Loading…

Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation

Objectives To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 ind...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of pediatrics 2017-01, Vol.180, p.200-205.e8
Main Authors: McCrory, Nicholas M., BA, Edick, Mathew J., PhD, Ahmad, Ayesha, MD, Lipinski, Susan, RD, Scott Schwoerer, Jessica A., MD, Zhai, Shaohui, PhD, Justice, Kaitlin, BS, Cameron, Cynthia A., PhD, Berry, Susan A., MD, Pena, Loren D.M., MD, PhD
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-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3
cites cdi_FETCH-LOGICAL-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3
container_end_page 205.e8
container_issue
container_start_page 200
container_title The Journal of pediatrics
container_volume 180
creator McCrory, Nicholas M., BA
Edick, Mathew J., PhD
Ahmad, Ayesha, MD
Lipinski, Susan, RD
Scott Schwoerer, Jessica A., MD
Zhai, Shaohui, PhD
Justice, Kaitlin, BS
Cameron, Cynthia A., PhD
Berry, Susan A., MD
Pena, Loren D.M., MD, PhD
description Objectives To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 individuals with PA enrolled in the Inborn Errors of Metabolism Information System (IBEM-IS) based on the type of initial ascertainment: abnormal newborn screening (NBS), clinical presentation (symptomatic), or family history. Results The average age at initial evaluation and treatment was significantly younger in patients ascertained via abnormal NBS compared with those referred for clinical symptoms. Furthermore, the majority of individuals ascertained because of abnormal NBS were asymptomatic at diagnosis, compared with a minority of clinical presentations. A notable difference in the frequency of metabolic acidosis at initial presentation was observed between those with abnormal NBS (12.5%; 2 of 16) and those with an abnormal clinical presentation (79%; 19 of 24). The frequency of hyperammonemia was similar in the 2 groups. Conclusion Our data support the continued value of NBS to identify individuals with PA, who are diagnosed and treated earlier than for other modes of ascertainment. There were no statistically significant correlations between genotype and NBS for C3 acylcarnitines. Although expanded use of NBS has allowed for early diagnosis and treatment, long-term outcomes of individuals with PA, especially with respect to mode of ascertainment, remain unclear and would benefit from a longitudinal study.
doi_str_mv 10.1016/j.jpeds.2016.09.050
format article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5183466</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0022347616310332</els_id><sourcerecordid>1835682613</sourcerecordid><originalsourceid>FETCH-LOGICAL-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3</originalsourceid><addsrcrecordid>eNqFUsuO0zAUjRCIKQNfgIS8ZNPixHl5wUijUmCkQSA6rC3HvpneEtvBdiv1d_kSnLaMgA0r27rncXV8suxlThc5zes328V2BB0WRXosKF_Qij7KZjnlzbxuGXuczSgtijkrm_oiexbCllLKS0qfZhdF0zR1U7FZ9nPpzCg9BmeJ68kniBunw3S9sRhRDuQ6KPBRojVgI0FLqpYsZYAj6It3IzqLilwr1GBQkpX1bhhAT9C4gaTTOW_Jynvnw9lDdm7AYNKsd97ImCTI-hAiGPIV9iCHQNZ4b7FHJZPpO-x78GBVMk2qd2iAREdWeznsTmRpdRIwY3QmEBnTXhDSusfh8-xJnxThxfm8zL69X90tP85vP3-4WV7fzlWVl3HeN23HJCt417egNW1bzksuZdc2tOmaElTVlopDVfOcsr7ntOyU1nnFeaWaSrPL7OqkO-46A1olfy8HMXo00h-Ekyj-nljciHu3F1XesrKuk8Drs4B3P3YQojCYwh8GacHtgkiwqm6LOmcJyk5Q5V0IHvoHm5yKqR1iK47tEFM7BOUitSOxXv254QPndx0S4O0JACmnPYIXQeGUu0YPKgrt8D8GV__w1YCpHXL4DgcIW7fzNn2ByEUoBBXrqaBTP_OapUxZwX4B6Sjnqg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1835682613</pqid></control><display><type>article</type><title>Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation</title><source>Elsevier</source><creator>McCrory, Nicholas M., BA ; Edick, Mathew J., PhD ; Ahmad, Ayesha, MD ; Lipinski, Susan, RD ; Scott Schwoerer, Jessica A., MD ; Zhai, Shaohui, PhD ; Justice, Kaitlin, BS ; Cameron, Cynthia A., PhD ; Berry, Susan A., MD ; Pena, Loren D.M., MD, PhD</creator><creatorcontrib>McCrory, Nicholas M., BA ; Edick, Mathew J., PhD ; Ahmad, Ayesha, MD ; Lipinski, Susan, RD ; Scott Schwoerer, Jessica A., MD ; Zhai, Shaohui, PhD ; Justice, Kaitlin, BS ; Cameron, Cynthia A., PhD ; Berry, Susan A., MD ; Pena, Loren D.M., MD, PhD ; Inborn Errors of Metabolism Collaborative</creatorcontrib><description>Objectives To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 individuals with PA enrolled in the Inborn Errors of Metabolism Information System (IBEM-IS) based on the type of initial ascertainment: abnormal newborn screening (NBS), clinical presentation (symptomatic), or family history. Results The average age at initial evaluation and treatment was significantly younger in patients ascertained via abnormal NBS compared with those referred for clinical symptoms. Furthermore, the majority of individuals ascertained because of abnormal NBS were asymptomatic at diagnosis, compared with a minority of clinical presentations. A notable difference in the frequency of metabolic acidosis at initial presentation was observed between those with abnormal NBS (12.5%; 2 of 16) and those with an abnormal clinical presentation (79%; 19 of 24). The frequency of hyperammonemia was similar in the 2 groups. Conclusion Our data support the continued value of NBS to identify individuals with PA, who are diagnosed and treated earlier than for other modes of ascertainment. There were no statistically significant correlations between genotype and NBS for C3 acylcarnitines. Although expanded use of NBS has allowed for early diagnosis and treatment, long-term outcomes of individuals with PA, especially with respect to mode of ascertainment, remain unclear and would benefit from a longitudinal study.</description><identifier>ISSN: 0022-3476</identifier><identifier>EISSN: 1097-6833</identifier><identifier>DOI: 10.1016/j.jpeds.2016.09.050</identifier><identifier>PMID: 27776753</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>C3 acylcarnitine ; Female ; Genotype ; history ; Humans ; hyperammonemia ; hyperglycinemia ; Infant ; Infant, Newborn ; longitudinal follow up ; Male ; Metabolism, Inborn Errors - diagnosis ; Metabolism, Inborn Errors - genetics ; natural ; Neonatal Screening - methods ; newborn screening ; nonketotic ; organic acidemia ; Pediatrics ; Propionic Acidemia - diagnosis ; Propionic Acidemia - genetics ; Retrospective Studies ; Time Factors</subject><ispartof>The Journal of pediatrics, 2017-01, Vol.180, p.200-205.e8</ispartof><rights>Elsevier Inc.</rights><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3</citedby><cites>FETCH-LOGICAL-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3</cites><orcidid>0000-0003-1253-6454 ; 0000-0002-2673-7145 ; 0000-0003-2149-9894 ; 0000-0001-7970-688X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27776753$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McCrory, Nicholas M., BA</creatorcontrib><creatorcontrib>Edick, Mathew J., PhD</creatorcontrib><creatorcontrib>Ahmad, Ayesha, MD</creatorcontrib><creatorcontrib>Lipinski, Susan, RD</creatorcontrib><creatorcontrib>Scott Schwoerer, Jessica A., MD</creatorcontrib><creatorcontrib>Zhai, Shaohui, PhD</creatorcontrib><creatorcontrib>Justice, Kaitlin, BS</creatorcontrib><creatorcontrib>Cameron, Cynthia A., PhD</creatorcontrib><creatorcontrib>Berry, Susan A., MD</creatorcontrib><creatorcontrib>Pena, Loren D.M., MD, PhD</creatorcontrib><creatorcontrib>Inborn Errors of Metabolism Collaborative</creatorcontrib><title>Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation</title><title>The Journal of pediatrics</title><addtitle>J Pediatr</addtitle><description>Objectives To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 individuals with PA enrolled in the Inborn Errors of Metabolism Information System (IBEM-IS) based on the type of initial ascertainment: abnormal newborn screening (NBS), clinical presentation (symptomatic), or family history. Results The average age at initial evaluation and treatment was significantly younger in patients ascertained via abnormal NBS compared with those referred for clinical symptoms. Furthermore, the majority of individuals ascertained because of abnormal NBS were asymptomatic at diagnosis, compared with a minority of clinical presentations. A notable difference in the frequency of metabolic acidosis at initial presentation was observed between those with abnormal NBS (12.5%; 2 of 16) and those with an abnormal clinical presentation (79%; 19 of 24). The frequency of hyperammonemia was similar in the 2 groups. Conclusion Our data support the continued value of NBS to identify individuals with PA, who are diagnosed and treated earlier than for other modes of ascertainment. There were no statistically significant correlations between genotype and NBS for C3 acylcarnitines. Although expanded use of NBS has allowed for early diagnosis and treatment, long-term outcomes of individuals with PA, especially with respect to mode of ascertainment, remain unclear and would benefit from a longitudinal study.</description><subject>C3 acylcarnitine</subject><subject>Female</subject><subject>Genotype</subject><subject>history</subject><subject>Humans</subject><subject>hyperammonemia</subject><subject>hyperglycinemia</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>longitudinal follow up</subject><subject>Male</subject><subject>Metabolism, Inborn Errors - diagnosis</subject><subject>Metabolism, Inborn Errors - genetics</subject><subject>natural</subject><subject>Neonatal Screening - methods</subject><subject>newborn screening</subject><subject>nonketotic</subject><subject>organic acidemia</subject><subject>Pediatrics</subject><subject>Propionic Acidemia - diagnosis</subject><subject>Propionic Acidemia - genetics</subject><subject>Retrospective Studies</subject><subject>Time Factors</subject><issn>0022-3476</issn><issn>1097-6833</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqFUsuO0zAUjRCIKQNfgIS8ZNPixHl5wUijUmCkQSA6rC3HvpneEtvBdiv1d_kSnLaMgA0r27rncXV8suxlThc5zes328V2BB0WRXosKF_Qij7KZjnlzbxuGXuczSgtijkrm_oiexbCllLKS0qfZhdF0zR1U7FZ9nPpzCg9BmeJ68kniBunw3S9sRhRDuQ6KPBRojVgI0FLqpYsZYAj6It3IzqLilwr1GBQkpX1bhhAT9C4gaTTOW_Jynvnw9lDdm7AYNKsd97ImCTI-hAiGPIV9iCHQNZ4b7FHJZPpO-x78GBVMk2qd2iAREdWeznsTmRpdRIwY3QmEBnTXhDSusfh8-xJnxThxfm8zL69X90tP85vP3-4WV7fzlWVl3HeN23HJCt417egNW1bzksuZdc2tOmaElTVlopDVfOcsr7ntOyU1nnFeaWaSrPL7OqkO-46A1olfy8HMXo00h-Ekyj-nljciHu3F1XesrKuk8Drs4B3P3YQojCYwh8GacHtgkiwqm6LOmcJyk5Q5V0IHvoHm5yKqR1iK47tEFM7BOUitSOxXv254QPndx0S4O0JACmnPYIXQeGUu0YPKgrt8D8GV__w1YCpHXL4DgcIW7fzNn2ByEUoBBXrqaBTP_OapUxZwX4B6Sjnqg</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>McCrory, Nicholas M., BA</creator><creator>Edick, Mathew J., PhD</creator><creator>Ahmad, Ayesha, MD</creator><creator>Lipinski, Susan, RD</creator><creator>Scott Schwoerer, Jessica A., MD</creator><creator>Zhai, Shaohui, PhD</creator><creator>Justice, Kaitlin, BS</creator><creator>Cameron, Cynthia A., PhD</creator><creator>Berry, Susan A., MD</creator><creator>Pena, Loren D.M., MD, PhD</creator><general>Elsevier Inc</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><orcidid>https://orcid.org/0000-0003-1253-6454</orcidid><orcidid>https://orcid.org/0000-0002-2673-7145</orcidid><orcidid>https://orcid.org/0000-0003-2149-9894</orcidid><orcidid>https://orcid.org/0000-0001-7970-688X</orcidid></search><sort><creationdate>20170101</creationdate><title>Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation</title><author>McCrory, Nicholas M., BA ; Edick, Mathew J., PhD ; Ahmad, Ayesha, MD ; Lipinski, Susan, RD ; Scott Schwoerer, Jessica A., MD ; Zhai, Shaohui, PhD ; Justice, Kaitlin, BS ; Cameron, Cynthia A., PhD ; Berry, Susan A., MD ; Pena, Loren D.M., MD, PhD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>C3 acylcarnitine</topic><topic>Female</topic><topic>Genotype</topic><topic>history</topic><topic>Humans</topic><topic>hyperammonemia</topic><topic>hyperglycinemia</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>longitudinal follow up</topic><topic>Male</topic><topic>Metabolism, Inborn Errors - diagnosis</topic><topic>Metabolism, Inborn Errors - genetics</topic><topic>natural</topic><topic>Neonatal Screening - methods</topic><topic>newborn screening</topic><topic>nonketotic</topic><topic>organic acidemia</topic><topic>Pediatrics</topic><topic>Propionic Acidemia - diagnosis</topic><topic>Propionic Acidemia - genetics</topic><topic>Retrospective Studies</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McCrory, Nicholas M., BA</creatorcontrib><creatorcontrib>Edick, Mathew J., PhD</creatorcontrib><creatorcontrib>Ahmad, Ayesha, MD</creatorcontrib><creatorcontrib>Lipinski, Susan, RD</creatorcontrib><creatorcontrib>Scott Schwoerer, Jessica A., MD</creatorcontrib><creatorcontrib>Zhai, Shaohui, PhD</creatorcontrib><creatorcontrib>Justice, Kaitlin, BS</creatorcontrib><creatorcontrib>Cameron, Cynthia A., PhD</creatorcontrib><creatorcontrib>Berry, Susan A., MD</creatorcontrib><creatorcontrib>Pena, Loren D.M., MD, PhD</creatorcontrib><creatorcontrib>Inborn Errors of Metabolism Collaborative</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>The Journal of pediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McCrory, Nicholas M., BA</au><au>Edick, Mathew J., PhD</au><au>Ahmad, Ayesha, MD</au><au>Lipinski, Susan, RD</au><au>Scott Schwoerer, Jessica A., MD</au><au>Zhai, Shaohui, PhD</au><au>Justice, Kaitlin, BS</au><au>Cameron, Cynthia A., PhD</au><au>Berry, Susan A., MD</au><au>Pena, Loren D.M., MD, PhD</au><aucorp>Inborn Errors of Metabolism Collaborative</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation</atitle><jtitle>The Journal of pediatrics</jtitle><addtitle>J Pediatr</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>180</volume><spage>200</spage><epage>205.e8</epage><pages>200-205.e8</pages><issn>0022-3476</issn><eissn>1097-6833</eissn><abstract>Objectives To compare time to evaluation and symptoms at diagnosis of propionic acidemia (PA) by method of ascertainment, and to explore correlations between genotype and biochemical variables. Study design Clinical symptoms, genotype, and biochemical findings were analyzed retrospectively in 58 individuals with PA enrolled in the Inborn Errors of Metabolism Information System (IBEM-IS) based on the type of initial ascertainment: abnormal newborn screening (NBS), clinical presentation (symptomatic), or family history. Results The average age at initial evaluation and treatment was significantly younger in patients ascertained via abnormal NBS compared with those referred for clinical symptoms. Furthermore, the majority of individuals ascertained because of abnormal NBS were asymptomatic at diagnosis, compared with a minority of clinical presentations. A notable difference in the frequency of metabolic acidosis at initial presentation was observed between those with abnormal NBS (12.5%; 2 of 16) and those with an abnormal clinical presentation (79%; 19 of 24). The frequency of hyperammonemia was similar in the 2 groups. Conclusion Our data support the continued value of NBS to identify individuals with PA, who are diagnosed and treated earlier than for other modes of ascertainment. There were no statistically significant correlations between genotype and NBS for C3 acylcarnitines. Although expanded use of NBS has allowed for early diagnosis and treatment, long-term outcomes of individuals with PA, especially with respect to mode of ascertainment, remain unclear and would benefit from a longitudinal study.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>27776753</pmid><doi>10.1016/j.jpeds.2016.09.050</doi><orcidid>https://orcid.org/0000-0003-1253-6454</orcidid><orcidid>https://orcid.org/0000-0002-2673-7145</orcidid><orcidid>https://orcid.org/0000-0003-2149-9894</orcidid><orcidid>https://orcid.org/0000-0001-7970-688X</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0022-3476
ispartof The Journal of pediatrics, 2017-01, Vol.180, p.200-205.e8
issn 0022-3476
1097-6833
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5183466
source Elsevier
subjects C3 acylcarnitine
Female
Genotype
history
Humans
hyperammonemia
hyperglycinemia
Infant
Infant, Newborn
longitudinal follow up
Male
Metabolism, Inborn Errors - diagnosis
Metabolism, Inborn Errors - genetics
natural
Neonatal Screening - methods
newborn screening
nonketotic
organic acidemia
Pediatrics
Propionic Acidemia - diagnosis
Propionic Acidemia - genetics
Retrospective Studies
Time Factors
title Comparison of Methods of Initial Ascertainment in 58 Cases of Propionic Acidemia Enrolled in the Inborn Errors of Metabolism Information System Reveals Significant Differences in Time to Evaluation and Symptoms at Presentation
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-04T16%3A04%3A24IST&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=Comparison%20of%20Methods%20of%20Initial%20Ascertainment%20in%2058%20Cases%20of%20Propionic%20Acidemia%20Enrolled%20in%20the%20Inborn%20Errors%20of%20Metabolism%20Information%20System%20Reveals%20Significant%20Differences%20in%20Time%20to%20Evaluation%20and%20Symptoms%20at%20Presentation&rft.jtitle=The%20Journal%20of%20pediatrics&rft.au=McCrory,%20Nicholas%20M.,%20BA&rft.aucorp=Inborn%20Errors%20of%20Metabolism%20Collaborative&rft.date=2017-01-01&rft.volume=180&rft.spage=200&rft.epage=205.e8&rft.pages=200-205.e8&rft.issn=0022-3476&rft.eissn=1097-6833&rft_id=info:doi/10.1016/j.jpeds.2016.09.050&rft_dat=%3Cproquest_pubme%3E1835682613%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c514t-f78b3a329bf8edd0889949aab8707b74ec584c9e569103ff904bcdd15995c75d3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1835682613&rft_id=info:pmid/27776753&rfr_iscdi=true