Discussion
In this systematic review, we investigated the efficacy of
non-pharmacological interventions to reduce SCD-related pain in children
with SCD. In half of the ten included studies non-pharmacological
interventions improved pain-related outcomes. These interventions
included CBT and biofeedback in the outpatient setting, and yoga and VR
in the inpatient setting. Despite the heterogeneity of the included
studies, these findings support that the addition of non-pharmacological
interventions to standard medical care seems promising in further
reducing SCD-related pain.
The efficacy of non-pharmacological interventions, and in particular
psychological interventions, has been well described in various pain
conditions.21,22,63-65 In this review, seven of the
included studies investigated psychological interventions. Four of the
seven psychological interventions were successful in reducing pain. Two
of successful psychological interventions included CBT, implying that
this intervention could be useful in targeting SCD-related pain in
children.44,52 One of the CBT studies specifically
looked at the effect of guided imagery. Guided imagery is expected to be
particularly effective in children, because of their capacity for active
and creative imaginations and their high degree of
suggestibility.66 The other three CBT interventions
did not show significant results most likely due to differences in CBT
procedures, despite the fact that CBT has the broadest evidence in
adults with SCD and in patients with other chronic pain conditions.
Schatz. et al focused on electronically delivered CBT. Although authors
did not show statistically significant changes on pain-related outcomes,
smartphone-assisted skill use was associated with a beneficial effect on
next day pain intensity using multilevel modeling.53
In SCD, there are two QED studies examining the effect of biofeedback in
children,45,47 and only one small observational study
in adults.67 In adults, biofeedback did not show any
significant reduction in pain, health service use nor analgesic
use.67 In the outpatient setting, massage therapy was
also described to result in a significant pain reduction in children
with SCD. 50 Although there are two studies with
massage therapy in adults with SCD showing positive results on
SCD-related pain68,69, this effect remains unclear in
children with SCD as the authors did not report any
outcomes50.
In the inpatient setting, yoga and the use of VR showed significant
positive effects on acute pain in the two included
studies.46,49 The effect of yoga on pain reduction was
previously explored in the outpatient setting and in other pain
conditions.70,71 Remarkably, a survey among children
and adolescents with chronic pain, showed that 32% preferred yoga as
first choice of complementary medicine.72 According to
a systematic review about the effect of yoga, nine out of ten RCTs also
reported significant reductions in pain intensity in ambulant
adolescents and adults with a variety of pain conditions including lower
back pain, osteoarthritis and irritable bowel
syndrome.73 The use of VR as a distraction tool may be
an effective, and easy-to-use tool in hospitalized children for a VOC.
VR is especially appealing for children, as they are often more engaged
in magical thinking,74 and become more captivated by
imaginative play.75 Despite the positive results after
VR, this study still needs replication in children with SCD, as the
study was focused on feasibility rather than
efficacy.46 Nevertheless, the efficacy of virtual
reality in reducing acute pain has previously been well described in
children undergoing painful medical procedures and in children
hospitalized with burn injuries.76-79
In several studies, painful early life experiences were associated with
hypersensitivity to pain and allodynia.37,80,81 Pain
experienced during early childhood has been suggested to be a
significant contributor to the development of chronic pain in children
and adults.82,83, 84-86 Meanwhile both the prevalence
and daily opioid dose in SCD patients increase significantly with
age.87-89 Therefore, it is important to reduce opioid
use with non-pharmacological interventions to target this issue. We
address the effect of these interventions by evaluating analgesic and
health service use as outcomes. Only one included study reported reduced
analgesic use,47 and none of the studies reported a
reduced health service use after intervention.44,48-52However, none of the included studies were designed and powered for
these outcomes. Also, most studies had a short or even absent period of
follow-up to measure these outcomes properly. Furthermore, pain in
children in general, is associated with fear of pain, pain anxiety and/
or pain catastrophizing.90 These psychological factors
could have played a role in the maintained use of analgesics and
frequent hospital visits. These psychological effects were not evaluated
in the included studies, so these effects on our outcomes could not be
ruled out.
There are several limitations of this systematic review that need to be
addressed. Due to the heterogeneity of the included studies, firm
conclusions about the effect of non-pharmacological interventions cannot
be drawn. Within the various interventions, there were great differences
with regards to the method or practice. There are no standardized
methods for any of the interventions; there is a lack of methodological
robustness. In addition, our included studies evaluated the
non-pharmacological interventions as add-on intervention. The effect of
the intervention alone has not been studied. Variation in managing pain
pharmacologically between centers, makes the comparison between our
included studies in this systematic review even more difficult. Also,
socio-cultural perceptions, socio-economic status and access to care are
important factors, that affect patient recruitment and may therefore
have biased selection of patients. This may limit the extrapolation and
representativeness of this systematic review.91,92Lastly, the majority of the included studies has small sample sizes
ranging from 8 to 101 participants.
Although significant pain reduction was reported in half of the studies
after non-pharmacological interventions in children with SCD, specific
interventions cannot be strongly recommended yet. We need further
studies that address the different subtypes of SCD-related pain (acute,
daily, chronic). In addition, to achieve more consistency in future
studies, well-designed, adequately-powered studies should incorporate
standardized administration and analysis procedures and for each type of
non-pharmacological intervention, allowing fair comparison and
replication. Lastly, outcome measures such as analgesic use at home and
healthcare use should be considered with an adequate duration of
follow-up, as these measures accurately reflect the home situation of
patients with SCD.
In conclusion, non-pharmacological interventions as a complementary
strategy, have the potential to lead to a faster recovery of SCD-related
pain with a substantial decrease of side effects and complications;
thereby improving quality of life in children with SCD.
Conflict of
interest
The authors have no conflicts of interest to declare.
Acknowledgements
This research did not receive any specific grant from funding agencies
in the public, commercial or not-for-profit sectors. We would like to
thank the medical information specialist René Spijker for performing the
literature search.
References
1 Rees, D. C., Williams, T. N. & Gladwin, M. T. Sickle-cell disease.Lancet (London, England) 376 , 2018-2031,
doi:10.1016/s0140-6736(10)61029-x (2010).
2 Piel, F. B., Steinberg, M. H. & Rees, D. C. Sickle Cell Disease.N Engl J Med 376 , 1561-1573, doi:10.1056/NEJMra1510865
(2017).
3 Eaton, W. A. & Hofrichter, J. Sickle cell hemoglobin polymerization.Advances in protein chemistry 40 , 63-279,
doi:10.1016/s0065-3233(08)60287-9 (1990).
4 Kato, G. J. et al. Sickle cell disease. Nat Rev Dis
Primers 4 , 18010, doi:10.1038/nrdp.2018.10 (2018).
5 Sundd, P., Gladwin, M. T. & Novelli, E. M. Pathophysiology of Sickle
Cell Disease. Annu Rev Pathol 14 , 263-292,
doi:10.1146/annurev-pathmechdis-012418-012838 (2019).
6 Schwartz, L. A., Radcliffe, J. & Barakat, L. P. Associates of school
absenteeism in adolescents with sickle cell disease. Pediatr Blood
Cancer 52 , 92-96, doi:10.1002/pbc.21819 (2009).
7 Yawn, B. P. et al. Management of sickle cell disease: summary
of the 2014 evidence-based report by expert panel members. Jama312 , 1033-1048, doi:10.1001/jama.2014.10517 (2014).
8 Sil, S., Cohen, L. L. & Dampier, C. Pediatric pain screening
identifies youth at risk of chronic pain in sickle cell disease.Pediatric blood & cancer 66 , e27538-e27538,
doi:10.1002/pbc.27538 (2019).
9 Palermo, T. M., Riley, C. A. & Mitchell, B. A. Daily functioning and
quality of life in children with sickle cell disease pain: relationship
with family and neighborhood socioeconomic distress. The journal
of pain : official journal of the American Pain Society 9 ,
833-840, doi:10.1016/j.jpain.2008.04.002 (2008).
10 Hijmans, C. T. et al. Double disadvantage: a case control
study on health-related quality of life in children with sickle cell
disease. Health and quality of life outcomes 8 , 121,
doi:10.1186/1477-7525-8-121 (2010).
11 Darbari, D. S., Ballas, S. K. & Clauw, D. J. Thinking beyond
sickling to better understand pain in sickle cell disease.European Journal of Haematology 93 , 89-95 (2014).
12 Tran, H., Gupta, M. & Gupta, K. Targeting novel mechanisms of pain
in sickle cell disease. Blood 130 , 2377-2385,
doi:10.1182/blood-2017-05-782003 (2017).
13 Graumlich, S. E. et al. Multidimensional assessment of pain in
pediatric sickle cell disease. J Pediatr Psychol 26 ,
203-214 (2001).
14 Brandow, A. M. et al. American Society of Hematology 2020
guidelines for sickle cell disease: management of acute and chronic
pain. Blood advances 4 , 2656-2701,
doi:10.1182/bloodadvances.2020001851 (2020).
15 Hagedorn, J. M. & Monico, E. C. Ketamine Infusion for Pain Control
in Acute Pediatric Sickle Cell Painful Crises. Pediatr Emerg Care35 , 78-79, doi:10.1097/pec.0000000000000978 (2019).
16 Glassberg, J. Evidence-based management of sickle cell disease in the
emergency department. Emergency medicine practice 13 ,
1-20; quiz 20 (2011).
17 Craske, M. Theories of psychotherapy. Cognitive-behavioral
therapy . (2010).
18 Hofmann, S. G., Asnaani, A., Vonk, I. J., Sawyer, A. T. & Fang, A.
The Efficacy of Cognitive Behavioral Therapy: A Review of Meta-analyses.Cognit Ther Res 36 , 427-440,
doi:10.1007/s10608-012-9476-1 (2012).
19 Shen, B. et al. Effects of cognitive behavioral therapy for
patients with rheumatoid arthritis: a systematic review and
meta-analysis. Psychol Health Med , 1-13,
doi:10.1080/13548506.2020.1736312 (2020).
20 Eccleston, C. et al. Psychological therapies for the
management of chronic and recurrent pain in children and adolescents.Cochrane Database of Systematic Reviews 12 , CD003968
(2012).
21 Williams, H. & Tanabe, P. Sickle Cell Disease: A Review of
Nonpharmacological Approaches for Pain. Journal of Pain and
Symptom Management 51 , 163-177 (2016).
22 Anie, K. A. & Green, J. Psychological therapies for sickle cell
disease and pain. The Cochrane database of systematic reviews5 , CD001916, doi:10.1002/14651858.CD001916.pub3 (2015).
23 Yucha, C. B. A. M., Doil D.
24 Loizzo, A., Loizzo, S. & Capasso, A. Neurobiology of pain in
children: an overview. Open Biochem J 3 , 18-25,
doi:10.2174/1874091x00903010018 (2009).
25 Eccleston, C. et al. Delivering transformative action in
paediatric pain: a Lancet Child & Adolescent Health Commission.Lancet Child Adolesc Health , doi:10.1016/s2352-4642(20)30277-7
(2020).
26 Hathway, G. J. Acute and chronic pain in children. Curr Top
Behav Neurosci 20 , 349-366, doi:10.1007/7854_2014_327
(2014).
27 Levy, J., Goldstein, A., Pratt, M. & Feldman, R. Maturation of Pain
Empathy from Child to Adult Shifts from Single to Multiple Neural
Rhythms to Support Interoceptive Representations. Sci Rep8 , 1810, doi:10.1038/s41598-018-19810-3 (2018).
28 Walco, G. A., Krane, E. J., Schmader, K. E. & Weiner, D. K. Applying
a Lifespan Developmental Perspective to Chronic Pain: Pediatrics to
Geriatrics. The journal of pain : official journal of the American
Pain Society 17 , T108-117, doi:10.1016/j.jpain.2015.11.003
(2016).
29 Edwards, R. R., Dworkin, R. H., Sullivan, M. D., Turk, D. C. &
Wasan, A. D. The Role of Psychosocial Processes in the Development and
Maintenance of Chronic Pain. The journal of pain : official
journal of the American Pain Society 17 , T70-92,
doi:10.1016/j.jpain.2016.01.001 (2016).
30 Palermo, T. M., Valrie, C. R. & Karlson, C. W. Family and parent
influences on pediatric chronic pain: a developmental perspective.Am Psychol 69 , 142-152, doi:10.1037/a0035216 (2014).
31 Buttelmann, F. & Karbach, J. Development and Plasticity of Cognitive
Flexibility in Early and Middle Childhood. Front Psychol8 , 1040-1040, doi:10.3389/fpsyg.2017.01040 (2017).
32 Walker, L. S., Dengler-Crish, C. M., Rippel, S. & Bruehl, S.
Functional abdominal pain in childhood and adolescence increases risk
for chronic pain in adulthood. PAIN 150 , 568-572,
doi:https://doi.org/10.1016/j.pain.2010.06.018 (2010).
33 Noel, M., Groenewald, C. B., Beals-Erickson, S. E., Gebert, J. T. &
Palermo, T. M. Chronic pain in adolescence and internalizing mental
health disorders: a nationally representative study. Pain157 , 1333-1338, doi:10.1097/j.pain.0000000000000522 (2016).
34 Mathews, L. Pain in children: neglected, unaddressed and mismanaged.Indian J Palliat Care 17 , S70-73,
doi:10.4103/0973-1075.76247 (2011).
35 Fearon, P. & Hotopf, M. Relation between headache in childhood and
physical and psychiatric symptoms in adulthood: national birth cohort
study. BMJ 322 , 1145, doi:10.1136/bmj.322.7295.1145
(2001).
36 Ranger, M. & Grunau, R. E. Early repetitive pain in preterm infants
in relation to the developing brain. Pain Manag 4 ,
57-67, doi:10.2217/pmt.13.61 (2014).
37 Valeri, B. O. et al. Neonatal Invasive Procedures Predict Pain
Intensity at School Age in Children Born Very Preterm. Clin J
Pain 32 , 1086-1093, doi:10.1097/AJP.0000000000000353 (2016).
38 Porter, F. L., Grunau, R. E. & Anand, K. J. Long-term effects of
pain in infants. Journal of developmental and behavioral
pediatrics : JDBP 20 , 253-261,
doi:10.1097/00004703-199908000-00008 (1999).
39 Boldt, I. et al. Non-pharmacological interventions for chronic
pain in people with spinal cord injury. The Cochrane database of
systematic reviews , Cd009177, doi:10.1002/14651858.CD009177.pub2
(2014).
40 Joanna Briggs Institute Reviewer’s Manual. (2017).
41 Schmidt, N. A. B., J.M. . in Evidence-Based Practice for
Nurses: Appraisal and Application of Research 177-180 (Jones & Barlett
Learning, 2019).
42 Mourad Ouzzani, H. H., Zbys Fedorowicz, and Ahmed Elmagarmid.Rayyan — a web and mobile app for systematic reviews. Systematic
Reviews 2016).
43 Higgins JPT, G. S. e. Cochrane Handbook for Systematic Reviews
of Interventions . Version 5.1.0 edn, (The Cochrane Collaboration,
updated March 2011).
44 Sil, S. et al. Preliminary evaluation of the clinical
implementation of cognitive-behavioral therapy for chronic pain
management in pediatric sickle cell disease. Complementary
Therapies in Medicine 49 , 102348,
doi:https://doi.org/10.1016/j.ctim.2020.102348 (2020).
45 Myrvik, M. P., Campbell, A. D. & Butcher, J. L. Single-session
biofeedback-assisted relaxation training in children with sickle cell
disease. Journal of Pediatric Hematology/Oncology 34 ,
340-343 (2012).
46 Agrawal, A. K. et al. Virtual reality as complementary pain
therapy in hospitalized patients with sickle cell disease.Pediatric Blood & Cancer 66 , e27525 (2019).
47 Cozzi, L., Tryon, W. W. & Sedlacek, K. The effectiveness of
biofeedback-assisted relaxation in modifying sickle cell crises.Biofeedback and self-regulation 12 , 51-61 (1987).
48 Barakat, L. P., Schwartz, L. A., Salamon, K. S. & Radcliffe, J. A
family-based randomized controlled trial of pain intervention for
adolescents with sickle cell disease. J Pediatr Hematol Oncol32 , 540-547, doi:10.1097/MPH.0b013e3181e793f9 (2010).
49 Moody, K. et al. A Randomized Trial of Yoga for Children
Hospitalized With Sickle Cell Vaso-Occlusive Crisis. J Pain
Symptom Manage 53 , 1026-1034,
doi:10.1016/j.jpainsymman.2016.12.351 (2017).
50 Lemanek, K. L., Ranalli, M. & Lukens, C. A randomized controlled
trial of massage therapy in children with sickle cell disease.Journal of Pediatric Psychology 34 , 1091-1096 (2009).
51 Gil, K. M. et al. Daily coping practice predicts treatment
effects in children with sickle cell disease. J Pediatr Psychol26 , 163-173 (2001).
52 Dobson, C. E. & Byrne, M. W. Original research: using guided imagery
to manage pain in young children with sickle cell disease.American Journal of Nursing 114 , 26-36; test 37, 47
(2014).
53 Schatz, J. et al. Changes in coping, pain, and activity after
cognitive-behavioral training: a randomized clinical trial for pediatric
sickle cell disease using smartphones. Clinical Journal of Pain31 , 536-547 (2015).
54 Thomas, V. Cognitive behavioural therapy in pain management for
sickle cell disease. International Journal of Palliative Nursing6 , 434-442 (2000).
55 McClellan, C. B. et al. Use of handheld wireless technology
for a home-based sickle cell pain management protocol. J Pediatr
Psychol 34 , 564-573, doi:10.1093/jpepsy/jsn121 (2009).
56 Yaster, M., Kost-Byerly, S. & Maxwell, L. G. The management of pain
in sickle cell disease. Pediatric Clinics of North America47 , 699-710 (2000).
57 Dobson, C. Guided imagery for pain management by children with sickle
cell disease ages 6 to 11 years. Dissertation Abstracts
International: Section B: The Sciences and Engineering 67 ,
5662 (2007).
58 Schwartz, L. A., Radcliffe, J. & Barakat, L. P. The development of a
culturally sensitive pediatric pain management intervention for African
American adolescents with sickle cell disease. Children’s Health
Care 36 , 267-283 (2007).
59 Leonard, S., Cortright, L., Tumin, D., Joyner, L. & Sridhar, S.
Benefits of aquatic therapy in pediatric patients with sickle cell
disease. Blood. Conference: 61st Annual Meeting of the American
Society of Hematology, ASH 134 (2019).
60 Myrick, R. et al. Impact of a pediatric sickle cell outpatient
pain clinic on health outcomes. Blood. Conference: 61st Annual
Meeting of the American Society of Hematology, ASH 134 (2019).
61 Sil, S. et al. Enhancing pain assessment in pediatric sickle
cell disease by applying quality improvement science. Clinical
Practice in Pediatric Psychology 7 , 335-346 (2019).
62 Sil, S. et al. Engagement in cognitive-behavioral therapy for
chronic pain management is associated with reductions in healthcare
utilization in pediatric sickle cell disease. Blood. Conference:
61st Annual Meeting of the American Society of Hematology, ASH134 (2019).
63 Palermo, T. M., Eccleston, C., Lewandowski, A. S., Williams, A. C. &
Morley, S. Randomized controlled trials of psychological therapies for
management of chronic pain in children and adolescents: an updated
meta-analytic review. Pain 148 , 387-397,
doi:10.1016/j.pain.2009.10.004 (2010).
64 Edwards, L. Y. & Edwards, C. L. Psychosocial Treatments in Pain
Management of Sickle Cell Disease. Journal of the National Medical
Association 102 , 1084-1094,
doi:https://doi.org/10.1016/S0027-9684(15)30737-9 (2010).
65 Ehde, D. M., Dillworth, T. M. & Turner, J. A. Cognitive-behavioral
therapy for individuals with chronic pain: efficacy, innovations, and
directions for research. The American psychologist 69 ,
153-166, doi:10.1037/a0035747 (2014).
66 Rusy, L. M. & Weisman, S. J. Complementary therapies for acute
pediatric pain management. Pediatr Clin North Am 47 ,
589-599, doi:10.1016/s0031-3955(05)70227-3 (2000).
67 Thomas, J. E., Koshy, M., Patterson, L., Dorn, L. & Thomas, K.
Management of pain in sickle cell disease using biofeedback therapy: a
preliminary study. Biofeedback & Self Regulation 9 ,
413-420 (1984).
68 Bodhise, P. B., Dejoie, M., Brandon, Z., Simpkins, S. & Ballas, S.
K. Non-pharmacologic management of sickle cell pain. Hematology9 , 235-237 (2004).
69 Myers, M. & Eckes, E. J. A novel approach to pain management in
persons with sickle cell disease. Medsurg nursing : official
journal of the Academy of Medical-Surgical Nurses 21 , 293-298
(2012).
70 Birdee, G. S. et al. Clinical applications of yoga for the
pediatric population: a systematic review. Acad Pediatr9 , 212-220.e211-219, doi:10.1016/j.acap.2009.04.002 (2009).
71 Galantino, M. L., Galbavy, R. & Quinn, L. Therapeutic effects of
yoga for children: a systematic review of the literature. Pediatr
Phys Ther 20 , 66-80, doi:10.1097/PEP.0b013e31815f1208 (2008).
72 Tsao, J. C. I., Meldrum, M., Kim, S. C., Jacob, M. C. & Zeltzer, L.
K. Treatment Preferences for CAM in children with chronic pain.Evid Based Complement Alternat Med 4 , 367-374,
doi:10.1093/ecam/nel084 (2007).
73 Posadzki, P., Ernst, E., Terry, R. & Lee, M. S. Is yoga effective
for pain? A systematic review of randomized clinical trials.Complement Ther Med 19 , 281-287,
doi:10.1016/j.ctim.2011.07.004 (2011).
74 Bolton, D., Dearsley, P., Madronal-Luque, R. & Baron-Cohen, S.
Magical thinking in childhood and adolescence: Development and relation
to obsessive compulsion. British Journal of Developmental
Psychology 20 , 479-494,
doi:https://doi.org/10.1348/026151002760390819 (2002).
75 Lillard, A. S. Pretend play skills and the child’s theory of mind.Child Development 64 , 348-371, doi:10.2307/1131255
(1993).
76 Das, D. A., Grimmer, K. A., Sparnon, A. L., McRae, S. E. & Thomas,
B. H. The efficacy of playing a virtual reality game in modulating pain
for children with acute burn injuries: a randomized controlled trial
[ISRCTN87413556]. BMC Pediatr 5 , 1,
doi:10.1186/1471-2431-5-1 (2005).
77 Kipping, B., Rodger, S., Miller, K. & Kimble, R. M. Virtual reality
for acute pain reduction in adolescents undergoing burn wound care: a
prospective randomized controlled trial. Burns 38 ,
650-657, doi:10.1016/j.burns.2011.11.010 (2012).
78 Malloy, K. M. & Milling, L. S. The effectiveness of virtual reality
distraction for pain reduction: A systematic review. Clinical
Psychology Review 30 , 1011-1018,
doi:https://doi.org/10.1016/j.cpr.2010.07.001 (2010).
79 Eijlers, R. et al. Systematic Review and Meta-analysis of
Virtual Reality in Pediatrics: Effects on Pain and Anxiety. Anesth
Analg 129 , 1344-1353, doi:10.1213/ane.0000000000004165 (2019).
80 Peters, J. W. B. et al. Does neonatal surgery lead to
increased pain sensitivity in later childhood? Pain 114 ,
444-454, doi:10.1016/j.pain.2005.01.014 (2005).
81 Schwaller, F. & Fitzgerald, M. The consequences of pain in early
life: injury-induced plasticity in developing pain pathways. Eur J
Neurosci 39 , 344-352, doi:10.1111/ejn.12414 (2014).
82 Walker, S. M. et al. Somatosensory function and pain in
extremely preterm young adults from the UK EPICure cohort: sex-dependent
differences and impact of neonatal surgery. British Journal of
Anaesthesia 121 , 623-635,
doi:https://doi.org/10.1016/j.bja.2018.03.035 (2018).
83 Low, L. A. & Fitzgerald, M. Acute Pain and a Motivational Pathway in
Adult Rats: Influence of Early Life Pain Experience. PLOS ONE7 , e34316, doi:10.1371/journal.pone.0034316 (2012).
84 Pancekauskaitė, G. & Jankauskaitė, L. Paediatric Pain Medicine: Pain
Differences, Recognition and Coping Acute Procedural Pain in Paediatric
Emergency Room. Medicina (Kaunas) 54 ,
doi:10.3390/medicina54060094 (2018).
85 Srouji, R., Ratnapalan, S. & Schneeweiss, S. Pain in children:
assessment and nonpharmacological management. Int J Pediatr2010 , doi:10.1155/2010/474838 (2010).
86 Williams, M. D. & Lascelles, B. D. X. Early Neonatal Pain-A Review
of Clinical and Experimental Implications on Painful Conditions Later in
Life. Front Pediatr 8 , 30, doi:10.3389/fped.2020.00030
(2020).
87 Dampier, C., Ely, B., Brodecki, D. & O’Neal, P. Characteristics of
pain managed at home in children and adolescents with sickle cell
disease by using diary self-reports. The Journal of Pain3 , 461-470 (2002).
88 Shapiro, B. S., Benjamin, L. J., Payne, R. & Heidrich, G. Sickle
cell-related pain: Perceptions of medical practitioners. Dulwich
Centre Review 14 , 168-174 (1997).
89 Han, J., Zhou, J., Saraf, S. L., Gordeuk, V. R. & Calip, G. S.
Characterization of opioid use in sickle cell disease.Pharmacoepidemiology and Drug Safety 27 , 479-486,
doi:https://doi.org/10.1002/pds.4291 (2018).
90 Fisher, E., Heathcote, L. C., Eccleston, C., Simons, L. E. &
Palermo, T. M. Assessment of Pain Anxiety, Pain Catastrophizing, and
Fear of Pain in Children and Adolescents With Chronic Pain: A Systematic
Review and Meta-Analysis. J Pediatr Psychol 43 , 314-325,
doi:10.1093/jpepsy/jsx103 (2018).
91 Stevens, E. M., Patterson, C. A., Li, Y. B., Smith-Whitley, K. &
Barakat, L. P. Mistrust of Pediatric Sickle Cell Disease Clinical Trials
Research. American journal of preventive medicine 51 ,
S78-S86, doi:10.1016/j.amepre.2016.01.024 (2016).
92 Liem, R. I., Cole, A. H., Pelligra, S. A., Mason, M. & Thompson, A.
A. Parental attitudes toward research participation in pediatric sickle
cell disease. Pediatric Blood & Cancer 55 , 129-133,
doi:https://doi.org/10.1002/pbc.22450 (2010).