Methods
Eligibility criteria
Randomized controlled trials (RCTs) and quasi-experimental designed
(QED) studies that investigated the efficacy of non-pharmacological
interventions for pediatric patients with SCD were considered for
inclusion. Non-pharmacological interventions were defined as ‘therapies
that do not involve taking medicines or any other active
substances’.39 QED studies are nonrandomized, pre-post
intervention studies or interrupted time-series designs with or without
control groups.40,41 Systematic reviews, comment
articles and case reports were excluded, as well as non-English
publications. Furthermore, studies with participants aged above 21
years, were excluded.
Outcome measures
The primary outcomes were pain frequency in a specific period of time
and pain intensity of any kind of pain episode. Pain frequency was
calculated as the number or percentage of pain days of the total
observed days. Secondary outcomes were frequency of hospital admissions
for SCD-related pain, emergency department (ED) visits, length of
hospital stay (LOS) and analgesic use.
Search strategy and study
selection
The complete study protocol was published in the PROSPERO database prior
to start (record ID 117416). Relevant articles were identified by the
medical information specialist from the electronic databases Medline,
PsycINFO and Embase using different terms for ‘sickle cell disease’,
‘pain’ and ‘psychotherapy’, ‘analgesic use’ and ‘health service use’
(Supplemental Table S1 ). Every article published before October
2022 was included for further assessment. Two investigators (SV, JG or
CV) independently screened titles and abstracts and identified all
studies that met the inclusion criteria using the Rayyan
application.42 Eligibility was assessed based on the
full text article of the remaining studies (SV, CV). Discrepancies were
solved by consensus or by the involvement of a third investigator (JG).
The reference lists of all included studies and related systematic
reviews were checked to ensure no relevant studies were missed. If the
full text of an eligible study was not available for full text
screening, authors of these studies were approached to provide their
data and articles.
Data extraction and analysis
Critical Appraisal
Methodological quality and risk of bias of the selected studies were
assessed by two independent investigators (SV, CV) using two modified
and extensive versions of the Critical Appraisal Checklist for
Randomized Controlled Trial and Quasi-Experimental Studies
(Non-Randomized Experimental Studies) by the Joanna Briggs
Institute.40 Additionally, attrition and selection
bias were assessed as well according to criteria of the Handbook of the
Cochrane Collaboration for systematic reviews.43
Data extraction
A standardized data extraction form was used to extract data from the
included studies for evidence synthesis. Extracted information included:
author, publication year, study setting, baseline characteristics of
included participants, details of randomization, study methodology and
outcomes that were relevant for our review. Data were independently
extracted by two reviewers (SV, CV) and any discrepancies were
identified and resolved through discussion. If the effect between groups
was not stated in the article, we calculated this based on the provided
data.
Data analysis
The non-pharmacological interventions were analyzed separately for the
inpatient and the outpatient setting and classified in one of the three
categories as described in the ASH guidelines:14
1. Psychological interventions;
2. Physical interventions;
3. Integrative medicine: passive modalities combining different
psychological and physical tools and approaches, tailored to individual
patient needs.
We described data narratively and
summarized the main findings in table format including study
characteristics, data of previously mentioned outcomes and a calculated
quality assessment.