Loading…
Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients
Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive tr...
Saved in:
Published in: | Transplant infectious disease 2016-08, Vol.18 (4), p.628-633 |
---|---|
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-c4570-f335119552692295ff85c19ef9579f35d6f808735e6ed26ae9c3083e86c12ab83 |
---|---|
cites | cdi_FETCH-LOGICAL-c4570-f335119552692295ff85c19ef9579f35d6f808735e6ed26ae9c3083e86c12ab83 |
container_end_page | 633 |
container_issue | 4 |
container_start_page | 628 |
container_title | Transplant infectious disease |
container_volume | 18 |
creator | Webb, B.J. Brunner, A. Ford, C.D. Gazdik, M.A. Petersen, F.B. Hoda, D. |
description | Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor‐derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25–75 interquartile range [IQR] 38–791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long‐term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso‐jejunal route in 6 of the 7 patients. Mean follow‐up was 265 days (IQR 51–288). Minor post‐FMT adverse effects included self‐limited bloating and urgency. One patient was suspected of having post‐FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all‐cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft‐versus‐host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects. |
doi_str_mv | 10.1111/tid.12550 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1810867505</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1810867505</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4570-f335119552692295ff85c19ef9579f35d6f808735e6ed26ae9c3083e86c12ab83</originalsourceid><addsrcrecordid>eNp1kU1rFTEUhgdRbK0u_AMScKOLafNx87WUq_2wpYJWFDchN3OCqTOTaZJBu_KvN_fetkjBbE4Wz3k4vG_TvCR4n9R3UEK3Tyjn-FGzS5jWLcOCPt78VUupZDvNs5wvMSZSL_TTZodKShZc8d3m7yE426MhuBRXIRaLSrJjnno7FltCHJGPCSVwc0owFrTsYy4pdGEeUBe8Dy70gMLowW3oMKKfMNgSpxigBIdygQE56Pt_xGtfmEL15efNE2_7DC9u517z9fDDxfK4Pft0dLJ8d9a6BZe49YxxQjTnVGhKNfdecUc0eM2l9ox3wiusJOMgoKPCgnYMKwZKOELtSrG95s3WO6V4NUMuZgh5fZYdIc7ZEEWwEpJjXtHXD9DLOKexXremCK8UJ5V6u6VqcDkn8GZKYbDp2hBs1q2Y2orZtFLZV7fGeTVAd0_e1VCBgy3wu6Z5_X-TuTh5f6dstxuhBvznfsOmX0ZIJrn5dn5kPi_Fl4-nP87Nd3YDTAengw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1811567551</pqid></control><display><type>article</type><title>Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients</title><source>Wiley</source><creator>Webb, B.J. ; Brunner, A. ; Ford, C.D. ; Gazdik, M.A. ; Petersen, F.B. ; Hoda, D.</creator><creatorcontrib>Webb, B.J. ; Brunner, A. ; Ford, C.D. ; Gazdik, M.A. ; Petersen, F.B. ; Hoda, D.</creatorcontrib><description>Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor‐derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25–75 interquartile range [IQR] 38–791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long‐term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso‐jejunal route in 6 of the 7 patients. Mean follow‐up was 265 days (IQR 51–288). Minor post‐FMT adverse effects included self‐limited bloating and urgency. One patient was suspected of having post‐FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all‐cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft‐versus‐host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.</description><identifier>ISSN: 1398-2273</identifier><identifier>EISSN: 1399-3062</identifier><identifier>DOI: 10.1111/tid.12550</identifier><identifier>PMID: 27214585</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>Adult ; Aged ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - therapeutic use ; Antibiotics ; Clostridium difficile - isolation & purification ; Clostridium difficile infection ; Clostridium Infections - microbiology ; Clostridium Infections - therapy ; Diarrhea - microbiology ; Diarrhea - therapy ; Dysbiosis - complications ; Dysbiosis - therapy ; fecal microbiota transplantation ; Fecal Microbiota Transplantation - adverse effects ; Fecal Microbiota Transplantation - methods ; Fecal Microbiota Transplantation - mortality ; Feces - chemistry ; Feces - microbiology ; Female ; Gastrointestinal Microbiome - immunology ; Graft vs Host Disease - drug therapy ; graft-versus-host disease ; hematopoietic stem cell transplantation ; Hematopoietic Stem Cell Transplantation - adverse effects ; Humans ; Immunocompromised Host - immunology ; Immunosuppression - adverse effects ; Immunosuppression - methods ; Infections ; Intestines - microbiology ; Laboratories ; Male ; microbiome ; Middle Aged ; Mortality ; Patients ; Stem cells ; Transplants & implants ; Treatment Outcome</subject><ispartof>Transplant infectious disease, 2016-08, Vol.18 (4), p.628-633</ispartof><rights>2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2016 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4570-f335119552692295ff85c19ef9579f35d6f808735e6ed26ae9c3083e86c12ab83</citedby><cites>FETCH-LOGICAL-c4570-f335119552692295ff85c19ef9579f35d6f808735e6ed26ae9c3083e86c12ab83</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/27214585$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Webb, B.J.</creatorcontrib><creatorcontrib>Brunner, A.</creatorcontrib><creatorcontrib>Ford, C.D.</creatorcontrib><creatorcontrib>Gazdik, M.A.</creatorcontrib><creatorcontrib>Petersen, F.B.</creatorcontrib><creatorcontrib>Hoda, D.</creatorcontrib><title>Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients</title><title>Transplant infectious disease</title><addtitle>Transpl Infect Dis</addtitle><description>Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor‐derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25–75 interquartile range [IQR] 38–791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long‐term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso‐jejunal route in 6 of the 7 patients. Mean follow‐up was 265 days (IQR 51–288). Minor post‐FMT adverse effects included self‐limited bloating and urgency. One patient was suspected of having post‐FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all‐cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft‐versus‐host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.</description><subject>Adult</subject><subject>Aged</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Antibiotics</subject><subject>Clostridium difficile - isolation & purification</subject><subject>Clostridium difficile infection</subject><subject>Clostridium Infections - microbiology</subject><subject>Clostridium Infections - therapy</subject><subject>Diarrhea - microbiology</subject><subject>Diarrhea - therapy</subject><subject>Dysbiosis - complications</subject><subject>Dysbiosis - therapy</subject><subject>fecal microbiota transplantation</subject><subject>Fecal Microbiota Transplantation - adverse effects</subject><subject>Fecal Microbiota Transplantation - methods</subject><subject>Fecal Microbiota Transplantation - mortality</subject><subject>Feces - chemistry</subject><subject>Feces - microbiology</subject><subject>Female</subject><subject>Gastrointestinal Microbiome - immunology</subject><subject>Graft vs Host Disease - drug therapy</subject><subject>graft-versus-host disease</subject><subject>hematopoietic stem cell transplantation</subject><subject>Hematopoietic Stem Cell Transplantation - adverse effects</subject><subject>Humans</subject><subject>Immunocompromised Host - immunology</subject><subject>Immunosuppression - adverse effects</subject><subject>Immunosuppression - methods</subject><subject>Infections</subject><subject>Intestines - microbiology</subject><subject>Laboratories</subject><subject>Male</subject><subject>microbiome</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Patients</subject><subject>Stem cells</subject><subject>Transplants & implants</subject><subject>Treatment Outcome</subject><issn>1398-2273</issn><issn>1399-3062</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNp1kU1rFTEUhgdRbK0u_AMScKOLafNx87WUq_2wpYJWFDchN3OCqTOTaZJBu_KvN_fetkjBbE4Wz3k4vG_TvCR4n9R3UEK3Tyjn-FGzS5jWLcOCPt78VUupZDvNs5wvMSZSL_TTZodKShZc8d3m7yE426MhuBRXIRaLSrJjnno7FltCHJGPCSVwc0owFrTsYy4pdGEeUBe8Dy70gMLowW3oMKKfMNgSpxigBIdygQE56Pt_xGtfmEL15efNE2_7DC9u517z9fDDxfK4Pft0dLJ8d9a6BZe49YxxQjTnVGhKNfdecUc0eM2l9ox3wiusJOMgoKPCgnYMKwZKOELtSrG95s3WO6V4NUMuZgh5fZYdIc7ZEEWwEpJjXtHXD9DLOKexXremCK8UJ5V6u6VqcDkn8GZKYbDp2hBs1q2Y2orZtFLZV7fGeTVAd0_e1VCBgy3wu6Z5_X-TuTh5f6dstxuhBvznfsOmX0ZIJrn5dn5kPi_Fl4-nP87Nd3YDTAengw</recordid><startdate>201608</startdate><enddate>201608</enddate><creator>Webb, B.J.</creator><creator>Brunner, A.</creator><creator>Ford, C.D.</creator><creator>Gazdik, M.A.</creator><creator>Petersen, F.B.</creator><creator>Hoda, D.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201608</creationdate><title>Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients</title><author>Webb, B.J. ; Brunner, A. ; Ford, C.D. ; Gazdik, M.A. ; Petersen, F.B. ; Hoda, D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4570-f335119552692295ff85c19ef9579f35d6f808735e6ed26ae9c3083e86c12ab83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Antibiotics</topic><topic>Clostridium difficile - isolation & purification</topic><topic>Clostridium difficile infection</topic><topic>Clostridium Infections - microbiology</topic><topic>Clostridium Infections - therapy</topic><topic>Diarrhea - microbiology</topic><topic>Diarrhea - therapy</topic><topic>Dysbiosis - complications</topic><topic>Dysbiosis - therapy</topic><topic>fecal microbiota transplantation</topic><topic>Fecal Microbiota Transplantation - adverse effects</topic><topic>Fecal Microbiota Transplantation - methods</topic><topic>Fecal Microbiota Transplantation - mortality</topic><topic>Feces - chemistry</topic><topic>Feces - microbiology</topic><topic>Female</topic><topic>Gastrointestinal Microbiome - immunology</topic><topic>Graft vs Host Disease - drug therapy</topic><topic>graft-versus-host disease</topic><topic>hematopoietic stem cell transplantation</topic><topic>Hematopoietic Stem Cell Transplantation - adverse effects</topic><topic>Humans</topic><topic>Immunocompromised Host - immunology</topic><topic>Immunosuppression - adverse effects</topic><topic>Immunosuppression - methods</topic><topic>Infections</topic><topic>Intestines - microbiology</topic><topic>Laboratories</topic><topic>Male</topic><topic>microbiome</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Patients</topic><topic>Stem cells</topic><topic>Transplants & implants</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Webb, B.J.</creatorcontrib><creatorcontrib>Brunner, A.</creatorcontrib><creatorcontrib>Ford, C.D.</creatorcontrib><creatorcontrib>Gazdik, M.A.</creatorcontrib><creatorcontrib>Petersen, F.B.</creatorcontrib><creatorcontrib>Hoda, D.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplant infectious disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Webb, B.J.</au><au>Brunner, A.</au><au>Ford, C.D.</au><au>Gazdik, M.A.</au><au>Petersen, F.B.</au><au>Hoda, D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients</atitle><jtitle>Transplant infectious disease</jtitle><addtitle>Transpl Infect Dis</addtitle><date>2016-08</date><risdate>2016</risdate><volume>18</volume><issue>4</issue><spage>628</spage><epage>633</epage><pages>628-633</pages><issn>1398-2273</issn><eissn>1399-3062</eissn><abstract>Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor‐derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25–75 interquartile range [IQR] 38–791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long‐term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso‐jejunal route in 6 of the 7 patients. Mean follow‐up was 265 days (IQR 51–288). Minor post‐FMT adverse effects included self‐limited bloating and urgency. One patient was suspected of having post‐FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all‐cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft‐versus‐host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>27214585</pmid><doi>10.1111/tid.12550</doi><tpages>6</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1398-2273 |
ispartof | Transplant infectious disease, 2016-08, Vol.18 (4), p.628-633 |
issn | 1398-2273 1399-3062 |
language | eng |
recordid | cdi_proquest_miscellaneous_1810867505 |
source | Wiley |
subjects | Adult Aged Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - therapeutic use Antibiotics Clostridium difficile - isolation & purification Clostridium difficile infection Clostridium Infections - microbiology Clostridium Infections - therapy Diarrhea - microbiology Diarrhea - therapy Dysbiosis - complications Dysbiosis - therapy fecal microbiota transplantation Fecal Microbiota Transplantation - adverse effects Fecal Microbiota Transplantation - methods Fecal Microbiota Transplantation - mortality Feces - chemistry Feces - microbiology Female Gastrointestinal Microbiome - immunology Graft vs Host Disease - drug therapy graft-versus-host disease hematopoietic stem cell transplantation Hematopoietic Stem Cell Transplantation - adverse effects Humans Immunocompromised Host - immunology Immunosuppression - adverse effects Immunosuppression - methods Infections Intestines - microbiology Laboratories Male microbiome Middle Aged Mortality Patients Stem cells Transplants & implants Treatment Outcome |
title | Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T22%3A12%3A54IST&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=Fecal%20microbiota%20transplantation%20for%20recurrent%20Clostridium%20difficile%20infection%20in%20hematopoietic%20stem%20cell%20transplant%20recipients&rft.jtitle=Transplant%20infectious%20disease&rft.au=Webb,%20B.J.&rft.date=2016-08&rft.volume=18&rft.issue=4&rft.spage=628&rft.epage=633&rft.pages=628-633&rft.issn=1398-2273&rft.eissn=1399-3062&rft_id=info:doi/10.1111/tid.12550&rft_dat=%3Cproquest_cross%3E1810867505%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4570-f335119552692295ff85c19ef9579f35d6f808735e6ed26ae9c3083e86c12ab83%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1811567551&rft_id=info:pmid/27214585&rfr_iscdi=true |