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Extracto de Cyclamen europaeum para la sinusitis aguda

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References

References to studies included in this review

Pfaar 2012 {published data only}

Pfaar O, Mullol J, Anders C, Hormann K, Klimek L. Cyclamen europaeum nasal spray, a novel phytotherapeutic product for the management of acute rhinosinusitis: a randomized double‐blind, placebo‐controlled trial. Rhinology 2012;50(1):37‐44. CENTRAL

Ponikau 2012 {published data only}

Ponikau JU, Hamilos DL, Barreto A, Cecil J, Jones SW, Manthei SE, et al. An exploratory trial of Cyclamen europaeum extract for acute rhinosinusitis. Laryngoscope 2012;122(9):1887‐92. CENTRAL

References to studies excluded from this review

Bogomil'skii 2010 {published data only}

Bogomil'skii MR, Garashchenko TI, Denisova OA. Assessment of the effectiveness of sinuforte used for the combined treatment of rhinosinusitis and exudative otitis media in children. Vestnik Otorinolaringologii 2010;4:74‐7. CENTRAL

Ianov 2007 {published data only}

Ianov IuK, Riazantsev SV, Timchuk LE. Efficacy of sinuforte monotherapy in patients with acute and chronic rhinosinusitis at an exacerbation stage. Vestnik Otorinolaringologii 2007;4:49‐51. CENTRAL

Kriukov 2007 {published data only}

Kriukov AI, Kunel'skaia NL, Turovskii AB, Artem'ev ME, Ibragimova ZS. New perspectives in non‐invasive treatment of sinusitis. Vestnik Otorinolaringologii 2007;2:33‐7. CENTRAL

Mashkova 2010 {published data only}

Mashkova TA, Matveeva VN, Panchenko IG. Comparative characteristic of different methods of conservative treatment of exudative rhinosinusitis. Vestnik Otorinolaringologii 2010;5:13‐4. CENTRAL

Ovchinnikov 2009 {published data only}

Ovchinnikov A, Dzhenzhera GE, Lopatin AS. Efficiency of sinuforte in combined therapy of acute suppurative rhinosinusitis. Vestnik Otorinolaringologii 2009;5:59‐62. CENTRAL

Rybak 2008 {published data only}

Rybak AA, Rybak AA, Matveeva TV, Nepri VG. Effects of sinuforte on quality of life in rhinosinusitis patients. Vestnik Otorinolaringologii 2008;3:56‐8. CENTRAL

Semenov 2011 {published data only}

Semenov VF, Banashek‐Meshcheriakova TV. The efficacy of sinuforte in the starting monotherapy of the patients presenting with acute rhinosinusitis. Vestnik Otorinolaringologii 2011;3:68‐70. CENTRAL

Svistushkin 2013 {published data only}

Svistushkin VM, Nikiforova GN, Vlasova NP. Experience with the application of sinuforte as starting monotherapy of acute rhinosinusitis associated with exudative otitis media in children and adolescents. Vestnik Otorinolaringologii 2013;3:56‐60. CENTRAL

Ahovuo‐Saloranta 2014

Ahovuo‐Saloranta A, Rautakorpi UM, Borisenko OV, Liira H, Williams JW, Mäkelä M. Antibiotics for acute maxillary sinusitis in adults. Cochrane Database of Systematic Reviews 2014, Issue 2. [DOI: 10.1002/14651858.CD000243.pub3]

Aring 2016

Aring AM, Chan MM. Current concepts in adult acute rhinosinusitis. American Family Physician 2016;94(2):97‐105.

Atkins 2004

Atkins D, Best D, Briss PA, Eccles M, Falk‐Ytter Y, Flottorp S, et al. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004;328(7454):1490.

Becker 2003

Becker DG. Medical treatment of sinusitis. Journal of Long‐Term Effects of Medical Implants 2003;13(3):195‐205.

Benninger 1997

Benninger MS, Anon J, Mabry RL. The medical management of rhinosinusitis. Otolaryngology‐Head and Neck Surgery 1997;117(3 Pt 2):S41‐9.

Burgstaller 2016

Burgstaller JM, Steurer J, Holzmann D, Geiges G, Soyka MB. Antibiotic efficacy in patients with a moderate probability of acute rhinosinusitis: a systematic review. European Archives of Oto‐rhino‐laryngology 2016;273(5):1067‐77.

Carr 2016

Carr TF. Complications of sinusitis. American Journal of Rhinology & Allergy 2016;30(4):241‐5.

Dallas 2017

Dallas A, van Driel M, Morgan S, Tapley A, Henderson K, Oldmeadow C. Antibiotic prescribing for acute otitis media and acute sinusitis: a cross‐sectional analysis of the ReCEnT study exploring the habits of early career doctors in family practice. Family Practice 2017;34(2):180‐7.

Dass 2016

Dass K, Peters AT. Diagnosis and management of rhinosinusitis: highlights from the 2015 practice parameter. Current Allergy and Asthma Reports 2016;16(4):29.

Feldt 2013

Feldt B, Dion GR, Weitzel EK, McMains KC. Acute sinusitis. Southern Medical Journal 2013;106(10):577‐81.

Fokkens 2007

Fokkens W, Lund V, Mullol J, European Position Paper on Rhinosinusitis and Nasal Polyps Group. EP3OS 2007. European position paper on rhinosinusitis and nasal polyps 2007. A summary for otorhinolaryngologists. Rhinology 2007;45(2):97‐101.

Gedevanishvili 2007

Gedevanishvili MD, Gogitidze NM, Sigharulidze IS. Reflex mechanisms of nasoparanasal secretion in the administration of Sinuforte. Vestnik Otorinolaringologii 2007;3:54‐6.

Georgy 2012

Georgy MS, Peters AT. Rhinosinusitis. Allergy Asthma Proceedings 2012;33(Suppl 1):24‐7.

GRADEpro GDT 2014 [Computer program]

GRADE Working Group, McMaster University. GRADEpro GDT. Version (accessed prior to 1 June 2017). Hamilton (ON): GRADE Working Group, McMaster University, 2014.

Gwaltney 1994

Gwaltney JM, Phillips CD, Miller RD, Riker DK. Computed tomographic study of the common cold. New England Journal of Medicine 1994;330(1):25‐30.

Harris 2016

Harris AM, Hicks LA, Qaseem A. Appropriate antibiotic use for acute respiratory tract infection in adults: advice for high‐value care from the American College of Physicians and the Centers for Disease Control and Prevention. Annals of Internal Medicine 2016;164(6):425‐34.

Hauer 2014

Hauer AJ, Luiten EL, van Erp NF, Blase PE, Aarts MC, Kaper NM, et al. No evidence for distinguishing bacterial from viral acute rhinosinusitis using fever and facial/dental pain: a systematic review of the evidence base. Otolaryngology‐Head and Neck Surgery 2014;150(1):28‐33.

Higgins 2011

Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Jurkiewicz 2016

Jurkiewicz D, Hassmann‐Poznanska E, Kazmierczak H, Skladzien J, Pietruszewska W, Burduk P, et al. Lyophilized Cyclamen europaeum tuber extract in the treatment of rhinosinusitis. Otolaryngologia Polska 2016;70(1):1‐9.

Kaliner 1997

Kaliner MA, Osguthorpe JD, Fireman P, Anon J, Georgitis J, Davis ML, et al. Sinusitis: bench to bedside. Current findings, future directions. Journal of Allergy and Clinical Immunology 1997;99(Suppl):829‐48.

Kaplan 2014

Kaplan 2014. Canadian guidelines for acute bacterial rhinosinusitis: clinical summary. Canadian Family Physician 2014;60(3):227‐34.

Lefebvre 2011

Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.

Libman 2017

Libman H, Brockmeyer DM, Gold HS. Should we prescribe antibiotics to this patient with persistent upper respiratory symptoms?: grand rounds discussion from Beth Israel Deaconess Medical Center. Annals of Internal Medicine 2017;166(3):201‐8.

Little 2000

Little DR, Mann BL, Godbout CJ. How family physicians distinguish acute sinusitis from upper respiratory tract infections: a retrospective analysis. Journal of the American Board of Family Practice 2000;13(2):101‐6.

Lopatin 2007

Lopatin AS, Shempelev OA. Influence of Sinuforte on the blood microcirculation in the nasal cavity mucosa. Vestnik Otorinolaringologii 2007;4:26‐8.

Marple 2006

Marple BF, Brunton S, Ferguson BJ. Acute bacterial rhinosinusitis ‐ a review of US treatment guidelines. Otolaryngology‐Head and Neck Surgery 2006;135(3):341‐8.

Meltzer 2011

Meltzer EO, Hamilos DL. Rhinosinusitis diagnosis and management for the clinician: a synopsis of recent consensus guidelines. Mayo Clinic Proceedings 2011;86(5):427‐43.

Micromedex 2.0 [Computer program]

Truven Health Analytics, Inc. Cyclamen. Micromedex Solutions 2.0. Ann Arbor, MI: Truven Health Analytics, Inc, (accessed prior to 1 June 2017).

Moher 2009

Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. Annals of Internal Medicine 2009;151(4):264‐9.

Mullol 2009

Mullol J. Trends on rhinosinusitis diagnosis and treatment. Otolaryngologia Polska 2009;63(7):3‐4.

Mullol 2013

Mullol J, Crespo Mstat C, Carre C, Brosa M. Pharmacoeconomics of Cyclamen europaeum in the management of acute rhinosinusitis. Laryngoscope 2013;123(11):2620‐5.

Padia 2016

Padia R, Thomas A, Alt J, Gale C, Meier JD. Hospital cost of pediatric patients with complicated acute sinusitis. International Journal of Pediatric Otorhinolaryngology 2016;80:17‐20.

Passali 2016

Passali D, Spinosi MC, Crisanti A, Bellussi LM. Momethasone furoate nasal spray: a systematic review. Multidisciplinary Respiratory Medicine 2016;11:18.

Review Manager 2014 [Computer program]

Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Rosenfeld 2015

Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, Brook I, Ashok Kumar K, Kramper M, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngology‐Head and Neck Surgery 2015;152(Suppl 2):1‐39.

Rudmik 2017

Rudmik L, Mattos J, Schneider J, Manes PR, Stokken JK, Lee J, et al. Quality measurement for rhinosinusitis: a review from the Quality Improvement Committee of the American Rhinologic Society. International Forum of Allergy & Rhinology 2017;XX:1‐8.

Savvateeva 2010

Savvateeva DM, Lopatin AS. Application of Sinuforte in domestic and foreign practices. Vestnik Otorinolaringologii 2010;1:88‐92.

Schappert 2006

Schappert SM, Burt CW. Ambulatory care visits to physician offices, hospital outpatient departments and emergency departments: United States, 2001‐02. Vital and Health Statistics. Series 13 2006;159:1‐66.

Shaikh 2014

Shaikh N, Wald ER. Decongestants, antihistamines and nasal irrigation for acute sinusitis in children. Cochrane Database of Systematic Reviews 2014, Issue 10. [DOI: 10.1002/14651858.CD007909.pub4]

Sharp 2015

Sharp AL, Klau MH, Keschner D, Macy E, Tang T, Shen E, et al. Low‐value care for acute sinusitis encounters: who's choosing wisely?. American Journal of Managed Care 2015;21(7):479‐85.

Shintani Smith 2015

Shintani Smith S, Henderson Ference E, Evans TC, Tan KB, Kern CR, Chandra KR. The prevalence of bacterial infection in acute rhinosinusitis: a systematic review and meta‐analysis. Laryngoscope 2015;125(1):57‐69.

Shrum 2001

Shrum KM, Grogg SE, Barton P, Shaw HH, Dyer RR. Sinusitis in children: the importance of diagnosis and treatment. Journal of the American Osteopathic Association 2001;101(Suppl 5):8‐13.

Smith 2012

Smith SR, Montgomery LG, Williams JW. Treatment of mild to moderate sinusitis. Archives of Internal Medicine 2012;172(6):510‐3.

Sng 2015

Sng WJ, Wang DY. Efficacy and side effects of antibiotics in the treatment of acute rhinosinusitis: a systematic review. Rhinology 2015;53(1):3‐9.

Snow 2001

Snow V, Mottur‐Pilson C, Hickner JM. Principles of appropriate antibiotic use for acute sinusitis in adults. Annals of International Medicine 2001;134(6):495‐7.

Tutkun 1996

Tutkun A, Inanli S, Batman C, Uneri C, Sehitoglu MA. The impact of intranasal steroid as an adjunct to therapy for sinusitis. Marmara Medical Journal 1996;9(1):11‐4.

Van den Broek 2014

Van den Broek MF, Gudden C, Kluijfhout WP, Stam‐Slob MC, Aarts MC, Kaper NM, et al. No evidence for distinguishing bacterial from viral acute rhinosinusitis using symptom duration and purulent rhinorrhea: a systematic review of the evidence base. Otolaryngology‐Head and Neck Surgery 2014;150(4):533‐7.

Venekamp 2014

Venekamp RP, Thompson MJ, Hayward G, Heneghan CJ, Del Mar CB, Perera R, et al. Systemic corticosteroids for acute sinusitis. Cochrane Database of Systematic Reviews 2014, Issue 3. [DOI: 10.1002/14651858.CD008115.pub3]

Zalmanovici Trestioreanu 2013

Zalmanovici Trestioreanu A, Yaphe J. Intranasal steroids for acute sinusitis. Cochrane Database of Systematic Reviews 2013, Issue 12. [DOI: 10.1002/14651858.CD005149.pub4]

References to other published versions of this review

Zalmanovici 2014

Zalmanovici Trestioreanu A, Barua A, Pertzov B. Cyclamen europaeum extract for acute sinusitis. Cochrane Database of Systematic Reviews 2014, Issue 10. [DOI: 10.1002/14651858.CD011341]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Jump to:

Pfaar 2012

Methods

Randomised, parallel, double‐blind; intention‐to‐treat

Participants

Age: 18 to 65 years, N = 99

Inclusion criteria: men/women, moderate or severe acute rhinosinusitis symptoms > 7 days and < 12 weeks, at least 2 of: nasal obstruction, nasal secretion, facial pain/tension/pressure, impaired or loss of smell and mucus oedema, nasal obstruction or mucopurulent secretion on nasal endoscopy

Exclusion criteria: chronic rhinosinusitis, nasal polyposis, severe mechanical nasal obstruction, severe asthmatic patients, intolerance to acetylsalicylic acid, treatment with anticoagulants or anticholinergic drugs, topical nasal corticosteroids within 72 hours of study start, or antibacterial agent within 48 hours

Interventions

1. Treatment: Cyclamen europaeum nasal spray, lyophilised extract, 1.3 mg once daily each nostril, N = 48

2. Control: placebo matching, once daily, N = 51

Concomitant amoxycillin 500 mg 3 times daily for 8 days or alternative if allergic to penicillin in both groups

Treatment duration: 15 days

Follow‐up: 15 days

Outcomes

Change from baseline in mean total symptom score on days 5 to 7

Individual symptoms scores on days 5 to 7 and 15

Total symptom score at day 15, endoscopic findings on days 5 to 7 and 15

Treatment failure/need for additional treatment

Complications

Sleep quality

Overall treatment satisfaction

Notes

Similar baseline characteristics, 13 centres in Germany, informed consent, intensity of rhinosinusitis symptoms assessed by visual analogue scale (0 to 10 cm). Subjective assessment; no concomitant treatment with corticosteroids or decongestants was allowed; symptom diaries completed by participants; endoscopic findings assessed by 4‐point Likert scales from 0 to 3; adverse events and complications of rhinosinusitis were monitored. Grant from Hartington Pharmaceutical Spain. We tried to contact trial authors for more information regarding the randomisation method and for data on participants, i.e. whether participants were inpatients, outpatients, or both, as this was not mentioned in the paper, but did not receive a reply.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomly assigned, method not mentioned

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blind, placebo matching

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not mentioned

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Dropouts described. Treatment group 8 total: 2 adverse events, 3 discontinued treatment, 1 immunosuppressive treatment, 2 other. Placebo group 9 total: 1 adverse event, 2 discontinued treatment, 1 consent withdrawal, 5 other. Dropouts balanced between study groups, reasons reported, analyses by intention‐to‐treat.

Selective reporting (reporting bias)

Low risk

Not observed

Other bias

Low risk

Not observed

Ponikau 2012

Methods

Randomised, parallel, double‐blind; intention‐to‐treat

Participants

Age: 18 to 70 years, N = 48

Inclusion criteria: men/women, outpatients with symptoms and endoscopy + radiology acute rhinosinusitis or acute exacerbation of chronic rhinosinusitis, total symptom score ≥ 3 (nasal obstruction/congestion, facial pain/fullness/pressure), endoscopy ‐ mucopurulence and inflammation, CT scan ‐ air fluid levels and/or air bubbles in at least 1 maxillary sinus

Exclusion criteria: pregnant, hypogammaglobulinaemia, immotile cilia syndrome, cystic fibrosis, atrophic rhinitis, rhinitis medicamentosa, hypersensitivity to Primulaceae, serious comorbidity, expansile mass or bony erosion on radiologic examination, viral upper respiratory tract infection in past 2 weeks, high fever, facial or periorbital oedema or local complications, recent nasal/sinus surgery within 3 months, radiation treatment or chemotherapy within 1 year, intranasal antibiotics within 30 days, systemic antibiotics within 15 days, oral/topical nasal decongestants within 7 days

Interventions

1. Treatment: Cyclamen europaeum nasal spray, 10% lyophilised (Sinuforte), 1.3 mg (0.13 mL) once daily each nostril, N = 24

2. Control: placebo spray sterile water, once daily, N = 24

Treatment duration: 7 days

Follow‐up: 90 days

Outcomes

Change from baseline in % sinus opacification on CT scans at days 15, 29 or endpoint

Reduction in total symptom score (6‐point scale: nasal obstruction, congestion, facial pain, pressure, fullness)

Other symptoms scores changes from baseline

Endoscopic inflammation at day 8

Notes

Similar baseline characteristics; outpatients 25 US centres; November 2007 to September 2008; intranasal/systemic antibiotics, oral/inhaled steroids, decongestants were not allowed. Visit 1: randomisation, visit 2: 7 days, follow‐up visit 3: 15 days, visit 4: 29 days, telephone follow‐up: 90 days; participants' diaries for symptoms, adverse events, concomitant medication. CT scans at visits 1, 3, 4, endoscopy at visits 1, 2, no serious adverse events. Funded by Hartington Pharmaceutical, Spain and Dey Pharma, LP, Napa, CA, USA

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomly assigned, computer‐generated scheme

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blind, matching product vials labelled to obscure the contents

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Mentioned only for 1 outcome, central reader of CT scans was blinded to treatment assignment

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Dropouts described. Treatment group 16 total dropouts: 11 excluded: 9 chronic rhinosinusitis, 2 unclassified; 13 included in analyses (5 discontinued: 2 protocol violation, 3 other); 8 completed study. Placebo group 13 total dropouts: 8 excluded: 4 chronic rhinosinusitis, 4 unclassified; 16 included in analyses (1 lost to follow‐up; 4 discontinued: 1 protocol violation, 3 other); 11 completed study. Reasons for dropout reported, analysis by intention‐to‐treat.

Selective reporting (reporting bias)

Low risk

Not observed

Other bias

Low risk

Not observed

CT: computed tomography

Characteristics of excluded studies [ordered by study ID]

Jump to:

Study

Reason for exclusion

Bogomil'skii 2010

The comparison did not meet inclusion criteria: combined interventions were used in the control group that differed from the intervention group.

Ianov 2007

The comparison did not meet inclusion criteria: combined interventions were used in the control group that differed from the intervention group.

Kriukov 2007

The comparison did not meet inclusion criteria: combined interventions were used in the control group that differed from the intervention group.

Mashkova 2010

Not randomised, combined different treatments in the intervention and control groups.

Ovchinnikov 2009

Randomisation not clear; we contacted the author, who confirmed quasi‐randomisation by odd/even numbers.

Rybak 2008

The comparison did not meet inclusion criteria: combined interventions were reported as "standard treatment" for the intervention and control groups, and the control group used punctures of the maxillary sinuses as comparison.

Semenov 2011

Not randomised, no control group

Svistushkin 2013

Not randomised, no control group

Data and analyses

Open in table viewer
Comparison 1. Cyclamen europaeum versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Proportion of participants with any adverse event ‐ intention‐to‐treat Show forest plot

2

147

Risk Ratio (M‐H, Fixed, 95% CI)

2.11 [1.35, 3.29]

Analysis 1.1

Comparison 1 Cyclamen europaeum versus placebo, Outcome 1 Proportion of participants with any adverse event ‐ intention‐to‐treat.

Comparison 1 Cyclamen europaeum versus placebo, Outcome 1 Proportion of participants with any adverse event ‐ intention‐to‐treat.

2 Proportion of participants with any adverse events ‐ best‐case sensitivity analysis Show forest plot

2

147

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.68, 1.30]

Analysis 1.2

Comparison 1 Cyclamen europaeum versus placebo, Outcome 2 Proportion of participants with any adverse events ‐ best‐case sensitivity analysis.

Comparison 1 Cyclamen europaeum versus placebo, Outcome 2 Proportion of participants with any adverse events ‐ best‐case sensitivity analysis.

3 Proportion of participants with any adverse event ‐ worst‐case sensitivity analysis Show forest plot

2

147

Risk Ratio (M‐H, Fixed, 95% CI)

3.49 [2.30, 5.30]

Analysis 1.3

Comparison 1 Cyclamen europaeum versus placebo, Outcome 3 Proportion of participants with any adverse event ‐ worst‐case sensitivity analysis.

Comparison 1 Cyclamen europaeum versus placebo, Outcome 3 Proportion of participants with any adverse event ‐ worst‐case sensitivity analysis.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Cyclamen europaeum versus placebo, Outcome 1 Proportion of participants with any adverse event ‐ intention‐to‐treat.
Figures and Tables -
Analysis 1.1

Comparison 1 Cyclamen europaeum versus placebo, Outcome 1 Proportion of participants with any adverse event ‐ intention‐to‐treat.

Comparison 1 Cyclamen europaeum versus placebo, Outcome 2 Proportion of participants with any adverse events ‐ best‐case sensitivity analysis.
Figures and Tables -
Analysis 1.2

Comparison 1 Cyclamen europaeum versus placebo, Outcome 2 Proportion of participants with any adverse events ‐ best‐case sensitivity analysis.

Comparison 1 Cyclamen europaeum versus placebo, Outcome 3 Proportion of participants with any adverse event ‐ worst‐case sensitivity analysis.
Figures and Tables -
Analysis 1.3

Comparison 1 Cyclamen europaeum versus placebo, Outcome 3 Proportion of participants with any adverse event ‐ worst‐case sensitivity analysis.

Summary of findings for the main comparison. Cyclamen europaeum compared to placebo for acute sinusitis

Cyclamen europaeum compared to placebo for acute sinusitis

Patient or population: adults with acute sinusitis
Setting: outpatients in Germany and the USA
Intervention:Cyclamen europaeum topical intranasal spray (1.3 mg once daily in each nostril for up to 15 days)
Comparison: placebo

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo

Risk with Cyclamen europaeum

Proportion of participants with resolution or improvement of symptoms up to 30 days

No studies reported this outcome.

Proportion of participants with any adverse event

Study population

RR 2.11
(1.35 to 3.29)

147
(2 RCTs)

⊕⊕⊕⊝

Moderate

We downgraded the quality of the evidence as concealment of allocation to treatment and blinding of outcome assessors were not reported in the studies. Also, 1 study had a small sample size with a high attrition rate.

240 per 1000

506 per 1000
(324 to 790)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)

CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Figures and Tables -
Summary of findings for the main comparison. Cyclamen europaeum compared to placebo for acute sinusitis
Table 1. Adverse events

Study ID

Cyclamen europaeum

Placebo

Pfaar 2012

67% total

50% nasal irritation mild/moderate

27% mild epistaxis

4% sneezing

3 discontinued treatment

29% total

4% nasal irritation

14% mild epistaxis

4% vertigo

2 discontinued treatment

Ponikau 2012

15.4% total

Influenza, throat irritation, migraine, sneezing

No serious adverse events

Did not discontinue treatment

12.5% total

Headache, ear pain, gastritis, back pain, conjunctival haemorrhage

No serious adverse events

Did not discontinue treatment

Figures and Tables -
Table 1. Adverse events
Comparison 1. Cyclamen europaeum versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Proportion of participants with any adverse event ‐ intention‐to‐treat Show forest plot

2

147

Risk Ratio (M‐H, Fixed, 95% CI)

2.11 [1.35, 3.29]

2 Proportion of participants with any adverse events ‐ best‐case sensitivity analysis Show forest plot

2

147

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.68, 1.30]

3 Proportion of participants with any adverse event ‐ worst‐case sensitivity analysis Show forest plot

2

147

Risk Ratio (M‐H, Fixed, 95% CI)

3.49 [2.30, 5.30]

Figures and Tables -
Comparison 1. Cyclamen europaeum versus placebo