Loading…
Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing’s disease
Cushing’s disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17...
Saved in:
| Published in: | Pituitary 2013-12, Vol.16 (4), p.536-544 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c438t-6f6833ca055890be36addc16358a7cf94632e3a5648357eeb9ee8301d1f9d6203 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c438t-6f6833ca055890be36addc16358a7cf94632e3a5648357eeb9ee8301d1f9d6203 |
| container_end_page | 544 |
| container_issue | 4 |
| container_start_page | 536 |
| container_title | Pituitary |
| container_volume | 16 |
| creator | van der Pas, R. de Bruin, C. Pereira, A. M. Romijn, J. A. Netea-Maier, R. T. Hermus, A. R. Zelissen, P. M. de Jong, F. H. van der Lely, A. J. de Herder, W. W. Webb, S. M. Lamberts, S. W. J. Hofland, L. J. Feelders, R. A. |
| description | Cushing’s disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17 patients, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. After 80 days, 15/17 (88 %) patients had reached normal urinary free cortisol excretion (UFC). Subsequently, patients continued medical therapy or underwent surgery. UFC, plasma and salivary CDR and QoL-related parameters (assessed using 5 questionnaires: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index-20, RAND-36, CushingQoL) were measured. At baseline, 5/17 patients had preserved CDR. In 6/12 patients with disturbed baseline CDR, recovery was observed, but without any correlation with QoL. QoL was significantly impaired according to 18/20 subscales in CD patients compared to literature-derived controls. According to the RAND-36 questionnaire, patients reported more pain at day 80 (
p
|
| doi_str_mv | 10.1007/s11102-012-0452-2 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_1449258218</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3120857061</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-6f6833ca055890be36addc16358a7cf94632e3a5648357eeb9ee8301d1f9d6203</originalsourceid><addsrcrecordid>eNp1kMtq3DAUhkVoySTTPkA3RdC1Ex1dbHkZhtwgkE0K3QmNfTTjwWMnOvJidnmNvF6eJJpOErrpQkig7_8P52PsB4gzEKI6JwAQshCQjzaykEfsBEylikoL9SW_lS0LpeHPjJ0SbYTIKaWP2UwqKQ1IOGG4GGPqaOx5201x8D2P611ab7kfWv40-b5LOz4G3ncBuQ8JI6epaZAoTD3fYts1OZMi-rTFIe3RxUTrbli9Pr9QLiX0hN_Y1-B7wu_v95z9vrp8WNwUd_fXt4uLu6LRyqaiDKVVqvHCGFuLJarSt20DpTLWV02odakkKm9KbZWpEJc1olUCWgh1W0qh5uzXofcxjk8TUnKb8e9W5EDrWhorwWYKDlQTR6KIwT3GbuvjzoFwe7HuINZlsW4v1smc-fnePC3z1p-JD5MZkAeA8tewwvjP6P-2vgGrd4Rq</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1449258218</pqid></control><display><type>article</type><title>Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing’s disease</title><source>Springer Link</source><creator>van der Pas, R. ; de Bruin, C. ; Pereira, A. M. ; Romijn, J. A. ; Netea-Maier, R. T. ; Hermus, A. R. ; Zelissen, P. M. ; de Jong, F. H. ; van der Lely, A. J. ; de Herder, W. W. ; Webb, S. M. ; Lamberts, S. W. J. ; Hofland, L. J. ; Feelders, R. A.</creator><creatorcontrib>van der Pas, R. ; de Bruin, C. ; Pereira, A. M. ; Romijn, J. A. ; Netea-Maier, R. T. ; Hermus, A. R. ; Zelissen, P. M. ; de Jong, F. H. ; van der Lely, A. J. ; de Herder, W. W. ; Webb, S. M. ; Lamberts, S. W. J. ; Hofland, L. J. ; Feelders, R. A.</creatorcontrib><description>Cushing’s disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17 patients, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. After 80 days, 15/17 (88 %) patients had reached normal urinary free cortisol excretion (UFC). Subsequently, patients continued medical therapy or underwent surgery. UFC, plasma and salivary CDR and QoL-related parameters (assessed using 5 questionnaires: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index-20, RAND-36, CushingQoL) were measured. At baseline, 5/17 patients had preserved CDR. In 6/12 patients with disturbed baseline CDR, recovery was observed, but without any correlation with QoL. QoL was significantly impaired according to 18/20 subscales in CD patients compared to literature-derived controls. According to the RAND-36 questionnaire, patients reported more pain at day 80 (
p
< 0.05), which might reflect steroid-withdrawal. Generally, QoL did not improve or deteriorate after 80 days. CushingQoL scores seemed to improve after 1 year of remission in three patients that continued medical therapy (
p
= 0.11). CDR can recover during successful pituitary- and adrenal-targeted medical therapy. Patients with CD have impaired QoL compared to controls. Despite the occurrence of side-effects, QoL does not deteriorate after short-term biochemical remission induced by medical therapy, but might improve after sustained control of hypercortisolism.</description><identifier>ISSN: 1386-341X</identifier><identifier>EISSN: 1573-7403</identifier><identifier>DOI: 10.1007/s11102-012-0452-2</identifier><identifier>PMID: 23225121</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>Adult ; Aged ; Circadian Rhythm ; Dopamine Agonists - therapeutic use ; Endocrinology ; Ergolines - therapeutic use ; Female ; Human Physiology ; Humans ; Hydrocortisone - blood ; Hydrocortisone - metabolism ; Ketoconazole - therapeutic use ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Pituitary ACTH Hypersecretion - blood ; Pituitary ACTH Hypersecretion - drug therapy ; Pituitary ACTH Hypersecretion - metabolism ; Quality of Life ; Somatostatin - analogs & derivatives ; Somatostatin - therapeutic use ; Surveys and Questionnaires ; Young Adult</subject><ispartof>Pituitary, 2013-12, Vol.16 (4), p.536-544</ispartof><rights>Springer Science+Business Media New York 2012</rights><rights>Springer Science+Business Media New York 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-6f6833ca055890be36addc16358a7cf94632e3a5648357eeb9ee8301d1f9d6203</citedby><cites>FETCH-LOGICAL-c438t-6f6833ca055890be36addc16358a7cf94632e3a5648357eeb9ee8301d1f9d6203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23225121$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van der Pas, R.</creatorcontrib><creatorcontrib>de Bruin, C.</creatorcontrib><creatorcontrib>Pereira, A. M.</creatorcontrib><creatorcontrib>Romijn, J. A.</creatorcontrib><creatorcontrib>Netea-Maier, R. T.</creatorcontrib><creatorcontrib>Hermus, A. R.</creatorcontrib><creatorcontrib>Zelissen, P. M.</creatorcontrib><creatorcontrib>de Jong, F. H.</creatorcontrib><creatorcontrib>van der Lely, A. J.</creatorcontrib><creatorcontrib>de Herder, W. W.</creatorcontrib><creatorcontrib>Webb, S. M.</creatorcontrib><creatorcontrib>Lamberts, S. W. J.</creatorcontrib><creatorcontrib>Hofland, L. J.</creatorcontrib><creatorcontrib>Feelders, R. A.</creatorcontrib><title>Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing’s disease</title><title>Pituitary</title><addtitle>Pituitary</addtitle><addtitle>Pituitary</addtitle><description>Cushing’s disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17 patients, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. After 80 days, 15/17 (88 %) patients had reached normal urinary free cortisol excretion (UFC). Subsequently, patients continued medical therapy or underwent surgery. UFC, plasma and salivary CDR and QoL-related parameters (assessed using 5 questionnaires: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index-20, RAND-36, CushingQoL) were measured. At baseline, 5/17 patients had preserved CDR. In 6/12 patients with disturbed baseline CDR, recovery was observed, but without any correlation with QoL. QoL was significantly impaired according to 18/20 subscales in CD patients compared to literature-derived controls. According to the RAND-36 questionnaire, patients reported more pain at day 80 (
p
< 0.05), which might reflect steroid-withdrawal. Generally, QoL did not improve or deteriorate after 80 days. CushingQoL scores seemed to improve after 1 year of remission in three patients that continued medical therapy (
p
= 0.11). CDR can recover during successful pituitary- and adrenal-targeted medical therapy. Patients with CD have impaired QoL compared to controls. Despite the occurrence of side-effects, QoL does not deteriorate after short-term biochemical remission induced by medical therapy, but might improve after sustained control of hypercortisolism.</description><subject>Adult</subject><subject>Aged</subject><subject>Circadian Rhythm</subject><subject>Dopamine Agonists - therapeutic use</subject><subject>Endocrinology</subject><subject>Ergolines - therapeutic use</subject><subject>Female</subject><subject>Human Physiology</subject><subject>Humans</subject><subject>Hydrocortisone - blood</subject><subject>Hydrocortisone - metabolism</subject><subject>Ketoconazole - therapeutic use</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Pituitary ACTH Hypersecretion - blood</subject><subject>Pituitary ACTH Hypersecretion - drug therapy</subject><subject>Pituitary ACTH Hypersecretion - metabolism</subject><subject>Quality of Life</subject><subject>Somatostatin - analogs & derivatives</subject><subject>Somatostatin - therapeutic use</subject><subject>Surveys and Questionnaires</subject><subject>Young Adult</subject><issn>1386-341X</issn><issn>1573-7403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp1kMtq3DAUhkVoySTTPkA3RdC1Ex1dbHkZhtwgkE0K3QmNfTTjwWMnOvJidnmNvF6eJJpOErrpQkig7_8P52PsB4gzEKI6JwAQshCQjzaykEfsBEylikoL9SW_lS0LpeHPjJ0SbYTIKaWP2UwqKQ1IOGG4GGPqaOx5201x8D2P611ab7kfWv40-b5LOz4G3ncBuQ8JI6epaZAoTD3fYts1OZMi-rTFIe3RxUTrbli9Pr9QLiX0hN_Y1-B7wu_v95z9vrp8WNwUd_fXt4uLu6LRyqaiDKVVqvHCGFuLJarSt20DpTLWV02odakkKm9KbZWpEJc1olUCWgh1W0qh5uzXofcxjk8TUnKb8e9W5EDrWhorwWYKDlQTR6KIwT3GbuvjzoFwe7HuINZlsW4v1smc-fnePC3z1p-JD5MZkAeA8tewwvjP6P-2vgGrd4Rq</recordid><startdate>20131201</startdate><enddate>20131201</enddate><creator>van der Pas, R.</creator><creator>de Bruin, C.</creator><creator>Pereira, A. M.</creator><creator>Romijn, J. A.</creator><creator>Netea-Maier, R. T.</creator><creator>Hermus, A. R.</creator><creator>Zelissen, P. M.</creator><creator>de Jong, F. H.</creator><creator>van der Lely, A. J.</creator><creator>de Herder, W. W.</creator><creator>Webb, S. M.</creator><creator>Lamberts, S. W. J.</creator><creator>Hofland, L. J.</creator><creator>Feelders, R. A.</creator><general>Springer US</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20131201</creationdate><title>Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing’s disease</title><author>van der Pas, R. ; de Bruin, C. ; Pereira, A. M. ; Romijn, J. A. ; Netea-Maier, R. T. ; Hermus, A. R. ; Zelissen, P. M. ; de Jong, F. H. ; van der Lely, A. J. ; de Herder, W. W. ; Webb, S. M. ; Lamberts, S. W. J. ; Hofland, L. J. ; Feelders, R. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-6f6833ca055890be36addc16358a7cf94632e3a5648357eeb9ee8301d1f9d6203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Circadian Rhythm</topic><topic>Dopamine Agonists - therapeutic use</topic><topic>Endocrinology</topic><topic>Ergolines - therapeutic use</topic><topic>Female</topic><topic>Human Physiology</topic><topic>Humans</topic><topic>Hydrocortisone - blood</topic><topic>Hydrocortisone - metabolism</topic><topic>Ketoconazole - therapeutic use</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Pituitary ACTH Hypersecretion - blood</topic><topic>Pituitary ACTH Hypersecretion - drug therapy</topic><topic>Pituitary ACTH Hypersecretion - metabolism</topic><topic>Quality of Life</topic><topic>Somatostatin - analogs & derivatives</topic><topic>Somatostatin - therapeutic use</topic><topic>Surveys and Questionnaires</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van der Pas, R.</creatorcontrib><creatorcontrib>de Bruin, C.</creatorcontrib><creatorcontrib>Pereira, A. M.</creatorcontrib><creatorcontrib>Romijn, J. A.</creatorcontrib><creatorcontrib>Netea-Maier, R. T.</creatorcontrib><creatorcontrib>Hermus, A. R.</creatorcontrib><creatorcontrib>Zelissen, P. M.</creatorcontrib><creatorcontrib>de Jong, F. H.</creatorcontrib><creatorcontrib>van der Lely, A. J.</creatorcontrib><creatorcontrib>de Herder, W. W.</creatorcontrib><creatorcontrib>Webb, S. M.</creatorcontrib><creatorcontrib>Lamberts, S. W. J.</creatorcontrib><creatorcontrib>Hofland, L. J.</creatorcontrib><creatorcontrib>Feelders, R. A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma 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)</collection><collection>ProQuest Central</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</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 China</collection><jtitle>Pituitary</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van der Pas, R.</au><au>de Bruin, C.</au><au>Pereira, A. M.</au><au>Romijn, J. A.</au><au>Netea-Maier, R. T.</au><au>Hermus, A. R.</au><au>Zelissen, P. M.</au><au>de Jong, F. H.</au><au>van der Lely, A. J.</au><au>de Herder, W. W.</au><au>Webb, S. M.</au><au>Lamberts, S. W. J.</au><au>Hofland, L. J.</au><au>Feelders, R. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing’s disease</atitle><jtitle>Pituitary</jtitle><stitle>Pituitary</stitle><addtitle>Pituitary</addtitle><date>2013-12-01</date><risdate>2013</risdate><volume>16</volume><issue>4</issue><spage>536</spage><epage>544</epage><pages>536-544</pages><issn>1386-341X</issn><eissn>1573-7403</eissn><abstract>Cushing’s disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17 patients, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. After 80 days, 15/17 (88 %) patients had reached normal urinary free cortisol excretion (UFC). Subsequently, patients continued medical therapy or underwent surgery. UFC, plasma and salivary CDR and QoL-related parameters (assessed using 5 questionnaires: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index-20, RAND-36, CushingQoL) were measured. At baseline, 5/17 patients had preserved CDR. In 6/12 patients with disturbed baseline CDR, recovery was observed, but without any correlation with QoL. QoL was significantly impaired according to 18/20 subscales in CD patients compared to literature-derived controls. According to the RAND-36 questionnaire, patients reported more pain at day 80 (
p
< 0.05), which might reflect steroid-withdrawal. Generally, QoL did not improve or deteriorate after 80 days. CushingQoL scores seemed to improve after 1 year of remission in three patients that continued medical therapy (
p
= 0.11). CDR can recover during successful pituitary- and adrenal-targeted medical therapy. Patients with CD have impaired QoL compared to controls. Despite the occurrence of side-effects, QoL does not deteriorate after short-term biochemical remission induced by medical therapy, but might improve after sustained control of hypercortisolism.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>23225121</pmid><doi>10.1007/s11102-012-0452-2</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1386-341X |
| ispartof | Pituitary, 2013-12, Vol.16 (4), p.536-544 |
| issn | 1386-341X 1573-7403 |
| language | eng |
| recordid | cdi_proquest_journals_1449258218 |
| source | Springer Link |
| subjects | Adult Aged Circadian Rhythm Dopamine Agonists - therapeutic use Endocrinology Ergolines - therapeutic use Female Human Physiology Humans Hydrocortisone - blood Hydrocortisone - metabolism Ketoconazole - therapeutic use Male Medicine Medicine & Public Health Middle Aged Pituitary ACTH Hypersecretion - blood Pituitary ACTH Hypersecretion - drug therapy Pituitary ACTH Hypersecretion - metabolism Quality of Life Somatostatin - analogs & derivatives Somatostatin - therapeutic use Surveys and Questionnaires Young Adult |
| title | Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing’s disease |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T13%3A35%3A23IST&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=Cortisol%20diurnal%20rhythm%20and%20quality%20of%20life%20after%20successful%20medical%20treatment%20of%20Cushing%E2%80%99s%20disease&rft.jtitle=Pituitary&rft.au=van%20der%20Pas,%20R.&rft.date=2013-12-01&rft.volume=16&rft.issue=4&rft.spage=536&rft.epage=544&rft.pages=536-544&rft.issn=1386-341X&rft.eissn=1573-7403&rft_id=info:doi/10.1007/s11102-012-0452-2&rft_dat=%3Cproquest_cross%3E3120857061%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c438t-6f6833ca055890be36addc16358a7cf94632e3a5648357eeb9ee8301d1f9d6203%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1449258218&rft_id=info:pmid/23225121&rfr_iscdi=true |