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.