Nina Rogers, MD

Illustrative case

A 63-year-old man presents with pain in both legs, which starts with activity and resolves with rest. He has a resting blood pressure of 135/77 mm Hg consistent with past measurements, and an ankle-brachial index (ABI) <0.90, which is consistent with peripheral artery disease (PAD). His daily medications are 81 mg aspirin, 25 mg hydrochlorothiazide, and 40 mg simvastatin. What additional agent could be added for his symptoms?

PAD, defined as an ABI <0.9, affects approximately 5% of Americans older than 40 years. About two-thirds of those with PAD are asymptomatic; the remaining third suffer from intermittent claudication (IC).²

Exercise and smoking cessation are effective at reducing IC symptoms, as well as the long-term cardiovascular event risk associated with PAD.³ But even with these lifestyle changes, patients with PAD are often troubled by persistent symptoms.

Few evidence-based treatments for IC

Compared with placebo, the antiplatelet agents indobufen and picotamide have been shown to improve pain-free walking distance (PFWD).⁴ So have cilostazol⁵ and naftidrofuryl,⁶ as well as lipid-lowering agents.⁷

In a pilot study of 40 patients, 10 mg ramipril was shown to improve pain-free walking time (PFWT) at 24 weeks by 227 seconds (95% confidence interval [CI]=175-278; P<.001). That represents a 164% increase from baseline, vs no change in PFWT at 24 weeks for the placebo group.⁸ A recent small (N=33), double-blinded RCT found similar improvements in maximum treadmill walking distance, PFWD, and patient-reported walking distance at 24 weeks with ramipril compared with placebo.⁹

In the HOPE study, a subsection of patients who were older than 55 years and had PAD were treated with a daily target dose of 10 mg ramipril for a mean of 4.5 years. Compared with placebo, ramipril reduced the primary outcome—cardiovascular mortality, myocardial infarction (MI), or stroke—by 25% (risk ratio=0.75; 95% CI, 0.61-0.92).¹⁰

In the study reported on here, Ahimastos et al took a closer look at ramipril.

STUDY SUMMARY: Patients on ramipril can walk longer pain free

The authors conducted a double-blind, randomized placebo-controlled trial evaluating the effectiveness of 10 mg/d ramipril for the improvement of maximum walk time (MWT) and PFWT in patients with PAD.¹ Eligible patients had an ABI <0.9 in at least one leg and a history of IC in at least one leg, with stable claudication symptoms and a stable medical regimen for 6 months or more. Exclusion criteria included a resting blood pressure >160/100 mm Hg; use of ACE inhibitors, angiotensin II receptor blockers, potassium sparing diuretics, or potassium supplements in the past 6 months; serum creatinine >2.3 mg/dL; renal artery stenosis; previous coronary or lower extremity revascularization procedure; MI in the past 3 months; major surgery planned for the following year; critical limb ischemia; or any condition other than PAD limiting walking ability.

In total, 212 patients underwent randomization, and either took 10 mg/d ramipril or placebo for 24 weeks. The participants had similar baseline characteristics. Most were male (83.5%), with a mean age of 65.5 years; 33.5% were current smokers; 50% had hypertension; and 24.1% had type 2 diabetes.

Ramipril not only reduces cardiovascular mortality, MI, and stroke in patients with PAD, but its effective in improving patient-oriented outcomes such as duration of walking without developing intermittent claudication. Primary outcomes—PFWT and MWT—improved in the ramipril group. Compared with the placebo group, those in the ramipril group had a mean PFWT increase of 75 seconds (95% CI, 60-89; P<.001) and a 255-second increase in MWT (95% CI, 215-295; P<.001), a 52% and 107% increase from baseline, respectively. Most secondary measures (including the Walking Impairment Questionnaire median distance score, the speed score, and the stair-climbing score) also improved significantly, relative to the placebo group. However, ABI did not change significantly in either group.

WHAT'S NEW: Evidence that ramipril improves patient-oriented outcomes

Ramipril not only reduces cardiovascular mortality, MI, and stroke in patients with PAD,¹⁰ but is effective in improving patient-oriented outcomes such as duration of walking without developing IC.

CAVEATS: Would ramipril help less stable patients?

Inclusion criteria used by Ahimastos et al limit the generalizability of this study to patients with stable symptoms for 6 months or more. Similarly, because the study lasted for 24 weeks, it is not known whether ramipril’s benefits for patients with claudication would continue indefinitely. Also of note: The ABI did not improve in the treatment cohort at the end of this 24-week period, and the authors did not report objective outcomes such as revascularization or mortality.

CHALLENGES TO IMPLEMENTATION: Monitoring, adverse effects may present problems

Use of ACE inhibitors requires monitoring of renal function and serum potassium. In addition, ACE inhibitors can induce a chronic cough that often limits their use in those affected; 6.6% of the treatment group withdrew from this study due to persistent cough.¹

ACKNOWLEDGEMENT
The PURLs surveillance system was supported in part by Grant Number UL1RR024999 from the National center for Research Resources, a clinical Translational science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National center for Research Resources or the National Institutes of Health.

Illustrative case

A 63-year-old man presents with pain in both legs, which starts with activity and resolves with rest. He has a resting blood pressure of 135/77 mm Hg consistent with past measurements, and an ankle-brachial index (ABI) <0.90, which is consistent with peripheral artery disease (PAD). His daily medications are 81 mg aspirin, 25 mg hydrochlorothiazide, and 40 mg simvastatin. What additional agent could be added for his symptoms?

PAD, defined as an ABI <0.9, affects approximately 5% of Americans older than 40 years. About two-thirds of those with PAD are asymptomatic; the remaining third suffer from intermittent claudication (IC).²

Exercise and smoking cessation are effective at reducing IC symptoms, as well as the long-term cardiovascular event risk associated with PAD.³ But even with these lifestyle changes, patients with PAD are often troubled by persistent symptoms.

Few evidence-based treatments for IC

Compared with placebo, the antiplatelet agents indobufen and picotamide have been shown to improve pain-free walking distance (PFWD).⁴ So have cilostazol⁵ and naftidrofuryl,⁶ as well as lipid-lowering agents.⁷

In a pilot study of 40 patients, 10 mg ramipril was shown to improve pain-free walking time (PFWT) at 24 weeks by 227 seconds (95% confidence interval [CI]=175-278; P<.001). That represents a 164% increase from baseline, vs no change in PFWT at 24 weeks for the placebo group.⁸ A recent small (N=33), double-blinded RCT found similar improvements in maximum treadmill walking distance, PFWD, and patient-reported walking distance at 24 weeks with ramipril compared with placebo.⁹

In the HOPE study, a subsection of patients who were older than 55 years and had PAD were treated with a daily target dose of 10 mg ramipril for a mean of 4.5 years. Compared with placebo, ramipril reduced the primary outcome—cardiovascular mortality, myocardial infarction (MI), or stroke—by 25% (risk ratio=0.75; 95% CI, 0.61-0.92).¹⁰

In the study reported on here, Ahimastos et al took a closer look at ramipril.

STUDY SUMMARY: Patients on ramipril can walk longer pain free

The authors conducted a double-blind, randomized placebo-controlled trial evaluating the effectiveness of 10 mg/d ramipril for the improvement of maximum walk time (MWT) and PFWT in patients with PAD.¹ Eligible patients had an ABI <0.9 in at least one leg and a history of IC in at least one leg, with stable claudication symptoms and a stable medical regimen for 6 months or more. Exclusion criteria included a resting blood pressure >160/100 mm Hg; use of ACE inhibitors, angiotensin II receptor blockers, potassium sparing diuretics, or potassium supplements in the past 6 months; serum creatinine >2.3 mg/dL; renal artery stenosis; previous coronary or lower extremity revascularization procedure; MI in the past 3 months; major surgery planned for the following year; critical limb ischemia; or any condition other than PAD limiting walking ability.

In total, 212 patients underwent randomization, and either took 10 mg/d ramipril or placebo for 24 weeks. The participants had similar baseline characteristics. Most were male (83.5%), with a mean age of 65.5 years; 33.5% were current smokers; 50% had hypertension; and 24.1% had type 2 diabetes.

Ramipril not only reduces cardiovascular mortality, MI, and stroke in patients with PAD, but its effective in improving patient-oriented outcomes such as duration of walking without developing intermittent claudication. Primary outcomes—PFWT and MWT—improved in the ramipril group. Compared with the placebo group, those in the ramipril group had a mean PFWT increase of 75 seconds (95% CI, 60-89; P<.001) and a 255-second increase in MWT (95% CI, 215-295; P<.001), a 52% and 107% increase from baseline, respectively. Most secondary measures (including the Walking Impairment Questionnaire median distance score, the speed score, and the stair-climbing score) also improved significantly, relative to the placebo group. However, ABI did not change significantly in either group.

WHAT'S NEW: Evidence that ramipril improves patient-oriented outcomes

Ramipril not only reduces cardiovascular mortality, MI, and stroke in patients with PAD,¹⁰ but is effective in improving patient-oriented outcomes such as duration of walking without developing IC.

CAVEATS: Would ramipril help less stable patients?

Inclusion criteria used by Ahimastos et al limit the generalizability of this study to patients with stable symptoms for 6 months or more. Similarly, because the study lasted for 24 weeks, it is not known whether ramipril’s benefits for patients with claudication would continue indefinitely. Also of note: The ABI did not improve in the treatment cohort at the end of this 24-week period, and the authors did not report objective outcomes such as revascularization or mortality.

CHALLENGES TO IMPLEMENTATION: Monitoring, adverse effects may present problems

Use of ACE inhibitors requires monitoring of renal function and serum potassium. In addition, ACE inhibitors can induce a chronic cough that often limits their use in those affected; 6.6% of the treatment group withdrew from this study due to persistent cough.¹

ACKNOWLEDGEMENT
The PURLs surveillance system was supported in part by Grant Number UL1RR024999 from the National center for Research Resources, a clinical Translational science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National center for Research Resources or the National Institutes of Health.

Illustrative case

A 63-year-old man presents with pain in both legs, which starts with activity and resolves with rest. He has a resting blood pressure of 135/77 mm Hg consistent with past measurements, and an ankle-brachial index (ABI) <0.90, which is consistent with peripheral artery disease (PAD). His daily medications are 81 mg aspirin, 25 mg hydrochlorothiazide, and 40 mg simvastatin. What additional agent could be added for his symptoms?

PAD, defined as an ABI <0.9, affects approximately 5% of Americans older than 40 years. About two-thirds of those with PAD are asymptomatic; the remaining third suffer from intermittent claudication (IC).²

Exercise and smoking cessation are effective at reducing IC symptoms, as well as the long-term cardiovascular event risk associated with PAD.³ But even with these lifestyle changes, patients with PAD are often troubled by persistent symptoms.

Few evidence-based treatments for IC

Compared with placebo, the antiplatelet agents indobufen and picotamide have been shown to improve pain-free walking distance (PFWD).⁴ So have cilostazol⁵ and naftidrofuryl,⁶ as well as lipid-lowering agents.⁷

In a pilot study of 40 patients, 10 mg ramipril was shown to improve pain-free walking time (PFWT) at 24 weeks by 227 seconds (95% confidence interval [CI]=175-278; P<.001). That represents a 164% increase from baseline, vs no change in PFWT at 24 weeks for the placebo group.⁸ A recent small (N=33), double-blinded RCT found similar improvements in maximum treadmill walking distance, PFWD, and patient-reported walking distance at 24 weeks with ramipril compared with placebo.⁹

In the HOPE study, a subsection of patients who were older than 55 years and had PAD were treated with a daily target dose of 10 mg ramipril for a mean of 4.5 years. Compared with placebo, ramipril reduced the primary outcome—cardiovascular mortality, myocardial infarction (MI), or stroke—by 25% (risk ratio=0.75; 95% CI, 0.61-0.92).¹⁰

In the study reported on here, Ahimastos et al took a closer look at ramipril.

STUDY SUMMARY: Patients on ramipril can walk longer pain free

The authors conducted a double-blind, randomized placebo-controlled trial evaluating the effectiveness of 10 mg/d ramipril for the improvement of maximum walk time (MWT) and PFWT in patients with PAD.¹ Eligible patients had an ABI <0.9 in at least one leg and a history of IC in at least one leg, with stable claudication symptoms and a stable medical regimen for 6 months or more. Exclusion criteria included a resting blood pressure >160/100 mm Hg; use of ACE inhibitors, angiotensin II receptor blockers, potassium sparing diuretics, or potassium supplements in the past 6 months; serum creatinine >2.3 mg/dL; renal artery stenosis; previous coronary or lower extremity revascularization procedure; MI in the past 3 months; major surgery planned for the following year; critical limb ischemia; or any condition other than PAD limiting walking ability.

In total, 212 patients underwent randomization, and either took 10 mg/d ramipril or placebo for 24 weeks. The participants had similar baseline characteristics. Most were male (83.5%), with a mean age of 65.5 years; 33.5% were current smokers; 50% had hypertension; and 24.1% had type 2 diabetes.

Ramipril not only reduces cardiovascular mortality, MI, and stroke in patients with PAD, but its effective in improving patient-oriented outcomes such as duration of walking without developing intermittent claudication. Primary outcomes—PFWT and MWT—improved in the ramipril group. Compared with the placebo group, those in the ramipril group had a mean PFWT increase of 75 seconds (95% CI, 60-89; P<.001) and a 255-second increase in MWT (95% CI, 215-295; P<.001), a 52% and 107% increase from baseline, respectively. Most secondary measures (including the Walking Impairment Questionnaire median distance score, the speed score, and the stair-climbing score) also improved significantly, relative to the placebo group. However, ABI did not change significantly in either group.

WHAT'S NEW: Evidence that ramipril improves patient-oriented outcomes

Ramipril not only reduces cardiovascular mortality, MI, and stroke in patients with PAD,¹⁰ but is effective in improving patient-oriented outcomes such as duration of walking without developing IC.

CAVEATS: Would ramipril help less stable patients?

Inclusion criteria used by Ahimastos et al limit the generalizability of this study to patients with stable symptoms for 6 months or more. Similarly, because the study lasted for 24 weeks, it is not known whether ramipril’s benefits for patients with claudication would continue indefinitely. Also of note: The ABI did not improve in the treatment cohort at the end of this 24-week period, and the authors did not report objective outcomes such as revascularization or mortality.

CHALLENGES TO IMPLEMENTATION: Monitoring, adverse effects may present problems

Use of ACE inhibitors requires monitoring of renal function and serum potassium. In addition, ACE inhibitors can induce a chronic cough that often limits their use in those affected; 6.6% of the treatment group withdrew from this study due to persistent cough.¹

ACKNOWLEDGEMENT
The PURLs surveillance system was supported in part by Grant Number UL1RR024999 from the National center for Research Resources, a clinical Translational science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National center for Research Resources or the National Institutes of Health.

PRACTICE CHANGER
Consider prescribing a single dose of corticosteroids for patients with sore throat; this has been found to provide quick pain relief and resolution of symptoms.¹

STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis of randomized controlled trials (RCTs) in ambulatory care settings.¹

ILLUSTRATIVE CASE
A 28-year-old woman comes to your clinic because she’s had a severe sore throat and low-grade fever for the past two days. She has no associated cough. Examination reveals erythematous posterior oropharynx with exudate. A rapid strep test is negative. The patient says the sore throat is very painful and asks for medication to make it better. What should you prescribe?

Most sore throats—particularly in adults—are viral and self-limiting.^2,3 Group A β-hemolytic Streptococcus infections account for just 10% of sore throats in adults and 15% to 30% in children.⁴ Yet US physicians have been found to prescribe antibiotics for more than half of patients who present with sore throat.^5-7

Do patients want antibiotics, or simply pain relief?
Antibiotics produce only a modest reduction in symptoms of pharyngitis (fever and throat soreness), presumably in patients with bacterial infections, and increase the risk for adverse events.^5,6 Research suggests that patients who request antibiotics for sore throat may be seeking primarily pain relief.⁸ Thus, a treatment that is more effective in alleviating symptoms of a sore throat would likely contribute to a decrease in unnecessary use of antibiotics.

A short course of corticosteroids has been used successfully and shown to be safe for conditions such as acute sinusitis, croup, and asthma.^9-11 Could the anti-inflammatory effects of corticosteroids reduce pain in patients with sore throat, as well? A 2010 systematic review suggested that was the case.¹² Cochrane reviewers recently took another look.¹

STUDY SUMMARY
Steroids bring speedier pain relief
This meta-analysis included eight RCTs (the same eight trials used in the systematic review⁹) that compared corticosteroids with placebo for the symptomatic treatment of exudative or severe sore throat.¹ Sore throat was defined as clinical evidence of pharyngitis and/or tonsillitis or the clinical syndrome of painful throat and odynophagia.

Five studies were conducted in the United States, and one each in Canada, Turkey, and Israel. Five studies focused on adults (n = 413); the other three studied children (n = 393). Overall, 47% of participants had exudative sore throat, and 44% were positive for group A β-hemolytic Streptococcus.

In all eight RCTs, antibiotics were given to those in both the treatment and placebo groups. In addition, all participants were allowed to use traditional analgesia (either acetaminophen or NSAIDs). Corticosteroids (oral dexamethasone, oral prednisone, or intramuscular [IM] dexamethasone) were used as an adjunctive treatment in all the RCTs.

Primary outcomes varied between studies. Four of the eight RCTs included the proportion of patients with improvement or complete resolution of symptoms within 24 to 48 hours. Mean time to onset of pain relief was the primary outcome in five of the eight studies. Some of the secondary outcomes in the individual trials included relapse rates, adverse events, and days missed from school or work.

Overall, patients who received corticosteroids were three times more likely to report complete resolution of symptoms at 24 hours (relative risk = 3.2) and had a reduced mean time to onset of pain relief of about six hours. The number needed to treat to prevent one patient from experiencing pain at 24 hours was < 4.

Adverse events were reported in only one of the trials (n = 125): Five patients (three in the steroid group and two receiving placebo) were hospitalized for fluid rehydration, and three patients (one in the steroid group and two receiving placebo) developed peritonsillar abscess.¹² Three RCTs did not find any significant difference in days missed from school or work, and four trials reported no difference in recurrence of symptoms. One of the trials found that 16% of the patients in the placebo group returned to seek additional care, while none in the steroid group did.¹³

WHAT’S NEW
Steroids haven’t been tested as standalone treatment
Steroids are not currently recommended for routine use to treat symptoms of sore throat. This Cochrane review found that patients with severe or exudative sore throat benefit from pain reduction with corticosteroids, used as an adjunct to antibiotics and other analgesics without increased risk for harm. Nonetheless, the use of steroids in this patient population would address a practical concern of those seeking symptom relief and has the potential to decrease unnecessary use of antibiotics.

CAVEATS
Questions about effects on antibiotic use, heterogeneity
The studies in this meta-analysis did not assess whether the use of corticosteroids would reduce unnecessary use of antibiotics, so we cannot conclude that this would be the case. Because the effect was similar in all subgroups analyzed, however, it is reasonable to expect that reduced antibiotic use could be a positive effect. The main documented benefit was resolution of pain, an important patient-centered outcome that justifies consideration of treating painful pharyngitis with corticosteroids.

Corticosteroids have an immunosuppressant effect and carry the theoretical risk for exacerbation of an existing infection. That did not occur in these studies. Nor has it occurred when short courses of corticosteroids are used for other illnesses, such as croup, infectious mononucleosis, asthma, contact dermatitis, and COPD.¹⁴ Thus, this theoretical risk is not a barrier to implementation.

It is important to note that single and multiple doses of corticosteroids and oral and IM routes were effective, with only minimal differences in results.

CHALLENGES TO 
IMPLEMENTATION
Determining the severity
Acetaminophen and NSAIDs are used for pain relief in sore throat and have been shown to be effective—but may be inadequate for severe pain.15 There are no head-to-head trials that have compared steroids to NSAIDs or acetaminophen in this clinical scenario. So the challenge for clinicians will be to decide when pharyngitis is severe enough to justify the use of corticosteroids, rather than simple analgesics alone.  

REFERENCES
1. Hayward G, Thompson M, Perera R, et al. Corticosteroids as stand-alone or add-on treatment for sore throat. Cochrane Database Syst Rev. 2012;(10):CDC008268.

2. Cherry DK, Woodwell DA. National Ambulatory Medical Care Survey: 2000 summary. Adv Data. 2002;328:1-32.

3. Bisno AL. Acute pharyngitis. N Engl J Med. 2001;344:205-211.

4. Del Mar CB, Glasziou PP, Sprinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2006;(4):CD000023.

5. Linder JA, Stafford RS. Antibiotic treatment of adults with sore throat by community primary care physicians: a national survey, 1989-1999. JAMA. 2001;286:1181-1186.

6. Linder JA, Bates DW, Lee GM, et al. Antibiotic treatment of children with sore throat. JAMA. 2005;294:2315-2322.

7. Hong SY, Taur Y, Jordan MR. Antimicrobial prescribing in the USA for adult acute pharyngitis in relation to treatment guidelines. J Eval Clin Pract. 2011;17:1176-1183.

8. 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;4:494-499.

9. Venekamp RP, Thompson MJ, Hayward G, et al. Systemic corticosteroids for acute sinusitis. Cochrane Database Syst Rev. 2011;(12): CD008115.

10. Russell KF, Liang Y, O’Gorman K, et al. Glucocorticoids for croup. Cochrane Database Syst Rev. 2011;(1):CD001955.

11. Rowe BH, Spooner C, Ducharme F, et al. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001;(1):CD002178.

12. Korb K, Scherer M, Cenot J. Steroids as adjuvant therapy for acute pharyngitis in ambulatory patients: a systematic review. Ann Fam Med. 2010;8:58-63.

13. 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;159:278-282.

14. Manson SC, Brown RE, Cerulli A, et al. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use. Respir Med. 2009;103:975-994.

15. Wei JL, Kasperbauer JL, Weaver AL, et al. Efficacy of single-dose dexamethasone as adjuvant therapy for acute pharyngitis. Laryngoscope. 2002;112:87-93.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2013. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2013;62(7):372-374.

PRACTICE CHANGER
Consider prescribing a single dose of corticosteroids for patients with sore throat; this has been found to provide quick pain relief and resolution of symptoms.¹

STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis of randomized controlled trials (RCTs) in ambulatory care settings.¹

ILLUSTRATIVE CASE
A 28-year-old woman comes to your clinic because she’s had a severe sore throat and low-grade fever for the past two days. She has no associated cough. Examination reveals erythematous posterior oropharynx with exudate. A rapid strep test is negative. The patient says the sore throat is very painful and asks for medication to make it better. What should you prescribe?

Most sore throats—particularly in adults—are viral and self-limiting.^2,3 Group A β-hemolytic Streptococcus infections account for just 10% of sore throats in adults and 15% to 30% in children.⁴ Yet US physicians have been found to prescribe antibiotics for more than half of patients who present with sore throat.^5-7

Do patients want antibiotics, or simply pain relief?
Antibiotics produce only a modest reduction in symptoms of pharyngitis (fever and throat soreness), presumably in patients with bacterial infections, and increase the risk for adverse events.^5,6 Research suggests that patients who request antibiotics for sore throat may be seeking primarily pain relief.⁸ Thus, a treatment that is more effective in alleviating symptoms of a sore throat would likely contribute to a decrease in unnecessary use of antibiotics.

A short course of corticosteroids has been used successfully and shown to be safe for conditions such as acute sinusitis, croup, and asthma.^9-11 Could the anti-inflammatory effects of corticosteroids reduce pain in patients with sore throat, as well? A 2010 systematic review suggested that was the case.¹² Cochrane reviewers recently took another look.¹

STUDY SUMMARY
Steroids bring speedier pain relief
This meta-analysis included eight RCTs (the same eight trials used in the systematic review⁹) that compared corticosteroids with placebo for the symptomatic treatment of exudative or severe sore throat.¹ Sore throat was defined as clinical evidence of pharyngitis and/or tonsillitis or the clinical syndrome of painful throat and odynophagia.

Five studies were conducted in the United States, and one each in Canada, Turkey, and Israel. Five studies focused on adults (n = 413); the other three studied children (n = 393). Overall, 47% of participants had exudative sore throat, and 44% were positive for group A β-hemolytic Streptococcus.

In all eight RCTs, antibiotics were given to those in both the treatment and placebo groups. In addition, all participants were allowed to use traditional analgesia (either acetaminophen or NSAIDs). Corticosteroids (oral dexamethasone, oral prednisone, or intramuscular [IM] dexamethasone) were used as an adjunctive treatment in all the RCTs.

Primary outcomes varied between studies. Four of the eight RCTs included the proportion of patients with improvement or complete resolution of symptoms within 24 to 48 hours. Mean time to onset of pain relief was the primary outcome in five of the eight studies. Some of the secondary outcomes in the individual trials included relapse rates, adverse events, and days missed from school or work.

Overall, patients who received corticosteroids were three times more likely to report complete resolution of symptoms at 24 hours (relative risk = 3.2) and had a reduced mean time to onset of pain relief of about six hours. The number needed to treat to prevent one patient from experiencing pain at 24 hours was < 4.

Adverse events were reported in only one of the trials (n = 125): Five patients (three in the steroid group and two receiving placebo) were hospitalized for fluid rehydration, and three patients (one in the steroid group and two receiving placebo) developed peritonsillar abscess.¹² Three RCTs did not find any significant difference in days missed from school or work, and four trials reported no difference in recurrence of symptoms. One of the trials found that 16% of the patients in the placebo group returned to seek additional care, while none in the steroid group did.¹³

WHAT’S NEW
Steroids haven’t been tested as standalone treatment
Steroids are not currently recommended for routine use to treat symptoms of sore throat. This Cochrane review found that patients with severe or exudative sore throat benefit from pain reduction with corticosteroids, used as an adjunct to antibiotics and other analgesics without increased risk for harm. Nonetheless, the use of steroids in this patient population would address a practical concern of those seeking symptom relief and has the potential to decrease unnecessary use of antibiotics.

CAVEATS
Questions about effects on antibiotic use, heterogeneity
The studies in this meta-analysis did not assess whether the use of corticosteroids would reduce unnecessary use of antibiotics, so we cannot conclude that this would be the case. Because the effect was similar in all subgroups analyzed, however, it is reasonable to expect that reduced antibiotic use could be a positive effect. The main documented benefit was resolution of pain, an important patient-centered outcome that justifies consideration of treating painful pharyngitis with corticosteroids.

Corticosteroids have an immunosuppressant effect and carry the theoretical risk for exacerbation of an existing infection. That did not occur in these studies. Nor has it occurred when short courses of corticosteroids are used for other illnesses, such as croup, infectious mononucleosis, asthma, contact dermatitis, and COPD.¹⁴ Thus, this theoretical risk is not a barrier to implementation.

It is important to note that single and multiple doses of corticosteroids and oral and IM routes were effective, with only minimal differences in results.

CHALLENGES TO 
IMPLEMENTATION
Determining the severity
Acetaminophen and NSAIDs are used for pain relief in sore throat and have been shown to be effective—but may be inadequate for severe pain.15 There are no head-to-head trials that have compared steroids to NSAIDs or acetaminophen in this clinical scenario. So the challenge for clinicians will be to decide when pharyngitis is severe enough to justify the use of corticosteroids, rather than simple analgesics alone.  

REFERENCES
1. Hayward G, Thompson M, Perera R, et al. Corticosteroids as stand-alone or add-on treatment for sore throat. Cochrane Database Syst Rev. 2012;(10):CDC008268.

2. Cherry DK, Woodwell DA. National Ambulatory Medical Care Survey: 2000 summary. Adv Data. 2002;328:1-32.

3. Bisno AL. Acute pharyngitis. N Engl J Med. 2001;344:205-211.

4. Del Mar CB, Glasziou PP, Sprinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2006;(4):CD000023.

5. Linder JA, Stafford RS. Antibiotic treatment of adults with sore throat by community primary care physicians: a national survey, 1989-1999. JAMA. 2001;286:1181-1186.

6. Linder JA, Bates DW, Lee GM, et al. Antibiotic treatment of children with sore throat. JAMA. 2005;294:2315-2322.

7. Hong SY, Taur Y, Jordan MR. Antimicrobial prescribing in the USA for adult acute pharyngitis in relation to treatment guidelines. J Eval Clin Pract. 2011;17:1176-1183.

8. 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;4:494-499.

9. Venekamp RP, Thompson MJ, Hayward G, et al. Systemic corticosteroids for acute sinusitis. Cochrane Database Syst Rev. 2011;(12): CD008115.

10. Russell KF, Liang Y, O’Gorman K, et al. Glucocorticoids for croup. Cochrane Database Syst Rev. 2011;(1):CD001955.

11. Rowe BH, Spooner C, Ducharme F, et al. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001;(1):CD002178.

12. Korb K, Scherer M, Cenot J. Steroids as adjuvant therapy for acute pharyngitis in ambulatory patients: a systematic review. Ann Fam Med. 2010;8:58-63.

13. 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;159:278-282.

14. Manson SC, Brown RE, Cerulli A, et al. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use. Respir Med. 2009;103:975-994.

15. Wei JL, Kasperbauer JL, Weaver AL, et al. Efficacy of single-dose dexamethasone as adjuvant therapy for acute pharyngitis. Laryngoscope. 2002;112:87-93.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2013. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2013;62(7):372-374.

PRACTICE CHANGER
Consider prescribing a single dose of corticosteroids for patients with sore throat; this has been found to provide quick pain relief and resolution of symptoms.¹

STRENGTH OF RECOMMENDATION
A: Based on a meta-analysis of randomized controlled trials (RCTs) in ambulatory care settings.¹

ILLUSTRATIVE CASE
A 28-year-old woman comes to your clinic because she’s had a severe sore throat and low-grade fever for the past two days. She has no associated cough. Examination reveals erythematous posterior oropharynx with exudate. A rapid strep test is negative. The patient says the sore throat is very painful and asks for medication to make it better. What should you prescribe?

Most sore throats—particularly in adults—are viral and self-limiting.^2,3 Group A β-hemolytic Streptococcus infections account for just 10% of sore throats in adults and 15% to 30% in children.⁴ Yet US physicians have been found to prescribe antibiotics for more than half of patients who present with sore throat.^5-7

Do patients want antibiotics, or simply pain relief?
Antibiotics produce only a modest reduction in symptoms of pharyngitis (fever and throat soreness), presumably in patients with bacterial infections, and increase the risk for adverse events.^5,6 Research suggests that patients who request antibiotics for sore throat may be seeking primarily pain relief.⁸ Thus, a treatment that is more effective in alleviating symptoms of a sore throat would likely contribute to a decrease in unnecessary use of antibiotics.

A short course of corticosteroids has been used successfully and shown to be safe for conditions such as acute sinusitis, croup, and asthma.^9-11 Could the anti-inflammatory effects of corticosteroids reduce pain in patients with sore throat, as well? A 2010 systematic review suggested that was the case.¹² Cochrane reviewers recently took another look.¹

STUDY SUMMARY
Steroids bring speedier pain relief
This meta-analysis included eight RCTs (the same eight trials used in the systematic review⁹) that compared corticosteroids with placebo for the symptomatic treatment of exudative or severe sore throat.¹ Sore throat was defined as clinical evidence of pharyngitis and/or tonsillitis or the clinical syndrome of painful throat and odynophagia.

Five studies were conducted in the United States, and one each in Canada, Turkey, and Israel. Five studies focused on adults (n = 413); the other three studied children (n = 393). Overall, 47% of participants had exudative sore throat, and 44% were positive for group A β-hemolytic Streptococcus.

In all eight RCTs, antibiotics were given to those in both the treatment and placebo groups. In addition, all participants were allowed to use traditional analgesia (either acetaminophen or NSAIDs). Corticosteroids (oral dexamethasone, oral prednisone, or intramuscular [IM] dexamethasone) were used as an adjunctive treatment in all the RCTs.

Primary outcomes varied between studies. Four of the eight RCTs included the proportion of patients with improvement or complete resolution of symptoms within 24 to 48 hours. Mean time to onset of pain relief was the primary outcome in five of the eight studies. Some of the secondary outcomes in the individual trials included relapse rates, adverse events, and days missed from school or work.

Overall, patients who received corticosteroids were three times more likely to report complete resolution of symptoms at 24 hours (relative risk = 3.2) and had a reduced mean time to onset of pain relief of about six hours. The number needed to treat to prevent one patient from experiencing pain at 24 hours was < 4.

Adverse events were reported in only one of the trials (n = 125): Five patients (three in the steroid group and two receiving placebo) were hospitalized for fluid rehydration, and three patients (one in the steroid group and two receiving placebo) developed peritonsillar abscess.¹² Three RCTs did not find any significant difference in days missed from school or work, and four trials reported no difference in recurrence of symptoms. One of the trials found that 16% of the patients in the placebo group returned to seek additional care, while none in the steroid group did.¹³

WHAT’S NEW
Steroids haven’t been tested as standalone treatment
Steroids are not currently recommended for routine use to treat symptoms of sore throat. This Cochrane review found that patients with severe or exudative sore throat benefit from pain reduction with corticosteroids, used as an adjunct to antibiotics and other analgesics without increased risk for harm. Nonetheless, the use of steroids in this patient population would address a practical concern of those seeking symptom relief and has the potential to decrease unnecessary use of antibiotics.

CAVEATS
Questions about effects on antibiotic use, heterogeneity
The studies in this meta-analysis did not assess whether the use of corticosteroids would reduce unnecessary use of antibiotics, so we cannot conclude that this would be the case. Because the effect was similar in all subgroups analyzed, however, it is reasonable to expect that reduced antibiotic use could be a positive effect. The main documented benefit was resolution of pain, an important patient-centered outcome that justifies consideration of treating painful pharyngitis with corticosteroids.

Corticosteroids have an immunosuppressant effect and carry the theoretical risk for exacerbation of an existing infection. That did not occur in these studies. Nor has it occurred when short courses of corticosteroids are used for other illnesses, such as croup, infectious mononucleosis, asthma, contact dermatitis, and COPD.¹⁴ Thus, this theoretical risk is not a barrier to implementation.

It is important to note that single and multiple doses of corticosteroids and oral and IM routes were effective, with only minimal differences in results.

CHALLENGES TO 
IMPLEMENTATION
Determining the severity
Acetaminophen and NSAIDs are used for pain relief in sore throat and have been shown to be effective—but may be inadequate for severe pain.15 There are no head-to-head trials that have compared steroids to NSAIDs or acetaminophen in this clinical scenario. So the challenge for clinicians will be to decide when pharyngitis is severe enough to justify the use of corticosteroids, rather than simple analgesics alone.  

REFERENCES
1. Hayward G, Thompson M, Perera R, et al. Corticosteroids as stand-alone or add-on treatment for sore throat. Cochrane Database Syst Rev. 2012;(10):CDC008268.

2. Cherry DK, Woodwell DA. National Ambulatory Medical Care Survey: 2000 summary. Adv Data. 2002;328:1-32.

3. Bisno AL. Acute pharyngitis. N Engl J Med. 2001;344:205-211.

4. Del Mar CB, Glasziou PP, Sprinks AB. Antibiotics for sore throat. Cochrane Database Syst Rev. 2006;(4):CD000023.

5. Linder JA, Stafford RS. Antibiotic treatment of adults with sore throat by community primary care physicians: a national survey, 1989-1999. JAMA. 2001;286:1181-1186.

6. Linder JA, Bates DW, Lee GM, et al. Antibiotic treatment of children with sore throat. JAMA. 2005;294:2315-2322.

7. Hong SY, Taur Y, Jordan MR. Antimicrobial prescribing in the USA for adult acute pharyngitis in relation to treatment guidelines. J Eval Clin Pract. 2011;17:1176-1183.

8. 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;4:494-499.

9. Venekamp RP, Thompson MJ, Hayward G, et al. Systemic corticosteroids for acute sinusitis. Cochrane Database Syst Rev. 2011;(12): CD008115.

10. Russell KF, Liang Y, O’Gorman K, et al. Glucocorticoids for croup. Cochrane Database Syst Rev. 2011;(1):CD001955.

11. Rowe BH, Spooner C, Ducharme F, et al. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001;(1):CD002178.

12. Korb K, Scherer M, Cenot J. Steroids as adjuvant therapy for acute pharyngitis in ambulatory patients: a systematic review. Ann Fam Med. 2010;8:58-63.

13. 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;159:278-282.

14. Manson SC, Brown RE, Cerulli A, et al. The cumulative burden of oral corticosteroid side effects and the economic implications of steroid use. Respir Med. 2009;103:975-994.

15. Wei JL, Kasperbauer JL, Weaver AL, et al. Efficacy of single-dose dexamethasone as adjuvant therapy for acute pharyngitis. Laryngoscope. 2002;112:87-93.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2013. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2013;62(7):372-374.

Illustrative case

A 28-year-old woman comes to your clinic because she’s had a severe sore throat and low-grade fever for the past 2 days. She has no associated cough. Examination reveals erythematous posterior oropharynx with exudate. A rapid strep test is negative. The patient says the sore throat is very painful and asks for medication to make it better. What should you prescribe?

Most sore throats—particularly in adults—are viral and self-limiting.^2,3 Group A B-hemolytic Streptococcusinfections account for just 10% of sore throats in adults and 15% to 30% in children.⁴ Yet US physicians have been found to prescribe antibiotics for more than half of patients who present with sore throat.^5-7

Do patients want antibiotics, or simply pain relief?Antibiotics produce only a modest reduction in symptoms of pharyngitis (fever and throat soreness), presumably in patients with bacterial infections, and increase the risk of adverse events.5,6 Research suggests that patients who request antibiotics for sore throat may primarily be seeking pain relief.⁸ Thus, a treatment that’s more effective in alleviating symptoms of a sore throat would likely contribute to a decrease in unnecessary use of antibiotics.

A short course of corticosteroids has been used successfully and shown to be safe for conditions such as acute sinusitis, croup, and asthma.^9-11 Could the anti-inflammatory effects of corticosteroids reduce pain in patients with sore throat, as well? A 2010 systematic review suggested that was the case.¹² Cochrane reviewers recently took another look.¹

Study summary: Steroids bring speedier pain relief

This meta-analysis included 8 RCTs (the same 8 trials used in the systematic review⁹) that compared corticosteroids with placebo for the symptomatic treatment of exudative or severe sore throat.¹ Sore throat was defined as clinical evidence of pharyngitis and/or tonsillitis or the clinical syndrome of painful throat and odynophagia.

Five studies were conducted in the United States, and one each in Canada, Turkey, and Israel. Five studies focused on adults (N=413); the other 3 studied children (N=393). Overall, 47% of participants had exudative sore throat, and 44% were positive for group A B-hemolytic Streptococcus.

In all 8 RCTs, antibiotics were given to those in both the treatment and placebo groups. In addition, all participants were allowed to use traditional analgesia— either acetaminophen or nonsteroidal anti-inflammatory drugs. Corticosteroids (oral dexamethasone, oral prednisone, or intramuscular [IM] dexamethasone) were used as an adjunctive treatment in all the RCTs.

Primary outcomes varied among the studies. Four of the 8 RCTs included the proportion of patients with improvement or complete resolution of symptoms within 24 to 48 hours. Mean time to onset of pain relief was the primary outcome in 5 of the 8 studies. Some of the secondary outcomes in the individual trials included relapse rates, adverse events, and days missed from school or work.

Overall, patients who received corticosteroids were 3 times more likely to report complete resolution of symptoms at 24 hours (relative risk=3.2; 95% confidence interval, 2.0-5.1; P<.001) and had a reduced mean time to onset of pain relief of about 6 hours. The number needed to treat to prevent one patient from experiencing pain at 24 hours was <4.

Adverse events were reported in only one of the trials (N=125): Five patients (3 in the steroid group and 2 on placebo) were hospitalized for fluid rehydration, and 3 patients (one in the steroid group and 2 on placebo) developed peritonsillar abscess.¹² Three RCTs did not find any significant difference in days missed from school or work, and 4 trials reported no difference in recurrence of symptoms. One of the trials found that 16% of the patients in the placebo group returned to seek additional care, while none in the steroid group did.¹³

What's new: Steroids haven't been tested as standalone treatment

Steroids are not currently recommended for routine use to treat symptoms of sore throat. This Cochrane review found that patients with severe or exudative sore throat benefit from pain reduction with corticosteroids, used as an adjunct to antibiotics and other analgesics without increased risk of harm. Nonetheless, the use of steroids in this patient population would address a practical concern of those seeking symptom relief and has the potential to decrease unnecessary antibiotic use.

Caveats: Questions about effects on antibiotic use, heterogeneity remain

The studies in this meta-analysis did not assess whether the use corticosteroids would reduce unnecessary use of antibiotics, so we cannot conclude that this would be the case. Because the effect was similar in all sub-groups analyzed, however, it is reasonable to expect that reduced antibiotic use could be a positive effect. The main documented benefit was resolution of pain, an important patient-centered outcome that justifies consideration of treating painful pharyngitis with corticosteroids.                                                                                                     

Corticosteroids have an immunosuppressant effect and carry the FAST TRACK
Research suggests that patients who request antibiotics for a sore throat may be seeking pain relief. theoretical risk of exacerbating an existing infection. That did not occur in these studies. Nor has it occurred when used for short courses in other illnesses such as croup, infectious mononucleosis, asthma, contact dermatitis, and chronic obstructive pulmonary disease.¹⁴ Thus, this theoretical risk is not a barrier to implementation.

It is important to note that single and multiple doses of corticosteroids and oral and IM routes were effective, with only minimal differences in results.  

Challenges to implementation: Determining the severity

Acetaminophen and NSAIDs are used for pain relief in sore throat, and have been shown to be effective—but may be inadequate for severe pain.¹⁵ There are no head-to-head trials that have compared steroids to NSAIDs or acetaminophen in this clinical scenario.  So the challenge for clinicians will be to decide when pharyngitis is severe enough to justify the use of corticosteroids, rather than simple analgesics alone.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant number ul1rr024999 from the national center for research resources, a clinical Translational Science award to the university of chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the national center for research resources or the national institutes of health.

Illustrative case

A 28-year-old woman comes to your clinic because she’s had a severe sore throat and low-grade fever for the past 2 days. She has no associated cough. Examination reveals erythematous posterior oropharynx with exudate. A rapid strep test is negative. The patient says the sore throat is very painful and asks for medication to make it better. What should you prescribe?

Most sore throats—particularly in adults—are viral and self-limiting.^2,3 Group A B-hemolytic Streptococcusinfections account for just 10% of sore throats in adults and 15% to 30% in children.⁴ Yet US physicians have been found to prescribe antibiotics for more than half of patients who present with sore throat.^5-7

Do patients want antibiotics, or simply pain relief?Antibiotics produce only a modest reduction in symptoms of pharyngitis (fever and throat soreness), presumably in patients with bacterial infections, and increase the risk of adverse events.5,6 Research suggests that patients who request antibiotics for sore throat may primarily be seeking pain relief.⁸ Thus, a treatment that’s more effective in alleviating symptoms of a sore throat would likely contribute to a decrease in unnecessary use of antibiotics.

A short course of corticosteroids has been used successfully and shown to be safe for conditions such as acute sinusitis, croup, and asthma.^9-11 Could the anti-inflammatory effects of corticosteroids reduce pain in patients with sore throat, as well? A 2010 systematic review suggested that was the case.¹² Cochrane reviewers recently took another look.¹

Study summary: Steroids bring speedier pain relief

This meta-analysis included 8 RCTs (the same 8 trials used in the systematic review⁹) that compared corticosteroids with placebo for the symptomatic treatment of exudative or severe sore throat.¹ Sore throat was defined as clinical evidence of pharyngitis and/or tonsillitis or the clinical syndrome of painful throat and odynophagia.

Five studies were conducted in the United States, and one each in Canada, Turkey, and Israel. Five studies focused on adults (N=413); the other 3 studied children (N=393). Overall, 47% of participants had exudative sore throat, and 44% were positive for group A B-hemolytic Streptococcus.

In all 8 RCTs, antibiotics were given to those in both the treatment and placebo groups. In addition, all participants were allowed to use traditional analgesia— either acetaminophen or nonsteroidal anti-inflammatory drugs. Corticosteroids (oral dexamethasone, oral prednisone, or intramuscular [IM] dexamethasone) were used as an adjunctive treatment in all the RCTs.

Primary outcomes varied among the studies. Four of the 8 RCTs included the proportion of patients with improvement or complete resolution of symptoms within 24 to 48 hours. Mean time to onset of pain relief was the primary outcome in 5 of the 8 studies. Some of the secondary outcomes in the individual trials included relapse rates, adverse events, and days missed from school or work.

Overall, patients who received corticosteroids were 3 times more likely to report complete resolution of symptoms at 24 hours (relative risk=3.2; 95% confidence interval, 2.0-5.1; P<.001) and had a reduced mean time to onset of pain relief of about 6 hours. The number needed to treat to prevent one patient from experiencing pain at 24 hours was <4.

Adverse events were reported in only one of the trials (N=125): Five patients (3 in the steroid group and 2 on placebo) were hospitalized for fluid rehydration, and 3 patients (one in the steroid group and 2 on placebo) developed peritonsillar abscess.¹² Three RCTs did not find any significant difference in days missed from school or work, and 4 trials reported no difference in recurrence of symptoms. One of the trials found that 16% of the patients in the placebo group returned to seek additional care, while none in the steroid group did.¹³

What's new: Steroids haven't been tested as standalone treatment

Steroids are not currently recommended for routine use to treat symptoms of sore throat. This Cochrane review found that patients with severe or exudative sore throat benefit from pain reduction with corticosteroids, used as an adjunct to antibiotics and other analgesics without increased risk of harm. Nonetheless, the use of steroids in this patient population would address a practical concern of those seeking symptom relief and has the potential to decrease unnecessary antibiotic use.

Caveats: Questions about effects on antibiotic use, heterogeneity remain

The studies in this meta-analysis did not assess whether the use corticosteroids would reduce unnecessary use of antibiotics, so we cannot conclude that this would be the case. Because the effect was similar in all sub-groups analyzed, however, it is reasonable to expect that reduced antibiotic use could be a positive effect. The main documented benefit was resolution of pain, an important patient-centered outcome that justifies consideration of treating painful pharyngitis with corticosteroids.                                                                                                     

Corticosteroids have an immunosuppressant effect and carry the FAST TRACK
Research suggests that patients who request antibiotics for a sore throat may be seeking pain relief. theoretical risk of exacerbating an existing infection. That did not occur in these studies. Nor has it occurred when used for short courses in other illnesses such as croup, infectious mononucleosis, asthma, contact dermatitis, and chronic obstructive pulmonary disease.¹⁴ Thus, this theoretical risk is not a barrier to implementation.

It is important to note that single and multiple doses of corticosteroids and oral and IM routes were effective, with only minimal differences in results.  

Challenges to implementation: Determining the severity

Acetaminophen and NSAIDs are used for pain relief in sore throat, and have been shown to be effective—but may be inadequate for severe pain.¹⁵ There are no head-to-head trials that have compared steroids to NSAIDs or acetaminophen in this clinical scenario.  So the challenge for clinicians will be to decide when pharyngitis is severe enough to justify the use of corticosteroids, rather than simple analgesics alone.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant number ul1rr024999 from the national center for research resources, a clinical Translational Science award to the university of chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the national center for research resources or the national institutes of health.

Illustrative case

A 28-year-old woman comes to your clinic because she’s had a severe sore throat and low-grade fever for the past 2 days. She has no associated cough. Examination reveals erythematous posterior oropharynx with exudate. A rapid strep test is negative. The patient says the sore throat is very painful and asks for medication to make it better. What should you prescribe?

Most sore throats—particularly in adults—are viral and self-limiting.^2,3 Group A B-hemolytic Streptococcusinfections account for just 10% of sore throats in adults and 15% to 30% in children.⁴ Yet US physicians have been found to prescribe antibiotics for more than half of patients who present with sore throat.^5-7

Do patients want antibiotics, or simply pain relief?Antibiotics produce only a modest reduction in symptoms of pharyngitis (fever and throat soreness), presumably in patients with bacterial infections, and increase the risk of adverse events.5,6 Research suggests that patients who request antibiotics for sore throat may primarily be seeking pain relief.⁸ Thus, a treatment that’s more effective in alleviating symptoms of a sore throat would likely contribute to a decrease in unnecessary use of antibiotics.

A short course of corticosteroids has been used successfully and shown to be safe for conditions such as acute sinusitis, croup, and asthma.^9-11 Could the anti-inflammatory effects of corticosteroids reduce pain in patients with sore throat, as well? A 2010 systematic review suggested that was the case.¹² Cochrane reviewers recently took another look.¹

Study summary: Steroids bring speedier pain relief

This meta-analysis included 8 RCTs (the same 8 trials used in the systematic review⁹) that compared corticosteroids with placebo for the symptomatic treatment of exudative or severe sore throat.¹ Sore throat was defined as clinical evidence of pharyngitis and/or tonsillitis or the clinical syndrome of painful throat and odynophagia.

Five studies were conducted in the United States, and one each in Canada, Turkey, and Israel. Five studies focused on adults (N=413); the other 3 studied children (N=393). Overall, 47% of participants had exudative sore throat, and 44% were positive for group A B-hemolytic Streptococcus.

In all 8 RCTs, antibiotics were given to those in both the treatment and placebo groups. In addition, all participants were allowed to use traditional analgesia— either acetaminophen or nonsteroidal anti-inflammatory drugs. Corticosteroids (oral dexamethasone, oral prednisone, or intramuscular [IM] dexamethasone) were used as an adjunctive treatment in all the RCTs.

Primary outcomes varied among the studies. Four of the 8 RCTs included the proportion of patients with improvement or complete resolution of symptoms within 24 to 48 hours. Mean time to onset of pain relief was the primary outcome in 5 of the 8 studies. Some of the secondary outcomes in the individual trials included relapse rates, adverse events, and days missed from school or work.

Overall, patients who received corticosteroids were 3 times more likely to report complete resolution of symptoms at 24 hours (relative risk=3.2; 95% confidence interval, 2.0-5.1; P<.001) and had a reduced mean time to onset of pain relief of about 6 hours. The number needed to treat to prevent one patient from experiencing pain at 24 hours was <4.

Adverse events were reported in only one of the trials (N=125): Five patients (3 in the steroid group and 2 on placebo) were hospitalized for fluid rehydration, and 3 patients (one in the steroid group and 2 on placebo) developed peritonsillar abscess.¹² Three RCTs did not find any significant difference in days missed from school or work, and 4 trials reported no difference in recurrence of symptoms. One of the trials found that 16% of the patients in the placebo group returned to seek additional care, while none in the steroid group did.¹³

What's new: Steroids haven't been tested as standalone treatment

Steroids are not currently recommended for routine use to treat symptoms of sore throat. This Cochrane review found that patients with severe or exudative sore throat benefit from pain reduction with corticosteroids, used as an adjunct to antibiotics and other analgesics without increased risk of harm. Nonetheless, the use of steroids in this patient population would address a practical concern of those seeking symptom relief and has the potential to decrease unnecessary antibiotic use.

Caveats: Questions about effects on antibiotic use, heterogeneity remain

The studies in this meta-analysis did not assess whether the use corticosteroids would reduce unnecessary use of antibiotics, so we cannot conclude that this would be the case. Because the effect was similar in all sub-groups analyzed, however, it is reasonable to expect that reduced antibiotic use could be a positive effect. The main documented benefit was resolution of pain, an important patient-centered outcome that justifies consideration of treating painful pharyngitis with corticosteroids.                                                                                                     

Corticosteroids have an immunosuppressant effect and carry the FAST TRACK
Research suggests that patients who request antibiotics for a sore throat may be seeking pain relief. theoretical risk of exacerbating an existing infection. That did not occur in these studies. Nor has it occurred when used for short courses in other illnesses such as croup, infectious mononucleosis, asthma, contact dermatitis, and chronic obstructive pulmonary disease.¹⁴ Thus, this theoretical risk is not a barrier to implementation.

It is important to note that single and multiple doses of corticosteroids and oral and IM routes were effective, with only minimal differences in results.  

Challenges to implementation: Determining the severity

Acetaminophen and NSAIDs are used for pain relief in sore throat, and have been shown to be effective—but may be inadequate for severe pain.¹⁵ There are no head-to-head trials that have compared steroids to NSAIDs or acetaminophen in this clinical scenario.  So the challenge for clinicians will be to decide when pharyngitis is severe enough to justify the use of corticosteroids, rather than simple analgesics alone.

Acknowledgement

The PURLs Surveillance System was supported in part by Grant number ul1rr024999 from the national center for research resources, a clinical Translational Science award to the university of chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the national center for research resources or the national institutes of health.

ILLUSTRATIVE CASE

Alarmed because she recently noticed a decrease in her hearing, a 61-year-old woman requests an urgent visit. When you examine her ears, you find bilateral occlusion with cerumen. The patient says that she’s needed office irrigation multiple times in the past and wants to know how to clean her ears at home to prevent wax build-up. What can you recommend?

Cerumen impaction is associated with a variety of symptoms, including hearing loss, pain, itching, and a feeling of fullness, as well as dizziness, tinnitus, and a reflex cough.² Eight million ear irrigations are carried out in US medical offices each year.³ Yet there is no reason to believe (and little evidence to suggest) that home irrigation would not be an effective approach.

Drops and wax removal kits are widely available
Patients can purchase wax-softening drops. Carbamide peroxide substances, for instance, are sold under a variety of trade names, such as Auraphene-B, Debrox, Mollifene, and Murine Ear Drops. Mineral oil is a common home remedy, as well, although it has no official indication for ear wax removal.

Home irrigation kits, which typically include a bulb syringe, are sold over the counter and cost anywhere from $3 to $400.⁴ These prices represent the varying degrees of automation available for cerumen removal, from wax-softening drops and a bulb syringe packed together in a “kit” to systems that connect to the faucet for continuous water pressure and include a temperature sensor. Most kits cost less than $20.

Bulb syringe irrigation is generally considered safe and effective. But it has never been compared with other methods⁵ and clinicians rarely recommend it, we suspect because of a lack of knowledge of its safety and efficacy.

STUDY SUMMARY: Every 2 patients given wax removal kits = 1 less office visit

Coppin et al conducted a blinded study of adults with cerumen impaction to assess the efficacy of bulb syringe irrigation compared with standard care.¹ The authors recruited patients from 7 practices in England. To be eligible for the study, patients had to have symptoms of blockage and visible occluding ear wax. The researchers assessed 434 patients and randomized 237; of these, only 3 were lost to follow-up.

Using concealed allocation, a nurse randomly gave all the patients identical-looking envelopes. Half of the envelopes contained ear drops and instructions in usual care (ear irrigation by a clinician after the use of ear drops). The other half contained ear drops and a 25-mL ear bulb syringe (not available over the counter in the United Kingdom). Instructions provided with the syringes indicated that they could be cleaned and reused, but did not specifically instruct patients as to when to use them. Baseline characteristics were balanced between the 2 groups.

After 2 weeks, the nurse reassessed the patients and irrigated the ears of any patient with evidence of occlusion. The authors used National Health Service computerized records to track ear wax–related visits over the next 2 years for participants in both groups.

During the 2-year follow-up, more of the patients in the control group returned to the clinic with episodes of ear wax compared with those in the intervention group (73% vs 60%; risk ratio=1.21; 95% confidence interval [CI], 1.01-1.37; P=.038).

The researchers also found that, among the returnees, patients in the control group had, on average, 50% more visits. That is, for every 2 patients who were given a bulb syringe, there was one less visit (incidence rate ratio=1.79; 95% CI, 1.05-3.04; P=.032). A secondary analysis found no significant difference in adverse events between the intervention and the control groups.

WHAT’S NEW: Do-it-yourself wax removal is now evidence-based

The American Academy of Otolaryngology-Head and Neck Surgery Foundation’s 2008 clinical practice guideline—based primarily on expert opinion—recommends clinician irrigation only, due to a lack of quality evidence.³

This RCT is the first to provide evidence that some patients do not need to spend time (or money) on a medical visit for ear wax irrigation. The fact that patients who were given bulb syringes had fewer visits, not only for the initial wax removal but also for subsequent episodes of cerumen impaction, suggests that they were self-treating at home without an increase in adverse effects.

CAVEATS: Home irrigation is not for every patient

This intervention cannot be extrapolated to young children or to others who are unable to perform self-irrigation. It is possible that if a patient self-irrigates without prior visualization by a clinician, a contraindication such as ruptured tympanic membrane or active infection could be present.

This study was performed in England, where bulb syringes are not readily available. It is possible that this intervention may be less effective at avoiding cerumen-related office visits in the United States, especially if patients are already using bulb syringes for this purpose. Finally, we note that 60% of the patients in the home irrigation group did return for a visit for cerumen removal during the 2-year follow-up, so home irrigation did not entirely replace office irrigation.

CHALLENGES TO IMPLEMENTATION: Getting buy-in from patients

The greatest challenge to implementation might be convincing patients that they can safely perform self-irrigation at home. This may require written patient instructions, preferably with illustrations. The steps will need to be written clearly and include details such as recommended ear wax softeners, water temperature, use of peroxide (or not), warning symptoms, and when to contact a physician.

A healthy physician-patient relationship, and perhaps, giving patients the bulb syringe and instructions in using it before they leave the clinic, will help to overcome patient hesitancy. Physician inertia may also be a problem, but it should be easy to put this new information into practice once provider resistance is overcome.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

Alarmed because she recently noticed a decrease in her hearing, a 61-year-old woman requests an urgent visit. When you examine her ears, you find bilateral occlusion with cerumen. The patient says that she’s needed office irrigation multiple times in the past and wants to know how to clean her ears at home to prevent wax build-up. What can you recommend?

Cerumen impaction is associated with a variety of symptoms, including hearing loss, pain, itching, and a feeling of fullness, as well as dizziness, tinnitus, and a reflex cough.² Eight million ear irrigations are carried out in US medical offices each year.³ Yet there is no reason to believe (and little evidence to suggest) that home irrigation would not be an effective approach.

Drops and wax removal kits are widely available
Patients can purchase wax-softening drops. Carbamide peroxide substances, for instance, are sold under a variety of trade names, such as Auraphene-B, Debrox, Mollifene, and Murine Ear Drops. Mineral oil is a common home remedy, as well, although it has no official indication for ear wax removal.

Home irrigation kits, which typically include a bulb syringe, are sold over the counter and cost anywhere from $3 to $400.⁴ These prices represent the varying degrees of automation available for cerumen removal, from wax-softening drops and a bulb syringe packed together in a “kit” to systems that connect to the faucet for continuous water pressure and include a temperature sensor. Most kits cost less than $20.

Bulb syringe irrigation is generally considered safe and effective. But it has never been compared with other methods⁵ and clinicians rarely recommend it, we suspect because of a lack of knowledge of its safety and efficacy.

STUDY SUMMARY: Every 2 patients given wax removal kits = 1 less office visit

Coppin et al conducted a blinded study of adults with cerumen impaction to assess the efficacy of bulb syringe irrigation compared with standard care.¹ The authors recruited patients from 7 practices in England. To be eligible for the study, patients had to have symptoms of blockage and visible occluding ear wax. The researchers assessed 434 patients and randomized 237; of these, only 3 were lost to follow-up.

Using concealed allocation, a nurse randomly gave all the patients identical-looking envelopes. Half of the envelopes contained ear drops and instructions in usual care (ear irrigation by a clinician after the use of ear drops). The other half contained ear drops and a 25-mL ear bulb syringe (not available over the counter in the United Kingdom). Instructions provided with the syringes indicated that they could be cleaned and reused, but did not specifically instruct patients as to when to use them. Baseline characteristics were balanced between the 2 groups.

After 2 weeks, the nurse reassessed the patients and irrigated the ears of any patient with evidence of occlusion. The authors used National Health Service computerized records to track ear wax–related visits over the next 2 years for participants in both groups.

During the 2-year follow-up, more of the patients in the control group returned to the clinic with episodes of ear wax compared with those in the intervention group (73% vs 60%; risk ratio=1.21; 95% confidence interval [CI], 1.01-1.37; P=.038).

The researchers also found that, among the returnees, patients in the control group had, on average, 50% more visits. That is, for every 2 patients who were given a bulb syringe, there was one less visit (incidence rate ratio=1.79; 95% CI, 1.05-3.04; P=.032). A secondary analysis found no significant difference in adverse events between the intervention and the control groups.

WHAT’S NEW: Do-it-yourself wax removal is now evidence-based

The American Academy of Otolaryngology-Head and Neck Surgery Foundation’s 2008 clinical practice guideline—based primarily on expert opinion—recommends clinician irrigation only, due to a lack of quality evidence.³

This RCT is the first to provide evidence that some patients do not need to spend time (or money) on a medical visit for ear wax irrigation. The fact that patients who were given bulb syringes had fewer visits, not only for the initial wax removal but also for subsequent episodes of cerumen impaction, suggests that they were self-treating at home without an increase in adverse effects.

CAVEATS: Home irrigation is not for every patient

This intervention cannot be extrapolated to young children or to others who are unable to perform self-irrigation. It is possible that if a patient self-irrigates without prior visualization by a clinician, a contraindication such as ruptured tympanic membrane or active infection could be present.

This study was performed in England, where bulb syringes are not readily available. It is possible that this intervention may be less effective at avoiding cerumen-related office visits in the United States, especially if patients are already using bulb syringes for this purpose. Finally, we note that 60% of the patients in the home irrigation group did return for a visit for cerumen removal during the 2-year follow-up, so home irrigation did not entirely replace office irrigation.

CHALLENGES TO IMPLEMENTATION: Getting buy-in from patients

The greatest challenge to implementation might be convincing patients that they can safely perform self-irrigation at home. This may require written patient instructions, preferably with illustrations. The steps will need to be written clearly and include details such as recommended ear wax softeners, water temperature, use of peroxide (or not), warning symptoms, and when to contact a physician.

A healthy physician-patient relationship, and perhaps, giving patients the bulb syringe and instructions in using it before they leave the clinic, will help to overcome patient hesitancy. Physician inertia may also be a problem, but it should be easy to put this new information into practice once provider resistance is overcome.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

ILLUSTRATIVE CASE

Alarmed because she recently noticed a decrease in her hearing, a 61-year-old woman requests an urgent visit. When you examine her ears, you find bilateral occlusion with cerumen. The patient says that she’s needed office irrigation multiple times in the past and wants to know how to clean her ears at home to prevent wax build-up. What can you recommend?

Cerumen impaction is associated with a variety of symptoms, including hearing loss, pain, itching, and a feeling of fullness, as well as dizziness, tinnitus, and a reflex cough.² Eight million ear irrigations are carried out in US medical offices each year.³ Yet there is no reason to believe (and little evidence to suggest) that home irrigation would not be an effective approach.

Drops and wax removal kits are widely available
Patients can purchase wax-softening drops. Carbamide peroxide substances, for instance, are sold under a variety of trade names, such as Auraphene-B, Debrox, Mollifene, and Murine Ear Drops. Mineral oil is a common home remedy, as well, although it has no official indication for ear wax removal.

Home irrigation kits, which typically include a bulb syringe, are sold over the counter and cost anywhere from $3 to $400.⁴ These prices represent the varying degrees of automation available for cerumen removal, from wax-softening drops and a bulb syringe packed together in a “kit” to systems that connect to the faucet for continuous water pressure and include a temperature sensor. Most kits cost less than $20.

Bulb syringe irrigation is generally considered safe and effective. But it has never been compared with other methods⁵ and clinicians rarely recommend it, we suspect because of a lack of knowledge of its safety and efficacy.

STUDY SUMMARY: Every 2 patients given wax removal kits = 1 less office visit

Coppin et al conducted a blinded study of adults with cerumen impaction to assess the efficacy of bulb syringe irrigation compared with standard care.¹ The authors recruited patients from 7 practices in England. To be eligible for the study, patients had to have symptoms of blockage and visible occluding ear wax. The researchers assessed 434 patients and randomized 237; of these, only 3 were lost to follow-up.

Using concealed allocation, a nurse randomly gave all the patients identical-looking envelopes. Half of the envelopes contained ear drops and instructions in usual care (ear irrigation by a clinician after the use of ear drops). The other half contained ear drops and a 25-mL ear bulb syringe (not available over the counter in the United Kingdom). Instructions provided with the syringes indicated that they could be cleaned and reused, but did not specifically instruct patients as to when to use them. Baseline characteristics were balanced between the 2 groups.

After 2 weeks, the nurse reassessed the patients and irrigated the ears of any patient with evidence of occlusion. The authors used National Health Service computerized records to track ear wax–related visits over the next 2 years for participants in both groups.

During the 2-year follow-up, more of the patients in the control group returned to the clinic with episodes of ear wax compared with those in the intervention group (73% vs 60%; risk ratio=1.21; 95% confidence interval [CI], 1.01-1.37; P=.038).

The researchers also found that, among the returnees, patients in the control group had, on average, 50% more visits. That is, for every 2 patients who were given a bulb syringe, there was one less visit (incidence rate ratio=1.79; 95% CI, 1.05-3.04; P=.032). A secondary analysis found no significant difference in adverse events between the intervention and the control groups.

WHAT’S NEW: Do-it-yourself wax removal is now evidence-based

The American Academy of Otolaryngology-Head and Neck Surgery Foundation’s 2008 clinical practice guideline—based primarily on expert opinion—recommends clinician irrigation only, due to a lack of quality evidence.³

This RCT is the first to provide evidence that some patients do not need to spend time (or money) on a medical visit for ear wax irrigation. The fact that patients who were given bulb syringes had fewer visits, not only for the initial wax removal but also for subsequent episodes of cerumen impaction, suggests that they were self-treating at home without an increase in adverse effects.

CAVEATS: Home irrigation is not for every patient

This intervention cannot be extrapolated to young children or to others who are unable to perform self-irrigation. It is possible that if a patient self-irrigates without prior visualization by a clinician, a contraindication such as ruptured tympanic membrane or active infection could be present.

This study was performed in England, where bulb syringes are not readily available. It is possible that this intervention may be less effective at avoiding cerumen-related office visits in the United States, especially if patients are already using bulb syringes for this purpose. Finally, we note that 60% of the patients in the home irrigation group did return for a visit for cerumen removal during the 2-year follow-up, so home irrigation did not entirely replace office irrigation.

CHALLENGES TO IMPLEMENTATION: Getting buy-in from patients

The greatest challenge to implementation might be convincing patients that they can safely perform self-irrigation at home. This may require written patient instructions, preferably with illustrations. The steps will need to be written clearly and include details such as recommended ear wax softeners, water temperature, use of peroxide (or not), warning symptoms, and when to contact a physician.

A healthy physician-patient relationship, and perhaps, giving patients the bulb syringe and instructions in using it before they leave the clinic, will help to overcome patient hesitancy. Physician inertia may also be a problem, but it should be easy to put this new information into practice once provider resistance is overcome.

Acknowledgement

The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY