Transcranial magnetic stimulation for the treatment of epilepsy
Background Epilepsy is a highly prevalent neurological condition characterized by repeated unprovoked seizures with various etiologies. Although antiepileptic medications produce clinical improvement in most individuals, nearly a third of individuals have drug‐resistant epilepsy that carries signifi...
Gespeichert in:
| Veröffentlicht in: | Cochrane database of systematic reviews 2016-08, Vol.2016 (8), p.CD011025-CD011025 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | CD011025 |
|---|---|
| container_issue | 8 |
| container_start_page | CD011025 |
| container_title | Cochrane database of systematic reviews |
| container_volume | 2016 |
| creator | Chen, Ricky Spencer, David C Weston, Jennifer Nolan, Sarah J Chen, Ricky |
| description | Background
Epilepsy is a highly prevalent neurological condition characterized by repeated unprovoked seizures with various etiologies. Although antiepileptic medications produce clinical improvement in most individuals, nearly a third of individuals have drug‐resistant epilepsy that carries significant morbidity and mortality. There remains a need for non‐invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low‐frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy.
Objectives
To assess the evidence for the use of TMS in individuals with drug‐resistant epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges, antiepileptic medication use, and side‐effects.
Search methods
We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 10 March 2016), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) up to March 2016. We also searched SCOPUS (1823 to June 2014) as a substitute for Embase (but it is no longer necessary to search SCOPUS, because randomized controlled trials (RCTs) and quasi‐RCTs in EMBASE are now included in CENTRAL).
Selection criteria
Eligible studies were RCTs that were double‐blinded, single‐blinded or unblinded, and placebo, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, duration, intensity, or setup (focal or vertex treatment) on patients with drug‐resistant epilepsy. The search revealed 274 records from the databases, that after selection provided seven full‐text relevant studies for inclusion. Of the seven studies included, five were completed studies with published data and included randomized, blinded trials. The total number of participants in the seven trials was 230.
Data collection and analysis
We extracted information from each trial including methodological data; participant demographics including baseline seizure frequency, type of epileptic drugs taken; intervention details and intervention groups for comparison; potential biases; and outcomes and time points, primarily change in s |
| doi_str_mv | 10.1002/14651858.CD011025.pub2 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1816637782</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1816637782</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4362-1c7e85e242d6f7833d701ecbce15ef37aba0982c05768e4b8f3758e964e2f84d3</originalsourceid><addsrcrecordid>eNqFkMlOwzAQhi0EoqXwClWOXFK8xEtPCMoqVeJSzpbjTGhQNmxHqG-Po1KEuHCZGc3884_mQ2hO8IJgTK9IJjhRXC1Wd5gQTPmiH3J6hKbjIB0nx7_qCTrz_h1jJpZUnqIJlZwwRfkUXW-cab2NoTJ10pi3FkJlEx-qZqhNqLo2KTuXhC0kwYEJDbQh6coE-qqG3u_O0Ulpag8X33mGXh_uN6undP3y-Ly6Wac2Y4KmxEpQHGhGC1FKxVghMQGbWyAcSiZNbvBSUYu5FAqyXMUeV7AUGdBSZQWbocu9b--6jwF80E3lLdS1aaEbvCaKCMGkVDRKxV5qXee9g1L3rmqM22mC9QhPH-DpAzw9wouL8-8bQ95A8bN2oBUFt3vBZ3x-p21ntxEc_OP758oXcat_CQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1816637782</pqid></control><display><type>article</type><title>Transcranial magnetic stimulation for the treatment of epilepsy</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><source>Cochrane Library</source><creator>Chen, Ricky ; Spencer, David C ; Weston, Jennifer ; Nolan, Sarah J ; Chen, Ricky</creator><creatorcontrib>Chen, Ricky ; Spencer, David C ; Weston, Jennifer ; Nolan, Sarah J ; Chen, Ricky</creatorcontrib><description>Background
Epilepsy is a highly prevalent neurological condition characterized by repeated unprovoked seizures with various etiologies. Although antiepileptic medications produce clinical improvement in most individuals, nearly a third of individuals have drug‐resistant epilepsy that carries significant morbidity and mortality. There remains a need for non‐invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low‐frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy.
Objectives
To assess the evidence for the use of TMS in individuals with drug‐resistant epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges, antiepileptic medication use, and side‐effects.
Search methods
We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 10 March 2016), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) up to March 2016. We also searched SCOPUS (1823 to June 2014) as a substitute for Embase (but it is no longer necessary to search SCOPUS, because randomized controlled trials (RCTs) and quasi‐RCTs in EMBASE are now included in CENTRAL).
Selection criteria
Eligible studies were RCTs that were double‐blinded, single‐blinded or unblinded, and placebo, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, duration, intensity, or setup (focal or vertex treatment) on patients with drug‐resistant epilepsy. The search revealed 274 records from the databases, that after selection provided seven full‐text relevant studies for inclusion. Of the seven studies included, five were completed studies with published data and included randomized, blinded trials. The total number of participants in the seven trials was 230.
Data collection and analysis
We extracted information from each trial including methodological data; participant demographics including baseline seizure frequency, type of epileptic drugs taken; intervention details and intervention groups for comparison; potential biases; and outcomes and time points, primarily change in seizure frequency or responder rates, as well as quality of life and epileptiform discharges, adverse effects, and changes in medication use.
Main results
Two of the seven studies analyzed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively). The other five studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls. We were not able to combine the results of the trials in analysis due to differences in the designs of the studies. Four studies evaluated our secondary endpoint of mean number of epileptic discharges, and three of the four showed a statistically significant reduction in discharges. Quality of life was not assessed in any of the studies. Adverse effects were uncommon among the studies and typically involved headache, dizziness, and tinnitus. No significant changes in medication use were found in the trials.
Authors' conclusions
Overall, we judged the quality of evidence for the primary outcomes of this review to be low. There is evidence that rTMS is safe and not associated with any adverse events, but given the variability in technique and outcome reporting that prevented meta‐analysis, the evidence for efficacy of rTMS for seizure reduction is still lacking despite reasonable evidence that it is effective at reducing epileptiform discharges.</description><identifier>ISSN: 1465-1858</identifier><identifier>EISSN: 1465-1858</identifier><identifier>EISSN: 1469-493X</identifier><identifier>DOI: 10.1002/14651858.CD011025.pub2</identifier><identifier>PMID: 27513825</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Child health ; Complementary & alternative medicine ; Drug Resistant Epilepsy ; Drug Resistant Epilepsy - physiopathology ; Drug Resistant Epilepsy - therapy ; Electroencephalography ; Epilepsy ; Epilepsy: other treatments ; Humans ; Medicine General & Introductory Medical Sciences ; Neurology ; Physical treatments ; Randomized Controlled Trials as Topic ; Transcranial Magnetic Stimulation ; Transcranial Magnetic Stimulation - adverse effects</subject><ispartof>Cochrane database of systematic reviews, 2016-08, Vol.2016 (8), p.CD011025-CD011025</ispartof><rights>Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4362-1c7e85e242d6f7833d701ecbce15ef37aba0982c05768e4b8f3758e964e2f84d3</citedby><cites>FETCH-LOGICAL-c4362-1c7e85e242d6f7833d701ecbce15ef37aba0982c05768e4b8f3758e964e2f84d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27513825$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Ricky</creatorcontrib><creatorcontrib>Spencer, David C</creatorcontrib><creatorcontrib>Weston, Jennifer</creatorcontrib><creatorcontrib>Nolan, Sarah J</creatorcontrib><creatorcontrib>Chen, Ricky</creatorcontrib><title>Transcranial magnetic stimulation for the treatment of epilepsy</title><title>Cochrane database of systematic reviews</title><addtitle>Cochrane Database Syst Rev</addtitle><description>Background
Epilepsy is a highly prevalent neurological condition characterized by repeated unprovoked seizures with various etiologies. Although antiepileptic medications produce clinical improvement in most individuals, nearly a third of individuals have drug‐resistant epilepsy that carries significant morbidity and mortality. There remains a need for non‐invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low‐frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy.
Objectives
To assess the evidence for the use of TMS in individuals with drug‐resistant epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges, antiepileptic medication use, and side‐effects.
Search methods
We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 10 March 2016), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) up to March 2016. We also searched SCOPUS (1823 to June 2014) as a substitute for Embase (but it is no longer necessary to search SCOPUS, because randomized controlled trials (RCTs) and quasi‐RCTs in EMBASE are now included in CENTRAL).
Selection criteria
Eligible studies were RCTs that were double‐blinded, single‐blinded or unblinded, and placebo, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, duration, intensity, or setup (focal or vertex treatment) on patients with drug‐resistant epilepsy. The search revealed 274 records from the databases, that after selection provided seven full‐text relevant studies for inclusion. Of the seven studies included, five were completed studies with published data and included randomized, blinded trials. The total number of participants in the seven trials was 230.
Data collection and analysis
We extracted information from each trial including methodological data; participant demographics including baseline seizure frequency, type of epileptic drugs taken; intervention details and intervention groups for comparison; potential biases; and outcomes and time points, primarily change in seizure frequency or responder rates, as well as quality of life and epileptiform discharges, adverse effects, and changes in medication use.
Main results
Two of the seven studies analyzed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively). The other five studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls. We were not able to combine the results of the trials in analysis due to differences in the designs of the studies. Four studies evaluated our secondary endpoint of mean number of epileptic discharges, and three of the four showed a statistically significant reduction in discharges. Quality of life was not assessed in any of the studies. Adverse effects were uncommon among the studies and typically involved headache, dizziness, and tinnitus. No significant changes in medication use were found in the trials.
Authors' conclusions
Overall, we judged the quality of evidence for the primary outcomes of this review to be low. There is evidence that rTMS is safe and not associated with any adverse events, but given the variability in technique and outcome reporting that prevented meta‐analysis, the evidence for efficacy of rTMS for seizure reduction is still lacking despite reasonable evidence that it is effective at reducing epileptiform discharges.</description><subject>Child health</subject><subject>Complementary & alternative medicine</subject><subject>Drug Resistant Epilepsy</subject><subject>Drug Resistant Epilepsy - physiopathology</subject><subject>Drug Resistant Epilepsy - therapy</subject><subject>Electroencephalography</subject><subject>Epilepsy</subject><subject>Epilepsy: other treatments</subject><subject>Humans</subject><subject>Medicine General & Introductory Medical Sciences</subject><subject>Neurology</subject><subject>Physical treatments</subject><subject>Randomized Controlled Trials as Topic</subject><subject>Transcranial Magnetic Stimulation</subject><subject>Transcranial Magnetic Stimulation - adverse effects</subject><issn>1465-1858</issn><issn>1465-1858</issn><issn>1469-493X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>RWY</sourceid><sourceid>EIF</sourceid><recordid>eNqFkMlOwzAQhi0EoqXwClWOXFK8xEtPCMoqVeJSzpbjTGhQNmxHqG-Po1KEuHCZGc3884_mQ2hO8IJgTK9IJjhRXC1Wd5gQTPmiH3J6hKbjIB0nx7_qCTrz_h1jJpZUnqIJlZwwRfkUXW-cab2NoTJ10pi3FkJlEx-qZqhNqLo2KTuXhC0kwYEJDbQh6coE-qqG3u_O0Ulpag8X33mGXh_uN6undP3y-Ly6Wac2Y4KmxEpQHGhGC1FKxVghMQGbWyAcSiZNbvBSUYu5FAqyXMUeV7AUGdBSZQWbocu9b--6jwF80E3lLdS1aaEbvCaKCMGkVDRKxV5qXee9g1L3rmqM22mC9QhPH-DpAzw9wouL8-8bQ95A8bN2oBUFt3vBZ3x-p21ntxEc_OP758oXcat_CQ</recordid><startdate>20160811</startdate><enddate>20160811</enddate><creator>Chen, Ricky</creator><creator>Spencer, David C</creator><creator>Weston, Jennifer</creator><creator>Nolan, Sarah J</creator><creator>Chen, Ricky</creator><general>John Wiley & Sons, Ltd</general><scope>7PX</scope><scope>RWY</scope><scope>ZYTZH</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>20160811</creationdate><title>Transcranial magnetic stimulation for the treatment of epilepsy</title><author>Chen, Ricky ; Spencer, David C ; Weston, Jennifer ; Nolan, Sarah J ; Chen, Ricky</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4362-1c7e85e242d6f7833d701ecbce15ef37aba0982c05768e4b8f3758e964e2f84d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Child health</topic><topic>Complementary & alternative medicine</topic><topic>Drug Resistant Epilepsy</topic><topic>Drug Resistant Epilepsy - physiopathology</topic><topic>Drug Resistant Epilepsy - therapy</topic><topic>Electroencephalography</topic><topic>Epilepsy</topic><topic>Epilepsy: other treatments</topic><topic>Humans</topic><topic>Medicine General & Introductory Medical Sciences</topic><topic>Neurology</topic><topic>Physical treatments</topic><topic>Randomized Controlled Trials as Topic</topic><topic>Transcranial Magnetic Stimulation</topic><topic>Transcranial Magnetic Stimulation - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Ricky</creatorcontrib><creatorcontrib>Spencer, David C</creatorcontrib><creatorcontrib>Weston, Jennifer</creatorcontrib><creatorcontrib>Nolan, Sarah J</creatorcontrib><creatorcontrib>Chen, Ricky</creatorcontrib><collection>Wiley-Blackwell Cochrane Library</collection><collection>Cochrane Library</collection><collection>Cochrane Library (Open Aceess)</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>Cochrane database of systematic reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Ricky</au><au>Spencer, David C</au><au>Weston, Jennifer</au><au>Nolan, Sarah J</au><au>Chen, Ricky</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcranial magnetic stimulation for the treatment of epilepsy</atitle><jtitle>Cochrane database of systematic reviews</jtitle><addtitle>Cochrane Database Syst Rev</addtitle><date>2016-08-11</date><risdate>2016</risdate><volume>2016</volume><issue>8</issue><spage>CD011025</spage><epage>CD011025</epage><pages>CD011025-CD011025</pages><issn>1465-1858</issn><eissn>1465-1858</eissn><eissn>1469-493X</eissn><abstract>Background
Epilepsy is a highly prevalent neurological condition characterized by repeated unprovoked seizures with various etiologies. Although antiepileptic medications produce clinical improvement in most individuals, nearly a third of individuals have drug‐resistant epilepsy that carries significant morbidity and mortality. There remains a need for non‐invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low‐frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy.
Objectives
To assess the evidence for the use of TMS in individuals with drug‐resistant epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges, antiepileptic medication use, and side‐effects.
Search methods
We searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid 1946 to 10 March 2016), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP) up to March 2016. We also searched SCOPUS (1823 to June 2014) as a substitute for Embase (but it is no longer necessary to search SCOPUS, because randomized controlled trials (RCTs) and quasi‐RCTs in EMBASE are now included in CENTRAL).
Selection criteria
Eligible studies were RCTs that were double‐blinded, single‐blinded or unblinded, and placebo, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, duration, intensity, or setup (focal or vertex treatment) on patients with drug‐resistant epilepsy. The search revealed 274 records from the databases, that after selection provided seven full‐text relevant studies for inclusion. Of the seven studies included, five were completed studies with published data and included randomized, blinded trials. The total number of participants in the seven trials was 230.
Data collection and analysis
We extracted information from each trial including methodological data; participant demographics including baseline seizure frequency, type of epileptic drugs taken; intervention details and intervention groups for comparison; potential biases; and outcomes and time points, primarily change in seizure frequency or responder rates, as well as quality of life and epileptiform discharges, adverse effects, and changes in medication use.
Main results
Two of the seven studies analyzed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively). The other five studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls. We were not able to combine the results of the trials in analysis due to differences in the designs of the studies. Four studies evaluated our secondary endpoint of mean number of epileptic discharges, and three of the four showed a statistically significant reduction in discharges. Quality of life was not assessed in any of the studies. Adverse effects were uncommon among the studies and typically involved headache, dizziness, and tinnitus. No significant changes in medication use were found in the trials.
Authors' conclusions
Overall, we judged the quality of evidence for the primary outcomes of this review to be low. There is evidence that rTMS is safe and not associated with any adverse events, but given the variability in technique and outcome reporting that prevented meta‐analysis, the evidence for efficacy of rTMS for seizure reduction is still lacking despite reasonable evidence that it is effective at reducing epileptiform discharges.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>27513825</pmid><doi>10.1002/14651858.CD011025.pub2</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-1858 |
| ispartof | Cochrane database of systematic reviews, 2016-08, Vol.2016 (8), p.CD011025-CD011025 |
| issn | 1465-1858 1465-1858 1469-493X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1816637782 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Cochrane Library |
| subjects | Child health Complementary & alternative medicine Drug Resistant Epilepsy Drug Resistant Epilepsy - physiopathology Drug Resistant Epilepsy - therapy Electroencephalography Epilepsy Epilepsy: other treatments Humans Medicine General & Introductory Medical Sciences Neurology Physical treatments Randomized Controlled Trials as Topic Transcranial Magnetic Stimulation Transcranial Magnetic Stimulation - adverse effects |
| title | Transcranial magnetic stimulation for the treatment of epilepsy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T06%3A28%3A29IST&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=Transcranial%20magnetic%20stimulation%20for%20the%20treatment%20of%20epilepsy&rft.jtitle=Cochrane%20database%20of%20systematic%20reviews&rft.au=Chen,%20Ricky&rft.date=2016-08-11&rft.volume=2016&rft.issue=8&rft.spage=CD011025&rft.epage=CD011025&rft.pages=CD011025-CD011025&rft.issn=1465-1858&rft.eissn=1465-1858&rft_id=info:doi/10.1002/14651858.CD011025.pub2&rft_dat=%3Cproquest_cross%3E1816637782%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=1816637782&rft_id=info:pmid/27513825&rfr_iscdi=true |