The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials
Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation. The parameters of inte...
Gespeichert in:
| Veröffentlicht in: | Medicine (Baltimore) 2017-05, Vol.96 (21), p.e6531-e6531 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e6531 |
|---|---|
| container_issue | 21 |
| container_start_page | e6531 |
| container_title | Medicine (Baltimore) |
| container_volume | 96 |
| creator | Jovanovski, Elena Li, Dandan Thanh Ho, Hoang Vi Djedovic, Vladimir Ruiz Marques, Any de Castro Shishtar, Esra Mejia, Sonia Blanco Sievenpiper, John L. de Souza, Russell J. Duvnjak, Lea Vuksan, Vladimir |
| description | Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation.
The parameters of interest were glycated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment for insulin resistance (HOMA-IR), fructosamine, and glycated albumin. A comprehensive search was conducted with MEDLINE, Embase, CINAHL, and Cochrane. Eligible studies included randomized controlled trials (RCTs) ≥1 month in duration that compared diets enriched in ALA with usual diets on glycemic parameters. For each study, the risk of bias as well as the study quality was assessed. Using the statistical software RevMan (v5.3), data were pooled using the generic inverse method with random effects model, and final results were expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed by the Cochran Q statistic and quantified by the I statistic.
A total of 8 trials (N = 212) were included in the meta-analysis. Compared to a control diet, a median dose of 4.4 g/day of ALA intake for a median duration of 3 months did not affect HbA1c (%) (MD = -.01; [95%: -.32, .31], P = .96). A median ALA dose of 5.4 g/day did not lower FBG (MD = .07; [95% CI: -.61, .76], P = .84) or FBI (MD = 7.03, [95% CI: -5.84, 19.89], P = .28). Summary effect estimates were generally compromised by considerable and unexplained heterogeneity (I ≥75%). In the subgroup analysis of continuous predictors, a reduction in HbA1c (%) and FBG (mmol/L) was significantly associated with an increased intake of ALA. Further adjustment for Publication Bias using Duval and Tweedie's trim-and-fill analysis provided an adjusted, significant MD of -.25 (95% CI: -.38, -.12; P |
| doi_str_mv | 10.1097/MD.0000000000006531 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5457843</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1902482976</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2854-51d97dbcfd58fdbfb8e3c832d8dc80b91b83710be9fcc78a27840e9d5f1e3a63</originalsourceid><addsrcrecordid>eNpdUUtv1DAQjhCILoVfgIR85JLWjzh2OCBVLY9Krbjs3XLsSWNw4sX27mr5SfxKHLatCpalGY2_lzVV9ZbgM4I7cX57dYafnJYz8qxaEc7amndt87xaYUx5LTrRnFSvUvqOMWGCNi-rEyo5k6xlq-r3egQEwwAmozAg7Tejrr2bg4fZGaSNsyjM6M4fDExlYMKcY_DIzeVat3N2q31Ce5dHlA8bQBRZp3vIkD6gC5QOKcOkc2FG2DnYIz1bNEHWtZ61PySXFttYpmFyv8A-GPilLTmc0R7l6IrJ6-rFUAq8ua-n1frzp_Xl1_rm25fry4ub2pRvNTUnthO2N4PlcrD90EtgRjJqpTUS9x3pJRME99ANxgipqZANhs7ygQDTLTutPh5lN9t-Amug5NFebaKbdDyooJ3692V2o7oLO8UbXqRYEXh_LxDDzy2krCaXDHivZwjbpEiHaSNpJxYvdoSaGFKKMDzaEKyWJavbK_X_kgvr3dOEj5yHrRZAcwTsg88Q0w-_3UNUI2ifx796XHS0ppgIzGmL62XUsD_m1Ldd</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1902482976</pqid></control><display><type>article</type><title>The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Wolters Kluwer Open Health</source><source>IngentaConnect Free/Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Jovanovski, Elena ; Li, Dandan ; Thanh Ho, Hoang Vi ; Djedovic, Vladimir ; Ruiz Marques, Any de Castro ; Shishtar, Esra ; Mejia, Sonia Blanco ; Sievenpiper, John L. ; de Souza, Russell J. ; Duvnjak, Lea ; Vuksan, Vladimir</creator><creatorcontrib>Jovanovski, Elena ; Li, Dandan ; Thanh Ho, Hoang Vi ; Djedovic, Vladimir ; Ruiz Marques, Any de Castro ; Shishtar, Esra ; Mejia, Sonia Blanco ; Sievenpiper, John L. ; de Souza, Russell J. ; Duvnjak, Lea ; Vuksan, Vladimir</creatorcontrib><description>Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation.
The parameters of interest were glycated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment for insulin resistance (HOMA-IR), fructosamine, and glycated albumin. A comprehensive search was conducted with MEDLINE, Embase, CINAHL, and Cochrane. Eligible studies included randomized controlled trials (RCTs) ≥1 month in duration that compared diets enriched in ALA with usual diets on glycemic parameters. For each study, the risk of bias as well as the study quality was assessed. Using the statistical software RevMan (v5.3), data were pooled using the generic inverse method with random effects model, and final results were expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed by the Cochran Q statistic and quantified by the I statistic.
A total of 8 trials (N = 212) were included in the meta-analysis. Compared to a control diet, a median dose of 4.4 g/day of ALA intake for a median duration of 3 months did not affect HbA1c (%) (MD = -.01; [95%: -.32, .31], P = .96). A median ALA dose of 5.4 g/day did not lower FBG (MD = .07; [95% CI: -.61, .76], P = .84) or FBI (MD = 7.03, [95% CI: -5.84, 19.89], P = .28). Summary effect estimates were generally compromised by considerable and unexplained heterogeneity (I ≥75%). In the subgroup analysis of continuous predictors, a reduction in HbA1c (%) and FBG (mmol/L) was significantly associated with an increased intake of ALA. Further adjustment for Publication Bias using Duval and Tweedie's trim-and-fill analysis provided an adjusted, significant MD of -.25 (95% CI: -.38, -.12; P <.001) for HbA1c (%).
ALA-enriched diets did not affect HbA1c, FBG, or FBI. The scarce number of existing RCTs and the presence of heterogeneity in our meta-analysis limit the ability to make firm conclusions about ALA in T2DM management. The potential for ALA to have dose-dependent effects warrants further research in this area.</description><identifier>ISSN: 0025-7974</identifier><identifier>EISSN: 1536-5964</identifier><identifier>DOI: 10.1097/MD.0000000000006531</identifier><identifier>PMID: 28538363</identifier><language>eng</language><publisher>United States: The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved</publisher><subject>alpha-Linolenic Acid - administration & dosage ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - diet therapy ; Humans ; Randomized Controlled Trials as Topic ; Systematic Review and Meta-Analysis</subject><ispartof>Medicine (Baltimore), 2017-05, Vol.96 (21), p.e6531-e6531</ispartof><rights>The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.</rights><rights>Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c2854-51d97dbcfd58fdbfb8e3c832d8dc80b91b83710be9fcc78a27840e9d5f1e3a63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457843/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457843/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28538363$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jovanovski, Elena</creatorcontrib><creatorcontrib>Li, Dandan</creatorcontrib><creatorcontrib>Thanh Ho, Hoang Vi</creatorcontrib><creatorcontrib>Djedovic, Vladimir</creatorcontrib><creatorcontrib>Ruiz Marques, Any de Castro</creatorcontrib><creatorcontrib>Shishtar, Esra</creatorcontrib><creatorcontrib>Mejia, Sonia Blanco</creatorcontrib><creatorcontrib>Sievenpiper, John L.</creatorcontrib><creatorcontrib>de Souza, Russell J.</creatorcontrib><creatorcontrib>Duvnjak, Lea</creatorcontrib><creatorcontrib>Vuksan, Vladimir</creatorcontrib><title>The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials</title><title>Medicine (Baltimore)</title><addtitle>Medicine (Baltimore)</addtitle><description>Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation.
The parameters of interest were glycated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment for insulin resistance (HOMA-IR), fructosamine, and glycated albumin. A comprehensive search was conducted with MEDLINE, Embase, CINAHL, and Cochrane. Eligible studies included randomized controlled trials (RCTs) ≥1 month in duration that compared diets enriched in ALA with usual diets on glycemic parameters. For each study, the risk of bias as well as the study quality was assessed. Using the statistical software RevMan (v5.3), data were pooled using the generic inverse method with random effects model, and final results were expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed by the Cochran Q statistic and quantified by the I statistic.
A total of 8 trials (N = 212) were included in the meta-analysis. Compared to a control diet, a median dose of 4.4 g/day of ALA intake for a median duration of 3 months did not affect HbA1c (%) (MD = -.01; [95%: -.32, .31], P = .96). A median ALA dose of 5.4 g/day did not lower FBG (MD = .07; [95% CI: -.61, .76], P = .84) or FBI (MD = 7.03, [95% CI: -5.84, 19.89], P = .28). Summary effect estimates were generally compromised by considerable and unexplained heterogeneity (I ≥75%). In the subgroup analysis of continuous predictors, a reduction in HbA1c (%) and FBG (mmol/L) was significantly associated with an increased intake of ALA. Further adjustment for Publication Bias using Duval and Tweedie's trim-and-fill analysis provided an adjusted, significant MD of -.25 (95% CI: -.38, -.12; P <.001) for HbA1c (%).
ALA-enriched diets did not affect HbA1c, FBG, or FBI. The scarce number of existing RCTs and the presence of heterogeneity in our meta-analysis limit the ability to make firm conclusions about ALA in T2DM management. The potential for ALA to have dose-dependent effects warrants further research in this area.</description><subject>alpha-Linolenic Acid - administration & dosage</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - diet therapy</subject><subject>Humans</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Systematic Review and Meta-Analysis</subject><issn>0025-7974</issn><issn>1536-5964</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUUtv1DAQjhCILoVfgIR85JLWjzh2OCBVLY9Krbjs3XLsSWNw4sX27mr5SfxKHLatCpalGY2_lzVV9ZbgM4I7cX57dYafnJYz8qxaEc7amndt87xaYUx5LTrRnFSvUvqOMWGCNi-rEyo5k6xlq-r3egQEwwAmozAg7Tejrr2bg4fZGaSNsyjM6M4fDExlYMKcY_DIzeVat3N2q31Ce5dHlA8bQBRZp3vIkD6gC5QOKcOkc2FG2DnYIz1bNEHWtZ61PySXFttYpmFyv8A-GPilLTmc0R7l6IrJ6-rFUAq8ua-n1frzp_Xl1_rm25fry4ub2pRvNTUnthO2N4PlcrD90EtgRjJqpTUS9x3pJRME99ANxgipqZANhs7ygQDTLTutPh5lN9t-Amug5NFebaKbdDyooJ3692V2o7oLO8UbXqRYEXh_LxDDzy2krCaXDHivZwjbpEiHaSNpJxYvdoSaGFKKMDzaEKyWJavbK_X_kgvr3dOEj5yHrRZAcwTsg88Q0w-_3UNUI2ifx796XHS0ppgIzGmL62XUsD_m1Ldd</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>Jovanovski, Elena</creator><creator>Li, Dandan</creator><creator>Thanh Ho, Hoang Vi</creator><creator>Djedovic, Vladimir</creator><creator>Ruiz Marques, Any de Castro</creator><creator>Shishtar, Esra</creator><creator>Mejia, Sonia Blanco</creator><creator>Sievenpiper, John L.</creator><creator>de Souza, Russell J.</creator><creator>Duvnjak, Lea</creator><creator>Vuksan, Vladimir</creator><general>The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved</general><general>Wolters Kluwer Health</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170501</creationdate><title>The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials</title><author>Jovanovski, Elena ; Li, Dandan ; Thanh Ho, Hoang Vi ; Djedovic, Vladimir ; Ruiz Marques, Any de Castro ; Shishtar, Esra ; Mejia, Sonia Blanco ; Sievenpiper, John L. ; de Souza, Russell J. ; Duvnjak, Lea ; Vuksan, Vladimir</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2854-51d97dbcfd58fdbfb8e3c832d8dc80b91b83710be9fcc78a27840e9d5f1e3a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>alpha-Linolenic Acid - administration & dosage</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - diet therapy</topic><topic>Humans</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Systematic Review and Meta-Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jovanovski, Elena</creatorcontrib><creatorcontrib>Li, Dandan</creatorcontrib><creatorcontrib>Thanh Ho, Hoang Vi</creatorcontrib><creatorcontrib>Djedovic, Vladimir</creatorcontrib><creatorcontrib>Ruiz Marques, Any de Castro</creatorcontrib><creatorcontrib>Shishtar, Esra</creatorcontrib><creatorcontrib>Mejia, Sonia Blanco</creatorcontrib><creatorcontrib>Sievenpiper, John L.</creatorcontrib><creatorcontrib>de Souza, Russell J.</creatorcontrib><creatorcontrib>Duvnjak, Lea</creatorcontrib><creatorcontrib>Vuksan, Vladimir</creatorcontrib><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Medicine (Baltimore)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jovanovski, Elena</au><au>Li, Dandan</au><au>Thanh Ho, Hoang Vi</au><au>Djedovic, Vladimir</au><au>Ruiz Marques, Any de Castro</au><au>Shishtar, Esra</au><au>Mejia, Sonia Blanco</au><au>Sievenpiper, John L.</au><au>de Souza, Russell J.</au><au>Duvnjak, Lea</au><au>Vuksan, Vladimir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials</atitle><jtitle>Medicine (Baltimore)</jtitle><addtitle>Medicine (Baltimore)</addtitle><date>2017-05-01</date><risdate>2017</risdate><volume>96</volume><issue>21</issue><spage>e6531</spage><epage>e6531</epage><pages>e6531-e6531</pages><issn>0025-7974</issn><eissn>1536-5964</eissn><abstract>Polyunsaturated fats (PUFAs) have been shown to reduce type 2 diabetes (T2DM) risk and improve insulin responsiveness in T2DM subjects, but whether the plant sources of omega-3 PUFA (alpha-linolenic acid [ALA]) have an effect on glycemic control requires further investigation.
The parameters of interest were glycated hemoglobin (HbA1c), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment for insulin resistance (HOMA-IR), fructosamine, and glycated albumin. A comprehensive search was conducted with MEDLINE, Embase, CINAHL, and Cochrane. Eligible studies included randomized controlled trials (RCTs) ≥1 month in duration that compared diets enriched in ALA with usual diets on glycemic parameters. For each study, the risk of bias as well as the study quality was assessed. Using the statistical software RevMan (v5.3), data were pooled using the generic inverse method with random effects model, and final results were expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed by the Cochran Q statistic and quantified by the I statistic.
A total of 8 trials (N = 212) were included in the meta-analysis. Compared to a control diet, a median dose of 4.4 g/day of ALA intake for a median duration of 3 months did not affect HbA1c (%) (MD = -.01; [95%: -.32, .31], P = .96). A median ALA dose of 5.4 g/day did not lower FBG (MD = .07; [95% CI: -.61, .76], P = .84) or FBI (MD = 7.03, [95% CI: -5.84, 19.89], P = .28). Summary effect estimates were generally compromised by considerable and unexplained heterogeneity (I ≥75%). In the subgroup analysis of continuous predictors, a reduction in HbA1c (%) and FBG (mmol/L) was significantly associated with an increased intake of ALA. Further adjustment for Publication Bias using Duval and Tweedie's trim-and-fill analysis provided an adjusted, significant MD of -.25 (95% CI: -.38, -.12; P <.001) for HbA1c (%).
ALA-enriched diets did not affect HbA1c, FBG, or FBI. The scarce number of existing RCTs and the presence of heterogeneity in our meta-analysis limit the ability to make firm conclusions about ALA in T2DM management. The potential for ALA to have dose-dependent effects warrants further research in this area.</abstract><cop>United States</cop><pub>The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved</pub><pmid>28538363</pmid><doi>10.1097/MD.0000000000006531</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0025-7974 |
| ispartof | Medicine (Baltimore), 2017-05, Vol.96 (21), p.e6531-e6531 |
| issn | 0025-7974 1536-5964 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5457843 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Wolters Kluwer Open Health; IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | alpha-Linolenic Acid - administration & dosage Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - diet therapy Humans Randomized Controlled Trials as Topic Systematic Review and Meta-Analysis |
| title | The effect of alpha-linolenic acid on glycemic control in individuals with type 2 diabetes: A systematic review and meta-analysis of randomized controlled clinical trials |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T01%3A09%3A10IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20effect%20of%20alpha-linolenic%20acid%20on%20glycemic%20control%20in%20individuals%20with%20type%202%20diabetes:%20A%20systematic%20review%20and%20meta-analysis%20of%20randomized%20controlled%20clinical%20trials&rft.jtitle=Medicine%20(Baltimore)&rft.au=Jovanovski,%20Elena&rft.date=2017-05-01&rft.volume=96&rft.issue=21&rft.spage=e6531&rft.epage=e6531&rft.pages=e6531-e6531&rft.issn=0025-7974&rft.eissn=1536-5964&rft_id=info:doi/10.1097/MD.0000000000006531&rft_dat=%3Cproquest_pubme%3E1902482976%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1902482976&rft_id=info:pmid/28538363&rfr_iscdi=true |