Virtual reality hypnosis during protective isolation: a parallel group randomized trial.

Introduction

Patients with severe neutropenia are highly susceptible to infection and are at risk of developing life-threatening complications. They are typically placed in protective isolation to reduce their exposure to environmental microbes and so lessen their risk of infection. Patients may stay for weeks or even months in a single room within a hospital, which is usually equipped with a high-efficiency particulate air filter. Visiting times are strictly limited, and people entering the room are usually required to wear protective clothing, such as face masks and medical gowns.

Although protective isolation is effective for preventing infection, the experience can be detrimental to the patients’ psychological well-being, and many patients report feelings of loneliness and fear [ 1 ]. Several studies have demonstrated that patients have higher levels of anxiety and depression as well as lower self-esteem during their time in isolation [ 1 ]. These negative effects may increase over time as the isolation continues, as has been previously found for measures of anxiety [ 2 , 3 ].

To limit these negative effects, hospitals generally ensure that there is a television in each isolation room. Psychological support and music therapy may also be provided. Patients are also encouraged to bring their own activities to the hospital, such as crafts, books, and mobile phones. However, despite these efforts, anxiety and other psychological difficulties are still commonly found to occur [ 4 ].

In recent years, there has been a surge of interest in the use of virtual reality in a clinical setting. This technology immerses patients in a simulated three-dimensional environment, where it is possible to look and move around. The sessions are typically designed to foster relaxation and a sense of well-being. Patients can often choose one of several appealing settings, such as a tropical beach or snowy mountains, and calming music may be played. Studies have shown that this can be effective for reducing anxiety and pain during medical procedures, such as venipuncture and dressing changes for burns [ 5 , 6 ]. It may also be helpful for patients with chronic pain and anxiety disorders [ 7 , 8 ]. During the COVID-19 pandemic, virtual reality therapy was also found to help patients on a COVID-19 recovery unit to cope with isolation and loneliness [ 9 ]. It therefore seems plausible that virtual reality therapy would also improve patients’ well-being during protective isolation for neutropenia.

Virtual reality sessions have been developed that can induce hypnosis, in what is known as virtual reality hypnosis (VRH). Hypnosis can be described as state of consciousness characterized by highly focused attention and an increased responsiveness to suggestion [ 10 ]. Previous studies have shown that this can be effective for treating pain and anxiety in a variety of clinical settings, such as during medical procedures and in cancer patients [ 11 – 14 ]. The use of VRH could therefore potentially increase the therapeutic effectiveness of virtual reality sessions.

In this study, we investigated whether VRH is of benefit to patients placed in protective isolation. This technology is of much potential interest for these patients, as the VRH sessions are delivered through a VR headset and headphones, and so contact with others can be avoided. The primary aim was to determine whether VRH can relieve the patients’ anxiety during protective isolation. The secondary aim was to determine whether VRH can also relieve any chronic pain. To investigate this, we assessed anxiety and pain in these patients both before and after a VRH session; this was then compared to a control group of patients who chose an alternative activity, such as reading a book, for the same length of time.

Methods

Design

This study was a 2-arm, parallel group, single-center, open-label, randomized trial. The study was approved by the local Committee for the Protection of Persons (under number 2020-A02561-38); it is registered with Clinical Trials under number NCT04794608 , on the date of 2021 March 3rd. All participants provided informed consent prior to taking part in the study and have signed a written consent. The study was conducted in accordance with the Declaration of Helsinki.

Participants

Participants were recruited by the investigators for the study at a private hospital in Brittany, France. The study was proposed to all patients who met the inclusion criteria and who were about to begin a period of protective isolation. Patients were included if they were 18 years of age or older, were covered by social security, had a hematological disease with neutropenia (neutrophils < 0.5 g/l), and were being treated and followed up at the medical center for the duration of the study. Patients were excluded if they were unable to take part in the study because of psychological, social, family, or geographical constraints, if they had an underlying or concomitant disease incompatible with inclusion in the trial, if they were under guardianship, or if there were any contra-indications to virtual reality, such as psychiatric, visual, or auditory disorders or intractable epilepsy.

11 patients left the study early: 6 because of recovery from aplasia and 5 because of refusal to continue.

Investigational device

The HYPNO VR® (HYPNO VR, Lampertheim, France) is a class I medical device. It consists of a computer program that is linked to a virtual reality headset (Oculus Go) and headphones (Bose Quiet Comfort 35 or equivalent). The device creates a virtual reality environment and is designed to induce hypnosis. It aims to reduce pain, stress, and anxiety, and so offer an alternative to drugs.

The VRH sessions include a hypnotic voice-over that follows a standard hypnosis session. Patients can also choose whether this is a man’s or a woman’s voice. The contents are adapted according to the therapeutic aims, the session duration, and the patients’ preferences. The sessions include cardiac coherence, which deepens the state of relaxation (3 min); this is then followed by a dissociation phase with suggestions to improve comfort and relieve pain (from 5 min). Following this, the patient is then taken through a ‘return’ phase and comes out of the hypnosis (2 min). The virtual reality is used to immerse the patients in an environment of comfort and security. The patients are given the choice of different visual environments (beach, wood, space…) and several different types of therapeutic background music (e.g., ambient, symphony, folk, Asian).

Procedure

The patients were randomly assigned to the VRH group or the control group in a 1:1 ratio.

Each participant took part in the study for four consecutive days. On the first day (inclusion: D0), the patients began their protective isolation. On the three remaining days (D1, D2, and D3), the patients in the VRH group had one 20-min VRH session per day, while the patients in the control group chose an alternative activity for the same duration each day: watching television, listening to music, or reading. The patients were able to stop the VRH session at any time. Of note, the control activities were not restricted to the 20-min sessions, as patients who undergo protective isolation are systematically offered these activities.

The intervention period was limited to three days in order to match the expected duration of aplasia in this population, which was approximately 3–4 days in our cohort.

Outcome measures

The French version of the state-trait anxiety inventory (STAI) was administered, which consists of 40 items that are rated on a 4-point scale [ 15 ]. The trait anxiety sub-Sect. (20 items, with scores ranging from 20–80) was administered just once at inclusion (D0). The state anxiety sub-section (S-anxiety; main outcome measure) was administered 15 min before and again 15 min after each VRH/control session (on D1, D2, and D3).

The patients were also asked to rate their level of pain on a visual analogue scale from 0–10 (“no pain” to “worst pain imaginable”), both before and after each 20-min session. The need for a socio-psychological intervention during the study period was also recorded. The patients in the VRH group were also asked to complete an additional questionnaire after each of the three sessions, which included rating their overall level of satisfaction on a scale from 0 to 10 (“not at all satisfied” to “very satisfied”) and indicating whether they had felt nauseous. They were also asked about any other side effects.

Sample size calculation

The main outcome of interest was the change in S-anxiety from before the intervention to after the intervention, and how this differed between the VRH group and the control group. T-tests or Mann–Whitney U tests were planned to analyze the differences. Previous studies have shown that the S-anxiety questionnaire has a mean score of 50 with a standard deviation of around 10–12 [ 16 – 18 ], and a difference of 10 points can be taken to indicate a clinically significant change. Based on these values, we ran a sample size calculation in R with 80% power and a Bonferroni-corrected alpha level of 0.017 (statistical comparison for each of the three days). The results showed that 30 participants would be required in each group.

Statistical analyses

The results were summarized by calculating the means, standard deviations, frequencies, and/or percentages, according to the type of data. For the quantitative variables, the VRH and control groups were compared using t-tests or Mann–Whitney U tests. For the qualitative variables, chi-square or Fisher’s exact tests were run, as appropriate. For repeated measures, Friedman test was used. The significance level was set at 5% and two-tailed tests were run.

To deal with missing responses on the S-anxiety questionnaire, we used Multiple Imputation by Chained Equations with predictive mean matching (MICE package in R). This was carried out for each patient who had four or fewer missing responses. The missing answers were filled in using imputation and then the S-anxiety score was calculated and included in the analyses. To analyze the overall change in S-anxiety over the three-day period, we used the Last Observation Carried Forward (for the change in S-anxiety score) for each patient and then analyzed the difference between the two patient groups.

Results

Participants

A total of 60 patients were included in the study between July 2, 2021, and January 31, 2024. Thirty patients were randomly assigned to the VRH group and 30 were assigned to the control group. The mean age of the patients was 64.5 years and just under half were women (46.7%), with no significant difference between the two groups (see Table 1 ). The underlying hematological malignancies are detailed in Table 1 . The most frequent underlying malignancies were large B-cell lymphoma (33.3% in group 1 vs 33.3% in group 2), Hodgkin lymphoma (16.7% vs 16.7%), and acute lymphoblastic leukemia (18.3% vs 16.7%). Other hematological malignancies were less frequently represented (Table 1 ). The most frequently administered treatments were rituximab-based combination chemotherapy (33.3% in group 1 vs 40% in group 2), combination cytotoxic chemotherapy (23.3% vs 23.3%), and hypomethylating agents combined with venetoclax (20% vs 16.7%). Other treatment regimens were less common (Table 1 ). The mean duration of aplasia was 3.6 days in group 1 and 3.5 days in group 2. Table 1 Baseline demographic and clinical characteristics of the patients All Patients ( n = 60) VRH group ( n = 30) Control group ( n = 30) Group difference P value Age, mean (SD) (range) 64.5 (16.5) (21.7–84.3) 66.1 (15.7) (23.4–84.3) 62.8 (17.3) (21.7–80.2) 0.34 a Sex, N (%) 0.792 b Female 28 (46.7) 17 (56.7) 11 (36.7) Male 32 (53.3) 13 (43.3) 19 (63.3) Pathology, N (%) 0.514 b Chronic lymphoid leukemia 2 (3.3%) 0 (0%) 2 (6.7%) Acute lymphoid leukemia 11 (18.3%) 5 (16.7%) 6 (20%) Chronic myeloid leukemia 2 (3.3%) 2 (6.7%) 0 (0%) Chronic myelomonocytic leukemia 2 (3.3%) 1 (3.3%) 1 (3.3%) T-cell prolymphocytic leukemia 1 (1.7%) 0 (0%) 1 (3.3%) Multiple myeloma 2 (3.3%) 2 (6.7%) 0 (0%) Large B-cell lymphoma 20 (33.3%) 10 (33.3%) 10 (33.3%) Burkitt lymphoma 1 (1.7%) 0 (0%) 1 (3.3%) Hodgkin lymphoma 10 (16.7%) 5 (16.7%) 5 (16.7%) T lymphoma 6 (10%) 3 (10%) 3 (10%) NA 3 (5%) 2 (6.7%) 1 (3.3%) Treatment, N (%) 0.559 b Brentuximab-based therapy 3 (5%) 2 (6.7%) 1 (3.3%) Rituximab-based combination chemotherapy 22 (36.7%) 10 (33.3%) 12 (40%) Single-agent cytotoxic chemotherapy 1 (1.7%) 0 (0%) 1 (3.3%) Combination cytotoxic chemotherapy 14 (23.3%) 7 (23.3%) 7 (23.3%) Hypomethylating agent alone (azacitidine) 4 (6.7%) 3 (10%) 1 (3.3%) Hypomethylating agent + venetoclax 12 (20%) 5 (16.7%) 7 (23.3%) venetoclax alone 1 (1.7%) 0 (0%) 1 (3.3%) Myeloma-directed therapy 2 (3.3%) 2 (6.7%) 0 (0%) Other 1 (1.7%) 1 (3.3%) 0 (0%) Aplasia duration (days), mean (SD) (range) 3.6 (3.37) (0–22) 3.5 (4.15) (0–22) 3.7 (2.46) (1–11) 0.314 a Curative treatment, N (%) 1 b Yes 58 (96.7%) 29 (96.7%) 29 (96.7%) No 1 (1.7%) 0 (0%) 1 (3.3%) NA 1 (1.7%) 1 (3.3%) 0 (0%) Trait anxiety score, mean (SD) 35.41 (7.21) 36.96 (7.35) 33.8 (7.0) 0.131 a a: Mann–Whitney test; b: chi-square test. Abbreviation: SD Standard deviation, VRH Virtual reality hypnosis

Overall, 11 patients discontinued the study early: 6 due to recovery from aplasia and discharge from protective isolation, and 5 because they declined to continue participation. Among the remaining participants, missing questionnaire data were mainly related to clinical or practical circumstances during hospitalization, including fatigue, fever, headaches, or temporary interruptions during the session (e.g., personal phone call). In addition, one patient required socio-psychological support during the study period. For some patients, the reason for missing data could not be clearly identified.

Main outcome measure: state anxiety

The mean S-anxiety scores before and after each session are shown in Table 2 . The change in anxiety was determined for each participant and the means were calculated for each of the three days. The VRH group was found to have a greater reduction in anxiety on all three days, with mean reductions of around 5–9 points compared to 1–2 points for the control group. Statistical analyses showed that this group difference was statistically significant on D2 (Mann–Whitney U test: p = 0.002), but not on D1 (Mann–Whitney U: p = 0.19) or D3 (Mann–Whitney U: p = 0.19). Analyses were also run using the last S-anxiety change that was obtained for each patient; this was on D3 for half of the patients, D2 for 13 patients, and D1 for 17 patients. The mean (SD) value was −6.4 (9.6) for the VRH group and −1.9 (5.3) for the control group. This group difference was statistically significant (t-test: p = 0.03). This indicates that the VRH sessions led to a greater reduction in anxiety than the control activities. Table 2 State anxiety scores before and after each virtual reality hypnosis or control session Before session After Session Change DAY 1 VRH group, mean (SD) 35.5 (10.0) 30.0 (9.5) −5.3 (8.9) Missing, N [1] [0] [1] Imputation, N [7] [5] Control group, mean (SD) 34.3 (10.1) 32.6 (9.8) −2.2 (4.4) Missing, N [1] [0] [1] Imputation, N [5] [7] DAY 2 VRH group, mean (SD) 38.2 (11.2) 29.3 (7.8) −8.8 (9.3) Missing, N [10] [11] [11] Imputation, N [3] [0] Control group, mean (SD) 32.2 (12.3) 30.8 (12.9) −1.4 (4.3) Missing, N [9] [9] [9] Imputation, N [6] [3] DAY 3 VRH group, mean (SD) 34.8 (9.6) 30.1 (9.6) −4.6 (5.6) Missing, N [14] [14] [14] Imputation, N [2] [2] Control group, mean (SD) 33.6 (11.4) 31.2 (12.1) −2.4 (5.4) Missing, N [16] [14] [16] Imputation, N [2] [1] Abbreviations: SD Standard deviation The means and standard deviations are shown for the scores on the state anxiety questionnaire. The number of questionnaires that were scored using imputation for missing responses is shown (“imputation”), as well as the number of questionnaires that could not be scored because there were more than four missing responses (“missing”).

Boxplots for the changes in state anxiety are shown in Fig. 1 . These reveal that certain patients in the VRH group had marked reductions in anxiety of 30 or more points (D1: one patient; D2 two patients). These patients were both men and were around 60 years of age. There were also some patients in the VRH group who had a slight increase in S-anxiety, mainly on D1; these patients were mostly women (D1: 6/8 patients; 75%). Fig. 1 Variation of state of anxiety before and after each session. The means and standard deviations are shown for difference before/after session for the scores on the state anxiety questionnaire. Days 0, 1, 2 and results for all sessions are shown. Mann-Whitney tests were used. ns: non-significant; * p -value ≤ 0.05; ** p -value ≤ 0.01

Secondary outcome measure: pain

The pain ratings before and after each session were generally low, with mean ratings all below 2 (see Table 3 ). However, a small number of patients had ratings above 4 (see Fig. 2 ). The change in pain was determined for each patient on each of the three days. Mann–Whitney U tests showed that these changes did not differ significantly between the two groups (D1: p = 0.33; D2: p = 0.30; D3: p = 0.34). This indicates that the VRH did not lead to greater pain relief than the control activities. Table 3 Pain ratings before and after each virtual reality hypnosis or control session Before session After Session DAY 1 VRH group, mean (SD) 1.1 (1.8) 0.8 (1.5) Missing, N [0] [0] Control group, mean (SD) (1.5) 0.8 (1.5) Missing, N [1] [0] DAY 2 VRH group, mean (SD) 1.0 (1.5) 0.8 (1.4) Missing, N [10] [10] Control group, mean (SD) 1.1 (2.4) 1.1 (2.3) Missing, N [9] [9] DAY 3 VRH group, mean (SD) 0.6 (1.4) 0.7 (1.4) Missing, N [14] [14] Control group, mean (SD) 0.5 (1.3) 0.4 (1.3) Missing, N [16] [16] The mean pain ratings (visual analogue scale) and standard deviations are shown. Fig. 2 Pain ratings before and after each virtual reality hypnosis or control session. The mean pain ratings (visual analogue scale) and standard deviations are shown. Mann–Whitney tests were used

In addition, one patient required a socio-psychological intervention during the study period.

Patient satisfaction

All patients in the VRH group rated their satisfaction on D1; there were fewer responses on D2 (N = 20) and D3 (N = 16). The available ratings showed that the satisfaction was generally high, with mean (SD) values of 7.5 (2.7) on D1, 7.9 (2.5) on D2, and 7.4 (2.7) on D3. However, although most patients rated the VRH highly, there were a small number who gave ratings as low as 0 (see Fig. 3 ). Two patients who presented nausea gave low satisfaction rating (0 and 2). Fig. 3 Satisfaction ratings about VRH after each virtual reality session. A . The mean satisfaction ratings and standard deviations are shown for each day. B . Repeated measures (Friedman test) of mean satisfaction ratings and standard deviations are shown for each day

Side effects

All patients in the VRH group indicated if they present side effects (such as headache or nausea) after each session of virtual hypnosis. In particular, nausea was rated from 0 (absence of nausea) to 10 (very important nausea). The available data showed that side effects were minor: 2 patients (6.67%) on D1, 1 patient (5%) on D2 and 2 patients (12.5%) on D3.

Few patients present nausea after the session, with mean (SD) values of 0.67 (2.17) on D1, 0.75 (1.89) on D2 and 0.19 (0.71) on D3 (see Table 4 ). Table 4 Side effects after each virtual reality hypnosis session n (%) Mean (SD) Min; Max DAY 1 30 Side effect Yes 2 (6.67%) No 28 (93.33%) Headache Yes 0 (0%) No 30 (100%) Dizziness Yes 0 (0%) No 30 (100%) Nausea Yes 4 (13.3%) 0.67 (2.17) No 26 (86.7%) 0.0; 10.0 DAY 2 20 Side effect Yes 1 (5%) No 19 (95%) Headache Yes 0 (0%) No 20 (100%) Dizziness Yes 0 (0%) No 20 (100%) Nausea Yes 4 (20%) 0.75 (1.89) No 16 (80%) 0.0; 8.0 DAY 3 16 Side effect Yes 2 (12.5%) No 14 (87.5%) Headache Yes 1 (6.25%) No 15 (93.75%) Dizziness Yes 1 (6.25%) No 15 (93.75%) Nausea Yes 2 (13.5%) 0.19 (0.71) No 14 (87.5%) 0.0; 2.0 The mean nausea ratings (visual analogue scale), standard deviations and minimum and maximum are shown.

VRH session was stopped before the end for 1 patient on D1 for vomiting and fever. One patient present headache and dizziness after session on D3, without stop of the session.

Discussion

This study found that VRH sessions reduced patients’ anxiety during protective isolation. The improvement was greater than for control activities. In contrast, the VRH sessions did not appear to relieve the patients’ pain, and the changes were similar to those seen in the control condition. Overall, these results indicate that VRH may be of benefit to patients undergoing protective isolation and could be used to relieve anxiety.

In this study, the patients were found to have lower middle levels of anxiety at baseline, with mean S-anxiety scores of around 35 [ 19 ]. The anxiety was therefore not excessive, although it is important to note that the testing took place during the first four days of isolation. It is likely that the levels of anxiety would have increased following a longer period in isolation, as has been found in previous studies [ 2 , 3 ]. Following the VRH sessions, the mean S-anxiety scores fell by 5 or more points, down to around 30, which indicates mild levels of anxiety [ 19 ]. This therefore indicates that VRH can reduce anxiety from moderate to mild levels. In contrast, the mean scores for the control group fell by just 1–2 points, thus remaining within the lower middle levels of anxiety [ 19 ]. This therefore indicates that VRH is more effective for reducing anxiety than activities.

We noted that there were two patients in the VRH group who had very large reductions in S-anxiety, with an improvement of around 30 points. These patients initially had relatively severe anxiety, with S-anxiety scores between 56 and 59; this then fell to levels indicating mild anxiety, with scores of around 26 [ 19 ]. Of note, there was another patient in the VRH group who also had high initial S-anxiety scores (up to 64), but these did not improve following the VRH sessions (except by one point on D2). This therefore indicates that some patients obtain more benefit from VRH than others. We speculate that the two patients with marked improvements may have had particularly high levels of hypnotic susceptibility, which is a relatively stable trait [ 20 ]; however, this was not assessed in this study. In contrast, the patients who showed no improvement or even worsening may have had low hypnotic susceptibility, which is estimated to concern around 20% of the general population [ 20 ].

Our analyses showed that the improvement in S-anxiety for the VRH group compared to the controls was only statistically significant on D2 and not on D1 or D3. This could be because certain patients experienced side effects from the VRH on D1, such as nausea, which may have led to S-anxiety worsening; this could have masked improvements that occurred for the other patients. These patients may not have completed the questionnaires on the remaining days, and so improvements for the other patients would then have become more apparent. This could therefore account for the significant improvement seen on D2. Alternatively, it is possible that certain patients were hesitant or wary about being hypnotized on D1 due to preconceived ideas about hypnosis, which could have affected the effectiveness of the VRH session. This hesitance may have resolved by D2 after having been through one VRH session, and so the intervention may then have been more effective. However, these possibilities are speculative and require further examination. In the case of D3, it is possible that the non-significant result could be due to a lack of data for this last session, as scores were only available for around half of the patients in both the VRH and control groups.

Our study did not support the use of VRH for relieving pain, as no group differences were found for the pain ratings. This goes against several previous studies, which found that VRH can effectively relieve patients’ pain, for instance during wound-care procedures [ 21 ] and following traumatic injuries [ 22 ]. However, these effects were described as inconsistent in a recent review [ 23 ]. It is important to note that the patients in our study had low levels of pain at baseline, with initial pain ratings that were mostly zero. This meant that it was not possible to see any improvement for most patients, and so any positive effect of the VRH on pain may have been missed. This therefore remains to be investigated further in future studies.

Previous studies on VRH have questioned whether improvements in anxiety and pain are due to the virtual reality environment or the use of hypnosis. This is an important question, as both have previously been shown to lead to improvements, and it is possible that by combining the two the effectiveness may be increased. It has previously been suggested that different mechanisms may underlie the improvements seen for hypnosis alone and virtual reality alone [ 23 ]. Specifically, the effectiveness of virtual reality may relate to distraction, while for hypnosis this is likely to be responsiveness to suggestion [ 23 ]. In support of this, a previous study found that hypnotic susceptibility is linked to pain relief when using hypnosis but not virtual reality alone [ 24 ].

Some studies have found that VRH is more effective than VR alone [ 21 , 22 ], but VRH may not be more effective than hypnosis alone [ 23 ]. However, it is possible that the virtual reality may enhance the ease and speed of hypnosis induction. This requires further investigation, as the results of the previous studies may have been affected by the VRH graphics and the technology used [ 25 ], as well as the specific patient group.

Although our results indicate that VRH is effective for improving patients’ anxiety, it is important to note that side effects can occur. For instance, hypnosis can lead to drowsiness and dizziness, while virtual reality can lead to nausea, headaches, and dizziness, also known as cybersickness [ 5 ]. Although estimates of the incidence of these side effects vary, it has been reported that 0%–8% of patients have side effects for virtual reality therapy [ 5 ], while 0.4% of patients have side effects for hypnosis [ 26 ]. As these are relatively rare as well as temporary, the benefits of VRH can be seen to outweigh the potential harms. Nevertheless, it would be of benefit to identify factors that could predict which patients will benefit the most from VRH and have the fewest side effects.

In further support of the clinical use of VRH, we found that the patients’ satisfaction ratings were mostly high, with very few patients giving ratings less than 5 on the 0–10 scale. This therefore indicates that the patients were happy to continue with the VRH sessions during their hospital stay.

Another important question concerns the optimal number and duration of VRH sessions required to achieve a sustained reduction in anxiety. In the present study, the intervention was limited to three sessions during the early days of protective isolation in order to ensure feasibility in a medically vulnerable population. Although a significant reduction in anxiety was observed, it is possible that a greater number of sessions, or sessions delivered over a longer period of isolation, could lead to more sustained or cumulative benefits. Future studies should therefore investigate the optimal frequency and duration of VRH interventions in this context. In addition, it would be valuable to assess whether regular VRH sessions could contribute to reducing the use of anxiolytic medications during hospitalization. Pharmacological management of anxiety is common in patients undergoing intensive hematological treatments, but may be associated with adverse effects such as sedation or cognitive impairment. Non-pharmacological approaches such as VRH may therefore represent a useful complementary strategy, although this hypothesis should be formally evaluated in future trials.

The main limitation of this study concerns the missing data. For instance, around half of the patients did not complete the S-anxiety questionnaire on D3, and our imputation method could not compensate for most of these. However, despite this, our study was still able to show a significant group difference. Another limitation is that the initial levels of pain and anxiety were not especially high, which would have made it harder to detect improvements. In the case of anxiety, it may have been of benefit to run the study at a later stage of the patients’ isolation, as previous studies have shown that longer periods of isolation are associated with greater anxiety [ 2 , 3 ]. This may therefore have led to more marked improvements in anxiety following VRH.

From a clinical perspective, these findings may contribute to improving the management of anxiety in patients undergoing protective isolation in hematology units. Anxiety is common during this period, yet non-pharmacological interventions remain limited in routine care. VRH represents a relatively simple intervention that can be delivered at the bedside and does not require extensive resources once the equipment and staff training are in place. Following this study, the integration of VRH sessions into supportive care practices is being considered in our department for selected patients during protective isolation. Future projects could also explore the implementation of VRH in other clinical situations associated with high levels of anxiety, such as before invasive procedures or during prolonged hospitalizations. In addition, further studies are needed to better identify patients who are most likely to benefit from VRH and to determine how this intervention can best be integrated into comprehensive supportive care programs.

To conclude, this study supports the use of VRH during protective isolation, as the intervention was found to reduce anxiety and was generally well-accepted by patients. The results are likely to generalize to patients who are isolated for other conditions, such as certain infectious diseases. It would be helpful to carry out further work to identify patients who would benefit the most from VRH, and to optimize the virtual reality scenery, background music, and voice-over to maximize the effectiveness.

Publisher's Note

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Acknowledgements

We thank Jessica Foxton, PhD, from Newmed Publishing, Paris, for medical writing assistance. We thank Clinical Research Direction from Vivalto Santé for funding.

Author contribution

All authors contributed to the study conception and design. Material preparation was performed by Stéphanie Masset. Data collection and analysis were performed by Anne-Violaine Doncker, Xavier Cahu and Benoît Bareau. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

This study was funded by Clinical Research Direction Vivalto Santé (France).

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Protocol

The study protocol (in French) is available from the authors upon reasonable request.

Competing interests

The authors declare no competing interests.

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