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Response to sequential treatment with prednisolone and vigabatrin in infantile spasms
Aim To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence. Methods In th...
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| Published in: | Journal of paediatrics and child health 2022-12, Vol.58 (12), p.2197-2202 |
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| container_end_page | 2202 |
| container_issue | 12 |
| container_start_page | 2197 |
| container_title | Journal of paediatrics and child health |
| container_volume | 58 |
| creator | Dzau, Winston Cheng, Sally Snell, Penny Fahey, Michael Scheffer, Ingrid E Harvey, A Simon Howell, Katherine B |
| description | Aim
To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence.
Methods
In this retrospective analysis, we compared effectiveness of prednisolone, vigabatrin and nonstandard treatments as first treatment for IS. In infants who commenced the UKISS treatment sequence, we evaluated response to each step. Primary outcome was spasm cessation after 42 days. Secondary outcomes were severe side effects and spasm relapse after 42 days.
Results
Treatment response data were available for 151 infants. First treatment was prednisolone in 99 infants, vigabatrin in 18 and nonstandard treatment in 34. The rate of spasm cessation with first treatment was significantly higher with prednisolone (62/99, 63%) than vigabatrin (5/18, 28%, P = 0.01) or nonstandard treatment (2/34, 5.9%, P |
| doi_str_mv | 10.1111/jpc.16181 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10087127</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2709734981</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4441-6e93307f00db23e231239bb042174d679911ed7b6f13d66acd1314cb6973bb253</originalsourceid><addsrcrecordid>eNp1kV9P5CAUxYnRrLPuPvgFNiS-uA8duUChfTJm4v4xJpqNPhNoqTJpoQsdJ_PtFx01q4mEBAi_eziXg9AhkDnkcbIcmzkIqGAHzYBzUoAs-W7eE8YLXgHZR59TWhJCaFlWn9A-E6TkUMoZuv1j0xh8sngKONm_K-snp3s8RaunIR_w2k33eIy29S6FPniLtW_xg7vTRk_Refw0O53reovTqNOQvqC9TvfJfn1eD9Dtj_Obxa_i8urn78XZZdFwzqEQtmaMyI6Q1lBmKQPKamMIpyB5K2RdA9hWGtEBa4XQTQsMeGNELZkxtGQH6HSrO67MYNsm-426V2N0g44bFbRTb2-8u1d34UEBIZUEKrPC8bNCDLn5NKnBpcb2vfY2rJKikuTHeF1BRo_eocuwij73lylesrIW9JH6vqWaGFKKtnt1A0Q9pqVyWuoprcx--9_-K_kSTwZOtsA6_-3mYyV1cb3YSv4Dv7qe9g</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2745359621</pqid></control><display><type>article</type><title>Response to sequential treatment with prednisolone and vigabatrin in infantile spasms</title><source>Wiley Online Library</source><creator>Dzau, Winston ; Cheng, Sally ; Snell, Penny ; Fahey, Michael ; Scheffer, Ingrid E ; Harvey, A Simon ; Howell, Katherine B</creator><creatorcontrib>Dzau, Winston ; Cheng, Sally ; Snell, Penny ; Fahey, Michael ; Scheffer, Ingrid E ; Harvey, A Simon ; Howell, Katherine B</creatorcontrib><description>Aim
To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence.
Methods
In this retrospective analysis, we compared effectiveness of prednisolone, vigabatrin and nonstandard treatments as first treatment for IS. In infants who commenced the UKISS treatment sequence, we evaluated response to each step. Primary outcome was spasm cessation after 42 days. Secondary outcomes were severe side effects and spasm relapse after 42 days.
Results
Treatment response data were available for 151 infants. First treatment was prednisolone in 99 infants, vigabatrin in 18 and nonstandard treatment in 34. The rate of spasm cessation with first treatment was significantly higher with prednisolone (62/99, 63%) than vigabatrin (5/18, 28%, P = 0.01) or nonstandard treatment (2/34, 5.9%, P < 0.01). Of 112 infants who commenced the UKISS treatment sequence, 71/112 (63%) responded to prednisolone 40 mg/day. Among non‐responders, 12/29 (41%) subsequently responded to prednisolone 60 mg/day, and 10/22 (45%) to vigabatrin. Severe side effects and spasm relapse were not significantly different between each treatment.
Conclusion
We confirm higher rates of spasm cessation with initial treatment with prednisolone than vigabatrin and nonstandard therapy. Non‐use of prednisolone as first treatment in over one third of infants highlights a concerning treatment gap. The UKISS treatment sequence has high overall treatment response (total 93/112; 83%), with similar benefit of subsequent prednisolone 60 mg/day and vigabatrin in prednisolone 40 mg/day non‐responders.</description><identifier>ISSN: 1034-4810</identifier><identifier>EISSN: 1440-1754</identifier><identifier>DOI: 10.1111/jpc.16181</identifier><identifier>PMID: 36054157</identifier><language>eng</language><publisher>Australia: John Wiley & Sons Australia, Ltd</publisher><subject>Anticonvulsants - adverse effects ; Babies ; Clinical outcomes ; Drug therapy ; Humans ; Infant ; infantile spasms ; Original ; Pediatrics ; prednisolone ; Prednisolone - therapeutic use ; Recurrence ; Retrospective Studies ; Spasm - chemically induced ; Spasm - complications ; Spasm - drug therapy ; Spasms, Infantile - chemically induced ; Spasms, Infantile - complications ; Spasms, Infantile - drug therapy ; Steroids ; treatment ; vigabatrin ; Vigabatrin - adverse effects</subject><ispartof>Journal of paediatrics and child health, 2022-12, Vol.58 (12), p.2197-2202</ispartof><rights>2022 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).</rights><rights>2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).</rights><rights>2022. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4441-6e93307f00db23e231239bb042174d679911ed7b6f13d66acd1314cb6973bb253</citedby><cites>FETCH-LOGICAL-c4441-6e93307f00db23e231239bb042174d679911ed7b6f13d66acd1314cb6973bb253</cites><orcidid>0000-0001-8591-6605 ; 0000-0002-2311-2174</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjpc.16181$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjpc.16181$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,315,786,790,891,27957,27958,50923,51032</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36054157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dzau, Winston</creatorcontrib><creatorcontrib>Cheng, Sally</creatorcontrib><creatorcontrib>Snell, Penny</creatorcontrib><creatorcontrib>Fahey, Michael</creatorcontrib><creatorcontrib>Scheffer, Ingrid E</creatorcontrib><creatorcontrib>Harvey, A Simon</creatorcontrib><creatorcontrib>Howell, Katherine B</creatorcontrib><title>Response to sequential treatment with prednisolone and vigabatrin in infantile spasms</title><title>Journal of paediatrics and child health</title><addtitle>J Paediatr Child Health</addtitle><description>Aim
To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence.
Methods
In this retrospective analysis, we compared effectiveness of prednisolone, vigabatrin and nonstandard treatments as first treatment for IS. In infants who commenced the UKISS treatment sequence, we evaluated response to each step. Primary outcome was spasm cessation after 42 days. Secondary outcomes were severe side effects and spasm relapse after 42 days.
Results
Treatment response data were available for 151 infants. First treatment was prednisolone in 99 infants, vigabatrin in 18 and nonstandard treatment in 34. The rate of spasm cessation with first treatment was significantly higher with prednisolone (62/99, 63%) than vigabatrin (5/18, 28%, P = 0.01) or nonstandard treatment (2/34, 5.9%, P < 0.01). Of 112 infants who commenced the UKISS treatment sequence, 71/112 (63%) responded to prednisolone 40 mg/day. Among non‐responders, 12/29 (41%) subsequently responded to prednisolone 60 mg/day, and 10/22 (45%) to vigabatrin. Severe side effects and spasm relapse were not significantly different between each treatment.
Conclusion
We confirm higher rates of spasm cessation with initial treatment with prednisolone than vigabatrin and nonstandard therapy. Non‐use of prednisolone as first treatment in over one third of infants highlights a concerning treatment gap. The UKISS treatment sequence has high overall treatment response (total 93/112; 83%), with similar benefit of subsequent prednisolone 60 mg/day and vigabatrin in prednisolone 40 mg/day non‐responders.</description><subject>Anticonvulsants - adverse effects</subject><subject>Babies</subject><subject>Clinical outcomes</subject><subject>Drug therapy</subject><subject>Humans</subject><subject>Infant</subject><subject>infantile spasms</subject><subject>Original</subject><subject>Pediatrics</subject><subject>prednisolone</subject><subject>Prednisolone - therapeutic use</subject><subject>Recurrence</subject><subject>Retrospective Studies</subject><subject>Spasm - chemically induced</subject><subject>Spasm - complications</subject><subject>Spasm - drug therapy</subject><subject>Spasms, Infantile - chemically induced</subject><subject>Spasms, Infantile - complications</subject><subject>Spasms, Infantile - drug therapy</subject><subject>Steroids</subject><subject>treatment</subject><subject>vigabatrin</subject><subject>Vigabatrin - adverse effects</subject><issn>1034-4810</issn><issn>1440-1754</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><recordid>eNp1kV9P5CAUxYnRrLPuPvgFNiS-uA8duUChfTJm4v4xJpqNPhNoqTJpoQsdJ_PtFx01q4mEBAi_eziXg9AhkDnkcbIcmzkIqGAHzYBzUoAs-W7eE8YLXgHZR59TWhJCaFlWn9A-E6TkUMoZuv1j0xh8sngKONm_K-snp3s8RaunIR_w2k33eIy29S6FPniLtW_xg7vTRk_Refw0O53reovTqNOQvqC9TvfJfn1eD9Dtj_Obxa_i8urn78XZZdFwzqEQtmaMyI6Q1lBmKQPKamMIpyB5K2RdA9hWGtEBa4XQTQsMeGNELZkxtGQH6HSrO67MYNsm-426V2N0g44bFbRTb2-8u1d34UEBIZUEKrPC8bNCDLn5NKnBpcb2vfY2rJKikuTHeF1BRo_eocuwij73lylesrIW9JH6vqWaGFKKtnt1A0Q9pqVyWuoprcx--9_-K_kSTwZOtsA6_-3mYyV1cb3YSv4Dv7qe9g</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Dzau, Winston</creator><creator>Cheng, Sally</creator><creator>Snell, Penny</creator><creator>Fahey, Michael</creator><creator>Scheffer, Ingrid E</creator><creator>Harvey, A Simon</creator><creator>Howell, Katherine B</creator><general>John Wiley & Sons Australia, Ltd</general><general>Blackwell Publishing Ltd</general><scope>24P</scope><scope>WIN</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>ASE</scope><scope>FPQ</scope><scope>K6X</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8591-6605</orcidid><orcidid>https://orcid.org/0000-0002-2311-2174</orcidid></search><sort><creationdate>202212</creationdate><title>Response to sequential treatment with prednisolone and vigabatrin in infantile spasms</title><author>Dzau, Winston ; Cheng, Sally ; Snell, Penny ; Fahey, Michael ; Scheffer, Ingrid E ; Harvey, A Simon ; Howell, Katherine B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4441-6e93307f00db23e231239bb042174d679911ed7b6f13d66acd1314cb6973bb253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Anticonvulsants - adverse effects</topic><topic>Babies</topic><topic>Clinical outcomes</topic><topic>Drug therapy</topic><topic>Humans</topic><topic>Infant</topic><topic>infantile spasms</topic><topic>Original</topic><topic>Pediatrics</topic><topic>prednisolone</topic><topic>Prednisolone - therapeutic use</topic><topic>Recurrence</topic><topic>Retrospective Studies</topic><topic>Spasm - chemically induced</topic><topic>Spasm - complications</topic><topic>Spasm - drug therapy</topic><topic>Spasms, Infantile - chemically induced</topic><topic>Spasms, Infantile - complications</topic><topic>Spasms, Infantile - drug therapy</topic><topic>Steroids</topic><topic>treatment</topic><topic>vigabatrin</topic><topic>Vigabatrin - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dzau, Winston</creatorcontrib><creatorcontrib>Cheng, Sally</creatorcontrib><creatorcontrib>Snell, Penny</creatorcontrib><creatorcontrib>Fahey, Michael</creatorcontrib><creatorcontrib>Scheffer, Ingrid E</creatorcontrib><creatorcontrib>Harvey, A Simon</creatorcontrib><creatorcontrib>Howell, Katherine B</creatorcontrib><collection>Wiley Online Library</collection><collection>Wiley Online Library</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>British Nursing Index</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>British Nursing Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of paediatrics and child health</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dzau, Winston</au><au>Cheng, Sally</au><au>Snell, Penny</au><au>Fahey, Michael</au><au>Scheffer, Ingrid E</au><au>Harvey, A Simon</au><au>Howell, Katherine B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Response to sequential treatment with prednisolone and vigabatrin in infantile spasms</atitle><jtitle>Journal of paediatrics and child health</jtitle><addtitle>J Paediatr Child Health</addtitle><date>2022-12</date><risdate>2022</risdate><volume>58</volume><issue>12</issue><spage>2197</spage><epage>2202</epage><pages>2197-2202</pages><issn>1034-4810</issn><eissn>1440-1754</eissn><notes>Conflict of interest: Doctor Howell has received support from RogCon Biosciences, Inc. and Praxis Precision Medicines, and has consulted for Praxis Precision Medicines. Professor Scheffer serves/has served on the editorial boards of the Annals of Neurology, Neurology and Epileptic Disorders; may accrue future revenue on pending patent WO61/010176 (filed: 2008): Therapeutic Compound; has a patent for</notes><notes>testing held by Bionomics Inc. and licensed to various diagnostic companies; has a patent molecular diagnostic/theranostic target for benign familial infantile epilepsy (BFIE) (PRRT2) 2011904493 and 2012900190 and PCT/AU2012/001321 (TECH ID:2012‐009) with royalties paid. She has served on scientific advisory boards for UCB, Eisai, GlaxoSmithKline, BioMarin, Nutricia, Rogcon, Chiesi, Encoded Therapeutics, Xenon Pharmaceuticals and Knopp Biosciences; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin and Eisai; has served as an investigator for Zogenix, Zynerba, Ultragenyx, GW Pharma, UCB, Eisai, Anavex Life Sciences, Ovid Therapeutics, Epigenyx, Encoded Therapeutics and Marinus; and has consulted for Zynerba Pharmaceuticals, Atheneum Partners, Ovid Therapeutics, Care Beyond Diagnosis, Epilepsy Consortium and UCB. She receives/has received research support from the National Health and Medical Research Council of Australia, the Australian Medical Research Future Fund, Health Research Council of New Zealand, CURE, Australian Epilepsy Research Fund and NIH/NINDS. Dr Fahey has served on scientific advisory boards for Actelion and has consulted for Fenix Consulting and Signant Health; has served as an investigator for UCB, Actelion and Marinus. He has received research support from the National Health and Medical Research Council of Australia, Medical Research Future Fund, NIH/NINDS, CP Alliance, Inner Wheel, The Bill and Melinda Gates Foundation, Perpetual Trustees and the Fulbright Foundation. The remaining authors have no conflicts of interest.</notes><notes>SCN1A</notes><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><notes>Conflict of interest: Doctor Howell has received support from RogCon Biosciences, Inc. and Praxis Precision Medicines, and has consulted for Praxis Precision Medicines. Professor Scheffer serves/has served on the editorial boards of the Annals of Neurology, Neurology and Epileptic Disorders; may accrue future revenue on pending patent WO61/010176 (filed: 2008): Therapeutic Compound; has a patent for SCN1A testing held by Bionomics Inc. and licensed to various diagnostic companies; has a patent molecular diagnostic/theranostic target for benign familial infantile epilepsy (BFIE) (PRRT2) 2011904493 and 2012900190 and PCT/AU2012/001321 (TECH ID:2012‐009) with royalties paid. She has served on scientific advisory boards for UCB, Eisai, GlaxoSmithKline, BioMarin, Nutricia, Rogcon, Chiesi, Encoded Therapeutics, Xenon Pharmaceuticals and Knopp Biosciences; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin and Eisai; has served as an investigator for Zogenix, Zynerba, Ultragenyx, GW Pharma, UCB, Eisai, Anavex Life Sciences, Ovid Therapeutics, Epigenyx, Encoded Therapeutics and Marinus; and has consulted for Zynerba Pharmaceuticals, Atheneum Partners, Ovid Therapeutics, Care Beyond Diagnosis, Epilepsy Consortium and UCB. She receives/has received research support from the National Health and Medical Research Council of Australia, the Australian Medical Research Future Fund, Health Research Council of New Zealand, CURE, Australian Epilepsy Research Fund and NIH/NINDS. Dr Fahey has served on scientific advisory boards for Actelion and has consulted for Fenix Consulting and Signant Health; has served as an investigator for UCB, Actelion and Marinus. He has received research support from the National Health and Medical Research Council of Australia, Medical Research Future Fund, NIH/NINDS, CP Alliance, Inner Wheel, The Bill and Melinda Gates Foundation, Perpetual Trustees and the Fulbright Foundation. The remaining authors have no conflicts of interest.</notes><abstract>Aim
To report response to first treatment in infants with infantile spasms (IS), including incremental benefit of prednisolone 60 mg/day and vigabatrin following prednisolone 40 mg/day failure in infants commenced on the United Kingdom Infantile Spasms Study (UKISS) treatment sequence.
Methods
In this retrospective analysis, we compared effectiveness of prednisolone, vigabatrin and nonstandard treatments as first treatment for IS. In infants who commenced the UKISS treatment sequence, we evaluated response to each step. Primary outcome was spasm cessation after 42 days. Secondary outcomes were severe side effects and spasm relapse after 42 days.
Results
Treatment response data were available for 151 infants. First treatment was prednisolone in 99 infants, vigabatrin in 18 and nonstandard treatment in 34. The rate of spasm cessation with first treatment was significantly higher with prednisolone (62/99, 63%) than vigabatrin (5/18, 28%, P = 0.01) or nonstandard treatment (2/34, 5.9%, P < 0.01). Of 112 infants who commenced the UKISS treatment sequence, 71/112 (63%) responded to prednisolone 40 mg/day. Among non‐responders, 12/29 (41%) subsequently responded to prednisolone 60 mg/day, and 10/22 (45%) to vigabatrin. Severe side effects and spasm relapse were not significantly different between each treatment.
Conclusion
We confirm higher rates of spasm cessation with initial treatment with prednisolone than vigabatrin and nonstandard therapy. Non‐use of prednisolone as first treatment in over one third of infants highlights a concerning treatment gap. The UKISS treatment sequence has high overall treatment response (total 93/112; 83%), with similar benefit of subsequent prednisolone 60 mg/day and vigabatrin in prednisolone 40 mg/day non‐responders.</abstract><cop>Australia</cop><pub>John Wiley & Sons Australia, Ltd</pub><pmid>36054157</pmid><doi>10.1111/jpc.16181</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0001-8591-6605</orcidid><orcidid>https://orcid.org/0000-0002-2311-2174</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1034-4810 |
| ispartof | Journal of paediatrics and child health, 2022-12, Vol.58 (12), p.2197-2202 |
| issn | 1034-4810 1440-1754 |
| language | eng |
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| source | Wiley Online Library |
| subjects | Anticonvulsants - adverse effects Babies Clinical outcomes Drug therapy Humans Infant infantile spasms Original Pediatrics prednisolone Prednisolone - therapeutic use Recurrence Retrospective Studies Spasm - chemically induced Spasm - complications Spasm - drug therapy Spasms, Infantile - chemically induced Spasms, Infantile - complications Spasms, Infantile - drug therapy Steroids treatment vigabatrin Vigabatrin - adverse effects |
| title | Response to sequential treatment with prednisolone and vigabatrin in infantile spasms |
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