Abcstract
Integrative practices have been incorporated into palliative care to provide holistic and multidimensional care for patients.
This study aims to identify the scope of integrative practices, specifically whole medical systems, and demonstrate its safety and efficacy, specially in children with cerebral palsy.
Key databases, including Embase, Cochrane, Medline/PubMed, Scopus, Google Scholar, Lilacs and Scielo were searched using specific terms.
Only randomized and non-randomized clinical trials were included for meta-analysis purposes. Case-control, cohort, cross-sectional or retrospective observational studies were also included for the systematic review. Participants included children aged 0–18 years receiving palliative care for cerebral palsy and undergoing Ayurvedic Medicine practices.
Descriptive analysis was conducted, including data such as year; author; design; sample size; intervention and comparison; outcomes and conclusion.
Two interventional studies compared Ayurvedic practices with each other or with physiotherapy in children with cerebral palsy. The meta-analysis demonstrated an improvement in spasticity for children using Ayurvedic medicine. However, there were limitations in terms of heterogeneity in interventions, control groups, and assessed outcomes.
Integrative practices, including Ayurvedic medicine have the potential to improve quality of life, manage disease symptoms and provide emotional support. However, more robust evidence is needed to support their widespread use. The use of Ayurvedic medicine showed evidence of improvement in spasticity for children with cerebral palsy.
Registration number
Prospero CRD 42020198399.
Keywords: Palliative care, Pediatrics, Complementary therapies, Ayurvedic medicine, Cerebral palsy
1. Background
The study of palliative care, specially in pediatrics, has gained importance due to the diagnosis of complex chronic conditions in children. These persist for at least 12 months (or until death intervenes) that affect one or more organ systems and require specialized pediatric care. Palliative care continues throughout life, irrespective of whether the child receives curative treatment [1,2].
Examples of pediatric conditions that can benefit from palliative care include congenital diseases incompatible with life or associated with severe limitations, chromosomal disorders, metabolic disorders, oncological and neurological conditions (example refractory epilepsy and cerebral palsy), retroviruses, complex cardiac conditions, neuromuscular diseases, and patients undergoing procedures such as tracheostomy or gastrostomy. These conditions significantly impact the quality of life of the child and their family [[3], [4], [5]].
One of the objectives of pediatric palliative care (PPC) is to control symptoms that interfere with the well-being and quality of life of children, such as, acute and chronic pain, dyspnea, nausea, vomiting, cough, hiccups, dysphagia, mucositis, sialorrhea, pruritus, edema, fatigue, anorexia/cachexia, constipation or diarrhea, sleep and mood disorders, etc. [5].
Children with cerebral palsy often experience symptoms such as sialorrhea, spasticity, and pain, which significantly interfere with their daily activities and overall well-being. These symptoms can also disrupt their sleep, lead to anxiety disorders and affect the child's overall quality of life. Additionally, for family, these symptoms can change the dynamics of daily life and become limiting factors [6,7].
Integrative medicine and its practices have been explored to control these symptoms and provide holistic care [8].
Initially, the National Center for Complementary and Alternative Medicine (NCCAM) [9] categorizes integrative practices into whole medical system, biological therapies, mind-body practices, body manipulation and energy therapies. Currently, known as National Center for Complementary and Integrative Health (NCCIH), since 2011 divided the practices into two categories: mind and body therapies and natural products [9].
Brazilian National Policy on Integrative and Complementary Practices and many European countries categorize them into: mindbody therapies, natural products and whole medical systems [10,11].
For study purposes, we understand that the initial categorization by classifying into five subgroups was more appropriate in order to facilitate searches. In this way, traditional Chinese medicine, Naturopathic Medicine, Homeopathy, Antroposophy and Ayurvedic medicine, as Whole Medical System's examples were studied in this research [12,13].
Their use has been increasingly sought after in pediatrics for various purposes, such as strengthening the immune system, improving the child's inner strength, providing physical and mental stabilization with reduced stress and anxiety, increasing the effectiveness of conventional medications, assisting in the management of secondary symptoms to side effects of basic treatment, and supporting the child in coping with the disease [[14], [15], [16], [17]].
This study aims to evaluate the safety and efficacy of Integrative Practices, specifically Ayurvedic Medicine in pediatric palliative care, focusing on children with cerebral palsy. The goal is to assess symptom control and improve quality of life.
2. Material and methods
This systematic review and meta-analysis were registered with PROSPERO (International Prospective Register of Systematic Reviews) at the University of York with number CRD42020198399. And approved by the Research Committee of promoting institution, under protocol 5575290720. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 Statement was followed throughout [18,19].
2.1. Information sources and search strategy
Electronic databases such as MEDLINE (Online system for the analysis and retrieval of international medical literature), LILACS (Latin American and Caribbean Literature in Health Sciences), Scopus, Scielo (Scientific Electronic Library Online), Scholar Google, Embase, COCHRANE Library and CINAHL (Cumulative Index to Nursing and Allied Health) were searched using specific descriptors related to pediatrics, palliative care and integrative practices. A manual search among the main references was subsequently performed.
The descriptors used were: child OR pediatrics OR childhood AND palliative care OR palliative medicine AND Traditional Chinese Medicine OR Naturopathic Medicine OR Anthroposophic medicine OR Homeopathy OR Homeopathic formularies OR Homeopathic pharmacopeia OR ayurvedic medicine.
According to the findings that were obtained in the analysis, a final complementary search was performed using only the descriptors: Ayurvedic medicine AND cerebral palsy.
2.2. Eligibility criteria
The PICO model was employed as a search strategy tool in this study. The population under investigation included patients aged 0–18 years receiving pediatric palliative care for conditions classified by the WHO in 2018 [1,3], such as cerebral palsy.
The desired comparison was between children with chronic and limiting illnesses who did not receive any integrative and complementary practices in their treatment. The outcomes sought were the improvements in quality of life, symptom control and reduction of adverse events associated with the disease or its treatment.
Randomized and non-randomized clinical trials were included for meta-analysis, while case-control, cohort, cross-sectional or retrospective observational studies were also considered for the systematic review.
Studies were excluded according to the following reasons: (1) did not have clear evidence of the use of integrative and complementary practices or used practices other than whole medical systems, (2) approached groups over 18 years of age (studies carried out with parents/guardians, physicians, etc.), (3) did not address the topic of palliative care or diseases with such indication, (4) abstracts without full text, conferences in symposiums and congresses and (5) narrative review studies or addressing basic research. As explicit in Fig. 1.
Fig. 1.
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021; 372:n71. https://doi.org/10.1136/bmj.n71: http://www.prisma-statement.org/.
2.3. Data extraction, collection and statistical analysis
Descriptive analysis of the selected studies was conducted including publication year; author; study design; sample size; country where the study was carried out; intervention and comparison; outcomes and conclusion.
The quality of the selected studies was assessed using MMAT (Mixed Methods Appraisal Tool) in its 2018 [20] version and GRADE, (Grading of Recommendations, Assessment, Development and Evaluations) tools, it was considered the lowest [18].
Risk of bias analysis was performed by Rob (Risk of bias) tool for randomized studies, the Robins I tool (Risk Of Bias In Non-randomized Studies – of Interventions and of Exposures) for non-randomized and the Robin tool for observational studies were used, as well as the help of the Review Manager 5.4 software [21,22].
They were represented using fixed effects model algorithm in the absence of heterogeneity, otherwise, random effects model was adopted. Continuous variables were presented as mean and standard deviation and dichotomous variables as frequency and proportion and had a CI (confidence interval) of 95%. The p value was considered significant when p < 0.05.
3. Results
3.1. Literature search results
The literature search was performed based on titles and abstracts by two of the researchers independently, who assessed whether the studies met the defined eligibility criteria. In the second step, the studies were screened in full text to confirm eligibility, also in a paired and independent manner. All steps were duly documented to ensure the transparency and accuracy of the review [22].
3.2. Characteristics of the included studies
Out of the included studies, eight articles were of an interventionist nature while 35 were observational research studies. The conditions addressed in the groups with an indication of palliative care according to the WHO [1,3], were mainly oncological conditions, followed by neurological conditions such as cerebral palsy and epilepsy, as well chronic diseases including hematology, painful conditions and genetic diseases. Among the analyzed studies, only three explicitly described patients under exclusive palliative care.
3.3. Analysis of observational studies
The prevalence of use of Whole Medical Systems and the main reasons for their use were graphically demonstrated in Fig. 2, taking into account all these subgroups.
Fig. 2.
Total number of participants from all studies who reported the main reasons for using integrative practices according to health conditions.
Additionally, subjective reports of satisfaction from the interviewees were collected and shown in Fig. 3, indicating a higher rate of satisfaction and recommendations by patients and parents for others under similar situations.
Fig. 3.
Prevalence in percentage (%) in the perception of satisfaction and/or benefits of general integrative practices, separated by groups.
Regarding the analysis of adverse events related to the practices, not all studies addressed these issues, which compromises the calculation of proportional incidence. The details are shown in Table 1.
Table 1.
Survey of adverse events in observational studies by disease group.
| Adverse events | |||
|---|---|---|---|
| Oncological diseases | Neurological diseases | Chronic complex diseases | |
| Mild | 33 | 21 | 9 |
| Moderates | 1 | 5 | 0 |
| Severe | 4 | 2 | 0 |
| Interruption | 18 | 1 | 0 |
3.4. Analysis of interventional studies [[23], [24], [25], [26], [27], [28], [29], [30]]
The studies demonstrating interventions were grouped into two categories: oncological diseases and neurological conditions, particularly cerebral palsy. Both of these categories were included as indications for palliative care in groups 1 and 4, respectively [2,3].
Among the studies that included cancer patients, each study evaluated a different aspect. The first study [23] evaluated fatigue and quality of life using Homeopathy, without a control group. The evaluation of fatigue and quality of life was conducted using general and specific questionnaires/quality of life scores, such as the Pediatric Quality of Life Inventory (PedsQL) and the Fatigue Severity Scale (SDS-distress scale) (1–5), with statistically significant improvement observed in SDS scores, as well as general and specific PedsQL (p 0.038) and sleep/rest with fatigue (p 0.004) over time. However, there was no change in cognitive fatigue with treatment (p 0.611). Some expected toxicities associated with chemotherapy were reported, but no serious adverse events occurred.
The second study [24] aimed to analyze overall and event-free survival using Anthroposophic Medicine compared to a placebo group, with no statistical difference observed in survival (p 0.6) or presence of events (0.42), although there were fewer recurrences and deaths in the intervention group. No adverse events were reported in the study.
The third study [25] focused on the control of post-chemotherapy mucositis in 32 children using Homeopathy compared with a placebo, revealing that the time for worsening or onset of symptoms was similar between the two groups. However, patients in the intervention group were less likely to experience worsening symptoms, with a lower severity of symptoms observed. Additionally, a higher percentage of patients in the intervention group (33%) did not develop stomatitis compared to the placebo group (7%).
Two patients reported nausea and one death occurred due to the underlying disease. The high incidence of serious complications inherent to the disease did not differ significantly between the groups [25].
Bias analysis was performed and the results are presented in Fig. 4.
Fig. 4.
Identification of risk of bias according to Robins-I of the PRISMA protocol of the analyzed studies with patients with oncological diseases.
In the second category of patients consisting of children with neurological conditions, various assessments were conducted to evaluate spasticity, gross and fine motor skills, performance, language abilities, and control of sialorrhea. Homeopathy, Traditional Chinese Medicine and Ayurvedic Medicine, were utilized in these studies.
The study by Sajedi [26] evaluated 24 children diagnosed with cerebral palsy, divided into two groups, to assess the effectiveness of homeopathy alone or in combination with occupational therapy in improving the severity of spasticity in the trunk, neck and four limbs, using the Modified Ashworth Scale [31]. The results showed no statistically significant differences the groups for the limbs (p = 0.114) or neck and trunk (p = 0.091). However, there was a noticeable trend towards improvement in the trunk. No adverse events were reported during the study.
Arun Raj [27] conducted a study involving 32 children with cerebral palsy, aiming to assess the effectiveness of Ayurvedic Medicine in improving spasticity. The interventions included oral applications and body manipulations, which were compared between groups. The modified Ashworth Scale was used as an outcome assessment tool [31]. Spasticity was reduced during treatment compared to previous assessment, and the improvement was maintained for a considerable period, particularly when body manipulation was included. No adverse events were reported in the study.
The study by Shailaja [28] evaluated 40 patients with cerebral palsy using Ayurveda Medicine to improve spasticity, gross and fine motor skills, performance and language. The study compared a group receiving exclusively oral treatment with another group receiving oral medication and body manipulation.
The ayurvedic interventions, oral route or corporal manipulation, were effective in the management of cerebral palsy, with statistical significance observed before and after therapy. The group with associated manual intervention showed a better response in fine and gross motor functions, while the oral treatment alone was more effective in improving of language and performance. No adverse events were reported [28].
Wong [29] evaluated 10 patients with cerebral palsy who underwent an intervention, without a control group, for improvement of sialorrhea over a 6-month follow-up period using Traditional Chinese Medicine. Various tools were used to assess performance, including visual scale described by parents (VAS), semiquantitative observation of salivation quotient and classification of salivation severity/frequency into different levels.
Statistically significant improvements were observed in all three measures. None of the children experienced any side effects during the study, although some initial crying occurred due fear of needles and potential mild pain. However, the majority of children quickly adapted and tolerated the technique well [29].
Lastly, Palande [30] evaluated 30 patients with cerebral palsy to assess the improvement of spasticity using Ayurvedic Medicine. The study utilized the Modified Ashworth Scale [31], with the patients divided into three groups: two groups receiving ayurvedic medicine (A and B), differing in the administration of oral medication and enemas with body manipulation and a third group receiving only physiotherapy (C).
Improvement before and after treatment was significant in all three groups, with no significant difference or superiority observed when comparing groups. Ayurvedic management was found to be equally effective as physiotherapy, with earlier improvements. No unpleasant side effects were observed [30].
The risk of bias analysis according to the ROBINS-I protocol is described in Fig. 5.
Fig. 5.
Identification of risk of bias according to Robins-I of the PRISMA protocol of the analyzed studies with patients with Cerebral Palsy.
Two [27,30] intervention studies carried out in children with Cerebral Palsy had similar methodologies and satisfactory clinical outcomes. The studies are described in Table 2, and a meta-analysis was conducted, as shown in Table 3 and Fig. 6.
Table 2.
Comparison between intervention studies using Ayurvedic medicine in patients with Cerebral Palsy and spasticity.
| Author | Design | Sample | Age | Inclusion Criteria | GRADE/MMAT | Place | Intervention | Control | Outcomes Found |
|---|---|---|---|---|---|---|---|---|---|
| Arun Raj, 2018 [27] |
|
32: 4 losses - final 28 (in 2 groups) | 3–8 years | Spasticity in limbs with motor coordination failure, developmental delay, hyperreflexia.Ashworth scale | Moderate/moderate | College and Hospital of Ayurveda Hassan, India |
|
|
|
| Palande, 2017 [30] |
|
30 (divided into 3 groups) | 1–12 years | Children with cerebral palsy. Ashworth spasticity scale | Moderate/low | Balaroga Department, National Institute of Ayurveda, Jaipur, India |
|
|
|
Table 3.
Comparison values between the intervention and control groups in the outcome of improvement in spasticity on Cerebral Palsy.
| Study | Intervention 1 |
Intervention 2 |
Control |
||||||
|---|---|---|---|---|---|---|---|---|---|
| N | Mean | SD | N | Mean | SD | N | Mean | SD | |
| Arun Raj 2018 (n: limbs and trunk) | 37 | 1.27 | 0.83 | – | – | – | 25 | 2.06 | 1.06 |
| Palande 2017 (n: participants) | 10 | 0.7 | 0.350 | 10 | 0.95 | 0.316 | 10 | 1.1 | 0.394 |
Fig. 6.
Forest plot graph between the two analyzed studies comparing the clinical response of spasticity improvement with the use of Ayurvedic Medicine.
4. Discussion
This study conducted comprehensive research to gather evidence on the main practices within the scope of Integrative Medicine, specifically Ayurvedic Medicine, in children requiring palliative care, particularly those with cerebral palsy. To the best of our knowledge, no similar research has been conducted involving this particular group thus far.
However, despite the extensive research, there is still a lack of robust evidence to support the effectiveness of integrative practices in the key aspects examined in this review, such as symptom improvement, sense of well-being and enhanced quality of life.
The exception to this statement is the use of Ayurvedic medicine for children with cerebral palsy and spasticity, which showed evidence of symptom improvement.
Adverse events reported were few and mostly mild and self-limited and there was a subjective perception of benefits by users.
A study by Bishop [32], which conducted a systematic review with children with cancer, identified the most commonly used practices as phytotherapy, dietary and nutritional adjustments and faith healing. Other modalities such as homeopathy, mind-body therapies, and therapeutic massage were reported less frequently.
In the case of neurological patients, the intention of using integrative practices was to reduce adverse events resulting from conventional treatments and focus on physical stabilization while adopting a holistic approach. On the other hand, individuals with chronic conditions primarily used these practices to cope better with adverse situations.
Among the three groups identified in this study, dissatisfaction with conventional medicine and a preference for a holistic and natural approach were cited as reasons for using integrative practices [[23], [24], [25], [26], [27], [28], [29], [30]].
Regarding safety, it is important to note that while these adverse events were rare or inadequately reported, integrative practices are not entirely without risks [26,27]. In our study, most adverse events were mild and manageable, not requiring medical intervention.
The studies employing an interventionist approach in our analysis exhibited heterogeneity in terms of interventions, control groups, and outcomes assessed. It is important to note that these studies did not strictly adhere to the experimental protocols typically expected in clinical trials. Instead, they were conducted with certain limitations, such as the absence of control groups or poorly defined interventions and outcomes.
A meta-analysis was conducted only with two studies that examined the use of Ayurvedic medicine in children with cerebral palsy. These studies compared different modalities of Ayurvedic medicine and isolated physiotherapy in a placebo-controlled model. The meta-analysis revealed an improvement in spasticity before and after the use of Ayurvedic medicine, with faster results observed in children who received this treatment.
These aspects highlighted in the interventional studies serve as a warning to scholars that future research is needed to evaluate the effectiveness of integrative practices in healthcare. Special attention should be given to assessing their safety by establishing well-structured protocols for analyzing adverse events. This will help dispel the notion that these practices can be used indiscriminately based solely in the belief that they do not cause harm.
Finally, this study aimed to determine the validity of using integrative practices as a complement to traditional medicine for symptom control and enhancing quality of life. The subjective evaluations of patients and/or parents revealed positive reports, emphasizing the benefits of these practices and recommending their use to other patients in similar situations. Integrative practices have the potential to improve quality of life, manage disease symptoms, support conventional treatment, and provide emotional support.
However, it is important to note that despite these positive accounts, there is a lack of sufficient robust evidence to support the indiscriminate use of integrative practices, except for the use of Ayurvedic medicine for children with cerebral palsy and spasticity, as suggested by this study.
5. Conclusions
There is a wide use of integrative and complementary practices in children with indications of palliative care. In regard to whole medical systems the use in this research was more identified among groups of oncological and neurological conditions, with several reasons being mentioned, such as disease control, improvement of adverse events arising from the basic treatment, strengthening of the immune system and improvement of mood and quality of life. In this meta-analysis the most beneficial findings was in spasticity and quality of life in patients with cerebral palsy using Ayurvedic Medicine.
Most studies have focused on children with oncological diseases, as they are an area where integrative practices have a role in treatment and supportive measures due to the aggressiveness of conventional medicine, which can significantly impact the child's quality of life.
Studying these practices presents complexities and methodological limitations. They propose individual and holistic approaches, making it challenging to conduct controlled studies and establish appropriate placebos.
Additionally, it is important to highlight the presence of stigmatization by conventional doctors, which can extend to their patients, making it difficult to recruit participants for these studies and discuss the optimal use of these practices. Due to this prejudice, patients using integrative practices may hesitate to openly discuss this matter with their attending physician, resulting in a lack of dialogue about associated risks and indications.
To overcome these limitations, it is crucial to continue conducting rigorous randomized clinical trials and systematic reviews that focus on the use of integrative practices in pediatrics across various health conditions that may benefit from their application.
Funding sources
One of the authors (A.M.O.R.) receives a doctoral scholarship from the Capes institution (Higher Education Personnel Improvement Coordination) to carry out this work. The funding sources had no influence on the study design, data collection, analysis and interpretation or the writing of the manuscript.
Conflict of interest
One of the authors (AMOR) receives a doctoral scholarship from the Capes institution (Higher Education Personnel Improvement Coordination) to carry out this work. The funding sources had no influence on the study design, data collection, analysis and interpretation or the writing of the manuscript.
Declaration of generative AI in scientific writing
During the preparation of this work the author(s) did not used any kind of Artificial Intelligence. The author(s) reviewed and edited the content and take(s) full responsibility for the content of the publication.
Author contribution
All the authors contributed in acquiring data and drafting the manuscript. Aline Maria de Oliveira Rocha: Conceptualization, Methodology, Software, Investigation, Formal analysis, Writing- Original Draft, Project administration. Flavia H. Santos: Methodology, Supervision, Writing - Review & Editing, Validation, Project administration. Simone Brasil de Oliveira Iglesias: Methodology, Supervision, Writing - Review & Editing, Validation, Project administration. João Roberto Bissoto: Methodology, Investigation, Data Curation, Validation, Writing - Review & Editing. Claudio A. Len: Conceptualization Methodology, Resources, Supervision, Writing - Review & Editing, Validation, Project administration.
Acknowledgement
The authors are thankful to Capes institution (Higher Education Personnel Improvement Coordination) for the doctoral scholarship to carry out this work. The funding sources had no influence on the study design, data collection, analysis and interpretation or the writing of the manuscript. The authors are also thankful to the authors of the clinical trials to sharing of their data andvaluable information for this paper.
Footnotes
Peer review under responsibility of Transdisciplinary University, Bangalore.
References
- 1.Radbruch L., De Lima L., Knaul F., Wenk R., Ali Z., Bhatnaghar S., et al. Redefining palliative care-A New Consensus-based definition. J Pain Symptom Manage. 2020;60(4):754–764. doi: 10.1016/j.jpainsymman.2020.04.027. Epub 2020 May 6. PMID: 32387576; PMCID: PMC8096724. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.van Teunenbroek K.C., Mulder R.L., Ahout I.M.L., Bindels-de Heus K.G.C.B., Delsman-van Gelder C.M., Galimont-Collen A.F.S., et al. A Dutch paediatric palliative care guideline: a systematic review and evidence-based recommendations for symptom treatment. BMC Palliat Care. 2024;23(1):72. doi: 10.1186/s12904-024-01367-w. PMID: 38481215; PMCID: PMC10935792. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Wachterman M.W., Pilver C., Smith D., Ersek M., Lipsitz S.R., Keating N.L. Quality of end-of-life care provided to patients with different serious illnesses. JAMA Intern Med. 2016;176(8):1095–1102. doi: 10.1001/jamainternmed.2016.1200. PMID: 27367547; PMCID: PMC5470549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Downing J., Powell R.A., Marston J., Huwa C., Chandra L., Garchakova A., Harding R. Children’s palliative care in low- and middle-income countries. Arch Dis Child. 2016;101(1):85–90. doi: 10.1136/archdischild-2015-308307. PMID: 26369576. [DOI] [PubMed] [Google Scholar]
- 5.Wood F., Simpson S., Barnes E., Hain R. Disease trajectories and ACT/RCPCH categories in paediatric palliative care. Palliat Med. 2010;24(8):796–806. doi: 10.1177/0269216310376555. PMID: 20719816. [DOI] [PubMed] [Google Scholar]
- 6.Schütze T., Längler A., Zuzak T.J., Schmidt P., Zernikow B. Use of complementary and alternative medicine by pediatric oncology patients during palliative care. Support Care Cancer. 2016;24(7):2869–2875. doi: 10.1007/s00520-016-3097-2. PMID: 26838025. [DOI] [PubMed] [Google Scholar]
- 7.McCann L.J., Newell S.J. Survey of paediatric complementary and alternative medicine use in health and chronic illness. Arch Dis Child. 2006;91(2):173–174. doi: 10.1136/adc.2004.052514. PMID: 16428365; PMCID: PMC2082683. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.April K.T., Walji R. The state of research on complementary and alternative medicine in pediatric rheumatology. Rheumatic Diseases Clinics of North America. 2011;37(1):85–94. doi: 10.1016/j.rdc.2010.11.011. PMID: 21220088. [DOI] [PubMed] [Google Scholar]
- 9.Exploring the science of complementary and Alternative medicine : third strategic plan, 2011-2015. Bethesda, Md: U.S. Dept. Of health and Human Services. National Institutes of Health; 2011. https://catalog.nlm.nih.gov/permalink/01NLM_INST/1o1phhn/alma9915576563406676 Library Catalog; MMS ID 9915576563406676; NLM ID 101557656. Available in. [Google Scholar]
- 10.Sousa L.A., Barros N.F. Integrative and complementary practices in the unified health system: progresses and challenges. Rev Lat Am Enfermagem. 2018;26 doi: 10.1590/1518-8345.2854.3041. PMID: 30234880; PMCID: PMC6145796. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Baars E.W., Hamre H.J. Whole medical systems versus the system of conventional biomedicine: a critical, narrative review of similarities, differences, and factors that promote the integration process. Evid Based Complement Alternat Med. 2017;2017 doi: 10.1155/2017/4904930. . PMID: 28785290; PMCID: PMC5530407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Grootenhuis M.A., Last B.F., de Graaf-Nijkerk J.H., van der Wel M. Use of alternative treatment in pediatric oncology. Cancer Nurs. 1998;21(4):282–288. doi: 10.1097/00002820-199808000-00010. PMID: 9691511. [DOI] [PubMed] [Google Scholar]
- 13.Brown J., Byers T., Thompson K., Eldridge B., Doyle C., Williams A.M. American cancer society workgroup on nutrition and physical activity for cancer survivors. Nutrition during and after cancer treatment: a guide for informed choices by cancer survivors. CA Cancer J Clin. 2001;51(3):153–187. doi: 10.3322/canjclin.51.3.153. quiz 189-187. doi: 10.3322/canjclin.51.3.153. Erratum in: CA Cancer J Clin 2001;51(5):320. PMID: 11577495. [DOI] [PubMed] [Google Scholar]
- 14.Kelly K.M. Integrative therapies for children with hematological malignancies. Hematology Am Soc Hematol Educ Program. 2009:307–312. doi: 10.1182/asheducation-2009.1.307. PMID: 20008215. [DOI] [PubMed] [Google Scholar]
- 15.Jacobs S.S. Integrative therapy use for management of side effects and toxicities experienced by pediatric oncology patients. Children. 2014;1(3):424–440. doi: 10.3390/children1030424. PMID: 27417488; PMCID: PMC4928739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Sencer S.F., Kelly K.M. Complementary and alternative therapies in pediatric oncology. Pediatr Clin North Am. 2007;54(6):1043–1060. doi: 10.1016/j.pcl.2007.10.007. PMID: 18061790. [DOI] [PubMed] [Google Scholar]
- 17.Yarney J., Donkor A., Opoku S.Y., Yarney L., Agyeman-Duah I., Abakah A.C., Asampong E. Characteristics of users and implications for the use of complementary and alternative medicine in Ghanaian cancer patients undergoing radiotherapy and chemotherapy: a cross- sectional study. BMC Complement Altern Med. 2013;13:16. doi: 10.1186/1472-6882-13-16. PMID: 23331546; PMCID: PMC3565863. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Brozek J.L., Akl E.A., Alonso-Coello P., Lang D., Jaeschke R., Williams J.W., Phillips B., Lelgemann M., Lethaby A., Bousquet J., Guyatt G.H., Schünemann H.J., GRADE Working Group Grading quality of evidence and strength of recommendations in clinical practice guidelines. Part 1 of 3. An overview of the GRADE approach and grading quality of evidence about interventions. Allergy. 2009;64(5):669–677. doi: 10.1111/j.1398-9995.2009.01973.x. PMID: 19210357. [DOI] [PubMed] [Google Scholar]
- 19.Moher D., Liberati A., Tetzlaff J., Altman D.G., PRISMA Group Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7) doi: 10.1371/journal.pmed.1000097. . PMID: 19621072; PMCID: PMC2707599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Hong Q.N., Pluye P., Fàbregues S., Bartlett G., Boardman F., Cargo M., et al. Improving the content validity of the mixed methods appraisal tool: a modified e-Delphi study. J Clin Epidemiol. 2019;111:49–59.e1. doi: 10.1016/j.jclinepi.2019.03.008. . PMID: 30905698. [DOI] [PubMed] [Google Scholar]
- 21.Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372 doi: 10.1136/bmj.n71. PMID: 33782057; PMCID: PMC8005924. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.McGowan J., Sampson M., Salzwedel D.M., Cogo E., Foerster V., Lefebvre C. PRESS peer review of electronic search strategies: 2015 guideline statement. J Clin Epidemiol. 2016;75:40–46. doi: 10.1016/j.jclinepi.2016.01.021. PMID: 27005575. [DOI] [PubMed] [Google Scholar]
- 23.Brulé D., Gillmeister B., Lee M., Alexander S., Gassas A., Hendershot E., et al. A feasibility pilot trial of individualized homeopathic treatment of fatigue in children receiving chemotherapy. Integr Cancer Ther. 2016;15(4):495–501. doi: 10.1177/1534735415617023. PMID: 26574487; PMCID: PMC5739153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Seifert G., Rutkowski S., Jesse P., Madeleyn R., Reif M., Henze G., Längler A. Anthroposophic supportive treatment in children with medulloblastoma receiving first-line therapy. J Pediatr Hematol Oncol. 2011;33(3):e105–e108. doi: 10.1097/MPH.0b013e31820946d3. PMID: 21368673. [DOI] [PubMed] [Google Scholar]
- 25.Oberbaum M., Yaniv I., Ben-Gal Y., Stein J., Ben-Zvi N., Freedman L.S., et al. A randomized, controlled clinical trial of the homeopathic medication TRAUMEEL S in the treatment of chemotherapy-induced stomatitis in children undergoing stem cell transplantation. Cancer. 2001;92(3):684–690. doi: 10.1002/1097-0142(20010801)92:3<684::aid-cncr1371>3.0.co;2-#. PMID: 11505416. [DOI] [PubMed] [Google Scholar]
- 26.Sajedi F., Alizad V., Alaeddini F., Fatemi R., Mazaherinezhad A. The effect of adding homeopathic treatment to rehabilitation on muscle tone of children with spastic cerebral palsy. Complement Ther Clin Pract. 2008;14(1):33–37. doi: 10.1016/j.ctcp.2007.11.001. PMID: 18243940. [DOI] [PubMed] [Google Scholar]
- 27.Arun Raj G.R., Shailaja U., Rao P.N., Pujar M.P., Srilakshmi M.K. Effectiveness of Ayurveda treatment modalities in the management of spasticity in children with cerebral palsy at a tertiary care teaching hospital of Southern India. Int J Res Ayurveda Pharm. 2018;9(2):96–100. doi: 10.7897/2277-4343.09242. [DOI] [Google Scholar]
- 28.Shailaja U., Rao P.N., Girish K.J., Arun Raj G.R. Clinical study on the efficacy of Rajayapana Basti and Baladi Yoga in motor disabilities of cerebral palsy in children. Ayu. 2014;35(3):294–299. doi: 10.4103/0974-8520.153748. PMID: 26664239; PMCID: PMC4649573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Wong V., Sun J.G., Wong W. Traditional Chinese medicine (tongue acupuncture) in children with drooling problems. Pediatr Neurol. 2001;25(1):47–54. doi: 10.1016/s0887-8994(01)00292-2. PMID: 11483396. [DOI] [PubMed] [Google Scholar]
- 30.Upasana Sonker, Mahapatra Arun Kumar, Rajagopala S. The Effect of Murcchita Tila Taila Based Panchakarma Procedure and Balapanchamrita Yoga in the Management of Cerebral Palsy in Children. A Single Arm Prospective Clinical Trial. AYUSHDHARA. 2020;7(6):3004–3008. [Google Scholar]
- 31.Bohannon R.W., Smith M.B. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987;67(2):206–207. doi: 10.1093/ptj/67.2.206. PMID: 3809245. [DOI] [PubMed] [Google Scholar]
- 32.Bishop F.L., Prescott P., Chan Y.K., Saville J., von Elm E., Lewith G.T. Prevalence of complementary medicine use in pediatric cancer: a systematic review. Pediatrics. 2010;125(4):768–776. doi: 10.1542/peds.2009-1775. PMID: 20308209. [DOI] [PubMed] [Google Scholar]