Corticosteroids for treatment of sore throat: systematic ... · Corticosteroids for treatment of...

the bmj | BMJ 2017;358:j3887 | doi: 10.1136/bmj.j3887 1

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Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trialsBehnam Sadeghirad,1,2 Reed A C Siemieniuk,1 Romina Brignardello-Petersen,1,3 Davide Papola,4 Lyubov Lytvyn,5 Per Olav Vandvik,6,7 Arnaud Merglen,8 Gordon H Guyatt,1 Thomas Agoritsas1,9

ABSTRACTOBJECTIVETo estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat.DESIGNSystematic review and meta-analysis of randomised control trials.DATA SOURCESMedline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries up to May 2017, reference lists of eligible trials, related reviews.STUDY SELECTIONRandomised controlled trials of the addition of corticosteroids to standard clinical care for patients aged 5 or older in emergency department and primary care settings with clinical signs of acute tonsillitis, pharyngitis, or the clinical syndrome of sore throat. Trials were included irrespective of language or publication status.REVIEW METHODSReviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. Random effects model was used for meta-analyses. Quality of evidence was assessed with the GRADE approach.RESULTS10 eligible trials enrolled 1426 individuals. Patients who received single low dose corticosteroids (the most common intervention was oral dexamethasone with a maximum dose of 10 mg) were twice as likely to

experience pain relief after 24 hours (relative risk 2.2, 95% confidence interval 1.2 to 4.3; risk difference 12.4%; moderate quality evidence) and 1.5 times more likely to have no pain at 48 hours (1.5, 1.3 to 1.8; risk difference 18.3%; high quality). The mean time to onset of pain relief in patients treated with corticosteroids was 4.8 hours earlier (95% confidence interval −1.9 to −7.8; moderate quality) and the mean time to complete resolution of pain was 11.1 hours earlier (−0.4 to −21.8; low quality) than in those treated with placebo. The absolute pain reduction at 24 hours (visual analogue scale 0-10) was greater in patients treated with corticosteroids (mean difference 1.3, 95% confidence interval 0.7 to 1.9; moderate quality). Nine of the 10 trials sought information regarding adverse events. Six studies reported no adverse effects, and three studies reported few adverse events, which were mostly complications related to disease, with a similar incidence in both groups.CONCLUSIONSingle low dose corticosteroids can provide pain relief in patients with sore throat, with no increase in serious adverse effects. Included trials did not assess the potential risks of larger cumulative doses in patients with recurrent episodes of acute sore throat.SYSTEMATIC REVIEW REGISTRATIONPROSPERO CRD42017067808.

IntroductionSore throat is among the most common presenting complaints in both emergency departments and outpatient care settings. It is the cause of about 5% of medical visits in children and about 2% of all outpatient visits in adults.1-3 The most common cause of sore throat is acute pharyngitis caused by self limiting viral infections. Pain management with paracetamol (acetaminophen) or non-steroidal anti-inflammatory drugs (NSAIDs) therefore represents the mainstay of care.4 5 These drugs provide limited pain relief but also sometimes cause serious harm.6 7

Treatment of sore throat with antibiotics also provides modest benefit in reduction of symptoms and fever when the infection is bacterial, but their use could contribute to antibiotic resistance.8 9 Although most cases of sore throat have a viral aetiology, and the risk of secondary complications is low, clinicians commonly prescribe antibiotics.4 10 Though this could be because clinicians think that patients seeking care expect a course of antibiotics, in reality pain relief might be more important to them.10

Corticosteroids represent an additional therapeutic option for symptom relief. Randomised control trials

1Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada2HIV/STI Surveillance Research Centre, and WHO Collaborating Centre for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran3Faculty of Dentistry, University of Chile, Santiago, Chile4Department of Public Health and Community Medicine, Section of Psychiatry, University of Verona, Italy5Oslo University Hospital, Oslo, Norway6Department of Medicine, Innlandet Hospital Trust, Division Gjøvik, Oslo, Norway7Institute of Health and Society, Faculty of Medicine, University of Oslo, Norway8Division of General Paediatrics, University Hospitals of Geneva and Faculty of Medicine, University of Geneva, Geneva, Switzerland9Division of General Internal Medicine and Division of Clinical Epidemiology, University Hospitals of Geneva, SwitzerlandCorrespondence to: B Sadeghirad [email protected] material is published online only. To view please visit the journal online.Cite this as: BMJ 2017;358:j3887 http://dx.doi.org/10.1136/bmj.j3887

Accepted: 9 August 2017

WhAT IS AlReAdy knoWn on ThIS TopICShort course corticosteroids are one adjunct treatment option for relief of symptoms in patients with sore throatCorticosteroids are not commonly prescribed as clinicians are uncertain about the balance of benefits and harms and the applicability of the evidence to patients with less severe disease

WhAT ThIS STudy AddSModerate to high quality evidence suggests the addition of one (or two) dose(s) of corticosteroids reduces the intensity and duration of pain in patients with sore throat with no increase in serious adverse effectsThe mean time to complete pain resolution was about 11 hours shorter with corticosteroids, and about 18% more patients experienced complete pain relief at 48 hoursThere were no subgroup effects between patients consulting at the emergency departments or primary care family practice

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suggest that a short course of low-to-moderate dose corticosteroids probably provides symptomatic benefit to patients with sore throat.11-14 Despite this evidence, clinicians do not commonly use steroids. Reasons might include uncertain applicability of the evidence to patients with less severe disease, as the initial studies enrolled only patients with severe sore throat presenting to emergency departments, almost all of whom received antibiotics.

This systematic review is part of the BMJ Rapid Recommendations project, a collaborative effort from the MAGIC research and innovation programme (www.magicproject.org) and BMJ. The aim of the project is to respond to new potentially practice changing evidence and provide a trustworthy practice guideline in a timely manner.15 In this case, the stimulus was the recent TOAST (Treatment Options without Antibiotics for Sore Throat) trial, which randomised over 500 patients with sore throat presenting to their primary care clinician who were not initially prescribed antibiotics; the TOAST authors reported beneficial effects of corticosteroids.16 In the light of this new potentially practice changing evidence, we updated the latest Cochrane review12 dealing with the effectiveness and safety of corticosteroids as an adjunct treatment for sore throat in addition to standard care compared with standard care alone. This systematic review informed the parallel guideline published in a multi-layered electronic format on bmj.com17 and MAGICapp (https://www.magicapp.org/goto/guideline/JjXYAL/section/j79pvn).

MethodsGuideline panel and patient involvementAccording to the BMJ Rapid Recommendations process,15 a guideline panel provided critical oversight to the review and identified populations, subgroups, and outcomes of interest. The panel included clinicians, methodologists, and patients with experience of sore throat. Patients received personal training and support to optimise contributions throughout the guideline development process. The patients on the panel led the interpretation of the results based on what they expected the typical patient values and preferences to be, as well as the variation between patients. Five patient representatives were full members of the guideline panel and contributed to the selection and prioritisation of outcomes, values and preferences assessments, and critical feedback to the protocol for the systematic review and the BMJ Rapid Recommendations manuscript.

Search strategyWe searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant published randomised controlled trials based on the strategy reported in the most recent Cochrane systematic review,12 modified under the guidance of a research librarian (appendix 1). We limited the search from 1 January 2010, which included a two month overlap with the previous Cochrane review search,12

to 1 May 2017. There were no language restrictions. We reviewed reference lists from eligible new trials and related reviews for additional eligible trials and searched ClinicalTrials.gov for ongoing or unpublished trials and for additional data from published trials.

Study selectionReviewers (BS, RACS, DP, RBP) independently and in duplicate screened the titles and abstracts of all identified studies using a priori selection criteria. Subsequently, the samereviewersindependently assessed eligibility of the full texts of potentially eligible studies. Reviewers resolved discrepancies through discussion or, if needed, by adjudication from a third reviewer.

We included randomised controlled trials that compared corticosteroids with standard of care or placebo and enrolled adults and/or children aged 5 and over in emergency departments and primary care settings with a clinical syndrome of sore throat (painful throat, odynophagia, or pharyngitis).

We excluded studies of participants who were admitted to hospital or immunocompromised and those with infectious mononucleosis, sore throat after any surgery or intubation (postoperative sore throat), gastroesophageal reflux disease, croup, or peritonsillar abscess. We also excluded studies that enrolled children aged under 5 because they would not be able to provide trustworthy outcome measurements, especially for self reported pain.

Our outcomes of interest were complete resolution of pain at 24 and 48 hours; mean time to onset of pain relief; mean time to complete resolution of pain; absolute reduction of pain at 24 hours; duration of bad/non-tolerable symptoms (such as problems for eating, drinking, swallowing); recurrence/relapse of symptoms; days missed from school or work; need for antibiotics; and rate of adverse events related to treatment. We included any adverse events reported by the authors.

Data abstraction and risk of bias assessmentReviewers extracted the following data, independently and in duplicate: general study information (authors, publication year, and study location); study population details (sample size, age, diagnosis, and percentage of participants with confirmed group A β haemolytic streptococcus (GAS) pharyngitis or culture positive for bacterial pathogens); setting (primary care versus hospital emergency department); details on the intervention and comparison (for example, type, form, duration, and dose of corticosteroids; type of control group); co-interventions (proportion of participants who received antibiotics and/or analgesics); and outcomes as listed above.

In randomised controlled trials with more than two arms, we extracted data from the arm closest to a single dose regimen or data from the arm that received corticosteroid as adjunct treatment to standard of care rather than instead of standard of care. In trials with data for both oral and parenteral corticosteroids, we



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used oral data for the main analysis and intramuscular data for the appropriate subgroup analysis.

Two reviewers independently assessed risk of bias us-ing the modified Cochrane risk of bias instrument,18 19 which deals with random sequence generation; allo-cation concealment; blinding of study participants, healthcare providers, and outcome assessors; incom-plete outcome data; and other potential sources of bias. Reviewers classified studies at high risk of bias when they had rated at least one item as high risk of bias.

To assess the quality of evidence, we used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach that classifies evidence as high, moderate, low, or very low quality based on considerations of risk of bias, consistency, directness, precision, and publication bias.20 We resolved disagreements between reviewers in data extraction and assessments of risk of bias or quality of evidence by discussion and, if needed, by third party adjudication. We used the MAGICapp platform to generate the GRADE summary of findings table.

Data synthesis and statistical methodsFor continuous outcomes, we calculated the mean difference and its corresponding 95% confidence interval. For dichotomous outcomes, we calculated the relative risk and its corresponding 95% confidence interval and determined the absolute effect by multiplying the relative risk and its confidence interval with the estimated baseline risk. The median of the placebo group of included randomised controlled trials provided the baseline risk.

Statistical heterogeneity was determined with the Q statistic and I2. We used the DerSimonian-Laird random effects model for the meta-analysis of all outcomes. Regardless of the observed statistical heterogeneity, we conducted the following prespecified subgroup analyses when each subgroup was represented by at least two studies: age (children v adults), postulating a larger effect in adults; route of administration of corticosteroids (oral v parenteral), postulating a larger effect for parenteral; presence or absence of positive results on culture for a bacterial pathogen or direct antigen test for group A β haemolytic streptococcus, postulating a larger effect in patients with positive test results; initial setting (emergency departments v family practice), postulating a larger effect in patients consulting the emergency department; and place of subsequent care (admitted to hospital v outpatient), postulating a larger effect among the patients admitted. For subgroup analysis, we tested for interaction using a χ2 significance test.21 We planned to examine publication bias using funnel plots for outcomes for which data from 10 or more studies were available.22 Data were analysed with STATA software (version 14.2, TX, USA).

Patient involvementFive patient representatives were full members of the guideline panel, and contributed to the

selection and prioritisation of outcomes, values and preferences assessments, and critical feedback to the protocol for the systematic review and the BMJ Rapid Recommendations manuscript.

ResultsDescription of included studiesWe identified 2349 titles and abstracts through our literature search, of which 46 were potentially eligible and 36 were excluded (19 were not randomised trials; 14 had no patients with sore throat/acute pharyngitis; in three corticosteroids were not among the interventions or were not compared with a placebo/usual care). Figure 1 shows the details of study selection process.

The 10 randomised controlled trials that proved eligible enrolled 1426 individuals. Eight studies recruited patients from hospital emergency departments23-30 and two from primary care.16 31 Three studies enrolled children,27-29 six studies enrolled adults,16 24-26 30 31 and one study included both children and adults.23 Oral dexamethasone (single dose of 10 mg for adults and 0.6 mg/kg, maximum 10 mg for children) was the most common intervention (five studies) followed by single dose intramuscular injection of dexamethasone (three studies). All patients in three trials received both antibiotics and analgesics as the usual care25 26 30; in two trials, all patients received antibiotics, while analgesics were prescribed at the physician’s discretion.23 24 In the five remaining trials, patients in usual care group received antibiotics or analgesics at the physician’s discretion.16 27-29 31 Table 1 presents study details.

Duplicates removed (n=286)

Total articles(n=2635)

Articles screened by title/abstract(n=2349)

Not randomised trial (n=19)Not sore throat/acute pharyngitis (n=14)No corticosteroid (n=2)Corticosteroids not compared withplacebo/usual care (n=1)

Full text articles assessedfor eligibility (n=46)

Additional records identi�edthrough other sources

(n=2)

Records identi�ed from electronic searches

(n=2633)

Articles excluded (n=2303)Main reasons for exclusion: observational study, post-surgical sore throat, not randomised to corticosteroids

Articles included inreview (n=10)

Fig 1 | Selection of studies in review of corticosteroids for treatment of sore throat



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| Cha

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Among the included studies, four randomised controlled trials were at high risk of bias.23 24 26 28 One study had issues in more than one category of risk.26 The three remaining studies had issues in concealment of the treatment allocation, incomplete outcome reporting, and blinding of outcome assessors. Appendix 2 summarises the risk of bias assessments.

Table 2 shows findings for all outcomes. Interactive tables summarising findings are available at https://www.magicapp.org/goto/guideline/JjXYAL/section/j79pvn

PainIn the five randomised controlled trials that reported complete resolution of symptoms at 24 hours,16 25 29-31 patients who received a single dose of corticosteroids were twice as likely to experience complete symptom resolution than placebo patients (relative risk 2.24, 95% confidence interval 1.17 to 4.29; I2=69%, 22.4% v 10.0%; moderate quality evidence; fig 2, table 2). All studies reporting this outcome were at low risk of bias. Tests of interaction showed no evidence of any subgroup effect (table A in appendix 3).

In the four trials that reported complete resolution of pain at 48 hours,16 29-31 patients treated with corticosteroids were 50% more likely to experience complete resolution (relative risk 1.48, 95% confidence interval 1.26 to 1.75; I2=3%, 60.8% v 42.5%; high quality; fig 3, table 2). These four studies were all at low risk of bias, and tests of interaction showed no evidence of any subgroup effect (table A in appendix 3).

In the eight studies that reported mean time to onset of pain relief,16 23-28 30 patients who received corticosteroids experienced onset of pain relief on average 4.8 hours earlier than those who received placebo (95% confidence interval −1.9 to −7.8; I2=78%; moderate quality; fig 4, table 2). We found no evidence of subgroup effect for this outcome (table A in appendix 3).

Time to complete resolution of pain was reported in six studies.16 23 24 27 28 30 On average, patients receiving a single dose corticosteroid experienced complete resolution 11.1 hours earlier (95% confidence interval −0.4 to −21.8; I2=85%; low quality; fig 5, table 2). In our subgroup analysis, we found a significantly larger effect among those treated with intramuscular corticosteroids (mean difference −22.4 (95% confidence interval −27.3 to −17.5) and −1.5 (−12.6 to 9.5), for intramuscular and oral corticosteroids, respectively; P=0.001 for interaction); however, the effect modification is suggested by comparison between rather than within studies. We found no other subgroup effect (table B in appendix 3).

Meta-analysis from eight studies that assessed pain with a visual analogue scale (0=no pain, 10=maximum pain) at baseline and after 24 hours16 23-28 31 showed a 1.3 points lower pain score among patients treated with corticosteroids compared with those treated with placebo at 24 hours (95% confidence interval 0.7 to 1.9; I2=65%; moderate quality; fig 6, table 2). We



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found no evidence of subgroup effect for this outcome (table B in appendix 3).

To assess the possibility that there was selective reporting, we examined the magnitude of effect on the time to onset of pain relief, time to complete resolution of pain, and absolute pain reduction in studies that did and did not report resolution of pain at 24 and 48 hours. The magnitude of effect on the other pain outcomes was similar in both sets of studies, making selective reporting less likely (table C in appendix 3).

Other outcomesThe authors of one study reported a possible decrease in the likelihood of receipt of antibiotics in patients

treated with corticosteroids (relative risk 0.83, 95% confidence interval 0.61 to 1.13; moderate quality).16 Three studies27 28 31 suggested a possible lower risk of recurrence/relapse of the symptoms (0.52, 0.16to 1.73; I2=23%; moderate quality, table D in appendix 3, table 2).

Kiderman and colleagues reported that 22/40 (55%) patients treated with corticosteroids and 27/39 (69%) taking placebo took time off work because of sore throat (relative risk 0.8, 95% confidence interval 0.6 to 1.1).31 Marvez-Valls and colleagues reported that adult patients treated with corticosteroids missed an average of 0.4 (SD 1.4) days, whereas patients in the placebo arm missed an average of 0.7 (SD 1.4) days (mean

Table 2 | GRADE summary of findings for corticosteroids (intervention) versus no corticosteroids (control) in patients with sore throat

Outcome and timeframe

Study results (95% CI) and measurements

Absolute effect estimates Quality of evidence SummaryNo corticosteroids Corticosteroids Difference (95% CI)

Complete resolution of pain at 24 hours

Relative risk: 2.24 (1.17 to 4.29). 1049 patients in 5 studies

100/1000 224/1000 124 more (17 more to 329 more

Moderate (in-consistency and imprecision)* † ‡

Corticosteroids probably increase chance of com-plete resolution of pain at 24 hours

Complete resolution of pain at 48 hours


425/1000 629/1000 204 more (111 more to 319 more)

High‡ Corticosteroids increase chance of complete resolu-tion of pain at 48 hours

Recurrence/relapse of symptoms


65/1000 34/1000 31 fewer (55 fewer to 47 more)

Moderate (serious imprecision)‡ § ¶

Corticosteroids probably have no important effect on chance that symptoms recur

Antibiotics prescription

Relative risk: 0.83 (0.61 to 1.13). 342 patients in 1 study. Follow-up 28 days

564/1000 468/1000 96 fewer (220 fewer to 73 more)

Low (very serious imprecision)**

Corticosteroids might decrease chance of taking antibiotics in patients given prescription with instruc-tions to take antibiotic if unimproved or worse

Mean time to onset of pain relief (hours)

907 patients in 8 studies 12.3 hours 7.4 hours 4.8 fewer (7.8 fewer to 1.9 fewer)

Moderate (incon-sistency and impre-cision)‡ †† ‡‡ §§

Corticosteroids probably shorten the time until pain starts to improve.

Mean time to complete resolution of pain (hours)

720 patients in 6 studies 44.0 hours 33.0 hours 11.1 fewer (21.8 fewer to 0.4 fewer)

Low (serious impre-cision and inconsist-ency)‡ †† ‡‡ ¶¶

Corticosteroids might short-en duration of pain

Pain reduction 24 hours

Scale: high better. 1247 patients in 8 studies

Mean 3.3 hours Mean 4.6 hours 1.3 higher (0.7 high-er to 1.9 higher)

Moderate (incon-sistency and impre-cision)‡ †† ‡‡ ***

Corticosteroids probably reduce severity of pain at 24 hours

Duration of bad/non-tolerable symptoms

— — — 0 (0 to 0) — No studies provided infor-mation on this outcome

Days missed from work or school

181 patients in 2 studies. Follow-up to 14 days

Two trials reported days missed from work/school. In Kiderman et al, 22/40 (55%) in steroids group and 27/39 (69%) in placebo group took time off work (relative risk 0.79, 95% CI 0.56 to 1.13). Marvez-Valls et al reported average time patients in each arm missed from work/school: average 0.4 (SD 1.4) days in interven-tion group adults v and 0.7 (SD 1.4) days in placebo group adults; mean difference 0.30 days, −0.28 to 0.88)

Moderate (serious imprecision and some concerns of risk of bias)††† ‡‡‡

Corticosteroids probably have no important effect on days missed from work or school

Serious adverse events

808 patients in 3 studies. Follow-up to 10 days

Few adverse effects reported in trials, mostly disease related complications, and occurred with similar frequency in intervention and control groups (see table 3)

Moderate§§§ Corticosteroids probably do not increase risk of adverse events

*Considerable heterogeneity (I2=69%). Not rated down because clinical inconsistency was deemed not important as all results of included studies have similar clinical implication.†Limits of confidence interval suggest small benefit in one extreme and benefit important to patients in other. Because imprecision is linked to inconsistency, certainty of evidence rated down by only one level.‡Publication bias not tested because of small number of studies.§Not rated down for risk of bias as one of three trials judged to be at high risk of bias from missing participant data.¶Confidence interval suggests that corticosteroids increase chance of recurrence of symptoms in one extreme but decrease this chance in other extreme.**Confidence interval suggest that corticosteroids could largely reduce chance of taking antibiotics in one extreme but could slightly increase this chance in other extreme.††Not rated down for risk of bias as equal number of trials judged to be at high and low risk of bias, but P value for test of interaction showed no difference between two estimates.‡‡Large unexplained clinical and statistical inconsistency.§§Confidence interval suggests small benefit in one extreme and benefit that some patients might consider important in other extreme. As this imprecision was result of inconsistency, certainty of evidence rated down by only one level.¶¶Confidence interval suggests trivial benefit in one extreme and benefit that would be considered important by most patients in other extreme.***Confidence interval suggests small benefit in one extreme and benefit important to patients in other. As this imprecision was related to inconsistency, rated down by only one level.†††One study was at high risk of bias from concerns with regards to allocate concealment.‡‡‡Studies showed that corticosteroids could increase days missed from school or work in one extreme but decrease them in other extreme.§§§High risk of bias studies showed similar results as low risk of bias studies; however, high risk of selective outcome reporting was possible.



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difference −0.3 days, 95% confidence interval −0.87 to 0.27).24 None of the trials reported duration of bad/non-tolerable symptoms.

All studies except one sought information on adverse effects using different methods including standardised questionnaire (two studies), open ended questions or diaries to capture self reported adverse events (five studies), or a checklist of complications (two studies). Table 3 provides details of adverse effects assessed and methods used for capturing them. Six studies reported no adverse effects, and three studies reported adverse events, in both steroids and comparator arms, which were mostly complications related to disease and occurred with similar frequency in the intervention and control groups (table 3). Hayward and colleagues reported two serious adverse events (admission to hospital for pharyngeal or peritonsillar abscess, tonsillitis, and pneumonia) in the corticosteroids group (0.7%) and three in the placebo group (1.1%).16

Olympia and colleagues reported one out of the 57 (1.8%) children in the corticosteroids group and two out of the 68 (2.9%) children in the placebo group developed a peritonsillar abscess (moderate quality, table 2 and table 3).28

discussionIn patients with acute sore throat, there is primarily moderate to high quality evidence that one or two low doses of corticosteroids reduces the intensity and duration of pain—pain scores at 24 hours, complete resolution of pain at 24 and at 48 hours, time to onset of pain relief, and time to complete pain relief. In this review, results were consistent across studies and across all pain outcomes (table 2). The reduction in pain achieved was modest—for example, mean time to complete resolution of pain was about 11 hours shorter, and about 18% more patients had complete pain relief at 48 hours. At 24 hours, the mean improvement in

0.1 0.5 1 10Favours placebo Favours corticosteroids

2

Study

Wei 2002

Kiderman 2005

Niland 2006

Tasar 2008

Hayward 2017

Overall (I²=69%, P=0.012)

12/41

17/40

12/39

13/31

65/288

119/439

Treatment

4/36

4/39

8/30

2/42

49/277

67/424

ControlEvents/total Weight (%) RR (95% CI)

18

18

22

13

30

100

2.63 (0.93 to 7.45)

4.14 (1.53 to 11.22)

1.15 (0.54 to 2.46)

8.81 (2.14 to 36.23)

1.28 (0.92 to 1.78)

2.24 (1.17 to 4.29)

Fig 2 | Relative risk for complete resolution of pain at 24 hours for corticosteroid v placebo groups in review of treatment of sore throat. Pooled relative risk calculated by DerSimonian-Laird random effects model

0.1 0.5 1 10Favours placebo Favours corticosteroids

2

Study

Kiderman 2005

Niland 2006

Tasar 2008

Hayward 2017

Overall (I²=3%, P=0.377)

23/40

21/27

29/31

102/288

175/386

Treatment

13/39

17/30

22/472

75/277

127/388

ControlEvents/total Weight (%) RR (95% CI)

10

19

29

42

100

1.73 (1.03 to 2.89)

1.37 (0.95 to 1.99)

1.79 (1.32 to 2.42)

1.31 (1.02 to 1.68)

1.48 (1.26 to 1.75)

Fig 3 | Relative risk for complete resolution of pain at 48 hours for corticosteroid v placebo groups in review of treatment of sore throat. Pooled relative risk calculated by DerSimonian-Laird random effects model



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pain scores was about 13 mm on a visual analogue scale from 0 to 100 mm (with the minimal important difference being about 10 mm).32 The relative effects were similar across severities, though patients with less severe sore throat had less absolute benefit from corticosteroids. The balance of benefits and harms therefore almost certainly depends on the severity of the patient’s sore throat.

Whether corticosteroids reduce recurrence/relapse of symptoms, number of days missed from school or work, duration of bad/intolerable symptoms, or antibiotic use remains uncertain. Regarding the safety of the short courses and low doses of corticosteroids, studies reported few adverse effects, with no apparent increase in events in patients treated with corticosteroid.

Strengths and limitations of studyStrengths of this review include explicit eligibility criteria; a comprehensive search developed with a research librarian; duplicate assessment of eligibility, risk of bias, and data abstraction; consideration of all outcomes important to patients; consideration of selective reporting bias; consideration of possible subgroup effects; and rigorous use of the GRADE approach to rate quality of evidence. The limitations of our review have to do with the underlying evidence. Only three trials explicitly reported adverse events, and they did so inconsistently.16 25 28 We observed substantial statistical heterogeneity in some of the outcomes. We explored the source(s) of heterogeneity by subgroup analysis and rated down for inconsistency in GRADE assessments for outcomes with unexplained heterogeneity.

-15 -5 0 10Favours placeboFavours corticosteroids

5

Study

O’Brien 1994

Marvez-Valls 1998

Wei 2002

Bulloch 2003

Ahn 2003

Olympia 2005

Tasar 2008

Hayward 2017

Overall (I²=78%, P=0.000)

26

46

42

92

36

57

31

129

459

Treatment

6.3 (5.3)

6.3 (8.1)

7.4 (5.32)

9.58 (18.4)

5.11 (6.4)

9.2 (7.5)

8.1 (4.9)

27.5 (17.4)

ControlNo in group

Weight (%)

Weighted MeanDi�erence (95% CI)

13

13

13

11

13

11

13

12

100

-6.10 (-10.1 to -2.19)

-5.00 (-8.31 to -1.69)

-4.66 (-7.97 to -1.36)

-0.51 (-5.39 to 4.37)

-1.37 (-4.74 to 2.00)

-9.00 (-13.77 to -4.23)

-11.80 (-15.13 to -8.47)

0.50 (-4.12 to 5.12)

-4.84 (-7.75 to -1.93

-10

Mean (SD) time No in group Mean (SD) time25

46

35

92

38

68

42

102

448

12.4 (8.5)

11.3 (8.1)

12.1 (8.7)

10.1 (15.2)

6.48 (8.3)

18.2 (18.3)

19.9 (9.4)

27.0 (18.1)

Fig 4 | Weighted mean difference in mean time to onset of pain relief (hours) between corticosteroids and placebo groups in review of treatment of sore throat. Pooled mean difference was calculated by DerSimonian-Laird random effects model

-15 -5 0 10Favours placebo

Favours corticosteroids

5

Study

O’Brien 1994

Marvez-Valls 1998

Bulloch 2003

Olympia 2005

Tasar 2008

Hayward 2017

Overall (I²=85%, P=0.000)

26

46

92

57

31

101

353

Treatment

15.0 (11.4)

42.0 (43.3)

45.1 (36.9)

30.3 (27.8)

28.9 (12.0)

65.8 (48.1)

ControlNo in group

Weight (%)


18

13

17

16

19

16

100

-20.40 (-28.67 to -12.13)

-13.80 (-31.62 to 4.02)

2.33 (-8.12 to 12.78)

-13.50 (-26.11 to -0.89)

-24.80 (-31.27 to -18.33)

5.80 (-6.45 to 18.05)

-11.11 (-21.83 to -0.40)

-10

Mean (SD) time No in group Mean (SD) time

25

46

92

68

42

94

367

35.4 (17.9)

55.8 (43.9)

42.8 (35.4)

43.8 (43.5)

53.7 (16.2)

60.0 (38.9)

Fig 5 | Weighted mean difference in mean time to complete resolution of pain (hours) between corticosteroids and placebo groups in review of treatment of sore throat. Pooled mean difference calculated by DerSimonian-Laird random effects model



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In comparison with previous systematic reviews,11 12 we included two additional randomised controlled trials,16 26 which almost doubled the number of participants. Results from our meta-analysis are consistent with previous findings that corticosteroids reduce pain at 48 hours and probably reduce other pain outcomes. In addition to enhanced precision with the additional studies, our meta-analysis adds to the

existing evidence in that we considered absolute in addition to relative effect measures, providing a clear picture of the magnitude of effect.33 In part because of input from the guideline panel, we considered additional outcomes that participating patients considered important, including risk of recurrence of symptoms, duration of bad/non-tolerable symptoms, need for antibiotics, and days missed from school or

-3 -1 0 2Favours corticosteroidsFavours placebo

1

Study

O’Brien 1994

Marvez-Valls 1998

Wei 2002

Bulloch 2003

Ahn 2003

Kiderman 2005

Olympia 2005

Hayward 2017

Overall (I²=65%, P=0.005)

26

46

41

92

36

40

57

288

626

Treatment

5.67 (2.4)

5.5 (2.7)

4.6 (1.9)

2.65 (2.79)

4.97 (2.2)

5.6 (2.27)

5.8 (2.6)

1.92 (1.94)

ControlNo in group

Weight (%)


10

12

13

15

13

12

13

12

100

1.33 (-0.04 to 2.71)

1.60 (0.50 to 2.70)

1.00 (-0.03 to 2.03)

0.19 (-0.55 to 0.92)

1.91 (0.91 to 2.91)

2.70 (1.64 to 3.76)

1.50 (0.52 to 2.48)

0.33 (-0.83 to 1.49)

1.30 (0.68 to 1.92)

-2

Mean (SD) time No in group Mean (SD) time

25

46

36

92

38

39

68

277

621

4.33 (2.6)

3.9 (2.7)

3.6 (2.6)

2.46 (2.29)

3.06 (2.2)

2.9 (2.54)

4.3 (3.0)

1.59 (9.67)

3 4 5

Fig 6 | Weighted mean difference in absolute reduction of pain at 24 hours (0-10; 0=no pain, 10=maximum pain) between corticosteroids and placebo groups in review of treatment of sore throat. Pooled mean difference calculated by DerSimonian-Laird random effects model

Table 3 | Summary of adverse event assessments among trials included in systematic review of corticosteroids for treatment of sore throatStudy Methods used to assess adverse effects Adverse effects assessed* Adverse effects reportedO’Brien, 1993 Standardised questionnaire Nausea, vomiting, or diarrhoea None reportedMarvez-Valls, 1998

Self reported side effects at follow-up call Any adverse event None reported

Wei, 2002 Self reported side effects at follow-up call Any adverse event 1 patient who received corticosteroids (3%) reported hiccups

Ahn, 2003 Not reported Not reported None reportedBulloch, 2003 Checklist of complication at follow-up call Rash, joint pain, movement disorder,

persistent fever, or blood in urine or “cola coloured” urine in past month, peritonsillar abscess

None reported

Kiderman, 2005

Not reported Any adverse event None reported

Olympia, 2005 Checklist of complication at daily follow-up calls Headache, nausea or vomiting, abdominal pain, myalgia, mood changes, dizziness, and swollen legs, peritonsillar abscess

1/57 (1.8%) children in corticosteroids group and 2/68 (2.9%) in control group developed peritonsillar abscess. 3/57 (5.3%) children in corticosteroid group and 2/68 (2.9%) in placebo group were admitted for dehydration

Niland, 2006 Patient completed diaries and by structured telephone interviews

Headache, abdominal pain (Wong-Baker FACES scale), fever, vomiting, and informa-tion sought regarding additional medical care

Steroid treatment did not result in additional patient adverse effects, symptom relapses, or complications related to disease

Tasar, 2008 Self reported side effects at follow-up call Complications related to dexamethasone and azithromycin

None reported

Hayward, 2017 Attendance or telephone contact at any healthcare facility (including GP clinic, urgent care clinic, emergency department, or hospital admission) with symptoms or complications associated with sore throat (defined as direct suppurative complications or presentation with sore throat symptoms)

Any adverse event 2 serious adverse events (admissions for phar-yngeal or peritonsillar abscess, tonsillitis, and pneumonia) in corticosteroids group (0.7%) and 3 in placebo group (1.1%)

*Reflect investigators’ attempts not only to detect adverse effect attributable to steroids, but also treatment failures, relapses, and complications related to disease.



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work. An important additional contribution of the new evidence is that it extends the applicability beyond patients with severe sore throat treated with antibiotics for group A β haemolytic streptococcus pharyngitis in the emergency department, to a broader range of patients not treated with antibiotics.

We explored and were able to dismiss subgroup effects, with one exception: the reduction in mean time to complete resolution of pain was greater with intramuscular than with oral corticosteroids. The subgroup effect and its direction was specified a priori, the difference between subgroups was relatively large (about 21 hours), and chance seems an unlikely explanation (P<0.001). Credibility of the effect, however, is undermined34 as the effect modification is suggested by comparison between rather than within studies, and we found no similar difference in any other outcome. In addition, the only randomised controlled trial that compared oral and intramuscular treatment with dexamethasone reported no significant difference in any outcome.25

The few serious adverse effects in the included trials occurred with similar frequency in the intervention and control groups, although some minor adverse effects reported by patients might not always have been noted. Potential adverse effects that appear later are more likely to occur after repeated use or are rare would not have been captured in the trials. Recent observational studies have raised the possibility of extremely rare but serious adverse effects after short courses of corticosteroids.35 The quality of this evidence is, for several reasons, low with respect to the current question. The studies used observational designs from large databases with suboptimal verification of diagnoses; serious confounding by indication raises the possibility that the association is a result of the underlying disease process (such as acute inflammation or exacerbation) rather than the corticosteroids themselves; and indirectness in that the doses used in the trials were lower and the duration of treatment was considerably shorter than the duration in the observational studies. Among children, a recent overview of reviews looked at evidence from 44 randomised controlled trials on conditions that required a short course of steroids (such as asthma, bronchiolitis, croup, wheeze, and pharyngitis/tonsillitis) and reported no major adverse events.36

Despite previous evidence that corticosteroids might be beneficial, several groups and guidelines currently recommend against their routine use on the basis that evidence was applicable only to patients with severe pharyngitis who were also prescribed antibiotics in an emergency department.1 37 38 The body of evidence now includes a broader representation of patients. The largest and most recent randomised controlled trial included 565 patients presenting to their general practitioner rather than an emergency department, and none of the patients initially received antibiotics.16 We found no subgroup differences with respect to patient group: the evidence seems to apply equally to patients who did and did not receive antibiotics. The

evidence also seems to apply equally to patients with sore throat from group A β haemolytic streptococcus pharyngitis and some with sore throat negative for group A β haemolytic streptococcus.

In the five trials that reported co-interventions, about 80% of the participants received additional analgesics such as paracetamol and NSAIDs. Therefore, a single dose of corticosteroids seems to further reduce pain when used in combination with other analgesics. Although the benefits are relatively small, many patients are likely to consider them important. Patients with less severe sore throat, however, will obtain less absolute benefit from corticosteroids. Thus, the balance of benefits and harms almost certainly depends on the severity of the patient’s sore throat. With available evidence suggesting that serious adverse effects are rare or absent, the addition of one or two doses of steroids to the symptomatic management of sore throat is likely to appeal to many patients. More high quality data would be helpful to fully understand the net balance of benefits and harms according to severity of symptoms, particularly in primary care settings.

We thank Rachel Couban, librarian at McMaster National Pain Centre Research, for her advice on the search strategies and members of the Rapid Recommendations panel for critical feedback on outcome and subgroup selection and manuscript feedbacks.Contributors: BS and RACS contributed equally to this work. TA, RACS, POV, and GHG conceived the study idea. BS, RACS, RB-P, TA coordinated the systematic review. BS, RACS, and TA wrote the first draft of the manuscript. BS and LL designed the search strategy. BS, RACS, LL, DP, and RB-P screened abstracts and full texts. BS, RACS, RB-P, and DP acquired the data and judged risk of bias in the studies. BS performed the data analysis and is guarantor. All authors interpreted the data analysis and critically revised the manuscript.Funding: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.Competing interests: All authors have completed the ICMJE uniform disclosure form and declare: no support from any organisation for the submitted work. RACS, AM, and GHG are members of the GRADE working group. There are no other relationships or activities that could appear to have influenced the submitted work.Ethical approval: Not required.Data sharing: All data are freely available within the appendices. No additional data available.Transparency: The lead author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different

Linked articles in this BMJ Rapid Recommendations cluster• Aertgeerts B, Agoritsas T, Siemieniuk RAC, et al.

Corticosteroids for sore throat: a clinical practice guideline. BMJ 2017;358:j4090 doi:10.1136/bmj.j4090summary of the results from the Rapid Recommendation process

• Magic App (www.magicapp.org)expanded version of the results with multilayered recommendations, evidence summaries, and decision aids for use on all devices



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terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/1 Pelucchi C, Grigoryan L, Galeone CESCMID Sore Throat Guideline

Group. Guideline for the management of acute sore throat. Clin Microbiol Infect 2012;18(Suppl 1):1-28. doi:10.1111/ j.1469-0691.2012.03766.x.

2 Principi N, Bianchini S, Baggi E, Esposito S. No evidence for the effectiveness of systemic corticosteroids in acute pharyngitis, community-acquired pneumonia and acute otitis media. Eur J Clin Microbiol Infect Dis 2013;32:151-60. doi:10.1007/s10096-012-1747-y.

3 Shaikh N, Leonard E, Martin JM. Prevalence of streptococcal pharyngitis and streptococcal carriage in children: a meta-analysis. Pediatrics 2010;126:e557-64. doi:10.1542/peds.2009-2648.

4 Herath VC, Carapetis J. Sore throat: Is it such a big deal anymore?J Infect 2015;71(Suppl 1):S101-5. doi:10.1016/j.jinf.2015.04.010.

5 Kenealy T. Sore throat. BMJ Clin Evid 2011;2011:1509.6 Bally M, Dendukuri N, Rich B. Risk of acute myocardial infarction with

NSAIDs in real world use: bayesian meta-analysis of individual patient data. BMJ 2017;357:j1909. doi:10.1136/bmj.j1909.

7 Thomas M, Del Mar C, Glasziou P. How effective are treatments other than antibiotics for acute sore throat?Br J Gen Pract 2000;50:817-20.

8 Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 2010;340:c2096. doi:10.1136/bmj.c2096.

9 Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database Syst Rev 2013;(11):CD000023. doi:10.1002/14651858.CD000023.pub4.

10 van Driel ML, De Sutter A, Deveugele M. Are sore throat patients who hope for antibiotics actually asking for pain relief?Ann Fam Med 2006;4:494-9. doi:10.1370/afm.609.

11 Hayward G, Thompson M, Heneghan C, Perera R, Del Mar C, Glasziou P. Corticosteroids for pain relief in sore throat: systematic review and meta-analysis. BMJ 2009;339:b2976. doi:10.1136/bmj.b2976.

12 Hayward G, Thompson MJ, Perera R, Glasziou PP, Del Mar CB, Heneghan CJ. Corticosteroids as standalone or add-on treatment for sore throat. Cochrane Database Syst Rev 2012;10:CD008268. doi:10.1002/14651858.CD008268.pub2.

13 Korb K, Scherer M, Chenot JF. Steroids as adjuvant therapy for acute pharyngitis in ambulatory patients: a systematic review. Ann Fam Med 2010;8:58-63. doi:10.1370/afm.1038.

14 Wing A, Villa-Roel C, Yeh B, Eskin B, Buckingham J, Rowe BH. Effectiveness of corticosteroid treatment in acute pharyngitis: a systematic review of the literature. Acad Emerg Med 2010;17: 476-83. doi:10.1111/j.1553-2712.2010.00723.x.

15 Siemieniuk RA, Agoritsas T, Macdonald H, Guyatt GH, Brandt L, Vandvik PO. Introduction to BMJ Rapid Recommendations. BMJ 2016;354:i5191. doi:10.1136/bmj.i5191.

16 Hayward GN, Hay AD, Moore MV. Effect of Oral Dexamethasone Without Immediate Antibiotics vs Placebo on Acute Sore Throat in Adults: A Randomized Clinical Trial. JAMA 2017;317:1535-43. doi:10.1001/jama.2017.3417.

17 Aertgeerts B, Agoritsas T, Siemieniuk RAC. Corticosteroids for sore throat: a clinical practice guideline. BMJ 2017;358:j4090.

18 Higgins JPT, Altman DG, Gøtzsche PCCochrane Bias Methods GroupCochrane Statistical Methods Group. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. doi:10.1136/bmj.d5928.

19 Akl EA, Sun X, Busse JW. Specific instructions for estimating unclearly reported blinding status in randomized trials were reliable and valid. J Clin Epidemiol 2012;65:262-7. doi:10.1016/j.jclinepi.2011.04.015.

20 Guyatt GH, Oxman AD, Vist GEGRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6. doi:10.1136/bmj.39489.470347.AD.

21 Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ 2003;326:219. doi:10.1136/bmj.326.7382.219

22 Sterne JA, Sutton AJ, Ioannidis JP. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 2011;343:d4002. doi:10.1136/bmj.d4002

23 O’Brien JF, Meade JL, Falk JL. Dexamethasone as adjuvant therapy for severe acute pharyngitis. Ann Emerg Med 1993;22:212-5. doi:10.1016/S0196-0644(05)80205-7

24 Marvez-Valls EG, Ernst AA, Gray J, Johnson WD. The role of betamethasone in the treatment of acute exudative pharyngitis. Acad Emerg Med 1998;5:567-72. doi:10.1111/j.1553-2712.1998.tb02462.x

25 Wei JL, Kasperbauer JL, Weaver AL, Boggust AJ. Efficacy of single-dose dexamethasone as adjuvant therapy for acute pharyngitis. Laryngoscope 2002;112:87-93. doi:10.1097/00005537-200201000-00016.

26 Ahn JH, Woo WK, Kim YS. Efficacy of adjuvant short term oral steroid therapy for acute pharyngitis. Korean J Otolaryngol Head Neck Surg 2003;46:971-4.

27 Bulloch B, Kabani A, Tenenbein M. Oral dexamethasone for the treatment of pain in children with acute pharyngitis: a randomized, double-blind, placebo-controlled trial. Ann Emerg Med 2003;41: 601-8. doi:10.1067/mem.2003.136.

28 Olympia RP, Khine H, Avner JR. Effectiveness of oral dexamethasone in the treatment of moderate to severe pharyngitis in children. Arch Pediatr Adolesc Med 2005;159:278-82. doi:10.1001/archpedi.159.3.278.

29 Niland ML, Bonsu BK, Nuss KE, Goodman DG. A pilot study of 1 versus 3 days of dexamethasone as add-on therapy in children with streptococcal pharyngitis. Pediatr Infect Dis J 2006;25:477-81. doi:10.1097/01.inf.0000219469.95772.3f.

30 Tasar A, Yanturali S, Topacoglu H, Ersoy G, Unverir P, Sarikaya S. Clinical efficacy of dexamethasone for acute exudative pharyngitis. J Emerg Med 2008;35:363-7. doi:10.1016/j.jemermed.2007.11.029.

31 Kiderman A, Yaphe J, Bregman J, Zemel T, Furst AL. Adjuvant prednisone therapy in pharyngitis: a randomised controlled trial from general practice. Br J Gen Pract 2005;55:218-21.

32 Powell CV, Kelly AM, Williams A. Determining the minimum clinically significant difference in visual analog pain score for children. Ann Emerg Med 2001;37:28-31. doi:10.1067/mem.2001.111517.

33 Alonso-Coello P, Carrasco-Labra A, Brignardello-Petersen R. Systematic reviews experience major limitations in reporting absolute effects. J Clin Epidemiol 2016;72:16-26. doi:10.1016/j.jclinepi.2015.11.002.

34 Sun X, Briel M, Walter SD, Guyatt GH. Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses. BMJ 2010;340:c117. doi:10.1136/bmj.c117.

35 Waljee AK, Rogers MA, Lin P. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ 2017;357:j1415. doi:10.1136/bmj.j1415.

36 Fernandes RM, Oleszczuk M, Woods CR, Rowe BH, Cates CJ, Hartling L. The Cochrane Library and safety of systemic corticosteroids for acute respiratory conditions in children: an overview of reviews. Evid Based Child Health 2014;9:733-47. doi:10.1002/ebch.1980.

37 Management of sore throat and indications for tonsillectomy. A national clinical guideline. Scottish Intercollegiate Guideline Network (SIGN), April 2010. http://www.sign.ac.uk/assets/sign117.pdf

38 Shulman ST, Bisno AL, Clegg HW. Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis 2012;55:1279-82. doi:10.1093/cid/cis847.

Appendix 1: Search terms and strategiesAppendix 2: Summary of risk of bias assessments among the included trialsAppendix 3: Supplementary tables and figure



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R A P I D R E C O M M E N DAT I O N S

Corticosteroids for sore throat: a clinical practice guidelineBert Aertgeerts,1 2 Thomas Agoritsas,3 4 Reed A C Siemieniuk,3 5 Jako Burgers,6 7 Geertruida E Bekkering,1 2 Arnaud Merglen,8 Mieke van Driel,9 Mieke Vermandere,1 Dominique Bullens,10 11 Patrick Mbah Okwen,12 Ricardo Niño,13 Ann van den Bruel,14 15 Lyubov Lytvyn,16 Carla Berg-Nelson,17 18 Shunjie Chua,19 Jack Leahy,20 Jennifer Raven,21 Michael Weinberg,22 Behnam Sadeghirad,3 23 Per O Vandvik,15 24 Romina Brignardello-Petersen2 25

What is the role of a single dose of oral corticos-teroids for those with acute sore throat? Using the GRADE framework according to the BMJ Rapid Rec-ommendation process, an expert panel make a weak recommendation in favour of corticosteroid use. The panel produced these recommendations based on a linked systematic review triggered by a large randomised trial published in April 2017. This trial reported that corticosteroids increased the propor-tion of patients with complete resolution of pain at 48 hours. Box 1 shows all of the articles and evidence linked in this Rapid Recommendation package. The infographic provides the recommendation together with an overview of the absolute benefits and harms of corticosteroids in the standard GRADE format. Table 2 below shows any evidence that has emerged since the publication of this article. Clinicians and their patients can find consultation decision aids to facilitate shared decision making in MAGICapp (www.magicapp.org/goto/guideline/JjXYAL/sec-tion/j79pvn).

Acute sore throat is defined as pain in the throat for less than 14 days. Acute sore throat could be caused by phar-yngitis, nasopharyngitis, tonsillitis, peritonsillar abscess, or retropharyngeal abscess. Some patients with sore throat also experience headache, fever, muscle stiffness, cough, and general malaise.

Acute sore throat is common, but only a minority of patients will visit their general practitioner.1 A survey reported that the main reasons are to establish the cause of the symptoms, obtain pain relief, and to gain informa-tion on the course of the disease.2 Data from Dutch and Flemish primary care databases show that, for every 1000 consecutive patients consulting a general practitioner, 50 present with an acute sore throat.3 4 In the US, more than 92 million visits by adults to primary care practices and emergency departments between 1997 and 2010 were recorded.5 Sore throat presenting as acute tonsillitis is also the commonest cause for emergency admission to otorhinolaryngology services in the US.6

Acute sore throat is a self limiting disease and typi-cally resolves after 7-10 days in adults and 2-7 days in children.7 Most infections are of viral origin; only a few are caused by a bacterial infection, of which group A

β-haemolytic streptococcus, Haemophilus influenzae, and Moraxella catarrhalis are the most common pathogens. Evidence suggests that the time to resolution is not asso-ciated with the type of pathogen.7 About 2% of patients initially presenting with sore throat will have a mononu-cleosis infection caused by an Epstein-Barr virus, which could prolong the duration of symptoms.8

Some patients experience unacceptable morbidity and inconvenience, and miss school or work due to recurrent sore throat.9 Pain is a common reason for work or school absence. Complications of sore throat are rare: about 0.2% of patients with tonsillitis will develop a periton-sillar abscess.10

The diagnosis of an acute sore throat is based on signs and symptoms. The Centor clinical prediction rules can be used to help predict whether the sore throat is caused by a bacterial pathogen, and thus guide the decision whether to prescribe an antibiotic.11 12

Full author details can be found at the end of the articleCorrespondence to: B Aertgeerts [email protected] this as: BMJ 2017;358:j4090doi: 10.1136/bmj.j4090

This BMJ Rapid Recommendation article is one of a series that provides clinicians with trustworthy recommendations for potentially practice changing evidence. BMJ Rapid Recommendations represent a collaborative effort between the MAGIC group (www.magicproject.org) and The BMJ. A summary is offered here and the full version including decision aids is on the MAGICapp (www.magicapp.org), for all devices in multilayered formats. Those reading and using these recommendations should consider individual patient circumstances, and their values and preferences and may want to use consultation decision aids in MAGICapp to facilitate shared decision making with patients. We encourage adaptation and contextualisation of our recommendations to local contexts. Those considering use or adaptation of content may go to MAGICapp to link or extract its content or contact The BMJ for permission to reuse content in this article.

WHAT YOU NEED TO KNOW:

• Sore throat is one of the most common reasons for primary care appointments, and international guidance varies about whether to use corticosteroids to treat it, but a trial published in April 2017 suggested that costicosteroids might be effective

• We make a weak recommendation to use a single dose of oral corticosteroids, in those presenting with acute sore throat, after performing a systematic review of the new evidence in this rapid recommendation publication package

• The recommendation is weak and shared decision making is needed because corticosteroids did not help all patient reported outcomes and patients’ preferences varied substantially

• Steroids somewhat reduced the severity and duration of pain by one day, but time off school or work was unchanged. Harm seems unlikely with one steroid dose.

• The treatment is inexpensive and likely to be offered in the context of a consultation that would have taken place anyway

on 30 April 2019 by guest. P


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Population

Comparison

or

Short course of steroids

No steroidsStandard clinical care, which typically includes analgesics, and may include antibiotics

1–2 doses of oral Dexamethasone(or equivalent dose of alternative corticosteroid)+ standard care

Favours steroids Favours no steroids

Comparison of benefits and harms

Favours steroids Favours no steroids

StrongStrong WeakWeak

We suggest short course of steroids. Discuss with patients in shared decision making.

The panel believes that there is a great variability on how much reduction in pain severity or time to complete pain resolution each patient would consider important. Shared decision making may help establish what matters most to each patient.

Preferences and values Serious adverse events Multiple doses

One-dose administration of steroids is not likely to cause serious adverse events. Very low quality evidence exists for extremely rare but serious adverse effects following higher doses or longer courses of steroids (up to 30 days).

Risks may outweigh benefits when cumulative doses of steroids are given for multiple episodes of sore throat. To mitigate this issue, clinicians could administer the medication in office if possible, or prescribe only one dose per visit.

183 more

11.1 fewer

124 moreComplete pain resolution (24 hrs) Moderate

Evidence quality

Antibiotics prescription Low

Disclaimer: This infographic is not a clinical decision aid. This information is provided without any representations, conditions or warranties that it is accurate or up to date. BMJ and its licensors assume no responsibility for any aspect of treatment administered with the aid of this information. Any reliance placed on this information is strictly at the user's own risk. For the full disclaimer wording see BMJ's terms and conditions: http://www.bmj.com/company/legal-information/

Events per 1000 people

100224

564

No important difference

Complete pain resolution (48 hrs) High608 425

Complete pain resolution Low33.0

Mean time to resolution (hours)

Events per 1000 people

44.0

Symptom recurrence or relapse Moderate34 65

This recommendation applies to almost all patients with sore throat:

10 mgAdults: Children:

Standard care

Analgesics

Antibiotics

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+Standard care

Analgesics

Antibiotics

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Children 5 years and older and all adults

Emergency and primary care settings

Patients with a viral or bacterial sore throat

Severe and not severe sore throat

Patients who receive immediate or deferred antibiotics

However the recommendation is not applicable to patients with:

Infectiousmononucleosis

Immunocompromising conditions

Sore throat following surgery or intubation

Children under 5 years old

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settings, and the panel was therefore confident that the evidence was applicable to them as well. Most of the stud-ies focused in adults only (60%). The studies that focused only on children (three studies, 2% of all the patients enrolled in the studies) did not include children younger than 5 years old, and thus the recommendation does not apply to younger ages.

Since the randomised controlled trials focused on patients who did not have recurrent episodes of sore throat, the panel was less confident of the applicability of the evidence to such patients, and the recommenda-tion therefore does not apply to them. Similarly, the panel did not consider patients with sore throat after surgery or intubation, nor immunocompromised patients.

Understanding the recommendationThe recommendation for using corticosteroids made by the panel was weak because of the modest reduction of symptoms and the large variability in patient preferences.

The panel is confident that the recommendation applies to almost all patients with acute sore throat: chil-dren 5 years and older and adults, severe and not severe sore throat, patients who receive immediate antibiotics and those who receive deferred antibiotics, patients with a viral or bacterial sore throat, and patients who seek

Most guidelines recommend paracetamol or ibuprofen as the first choice treatment.13 The use of corticosteroids is mentioned in few, and is generally discouraged (table 1). Antibiotics are probably not helpful for pain relief in an episode of acute sore throat caused by viruses, but may help those with a bacterial infection.14 15 Recommended management of sore throat varies widely, and table 1 summarises current guidelines.

The evidenceThe linked systematic review reports the effects of corti-costeroids when added to standard care in patients with acute sore throat.16

Figure 1 gives an overview of the number and types of patients included, the study funding, and patient involve-ment, as well as a summary of the benefits and harms of corticosteroids for treating acute sore throat.

The panel identified eight patient-important outcomes needed to inform the recommendation: complete resolu-tion of pain, time to onset of pain relief, pain severity, need for antibiotics, days missed from school or work, recurrence of symptoms, duration of bad or non-tolera-ble symptoms, and adverse effects. The included studies reported on all patient-important outcomes, except for duration of bad or non-tolerable symptoms. Regarding pain, the panel appraised the likelihood of complete reso-lution of pain at 24 hours and 48 hours, as well as the mean time to complete resolution of pain and the mean time to onset of pain relief.

Although most of the studies (80%) were conducted in emergency departments, they accounted for 54% of all patients enrolled across studies. The remaining 46% were enrolled in the studies conducted in primary care

Box 1 | Linked articles in this BMJ Rapid Recommendations cluster• Aertgeerts B, Agoritsas T, Siemieniuk RAC, et al.

Corticosteroids for sore throat: a clinical practice guideline. BMJ 2017;358:j4090. doi:10.1136/bmj.j4090

– Summary of the results from the Rapid Recommendation process

• Sadeghirad B, Siemieniuk RA, Brignardello-Petersen R, et al. Corticosteroids for treatment of sore throat: a systematic review and meta-analysis of randomised trials. BMJ 2017;358:j3887. doi:10.1136/bmj.j3887

– Review of all available randomised trials that assessed corticosteroids as adjunct treatment versus standard care for sore throat.

• MAGICapp (www.magicapp.org/goto/guideline/JjXYAL/section/j79pvn)

– Expanded version of the results with multilayered recommendations, evidence summaries, and decision aids for use on all devices

Table 1 | Current guidance for treatment of patients with sore throat

Ibuprofen Paracetamol AntibioticsCorticosteroids For adults For children

EBM guidelines11 Supportive Supportive Conditionally Supportive Not applicableSIGN6 Supportive Supportive Conditionally Not supportive No commentNHG12 Supportive Supportive Conditionally Not recommended No commentBC guidelines13 No comment No comment Against No comment No commentUpToDate14 Against No comment No comment Supportive No comment

HOW THE RECOMMENDATION WAS CREATEDA large randomised controlled trial published in April 201721 found that corticosteroids increased the proportion of patients with complete resolution of symptoms at 48 hours. However, corticosteroids did not seem to decrease the duration of moderately bad symptoms, pain severity, healthcare attendance, days missed from school or work, or the consumption of delayed antibiotics. This study adds to the body of evidence that suggests that, although corticosteroids probably have benefits in patients with sore throat, these benefits may be modest.22-25 The Rapid Recommendations team felt that the study, when considered in context of the full body of evidence, might change practice.26

Our international panel—including general practitioners, general internists, paediatricians, an otorhinolaryngologist, epidemiologists, methodologists, statisticians, and people with lived experience of sore throat—decided what was the scope of the recommendation and the outcomes that are most important to patients. After a parallel team conducted a systematic review on the benefits and harms of corticosteroids,16 and a systematic search for evidence about patients’ values and preferences (appendix 1 on bmj.com), the panel met to discuss the evidence and formulate a recommendation. No person had financial conflicts of interest; intellectual and professional conflicts were minimised and managed (appendix 2 on bmj.com).

The panel followed the BMJ Rapid Recommendations procedures for creating a trustworthy recommendation,26 27 including using the GRADE approach to critically appraise the evidence and create recommendations (appendix 3 on bmj.com).28 The panel considered the balance of benefits, harms, and burdens of the drug, the quality of the evidence for each outcome, typical and expected variations in patient values and preferences, and acceptability.29 Recommendations can be strong or weak, for or against a course of action.



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• A single dose of corticosteroids is unlikely to cause serious adverse events

– The randomised trials did not report any major event attributable to single dose corticosteroids (GRADE moderate quality evidence)

– The panel also considered evidence from observational studies that used higher doses of steroids. A large retrospective US cohort study of private insurance claims assessed adverse events in 327 452 adults who received an outpatient prescription of corticosteroids.18 There was a small absolute increase in the rate of sepsis, venous thromboembolism, and fracture in the first 30 days (GRADE low quality evidence, due to suboptimal verification of diagnosis in large databases and confounding by indication19). The panel agreed that such events seemed unlikely with single dose steroids

– Similarly, among paediatric populations, indirect evidence from a meta-analysis of 44 randomised trials did not report any major adverse events in patients with conditions requiring a short course of corticosteroids (such as asthma, bronchiolitis, croup, wheeze, and pharyngitis or tonsillitis)20

• There are no differences in the relative effects of corticosteroids (when compared with usual care) between primary care settings and emergency departments

• It is unlikely that new information will change interpretation for outcomes that are high to moderate quality of evidence.

care in the emergency department as well as those who attend primary care. The systematic review contained adequate representation from such groups and settings, and results were consistent (that is, absence of credible subgroup effects), for example, between trials of children and adults, and those seen in emergency departments and in primary care offices.16

Absolute benefits and harmsAlthough the evidence indicates that the treatment works on average, it did not reduce the severity of pain dramati-cally and failed to improve several other patient-impor-tant outcomes.

The infographic explains the recommendation and pro-vides an overview (GRADE summary of findings) of the absolute benefits and harms of corticosteroids. Estimates of baseline risk for effects come from the control arms of the trials.16 The infographic also leads to point-of-care formats in the MAGICapp, including consultation deci-sion aids designed to support shared decision making with patients.17

Considering the evidence and its certainty, the panel was confident that:• Corticosteroids increase the chance of complete

resolution of pain at 24 and 48 hours, reduce the severity of pain, and shorten the time to onset of pain relief (GRADE high to moderate quality evidence)

• Corticosteroids are unlikely to reduce recurrence or relapse of symptoms or days missed from school or work (GRADE moderate quality evidence)

NUMBER OF TRIALS 10 NUMBER OF PATIENTS 1426

PATIENT CHARACTERISTICS

0 200 400 600

153Mean

57658Min

MEAN NUMBER OFPATIENTS ENROLLED

0 10 20 30 40

26Mean

34Max

10Min

SEX % women

STREPTOCOCCUS POSITIVE % of patients

ANALGESIC USE % of patients

ANTIBIOTIC PRESCRIPTION % of patients

0

15Min

20 40 80 10060

57Mean

75MaxMax

37Min

51Mean

100Max

PATI

ENT PARTNERSHIP

FUNDING

DATA SOURCES Use this information to gauge how similar your patients’ conditions are to those of people studied in the trials

MEAN AGEat baseline

No trials involved patientsin design or conduct

80% of trials did not report the source of fundingand 20% of trials reported non-industry funding

0 20 40 60 10080

40Min

78Mean

100Max

0 20 40 60 10080

38Min

83Mean

100Max

0 20 40 60 10080

The proportion of Streptococcus positive people across all trials was 37%

TRIAL CHARACTERISTICS

8

8Trials conducted in emergency departments

771

2Trials conducted in primary care practices 655

Drugs studied in trials

Dexamethasone

1

Prednisone Betamethasone

1791255 92

5Oraldelivery 1044

3Intramuscular delivery 211

Fig 1 | Characteristics of patients and trials included in systematic review of effects of corticosteroids on acute sore throat



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to school or to perform at work are compromised, care givers wishing to reduce their children’s pain, or patients experiencing their pain as severe.

The panel believes that there is great variability in how much reduction in pain severity or time to complete pain resolution each patient would consider important. However, the greater the reduction in hours to achieve complete resolution of pain, the more likely it is that typi-cal patients would place high value on those outcomes. Patients who place a high value in reducing the symptoms by any amount (such as patients with lower tolerance to pain or with severe symptoms) are more likely to accept receiving corticosteroids.

The weak recommendation for corticosteroids also reflects the concerns that the panel had with accepta-bility. Specifically, how acceptable is it to treat a condi-tion that is usually not severe and is self limiting with a drug that many patients, practitioners, and other stake-holders know is almost always used for more severe dis-eases.

The systematic search for empirical data on patients’ values and preferences related to sore throat identi-fied 4149 references that were screened at the title and abstract level. From these, we screened 99 full text a rticles, from which only two provided relevant in formation on patients’ values and preferences (see appendix 1 on bmj.com). Neither of the studies provided additional data that had not been raised by the panel members: the panel had identified appropriate patient-important outcomes and considered the variability in patient values and preferences regarding sore throat management.

The panel was less confident about whether:• Corticosteroids reduced antibiotic use, due to a

lack of improvement or worsening of symptoms in patients not prescribed antibiotics immediately when consulting the physician (GRADE low quality evidence)

• Corticosteroids reduced the average time to complete resolution of pain (GRADE low quality evidence).

Values and preferencesThe weak recommendation for corticosteroids reflects a high value on a modest reduction of symptom severity and the time that it takes to achieve such improvement, and a substantial and important increase in the chance of complete resolution of pain at 48 hours.

The panel, including the patient representatives, felt that the values and preferences are likely to vary greatly across patients, which justifies a weak recommenda-tion. For example, achieving complete pain resolution 12 hours earlier may be of little importance for patients who feel less busy in their daily life, have higher tolerance to pain, or whose symptoms are not so severe; whereas it may be very important to patients whose ability to go

HOW PATIENTS WERE INVOLVED IN THE CREATION OF THIS ARTICLEFive people with lived experience of sore throat were full panel members. These panel members identified important outcomes, and led the discussion on values and preferences. These patient representatives agreed that while small reductions in pain severity and time to complete pain resolution (for example 12 compared to 24 hours) were important to them, these values may not be shared by all patients; they expected moderate to great variability in how much importance other patients would place in small reductions in pain. These panel members participated in the teleconferences and email discussions and met all authorship criteria.

P

EDUCATION IN PRACTICE• How do you currently approach giving advice for

those with acute sore throat? Do you consider offering corticosteroids?

• The recommendation for corticosteroid use is weak, and patient’s preferences are likely to vary. What information could you share with your patient to help reach a decision together?

• Have you learnt one thing from this article that might alter how you consult with patients with sore throat? How might you share this information with colleagues to learn together?

• To what extent do you practice shared decision making for such preference-sensitive decisions?

PRACTICAL ISSUES

No steroids Steroids

MEDICATIONROUTINE

PREGNANCY & NURSING

TESTS & VISITS

COSTS & ACCESS

FOOD & DRINK

ADVERSE EFFECTS

EMOTIONAL WELL-BEING

One (or two) doses of steroids, taken as pill(s) or intramuscular injection(s)

Serious adverse events are unlikely with one-dose steroids. There may be risks with repeated doses across multiple episodes of sore throat, or through self-medication

Dexamethasone crosses the placenta, and is generally avoided during pregnancy. There is, however, probably no risk of malformation

Inexpensive, available by prescription

May increase appetite, particularly in children

May cause transient sleep disturbance and excitability, although infrequently with one-dose steroids

May require concomitant antibiotics, and or over the counter pain relievers

May require concomitant antibiotics, and/or over the counter pain relievers

May need additional visits if symptoms do not resolve or worsen

Fig2 Practical issues about use of corticosteroids to treat acute sore throat



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1 Evans CE, McFarlane AH, Norman GR, Neale KA, Streiner DL. Sore throats in adults: who sees a doctor?Can Fam Physician 1982;28:453-8.pmid:21286075.

2 van Driel ML, De Sutter A, Deveugele M, et al. Are sore throat patients who hope for antibiotics actually asking for pain relief?Ann Fam Med 2006;4:494-9. doi:10.1370/afm.609 pmid:17148626.

3 NIVEL Primary care database: Netherlands Institute for Health Services Research; 2012. www.nivel.nl/en/dossier/nivel-primary-care-database.

4 Truyers C, Goderis G, Dewitte H, Akker Mv, Buntinx F. The Intego database: background, methods and basic results of a Flemish general practice-based continuous morbidity registration project. BMC Med Inform Decis Mak 2014;14:48. doi:10.1186/1472-6947-14-48 pmid:24906941.

5 Barnett ML, Linder JA. Antibiotic prescribing to adults with sore throat in the United States, 1997-2010. JAMA Intern Med 2014;174:138-40. doi:10.1001/jamainternmed.2013.11673. pmid:24091806.

6 Bird JH, Biggs TC, King EV. Controversies in the management of acute tonsillitis: an evidence-based review. Clin Otolaryngol 2014;39:368-74. doi:10.1111/coa.12299. pmid:25418818.

7 Thompson M, Vodicka TA, Blair PS, Buckley DI, Heneghan C, Hay AD. TARGET Programme Team. Duration of symptoms of respiratory tract infections in children: systematic review. BMJ 2013;347:f7027. doi:10.1136/bmj.f7027. pmid:24335668.

8 Rea TD, Russo JE, Katon W, Ashley RL, Buchwald DS. Prospective study of the natural history of infectious mononucleosis caused by Epstein-Barr virus. J Am Board Fam Pract 2001;14:234-42.pmid:11458965.

9 Scottish Intercollegiate Guidelines Network. Management of sore throat and indications for tonsillectomy (SIGN 117). 2010. www.sign.ac.uk/sign-117-management-of-sore-throat-and-indications-for-tonsillectomy.html.

10 Little P, Stuart B, Hobbs FD, et al. DESCARTE investigators. Predictors of suppurative complications for acute sore throat in primary care: prospective clinical cohort study. BMJ 2013;347:f6867. doi:10.1136/bmj.f6867 pmid:24277339.

11 Atula T. Corticosteroids for sore throat. Evidence-Based Medicine Guidelines. 2014. www.ebm-guidelines.com/ebmga/ltk.naytaartikkeli?p_artikkeli=evd07095#refs.

12 Ebell MH, Smith MA, Barry HC, Ives K, Carey M. The rational clinical examination. Does this patient have strep throat?JAMA 2000;284:2912-8. doi:10.1001/jama.284.22.2912 pmid:11147989.

13 Chiappini E, Regoli M, Bonsignori F, et al. Analysis of different recommendations from international guidelines for the management of acute pharyngitis in adults and children. Clin Ther 2011;33:48-58. doi:10.1016/j.clinthera.2011.02.001. pmid:21397773.

14 Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev 2006;(4):CD000023. doi:10.1002/14651858.CD000023.pub3. pmid:17054126.

15 van Driel ML, De Sutter AI, Habraken H, Thorning S, Christiaens T. Different antibiotic treatments for group A streptococcal pharyngitis. Cochrane Database Syst Rev 2016;9:CD004406. doi:10.1002/14651858.CD004406.pub4. pmid:27614728.

16 Sadhegirad B, Siemieniuk R, Brignardello-Petersen R, et al. Corticosteroids for treatment of sore thoat: a systematic review and meta-analysis of randomized trials. BMJ 2017;358:j3887. doi:10.1136/bmj.j3887.

17 Agoritsas T, Heen AF, Brandt L, et al. Decision aids that really promote shared decision making: the pace quickens. BMJ 2015;350:g7624. doi:10.1136/bmj.g7624. pmid:25670178.

18 Waljee AK, Rogers MA, Lin P, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ 2017;357:j1415. doi:10.1136/bmj.j1415. pmid:28404617.

19 Agoritsas T, Merglen A, Shah ND, O’Donnell M, Guyatt GH. Adjusted analyses in studies addressing therapy and harm: users’ guides to the medical literature. JAMA 2017;317:748-59. doi:10.1001/jama.2016.20029. pmid:28241362.

20 Fernandes RM, Oleszczuk M, Woods CR, Rowe BH, Cates CJ, Hartling L. The Cochrane Library and safety of systemic corticosteroids for acute respiratory conditions in children: an overview of reviews. Evid Based Child Health 2014;9:733-47. doi:10.1002/ebch.1980 pmid:25236311.

21 Hayward GN, Hay AD, Moore MV, et al. Effect of oral dexamethasone without immediate antibiotics vs placebo on acute sore throat in adults: a randomized clinical trial. JAMA 2017;317:1535-43. doi:10.1001/jama.2017.3417 pmid:28418482.

22 Hayward G, Thompson M, Heneghan C, Perera R, Del Mar C, Glasziou P. Corticosteroids for pain relief in sore throat: systematic review and meta-analysis. BMJ 2009;339:b2976. doi:10.1136/bmj.b2976. pmid:19661138.

23 Hayward G, Thompson MJ, Perera R, Glasziou PP, Del Mar CB, Heneghan CJ. Corticosteroids as standalone or add-on treatment for sore throat. Cochrane Database Syst Rev 2012;10:CD008268. doi:10.1002/14651858.CD008268.pub2. pmid:23076943.

24 Korb K, Scherer M, Chenot JF. Steroids as adjuvant therapy for acute pharyngitis in ambulatory patients: a systematic review. Ann Fam Med 2010;8:58-63. doi:10.1370/afm.1038. pmid:20065280.

25 Wing A, Villa-Roel C, Yeh B, Eskin B, Buckingham J, Rowe BH. Effectiveness of corticosteroid treatment in acute pharyngitis: a systematic review of the literature. Acad Emerg Med 2010;17:476-83. doi:10.1111/j.1553-2712.2010.00723.x pmid:20536799.

Practical issues and other considerationsFigure 2 outlines the key practical issues for patients and clinicians discussing adjunct steroids for sore throat, which are also accessible along with the evidence as decision aids to support shared decision-making in MAGI-Capp. Steroids are typically given as 10 mg dexametha-sone (or adapted to weight for children: 0.6 mg/kg, up to a maximum dose of 10 mg), typically taken as pill or intramuscular injection.

The risks may outweigh the benefits when larger cumulative doses of corticosteroids are given to patients who experience multiple episodes of sore throat, either through multiple visits or for patients who self medicate if prescribed more than one pill for their previous episode. To mitigate this issue, clinicians should administer the medication in office if possible or prescribe only one dose per visit.

Costs and resourcesThe panel focused on the patient perspective rather than that of society when formulating the recommen-dation. Given the low cost of corticosteroids for treating sore throat, implementation of this recommendation is unlikely to have an important impact on the costs for health funders. The treatment is inexpensive and likely to be offered in the context of a consultation that would have taken place anyway. Nevertheless, it remains uncer-tain whether it may increase the proportion of patients visiting a doctor to get a prescription of corticosteroids.

Uncertainties for future researchKey research questions to inform decision makers and future guidelines include:• Are there any severe adverse effects of using one-

dose of steroids for treating sore throat?• What are the effects of corticosteroids, in addition to

standard care, in patients with recurrent episodes of acute sore throat?

Updates to this articleTable 2 shows evidence which has emerged since the publication of this article. As new evidence is published, a group will assess the new evidence and make a judg-ment on to what extent it is expected to alter the recom-mendation.

Competing interests: All authors have completed the BMJ Rapid Recommendations interests disclosure form and a detailed, contextualised description of all disclosures is reported in appendix 2 on bmj.com. As with all BMJ Rapid Recommendations, the executive team and The BMJ judged that no panel member had any financial conflict of interest. Professional and academic interests are minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions.

Funding: This guideline was not funded.

Transparency: B Aertgeerts affirms that the manuscript is an honest, accurate, and transparent account of the recommendation being reported; that no important aspects of the recommendation have been omitted; and that any discrepancies from the recommendation as planned (and, if relevant, registered) have been explained.

Table 2 | New evidence which has emerged after initial publicationDate New evidence Citation Findings Implications for recommendation(s)There are currently no updates to the article



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26 Siemieniuk RA, Agoritsas T, Macdonald H, Guyatt GH, Brandt L, Vandvik PO. Introduction to BMJ Rapid Recommendations. BMJ 2016;354:i5191. doi:10.1136/bmj.i5191. pmid:27680768.

27 Vandvik PO, Otto CM, Siemieniuk RA, et al. Transcatheter or surgical aortic valve replacement for patients with severe, symptomatic, aortic stenosis at low to intermediate surgical risk: a clinical practice guideline. BMJ 2016;354:i5085. doi:10.1136/bmj.i5085. pmid:27680583.

28 Guyatt GH, Oxman AD, Vist GE, et al. GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6. doi:10.1136/bmj.39489.470347.AD. pmid:18436948.

29 Andrews JC, Schünemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to recommendation-determinants of a recommendation’s direction and strength. J Clin Epidemiol 2013;66:726-35. doi:10.1016/j.jclinepi.2013.02.003. pmid:23570745.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

1Academic Centre for General Practice, Department of Public Health and Primary Care, KU Leuven, Belgium2CEBAM, Belgian Centre for Evidence-Based Medicine, Cochrane Belgium, Leuven, Belgium3Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada L8S 4L84Division General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, CH-1211, Geneva, Switzerland5Department of Medicine, University of Toronto, Toronto, Ontario, Canada6Dutch College of General Practitioners, Utrecht, The Netherlands7School CAPHRI, Department Family Medicine, Maastricht, The Netherlands8Division of General Pediatrics, University Hospitals of Geneva & Faculty of Medicine, University of Geneva, Geneva, Switzerland9Primary Care Clinical Unit, Faculty of Medicine, University of Queensland, Brisbane, Australia10Pediatric Immunology, Department of microbiology and immunology, KU Leuven, Belgium11Pediatric allergy, Clinical division of pediatrics UZ Leuven, Leuven, Belgium12Bali District Hospital, Bali and Centre for Development of Best practices in Health Yaounde, Cameroon13Otorhinolaryngology—Head and Neck Surgery, Clinica del Country, Bogota, Colombia14NIHR Oxford Diagnostic Evidence Cooperative, Oxford, UK15Department of Primary Care Health Sciences, University of Oxford, Oxford, UK16Oslo University Hospital, Forskningsveien 2b, Blindern 0317 Oslo, Norway17The Society for Participatory Medicine, Newburyport, MA 01950-1183, USA18Arizona Senior Academy, Tucson, AZ 85747, USA19MOH Holdings, 1 Maritime Square, Singapore, Singapore 09925320Cochrane UK, London, UK21Cochrane Consumers Group, Halifax, Canada22Washington DC, USA23HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran24Department of Medicine, Innlandet Hospital Trust - division Gjøvik, Norway25Faculty of Dentistry, Universidad de Chile, Santiago, Chile



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Corticosteroids for sore throat: a clinical practiceguideline

OPEN ACCESS

On publication of this Practice paper (BMJ 2017;358:j4090,doi:10.1136/bmj.j4090), the main graphical summary of theevidence for this recommendation contained an error. For theoutcome “Complete pain resolution (48 hrs),” the value of 608people per 1000 (183 more) was stated for those people taking

steroids. The correct value should have been 629 per 1000 (204more), as stated in the systematic review supporting therecommendation (www.bmj.com/content/358/bmj.j3887). Thiserror has been corrected in the graphical summary.

No commercial reuse: See rights and reprints http://www.bmj.com/permissions Subscribe: http://www.bmj.com/subscribe

BMJ 2017;359:j5654 doi: 10.1136/bmj.j5654 (Published 5 December 2017) Page 1 of 1

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