Effects of music and conversation on pain and anxiety levels during transrectal ultrasound-guided prostate biopsy: a randomized-controlled prospective studyABSTRACT
BACKGROUND: Prostate biopsy is the recommended diagnostic test for prostate cancer in patients with abnormal findings on digital rectal examinations (DRE) or elevated PSA (prostate-specific antigen) levels. Biopsies can cause severe anxiety and pain.
OBJECTIVE: To evaluate the effects of music and conversation on pain and anxiety in patients undergoing transrectal ultrasound-guided prostate biopsy.
DESIGN AND SETTING: Prospective trial at a Tertiary University Hospital in Türkiye.
METHODS: A prospective randomized controlled study was conducted. Ninety patients who had abnormal findings on DRE and/or a PSA value greater than 2.5 ng/ml and were scheduled to undergo TRUS-PBx were randomly assigned to one of three groups (n = 30) via the sealed envelope randomization method: control, music, and conversation groups. VAS pain, VAS anxiety, and STAI scores were recorded before and after the procedure. Statistical analysis was performed using One-Way ANOVA and Kruskal–Wallis tests. Pairwise comparison tests were conducted for the parameters that yielded significant differences among the control, conversation, and music groups. For all statistical analyses, a P value < 0.05 was considered statistically significant.
RESULTS: Conversation reduced pain and anxiety significantly (P < 0.001 and P = 0.01 respectively). Post-Bx VAS pain and STAI-State scores were lower in the conversation group. Pairwise comparisons revealed significant differences between the music and conversation groups (VAS pain, P < 0.001; STAI-State, P = 0.006). However, pain and STAI-State scores were similar in both the groups (VAS pain P = 0.645; STAI-State P = 0.597).
CONCLUSIONS: The study demonstrated that listening to music had no significant effect on pain and anxiety in patients undergoing TRUS-PBx. Conversely, the findings showed that engaging patients in conversation significantly reduced pain and anxiety during the procedure.
CLINICAL TRIAL OR SYSTEMATIC REVIEW REGISTRATION: The trial is registered at clinicaltrials.gov (registration number: NCT07006779) and is accessible at https://clinicaltrials.gov/ct2/show/NCT07006779.
KEYWORDS (MeSH terms):
Prostate; Biopsy; Anxiety; Pain; Ultrasound, high-intensity focused, transrectal
INTRODUCTION
Prostate cancer is one of the most common cancers affecting men. Prostate biopsy is the recommended diagnostic test for prostate cancer in patients with abnormal findings during digital rectal examination (DRE) or elevated prostate-specific antigen (PSA) levels.1 Although transperineal prostate biopsy is increasing, standard transrectal ultrasound-guided prostate biopsy (TRUS-PBx) shows similar prostate cancer detection rates.2 When the procedure is explained, patients with no prior experience are particularly susceptible to anxiety.3 Moreover, increased anxiety during the procedure is associated with higher pain perception and irritation. Therefore, biopsy procedures can cause intense anxiety and severe pain for patients.4
Since the biopsy procedure is performed under local anesthesia, anxiolytic or sedative drugs are rarely administered.5 Patients who experience severe pain during the intervention often avoid undergoing re-biopsy when necessary.6 For these reasons, numerous studies and interventions have been conducted to reduce pain and anxiety in patients undergoing TRUS-PBx. A wide range of methods has been evaluated, from general anesthesia to combinations of local anesthesia with other techniques. Many nonpharmacological interventions, including distraction and anxiety-pain reduction techniques, have been investigated because of their practicality, accessibility, convenience, and minimal side effects.7-10
Music reduces pain, anxiety, and stress. Its effectiveness is attributed to its ability to divert patients’ attention away from negative stimuli and create a calm environment.11,12 The positive effects of music on patients undergoing TRUS-PBx have also been evaluated in several studies.13-19
Conversation is another effective distraction method that is free, easily accessible, and has no side effects. As anxiety levels increase, the pain experienced by patients also tends to increase. Consequently, reducing patients’ anxiety through conversation can lower the pain level.20 Reportedly, conversing with patients can reduce the anxiety and pain they experience.20-26 However, there is limited research on the impact of conversation in reducing pain, anxiety, and stress, specifically in patients undergoing prostate biopsy.
This is the first prospective randomized controlled study to investigate the effects of listening to music or engaging in conversation on procedure-related anxiety and pain in patients undergoing TRUS-PBx.
OBJECTIVE
To evaluate the effects of music and conversation on pain and anxiety levels in patients undergoing TRUS-PBx.
METHODS
Study design and population
This prospective randomized controlled study was approved by the Local Clinical Research Ethics Committee (2017KAEK-189-2021.05.05-08). The clinical trials. gov registration number for the trial is NCT07006779. Patients included in the study were those who presented to the Yozgat Bozok University Hospital Urology Clinic between June 2021 and October 2021, had abnormal findings on DRE and/or had a PSA value greater than 2.5 ng/ml and were scheduled to undergo TRUS-PBx. Sample sizes were calculated using the program GPower v.3.1.9.4 (Franz Faul, University of Kiel) with an alpha value of 0.05, 95% confidence interval (95% CI) power, and 0.19 effect size. Ninety patients were randomly assigned to one of three groups (n = 30) using the sealedenvelope randomization method: control, music, and conversation groups. An experienced urologist generated a randomized allocation sequence, enrolled the participants, and assigned them to the interventions. An experienced urologist performed all procedures.
Inclusion and exclusion criteria
Patients with psychiatric disorders, those who declined to participate, and those who were unable or unwilling to complete the questionnaires were excluded. Additionally, patients with hearing or perceptual impairments, continuous analgesic use, history of prior prostate biopsy, or prilocaine allergy were excluded. Patients for whom the biopsy procedure could not be completed for any reason were excluded. Informed consent was obtained from all the participants.
Data collection and definitions
Patients’ sociodemographic data such as age, height, weight, and body mass index were documented. Medication and medical histories were recorded. The International Prostate Symptom Score (IPSS), PSA levels, and prostate volumes of all patients were recorded before the procedure. The blood pressure and heart rate were measured before and after the procedure.
The patients completed the State-Trait Anxiety Inventory (STAI) test. Low scores indicate low anxiety levels, whereas high scores reflect higher anxiety levels. Also, anxiety and pain levels were assessed using a visual analog scale (VAS), where a score of "0" indicated "no pain or anxiety," and a score of "10" represented "the most severe pain or anxiety."
Prophylactic ciprofloxacin was administered to patients 1 day before the procedure. The procedure room was designed to minimize external disturbances (e.g., sound or noise). Prior to biopsy, the patients received detailed information according to their assigned groups. In the music group, patient-selected music was played throughout the procedure. In the conversation group, discussions based on patients’ interests were initiated and continued during the procedure. In the control group, no additional interactions beyond the informational briefings were provided.
The biopsy procedure was performed with patients in the lateral decubitus position with their lower extremities flexed. Rectal povidone-iodine was used for local cleaning. Lidocaine gel was applied rectally in all patients. After placing the rectal ultrasound probe, a periprostatic nerve block was performed by injecting 5 ml of 2% prilocaine solution. Twelve core biopsies were collected: six from each lobe.
All patients in the allocated groups underwent TRUS-PBx as described previously. After the procedure, the patients were asked whether they would be willing to undergo the procedure again if necessary. Responses were categorized as "positive," "negative," or "abstained."
Primary and secondary outcomes
The primary outcome of the study was to determine whether listening to music or engaging patients in conversation during the procedure reduced their anxiety and pain levels. The secondary outcome was to determine which was better for decreasing anxiety and/or pain levels: listening to music or engaging in conversation.
Statistical analysis
Statistical analyses were performed using the IBM SPSS Statistics version 26.0 (Armonk, New York). Nominal data were analyzed using the Chi-square test. Parametric numerical data were evaluated using the One-Way ANOVA variance, whereas non-parametric data were analyzed using the Kruskal–Wallis test. Pairwise comparisons were performed to identify significant differences among the control, conversation, and music groups. Pre- and post-procedure comparisons were also performed within each group. For all analyses, a P value < 0.05 was considered statistically significant.
RESULTS
Between June 2021 and October 2021, 101 patients at Yozgat Bozok University Training and Research Hospital Urology Clinic, were assessed for eligibility; however, 10 patients were not eligible and one declined to participate. Thus, 90 patients were randomly assigned to three groups (n = 30 each). Mean age and BMI were not significantly different among the groups (P = 0.339 and P = 0.383, respectively). Additionally, the mean IPSS, PSA value, and prostate volume were statistically similar among the three groups (P = 0.591, P = 0.582, and P = 0.262, respectively). The patient demographic data are shown in Table 1.
Hemodynamic parameters, such as systolic and diastolic blood pressure and heart rate measured before biopsy, showed no significant differences among the three groups (P = 0.619, P = 0.684, and P = 0.723, respectively). Additionally, the pre-procedure VAS anxiety (P = 0.299), STAI (P = 0.560), STAI-State (P = 0.850), and STAITrait (P = 0.515) scores were similar across the groups (Table 2).
No statistically significant differences were found in the post-biopsy blood pressure or heart rate among the three groups (P = 0.284 and P = 0.355, respectively). The scores of VAS pain, VAS anxiety, and the STAI-State recorded after the biopsy procedure were significantly lower in the conversation group (P < 0.001, P < 001 and P = 0.010, respectively).
Statistically significant decreases in STAI-State scores, which were recorded before and after the biopsy, were observed only in the conversation group, whereas the scores increased in the other groups (P < 0.001) (Table 3).
Pairwise analysis showed that the conversation group differed significantly in post-biopsy VAS pain score, STAI-State score, and STAI score when compared to those of both the music and control groups. However, listening to music did not lead to a significant reduction compared to that in the control group (Table 4).
The patient opinion ("positive," "negative," or "abstained") on the repetition of the procedure was similar among the three groups.
DISCUSSION
Previous studies evaluating different methods of reducing pain and anxiety during prostate biopsy reported varied outcomes. Some participants observed a significant reduction in anxiety scores, others in pain scores, whereas others in both scores. Conversely, certain methods have been shown to be ineffective in alleviating pain or anxiety during prostate biopsy. This study evaluated the effects of music, a method that has been explored in previous studies, and conversation, which has rarely been studied–on anxiety and pain in patients undergoing prostate biopsies. The findings revealed that listening to music did not reduce anxiety or pain; however, engaging the patient in conversations significantly reduced both.
Various techniques have been used to alleviate pain and anxiety during prostate biopsy. For instance, diaphragmatic breathing during TRUS-PBx significantly reduced anxiety, whereas hypnotherapy effectively reduced both pain and anxiety.7,10 The use of nitrous oxide (N2O) during TRUS-PBx had no impact on anxiety, but caused a slight reduction in pain levels.27 Similarly, patients who received video-based education before TRUS-PBx experienced lower anxiety levels than did those who only received verbal information. The use of augmented reality glasses during the procedure has also been shown to reduce pain.8,9 The results of this study revealed that conversion to TRUS-PBx significantly reduced both pain and anxiety, highlighting the potential of this simple, cost-effective, and accessible method for improving patient experience during prostate biopsy.
The effects of music have been investigated in several studies. A randomized controlled trial demonstrated that music had no significant difference in VAS and STAI scores compared to the control group.18 Two studies reported that music decreased the STAI-state state and VAS pain scores of patients undergoing TRUS-PBx.17,19 There are also studies in the literature showing that music only reduces STAI-State or VAS anxiety levels in patients undergoing TRUS-PBx and does not change pain level.14-16 The influence of listening to music during prostate biopsy is controversial; however, the findings of this study revealed that music has no effect on VAS pain, VAS anxiety, and STAI score.
The effect of music on hemodynamic parameters remains controversial. Two studies demonstrated no significant difference between the music and control groups.18,19 However, in other studies, significant differences were found in some hemodynamic parameters.13-15,17 The outcome of this study showed no significant difference in the hemodynamics of the patients.
The controversial findings in literature may depend on various factors such as the type of music chosen, use of headphones, volume level of music, and other variables. Reportedly, music can produce different clinical effects depending on its tempo.28
In some studies, patient satisfaction and willingness to repeat the procedure were reported to be higher in the music group.17,19 However, in this study, there was no significant difference between the music and conversation groups. This may be attributed to the fact that this variable was recorded by using three categorical options instead of a continuous scale.
Packiam et al. indicated that crying or verbal distractions may be more effective than music. However, there is a lack of data on the effects of conversing with patients on pain and anxiety during prostate biopsy.18 Some studies have evaluated the impact of conversation and verbal distractions on pain and anxiety in other contexts. For example, pregnant women experience less pain during labor with distraction techniques such as conversation.23 The effect of conversation was compared with lidocaine/prilocaine cream in patients undergoing peripheral venous catheterization, and pain was found to be significantly lower in the conversation group.22 In another study, hand-holding combined with conversation was reported to be more effective than midazolam in reducing preoperative anxiety.20 Verbal distraction during burn dressing procedures was observed to alleviate anxiety but did not reduce pain.29 Similarly, a survey revealed that more patients preferred conversation as a distraction over receiving procedural information before venipuncture.21 Studies conducted with children have also shown that verbal distraction provided by parents significantly reduced pain during invasive procedures.25 This study is consistent with current data and demonstrated that engaging patients in conversation significantly reduced both pain and anxiety during TRUS-PBx. However, some studies have reported that conversation is ineffective in alleviating pain and anxiety. For example, conversation does not reduce pain in burn patients during rehabilitation or in patients presenting to the emergency department with acute pain.26-30
The success of doctor-patient conversations depends on the selection of topics that the patient finds engaging and captivating. In this study, patients engaged in conversations about their interests and actively participated. During these conversations, the patients appeared to forget the procedure and distanced themselves from the pain and anxiety.
Although the study was planned as a prospective randomized controlled trial, it has limitations; due to the design, it was not a double-blind study. The pain level was assessed only before and after the procedure, whereas it should be assessed at each step of the process. The study was conducted at a single center with a relatively small sample size. In addition, the music was provided as ambient background music and not through headphones.
CONCLUSIONS
This study demonstrated that listening to music has no significant effect on pain or anxiety in patients undergoing TRUS-PBx. Conversely, the findings showed that engaging patients in conversation significantly reduced pain and anxiety during the procedure. Distracting patients via conversation during the biopsy procedure increases patient comfort. However, further studies with larger sample sizes are necessary to validate and expand on these findings.
Data availability statement:
The data that support the findings of this study are available from the corresponding author, Volkan Selmi, upon reasonable request.
Declaration of generative AI in scientific writing:
During the preparation of this work, the authors did not use any generative AI or AI-assisted technologies.
REFERENCES
-
1. 1. Sekhoacha M, Riet K, Motloung P, et al. Prostate cancer review: genetics, diagnosis, treatment options, and alternative approaches. Molecules. 2022;27(17):5730. PMID: 36080493; https://doi.org/10.3390/molecules27175730.
» https://doi.org/10.3390/molecules27175730 -
2. Fang Y, Xia L, Lu H, He H. Meta-analysis of transperineal and transrectal ultrasound-guided prostate biopsy in the detection of prostate cancer. Arch Esp Urol. 2024;77(9):1089–99. PMID: 39632532; https://doi.org/10.56434/j.arch.esp.urol.20247709.152.
» https://doi.org/10.56434/j.arch.esp.urol.20247709.152 -
3. He H, Li Z, Zhao X, Chen X. The effect of music therapy on anxiety and pain in patients undergoing prostate biopsy: a systematic review and meta-analysis. Complement Ther Med. 2023;72:102913. PMID: 36581055; https://doi.org/10.1016/j.ctim.2022.102913.
» https://doi.org/10.1016/j.ctim.2022.102913 -
4. Zisman A, Leibovici D, Kleinmann J, Siegel YI, Lindner A. The impact of prostate biopsy on patient well-being: a prospective study of pain, anxiety and erectile dysfunction. J Urol. 2001;165(2):445–54. PMID: 11176394; https://doi.org/10.1097/00005392-200102000-00023.
» https://doi.org/10.1097/00005392-200102000-00023 - 5. Soloway MS, Obek C. Periprostatic local anesthesia before ultrasound guided prostate biopsy. J Urol. 2000;163(1):172–3. PMID: 10604339.
-
6. Crundwell MC, Cooke PW, Wallace DM. Patients’ tolerance of transrectal ultrasound-guided prostatic biopsy: an audit of 104 cases. BJU Int. 1999;83(7):792–5. PMID: 10368198; https://doi.org/10.1046/j.1464410x.1999.00011.x.
» https://doi.org/10.1046/j.1464410x.1999.00011.x -
7. Grinberg AS, Sellinger JJ, Sprenkle PC, et al. Effect of diaphragmatic breathing on procedural anxiety during transrectal prostate biopsy. Urology. 2020;137:26–32. PMID: 31893532; https://doi.org/10.1016/j.urology.2019.12.024.
» https://doi.org/10.1016/j.urology.2019.12.024 -
8. Tarhan H, Cakmak O, Unal E, et al. The effect of video-based education on patient anxiety in men undergoing transrectal prostate biopsy. Can Urol Assoc J. 2014;8(11–12):E894–E900. PMID: 25553162; https://doi.org/10.5489/cuaj.2208.
» https://doi.org/10.5489/cuaj.2208 -
9. Genç H, Korkmaz M, Akkurt A. The effect of virtual reality glasses and stress balls on pain and vital findings during transrectal prostate biopsy: a randomized controlled trial. J Perianesth Nurs. 2022;37(3):344–50. PMID: 35397973; https://doi.org/10.1016/j.jopan.2021.09.006.
» https://doi.org/10.1016/j.jopan.2021.09.006 -
10. Hızlı F, Özcan O, Selvi İ, et al. The effects of hypnotherapy during transrectal ultrasound-guided prostate needle biopsy for pain and anxiety. Int Urol Nephrol. 2015;47(11):1773–7. PMID: 26377497; https://doi.org/10.1007/s11255-015-1111-0.
» https://doi.org/10.1007/s11255-015-1111-0 -
11. Dell’Atti L. Impact of music on anxiety and pain perception among men undergoing prostate biopsy: synthesis of qualitative literature. Complement Ther Clin Pract. 2021;43:101330. PMID: 33578321; https://doi.org/10.1016/j.ctcp.2021.101330.
» https://doi.org/10.1016/j.ctcp.2021.101330 -
12. Nilsson U. The anxiety- and pain-reducing effects of music interventions: a systematic review. AORN J. 2008;87(4):780–807. PMID: 18395022; https://doi.org/10.1016/j.aorn.2007.09.013.
» https://doi.org/10.1016/j.aorn.2007.09.013 -
13. Tsivian M, Qi P, Kimura M, et al. The effect of noise-cancelling headphones or music on pain perception and anxiety in men undergoing transrectal prostate biopsy. Urology. 2012;79(1):32–6. PMID: 22202544; https://doi.org/10.1016/j.urology.2011.09.037.
» https://doi.org/10.1016/j.urology.2011.09.037 -
14. Turgut H, Özgğür GK. The effect of an animation video and music on anxiety and pain scores before TRUS-guided biopsy. Uroonkoloji Bul. 2021;20:7–10. PMID: WOS:000625432300002. https://doi.org/10.4274/uob.galenos.2020.1791.
» https://doi.org/10.4274/uob.galenos.2020.1791 -
15. Chiu LP, Tung HH, Lin KC, et al. Effectiveness of stress management in patients undergoing transrectal ultrasound-guided biopsy of the prostate. Patient Prefer Adherence. 2016;10:147–52. PMID: 26929606; https://doi.org/10.2147/PPA.S96991.
» https://doi.org/10.2147/PPA.S96991 - 16. Cho SW, Choi HJ. Effect of music on reducing anxiety for patients undergoing transrectal ultrasound-guided prostate biopsies: randomized prospective trial. Urol J. 2016;13(2):2612–4. PMID: 27085561.
-
17. Chang YH, Oh TH, Lee JW, et al. Listening to music during transrectal ultrasound-guided prostate biopsy decreases anxiety, pain and dissatisfaction in patients: a pilot randomized controlled trial. Urol Int. 2015;94(3):337–41. PMID: 25531837; https://doi.org/10.1159/000368420.
» https://doi.org/10.1159/000368420 -
18. Packiam VT, Nottingham CU, Cohen AJ, Eggener SE, Gerber GS. No effect of music on anxiety and pain during transrectal prostate biopsies: a randomized trial. Urology. 2018;117:31–5. PMID: 29709434; https://doi.org/10.1016/j.urology.2018.04.014.
» https://doi.org/10.1016/j.urology.2018.04.014 -
19. Lee BC, Kim HO, Chung HS, et al. Does music from noise-canceling headphones have a beneficial effect on men undergoing transrectal ultrasound-guided prostate biopsy? Prostate Int. 2021;9(3):145–50. PMID: 34692587; https://doi.org/10.1016/j.prnil.2021.02.001.
» https://doi.org/10.1016/j.prnil.2021.02.001 -
20. Sriramka B, Mallik D, Singh J, Khetan M. Effect of hand-holding and conversation alone or with midazolam premedication on preoperative anxiety in adult patients: a randomised controlled trial. Indian J Anaesth. 2021;65(2):128–32. PMID: 33776087; https://doi.org/10.4103/ija.IJA_705_20.
» https://doi.org/10.4103/ija.IJA_705_20 -
21. Vijayan R, Scott G, Brownlie W, Male P, Chin K. How sharp is a "sharp scratch"?: a mixed methods study of verbal warnings issued before venipuncture. Pain Pract. 2015;15(2):132–9. PMID: 24373198; https://doi.org/10.1111/papr.12159.
» https://doi.org/10.1111/papr.12159 -
22. Balanyuk I, Ledonne G, Provenzano M, et al. Distraction technique for pain reduction in peripheral venous catheterization: randomized, controlled trial. Acta Biomed. 2018;89(4–S):55–63. PMID: 29644990; https://doi.org/10.23750/abm.v89i4-S.7115.
» https://doi.org/10.23750/abm.v89i4-S.7115 -
23. Amiri P, Mirghafourvand M, Esmaeilpour K, Kamalifard M, Ivanbagha R. The effect of distraction techniques on pain and stress during labor: a randomized controlled clinical trial. BMC Pregnancy Childbirth. 2019;19(1):534. PMID: 31888543; https://doi.org/10.1186/s12884-019-2683-y.
» https://doi.org/10.1186/s12884-019-2683-y -
24. Birnie KA, Chambers CT, Taddio A, et al; HELPinKids&Adults Team. Psychological interventions for vaccine injections in children and adolescents: systematic review of randomized and quasi-randomized controlled trials. Clin J Pain. 2015;31(10 Suppl):S72–S89. PMID: 26348163; https://doi.org/10.1097/AJP.0000000000000265.
» https://doi.org/10.1097/AJP.0000000000000265 -
25. Inan G, Inal S. The impact of 3 different distraction techniques on the pain and anxiety levels of children during venipuncture: a clinical trial. Clin J Pain. 2019;35(2):140–7. PMID: 30362982; https://doi.org/10.1097/AJP.0000000000000666.
» https://doi.org/10.1097/AJP.0000000000000666 -
26. Shillington K, Thompson C, Saraga S, et al. The effect of a nurse initiated therapeutic conversation compared to standard care for patients with acute pain in the ED: a randomized controlled trial. Adv Emerg Nurs J. 2021;43(3):217–24. PMID: 34397500; https://doi.org/10.1097/TME.0000000000000363.
» https://doi.org/10.1097/TME.0000000000000363 -
27. Spie R, Watfa J, Dubruille T, Michel F. Intérêt du mélange équimolaire d’oxygène et de protoxyde d’azote (Meopa) dans les biopsies transrectales de prostate [Value of nitrous oxide-oxygen mixture (Entonox) in transrectal prostate biopsies]. Prog Urol. 2008;18(6):358–63. French. Erratum in: Prog Urol. 2009;19(11):861. PMID: 18558324; https://doi.org/10.1016/j.purol.2008.03.028.
» https://doi.org/10.1016/j.purol.2008.03.028 -
28. Miller JS, Terbizan DJ. Clinical outcomes of different tempos of music during exercise in cardiac rehabilitation patients. Int J Exerc Sci. 2017;10(5):681–9. PMID: 28966708; https://doi.org/10.70252/ATNA1869.
» https://doi.org/10.70252/ATNA1869 -
29. Moradipoor Y, Rejeh N, Heravi Karimooi M, et al. Comparing auditory and visual distractions for reducing pain severity and pain anxiety in older outpatients with burn: a randomized controlled trial. Geriatrics (Basel). 2022;7(3):54. PMID: 35645277; https://doi.org/10.3390/geriatrics7030054.
» https://doi.org/10.3390/geriatrics7030054 -
30. Ferguson SL, Voll KV. Burn pain and anxiety: the use of music relaxation during rehabilitation. J Burn Care Rehabil. 2004;25(1):8–14. PMID: 14726734; https://doi.org/10.1097/01.BCR.0000105056.74606.9E.
» https://doi.org/10.1097/01.BCR.0000105056.74606.9E
Edited by
-
Editor responsible for the evaluation process:
Paulo Manuel Pêgo-Fernandes, MD, PhD
