Changing Faces of Obstructive Sleep Apnea: Treatment Effects by Cluster Designation in the Icelandic Sleep Apnea Cohort | SLEEP

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class="widget widget-ArticleJumpLinks widget-instance-OUP_ArticleJumpLinks_Widget"> <h3 class="contents-title" >Article Contents</h3> <ul class="jumplink-list js-jumplink-list"> <li class="section-jump-link head-1" link-destination="118223224"> <div class="section-jump-link__link-wrap"> <a class="js-jumplink scrollTo" href="#118223224">Abstract</a> </div> </li> <li class="section-jump-link head-1" link-destination="118223227"> <div class="section-jump-link__link-wrap"> <a class="js-jumplink scrollTo" href="#118223227">Introduction</a> </div> </li> <li class="section-jump-link head-1" link-destination="118223230"> <div class="section-jump-link__link-wrap"> <a class="js-jumplink scrollTo" href="#118223230">Methods</a> </div> </li> <li class="section-jump-link head-1" link-destination="118223249"> <div class="section-jump-link__link-wrap"> <a class="js-jumplink scrollTo" href="#118223249">Results</a> </div> </li> <li class="section-jump-link head-1" link-destination="118223276"> <div 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<div class="article-browse-top article-browse-mobile-nav mobile-sticky-toolbar js-mobile-nav-sticky"> <div class="article-browse-mobile-nav-inner"> <button class="toggle-left-col toggle-left-col__article btn-as-link"> Article Navigation </button> </div> </div> <div class="content-inner-wrap"> <div class="widget widget-ArticleTopInfo widget-instance-OUP_ArticleTop_Info_Widget"> <div class="module-widget article-top-widget"> <div class="access-state-logos all-viewports"> <span class="journal-info__format-label">Journal Article</span> <span class="article-flag"><a href="https://academic.oup.com/sleep/search-results?f_OUPSeries=Editor's+Choice">Editor's Choice</a></span> </div> <div class="widget-items"> <div class="title-wrap"> <h1 class="wi-article-title article-title-main accessible-content-title at-articleTitle"> Changing Faces of Obstructive Sleep Apnea: Treatment Effects by Cluster Designation in the Icelandic Sleep Apnea Cohort <i class='icon-availability_free' title='Free' ></i> </h1> </div> <div class="wi-authors at-ArticleAuthors"> <div class="al-authors-list"> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Grace W Pien, MD, MSCE</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Grace W Pien, MD, MSCE <span class="info-card-footnote"><span class="xrefLink" id="jumplink-c1"></span><a href="javascript:;" reveal-id="c1" data-open="c1" class="link link-ref link-reveal xref-default"></a></span> </div> </div> <div class="info-card-affilitation"> <div class="aff">Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</div> </div> <div class="info-author-correspondence"> <div content-id="c1">Corresponding Author: Grace W. Pien, MD, MSCE, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Allergy and Asthma Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. Telephone: 410-550-2512; Fax: 443-287-3313; E-mail: <a href="mailto:gpien1@jhmi.edu" target="_blank">gpien1@jhmi.edu</a></div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/sleep/search-results?f_Authors=Grace+W+Pien" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Pien Grace W%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Lichuan Ye, PhD, RN</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Lichuan Ye, PhD, RN </div> </div> <div class="info-card-affilitation"> <div 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of Sleep, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland</div><div class="aff">Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/sleep/search-results?f_Authors=Erla+Bj%c3%b6rnsd%c3%b3ttir" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Björnsdóttir Erla%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Erna Sif Arnardottir, PhD</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Erna Sif Arnardottir, PhD </div> </div> <div class="info-card-affilitation"> <div class="aff">Department of Sleep, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland</div><div class="aff">Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/sleep/search-results?f_Authors=Erna+Sif+Arnardottir" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Arnardottir Erna Sif%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Bryndis Benediktsdottir, MD</button><span class='delimiter'>, </span> <span 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class="linked-name js-linked-name-trigger btn-as-link">Thorarinn Gislason, MD</button><span class='delimiter'>, </span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Thorarinn Gislason, MD </div> </div> <div class="info-card-affilitation"> <div class="aff">Department of Sleep, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland</div><div class="aff">Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland</div> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/sleep/search-results?f_Authors=Thorarinn+Gislason" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Gislason Thorarinn%22">Google Scholar</a> </div> </div> </span> </span> <span class="al-author-name-more js-flyout-wrap"> <button type="button" class="linked-name js-linked-name-trigger btn-as-link">Allan I Pack, MBChB, PhD</button><span class='delimiter'></span> <span class="al-author-info-wrap arrow-up"> <div class="info-card-author authorInfo_OUP_ArticleTop_Info_Widget"> <div class="name-role-wrap"> <div class="info-card-name"> Allan I Pack, MBChB, PhD </div> </div> <div class="info-card-affilitation"> <div class="aff">Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</div><div class="aff">Division of Sleep Medicine or Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA</div> </div> <div class="info-card-location"> <a id="contrib-orcid-0000-0002-2879-0484" href="https://orcid.org/0000-0002-2879-0484"> <img class="orchid-icon" alt="ORCID logo" aria-hidden="true" src="//oup.silverchair-cdn.com/Themes/Silver/app/img/mini-icon.png"/>  https://orcid.org/0000-0002-2879-0484 </a> </div> <div class="info-card-search-label"> Search for other works by this author on: </div> <div class="info-card-search info-card-search-internal"> <a href="/sleep/search-results?f_Authors=Allan+I+Pack" rel="nofollow">Oxford Academic</a> </div> <div class="info-card-search info-card-search-google"> <a href="http://scholar.google.com/scholar?q=author:%22Pack Allan I%22">Google Scholar</a> </div> </div> </span> </span> <div class="al-author-name al-author-footnotes"> <div class="al-author-info-wrap arrow-up"> <div class="widget widget-SingleSection widget-instance-OUP_FootnoteSection"> <div content-id="fn-0001" class="footnote"><span class="fn"><div class="footnote-content"><p class="footnote-compatibility">Co-senior authors</p></div></span></div> </div> </div> <a class="js-linked-footnotes" href="javascript:;">Author Notes</a> </div> </div> </div> <div class="pub-history-wrap clearfix js-history-dropdown-wrap"> <div class="pub-history-row clearfix"> <div class="ww-citation-primary"><em>Sleep</em>, Volume 41, Issue 3, March 2018, zsx201, <a href='https://doi.org/10.1093/sleep/zsx201'>https://doi.org/10.1093/sleep/zsx201</a></div> </div> <div class="pub-history-row clearfix"> <div class="ww-citation-date-wrap"> <div class="citation-label">Published:</div> <div class="citation-date">02 January 2018</div> </div> <a href="javascript:;" class="history-label js-history-dropdown-trigger st-article-history at-ArticleHistory"> <span>Article history</span><i class="icon-general-arrow-filled-down arrow-icon"></i> </a> </div> <div class="ww-history js-history-entries-wrap at-history-entries-wrap"> <div class="history-entry at-history-entry"> <div class="wi-state">Received:</div> <div class="wi-date">21 April 2017</div> </div> <div class="history-entry at-history-entry"> <div class="wi-state">Accepted:</div> <div class="wi-date">19 September 2017</div> </div> <div class="history-entry at-history-entry"> <div class="wi-state">Published:</div> <div class="wi-date">02 January 2018</div> </div> </div> </div> </div> </div> <script> $(document).ready(function () { $('.article-top-widget').on('click', '.ati-toggle-trigger', function () { $(this).find('.icon-general-add, .icon-minus').toggleClass('icon-minus icon-general-add'); $(this).siblings('.ati-toggle-content').toggleClass('hide'); }); // In Chrome, an anchor tag with target="_blank" and a "mailto:" href opens a new tab/window as well as the email client // I suspect this behavior will be corrected in the future // Remove the target="_blank" $('ul.wi-affiliationList').find('a[href^="mailto:"]').each(function () { $(this).removeAttr('target'); }); }); </script> </div> <div class="widget widget-ArticleLinks widget-instance-OUP_Article_Links_Widget"> </div> <div class="article-body js-content-body"> <div class="toolbar-wrap js-toolbar-wrap"> <div class="toolbar-inner-wrap"> <ul 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class="abstract"><div class=" sec"><div class="title">Study Objectives</div><p class="chapter-para">Distinct clinical phenotypes of obstructive sleep apnea (OSA) have been identified: Disturbed Sleep, Minimally Symptomatic, and Sleepy. Determining whether these phenotypes respond differently to standard treatment helps us to create a foundation for personalized therapies. We compared responses to positive airway pressure (PAP) therapy in these clinical OSA phenotypes.</p></div><div class=" sec"><div class="title">Methods</div><p class="chapter-para">The study sample included 706 patients from the Icelandic Sleep Apnea Cohort with moderate-to-severe OSA who were prescribed PAP. Linear and logistic mixed models were used to compare 2-year changes in demographics, comorbid diseases, and sleep-related health issues within and across OSA clinical phenotypes. Relationships between changes in symptoms and PAP adherence were also examined.</p></div><div class=" sec"><div class="title">Results</div><p class="chapter-para">Overall, effect sizes were moderate to large when comparing sleepiness, insomnia-related, and apneic symptom changes in the Sleepy group with changes in other two groups, especially those in the Minimally Symptomatic group. Within the Disturbed Sleep group, PAP users and nonusers demonstrated similar changes in insomnia-related symptoms. The Minimally Symptomatic group remained relatively asymptomatic, but reported significant decreases in daytime sleepiness and physical fatigue; PAP users generally had larger improvements. The Sleepy group had reductions in nearly all measured symptoms, including large reductions in drowsy driving; almost all of these improvements were greater among PAP users than nonusers.</p></div><div class=" sec"><div class="title">Conclusions</div><p class="chapter-para">OSA treatment response patterns differed by initial clinical phenotype and PAP adherence. Individuals with insomnia-related symptoms may require additional targeted therapy for these complaints. These findings underscore the need for a personalized approach to management that recognizes patients with a range of OSA presentations.</p></div></section> <div class="article-metadata-panel clearfix at-ArticleMetadata"></div> <div class="kwd-group"><a class="kwd-part kwd-main" href="javascript:;" data-keyword=""obstructive sleep apnea"">obstructive sleep apnea</a>, <a class="kwd-part kwd-main" href="javascript:;" data-keyword=""phenotypes of OSA"">phenotypes of OSA</a>, <a class="kwd-part kwd-main" href="javascript:;" data-keyword=""treatment outcome"">treatment outcome</a>, <a class="kwd-part kwd-main" href="javascript:;" data-keyword=""cluster analysis"">cluster analysis</a>, <a class="kwd-part kwd-main" href="javascript:;" data-keyword=""positive airway pressure"">positive airway pressure</a></div><div id="" class="boxed-text boxed-matter no-caption"><div class=" sec"><div class="title">Statement of Significance</div><p class="chapter-para">This study examined responses to positive airway pressure (PAP) therapy in people with obstructive sleep apnea (OSA) with three distinct clinical phenotypes (Disturbed Sleep, Minimally Symptomatic, and Sleepy) initially identified using cluster analysis, a novel methodology for grouping similar individuals together and distinguishing them from each other. After 2 years of PAP treatment, patterns of treatment response in the three clinical phenotypes of OSA varied by initial clinical presentation. Thus, traditional practice assessing limited measures of treatment response within all people with OSA probably underestimates treatment effects. These findings underscore the need to recognize that patients with a range of OSA presentations benefit from treatment and to consider initial OSA phenotype in future clinical trials.</p></div></div> <h2 scrollto-destination=118223227 id="118223227" class="section-title js-splitscreen-section-title" data-legacy-id=s6>Introduction</h2> <p class="chapter-para">While long recognized, the heterogeneity of obstructive sleep apnea (OSA) clinical presentations has been formally characterized only recently. Our team first applied cluster analysis to identify clinical phenotypes of patients with moderate-to-severe OSA in the Icelandic Sleep Apnea Cohort (ISAC), using self-reported symptoms and relevant comorbidities.<sup><span class="xrefLink" id="jumplink-CIT0001"></span><a href="javascript:;" reveal-id="CIT0001" data-open="CIT0001" class="link link-ref link-reveal xref-bibr">1</a></sup> Cluster analysis groups individuals together based on the specified variables so that members of each cluster are as similar as possible to others within the cluster, but as different as possible compared with those in other clusters. We identified three distinct clusters, including a Disturbed Sleep group, a Minimally Symptomatic group, and an Excessive Daytime Sleepiness (Sleepy) group.<sup><span class="xrefLink" id="jumplink-CIT0001"></span><a href="javascript:;" reveal-id="CIT0001" data-open="CIT0001" class="link link-ref link-reveal xref-bibr">1</a></sup> The Disturbed Sleep group had the highest probability of experiencing insomnia-related symptoms, including difficulty falling asleep, waking too early, and waking often during the night. Patients in the Minimally Symptomatic group were markedly less likely to report sleep-related symptoms, and they were much more likely to feel rested upon waking. The Sleepy group had a mean Epworth Sleepiness Scale (ESS) score of nearly 16 and a markedly higher probability of sleepiness-related symptoms, such as falling asleep involuntarily and dozing off when driving. Understanding how patients with distinct clinical phenotypes and specific underlying symptoms respond to standard treatment for OSA (i.e., positive airway pressure, PAP) creates a foundation for personalized therapies and optimal clinical approaches for management of OSA.</p><p class="chapter-para">In the current study, we examined symptom changes in the three OSA clinical phenotypes in the ISAC study 2 years after PAP initiation. We hypothesized that specific symptom changes at follow-up would vary depending on baseline cluster assignment. Furthermore, we compared PAP adherence and changes in other clinical outcomes including health status and comorbidities by clinical phenotypes among the clusters and examined how PAP adherence may influence treatment responses among and within the clusters. Some of the results of this study have previously been reported in the form of an abstract.<sup><span class="xrefLink" id="jumplink-CIT0002"></span><a href="javascript:;" reveal-id="CIT0002" data-open="CIT0002" class="link link-ref link-reveal xref-bibr">2</a></sup></p> <h2 scrollto-destination=118223230 id="118223230" class="section-title js-splitscreen-section-title" data-legacy-id=s7>Methods</h2> <h3 scrollto-destination=118223231 id="118223231" class="section-title js-splitscreen-section-title" data-legacy-id=s8>Study Sample</h3> <p class="chapter-para">This report includes 706 participants with baseline and 2-year follow-up data from the ISAC, a prospective clinical cohort of people with moderate-to-severe OSA (apnea–hypopnea index [AHI] ≥ 15 events per hour) from the entire population of Iceland, described previously in detail.<sup><span class="xrefLink" id="jumplink-CIT0001"></span><a href="javascript:;" reveal-id="CIT0001" data-open="CIT0001" class="link link-ref link-reveal xref-bibr">1</a>,<span class="xrefLink" id="jumplink-CIT0003 CIT0004 CIT0005"></span><a href="javascript:;" reveal-id="CIT0003 CIT0004 CIT0005" data-open="CIT0003 CIT0004 CIT0005" class="link link-ref link-reveal xref-bibr">3–5</a></sup> There were no significant differences in gender, age, body mass index (BMI), OSA severity, quality of life, or cluster assignment between included participants (<em>n</em> = 706) and those from the original sample lost to follow-up (<em>n</em> = 79; <span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S1</a></span>). The Iceland National Bioethics Committee, Data Protection Authority of Iceland, and University of Pennsylvania Institutional Review Board approved the study. Written consent was obtained from all participants.</p> <h3 scrollto-destination=118223233 id="118223233" class="section-title js-splitscreen-section-title" data-legacy-id=s9>Study Design</h3> <p class="chapter-para">Before starting PAP, each participant completed a type 3 sleep study, physical examination, and questionnaires including the Basic Nordic Sleep Questionnaire (BNSQ),<sup><span class="xrefLink" id="jumplink-CIT0006"></span><a href="javascript:;" reveal-id="CIT0006" data-open="CIT0006" class="link link-ref link-reveal xref-bibr">6</a></sup> ESS,<sup><span class="xrefLink" id="jumplink-CIT0007"></span><a href="javascript:;" reveal-id="CIT0007" data-open="CIT0007" class="link link-ref link-reveal xref-bibr">7</a></sup> International Restless Legs Syndrome Study Group Questionnaire,<sup><span class="xrefLink" id="jumplink-CIT0008"></span><a href="javascript:;" reveal-id="CIT0008" data-open="CIT0008" class="link link-ref link-reveal xref-bibr">8</a></sup> and 12-Item Short Form Health Survey (SF-12).<sup><span class="xrefLink" id="jumplink-CIT0009"></span><a href="javascript:;" reveal-id="CIT0009" data-open="CIT0009" class="link link-ref link-reveal xref-bibr">9</a></sup> Self-reported comorbid conditions were validated against medical records. BNSQ is a scale assessing the frequency of subjective sleep complaints in the past 3 months, ranging from 1 (never or less than once per month), 2 (less than once in a week), 3 (once or twice in a week), 4 (three to five times a week), to 5 (every night or almost daily).<sup><span class="xrefLink" id="jumplink-CIT0006"></span><a href="javascript:;" reveal-id="CIT0006" data-open="CIT0006" class="link link-ref link-reveal xref-bibr">6</a></sup> This instrument is frequently used in epidemiological and genetic research for OSA with demonstrated validity<sup><span class="xrefLink" id="jumplink-CIT0010"></span><a href="javascript:;" reveal-id="CIT0010" data-open="CIT0010" class="link link-ref link-reveal xref-bibr">10</a></sup> and has been used widely in routine clinical practice in the Nordic countries.<sup><span class="xrefLink" id="jumplink-CIT0006"></span><a href="javascript:;" reveal-id="CIT0006" data-open="CIT0006" class="link link-ref link-reveal xref-bibr">6</a></sup> Participants were followed for 2 years to allow adequate opportunity to evaluate changes in OSA symptoms. Patients using PAP were assisted by trained staff in optimizing PAP therapy and followed in a continuously updated register. Baseline assessments were repeated and PAP adherence was examined at the follow-up visit.<sup><span class="xrefLink" id="jumplink-CIT0011"></span><a href="javascript:;" reveal-id="CIT0011" data-open="CIT0011" class="link link-ref link-reveal xref-bibr">11</a></sup></p> <h3 scrollto-destination=118223235 id="118223235" class="section-title js-splitscreen-section-title" data-legacy-id=s10>Outcome Variables</h3> <p class="chapter-para">In the original cluster analyses, we identified three clinical phenotypes using 23 variables representing clinically significant and prevalent symptoms and comorbidities in the OSA population, mostly drawn from the BNSQ, ESS, SF-12, and the validated medical history.<sup><span class="xrefLink" id="jumplink-CIT0001"></span><a href="javascript:;" reveal-id="CIT0001" data-open="CIT0001" class="link link-ref link-reveal xref-bibr">1</a></sup> Detailed descriptions of these variables are available in the original report and other reports from the ISAC cohort.<sup><span class="xrefLink" id="jumplink-CIT0001"></span><a href="javascript:;" reveal-id="CIT0001" data-open="CIT0001" class="link link-ref link-reveal xref-bibr">1</a>,<span class="xrefLink" id="jumplink-CIT0003"></span><a href="javascript:;" reveal-id="CIT0003" data-open="CIT0003" class="link link-ref link-reveal xref-bibr">3</a>,<span class="xrefLink" id="jumplink-CIT0005"></span><a href="javascript:;" reveal-id="CIT0005" data-open="CIT0005" class="link link-ref link-reveal xref-bibr">5</a></sup> We retained these variables for examination as outcomes in the current analyses, including symptom profiles, daytime sleepiness (evaluated by the ESS score), comorbid conditions (existence of hypertension, diabetes, cardiovascular disease, and obstructive lung disease), health status (SF-12), and blood pressure (BP). Symptom profiles were primarily derived from the responses to the questions on the BNSQ. To comprehensively evaluate symptom responses to PAP treatment and avoid focusing exclusively on a few hallmark symptoms of OSA, we examined changes in the individual symptoms that were used to define the symptom clusters at baseline. To highlight responses in symptom-related measures, similar symptoms were grouped together to create symptom “domains,” including sleepiness and fatigue-related symptoms, insomnia-related symptoms, apneic symptoms, and other sleep-related complaints.</p> <h3 scrollto-destination=118223237 id="118223237" class="section-title js-splitscreen-section-title" data-legacy-id=s11>PAP Adherence</h3> <p class="chapter-para">PAP adherence was assessed using both questionnaire and memory card data, as described previously.<sup><span class="xrefLink" id="jumplink-CIT0011"></span><a href="javascript:;" reveal-id="CIT0011" data-open="CIT0011" class="link link-ref link-reveal xref-bibr">11</a></sup> At follow-up, 457 of 706 participants (64.7%) reported using PAP. Objective PAP usage measures were available for 351 (76.8%) PAP users. The remaining 106 (23.2%) had devices without downloadable cards; their PAP adherence was determined using subjective data. Individuals using PAP for ≥5 days per week and ≥4 hr per night for the 28 nights prior to follow-up assessment<sup><span class="xrefLink" id="jumplink-CIT0003"></span><a href="javascript:;" reveal-id="CIT0003" data-open="CIT0003" class="link link-ref link-reveal xref-bibr">3</a>,<span class="xrefLink" id="jumplink-CIT0011 CIT0012 CIT0013 CIT0014 CIT0015"></span><a href="javascript:;" reveal-id="CIT0011 CIT0012 CIT0013 CIT0014 CIT0015" data-open="CIT0011 CIT0012 CIT0013 CIT0014 CIT0015" class="link link-ref link-reveal xref-bibr">11–15</a></sup> were classified as full users (51.1% of all participants; mean 26.7 ± 2.0 nights, 7.1 ± 1.2 hr per night from machines with memory cards). PAP users not meeting these criteria were classified as partial users (13.6%; mean 14.2 ± 7.2 nights, 3.7 ± 2.2 hr per night). Non-users (<em>n</em> = 249 [35.3%]) had given up their machines, self-reported nonuse, or had no objective usage in the past 28 days. Prior analyses validating self-reported use against objective PAP data in the ISAC demonstrated 98.6% sensitivity and 45.1% specificity for distinguishing full users from partial users.<sup><span class="xrefLink" id="jumplink-CIT0011"></span><a href="javascript:;" reveal-id="CIT0011" data-open="CIT0011" class="link link-ref link-reveal xref-bibr">11</a></sup></p> <h3 scrollto-destination=118223239 id="118223239" class="section-title js-splitscreen-section-title" data-legacy-id=s12>Statistical Analysis</h3> <p class="chapter-para">Participants were grouped into clusters (Disturbed Sleep, Minimally Symptomatic, or Sleepy) by their baseline characteristics, as identified originally.<sup><span class="xrefLink" id="jumplink-CIT0001"></span><a href="javascript:;" reveal-id="CIT0001" data-open="CIT0001" class="link link-ref link-reveal xref-bibr">1</a></sup> Cross-sectional comparisons of demographic, symptom, and comorbidity measures between groups were performed using <em>t</em>-tests or analysis of variance (ANOVA) for continuous variables and chi-squared or Fisher’s exact tests for categorical variables.</p><p class="chapter-para">To compare changes in variables among clusters, we used linear (continuous variables) or logistic (binary variables) mixed models and assessed the significance of the time by cluster interaction term among all participants. Significance of this interaction term was based on an <em>F</em>-statistic with two numerator degrees of freedom and denominator degrees of freedom estimated using the containment method in SAS PROC GLIMMIX. A significant interaction term in the mixed model indicates a difference in the 2-year change in the symptom variable among clusters. Primary analyses examined symptom frequency change using the five-level response variable via linear mixed models; change scores were generally normally distributed around zero, allowing for parametric analysis.</p><p class="chapter-para">In secondary analyses, we categorized each symptom as “present” if it occurred at least once or twice weekly, as in the original study,<sup><span class="xrefLink" id="jumplink-CIT0001"></span><a href="javascript:;" reveal-id="CIT0001" data-open="CIT0001" class="link link-ref link-reveal xref-bibr">1</a></sup> and examined change in the likelihood of individual symptoms being present using logistic mixed models; detailed results are presented in Supplemental Material. For these binary outcomes, an a priori rule requiring an adequate number of changes in symptom status (e.g., variability in responses) within a cluster was applied prior to conducting statistical models to prevent model instability and lack of convergence. Specifically, in order to fit the logistic mixed model, we required more than five changes in the symptom presence or absence from baseline to follow-up overall, including at least one change from presence to absence and one change from absence to presence; if a cluster did not meet these criteria, results for that group are presented as N/A.</p><p class="chapter-para">When comparisons among the clusters achieved statistical significance after correction for multiple comparisons (see below), we performed between cluster contrasts to determine which clusters were driving the overall results. To provide more clinically meaningful effect estimates, results of these comparisons are presented as standardized mean differences in change scores for continuous measures (equivalent to Cohen’s D) or ratios of within-group odds ratios, along with corresponding 95% confidence intervals. Standardized mean differences were obtained by dividing the observed difference on the original scale by the total phenotypic standard deviation estimated from the mixed model. Based on prior publications on effects for biological sciences,<sup><span class="xrefLink" id="jumplink-CIT0016"></span><a href="javascript:;" reveal-id="CIT0016" data-open="CIT0016" class="link link-ref link-reveal xref-bibr">16</a></sup> the magnitude of these standardized effect sizes can be interpreted as small (~0.20), medium (~0.50), or large (~0.80), thus providing more clinically relevant interpretations.</p><p class="chapter-para">Within-group estimates are presented on the observed scales, wherever relevant, to help inform clinical expectations in response. Ratio measures such as the within-group odds ratio provide a relative interpretation of the proportional differences in effects between clusters. Analyses comparing clusters were adjusted for primary confounders of gender and baseline age, BMI, and AHI. Moreover, to examine whether the level of PAP adherence mediated the relationship between clinical phenotype and treatment responses, we examined changes in association between clusters and changes in outcome variables after further controlling for PAP adherence group (“full,” “partial,” or nonuser).</p><p class="chapter-para">Next, we evaluated the effect of PAP both within and among clusters. Analyses were restricted to adherent (“full”) and nonusers, to obtain more robust estimates of PAP effects. First, to test whether there were differences in the PAP effect among OSA clusters, we examined the significance of a three-way interaction term between time, cluster, and PAP adherence group in mixed models similar to those described above. A significant three-way interaction suggests that the effect of PAP adherence on changes in symptoms differs among the three clusters. In addition to this overall evaluation, within each cluster, we examined relationships between changes in symptoms and PAP adherence using similar techniques to those described above. Clinically interpretable effect estimates comparing full users and nonusers within clusters were derived in a similar fashion to between-cluster effects.</p><p class="chapter-para">To reduce bias and improve causal interpretations of PAP effects, models comparing full users and nonusers were adjusted using a propensity score derived from baseline age, gender, BMI and AHI main effects, squares, and interaction terms.<sup><span class="xrefLink" id="jumplink-CIT0017"></span><a href="javascript:;" reveal-id="CIT0017" data-open="CIT0017" class="link link-ref link-reveal xref-bibr">17</a></sup> To account for other sources of potential bias in PAP effect estimates, we performed three sensitivity analyses: (1) excluding nonusers who reported alternative OSA treatments (e.g., oral appliance); (2) excluding any patient with >5% weight loss at follow-up; and (3) excluding individuals who reported using PAP but whose PAP devices lacked downloadable memory cards to verify adherence objectively.</p><p class="chapter-para">We utilized the Hochberg step-up method to control α at 5% given multiple comparisons when comparing symptoms among clusters and within a given OSA cluster.<sup><span class="xrefLink" id="jumplink-CIT0018"></span><a href="javascript:;" reveal-id="CIT0018" data-open="CIT0018" class="link link-ref link-reveal xref-bibr">18</a>,<span class="xrefLink" id="jumplink-CIT0019"></span><a href="javascript:;" reveal-id="CIT0019" data-open="CIT0019" class="link link-ref link-reveal xref-bibr">19</a></sup> Statistically significant <em>p</em>-values after Hochberg correction are shown in bold or specifically noted in results’ tables. For comparisons of change scores among clusters, pairwise comparisons were only performed if overall tests were significant after Hochberg correction. In addition, when performing pairwise comparisons among clusters, statistical significance was based on a Bonferroni-corrected <em>p</em> < .0167 (given three pairwise comparisons).</p><p class="chapter-para">All analyses were conducted using STATA, Version 14 (StataCorp LP, College Station, TX) or SAS Version 9.4 (SAS Institute, Cary, NC).</p> <h2 scrollto-destination=118223249 id="118223249" class="section-title js-splitscreen-section-title" data-legacy-id=s13>Results</h2> <h3 scrollto-destination=118223250 id="118223250" class="section-title js-splitscreen-section-title" data-legacy-id=s14>Characteristics of the Study Cohort</h3> <p class="chapter-para">The majority of study participants were obese, middle-aged men with severe OSA (<span class="xrefLink" id="jumplink-T1"></span><a href="javascript:;" reveal-id="T1" data-open="T1" class="link link-reveal link-table xref-fig">Table 1</a>). There were no baseline differences in gender, BMI, or OSA severity among groups. The Minimally Symptomatic group was slightly older and reported better physical and mental health than the other groups.</p> <a id="118223252" scrollto-destination="118223252"></a> <div content-id="T1" class="table-modal table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T1" data-id="T1"><span class="label title-label" id="label-18145">Table 1.</span><div class="
 graphic-wrap table-open-button-wrap
 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223252" aria-describedby="label-18145"> Open in new tab </a></div><div class="caption caption-id-" id="caption-18145"><p class="chapter-para">Demographic and Clinical Characteristics of the ISAC Symptom Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-18145" aria-describedby="
 caption-18145"><thead><tr><th rowspan="2">Variable<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="5">Baseline characteristics<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Overall<span aria-hidden="true" style="display: none;"> . </span></th><th>Disturbed sleep<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy<span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td><em>N</em> (%)</td><td>706 (100)</td><td>229 (32.4)</td><td>170 (24.1)</td><td>307 (43.5)</td><td><em>—</em></td></tr><tr><td>Male, %</td><td>80.6%</td><td>77.7%</td><td>84.1%</td><td>80.8%</td><td>.278</td></tr><tr><td>Age, years</td><td>54.7 ± 10.3</td><td>54.4 ± 10.8</td><td>56.8 ± 10.0</td><td>53.8 ± 10.0</td><td><strong>.008</strong></td></tr><tr><td>BMI, kg/m<sup>2</sup></td><td>33.6 ± 5.7</td><td>33.7 ± 5.6</td><td>33.0 ± 5.4</td><td>34.0 ± 5.9</td><td>.194</td></tr><tr><td>AHI, events/hr</td><td>45.9 ± 19.9</td><td>44.8 ± 18.8</td><td>43.6 ± 18.0</td><td>47.9 ± 21.5</td><td>.135</td></tr><tr><td>ODI, events/hr</td><td>36.3 ± 19.8</td><td>34.4 ± 17.4</td><td>34.5 ± 18.6</td><td>38.7 ± 21.9</td><td>.132</td></tr><tr><td>SaO<sub>2</sub> Nadir</td><td>76.1 ± 8.1</td><td>76.4 ± 7.9</td><td>76.5 ± 7.6</td><td>75.5 ± 8.5</td><td>.447</td></tr><tr><td>% Time SaO<sub>2</sub> < 90</td><td>14.1 ± 18.2</td><td>13.3 ± 18.7</td><td>12.4 ± 16.2</td><td>15.7 ± 18.8</td><td>.166</td></tr><tr><td>SF-12 physical<sup>a</sup></td><td>40.1 ± 11.0</td><td>39.7 ± 10.7</td><td>45.2 ± 10.0</td><td>37.6 ± 10.7</td><td><strong><.0001</strong></td></tr><tr><td>SF-12 mental<sup>a</sup></td><td>48.3 ± 10.7</td><td>47.2 ± 11.1</td><td>52.7 ± 9.8</td><td>46.8 ± 10.2</td><td><strong><.0001</strong></td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th rowspan="2">Variable<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="5">Baseline characteristics<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Overall<span aria-hidden="true" style="display: none;"> . </span></th><th>Disturbed sleep<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy<span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td><em>N</em> (%)</td><td>706 (100)</td><td>229 (32.4)</td><td>170 (24.1)</td><td>307 (43.5)</td><td><em>—</em></td></tr><tr><td>Male, %</td><td>80.6%</td><td>77.7%</td><td>84.1%</td><td>80.8%</td><td>.278</td></tr><tr><td>Age, years</td><td>54.7 ± 10.3</td><td>54.4 ± 10.8</td><td>56.8 ± 10.0</td><td>53.8 ± 10.0</td><td><strong>.008</strong></td></tr><tr><td>BMI, kg/m<sup>2</sup></td><td>33.6 ± 5.7</td><td>33.7 ± 5.6</td><td>33.0 ± 5.4</td><td>34.0 ± 5.9</td><td>.194</td></tr><tr><td>AHI, events/hr</td><td>45.9 ± 19.9</td><td>44.8 ± 18.8</td><td>43.6 ± 18.0</td><td>47.9 ± 21.5</td><td>.135</td></tr><tr><td>ODI, events/hr</td><td>36.3 ± 19.8</td><td>34.4 ± 17.4</td><td>34.5 ± 18.6</td><td>38.7 ± 21.9</td><td>.132</td></tr><tr><td>SaO<sub>2</sub> Nadir</td><td>76.1 ± 8.1</td><td>76.4 ± 7.9</td><td>76.5 ± 7.6</td><td>75.5 ± 8.5</td><td>.447</td></tr><tr><td>% Time SaO<sub>2</sub> < 90</td><td>14.1 ± 18.2</td><td>13.3 ± 18.7</td><td>12.4 ± 16.2</td><td>15.7 ± 18.8</td><td>.166</td></tr><tr><td>SF-12 physical<sup>a</sup></td><td>40.1 ± 11.0</td><td>39.7 ± 10.7</td><td>45.2 ± 10.0</td><td>37.6 ± 10.7</td><td><strong><.0001</strong></td></tr><tr><td>SF-12 mental<sup>a</sup></td><td>48.3 ± 10.7</td><td>47.2 ± 11.1</td><td>52.7 ± 9.8</td><td>46.8 ± 10.2</td><td><strong><.0001</strong></td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-01"></span><div content-id="fn-01" class="footnote"><span class="fn"><p class="chapter-para">*<em>P</em>-value from ANOVA or Kruskal–Wallis test (continuous variables) or chi-square test (categorical variables) comparing the three clusters.</p></span></div><span id="fn-fn-02"></span><div content-id="fn-02" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup><em>N</em> = 681 with available data.</p></span></div><span id="fn-fn-03"></span><div content-id="fn-03" class="footnote"><span class="fn"><p class="chapter-para">BMI = body mass index; AHI = apnea–hypopnea index; ODI = oxygen desaturation index; SaO<sub>2</sub> = oxygen saturation.</p></span></div><span id="fn-fn-04"></span><div content-id="fn-04" class="footnote"><span class="fn"><p class="chapter-para"><em>P</em>-values <0.05 have been bolded.</p></span></div></div></div></div><div class="table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T1" data-id="T1"><span class="label title-label" id="label-18145">Table 1.</span><div class="
 graphic-wrap table-open-button-wrap
 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223252" aria-describedby="label-18145"> Open in new tab </a></div><div class="caption caption-id-" id="caption-18145"><p class="chapter-para">Demographic and Clinical Characteristics of the ISAC Symptom Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-18145" aria-describedby="
 caption-18145"><thead><tr><th rowspan="2">Variable<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="5">Baseline characteristics<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Overall<span aria-hidden="true" style="display: none;"> . </span></th><th>Disturbed sleep<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy<span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td><em>N</em> (%)</td><td>706 (100)</td><td>229 (32.4)</td><td>170 (24.1)</td><td>307 (43.5)</td><td><em>—</em></td></tr><tr><td>Male, %</td><td>80.6%</td><td>77.7%</td><td>84.1%</td><td>80.8%</td><td>.278</td></tr><tr><td>Age, years</td><td>54.7 ± 10.3</td><td>54.4 ± 10.8</td><td>56.8 ± 10.0</td><td>53.8 ± 10.0</td><td><strong>.008</strong></td></tr><tr><td>BMI, kg/m<sup>2</sup></td><td>33.6 ± 5.7</td><td>33.7 ± 5.6</td><td>33.0 ± 5.4</td><td>34.0 ± 5.9</td><td>.194</td></tr><tr><td>AHI, events/hr</td><td>45.9 ± 19.9</td><td>44.8 ± 18.8</td><td>43.6 ± 18.0</td><td>47.9 ± 21.5</td><td>.135</td></tr><tr><td>ODI, events/hr</td><td>36.3 ± 19.8</td><td>34.4 ± 17.4</td><td>34.5 ± 18.6</td><td>38.7 ± 21.9</td><td>.132</td></tr><tr><td>SaO<sub>2</sub> Nadir</td><td>76.1 ± 8.1</td><td>76.4 ± 7.9</td><td>76.5 ± 7.6</td><td>75.5 ± 8.5</td><td>.447</td></tr><tr><td>% Time SaO<sub>2</sub> < 90</td><td>14.1 ± 18.2</td><td>13.3 ± 18.7</td><td>12.4 ± 16.2</td><td>15.7 ± 18.8</td><td>.166</td></tr><tr><td>SF-12 physical<sup>a</sup></td><td>40.1 ± 11.0</td><td>39.7 ± 10.7</td><td>45.2 ± 10.0</td><td>37.6 ± 10.7</td><td><strong><.0001</strong></td></tr><tr><td>SF-12 mental<sup>a</sup></td><td>48.3 ± 10.7</td><td>47.2 ± 11.1</td><td>52.7 ± 9.8</td><td>46.8 ± 10.2</td><td><strong><.0001</strong></td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th rowspan="2">Variable<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="5">Baseline characteristics<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Overall<span aria-hidden="true" style="display: none;"> . </span></th><th>Disturbed sleep<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy<span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td><em>N</em> (%)</td><td>706 (100)</td><td>229 (32.4)</td><td>170 (24.1)</td><td>307 (43.5)</td><td><em>—</em></td></tr><tr><td>Male, %</td><td>80.6%</td><td>77.7%</td><td>84.1%</td><td>80.8%</td><td>.278</td></tr><tr><td>Age, years</td><td>54.7 ± 10.3</td><td>54.4 ± 10.8</td><td>56.8 ± 10.0</td><td>53.8 ± 10.0</td><td><strong>.008</strong></td></tr><tr><td>BMI, kg/m<sup>2</sup></td><td>33.6 ± 5.7</td><td>33.7 ± 5.6</td><td>33.0 ± 5.4</td><td>34.0 ± 5.9</td><td>.194</td></tr><tr><td>AHI, events/hr</td><td>45.9 ± 19.9</td><td>44.8 ± 18.8</td><td>43.6 ± 18.0</td><td>47.9 ± 21.5</td><td>.135</td></tr><tr><td>ODI, events/hr</td><td>36.3 ± 19.8</td><td>34.4 ± 17.4</td><td>34.5 ± 18.6</td><td>38.7 ± 21.9</td><td>.132</td></tr><tr><td>SaO<sub>2</sub> Nadir</td><td>76.1 ± 8.1</td><td>76.4 ± 7.9</td><td>76.5 ± 7.6</td><td>75.5 ± 8.5</td><td>.447</td></tr><tr><td>% Time SaO<sub>2</sub> < 90</td><td>14.1 ± 18.2</td><td>13.3 ± 18.7</td><td>12.4 ± 16.2</td><td>15.7 ± 18.8</td><td>.166</td></tr><tr><td>SF-12 physical<sup>a</sup></td><td>40.1 ± 11.0</td><td>39.7 ± 10.7</td><td>45.2 ± 10.0</td><td>37.6 ± 10.7</td><td><strong><.0001</strong></td></tr><tr><td>SF-12 mental<sup>a</sup></td><td>48.3 ± 10.7</td><td>47.2 ± 11.1</td><td>52.7 ± 9.8</td><td>46.8 ± 10.2</td><td><strong><.0001</strong></td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-01"></span><div content-id="fn-01" class="footnote"><span class="fn"><p class="chapter-para">*<em>P</em>-value from ANOVA or Kruskal–Wallis test (continuous variables) or chi-square test (categorical variables) comparing the three clusters.</p></span></div><span id="fn-fn-02"></span><div content-id="fn-02" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup><em>N</em> = 681 with available data.</p></span></div><span id="fn-fn-03"></span><div content-id="fn-03" class="footnote"><span class="fn"><p class="chapter-para">BMI = body mass index; AHI = apnea–hypopnea index; ODI = oxygen desaturation index; SaO<sub>2</sub> = oxygen saturation.</p></span></div><span id="fn-fn-04"></span><div content-id="fn-04" class="footnote"><span class="fn"><p class="chapter-para"><em>P</em>-values <0.05 have been bolded.</p></span></div></div></div></div> <h3 scrollto-destination=118223253 id="118223253" class="section-title js-splitscreen-section-title" data-legacy-id=s15>Symptoms at Baseline and Follow-up in Each Group</h3> <p class="chapter-para">We examined how symptom profiles changed within each group while controlling for gender and baseline age, BMI, and AHI (<span class="xrefLink" id="jumplink-F1"></span><a href="javascript:;" data-modal-source-id="F1" class="link xref-fig">Figure 1</a>; <span class="xrefLink" id="jumplink-T2"></span><a href="javascript:;" reveal-id="T2" data-open="T2" class="link link-reveal link-table xref-fig">Table 2</a> and <span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Tables S2 </a></span>and <span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">S3</a></span>). In general, each group exhibited improvement in those symptoms representative of their baseline symptom profile. Greater improvements were observed in the Disturbed Sleep and Sleepy groups, which were more symptomatic at baseline than the Minimally Symptomatic group.</p> <a id="118223255" scrollto-destination="118223255"></a> <div data-id="f1" data-content-id="f1" class="fig fig-section js-fig-section" swap-content-for-modal="true"><div class="graphic-wrap"><img class="content-image" src="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/m_zsx20101.jpeg?Expires=1735725789&Signature=IxgqQL5D0o01wzURasFYTfxTi9oO3fY3VfkoEXCr99x9sAyMqAVnUoC12~3CA1Yl8ivkascPhPuIG4C8z53aEu14RQs3kqJYd609IORDZRMF9~TZiRxgJV21-8XTaLQtBL1dCbYy3-RVjhQsaohYAMroDdiH21SX3lsxemg4f1g-U3bTxZUuGyfyDdxvP4sX0vs7A9pQ69IExJ113y45TR4Dy0-wtYobaGHOTuBQZuai2K1G5xCmCUO0NvTFsvwxs7183JZHhpXeef-qpkuJbN09JhYFTwCmvRpYqbj9B-qXqXZIqkQrz6H3AqMUmFLNjCqCGVdJgewLxKWKr7P8BQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" alt="Symptom profiles in each cluster at baseline and follow-up. Radar plots are shown, illustrating the mean frequency scores reported by participants within the specified cluster for each indicated symptom at baseline and follow-up. Note the clear reduction in cluster-specific symptoms at follow-up." data-path-from-xml="zsx20101.jpeg" /><div class="graphic-bottom"><div class="label fig-label" id="label-118223255">Figure 1.</div><div class="caption fig-caption"><p class="chapter-para">Symptom profiles in each cluster at baseline and follow-up. Radar plots are shown, illustrating the mean frequency scores reported by participants within the specified cluster for each indicated symptom at baseline and follow-up. Note the clear reduction in cluster-specific symptoms at follow-up.</p></div><div class="ajax-articleAbstract-exclude-regex fig-orig original-slide figure-button-wrap"><a class="fig-view-orig js-view-large at-figureViewLarge openInAnotherWindow" role="button" aria-describedby="label-118223255" href="/view-large/figure/118223255/zsx20101.jpeg" data-path-from-xml="zsx20101.jpeg" target="_blank">Open in new tab</a><a class="download-slide" role="button" aria-describedby="label-118223255" data-section="118223255" href="/DownloadFile/DownloadImage.aspx?image=https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx20101.jpeg?Expires=1735725789&Signature=l-PO3V48fd6jiNJFfaGnFd-4bm27qb59j5b3Fj4ACiFFo4YQHTfwZNSvEyfFguxoX5NVU70tCzb1pRu6QbFv9EYonNTkqRIcYsimtFn8V1zrXbWWV48bRcGSZb0pqq2O4xNd7UyE7kXUp8nJ2lAkJ8soAhAvfoxty3NRUSXhWNwFSqWu-HpH4kDnBWuGb0Sg200WQbgpTMBpibygKvrbKmJ-bGR-zsIlcpjTFWgJV2iO3uOZxsk0uM7uEpBy3eko442fXXLQXL3Yo2xwNAeC-kma19IxW6Vn6ehpxIuCsqAZqJ732ZEe4b6-6TWkSeqfYUV2Ca1A8V~9zkxrI~ccyA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA&sec=118223255&ar=4782667&xsltPath=~/UI/app/XSLT&imagename=&siteId=5573" data-path-from-xml="zsx20101.jpeg">Download slide</a></div></div></div></div> <a id="118223256" scrollto-destination="118223256"></a> <div content-id="T2" class="table-modal table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T2" data-id="T2"><span class="label title-label" id="label-54025">Table 2.</span><div class="
 graphic-wrap table-open-button-wrap
 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223256" aria-describedby="label-54025"> Open in new tab </a></div><div class="caption caption-id-" id="caption-54025"><p class="chapter-para">Adjusted Models for Changes in Symptom Variables Within and Between Symptom Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-54025" aria-describedby="
 caption-54025"><thead><tr><th rowspan="2"><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Symptom measures<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Estimate (95% CI)<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Overall <em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Pairwise differences estimates<sup>b</sup><span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed sleep (DS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic (MS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy (S)<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. MS<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. S<span aria-hidden="true" style="display: none;"> . </span></th><th>MS vs. S<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td rowspan="7">Sleepiness and fatigue</td><td>Epworth Sleepiness Scale</td><td>−2.06 (−2.64, −1.48)<sup>c</sup></td><td>−1.33 (−2.00, −0.66)<sup>c</sup></td><td>−5.31 (−5.81, −4.81)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.19 (−0.42, 0.04)</td><td>0.84 (0.65, 1.04)<sup>d</sup></td><td>1.03 (0.82, 1.25)<sup>d</sup></td></tr><tr><td>I feel sleepy during the day</td><td>−0.94 (−1.13, −0.75)<sup>c</sup></td><td>−0.68 (−0.91, −0.46)<sup>c</sup></td><td>−1.41 (−1.57, −1.24)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.22 (−0.47, 0.03)</td><td>0.40 (0.18, 0.62)<sup>d</sup></td><td>0.62 (0.38, 0.86)<sup>d</sup></td></tr><tr><td>I fall asleep involuntarily during the day</td><td>−0.04 (−0.21, 0.13)</td><td>−0.04 (−0.24, 0.16)</td><td>−1.31 (−1.45, −1.16)<sup>§</sup></td><td><strong><.0001</strong></td><td>0.00 (−0.24, 0.25)</td><td>1.18 (0.97, 1.39)<sup>d</sup></td><td>1.18 (0.94, 1.41)<sup>d</sup></td></tr><tr><td>I fall asleep if I relax (TV)</td><td>−0.56 (−0.73, −0.39)<sup>c</sup></td><td>−0.58 (−0.78, −0.39)<sup>c</sup></td><td>−1.21 (−1.36, −1.07)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.02 (−0.19, 0.23)</td><td>0.53 (0.35, 0.71)<sup>d</sup></td><td>0.51 (0.31, 0.70)<sup>d</sup></td></tr><tr><td>I take a nap during the day</td><td>−0.48 (−0.65, −0.30)<sup>c</sup></td><td>−0.01 (−0.22, 0.19)</td><td>−0.58 (−0.73, −0.43)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.36 (−0.56, −0.15)<sup>d</sup></td><td>0.08 (−0.10, 0.26)</td><td>0.44 (0.24, 0.63)<sup>d</sup></td></tr><tr><td>I doze off at the steering wheel when driving</td><td>−0.11 (−0.23, 0.02)</td><td>−0.09 (−0.24, 0.05)</td><td>−0.82 (−0.92, −0.71)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.02 (−0.26, 0.23)</td><td>0.92 (0.71, 1.13)<sup>d</sup></td><td>0.94 (0.71, 1.17)<sup>d</sup></td></tr><tr><td>I feel physically tired during the day</td><td>−1.07 (−1.25, −0.88)<sup>c</sup></td><td>−0.53 (−0.74, −0.32)<sup>c</sup></td><td>−1.54 (−1.70, −1.39)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.48 (−0.73, −0.23)<sup>d</sup></td><td>0.43 (0.21, 0.64)<sup>d</sup></td><td>0.91 (0.67, 1.15)<sup>d</sup></td></tr><tr><td rowspan="5">Insomnia- related</td><td>I have difficulties falling asleep at night</td><td>−0.28 (−0.44, −0.13)<sup>c</sup></td><td>−0.03 (−0.21, 0.15)</td><td>−0.01 (−0.14, 0.13)</td><td>.021</td><td>—</td><td>—</td><td>—</td></tr><tr><td>I wake up too early/it’s hard to fall back to sleep</td><td>−0.54 (−0.73, −0.35)<sup>c</sup></td><td>0.09 (−0.13, 0.31)</td><td>−0.04 (−0.2, 0.13)</td><td><strong><.0001</strong></td><td>−0.46 (−0.68, −0.25)<sup>d</sup></td><td>−0.37 (−0.55, −0.19)<sup>d</sup></td><td>0.09 (−0.11, 0.29)</td></tr><tr><td>I wake up often during the night</td><td>−0.90 (−1.1, −0.69)<sup>c</sup></td><td>−0.26 (−0.50, −0.03)</td><td>−0.92 (−1.1, −0.74)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.46 (−0.68, −0.23)<sup>d</sup></td><td>0.02 (−0.18, 0.21)</td><td>0.47 (0.26, 0.69)<sup>d</sup></td></tr><tr><td>I’m restless in my sleep</td><td>−1.25 (−1.46, −1.05)<sup>c</sup></td><td>−0.13 (−0.37, 0.11)</td><td>−1.10 (−1.27, −0.92)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.81 (−1.04, −0.59)<sup>d</sup></td><td>−0.11 (−0.31, 0.08)</td><td>0.70 (0.49, 0.91)<sup>d</sup></td></tr><tr><td>I feel rested when I wake up</td><td>1.27 (1.07, 1.47)<sup>c</sup></td><td>0.52 (0.29, 0.74)<sup>c</sup></td><td>1.69 (1.52, 1.86)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.60 (0.36, 0.83)<sup>d</sup></td><td>−0.34 (−0.54, −0.13)<sup>d</sup></td><td>−0.93 (−1.16, −0.71)<sup>d</sup></td></tr><tr><td rowspan="5">Apneic</td><td>I wake up suddenly and feel as if I can’t breathe</td><td>−0.51 (−0.65, −0.37)<sup>c</sup></td><td>−0.04 (−0.20, 0.12)</td><td>−0.53 (−0.65, −0.41)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.55 (−0.80, −0.30)<sup>d</sup></td><td>0.03 (−0.19, 0.25)</td><td>0.58 (0.35, 0.82)<sup>d</sup></td></tr><tr><td>I have been told that I stop breathing at night</td><td>−1.29 (−1.55, −1.04)<sup>c</sup></td><td>−1.32 (−1.62, −1.03)<sup>c</sup></td><td>−1.77 (−1.99, −1.55)<sup>c</sup></td><td><strong>.009</strong></td><td>0.02 (−0.25, 0.29)</td><td>0.32 (0.09, 0.56)<sup>d</sup></td><td>0.30 (0.05, 0.56)</td></tr><tr><td>Any loud snoring</td><td>0.02 (0.01, 0.07)<sup>c</sup></td><td>0.06 (0.02, 0.17)<sup>c</sup></td><td>N/A</td><td>N/A</td><td>0.35 (0.11, 1.09)</td><td>N/A</td><td>N/A</td></tr><tr><td>I snore loudly and it disturbs my spouse’s sleep</td><td>0.10 (0.05, 0.19)<sup>c</sup></td><td>0.14 (0.07, 0.28)<sup>c</sup></td><td>0.02 (0.01, 0.05)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.70 (0.30, 1.66)</td><td>5.01 (2.11, 11.9)<sup>d</sup></td><td>7.14 (2.86, 17.8)<sup>d</sup></td></tr><tr><td>My nose is congested at night</td><td>−0.28 (−0.48, −0.08)<sup>c</sup></td><td>−0.25 (−0.48, −0.02)</td><td>−0.54 (−0.71, −0.37)<sup>c</sup></td><td>.065</td><td>—</td><td>—</td><td>—</td></tr><tr><td rowspan="3">Other</td><td>I wake up with a headache</td><td>−0.30 (−0.42, −0.17)<sup>c</sup></td><td>−0.08 (−0.23, 0.07)</td><td>−0.50 (−0.61, −0.39)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.23 (−0.44, −0.03)</td><td>0.21 (0.04, 0.39)</td><td>0.44 (0.25, 0.64)<sup>d</sup></td></tr><tr><td>I perspire heavily during the night</td><td>−0.90 (−1.08, −0.72)<sup>c</sup></td><td>−0.26 (−0.47, −0.05)</td><td>−0.65 (−0.81, −0.5)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.49 (−0.70, −0.28)<sup>d</sup></td><td>−0.19 (−0.37, −0.01)</td><td>0.30 (0.10, 0.50)<sup>d</sup></td></tr><tr><td>Presence of RLS</td><td>0.43 (0.26, 0.72)<sup>c</sup></td><td>0.57 (0.25, 1.26)</td><td>0.33 (0.21, 0.52)<sup>c</sup></td><td>.445</td><td>—</td><td>—</td><td>—</td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th rowspan="2"><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Symptom measures<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Estimate (95% CI)<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Overall <em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Pairwise differences estimates<sup>b</sup><span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed sleep (DS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic (MS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy (S)<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. MS<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. S<span aria-hidden="true" style="display: none;"> . </span></th><th>MS vs. S<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td rowspan="7">Sleepiness and fatigue</td><td>Epworth Sleepiness Scale</td><td>−2.06 (−2.64, −1.48)<sup>c</sup></td><td>−1.33 (−2.00, −0.66)<sup>c</sup></td><td>−5.31 (−5.81, −4.81)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.19 (−0.42, 0.04)</td><td>0.84 (0.65, 1.04)<sup>d</sup></td><td>1.03 (0.82, 1.25)<sup>d</sup></td></tr><tr><td>I feel sleepy during the day</td><td>−0.94 (−1.13, −0.75)<sup>c</sup></td><td>−0.68 (−0.91, −0.46)<sup>c</sup></td><td>−1.41 (−1.57, −1.24)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.22 (−0.47, 0.03)</td><td>0.40 (0.18, 0.62)<sup>d</sup></td><td>0.62 (0.38, 0.86)<sup>d</sup></td></tr><tr><td>I fall asleep involuntarily during the day</td><td>−0.04 (−0.21, 0.13)</td><td>−0.04 (−0.24, 0.16)</td><td>−1.31 (−1.45, −1.16)<sup>§</sup></td><td><strong><.0001</strong></td><td>0.00 (−0.24, 0.25)</td><td>1.18 (0.97, 1.39)<sup>d</sup></td><td>1.18 (0.94, 1.41)<sup>d</sup></td></tr><tr><td>I fall asleep if I relax (TV)</td><td>−0.56 (−0.73, −0.39)<sup>c</sup></td><td>−0.58 (−0.78, −0.39)<sup>c</sup></td><td>−1.21 (−1.36, −1.07)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.02 (−0.19, 0.23)</td><td>0.53 (0.35, 0.71)<sup>d</sup></td><td>0.51 (0.31, 0.70)<sup>d</sup></td></tr><tr><td>I take a nap during the day</td><td>−0.48 (−0.65, −0.30)<sup>c</sup></td><td>−0.01 (−0.22, 0.19)</td><td>−0.58 (−0.73, −0.43)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.36 (−0.56, −0.15)<sup>d</sup></td><td>0.08 (−0.10, 0.26)</td><td>0.44 (0.24, 0.63)<sup>d</sup></td></tr><tr><td>I doze off at the steering wheel when driving</td><td>−0.11 (−0.23, 0.02)</td><td>−0.09 (−0.24, 0.05)</td><td>−0.82 (−0.92, −0.71)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.02 (−0.26, 0.23)</td><td>0.92 (0.71, 1.13)<sup>d</sup></td><td>0.94 (0.71, 1.17)<sup>d</sup></td></tr><tr><td>I feel physically tired during the day</td><td>−1.07 (−1.25, −0.88)<sup>c</sup></td><td>−0.53 (−0.74, −0.32)<sup>c</sup></td><td>−1.54 (−1.70, −1.39)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.48 (−0.73, −0.23)<sup>d</sup></td><td>0.43 (0.21, 0.64)<sup>d</sup></td><td>0.91 (0.67, 1.15)<sup>d</sup></td></tr><tr><td rowspan="5">Insomnia- related</td><td>I have difficulties falling asleep at night</td><td>−0.28 (−0.44, −0.13)<sup>c</sup></td><td>−0.03 (−0.21, 0.15)</td><td>−0.01 (−0.14, 0.13)</td><td>.021</td><td>—</td><td>—</td><td>—</td></tr><tr><td>I wake up too early/it’s hard to fall back to sleep</td><td>−0.54 (−0.73, −0.35)<sup>c</sup></td><td>0.09 (−0.13, 0.31)</td><td>−0.04 (−0.2, 0.13)</td><td><strong><.0001</strong></td><td>−0.46 (−0.68, −0.25)<sup>d</sup></td><td>−0.37 (−0.55, −0.19)<sup>d</sup></td><td>0.09 (−0.11, 0.29)</td></tr><tr><td>I wake up often during the night</td><td>−0.90 (−1.1, −0.69)<sup>c</sup></td><td>−0.26 (−0.50, −0.03)</td><td>−0.92 (−1.1, −0.74)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.46 (−0.68, −0.23)<sup>d</sup></td><td>0.02 (−0.18, 0.21)</td><td>0.47 (0.26, 0.69)<sup>d</sup></td></tr><tr><td>I’m restless in my sleep</td><td>−1.25 (−1.46, −1.05)<sup>c</sup></td><td>−0.13 (−0.37, 0.11)</td><td>−1.10 (−1.27, −0.92)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.81 (−1.04, −0.59)<sup>d</sup></td><td>−0.11 (−0.31, 0.08)</td><td>0.70 (0.49, 0.91)<sup>d</sup></td></tr><tr><td>I feel rested when I wake up</td><td>1.27 (1.07, 1.47)<sup>c</sup></td><td>0.52 (0.29, 0.74)<sup>c</sup></td><td>1.69 (1.52, 1.86)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.60 (0.36, 0.83)<sup>d</sup></td><td>−0.34 (−0.54, −0.13)<sup>d</sup></td><td>−0.93 (−1.16, −0.71)<sup>d</sup></td></tr><tr><td rowspan="5">Apneic</td><td>I wake up suddenly and feel as if I can’t breathe</td><td>−0.51 (−0.65, −0.37)<sup>c</sup></td><td>−0.04 (−0.20, 0.12)</td><td>−0.53 (−0.65, −0.41)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.55 (−0.80, −0.30)<sup>d</sup></td><td>0.03 (−0.19, 0.25)</td><td>0.58 (0.35, 0.82)<sup>d</sup></td></tr><tr><td>I have been told that I stop breathing at night</td><td>−1.29 (−1.55, −1.04)<sup>c</sup></td><td>−1.32 (−1.62, −1.03)<sup>c</sup></td><td>−1.77 (−1.99, −1.55)<sup>c</sup></td><td><strong>.009</strong></td><td>0.02 (−0.25, 0.29)</td><td>0.32 (0.09, 0.56)<sup>d</sup></td><td>0.30 (0.05, 0.56)</td></tr><tr><td>Any loud snoring</td><td>0.02 (0.01, 0.07)<sup>c</sup></td><td>0.06 (0.02, 0.17)<sup>c</sup></td><td>N/A</td><td>N/A</td><td>0.35 (0.11, 1.09)</td><td>N/A</td><td>N/A</td></tr><tr><td>I snore loudly and it disturbs my spouse’s sleep</td><td>0.10 (0.05, 0.19)<sup>c</sup></td><td>0.14 (0.07, 0.28)<sup>c</sup></td><td>0.02 (0.01, 0.05)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.70 (0.30, 1.66)</td><td>5.01 (2.11, 11.9)<sup>d</sup></td><td>7.14 (2.86, 17.8)<sup>d</sup></td></tr><tr><td>My nose is congested at night</td><td>−0.28 (−0.48, −0.08)<sup>c</sup></td><td>−0.25 (−0.48, −0.02)</td><td>−0.54 (−0.71, −0.37)<sup>c</sup></td><td>.065</td><td>—</td><td>—</td><td>—</td></tr><tr><td rowspan="3">Other</td><td>I wake up with a headache</td><td>−0.30 (−0.42, −0.17)<sup>c</sup></td><td>−0.08 (−0.23, 0.07)</td><td>−0.50 (−0.61, −0.39)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.23 (−0.44, −0.03)</td><td>0.21 (0.04, 0.39)</td><td>0.44 (0.25, 0.64)<sup>d</sup></td></tr><tr><td>I perspire heavily during the night</td><td>−0.90 (−1.08, −0.72)<sup>c</sup></td><td>−0.26 (−0.47, −0.05)</td><td>−0.65 (−0.81, −0.5)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.49 (−0.70, −0.28)<sup>d</sup></td><td>−0.19 (−0.37, −0.01)</td><td>0.30 (0.10, 0.50)<sup>d</sup></td></tr><tr><td>Presence of RLS</td><td>0.43 (0.26, 0.72)<sup>c</sup></td><td>0.57 (0.25, 1.26)</td><td>0.33 (0.21, 0.52)<sup>c</sup></td><td>.445</td><td>—</td><td>—</td><td>—</td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-05"></span><div content-id="fn-05" class="footnote"><span class="fn"><p class="chapter-para">Models adjusted for gender, baseline age, BMI, and AHI. To ensure reliable estimates of group-specific odds ratios with binary outcomes, we required >5 changes in the symptom overall in order to fit a logistic mixed model, and ≥1 change from presence to absence and ≥1 change from absence to presence over the follow-up; if a cluster did not meet these criteria, results for that model are presented as “N/A.” If this occurred only within one of the three clusters, we present estimates and pairwise comparisons between the two remaining clusters.</p></span></div><span id="fn-fn-06"></span><div content-id="fn-06" class="footnote"><span class="fn"><p class="chapter-para">*<em>p</em>-Value comparing change scores among clusters, with <em>p</em>-values in <strong>bold</strong> are statistically significant after Hochberg correction between clusters.</p></span></div><span id="fn-fn-07"></span><div content-id="fn-07" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup>Estimate presented as mean change (for continuous measures) or odds ratio (for binary measures) and 95% confidence interval.</p></span></div><span id="fn-fn-08"></span><div content-id="fn-08" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>b</em></sup>Between-cluster comparisons performed if overall <em>P</em>-value among clusters was statistically significant after Hochberg correction and results are presented as between-group standardized mean differences in change scores or ratios of within-groups odds ratios (RORs) for symptom development at follow-up.</p></span></div><span id="fn-fn-09"></span><div content-id="fn-09" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>c</em></sup>Within-group estimate statistically significant after Hochberg correction.</p></span></div><span id="fn-fn-10"></span><div content-id="fn-10" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>d</em></sup>Comparison significant at within-outcome Bonferroni corrected <em>p</em> < .017.</p></span></div><span id="fn-fn-11"></span><div content-id="fn-11" class="footnote"><span class="fn"><p class="chapter-para">DS = Disturbed Sleep; MS = Minimally Symptomatic; S = Sleepy; CI = confidence interval; RLS = restless leg syndrome.</p></span></div></div></div></div><div class="table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T2" data-id="T2"><span class="label title-label" id="label-54025">Table 2.</span><div class="
 graphic-wrap table-open-button-wrap
 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223256" aria-describedby="label-54025"> Open in new tab </a></div><div class="caption caption-id-" id="caption-54025"><p class="chapter-para">Adjusted Models for Changes in Symptom Variables Within and Between Symptom Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-54025" aria-describedby="
 caption-54025"><thead><tr><th rowspan="2"><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Symptom measures<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Estimate (95% CI)<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Overall <em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Pairwise differences estimates<sup>b</sup><span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed sleep (DS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic (MS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy (S)<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. MS<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. S<span aria-hidden="true" style="display: none;"> . </span></th><th>MS vs. S<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td rowspan="7">Sleepiness and fatigue</td><td>Epworth Sleepiness Scale</td><td>−2.06 (−2.64, −1.48)<sup>c</sup></td><td>−1.33 (−2.00, −0.66)<sup>c</sup></td><td>−5.31 (−5.81, −4.81)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.19 (−0.42, 0.04)</td><td>0.84 (0.65, 1.04)<sup>d</sup></td><td>1.03 (0.82, 1.25)<sup>d</sup></td></tr><tr><td>I feel sleepy during the day</td><td>−0.94 (−1.13, −0.75)<sup>c</sup></td><td>−0.68 (−0.91, −0.46)<sup>c</sup></td><td>−1.41 (−1.57, −1.24)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.22 (−0.47, 0.03)</td><td>0.40 (0.18, 0.62)<sup>d</sup></td><td>0.62 (0.38, 0.86)<sup>d</sup></td></tr><tr><td>I fall asleep involuntarily during the day</td><td>−0.04 (−0.21, 0.13)</td><td>−0.04 (−0.24, 0.16)</td><td>−1.31 (−1.45, −1.16)<sup>§</sup></td><td><strong><.0001</strong></td><td>0.00 (−0.24, 0.25)</td><td>1.18 (0.97, 1.39)<sup>d</sup></td><td>1.18 (0.94, 1.41)<sup>d</sup></td></tr><tr><td>I fall asleep if I relax (TV)</td><td>−0.56 (−0.73, −0.39)<sup>c</sup></td><td>−0.58 (−0.78, −0.39)<sup>c</sup></td><td>−1.21 (−1.36, −1.07)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.02 (−0.19, 0.23)</td><td>0.53 (0.35, 0.71)<sup>d</sup></td><td>0.51 (0.31, 0.70)<sup>d</sup></td></tr><tr><td>I take a nap during the day</td><td>−0.48 (−0.65, −0.30)<sup>c</sup></td><td>−0.01 (−0.22, 0.19)</td><td>−0.58 (−0.73, −0.43)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.36 (−0.56, −0.15)<sup>d</sup></td><td>0.08 (−0.10, 0.26)</td><td>0.44 (0.24, 0.63)<sup>d</sup></td></tr><tr><td>I doze off at the steering wheel when driving</td><td>−0.11 (−0.23, 0.02)</td><td>−0.09 (−0.24, 0.05)</td><td>−0.82 (−0.92, −0.71)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.02 (−0.26, 0.23)</td><td>0.92 (0.71, 1.13)<sup>d</sup></td><td>0.94 (0.71, 1.17)<sup>d</sup></td></tr><tr><td>I feel physically tired during the day</td><td>−1.07 (−1.25, −0.88)<sup>c</sup></td><td>−0.53 (−0.74, −0.32)<sup>c</sup></td><td>−1.54 (−1.70, −1.39)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.48 (−0.73, −0.23)<sup>d</sup></td><td>0.43 (0.21, 0.64)<sup>d</sup></td><td>0.91 (0.67, 1.15)<sup>d</sup></td></tr><tr><td rowspan="5">Insomnia- related</td><td>I have difficulties falling asleep at night</td><td>−0.28 (−0.44, −0.13)<sup>c</sup></td><td>−0.03 (−0.21, 0.15)</td><td>−0.01 (−0.14, 0.13)</td><td>.021</td><td>—</td><td>—</td><td>—</td></tr><tr><td>I wake up too early/it’s hard to fall back to sleep</td><td>−0.54 (−0.73, −0.35)<sup>c</sup></td><td>0.09 (−0.13, 0.31)</td><td>−0.04 (−0.2, 0.13)</td><td><strong><.0001</strong></td><td>−0.46 (−0.68, −0.25)<sup>d</sup></td><td>−0.37 (−0.55, −0.19)<sup>d</sup></td><td>0.09 (−0.11, 0.29)</td></tr><tr><td>I wake up often during the night</td><td>−0.90 (−1.1, −0.69)<sup>c</sup></td><td>−0.26 (−0.50, −0.03)</td><td>−0.92 (−1.1, −0.74)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.46 (−0.68, −0.23)<sup>d</sup></td><td>0.02 (−0.18, 0.21)</td><td>0.47 (0.26, 0.69)<sup>d</sup></td></tr><tr><td>I’m restless in my sleep</td><td>−1.25 (−1.46, −1.05)<sup>c</sup></td><td>−0.13 (−0.37, 0.11)</td><td>−1.10 (−1.27, −0.92)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.81 (−1.04, −0.59)<sup>d</sup></td><td>−0.11 (−0.31, 0.08)</td><td>0.70 (0.49, 0.91)<sup>d</sup></td></tr><tr><td>I feel rested when I wake up</td><td>1.27 (1.07, 1.47)<sup>c</sup></td><td>0.52 (0.29, 0.74)<sup>c</sup></td><td>1.69 (1.52, 1.86)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.60 (0.36, 0.83)<sup>d</sup></td><td>−0.34 (−0.54, −0.13)<sup>d</sup></td><td>−0.93 (−1.16, −0.71)<sup>d</sup></td></tr><tr><td rowspan="5">Apneic</td><td>I wake up suddenly and feel as if I can’t breathe</td><td>−0.51 (−0.65, −0.37)<sup>c</sup></td><td>−0.04 (−0.20, 0.12)</td><td>−0.53 (−0.65, −0.41)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.55 (−0.80, −0.30)<sup>d</sup></td><td>0.03 (−0.19, 0.25)</td><td>0.58 (0.35, 0.82)<sup>d</sup></td></tr><tr><td>I have been told that I stop breathing at night</td><td>−1.29 (−1.55, −1.04)<sup>c</sup></td><td>−1.32 (−1.62, −1.03)<sup>c</sup></td><td>−1.77 (−1.99, −1.55)<sup>c</sup></td><td><strong>.009</strong></td><td>0.02 (−0.25, 0.29)</td><td>0.32 (0.09, 0.56)<sup>d</sup></td><td>0.30 (0.05, 0.56)</td></tr><tr><td>Any loud snoring</td><td>0.02 (0.01, 0.07)<sup>c</sup></td><td>0.06 (0.02, 0.17)<sup>c</sup></td><td>N/A</td><td>N/A</td><td>0.35 (0.11, 1.09)</td><td>N/A</td><td>N/A</td></tr><tr><td>I snore loudly and it disturbs my spouse’s sleep</td><td>0.10 (0.05, 0.19)<sup>c</sup></td><td>0.14 (0.07, 0.28)<sup>c</sup></td><td>0.02 (0.01, 0.05)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.70 (0.30, 1.66)</td><td>5.01 (2.11, 11.9)<sup>d</sup></td><td>7.14 (2.86, 17.8)<sup>d</sup></td></tr><tr><td>My nose is congested at night</td><td>−0.28 (−0.48, −0.08)<sup>c</sup></td><td>−0.25 (−0.48, −0.02)</td><td>−0.54 (−0.71, −0.37)<sup>c</sup></td><td>.065</td><td>—</td><td>—</td><td>—</td></tr><tr><td rowspan="3">Other</td><td>I wake up with a headache</td><td>−0.30 (−0.42, −0.17)<sup>c</sup></td><td>−0.08 (−0.23, 0.07)</td><td>−0.50 (−0.61, −0.39)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.23 (−0.44, −0.03)</td><td>0.21 (0.04, 0.39)</td><td>0.44 (0.25, 0.64)<sup>d</sup></td></tr><tr><td>I perspire heavily during the night</td><td>−0.90 (−1.08, −0.72)<sup>c</sup></td><td>−0.26 (−0.47, −0.05)</td><td>−0.65 (−0.81, −0.5)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.49 (−0.70, −0.28)<sup>d</sup></td><td>−0.19 (−0.37, −0.01)</td><td>0.30 (0.10, 0.50)<sup>d</sup></td></tr><tr><td>Presence of RLS</td><td>0.43 (0.26, 0.72)<sup>c</sup></td><td>0.57 (0.25, 1.26)</td><td>0.33 (0.21, 0.52)<sup>c</sup></td><td>.445</td><td>—</td><td>—</td><td>—</td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th rowspan="2"><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Symptom measures<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Estimate (95% CI)<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Overall <em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Pairwise differences estimates<sup>b</sup><span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed sleep (DS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic (MS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy (S)<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. MS<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. S<span aria-hidden="true" style="display: none;"> . </span></th><th>MS vs. S<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td rowspan="7">Sleepiness and fatigue</td><td>Epworth Sleepiness Scale</td><td>−2.06 (−2.64, −1.48)<sup>c</sup></td><td>−1.33 (−2.00, −0.66)<sup>c</sup></td><td>−5.31 (−5.81, −4.81)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.19 (−0.42, 0.04)</td><td>0.84 (0.65, 1.04)<sup>d</sup></td><td>1.03 (0.82, 1.25)<sup>d</sup></td></tr><tr><td>I feel sleepy during the day</td><td>−0.94 (−1.13, −0.75)<sup>c</sup></td><td>−0.68 (−0.91, −0.46)<sup>c</sup></td><td>−1.41 (−1.57, −1.24)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.22 (−0.47, 0.03)</td><td>0.40 (0.18, 0.62)<sup>d</sup></td><td>0.62 (0.38, 0.86)<sup>d</sup></td></tr><tr><td>I fall asleep involuntarily during the day</td><td>−0.04 (−0.21, 0.13)</td><td>−0.04 (−0.24, 0.16)</td><td>−1.31 (−1.45, −1.16)<sup>§</sup></td><td><strong><.0001</strong></td><td>0.00 (−0.24, 0.25)</td><td>1.18 (0.97, 1.39)<sup>d</sup></td><td>1.18 (0.94, 1.41)<sup>d</sup></td></tr><tr><td>I fall asleep if I relax (TV)</td><td>−0.56 (−0.73, −0.39)<sup>c</sup></td><td>−0.58 (−0.78, −0.39)<sup>c</sup></td><td>−1.21 (−1.36, −1.07)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.02 (−0.19, 0.23)</td><td>0.53 (0.35, 0.71)<sup>d</sup></td><td>0.51 (0.31, 0.70)<sup>d</sup></td></tr><tr><td>I take a nap during the day</td><td>−0.48 (−0.65, −0.30)<sup>c</sup></td><td>−0.01 (−0.22, 0.19)</td><td>−0.58 (−0.73, −0.43)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.36 (−0.56, −0.15)<sup>d</sup></td><td>0.08 (−0.10, 0.26)</td><td>0.44 (0.24, 0.63)<sup>d</sup></td></tr><tr><td>I doze off at the steering wheel when driving</td><td>−0.11 (−0.23, 0.02)</td><td>−0.09 (−0.24, 0.05)</td><td>−0.82 (−0.92, −0.71)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.02 (−0.26, 0.23)</td><td>0.92 (0.71, 1.13)<sup>d</sup></td><td>0.94 (0.71, 1.17)<sup>d</sup></td></tr><tr><td>I feel physically tired during the day</td><td>−1.07 (−1.25, −0.88)<sup>c</sup></td><td>−0.53 (−0.74, −0.32)<sup>c</sup></td><td>−1.54 (−1.70, −1.39)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.48 (−0.73, −0.23)<sup>d</sup></td><td>0.43 (0.21, 0.64)<sup>d</sup></td><td>0.91 (0.67, 1.15)<sup>d</sup></td></tr><tr><td rowspan="5">Insomnia- related</td><td>I have difficulties falling asleep at night</td><td>−0.28 (−0.44, −0.13)<sup>c</sup></td><td>−0.03 (−0.21, 0.15)</td><td>−0.01 (−0.14, 0.13)</td><td>.021</td><td>—</td><td>—</td><td>—</td></tr><tr><td>I wake up too early/it’s hard to fall back to sleep</td><td>−0.54 (−0.73, −0.35)<sup>c</sup></td><td>0.09 (−0.13, 0.31)</td><td>−0.04 (−0.2, 0.13)</td><td><strong><.0001</strong></td><td>−0.46 (−0.68, −0.25)<sup>d</sup></td><td>−0.37 (−0.55, −0.19)<sup>d</sup></td><td>0.09 (−0.11, 0.29)</td></tr><tr><td>I wake up often during the night</td><td>−0.90 (−1.1, −0.69)<sup>c</sup></td><td>−0.26 (−0.50, −0.03)</td><td>−0.92 (−1.1, −0.74)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.46 (−0.68, −0.23)<sup>d</sup></td><td>0.02 (−0.18, 0.21)</td><td>0.47 (0.26, 0.69)<sup>d</sup></td></tr><tr><td>I’m restless in my sleep</td><td>−1.25 (−1.46, −1.05)<sup>c</sup></td><td>−0.13 (−0.37, 0.11)</td><td>−1.10 (−1.27, −0.92)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.81 (−1.04, −0.59)<sup>d</sup></td><td>−0.11 (−0.31, 0.08)</td><td>0.70 (0.49, 0.91)<sup>d</sup></td></tr><tr><td>I feel rested when I wake up</td><td>1.27 (1.07, 1.47)<sup>c</sup></td><td>0.52 (0.29, 0.74)<sup>c</sup></td><td>1.69 (1.52, 1.86)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.60 (0.36, 0.83)<sup>d</sup></td><td>−0.34 (−0.54, −0.13)<sup>d</sup></td><td>−0.93 (−1.16, −0.71)<sup>d</sup></td></tr><tr><td rowspan="5">Apneic</td><td>I wake up suddenly and feel as if I can’t breathe</td><td>−0.51 (−0.65, −0.37)<sup>c</sup></td><td>−0.04 (−0.20, 0.12)</td><td>−0.53 (−0.65, −0.41)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.55 (−0.80, −0.30)<sup>d</sup></td><td>0.03 (−0.19, 0.25)</td><td>0.58 (0.35, 0.82)<sup>d</sup></td></tr><tr><td>I have been told that I stop breathing at night</td><td>−1.29 (−1.55, −1.04)<sup>c</sup></td><td>−1.32 (−1.62, −1.03)<sup>c</sup></td><td>−1.77 (−1.99, −1.55)<sup>c</sup></td><td><strong>.009</strong></td><td>0.02 (−0.25, 0.29)</td><td>0.32 (0.09, 0.56)<sup>d</sup></td><td>0.30 (0.05, 0.56)</td></tr><tr><td>Any loud snoring</td><td>0.02 (0.01, 0.07)<sup>c</sup></td><td>0.06 (0.02, 0.17)<sup>c</sup></td><td>N/A</td><td>N/A</td><td>0.35 (0.11, 1.09)</td><td>N/A</td><td>N/A</td></tr><tr><td>I snore loudly and it disturbs my spouse’s sleep</td><td>0.10 (0.05, 0.19)<sup>c</sup></td><td>0.14 (0.07, 0.28)<sup>c</sup></td><td>0.02 (0.01, 0.05)<sup>c</sup></td><td><strong><.0001</strong></td><td>0.70 (0.30, 1.66)</td><td>5.01 (2.11, 11.9)<sup>d</sup></td><td>7.14 (2.86, 17.8)<sup>d</sup></td></tr><tr><td>My nose is congested at night</td><td>−0.28 (−0.48, −0.08)<sup>c</sup></td><td>−0.25 (−0.48, −0.02)</td><td>−0.54 (−0.71, −0.37)<sup>c</sup></td><td>.065</td><td>—</td><td>—</td><td>—</td></tr><tr><td rowspan="3">Other</td><td>I wake up with a headache</td><td>−0.30 (−0.42, −0.17)<sup>c</sup></td><td>−0.08 (−0.23, 0.07)</td><td>−0.50 (−0.61, −0.39)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.23 (−0.44, −0.03)</td><td>0.21 (0.04, 0.39)</td><td>0.44 (0.25, 0.64)<sup>d</sup></td></tr><tr><td>I perspire heavily during the night</td><td>−0.90 (−1.08, −0.72)<sup>c</sup></td><td>−0.26 (−0.47, −0.05)</td><td>−0.65 (−0.81, −0.5)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.49 (−0.70, −0.28)<sup>d</sup></td><td>−0.19 (−0.37, −0.01)</td><td>0.30 (0.10, 0.50)<sup>d</sup></td></tr><tr><td>Presence of RLS</td><td>0.43 (0.26, 0.72)<sup>c</sup></td><td>0.57 (0.25, 1.26)</td><td>0.33 (0.21, 0.52)<sup>c</sup></td><td>.445</td><td>—</td><td>—</td><td>—</td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-05"></span><div content-id="fn-05" class="footnote"><span class="fn"><p class="chapter-para">Models adjusted for gender, baseline age, BMI, and AHI. To ensure reliable estimates of group-specific odds ratios with binary outcomes, we required >5 changes in the symptom overall in order to fit a logistic mixed model, and ≥1 change from presence to absence and ≥1 change from absence to presence over the follow-up; if a cluster did not meet these criteria, results for that model are presented as “N/A.” If this occurred only within one of the three clusters, we present estimates and pairwise comparisons between the two remaining clusters.</p></span></div><span id="fn-fn-06"></span><div content-id="fn-06" class="footnote"><span class="fn"><p class="chapter-para">*<em>p</em>-Value comparing change scores among clusters, with <em>p</em>-values in <strong>bold</strong> are statistically significant after Hochberg correction between clusters.</p></span></div><span id="fn-fn-07"></span><div content-id="fn-07" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup>Estimate presented as mean change (for continuous measures) or odds ratio (for binary measures) and 95% confidence interval.</p></span></div><span id="fn-fn-08"></span><div content-id="fn-08" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>b</em></sup>Between-cluster comparisons performed if overall <em>P</em>-value among clusters was statistically significant after Hochberg correction and results are presented as between-group standardized mean differences in change scores or ratios of within-groups odds ratios (RORs) for symptom development at follow-up.</p></span></div><span id="fn-fn-09"></span><div content-id="fn-09" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>c</em></sup>Within-group estimate statistically significant after Hochberg correction.</p></span></div><span id="fn-fn-10"></span><div content-id="fn-10" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>d</em></sup>Comparison significant at within-outcome Bonferroni corrected <em>p</em> < .017.</p></span></div><span id="fn-fn-11"></span><div content-id="fn-11" class="footnote"><span class="fn"><p class="chapter-para">DS = Disturbed Sleep; MS = Minimally Symptomatic; S = Sleepy; CI = confidence interval; RLS = restless leg syndrome.</p></span></div></div></div></div><p class="chapter-para">At baseline, the Disturbed Sleep group was characterized by individuals with insomnia-related symptoms, such as difficulty falling asleep (43.2%), waking often at night (90.8%), restless sleep (74.2%), and waking up early (62.3%) (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S2</a></span>). At follow-up, improvements in the frequency of insomnia-related symptoms such as difficulty falling asleep and restless sleep ranged from 0.28 to 1.25 points on the frequency scale (<span class="xrefLink" id="jumplink-T2"></span><a href="javascript:;" reveal-id="T2" data-open="T2" class="link link-reveal link-table xref-fig">Table 2</a>). The ESS score fell significantly (−2.06 points [−2.64, −1.48]). Reductions in the proportion of patients with these symptoms ranged from 13.1% (adjusted OR = 0.35 [0.20, 0.59]) for difficulty falling asleep to 39.0% (adjusted OR = 0.08 [0.04, 0.14]) for restless sleep (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Tables S2</a></span> and <span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">S3</a></span>). When comparing changes in these insomnia-related symptoms between clusters, we observed moderate-to-large effects between the Disturbed Sleep and Minimally Symptomatic patients, with standardized differences ranging from 0.46 to 0.81 in absolute values (<span class="xrefLink" id="jumplink-T2"></span><a href="javascript:;" reveal-id="T2" data-open="T2" class="link link-reveal link-table xref-fig">Table 2</a>). On the other hand, effects were either small to moderate (~0.35) or nonsignificant when comparing Disturbed Sleep with Sleepy patients. For changes in physical fatigue (<span class="xrefLink" id="jumplink-T2"></span><a href="javascript:;" reveal-id="T2" data-open="T2" class="link link-reveal link-table xref-fig">Table 2</a>), the change among the Disturbed Sleep group was moderately larger than that in the Minimally Symptomatic group (−0.48 [−0.73, −0.23]), but moderately smaller than the effect in the Sleepy group (0.43 [0.21, 0.64]).</p><p class="chapter-para">Members of the Minimally Symptomatic group reported the presence of symptoms at lower rates than other groups prior to starting PAP, despite similar AHI, and they remained relatively asymptomatic at follow-up (<span class="xrefLink" id="jumplink-F1"></span><a href="javascript:;" data-modal-source-id="F1" class="link xref-fig">Figure 1</a>; <span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S2</a></span>). Nevertheless, the proportion of patients in the Minimally Symptomatic group reporting daytime sleepiness fell 23.6% (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S2</a></span>). Self-reported frequency of sleepiness and fatigue-related symptoms (e.g., feeling rested on waking, daytime sleepiness, and being physically tired during the day) all showed statistically significant changes (<span class="xrefLink" id="jumplink-T2"></span><a href="javascript:;" reveal-id="T2" data-open="T2" class="link link-reveal link-table xref-fig">Table 2</a>); these within-group effects correspond to generally moderate effects after standardization. A small decrease in ESS (−1.33 points [−2.00, −0.66]) was statistically significant but likely clinically insignificant. Thus, among Minimally Symptomatic patients, effect sizes were comparable to analogous changes in the Disturbed Sleep group only for changes in sleepiness-related symptoms and were otherwise modest in comparison to symptom changes reported by the Disturbed Sleep and Sleepy groups.</p><p class="chapter-para">Patients in the Sleepy group reported the highest baseline ESS scores (16.0 ± 3.4); at follow-up, ESS fell five points (mean [95% CI] change = −5.3 [−5.8, −4.8]), much more than in the other groups. Significant reductions were observed in all other symptoms at follow-up except for difficulty falling asleep and waking up too early (<span class="xrefLink" id="jumplink-T2"></span><a href="javascript:;" reveal-id="T2" data-open="T2" class="link link-reveal link-table xref-fig">Table 2</a>). Importantly, the Sleepy group acknowledged markedly higher rates of drowsy driving (37.8%) than the other groups at baseline, and the proportion of patients with this symptom fell dramatically at follow-up to 8.1% (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Tables S2</a></span> and <span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">S3</a></span>, adjusted OR = 0.06 [0.03, 0.14]). Although the statistical significance of symptoms demonstrating improvement largely overlapped across the Sleepy and Disturbed Sleep groups, moderate-to-large differences based on standardized effect sizes were generally observed for symptom changes in the Sleepy group compared with the Disturbed Sleep group, consistent with changes of larger magnitude among Sleepy patients (<span class="xrefLink" id="jumplink-T2"></span><a href="javascript:;" reveal-id="T2" data-open="T2" class="link link-reveal link-table xref-fig">Table 2</a>). Similarly, moderate-to-large effect sizes for differences in symptom change between the Sleepy and the Minimally Symptomatic groups were noted for most sleepiness and sleep quality symptoms.</p> <h3 scrollto-destination=118223260 id="118223260" class="section-title js-splitscreen-section-title" data-legacy-id=s16>Comparisons of PAP Adherence Among Groups</h3> <p class="chapter-para">In general, patients in the Sleepy group were more likely to be PAP users compared with the Disturbed Sleep and Minimally Symptomatic groups (<span class="xrefLink" id="jumplink-T3"></span><a href="javascript:;" reveal-id="T3" data-open="T3" class="link link-reveal link-table xref-fig">Table 3</a>; 70.0% vs. 61.1% and 60.0%, <em>p</em> = .034). Mean hours per night and number of nights of PAP use over the last 28 days, however, were similar for full users and partial PAP users across all three groups.</p> <a id="118223262" scrollto-destination="118223262"></a> <div content-id="T3" class="table-modal table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T3" data-id="T3"><span class="label title-label" id="label-37663">Table 3.</span><div class="
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 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223262" aria-describedby="label-37663"> Open in new tab </a></div><div class="caption caption-id-" id="caption-37663"><p class="chapter-para">Comparisons of PAP Adherence and Usage Among Symptom Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-37663" aria-describedby="
 caption-37663"><thead><tr><th rowspan="2">Variable<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="4">Symptom clusters<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed sleep<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy<span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em><span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td><em>N</em> (%)</td><td>229 (32.4)</td><td>170 (24.1)</td><td>307 (43.5)</td><td><em>—</em></td></tr><tr><td>Any PAP usage, <em>n</em> (%)</td><td><strong>140 (61.1</strong>)</td><td><strong>102 (60.0</strong>)</td><td><strong>215 (70.0</strong>)</td><td><strong>.034*</strong></td></tr><tr><td>PAP usage group, <em>n</em> (%)</td><td></td><td></td><td></td><td>.085</td></tr><tr><td>Full user</td><td>112 (48.9)</td><td>84 (49.1)</td><td>165 (53.8)</td><td></td></tr><tr><td>Partial user</td><td>28 (12.2)</td><td>18 (10.6)</td><td>50 (16.3)</td><td></td></tr><tr><td>Nonuser</td><td>89 (38.9)</td><td>68 (40.0)</td><td>92 (30.0)</td><td></td></tr><tr><td colspan="5">Hours PAP usage<sup>a</sup></td></tr><tr><td>Mean ± SD</td><td>6.5 ± 2.3</td><td>6.2 ± 1.7</td><td>6.4 ± 1.9</td><td>.596</td></tr><tr><td>Median (Range)</td><td>6.9 (0.1, 10.4)</td><td>6.5 (0.3, 9.7)</td><td>6.9 (0.6, 10.4)</td><td>.160</td></tr><tr><td colspan="5">Nights PAP used<sup>a</sup></td></tr><tr><td>Mean ± SD</td><td>24.2 ± 6.6</td><td>23.8 ± 6.2</td><td>24.5 ± 5.9</td><td>.720</td></tr><tr><td>Median (range)</td><td>28 (1, 28)</td><td>26 (1, 28)</td><td>27 (2, 28)</td><td>.183</td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th rowspan="2">Variable<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="4">Symptom clusters<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed sleep<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy<span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em><span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td><em>N</em> (%)</td><td>229 (32.4)</td><td>170 (24.1)</td><td>307 (43.5)</td><td><em>—</em></td></tr><tr><td>Any PAP usage, <em>n</em> (%)</td><td><strong>140 (61.1</strong>)</td><td><strong>102 (60.0</strong>)</td><td><strong>215 (70.0</strong>)</td><td><strong>.034*</strong></td></tr><tr><td>PAP usage group, <em>n</em> (%)</td><td></td><td></td><td></td><td>.085</td></tr><tr><td>Full user</td><td>112 (48.9)</td><td>84 (49.1)</td><td>165 (53.8)</td><td></td></tr><tr><td>Partial user</td><td>28 (12.2)</td><td>18 (10.6)</td><td>50 (16.3)</td><td></td></tr><tr><td>Nonuser</td><td>89 (38.9)</td><td>68 (40.0)</td><td>92 (30.0)</td><td></td></tr><tr><td colspan="5">Hours PAP usage<sup>a</sup></td></tr><tr><td>Mean ± SD</td><td>6.5 ± 2.3</td><td>6.2 ± 1.7</td><td>6.4 ± 1.9</td><td>.596</td></tr><tr><td>Median (Range)</td><td>6.9 (0.1, 10.4)</td><td>6.5 (0.3, 9.7)</td><td>6.9 (0.6, 10.4)</td><td>.160</td></tr><tr><td colspan="5">Nights PAP used<sup>a</sup></td></tr><tr><td>Mean ± SD</td><td>24.2 ± 6.6</td><td>23.8 ± 6.2</td><td>24.5 ± 5.9</td><td>.720</td></tr><tr><td>Median (range)</td><td>28 (1, 28)</td><td>26 (1, 28)</td><td>27 (2, 28)</td><td>.183</td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-12"></span><div content-id="fn-12" class="footnote"><span class="fn"><p class="chapter-para">*Sleepy cluster significantly (<em>p</em> < .05) more likely to use PAP compared with both DS and MS clusters in pairwise comparisons.</p></span></div><span id="fn-fn-13"></span><div content-id="fn-13" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup>Analyses on objective PAP usage data in 351 full or partial users with available data: 111 Disturbed Sleep, 72 Minimally Symptomatic, and 168 Sleepy.</p></span></div><span id="fn-fn-14"></span><div content-id="fn-14" class="footnote"><span class="fn"><p class="chapter-para">PAP = positive airway pressure; DS = Disturbed Sleep; MS = Minimally Symptomatic; S = Sleepy; SD = standard deviation.</p></span></div></div></div></div><div class="table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T3" data-id="T3"><span class="label title-label" id="label-37663">Table 3.</span><div class="
 graphic-wrap table-open-button-wrap
 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223262" aria-describedby="label-37663"> Open in new tab </a></div><div class="caption caption-id-" id="caption-37663"><p class="chapter-para">Comparisons of PAP Adherence and Usage Among Symptom Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-37663" aria-describedby="
 caption-37663"><thead><tr><th rowspan="2">Variable<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="4">Symptom clusters<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed sleep<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy<span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em><span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td><em>N</em> (%)</td><td>229 (32.4)</td><td>170 (24.1)</td><td>307 (43.5)</td><td><em>—</em></td></tr><tr><td>Any PAP usage, <em>n</em> (%)</td><td><strong>140 (61.1</strong>)</td><td><strong>102 (60.0</strong>)</td><td><strong>215 (70.0</strong>)</td><td><strong>.034*</strong></td></tr><tr><td>PAP usage group, <em>n</em> (%)</td><td></td><td></td><td></td><td>.085</td></tr><tr><td>Full user</td><td>112 (48.9)</td><td>84 (49.1)</td><td>165 (53.8)</td><td></td></tr><tr><td>Partial user</td><td>28 (12.2)</td><td>18 (10.6)</td><td>50 (16.3)</td><td></td></tr><tr><td>Nonuser</td><td>89 (38.9)</td><td>68 (40.0)</td><td>92 (30.0)</td><td></td></tr><tr><td colspan="5">Hours PAP usage<sup>a</sup></td></tr><tr><td>Mean ± SD</td><td>6.5 ± 2.3</td><td>6.2 ± 1.7</td><td>6.4 ± 1.9</td><td>.596</td></tr><tr><td>Median (Range)</td><td>6.9 (0.1, 10.4)</td><td>6.5 (0.3, 9.7)</td><td>6.9 (0.6, 10.4)</td><td>.160</td></tr><tr><td colspan="5">Nights PAP used<sup>a</sup></td></tr><tr><td>Mean ± SD</td><td>24.2 ± 6.6</td><td>23.8 ± 6.2</td><td>24.5 ± 5.9</td><td>.720</td></tr><tr><td>Median (range)</td><td>28 (1, 28)</td><td>26 (1, 28)</td><td>27 (2, 28)</td><td>.183</td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th rowspan="2">Variable<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="4">Symptom clusters<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed sleep<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy<span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em><span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td><em>N</em> (%)</td><td>229 (32.4)</td><td>170 (24.1)</td><td>307 (43.5)</td><td><em>—</em></td></tr><tr><td>Any PAP usage, <em>n</em> (%)</td><td><strong>140 (61.1</strong>)</td><td><strong>102 (60.0</strong>)</td><td><strong>215 (70.0</strong>)</td><td><strong>.034*</strong></td></tr><tr><td>PAP usage group, <em>n</em> (%)</td><td></td><td></td><td></td><td>.085</td></tr><tr><td>Full user</td><td>112 (48.9)</td><td>84 (49.1)</td><td>165 (53.8)</td><td></td></tr><tr><td>Partial user</td><td>28 (12.2)</td><td>18 (10.6)</td><td>50 (16.3)</td><td></td></tr><tr><td>Nonuser</td><td>89 (38.9)</td><td>68 (40.0)</td><td>92 (30.0)</td><td></td></tr><tr><td colspan="5">Hours PAP usage<sup>a</sup></td></tr><tr><td>Mean ± SD</td><td>6.5 ± 2.3</td><td>6.2 ± 1.7</td><td>6.4 ± 1.9</td><td>.596</td></tr><tr><td>Median (Range)</td><td>6.9 (0.1, 10.4)</td><td>6.5 (0.3, 9.7)</td><td>6.9 (0.6, 10.4)</td><td>.160</td></tr><tr><td colspan="5">Nights PAP used<sup>a</sup></td></tr><tr><td>Mean ± SD</td><td>24.2 ± 6.6</td><td>23.8 ± 6.2</td><td>24.5 ± 5.9</td><td>.720</td></tr><tr><td>Median (range)</td><td>28 (1, 28)</td><td>26 (1, 28)</td><td>27 (2, 28)</td><td>.183</td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-12"></span><div content-id="fn-12" class="footnote"><span class="fn"><p class="chapter-para">*Sleepy cluster significantly (<em>p</em> < .05) more likely to use PAP compared with both DS and MS clusters in pairwise comparisons.</p></span></div><span id="fn-fn-13"></span><div content-id="fn-13" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup>Analyses on objective PAP usage data in 351 full or partial users with available data: 111 Disturbed Sleep, 72 Minimally Symptomatic, and 168 Sleepy.</p></span></div><span id="fn-fn-14"></span><div content-id="fn-14" class="footnote"><span class="fn"><p class="chapter-para">PAP = positive airway pressure; DS = Disturbed Sleep; MS = Minimally Symptomatic; S = Sleepy; SD = standard deviation.</p></span></div></div></div></div> <h3 scrollto-destination=118223263 id="118223263" class="section-title js-splitscreen-section-title" data-legacy-id=s17>Impact of PAP Adherence on Symptom Changes Within Groups</h3> <p class="chapter-para">Although full PAP users were more obese and had more severe OSA than nonusers, there were no significant differences between them in age and gender (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S4</a></span>). Overall, we observed statistically significant differences in the PAP effect across clusters for ESS (<em>p</em> < .0001), falling asleep involuntarily (<em>p</em> < .0001), drowsy driving (<em>p</em> = .0017), and feeling rested when waking up (<em>p</em> = .0017) based on three-way interaction tests (<span class="xrefLink" id="jumplink-T4"></span><a href="javascript:;" reveal-id="T4" data-open="T4" class="link link-reveal link-table xref-fig">Table 4</a>). For each of the sleepiness measurements, this difference was driven by large effects related to full PAP usage among the Sleepy patients, compared with no significant differences in changes between full users and nonusers in the Disturbed Sleep or Minimally Symptomatic patients. For feeling rested upon waking, the largest effect was seen when comparing full users and nonusers in the Sleepy group, a moderate effect in the Disturbed sleep group, and a smaller, nonsignificant effect in the Minimally Symptomatic group.</p> <a id="118223265" scrollto-destination="118223265"></a> <div content-id="T4" class="table-modal table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T4" data-id="T4"><span class="label title-label" id="label-73544">Table 4.</span><div class="
 graphic-wrap table-open-button-wrap
 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223265" aria-describedby="label-73544"> Open in new tab </a></div><div class="caption caption-id-" id="caption-73544"><p class="chapter-para">Propensity Score Adjusted Differences in Changes in Symptom Variables Between PAP Adherence Groups Within Individual Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-73544" aria-describedby="
 caption-73544"><thead><tr><th colspan="2" rowspan="2">Symptom measures<span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2"><em>p</em>-Value for three- way interaction*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Disturbed Sleep<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Minimally Symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Sleepy<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>**<span aria-hidden="true" style="display: none;"> . </span></th><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>**<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td rowspan="7">Sleepiness and fatigue</td><td>Epworth Sleepiness Scale</td><td><strong><.0001</strong></td><td>−0.19 (−0.49, 0.12)</td><td>.227</td><td>−0.32 (−0.62, −0.02)</td><td>.037</td><td>−0.98 (−1.31, −0.66)</td><td><strong><.0001</strong></td></tr><tr><td>I feel sleepy during the day</td><td>.089</td><td>−0.76 (−1.12, −0.41)</td><td><strong><.0001</strong></td><td>−0.38 (−0.76, 0.00)</td><td>.052</td><td>−1.19 (−1.53, −0.85)</td><td><strong><.0001</strong></td></tr><tr><td>I fall asleep involuntarily during the day</td><td><strong><.0001</strong></td><td>−0.06 (−0.41, 0.28)</td><td>.716</td><td>−0.02 (−0.40, 0.35)</td><td>.903</td><td>−0.83 (−1.14, −0.52)</td><td><strong><.0001</strong></td></tr><tr><td>I fall asleep if I relax (TV)</td><td>.1303</td><td>−0.35 (−0.61, −0.09)</td><td>.009</td><td>−0.45 (−0.73, −0.17)</td><td><strong>.002</strong></td><td>−0.91 (−1.22, −0.59)</td><td><strong><.0001</strong></td></tr><tr><td>I take a nap during the day</td><td>.3403</td><td>−0.31 (−0.58, −0.04)</td><td>.025</td><td>−0.11 (−0.43, 0.21)</td><td>.503</td><td>−0.39 (−0.66, −0.12)</td><td><strong>.005</strong></td></tr><tr><td>I doze off at the steering wheel when driving</td><td><strong>.0017</strong></td><td>−0.24 (−0.58, 0.10)</td><td>.167</td><td>0.35 (−0.07, 0.76)</td><td>.100</td><td>−0.47 (−0.77, −0.18)</td><td><strong>.002</strong></td></tr><tr><td>I feel physically tired during the day</td><td>.0766</td><td>−0.49 (−0.83, −0.15)</td><td>.006</td><td>−0.66 (−1.03, −0.29)</td><td><strong>.001</strong></td><td>−1.16 (−1.49, −0.82)</td><td><strong><.0001</strong></td></tr><tr><td rowspan="5">Insomnia-related</td><td>I have difficulties falling asleep at night</td><td>.5419</td><td>0.09 (−0.19, 0.37)</td><td>.528</td><td>−0.16 (−0.43, 0.12)</td><td>.273</td><td>−0.04 (−0.30, 0.21)</td><td>.725</td></tr><tr><td>I wake up too early/it’s hard to fall back to sleep</td><td>.1719</td><td>0.22 (−0.09, 0.53)</td><td>.159</td><td>0.41 (0.05, 0.78)</td><td>.025</td><td>−0.04 (−0.30, 0.23)</td><td>.793</td></tr><tr><td>I wake up often during the night</td><td>.0871</td><td>−0.42 (−0.75, −0.09)</td><td>.012</td><td>−0.13 (−0.49, 0.23)</td><td>.471</td><td>−0.65 (−0.95, −0.36)</td><td><strong><.0001</strong></td></tr><tr><td>I’m restless in my sleep</td><td>.5192</td><td>−0.62 (−0.92, −0.32)</td><td><strong><.0001</strong></td><td>−0.45 (−0.83, −0.06)</td><td>.024</td><td>−0.42 (−0.73, −0.12)</td><td><strong>.007</strong></td></tr><tr><td>I feel rested when I wake up</td><td><strong>.0017</strong></td><td>0.61 (0.28, 0.93)</td><td><strong><.001</strong></td><td>0.35 (−0.03, 0.73)</td><td>.073</td><td>1.28 (0.98, 1.57)</td><td><strong><.0001</strong></td></tr><tr><td rowspan="5"><strong>Apneic</strong></td><td>I wake up suddenly and feel as if I can’t breathe</td><td>.3029</td><td>−0.21 (−0.56, 0.14)</td><td>.230</td><td>0.15 (−0.28, 0.58)</td><td>.489</td><td>−0.30 (−0.63, 0.02)</td><td>.069</td></tr><tr><td>I have been told that I stop breathing at night</td><td>.5358</td><td>−1.16 (−1.51, −0.81)</td><td><strong><.0001</strong></td><td>−0.88 (−1.29, −0.46)</td><td><strong><.0001</strong></td><td>−1.06 (−1.41, −0.71)</td><td><strong><.0001</strong></td></tr><tr><td>Any loud snoring</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>I snore loudly and it disturbs my spouse’s sleep</td><td>.9238</td><td>0.15 (0.05, 0.51)</td><td><strong>.003</strong></td><td>N/A</td><td>N/A</td><td><strong>0.10 (0.02, 0.51</strong>)</td><td><strong>.006</strong></td></tr><tr><td>My nose is congested at night</td><td>.6395</td><td>−0.07 (−0.34, 0.21)</td><td>.639</td><td>0.00 (−0.40, 0.39)</td><td>.989</td><td>−0.20 (−0.46, 0.07)</td><td>.144</td></tr><tr><td rowspan="3"><strong>Other</strong></td><td>I wake up with a headache</td><td>.0093</td><td>0.17 (−0.08, 0.42)</td><td>.188</td><td>0.01 (−0.34, 0.37)</td><td>.938</td><td>−0.37 (−0.64, −0.10)</td><td><strong>.008</strong></td></tr><tr><td>I perspire heavily during the night</td><td>.7291</td><td>−0.36 (−0.65, −0.07)</td><td>.015</td><td>−0.29 (−0.64, 0.06)</td><td>.101</td><td>−0.38 (−0.65, −0.11)</td><td><strong>.005</strong></td></tr><tr><td>Presence of RLS</td><td>.1566</td><td>0.52 (0.18, 1.56)</td><td>.246</td><td>0.26 (0.04, 1.69)</td><td>.158</td><td>1.64 (0.56, 4.85)</td><td>.368</td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th colspan="2" rowspan="2">Symptom measures<span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2"><em>p</em>-Value for three- way interaction*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Disturbed Sleep<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Minimally Symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Sleepy<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>**<span aria-hidden="true" style="display: none;"> . </span></th><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>**<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td rowspan="7">Sleepiness and fatigue</td><td>Epworth Sleepiness Scale</td><td><strong><.0001</strong></td><td>−0.19 (−0.49, 0.12)</td><td>.227</td><td>−0.32 (−0.62, −0.02)</td><td>.037</td><td>−0.98 (−1.31, −0.66)</td><td><strong><.0001</strong></td></tr><tr><td>I feel sleepy during the day</td><td>.089</td><td>−0.76 (−1.12, −0.41)</td><td><strong><.0001</strong></td><td>−0.38 (−0.76, 0.00)</td><td>.052</td><td>−1.19 (−1.53, −0.85)</td><td><strong><.0001</strong></td></tr><tr><td>I fall asleep involuntarily during the day</td><td><strong><.0001</strong></td><td>−0.06 (−0.41, 0.28)</td><td>.716</td><td>−0.02 (−0.40, 0.35)</td><td>.903</td><td>−0.83 (−1.14, −0.52)</td><td><strong><.0001</strong></td></tr><tr><td>I fall asleep if I relax (TV)</td><td>.1303</td><td>−0.35 (−0.61, −0.09)</td><td>.009</td><td>−0.45 (−0.73, −0.17)</td><td><strong>.002</strong></td><td>−0.91 (−1.22, −0.59)</td><td><strong><.0001</strong></td></tr><tr><td>I take a nap during the day</td><td>.3403</td><td>−0.31 (−0.58, −0.04)</td><td>.025</td><td>−0.11 (−0.43, 0.21)</td><td>.503</td><td>−0.39 (−0.66, −0.12)</td><td><strong>.005</strong></td></tr><tr><td>I doze off at the steering wheel when driving</td><td><strong>.0017</strong></td><td>−0.24 (−0.58, 0.10)</td><td>.167</td><td>0.35 (−0.07, 0.76)</td><td>.100</td><td>−0.47 (−0.77, −0.18)</td><td><strong>.002</strong></td></tr><tr><td>I feel physically tired during the day</td><td>.0766</td><td>−0.49 (−0.83, −0.15)</td><td>.006</td><td>−0.66 (−1.03, −0.29)</td><td><strong>.001</strong></td><td>−1.16 (−1.49, −0.82)</td><td><strong><.0001</strong></td></tr><tr><td rowspan="5">Insomnia-related</td><td>I have difficulties falling asleep at night</td><td>.5419</td><td>0.09 (−0.19, 0.37)</td><td>.528</td><td>−0.16 (−0.43, 0.12)</td><td>.273</td><td>−0.04 (−0.30, 0.21)</td><td>.725</td></tr><tr><td>I wake up too early/it’s hard to fall back to sleep</td><td>.1719</td><td>0.22 (−0.09, 0.53)</td><td>.159</td><td>0.41 (0.05, 0.78)</td><td>.025</td><td>−0.04 (−0.30, 0.23)</td><td>.793</td></tr><tr><td>I wake up often during the night</td><td>.0871</td><td>−0.42 (−0.75, −0.09)</td><td>.012</td><td>−0.13 (−0.49, 0.23)</td><td>.471</td><td>−0.65 (−0.95, −0.36)</td><td><strong><.0001</strong></td></tr><tr><td>I’m restless in my sleep</td><td>.5192</td><td>−0.62 (−0.92, −0.32)</td><td><strong><.0001</strong></td><td>−0.45 (−0.83, −0.06)</td><td>.024</td><td>−0.42 (−0.73, −0.12)</td><td><strong>.007</strong></td></tr><tr><td>I feel rested when I wake up</td><td><strong>.0017</strong></td><td>0.61 (0.28, 0.93)</td><td><strong><.001</strong></td><td>0.35 (−0.03, 0.73)</td><td>.073</td><td>1.28 (0.98, 1.57)</td><td><strong><.0001</strong></td></tr><tr><td rowspan="5"><strong>Apneic</strong></td><td>I wake up suddenly and feel as if I can’t breathe</td><td>.3029</td><td>−0.21 (−0.56, 0.14)</td><td>.230</td><td>0.15 (−0.28, 0.58)</td><td>.489</td><td>−0.30 (−0.63, 0.02)</td><td>.069</td></tr><tr><td>I have been told that I stop breathing at night</td><td>.5358</td><td>−1.16 (−1.51, −0.81)</td><td><strong><.0001</strong></td><td>−0.88 (−1.29, −0.46)</td><td><strong><.0001</strong></td><td>−1.06 (−1.41, −0.71)</td><td><strong><.0001</strong></td></tr><tr><td>Any loud snoring</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>I snore loudly and it disturbs my spouse’s sleep</td><td>.9238</td><td>0.15 (0.05, 0.51)</td><td><strong>.003</strong></td><td>N/A</td><td>N/A</td><td><strong>0.10 (0.02, 0.51</strong>)</td><td><strong>.006</strong></td></tr><tr><td>My nose is congested at night</td><td>.6395</td><td>−0.07 (−0.34, 0.21)</td><td>.639</td><td>0.00 (−0.40, 0.39)</td><td>.989</td><td>−0.20 (−0.46, 0.07)</td><td>.144</td></tr><tr><td rowspan="3"><strong>Other</strong></td><td>I wake up with a headache</td><td>.0093</td><td>0.17 (−0.08, 0.42)</td><td>.188</td><td>0.01 (−0.34, 0.37)</td><td>.938</td><td>−0.37 (−0.64, −0.10)</td><td><strong>.008</strong></td></tr><tr><td>I perspire heavily during the night</td><td>.7291</td><td>−0.36 (−0.65, −0.07)</td><td>.015</td><td>−0.29 (−0.64, 0.06)</td><td>.101</td><td>−0.38 (−0.65, −0.11)</td><td><strong>.005</strong></td></tr><tr><td>Presence of RLS</td><td>.1566</td><td>0.52 (0.18, 1.56)</td><td>.246</td><td>0.26 (0.04, 1.69)</td><td>.158</td><td>1.64 (0.56, 4.85)</td><td>.368</td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-15"></span><div content-id="fn-15" class="footnote"><span class="fn"><p class="chapter-para">Models adjusted for gender, baseline age, BMI, and AHI-derived propensity score. To ensure reliable estimates of group-specific odds ratios with binary outcomes, we required >5 changes in the symptom overall in order to fit a logistic mixed model, as well as ≥1 change from presence to absence and ≥1 change from absence to presence over the follow-up period; if a given group did not meet these criteria, results for that model are presented as “N/A.” <em>p</em>-Values shown in <strong>bold</strong> are statistically significant after Hochberg correction.</p></span></div><span id="fn-fn-16"></span><div content-id="fn-16" class="footnote"><span class="fn"><p class="chapter-para">*<em>p</em>-Value testing for a three-way interaction among cluster, time, and PAP adherence within the linear mixed model, which tests whether differences in symptom response between full users and nonusers differ among clusters.</p></span></div><span id="fn-fn-17"></span><div content-id="fn-17" class="footnote"><span class="fn"><p class="chapter-para">**<em>p</em>-Value comparing full users vs. nonusers within each cluster.</p></span></div><span id="fn-fn-18"></span><div content-id="fn-18" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup>Estimates presented as standardized mean difference in change scores (for continuous variables) or ratio of odds ratios (for categorical variables) and associated 95% confidence interval comparing full users vs. nonusers.</p></span></div><span id="fn-fn-19"></span><div content-id="fn-19" class="footnote"><span class="fn"><p class="chapter-para">CI = confidence interval; RLS = restless leg syndrome.</p></span></div></div></div></div><div class="table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T4" data-id="T4"><span class="label title-label" id="label-73544">Table 4.</span><div class="
 graphic-wrap table-open-button-wrap
 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223265" aria-describedby="label-73544"> Open in new tab </a></div><div class="caption caption-id-" id="caption-73544"><p class="chapter-para">Propensity Score Adjusted Differences in Changes in Symptom Variables Between PAP Adherence Groups Within Individual Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-73544" aria-describedby="
 caption-73544"><thead><tr><th colspan="2" rowspan="2">Symptom measures<span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2"><em>p</em>-Value for three- way interaction*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Disturbed Sleep<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Minimally Symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Sleepy<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>**<span aria-hidden="true" style="display: none;"> . </span></th><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>**<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td rowspan="7">Sleepiness and fatigue</td><td>Epworth Sleepiness Scale</td><td><strong><.0001</strong></td><td>−0.19 (−0.49, 0.12)</td><td>.227</td><td>−0.32 (−0.62, −0.02)</td><td>.037</td><td>−0.98 (−1.31, −0.66)</td><td><strong><.0001</strong></td></tr><tr><td>I feel sleepy during the day</td><td>.089</td><td>−0.76 (−1.12, −0.41)</td><td><strong><.0001</strong></td><td>−0.38 (−0.76, 0.00)</td><td>.052</td><td>−1.19 (−1.53, −0.85)</td><td><strong><.0001</strong></td></tr><tr><td>I fall asleep involuntarily during the day</td><td><strong><.0001</strong></td><td>−0.06 (−0.41, 0.28)</td><td>.716</td><td>−0.02 (−0.40, 0.35)</td><td>.903</td><td>−0.83 (−1.14, −0.52)</td><td><strong><.0001</strong></td></tr><tr><td>I fall asleep if I relax (TV)</td><td>.1303</td><td>−0.35 (−0.61, −0.09)</td><td>.009</td><td>−0.45 (−0.73, −0.17)</td><td><strong>.002</strong></td><td>−0.91 (−1.22, −0.59)</td><td><strong><.0001</strong></td></tr><tr><td>I take a nap during the day</td><td>.3403</td><td>−0.31 (−0.58, −0.04)</td><td>.025</td><td>−0.11 (−0.43, 0.21)</td><td>.503</td><td>−0.39 (−0.66, −0.12)</td><td><strong>.005</strong></td></tr><tr><td>I doze off at the steering wheel when driving</td><td><strong>.0017</strong></td><td>−0.24 (−0.58, 0.10)</td><td>.167</td><td>0.35 (−0.07, 0.76)</td><td>.100</td><td>−0.47 (−0.77, −0.18)</td><td><strong>.002</strong></td></tr><tr><td>I feel physically tired during the day</td><td>.0766</td><td>−0.49 (−0.83, −0.15)</td><td>.006</td><td>−0.66 (−1.03, −0.29)</td><td><strong>.001</strong></td><td>−1.16 (−1.49, −0.82)</td><td><strong><.0001</strong></td></tr><tr><td rowspan="5">Insomnia-related</td><td>I have difficulties falling asleep at night</td><td>.5419</td><td>0.09 (−0.19, 0.37)</td><td>.528</td><td>−0.16 (−0.43, 0.12)</td><td>.273</td><td>−0.04 (−0.30, 0.21)</td><td>.725</td></tr><tr><td>I wake up too early/it’s hard to fall back to sleep</td><td>.1719</td><td>0.22 (−0.09, 0.53)</td><td>.159</td><td>0.41 (0.05, 0.78)</td><td>.025</td><td>−0.04 (−0.30, 0.23)</td><td>.793</td></tr><tr><td>I wake up often during the night</td><td>.0871</td><td>−0.42 (−0.75, −0.09)</td><td>.012</td><td>−0.13 (−0.49, 0.23)</td><td>.471</td><td>−0.65 (−0.95, −0.36)</td><td><strong><.0001</strong></td></tr><tr><td>I’m restless in my sleep</td><td>.5192</td><td>−0.62 (−0.92, −0.32)</td><td><strong><.0001</strong></td><td>−0.45 (−0.83, −0.06)</td><td>.024</td><td>−0.42 (−0.73, −0.12)</td><td><strong>.007</strong></td></tr><tr><td>I feel rested when I wake up</td><td><strong>.0017</strong></td><td>0.61 (0.28, 0.93)</td><td><strong><.001</strong></td><td>0.35 (−0.03, 0.73)</td><td>.073</td><td>1.28 (0.98, 1.57)</td><td><strong><.0001</strong></td></tr><tr><td rowspan="5"><strong>Apneic</strong></td><td>I wake up suddenly and feel as if I can’t breathe</td><td>.3029</td><td>−0.21 (−0.56, 0.14)</td><td>.230</td><td>0.15 (−0.28, 0.58)</td><td>.489</td><td>−0.30 (−0.63, 0.02)</td><td>.069</td></tr><tr><td>I have been told that I stop breathing at night</td><td>.5358</td><td>−1.16 (−1.51, −0.81)</td><td><strong><.0001</strong></td><td>−0.88 (−1.29, −0.46)</td><td><strong><.0001</strong></td><td>−1.06 (−1.41, −0.71)</td><td><strong><.0001</strong></td></tr><tr><td>Any loud snoring</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>I snore loudly and it disturbs my spouse’s sleep</td><td>.9238</td><td>0.15 (0.05, 0.51)</td><td><strong>.003</strong></td><td>N/A</td><td>N/A</td><td><strong>0.10 (0.02, 0.51</strong>)</td><td><strong>.006</strong></td></tr><tr><td>My nose is congested at night</td><td>.6395</td><td>−0.07 (−0.34, 0.21)</td><td>.639</td><td>0.00 (−0.40, 0.39)</td><td>.989</td><td>−0.20 (−0.46, 0.07)</td><td>.144</td></tr><tr><td rowspan="3"><strong>Other</strong></td><td>I wake up with a headache</td><td>.0093</td><td>0.17 (−0.08, 0.42)</td><td>.188</td><td>0.01 (−0.34, 0.37)</td><td>.938</td><td>−0.37 (−0.64, −0.10)</td><td><strong>.008</strong></td></tr><tr><td>I perspire heavily during the night</td><td>.7291</td><td>−0.36 (−0.65, −0.07)</td><td>.015</td><td>−0.29 (−0.64, 0.06)</td><td>.101</td><td>−0.38 (−0.65, −0.11)</td><td><strong>.005</strong></td></tr><tr><td>Presence of RLS</td><td>.1566</td><td>0.52 (0.18, 1.56)</td><td>.246</td><td>0.26 (0.04, 1.69)</td><td>.158</td><td>1.64 (0.56, 4.85)</td><td>.368</td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th colspan="2" rowspan="2">Symptom measures<span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2"><em>p</em>-Value for three- way interaction*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Disturbed Sleep<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Minimally Symptomatic<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="2">Sleepy<span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>**<span aria-hidden="true" style="display: none;"> . </span></th><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th>Full user vs. nonuser comparison<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th><em>P</em>**<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td rowspan="7">Sleepiness and fatigue</td><td>Epworth Sleepiness Scale</td><td><strong><.0001</strong></td><td>−0.19 (−0.49, 0.12)</td><td>.227</td><td>−0.32 (−0.62, −0.02)</td><td>.037</td><td>−0.98 (−1.31, −0.66)</td><td><strong><.0001</strong></td></tr><tr><td>I feel sleepy during the day</td><td>.089</td><td>−0.76 (−1.12, −0.41)</td><td><strong><.0001</strong></td><td>−0.38 (−0.76, 0.00)</td><td>.052</td><td>−1.19 (−1.53, −0.85)</td><td><strong><.0001</strong></td></tr><tr><td>I fall asleep involuntarily during the day</td><td><strong><.0001</strong></td><td>−0.06 (−0.41, 0.28)</td><td>.716</td><td>−0.02 (−0.40, 0.35)</td><td>.903</td><td>−0.83 (−1.14, −0.52)</td><td><strong><.0001</strong></td></tr><tr><td>I fall asleep if I relax (TV)</td><td>.1303</td><td>−0.35 (−0.61, −0.09)</td><td>.009</td><td>−0.45 (−0.73, −0.17)</td><td><strong>.002</strong></td><td>−0.91 (−1.22, −0.59)</td><td><strong><.0001</strong></td></tr><tr><td>I take a nap during the day</td><td>.3403</td><td>−0.31 (−0.58, −0.04)</td><td>.025</td><td>−0.11 (−0.43, 0.21)</td><td>.503</td><td>−0.39 (−0.66, −0.12)</td><td><strong>.005</strong></td></tr><tr><td>I doze off at the steering wheel when driving</td><td><strong>.0017</strong></td><td>−0.24 (−0.58, 0.10)</td><td>.167</td><td>0.35 (−0.07, 0.76)</td><td>.100</td><td>−0.47 (−0.77, −0.18)</td><td><strong>.002</strong></td></tr><tr><td>I feel physically tired during the day</td><td>.0766</td><td>−0.49 (−0.83, −0.15)</td><td>.006</td><td>−0.66 (−1.03, −0.29)</td><td><strong>.001</strong></td><td>−1.16 (−1.49, −0.82)</td><td><strong><.0001</strong></td></tr><tr><td rowspan="5">Insomnia-related</td><td>I have difficulties falling asleep at night</td><td>.5419</td><td>0.09 (−0.19, 0.37)</td><td>.528</td><td>−0.16 (−0.43, 0.12)</td><td>.273</td><td>−0.04 (−0.30, 0.21)</td><td>.725</td></tr><tr><td>I wake up too early/it’s hard to fall back to sleep</td><td>.1719</td><td>0.22 (−0.09, 0.53)</td><td>.159</td><td>0.41 (0.05, 0.78)</td><td>.025</td><td>−0.04 (−0.30, 0.23)</td><td>.793</td></tr><tr><td>I wake up often during the night</td><td>.0871</td><td>−0.42 (−0.75, −0.09)</td><td>.012</td><td>−0.13 (−0.49, 0.23)</td><td>.471</td><td>−0.65 (−0.95, −0.36)</td><td><strong><.0001</strong></td></tr><tr><td>I’m restless in my sleep</td><td>.5192</td><td>−0.62 (−0.92, −0.32)</td><td><strong><.0001</strong></td><td>−0.45 (−0.83, −0.06)</td><td>.024</td><td>−0.42 (−0.73, −0.12)</td><td><strong>.007</strong></td></tr><tr><td>I feel rested when I wake up</td><td><strong>.0017</strong></td><td>0.61 (0.28, 0.93)</td><td><strong><.001</strong></td><td>0.35 (−0.03, 0.73)</td><td>.073</td><td>1.28 (0.98, 1.57)</td><td><strong><.0001</strong></td></tr><tr><td rowspan="5"><strong>Apneic</strong></td><td>I wake up suddenly and feel as if I can’t breathe</td><td>.3029</td><td>−0.21 (−0.56, 0.14)</td><td>.230</td><td>0.15 (−0.28, 0.58)</td><td>.489</td><td>−0.30 (−0.63, 0.02)</td><td>.069</td></tr><tr><td>I have been told that I stop breathing at night</td><td>.5358</td><td>−1.16 (−1.51, −0.81)</td><td><strong><.0001</strong></td><td>−0.88 (−1.29, −0.46)</td><td><strong><.0001</strong></td><td>−1.06 (−1.41, −0.71)</td><td><strong><.0001</strong></td></tr><tr><td>Any loud snoring</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td><td>N/A</td></tr><tr><td>I snore loudly and it disturbs my spouse’s sleep</td><td>.9238</td><td>0.15 (0.05, 0.51)</td><td><strong>.003</strong></td><td>N/A</td><td>N/A</td><td><strong>0.10 (0.02, 0.51</strong>)</td><td><strong>.006</strong></td></tr><tr><td>My nose is congested at night</td><td>.6395</td><td>−0.07 (−0.34, 0.21)</td><td>.639</td><td>0.00 (−0.40, 0.39)</td><td>.989</td><td>−0.20 (−0.46, 0.07)</td><td>.144</td></tr><tr><td rowspan="3"><strong>Other</strong></td><td>I wake up with a headache</td><td>.0093</td><td>0.17 (−0.08, 0.42)</td><td>.188</td><td>0.01 (−0.34, 0.37)</td><td>.938</td><td>−0.37 (−0.64, −0.10)</td><td><strong>.008</strong></td></tr><tr><td>I perspire heavily during the night</td><td>.7291</td><td>−0.36 (−0.65, −0.07)</td><td>.015</td><td>−0.29 (−0.64, 0.06)</td><td>.101</td><td>−0.38 (−0.65, −0.11)</td><td><strong>.005</strong></td></tr><tr><td>Presence of RLS</td><td>.1566</td><td>0.52 (0.18, 1.56)</td><td>.246</td><td>0.26 (0.04, 1.69)</td><td>.158</td><td>1.64 (0.56, 4.85)</td><td>.368</td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-15"></span><div content-id="fn-15" class="footnote"><span class="fn"><p class="chapter-para">Models adjusted for gender, baseline age, BMI, and AHI-derived propensity score. To ensure reliable estimates of group-specific odds ratios with binary outcomes, we required >5 changes in the symptom overall in order to fit a logistic mixed model, as well as ≥1 change from presence to absence and ≥1 change from absence to presence over the follow-up period; if a given group did not meet these criteria, results for that model are presented as “N/A.” <em>p</em>-Values shown in <strong>bold</strong> are statistically significant after Hochberg correction.</p></span></div><span id="fn-fn-16"></span><div content-id="fn-16" class="footnote"><span class="fn"><p class="chapter-para">*<em>p</em>-Value testing for a three-way interaction among cluster, time, and PAP adherence within the linear mixed model, which tests whether differences in symptom response between full users and nonusers differ among clusters.</p></span></div><span id="fn-fn-17"></span><div content-id="fn-17" class="footnote"><span class="fn"><p class="chapter-para">**<em>p</em>-Value comparing full users vs. nonusers within each cluster.</p></span></div><span id="fn-fn-18"></span><div content-id="fn-18" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup>Estimates presented as standardized mean difference in change scores (for continuous variables) or ratio of odds ratios (for categorical variables) and associated 95% confidence interval comparing full users vs. nonusers.</p></span></div><span id="fn-fn-19"></span><div content-id="fn-19" class="footnote"><span class="fn"><p class="chapter-para">CI = confidence interval; RLS = restless leg syndrome.</p></span></div></div></div></div><p class="chapter-para">Within each cluster, we also compared the magnitude of changes in symptoms between full users and non-PAP users, adjusting for gender and baseline age, BMI, and AHI using a derived propensity score to robustly control for any covariate imbalance (<span class="xrefLink" id="jumplink-T4"></span><a href="javascript:;" reveal-id="T4" data-open="T4" class="link link-reveal link-table xref-fig">Table 4</a>). As expected, full users generally demonstrated larger changes in specific symptom frequency compared with non-PAP users (<span class="xrefLink" id="jumplink-F2"></span><a href="javascript:;" data-modal-source-id="F2" class="link xref-fig">Figure 2</a>; <span class="xrefLink" id="jumplink-T4"></span><a href="javascript:;" reveal-id="T4" data-open="T4" class="link link-reveal link-table xref-fig">Table 4</a>). Reflecting the established efficacy of PAP for typical OSA symptoms, users in the Sleepy group, which represents the classical clinical presentation of OSA, demonstrated a wider range of clinically and statistically significant PAP effects than either the Disturbed Sleep group or the Minimally Symptomatic group.</p> <a id="118223267" scrollto-destination="118223267"></a> <div data-id="f2" data-content-id="f2" class="fig fig-section js-fig-section" swap-content-for-modal="true"><div class="graphic-wrap"><img class="content-image" src="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/m_zsx20102.jpeg?Expires=1735725789&Signature=wvtwgP4g--EhPHzb6XuRnitQwx9nDK7hnagVErVynadZWCM5OnsxSh7qfsLwrP9yXBYPrA4BSfGCnG92Tty4~1dXIHWRh47ebA-desdflo1tQAHtQGEy0SnnzFq0fDusH7hvirA-KmEG0Hr66xtQnZ5Z3GXdUDoYIgpji3JmuZ5OMnBEdIiTJEDbqlZYQ89BGi7EcE77q3qdITvX4qE5~jp0gPJ04zg-iyPqDMXl9Sosm-BnKRCrKLboyHhMaYIXHncYSwTxfm8Q3DI2I5Pp4YtRbLa6x1pNTe~L4WBgzXjeXDgaGZcyTJCt~6bv542DdB23ExDkYgRm6TVIXTQGnQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA" alt="Follow-up symptom profiles in adherent and nonusers of PAP. Radar plots are shown, illustrating the follow-up symptom profile in PAP full users and nonusers separately for each cluster. Larger reductions in symptoms were generally seen for full users compared with nonusers. This effect was most pronounced in the Sleepy group, but also observed among Minimally Symptomatic patients. Nonusers reported modest improvements in symptoms at follow-up." data-path-from-xml="zsx20102.jpeg" /><div class="graphic-bottom"><div class="label fig-label" id="label-118223267">Figure 2.</div><div class="caption fig-caption"><p class="chapter-para">Follow-up symptom profiles in adherent and nonusers of PAP. Radar plots are shown, illustrating the follow-up symptom profile in PAP full users and nonusers separately for each cluster. Larger reductions in symptoms were generally seen for full users compared with nonusers. This effect was most pronounced in the Sleepy group, but also observed among Minimally Symptomatic patients. Nonusers reported modest improvements in symptoms at follow-up.</p></div><div class="ajax-articleAbstract-exclude-regex fig-orig original-slide figure-button-wrap"><a class="fig-view-orig js-view-large at-figureViewLarge openInAnotherWindow" role="button" aria-describedby="label-118223267" href="/view-large/figure/118223267/zsx20102.jpeg" data-path-from-xml="zsx20102.jpeg" target="_blank">Open in new tab</a><a class="download-slide" role="button" aria-describedby="label-118223267" data-section="118223267" href="/DownloadFile/DownloadImage.aspx?image=https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx20102.jpeg?Expires=1735725789&Signature=SJLSnMLwA~Lz3ZhlwsDbf6JAxG23nT7z75JR2oURow2HDsHK~bPXx~qjXUgNaXMuHuv-sV~mAjxAj12izDuMzb2UrCw3FeoEjkafkW88U7wDxp4QqGMafK2q1hFt14nr0A7jhzLgJZKcd4KjB1KXzineVvoMwfh7IbPHqWY~urAyRLfQr3zqCAXHsNWWXL-MejB8~~X-k~7Tw3SNx1Kbg1K8~5swENzrFJbYj5L0yDYHzVR27Dx2HrBk13d2e9IZNhVUgngdehyluLmKMBJercueJ5UQA-HwXTMUHkz0~O~c0KVz5AH8xSpBKakUWy56n7DUMKZvQNuOWdZ7r~y9mw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA&sec=118223267&ar=4782667&xsltPath=~/UI/app/XSLT&imagename=&siteId=5573" data-path-from-xml="zsx20102.jpeg">Download slide</a></div></div></div></div><p class="chapter-para">In the Disturbed Sleep group, although significant improvements within both full PAP and non-PAP users were noted at follow-up for a number of symptoms (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S5</a></span>), moderately large differences in changes (effect sizes between 0.42 and 0.76) were observed when comparing full users and nonusers for sleep quality and insomnia-related symptoms, particularly feeling rested when waking, having restless sleep, waking frequently, and daytime sleepiness. Effect sizes between PAP users and nonusers for other insomnia-related symptoms, such as frequency of difficulty falling asleep and early awakening, were not significant.</p><p class="chapter-para">In the Minimally Symptomatic group, moderate-to-large effects were observed for falling asleep when relaxed, feeling physically tired, and for witnessed apneas when comparing improvements in full PAP users with nonusers. Smaller effect sizes among full users were noted for sleep quality and sleepiness symptoms compared with nonusers (<span class="xrefLink" id="jumplink-T4"></span><a href="javascript:;" reveal-id="T4" data-open="T4" class="link link-reveal link-table xref-fig">Table 4</a>).</p><p class="chapter-para">Within the Sleepy group, full PAP users reported much greater improvement in numerous symptoms compared with nonusers, with large effect sizes noted for characteristic OSA symptoms including falling asleep involuntarily, drowsy driving, and daytime sleepiness. Improvement in ESS scores was four points larger in full PAP users compared with nonusers (−7.0 vs. −3.0, <em>p</em> < .0001). Moderate differences in the improvement in other symptoms, including waking up with headache and perspiring heavily at night, were also observed.</p><p class="chapter-para">Within each of the three groups, results were similar in secondary analyses comparing the presence of symptoms in PAP users and nonusers (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S6</a></span>). In sensitivity analyses, we compared full users and non-PAP users after excluding 45 nonusers who reported alternative OSA treatments (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S7</a></span>), excluding 55 full users and non-PAP users with >5% weight loss at follow-up (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S8</a></span>), and removing 79 full PAP users who did not have available objective usage data to confirm their adherence level (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S9</a></span>). Results from each of these sensitivity analyses were similar to analyses including all participants, suggesting that alternative treatments or potential misclassification did not bias overall associations. Analyses to examine the association between cluster membership and change in outcome while controlling for PAP adherence group demonstrated little or no change in associations, indicating that observed associations between cluster and outcome were not mediated or explained by differential adherence to PAP.</p> <h3 scrollto-destination=118223272 id="118223272" class="section-title js-splitscreen-section-title" data-legacy-id=s18>Comorbid Conditions, BP, and BMI</h3> <p class="chapter-para">When examining changes in BMI, BP, comorbid conditions, and quality of life (<span class="xrefLink" id="jumplink-T5"></span><a href="javascript:;" reveal-id="T5" data-open="T5" class="link link-reveal link-table xref-fig">Table 5</a>), significant differences among the clinical subgroups in diastolic BP (<em>p</em> = .004) and SF-12 physical component score (<em>p</em> < .0001) were observed. For physical health assessed by the SF-12 Physical Component score, the Sleepy group showed an improvement of nearly five points after 2 years of PAP treatment, which corresponded to a small-to-moderate effect when compared with nonsignificant changes in the other groups. In the Minimally Symptomatic and Sleepy groups, diastolic BP decreased by 2.6 (<em>p</em> = .001) and 2.8 (<em>p</em> < .0001) mm Hg, respectively, but showed no change in the Disturbed Sleep group. These effects were statistically greater than the change observed in the Disturbed Sleep group, although the clinical difference was small (effect sizes of ~0.27). When examining the effect of PAP, a moderate difference between full users and nonusers in diastolic BP was observed in the Minimally Symptomatic (−0.42 [−0.75, −0.08]) group (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S10</a></span>). BMI increased significantly from baseline to 2-year follow-up in all groups; the magnitude of change was similar across groups (<span class="xrefLink" id="jumplink-T5"></span><a href="javascript:;" reveal-id="T5" data-open="T5" class="link link-reveal link-table xref-fig">Table 5</a>). Similar to previous studies,<sup><span class="xrefLink" id="jumplink-CIT0020 CIT0021 CIT0022"></span><a href="javascript:;" reveal-id="CIT0020 CIT0021 CIT0022" data-open="CIT0020 CIT0021 CIT0022" class="link link-ref link-reveal xref-bibr">20–22</a></sup> modest effect sizes for increased BMI were observed among full PAP users in the Disturbed Sleep and Sleepy groups (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S10</a></span>) compared with nonusers.</p> <a id="118223274" scrollto-destination="118223274"></a> <div content-id="T5" class="table-modal table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T5" data-id="T5"><span class="label title-label" id="label-93062">Table 5.</span><div class="
 graphic-wrap table-open-button-wrap
 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223274" aria-describedby="label-93062"> Open in new tab </a></div><div class="caption caption-id-" id="caption-93062"><p class="chapter-para">Adjusted Models for Changes in Comorbidities, BMI, BP, and Quality of Life Within and Between Symptom Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-93062" aria-describedby="
 caption-93062"><thead><tr><th rowspan="2">Measure<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Estimate (95% CI)<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Overall <em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Pairwise differences estimates<sup>b</sup><span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed Sleep (DS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally Symptomatic (MS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy (S)<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. MS<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. S<span aria-hidden="true" style="display: none;"> . </span></th><th>MS vs. S<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td>Hypertension</td><td>0.67 (0.32, 1.41)</td><td>2.25 (0.93, 5.40)</td><td>0.97 (0.52, 1.82)</td><td>.116</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Cardiovascular disease</td><td>0.65 (0.18, 2.39)</td><td>5.40 (1.34, 21.8)</td><td>1.16 (0.37, 3.64)</td><td>.083</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Obstructive lung disease</td><td>1.38 (0.58, 3.28)</td><td>1.12 (0.37, 3.41)</td><td>1.11 (0.52, 2.35)</td><td>.925</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Diabetes mellitus</td><td>2.07 (0.51, 8.40)</td><td>4.15 (0.69, 25.1)</td><td>N/A</td><td>N/A</td><td>0.50 (0.05, 4.66)</td><td>N/A</td><td>N/A</td></tr><tr><td>Body mass index</td><td>0.66 (0.37, 0.96)<sup>c</sup></td><td>0.66 (0.32, 1.01)<sup>c</sup></td><td>0.35 (0.09, 0.60)<sup>c</sup></td><td>.188</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Diastolic blood pressure</td><td>−0.11 (−1.37, 1.16)</td><td>−2.58 (−4.06, −1.10)<sup>§</sup></td><td>−2.81 (−3.9, −1.71)<sup>c</sup></td><td><strong>.004</strong></td><td>0.26 (0.06, 0.46)<sup>d</sup></td><td>0.28 (0.11, 0.46)<sup>d</sup></td><td>0.02 (−0.17, 0.22)</td></tr><tr><td>Systolic blood pressure</td><td>2.01 (0.20, 3.81)</td><td>−0.41 (−2.53, 1.70)</td><td>1.31 (−0.25, 2.88)</td><td>.223</td><td>—</td><td>—</td><td>—</td></tr><tr><td>SF-12 physical component</td><td>0.96 (−0.27, 2.20)</td><td>1.23 (−0.21, 2.67)</td><td>4.82 (3.77, 5.88)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.03 (−0.22, 0.16)</td><td>−0.38 (−0.55, −0.22)<sup>d</sup></td><td>−0.36 (−0.53, −0.18)<sup>d</sup></td></tr><tr><td>SF-12 mental component</td><td>3.26 (1.77, 4.75)<sup>c</sup></td><td>0.61 (−1.12, 2.35)</td><td>2.80 (1.53, 4.07)<sup>c</sup></td><td>.057</td><td>—</td><td>—</td><td>—</td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th rowspan="2">Measure<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Estimate (95% CI)<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Overall <em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Pairwise differences estimates<sup>b</sup><span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed Sleep (DS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally Symptomatic (MS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy (S)<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. MS<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. S<span aria-hidden="true" style="display: none;"> . </span></th><th>MS vs. S<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td>Hypertension</td><td>0.67 (0.32, 1.41)</td><td>2.25 (0.93, 5.40)</td><td>0.97 (0.52, 1.82)</td><td>.116</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Cardiovascular disease</td><td>0.65 (0.18, 2.39)</td><td>5.40 (1.34, 21.8)</td><td>1.16 (0.37, 3.64)</td><td>.083</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Obstructive lung disease</td><td>1.38 (0.58, 3.28)</td><td>1.12 (0.37, 3.41)</td><td>1.11 (0.52, 2.35)</td><td>.925</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Diabetes mellitus</td><td>2.07 (0.51, 8.40)</td><td>4.15 (0.69, 25.1)</td><td>N/A</td><td>N/A</td><td>0.50 (0.05, 4.66)</td><td>N/A</td><td>N/A</td></tr><tr><td>Body mass index</td><td>0.66 (0.37, 0.96)<sup>c</sup></td><td>0.66 (0.32, 1.01)<sup>c</sup></td><td>0.35 (0.09, 0.60)<sup>c</sup></td><td>.188</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Diastolic blood pressure</td><td>−0.11 (−1.37, 1.16)</td><td>−2.58 (−4.06, −1.10)<sup>§</sup></td><td>−2.81 (−3.9, −1.71)<sup>c</sup></td><td><strong>.004</strong></td><td>0.26 (0.06, 0.46)<sup>d</sup></td><td>0.28 (0.11, 0.46)<sup>d</sup></td><td>0.02 (−0.17, 0.22)</td></tr><tr><td>Systolic blood pressure</td><td>2.01 (0.20, 3.81)</td><td>−0.41 (−2.53, 1.70)</td><td>1.31 (−0.25, 2.88)</td><td>.223</td><td>—</td><td>—</td><td>—</td></tr><tr><td>SF-12 physical component</td><td>0.96 (−0.27, 2.20)</td><td>1.23 (−0.21, 2.67)</td><td>4.82 (3.77, 5.88)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.03 (−0.22, 0.16)</td><td>−0.38 (−0.55, −0.22)<sup>d</sup></td><td>−0.36 (−0.53, −0.18)<sup>d</sup></td></tr><tr><td>SF-12 mental component</td><td>3.26 (1.77, 4.75)<sup>c</sup></td><td>0.61 (−1.12, 2.35)</td><td>2.80 (1.53, 4.07)<sup>c</sup></td><td>.057</td><td>—</td><td>—</td><td>—</td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-20"></span><div content-id="fn-20" class="footnote"><span class="fn"><p class="chapter-para">Models adjusted for gender, baseline age, BMI, and AHI. To ensure reliable estimates of group-specific odds ratios with binary outcomes, we required >5 changes in the symptom overall in order to fit a logistic mixed model, as well as ≥1 change from presence to absence and ≥1 change from absence to presence over the follow-up period; if a given cluster did not meet these criteria, results for that model are presented as “N/A.” If this occurred only within one of the three clusters, we present estimates and pairwise comparisons between the two remaining clusters.</p></span></div><span id="fn-fn-21"></span><div content-id="fn-21" class="footnote"><span class="fn"><p class="chapter-para">*<em>P</em>-value comparing change scores or odds ratios among clusters, with <em>P</em>-values in <strong>bold</strong> statistically significant after Hochberg correction between clusters.</p></span></div><span id="fn-fn-22"></span><div content-id="fn-22" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup>Estimate presented as mean change (for continuous measures) or odds ratio (for binary measures) and 95% confidence interval.</p></span></div><span id="fn-fn-23"></span><div content-id="fn-23" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>b</em></sup>Between-cluster comparisons performed if overall <em>p</em>-value among clusters was statistically significant after Hochberg correction and results are presented as between-group standardized mean differences in change scores or ratios of within groups odds ratios (RORs) for symptom development at follow-up.</p></span></div><span id="fn-fn-24"></span><div content-id="fn-24" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>c</em></sup>Within-group estimate statistically significant after Hochberg correction.</p></span></div><span id="fn-fn-25"></span><div content-id="fn-25" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>d</em></sup>Comparison between groups significant at within outcome Bonferroni corrected <em>p</em> < .017.</p></span></div><span id="fn-fn-26"></span><div content-id="fn-26" class="footnote"><span class="fn"><p class="chapter-para">DS = Disturbed Sleep; MS = Minimally Symptomatic; S = Sleepy; CI = confidence interval.</p></span></div></div></div></div><div class="table-full-width-wrap"><div class="table-wrap table-wide standard-table"><div class="table-wrap-title" id="T5" data-id="T5"><span class="label title-label" id="label-93062">Table 5.</span><div class="
 graphic-wrap table-open-button-wrap
 "><a class="fig-view-orig at-tableViewLarge openInAnotherWindow btn js-view-large" role="button" target="_blank" href="
 /view-large/118223274" aria-describedby="label-93062"> Open in new tab </a></div><div class="caption caption-id-" id="caption-93062"><p class="chapter-para">Adjusted Models for Changes in Comorbidities, BMI, BP, and Quality of Life Within and Between Symptom Clusters</p></div> </div><div class="table-overflow"><table role="table" aria-labelledby="
 label-93062" aria-describedby="
 caption-93062"><thead><tr><th rowspan="2">Measure<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Estimate (95% CI)<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Overall <em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Pairwise differences estimates<sup>b</sup><span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed Sleep (DS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally Symptomatic (MS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy (S)<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. MS<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. S<span aria-hidden="true" style="display: none;"> . </span></th><th>MS vs. S<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td>Hypertension</td><td>0.67 (0.32, 1.41)</td><td>2.25 (0.93, 5.40)</td><td>0.97 (0.52, 1.82)</td><td>.116</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Cardiovascular disease</td><td>0.65 (0.18, 2.39)</td><td>5.40 (1.34, 21.8)</td><td>1.16 (0.37, 3.64)</td><td>.083</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Obstructive lung disease</td><td>1.38 (0.58, 3.28)</td><td>1.12 (0.37, 3.41)</td><td>1.11 (0.52, 2.35)</td><td>.925</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Diabetes mellitus</td><td>2.07 (0.51, 8.40)</td><td>4.15 (0.69, 25.1)</td><td>N/A</td><td>N/A</td><td>0.50 (0.05, 4.66)</td><td>N/A</td><td>N/A</td></tr><tr><td>Body mass index</td><td>0.66 (0.37, 0.96)<sup>c</sup></td><td>0.66 (0.32, 1.01)<sup>c</sup></td><td>0.35 (0.09, 0.60)<sup>c</sup></td><td>.188</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Diastolic blood pressure</td><td>−0.11 (−1.37, 1.16)</td><td>−2.58 (−4.06, −1.10)<sup>§</sup></td><td>−2.81 (−3.9, −1.71)<sup>c</sup></td><td><strong>.004</strong></td><td>0.26 (0.06, 0.46)<sup>d</sup></td><td>0.28 (0.11, 0.46)<sup>d</sup></td><td>0.02 (−0.17, 0.22)</td></tr><tr><td>Systolic blood pressure</td><td>2.01 (0.20, 3.81)</td><td>−0.41 (−2.53, 1.70)</td><td>1.31 (−0.25, 2.88)</td><td>.223</td><td>—</td><td>—</td><td>—</td></tr><tr><td>SF-12 physical component</td><td>0.96 (−0.27, 2.20)</td><td>1.23 (−0.21, 2.67)</td><td>4.82 (3.77, 5.88)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.03 (−0.22, 0.16)</td><td>−0.38 (−0.55, −0.22)<sup>d</sup></td><td>−0.36 (−0.53, −0.18)<sup>d</sup></td></tr><tr><td>SF-12 mental component</td><td>3.26 (1.77, 4.75)<sup>c</sup></td><td>0.61 (−1.12, 2.35)</td><td>2.80 (1.53, 4.07)<sup>c</sup></td><td>.057</td><td>—</td><td>—</td><td>—</td></tr></tbody></table></div><div class="table-modal"><table><thead><tr><th rowspan="2">Measure<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Estimate (95% CI)<sup>a</sup><span aria-hidden="true" style="display: none;"> . </span></th><th rowspan="2">Overall <em>P</em>*<span aria-hidden="true" style="display: none;"> . </span></th><th colspan="3">Pairwise differences estimates<sup>b</sup><span aria-hidden="true" style="display: none;"> . </span></th></tr><tr><th>Disturbed Sleep (DS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Minimally Symptomatic (MS)<span aria-hidden="true" style="display: none;"> . </span></th><th>Sleepy (S)<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. MS<span aria-hidden="true" style="display: none;"> . </span></th><th>DS vs. S<span aria-hidden="true" style="display: none;"> . </span></th><th>MS vs. S<span aria-hidden="true" style="display: none;"> . </span></th></tr></thead><tbody><tr><td>Hypertension</td><td>0.67 (0.32, 1.41)</td><td>2.25 (0.93, 5.40)</td><td>0.97 (0.52, 1.82)</td><td>.116</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Cardiovascular disease</td><td>0.65 (0.18, 2.39)</td><td>5.40 (1.34, 21.8)</td><td>1.16 (0.37, 3.64)</td><td>.083</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Obstructive lung disease</td><td>1.38 (0.58, 3.28)</td><td>1.12 (0.37, 3.41)</td><td>1.11 (0.52, 2.35)</td><td>.925</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Diabetes mellitus</td><td>2.07 (0.51, 8.40)</td><td>4.15 (0.69, 25.1)</td><td>N/A</td><td>N/A</td><td>0.50 (0.05, 4.66)</td><td>N/A</td><td>N/A</td></tr><tr><td>Body mass index</td><td>0.66 (0.37, 0.96)<sup>c</sup></td><td>0.66 (0.32, 1.01)<sup>c</sup></td><td>0.35 (0.09, 0.60)<sup>c</sup></td><td>.188</td><td>—</td><td>—</td><td>—</td></tr><tr><td>Diastolic blood pressure</td><td>−0.11 (−1.37, 1.16)</td><td>−2.58 (−4.06, −1.10)<sup>§</sup></td><td>−2.81 (−3.9, −1.71)<sup>c</sup></td><td><strong>.004</strong></td><td>0.26 (0.06, 0.46)<sup>d</sup></td><td>0.28 (0.11, 0.46)<sup>d</sup></td><td>0.02 (−0.17, 0.22)</td></tr><tr><td>Systolic blood pressure</td><td>2.01 (0.20, 3.81)</td><td>−0.41 (−2.53, 1.70)</td><td>1.31 (−0.25, 2.88)</td><td>.223</td><td>—</td><td>—</td><td>—</td></tr><tr><td>SF-12 physical component</td><td>0.96 (−0.27, 2.20)</td><td>1.23 (−0.21, 2.67)</td><td>4.82 (3.77, 5.88)<sup>c</sup></td><td><strong><.0001</strong></td><td>−0.03 (−0.22, 0.16)</td><td>−0.38 (−0.55, −0.22)<sup>d</sup></td><td>−0.36 (−0.53, −0.18)<sup>d</sup></td></tr><tr><td>SF-12 mental component</td><td>3.26 (1.77, 4.75)<sup>c</sup></td><td>0.61 (−1.12, 2.35)</td><td>2.80 (1.53, 4.07)<sup>c</sup></td><td>.057</td><td>—</td><td>—</td><td>—</td></tr></tbody></table></div><div class="table-wrap-foot"><span id="fn-fn-20"></span><div content-id="fn-20" class="footnote"><span class="fn"><p class="chapter-para">Models adjusted for gender, baseline age, BMI, and AHI. To ensure reliable estimates of group-specific odds ratios with binary outcomes, we required >5 changes in the symptom overall in order to fit a logistic mixed model, as well as ≥1 change from presence to absence and ≥1 change from absence to presence over the follow-up period; if a given cluster did not meet these criteria, results for that model are presented as “N/A.” If this occurred only within one of the three clusters, we present estimates and pairwise comparisons between the two remaining clusters.</p></span></div><span id="fn-fn-21"></span><div content-id="fn-21" class="footnote"><span class="fn"><p class="chapter-para">*<em>P</em>-value comparing change scores or odds ratios among clusters, with <em>P</em>-values in <strong>bold</strong> statistically significant after Hochberg correction between clusters.</p></span></div><span id="fn-fn-22"></span><div content-id="fn-22" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>a</em></sup>Estimate presented as mean change (for continuous measures) or odds ratio (for binary measures) and 95% confidence interval.</p></span></div><span id="fn-fn-23"></span><div content-id="fn-23" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>b</em></sup>Between-cluster comparisons performed if overall <em>p</em>-value among clusters was statistically significant after Hochberg correction and results are presented as between-group standardized mean differences in change scores or ratios of within groups odds ratios (RORs) for symptom development at follow-up.</p></span></div><span id="fn-fn-24"></span><div content-id="fn-24" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>c</em></sup>Within-group estimate statistically significant after Hochberg correction.</p></span></div><span id="fn-fn-25"></span><div content-id="fn-25" class="footnote"><span class="fn"><p class="chapter-para"><sup><em>d</em></sup>Comparison between groups significant at within outcome Bonferroni corrected <em>p</em> < .017.</p></span></div><span id="fn-fn-26"></span><div content-id="fn-26" class="footnote"><span class="fn"><p class="chapter-para">DS = Disturbed Sleep; MS = Minimally Symptomatic; S = Sleepy; CI = confidence interval.</p></span></div></div></div></div><p class="chapter-para">We observed significant differences between clinical subgroups in the proportion of patients reporting hypertension and cardiovascular disease at follow-up (<span class="link link-data-supplement" data-supplement-target="sup1"></span><span class="content-section supplementary-material"><a path-from-xml="sup1" href="https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/sleep/41/3/10.1093_sleep_zsx201/2/zsx201_suppl_supplemental_tables.pdf?Expires=1735725789&Signature=Bgukbqtzl6YKW45JV5lHxrImr4IkDZJhbfRFu16RAKJRlII218nYt7gjO5IkxzBvZUQ5rSIQdakOoerSBVIQINSJ2IE5MOqHV~Pcf1GZTEaFmnw7ZsWgBbaOMm1BXT9v3hQGuVx7DOBLHE0Kx4VMnb47gqlyGj9fehqrv7qw-TuT0~Tnw3vTSO2w0JLhRECPMsEediagZAFyxBUcYkcdVY516KJRaQHd8N5n6X3p-VFWLVolix7zHhCQng8CoblXfCqzI2zqLJyD4jdPdhONaeChDefQz5mYam1KimuvoMRZuSRwBHqfaJr5WTVPy~Wah854hzd-8QqzEcYxjq3Edw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA">Supplementary Table S2</a></span>). The Minimally Symptomatic group had higher rates of hypertension (55.0% vs. 46.7% and 41.6%; <em>p</em> = .020) and cardiovascular disease (24.1% vs. 13.5% and 13.4%; <em>p</em> = .002) than the Disturbed Sleep and Sleepy groups. At baseline, comparisons of these major comorbidities had been suggestive, but not statistically different. In adjusted models, the changes in likelihood of incident hypertension or cardiovascular disease were not significantly different among groups (<span class="xrefLink" id="jumplink-T5"></span><a href="javascript:;" reveal-id="T5" data-open="T5" class="link link-reveal link-table xref-fig">Table 5</a>). Changes in reported comorbidities over the 2-year follow-up were insufficiently frequent to obtain robust estimates of PAP effects within groups.</p> <h2 scrollto-destination=118223276 id="118223276" class="section-title js-splitscreen-section-title" data-legacy-id=s19>Discussion</h2> <p class="chapter-para">Consistent with our hypotheses, the results of this study demonstrate that although symptoms improved overall among each of the three clinical phenotypes of moderate-to-severe OSA, patterns of treatment response after 2 years of PAP therapy varied based on initial clinical presentation. Participants in the Sleepy group experienced broad improvement in daytime and nocturnal OSA symptoms, particularly those related to daytime fatigue and falling asleep involuntarily (including drowsy driving). Physical health was lowest at baseline in this group and improved significantly more in the Sleepy group compared with the others. In contrast, prior analyses in the ISAC cohort using the ESS alone to categorize sleepy patients did not identify patients likely to report a greater improvement in quality of life.<sup><span class="xrefLink" id="jumplink-CIT0012"></span><a href="javascript:;" reveal-id="CIT0012" data-open="CIT0012" class="link link-ref link-reveal xref-bibr">12</a></sup> Overall, effect sizes were moderate to large when comparing sleepiness, sleep quality, and apneic symptom changes in the Sleepy group to changes in other two groups, especially those in the Minimally Symptomatic group. PAP adherence was most clearly associated with symptom responses in the Sleepy group, within which PAP effect sizes for symptom improvement in adherent patients were generally moderate or large compared with nonusers.</p><p class="chapter-para">In contrast, Minimally Symptomatic patients initially had fewer complaints and thus, unsurprisingly, reported fewer improvements in symptoms. Membership in the Minimally Symptomatic group was associated with a small drop in diastolic BP at follow-up, a finding of potential clinical significance across a larger population of such patients. Daytime sleepiness and physical fatigue also improved significantly at follow-up in this group.</p><p class="chapter-para">Finally, the Disturbed Sleep group reported significant improvements in a number of symptoms, including those related to insomnia (e.g., difficulty falling asleep and waking often during the night). However, PAP users and nonusers generally reported similar changes in insomnia symptoms, suggesting that factors aside from PAP treatment play important roles in the evolution of insomnia complaints. Other analyses of the relationship between OSA and insomnia in the ISAC cohort have demonstrated that difficulty maintaining sleep responds to PAP therapy while difficulty initiating sleep is not responsive to PAP.<sup><span class="xrefLink" id="jumplink-CIT0023"></span><a href="javascript:;" reveal-id="CIT0023" data-open="CIT0023" class="link link-ref link-reveal xref-bibr">23</a></sup></p><p class="chapter-para">Our findings are derived from a large cohort representative of the spectrum of people with moderate–severe OSA across Iceland, with high initial participation (>90%) and retention (>85%) rates. Importantly, they suggest that identifying patients by their clinical phenotypes provides a new paradigm for informing treatment expectations among both providers and patients with OSA. Furthermore, they demonstrate that limiting definitions of treatment response to one or a few indicators, such as change in ESS, may fail to fully capture the benefits of PAP therapy in some subgroups. For instance, members of the Sleepy group reported both an elevated baseline ESS and daytime sleepiness or drowsiness; both complaints improved with treatment. In contrast, despite normal mean ESS scores in the Disturbed Sleep and Minimally Symptomatic groups at baseline, more than two-thirds of patients in both groups acknowledged daytime sleepiness or drowsiness. With treatment, the absolute proportion describing this symptom fell more than 15% in each group. These different patterns support the idea of sleepiness as a multidimensional construct<sup><span class="xrefLink" id="jumplink-CIT0024"></span><a href="javascript:;" reveal-id="CIT0024" data-open="CIT0024" class="link link-ref link-reveal xref-bibr">24</a></sup> and invite caution when considering how to measure treatment response, especially since fewer than half of patients in this sample fit the “traditional” Sleepy OSA phenotype.</p><p class="chapter-para">Our approach and results contrast with a recent report describing five clinical and demographic-based phenotypes of OSA, in which effects of OSA therapy were examined using a uniform definition of treatment response (defined as daily CPAP use ≥4 hr and either a decrease in ESS of ≥4 points if ESS > 10 at baseline or an increase in SF-36 energy or vitality of at least seven points) across groups.<sup><span class="xrefLink" id="jumplink-CIT0025"></span><a href="javascript:;" reveal-id="CIT0025" data-open="CIT0025" class="link link-ref link-reveal xref-bibr">25</a></sup> Groups characterized by milder symptoms with or without comorbid disease (similar to our Disturbed Sleep and Minimally Symptomatic groups) were less likely to achieve successful CPAP treatment response compared with more symptomatic groups. We propose that, alternatively, such patients may not be less likely to respond, but rather, that the nature and magnitude of their treatment success differs from patients with “traditional” OSA characteristics. Among other recent studies in which investigators have used demographic, clinical, and sleep study characteristics to perform cluster analyses in a range of people with OSA, none have assessed response to treatment by initial cluster assignment.<sup><span class="xrefLink" id="jumplink-CIT0026 CIT0027 CIT0028 CIT0029"></span><a href="javascript:;" reveal-id="CIT0026 CIT0027 CIT0028 CIT0029" data-open="CIT0026 CIT0027 CIT0028 CIT0029" class="link link-ref link-reveal xref-bibr">26–29</a></sup></p><p class="chapter-para">Adherence to PAP was significantly higher among patients in the Sleepy group compared with those in the Disturbed Sleep and Minimally Symptomatic groups. A similar finding was reported by a group of European investigators examining PAP adherence in people with OSA defined a priori by clinical phenotype into groups analogous to ours.<sup><span class="xrefLink" id="jumplink-CIT0029"></span><a href="javascript:;" reveal-id="CIT0029" data-open="CIT0029" class="link link-ref link-reveal xref-bibr">29</a></sup> Nevertheless, we find it notable that rates of CPAP adherence in the Disturbed Sleep and Minimally Symptomatic groups were greater than 60% at 2-year follow-up. Although evidence suggests that greater daytime sleepiness predicts better PAP adherence,<sup><span class="xrefLink" id="jumplink-CIT0030"></span><a href="javascript:;" reveal-id="CIT0030" data-open="CIT0030" class="link link-ref link-reveal xref-bibr">30</a></sup> patients’ perceived benefit from PAP—including improvement in functional status—also predicts continued use.<sup><span class="xrefLink" id="jumplink-CIT0031 CIT0032 CIT0033"></span><a href="javascript:;" reveal-id="CIT0031 CIT0032 CIT0033" data-open="CIT0031 CIT0032 CIT0033" class="link link-ref link-reveal xref-bibr">31–33</a></sup> Recognizing that patients with atypical OSA symptoms or normal ESS scores can derive meaningful benefit from PAP treatment helps explain why Minimally Symptomatic and Disturbed Sleep patients remained motivated to use PAP at rates approaching those among traditionally “Sleepy” patients. Consistent with these relatively high adherence rates within each group, our analyses did not support that differential amounts of PAP adherence played a role in different treatment response among three clinical phenotypes.</p><p class="chapter-para">We were initially surprised that across all subgroups, even non-PAP users reported improvements in symptoms, albeit generally modest ones compared with full PAP users. Numerous studies have reported small reductions in OSA symptoms with PAP placebo therapies.<sup><span class="xrefLink" id="jumplink-CIT0034 CIT0035 CIT0036 CIT0037"></span><a href="javascript:;" reveal-id="CIT0034 CIT0035 CIT0036 CIT0037" data-open="CIT0034 CIT0035 CIT0036 CIT0037" class="link link-ref link-reveal xref-bibr">34–37</a></sup> Fewer reports have described whether OSA symptoms stabilize, worsen, or improve in untreated individuals. Two studies examining PAP use in moderate and severe OSA observed small symptom improvements after 3 months even among patients with mean use of ≤2 hr per night, including 10%–20% of participants in each study with no nightly PAP use.<sup><span class="xrefLink" id="jumplink-CIT0038"></span><a href="javascript:;" reveal-id="CIT0038" data-open="CIT0038" class="link link-ref link-reveal xref-bibr">38</a>,<span class="xrefLink" id="jumplink-CIT0039"></span><a href="javascript:;" reveal-id="CIT0039" data-open="CIT0039" class="link link-ref link-reveal xref-bibr">39</a></sup> These findings suggest that, as we observed, untreated patients are likely to report fewer symptoms at follow-up, perhaps due in part to regression to the mean, i.e., the tendency of an extreme observation to be less extreme when re-evaluated. Another possibility is that some participants benefited from alternative treatments (e.g., weight loss and oral appliance); however, we observed similar results after excluding these individuals in sensitivity analyses.</p><p class="chapter-para">Individuals in the ISAC cohort with initial and late insomnia have previously been observed to be less likely to use PAP.<sup><span class="xrefLink" id="jumplink-CIT0011"></span><a href="javascript:;" reveal-id="CIT0011" data-open="CIT0011" class="link link-ref link-reveal xref-bibr">11</a></sup> In the current analyses, we observed that full PAP users in the Disturbed Sleep group reported moderately greater improvements compared with nonusers in symptoms likely directly related to sleep-disordered breathing, e.g., restless sleep, feeling rested upon waking, daytime sleepiness, and witnessed apneas. However, insomnia-related symptoms such as difficulty falling asleep and waking up early appeared relatively resistant to PAP, as changes did not differ significantly between full PAP users and nonusers.</p><p class="chapter-para">In our study, small reductions in diastolic BP 2 years after treatment initiation were limited to the Minimally Symptomatic and Sleepy groups. This is an intriguing finding that needs to be replicated in a larger cohort with the ability to estimate PAP effects, but may have important implications for patient care, especially as a recent study examining rates of cardiovascular comorbidity among patients with similarly defined clinical OSA phenotypes observed that the excessively somnolent group had the lowest comorbidity rate and the insomnia group had the highest.<sup><span class="xrefLink" id="jumplink-CIT0029"></span><a href="javascript:;" reveal-id="CIT0029" data-open="CIT0029" class="link link-ref link-reveal xref-bibr">29</a></sup> We also found higher proportions of hypertension and cardiovascular disease in the Minimally Symptomatic group at follow-up compared with the Sleepy and Disturbed Sleep groups; however, these changes in comorbidities over the follow-up period were not significantly different.</p><p class="chapter-para">We believe that our results are a necessary first step towards the development of personalized therapies for OSA. Our finding that each of the clinical phenotypes derives benefit suggests that patients in all groups should be considered for OSA treatment and for testing of new clinical options. Our analyses identified the various ways in which patients with specific clinical phenotypes respond to standard therapy, which can help inform the clinical expectations of both patients and providers. For example, clinicians may be more careful to caution people with OSA with insomnia symptoms—i.e., those similar to the Disturbed Sleep phenotype—that these symptoms may not improve with PAP therapy. Meanwhile, providers can suggest more confidently to Minimally Symptomatic patients with moderate-to-severe OSA that they, too, can expect to see moderate improvement in certain OSA symptoms with PAP treatment. Our findings also identify resistant symptoms and other characteristics that can be constructively targeted in future studies.</p><p class="chapter-para">We anticipate two types of approaches in future investigations—studies that compare the relative efficacy of two or more approaches within a specific clinical phenotype and studies that examine whether a single OSA treatment is more effective for one clinical phenotype than another. For example, whether people with OSA with the Disturbed Sleep phenotype may benefit from targeted therapy for insomnia-related symptoms (e.g., cognitive behavioral therapy for insomnia) should be evaluated in future phenotype-specific trials. Other studies could examine whether treatments such as oral appliances or hypoglossal nerve stimulation are more effective for patients with specific clinical phenotypes or whether different clinical phenotypes vary in their susceptibility to cardiovascular disease and the degree to which antihypertensive effect or cardiovascular risk reduction can be achieved with PAP or other therapies. This latter point is especially important given evidence from the recent SAVE trial that CPAP use may not reduce cardiovascular events in nonsleepy individuals with OSA.<sup><span class="xrefLink" id="jumplink-CIT0040"></span><a href="javascript:;" reveal-id="CIT0040" data-open="CIT0040" class="link link-ref link-reveal xref-bibr">40</a></sup> Additionally, given the modest improvement in global physical health reported by the Sleepy group, but not the other clinical phenotypes, future studies could examine quality of life differences among OSA phenotypes in greater depth, as group membership may predict improvement in more general measures.</p><p class="chapter-para">Strengths of this study included its large sample size, long-term follow-up, high participation and retention rate, and use of validated instruments and study procedures. All people with OSA in Iceland are referred to a single location for treatment, and in this large prospective observational study, all patients followed the same treatment protocol; neither participants nor study staff was aware of individuals’ cluster assignments. Although participants were cognizant of their own PAP use, and thus treatment effects may have been exaggerated among adherent PAP users, the need for observational studies was endorsed recently by the National Institutes of Health.<sup><span class="xrefLink" id="jumplink-CIT0041"></span><a href="javascript:;" reveal-id="CIT0041" data-open="CIT0041" class="link link-ref link-reveal xref-bibr">41</a></sup> In this context, the use of propensity score adjustment in the examination of PAP treatment effects is an important strength as it reduces biases inherent in observational studies and allows for more robust estimates of treatment effects. Although propensity score methods can adjust for imbalance in measured covariates, we note that unmeasured confounders are controlled for only to the extent that they are correlated with the variables included in the model. Overall, our results highlight the heterogeneity of both OSA clinical presentation and response to PAP treatment.</p><p class="chapter-para">Our study has limitations. As the ISAC cohort included only patients with moderate–severe OSA from Iceland, results may not be applicable to individuals with mild OSA and/or those from other world populations. There were relatively few female participants and adults >65 years of age, reflecting the population of people with OSA in Iceland. Objective PAP adherence data were available for most (76%), but not all participants who used PAP. Standardized self-estimates of PAP use were, however, validated against objective data,<sup><span class="xrefLink" id="jumplink-CIT0011"></span><a href="javascript:;" reveal-id="CIT0011" data-open="CIT0011" class="link link-ref link-reveal xref-bibr">11</a></sup> and overestimates of PAP usage should bias results towards the null. Furthermore, secondary analyses performed after excluding participants without objective PAP adherence data showed similar results. Although PAP adherence may have been overestimated by our use of data from 28 days prior to follow-up assessment, PAP usage has generally been observed to be stable over time.<sup><span class="xrefLink" id="jumplink-CIT0042"></span><a href="javascript:;" reveal-id="CIT0042" data-open="CIT0042" class="link link-ref link-reveal xref-bibr">42</a>,<span class="xrefLink" id="jumplink-CIT0043"></span><a href="javascript:;" reveal-id="CIT0043" data-open="CIT0043" class="link link-ref link-reveal xref-bibr">43</a></sup> For non-PAP users, a financial disincentive against keeping the device also existed, as patients in Iceland pay a monthly fee for this equipment. Although we are confident in how PAP adherence was estimated, the lack of objective PAP data for all individuals prevented our inclusion of residual AHI, a measure of PAP efficacy, as a covariate in our analyses. Among individuals prescribed an oral appliance, information on usage of the appliance was unavailable. However, utilization of alternative treatments by PAP nonusers should also bias results towards the null (i.e., no effect of PAP), and sensitivity analyses excluding nonusers reporting alternate treatments produced similar results to those in the full sample. As the groups are based on self-reported symptoms, we note that although symptoms are important in defining a patient’s perception of disease and developing clinical treatments, patients can also misclassify or misreport their symptoms. Finally, changes in medications may have affected changes in patient symptoms over the follow-up period.</p> <h2 scrollto-destination=118223290 id="118223290" class="section-title js-splitscreen-section-title" data-legacy-id=s20>Conclusions</h2> <p class="chapter-para">Different clinical phenotypes of OSA respond differently to PAP treatment, varying by initial OSA presentation. Although we plan to evaluate the generalizability of our results in other, more diverse populations, the results of our study can be applied directly to both current clinical practice and future research. In practice, recommending against treatment for people with OSA who do not initially present with elevated Epworth scores or who articulate insomnia symptoms fails to recognize that such individuals may derive meaningful benefits from treatment of OSA. Assessing a limited spectrum of treatment response measures (e.g., Epworth score) within all people with OSA is likely to underestimate treatment effects, as this benefit varies between subgroups. Our findings underscore the need to consider initial OSA phenotype when designing future trials, perhaps by prospectively defining outcomes specific to different clinical subtypes, or by conducting clinical trials within individuals with specific OSA phenotypes.</p> <h2 scrollto-destination=118223292 id="118223292" class="section-title js-splitscreen-section-title" data-legacy-id=s21>Supplementary Material</h2> <p class="chapter-para">Supplementary material is available at <em>SLEEP</em> online.</p> <h2 scrollto-destination=118223294 id="118223294" class="section-title js-splitscreen-section-title" data-legacy-id=s22>Funding</h2> <p class="chapter-para">This study was supported by a grant from the National Institutes of Health (P01 HL094307).</p> <h2 scrollto-destination=118223296 id="118223296" class="section-title js-splitscreen-section-title" data-legacy-id=s23>Disclosure Statement</h2> <p class="chapter-para">ESA has been a consultant for Nox Medical and has received a lecture fee from Weinmann.</p> <h2 scrollto-destination=118223298 id="118223298" class="backacknowledgements-title js-splitscreen-backacknowledgements-title" >Acknowledgments</h2> <p class="chapter-para">We are grateful to Sigrun Gudmundsdottir, Lovisa Gudmundsdottir, Magdalena Osk Sigurgunnarsdottir, Kristján Andri Kristjánsson, Matthew Thorne-Fitzgerald, Bethany Staley, and the other staff at the Sleep Centers of Landspitali University Hospital and the University of Pennsylvania who helped assemble and analyze the data. 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Changing Faces of Obstructive Sleep Apnea: Treatment Effects by Cluster Designation in the Icelandic Sleep Apnea Cohort | SLEEP | Oxford Academic