satisfaction of the VR intervention, 82.41% of the participants rated the experience as ‘Good’ or ‘Excellent’ (Table 4). In terms of immersive VR scenario selection, majority of the participants (n=24, 22.22%) selected Wine Glass Bay Beach, Australia, followed by Northern Lights, USA (n=20, 18.51%), Tropical beach, Philippines (n=19, 17.59%), Daisy Garden, Germany (n=15, 13.89%), 12 Apostles, Australia (n=9, 8.33%), Fern Bern, New Zealand (n=6, 5.56%) and Forest Creek, Germany (n=6, 5.56%). Discussion By examining patients using VR intervention before undergoing minor gynecological procedures, we found that the use of a 10-minute VR intervention resulted in a statistically significant reduction of pre-operative anxiety and depressive symptoms as measured using the HADS. While the pain scores collected pre- and post-VR intervention did not reveal any significantly changes, EQ-5D-3L measures further revealed that pre-operative self-reported perception of pain and discomfort and perceived health states were improved after VR intervention. This study revealed that there is significant preoperative anxiety amongst the gynecological patients recruited, and is in congruence with other studies using HADS to measure changes in pre-operative anxiety for VR interventions in oncology patients [29, 30] and patients in intensive care [31]. Surgery is a daunting experience that comes with emotional vulnerabilities. These emotions are often intensified moments before surgery, causing overwhelming anxiety and even depressive moods [32]. Increased preoperative anxiety is associated with postponement or even cancellation of planned surgeries, increase in anesthetic requirements, prolonged hospital stay and poorer overall patient satisfaction [33, 34]. Patient-centric outcomes were investigated as part of our secondary outcomes in this study using the EQ-5D-3L. This provided other insights into patients’ health conditions, baseline functional status and quality of life. In this study, EQ-5D-3L assessment showed statistically significant improvement on self-reported pain/ discomfort and anxiety/ depression dimensions before gynecological surgery when VR was used. In addition, self-reported perception of ‘usual activities’ dimension also showed improvement post-VR. Furthermore, patients had overall positive self-reported satisfaction for the VR experience prior to their scheduled gynecological procedure. In previous studies, patients who received VR treatment reported a reduction in pain and anxiety [16], faster wound healing [35], decreased chronic pain intensity [15] and other neuro-rehabilitation improvements [36]. These results largely corroborated with our findings, which showed reduction in anxiety. While the exact neurobiological mechanistic theory behind VR’s action remain unclear, it is generally suggested that VR acts as a distraction by rendering several possible mechanisms by: i) engaging different senses simultaneously and inducing a sense of presence in the virtual environment, thus diverting one’s attention from painful stimuli and other negative emotions such as stress and anxiety [37]; ii) employing attentional resources in immersive and interactive virtual environments to modulate ascending nociceptive stimuli and thus reduce pain experience [38]; iii) isolating the user both visually and acoustically from the actual environment to escape from the painful world cognitively [39]. VR could serve as a non-pharmacological intervention in clinical settings to modulate emotional affective, emotion-based cognitive and attentional processes [40]. Interestingly, although the mean pain scores pre- and post-VR intervention were not statistically significant, there was an improvement of self-reported perception in the dimension of ‘pain/discomfort’ in the EQ-5D-3L. The pain score changes could be attributed to pre-surgical administration of vaginal or oral prostaglandins for cervical softening. Study limitations There were several limitations in our study. Firstly, the instruments used for assessment of anxiety were dependent on self-reported psychometric questionnaires. Although these psychometric tools have been validated in previous studies with similar target populations, there might be more suitable and sensitive measures of anxiety (e.g. STAI) and other psychometric measures (e.g. pain catastrophizing scale (PCS), perceived stress scale (PSS)) to reflect the effects of VR intervention on patients’ psychological profiles [41, 42]. Secondly, the patient population selected had to have the ability to read and understand English, which might limit the sociodemographic profiles of patients. Thirdly, multiple factors unrelated to surgery could influence pre-operative anxiety. For example, we did not investigate interactions between study team investigator and the patient. Non-study team members and the surrounding environment may also affect the patient’s mood and anxiety. The effects of different scenarios on anxiety scores were also not studied due to an unequal distribution of scenarios that were chosen by patients. Finally, there was a lack of a control group to compare anxiety scores without VR intervention, making it difficult to assess the true effect of VR on pre-operative anxiety. Future randomized controlled trials are needed to validate our findings in this study. Conclusions This study might have given some indication that VR relaxation technique could be a promising method for anxiety alleviation, improvement on pain perception and perceived health states during perioperative settings which could be extended for hospital use (rehabilitation, outpatient procedures, diagnostic scanning and perioperative period). This strategy may hence potentially increase patient satisfaction while providing non-pharmacological anxiolytic effects with minimal side effects. List Of Abbreviations ASA: American Society of Anesthesiologists; HADS: Hospital Anxiety and Depression Scale; SD: standard deviation; STAI: State-Trait Anxiety Inventory; STROBE: Strengthening the Reporting of Observational studies in Epidemiology; VAS: visual analog scale; VR: virtual reality Declarations Ethics approval and consent to participate The study was approved by the SingHealth Centralized Institutional Review Board, Singapore (SingHealth CIRB Ref: 2018/2200), and registered on Clinicaltrials.gov (NCT03685422). The authors declare that all the recruited patients provided informed consent, and that this work was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients. Consent for publication Not applicable. Availability of data and materials The datasets generated and analyzed in this work are available for anyone who wishes to access the data by contacting the corresponding author. Competing interests Ban Leong Sng is an associate editor of BMC Anesthesiology. All other authors report no conflicts of interest in this work. Funding This work was supported by the funding from the SingHealth Duke-NUS Anesthesiology and Perioperative Science Academic Programme, Clinical Innovation Support Grant (Grant no. 12/FY2018/P1/06-A21). The aforementioned sponsor was not involved in the study activities. Authors' contributions JJI Chan reviewed the literature, planned the study, oversaw patient recruitment, data analysis and interpretation, and wrote the manuscript. YCT reviewed the literature, helped in patient recruitment, managed the raw data, helped in data analysis and interpretation. KHM helped in patient recruitment, data management, data analysis and interpretation. CW reviewed the literature, helped in funding, oversaw data management, data analysis and interpretation. SR reviewed the literature, helped in the study design, performed data analysis and interpretation. SATH reviewed the literature, helped in the study design, and reviewed the data analysis and interpretation. SBL reviewed the literature, planned the study, and oversaw the study including the design, data analysis and interpretation. All authors approved the final version of the manuscript and agree to be accountable for all aspects of this work. Acknowledgments The authors would like to thank Ms. Agnes Teo (Clinical Research Coordinator) for her administrative support during this study. References Johnston M. Anxiety in surgical patients. Psychol Med 1980, 10(1):145-152. Carr E, Brockbank K, Allen S, Strike P. Patterns and frequency of anxiety in women undergoing gynaecological surgery. J Clin Nurs 2006, 15(3):341-352. Suffeda A, Meissner W, Rosendahl J, Guntinas-Lichius O. Influence of depression, catastrophizing, anxiety, and resilience on postoperative pain at the first day after otolaryngological surgery: A prospective single center cohort observational study. 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Tables Table 1 Patient Demographics Characteristics Mean ± SD/ n (%) Age (years) 43.56 ± 6.68 Race Chinese 76 (70.37) Malay 15 (13.89) Indian 4 (3.70) Others 13 (12.04) ASA status Class 1 78 (72.22) Class 2 30 (27.78) Weight (kg) 64.60 ± 12.54 Height (cm) 158.56 ± 5.97 Duration of Surgery (min) Type of surgery Dilatation and Curettage, Hysteroscopy Others 26.43 ± 41.86 89 (82.41) 19 (17.59) Values are represented as mean ± standard deviation (SD) or number (%). ASA American Society of Anesthesiologists Table 2 Pre-Virtual Reality and Post-Virtual Reality psychological outcomes Variables Pre-VR Post-VR P value STAI S-anxiety score 39.59 ± 11.14 -- -- STAI T-anxiety score 40.10 ± 9.07 -- -- STAI total score 79.69 ± 18.78 -- -- HADS score Anxiety 7.23 ± 3.27 4.62 ± 3.03 <0.0001 Depression 4.12 ± 3.34 2.92 ± 2.51 <0.0001 EQ-5D-3L dimensions anxiety/ depression <0.0001 Not anxious/ depressed 62 (57.41) 90 (83.33) Having anxious/ depressed 46 (42.59) 18 (16.67) EQ-5D-3L dimensions Pain/ Discomfort 0.0073 No pain/discomfort 72 (66.67) 84 (77.78) Having pain/discomfort 36 (33.33) 24 (22.22) EQ-5D-3L VAS health state 71.57 ± 17.75 76.05 ± 15.07 <0.0001 Values are represented as mean ± standard deviation (SD) or number (%) HADS Hospital Anxiety and Depression Scale, STAI State-Trait Anxiety Inventory, VAS Visual analog scale, VR Virtual reality Table 3 EQ-5D-3L individual dimensions Dimension Level 1 Level 2 Level 3 P value Pre-VR Post-VR Pre-VR Post-VR Pre-VR Post-VR Mobility 106 (98.15) 107 (99.07) 1 (0.93) 1 (0.93) 1 (0.93) 0 (0.00) 0.3170 Self-care 108 (100.00) 108 (100.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) - Usual Activities 102 (94.44) 107 (99.07) 6 (5.56) 1 (0.93) 0 (0.00) 0 (0.00) 0.0250 Pain/ Discomfort 72 (66.67) 84 (77.78) 36 (33.33) 24 (22.22) 0 (0.00) 0 (0.00) 0.007 Anxiety/ Depression 62 (57.41) 90 (83.33) 46 (42.59) 18 (16.67) 0 (0.00) 0 (0.00) <0.0001 Values are represented as number (%) Table 4 Pain and Satisfaction Scores Characteristics Mean ± SD/ n (%) Pre-operative pain score pre-VR 0.44 ± 1.24 Pre-operative pain score post-VR 0.60 ± 1.21 Patient satisfaction on VR experience Excellent Good Fair Poor 35 (32.41) 54 (50.00) 17 (15.74) 2 (1.85) Maximum pain score post-operative in recovery 2.22 ± 2.41 Mean dose of Fentanyl used intra-operatively (mcg) 84.55 ± 19.49 Mean dose of Morphine used intra-operatively (mg) 5.79 ± 2.72 Paracetamol use intra-operatively 56 (51.85) Duration of stay in the recovery unit (min) 64.50 ± 31.89 Fentanyl use in the recovery unit 16 (14.81) Morphine use in the recovery unit 6 (5.56) Paracetamol use in the recovery unit 9 (8.33) Values are represented as mean ± standard deviation (SD) or number (%). VR Virtual Reality Supplementary Files CONSORTChecklistVR.doc STROBEVRperiopanxiety.pdf Cite Share Download PDF Status: Published Journal Publication published 09 Oct, 2020 Read the published version in BMC Anesthesiology → Version 4 posted Submission checks completed at journal 28 Sep, 2020 Editorial decision: Accept 25 Sep, 2020 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-20956","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":2839259,"identity":"409fd8b4-1fe7-4d86-9e29-3d09041d334f","order_by":0,"name":"Jason Ju In Chan","email":"","orcid":"","institution":"KK Women's and Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jason","middleName":"Ju In","lastName":"Chan","suffix":""},{"id":2839260,"identity":"bc408448-4871-44d1-b6f6-06ad960fecc5","order_by":1,"name":"Cheng Teng Yeam","email":"","orcid":"","institution":"Duke-NUS Medical School","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Cheng","middleName":"Teng","lastName":"Yeam","suffix":""},{"id":2839261,"identity":"845c82b6-1192-4afd-b93a-accd496c4714","order_by":2,"name":"Hwei Min Kee","email":"","orcid":"","institution":"KK Women's and Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hwei","middleName":"Min","lastName":"Kee","suffix":""},{"id":2839262,"identity":"b6049d68-8ea5-4060-95a8-92c4d3845b30","order_by":3,"name":"Chin Wen Tan","email":"","orcid":"","institution":"KK Women's and Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chin","middleName":"Wen","lastName":"Tan","suffix":""},{"id":2839263,"identity":"3ae8b7a9-2373-4388-83d1-0052ec0709a5","order_by":4,"name":"Rehena Sultana","email":"","orcid":"","institution":"Duke-NUS Medical School","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Rehena","middleName":"","lastName":"Sultana","suffix":""},{"id":2839264,"identity":"5e672aac-a864-45f5-8979-c6c820dfa370","order_by":5,"name":"Alex Tiong Heng Sia","email":"","orcid":"","institution":"KK Women's and Children's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alex","middleName":"Tiong Heng","lastName":"Sia","suffix":""},{"id":2839265,"identity":"82ff9bd4-0826-4e1a-9c15-6b293ae7da4b","order_by":6,"name":"Ban Leong SNG","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABR0lEQVRIie2RMUvDQBTHXzi4LE+7JqS2X+GVQoqTXyVBaJciAZcONRSEuBRdK4rfQHDqXDmMS6COGTq0FJyK2EGJEMRcpAU9oY6C+XM8Hnf87v+/ewCFCv1RMVm287YDCHKBB85GhOdttEKIfologawbkOrFyQPzuhPg+nE4e7nyy43S9e00ofQAdHF3A+nRd4QmkccG4SNwDFv1naHA3cHTfq1PdAjYbMZacK8gRtthyAVwo21b5nCEFEe2gURuz0A71nqhEmwgkfcMqS4y5NKXSOMtXSGQKgjErRHbCqQL2uayx5DGfZutXYB3lWBxG8T5qUCeJbcgFJkL1q0y1d1AvsUNRmqw1mzuvYpKSRehmXT9PRpHteWiU3HPsp34OfXVb0aS98hZAMur4Xwe5JNyQKiIPl23WiJr6WuUH1wKFSpU6J/pAyr4bHdQV7yYAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0001-5374-4271","institution":"KK Women's and Children's Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ban","middleName":"Leong","lastName":"SNG","suffix":""}],"badges":[],"createdAt":"2020-04-02 11:53:48","currentVersionCode":4,"declarations":"","doi":"10.21203/rs.3.rs-20956/v4","doiUrl":"https://doi.org/10.21203/rs.3.rs-20956/v4","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-020-01177-6","type":"published","date":"2020-10-09T12:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":2706435,"identity":"c4e57c42-065e-469f-ad69-8425e5cd10fb","added_by":"auto","created_at":"2020-09-30 18:42:10","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":76711,"visible":true,"origin":"","legend":"Study flowchart","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-20956/v4/Figure1.jpg"},{"id":2706438,"identity":"2448fd5b-7037-4eba-98b3-1823b1a26819","added_by":"auto","created_at":"2020-09-30 18:42:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5606290,"visible":true,"origin":"","legend":"The setting of VR intervention. (A) The Samsung 8 smartphone for attaching onto a Samsung Gear VR 3; (B) Disposable sanitary covers and earbuds were provided for each use; and (C) A screenshot of menus of Relax VR. Used with permission from Relax VR [27].","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-20956/v4/Figure2.png"},{"id":13596921,"identity":"637dea7f-1b2c-4e1b-aa43-20120c628b1b","added_by":"auto","created_at":"2021-09-17 05:30:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1383493,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-20956/v4/ef92248f-0a03-470c-9456-3700fa9fb565.pdf"},{"id":2706436,"identity":"c13ab92d-93a6-4a34-9e04-817c4711b88e","added_by":"auto","created_at":"2020-09-30 18:42:11","extension":"doc","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":233472,"visible":true,"origin":"","legend":"","description":"","filename":"CONSORTChecklistVR.doc","url":"https://assets-eu.researchsquare.com/files/rs-20956/v4/CONSORTChecklistVR.doc"},{"id":2706437,"identity":"e1c3f745-ac41-4826-a3ef-a46815987542","added_by":"auto","created_at":"2020-09-30 18:42:11","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":175816,"visible":true,"origin":"","legend":"","description":"","filename":"STROBEVRperiopanxiety.pdf","url":"https://assets-eu.researchsquare.com/files/rs-20956/v4/STROBEVRperiopanxiety.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eThe use of pre-operative Virtual Reality to reduce anxiety in women undergoing gynecological surgeries: a prospective cohort study\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eAnxiety can be defined as emotions of fear, tension or unease and is often encountered before surgery [1, 2]. Pre-operative anxiety has been shown to be correlated with acute and chronic post-surgical pain, increased use of post-operative analgesia and post-operative nausea and vomiting [3-5]. It also has significant impact on recovery, including longer post-operative hospital stay and even cognitive and behavioral ramifications [2-5]. Furthermore, women often experiencing higher levels of pre-operative anxiety compared to men [2, 6, 7]. While pharmacological interventions for pre-operative anxiety are available, reservations such as safety profile and cost often hinder physicians to fully utilize them. Therefore, non-pharmacological methods such as music and Virtual Reality (VR) are gradually growing in popularity to improve the overall patient surgical experience [8-12].\u003c/p\u003e\n\u003cp\u003eThe use of VR therapy in various clinical settings is well documented, such as physical rehabilitation, pain distraction, overcoming phobias, anxiety disorders, and post-traumatic stress disorder (PTSD) [13, 14]. It is reported that VR therapy results in significantly reduced anxiety, persistent pain intensity, faster wound healing, and improved neurorehabilitation outcomes in patients with burns and complex regional pain syndrome [15, 16]. The technology usually consists of an audio system (earphones or headphones), a visual system (head-mounted displays) and an integrated set up (motion tracking systems). By providing multiple stimuli to the human senses, VR systems are able to allow the user an immersive experience and presence in the virtual world [17-19].\u003c/p\u003e\n\u003cp\u003eIn the gynecological population, limited evidence has been reported on the use of VR therapy for postoperative care and management. In a non-randomized controlled study recruiting patients undergoing colposcopy (cervical examination), Vasquez et al. showed that patients assigned to VR group reported reduced pain scores post-VR intervention [20]. Another prospective randomized controlled trial in an outpatient hysteroscopy setting showed that the use of VR during the procedure resulted in significantly decreased average pain score and anxiety when compared to controls [21]. Nevertheless, there are limited studies conducted in a gynecological population, and no formal sample size calculations were performed to study the expected clinical effect size related to pre-operative anxiety.\u003c/p\u003e\n\u003cp\u003eIn view of the potential clinical benefits of VR, our study aimed to assess pre-operative anxiety (primary outcome) and self-reported satisfaction of VR and health state (secondary outcomes) in women undergoing minor gynecological procedures.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis prospective cohort study was conducted between March 2019 and January 2020 at KK Women\u0026rsquo;s and Children\u0026rsquo;s Hospital, Singapore. The study protocol adhered to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines and was approved by the SingHealth Centralized Institutional Review Board, Singapore (SingHealth CIRB Ref: 2018/2200), and registered on Clinicaltrials.gov (ID: NCT03685422).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eInclusion and Exclusion Criteria\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWomen aged 21 \u0026ndash; 70 years old, American Society of Anesthesiologist (ASA) physical status I or II, with no visual or mental impairment and undergoing gynecological surgery were included in this study. Patients with severe motion sickness, significant respiratory disease or obstructive sleep apnea, oncological gynecology and obstetrics patients were excluded. Women who were unable to communicate in English or unable to understand the administered questionnaires were also excluded from this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePsychometric Assessment Tools Used\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe State-Trait Anxiety Inventory (STAI) designed by Spielberger et al. has been used extensively in research and clinical settings [22]. It has been used to measure the presence and severity of current symptoms of anxiety and a generalized propensity to be anxious. The tool consists of 40 items, 20 allocated each to state-anxiety and trait-anxiety. All items are rated on a 4-point Likert scale (e.g. from \u0026ldquo;Not at all\u0026rdquo; to \u0026ldquo;Very much so\u0026rdquo;; or from \u0026ldquo;Almost never\u0026rdquo; to \u0026ldquo;Almost always\u0026rdquo;).Test-retest reliability coefficients on initial development ranged from 0.31 to 0.86, with intervals ranging from 1 hour to 104 days [22].\u003c/p\u003e\n\u003cp\u003eThe Hospital Anxiety and Depression Scale (HADS) is commonly used to assess the patients\u0026rsquo; level of anxiety and depression during their hospitalization and is preferentially used as an indicator for global psychological distress [23]. Each item on the questionnaire is scored from 0 to 3, thus a patient may have a total score from 0 to 21 for the anxiety and depression subscales, respectively. A score of 0-7 indicates normal level of anxiety/depression while 8-10 indicates borderline abnormal and 11-21 indicates abnormal. Validity of the HADS was deemed \u0026ldquo;good\u0026rdquo; to \u0026ldquo;very good\u0026rdquo;, with comparable sensitivity and specificity of longer scales including the STAI and the Symptom Checklist-90 anxiety scales [24]. HADS has been validated in gynecological populations undergoing procedures, achieving good levels of internal consistency with Cronbach\u0026rsquo;s \u0026alpha; of 0.78 and 0.84 for anxiety and depression subscales, respectively, and 0.88 for the whole instrument [25]. As compared with conventional instruments that measure anxiety (e.g. STAI), the shorter HADS provides increased convenience for patients and allows for multiple measurements at different time points pre and post intervention.\u003c/p\u003e\n\u003cp\u003eThe EuroQol 5-dimension 3-level (EQ-5D-3L) questionnaire [26] is one of the most widely used instruments for measuring health-related quality of life. It consists of a descriptive system on health state comprising five dimensions (5D) with three levels (3L) of self-reporting in each dimension: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression; each dimension ranging from 1 to 3 to reflect level of impairment of \u0026ldquo;with no problem\u0026rdquo;, \u0026ldquo;with some problems\u0026rdquo; or \u0026ldquo;with severe problems\u0026rdquo;. The evaluation component involves a visual analog scale (VAS), asking to mark health state on the day of interview on a 20 cm vertical scale with end point of 0 and 100. Zero corresponds to \"the worst health you can imagine\" and hundred corresponds to \"the best health you can imagine\". For measuring patient satisfaction with regards to the VR intervention, a self-reported 4-point Likert scale with the following items: \u0026ldquo;Poor\u0026rdquo;, \u0026ldquo;Fair\u0026rdquo;, \u0026ldquo;Good\u0026rdquo; and \u0026ldquo;Excellent\u0026rdquo; was used. Pain score at rest was scored using a 0-10 Numerical Rating Scale (NRS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003ePatient Recruitment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients presenting to the day surgery service for a variety of minor gynecological procedures were initially screened by study investigators using the operative room surgical listing schedule. The investigators then evaluated the patient\u0026rsquo;s medical records to determine her eligibility. Patients meeting inclusion criteria were approached in a pre-operative holding area. Risks and benefits of the study were explained, and informed consent was obtained. No patient remuneration was provided in this study.\u003c/p\u003e\n\u003cp\u003ePre-VR intervention assessments included demographic data, pain score and psychometric questionnaires (STAI, HADS and EQ-5D-3L; Figure 1). Patients were then given a Samsung Gear VR3 (Samsung Co. Ltd) headset and audio earpieces, fitted with a Samsung 8 smartphone (Figure 2A) running \u0026lsquo;Oculus Relax VR\u0026rsquo; program (Figure 2C) [27]. Disposable sanitary covers and earbuds were provided, that were discarded and replaced between each user (Figure 2B). Patients were given 11 immersive scenarios to choose from, and the experience was integrated with background meditation music and breathing exercises. The 11 scenarios included sceneries from a tropical beach in the Philippines, a rice terrace in the Philippines, wine glass bay beach in Australia, 12 Apostles in Australia, Fern Bern in New Zealand, a forest creek in Germany, a daisy garden in Germany, the Grand Canyon in the (United States of America) USA, watching northern lights in the USA, floating in the sky in clouds and being on the moon in outer space. The VR intervention was conducted with patients lying in bed in the fowler\u0026rsquo;s position with knees straight, in a quiet pre-operative waiting area. Patients were able to move their body freely in bed while on the headsets and were also instructed to discontinue the VR intervention if they experienced any side effects such as motion sickness or dizziness.\u003c/p\u003e\n\u003cp\u003eAfter the VR intervention, pain score, satisfaction score and psychometric assessments (HADS, EQ-5D-3L) were performed and collected. The VR intervention lasted for 10 minutes, with pre- and post-intervention surveys all done 1-2 hours before surgery. The patients subsequently underwent their intended surgical procedure under general anesthesia. Intra- and post-operative care provided adhered to standard hospital protocol. Data on intra- and post-operative analgesic use was also collected. Patients were all admitted to the day surgery unit in the hospital post-operatively before being further assessed to be discharged or for longer hospital stay. Data on analgesic use and pain score were also collected post-operatively in the recovery area.\u003c/p\u003e\n\u003cp\u003eThe primary outcome for this study was the change in pre-operative anxiety as quantified by the HADS scale. The HADS anxiety scores pre- and post-VR were compared for data analysis. For secondary outcomes, EQ-5D-3L and patient satisfaction of the VR intervention were targeted and used for data analysis of the patient\u0026rsquo;s health state and anxiety levels.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSample size calculation and statistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTan et al. [28] reported difference in mean (SD) HADs anxiety between pre- and post-intervention in music experiences as 4.61 (4.08). The calculated sample size of 70 was based on the following assumptions: considering a conservative mean (SD) HADS difference of 2.0 (8.0), level of significance as 5% and power as 90%. After adjusting for 40% loss to follow up, ineligibility and withdrawal, a recruitment goal of 110 patients was targeted.\u003c/p\u003e\n\u003cp\u003eCategorical and continuous variables were summarized as frequency (proportion) and mean \u0026plusmn; standard deviation (SD) respectively. Difference between pre- and post-VR experiences were compared using paired t \u0026ndash; test and McNemar test for paired continuous and paired categorical data respectively. P-value \u0026lt; 0.05 was considered as statistical significance and all the tests were two \u0026ndash; sided. Analyses were done using SAS version 9.4 software (SAS Institute; Cary, North Carolina, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 110 patients aged 24\u0026ndash; 59 years old were recruited but only 108 patients\u0026rsquo; data were analyzed as 2 patients withdrew prior to the intervention. Table 1 shows the demographic data for the patients. Majority of the patients were of Chinese ethnicity (70.37%), ASA 1 status (72.22%) and underwent dilatation, curettage and hysteroscopy (82.41%) (Table 1). No adverse events were reported during and post VR intervention, and we observed no motion sickness nor dizziness in the recruited patients. Pre-operative HADS scores compared between types of surgery showed no significant difference (p = 0.4879). Eighty-eight patients (81.5%) were discharged on the same day of their surgery, whereas the rest (n=20 or 18.5%) were hospitalized overnight.\u003c/p\u003e\n\u003cp\u003ePre- and post-VR psychological outcomes are displayed in Table 2. Importantly, for our primary outcome, there were statistically significant reduction in anxiety and depression using HADS (p\u0026lt;0.0001). Furthermore, for our secondary outcome, anxiety/depression (p\u0026lt;0.0001), self-reported perception of pain and discomfort (p = 0.0073) and perceived health states (p\u0026lt;0.0001) in EQ-5D-3L also showed statistically significant improvements post-VR intervention pre-operatively. There was no significant association between STAI and change in HADS anxiety scores (p = 0.6352).\u003c/p\u003e\n\u003cp\u003eTable 3 displays values of EQ-5D-3L for all five dimensions and three levels in detail, with the number of patients reporting each level within each dimension pre-VR and post-VR intervention. There was a statistically significant difference on EQ-5D-3L VAS health state (mean \u0026plusmn; SD) of pre- and post-VR intervention (71.57 \u0026plusmn; 17.75 vs 76.05 \u0026plusmn; 15.07; p\u0026lt;0.001). Table 4 shows the pain and satisfaction scores collected. Notably, pain scores collected pre- and post-VR intervention did not reveal any significantly changes (p = 0.2178). Intra- and post-operative pharmacological information, including type, dosage and route of analgesia, are displayed in Table 4. Significantly, for the secondary outcome of patient satisfaction of the VR intervention, 82.41% of the participants rated the experience as \u0026lsquo;Good\u0026rsquo; or \u0026lsquo;Excellent\u0026rsquo; (Table 4).\u003c/p\u003e\n\u003cp\u003eIn terms of immersive VR scenario selection, majority of the participants (n=24, 22.22%) selected Wine Glass Bay Beach, Australia, followed by Northern Lights, USA (n=20, 18.51%), Tropical beach, Philippines (n=19, 17.59%), Daisy Garden, Germany (n=15, 13.89%), 12 Apostles, Australia (n=9, 8.33%), Fern Bern, New Zealand (n=6, 5.56%) and Forest Creek, Germany (n=6, 5.56%).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBy examining patients using VR intervention before undergoing minor gynecological procedures, we found that the use of a 10-minute VR intervention resulted in a statistically significant reduction of pre-operative anxiety and depressive symptoms as measured using the HADS. While the pain scores collected pre- and post-VR intervention did not reveal any significantly changes, EQ-5D-3L measures further revealed that pre-operative self-reported perception of pain and discomfort and perceived health states were improved after VR intervention.\u003c/p\u003e\n\u003cp\u003eThis study revealed that there is significant preoperative anxiety amongst the gynecological patients recruited, and is in congruence with other studies using HADS to measure changes in pre-operative anxiety for VR interventions in oncology patients [29, 30] and patients in intensive care [31]. Surgery is a daunting experience that comes with emotional vulnerabilities. These emotions are often intensified moments before surgery, causing overwhelming anxiety and even depressive moods [32]. Increased preoperative anxiety is associated with postponement or even cancellation of planned surgeries, increase in anesthetic requirements, prolonged hospital stay and poorer overall patient satisfaction [33, 34].\u003c/p\u003e\n\u003cp\u003ePatient-centric outcomes were investigated as part of our secondary outcomes in this study using the EQ-5D-3L. This provided other insights into patients\u0026rsquo; health conditions, baseline functional status and quality of life. In this study, EQ-5D-3L assessment showed statistically significant improvement on self-reported pain/ discomfort and anxiety/ depression dimensions before gynecological surgery when VR was used. In addition, self-reported perception of \u0026lsquo;usual activities\u0026rsquo; dimension also showed improvement post-VR. Furthermore, patients had overall positive self-reported satisfaction for the VR experience prior to their scheduled gynecological procedure.\u003c/p\u003e\n\u003cp\u003eIn previous studies, patients who received VR treatment reported a reduction in pain and anxiety [16], faster wound healing [35], decreased chronic pain intensity [15] and other neuro-rehabilitation improvements [36]. These results largely corroborated with our findings, which showed reduction in anxiety. While the exact neurobiological mechanistic theory behind VR\u0026rsquo;s action remain unclear, it is generally suggested that VR acts as a distraction by rendering several possible mechanisms by: i) engaging different senses simultaneously and inducing a sense of presence in the virtual environment, thus diverting one\u0026rsquo;s attention from painful stimuli and other negative emotions such as stress and anxiety [37]; ii) employing attentional resources in immersive and interactive virtual environments to modulate ascending nociceptive stimuli and thus reduce pain experience [38]; iii) isolating the user both visually and acoustically from the actual environment to escape from the painful world cognitively [39]. VR could serve as a non-pharmacological intervention in clinical settings to modulate emotional affective, emotion-based cognitive and attentional processes [40]. Interestingly, although the mean pain scores pre- and post-VR intervention were not statistically significant, there was an improvement of self-reported perception in the dimension of \u0026lsquo;pain/discomfort\u0026rsquo; in the EQ-5D-3L. The pain score changes could be attributed to pre-surgical administration of vaginal or oral prostaglandins for cervical softening.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy limitations\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere were several limitations in our study. Firstly, the instruments used for assessment of anxiety were dependent on self-reported psychometric questionnaires. Although these psychometric tools have been validated in previous studies with similar target populations, there might be more suitable and sensitive measures of anxiety (e.g. STAI) and other psychometric measures (e.g. pain catastrophizing scale (PCS), perceived stress scale (PSS)) to reflect the effects of VR intervention on patients\u0026rsquo; psychological profiles [41, 42]. Secondly, the patient population selected had to have the ability to read and understand English, which might limit the sociodemographic profiles of patients.\u003c/p\u003e\n\u003cp\u003eThirdly, multiple factors unrelated to surgery could influence pre-operative anxiety. For example, we did not investigate interactions between study team investigator and the patient. Non-study team members and the surrounding environment may also affect the patient\u0026rsquo;s mood and anxiety. The effects of different scenarios on anxiety scores were also not studied due to an unequal distribution of scenarios that were chosen by patients. Finally, there was a lack of a control group to compare anxiety scores without VR intervention, making it difficult to assess the true effect of VR on pre-operative anxiety. Future randomized controlled trials are needed to validate our findings in this study.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study might have given some indication that VR relaxation technique could be a promising method for anxiety alleviation, improvement on pain perception and perceived health states during perioperative settings which could be extended for hospital use (rehabilitation, outpatient procedures, diagnostic scanning and perioperative period). This strategy may hence potentially increase patient satisfaction while providing non-pharmacological anxiolytic effects with minimal side effects.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cp\u003eASA: American Society of Anesthesiologists; HADS: Hospital Anxiety and Depression Scale; SD: standard deviation; STAI: State-Trait Anxiety Inventory; STROBE: Strengthening the Reporting of Observational studies in Epidemiology; VAS: visual analog scale; VR: virtual reality\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the SingHealth Centralized Institutional Review Board, Singapore (SingHealth CIRB Ref: 2018/2200), and registered on Clinicaltrials.gov (NCT03685422).\u0026nbsp; The authors declare that all the recruited patients provided informed consent, and that this work was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed in this work are available for anyone who wishes to access the data by contacting the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBan Leong Sng is an associate editor of BMC Anesthesiology. All other authors report no conflicts of interest in this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the funding from the SingHealth Duke-NUS Anesthesiology and Perioperative Science Academic Programme, Clinical Innovation Support Grant (Grant no. 12/FY2018/P1/06-A21). The aforementioned sponsor was not involved in the study activities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJJI Chan reviewed the literature, planned the study, oversaw patient recruitment, data analysis and interpretation, and wrote the manuscript. YCT reviewed the literature, helped in patient recruitment, managed the raw data, helped in data analysis and interpretation. KHM helped in patient recruitment, data management, data analysis and interpretation. CW reviewed the literature, helped in funding, oversaw data management, data analysis and interpretation. SR reviewed the literature, helped in the study design, performed data analysis and interpretation. SATH reviewed the literature, helped in the study design, and reviewed the data analysis and interpretation. SBL reviewed the literature, planned the study, and oversaw the study including the design, data analysis and interpretation. All authors approved the final version of the manuscript and agree to be accountable for all aspects of this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Ms. Agnes Teo (Clinical Research Coordinator) for her administrative support during this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJohnston M. Anxiety in surgical patients. Psychol Med 1980, 10(1):145-152.\u003c/li\u003e\n\u003cli\u003eCarr E, Brockbank K, Allen S, Strike P. Patterns and frequency of anxiety in women undergoing gynaecological surgery. J Clin Nurs 2006, 15(3):341-352.\u003c/li\u003e\n\u003cli\u003eSuffeda A, Meissner W, Rosendahl J, Guntinas-Lichius O. Influence of depression, catastrophizing, anxiety, and resilience on postoperative pain at the first day after otolaryngological surgery: A prospective single center cohort observational study. 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Int J Environ Res Public Health 2020, 17(13).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cstrong\u003e\u003cspan style=\"font-family: Arial, sans-serif; color: rgb(0, 0, 0);\"\u003eTable 1\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePatient Demographics\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 315pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eCharacteristics\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eMean \u0026plusmn; SD/ n (%)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 315pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eAge (years)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e43.56 \u0026plusmn; 6.68\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 315pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp 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200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Others\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e13 (12.04)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 315pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eASA status\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 315pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Class 1\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e78 (72.22)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 315pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Class 2\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e30 (27.78)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 315pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eWeight (kg)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e64.60 \u0026plusmn; 12.54\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 315pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eHeight (cm)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e158.56 \u0026plusmn; 5.97\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 315pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eDuration of Surgery (min)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eType of surgery\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Dilatation and Curettage, Hysteroscopy\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Others\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e26.43 \u0026plusmn; 41.86\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e89 (82.41)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e19 (17.59)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eValues are represented as mean \u0026plusmn; standard deviation (SD) or number (%). \u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eASA\u003c/span\u003e\u003c/em\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;American Society of Anesthesiologists\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u003cbr\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 2\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePre-Virtual Reality and Post-Virtual Reality psychological outcomes\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 4.5e+2pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eVariables\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePre-VR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePost-VR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eP value\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eSTAI S-anxiety score\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e39.59 \u0026plusmn; 11.14\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e--\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e--\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eSTAI T-anxiety score\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e40.10 \u0026plusmn; 9.07\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e--\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e--\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eSTAI total score\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e79.69 \u0026plusmn; 18.78\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e--\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e--\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eHADS score\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Anxiety\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e7.23 \u0026plusmn; 3.27\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e4.62 \u0026plusmn; 3.03\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026lt;0.0001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Depression\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e4.12 \u0026plusmn; 3.34\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e2.92 \u0026plusmn; 2.51\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026lt;0.0001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eEQ-5D-3L dimensions anxiety/ depression\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026lt;0.0001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Not anxious/ depressed\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e62 (57.41)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e90 (83.33)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Having anxious/ depressed\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e46 (42.59)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e18 (16.67)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eEQ-5D-3L dimensions Pain/ Discomfort\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e0.0073\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;No pain/discomfort\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e72 (66.67)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e84 (77.78)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; \u0026nbsp;Having pain/discomfort\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e36 (33.33)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e24 (22.22)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 175.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eEQ-5D-3L VAS health state\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 1.5in;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e71.57 \u0026plusmn; 17.75\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e76.05 \u0026plusmn; 15.07\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026lt;0.0001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eValues are represented as mean \u0026plusmn; standard deviation (SD) or number (%)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eHADS\u003c/span\u003e\u003c/em\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;Hospital Anxiety and Depression Scale, \u003cem\u003eSTAI\u003c/em\u003e State-Trait Anxiety Inventory, \u003cem\u003eVAS\u003c/em\u003e Visual analog scale, \u003cem\u003eVR\u003c/em\u003e Virtual reality\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:16px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u003cbr\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 3\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eEQ-5D-3L individual dimensions\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"width: 5.2e+2pt;margin-left:-35.15pt;border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 91.85pt;border-right: none;border-bottom: none;border-left: none;border-image: initial;border-top: 1pt solid windowtext;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eDimension\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:120.5pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:12.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eLevel 1\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:127.6pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:12.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eLevel 2\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width:120.45pt;border-top:solid windowtext 1.0pt;border-left:none;border-bottom:solid windowtext 1.0pt;border-right:none;padding:0in 5.4pt 0in 5.4pt;height:12.65pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eLevel 3\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 56.7pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;height: 12.65pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eP value\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width:56.7pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:9.9pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePre-VR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:9.9pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePost-VR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:9.9pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePre-VR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.8pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:9.9pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePost-VR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:56.7pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:9.9pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePre-VR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width:63.75pt;border:none;border-bottom:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:9.9pt;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePost-VR\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 91.85pt;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eMobility\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border: none;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e106 (98.15)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border: none;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e107 (99.07)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n 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56.7pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e108 (100.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e108 (100.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e-\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 91.85pt;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eUsual Activities\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e102 (94.44)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e107 (99.07)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e6 (5.56)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e1 (0.93)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 15.95pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e0.0250\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 91.85pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePain/ Discomfort\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e72 (66.67)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e84 (77.78)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e36 (33.33)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e24 (22.22)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e0.007\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 91.85pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eAnxiety/ Depression\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e62 (57.41)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e90 (83.33)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e46 (42.59)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.8pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e18 (16.67)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63.75pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:15px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e0 (0.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56.7pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;height: 15.2pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026lt;0.0001\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eValues are represented as number (%)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u003cbr\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-size:13px;line-height:200%;font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eTable 4\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePain and Satisfaction Scores\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003ctable style=\"border-collapse:collapse;border:none;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eCharacteristics\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;border-top: 1pt solid windowtext;border-left: none;border-bottom: 1pt solid windowtext;border-right: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cstrong\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eMean \u0026plusmn; SD/ n (%)\u003c/span\u003e\u003c/strong\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePre-operative pain score pre-VR\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;border: none;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e0.44 \u0026plusmn; 1.24\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePre-operative pain score post-VR\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e0.60 \u0026plusmn; 1.21\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003ePatient satisfaction on VR experience\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Excellent\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Good\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Fair\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp; Poor\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e35 (32.41)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e54 (50.00)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e17 (15.74)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e2 (1.85)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eMaximum pain score post-operative in recovery\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e2.22 \u0026plusmn; 2.41\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eMean dose of Fentanyl used intra-operatively (mcg)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e84.55 \u0026plusmn; 19.49\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eMean dose of Morphine used intra-operatively (mg)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e5.79 \u0026plusmn; 2.72\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eParacetamol use intra-operatively\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e56 (51.85)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eDuration of stay in the recovery unit (min)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e64.50 \u0026plusmn; 31.89\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eFentanyl use in the recovery unit\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e16 (14.81)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eMorphine use in the recovery unit\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e6 (5.56)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 333pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height: 200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eParacetamol use in the recovery unit\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 117.5pt;border-top: none;border-right: none;border-left: none;border-image: initial;border-bottom: 1pt solid windowtext;padding: 0in 5.4pt;vertical-align: top;\"\u003e\n \u003cp style='margin-top:0in;margin-right:0in;margin-bottom:0in;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:center;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e9 (8.33)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eValues are represented as mean\u0026nbsp;\u003c/span\u003e\u003cspan style=\"font-family:Symbol;\"\u003e\u0026plusmn;\u003c/span\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;standard deviation (SD) or number (%). \u0026nbsp;\u0026nbsp;\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp style='margin-top:0in;margin-right:0in;margin-bottom:8.0pt;margin-left:0in;line-height:200%;font-size:16px;font-family:\"Calibri\",sans-serif;text-align:justify;'\u003e\u003cspan style=\"color: rgb(0, 0, 0);\"\u003e\u003cem\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003eVR\u003c/span\u003e\u003c/em\u003e\u003cspan style='font-family:\"Arial\",sans-serif;'\u003e\u0026nbsp;Virtual Reality\u003c/span\u003e\u003c/span\u003e\u003cspan style=\"font-size: 13px; line-height: 200%; font-family: Arial, sans-serif; color: rgb(0, 0, 0);\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Virtual reality, preoperative anxiety, patient satisfaction","lastPublishedDoi":"10.21203/rs.3.rs-20956/v4","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-20956/v4","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Pre-operative anxiety is common and is associated with negative surgical outcomes. Virtual reality (VR) is a promising new technology that offers opportunities to modulate patient experience and cognition and has been shown to be associated with lower levels of anxiety. In this study, we investigated changes in pre-operative anxiety levels before and after using VR in patients undergoing minor gynecological surgery. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Patients who underwent elective minor gynecological surgeries in KK Women’s and Children’s hospital, Singapore were recruited. The VR intervention consisted of 10-minute exposure via a headset loaded with sceneries, background meditation music and breathing exercises. For the primary outcome of pre-operative anxiety, patients were assessed at pre- and post-intervention using the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes of self-reported satisfaction scores and EurQol 5-dimension 3-level (EQ-5D-3L) were also collected. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Data analysis from 108 patients revealed that HADS anxiety scores were significantly reduced from 7.2 ± 3.3 pre-intervention to 4.6 ± 3.0 post-intervention (p\u0026lt;0.0001). Furthermore, HADS depression scores were significantly reduced from 4.7 ± 3.3 pre-intervention to 2.9 ± 2.5 post-intervention (p\u0026lt;0.0001). Eighty-two percent of the patients self-reported VR intervention as ‘Good’ or ‘Excellent’. EQ-5D-3L showed significant changes in dimensions of ‘usual activities’ (p=0.025), ‘pain/discomfort’ (p=0.008) and ‘anxiety/ depression’ (p\u0026lt;0.0001). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e For patients undergoing minor gynecological procedures, the VR intervention brought about a significant reduction in pre-operative anxiety. This finding may be clinically important to benefit patients with high pre-operative anxiety without the use of anxiolytics. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTrial registration: \u003c/strong\u003eThis study was registered on clinicaltrials.gov registry (NCT03685422) on 26 Sep 2018.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"The use of pre-operative Virtual Reality to reduce anxiety in women undergoing gynecological surgeries: a prospective cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":4,"date":"2020-09-30 18:37:24","doi":"10.21203/rs.3.rs-20956/v4","editorialEvents":[{"type":"communityComments","content":0},{"type":"checksComplete","content":"","date":"2020-09-28T12:00:00+00:00","index":"","fulltext":""},{"type":"decision","content":"Accept","date":"2020-09-25T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":3,"date":"2020-08-31 10:18:38","doi":"10.21203/rs.3.rs-20956/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2020-09-04T12:00:00+00:00","index":1,"fulltext":"Recommendation: Reviewer's comments unavailable pending editorial decision\n"},{"type":"editorInvitedReview","content":"","date":"2020-09-04T12:00:00+00:00","index":2,"fulltext":"Recommendation: Reviewer's comments unavailable pending editorial decision\n"},{"type":"reviewersInvited","content":"","date":"2020-08-31T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-08-31T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-08-31T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorAssigned","content":"","date":"2020-08-27T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-08-26T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-08-26T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-08-11 16:17:53","doi":"10.21203/rs.3.rs-20956/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-08-24T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-08-08T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nReview BANE-20-00278R1\n\nOverall the manuscript has been much improved.\nHowever I still have some concerns and remarks:\n1. The authors should be very careful with their overall conclusions: this is not an RCT and it is difficult to assess the true effect. This is basically a study about associations and this study tries to explore the usefulness of VR in anxiety management in a perioperative setting.\nIn my opinion the conclusion should read something along the lines of: This study might have given some indication that VR could be a beneficial tool to reduce perioperative (state?) anxiety …. \nAnd what about EQ-D-3L with showed significant changes? Should this not be mentioned?\n(abstract: it should not be mentioned that further studies are needed);\n2. Why did the authors include the STAI as an assessment of baseline anxiety? They do not use it in their further analysis. It still might be interesting to assess an association between STAI measurements and changes in HADS scores. The authors also describe this in their introduction and discussion.\n3. The introduction is still too wordy and should focus on why the authors specially carried out this study. Mentioning (lines 105-106) that there are few or no studies investigating the effectiveness of VR in the preoperative period in Singapore is not necessary.\n4. Methods:\nlines 111- 112: it is not necessary to mention the aim of this study again.\nline 163: pain scores?\n5. The discussion: Overall this section has been much improved.\nStill the discussion should start with reporting all findings and this should be compared and incorporated into the state of the field. Some parts of the discussion are still too speculative.\nThis section should not start with …' this is the first study'…\n\n\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **Yes**\n* Are the methods sufficiently described to allow the study to be repeated?: **Yes**\n* Is the use of statistics and treatment of uncertainties appropriate?: **No**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"editorInvitedReview","content":"","date":"2020-08-08T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThank you to the authors for diligently revising their manuscript. While I feel that this version is an improvement, there are still a couple of issues which need to be resolved before publication.\n* Abstract: p=NA - this seems a bit confusing.\n* Background: on p4 you write that [anxiety] is pertinent for women undergoing gynecological procedures due to the nature of their treatment - this is quite unspecific. What is this specific nature and how/why does it differ from other surgical procedures?\n* P 5. The citation 22 seems not to fit well. There is better or more specific literature on the phenomena of immersion and presence (see IJsselsteijn or Slater or Lombard \u0026 Ditton). Also, I would suggest deleting the \"\" around presence.\n* P. 5: \"few or no studies\" - it is rather an either or thing. Are there studies or are there no studies? I would specify this to be more precise.\n* P. 5: instead of citing the EQ-5D-3L (which at this point is mentioned for the first time), it would be better to mentioned the related construct.\n* P. 6: in my opinion it is not right to state that this study assessed the efficacy of the VR intervention, as this would require a RCT. This should be corrected as this is misleading.\n* The presentation of the used measures could be more consistent, i.e. stating the type of Likert scale for all questionnaires, as well as indicating each Cronbach's alpha (as it was in this study). Also, the five dimensions of the QoL-measure should be mentioned and explained in a little more detail, as it is hard for the naïve reader to judge what this instrument assesses.\n* Consider indicating how often motion sickness or dizziness occurred in your sample. Generally, it is expected to find more motion sickness among people lying down while using a fully immersive VR. This may also be a limiting factor.\n* The authors write that patients were either discharged after the surgery of had a longer hospital stay. This seems contradictory to the statement that all surgeries were minor. Please explicate. Also, consider indicating how many % of the sample were discharged and how many were kept in hospital.\n* Results: the STAI results are not reported. Also, with regards to improved readability, consider adding a n= to all frequencies (last paragraph on p 11 and p 12).\n* The conclusion on p 13 that \"significant improvement [was achieved] when VR was used\" does not seem to be correct, as this kind of conclusion would require another study design including a control group. Thus, the observed changes may have also been due to other factors, not (only) the VR.\n* On P14. More gynecological studies should be cited/more reference to past results in the field of gynecology should be included as this has more relevance to the current study.\n* I still struggle with the fact that the HADS was used. Consider discussing that there are more suited and more sensitive measures of anxiety (i.e., STAI-S) which should be used in future studies. This is a major limitation of this study.\n* I do not quite understand why the patient recruitment target was maximized to mitigate the limitation that not all potential participants were able to understand English. Please explicate.\n* Table 3 does not conform to APA standards (and is different from the other tables)\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n* Is the study design appropriate to answer the research question (including the use of appropriate controls), and are the conclusions supported by the evidence presented?: **No**\n* Are the methods sufficiently described to allow the study to be repeated?: **No**\n* Is the use of statistics and treatment of uncertainties appropriate?: **Yes**\n* Is the presentation of the work clear?: **Yes**\n* Are the images in this manuscript (including electrophoretic gels and blots) free from apparent manipulation?: **Yes**\n"},{"type":"reviewerAgreed","content":"","date":"2020-08-05T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-08-05T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorAssigned","content":"","date":"2020-08-04T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-08-04T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-08-03T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-08-03T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2020-04-10 16:30:26","doi":"10.21203/rs.3.rs-20956/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-07-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-07-03T12:00:00+00:00","index":2,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nThis manuscript evaluates an immersive VR intervention in a sample of N=108 women prior to a gynecological surgical procedure with regards to its potential of decreasing anxiety, depressive mood and pain. Overall, the authors report positive effects on the mentioned variables, pain, however, increased post-surgery. While I find this paper to be a useful addition to the body of literature on the usage of VR in the context of surgery, there are a number of issues which need additional attention. Most of all, information on the used methods as well as on the sample and statistical procedures is quite scarce, which makes it hard to judge the study. I will try to provide more detailed comments below.\n\nMAJOR POINTS:\n\n- Include a more comprehensive overview over the according literature in your introduction; there is, indeed, a considerable body of literature on this topic (see the following review: Alanazi, A. A. (2014). Reducing anxiety in preoperative patients: a systematic review. British Journal of Nursing, 23(7), 387-393), none of these studies are reported at this point. See also the following, more suitable for the field of gynecology: Vasquez, J. M., Vaca, V. L., Wiederhold, B. K., Miller, I., \u0026 Wiederhold, M. D. (2017). Virtual reality pain distraction during gynecological surgery—A report of 44 cases. Surgical Research Updates, 5, 12-16.\n- On the basis of this literature, it should be made clear what makes up the incremental value of the current approach. What is new? What is already known? Which additional benefit is expected?\n- Provide more details on the used measures, i.e., references, number of items and subscales, range of values, item wording (i.e., include item examples). In the discussion section, some more details are described about the measures, however, they should already be mentioned in a measures section and not only in the discussion. Also, how were satisfaction and pain measured? (VAS?)\n- Provide more details on the VR scenarios: how were they presented to the patients in the process of choosing them, how were movements controlled, were patients seated, were they only able to move their heads?\n- Duration of overall study: how long did everything take? When were the post-measures assessed, particularly those post surgery? Immediately after surgery or several hours later? Was this controlled across patients? Was surgery done in an outpatient setting or were participants admitted to hospital?\n- A key point is the following question: What type of surgery was performed? Was local anesthesia or general anesthesia applied? What type of medication? Would you expect different levels of anxiety depending on the type of surgery? If yes, this variable should be controlled for.\n- How were patients recruited? How were they approached? Did they receive a remuneration for their participation? How many drop-outs were there? How many patients refused to participate upon being approached?\n- Provide effect sizes for all reported differences (i.e., Cohens d)\n- Another key issue is the question of what the used questionnaires actually measure. As far as I understand, the HADS assesses symptoms of anxiety disorders/depression, and hence, constitutes a trait measure. If this is true, using the HADS for repeated measures (more importantly: For such a short interval), is a major limiting factor. Usually, sensitive state scales are needed to assess short-term changes in emotion/affect.\n- Another key limiting factor is that no control group (without VR preparation) was included. This makes it difficult to assess the true effect of VR on anxiety. This should be discussed as a limitation.\n- The discussion needs to be more comprehensive and take already published papers on this issue into account.\n\n\nMINOR POINTS:\n- I recommend the usage of consistent reporting of statistical values, i.e., M = XY and SD = XY (according to the APA guidelines) throughout the manuscript, otherwise it is hard to read the reported results.\n- Use 2 decimal places for M and SD\n- Check language throughout the manuscript; see for instance p 7 last sentence, which seems to be off\n- Check citations; for instance, the author of the STAI is Spielberger, p. 9\n- Explain the acronym ASA in a note in Table 1; include an age range in table 1\n- \"number\" - is this the sample size? Or relative frequencies?\n- Consider the style of table 3, which seems not to fit the other tables; Also, it is unclear what numbers are reported in table 3 (M, SD?)\n- Report the p value for pain pre and post scores in table 4\n- Is there a difference between the scenarios with regards to the outcome variables?\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"editorInvitedReview","content":"","date":"2020-06-27T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nReview BMC Anesthesiology BANE-D-20-00278\n'The use of pre-operative virtual reality to reduce anxiety in women undergoing gynaecological surgeries: a prospective cohort study'\nThank you for the opportunity to revise this manuscript.\nThis is a prospective cohort study investigating the effect of the use (feasibility/practicability) of pre-operative VR on patients' anxiety level. VR patients had the opportunity to choose between 11 scenarios which could be a concern of bias.\nAll included patients underwent gynaecological surgery but it was not specified which kind of surgery (cancer?).\nOverall the aims of this study are not well described. This study is not an RCT and the authors should be very careful about their conclusions. This is a study about possible associations and I wonder why the authors did not employ any sort of regression analysis. The main objective of this study is in my opinion to investigate a possible association between predictors (f.i. between state and trait anxiety on the one hand and an outcome parameter - in this case the HADS scores - on the other).\nRelevance:\nInvestigating new tools like VR in a preoperative setting to prepare patients for their surgery is a relevant study subject.\nClarity of writing, data and tables:\nThe manuscript needs a linguistic amendment. The data and tables are not well presented.\n\nTitle:\nDoes not entirely cover the content of this manuscript.\nAims:\nThe aims of this study are not well defined.\n\nAbstract\nMethods: time frame between start and end of inclusion of patients should not be mentioned in the abstract. Different assessment tools should be mentioned. How were feasibility and practicability of VR assessed?\nResults: what is the purpose of mentioning moderate anxiety levels with STAI assessment - any changes?\nConclusions: the authors state that there is a significant reduction in state (?) anxiety after VR and that VR may be suitable for patients with high anxiety. Little evidence can be found for such statements in the results section.\n\n\nIntroduction/background\nOverall more information about VR should be added and a precise justification why the authors performed this study.\np. 4 line 66: what is meant with … experience different levels of anxiety …\np. 4 line 84: Aim of the study: … feasibility and practicability of employing VR in anxiety …\nWhat is meant by this? Anxiety reduction?\n\nMethods\nOverall not well described and too short!\nAs this is a prospective cohort one should use STROBE statement instead of CONSORT!\nWhat about the demographic data?\nInclusion criteria\nWere patients with mental disability included?\nWhich type of gynaecological surgery - cancer therapy? Could be a source of bias regarding anxiety levels.\nFlow of the study: it is not clear when the different assessments were done? Was this in the direct preoperative setting just before anesthesia or at the consultation?\nDescription of the used assessment tools under a separate subheading could enhance clearness.\nA description of all used assessment tools (STAI, HADS, EQ-5D-3L) with appropriate psychometric information (about validity and reliability) and the references should be included in the method section.\nThe HADS is specifically designed for hospital use. Please comment.\nEQ-5D-3L is about health status in terms of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems and extreme problems. Why was this scale opted for?\nHow did the authors assess satisfaction regarding VR?\nStatistical analysis\nPower analysis: it is not clear why a difference in HADS scores is opted for. This is not an RCT. This is a within-group study design. Why include 110 patients if power calculation estimates that 70 is enough? Please comment.\nShould a Bonferroni correction not be applied?\nAs I already stated the main objective of this study is in my opinion to investigate a possible association between predictors (f.i. between state and trait anxiety on the one hand and an outcome in this case the obtained HADS scores as outcome parameter on the other. Any form of multiple regression? Or repeated measures?\nIn this section the authors also mention pain scores as a secondary outcome. This has not been described earlier (cf. aims of the study). Also take into account that no standardized anesthesia/pain management has been opted for and this can be a source of bias.\nResults\nVery confusedly written and also the tables are not clear.\nWhat can be found in a table should not appear again in the text or vice versa.\nPain scores and analgesic use and which scenario patients prefer is not described in the aims.\nWhat about satisfaction of VR?\n\nDiscussion\nOverall the discussion is not well substantiated and speculative. The discussion should start with describing the main findings. Furthermore the findings should be compared and incorporated into the state of the field. It has too much of a review character.\nNot all limitations are mentioned.\nThere is no general conclusion.\n* Publons Reviewer Recognition. Springer Nature can send verification of this review directly to Publons (a subsidiary of Clarivate Analytics). If you would like to take advantage of this service, please click on the “Yes” option below. Your name, email address, title of the reviewed manuscript, name of the journal, and date of your review submission (the “Review Data”) will then be transmitted to Publons upon publication of the manuscript. If you have already registered at Publons, they will notify you of the receipt of this review and update your profile as per your settings and their policy. If you are not registered with Publons, you will receive an email from them asking you to register in order for them to be able to recognize your review on your new profile page. Publons may use the Review Data to generate derivative metadata for the benefit of Publons and you as a reviewer, carefully considering the sensitivity of such information. For example, Publons may verify your record as a reviewer by updating your profile published on its webservice if you have registered for such service or help editors to identify candidate reviewers. Please find the details of processing in Publons’ privacy policy https://publons.com/about/terms: **Yes**\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests'**\n* Reviewer Publication Consent. I agree for my report to be made available under an Open Access Creative Commons CC-BY License (http://creativecommons.org/licenses/by/4.0) if this manuscript is accepted for publication. Any comments that I do not wish to be included in the published report have been included as confidential comments to the editor, which will not be published.: **I agree to the terms of the CC-BY 4.0 license; please do not publish my name with my report. (default)**\n"},{"type":"reviewerAgreed","content":"","date":"2020-06-23T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-06-07T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-04-14T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2020-04-02T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-04-02T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-04-01T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-04-01T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d0a01308-fcc5-473c-8927-af02b739360e","owner":[],"postedDate":"September 30th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":658869,"name":"Psychiatry"},{"id":658870,"name":"Surgery"}],"tags":[],"updatedAt":"2020-10-11T15:01:50+00:00","versionOfRecord":{"articleIdentity":"rs-20956","link":"https://doi.org/10.1186/s12871-020-01177-6","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2020-10-09 12:00:00","publishedOnDateReadable":"October 9th, 2020"},"versionCreatedAt":"2020-09-30 18:37:24","video":"","vorDoi":"10.1186/s12871-020-01177-6","vorDoiUrl":"https://doi.org/10.1186/s12871-020-01177-6","workflowStages":[]},"version":"v4","identity":"rs-20956","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-20956","identity":"rs-20956","version":["v4"]},"buildId":"pf3fE39SIOqb-0xH_OWvX","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}