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Incidence and burden of comorbid pain and depression in patients with chronic rhinosinusitis awaiting… Hanna, Bassem M N; Crump, R. T; Liu, Guiping; Sutherland, Jason M; Janjua, Arif S Mar 27, 2017

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ORIGINAL RESEARCH ARTICLE Open AccessIncidence and burden of comorbid painand depression in patients with chronicrhinosinusitis awaiting endoscopic sinussurgery in CanadaBassem M. N. Hanna1, R. Trafford Crump2, Guiping Liu3, Jason M. Sutherland3* and Arif S. Janjua1AbstractBackground: This study sheds important light on the association between sino-nasal symptoms and global qualityof life in patients with chronic rhinosinusitis waiting for endoscopic sinus surgery. Using patient-reportedinformation collected pre-operatively, the primary objective was to report on patients’ pre-surgical sino-nasalsymptoms and their association with self-reported pain and depression. The secondary objective was to report onlevels of depression and pain among patients in the sample reporting severe sleep problems.Methods: This is a cross-sectional study of patient-reported outcomes collected prospectively from a cohort of 261patients assigned to the wait list for elective endoscopic sinus surgery in a large urban region of Canada.Results: Younger patients and patients with other medical comorbidities were most likely to report significantsymptoms of chronic rhinosinusitis and substantial associated pain and depression. In the primary analyses, patientsreporting significant symptoms of chronic rhinosinusitis were more likely to report moderate depression or highpain (p < 0.01). Subsequently, chronic rhinosinusitis patients with severe sleep problems were 82% likely to reportmoderate or severe depression and pain.Conclusion: Preoperative management of depression and pain may be considered in order to improve the health-related quality of life of patients waiting for ESS. As depression and pain were highly prevalent, patients with severesleep problems may be candidates for prioritized access.Keywords: Chronis sinusitis, Depression, Endoscopic sinus surgery, Pain, Patient-reported outcomes, Sleep, Qualityof lifeBackgroundThe syndrome of chronic rhinosinusitis (CRS) is a het-erogeneous cluster of sino-nasal symptoms associatedwith mucosal inflammation. First line treatment for CRSincludes medical/pharmacological interventions, such assteroids (topical and/or systemic) and antibiotics. It isestimated that more than 5% of the Canadian populationsuffer from CRS-related symptoms, resulting in almostone million prescriptions per year [1, 2] and cause sig-nificant demands on provincial health care systems.Many patients with CRS eventually fail pharmaco-logical intervention and progress to endoscopic sinussurgery (ESS) for treatment. This is problematic formany provincial health care systems, where demand forelective (scheduled) surgery outstrips supply which, inturn, results in substantial wait times for CRS patients.For example, in 2016, Nova Scotia reported the medianwait time for ESS of approximately 4 months [3] – similarmedian wait times have been reported in British Columbia(BC) [4]. Wait times are not unique to ESS, asCanada lags many of its peer countries in access tospecialized care [5] – despite significant investments,* Correspondence: jason.sutherland@ubc.ca3Centre for Health Services and Policy Research, School of Population andPublic Health, University of British Columbia, 201 – 2206 East Mall, V6T 1Z3Vancouver, CanadaFull list of author information is available at the end of the article© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Hanna et al. Journal of Otolaryngology - Head and Neck Surgery  (2017) 46:23 DOI 10.1186/s40463-017-0205-3wait times for elective surgery continue to be a majorpolicy issue for provincial governments [6–8].To manage those patients awaiting elective surgery, re-gional health authorities in Canada use wait lists. Thesewait lists are registries for elective surgeries, recordingdemographics, diagnosis, surgery and date information –including the date that patients were assigned to thewait list and the date of their scheduled surgery. TheAchilles heel of the wait list is that very little is knownregarding symptom severity or the health status of thosepatients in the registry. As previous study into the waitlist registry has observed, there is no relationship be-tween the self-reported severity of patients’ symptomsand their level of triage on the wait list [9].The discordance between the severity of patients’symptoms and the length of time they wait for surgery isconcerning, particularly in the case of CRS. Sino-nasalsymptoms have been documented to be associated withsignificant anxiety and depression [10, 11]; especially inpatients without polyps [11], and more than half of pa-tients with CRS reportedly suffer from pain [12, 13].Dysfunction of sleep and pain have been seen to beinter-related in the presence of depression [13]. How-ever, very little is known about the health status of thosepatients with CRS on the wait list for ESS, representinga significant knowledge gap that can impair clinicaldecision making.To address this knowledge gap, the purpose of this de-scriptive study is to measure the symptom burden andthe prevalence of pain or depression among CRS pa-tients waiting for ESS after failed medical management.Previous work has established a need for this informa-tion in order to identify opportunities to improve thehealth status of waiting patients [14].To do so, this study uses validated patient-reportedoutcomes (PROs) designed to systematically measure theseverity of symptom and functional impairments. Theprimary analyses is to measure the association betweendepression or pain with patients’ self-reported symptomsof chronic rhinosinusitis. The secondary objective is ex-plore emerging findings regarding relationship betweenself-reported sleep problems with depression or pain[15]. The results from cross-sectional analyses of PROscould be used to identify potential gaps in patients’ carewhile waiting for ESS and potentially provide insightinto policies for refining surgical wait times.MethodsPROs were prospectively collected from a cohort of CRSpatients assigned to the surgical wait list for ESS in theVancouver Coastal Health (VCH) Authority, a regionencompassing Vancouver, Canada – home to over onemillion residents. Vancouver Coastal Health is responsiblefor managing the wait list for elective surgeries performedin its acute hospitals.The population of potential study participants in-cluded all patients newly enrolled on VCH’s wait list forbilateral endoscopic sino-nasal surgery with a surgeonidentified diagnosis of ‘chronic sinusitis/nasal polyposis’.Specific surgical codes are provided in Additional file 1.Potential participants were identified from VCH’s waitlist registry, which includes patients’ contact information.A VCH surveyor contacted potential participants using astandardized telephone script within 2 weeks of beingenrolled on the wait list. To be eligible, patients had tobe community-dwelling, 19 years or older, scheduled forsurgery at least 14 days from being enrolled on the waitlist, and able to respond (with or without assistance) tosurvey questions in English. Patients agreeing to partici-pate were sent the initial survey package, which includedsurvey instructions, the PRO instruments, and a stampedreturn envelope.Comorbidity information was collected from partici-pants using a checklist of common chronic and acute con-ditions. Age and sex was collected via the wait list fromparticipants and non-participants; these groups were com-pared based on available demographic information. Thisstudy reports on participants’ cross-sectional PROs datacollected between September 2012 and April 2016. TheUniversity of British Columbia’s Behavioral ResearchEthics Board (BREB) approved the study.InstrumentsA number of different PRO instruments were completedby participants, including the Sino-Nasal Outcomes Test(SNOT)-22, the Patient Health Questionnaire (PHQ)-9,and the PEG, representing pain intensity (P) and inter-ference with enjoyment of life (E) and general activity(G). The SNOT-22 was used to measure the severity ofCRS-related symptoms. The SNOT-22 is a widely used in-strument that has previously demonstrated strong validity,reliability, responsiveness, and ease of interpretation [16].As its name implies, it is comprised of 22 items scoredfrom 0 to 5. The scores for each item are aggregated toarrive at a global score that ranges from 0 (i.e., perfecthealth) to 110 (i.e., worst health). The average SNOT-22score in a healthy non-symptomatic adult is 7 [17].Depression in patients was measured using the PHQ-9[18]. This PRO instrument assesses depression in twodimensions: symptoms and functional impairment. Itincludes nine items, each of which is scored using afour-point Likert scale ranging from 0 (i.e., “Not at allbothered”) to 3 (i.e., “Bothered nearly every day”). Thescore for each item is aggregated to arrive at a globalscore that ranges from 0 to 27. PHQ-9 scores of 10, 15and 20 represent, respectively, moderate, moderately se-vere, and severe depression [18].Hanna et al. Journal of Otolaryngology - Head and Neck Surgery  (2017) 46:23 Page 2 of 6The PEG was used to measure comorbid pain [19].The PEG has three items; one representing pain inten-sity and two items for interference. Each item is scoredon a 0–10 scale. The overall score is reported as theaverage of the three items, and scores greater than threehave been indicative of high level of pain [20].Statistical analysisAnonymized data was analyzed using SAS 9.4 (Cary,NC). Age and gender sub-groups were compared be-tween participants and non-participants to ascertainpossible participant bias. Univariate analyses of theSNOT-22 score were presented overall, by age group,gender and count of reported comorbidities. Few partici-pants reported more than three chronic health condi-tions, so comorbidity data was categorized into countsof 0, 1, 2, 3 and greater than 3.Depression scores (PHQ-9) and pain scores (PEG)were summarized, presented using cut-points validatedin the literature [18, 20]. Participants’ depression andpain scores were examined relative to their SNOT-22scores to provide in-depth insight into associationsbetween CRS symptoms and general health.Independent multivariate models were used to meas-ure associations between patients’ SNOT-22 score withtheir PHQ-9 and PEG scores and other variables in thethree models, including age, sex and category of countof comorbidity. Residuals were assessed visually to detectdepartures from the models’ assumptions. P-values forthe regression models were reported. Since the analyseswere exploratory, no attempt was made to adjust p-valuesfor multiple comparisons.A linear model was used to analyze SNOT-22 scoresto measure whether there was an association betweenSNOT-22 scores with PHQ-9 depression or PEG painscores, after adjusting for age, sex and comorbidities.The PHQ-9 and PEG scores were included in theanalysis of covariance model as continuous variables.P-values were reported after assessing goodness of fit.Patients’ sleep quality was evaluated. The SNOT-22sleep score was calculated as the sum of the items asso-ciated with sleep quality, items 11–18. The sleep scoreranged from 0 to 40, where a score of 40 representedthe worst state of sleep health-related quality of life.Patients’ sleep scores were stratified by cut-points of thePHQ-9 and PEG representing moderate depression andhigh pain, respectively. For each quintile of SNOT-22sleep score, mean (and standard deviation) PHQ-9 andPEG scores were calculated.ResultsThe study sample included 261 participants, evenly splitbetween males and females, with the modal age groupbetween 51 and 70 years of age (Additional file 1). Therewere no significant differences between study partici-pants and patients that did not participate on the char-acteristics of age or gender which would have indicatedselection bias; see Additional file 1 for a summary ofparticipants and non-participants.Analysis of participants’ SNOT-22 scores are providedin Table 1. The average SNOT-22 score was 42.1. Theresults from the univariate analyses show that youngerage tended to be associated with higher SNOT-22 scoresrelative to older participants; participants between 31 and50 years of age had SNOT-22 scores 18 points higher thanparticipants aged 70 years and older (p < 0.01). Partici-pants with more comorbidities reported higher SNOT-22scores than those without – participants with three ormore comorbidities reported SNOT-22 scores 28 pointshigher than those participants without comorbidities(p < 0.01). There were no differences in SNOT-22 scoresbetween genders (p = 0.16).Overall, 19.2% of participants reported symptoms as-sociated with clinical depression. As shown in Table 2,depression was unevenly reported among the study’sparticipants. Those between 31 and 50 years of age re-ported significantly higher PHQ-9 scores than partici-pants older than 70 years (p < 0.01). Participants withmore than one comorbidity reported higher levels of de-pression. Further, participants with three or more comor-bidities reported PHQ-9 scores 2.7 points higher thanthose without any significant comorbidities (p < 0.01).Among participants, 44.6% reported PEG scores ofthree or greater, indicating high pain. Pain was highestamong participants 50 years of age or less; relative to theTable 1 Multivariate analysis of patients’ SNOT-22 scores, adjustingfor demographics and comorbiditiesModel parameter Coefficient Standard error F-StatisticP-ValueIntercept 19.39 4.88 <0.01GenderMale ReferenceFemale 3.50 2.52 0.16Age group< = 30 14.00 6.26 0.0231–50 18.72 4.67 <0.0151–70 12.70 4.30 <0.0170+ ReferenceNumber of comorbidities0 Reference1 4.04 3.41 0.232 10.50 3.86 <0.013 4.31 4.77 0.363+ 28.45 4.12 <0.01Hanna et al. Journal of Otolaryngology - Head and Neck Surgery  (2017) 46:23 Page 3 of 6oldest age group, this age group reported PEG scores 1.6points higher. There were no differences in pain scoresbetween genders (p = 0.20). Participants with comorbidi-ties reported higher pain scores. Participants with threeor more comorbidities reported pain scores 0.78 highercompared to those with no comorbidities (p < 0.01).As shown in Table 3, higher SNOT-22 scores werehighly, and independently, associated with depression andpain scores (both p < 0.01). Adjusting for patient demo-graphics and comorbidities, each point increase in PHQ-9score was associated with a 1.41 point increase in SNOT-22 score (p < 0.01). For a CRS patient with treatabledepression, and PHQ-9 score of 10, there was an expectedincrease of 14 points in the participants’ SNOT-22 score.Pain was also highly significantly associated with SNOT-22 score after adjusting for patient demographics andcomorbidities (p < 0.01). Each point increase in the PEGwas associated with a 2.42 point increase in SNOT-22score. This relationship meant that for a patient with highpain – a PEG score of 3 – there was an expected 7 pointincrease in the participants’ SNOT-22 score.The results of Table 4 show the association betweenparticipants’ quintile of SNOT-22 sleep score and de-pression and pain. There was a positive association be-tween sleep scores and depression scores – participantsreporting the most severe problems with sleep wereseveral-fold more likely to report moderate depressionand high pain as participants with high quality of sleep.Among participants, patients with significant sleep prob-lems were at least 80% likely to have at least moderatedepression and high pain.DiscussionThis study focused on patients’ self-reported CRS-related symptoms at the time they were enrolled on theVCH’s wait list for ESS. Our primary interest was in theprevalence of pain and depression, and the relationshipbetween these morbidities and CRS symptoms (as mea-sured by the SNOT-22). Younger participants were morelikely to have worse SNOT-22 scores, higher rates of de-pression and pain after adjusting for other comorbidities.This finding is important, as the relationship betweenthe SNOT-22 score (a condition-specific instrument)and other specific instruments designed to be sensitiveto depression and pain, was previously unclear. TheseTable 2 Multivariate analysis of patients’ PHQ-9 and PEG scores,adjusting for demographics and comorbiditiesPHQ-9 PEGParameter Coefficient Std Err. P-Value Coefficient Std Err. P-ValueIntercept 2.13 0.21 <0.001 1.35 0.18 <0.01GenderMale Reference ReferenceFemale 0.97 0.11 0.75 1.13 0.09 0.20Age group< =30 1.52 0.26 0.11 1.61 0.23 0.0431–50 1.76 0.2 <0.01 1.62 0.17 <0.0151–70 1.34 0.18 0.10 1.40 0.16 0.0370+ Reference ReferenceNumber of comorbidities0 Reference Reference1 1.03 0.14 0.84 1.33 0.13 0.022 1.74 0.16 <0.01 1.72 0.14 <0.013 1.61 0.2 0.02 1.83 0.18 <0.01> 3 3.16 6.58 <0.01 2.39 0.15 <0.01Table 3 Multivariate analysis of patients’ SNOT-22 scores, adjust-ing for demographics and comorbiditiesParameter Estimate Standard error F-StatisticP-ValueIntercept 16.31 4.04 <0.01GenderMale ReferenceFemale 2.68 2.12 0.20Age group< = 30 6.53 5.31 0.2231–50 11.04 3.92 <0.0151–70 7.41 3.58 0.0370+ ReferenceNumber of comorbidities0 Reference1 1.92 2.87 0.502 2.44 3.31 0.463 −2.66 4.07 0.513+ 10.23 3.83 <0.01Patient-reported outcomesPHQ-9 1.41 0.26 <0.01PEG 2.42 0.50 <0.01Table 4 PHQ-9 and PEG scores shown by quintile of the sleepfunction score of SNOT-22Depression PHQ-9 Pain PEGSNOT-22 sleepfunction scoreN Mean (SD) Score > =10(%)Mean (SD) Score > =3(%)Overall 261 5.2 (5.4) 19.2% 2.9 (2.7) 44.6%0–8 62 0.8 (1.6) 1.6% 0.7 (1.1) 6.6%9–16 61 3.5 (3.9) 8.2% 2.3 (2.4) 37.7%17–24 75 5.6 (3.6) 12.0% 3.2 (2.0) 53.3%25–32 46 9.4 (5.7) 45.7% 5.2 (2.7) 76.1%33–40 17 14.4 (6.1) 82.4% 6.0 (3.2) 82.4%PHQ-9 scores of ten above and PEG scores of three and above are associatedwith moderate depression and high pain, respectivelyHanna et al. Journal of Otolaryngology - Head and Neck Surgery  (2017) 46:23 Page 4 of 6are important domains which have been previously re-ported to be inadequately measured by the SNOT-22[21], though the effects of which have been suggestedelsewhere [11, 13].The results also found that the worst pain and depres-sion was reported by a subset of patients with severesleep problems. Indeed, relationships between depres-sion, pain and sleep have been raised by others [15]. Theassociations between these factors in this study suggestthat surgeons could prioritize patients, and improvehealth status, on the basis of sleep problems alone.The implications of these findings are substantial. Sincethis study’s participants’ SNOT-22 scores were comparableto those reported in literature [17, 22, 23], there is verylikely to be substantial depression and pain among thepopulation of patients waiting for ESS. In light of thesefindings, an effective strategy for improving global healthcould consider complementary non-surgical interventionsfor depression and pain, focused on patients whose pre-surgical SNOT-22 scores were in the highest quintile,reporting a number of comorbid conditions or reportingpoor sleep quality.There are some limitations of these findings. Studyparticipants were a subset of patients recruited from theVCH wait list, though there was no evidence to believethat patients participating in this study were substan-tially different from those that declined to participate.Nor do these findings mean that the results are true in allregions of Canada. Finally, as this was a cross-sectionalanalysis, one cannot draw conclusions regarding possiblecausal pathways between waiting for ESS for CRS andphysical and mental health.The knowledge generated from this study is timelyfrom a policy perspective, as BC has been directingadditional funding into elective surgeries to reducewait times [24]. The process used to generate patient-reported outcomes data for this study will also havean impact on BC’s Ministry of Health, the funderseeking to improve the patient-centredness of surgicaltreatment in the province [25], by identifying gaps inmedical treatment related to its management of surgi-cal wait lists.ConclusionCRS is a highly prevalent condition and its treatment byESS is very common. This study underscores that ap-proximately one-fifth of patients waiting for ESS reportclinically significant depression and/or pain. While anOtolaryngologist should be attentive to pain and depres-sive symptoms in all patients, when faced with lengthywaits for ESS, multi-disciplinary treatment, such asinvolving psychologists or pain management, is indi-cated for patients who pre-operatively screen withhigh SNOT-22 scores.Additional fileAdditional file 1: Appendix A. Surgical codes for defining study cohort.(DOCX 15 kb)AbbreviationsBC: British Columbia; BREB: Behavioral Research Ethics Board; CRS: Chronicrhinosinusitis; ESS: Endoscopic sinus surgery; PEG: Pain intensity (P),interference with enjoyment of life (E) and general (G) activity; PHQ-9: PatientHealth Questionnaire; PROs: Patient-reported outcomes; SNOT-22: Sino-NasalOutcomes Test-22; VCH: Vancouver Coastal Health AuthorityAcknowledgementsThis study was partially funded by the Canadian Institutes for HealthResearch (CIHR) and by in-kind contributions from Vancouver Coastal Healthauthority (VCH). Sutherland is a Scholar of the Michael Smith Foundation forHealth Research (MSFHR). CIHR, MSFHR and VCH had no role in developingthe methods, analyzing the data, or interpreting the results.FundingThis study was partially funded by a grant from the Canadian Institutes ofHealth Research (CIHR) and by in-kind contributions from Vancouver CoastalHealth authority (VCH).Availability of data and materialsThe authors have control of the anonymized analytic dataset used in this study.Authors’ contributionsJS and TC wrote the peer-reviewed grant securing the funding for the studyfrom the Canadian Institutes of Health Research. BH, TC, GL, JS and AJ (seniorauthor) each provided substantial input into research the topic’s background,interpreting the data and analyses and writing the text. GL was responsiblefor analyzing the data. All authors read and approved the final manuscript.Competing interestsThe authors declare that they have no competing interests.Consent for publicationAll authors consent to submission of this manuscript to review with theJournal of Otolaryngology - Head & Neck Surgery.Ethics approval and consent to participateThe University of British Columbia’s Behavioral Research Ethics Board (BREB)approved the study.DeclarationsThis study is not a clinical trial.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.Author details1Otolaryngology – Head and Neck Surgery, University of British Columbia,Vancouver, BC, Canada. 2Department of Surgery, University of Calgary,Calgary, Canada. 3Centre for Health Services and Policy Research, School ofPopulation and Public Health, University of British Columbia, 201 – 2206 EastMall, V6T 1Z3 Vancouver, Canada.Received: 19 January 2017 Accepted: 20 March 2017References1. 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Europeanposition paper on rhinosinusitis and nasal polyps 2012. Rhinology. 2012;50(23):4–305.18. Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: Validity of a briefdepression severity measure. J Gen Intern Med. 2001;16(9):606–13.19. Krebs EE, Lorenz KA, Bair MJ, Damush TM, Wu J, Sutherland JM, et al.Development and initial validation of the PEG, a three-item scale assessingpain intensity and interference. J Gen Intern Med. 2009;24(6):733–8.20. Miller K, Combs S, Van Puymbroeck M, Alternberger P, Kean J, Dierks T, et al.Fatigue and pain: Relationships with physical performance and patientbeliefs after stroke. Top Stroke Rehabil. 2013;20(4):347–55.21. Crump RT, Liu G, Janjua A, Sutherland JM. Analyzing the 22-item Sino-NasalOutcome Test using item response theory. Int Forum Allergy Rhinol. 2016;6(9):914–20.22. Nanayakkara J, Igwe C, Roberts D, Hopkins C. The impact of mental healthon chronic rhinosinusitis symptom scores. Eur Arch Otorhinolaryngol. 2013;270:1361–4.23. DeConde AS, Mace JC, Bodner T, Hwang PH, Rudmik L, Soler ZM, et al.SNOT-22 quality of life domains differentially predict treatment modalityselection in chronic rhinosinusitis. Int Forum Allergy Rhinol. 2014;4(12):972–9.24. Nagel J. B.C. adds $10m to cut surgery wait times [Internet]. Tri City News.2015 [cited 2015 Nov 24]. Available from: http://www.tricitynews.com/news/b-c-adds-10m-to-cut-surgery-wait-times-1.195528725. BC Ministry of Health. Provincial Surgical Executive Committee. Victoria:Future directions for surgical services in British Columbia; 2015.•  We accept pre-submission inquiries •  Our selector tool helps you to find the most relevant journal•  We provide round the clock customer support •  Convenient online submission•  Thorough peer review•  Inclusion in PubMed and all major indexing services •  Maximum visibility for your researchSubmit your manuscript atwww.biomedcentral.com/submitSubmit your next manuscript to BioMed Central and we will help you at every step:Hanna et al. Journal of Otolaryngology - Head and Neck Surgery  (2017) 46:23 Page 6 of 6

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