Development of a screening tool for sleep disordered breathing in children using the phone Oximeter
Sleep disordered breathing (SDB) can lead to daytime sleepiness, growth failure and developmental delay in children. Polysomnography (PSG), the gold standard to diagnose SDB, is a highly resource-intensive test, confined to the sleep laboratory. To combine the blood oxygen saturation (SpO2) characte...
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| creator | Garde, Ainara Dehkordi, Parastoo Karlen, Walter Wensley, David Ansermino, J Mark Dumont, Guy A |
| description | Sleep disordered breathing (SDB) can lead to daytime sleepiness, growth failure and developmental delay in children. Polysomnography (PSG), the gold standard to diagnose SDB, is a highly resource-intensive test, confined to the sleep laboratory.
To combine the blood oxygen saturation (SpO2) characterization and cardiac modulation, quantified by pulse rate variability (PRV), to identify children with SDB using the Phone Oximeter, a device integrating a pulse oximeter with a smartphone.
Following ethics approval and informed consent, 160 children referred to British Columbia Children's Hospital for overnight PSG were recruited. A second pulse oximeter sensor applied to the finger adjacent to the one used for standard PSG was attached to the Phone Oximeter to record overnight pulse oximetry (SpO2 and photoplethysmogram (PPG)) alongside the PSG.
We studied 146 children through the analysis of the SpO2 pattern, and PRV as an estimate of heart rate variability calculated from the PPG. SpO2 variability and SpO2 spectral power at low frequency, was significantly higher in children with SDB due to the modulation provoked by airway obstruction during sleep (p-value |
| doi_str_mv | 10.1371/journal.pone.0112959 |
| format | Article |
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To combine the blood oxygen saturation (SpO2) characterization and cardiac modulation, quantified by pulse rate variability (PRV), to identify children with SDB using the Phone Oximeter, a device integrating a pulse oximeter with a smartphone.
Following ethics approval and informed consent, 160 children referred to British Columbia Children's Hospital for overnight PSG were recruited. A second pulse oximeter sensor applied to the finger adjacent to the one used for standard PSG was attached to the Phone Oximeter to record overnight pulse oximetry (SpO2 and photoplethysmogram (PPG)) alongside the PSG.
We studied 146 children through the analysis of the SpO2 pattern, and PRV as an estimate of heart rate variability calculated from the PPG. SpO2 variability and SpO2 spectral power at low frequency, was significantly higher in children with SDB due to the modulation provoked by airway obstruction during sleep (p-value <0.01). PRV analysis reflected a significant augmentation of sympathetic activity provoked by intermittent hypoxia in SDB children. A linear classifier was trained with the most discriminating features to identify children with SDB. The classifier was validated with internal and external cross-validation, providing a high negative predictive value (92.6%) and a good balance between sensitivity (88.4%) and specificity (83.6%). Combining SpO2 and PRV analysis improved the classification performance, providing an area under the receiver operating characteristic curve of 88%, beyond the 82% achieved using SpO2 analysis alone.
These results demonstrate that the implementation of this algorithm in the Phone Oximeter will provide an improved portable, at-home screening tool, with the capability of monitoring patients over multiple nights.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0112959</identifier><identifier>PMID: 25401696</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Augmentation ; Biology and Life Sciences ; Biomedical engineering ; Blood ; Breathing ; Cell Phone ; Child ; Child, Preschool ; Children ; Children & youth ; Classifiers ; Computer engineering ; Critical care ; Ethics ; Female ; Heart diseases ; Heart rate ; Hospitals ; Humans ; Hypoxia ; Informed consent ; Male ; Medical screening ; Medicine ; Medicine and Health Sciences ; Oximetry ; Oximetry - instrumentation ; Oximetry - methods ; Oxygen ; Oxygen content ; Physiology ; Pulse rate ; Reproducibility of Results ; Respiration ; Respiratory tract ; ROC Curve ; Saturation ; Screening ; Sensitivity analysis ; Sensors ; Sleep ; Sleep and wakefulness ; Sleep apnea ; Sleep Apnea Syndromes - diagnosis ; Sleep Apnea Syndromes - physiopathology ; Sleep disorders ; Sleepiness ; Smartphones ; Teenagers ; Variability</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e112959-e112959</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Garde et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Garde et al 2014 Garde et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-176e197f4858c493686c034b73014be897b0e53c6b7cafdf78bc662d0af701a13</citedby><cites>FETCH-LOGICAL-c758t-176e197f4858c493686c034b73014be897b0e53c6b7cafdf78bc662d0af701a13</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/PMC4234680/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234680/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23847,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25401696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Murillo-Rodriguez, Eric</contributor><creatorcontrib>Garde, Ainara</creatorcontrib><creatorcontrib>Dehkordi, Parastoo</creatorcontrib><creatorcontrib>Karlen, Walter</creatorcontrib><creatorcontrib>Wensley, David</creatorcontrib><creatorcontrib>Ansermino, J Mark</creatorcontrib><creatorcontrib>Dumont, Guy A</creatorcontrib><title>Development of a screening tool for sleep disordered breathing in children using the phone Oximeter</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Sleep disordered breathing (SDB) can lead to daytime sleepiness, growth failure and developmental delay in children. Polysomnography (PSG), the gold standard to diagnose SDB, is a highly resource-intensive test, confined to the sleep laboratory.
To combine the blood oxygen saturation (SpO2) characterization and cardiac modulation, quantified by pulse rate variability (PRV), to identify children with SDB using the Phone Oximeter, a device integrating a pulse oximeter with a smartphone.
Following ethics approval and informed consent, 160 children referred to British Columbia Children's Hospital for overnight PSG were recruited. A second pulse oximeter sensor applied to the finger adjacent to the one used for standard PSG was attached to the Phone Oximeter to record overnight pulse oximetry (SpO2 and photoplethysmogram (PPG)) alongside the PSG.
We studied 146 children through the analysis of the SpO2 pattern, and PRV as an estimate of heart rate variability calculated from the PPG. SpO2 variability and SpO2 spectral power at low frequency, was significantly higher in children with SDB due to the modulation provoked by airway obstruction during sleep (p-value <0.01). PRV analysis reflected a significant augmentation of sympathetic activity provoked by intermittent hypoxia in SDB children. A linear classifier was trained with the most discriminating features to identify children with SDB. The classifier was validated with internal and external cross-validation, providing a high negative predictive value (92.6%) and a good balance between sensitivity (88.4%) and specificity (83.6%). Combining SpO2 and PRV analysis improved the classification performance, providing an area under the receiver operating characteristic curve of 88%, beyond the 82% achieved using SpO2 analysis alone.
These results demonstrate that the implementation of this algorithm in the Phone Oximeter will provide an improved portable, at-home screening tool, with the capability of monitoring patients over multiple nights.</description><subject>Adolescent</subject><subject>Augmentation</subject><subject>Biology and Life Sciences</subject><subject>Biomedical engineering</subject><subject>Blood</subject><subject>Breathing</subject><subject>Cell Phone</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Children & youth</subject><subject>Classifiers</subject><subject>Computer engineering</subject><subject>Critical care</subject><subject>Ethics</subject><subject>Female</subject><subject>Heart diseases</subject><subject>Heart rate</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Informed consent</subject><subject>Male</subject><subject>Medical screening</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Oximetry</subject><subject>Oximetry - instrumentation</subject><subject>Oximetry - methods</subject><subject>Oxygen</subject><subject>Oxygen content</subject><subject>Physiology</subject><subject>Pulse rate</subject><subject>Reproducibility of Results</subject><subject>Respiration</subject><subject>Respiratory tract</subject><subject>ROC Curve</subject><subject>Saturation</subject><subject>Screening</subject><subject>Sensitivity analysis</subject><subject>Sensors</subject><subject>Sleep</subject><subject>Sleep and wakefulness</subject><subject>Sleep apnea</subject><subject>Sleep Apnea Syndromes - diagnosis</subject><subject>Sleep Apnea Syndromes - physiopathology</subject><subject>Sleep disorders</subject><subject>Sleepiness</subject><subject>Smartphones</subject><subject>Teenagers</subject><subject>Variability</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L3CAYhUNp6W63_QelFQqlvZipRmPiTWHZfg0sDPTrVoy-mbg4MavJsv33dWayy6TsRRGJ6HOOesybZS8JXhJakg9Xfgydcsved7DEhOSiEI-yUyJovuA5po-PxifZsxivMC5oxfnT7CQvGCZc8NNMf4IbcL7fQjcg3yCFog4Ane02aPDeocYHFB1Aj4yNPhgIYFAdQA3tjrEd0q11JkCHxrhXtYD6Nh0KrW_tFgYIz7MnjXIRXkzfs-zXl88_L74tLtdfVxfnlwtdFtWwICUHIsqGVUWlmaC84hpTVpcUE1ZDJcoaQ0E1r0utGtOUVa05zw1WTYmJIvQse33w7Z2PcsonSsLzoqh2LRGrA2G8upJ9sFsV_kivrNxP-LCRKgxWO5DY5E2ja8pTTMxoI0TJtCoUMwJzzSF5fZx2G-stGJ0CDMrNTOcrnW3lxt9IllPGK5wM3k0GwV-PEAe5tVGDc6oDP-7PzVMXokjom3_Qh283URuVLmC7xqd99c5UnjNSsZzxIk_U8gEqNQNbq9O7NTbNzwTvZ4LEDHA7bNQYo1z9-P7_7Pr3nH17xLag3NBG78bB-i7OQXYAdfAxBmjuQyZY7mrhLg25qwU51UKSvTp-oHvR3c9P_wLihgRV</recordid><startdate>20141117</startdate><enddate>20141117</enddate><creator>Garde, Ainara</creator><creator>Dehkordi, Parastoo</creator><creator>Karlen, Walter</creator><creator>Wensley, David</creator><creator>Ansermino, J Mark</creator><creator>Dumont, Guy A</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141117</creationdate><title>Development of a screening tool for sleep disordered breathing in children using the phone Oximeter</title><author>Garde, Ainara ; Dehkordi, Parastoo ; Karlen, Walter ; Wensley, David ; Ansermino, J Mark ; Dumont, Guy A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-176e197f4858c493686c034b73014be897b0e53c6b7cafdf78bc662d0af701a13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Augmentation</topic><topic>Biology and Life Sciences</topic><topic>Biomedical engineering</topic><topic>Blood</topic><topic>Breathing</topic><topic>Cell Phone</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Children & youth</topic><topic>Classifiers</topic><topic>Computer engineering</topic><topic>Critical care</topic><topic>Ethics</topic><topic>Female</topic><topic>Heart diseases</topic><topic>Heart rate</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>Informed consent</topic><topic>Male</topic><topic>Medical screening</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Oximetry</topic><topic>Oximetry - instrumentation</topic><topic>Oximetry - methods</topic><topic>Oxygen</topic><topic>Oxygen content</topic><topic>Physiology</topic><topic>Pulse rate</topic><topic>Reproducibility of Results</topic><topic>Respiration</topic><topic>Respiratory tract</topic><topic>ROC Curve</topic><topic>Saturation</topic><topic>Screening</topic><topic>Sensitivity analysis</topic><topic>Sensors</topic><topic>Sleep</topic><topic>Sleep and wakefulness</topic><topic>Sleep apnea</topic><topic>Sleep Apnea Syndromes - diagnosis</topic><topic>Sleep Apnea Syndromes - physiopathology</topic><topic>Sleep disorders</topic><topic>Sleepiness</topic><topic>Smartphones</topic><topic>Teenagers</topic><topic>Variability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garde, Ainara</creatorcontrib><creatorcontrib>Dehkordi, Parastoo</creatorcontrib><creatorcontrib>Karlen, Walter</creatorcontrib><creatorcontrib>Wensley, David</creatorcontrib><creatorcontrib>Ansermino, J Mark</creatorcontrib><creatorcontrib>Dumont, Guy 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>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>TestCollectionTL3OpenAccess</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garde, Ainara</au><au>Dehkordi, Parastoo</au><au>Karlen, Walter</au><au>Wensley, David</au><au>Ansermino, J Mark</au><au>Dumont, Guy A</au><au>Murillo-Rodriguez, Eric</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a screening tool for sleep disordered breathing in children using the phone Oximeter</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-17</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e112959</spage><epage>e112959</epage><pages>e112959-e112959</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Sleep disordered breathing (SDB) can lead to daytime sleepiness, growth failure and developmental delay in children. Polysomnography (PSG), the gold standard to diagnose SDB, is a highly resource-intensive test, confined to the sleep laboratory.
To combine the blood oxygen saturation (SpO2) characterization and cardiac modulation, quantified by pulse rate variability (PRV), to identify children with SDB using the Phone Oximeter, a device integrating a pulse oximeter with a smartphone.
Following ethics approval and informed consent, 160 children referred to British Columbia Children's Hospital for overnight PSG were recruited. A second pulse oximeter sensor applied to the finger adjacent to the one used for standard PSG was attached to the Phone Oximeter to record overnight pulse oximetry (SpO2 and photoplethysmogram (PPG)) alongside the PSG.
We studied 146 children through the analysis of the SpO2 pattern, and PRV as an estimate of heart rate variability calculated from the PPG. SpO2 variability and SpO2 spectral power at low frequency, was significantly higher in children with SDB due to the modulation provoked by airway obstruction during sleep (p-value <0.01). PRV analysis reflected a significant augmentation of sympathetic activity provoked by intermittent hypoxia in SDB children. A linear classifier was trained with the most discriminating features to identify children with SDB. The classifier was validated with internal and external cross-validation, providing a high negative predictive value (92.6%) and a good balance between sensitivity (88.4%) and specificity (83.6%). Combining SpO2 and PRV analysis improved the classification performance, providing an area under the receiver operating characteristic curve of 88%, beyond the 82% achieved using SpO2 analysis alone.
These results demonstrate that the implementation of this algorithm in the Phone Oximeter will provide an improved portable, at-home screening tool, with the capability of monitoring patients over multiple nights.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25401696</pmid><doi>10.1371/journal.pone.0112959</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-11, Vol.9 (11), p.e112959-e112959 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1625585858 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; TestCollectionTL3OpenAccess; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Augmentation Biology and Life Sciences Biomedical engineering Blood Breathing Cell Phone Child Child, Preschool Children Children & youth Classifiers Computer engineering Critical care Ethics Female Heart diseases Heart rate Hospitals Humans Hypoxia Informed consent Male Medical screening Medicine Medicine and Health Sciences Oximetry Oximetry - instrumentation Oximetry - methods Oxygen Oxygen content Physiology Pulse rate Reproducibility of Results Respiration Respiratory tract ROC Curve Saturation Screening Sensitivity analysis Sensors Sleep Sleep and wakefulness Sleep apnea Sleep Apnea Syndromes - diagnosis Sleep Apnea Syndromes - physiopathology Sleep disorders Sleepiness Smartphones Teenagers Variability |
| title | Development of a screening tool for sleep disordered breathing in children using the phone Oximeter |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T15%3A29%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Development%20of%20a%20screening%20tool%20for%20sleep%20disordered%20breathing%20in%20children%20using%20the%20phone%20Oximeter&rft.jtitle=PloS%20one&rft.au=Garde,%20Ainara&rft.date=2014-11-17&rft.volume=9&rft.issue=11&rft.spage=e112959&rft.epage=e112959&rft.pages=e112959-e112959&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0112959&rft_dat=%3Cgale_plos_%3EA418424652%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1625585858&rft_id=info:pmid/25401696&rft_galeid=A418424652&rft_doaj_id=oai_doaj_org_article_0d2ffcb366964dcd9974ca5a4d906c6e&rfr_iscdi=true |