Feature and Review Paper
Non-pharmacological interventions to manage fatigue and psychological stress in children and adolescents with cancer: an integrative review ~o Paulo at Ribeira ~o Preto College of Nursing – L.C. LOPES-JUNIOR, RN, MSC, PHD CANDIDATE, University of Sa ~o Preto, SP, Brazil, E.O. USP, WHO Collaborating Centre for the Development of Nursing Research, Ribeira BOMFIM, RN, MSC, PHD CANDIDATE, University of Saskatchewan at College of Medicine – UofS, Saskatoon, SK, Canada, L.C. NASCIMENTO, RN, PHD, ASSOCIATE PROFESSOR, Department Maternal-Infant Nursing and Public ~o Paulo at Ribeira ~o Preto College of Nursing – USP, Ribeira ~o Preto, SP, M.D.R. NUNES, Health, University of Sa RN, MSC, PHD, ADJUNCT PROFESSOR, Rio de Janeiro State University, College of Nursing – UERJ, Rio de Janeiro, RJ, G. PEREIRA-DA-SILVA, BS IN BIOLOGY, PHD, ASSOCIATE PROFESSOR, Department Maternal-Infant Nursing and Public ~o Paulo at Ribeira ~o Preto College of Nursing – USP, Ribeira ~o Preto, SP, & R.A.G. LIMA, Health, University of Sa ~o Paulo at RN, PHD, FULL PROFESSOR, Department Maternal-Infant Nursing and Public Health, University of Sa ~o Preto College of Nursing – USP, Ribeira ~o Preto, SP, Brazil Ribeira LOPES-JUNIOR L.C., BOMFIM E.O., NASCIMENTO L.C., NUNES M.D.R., PEREIRA-DA-SILVA G. & LIMA R.A.G. (2016) European Journal of Cancer Care 25, 921–935 Non-pharmacological interventions to manage fatigue and psychological stress in children and adolescents with cancer: an integrative review
Cancer-related fatigue (CRF) is the most stressful and prevalent symptom in paediatric oncology patients. This integrative review aimed to identify, analyse and synthesise the evidence of nonpharmacological intervention studies to manage fatigue and psychological stress in a paediatric population with cancer. Eight electronic databases were used for the search: PubMed, Web of Science, CINAHL, LILACS, EMBASE, SCOPUS, PsycINFO and the Cochrane Library. Initially, 273 articles were found; after the exclusion of repeated articles, reading of the titles, abstracts and the full articles, a final sample of nine articles was obtained. The articles were grouped into five categories: physical exercise, healing touch, music therapy, therapeutic massage, nursing interventions and health education. Among the nine studies, six showed statistical significance regarding the fatigue and/or stress levels, showing that the use of the interventions led to symptoms decrease. The most frequently tested intervention was programmed physical exercises. It is suggested that these interventions are complementary to conventional treatment and that their use can indicate an improvement in CRF and psychological stress. Keywords: cancer-related fatigue, psychological stress, non-pharmacological intervention, symptom management, paediatric oncology.
Correspondence address: Luis Carlos Lopes-J unior, University of S~ao Paulo at Ribeir~ ao Preto College of Nursing – USP, WHO Collaborating Centre for the Development of Nursing Research, Av. Bandeirantes, 3900, Ribeir~ ao Preto, SP 14040-902, Brazil (e-mail:
[email protected]).
Accepted 3 August 2015 DOI: 10.1111/ecc.12381 European Journal of Cancer Care, 2016, 25, 921–935
© 2015 John Wiley & Sons Ltd
I N TR O DU C TI O N Cancer-related fatigue (CRF) has been described as the most prevalent symptom in patients and survivors reported by both adults, and children and adolescents with cancer population (Stasi et al. 2003; Gordijn et al. 2013; Saligan et al. 2015). In the paediatric oncologic popula-
LOPES-JUNIOR ET AL.
tion, CRF affects between 35.6% (Collins et al. 2000) and 93% of the cases (Enskar & Von Essen 2007), with higher levels of fatigue experienced by those undergoing chemoradiation and chemotherapy if compared to those who are receiving the radiotherapy alone (Karthikeyan et al. 2012; Lopes-J unior et al. 2015a). The National Comprehensive Cancer Network (NCCN) defines CRF as a persistent symptom, a subjective sense of physical, emotional and cognitive fatigue or exhaustion related to cancer or its treatment, which is not proportional to the activity recently undertaken, which could interfere in the patient’s usual functional capacity (NCCN 2011). Children and adolescents consistently report CRF as one of the most persistent, uncomfortable and stressful symptoms related to cancer and its treatment (Hockenberry et al. 2011; Daniel et al. 2013; Lopes-J unior et al. 2015b). The Fatigue Adaptation Model (FAM) presents a framework for the study of fatigue, which refers to a possible link between behavioural and physiological indices of tiredness, fatigue and exhaustion as they occur in both ill and non-ill states. The central thesis of this approach is that stressors related to the disease processes in cancer and its treatment declines the cognition, the sleep quality, the nutrition and the muscle endurance. This decline inhibits the ability to adapt to stressors increasing the risk to develop fatigue. Due to this fact, fatigue is considered a stress response and defined as a marker for the inability to adapt to stressors caused by the disease and treatment (Olson et al. 2008). The FAM is the rational framework of this article because it provides the conceptual basis to support the association between stress and fatigue and consider stress as a key element in the development of fatigue rather than consider stress and fatigue as distinguished endpoints (Olson 2007; Olson et al. 2008). In healthy individuals, stressors induce an adaptive response to maintain homoeostasis. However, in cancer, the body’s ability to generate an adaptive response to stressors related to disease is challenging and this inability is marked by the onset of fatigue and a decline in quality of life (Olson 2007; Olson et al. 2008). Stressors frequency and magnitude varies with the course of the disease. Fatigue exerts a significant adverse effect on the functional and psychosocial capacity, reducing the cancer patients’ quality of life (Patterson et al. 2009). The risk factors for CRF have not been well established yet, but recent study have suggested stress as one of the main factors related to the development, intensity and latency of CRF (Bower et al. 2013). A current study with the aim to assess whether the exposure to stress during childhood and across the lifetime was associated with fatigue in breast cancer sur922
vivors stated that the cancer survivors who experienced fatigue reported significant higher levels of exposure to cumulative stress when compared to a control group of survivors without fatigue. These results suggest that stress can be a possible risk factor for CRF and indicate that stress associated with CRF should also be a target of non-pharmacological and, if necessary, pharmacological treatment (Bower et al. 2013). Psychological stress is a construction of meaning related to situations that cause damage or loss or that threaten the subject’s wellbeing, or to situations that represent a challenge. The experience of psychological stress is particular and its meaning varies from individual to individual, depending on its subjectivity and interaction with the environment (Modia 2008). Cancer and the hospitalisation process often have a psychological impact on the children and adolescents, usually leading to intense stress (Kaminski et al. 2002; Barlow & Durand 2005). Various interventions have been used to manage fatigue and psychological stress in cancer patients (Chang et al. 2013). The NCCN indicates that during aggressive treatments with long-term follow-up or in temporal phases of tumours, non-pharmacological interventions should be complementary to the pharmacological treatments (NCCN 2011). Regarding the pharmacological interventions, the use of psychostimulant drugs has shown to be a promising option for the treatment of CRF as part of a multimodal therapy (e.g. methylphenidate) (Kerr et al. 2012). In addition, erythropoietin stimulants for the correction of anaemia and corticoids have also been used (Campos et al. 2011). The non-pharmacological practices include: natural products (e.g. dietary supplements), mind and body medicine (e.g. yoga, cognitive-behavioural therapy), manipulative and body-based practices (e.g. massage therapy), and other complementary and alternative medicine (CAM) practices (e.g. healing touch, HT) (National Center for Complementary and Alternative Medicine 2012). Researchers confirm that most patients with fatigue will benefit from some non-pharmacological intervention along the disease treatment (McGregor & Antoni 2009). A recent systematic review and meta-analysis aimed at summarising the best scientific evidence available between 1960 and 2010 regarding the effect of non-pharmacological interventions to control fatigue in children and adolescents with cancer, identified six studies that showed statistical significance for interventions that used physical exercise to reduce fatigue in this population [effect magnitude = 0.76; CI95% = ( 1.35, 0.17)] (Chang et al. 2013). In summary, results of a growing number of reviews have reported the use of different non-pharmacological © 2015 John Wiley & Sons Ltd
Non-pharmacological interventions to manage symptoms
interventions, including nursing interventions for the management of fatigue in both adult and paediatric population (Ekti & Conk 2008; Patterson et al. 2009; Chang et al. 2013). However, so far, the psychological stress associated with the experience of CRF symptom has not been addressed in any review in the paediatric oncology population. Hence, the purpose of this integrative review was to identify, analyse and synthesise the evidence of non-pharmacological intervention studies to manage fatigue and psychological stress in the paediatric population with cancer. We intend to offer support for future researchers and improve the support for health professionals and particularly nurses’ reflections about the awareness of use of non-pharmacological health care interventions, with a view to provide evidence to apply these practices and to demystify their use. METHODS Design and criteria for including the studies This study is an integrative review of the literature regarding non-pharmacological interventions to manage fatigue and psychological stress in children and adolescents with cancer. An integrative review is used to synthesise current evidence in a particular area when published studies used a variety of different designs to address a particular problem (Whittemore & Knafl 2005). The eligibility of the articles was assessed and references were selected according to the research question of the review. The following inclusion criteria were applied: 1. The primary focus of the article was about the use of non-pharmacological interventions to reduce fatigue and psychological stress in children and adolescents with cancer. 2. Full papers published between January 2000 and December 2013, in English, Spanish and Portuguese. 3. Studies whose samples were comprised of children and adolescents between 0 and 19 years of age, in any phase of the treatment. 4. Studies that used a validated tool to assess the construct. The following exclusion criteria were applied: 1. Non-peer reviewed literature was excluded from the review. This included editorials, thesis, dissertations, letters to the editor, government reports, reflective studies, case reports and annals of scientific events (abstracts). 2. Experimental animal studies were also excluded. © 2015 John Wiley & Sons Ltd
Search strategy The aim of the review was deconstructed into the PICOS strategy to ensure the systematic search of the available literature (Doig & Simpson 2003; Centre for Reviews and Dissemination 2009). In addition, the inclusion and exclusion criteria were developed based on the PICOS strategy (O’Connor et al. 2011): Population (P), Intervention (I), Comparison (C), Outcome (O) and Study design (S). In our review, we established Population (P) as being consisted of children and adolescents with cancer; Intervention (I): studies that evaluate the effect of non-pharmacological interventions for the management of CRF and psychological stress; Comparison (C): studies that compared nonpharmacological intervention with another type of intervention to manage those symptoms or with a control group not receiving the intervention assessed; Outcomes (O): levels of CRF and psychological stress manifested after the use of non-pharmacological interventions; and Study design (S) included all the designs except cross-sectional studies, surveys and qualitative studies. The studies for this review were selected through the Internet and eight electronic databases were used for the search: (1) Medical Literature Analysis and Retrieval System Online (MEDLINE) via PubMED; (2) Literatura de Latino-Americana e do Caribe em Ci^ encias da Sau (LILACS); (3) Cumulative Index to Nursing and Allied Health Literature (CINAHL); (4) Excerpta Medica (EMBASE); (5) Cochrane Library; (6) SCOPUS; (7) Web of Science and (8) PsycINFO. The primary studies were located in June 2013 and were updated in December 2013. To organise and manage the references, the bibliographic technology EndNote (https://www.myendnoteweb.com/) was used to store the entire search. We were also able to enlist the help of a librarian from the University of S~ ao Paulo with great expertise in bibliographic searches and review methods. Initially, the existence of key terms and their synonyms was verified in each of the eight databases. Nine key terms were used to build the search strategy: “fatigue; cancer-related fatigue; cancer; neoplasm; stress, psychological; child; adolescent; complementary alternative medicine and non-pharmacological interventions”. Next, the primary studies were located with the help of advanced search tools, in which the search terms were crossed and combined using the Boolean operators “AND” and “OR” (Lefebvre et al. 2011). The two reviewers, both nurse researchers with a background in paediatric oncology, worked independently on the following review phases: selection of the articles (based on the established inclusion and exclusion criteria),
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scored as 1 and the overall score was calculated by the total of the scores and converted into percentages for ease interpretation. Scoring was performed by two reviewers and was supervised by a third one. Table 2 presents the methodological assessment of the studies included in the review.
Table 1. Hierarchy of evidence (Melnyk & Fineout-Overholt 2011) Level of evidence I II III IV V VI VII
Study design Systematic reviews and meta-analysis of RCT RCT Non-randomised controlled trial (quasi-experiment) Case–control or cohort studies Systematic reviews of qualitative or descriptive studies Qualitative or descriptive studies Opinion of authorities and/or reports of expert committees
Data extraction The Ursi and Galv~ ao (2006) tool was adopted to extract the data from the studies. It has also been used in earlier studies (Silveira et al. 2010; Vasconcelos et al. 2011; Vilar et al. 2013). To decide which articles should be included, two reviewers (L.C.L.J. and E.O.B.) independently screened the titles and assessed study quality using the above-mentioned tool. Two independent Microsoft Excel spreadsheets were developed to summarise the extracted data. After that phase, the databases were combined to build a single database. The adopted tool consists of three domains: (1) Identification of the study (article title; journal title; authors; country of the study; language; publication year); (2) Host institution of the study (hospital; university; research centre; single institution; multicentre study; other institutions involved; non-identified location); (3) Methodological characteristics of the study (study design; study objective or research question; sample characteristics, e.g. sample size, gender, age, race; age of diagnosis; type of tumour, location, and treatment; data treatment; type of intervention; results; data analysis; implications for nursing practice; evidence levels).
RCT, randomised controlled trials.
data extraction and data analysis. In case of disagreement in any of the phases, new readings took place followed by discussions between the researchers until a consensus was reached.
Hierarchy of evidence The primary studies were read in detail and their contents were critically analysed according to Melnyk and FineoutOverholt (2011) (Table 1). The evidence level of the studies was identified based on the study design and classified as follows: levels I and II were classified as strong, III to V as moderate and VI to VII as weak (Melnyk & FineoutOverholt 2011).
Methodological assessment The methodological quality of the selected studies were assessed using the generic quantitative appraisal tool developed by Law et al. and modified by Machotka et al. (2009). This modified tool has 12 criteria representing key elements to assess the methodological quality of the studies. Each statement of the tool was
Data analyses In view of clinical heterogeneity among the included studies and their methodological limitations, authors decided that summary statistical calculation would be
Table 2. Methodological quality of studies Criteria Study
1
2
3
4
5
6
7
8
9
10
11
12
Score
%
Hinds et al. (2007) Kemper et al. (2008) Ekti and Conk (2008) Keats and Culos-Reed (2008) Takken et al. (2009) Post-White et al. (2009) Kemper et al. (2009) Yeh et al. (2011) Wong et al. (2013)
Y Y Y Y Y Y Y Y Y
Y Y Y Y Y Y Y Y Y
Y Y Y Y Y Y Y Y Y
N N N N N N N N N
Y NR Y Y Y Y NR Y Y
Y Y Y Y Y Y Y Y Y
NR NA NR Y NR Y Y Y Y
Y Y Y Y Y Y Y Y Y
Y Y Y Y Y Y Y Y Y
Y Y Y Y Y Y N Y Y
Y Y N N Y Y N Y Y
Y Y Y Y Y Y Y Y Y
10/12 9/12 9/12 10/12 10/12 11/12 8/12 11/12 11/12
83.33 75.00 75.00 83.33 83.33 91.66 66.66 91.66 91.66
1 = Study purpose reported; 2 = Relevant background literature; 3 = Sample description; 4 = Sample size justification; 5 = Reliable and valid outcome measures; 6 = Intervention description; 7 = Contamination and co-intervention; 8 = Statistical significance; 9 = Appropriate analysis method(s); 10 = Clinical importance; 11 = Drop outs; 12 = Appropriate conclusions. N, no; NA, not applicable; NR, not reported; Y, yes.
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Non-pharmacological interventions to manage symptoms
273 records searching
identified
through
PubMED SCOPUS EMBASE Cochrane library Web of Science PsucINFO CINAHL LILACS Other sources (Google Scholar e.g)
database
106 51 49 27 15 12 09 04 00
182 records after duplicates removed
23 full-text articles assessed for eligibility
91 records duplicates
159 records excluded after reading of the title and abstract
14 full-text articles excluded due to lack of relation with the theme or no relation to the research question
9 studies included in descriptive and qualitative synthesis
Figure 1. Flow chart of study selection for integrative review.
inappropriate. Hence, study results were presented descriptively according to their outcomes. RESULTS Study selection Initially, 273 articles were retrieved. Among them, 91 duplicated articles were located and excluded. After detailed reading of the 182 records regarding their titles and abstracts, 159 publications were excluded, resulting in 23 full-text articles which were assessed for eligibility. These 23 articles were fully read to identify those that were included in the final sample. After this selection, nine articles were included in the final sample and authors proceed to the detailed reading phase of the articles (Fig. 1). In this last phase, the specific data collection instrument was completed (Silveira et al. 2010).
Study characteristics and quality of the studies The final sample of this integrative review consisted of nine studies. Table 3, presents the studies in a chronological order, according to their title, authors, origin, journal, year of publication, language, database from which the study was accessed, study category, study design and evidence level. The studies included were published between 2007 and 2013. Most of the studies were conducted in the United States of America (Hinds et al. 2007; Kemper et al. © 2015 John Wiley & Sons Ltd
2008, 2009; Post-White et al. 2009; Wong et al. 2013). The authorship of most studies (six) pertain to nurses and physicians (Hinds et al. 2007; Ekti & Conk 2008; Kemper et al. 2009; Post-White et al. 2009; Yeh et al. 2011; Wong et al. 2013). Other professional categories included were physical therapist, psychologist, statistician and biomedical engineer (Keats & Culos-Reed 2008; Kemper et al. 2008; Takken et al. 2009). The most used methodological design was the randomised controlled trials (Evidence level II) which was applied in four studies (Hinds et al. 2007; Ekti & Conk 2008; Post-White et al. 2009; Wong et al. 2013). Three studies were quasi-experimental (Level III) (Keats & Culos-Reed 2008; Takken et al. 2009; Yeh et al. 2011) and two were prospective cohort studies (Level IV) (Kemper et al. 2008, 2009). Four studies were classified as level II; three as level III and two as evidence level IV. Therefore, according to the evidence level, this integrative review presents most of its studies classified as strong (levels I or II) or moderate (levels III, IV or V) and none classified as weak evidence levels (VI and VII) (Melnyk & FineoutOverholt 2011). The number of patients included in the nine studies’ sample ranged from 9 to 63 and the participants’ age ranged from 1 to 18 years old. The research participants were either outpatients or hospitalised patients. The most prevalent cancer types in the review sample were acute lymphoid leukaemia (ALL), solid tumour, 925
926
Takken et al. (2009)
Post-White et al. (2009)
05
06
Yeh et al. (2011)
Keats and Culos-Reed (2008)
04
08
Ekti and Conk (2008)
03
Kemper et al. (2009)
Kemper et al. (2008)
02
07
Hinds et al. (2007)
Authors
01
Study number
A pilot study to examine the feasibility and effects of a home-based aerobic programme on reducing fatigue in children with acute lymphoblastic leukaemia
Impact of healing touch on paediatric oncology outpatients: pilot study
Impact of music on paediatric oncology outpatients Impact of effective nursing interventions to the fatigue syndrome in children who receive chemotherapy A community-based physical activity programme for adolescent with cancer (Project TREK) Development, feasibility and efficacy of a community-based exercise training programme in paediatric cancer survivors Massage therapy for children with cancer
Clinical field testing of an enhanced-activity intervention in hospitalised children with cancer
Title
Taiwan
USA
PubMED SCOPUS Web of Science PubMED CINAHL Web of Science SCOPUS
PubMED Cochrane Web of Science
PubMED Web of Science SCOPUS PsycINFO
The Netherlands
USA
PubMED Web of Science SCOPUS
Canada
Turkey
PubMED PsycINFO SCOPUS PubMED Cochrane CINAHL
PubMED Cochrane CINAHL
USA
USA
Database
Country
Physical exercises
Healing touch
Quasiexperiment (pilot)
Prospective cohort (pilot)
RCT (crossover)
Quasiexperiment (pre-/posttest)
Physical exercises
Massage therapy
Quasiexperiment
RCT
Prospective cohort
Prospective RCT (pilot)
Study design
Physical exercises
Nursing Interventions
Music therapy
Physical exercises
Study category
To examine the feasibility of a home-based aerobic exercise intervention to reduce fatigue in children with acute lymphoblastic leukaemia
III
IV
II
III To develop an exercise training programme and to study the feasibility and efficacy of this exercise programme in children who survived acute lymphoblastic leukaemia To determine the feasibility of providing massage to children with cancer to reduce symptoms in children and anxiety in parents To assess the healing touch effects in paediatric oncology patients
III
II
IV
II
Evidence level
To examine the feasibility of a theoretically based physical activity intervention in adolescents with cancer
To assess the feasibility of an enhanced physical activity intervention in hospitalised children and adolescents receiving treatment for a solid tumour or for acute myeloid leukaemia To assess music’s effect on paediatric oncology outpatients To detect the impact of appropriate nursing interventions on decreasing the fatigue syndrome
Aim
Table 3. Studies included in the integrative review according to title, authors, country of development, journal and year of publication, language, database, study category, study design and evidence level
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Healing touch (HT)
RCT (prospective)
Evaluated the feasibility of administering HT in paediatric oncology inpatient and outpatient units at Kapi’s Olani Medical Center for Women and Children
II
acute myeloid leukaemia and lymphoma. The disease stage varied in these studies. While some patients had just received the first chemotherapy cycle (Hinds et al. 2007; Ekti & Conk 2008), some had completed two treatment cycles (Takken et al. 2009) and others had entered in the remission phase (Keats & Culos-Reed 2008). The intervention methods included exercise training programme or enhanced physical activity – EPA (Hinds et al. 2007; Keats & Culos-Reed 2008; Takken et al. 2009; Yeh et al. 2011), HT (Kemper et al. 2009; Wong et al. 2013), music therapy (Kemper et al. 2008), massage therapy (Post-White et al. 2009) and effective nursing interventions and health education (Ekti & Conk 2008). These interventions occurred in three different environments: at home (Takken et al. 2009), in the community (Keats & Culos-Reed 2008) or in the hospital (Hinds et al. 2007; Ekti & Conk 2008; Kemper et al. 2008, 2009; Takken et al. 2009; Yeh et al. 2011; Wong et al. 2013). In total, five studies assessed the intervention and it is impact on fatigue (Hinds et al. 2007; Ekti & Conk 2008; Keats & Culos-Reed 2008; Takken et al. 2009; Yeh et al. 2011), two studies assessed stress and other symptoms except fatigue (Kemper et al. 2008, 2009), and two others assessed fatigue and stress, among other symptoms (PostWhite et al. 2009; Wong et al. 2013). The following fatigue measuring instruments were used in these studies: Pediatric Quality of Life Multidimensional Fatigue Scale – PedsQL-MFS (Varni et al. 2007), the Childhood Fatigue Scale (CFS) (Hockenberry et al. 2003), the Checklist Individual Strength (Pizzo & Poplack 2006), the Fatigue Scale – Child (FS-C) for 7–12 years olds (Hockenberry et al. 2003) and the Fatigue Scale for 13–18 years olds (FS-A) (Hockenberry et al. 2003).
PubMED EMBASE Cochrane PsycINFO
© 2015 John Wiley & Sons Ltd
Integrated results according to the thematic categories
RCT, randomised controlled trials.
USA The impact of healing touch on paediatric oncology patients 09
Wong et al. (2013)
Country Title Authors Study number
Table 3. Continued
Database
Study category
Study design
Aim
Evidence level
Non-pharmacological interventions to manage symptoms
The articles were grouped into categories which were, in turn, established based on the analysis of the data extracted: four studies in the physical exercise category which evaluated their impact on fatigue (Hinds et al. 2007; Keats & Culos-Reed 2008; Takken et al. 2009; Yeh et al. 2011), two studies in the HT category which assessed its impact on fatigue and stress levels, (Kemper et al. 2009; Wong et al. 2013), one study in the music therapy category which evaluated its impact on stress (Kemper et al. 2008), one in the massage therapy category which assessed its impact on fatigue (Post-White et al. 2009), and one in the effective nursing intervention and health education category which evaluated its impact on fatigue (Ekti & Conk 2008). 927
928
Ekti and Conk (2008)
Keats and Culos-Reed (2008) Takken et al. (2009)
Post-White et al. (2009)
Kemper et al. (2009)
Yeh et al. (2011)
03
04
06
07
08
Sample
Children with cancer, N = 60, age between 7 and 12 years Survivors of ALL, N = 9, age between 6 and 14 years Children/adolescents with cancer, N = 17, age between 1 and 18 years Children/adolescents with cancer, N = 9, age between 1 and 18 years Children/adolescents with cancer, N = 22, age between 1 and 18 years Children/adolescents with cancer, N = 9, age between 3 and 18 years
Children/adolescents with cancer, N = 29, age between 7 and 18 years Children/adolescents with cancer, N = 63, age between 1 and 18 years Children with cancer, N = 60, age between 7 and 12 years
Healing touch
Physical exercises
Fatigue/ PedsQL-MFS
Fatigue/my Fatigue Meter Stress/WBFS
Healing touch
Massage therapy
Physical exercises
Physical exercises
Nursing interventions
Music therapy
Physical exercises
Delivered method
Stress/VAS
Fatigue/PPS CFS
Fatigue/CSI-20
Fatigue/PedsQlMFS
Fatigue/FS-C FS-P
Stress/VAS
Fatigue/FS-C; FS-A FS-P; FS-S
Variables/ instruments Intervention
One group with HT and the control group received reading activities/games
6 weeks training at home with aerobics exercises
2 visits of 40 min (one with HT and one with rest only)
4 weeks of massage therapy
12 weeks of physical exercises
16 weeks of physical exercises
Effective nursing interventions
30 min of physical exercises twice daily for 2–4 days of hospitalisation 2 visits (one with music + rest and one with rest only)
Yes
Yes
Patients acted as their own controls
Yes
No
No
Male and female
Male and female
Male and female
Male and female
Male and female
Male and female
Male and female
Statistically significant differences in VAS scores between the groups Statistically significant differences in general fatigue scores between the groups Statistically significant differences in general fatigue scores between the groups
No significant difference between the groups
Statistically significant differences in VAS scores for stress between the groups Statistically significant differences in FS-C scores between the groups Significant differences in short and long-term effects No significant difference after the training
Male and female
Patients were analysed as their own controls Yes
Outcomes No significant difference between the groups
Male and female
Control group Patients acted as their own controls
Gender of the sample
RCT, Randomised Controlled Trial; FS-C, Fatigue Scale for children; FS-A, for adolescents; FS-P, for parents; FS-S, and for staff; VAS, Visual Analogue Scale; HT, Healing Touch; HRV, Heart Rate Variability; CFS, Childhood Fatigue Scale; PedsQL-MFS, Pediatric Quality of Life Inventory Multidimensional Fatigue Scale; CSI-20, Children’s Somatization Inventory; PPS, Palliative Performance Scale; WBFS, Wong-Baker Faces Scale.
09
Wong et al. (2013)
Kemper et al. (2008)
02
05
Hinds et al. (2007)
Author/year
01
Study number
Table 4. Final and integrated synthesis of studies included in the review of non-pharmacological interventions for fatigue and/or stress management in children and adolescents with cancer
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Non-pharmacological interventions to manage symptoms
Among the nine studies, six showed statistical significance on fatigue scores and/or stress levels demonstrating that the use of the interventions led to a decrease in the symptoms and positive results (Ekti & Conk 2008; Keats & Culos-Reed 2008; Kemper et al. 2009; Post-White et al. 2009; Yeh et al. 2011; Wong et al. 2013). The massage therapy intervention did not demonstrate a significant effect on fatigue scores between the experimental group and the control group. It was, however, more effective than in the control group to reduce the heart rate (P = 0.02) and anxiety in children under 14 years of age (P < 0.05) and in the parents (P < 0.05) (Post-White et al. 2009). The most frequent tested intervention using different CRF management methods involved exercise training programmes or EPA. In the present review, 44.4% of the final sample assessed the feasibility and effectiveness on physical activities on symptoms (Hinds et al. 2007; Keats & Culos-Reed 2008; Takken et al. 2009; Yeh et al. 2011). The Table 4 presents a summary of the studies included in this review, grouped into the five thematic categories.
D I S C U S S I ON The aim of this integrative review was to analyse the evidence from the studies about the use of non-pharmacological interventions to manage fatigue and psychological stress in children and adolescents with cancer. Although interventions for CRF and psychological stress in adults have been widely assessed, most of the studies involving child and adolescents with cancer are pilots or feasibility studies (Patterson et al. 2009). Evidence on effective strategies for CRF management during treatment remains limited (Yeh et al. 2011; Chang et al. 2013). Non-pharmacological interventions, including counselling and education, or pharmacological management (for pain, medicines to sleep or anaemia treatment) are general strategies to control CRF (NCCN 2011). A systematic review of studies that used physical exercise as a non-pharmacological intervention has shown that this intervention is a promising strategy to reduce fatigue in adult patients during and after the oncology treatment, with greater efficacy than psychosocial interventions (Cramp & Daniel 2008). In addition, other strategies, besides physical exercise such as the promotion of sleep, education and counselling, or distraction and relaxation, have to be useful to reduce fatigue in adults undergoing oncologic treatment (Kangas et al. 2008). As presented in our results, a study (study 1) on an EPA for hospitalised children with cancer demonstrated that there were no differences in fatigue levels between the intervention and control groups. The sleep duration was © 2015 John Wiley & Sons Ltd
longer in the intervention group (Ekti & Conk 2008). Another study (study 5) also indicated that the exercise training programme did not affect the muscle strength, exercise capacity, functional mobility or fatigue between the pre- and post-training phases (Post-White et al. 2009). When well-structured and supervised, exercise training has shown to be effective to increase the functional capacity and improve the quality of life in adult cancer survivors (Lucia et al. 2003). Several pilot studies using aerobic training have been developed with cancer patients and have shown better functional mobility (Marchese et al. 2004; San Juan et al. 2007a; Keats & Culos-Reed 2008; Yeh et al. 2011). Hence, aerobic exercise, in particular, is recommended as a strategy in which parents can accompany their children, given that it has been shown to improve the physical function and reduce the CRF. Motivating children and adolescents to adhere to an exercise training programme represents a challenge, due to the high dropout rate reported in some studies (Marchese et al. 2004; San Juan et al. 2007a,b). The authors emphasised that some of the barriers to physical training are: stage of the disease, the age of the children, the variety of exercises, the location of implementation, and especially for a greater adherence, the views and motivation of the parents to execute a physical activity programme (Marchese et al. 2004; San Juan et al. 2007b; Keats & Culos-Reed 2008; Yeh et al. 2011). A study undertaken in Taiwan (study 8) indicated that the intervention involving home-based aerobic activity to reduce CRF produced a positive effect and was feasible to be implemented in children with ALL in the maintenance phase, at least for short periods. The results indicated that the patients from the intervention group tended towards lower general fatigue levels than patients from the control group during 1 month of follow-up. The high adherence level to this aerobic programme (86%) was due to the parents’ involvement, as they also participated in the study by accompanying the patients in the aerobic activity (Yeh et al. 2011). The large number of dropouts in studies involving exercise training programmes suggests that, at times, it is difficult to keep the children and their parents motivated to complete a home-based exercise training programme. This is especially common because of the highly protective environment and also because some children may evaluate the training as somewhat tiresome (Takken et al. 2009). A review has shown that physical aptitude, aerobic, and anaerobic physical conditioning and knee extensor strength in cancer survivors tend to be reduced in comparison with healthy children (Van Brussel et al. 2006). These changes do not only imply consequences for their 929
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activities of daily living, but also for their health when they reach adulthood. The children treated for cancer are generally shorter, have reduced bone mineral density and are more obese than their healthy peers (Warner et al. 2002; Murphy et al. 2006). In addition, children treated with radiotherapy are particularly at greater risk for obesity which also contributes to greater health risks in adulthood (Takken et al. 2009). The main causes of reduced muscle strength and physical aptitude in cancer survivors are probably due to short- and long-term effects of chemotherapy, such as neuropathy and myopathy (HarilaSaari et al. 2001). The sedentary lifestyle is another contributing factor, as it occurs during and after the treatment of the child and adolescent cancer patients. Also, survivors of ALL have lower daily energy consumption when compared to healthy individuals (Hover-Kramer et al. 2001). Another study involving children who were receiving maintenance chemotherapy for different types of tumours has assessed the effects of a 4-month intervention programme combined with physiotherapy sessions and exercises at home (aerobic training and stretching exercises). The results showed that the ankle dorsiflexion movement and knee extension strength improved significantly after the above-mentioned intervention (Marchese et al. 2004). Another research was undertaken to evaluate an intervention with a 16-week physical exercises training programme for seven children in the treatment maintenance phase against ALL (San Juan et al. 2007a). Its results demonstrated that these patients can safely execute both aerobic and resistance exercises. This training resulted in significant increases in the aerobic aptitude, strength and functional mobility scores. The exercise capacity was partially maintained during training (San Juan et al. 2007a). It should be noted that resting during hospitalisation contributes to fatigue (Hinds et al. 2007), immunosuppression, anorexia, inability to concentrate and that it makes the physical care process more difficult (Fallone et al. 2001). Nurses have used the HT as a complementary therapy based on the millenary technique of hand laying to treat patients with different clinical conditions (Santos et al. 2013b). HT is based on the theory that affirms that if an energy field is present, balanced and flowing appropriately, the patient experiences well-being (Hover-Kramer et al. 2001). In addition, the practitioners can feel this subtle energy and intervene to improve it, using their intention, presence and hands (Wilkinson et al. 2002). The mechanisms for the effects of HT remain obscure, but case reports and some clinical trials suggest that it can be useful to relieve some symptoms such as pain, anxiety and fatigue (Wilkinson et al. 2002; Kemper & Kelly 2004; 930
Wardell & Weymouth 2004; Wardell et al. 2006). A quantitative study that assessed the application of HT to reduce fatigue in oncologic patients demonstrated that the intervention was effective to reduce its intensity with statistically significant results (P = 0.028). In addition, there were lower salivary cortisol levels among the patients treated by an experienced HT physician (Wilkinson et al. 2002). In (study 7) involving a small sample of paediatric oncology patients who experienced low to moderate stress levels, it was demonstrated that when submitted to the specific HT treatment, they presented a reduction in the stress levels and sympathetic excitation (Post-White et al. 2009). In another study conducted at an intensive care unit, the results demonstrated that infants tended to feel less stressed after receiving HT sessions and that they were capable of falling into profound sleep after this type of care (Wilkinson et al. 2002). The results of the clinical trial (study 9) that involved nine children/adolescents between 3 and 18 years old showed significant reductions in pain, stress and fatigue scores of the participants, parents and caregivers in the experimental group (which received TT) (P = 0.0001). Despite the limitations, such as a small sample size (n = 9), the feasibility of using HT in the paediatric oncology population was shown to be promising. These results suggest that the HT positively influence pain, stress and fatigue related to the oncology treatment (Aghabati et al. 2010; Wong et al. 2013). Although the efficacy of the HT has been demonstrated in the adult population, little research exists about the feasibility and efficacy of this non-pharmacological intervention in the paediatric population (Post-White et al. 2009). The effects of music on the autonomic activity and equilibrium in paediatric oncology patients in outpatient care are largely unknown. Many studies on the impact of music has been focused on music therapy, a modality that involves a therapist who performs an assessment, offers individual treatment and seeks feedback to change the interventions needed to achieve the desired results. Given the cost of formal music therapy, many clinics simply use recorded music or a radio to entertain or distract the clients during the clinical visits (Kemper et al. 2009). One investigation (study 2) aimed at identifying whether one type of music could improve the heart rate variability (HRV) and subjective feelings of well-being in paediatric oncology patients at an outpatient clinic. It found similar values on the five parameters of the visual analogue scale (VAS) for the clinical visits for rest purposes and visits using music. No significant differences were found in HRV parameter, except for higher heart © 2015 John Wiley & Sons Ltd
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rates. In such cases, the HRV was about 50% lower with the music than with the rest visit (Kemper et al. 2009). Various possible reasons exist for the lack of differences in the effect of music on subjective well-being in this study. First of all, a ceiling effect may have occurred, which means that the patients may have reported high levels of well-being and low stress levels at the start of the study. Second, the questionnaires of the proxy version the parents answered may not be sensitive enough to the subtle changes in a child’s subjective sense of well-being (Hockenberry et al. 2003; Davis et al. 2007). Finally, short VAS instruments were used instead of longer questionnaires, which could be more sensitive to the statistical tests. Massage therapy consistently stands out among the five most used complementary therapies for children and adolescents with cancer (Post-White et al. 2000; Bold & Leis 2001; McCurdy et al. 2003; Molassiotis & Cubbin 2004). Studies have shown that massage therapy reduces anxiety, depression, and cortisol levels in children and adolescents suffering from depression, post-traumatic stress disorders and juvenile arthritis (Field 2002; Field et al. 2005). In a recent study to assess the efficacy of a massage protocol on pain relief in hospitalised children with cancer, massage therapy was shown to effectively reduce the pain when walking (P < 0.05). After each massage session, the intensity of the pain the child felt decreased (P < 0.001) (Batalha & Mota 2013). The release of endogenous oxytocin, serotonin and dopamine, and salivary and urinary cortisol reductions can bring about the positive effects of massage therapy on pain, stress relief and mood (Lund et al. 2002; Diego et al. 2004; Field et al. 2005; Hernandez-Reif et al. 2005). A study conducted with children submitted to haematopoietic stem cell transplantation (HSCT) had children randomised into two groups: one group receiving professional massage or massage by the parents three times per week and another one (control group) receiving no massage. Children submitted to HSCT experienced less anxiety after the first professional massage (Phipps et al. 2005). Other researchers found that 15-min massage sessions by the parents were effective to reduce anxiety and depression in children with leukaemia (Field et al. 2001). A randomised controlled crossover clinical trial study (study 6) showed that offering massage to children with cancer is feasible and most of them reported that the massage reduced the stress and was relaxing. Although the small sample size reduced the statistical power to detect a significant difference in the highly variable results, such as cortisol, the study provided preliminary evidence for the efficacy of massaging to reduce anxiety in children, © 2015 John Wiley & Sons Ltd
especially for children under 14 years of age (Takken et al. 2009). With regard to the effective nursing interventions and health education for symptom control and relief (study 3), it has been confirmed that nursing professionals act on the frontline of health care management. Their actions are based on a comprehensive care principle and the following nursing interventions were performed: education about fatigue along with the chemotherapy and fatigue handbook developed by the authors; children and mothers were advised on effective interventions and activities that could decrease fatigue; efforts were made to decrease naps in the daytime (the treatment team was asked to avoid waking the child at night as much as possible and to decrease the length of daytime naps); children were supported in doing activities at specific times according to their developmental level and interest, such as reading a book, drawing a picture and listening to music. They were walked in the hallway for 10–15 min at a time for physical activity. They were also informed about nutrition and energy preservation. For a 7-day period, 45–60 min was set aside every day for each child to ask questions about all the instructions they have received and activities they have performed. Nursing professionals perform a leadership role in a critical-reflexive manner and are trained for teaching and education activities because of their technical-scientific background and because they deliver uninterrupted care to the patient (Assega et al. 2015b). Moreover, nurses are in an ideal position to educate oncologic patients and should use their position to suggest the treatment options and the best strategies to relieve persistent symptoms such as psychological stress and CRF to the patients who receive cancer treatment (Fl oria-Santos et al. 2013). Paediatric oncology nursing experts confirm that the experiences with symptoms should be assessed in view of the child’s development and maturity level (Hockenberry & Hinds 2000), keeping in mind the family’s perspective (Ekti & Conk 2008). Although the nurses are involved in the implementation of pharmacological and non-pharmacological interventions to relieve fatigue, they are in a position to start and conduct several types of interventions independently (Patterson et al. 2009). Offering non-pharmacological interventions is one of the scopes of nursing practice as outlined by professional organisations (Canadian and American Nurses Associations and the Brazilian Federal Nursing Council – COFEN, e.g.) and as identified in the NCCN’s best practice guidelines for managing fatigue (Conselho Federal de Enfermagem, 1997; NCCN 2011). 931
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In a review, eight interventions for fatigue management were identified in which nurses can take the leadership and perform them. The interventions were psycho-education, cognitive-behavioural therapy, acupuncture, energy preservation, and management of relaxation activities, such as breathing exercise and distraction, in combination with exercise, education and support. All interventions were implemented by teams of nurse researchers and, except for the cognitive-behavioural therapy; they were all effective to relieve the fatigue (Patterson et al. 2009). In addition, it was demonstrated that psycho-education is the most reported intervention for fatigue management (Patterson et al. 2009). This differs from the conclusions reached in previously published systematic reviews, which suggest physical exercise as the most effective and most frequently recommended non-pharmacological intervention to relieve fatigue (Chang et al. 2013).
L I M I T AT I ON S A limitation of our study to be considered is that some of the studies included in this review are pilot studies. Such studies are not able to detect differences in treatment groups and this may have reflected in the lack of significance in the results of some studies. However, it should be emphasised that it represents an area of study in its initial stage. Furthermore, many studies involving paediatric oncology patients have investigated a range of tumours simultaneously, instead of focusing on a specific tumour type. This is because it is challenging to conduct research with large samples when a specific type of cancer diagnosis is scarce or when the study encompasses a certain treatment phase. Many of the studies included in this review do not also clearly explain the disease or treatment phase, and the majority does not include the treatment variables in the control group. When the mentioned aspects are not considered, they can act as a potential confounders and mask the effectiveness of the evaluated intervention. In addition, it has been suggested that the impact of the intervention can be modulated according to the phase of the treatment that the patient is in and can present different results (Cramp & Daniel 2008). Undoubtedly, the type of diagnosis and treatment can influence the fatigue and stress levels of children and adolescents with cancer (Lopes-J unior et al. 2015a,b; Noia et al. 2015). It is important to consider the chemotherapeutic agents used including the period when general steroids are used and the haematocrit and haemoglobin levels which can, in turn, interfere with the patients’ fatigue experience. 932
PRACTICE IMPLICATIONS In view of the prevalence of the fatigue and psychological stress symptoms in the paediatric oncology population, the evidence shown in this research can be useful in supporting the clinical practices and improving the quality of care for these patients. Identified cases could also be evaluated further for any underlying factors and co-morbidities and treated according to the current NCCN guidelines for CRF. It is important to note that successful symptom management is a multistep and complex process, and attributions of success are difficult. Paramount importance should be given to the multidisciplinary care and to the involvement of patients in decisions about their care (National Breast and Ovarian Cancer Centre (NBOCC) 2008; Assega et al. 2010; Fl oria-Santos et al. 2013; Harish & Kirthi Koushik 2015). The importance of timely multidisciplinary interventions leads to the achievement of care planning that is unlikely to be achieved by health professionals acting in isolation (NBOCC, 2008; Assega et al. 2015a). Furthermore, the results of this research also point to the fact that in the past researchers used to believe that repeated intervention sessions would promote sustained cumulative effects. Nowadays, it has been proven that different dosages of intervention could result in changes in biobehavioural outcomes, such as biological activity, mainly based on the genetic constitution of an individual (Santos et al. 2013a; Lopes-J unior et al. 2015c). It means that it is critical not only to demonstrate the interventions’ efficacy but also to adjust the recommended dosage based on the desired effect; all of these factors are vital to achieve the success of the selected intervention (Wasik et al. 2013).
C ON CL US I ON The nine studies included in this review offer important updates on the non-pharmacological interventions used to manage fatigue and psychological stress in children and adolescents with cancer and complement earlier publications which did not include stress as a variable to be considered in the context of CRF. Considering the evidence level of the studies reviewed, as well as their limitations, mainly regarding the therapies used, the data presented here support those of other studies published and their development helps to gradually build a significant body of evidence for clinical practice. Numerous articles were found that reflect the researchers’ efforts in the search for new evidences and strategies for health care, which allied © 2015 John Wiley & Sons Ltd
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with conventional therapies, can enhance the quality of life of patients, especially for children and adolescents suffering from cancer. Given the persisting gaps on the theme, further research is needed.
ACKNOWLEDGEMENTS This study was supported by the Coordination of Improvement of Higher Education Personnel - CAPES, Brazil.
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