Evidence review of hydroxyurea for the prevention of sickle cell complications in low-income countries
Hydroxyurea is widely used in high-income countries for the management of sickle cell disease (SCD) in children. In Kenyan clinical guidelines, hydroxyurea is only recommended for adults with SCD. Yet many deaths from SCD occur in early childhood, deaths that might be prevented by an effective, dise...
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| Veröffentlicht in: | Archives of disease in childhood 2013-11, Vol.98 (11), p.908-914 |
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| creator | Mulaku, Mercy Opiyo, Newton Karumbi, Jamlick Kitonyi, Grace Thoithi, Grace English, Mike |
| description | Hydroxyurea is widely used in high-income countries for the management of sickle cell disease (SCD) in children. In Kenyan clinical guidelines, hydroxyurea is only recommended for adults with SCD. Yet many deaths from SCD occur in early childhood, deaths that might be prevented by an effective, disease modifying intervention. The aim of this review was to summarise the available evidence on the efficacy, effectiveness and safety of hydroxyurea in the management of SCD in children below 5 years of age to support guideline development in Kenya. We undertook a systematic review and used the Grading of Recommendations Assessment, Development and Evaluation system to appraise the quality of identified evidence. Overall, available evidence from 1 systematic review (n=26 studies), 2 randomised controlled trials (n=354 children), 14 observational studies and 2 National Institute of Health reports suggest that hydroxyurea may be associated with improved fetal haemoglobin levels, reduced rates of hospitalisation, reduced episodes of acute chest syndrome and decreased frequency of pain events in children with SCD. However, it is associated with adverse events (eg, neutropenia) when high to maximum tolerated doses are used. Evidence is lacking on whether hydroxyurea improves survival if given to young children. Majority of the included studies were of low quality and mainly from high-income countries. Overall, available limited evidence suggests that hydroxyurea may improve morbidity and haematological outcomes in SCD in children aged below 5 years and appears safe in settings able to provide consistent haematological monitoring. |
| doi_str_mv | 10.1136/archdischild-2012-302387 |
| format | Article |
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In Kenyan clinical guidelines, hydroxyurea is only recommended for adults with SCD. Yet many deaths from SCD occur in early childhood, deaths that might be prevented by an effective, disease modifying intervention. The aim of this review was to summarise the available evidence on the efficacy, effectiveness and safety of hydroxyurea in the management of SCD in children below 5 years of age to support guideline development in Kenya. We undertook a systematic review and used the Grading of Recommendations Assessment, Development and Evaluation system to appraise the quality of identified evidence. Overall, available evidence from 1 systematic review (n=26 studies), 2 randomised controlled trials (n=354 children), 14 observational studies and 2 National Institute of Health reports suggest that hydroxyurea may be associated with improved fetal haemoglobin levels, reduced rates of hospitalisation, reduced episodes of acute chest syndrome and decreased frequency of pain events in children with SCD. However, it is associated with adverse events (eg, neutropenia) when high to maximum tolerated doses are used. Evidence is lacking on whether hydroxyurea improves survival if given to young children. Majority of the included studies were of low quality and mainly from high-income countries. Overall, available limited evidence suggests that hydroxyurea may improve morbidity and haematological outcomes in SCD in children aged below 5 years and appears safe in settings able to provide consistent haematological monitoring.</description><identifier>ISSN: 0003-9888</identifier><identifier>EISSN: 1468-2044</identifier><identifier>DOI: 10.1136/archdischild-2012-302387</identifier><identifier>PMID: 23995076</identifier><identifier>CODEN: ADCHAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health</publisher><subject>Age ; Anemia ; Anemia, Sickle Cell - blood ; Anemia, Sickle Cell - complications ; Anemia, Sickle Cell - drug therapy ; Antisickling Agents - adverse effects ; Antisickling Agents - therapeutic use ; Attrition (Research Studies) ; Biological and medical sciences ; Blood transfusions ; Child, Preschool ; Clinical outcomes ; Complications and side effects ; Control Groups ; Cost analysis ; Developing Countries ; Dosage and administration ; Drug therapy ; Evidence ; Evidence-Based Medicine - methods ; Fetal Hemoglobin - metabolism ; General aspects ; Genetics ; Haematology ; Hematology ; Hospitalization - statistics & numerical data ; Humans ; Hydroxyurea ; Hydroxyurea - adverse effects ; Hydroxyurea - therapeutic use ; Infant ; Information Seeking ; Low Income ; Low income areas ; Low income groups ; Malaria ; Medical sciences ; Miscellaneous ; Mortality ; Observational studies ; Pain ; Pain - etiology ; Pain - prevention & control ; Pathogenesis ; Pragmatism ; Prevention ; Prevention and actions ; Public health. Hygiene ; Public health. Hygiene-occupational medicine ; Quality of life ; Review ; Search Strategies ; Selection Criteria ; Sickle cell anemia ; Sickle cell disease ; Spleen ; Studies ; Young Children</subject><ispartof>Archives of disease in childhood, 2013-11, Vol.98 (11), p.908-914</ispartof><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>2014 INIST-CNRS</rights><rights>Copyright: 2013 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions</rights><rights>Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b598t-978447db6eb783d33041ed92fca52143a4de0f476688946293069c549621dafd3</citedby><cites>FETCH-LOGICAL-b598t-978447db6eb783d33041ed92fca52143a4de0f476688946293069c549621dafd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://adc.bmj.com/content/98/11/908.full.pdf$$EPDF$$P50$$Gbmj$$Hfree_for_read</linktopdf><linktohtml>$$Uhttp://adc.bmj.com/content/98/11/908.full$$EHTML$$P50$$Gbmj$$Hfree_for_read</linktohtml><link.rule.ids>114,115,230,313,314,776,780,788,881,3183,23550,27899,27901,27902,77343,77374</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27909260$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23995076$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mulaku, Mercy</creatorcontrib><creatorcontrib>Opiyo, Newton</creatorcontrib><creatorcontrib>Karumbi, Jamlick</creatorcontrib><creatorcontrib>Kitonyi, Grace</creatorcontrib><creatorcontrib>Thoithi, Grace</creatorcontrib><creatorcontrib>English, Mike</creatorcontrib><title>Evidence review of hydroxyurea for the prevention of sickle cell complications in low-income countries</title><title>Archives of disease in childhood</title><addtitle>Arch Dis Child</addtitle><description>Hydroxyurea is widely used in high-income countries for the management of sickle cell disease (SCD) in children. In Kenyan clinical guidelines, hydroxyurea is only recommended for adults with SCD. Yet many deaths from SCD occur in early childhood, deaths that might be prevented by an effective, disease modifying intervention. The aim of this review was to summarise the available evidence on the efficacy, effectiveness and safety of hydroxyurea in the management of SCD in children below 5 years of age to support guideline development in Kenya. We undertook a systematic review and used the Grading of Recommendations Assessment, Development and Evaluation system to appraise the quality of identified evidence. Overall, available evidence from 1 systematic review (n=26 studies), 2 randomised controlled trials (n=354 children), 14 observational studies and 2 National Institute of Health reports suggest that hydroxyurea may be associated with improved fetal haemoglobin levels, reduced rates of hospitalisation, reduced episodes of acute chest syndrome and decreased frequency of pain events in children with SCD. However, it is associated with adverse events (eg, neutropenia) when high to maximum tolerated doses are used. Evidence is lacking on whether hydroxyurea improves survival if given to young children. Majority of the included studies were of low quality and mainly from high-income countries. Overall, available limited evidence suggests that hydroxyurea may improve morbidity and haematological outcomes in SCD in children aged below 5 years and appears safe in settings able to provide consistent haematological monitoring.</description><subject>Age</subject><subject>Anemia</subject><subject>Anemia, Sickle Cell - blood</subject><subject>Anemia, Sickle Cell - complications</subject><subject>Anemia, Sickle Cell - drug therapy</subject><subject>Antisickling Agents - adverse effects</subject><subject>Antisickling Agents - therapeutic use</subject><subject>Attrition (Research Studies)</subject><subject>Biological and medical sciences</subject><subject>Blood transfusions</subject><subject>Child, Preschool</subject><subject>Clinical outcomes</subject><subject>Complications and side effects</subject><subject>Control Groups</subject><subject>Cost analysis</subject><subject>Developing Countries</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Evidence</subject><subject>Evidence-Based Medicine - methods</subject><subject>Fetal Hemoglobin - metabolism</subject><subject>General aspects</subject><subject>Genetics</subject><subject>Haematology</subject><subject>Hematology</subject><subject>Hospitalization - statistics & numerical data</subject><subject>Humans</subject><subject>Hydroxyurea</subject><subject>Hydroxyurea - adverse effects</subject><subject>Hydroxyurea - therapeutic use</subject><subject>Infant</subject><subject>Information Seeking</subject><subject>Low Income</subject><subject>Low income areas</subject><subject>Low income groups</subject><subject>Malaria</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Mortality</subject><subject>Observational studies</subject><subject>Pain</subject><subject>Pain - etiology</subject><subject>Pain - prevention & control</subject><subject>Pathogenesis</subject><subject>Pragmatism</subject><subject>Prevention</subject><subject>Prevention and actions</subject><subject>Public health. Hygiene</subject><subject>Public health. Hygiene-occupational medicine</subject><subject>Quality of life</subject><subject>Review</subject><subject>Search Strategies</subject><subject>Selection Criteria</subject><subject>Sickle cell anemia</subject><subject>Sickle cell disease</subject><subject>Spleen</subject><subject>Studies</subject><subject>Young Children</subject><issn>0003-9888</issn><issn>1468-2044</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>9YT</sourceid><sourceid>ACMMV</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNkUtvEzEUhUcIREPhLyBLiOWAx_b4sUEqUXmohSIB3VqOfSdx6oyDPZM2_x5HCSHsWFm657tX5_hUFWrwm6ah_K1JduF8tgsfXE1wQ2qKCZXiUTVpGJdlxNjjaoIxprWSUp5Vz3Je4gJKSZ9WZ4Qq1WLBJ1V3ufEOegsowcbDPYodWmxdig_bMYFBXUxoWABaFxn6wcd-R2Rv7wIgCyEgG1fr4K3ZaRn5HoV4X_u-jAsQx35IHvLz6klnQoYXh_e8-vnh8sf0U3198_Hz9OK6nrVKDrUSkjHhZhxmQlJHKWYNOEU6a1rSMGqYA9wxwbmUinGiKObKtkxx0jjTOXpevdvfXY-zFThbLCcT9Dr5lUlbHY3X_yq9X-h53Ggqy98IUg68OhxI8dcIedDLOKa-eNaNJFIR0SpcqHpPzU0AvQvbD_Aw2BgCzEGXSNMbfUFbTBjHvC283PM2xZwTdEdHDda7RvVpo3rXqN43WlZfniY6Lv6psACvD4DJ1oQumd76_JcTCivCTzz7XLwedZPuNBdUtPrr7VSzb9-vvpD3t_qq8HTPz1bL_7f7GzipziM</recordid><startdate>20131101</startdate><enddate>20131101</enddate><creator>Mulaku, Mercy</creator><creator>Opiyo, Newton</creator><creator>Karumbi, Jamlick</creator><creator>Kitonyi, Grace</creator><creator>Thoithi, Grace</creator><creator>English, Mike</creator><general>BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health</general><general>BMJ Publishing Group</general><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><scope>9YT</scope><scope>ACMMV</scope><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>0-V</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88B</scope><scope>88E</scope><scope>88I</scope><scope>8A4</scope><scope>8AF</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ALSLI</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>CJNVE</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>LK8</scope><scope>M0P</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEDU</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20131101</creationdate><title>Evidence review of hydroxyurea for the prevention of sickle cell complications in low-income countries</title><author>Mulaku, Mercy ; Opiyo, Newton ; Karumbi, Jamlick ; Kitonyi, Grace ; Thoithi, Grace ; English, Mike</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b598t-978447db6eb783d33041ed92fca52143a4de0f476688946293069c549621dafd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Age</topic><topic>Anemia</topic><topic>Anemia, Sickle Cell - blood</topic><topic>Anemia, Sickle Cell - complications</topic><topic>Anemia, Sickle Cell - drug therapy</topic><topic>Antisickling Agents - adverse effects</topic><topic>Antisickling Agents - therapeutic use</topic><topic>Attrition (Research Studies)</topic><topic>Biological and medical sciences</topic><topic>Blood transfusions</topic><topic>Child, Preschool</topic><topic>Clinical outcomes</topic><topic>Complications and side effects</topic><topic>Control Groups</topic><topic>Cost analysis</topic><topic>Developing Countries</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Evidence</topic><topic>Evidence-Based Medicine - methods</topic><topic>Fetal Hemoglobin - metabolism</topic><topic>General aspects</topic><topic>Genetics</topic><topic>Haematology</topic><topic>Hematology</topic><topic>Hospitalization - statistics & numerical data</topic><topic>Humans</topic><topic>Hydroxyurea</topic><topic>Hydroxyurea - adverse effects</topic><topic>Hydroxyurea - therapeutic use</topic><topic>Infant</topic><topic>Information Seeking</topic><topic>Low Income</topic><topic>Low income areas</topic><topic>Low income groups</topic><topic>Malaria</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Mortality</topic><topic>Observational studies</topic><topic>Pain</topic><topic>Pain - etiology</topic><topic>Pain - prevention & control</topic><topic>Pathogenesis</topic><topic>Pragmatism</topic><topic>Prevention</topic><topic>Prevention and actions</topic><topic>Public health. 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Hygiene-occupational medicine</topic><topic>Quality of life</topic><topic>Review</topic><topic>Search Strategies</topic><topic>Selection Criteria</topic><topic>Sickle cell anemia</topic><topic>Sickle cell disease</topic><topic>Spleen</topic><topic>Studies</topic><topic>Young Children</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mulaku, Mercy</creatorcontrib><creatorcontrib>Opiyo, Newton</creatorcontrib><creatorcontrib>Karumbi, Jamlick</creatorcontrib><creatorcontrib>Kitonyi, Grace</creatorcontrib><creatorcontrib>Thoithi, Grace</creatorcontrib><creatorcontrib>English, Mike</creatorcontrib><collection>BMJ Open Access Journals</collection><collection>BMJ Journals:Open Access</collection><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Social Sciences Premium Collection</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Education Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>Education Periodicals</collection><collection>STEM Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Social Science Premium Collection</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Education Collection</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Education Database</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Education</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Archives of disease in childhood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mulaku, Mercy</au><au>Opiyo, Newton</au><au>Karumbi, Jamlick</au><au>Kitonyi, Grace</au><au>Thoithi, Grace</au><au>English, Mike</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evidence review of hydroxyurea for the prevention of sickle cell complications in low-income countries</atitle><jtitle>Archives of disease in childhood</jtitle><addtitle>Arch Dis Child</addtitle><date>2013-11-01</date><risdate>2013</risdate><volume>98</volume><issue>11</issue><spage>908</spage><epage>914</epage><pages>908-914</pages><issn>0003-9888</issn><eissn>1468-2044</eissn><coden>ADCHAK</coden><abstract>Hydroxyurea is widely used in high-income countries for the management of sickle cell disease (SCD) in children. In Kenyan clinical guidelines, hydroxyurea is only recommended for adults with SCD. Yet many deaths from SCD occur in early childhood, deaths that might be prevented by an effective, disease modifying intervention. The aim of this review was to summarise the available evidence on the efficacy, effectiveness and safety of hydroxyurea in the management of SCD in children below 5 years of age to support guideline development in Kenya. We undertook a systematic review and used the Grading of Recommendations Assessment, Development and Evaluation system to appraise the quality of identified evidence. Overall, available evidence from 1 systematic review (n=26 studies), 2 randomised controlled trials (n=354 children), 14 observational studies and 2 National Institute of Health reports suggest that hydroxyurea may be associated with improved fetal haemoglobin levels, reduced rates of hospitalisation, reduced episodes of acute chest syndrome and decreased frequency of pain events in children with SCD. However, it is associated with adverse events (eg, neutropenia) when high to maximum tolerated doses are used. Evidence is lacking on whether hydroxyurea improves survival if given to young children. Majority of the included studies were of low quality and mainly from high-income countries. Overall, available limited evidence suggests that hydroxyurea may improve morbidity and haematological outcomes in SCD in children aged below 5 years and appears safe in settings able to provide consistent haematological monitoring.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health</pub><pmid>23995076</pmid><doi>10.1136/archdischild-2012-302387</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Archives of disease in childhood, 2013-11, Vol.98 (11), p.908-914 |
| issn | 0003-9888 1468-2044 |
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| source | MEDLINE; BMJ Journals - NESLi2 |
| subjects | Age Anemia Anemia, Sickle Cell - blood Anemia, Sickle Cell - complications Anemia, Sickle Cell - drug therapy Antisickling Agents - adverse effects Antisickling Agents - therapeutic use Attrition (Research Studies) Biological and medical sciences Blood transfusions Child, Preschool Clinical outcomes Complications and side effects Control Groups Cost analysis Developing Countries Dosage and administration Drug therapy Evidence Evidence-Based Medicine - methods Fetal Hemoglobin - metabolism General aspects Genetics Haematology Hematology Hospitalization - statistics & numerical data Humans Hydroxyurea Hydroxyurea - adverse effects Hydroxyurea - therapeutic use Infant Information Seeking Low Income Low income areas Low income groups Malaria Medical sciences Miscellaneous Mortality Observational studies Pain Pain - etiology Pain - prevention & control Pathogenesis Pragmatism Prevention Prevention and actions Public health. Hygiene Public health. Hygiene-occupational medicine Quality of life Review Search Strategies Selection Criteria Sickle cell anemia Sickle cell disease Spleen Studies Young Children |
| title | Evidence review of hydroxyurea for the prevention of sickle cell complications in low-income countries |
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