Williamson 2007.

Methods	Study design: RCT (factorial design) Study duration: from November 2001 to November 2005
Participants	Setting: ambulatory care (58 family practices, 74 family physicians) Country: UK Health status: people presenting with uncomplicated acute illness (< 28 days) and at least 2 symptoms and 1 clinical sign of sinusitis (according to the Berg and Carenfelt criteria: purulent nasal discharge predominating on 1 side, local facial pain predominating on 1 side, purulent nasal discharge on both sides, pus in the nasal cavity) Numbers: total: treatment (113, including treatment group 1 and 2); control (127, including treatment group 3 and control group) analysed: treatment (101, including treatment group 1 and 2); control (108, including treatment group 3 and control group) Age: mean 43 in amoxicillin group and 42 in placebo group Sex: 72.5% women Exclusion criteria: < 2 of the Berg and Carenfelt criteria (low probability of sinusitis), history of recurrent sinusitis (≥ 2 attacks of acute sinusitis in the previous 12 months), significant morbidities (poorly controlled diabetes or heart failure), pregnant or breastfeeding, allergies, a history of adverse reactions to either medications, and receiving antibiotics or steroids in the previous month
Interventions	Treatment group: Group 1 intervention: amoxicillin dose, duration, frequency, administration: 750 mg, 7 days, twice daily, orally intervention: budesonide dose, duration, frequency, administration: 1 dosis, 10 days, once daily, nose spray (in each nostril) Group 2 intervention: amoxicillin dose, duration, frequency, administration: 750 mg, 7 days, twice daily, orally intervention: placebo dose, duration, frequency, administration: 10 days, once daily, nose spray (in each nostril) Group 3 intervention: placebo dose, duration, frequency, administration: 7 days, twice daily, orally intervention: budesonide dose, duration, frequency, administration: 1 dosis, 10 days, once daily, nose spray (in each nostril) Control group: intervention: placebo dose, duration, frequency, administration: 7 days, twice daily, orally intervention: placebo dose, duration, frequency, administration: 1 dosis, 10 days, once daily, nose spray (in each nostril) For this review, we reduced the 4 treatment arms to 2 (factorial design): treatment group 1 and 2 (treatment group) versus treatment group 3 and control group (control group)
Outcomes	Primary outcome: symptom resolution (all symptoms score 0 in the diary) Secondary outcome: symptom severity score
Notes	Funding source: supported by the UK Department of Health. The UK Department of Health did not participate in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. Contact with study authors for additional information: none Other notes: Registration at inclusion: baseline questionnaire including clinical signs and confirmation of entry criteria completed by general practitioners, basic physical examination of temperature recording, sinus tenderness, and anterior nasal cavity inspection (anterior rhinoscopy), recording of symptom duration and pain severity, collection of baseline demographic details. Follow‐up: diary for 14 days (11 symptom variables, 7‐point Likert scale) questionnaire on other variables (clinical features and satisfaction), and a telephone call during the first week to encourage adherence and improve the quality of the diary returns Subgroup analysis of the pain and unwell group Results: Symptom resolution at day 10: treatment group: 71/101 control group: 71/108 Side effects: no information available Clinical failure (withdrawal because of ongoing symptoms) treatment group: 1/101 control group: 1/108 no serious adverse events
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Recruitment plan was for 4 recruited cases per family physician (1 block randomised pack of 4 per physician and 2 physicians per practice)." Quote: "The packs were made up using random number tables." Quote: "Randomisation was performed at the level of the patient." Quote: "Each randomized pack therefore consisted of an auditable sequence of the 4 possible combinations of the 2 interventions and physicians were instructed to use the packs in sequence."
Allocation concealment (selection bias)	Low risk	Quote: "An independent person to the trial team was employed for distribution using the random sequence and trial code." Quote: "The code break was kept in a sealed envelope in a locked filing cabinet at the university throughout the study period." Quote: "All drug containers and all trial materials were identifiable only by the randomisation code number." Comment: blind‐sequenced trial packs. Quote: "The sealed, opaque, numbered packages contained physician instructions and either active or placebo drugs that were distributed in batches in randomised blocks of 4."
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "Neither the antibiotic nor the nasal steroid spray was recognisable as active or placebo medication, identical in taste and appearance." Comment: no significant difference in participant's belief in the effectiveness of the treatment allocated (0‐to‐5 scales) for the antibiotic tablet versus placebo tablet (P = 0.07), or for steroid spray versus placebo spray (P = 0.25). Comment: the single code break envelope was not opened until all data collection had been completed and all variables had been entered into the database. All outcome assessments were recorded on a central database and checked and verified when necessary by a research fellow blinded to treatment grouping.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Post‐randomisation dropout rate: 31/240 (12.9%) due to loss to follow‐up treatment group: 12 control group: 19 Reasons for missing data: loss to follow‐up 2 additional participants withdrew (1 in the amoxicillin group and 1 in the placebo group) because of ongoing symptoms; we considered these as failures in our review. Ratio of participants with missing data to participants with events: 0.23 Comment: the authors remarked that participants who had pus on examination and were male were more likely to be lost to follow‐up the authors performed a sensitivity analysis in 2 ways: with imputation of data (assuming those lost to follow‐up were still symptomatic at day 14) and with and without the additional telephone information obtained. They found no significant difference in results.
Selective reporting (reporting bias)	Low risk	Comment: the study protocol is described in the methods section. The primary and secondary endpoints were predefined.
Other bias	Low risk	Comment: there was no significant imbalance of participant characteristics at baseline, except for temperature (slightly higher temperature in the placebo group, but the difference was too small to have any clinical importance). with the available information, we could not detect other reasons for bias (no design‐specific risks of bias, the study was not stopped early, no imbalance of participant characteristics at baseline, blinding was not broken due to side effects, no bias due to increased or different diagnostic activity). Dr Little reported receiving consultancy fees for 2 half days from Abbott Pharmaceuticals regarding complications of respiratory tract infections. No other authors reported financial disclosures. Family physicians received USD 50 per participant recruited from government funding, but participants received no reimbursement. average number of participants per practice: 3.6

CRP: C‐reactive protein
 CT: computed tomography
 ENT: ear, nose, and throat
 ITT: intention‐to‐treat
 RCT: randomised controlled trial
 SNOT: Sino‐Nasal Outcome Test
 VAS: visual analogue scale