Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ+ thalassemia with IVS1-5(G→C) mutation
Background Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out th...
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| Veröffentlicht in: | Pediatric blood & cancer 2015-06, Vol.62 (6), p.1017-1023 |
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| creator | Dehury, Snehadhini Purohit, Prasanta Patel, Siris Meher, Satyabrata Kullu, Bipin Kishore Sahoo, Lulup Kumar Patel, Nayan Kumar Mohapatra, Alok Kumar Das, Kishalaya Patel, Dilip Kumar |
| description | Background
Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSβ+‐thalassemia with IVS1–5(G→C) mutation.
Procedure
We registered 318 patients with HbSβ+‐thalassemia with IVS1–5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group‐I: 37 children and Group‐II: 67 adults) with ≥2 years of hydroxyurea treatment were studied.
Results
The rate of vaso‐occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group‐I and 3 to 0, 1 to 0 and 0.5 to 0 in Group‐II respectively after HU therapy (P |
| doi_str_mv | 10.1002/pbc.25391 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2035651842</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2035651842</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4261-7c31bea52b2dab3f0a279315ce2d4e314aa7dfe25c30f37c1867f89938d629ac3</originalsourceid><addsrcrecordid>eNp1kE9O3DAUh62qVaHQRS9QWeoGVAX8J46TZUlhAI1oJQqztBz7WWM6k0zthJm5QA_AUThID8FJCARm19V7evp-vyd9CH2i5IASwg4XlTlgghf0DdqmIhWJIFS-3eyk2EIfYrzp0YyI_D3aYkKkGSnoNlqOmyXWtcXOr8Bi20TAjcPTtQ3Nat0F0NhHDM6Baf0tPKNRO8C-xgvdeqjbiJe-neLT6vLf_VfcTvVMxwhzr4f72fUlTcTe6OHvXbmP513bp5p6F71zehbh48vcQVcnx7_K02T8Y3RWfhsnJmUZTaThtAItWMWsrrgjmsmCU2GA2RQ4TbWW1gEThhPHpaF5Jl1eFDy3GSu04Tvoy9C7CM2fDmKrbpou1P1LxQgXmaB5ynpqf6BMaGIM4NQi-LkOa0WJelKsesXqWXHPfn5p7Ko52A356rQHDgdg6Wew_n-T-nlUvlYmQ8LHFlabhA6_VSa5FGpyMVKT7yd5eT6aKMkfAcFvlS0</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2035651842</pqid></control><display><type>article</type><title>Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ+ thalassemia with IVS1-5(G→C) mutation</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Dehury, Snehadhini ; Purohit, Prasanta ; Patel, Siris ; Meher, Satyabrata ; Kullu, Bipin Kishore ; Sahoo, Lulup Kumar ; Patel, Nayan Kumar ; Mohapatra, Alok Kumar ; Das, Kishalaya ; Patel, Dilip Kumar</creator><creatorcontrib>Dehury, Snehadhini ; Purohit, Prasanta ; Patel, Siris ; Meher, Satyabrata ; Kullu, Bipin Kishore ; Sahoo, Lulup Kumar ; Patel, Nayan Kumar ; Mohapatra, Alok Kumar ; Das, Kishalaya ; Patel, Dilip Kumar</creatorcontrib><description>Background
Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSβ+‐thalassemia with IVS1–5(G→C) mutation.
Procedure
We registered 318 patients with HbSβ+‐thalassemia with IVS1–5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group‐I: 37 children and Group‐II: 67 adults) with ≥2 years of hydroxyurea treatment were studied.
Results
The rate of vaso‐occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group‐I and 3 to 0, 1 to 0 and 0.5 to 0 in Group‐II respectively after HU therapy (P < 0.0001). %HbF level, hemoglobin, MCV and MCH increased significantly, whereas HbS, WBC, platelet count, serum‐bilirubin and LDH levels decreased significantly after HU therapy. It has been observed that along with fairly subtle hematological changes following HU therapy, there was a substantial clinical improvement occurred in these patients. Transient myelotoxicity was observed in 4.8%. There was minimal gonadal toxicity without affecting reproductive function.
Conclusion
In view of easy affordability, better acceptability, minimal toxicity, the need of infrequent monitoring and its potential effectiveness, low and fixed dose of hydroxyurea is suitable for treatment of patients with HbSβ+‐thalassemia in resource poor setting. Pediatr Blood Cancer 2015;62:1017–1023. © 2014 Wiley Periodicals, Inc.</description><identifier>ISSN: 1545-5009</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.25391</identifier><identifier>PMID: 25546091</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adolescent ; Adult ; Bilirubin ; Blood cancer ; Blood transfusion ; Cancer ; Child ; Child, Preschool ; Children ; Female ; Fertility ; Genotypes ; HbF ; HbSβ+ thalassemia ; Hematology ; Hemoglobin ; Hemoglobin, Sickle - analysis ; Hemoglobin, Sickle - genetics ; Humans ; Hydroxyurea ; Hydroxyurea - administration & dosage ; Hydroxyurea - adverse effects ; low dose ; Male ; Mutation ; Myelosuppression ; Oncology ; Patients ; Pediatrics ; Prospective Studies ; Sickle cell disease ; Thalassemia ; Thalassemia - blood ; Thalassemia - drug therapy ; Thalassemia - genetics ; Toxicity ; Transfusion ; vaso occlusive crisis (VOC)</subject><ispartof>Pediatric blood & cancer, 2015-06, Vol.62 (6), p.1017-1023</ispartof><rights>2014 Wiley Periodicals, Inc.</rights><rights>2015 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4261-7c31bea52b2dab3f0a279315ce2d4e314aa7dfe25c30f37c1867f89938d629ac3</citedby><cites>FETCH-LOGICAL-c4261-7c31bea52b2dab3f0a279315ce2d4e314aa7dfe25c30f37c1867f89938d629ac3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.25391$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.25391$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25546091$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dehury, Snehadhini</creatorcontrib><creatorcontrib>Purohit, Prasanta</creatorcontrib><creatorcontrib>Patel, Siris</creatorcontrib><creatorcontrib>Meher, Satyabrata</creatorcontrib><creatorcontrib>Kullu, Bipin Kishore</creatorcontrib><creatorcontrib>Sahoo, Lulup Kumar</creatorcontrib><creatorcontrib>Patel, Nayan Kumar</creatorcontrib><creatorcontrib>Mohapatra, Alok Kumar</creatorcontrib><creatorcontrib>Das, Kishalaya</creatorcontrib><creatorcontrib>Patel, Dilip Kumar</creatorcontrib><title>Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ+ thalassemia with IVS1-5(G→C) mutation</title><title>Pediatric blood & cancer</title><addtitle>Pediatr Blood Cancer</addtitle><description>Background
Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSβ+‐thalassemia with IVS1–5(G→C) mutation.
Procedure
We registered 318 patients with HbSβ+‐thalassemia with IVS1–5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group‐I: 37 children and Group‐II: 67 adults) with ≥2 years of hydroxyurea treatment were studied.
Results
The rate of vaso‐occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group‐I and 3 to 0, 1 to 0 and 0.5 to 0 in Group‐II respectively after HU therapy (P < 0.0001). %HbF level, hemoglobin, MCV and MCH increased significantly, whereas HbS, WBC, platelet count, serum‐bilirubin and LDH levels decreased significantly after HU therapy. It has been observed that along with fairly subtle hematological changes following HU therapy, there was a substantial clinical improvement occurred in these patients. Transient myelotoxicity was observed in 4.8%. There was minimal gonadal toxicity without affecting reproductive function.
Conclusion
In view of easy affordability, better acceptability, minimal toxicity, the need of infrequent monitoring and its potential effectiveness, low and fixed dose of hydroxyurea is suitable for treatment of patients with HbSβ+‐thalassemia in resource poor setting. Pediatr Blood Cancer 2015;62:1017–1023. © 2014 Wiley Periodicals, Inc.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Bilirubin</subject><subject>Blood cancer</subject><subject>Blood transfusion</subject><subject>Cancer</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Female</subject><subject>Fertility</subject><subject>Genotypes</subject><subject>HbF</subject><subject>HbSβ+ thalassemia</subject><subject>Hematology</subject><subject>Hemoglobin</subject><subject>Hemoglobin, Sickle - analysis</subject><subject>Hemoglobin, Sickle - genetics</subject><subject>Humans</subject><subject>Hydroxyurea</subject><subject>Hydroxyurea - administration & dosage</subject><subject>Hydroxyurea - adverse effects</subject><subject>low dose</subject><subject>Male</subject><subject>Mutation</subject><subject>Myelosuppression</subject><subject>Oncology</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Prospective Studies</subject><subject>Sickle cell disease</subject><subject>Thalassemia</subject><subject>Thalassemia - blood</subject><subject>Thalassemia - drug therapy</subject><subject>Thalassemia - genetics</subject><subject>Toxicity</subject><subject>Transfusion</subject><subject>vaso occlusive crisis (VOC)</subject><issn>1545-5009</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE9O3DAUh62qVaHQRS9QWeoGVAX8J46TZUlhAI1oJQqztBz7WWM6k0zthJm5QA_AUThID8FJCARm19V7evp-vyd9CH2i5IASwg4XlTlgghf0DdqmIhWJIFS-3eyk2EIfYrzp0YyI_D3aYkKkGSnoNlqOmyXWtcXOr8Bi20TAjcPTtQ3Nat0F0NhHDM6Baf0tPKNRO8C-xgvdeqjbiJe-neLT6vLf_VfcTvVMxwhzr4f72fUlTcTe6OHvXbmP513bp5p6F71zehbh48vcQVcnx7_K02T8Y3RWfhsnJmUZTaThtAItWMWsrrgjmsmCU2GA2RQ4TbWW1gEThhPHpaF5Jl1eFDy3GSu04Tvoy9C7CM2fDmKrbpou1P1LxQgXmaB5ynpqf6BMaGIM4NQi-LkOa0WJelKsesXqWXHPfn5p7Ko52A356rQHDgdg6Wew_n-T-nlUvlYmQ8LHFlabhA6_VSa5FGpyMVKT7yd5eT6aKMkfAcFvlS0</recordid><startdate>201506</startdate><enddate>201506</enddate><creator>Dehury, Snehadhini</creator><creator>Purohit, Prasanta</creator><creator>Patel, Siris</creator><creator>Meher, Satyabrata</creator><creator>Kullu, Bipin Kishore</creator><creator>Sahoo, Lulup Kumar</creator><creator>Patel, Nayan Kumar</creator><creator>Mohapatra, Alok Kumar</creator><creator>Das, Kishalaya</creator><creator>Patel, Dilip Kumar</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>201506</creationdate><title>Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ+ thalassemia with IVS1-5(G→C) mutation</title><author>Dehury, Snehadhini ; Purohit, Prasanta ; Patel, Siris ; Meher, Satyabrata ; Kullu, Bipin Kishore ; Sahoo, Lulup Kumar ; Patel, Nayan Kumar ; Mohapatra, Alok Kumar ; Das, Kishalaya ; Patel, Dilip Kumar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4261-7c31bea52b2dab3f0a279315ce2d4e314aa7dfe25c30f37c1867f89938d629ac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Bilirubin</topic><topic>Blood cancer</topic><topic>Blood transfusion</topic><topic>Cancer</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Female</topic><topic>Fertility</topic><topic>Genotypes</topic><topic>HbF</topic><topic>HbSβ+ thalassemia</topic><topic>Hematology</topic><topic>Hemoglobin</topic><topic>Hemoglobin, Sickle - analysis</topic><topic>Hemoglobin, Sickle - genetics</topic><topic>Humans</topic><topic>Hydroxyurea</topic><topic>Hydroxyurea - administration & dosage</topic><topic>Hydroxyurea - adverse effects</topic><topic>low dose</topic><topic>Male</topic><topic>Mutation</topic><topic>Myelosuppression</topic><topic>Oncology</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Prospective Studies</topic><topic>Sickle cell disease</topic><topic>Thalassemia</topic><topic>Thalassemia - blood</topic><topic>Thalassemia - drug therapy</topic><topic>Thalassemia - genetics</topic><topic>Toxicity</topic><topic>Transfusion</topic><topic>vaso occlusive crisis (VOC)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dehury, Snehadhini</creatorcontrib><creatorcontrib>Purohit, Prasanta</creatorcontrib><creatorcontrib>Patel, Siris</creatorcontrib><creatorcontrib>Meher, Satyabrata</creatorcontrib><creatorcontrib>Kullu, Bipin Kishore</creatorcontrib><creatorcontrib>Sahoo, Lulup Kumar</creatorcontrib><creatorcontrib>Patel, Nayan Kumar</creatorcontrib><creatorcontrib>Mohapatra, Alok Kumar</creatorcontrib><creatorcontrib>Das, Kishalaya</creatorcontrib><creatorcontrib>Patel, Dilip Kumar</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dehury, Snehadhini</au><au>Purohit, Prasanta</au><au>Patel, Siris</au><au>Meher, Satyabrata</au><au>Kullu, Bipin Kishore</au><au>Sahoo, Lulup Kumar</au><au>Patel, Nayan Kumar</au><au>Mohapatra, Alok Kumar</au><au>Das, Kishalaya</au><au>Patel, Dilip Kumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ+ thalassemia with IVS1-5(G→C) mutation</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2015-06</date><risdate>2015</risdate><volume>62</volume><issue>6</issue><spage>1017</spage><epage>1023</epage><pages>1017-1023</pages><issn>1545-5009</issn><eissn>1545-5017</eissn><abstract>Background
Despite compelling evidence that hydroxyurea is safe and effective in sickle cell disease, it is prescribed sparingly due to several barriers like knowledge gaps in certain genotypes, apprehension about its safety and toxicity, and limited resources. We undertook this study to find out the efficacy and safety of HU in patients with HbSβ+‐thalassemia with IVS1–5(G→C) mutation.
Procedure
We registered 318 patients with HbSβ+‐thalassemia with IVS1–5(G→C) mutation. Of these, 203 were enrolled for hydroxyurea treatment at a low and fixed dose of 10 mg/kg/day. One hundred four patients (Group‐I: 37 children and Group‐II: 67 adults) with ≥2 years of hydroxyurea treatment were studied.
Results
The rate of vaso‐occlusive crises, requirement of blood transfusion and rate of hospitalization reduced from 3 to 0.5, 1 to 0 and 1 to 0 in Group‐I and 3 to 0, 1 to 0 and 0.5 to 0 in Group‐II respectively after HU therapy (P < 0.0001). %HbF level, hemoglobin, MCV and MCH increased significantly, whereas HbS, WBC, platelet count, serum‐bilirubin and LDH levels decreased significantly after HU therapy. It has been observed that along with fairly subtle hematological changes following HU therapy, there was a substantial clinical improvement occurred in these patients. Transient myelotoxicity was observed in 4.8%. There was minimal gonadal toxicity without affecting reproductive function.
Conclusion
In view of easy affordability, better acceptability, minimal toxicity, the need of infrequent monitoring and its potential effectiveness, low and fixed dose of hydroxyurea is suitable for treatment of patients with HbSβ+‐thalassemia in resource poor setting. Pediatr Blood Cancer 2015;62:1017–1023. © 2014 Wiley Periodicals, Inc.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25546091</pmid><doi>10.1002/pbc.25391</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Bilirubin Blood cancer Blood transfusion Cancer Child Child, Preschool Children Female Fertility Genotypes HbF HbSβ+ thalassemia Hematology Hemoglobin Hemoglobin, Sickle - analysis Hemoglobin, Sickle - genetics Humans Hydroxyurea Hydroxyurea - administration & dosage Hydroxyurea - adverse effects low dose Male Mutation Myelosuppression Oncology Patients Pediatrics Prospective Studies Sickle cell disease Thalassemia Thalassemia - blood Thalassemia - drug therapy Thalassemia - genetics Toxicity Transfusion vaso occlusive crisis (VOC) |
| title | Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ+ thalassemia with IVS1-5(G→C) mutation |
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