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Implementation of the therapeutic use of hydroxyurea for sickle cell disease management in resource-constrained settings: a systematic review of adoption, cost and acceptability.

ABSTRACT: OBJECTIVES:Mortality associated with sickle cell disease (SCD) is high in many low- and middle-income countries (LMICs). Hydroxyurea, a medicine to effectively manage SCD, is not widely available in resource-constrained settings. We identified and synthesised the reported implementation outcomes for the therapeutic use of hydroxyurea for SCD in these settings. DESIGN:Systematic review. DATA SOURCES:PubMed, Embase, Cochrane, Web of Science Plus, Global Health, CINAHL, and PsycINFO were searched February through May 2019 without any restrictions on publication date. ELIGIBILITY CRITERIA:We included empirical studies of hydroxyurea for management of SCD that were carried out in LMICs and reported on implementation outcomes. DATA EXTRACTION AND SYNTHESIS:Two reviewers independently assessed studies for inclusion, carried out data extraction using Proctor et al.'s implementation and health service outcomes, and assessed the risk of bias using ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions). RESULTS:Two cross-sectional surveys (n=2) and one cohort study (n=1) reported implementation of hydroxyurea for SCD management, namely regarding outcomes of adoption (n=3), cost (n=3) and acceptability (n=1). These studies were conducted exclusively among paediatric and adults populations in clinical settings in Nigeria (n=2) or Jamaica (n=1). Adoption is low, as observed through reported provider practices and patient adherence, in part shaped by misinformation and fear of side effects among patients, provider beliefs regarding affordability and organisational challenges with procuring the medicine. There was no difference in the cost of hydroxyurea therapy compared with blood transfusion in the paediatric population in urban Jamaica. Risk of bias was low or moderate across the included studies. CONCLUSIONS:This review rigorously and systematically assessed the evidence on implementation of hydroxyurea in resource-constrained settings such as LMICs. Findings suggest that knowledge regarding implementation is low. To address the know-do gap and guide clinical practice, implementation research is needed. Integrating effective interventions into existing health systems to improve hydroxyurea uptake is essential to reducing SCD-associated mortality. PROSPERO REGISTRATION NUMBER:CRD42020155953.

SUBMITTER: Ryan N

PROVIDER: S-EPMC7654121 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Implementation of the therapeutic use of hydroxyurea for sickle cell disease management in resource-constrained settings: a systematic review of adoption, cost and acceptability.

Ryan Nessa N Dike Lotanna L Ojo Temitope T Vieira Dorice D Nnodu Obiageli O Gyamfi Joyce J Peprah Emmanuel E

BMJ open 20201109 11

<h4>Objectives</h4>Mortality associated with sickle cell disease (SCD) is high in many low- and middle-income countries (LMICs). Hydroxyurea, a medicine to effectively manage SCD, is not widely available in resource-constrained settings. We identified and synthesised the reported implementation outcomes for the therapeutic use of hydroxyurea for SCD in these settings.<h4>Design</h4>Systematic review.<h4>Data sources</h4>PubMed, Embase, Cochrane, Web of Science Plus, Global Health, CINAHL, and Ps ...[more]

PMID: 33168553

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Project description:Harmonizing measures across studies can facilitate comparisons and strengthen the science, but procedures for establishing common data elements are rarely documented. We detail a rigorous, 2-year process to harmonize measures across the Prevention And Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings (PATC3H) consortium, consisting of eight federally-funded studies. We created a repository of measured constructs from each study, classified and selected constructs for harmonization, and identified survey instruments. Measures were harmonized for implementation science, HIV prevention and care, demographics and sexual behavior, mental health and substance use, and economic assessment. Importantly, we present our harmonized implementation science constructs. A common set of implementation science constructs have yet to be recommended in the literature for low-to-middle-income countries despite increasing recognition of their importance to delivering and scaling up effective interventions. Drawing on RE-AIM (Reach Effectiveness Adoption Implementation Maintenance) and the Implementation Outcomes Framework, items were harmonized for staff/administrators and study participants to measure reach, adoption, implementation, maintenance, feasibility, acceptability, appropriateness, and fidelity. The process undertaken to harmonize measures and the codified set of implementation science measures developed by our consortium can inform future data harmonization efforts, critical to strengthening the replication and generalizability of findings while facilitating collaborative research-especially in resource-limited settings. We conclude with recommendations for research consortia, namely ensuring representation from all study teams and research priorities; adopting a flexible, transparent, and systematic approach; strengthening the literature on implementation science harmonization; and being responsive to life events (e.g., COVID-19).Supplementary informationThe online version contains supplementary material available at 10.1007/s43477-022-00042-7.

Project description:The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert.To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting.Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM ("CXR algorithm"). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM ("HIV algorithm").Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively.Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients where Xpert was used in conjunction with CXR.

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Dataset Information

Implementation of the therapeutic use of hydroxyurea for sickle cell disease management in resource-constrained settings: a systematic review of adoption, cost and acceptability.

Publications

Implementation of the therapeutic use of hydroxyurea for sickle cell disease management in resource-constrained settings: a systematic review of adoption, cost and acceptability.

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