Virtual reality and hypnosis for symptom alleviation before bone marrow procedure.

Introduction

Bone marrow aspiration biopsy (BMAB) is a critical diagnostic procedure in hematology, enabling detailed assessment of hematopoiesis necessary for diagnosis, staging, and management of various hematologic conditions. Typically performed on the iliac crest without general anesthesia, BMAB relies on local anesthetics and mild sedation 1 . Despite these measures, over 70% of patients undergoing BMAB report significant anxiety, negatively affecting their pain perception and overall procedural experience 2 – 5 .

Current standard-of-care (SOC) methods for periprocedural anxiety and pain management involve benzodiazepines and local anesthetics 6 . Although effective, these medications may cause undesirable side effects such as dizziness, cognitive impairment, nausea, and residual anxiety, particularly challenging in outpatient settings 6 , 7 . Consequently, there is increasing interest in safe, non-pharmacological interventions to enhance patient comfort during invasive procedures.

Hypnosis, a state of heightened suggestibility with focused attention and reduced peripheral awareness, has emerged as an effective non-pharmacological intervention for procedural anxiety 8 , 9 . Clinical studies and systematic reviews have consistently demonstrated hypnosis efficacy in reducing anxiety and pain during invasive procedures. A recent meta-analysis involving 1,250 patients from 20 randomized-controlled trials confirmed significant reductions in anxiety and pain with hypnosis compared to SOC, with minimal side effects 10 . Specifically, hypnosis significantly reduced anxiety in adult cancer patients undergoing bone marrow procedures 11 .

Virtual reality (VR) — an immersive, computer-generated environment — has also shown promise for managing anxiety and pain during procedures through distraction and sensory engagement 8 , 12 , 13 . Although the REVEH trial comparing VR to nitrous oxide sedation during BMAB found no significant difference in anxiety or pain outcomes, VR was well-received, demonstrating feasibility and patient satisfaction, particularly for those contraindicated for sedation 14 .

Few studies have directly compared hypnosis, VR, and SOC concurrently. A randomized-controlled trial involving 100 cardiac surgery patients compared these interventions, finding reduced anxiety across all methods but no significant differences among them 15 . Such studies highlight the need for rigorous randomized trials to determine clearly the relative effectiveness of these interventions.

Given the clinical need and gaps in evidence, we conducted an exploratory randomized-controlled trial to evaluate the effectiveness of hypnosis and VR compared to SOC in improving anxiety-related concerns among patients undergoing BMAB. Clarifying these non-pharmacological strategies’ effectiveness will meaningfully enhance patient-centered care and optimize supportive interventions in clinical hematology practice.

Methods

Study design and setting

This was an exploratory prospective three-arm (1:1:1) open-label randomized-controlled trial evaluating the effectiveness of the addition of VR or hypnosis to SOC in the improvement of anxiety-related concerns of patients undergoing BMAB procedure. It was conducted at the Hematology Unit of Bnai Zion Medical Center in Haifa, Israel. Trial methods and results were reported according to the Consolidated Standards of Reporting Trials (CONSORT) 2010 guidelines 16 .

Ethics

The study protocol was reviewed and approved by the institutional ethics committee of Bnai Zion Medical Center (Haifa, Israel) in accordance with the declaration of Helsinki (approval number: 0053-23-BNZ) and it was prospectively registered at www.clinicaltrials.org ( NCT05982249 ) on 16 July 2023.

Study population

Patients were recruited for participation in the study by the medical or nursing staff of the Hematology Unit at Bnai Zion Medical Center, based on the following inclusion criteria: (1) age 18 years or older; (2) scheduled for a BMAB; (3) presence of anxiety-associated concerns related to the BMAB (e.g. fear of pain, fear of results, etc.); (4) ability to complete questionnaires in Hebrew, Arabic or Russian and (5) ability to provide informed consent. Exclusion criteria included: (1) significant hearing impairments preventing from listening to audio recordings through headphones and (2) significant visual impairment preventing from viewing a 3-dimensional (3D) display on the VR device. All participants received a full explanation about the study and signed a written informed consent form.

Randomization and blinding

Patients meeting eligibility criteria were randomly assigned in a 1:1:1 permuted block randomization list generated with Microsoft Excel software to one of the following groups: hypnosis, virtual reality (VR), or control. The random allocation sequence was generated prior to study initiation by an independent investigator who was not involved in patient recruitment, assessment, or intervention delivery. Group allocation was performed using concealed envelopes, each labeled only with a sequential patient number and opened only after consent and enrollment. Participants were enrolled by study physicians and nurses on-site at the Hematology Unit of Bnai Zion Medical Center. Enrolling clinicians were blinded to the allocation sequence and had no access to randomization materials in advance. Upon enrollment, the next envelope in sequence was opened by the recruiter, and the group allocation was communicated to the intervention team. Allocation concealment was strictly maintained throughout the recruitment phase to prevent selection bias. To verify the integrity of the randomization process, we retrospectively reviewed the randomization logs to ensure that all patients were enrolled consecutively according to their assigned randomization code, with no deviations or protocol violations. Additionally, we verified that the number of patients assigned to each group matched the expected distribution. Due to the nature of the interventions, blinding was clearly not possible.

Interventions

In the hypnosis group, patients listened through headphones to a 7-minute prerecorded hypnosis script created by Z.A., a certified psychologist specializing in hypnosis and a co-author of the manuscript. The script was initially recorded in Hebrew by Z.A. after observing more than ten BMAB procedures and conducting discussions about the process with both patients and staff at the Hematology Unit of Bnai Zion Medical Center before and after the procedure. Consequently, the script was specifically tailored to the BMAB procedure, with the objective of preparing patients and reducing peri-procedural anxiety. Subsequently, the Hebrew script was translated and recorded into Arabic and Russian by two nurses fluent in both Hebrew and Arabic or Russian, in order to allow patients to choose the script language.

In the VR group, patients used a VR headset that displayed a calming 3D visual environment of their choosing, accompanied by relaxing background sounds for approximately 7 min.

Patients in the control group received no intervention and waited passively for the BMAB to begin. In the 3 arms, patients received SOC management of BMAB including local anesthesia (intraosseous lidocaine 2%) for all patients; benzodiazepine sedation (intravenous midazolam) for patients that wished to be sedated during the procedure; and post-BMAB analgesics (generally paracetamol or dipyrone) for patients with postprocedural pain. Accepted lidocaine 2% dose was 10 cc and accepted midazolam dose was 5 mg, but dosages were adapted to patients according to pain and anxiety level and physician judgment.

Assessments

Demographic and clinical data

Sociodemographic and clinical data were collected from patients and their medical charts. Sociodemographic data included age, gender, origin, family status, work. Clinical data included hematologic diagnosis, comorbidities and number of previous BMAB procedures.

Patients’ concerns

The Measure Yourself Concerns And Wellbeing (MYCAW) questionnaire was completed by participants at three different time points: (1) Upon admission to the department (T1); (2) Ten minutes after the intervention for the hypnosis and VR groups, and 20 min after enrollment for the control group (T2); and (3) After the BMAB procedure (T3). The first MYCAW questionnaire is divided into two stages. In the first stage, the patients are asked to define 1 or 2 concerns that are troubling them. By this stage, patients were required to record anxiety-associated concerns related to the BMAB (e.g. fear of pain, fear of results, etc.). In the second stage, they are asked to rate the concerns they defined on a scale from 0 (does not bother me at all) to 6 (bothers me very much). In the second and third MYCAW questionnaires, patients are presented with the concerns they previously defined without showing them their previous ratings and are asked to rate them again on a scale from 0 to 6. This questionnaire was appropriate due to its validity, translation into relevant languages, combination of both quantitative and qualitative data, and its suitability for complementary and integrative medicine research 17 . In the current study, it was available in Hebrew, Arabic and Russian.

Psychological variables

Absorption, dissociation, immersion, and time perception were assessed using a validated short questionnaire given to patients of the VR and hypnosis groups at T2 15 , 18 . Absorption, which is the “tendency to become fully involved in a perceptual, imaginative, or ideational experience” was evaluated by asking patients to rate on a 0–10 scale how deeply they felt absorbed and felt their attention as focalized and focused by the experience they have just lived. Dissociation, which is “a mental separation of components of experience that would ordinarily be processed together” was evaluated by asking patients to rate on a 0–10 scale if they felt a dissociation between bodily sensation and the actual environment. Immersion was assessed in a 0–10 scale of feeling present in the environment. Finally, time perception was evaluated by the difference between the perception of time patients felt and the actual elapsed time during intervention.

Physiological variables

These included vital signs (systolic, diastolic and mean arterial pressure, heart rate, respiratory rate and oxygen saturation) that were evaluated at T1, T2 and T3. Moreover, sedation and analgesic requirements during and after BMAB were evaluated through documentation of the type and dosage of sedative and analgesic medications administered to patients during and after the procedure.

Outcomes

Primary outcome

The effect of the intervention on the improvement of patients’ concerns score experienced by patients undergoing BMAB was assessed by Group x Time interaction of MYCAW at T1-T2 and T1-T3 periods. In order to evaluate the symptomatic evolution through time, we analyzed each of the patients’ conditions rating (1 or 2 per patient) at each time point (T1, T2, T3) and compared the trajectory between the 3 arms (hypnosis, VR, control).

Secondary outcomes

The effect of different covariates such as sociodemographic and clinical data, psychological and physiological variables on the MYCAW evolution through time was evaluated. Finally, the effect of interventions on sedation and analgesic requirements during and after BMAB were evaluated through documentation of the type and dosage of sedative and analgesic medications administered to patients during and after the procedure.

Sample size calculation

Under a two-tailed hypothesis with conventional research conditions of 80% power and a significance level (alpha) of 0.05, sample size was calculated for 3 groups. According to ANOVA test and in order to achieve an effect size f of 0.4 (large effect size), a minimum sample size of 66 patients was calculated. The calculation was performed using R software.

Data analysis

The data underwent statistical processing using SPSS software, version 22. For all continuous variables, medians, means, minimum and maximum values, and standard deviations were calculated. For discrete, nominal, and ordinal variables, a frequency table was presented. Comparison of continuous variables between the 3 groups was performed using repeated measures ANOVA for normally distributed variables. Comparison of categorical variables between the 3 groups was performed using Chi-square and Fisher’s exact tests. Due to the baseline between-groups imbalance of MYCAW score, we ran sensitivity analyses with repeated measures ANCOVA adjusting for such differences. Because sphericity is an assumption for within-subjects factors with ≥ 3 levels, we evaluated it with Mauchly’s test. Normality and homogeneity of variance assumptions were evaluated with Levene’s tests. For transparency, we reported Greenhouse–Geisser (GG)–adjusted statistics for Time and Time × Group (Huynh–Feldt led to identical conclusions). Given three groups across three time points, we controlled familywise error using Holm–Bonferroni for pairwise contrasts of group means at each time point, following the GG-adjusted omnibus tests. There was no missing data. The significance level was set at p value < 0.05. Assumption testing and diagnostic plots were reported in Supplementary data.

Results

Baseline characteristics

A total of 113 patients were screened for eligibility. Among them, 67 met eligibility criteria and were recruited between February 2024 and June 2025. Twenty-four of them were assigned to the VR arm, 22 to the hypnosis arm, and 21 to the control arm. All patients randomized (regardless of group allocation) completed treatments per-protocol (Fig. 1 ). Mean age was 61 ± 18 years and 30 (45%) patients were women. Baseline demographic and clinical characteristics were similar in patients from the three study arms, except for neurologic comorbidities that were more frequent in the hypnosis arm (8 (36%)) as compared to the VR (2 (8%)) or control (3 (14%)) arms ( p = 0.043) as shown in Table 1 .

Symptomatic evolution over time

As presented in Table 1, mean MYCAW score at screening was significantly lower in the control group (3.3 ± 1.7) as compared to both the hypnosis (4.9 ± 1.2) and VR (4.3 ± 1.7) groups ( p < 0.001) with a large baseline effect (partial η² = 0.293; Cohen’s f = 0.64), therefore sensitivity analyses included baseline MYCAW scores in the 3 study arms. Overall, 107 concerns were reported (an average of 1.6 concerns per patient). Main concerns reported by patients included anxiety or fear of the procedure in 29% of concerns, fear of results in 24% of cases, and fear of pain in 16% of concerns. These symptoms were well balanced between the 3 arms ( p = 0.09). It should be noted that age and hematological diagnosis/suspicion were associated with baseline MYCAW: older patients ( p = 0.025) and patients evaluated for myeloid malignancies ( p < 0.001) had higher baseline MYCAW.

According to repeated measures ANOVA, MYCAW scores significantly decreased from T1 to T2 ( p < 0.001) and from T1 to T3 ( p < 0.001) (Fig. 2 ).

In the T1-T3 time period, there was no significant Time x Group interaction ( p = 0.62), meaning that the general trajectory of the 3 arms were similar between screening and post-BMAB evaluation. However, in the T1-T2 time period, a repeated measures ANCOVA including baseline MYCAW as a subject-level covariate (sensitivity analysis) revealed a modest but significant Time × Group interaction (F = 3.11, p = 0.049, partial η²=0.06, Cohen’s f effect size = 0.25, small-to-medium interaction effect), reflecting a steeper decline in MYCAW scores from T1 to T2 in VR compared to control group ( p = 0.003) according to pairwise post hoc comparisons (Holm-Bonferroni-corrected).

In the T1-T3 period, the mean MYCAW change was − 1.91 (95% CI − 2.49 to − 1.33) for VR, − 1.91 (95% CI − 2.68 to − 1.14) for hypnosis, and − 1.59 (95% CI − 2.34 to − 0.84) for control.

Using a ≥ 2-point MYCAW reduction to define response as considered clinically significant in previous studies (19), responder rates were 0.57 (VR), 0.44 (hypnosis), and 0.44 (control), corresponding to a number-needed-to-treat (NNT) of 7.7 (VR vs. hypnosis) and 7.5 (VR vs. control); while hypnosis and control groups were indistinguishable (NNT ≈ 272).

Effect of clinical and psychological factors

After adjusting for demographic, clinical, and psychological covariates, the Time × Group interaction remained significant in the T1-T2 period and was further qualified by interactions involving age ( p = 0.003), comorbidity burden ( p = 0.026), and absorption ( p < 0.001). Specifically, younger participants and those with fewer comorbidities showed greater improvement from T1 to T2 and the absorption-by-group interaction was particularly pronounced ( p < 0.001), indicating that participants with higher absorption levels exhibited notably different MYCAW trajectories depending on group assignment and derived the largest benefit from VR.

Physiological variables

Participants’ mean arterial pressure (MAP) and pulse significantly decreased over the 3 measurements (both p < 0.001) regardless of group assignment. However, any intervention or baseline difference represented by the different groups did not measurably influence MAP or pulse trajectory neither in the T1-T3 nor in the T1-T2 period. On the other hand, respiratory rate (RR) and oxygen saturation (SaO2) both remained stable and normal over both T1-T2 and T1-T3 periods in all 3 groups (Fig. 3 ).

Sedation and local anesthesia

There was a non-significant trend of lower mean doses of midazolam (sedation) in the VR group (4.6 ± 2.6 mg vs. 5.5 ± 2.5 mg in the hypnosis group and 5.3 ± 2.3 in the control group, p = 0.48). Similarly, there was a non-significant trend of higher mean doses of lidocaine (local anesthesia) in the control group (12.9 ± 5.6 vs. 10.7 ± 2.9 in the VR group and 10.4 ± 3.7 in the hypnosis group, p = 0.13).

Discussion

In this exploratory randomized-controlled trial (RCT), we evaluated the effectiveness of hypnosis and VR compared to SOC for reducing anxiety among patients undergoing BMAB. Our findings indicate that VR significantly reduced patient-reported anxiety-related concerns immediately post-intervention compared to the control group, although this effect did not persist post-procedure. These outcomes highlight the potential immediate benefit of VR in managing procedural anxiety during BMAB.

Our study has several limitations. First, the single-center design and modest sample size may limit generalizability. Despite meeting sample size calculations, larger multicenter studies could provide stronger evidence and explore subgroup differences more robustly. Second, blinding was inherently impossible due to the nature of interventions, possibly introducing bias. However, rigorous adherence to standardized protocols and validated assessment tools mitigated potential bias effects. Third, our brief and preprocedural-only interventions might underestimate true clinical potential, especially for hypnosis. Future research should explore varying lengths and intensities of these interventions to optimize their effectiveness. Finally, a major limitation of our study is the substantial baseline imbalance in MYCAW scores between groups, despite proper randomization procedures. The control group exhibited significantly lower baseline anxiety-related concern scores compared to the hypnosis and VR groups. This difference, with a large effect size, may confound the interpretation of group comparisons over time and raises concerns about the internal validity of the findings. Possible explanations include chance imbalance due to small sample size, or unmeasured post-randomization selection influences. Although the randomization protocol was appropriately applied, these differences suggest caution in attributing post-intervention changes solely to the interventions.

Baseline imbalances in patient-reported outcomes, although unexpected in RCTs, are not unprecedented—particularly in small-to-moderate-sized trials with subjective outcomes such as anxiety. We acknowledge that the large and statistically significant baseline imbalance in MYCAW scores between the control, hypnosis, and VR groups is a limitation of this study. However, as Stang & Baethge point out, RCTs, even when properly randomized, often show chance imbalances in baseline covariates, particularly for subjective or self-reported measures, especially with modest sample sizes 20 . Such imbalances are not, per se, evidence of flawed randomization, but rather a reason to apply adjusted analyses, explicitly consider their impact, and interpret effects with caution. In our study, after adjusting for baseline MYCAW scores (sensitivity analyses), the primary immediate effects persisted, indicating that while the imbalance likely inflated raw between-group differences, it does not fully account for them. Nonetheless, because of this imbalance, conclusions particularly regarding comparative efficacy of VR vs. hypnosis vs. control must be regarded as preliminary and exploratory, and future trials should seek larger sample sizes and/or use stratified randomization to reduce the risk of such imbalances.

Our results are consistent with previous studies that demonstrated VR’s immediate anxiolytic effect in various invasive procedures, primarily through distraction and immersive engagement 21 . In particular, the REVEH trial highlighted VR’s acceptability among patients undergoing BMAB, despite no significant difference compared to nitrous oxide sedation 14 . Similarly, VR interventions have shown promising outcomes in pediatric oncology settings, supporting VR as a feasible and patient-friendly approach to anxiety and pain management 13 , 22 .

The lack of efficacy observed with hypnosis as compared to control in our study contrasts somewhat with existing literature, where hypnosis is frequently reported as significantly effective for anxiety reduction during medical procedures 10 , 11 . The recent meta-analysis by Walter et al. emphasizes the consistent efficacy of hypnosis across various clinical contexts, though variability in outcomes among studies is acknowledged, potentially influenced by differing hypnosis protocols and practitioner experience 10 . On the other hand, Rosendahl et al. conducted a broad meta-analysis on hypnosis for mental and somatic health outcomes and reported variability in hypnosis efficacy depending on context and outcome 23 . Our study employed a standardized, brief hypnosis session, potentially limiting its effectiveness. Moreover, and due to technical issues, both hypnosis and VR were delivered to patients very close to the procedure. Therefore and although it was planned in this way in the original protocol, this limits comparisons with previous studies in which patients were exposed to these interventions the day/week before BMAB 12 . Moreover, this may explain the lack of hypnosis effectiveness in the current study. Future research should investigate optimal duration, individual tailoring, and training requirements for hypnotic interventions in hematologic procedures.

In interpreting these findings, it is important to consider the clinical as well as statistical significance of the observed changes. Although a ≥ 2-point MYCAW reduction has been proposed as a meaningful individual improvement in previous studies 19 , the minimal clinically important difference may vary across populations and settings, especially in invasive procedures such as BMAB. In our trial, the proportion of patients achieving this threshold was highest in the VR group (57%) compared to both hypnosis and control (44%), corresponding to an NNT of approximately 7.5. While this NNT is modest and compares favorably with some other non-pharmacologic interventions for procedural anxiety, the exploratory nature of our study and the baseline imbalance warrant cautious interpretation. Larger, adequately powered trials will be needed to confirm the clinical relevance of VR’s effect size and to refine the optimal content and timing of hypnosis sessions to maximize their impact.

Main concerns reported by patients included anxiety or fear of the procedure, fear of results, and fear of pain. In a previous systematic review evaluating among all the areas of anxiety-related concerns before colonoscopy, similar results were detected including difficulties with preparation or procedure itself (pain, sedation, etc.) and concerns about diagnosis (fear of results) 24 . Although all of these concerns may broadly be classified as “anxiety,” some, such as fear of pain and of the procedure itself, will naturally resolve following the procedure (T3), whereas worries related to the diagnosis might persist even into the post-procedural period (T3). Therefore, this distribution highlights the multifaceted nature of patient anxiety associated with BMAB (as it is for other procedures) and underscores the importance to adapt VR/hypnosis content to address both procedural anxiety and anticipatory fears regarding outcomes. Unfortunately, due to the low number of patients in each concern category, we were unable to identify any trends suggesting greater efficacy of VR or hypnosis for specific anxiety-related concerns. However, a previous study showed that a VR-based preoperative education significantly improved preoperative anxiety as compared to SOC 25 , emphasizing that specific VR content may be adapted to patients’ specific fears and procedures. Future studies should evaluate the specific benefits of integrative interventions like VR or hypnosis when specifically tailored to target these distinct patient concerns, potentially enhancing their overall effectiveness.

Notably, baseline anxiety was significantly associated with age and hematological diagnosis, with older patients and those undergoing evaluation for myeloid malignancies reporting higher anxiety levels. Previous studies have indeed emphasized the high level of periprocedural anxiety in older patients, especially those with high depression levels 26 , or with myeloid malignancies such as acute leukemia 27 . These observations highlight the importance of considering baseline patient characteristics when evaluating anxiety interventions and underscore the potential need for personalized anxiety management approaches in hematology.

Our findings also support the broader role of integrative medicine within hematology. Mind-body interventions such as hypnosis and VR are increasingly recognized for their potential to enhance patient-centered care by addressing unmet needs and improving overall patient experience. Notably, the Society for Integrative Oncology (SIO) and American Society of Clinical Oncology (ASCO) recently recommended integrating mind-body interventions and acupuncture into periprocedural settings including BMAB to reduce periprocedural pain in patients with cancer 28 . These recommendations underscore the relevance and timeliness of our findings, further encouraging hematologists to consider integrative strategies as standard supportive care practices.

Interestingly, we observed differential outcomes based on patients’ psychological profiles. Specifically, higher absorption levels correlated significantly with greater benefits from VR, suggesting that patient engagement and psychological traits may moderate intervention efficacy. This aligns with previous research emphasizing absorption as a critical factor influencing response to immersive interventions 18 , 21 . Clinically, this underscores the potential for personalizing anxiety management strategies by assessing patient characteristics such as psychological absorption prior to intervention.

Furthermore, younger patients and those with fewer comorbidities appeared to derive the greatest benefit from VR during the periprocedural period of BMAB. A recent meta-analysis examining effect modifiers of VR in pain management delineated a similar trend of improved effect of VR in younger patients 29 . This may be related to their greater familiarity with and openness to technology-based interventions. Similarly, patients with fewer comorbidities may be better able to engage with immersive interventions due to fewer distractions or physical discomforts.

Regarding physiological variables, neither intervention significantly impacted vital signs or sedation requirements compared to SOC. Previous studies similarly reported minimal physiological impact despite significant psychological benefits 12 , 21 . Nonetheless, trends toward lower benzodiazepine doses in the VR group suggest potential clinical implications in reducing sedative use, aligning with broader goals of minimizing pharmacological intervention during outpatient procedures.

In conclusion, VR demonstrated an immediate beneficial effect on anxiety management prior to BMAB. These findings reinforce the viability of non-pharmacological strategies in clinical hematology practice, emphasizing their potential role in personalized patient care. While these findings support the feasibility and potential immediate benefit of VR for procedural anxiety, they should be interpreted as preliminary due to the significant baseline differences and limited sample size. Future studies should focus on optimizing intervention protocols, evaluating long-term outcomes, and clarifying mechanisms underlying patient responses to VR and hypnosis.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1

Acknowledgements

We thank the Bnai Zion Medical Center Innovation Authority for providing the VR equipment used in this study. We acknowledge Ms. Ida Danilov, Ms. Milana Gavrilov, Ms. Angam Ammar, Ms. Montaha Abo-Aziza and Ms. Svetlana Dmitriev for their contribution in interviewing patients and VR/hypnosis equipment’s technical adjustments.

Author contributions

ILY and DL designed the study. MM entered the data in Excel table. ZA wrote the hypnosis script. ILY, DL, NK, WG, GL, AA, IA, NK, EK and TT recruited patients. ILY and MM wrote the manuscript’s first draft. All authors reviewed the manuscript.

Data availability

The data that supports the findings of this study is subject to controlled access due to participant privacy. Restrictions apply to the availability of the data and so are not publicly available but are available from corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

Supplementary Materials

Supplementary Material 1

Data Availability Statement

The data that supports the findings of this study is subject to controlled access due to participant privacy. Restrictions apply to the availability of the data and so are not publicly available but are available from corresponding author on reasonable request.