Evaluation of Injection Frequency and Visual Acuity Outcomes for Ranibizumab Monotherapy in Exudative Age-related Macular Degeneration
Objective To evaluate the visual outcomes for intravitreal ranibizumab administered on an as-needed basis for exudative age-related macular degeneration (AMD) and to investigate the relationship between injection frequency and visual outcome in this setting. Design Retrospective, interventional case...
Gespeichert in:
Veröffentlicht in: | Ophthalmology (Rochester, Minn.) Minn.), 2009-09, Vol.116 (9), p.1740-1747 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1747 |
---|---|
container_issue | 9 |
container_start_page | 1740 |
container_title | Ophthalmology (Rochester, Minn.) |
container_volume | 116 |
creator | Dadgostar, Hajir, MD, PhD Ventura, Alexandre A.C.M., MD Chung, Jeffrey Y., MD Sharma, Sumit, BS Kaiser, Peter K., MD |
description | Objective To evaluate the visual outcomes for intravitreal ranibizumab administered on an as-needed basis for exudative age-related macular degeneration (AMD) and to investigate the relationship between injection frequency and visual outcome in this setting. Design Retrospective, interventional case series. Participants A total of 131 eyes with treatment-naïve, exudative AMD undergoing ranibizumab monotherapy. Methods Intravitreal ranibizumab was administered on an as-needed basis guided by clinical examination and optical coherence tomography (OCT). The OCT scans were evaluated by the treating physicians for the presence of intraretinal fluid, subretinal fluid, intraretinal cysts, or increasing pigment epithelial detachment size. Clinical data including visual acuity (VA), choroidal neovascularization lesion morphology, and treatment course were collected retrospectively for analysis. Main Outcome Measures Mean change in best-corrected Snellen VA. Results The mean age was 81.3 years, mean follow-up was 12±4.3 months (minimum 6 months, median 12 months), and mean number of injections was 5.2±2.8. Mean baseline Snellen VA for the entire population was 20/110 and significantly improved at 6 months (20/80; P = 0.0002) and at last follow-up (20/90; P = 0.0066). At 6 months, 31% of eyes had gained at least 3 lines of VA and 90.5% had avoided loss of 3 lines. On average, it took 3.0 injections and 3.5 months to achieve a “dry” or “flat” macula on OCT after initiating treatment. Resolution of intra- and subretinal fluid on OCT did not correlate with the degree of vision improvement. Eyes receiving more frequent injections (defined as 3 lines of vision compared with 15.9% in the >2 months interval group ( P = 0.011). Conclusions In a population receiving as-needed injections of ranibizumab for exudative AMD, visual improvement was related to the frequency of injections received but not to the resolution of fluid by OCT. Treatment with ranibizumab on a strictly as-needed basis may result in undertreatment and significantly less visual gain. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references. |
doi_str_mv | 10.1016/j.ophtha.2009.05.033 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67635363</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0161642009005685</els_id><sourcerecordid>67635363</sourcerecordid><originalsourceid>FETCH-LOGICAL-c511t-1eebf99f9b5e1cae5c1ff99fb4e1acd6fc2a91d03aaa34095802cdab62e22e803</originalsourceid><addsrcrecordid>eNqFks2O0zAQgC0EYruFN0DIF7il2LHjbS5I1dKFlXa1En9Xa-JMtg6pXey4ovsAPDcOrUDiwska6ZsffzOEvOBswRlXb_qF323GDSxKxuoFqxZMiEdkxitZF_KCi8dkljFeKFmyM3IeY88YU0rIp-SM10oKuZQz8nO9hyHBaL2jvqPXrkfzO7gK-D2hMwcKrqVfbUww0JVJdjzQuzQav8VIOx_oR3C2sQ9pCw299c6PGwywO1Dr6PpHanPpPdLVPRYBBxixpbdg0gCBvsN7dJmd2j0jTzoYIj4_vXPy5Wr9-fJDcXP3_vpydVOYivOx4IhNV9dd3VTIDWBleDfFjUQOplWdKaHmLRMAICSrqyUrTQuNKrEsccnEnLw-1t0Fn78XR7210eAwgEOfolYXSlRCiQzKI2iCjzFgp3fBbiEcNGd68q97ffSvJ_-aVTr7z2kvT_VTs8X2b9JJeAZenQCIBoYugDM2_uFKXkvB8wBz8vbIYbaxtxh0NDavA1sb8oZ06-3_Jvm3gBmss7nnNzxg7H0KLpvWXMdSM_1pupXpVFjNWKWWlfgFb1W9_g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67635363</pqid></control><display><type>article</type><title>Evaluation of Injection Frequency and Visual Acuity Outcomes for Ranibizumab Monotherapy in Exudative Age-related Macular Degeneration</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Dadgostar, Hajir, MD, PhD ; Ventura, Alexandre A.C.M., MD ; Chung, Jeffrey Y., MD ; Sharma, Sumit, BS ; Kaiser, Peter K., MD</creator><creatorcontrib>Dadgostar, Hajir, MD, PhD ; Ventura, Alexandre A.C.M., MD ; Chung, Jeffrey Y., MD ; Sharma, Sumit, BS ; Kaiser, Peter K., MD</creatorcontrib><description>Objective To evaluate the visual outcomes for intravitreal ranibizumab administered on an as-needed basis for exudative age-related macular degeneration (AMD) and to investigate the relationship between injection frequency and visual outcome in this setting. Design Retrospective, interventional case series. Participants A total of 131 eyes with treatment-naïve, exudative AMD undergoing ranibizumab monotherapy. Methods Intravitreal ranibizumab was administered on an as-needed basis guided by clinical examination and optical coherence tomography (OCT). The OCT scans were evaluated by the treating physicians for the presence of intraretinal fluid, subretinal fluid, intraretinal cysts, or increasing pigment epithelial detachment size. Clinical data including visual acuity (VA), choroidal neovascularization lesion morphology, and treatment course were collected retrospectively for analysis. Main Outcome Measures Mean change in best-corrected Snellen VA. Results The mean age was 81.3 years, mean follow-up was 12±4.3 months (minimum 6 months, median 12 months), and mean number of injections was 5.2±2.8. Mean baseline Snellen VA for the entire population was 20/110 and significantly improved at 6 months (20/80; P = 0.0002) and at last follow-up (20/90; P = 0.0066). At 6 months, 31% of eyes had gained at least 3 lines of VA and 90.5% had avoided loss of 3 lines. On average, it took 3.0 injections and 3.5 months to achieve a “dry” or “flat” macula on OCT after initiating treatment. Resolution of intra- and subretinal fluid on OCT did not correlate with the degree of vision improvement. Eyes receiving more frequent injections (defined as <2 months mean inter-injection interval) gained more vision (+2.3 lines at 6 months) than eyes receiving injections less frequently (+0.46 lines at 6 months; P = 0.012). At 6 months, 3.1% of those in the more frequent injection group lost >3 lines of vision compared with 15.9% in the >2 months interval group ( P = 0.011). Conclusions In a population receiving as-needed injections of ranibizumab for exudative AMD, visual improvement was related to the frequency of injections received but not to the resolution of fluid by OCT. Treatment with ranibizumab on a strictly as-needed basis may result in undertreatment and significantly less visual gain. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.</description><identifier>ISSN: 0161-6420</identifier><identifier>EISSN: 1549-4713</identifier><identifier>DOI: 10.1016/j.ophtha.2009.05.033</identifier><identifier>PMID: 19643484</identifier><identifier>CODEN: OPHTDG</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Aged, 80 and over ; Angiogenesis Inhibitors - administration & dosage ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal, Humanized ; Biological and medical sciences ; Choroidal Neovascularization - drug therapy ; Exudates and Transudates ; Female ; Follow-Up Studies ; Humans ; Injections ; Macular Degeneration - drug therapy ; Male ; Medical sciences ; Miscellaneous ; Ophthalmology ; Ranibizumab ; Retinopathies ; Retreatment ; Retrospective Studies ; Tomography, Optical Coherence ; Vascular Endothelial Growth Factor A - antagonists & inhibitors ; Visual Acuity - physiology ; Vitreous Body</subject><ispartof>Ophthalmology (Rochester, Minn.), 2009-09, Vol.116 (9), p.1740-1747</ispartof><rights>American Academy of Ophthalmology</rights><rights>2009 American Academy of Ophthalmology</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-1eebf99f9b5e1cae5c1ff99fb4e1acd6fc2a91d03aaa34095802cdab62e22e803</citedby><cites>FETCH-LOGICAL-c511t-1eebf99f9b5e1cae5c1ff99fb4e1acd6fc2a91d03aaa34095802cdab62e22e803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ophtha.2009.05.033$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21943136$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19643484$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dadgostar, Hajir, MD, PhD</creatorcontrib><creatorcontrib>Ventura, Alexandre A.C.M., MD</creatorcontrib><creatorcontrib>Chung, Jeffrey Y., MD</creatorcontrib><creatorcontrib>Sharma, Sumit, BS</creatorcontrib><creatorcontrib>Kaiser, Peter K., MD</creatorcontrib><title>Evaluation of Injection Frequency and Visual Acuity Outcomes for Ranibizumab Monotherapy in Exudative Age-related Macular Degeneration</title><title>Ophthalmology (Rochester, Minn.)</title><addtitle>Ophthalmology</addtitle><description>Objective To evaluate the visual outcomes for intravitreal ranibizumab administered on an as-needed basis for exudative age-related macular degeneration (AMD) and to investigate the relationship between injection frequency and visual outcome in this setting. Design Retrospective, interventional case series. Participants A total of 131 eyes with treatment-naïve, exudative AMD undergoing ranibizumab monotherapy. Methods Intravitreal ranibizumab was administered on an as-needed basis guided by clinical examination and optical coherence tomography (OCT). The OCT scans were evaluated by the treating physicians for the presence of intraretinal fluid, subretinal fluid, intraretinal cysts, or increasing pigment epithelial detachment size. Clinical data including visual acuity (VA), choroidal neovascularization lesion morphology, and treatment course were collected retrospectively for analysis. Main Outcome Measures Mean change in best-corrected Snellen VA. Results The mean age was 81.3 years, mean follow-up was 12±4.3 months (minimum 6 months, median 12 months), and mean number of injections was 5.2±2.8. Mean baseline Snellen VA for the entire population was 20/110 and significantly improved at 6 months (20/80; P = 0.0002) and at last follow-up (20/90; P = 0.0066). At 6 months, 31% of eyes had gained at least 3 lines of VA and 90.5% had avoided loss of 3 lines. On average, it took 3.0 injections and 3.5 months to achieve a “dry” or “flat” macula on OCT after initiating treatment. Resolution of intra- and subretinal fluid on OCT did not correlate with the degree of vision improvement. Eyes receiving more frequent injections (defined as <2 months mean inter-injection interval) gained more vision (+2.3 lines at 6 months) than eyes receiving injections less frequently (+0.46 lines at 6 months; P = 0.012). At 6 months, 3.1% of those in the more frequent injection group lost >3 lines of vision compared with 15.9% in the >2 months interval group ( P = 0.011). Conclusions In a population receiving as-needed injections of ranibizumab for exudative AMD, visual improvement was related to the frequency of injections received but not to the resolution of fluid by OCT. Treatment with ranibizumab on a strictly as-needed basis may result in undertreatment and significantly less visual gain. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.</description><subject>Aged, 80 and over</subject><subject>Angiogenesis Inhibitors - administration & dosage</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Biological and medical sciences</subject><subject>Choroidal Neovascularization - drug therapy</subject><subject>Exudates and Transudates</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Injections</subject><subject>Macular Degeneration - drug therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Miscellaneous</subject><subject>Ophthalmology</subject><subject>Ranibizumab</subject><subject>Retinopathies</subject><subject>Retreatment</subject><subject>Retrospective Studies</subject><subject>Tomography, Optical Coherence</subject><subject>Vascular Endothelial Growth Factor A - antagonists & inhibitors</subject><subject>Visual Acuity - physiology</subject><subject>Vitreous Body</subject><issn>0161-6420</issn><issn>1549-4713</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks2O0zAQgC0EYruFN0DIF7il2LHjbS5I1dKFlXa1En9Xa-JMtg6pXey4ovsAPDcOrUDiwska6ZsffzOEvOBswRlXb_qF323GDSxKxuoFqxZMiEdkxitZF_KCi8dkljFeKFmyM3IeY88YU0rIp-SM10oKuZQz8nO9hyHBaL2jvqPXrkfzO7gK-D2hMwcKrqVfbUww0JVJdjzQuzQav8VIOx_oR3C2sQ9pCw299c6PGwywO1Dr6PpHanPpPdLVPRYBBxixpbdg0gCBvsN7dJmd2j0jTzoYIj4_vXPy5Wr9-fJDcXP3_vpydVOYivOx4IhNV9dd3VTIDWBleDfFjUQOplWdKaHmLRMAICSrqyUrTQuNKrEsccnEnLw-1t0Fn78XR7210eAwgEOfolYXSlRCiQzKI2iCjzFgp3fBbiEcNGd68q97ffSvJ_-aVTr7z2kvT_VTs8X2b9JJeAZenQCIBoYugDM2_uFKXkvB8wBz8vbIYbaxtxh0NDavA1sb8oZ06-3_Jvm3gBmss7nnNzxg7H0KLpvWXMdSM_1pupXpVFjNWKWWlfgFb1W9_g</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Dadgostar, Hajir, MD, PhD</creator><creator>Ventura, Alexandre A.C.M., MD</creator><creator>Chung, Jeffrey Y., MD</creator><creator>Sharma, Sumit, BS</creator><creator>Kaiser, Peter K., MD</creator><general>Elsevier Inc</general><general>Elsevier</general><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>7X8</scope></search><sort><creationdate>20090901</creationdate><title>Evaluation of Injection Frequency and Visual Acuity Outcomes for Ranibizumab Monotherapy in Exudative Age-related Macular Degeneration</title><author>Dadgostar, Hajir, MD, PhD ; Ventura, Alexandre A.C.M., MD ; Chung, Jeffrey Y., MD ; Sharma, Sumit, BS ; Kaiser, Peter K., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-1eebf99f9b5e1cae5c1ff99fb4e1acd6fc2a91d03aaa34095802cdab62e22e803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Aged, 80 and over</topic><topic>Angiogenesis Inhibitors - administration & dosage</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Biological and medical sciences</topic><topic>Choroidal Neovascularization - drug therapy</topic><topic>Exudates and Transudates</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Injections</topic><topic>Macular Degeneration - drug therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Miscellaneous</topic><topic>Ophthalmology</topic><topic>Ranibizumab</topic><topic>Retinopathies</topic><topic>Retreatment</topic><topic>Retrospective Studies</topic><topic>Tomography, Optical Coherence</topic><topic>Vascular Endothelial Growth Factor A - antagonists & inhibitors</topic><topic>Visual Acuity - physiology</topic><topic>Vitreous Body</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dadgostar, Hajir, MD, PhD</creatorcontrib><creatorcontrib>Ventura, Alexandre A.C.M., MD</creatorcontrib><creatorcontrib>Chung, Jeffrey Y., MD</creatorcontrib><creatorcontrib>Sharma, Sumit, BS</creatorcontrib><creatorcontrib>Kaiser, Peter K., MD</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>Ophthalmology (Rochester, Minn.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dadgostar, Hajir, MD, PhD</au><au>Ventura, Alexandre A.C.M., MD</au><au>Chung, Jeffrey Y., MD</au><au>Sharma, Sumit, BS</au><au>Kaiser, Peter K., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of Injection Frequency and Visual Acuity Outcomes for Ranibizumab Monotherapy in Exudative Age-related Macular Degeneration</atitle><jtitle>Ophthalmology (Rochester, Minn.)</jtitle><addtitle>Ophthalmology</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>116</volume><issue>9</issue><spage>1740</spage><epage>1747</epage><pages>1740-1747</pages><issn>0161-6420</issn><eissn>1549-4713</eissn><coden>OPHTDG</coden><abstract>Objective To evaluate the visual outcomes for intravitreal ranibizumab administered on an as-needed basis for exudative age-related macular degeneration (AMD) and to investigate the relationship between injection frequency and visual outcome in this setting. Design Retrospective, interventional case series. Participants A total of 131 eyes with treatment-naïve, exudative AMD undergoing ranibizumab monotherapy. Methods Intravitreal ranibizumab was administered on an as-needed basis guided by clinical examination and optical coherence tomography (OCT). The OCT scans were evaluated by the treating physicians for the presence of intraretinal fluid, subretinal fluid, intraretinal cysts, or increasing pigment epithelial detachment size. Clinical data including visual acuity (VA), choroidal neovascularization lesion morphology, and treatment course were collected retrospectively for analysis. Main Outcome Measures Mean change in best-corrected Snellen VA. Results The mean age was 81.3 years, mean follow-up was 12±4.3 months (minimum 6 months, median 12 months), and mean number of injections was 5.2±2.8. Mean baseline Snellen VA for the entire population was 20/110 and significantly improved at 6 months (20/80; P = 0.0002) and at last follow-up (20/90; P = 0.0066). At 6 months, 31% of eyes had gained at least 3 lines of VA and 90.5% had avoided loss of 3 lines. On average, it took 3.0 injections and 3.5 months to achieve a “dry” or “flat” macula on OCT after initiating treatment. Resolution of intra- and subretinal fluid on OCT did not correlate with the degree of vision improvement. Eyes receiving more frequent injections (defined as <2 months mean inter-injection interval) gained more vision (+2.3 lines at 6 months) than eyes receiving injections less frequently (+0.46 lines at 6 months; P = 0.012). At 6 months, 3.1% of those in the more frequent injection group lost >3 lines of vision compared with 15.9% in the >2 months interval group ( P = 0.011). Conclusions In a population receiving as-needed injections of ranibizumab for exudative AMD, visual improvement was related to the frequency of injections received but not to the resolution of fluid by OCT. Treatment with ranibizumab on a strictly as-needed basis may result in undertreatment and significantly less visual gain. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>19643484</pmid><doi>10.1016/j.ophtha.2009.05.033</doi><tpages>8</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0161-6420 |
ispartof | Ophthalmology (Rochester, Minn.), 2009-09, Vol.116 (9), p.1740-1747 |
issn | 0161-6420 1549-4713 |
language | eng |
recordid | cdi_proquest_miscellaneous_67635363 |
source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
subjects | Aged, 80 and over Angiogenesis Inhibitors - administration & dosage Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal, Humanized Biological and medical sciences Choroidal Neovascularization - drug therapy Exudates and Transudates Female Follow-Up Studies Humans Injections Macular Degeneration - drug therapy Male Medical sciences Miscellaneous Ophthalmology Ranibizumab Retinopathies Retreatment Retrospective Studies Tomography, Optical Coherence Vascular Endothelial Growth Factor A - antagonists & inhibitors Visual Acuity - physiology Vitreous Body |
title | Evaluation of Injection Frequency and Visual Acuity Outcomes for Ranibizumab Monotherapy in Exudative Age-related Macular Degeneration |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T19%3A48%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Evaluation%20of%20Injection%20Frequency%20and%20Visual%20Acuity%20Outcomes%20for%20Ranibizumab%20Monotherapy%20in%20Exudative%20Age-related%20Macular%20Degeneration&rft.jtitle=Ophthalmology%20(Rochester,%20Minn.)&rft.au=Dadgostar,%20Hajir,%20MD,%20PhD&rft.date=2009-09-01&rft.volume=116&rft.issue=9&rft.spage=1740&rft.epage=1747&rft.pages=1740-1747&rft.issn=0161-6420&rft.eissn=1549-4713&rft.coden=OPHTDG&rft_id=info:doi/10.1016/j.ophtha.2009.05.033&rft_dat=%3Cproquest_cross%3E67635363%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=67635363&rft_id=info:pmid/19643484&rft_els_id=1_s2_0_S0161642009005685&rfr_iscdi=true |