Cancer continues to cause a menace all over the world. In 2008, cancer-linked deaths were approximated to be 7.6 million which was about 13% of all deaths (Tao et al., 2016). Cancer causes different emotional, physical, and social suffering. This has created an increased need for developing cancer care that works best for the patients. Music therapy and music medicine interventions have been used to alleviate symptoms, deal with side effects and address the psychosocial need for people with cancer.
The research is a review of articles on music therapy and music intervention on cancer patients. The articles reviewed were peer-reviewed and opensource within a time frame of 20 years.
Various articles reviewed have indicated the effectiveness of music therapy in assisting the pain-relieving process among cancer patients. Traditional Chinese Five-element Therapy is one music therapy that has been reviewed to establish its effectiveness in pain management among cancer patients. Most of the articles reviewed were meta-analysis and systematic reviews. Some analysis indicated patients under music therapy need 29.7% of the analgesia.
The use of music intervention and music therapy is a commonly accepted Complementary and Alternative Medicine for pain management. Music therapy is offered by a trained music-professional care team. To enhance the effectiveness, the patients need to be allowed to determine the music therapy techniques and content for each session. Music-based intervention has been indicated to be valuable tools for helping cancer patients get relief their suffering. Music has been noted to have a potential in helping reduce pain, anxiety, and mood disturbance that are common traits among cancer patients.
PubMed Health and PubMed.gov journals were a perfect choice due to their vast articles in their database. PubMed has over 21 million citations for biomedical literature especially for the US National Library of Medicine. This makes a credible journal that one can rely on for search of articles. PubMed includes indexing of articles with more 5000 journals published in the US and other from other countries. The journals were relevant to the project at hand as they also have links to some free and open-access full text. Their vast coverage in the fields of medicine, nursing, dentistry, healthcare systems and other preclinical sciences makes these journals relevant for doing a literature search for articles in the medical field.
MedlinePlus database was chosen as a source of articles for literature review due to its vast resources in the medical field. It is a web-based consumer health information resource that is provided by the National Library of Medicine. The journal has a great design that facilitates a well-organized and selective search for reliable full-text health information. The journal offers for to researchers in terms of dictionaries, organizations, directories, organizations, and libraries that allow easy access to answer to health questions.
Cancer continues to cause a menace all over the world. In 2008, cancer-linked deaths were approximately 7.6 million which was about 13% of all deaths (Tao et al., 2016). The World Health Organization expects this to rise to more about 11 million by 2013. The most common treatment plans for cancer include surgery, chemotherapy, radiotherapy, and endocrine therapy. While these methods have been aimed at providing a cure for the disease and increasing the lifespan of life through producing beneficial outcomes, they are often accompanied by adverse effects. Among the adverse effects of the above-mentioned care plans, pain is one effect that requires being addressed in an attempt to improve the quality of life and create long-term-health outcomes.
Cancer causes different emotional, physical, and social suffering. This has created an increased need for developing cancer care that works best for the patients. Music therapy and music medicine interventions have been used to alleviate symptoms, deal with side effects and address the psychosocial need for people with cancer. In music medicine interventions, the cancer patients listen to pre-recorded music provided by a medical professional. Music therapy involves the implementation of a music intervention provided by a trained medical music therapist. In music therapy, it includes the therapeutic process and also uses personalized tailor music experiences. Understanding this topic will help the caregiver in determining which non-pharmacological method is better in assisting the cancer patients in pain management.
Music therapy has developed into an allied health profession. The music therapists are certified by the Certification Board for Music Therapists (CBMT). The certification is done after the completion of the course the lowest level is an undergraduate degree in music therapy or an equivalent. Music therapist’s students are required to undergo a clinical internship for 1040 hours and after that undertake a CBMT examination. The music therapists are specialists in songwriting, improvisation, guided imagery and music, lyrics analysis, singing, and instrument playing (Hilliard, 2005).
Pain management is necessary for the oncologic care and is considered as important in enhancing the outcomes of the patient. There has been piling evidence suggesting that the presence of unrelieved pain contributes significantly to the reduced quality of life. Healthcare practitioner continues to rely heavily on opioid treatment in dealing with the pain related to cancer. While the opioid therapy is known to be effective, it bears a lot of side effects including constipation, urinary retention, respiratory depression, and overdependence after prolonged use. This has, therefore, lead to the increased search of how to reduce the dependence on the opioid therapy. Among the complementary alternative medicine being adopted, music therapy is a crucial one. It is for this reason that this paper seeks to conduct a review of previous studies on the effectiveness of music therapy and intervention in pain management among cancer patients.
P (Population) – Cancer Patients
I (Intervention) – Music Therapy
C (Comparison) – Music Interventions (Music Medicine)
O (Outcome) – Pain Management
Research Question: What is the effectiveness of music therapy and music intervention (music medicine) in pain management among cancer patients?
A search for relevant articles was conducted on databases such as PubMed Health. PMC, Pubmed.gov, Medline Plus. The search terms used for this review, including the number of articles found using this method is shown in Table 1. The search was limited to articles published between January 1997 and December 2016 that met the following inclusion criteria:
The articles to be included in the literature review would be either be systematic reviews or meta-analysis. The systematic reviews are more comprehensive as compared to narrative reviews and due to their systematic search of literature tend to avoid the element of bias in selection. The systematic reviews were adopted for the study as they are more comprehensive in their means of collecting and summarizing empirical evidence based on the topic.
Meta-analysis involves the use of statistical methods to summarize the results of these studies. For this literature search, meta-analysis studies to be used would be reviewed to ensure that they had clearly stated objectives with pre-defined eligibility criteria for studies, an explicit, reproducible methodology, involved a systematic search that sought to identify all studies, an assessment of the validity of the included studies such as risk of bias, a systematic presentation, synthesis, and finds included in the study.
Some systematic reviews normally include a meta-analysis component that involves the use of statistical techniques to synthesize the data from several studies into a single quantitative estimate. Such articles would also be included. Articles that were not systematic review or meta-analysis (Ben-Arye et al., 2015; Kongsawatvrakul et al., 2016) were excluded.
For this study, the analysis would cover the articles on the use of music therapy and interventions among cancer patients. The inclusion criteria will allow the use of articles covering different types of cancers, in different stages, irrespective of the setting.
For this study, the only open-access journal will be included. These include the articles that are available online to any reader without financial, legal, or technical barriers. The scholarly open access journals are effective since they are produced by knowledgeable scientists and reviewed by peers. The articles should, therefore, be free to read and download. The articles also need to be peer-reviewed. The articles will be checked to ensure that they cite their sources either through the use of references, or bibliographies. Only articles published in English were included.
Acquiring articles through multiple databases creates a scenario where numerous duplicate citation are duplicated. The problem of duplication is also contributed by the publishing cycle in the medical field where articles reporting the same information are retrieved concurrently. Therefore, this called for a de-duplication process (first cull) where the duplicate articles would be removed from the list.
The first cull of article involved checking for duplicates in the articles identified. In this case, the reference list of the databases used was downloaded as a file or an excel spreadsheet. These were compared manually to identify any duplicates. To be considered as duplicates, two or more citations had to share the same author, publication date, volume, issue and similar information on their start page. Whenever doubts arose on whether the articles were duplicates, the full-text versions were used where their population sizes, methodology, and outcomes to establish whether the articles were duplicates. Where different versions of an article were present, the order version was deleted while the newer version was adopted. All citations determined and grouped as duplicates were deleted from the references list.
This literature search method yielded 396 articles. Once duplicates (n=87 articles) were removed, the abstract of 100 articles were screened for inclusion in this review. The majority of the articles (n=196) were not systematic reviews. These were excluded.
The remaining 213 full-test articles were screened for inclusion in this review. A further 120 articles were excluded for the following reasons:
1. The subjects of the study were not cancer patients thus would be inconsistent with the inclusion criteria set as per the research questions (Gold et al., 2005; Zhang et al. 2014)
2. The intervention describes in the article was not on music therapy or intervention (Tao et al., 2015; Knight et al., 2016; Li et al., 2013).
3. The publications of the articles were not open access (Archer & Sheffield, 2015)
4. The articles failed to meet the inclusion criteria of peer-reviewed articles (National Centre for Complementary and Integrative Health, 2016)
See Graphic 1 for the modified PRISMA flow diagram
References in APA 6th style.
Table 1. Databases and search terms used to identify literature for review
|Database||Search terms||No. articles|
|PubMed Health||(“music therapy”[MeSH Terms] OR (“music”[All Fields] AND “therapy”[All Fields]) OR “music therapy”[All Fields]) AND (“music”[MeSH Terms] OR “music”[All Fields])||122|
|AND||interventions [All Fields] AND (“neoplasms”[MeSH Terms] OR “neoplasms”[All Fields]|
|OR||“cancer”[All Fields]) AND (“patients”[MeSH Terms] OR “patients”[All Fields])|
((“music therapy”[MeSH Terms] OR (“music”[All Fields] AND “therapy”[All Fields]) OR “music therapy”[All Fields])
|AND||(“music”[MeSH Terms] OR “music”[All Fields]) AND interventions[All Fields] AND (“neoplasms”[MeSH Terms] OR “neoplasms”[All Fields]|
|OR||“cancer”[All Fields]) AND (“patients”[MeSH Terms] OR “patients”[All Fields])|
|Limiters:||(“1997/01/01″[PubDate] : “2016/12/31″[PubDate]))|
|Pubmed.gov||((“music therapy”[MeSH Terms] OR (“music”[All Fields] AND “therapy”[All Fields]) OR “music therapy”[All Fields]) AND (“music”[MeSH Terms] OR “music”[All Fields])||65|
|AND||interventions[All Fields] AND (“neoplasms”[MeSH Terms] OR “neoplasms”[All Fields]|
|OR||“cancer”[All Fields]) AND (“patients”[MeSH Terms] OR “patients”[All Fields])) AND (hasabstract[text]|
|Limiters:||(“1997/01/01″[PDAT] : “2016/12/31″[PDAT]) AND English[lang])|
|Medline Plus||Music therapy||12|
|Limiters:||1995-2012, Article [Publication type], article title, abstract and keywords|
|Total records identified after database searching||396|
|Total records after duplicates removed||309|
Graphic 1 Modified PRISMA flow diagram of article screening and selection
|Author||Country of origin||Sample size (Number of articles reviewed)||Type of Cancer||Research design||Treatment|
|Nightingale et al (2013)||America||13||all||Meta-analysis and systematic review||Music Interventions|
|Tao et al. (2016)||China||67 RCT||All||Meta-analysis||Traditional Chinese Medicine Five-Element Music Therapy|
|Zhang et al. (2012)||China||32 randomized trials||All||Systematic review and meta-analysis||Music intervention|
|Hilliard (2005)||USA||11 studies||Terminal cancer||Systematic review||Music therapy|
|Preissler et al. (2016)||Germany||41 patients||all||Content analysis||Music therapy|
|Archie et al. (2013)||Articles published between 1970 and 2012||Palliative cancer care||Meta-analysis||Music-based interventions|
|Lee (2016)||USA||Review of 5 therapists||All types||Qualitative review||Music therapy|
|Tao et al. (2015)||China||288 articles||All types||Systematic review and meta-analysis||Traditional Chinese Medicine Five-Element Musical Intervention|
|Bao et al. (2014)||China||27 systematic reviews||Adult cancer||Systematic review||Music therapy|
|Boyde et al. (2012)||12 clinical studies||All types||Systematic review||Music therapy|
In their article, (Tao et al., 2016), carries out a meta-analysis seeking to establish the effect of acupuncture, Tuina, Tai Chi, Qigong, and Traditional Chinese Medicine Five-Element Therapy on dealing with different symptoms such as pain and quality of life in patients with cancer. The articles are based on a search of medical database such as MEDLINE through PubMed and Ovid for articles with randomized controlled trials on the interventions. The analysis indicated that acupuncture had no significant effect on adverse symptoms such as pain, fatigue, improper sleep patterns and gastrointestinal discomfort. TCM-FEMT was mainly found to be effective in lowering depression level. In another meta-analysis, Tao et al. 2015, reviewed assessments of a clinical trial that had Jadad scores of < 2 for the TCM five element musical intervention. One study had carried out an analysis of the effectiveness of the musical intervention to at the commencement of the chemotherapy. The intervention was then offered once a day for a duration of 3 cycles in 4 weeks. These were offered together with chemotherapy. A comparison of these results with typical chemotherapy indicated that the TCM FEMI intervention had reduced the cancer-related fatigue as portrayed in the Brief Fatigue Inventory.
In their article, Nightingale et al. (2013) sought to establish the impact of music interventions on anxiety among adult cancer patients by conducting a meta-analysis and systematic review. The patients included in the study were cancer patients undergoing pain and anxiety-inducing treatments. The articles considered in the article were those that included randomized control trials on music interventions on cancer patients where 13 articles were used. The intervention methodology in the article considered was different. For the analysis, most of the articles indicated a significant difference in anxiety between intervention groups, with reduced anxiety and pain levels. 4 studies, however, indicated insignificant differences in anxiety and pain levels amongst the experimental and control group.
Zhang et al. (2012) sought to establish the application of psychological and physical outcomes in cancer patients. The meta-analysis and systematic review were carried out for articles from 6 English-language and 3 major Chinese-Language databases. The articles compared were randomized controlled trials that compared music intervention with other intervention on the placebo for psychology and physical outcomes. 32 articles with randomized trials were used. Seven of these articles indicated a positive effect of music on the coping with anxiety based on Self-Rating Anxiety Scale. Seven moderate quality studies indicated that music therapy had positive effects on pain management (Zhang et al., 2012).
In their analytical article Preissler et al. (2016) sought to understand the effects of music therapy in the physical and mental wellbeing of the terminally ill cancer patients. For the analysis, the categories of subjects used included condition, treatment, further care, music and music therapy, biography and social environment. The review indicated that the number of subjects per sessions was lower in when receptive music therapy methods were used. Patients were found to have expressed an average of 4.9 psychosocial need (ranging from 1-8). Needs were found to be related to age, parallel art therapy, the role of music in patient’s life and the method of application method of the music therapy. The study indicated the psychosocial needs into nine main dimensions including relaxing and finding comfort, communication and dialogue, activity and vitality, finding expression, and sense of self-reflection, finding an emotional response and de-focusing and diversion (Preissler et al. 2016).
Archie et al., (2013) carried out a review of quantitative studies and neurobiological literature on studies on music-based interventions in palliative cancer care. The review by Archie et al. (2013) on more than 52 studies indicate that pain occurred in approximately 33% of the patients who had finished treatment, 59% of patients under the cancer treatment, and 64% of the patients with the disease at an advanced stage (Archie et al., 2013). Another meta-analysis of a 64 studies pointed out a high prevalence of pain in patients. This has seen the exploration of various pain management strategies expanded. Music-based intervention has become be shown to have mild to mild analgesic effect. Analysis of RCTs, where prerecorded music was played to the cancer patients for about 30-minutes session indicated the analgesic effect of the music therapy was moderate. Further analysis indicated that patients who got music therapy required 29.7% less analgesia with meperidine, alternative or pethidine (Archie et al., 2013). A meta-analysis of articles also pointed to results in some articles where the cancer patients indicate that their self-reported pain scored reduced from 2.7 to 2.1 on the five-point scale after just one music therapy session (Archie et al., 2013).
Lee (2016) conducted a qualitative inquiry on the experiences of music therapists who had survived cancer and were working with medical and hospice patients. The review was based on an inductive analysis of four themes; personal significance, relational significance, and professional significance. The analysis indicated that music had played an important role in providing a coping mechanism for the patients. The finding indicates that they had even gained new insights on the therapeutic power of music based on their personal experience in relying on music during their healing process. The participants in the review indicate that with their experience with music as both patients and therapists had helped them gain an increased trust in the therapeutical power of music Lee (2016).
In their analysis of complementary and alternative medicine, Bao et al. (2014) evaluate other studies conducted on practices such as psychoeducational interventions, music interventions, acupuncture and drug therapy. The general results from the systematic review indicated that use complementary alternative Medicine had benefits in the alleviation of cancer pain. This was based on two systematic reviews that were conducted where several studies under the review pointed out to the moderate association of music intervention and pain-reducing effect for cancer patients (Bao et al. 2014).
Boyde et al. (2012) conducted a review of the 12 clinical studies that had taken place between 2001 and 2011 and had covered a total of 92 patients. The results from the studies indicate a that there was a notable short-term improvement in patients’ mood, relaxation, reduced exhaustion, and anxiety as well as coping with the pain due to cancer disease.
Hilliard (2005), carried out an analytical review of empirical data on the use of music therapy in hospice and palliative care. Out of 11 articles that were studied, six indicated significant differences in support of the use of music therapy in the treatment of the patients with terminal illness. The variable considered for the review include the effect of music therapy on pain, physical comfort, fatigue and energy, relaxation, mood, and spirituality. The results of music therapy for one year were analyzed using Wilcoxon indicated a rank teat at the P<0.05.
Through the analysis of the findings by Tao et al. (2016), it was evident that despite some limitations faced, through the process of acquiring a tentative conclusion on the effectiveness of acupuncture, Tuina, Tai Chi, Qigong and TCM-FEMT indicated that these were beneficial adjunctive therapy. The exact effects of these practices on pain management among the breast cancer patients could not, however, be strictly pointed out. The use of these Chinese medical interventions could be traced back to the ancient time in China. The music interventions are used to attain individualized goals within a therapeutic relationship. The music that Chinese researchers use is mainly the traditional music that is based on five elements of TCM.
The analysis by Nightingale et al. (2013), could not demonstrate a positive effect on anxiety and pain management among cancer patients introduced to pain management. This could be attributed to small sample size.
As the individualized trials indicated, the use of music intervention was a commonly accepted care plan that enhanced the improvement of psychological outcomes. Preissler et al. (2016) indicated that over the last few years, music therapy has increasingly been included in the multi-palliative care. Case series, qualitative analysis, retrospective and single arm interventional studies have pointed to the effects of music and music therapy on pain. A review of randomized studies has also alluded the effectiveness of music therapy in improving the quality of life, pain reduction and dealing with anxiety.
Music therapy is offered by a team of trained music therapists within the multi-professional care team. The therapy is offered in individualized sessions on one-on-one basis. To increase its overall effectiveness, a variety of music therapy techniques are used and are categorized as receptive and active methods. Preissler et al., (2016) indicated that the music therapy need be carried out in at least two sessions. The therapy of 20-90 minutes was found to be effective. To enhance the effectiveness, the patients need to be allowed to determine the music therapy techniques and content for each session.
Music-based intervention has been indicated as valuable tools for helping cancer patients get relief from their suffering. This value is expected to even be much higher in the future following extensive research on the same. Music has been noted to have a potential in helping reduce pain, anxiety, and mood disturbance that are common traits among caner patients. The use of music has been noted to reduce the need for using pain-relieving analgesic or anxiolytics even is this is by a small major. This is noted as having a major clinical implication especially noting the rate with which the advanced age and hepto-renal dysfunction co-exist in palliative cancer care population. Cancer patients who may be not familiar with the standard inpatient healthcare procedures in a hospital setting tend to experience unexpected pain resulting from actions like repeated injections, drawing of blood, and invasive procedures. In such a case, music has been indicated to have a capacity to restore familiarity to the patient, and a therapeutic value is acquired from the reassuring stimulus. This may be in the form of listening to a playlist comprised of favorite songs or a melodic arrangement by a live music therapist which matches with the tones in the surrounding environment.
It has been noted that there is limited quantitative data in this field. Use of meta-analysis has a high potential for deriving the assessment of these interventions. Challenges in the use of meta-analysis are deriving a quantitative assessment of impacts is caused by the difficultness for controlling variations in study design, study population, interventions and assessment methods applied in different studies. The use of different music therapists has been noted as having a potential of introducing great variability in the outcomes despite the same specific interventions being used.
Advances in neurobiology have attempted to offer insights into the effects of music in pain reduction. Many researchers had proposed that music acts by competing with noxious stimuli for pain leading to the closure of the neurological gate for the pain signal transmission. Functional imaging data has indicated that music modulates the activity of multiple limbic and paralimbic brain structure more specifically in the ventral striatum, dorsomedial midbrain, and periaqueductal (Archie et al., 2013). The functional abnormalities in these structures are linked with the pathophysiology of pain and depression. The structures are also noted to have abundant receptors of ligands associated with pain. Experiments have shown that piloerection that is commonly associated is closely tied to the increased regional cerebral blood flow to ventral striatum and the dorsomedial midbrain but caused a decrease in the flow of blood to the hippocampus and amygdala (Archie et al., 2013).
The literature review discussed above was conducted for the research topic of establishing the effectiveness of music therapy and music intervention in pain management, among cancer patients. The articles for review were searched in different databases such as PubMed Health, PubMed.gov, PMC and MedlinePlus. The keywords used for the search literature include ‘music therapy’, ‘music intervention’,’ ‘music medicine’, ‘pain management’, and ‘cancer patients. The most common therapy for pain management in the opioid therapy. The numerous side effects of this therapy have caused the healthcare practitioners increase the use of complementary and alternative medicine including music therapy and music intervention. Music intervention involves a patient listening to pre-recorded music provided by a medical professional. On the other hand, music therapy is the implementation of a music intervention by a trained medical music therapist. Medical therapists are certified by the Certification Board for Music Therapists upon completion of an undergraduate course, clinical internship, and passing of the CBMT examination.
Among the forms of music therapies discussed in the paper ins the Traditional Chinese Five-Element Therapy (TM FEMI) which has been found to be effective in the reducing pain among cancer patients as patients reported fewer pain scores when their chemotherapy was combined with the TM FEMI in comparison to undergoing chemo only.
Advances in neurobiology have been noted as an important element in providing a scientific understanding of how music therapy creates a reduction in levels of pain. The common grounding that most researchers was that music initiates competition with the noxious stimuli pain thereby creating closure in the neurological avenue used for pain transmission. Functional imaging data have offered a more comprehensive explanation that has been based on the flow of blood in the multiple limbic and paralimbic parts of the brain.
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Ben-Arye, E., Ben-Arye, Y., & Barak, Y. (2015). Eva Between Anxiety and Hope: Integrating Anthroposophic Music Therapy in Supportive Oncology Care . Health Psychology Research, 2199.
Boyde, C., Linden, U., Boehm, K., & Ostermann, T. (2012). The Use of Music Therapy During the Treatment of Cancer Patients: A Collection of Evidence. Global Advances in Health and Medicine, 1(5), 24–29
Burns, D., AN, M., Althouse, S., Perkins, S., & Cripe, L. (2018). Differences Between Suppportive Music and Imagery and Music Listening During Outpatient Chemotherapy and Potential Moderator of Treatment Effects. Journal of Music Therapy, 83-108.
Hilliard, R. E. (2005). Music Therapy in Hospice and Palliative Care: a Review of the Empirical Data. Evidence-Based Complementary and Alternative Medicine, 2(2), 173–178.
Kongsawatvrakul, C., Charakon, C., Paiwattananupant, K., Lekskul, N., Rattanasiri, & Lertkhachonsuk, A. (2016). Limited Impact of Music Therapy of Patient Anxiety with the Large Loop Excision of Transformation Zone Procedure- A Randomized Controlled Trial. Asian Pacific Journal of Cancer Prevention , 2853-6.
Lee, Jin Hyung. “A Qualitative Inquiry of the Lived Experiences of Music Therapists Who Have Survived Cancer Who Are Working with Medical and Hospice Patients.” Frontiers in Psychology 7 (2016): 1840. PMC. Web. 22 Mar. 2018.
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Preissler, Pia et al. “Favored Subjects and Psychosocial Needs in Music Therapy in Terminally Ill Cancer Patients: A Content Analysis.” BMC Palliative Care 15 (2016): 48. PMC. Web. 22 Mar. 2018.
Tao, W.-W., Jiang, H., Tao, X., Jiang, P., Li-Yan, S., & Sun, X.-C. (2016). Effects of Apuncture, Tuina, Tai Chi, Qigong,a nd Traditional Chinese Medicine Five-Element Music Therapy on Symptom Management and Quality of Life for Cancer Patient: A Meta-Anlaysis. Journal of Pain ad Sympton Management , 728-747.
Tao, W., Luo, X., Cui, B., Liang, D., Wang, C., Duan, Y., … Liu, Q. (2015). Practice of traditional Chinese medicine for psycho-behavioral intervention improves quality of life in cancer patients: A systematic review and meta-analysis. Oncotarget, 6(37), 39725–39739.
Zhang, J., Wang, P., Yao, J., Zhao, L., Davis, M., Walsh, D., & Yue, G. (2012). Music Interventions for Psychological and Physical Outcomes in Cancer: A Systematic Review adn Meta-Analysis. Supportive Care in Cancer , 3043-3053.
Van der Heijden, M. J. E., Oliai Araghi, S., van Dijk, M., Jeekel, J., & Hunink, M. G. M. (2015). The Effects of Perioperative Music Interventions in Pediatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. PLoS ONE, 10(8), e0133608.
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