Steroid-eluting sinus stents for improving symptoms in chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery.

Cochrane Database of Systematic Reviews

Steroid-eluting sinus stents for improving symptoms in chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery (Review) Huang Z, Hwang P, Sun Y, Zhou B

Huang Z, Hwang P, Sun Y, Zhou B. Steroid-eluting sinus stents for improving symptoms in chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery. Cochrane Database of Systematic Reviews 2015, Issue 6. Art. No.: CD010436. DOI: 10.1002/14651858.CD010436.pub2.

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Steroid-eluting sinus stents for improving symptoms in chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW INDEX TERMS . . . . . . . . . . . . . . .

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[Intervention Review]

Steroid-eluting sinus stents for improving symptoms in chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery Zhenxiao Huang1 , Peter Hwang2 , Yan Sun1 , Bing Zhou1 1 Department

of Otolaryngology - Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China. of Rhinology, Department of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, California, USA

2 Division

Contact address: Bing Zhou, Department of Otolaryngology - Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, No.1, Dong Jiao Min Xiang, Dongcheng District, Beijing, 100730, China. [email protected]. Editorial group: Cochrane ENT Group. Publication status and date: New, published in Issue 6, 2015. Review content assessed as up-to-date: 14 May 2015. Citation: Huang Z, Hwang P, Sun Y, Zhou B. Steroid-eluting sinus stents for improving symptoms in chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery. Cochrane Database of Systematic Reviews 2015, Issue 6. Art. No.: CD010436. DOI: 10.1002/14651858.CD010436.pub2. Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT Background Functional endoscopic sinus surgery (FESS) has become a well-established approach for treating patients with chronic rhinosinusitis (CRS) refractory to medical management. However, the surgical outcome may be compromised by postoperative inflammation, polyposis and adhesions, which often require subsequent intervention. Bioabsorbable, steroid-eluting sinus stents are inserted into the nose, sinuses or both following surgery to prevent stenosis of the sinus openings during the postoperative healing period. The slow release of corticosteroid aims to decrease mucosal oedema and expedite wound healing. Whether a steroid-eluting stent offers any beneficial effects in terms of improving sinonasal symptoms has not been systematically reviewed. Objectives To assess the safety and efficacy of steroid-eluting sinus stent placement in CRS patients after FESS. Search methods The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 4); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 May 2015. Selection criteria We included all randomised controlled trials (RCTs) comparing steroid-eluting sinus stents with non-steroid-eluting sinus stents, nasal packing or no treatment in adult CRS patients undergoing FESS. Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration. Steroid-eluting sinus stents for improving symptoms in chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery (Review) Copyright © 2015 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Main results We identified no RCTs that met our inclusion criteria. Among the 159 records retrieved using our search strategy, 21 trials had the potential to be included given that they had tested sinus stents, spacers and packing materials for patients with CRS undergoing FESS. However, we excluded these trials from the review because they met some but not all of the inclusion criteria. Authors’ conclusions We are unable to provide evidence to establish whether steroid-eluting sinus stents have potential advantages and disadvantages for patients with CRS undergoing FESS. Future, high-quality RCTs are needed to assess whether or not steroid-eluting sinus stents confer any beneficial effects, over those of surgery alone, when compared to non-steroid sinus stents.

PLAIN LANGUAGE SUMMARY Steroid-eluting sinus stents for improving symptoms in chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery Background Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nasal and paranasal sinus mucosa. Although the cause of CRS remains unclear, multiple factors are likely to contribute to its development. CRS is treated with medical therapy (topical or oral steroids) and surgery. While medical treatments offer relief for most patients with CRS, functional endoscopic sinus surgery (FESS) is commonly performed. However, the surgical outcome of FESS can be compromised by postoperative inflammation, polyposis (formation of polyps) and adhesions of the nasal mucous lining, which often require subsequent interventions. Postoperative treatments are therefore required to achieve optimal long-term results. Steroid-eluting sinus stents are devices that are inserted into the nose, sinuses or both, and gradually release a steroid after FESS. They are used to prevent stenosis (narrowing) of the sinus openings and provide anti-inflammatory benefits during the postoperative healing period. However, it is unknown whether steroid-eluting sinus stents offer any beneficial effect in improving nasal symptoms of patients with CRS. Study characteristics We searched for all randomised controlled trials (RCTs) that studied the effects of steroid-eluting sinus stents compared to non-steroideluting sinus stents, nasal packing or no treatment in adult patients with CRS who underwent FESS. From the 159 records we retrieved using our search strategy, we identified 21 trials that could potentially be included as they used sinus stents for patients undergoing FESS. However, we had to exclude these trials from the review because they met some but not all of the inclusion criteria. We therefore identified no trials that could be included in the review. Key results No trials met our inclusion criteria. Quality of evidence We are unable to conclude whether or not steroid-eluting sinus stents offer more beneficial effects, over those of surgery alone, than non-steroid-eluting sinus stents, nasal packing or no treatment in patients with CRS undergoing FESS. High-quality RCTs are needed to answer this question. This review is current to May 2015.

Description of the condition

BACKGROUND

Chronic rhinosinusitis (CRS) is an inflammatory disease of the mucosa of the nose and paranasal sinuses that is present for at


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least 12 weeks. A diagnosis of CRS is based on both subjective and objective criteria: the presence of distinctive symptoms (e.g. nasal obstruction and nasal discharge) and either endoscopic or computed tomography (CT) evidence of inflammation within the nose, sinuses or both (Fokkens 2012). CRS has been subclassified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Epidemiological studies have shown that CRS affects 5% to 16% of the population and causes significant reduction in quality of life (Chen 2003; Collins 1997; Hastan 2011). Multiple factors have been implicated in the development of CRS, including environmental and host factors. Environmental factors, such as bacteria, biofilms, fungi and allergens, have been described as disease-modifying factors that lead to inflammation of the mucosa of the nose and paranasal cavities. Host factors, such immunodeficiency and eicosanoid dysregulation, also contribute to refractory infections or inflammation and have a significant impact on the severity of CRS (Kennedy 2004; Tan 2010). Although medical treatments offer relief for most patients with CRS, functional endoscopic sinus surgery (FESS) is commonly performed (about 500,000 cases of ESS are performed in the US each year). Surgical treatment is not considered a curative treatment for CRS; approximately 14% of CRS patients who undergo surgery will require revision ESS (Bhattacharyya 2004). There are many reasons for surgical failure, but common causes of suboptimal results include scarring of the sinus ostia, adhesion formation and middle turbinate lateralisation (Otto 2010). Most importantly, persistent inflammation presenting as mucosal oedema, polypoid mucosal change and recurrent polyps will also compromise the results (Bugten 2006; Ramadan 1999; Wei 2012). Evidence has shown that controlling for these postoperative issues may lead to better long-term outcomes (Kennedy 2000).

Description of the intervention Sinus stents are devices that are inserted into the nose, sinuses or both following FESS to prevent stenosis of the sinus openings during the postoperative healing period (Weber 2000). Sinus stents may be composed of non-absorbable alloplastic materials (e.g. silicone, plastic), to be removed in the office setting after a period of several days; or absorbable biomaterials (e.g. bovine gelatin, poly(lactic-co-glycolic acid)), which degrade in a controlled fashion over days to weeks following surgery. Sinus stents are also known as ’spacers’ because they maintain separation between critical areas of healing to prevent synechia formation. For example, middle meatal stents provide a mechanical barrier between the middle turbinate and lateral nasal wall; the goal of stent placement here is to avoid middle turbinate lateralisation, a complication that can lead to recurrence and propagation of chronic sinusitis. Recent advances in biomaterial technology have resulted in the development of corticosteroid-coated sinus stents, which can elute the drug in a controlled fashion via a bioabsorbable core. Currently, only one drug-eluting stent design has been approved by the

US Food and Drug Administration (FDA). However, there have been published descriptions of the off-label use of absorbable nasal packs as vehicles for steroid delivery by impregnating the packs with corticosteroid suspension after placement in the sinus cavity. Although not formally designed as stents, the bioabsorbable packs are intended to offer spacing functions in addition to delivery of the drug.

How the intervention might work Steroid-eluting sinus stents are placed in the ethmoid sinus and middle meatus of patients with CRS at the conclusion of ESS. The drug-eluting stents offer the potential for the dual benefits of mechanical spacing and anti-inflammatory pharmacotherapy. The stenting action of the device aims to separate the raw edges of the mucosal wound surface to prevent adhesion formation and stenosis. The slow release of corticosteroid aims to decrease mucosal oedema and expedite wound healing (Bednarski 2009).

Why it is important to do this review Surgical outcomes of ESS are influenced by postoperative inflammation, crusting, polyposis, formation of synechiae and stenosis (Gaskins 1994; Otto 2010; Ramadan 1999). Multimodal postoperative therapy, including saline irrigations, topical steroid sprays, systemic steroids and meticulous postoperative debridement, can lead to better long-term ESS outcomes (Bugten 2006; Kennedy 2000). Due to its position as an emerging technology, the role of steroid-eluting stents in the care of the surgical CRS patient has yet to be assessed fully. Three studies, including two randomised controlled trials, have shown that steroid-eluting sinus stents can preserve sinus patency and enhance mucosal wound healing after ESS by reducing inflammation, polyposis and the formation of adhesion (Forwith 2012; Murr 2011; Marple 2012). Minimal adverse effects were reported in these trials (they included sinus infection, crusting and granulation tissue formation). However, to our knowledge, there has been no high-quality systematic review of all the available data. The aim of this Cochrane review is to assess subjective and objective clinical outcomes of the use of steroid-eluting sinus stents in endoscopic sinus surgery.

OBJECTIVES To assess the safety and efficacy of steroid-eluting sinus stent placement in CRS patients after FESS.

METHODS


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Criteria for considering studies for this review

Search methods for identification of studies

Types of studies

The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator (TSC) conducted systematic searches for randomised controlled trials and controlled clinical trials. There were no language, publication year or publication status restrictions. The date of the search was 14 May 2015.

Randomised controlled trials. We excluded cluster-randomised and cross-over trials. We also excluded studies using within-patient randomisation (i.e. where patients were randomised by ’sides’, for example receiving a steroid-eluting sinus implant on one side and an identical non-steroid eluting control implant on the contralateral side). The reason for excluding these studies is because it is very difficult to assess our primary outcome, symptoms, by sides.

Types of participants We included adult patients with chronic rhinosinusitis (CRS), with or without nasal polyps, undergoing FESS. CRS was diagnosed based on the EPOS (European position paper on rhinosinusitis and nasal polyps) criteria (Fokkens 2012): 1) the presence of symptoms for 12 weeks, including nasal obstruction, nasal discharge, 2) either endoscopic signs or CT images showing mucosal changes within the ostiomeatal complex, sinuses, or both. We excluded patients with known history of malignancy, immune deficiency and allergic fungal rhinosinusitis.

Types of interventions • Steroid-eluting sinus stent versus non-steroid eluting sinus stent • Steroid-eluting sinus stent versus nasal packing • Steroid-eluting sinus stent versus no treatment

Types of outcome measures

Primary outcomes

• Improvement in symptom scores (i.e. visual analogue scale (VAS) and Sino-Nasal Outcome Test-22 (SNOT-22))

Electronic searches The TSC searched: • the CENTDG Trials Register (searched 14 May 2015); • the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 4); • PubMed (1946 to 14 May 2015); • Ovid EMBASE (1974 to 2015 week 19); • Ovid CAB Abstracts (1910 to 2015 week 18); • EBSCO CINAHL (1982 to 14 May 2015); • LILACS, lilacs.bvsalud.org (searched 14 May 2015); • KoreaMed (searched via Google Scholar 14 May 2015); • IndMed, www.indmed.nic.in (searched 14 May 2015); • PakMediNet, www.pakmedinet.com (searched 14 May 2015); • Web of Knowledge, Web of Science (1945 to 14 May 2015); • ClinicalTrials.gov, (searched via the Cochrane Register of Studies 14 May 2015); • ICTRP, www.who.int/ictrp (searched 14 May 2015); • ISRCTN, www.isrctn.com (searched 14 May 2015); • Google Scholar, scholar.google.co.uk (searched 14 May 2015); • Google, www.google.com (searched 14 May 2015). The TSC modelled subject strategies for databases on the search strategy designed for CENTRAL. Where appropriate, they were combined with subject strategy adaptations of the highly sensitive search strategy designed by The Cochrane Collaboration for identifying randomised controlled trials and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, Box 6.4.b. (Handbook 2011). Search strategies for major databases including CENTRAL are provided in Appendix 1.

Searching other resources Secondary outcomes

• Improvement in quality of life • Adverse effects (i.e. worsening of symptoms, nasal bleeding) • Surrogate outcomes: ◦ endoscopic scores: polypoid change, middle turbinate position, adhesion ◦ radiographic scores (i.e. Lund-Mackay)

We scanned the reference lists of identified publications for additional trials and contacted trial authors if necessary. We searched PubMed, TRIPdatabase, The Cochrane Library and Google to retrieve existing systematic reviews relevant to this systematic review, so that we could scan their reference lists for additional trials. We searched for conference abstracts using the Cochrane Ear, Nose and Throat Disorders Group Trials Register.


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Data collection and analysis

Unit of analysis issues

Selection of studies

We only included individually randomised controlled trials. We excluded non-standard designs such as cluster-randomised and cross-over trials.

Two review authors (Zhenxiao Huang and Bing Zhou) assessed the initial search results to identify studies that met the inclusion criteria. The two authors resolved any disagreement by group discussion.

Dealing with missing data We contacted study authors to try to retrieve relevant missing data.

Data extraction and management The same two review authors were to perform data extraction independently using a standardised data form. Each review author would review approximately the same number of studies. We planned to refer unresolved disagreements on inclusion, ’Risk of bias’ assessment and data collection to the other two authors (Yan Sun and Peter Hwang). Data to be extracted included the following: • study design; • study eligibility criteria; • methodology; • information on methods for ’Risk of bias’ assessment; • outcome/measurements; • follow-up; • conclusions.

Assessment of heterogeneity We planned to test for heterogeneity by inspecting the forest plots and using the Chi2 test and I2 statistic. We used the rough guide to interpretation as follows (Handbook 2011): • 0% to 40%: might not be important; • 30% to 60%: may represent moderate heterogeneity; • 50% to 90%: may represent substantial heterogeneity; • 75% to 100%: considerable heterogeneity. The importance of the observed value of I2 depends on (i) the magnitude and direction of effects and (ii) the strength of evidence for heterogeneity (e.g. P value from the Chi2 test, or a confidence interval for I2 ) (Handbook 2011).

We contacted authors for clarification and missing data. Assessment of reporting biases Assessment of risk of bias in included studies Zhenxiao Huang and Bing Zhou were to undertake assessment of the risk of bias of the included trials independently, with the following taken into consideration, as guided by theCochrane Handbook for Systematic Reviews of Interventions (Handbook 2011): • sequence generation; • allocation concealment; • blinding; • incomplete outcome data; • selective outcome reporting; and • other sources of bias. We planned to use the Cochrane ’Risk of bias’ tool in Review Manager 5 (RevMan) (RevMan 2014), which involves describing each of these domains as reported in the trial and then assigning a judgement about the adequacy of each entry: ’low’, ’high’ or ’unclear’ risk of bias. Measures of treatment effect We planned to use RevMan 5 for data analysis. We were to assess continuous data by calculating the mean difference (MD) and/or standardised mean difference (SMD) with 95% confidence intervals (CI). For dichotomous data, we were to calculate the risk ratio (RR).

We intended to assess potential publication bias by using a funnel plot and other appropriate statistics (Handbook 2011).

Data synthesis We planned a fixed-effect model in the absence of statistical heterogeneity and a random-effects model in the presence of statistical heterogeneity.

Subgroup analysis and investigation of heterogeneity We planned to examine statistical heterogeneity by subgroup analysis as appropriate. We would have considered the following subgroups for analysis: 1. CRS without nasal polyps (CRSsNP) or CRS with nasal polyps (CRSwNP); 2. nasal polyps of grade < 3+ or > 3+; 3. asthmatic or non-asthmatic patients.

Sensitivity analysis We planned to perform sensitivity analysis based on the exclusion of small and low-quality studies.


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RESULTS

Description of studies

Results of the search We retrieved a total of 159 references after duplicates were removed and one study protocol from correspondence. We discarded 119 clearly irrelevant records at first-level screening. After second-level

screening we were left with 21 RCTs for further assessment. Following assessment of the full text of these studies, we excluded all 21 RCTs (Akbari 2012; Bardaranfar 2014; Berlucchi 2009; Cote 2010; Dautremont 2014; Frenkiel 2002; Han 2014; Hong 2013; Huvenne 2008; Jahanshahi 2014; Jin 2012; Kim 2012; Marple 2012; Matheny 2014; Miller 2003; Mo 2013; Murr 2011; Rudmik 2012; Shoman 2009; Wormald 2006; Yilmaz 2013). We identified one ongoing study, Wang 2014 (see Characteristics of ongoing studies). No studies are awaiting assessment. The study selection flow chart is shown in Figure 1.


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Figure 1. Process for sifting search results and selecting studies for inclusion.


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Included studies

DISCUSSION

We included no studies in this review.

Summary of main results Excluded studies See Characteristics of excluded studies. We excluded 21 RCTs at third-level screening for the following reasons:

Within-patient comparison

We excluded two studies that compared a steroid-eluting sinus stent and a non-steroid-eluting sinus stent because the authors used a within-patient comparison (Marple 2012; Murr 2011).

Use of oral prednisone and a steroid-eluting sinus stent

We excluded one study that used both oral prednisone and a steroid-eluting sinus stent (Dautremont 2014).

Use of steroid-eluting sinus stent in the office setting

We excluded one study that used a steroid-eluting sinus stent for office treatment (Han 2014).

Non-sinus stent interventions

We excluded five studies of gel (Berlucchi 2009; Frenkiel 2002; Miller 2003; Rudmik 2012; Wormald 2006), two studies of gloved middle meatal spacers (Akbari 2012; Kim 2012), four studies of Nasopore (Cote 2010; Jin 2012; Mo 2013; Shoman 2009), one study of gelatin (Bardaranfar 2014), one study of sponge (Yilmaz 2013), one study of topical tranexamic acid (Jahanshahi 2014), one study of hyaluronic acid hydrogel (Matheny 2014), and one study of nasal dressing (Hong 2013).

Non-steroid eluting and non-absorbable stent interventions

We excluded one study that used a doxycycline-releasing, nonabsorbable sinus stent (Huvenne 2008).

Risk of bias in included studies No studies were included in this review.

Effects of interventions No studies were included in this review.

No studies met the inclusion criteria for this review.

Overall completeness and applicability of evidence We found no high-quality trials fulfilling the study eligibility criteria.

Potential biases in the review process A strength of this systemic review is the comprehensive literature search, including several databases and clinical trial registers. We applied no language restrictions in our search strategy. Two authors selected studies, extracted data and assessed the outcomes strictly according to protocol. There was no disagreement between the two authors with regard to study inclusion. However, the review authors were not blinded to the authors of the studies, which is a potential source of bias.

Agreements and disagreements with other studies or reviews We identified one meta-analysis on this subject (Han 2012), which included two trials (Marple 2012; Murr 2011). The authors reported that steroid-eluting sinus implants offer short-term (30 days) beneficial effects in patients with chronic rhinosinusitis (CRS) undergoing functional endoscopic sinus surgery (FESS) by reducing the rate of nasal polyp formation, middle turbinate lateralisation, significant adhesion of the sinuses and the need for postoperative interventions. However, in our review we excluded these two trials because the authors used a within-patient comparison. In our review, we identified no randomised controlled trials (RCTs) meeting our eligibility criteria (see Characteristics of excluded studies). Murr 2011 was a prospective, randomised study that included 43 patients with CRS. In one group (n = 38) they used a within-patient control design, comparing a steroid-eluting sinus stent to a non-steroid-eluting sinus stent. In the other group (n = 5) they used bilateral steroid-eluting sinus stents. This study reported that steroid-eluting sinus stents offer short-term (30 days) beneficial effects in patients with CRS undergoing FESS (in terms of nasal polyp formation, middle turbinate lateralisation, significant adhesion and need for postoperative interventions). In this


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study, the primary outcome measures were endoscopic findings and the need for postoperative interventions, therefore they also did not address our primary outcome, subjective measurement of sinonasal symptoms. Marple 2012 was also a prospective, randomised study that enrolled 105 patients with CRS undergoing FESS and compared the effect of steroid-eluting sinus stents to non-steroid-eluting sinus stents, again using an intra-patient control design. Postoperative interventions, polyposis and adhesions were assessed 30 days postoperatively. This study showed that steroid-eluting sinus stents, providing sustained release of corticosteroid, improve surgical outcomes by reducing polyp formation, sinus adhesions, middle turbinate lateralisation and the need for further surgical intervention and oral steroid treatment. As with Murr 2011, the authors also failed to report our primary outcome, subjective measurement of sinonasal symptoms. Dautremont 2014 was a prospective, randomised, controlled study evaluating the effectiveness of a short course postoperative systemic corticosteroid therapy when utilising a middle meatal steroideluting spacer in 36 CRS patients with nasal polyposis following FESS. All patients were randomised into either the treatment arm (postoperative prednisone plus steroid-eluting sinus spacer) or placebo arm (postoperative placebo plus steroid-eluting sinus spacer). The primary and secondary outcome measurements were Lund-Kennedy system and Sinonasal Outcome Test (SNOT-22) scores. The authors concluded that postoperative systemic corticosteroids immediately following FESS for CRS with nasal polyposis may not confer any additional benefits when utilising a steroid-eluting spacer. The remaining 18 trials of sinus stents or nasal packing, which we identified while conducting this review and excluded, provide insufficient evidence either because they studied a steroid-eluting sinus stent for office treatment (Han 2014), studied non-sinus stent interventions (Akbari 2012; Bardaranfar 2014; Berlucchi 2009; Cote 2010; Frenkiel 2002; Hong 2013; Jahanshahi 2014; Jin 2012; Kim 2012; Matheny 2014; Miller 2003; Mo 2013; Rudmik 2012; Shoman 2009; Wormald 2006; Yilmaz 2013), or assessed a non-steroid-eluting, non-absorbable stent intervention (Huvenne 2008).

AUTHORS’ CONCLUSIONS Implications for practice There is currently no evidence from high-quality randomised controlled trials to demonstrate the benefits, over those of surgery alone, of steroid-eluting sinus stents for patients with chronic rhinosinusitis (CRS) undergoing functional endoscopic sinus surgery (FESS), when compared to non-steroid-eluting sinus stents, nasal packing or no treatment. Similarly, there is no evidence from suitable randomised controlled trials to show that one steroid-eluting sinus stent is superior to another.

Implications for research Well-designed randomised controlled trials are required to evaluate the efficacy of steroid-eluting sinus stents for CRS patients undergoing FESS in terms of improving sinonasal symptoms and quality of life. Study investigators should use between-patient rather than within-patient comparisons for future trials.

ACKNOWLEDGEMENTS We acknowledge Jenny Bellorini and the editorial panel of Cochrane Ear, Nose and Throat (ENT) Disorders Group for their support during the review process. We also acknowledge Mr. James W. Stambaugh from Intersect ENT, Palo Alto, California, USA for providing the information about steroid-eluting sinus stents and raw data from their studies. Finally, we would like to thank Prof. Wytske Fokkens for peer reviewing the manuscript. This project was supported by the National Institute for Health Research, via Cochrane Infrastructure, Cochrane Programme Grant or Cochrane Incentive funding to the Cochrane ENT Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

REFERENCES

References to studies excluded from this review Akbari 2012 {published data only} Akbari E, Philpott CM, Ostry AJ, Clark A, Javer AR. A double-blind randomised controlled trial of gloved versus ungloved Merocel middle meatal spacers for endoscopic sinus surgery. Rhinology 2012;50(3):306–10. Bardaranfar 2014 {published data only} Bardaranfar MH, Ranjbar Z, Dadgarnia MH, Atighechi S, Mirvakili A, Behniafard N, et al. The effect of an absorbable

gelatin dressing impregnated with triamcinolone within the olfactory cleft on polypoid rhinosinusitis smell disorders. American Journal of Rhinology and Allergy 2014;28(2): 172–5. Berlucchi 2009 {published data only} Berlucchi M, Castelnuovo P, Vincenzi A, Morra B, Pasquini E. Endoscopic outcomes of resorbable nasal packing after functional endoscopic sinus surgery: a multicenter prospective randomized controlled study. European Archives of Oto-Rhino-Laryngology 2009;266(6):839–45.


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Cote 2010 {published data only} Cote DW, Wright ED. Triamcinolone-impregnated nasal dressing following endoscopic sinus surgery: a randomized, double-blind, placebo-controlled study. Laryngoscope 2010; 120(6):1269–73. Dautremont 2014 {published data only} Dautremont JF, Mechor B, Rudmik L. The role of immediate postoperative systemic corticosteroids when utilizing a steroid-eluting spacer following sinus surgery. Otolaryngology - Head and Neck Surgery 2014;150(4): 689–95. Frenkiel 2002 {published data only} Frenkiel S, Desrosiers MY, Nachtigal D. Use of hylan B gel as a wound dressing after endoscopic sinus surgery. Journal of Otolaryngology 2002 ;Suppl 1:S41–4. Han 2014 {published data only} Han JK, Forwith KD, Smith TL, Kern RC, Brown WJ, Miller SK, et al. RESOLVE: a randomized, controlled, blinded study of bioabsorbable steroid-eluting sinus implants for in-office treatment of recurrent sinonasal polyposis. International Forum of Allergy & Rhinology 2014; 4(11):861–70. Hong 2013 {published data only} Hong SD, Kim JH, Dhong HJ, Kim HY, Chung SK, Chang YS, et al. Systemic effects and safety of triamcinoloneimpregnated nasal packing after endoscopic sinus surgery: a randomized, double-blinded, placebo-controlled study. American Journal of Rhinology and Allergy 2013;27(5): 407–10. Huvenne 2008 {published data only} Huvenne W, Zhang N, Tijsma E, Hissong B, Huurdeman J, Holtappels G, et al. Pilot study using doxycyclinereleasing stents to ameliorate postoperative healing quality after sinus surgery. Wound Repair and Regeneration 2008;16 (6):757–67. Jahanshahi 2014 {published data only} Jahanshahi J, Hashemian F, Pazira S, Bakhshaei MH, Farahani F, Abasi R, et al. Effect of topical tranexamic acid on bleeding and quality of surgical field during functional endoscopic sinus surgery in patients with chronic rhinosinusitis: a triple blind randomized clinical trial. PLoS One 2014;9(8):e104477. Jin 2012 {published data only} Jin KH, Choi JS, Kim YH, Kang SH, Kim BH, Yu MS, et al. Use of triamcinolone-impregnated nasal packing following endoscopic sinus surgery. Journal of Rhinology 2012;19(2):119–22. Kim 2012 {published data only} Kim DW, Lee EJ, Kim SW, Jeon SY. Advantages of glove finger-coated polyvinyl acetate pack in endoscopic sinus surgery. American Journal of Rhinology and Allergy 2012;26 (5):e147–9. Marple 2012 {published data only} Marple BF, Smith TL, Han JK, Gould AR, Jampel HD, Stambaugh JW, et al. Advance II: a prospective, randomized

study assessing safety and efficacy of bioabsorbable steroidreleasing sinus implants. Otolaryngology - Head and Neck Surgery 2012;146(6):1004–11. Matheny 2014 {published data only} Matheny KE, Tseng EY, Carter KB Jr, Cobb WB, Fong KJ. Self-cross-linked hyaluronic acid hydrogel in ethmoidectomy: a randomized, controlled trial. American Journal of Rhinology and Allergy 2014;28(6):508–13. Miller 2003 {published data only} Miller RS, Steward DL, Tami TA, Sillars MJ, Seiden AM, Shete M, et al. The clinical effects of hyaluronic acid ester nasal dressing (MeroGel) on intranasal wound healing after functional endoscopic sinus surgery. Otolaryngology - Head and Neck Surgery 2003;128(6):862–9. Mo 2013 {published data only} Mo JH, Park YM, Chung YJ. Effect of lidocaine-soaked nasal packing on pain relief after endoscopic sinus surgery. American Journal of Rhinology and Allergy 2013;27(6): e174–7. Murr 2011 {published data only} Murr AH, Smith TL, Hwang PH, Bhattacharyya N, Lanier BJ, Stambaugh JW, et al. Safety and efficacy of a novel bioabsorbable, steroid-eluting sinus stent. International Forum of Allergy & Rhinology 2011;1(1):23–32. Rudmik 2012 {published data only} Rudmik L, Mace J, Mechor B. Effect of a dexamethasone Sinu-Foam™ middle meatal spacer on endoscopic sinus surgery outcomes: a randomized, double-blind, placebocontrolled trial. International Forum of Allergy & Rhinology 2012;2(3):248–51. Shoman 2009 {published data only} Shoman N, Gheriani H, Flamer D, Javer A. Prospective, double-blind, randomized trial evaluating patient satisfaction, bleeding, and wound healing using biodegradable synthetic polyurethane foam (Nasopore) as a middle meatal spacer in functional endoscopic sinus surgery. Journal of Otolaryngology - Head & Neck Surgery 2009;38 (1):112–8. Wormald 2006 {published data only} Wormald PJ, Boustred RN, Le T, Hawke L, Sacks R. A prospective single-blind randomized controlled study of use of hyaluronic acid nasal packs in patients after endoscopic sinus surgery. American Journal of Rhinology 2006;20(1): 7–10. Yilmaz 2013 {published data only} Yilmaz S, Yildizbas S, Güçlü E, Yaman H, Yalçin Sezen G. Topical levobupivacaine efficacy in pain control after functional endoscopic sinus surgery. Otolaryngology - Head and Neck Surgery 2013;149(5):777–81.

References to ongoing studies Wang 2014 {unpublished data only} Shanghai PUYI Biotechnology Co. Ltd. Study protocol (received 14 January 2015).


10

Additional references Bednarski 2009 Bednarski KA, Kuhn FA. Stents and drug-eluting stents. Otolaryngologic Clinics of North America 2009;42(5): 857–66.

Handbook 2011 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.

Bhattacharyya 2004 Bhattacharyya N. Clinical outcomes after revision endoscopic sinus surgery. Archives of Otolaryngology -- Head and Neck Surgery 2004;130(8):975–8.

Hastan 2011 Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, et al. Chronic rhinosinusitis in Europe--an underestimated disease. A GA²LEN study. Allergy 2011;66(9):1216–23.

Bugten 2006 Bugten V, Nordgård S, Skogvoll E, Steinsvåg S. Effects of nonabsorbable packing in middle meatus after sinus surgery. Laryngoscope 2006;116(1):83–8.

Kennedy 2000 Kennedy DW, Wright ED, Goldberg AN. Objective and subjective outcomes in surgery for chronic sinusitis. Laryngoscope 2000;110(3):29–31.

Chen 2003 Chen Y, Dales R, Lin M. The epidemiology of chronic rhinosinusitis in Canadians. Laryngoscope 2003;113(7): 1199–205. Collins 1997 Collins JG. Prevalence of selected chronic conditions: United States, 1990-1992. Vital and Health Statistics. Series 10: Data from the National Health Survey 1997;194:1–89. Fokkens 2012 Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology 2012;50(1):1–12. Forwith 2012 Forwith KD, Chandra RK, Yun PT, Miller SK, Jampel HD. ADVANCE: a multisite trial of bioabsorbable steroideluting sinus implants. Laryngoscope 2011;121(11): 2473–80. Gaskins 1994 Gaskins R. Scarring in endoscopic ethmoidectomy. American Journal of Rhinology 1994;8(6):271–4. Han 2012 Han JK, Marple BF, Smith TL, Murr AH, Lanier BJ, Stambaugh JW, et al. Effect of steroid-releasing sinus implants on postoperative medical and surgical interventions: an efficacy meta-analysis. International Forum of Allergy & Rhinology 2012;2(4):271–9.

Kennedy 2004 Kennedy DW. Pathogenesis of chronic rhinosinusitis. Annals of Otology, Rhinology, and Laryngology. Supplement 2004;193:6–9. Otto 2010 Otto KJ, DelGaudio JM. Operative findings in the frontal recess at time of revision surgery. American Journal of Otolaryngology 2010;31(3):175–80. Ramadan 1999 Ramadan HH. Surgical causes of failure in endoscopic sinus surgery. Laryngoscope 1999;109(1):27–9. RevMan 2014 [Computer program] The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. Tan 2010 Tan BK, Schleimer RP, Kern RC. Perspectives on the etiology of chronic rhinosinusitis. Current Opinion in Otolaryngology & Head and Neck Surgery 2010;18(1):21–6. Weber 2000 Weber R, Hochapfel F, Draf W. Packing and stents in endonasal surgery. Rhinology 2000;38(2):49–62. Wei 2012 Wei CC, Kennedy DW. Mometasone implant for chronic rhinosinusitis. Medical Devices (Auckland, New Zealand) 2012 Aug 17 [Epub ahead of print]. ∗ Indicates the major publication for the study


11

CHARACTERISTICS OF STUDIES

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Akbari 2012

ALLOCATION: Randomised PARTICIPANTS: 37 patients with CRS undergoing bilateral ESS INTERVENTIONS: Gloved Merocel middle meatal spacers versus ungloved Merocel middle meatal spacers, therefore outside the remit of this review

Bardaranfar 2014

ALLOCATION: Randomised PARTICIPANTS: Patients who had CRS with polyposis and undergoing FESS INTERVENTIONS: Gelatin dressing + triamcinolone versus gelatin dressing + saline, therefore outside the remit of this review

Berlucchi 2009

ALLOCATION: Randomised PARTICIPANTS: 66 CRS patients (88 nasal cavities) who had undergone FESS INTERVENTIONS: Hyaluronan resorbable packing (MeroGel) versus standard non-resorbable nasal dressing, therefore outside the remit of this review

Cote 2010

ALLOCATION: Randomised PARTICIPANTS: CRS patients with polyposis who were to undergo bilateral ESS INTERVENTIONS: Triamcinolone + Nasopore versus saline + Nasopore, therefore outside the remit of this review

Dautremont 2014

ALLOCATION: Randomised PARTICIPANTS: CRS patients with nasal polyposis who failed medical therapy and elected to have ESS INTERVENTIONS: Prednisone + steroid-eluting sinus stent versus saline + steroid-eluting sinus stent, therefore outside the remit of this review

Frenkiel 2002

ALLOCATION: Randomised PARTICIPANTS: 20 patients with a diagnosis of chronic sinusitis who underwent FESS INTERVENTIONS:


12

(Continued)

Gel dressing versus no treatment, therefore outside the remit of this review Han 2014

ALLOCATION: Randomised PARTICIPANTS: 100 patients with CRS with nasal polyposis (CRSwNP) refractory to medical therapy and considered candidates for revision ESS INTERVENTIONS: Treated patients underwent in-office bilateral placement of steroid-eluting sinus stents. Control patients underwent a sham procedure. This study used the steroid-eluting sinus stent for in-office treatment and therefore is outside the remit of this review

Hong 2013

ALLOCATION: Randomised PARTICIPANTS: Patients who underwent bilateral ESS for CRS INTERVENTIONS: Triamcinolone-soaked bioabsorbable dressing versus saline-impregnated dressing, therefore outside the remit of this review

Huvenne 2008

ALLOCATION: Randomised PARTICIPANTS: 10 CRS patients with and without nasal polyposis who underwent FESS INTERVENTIONS: Doxycycline-releasing stent versus contralateral placebo stent, therefore outside the remit of this review

Jahanshahi 2014

ALLOCATION: Randomised PARTICIPANTS: 60 CRS patients who underwent FESS INTERVENTIONS: Pledgets soaked with tranexamic acid 5% and phenylephrine 0.5% versus phenylephrine 0.5%, therefore outside the remit of this review

Jin 2012

ALLOCATION: Randomised PARTICIPANTS: CRS patients who underwent FESS INTERVENTIONS: Triamcinolone-impregnated Nasopore versus saline-impregnated Nasopore, therefore outside the remit of this review

Kim 2012

ALLOCATION: Randomised PARTICIPANTS: 30 CRS patients who underwent bilateral ESS INTERVENTIONS: Glove finger-coated polyvinyl acetate (PA) pack versus PA pack, therefore outside the remit of this review


13

(Continued)

Marple 2012

ALLOCATION: Within-patient randomisation, therefore outside the remit of this review (participants were 105 CRS patients who underwent bilateral ESS; steroid-eluting sinus stent versus non-steroid-eluting sinus stent)

Matheny 2014

ALLOCATION: Randomised PARTICIPANTS: 30 CRS patients who underwent bilateral total ethmoidectomy INTERVENTIONS: Hyaluronic acid versus carboxymethylcellulose viscous foam, therefore outside the remit of this review

Miller 2003

ALLOCATION: Randomised PARTICIPANTS: 37 patients requiring bilateral FESS for chronic sinusitis INTERVENTIONS: Hyaluronic acid nasal dressing versus MeroGel, therefore outside the remit of this review

Mo 2013

ALLOCATION: Randomised PARTICIPANTS: Patients with CRS undergoing ESS INTERVENTIONS: Lidocaine-soaked Nasopore versus saline-soaked Nasopore, therefore outside the remit of this review

Murr 2011

ALLOCATION: Within-patient randomisation, therefore outside the remit of this review (participants were 38 CRS patients who underwent bilateral ESS; steroid-eluting sinus stent versus non-steroid-eluting sinus stent)

Rudmik 2012

ALLOCATION: Randomised PARTICIPANTS: Patients with CRS without nasal polyps who underwent bilateral ESS INTERVENTIONS: Dexamethasone Sinu-Foam spacer versus Sinu-Foam spacer alone, therefore outside the remit of this review

Shoman 2009

ALLOCATION: Randomised PARTICIPANTS: 30 consecutive adults (age > 16 years) with chronic or recurrent acute rhinosinusitis undergoing bilateral FESS INTERVENTIONS: Nasopore versus Merocel, therefore outside the remit of this review

Wormald 2006

ALLOCATION: Randomised PARTICIPANTS: Patients with CRS without nasal polyps who underwent bilateral ESS INTERVENTIONS:


14

(Continued)

Hyaluronic acid pack (MeroGel) versus no packing, therefore outside the remit of this review Yilmaz 2013

ALLOCATION: Randomised PARTICIPANTS: Patients who underwent FESS INTERVENTIONS: Polyvinyl alcohol (PVA) sponge soaked with levobupivacaine hydrochloride versus PVA sponge soaked with saline, therefore outside the remit of this review

CRS: chronic rhinosinusitis ESS: endoscopic sinus surgery FESS: functional endoscopic sinus surgery

Characteristics of ongoing studies [ordered by study ID] Wang 2014 Trial name or title

Drug-eluting sinus bio-polymer stent system for patients with CRS who underwent endoscopic sinus surgery

Methods

Prospective randomised controlled trial

Participants

Patients with CRS undergoing bilateral ESS

Interventions

Steroid-eluting sinus stent versus Nasopore

Outcomes

Endoscopic scores

Starting date

June 2014

Contact information

Shanghai Puyi Biotech Company Ltd. No.199 Guoshoujing Avenue, Zhangjiang Science Park of Pudong new area, Shanghai, China

Notes

This study is currently recruiting participants

CRS: chronic rhinosinusitis ESS: endoscopic sinus surgery


15

DATA AND ANALYSES This review has no analyses.

APPENDICES Appendix 1. Search strategies

CENTRAL

PubMed

EMBASE (Ovid)

CINAHL (EBSCO)

#1 MeSH descriptor: [Sinusitis] explode all trees #2 rhinosinusitis or nasosinusitis or sinusitis or pansinusitis or ethmoiditis or sphenoiditis #3 kartagener* and syndrome* #4 inflamm* and sinus* #5 #1 or #2 or #3 or #4 #6 MeSH descriptor: [Chronic Disease] explode all trees #7 chronic or persis* or recur* #8 MeSH descriptor: [Recurrence] explode all trees and with qualifiers: [Prevention & control - PC] #9 #6 or #7 or #8 #10 #5 and #9 #11 CRSwNP or CRSsNP #12 #10 or #11 #13 MeSH descriptor: [Endoscopy] explode all trees #14 endoscop* or uncinectomy or antrostomy or antrotomy or ethmoidectomy or sphenoidotomy #15 sinus and surg* #16 fess or ess #17 MeSH descriptor: [Surgical Procedures, Operative] explode all trees #18 #13 or #14 or #15 or #16 or #17 #19 #12 and #18 #20 MeSH descriptor: [Sinusitis] explode all trees and with qualifiers: [Surgery - SU]

#1 “Sinusitis”[Mesh] #2 rhinosinusitis OR nasosinusitis OR sinusitis OR pansinusitis OR ethmoiditis OR sphenoiditis #3 kartagener* AND syndrome* #4 (inflammat* OR inflame*) AND sinus*) #5 (#1 OR #2 OR #3 OR #4) #6 Chronic Disease“[Mesh] #7 chronic OR persis* OR recur* #8 ”Recurrence/prevention and control“[Mesh] #9 (#6 OR #7 OR #8) #10 (#5 AND #9) #11 CRSwNP or CRSsNP #12 (#10 OR #11) #13 ”Endoscopy“[Mesh] #14 endoscop* OR uncinectomy OR antrostomy OR antrotomy OR ethmoidectomy OR sphenoidotomy #15 sinus AND surg* #16 fess OR ess #17 “Surgical Procedures, Operative”[Mesh] #18 (#13 OR #14 OR #15 OR #16 OR #17) #19 (#12 AND #18) #20 “Sinusitis/surgery”[Mesh] #21 (#9 AND #20) #22 (#19 OR #21) #23 “Drug-Eluting

1 exp sinusitis/ 2 (rhinosinusitis or nasosinusitis or sinusitis or pansinusitis or ethmoiditis or sphenoiditis).tw 3 (kartagener* and syndrome*) .tw. 4 ((inflammat* or inflame*) and sinus*).tw. 5 1 or 2 or 3 or 4 6 exp chronic disease/ 7 (chronic or persis* or recur*). tw. 8 exp recurrent disease/pc [Prevention] 9 6 or 7 or 8 10 5 and 9 11 (CRSwNP or CRSsNP).tw. 12 10 or 11 13 exp endoscopy/ 14 (endoscop* or uncinectomy or antrostomy or antrotomy or ethmoidectomy or sphenoidotomy).tw 15 (sinus and surg*).tw. 16 (fess or ess).tw. 17 exp surgery/ 18 13 or 14 or 15 or 16 or 17 19 12 and 18 20 exp sinusitis/su [Surgery] 21 9 and 20 22 19 or 21 23 exp drug eluting stent/ 24 ((elut* or medicat* or coat* or impreg* or infus* or soak* or releas*) and (stent* or implant

S43 S22 AND S42 S42 S23 OR S24 OR S41 S41 S30 AND S40 S40 S31 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 S39 TX Corticosterone or Tetrahydrocortisol or Cortodoxone or Tetrahydrocortisone or Desoxycorticosterone or Pregnenolone or Hydroxydesoxycorticosterone or Hydroxypregnenolone S38 TX cortisone or cortisol* or Prednisone* or Prednisolone* or Methylprednisolone* or Fludrocortisone* or Deoxycorticosterone* or Aldosterone* S37 TX Beclomethasone* or Budesonide* or Beclomethasone* or Flunisolide* or Fluticasone* or Mometasone* or Dexamethasone* or Prednisone* or Triamcinolone* or Betamethasone* or Hydrocortisone* S36 TX steroid* or corticosteroid* or glucocorticoid* or Hydroxycorticosteroid* or corticoid* S35 (MH “Glucocorticoids+”) S34 S32 NOT S33 S33 (MH “Antiinflammatory Agents, Non-Steroidal+”) S32 (MH “Antiinflammatory Agents+”)


16

(Continued)

#21 #9 and #20 #22 #19 or #21 #23 MeSH descriptor: [DrugEluting Stents] explode all trees #24 (elut* or medicat* or coat* or impreg* or infus* or soak* or releas*) and (stent* or implant* or spacer* or spong* or “place holder*” or Pipe* or tube* or material* or dress* or matrix or sheet* or mms or pledget or pack* or band*) #25 MeSH descriptor: [Stents] explode all trees #26 MeSH descriptor: [Surgical Sponges] explode all trees #27 MeSH descriptor: [Absorbable Implants] explode all trees #28 MeSH descriptor: [Bandages] explode all trees #29 MeSH descriptor: [Delayed-Action Preparations] explode all trees and with qualifiers: [Administration & dosage - AD] #30 stent* or implant* or spacer* or spong* or “place holder*” or Pipe* or tube* or material* or dress* or matrix or sheet* or mms or pledget or band* or pack* #31 #25 or #26 or #27 or #29 or #28 or #30 #32 MeSH descriptor: [Steroids] explode all trees #33 MeSH descriptor: [AntiInflammatory Agents] explode all trees #34 MeSH descriptor: [AntiInflammatory Agents, NonSteroidal] explode all trees #35 #33 not #34 #36 MeSH descriptor: [Glucocorticoids] explode all trees 3075 #37 steroid* or corticosteroid* or glucocorticoid* or Hydroxycorticosteroid* or corticoid*

Stents”[Mesh] #24 (elut* OR medicat* OR coat* OR impreg* OR infus* OR soak* OR releas*) AND (stent* OR implant OR implants OR spacer* OR spong* OR “place holder*” OR Pipe OR tube OR tubes OR material* OR dress* OR matrix OR sheet* OR mms OR pledget OR pack* OR bandag*) #25 “Stents”[Mesh] #26 “Surgical Sponges”[Mesh] #27 “Absorbable Implants”[Mesh] #28 “Bandages”[Mesh] #29 “Delayed-Action Preparations/administration and dosage”[Mesh] #30 stent* OR implant OR implants OR spacer* OR spong* OR “place holder*” OR Pipe OR tube OR tubes OR material* OR dress* OR matrix OR sheet* OR mms OR pledget OR pack* OR bandag* #31 (#23 OR #24 OR #25 OR #26 OR #28 OR #29 OR #30) #32 “Steroids”[Mesh] #33 “Anti-Inflammatory Agents”[Mesh] #34 “Anti-Inflammatory Agents, Non-Steroidal”[Mesh] #35 (#33 NOT #34) #36 “Glucocorticoids”[Mesh] #37 steroid* OR corticosteroid* OR glucocorticoid* OR Hydroxycorticosteroid* OR corticoid* #38 Beclomethasone* OR Budesonide* OR Beclomethasone* OR Flunisolide* OR Fluticasone* OR Mometasone* OR Dexamethasone* OR Prednisone* OR Triamcinolone* OR Betamethasone* OR Hydrocortisone* #39 cortisone OR cortisol* OR

or implants or spacer* or spong* or “place holder*” or Pipe or tube or tubes or material* or dress* or matrix or sheet* or mms or pledget or pack* or bandag*)).tw 25 exp stent/ 26 exp surgical sponge/ 27 exp biodegradable implant/ 28 exp bandage/ 29 exp delayed release formulation/ad [Drug Administration] 30 (stent* or implant or implants or spacer* or spong* or “place holder*” or Pipe or tube or tubes or material* or dress* or matrix or sheet* or mms or pledget or pack* or bandag*).tw 31 25 or 26 or 27 or 28 or 29 or 30 32 exp steroid/ 33 exp antiinflammatory agent/ 34 exp nonsteroid antiinflammatory agent/ 35 33 not 34 36 exp glucocorticoid/ 37 (steroid* or corticosteroid* or glucocorticoid* or Hydroxycorticosteroid* or corticoid*). tw 38 (Beclomethasone* or Budesonide* or Beclomethasone* or Flunisolide* or Fluticasone* or Mometasone* or Dexamethasone* or Prednisone* or Triamcinolone* or Betamethasone* or Hydrocortisone*).tw 39 (cortisone or cortisol* or Prednisone* or Prednisolone* or Methylprednisolone* or Fludrocortisone* or Deoxycorticosterone* or Aldosterone*).tw 40 (Corticosterone or Tetrahydrocortisol or Cortodoxone or Tetrahydrocortisone or Desoxycorticosterone or Pregnenolone or Hydroxydesoxycorticosterone or Hy-

S31 (MH “Steroids+”) S30 S25 OR S26 OR S27 OR S28 OR S29 S29 TX stent* or implant or implants or spacer* or spong* or “place holder*” or Pipe or tube or tubes or material* or dress* or matrix or sheet* or mms or pledget or pack* or bandag* S28 (MH “Delayed-Action Preparations+/AD”) S27 (MH “Bandages and Dressings+”) S26 (MH “Surgical Sponges”) S25 (MH “Stents+”) S24 TX (elut* or medicat* or coat* or impreg* or infus* or soak* or releas*) and (stent* or implant or implants or spacer* or spong* or “place holder*” or Pipe or tube or tubes or material* or dress* or matrix or sheet* or mms or pledget or pack* or bandag*) S23 (MH “Drug-Eluting Stents”) S22 S19 OR S21 S21 S9 AND S20 S20 (MH “Sinusitis+/SU”) S19 S12 AND S18 S18 S13 OR S14 OR S15 OR S16 OR S17 S17 (MH “Surgery, Operative+”) S16 TX fess OR ess S15 TX sinus and surg* S14 TX endoscop* or uncinectomy or antrostomy or antrotomy or ethmoidectomy or sphenoidotomy S13 (MH “Endoscopy+”) S12 S10 OR S11 S11 TX CRSwNP or CRSsNP S10 S5 AND S9 S9 S6 OR S7 OR S8 S8 (MH “Recurrence/PC”) S7 TX chronic or persis* or re-


17

(Continued)

#38 Beclomethasone* or Budesonide* or Beclomethasone* or Flunisolide* or Fluticasone* or Mometasone* or Dexamethasone* or Prednisone* or Triamcinolone* or Betamethasone* or Hydrocortisone* #39 cortisone or cortisol* or Prednisone* or Prednisolone* or Methylprednisolone* or Fludrocortisone* or Deoxycorticosterone* or Aldosterone* #40 Corticosterone or Tetrahydrocortisol or Cortodoxone or Tetrahydrocortisone or Desoxycorticosterone or Pregnenolone or Hydroxydesoxycorticosterone or Hydroxypregnenolone #41 #32 or #35 or #36 or #37 or #38 or #39 or #40 #42 #31 and #41 #43 #23 or #24 or #42 #44 #22 and #43

Prednisone* OR Prednisolone* OR Methylprednisolone* OR Fludrocortisone* OR Deoxycorticosterone* OR Aldosterone* #40 Corticosterone OR Tetrahydrocortisol OR Cortodoxone OR Tetrahydrocortisone OR Desoxycorticosterone OR Pregnenolone OR Hydroxydesoxycorticosterone OR Hydroxypregnenolone #41 (#32 OR #35 OR #36 Or #37 OR #38 OR #39 OR #40) #42 (#31 AND #41) #43 (#23 OR #24 OR #42) #44 (#22 AND #43)

droxypregnenolone).tw cur* 41 32 or 35 or 36 or 37 or 38 S6 (MH “Chronic Disease”) or 39 or 40 S5 S1 OR S2 OR S3 OR S4 42 31 and 41 S4 TX (inflammat* OR in43 23 or 24 or 42 flame*) AND sinus* 44 22 and 43 S3 TX kartagener* and syndrome* S2 TX rhinosinusitis or nasosinusitis or sinusitis or pansinusitis or ethmoiditis or sphenoiditis S1 (MH “Sinusitis+”)

Web of Science

CAB Abstracts (Ovid)

ICTRP

#1 TS=(rhinosinusitis or nasosinusitis or sinusitis or pansinusitis or ethmoiditis or sphenoiditis) #2 TS=(kartagener* and syndrome*) #3 TS=((inflammat* or inflame*) and sinus*) #4 #3 OR #2 OR #1 #5 TS=(chronic or persis* or recur*) #6 #5 AND #4 #7 TS=(CRSwNP or CRSsNP) #8 #7 OR #6 #9 WC=Surgery #10 TS=(endoscop* or uncinectomy or antrostomy or antrotomy or ethmoidectomy or sphenoidotomy) #11 TS=(sinus and surg*) #12 TS=(fess OR ess) #13 #12 OR #11 OR #10 OR

1 exp sinusitis/ 2 (rhinosinusitis or nasosinusitis or sinusitis or pansinusitis or ethmoiditis or sphenoiditis).tw 3 (kartagener* and syndrome*) .tw. 4 ((inflammat* or inflame*) and sinus*).tw. 5 1 or 2 or 3 or 4 6 exp chronic diseases/ 7 (chronic or persis* or recur*). tw. 8 6 or 7 9 5 and 8 10 (CRSwNP or CRSsNP).tw. 11 9 or 10 12 exp endoscopy/ 13 (endoscop* or uncinectomy or antrostomy or antrotomy or ethmoidectomy or sphenoidotomy).tw 14 (sinus and surg*).tw.

steroid AND stent OR steroid AND spacer OR steroid AND stent OR steroid AND spacer OR steroid AND implant

clinicaltrial.gov eluting AND ((Sinus AND surgery) OR fess OR rhinosinusitis OR sinusitis) ) AND (eluting OR coated OR eluting AND impregnated OR soaked OR releasing OR steroid OR medicated OR drug) AND (stents releasing AND OR implant OR spacer OR place OR holder OR pipe OR dressing OR packing OR mms releasing AND OR pledget OR matrix)

releasing AND


18

(Continued)

#9 #14 #13 AND #8 #15 TS=(stent* or implant or implants or spacer* or spong* or “place holder*” or Pipe or tube or tubes or material* or dress* or matrix or sheet* or mms or pledget or pack* or bandag*) #16 TS=(steroid* or corticosteroid* or glucocorticoid* or Hydroxycorticosteroid* or corticoid*) #17 TS=(Beclomethasone* or Budesonide* or Beclomethasone* or Flunisolide* or Fluticasone* or Mometasone* or Dexamethasone* or Prednisone* or Triamcinolone* or Betamethasone* or Hydrocortisone*) #18 TS=(cortisone or cortisol* or Prednisone* or Prednisolone* or Methylprednisolone* or Fludrocortisone* or Deoxycorticosterone* or Aldosterone*) #19 TS=(Corticosterone or Tetrahydrocortisol or Cortodoxone or Tetrahydrocortisone or Desoxycorticosterone or Pregnenolone or Hydroxydesoxycorticosterone or Hydroxypregnenolone) #20 #19 OR #18 OR #17 OR #16 #21 #20 AND #15 #22 TS=((elut* or medicat* or coat* or impreg* or infus* or soak* or releas*) and (stent* or implant or implants or spacer* or spong* or “place holder*” or Pipe or tube or tubes or material* or dress* or matrix or sheet* or mms or pledget or pack* or bandag*)) #23 #22 OR #21 #24 #23 AND #14

15 (fess or ess).tw. 16 exp surgery/ 17 12 or 13 or 14 or 15 or 16 18 11 and 17 19 exp bandages/ 20 (stent* or implant or implants or spacer* or spong* or “place holder*” or Pipe or tube or tubes or material* or dress* or matrix or sheet* or mms or pledget or pack* or bandag*).tw 21 19 or 20 22 exp steroids/ 23 exp antiinflammatory agents/ 24 exp non-steroidal antiinflammatory agents/ 25 23 not 24 26 exp glucocorticoids/ 27 (steroid* or corticosteroid* or glucocorticoid* or Hydroxycorticosteroid* or corticoid*). tw 28 (Beclomethasone* or Budesonide* or Beclomethasone* or Flunisolide* or Fluticasone* or Mometasone* or Dexamethasone* or Prednisone* or Triamcinolone* or Betamethasone* or Hydrocortisone*).tw 29 (cortisone or cortisol* or Prednisone* or Prednisolone* or Methylprednisolone* or Fludrocortisone* or Deoxycorticosterone* or Aldosterone*).tw 30 (Corticosterone or Tetrahydrocortisol or Cortodoxone or Tetrahydrocortisone or Desoxycorticosterone or Pregnenolone or Hydroxydesoxycorticosterone or Hydroxypregnenolone).tw 31 22 or 25 or 26 or 27 or 28 or 29 or 30 32 21 and 31 33 ((elut* or medicat* or coat* or impreg* or infus* or soak* or releas*) and (stent* or implant


19

(Continued)

or implants or spacer* or spong* or “place holder*” or Pipe or tube or tubes or material* or dress* or matrix or sheet* or mms or pledget or pack* or bandag*)).tw 34 32 or 33 35 18 and 34

CONTRIBUTIONS OF AUTHORS Zhenxiao Huang: initial searching, selection of studies, data extraction, data analysis, drafting protocol and reviewing main text, updating the review. Peter Hwang: co-drafting of protocol and reviewing main text. Yan Sun: selection of studies, assistance with data extraction and analysis. Bing Zhou: assistance with statistics, reviewing main text.

DECLARATIONS OF INTEREST Zhenxiao Huang: no disclosures to report. Sun Yan: no disclosures to report. Bing Zhou: no disclosures to report. Peter Hwang is a consultant for Intersect ENT, manufacturer of a steroid-eluting sinus stent.

SOURCES OF SUPPORT Internal sources • None, Other.

External sources • National Institute for Health Research, UK. Infrastructure funding for the Cochrane ENT Group


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DIFFERENCES BETWEEN PROTOCOL AND REVIEW • In Types of studies we have clarified that studies with within-patient randomisation are excluded (i.e. where patients were randomised by ’sides’, for example receiving a steroid-eluting sinus implant on one side and an identical non-steroid eluting control implant on the contralateral side). The reason for excluding these studies is because ongoing sinus inflammation on one side may affect the inflammation on contralateral side. It is very difficult to assess our primary outcome, symptoms, by sides. • We removed the word ’blinded’ from Types of studies, as this is a ’Risk of bias’ issue and not a study inclusion criterion. No studies were excluded on the basis of blinding.

INDEX TERMS Medical Subject Headings (MeSH) ∗ Drug-Eluting

Stents; Chronic Disease; Endoscopy [∗ methods]; Rhinitis [∗ surgery]; Sinusitis [∗ surgery]; Steroids [∗ administration &

dosage]

MeSH check words Humans


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Risk Factors of Chronic Rhinosinusitis After Functional Endoscopic Sinus Surgery.

Improvements in sleep-related symptoms after endoscopic sinus surgery in patients with chronic rhinosinusitis.

Outcomes and cost benefits of functional endoscopic sinus surgery in severely asthmatic patients with chronic rhinosinusitis.

Comparison of different surgical approaches of functional endoscopic sinus surgery on patients with chronic rhinosinusitis.

Economic Evaluation of a Steroid-Eluting Sinus Implant following Endoscopic Sinus Surgery for Chronic Rhinosinusitis.

The predictive value of the preoperative Sinonasal Outcome Test-22 score in patients undergoing endoscopic sinus surgery for chronic rhinosinusitis.

Functional endoscopic sinus surgery in the management of chronic rhinosinusitis. An objective assessment.

Improvements in psychological dysfunction after endoscopic sinus surgery for patients with chronic rhinosinusitis.

Long-term results of functional endoscopic sinus surgery in children with chronic rhinosinusitis with nasal polyps.

Effects of functional endoscopic sinus surgery on chronic rhinosinusitis resistant to medication.

Productivity outcomes following endoscopic sinus surgery for recurrent acute rhinosinusitis.

Causes of failure in endoscopic frontal sinus surgery in chronic rhinosinusitis patients.

Sleep and quality of life improvements after endoscopic sinus surgery in patients with chronic rhinosinusitis.

Early versus delayed endoscopic sinus surgery in patients with chronic rhinosinusitis: impact on health care utilization.

The impact of endoscopic sinus surgery on total direct healthcare costs among patients with chronic rhinosinusitis.

Response shift in quality of life after endoscopic sinus surgery for chronic rhinosinusitis.

Preoperative concerns of patients undergoing endoscopic sinus surgery.

Functional endoscopic sinus surgery in children.

Trends of ambulatory sinus surgery for chronic rhinosinusitis.

Impact of Functional Endoscopic Sinus Surgery on the Pulmonary Function of Patients with Chronic Rhinosinusitis: A Prospective Study.

Productivity costs decrease after endoscopic sinus surgery for refractory chronic rhinosinusitis.

Availability of preoperative systemic steroids on endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis.

Impact of intranasal sodium hyaluronate on the short-term quality of life of patients undergoing functional endoscopic sinus surgery for chronic rhinosinusitis.

Squeeze bottle versus saline spray after endoscopic sinus surgery for chronic rhinosinusitis: a pilot multicentre trial.