Sore throat: effective communication delivers improved diagnosis, enhanced self-care and more rational use of antibiotics

ORIGINAL PAPER Sore throat: effective communication delivers improved diagnosis, enhanced self-care and more rational use of antibiotics A. W. van der Velden, 1 J. Bell, 2 A. Sessa, 3 M. Duerden, 4 A. Altiner 5 * 1 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, The Netherlands 2 Pharmacy School, University of Technology Sydney, Broadway, Australia 3 Italian College of General Practitioners, Florence, Italy 4 Office of Medical Director BCUHB, Wrexham, UK 5 Institute of General Practice, Rostock University Medical Centre, Rostock, Germany Correspondence to: Alike van der Velden, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands Tel.: +31-0-88-756-8511 Fax: +31-0-88-756-8099. Email: a.w.vandervelden@ umcutrecht.nl *In collaboration with the Global Respiratory Infection Partnership: Attila Altiner (Germany), John Bell (Australia), Martin Duerden (UK), Sabiha Essack (South Africa), Roman Kozlov (Russia), John Oxford (UK), Antonio Carlos Pignatari (Brazil), Aurelio Sessa (Italy), Alike van der Velden (The Netherlands). SUMMARY The majority of throat infections are of viral origin and resolve without antibiotic treatment. Despite this, antibiotic use for sore throat infections remains high, partly because it is difficult to determine when antibiotics may be useful, on the basis of physical findings alone. Antibiotics may be beneficial in bacterial throat infections under certain clinical and epidemiological circumstances; however, even many of those infections in which bacteria play a role do resolve just as quickly without antibiotics. Furthermore, non-medical factors such as patient expectations and patient pressure are also important drivers of antibiotic use. To address these issues, a behavioural change is required that can be facilitated by improved communication between primary healthcare providers and patients. In this article, we provide doctors, nurses and pharmacy staff, working in primary care or in the community, with a structured approach to sore throat management, with the aim of educating and empowering patients to self-manage their condition. The first component of this approach involves identifying and addressing patients expectations and concerns with regard to their sore throat and eliciting their opinion on antibiotics. The second part is dedicated to a pragmatic assessment of the severity of the condition, with attention to red-flag symptoms and risk factors for serious complications. Rather than just focusing on the cause (bacterial or viral) of the upper respiratory tract infections as a rationale for antibiotic use, healthcare providers should instead consider the severity of the patient s condition and whether they are at high risk of complications. The third part involves counselling patients on effective self-management options and providing information on the expected clinical course. Such a structured approach to sore throat management, using empathetic, non-paternalistic language, combined with written patient information, will help to drive patient confidence in self-care and encourage them to accept the self-limiting character of the illness important steps towards improving antibiotic stewardship in acute throat infections. Introduction What s new The Global Respiratory Infection Partnership has developed a toolkit comprising educational materials for primary healthcare providers and patients. Toolkit materials: www.grip-initiative.com Implementation of the toolkit is expected to enhance patients self-care of sore throat, thereby limiting antibiotic use. What s known Antibiotics have very limited effectiveness in treatment of sore throat. Improved communication between healthcare provider and patient could facilitate a behavioural change towards appropriate use of antibiotics for sore throat. In the first part of this supplement, the Global Respiratory Infection Partnership (GRIP) proposed a global framework for the non-antibiotic management of upper respiratory tract infections (URTIs). Here, we apply the outlined principles to the management of sore throat (as an example of a common symptom of URTIs), offering practical advice to primary care teams on how to implement the guidance in their daily practice. Sore throat is one of the top 10 reasons for patients to visit ambulatory care (1), and the use of antibiotics for the treatment of sore throat is widespread (2). However, up to 95% of infections in adults are of viral origin (3). These infections are usually self-limiting, with symptoms typically resolving within 1 2 weeks (4), and complications are rare (5). For the vast majority of throat infections, antibiotics do not have any impact on the severity of symptoms or the course of the disease, and do not prevent complications (6). A recent review assessing the effect of antibiotics in sore throat at one week, described that 21 patients have to be treated in order to see one patient benefitting from a course of antibiotics (7). Moreover, a systematic review found that antibiotics are among the least effective treatment options for sore throat (8). By contrast, the efficacy 10 doi: 10.1111/ijcp.12336

Sore throat: encourage self-care, reduce antibiotic use 11 of symptomatic treatments, such as NSAIDs and paracetamol, was up to 93% higher than placebo. Group A beta-haemolytic streptococcus infections are the most common bacterial cause of sore throat, yet they are responsible for only 10% of sore throats (3). It is these infections where antibiotics may be beneficial in shortening the clinical course and preventing complications (e.g. rheumatic fever), notably in settings where risk of complications may be high (9). However, in clinical practice it is notoriously difficult to distinguish between URTIs of viral and bacterial origin, as physical signs and symptoms are similar in both types of infection (9 11). Diagnostic certainty can only be achieved with a throat culture (3,9). As this delays treatment and does not accurately predict benefit from antibiotics, physicians in many countries tend to base their treatment decision on other (non-medical) factors. Many authors therefore recommend the management of sore throat based on the severity of the infection, combined with how unwell the patient appears and on the risk profile of the patient (4). Several prediction rules have been developed that use a combination of signs and symptoms to evaluate the risk of bacterial infection, where antibiotic treatment may be indicated. The most commonly used is the Centor score (1,9). This score incorporates the following symptoms: tonsillar exudate; tender anterior cervical adenopathy; absence of cough and history of fever (> 38.0 C). Patients meeting three or four Centor criteria have a higher likelihood of streptococcal infection (12); however, although the Centor criteria predict the likelihood of streptococcal infection, they do not predict the patient s response to antibiotic treatment. There are also certain patient subgroups that should be monitored more closely, or treated, because they have an elevated risk of severe respiratory disease. Factors associated with an increased risk include advanced age, respiratory or immunocompromising comorbidity and long duration of symptoms (13,14). Diagnostic certainty can be increased by the use of point-of-care testing, the rapid Strep A test for sore throat, if available. A point-of-care test may also prove useful as a tool to reassure patients and increase their understanding of the prescribing decision (2,15). Finally, any prescribing decision needs to include consideration of the risks and disadvantages associated with antibiotic therapy. These include side effects such as diarrhoea, nausea and rash (4,16,17), and disturbance of the microbiota. Wilton et al. reported an increased risk of developing vaginal candidiasis after antibiotic therapy (17). In addition, bacteria may become resistant to the antibiotic used (16,18); resistant bacteria can be found for up to one year in the individual (18). This could make future infections more difficult to treat, not only in this individual patient but also in the community, because resistant bacteria can be passed on to family members, work colleagues and friends. Antimicrobial resistance is a major public health threat, as it makes infections more difficult to treat or even untreatable (18,19). Interaction between prescriber/ pharmacy team and patient Treatment decisions are not only influenced by medical factors; non-medical factors such as cultural issues or patient expectations and pressure also affect prescribing behaviour (20). Tackling the overuse of antibiotics in the management of sore throat therefore requires a broader approach that focuses on the relationship between healthcare provider and patient. In this interaction it is the responsibility of the prescriber to firstly identify the need for an antibiotic, bearing in mind that most URTIs are of viral origin and self-limiting (14,21). Prescribers can help combat the overuse of antibiotics for sore throat management by addressing any misperceptions and expectations about antibiotics that the patient may bring to the consultation (2,20,22). In fact, antibiotic demand may not be the main reason patients consult their healthcare provider for sore throat. Primary reasons for patients with respiratory tract infections visiting healthcare providers include: To establish the cause of symptoms and disease To exclude serious illness (and seek reassurance) To obtain symptomatic relief To gain more information on the course and duration of the disease (20). Pharmacy staff tend to see patients who have already chosen the self-management route. Their role is important and diverse. They need to support this approach by offering reassurance and advice on appropriate treatment to increase the chances of optimum symptomatic relief and patient satisfaction. Furthermore, they need knowledge for patient-centred advice on when to consult another healthcare provider. Applying a structured approach to patient consultations may help healthcare providers to fulfil these roles in a time-efficient manner. Such a structured approach could have the following components: (i) Address patient s concerns; (ii) Be vigilant; assess severity; (iii) Counsel on effective self-management.

12 Sore throat: encourage self-care, reduce antibiotic use Address patient s concerns The first task for prescribers and pharmacy staff is to identify the concerns and expectations of the patient (4). It is crucial not to trivialise patient complaints, to listen with interest and to react to the patient with tailored advice (23). For prescribers, it is particularly important to determine the primary reason for patients presenting with sore throat and what their treatment expectations are. In practice, fewer patients want an antibiotic than some physicians believe (4). In a study by van Driel et al., over 80% of patients who visited a doctor for sore throat did so first and foremost to be examined for the cause of their symptoms, to obtain pain relief and/or to gain information on the course of their condition (20). Antibiotics ranked 11th out of 13 reasons in total. Further analysis indicated that many patients who request an antibiotic may, in fact, want an effective medication to relieve their pain, yet mistakenly believe that they can achieve this quickly with an antibiotic. Be vigilant: assess severity As the next step, primary care providers should evaluate the severity of the infection and the risk of complications. This involves physical examination for red-flag symptoms, asking questions about risk factors for complications and symptom duration. Pharmacy staff do not conduct a full consultation; they should, however, be aware of an increased risk for serious infection and, if necessary, refer the patient to the primary care physician for further evaluation, i.e. if symptoms get worse or last longer than 2 weeks. Medical-history taking and physical examination by prescribers can be complemented by point-of-care testing where this is available, to reassure both themselves and the patient that a non-antibiotic treatment strategy is appropriate. A Dutch study reported that patients with respiratory tract symptoms who were carefully examined during a GP consultation were more likely to be satisfied with their visit to the GP, regardless of whether or not they had received antibiotics (13). Counsel on effective self-management At this point of the consultation, after having addressed patients concerns, history-taking and physical examination, the key tasks for primary care providers are to reassure patients that their condition is self-limiting, to recommend symptomatic relief and to advise on next steps. Prescribers should encourage patients at low risk to self-manage their condition without using antibiotics. Depending on the patient expectations identified at the beginning of the consultation, a more detailed discussion about appropriate use of antibiotics may be helpful, also highlighting the advantages of not taking antibiotics, such as avoiding side effects and a reduced likelihood that antibiotics will fail if needed to treat a serious illness in future (23). Another helpful approach is to stress the self-limiting nature of the condition and explain that the patient s own immune system can deal with the infection. Patients will also need and appreciate specific advice on symptomatic treatment options and formulations (Table 1) that meet their individual preferences. Finally, patients benefit from information on the expected course of the illness and on red-flag symptoms that warrant a return visit (4,23). Written information can aid in this process by reinforcing the GP s face-to-face explanation. The value of spending time with the patient and providing information and reassurance is not to be underestimated (23,24). In a survey by Welschen et al., these factors were strongly linked to patient satisfaction (25). In addition, directing patients to effective self-care and providing information on the expected duration of symptoms reduces re-consultation rates (23,26). In a similar manner, pharmacy staff should reassure patients that symptoms typically resolve within one week. They should provide reassurance to patients by offering more detailed advice on symptomatic treatment options in line with the patient s primary concerns (fever, pain, swelling) and preferences. This will include information on suitable formulations (Table 1) and on the correct use of any purchased medication. Patient communication To facilitate a cultural change towards the appropriate use of antibiotics for sore throat management, healthcare providers need to communicate effectively about self-limitedness of disease, appropriate treatment and antibiotic resistance, and work towards creating a partnership with the patient (22). Research has shown that the way healthcare providers communicate with their patients has a strong impact on treatment outcome and patient satisfaction. For example, Thomas et al. report that better doctor patient communication with an increase in consultation time from 6 to 10 minutes and improved courtesy from the doctor resulted in improved sore throat management (8). In another study among patients who visited a physician because of respiratory tract symptoms (24), there was no link between

Sore throat: encourage self-care, reduce antibiotic use 13 Table 1 Tailoring sore throat treatment Formulation Local delivery Relieves pain Antiinflammatory effect Demulcent effect Low dose, reduced side effect risk Note on formulation... Oral NSAIDs No Yes (28,29) Yes No No Slower action than local treatments (30) Other analgesics No Yes (31,32) No No No Slower action than local treatments (30) Local NSAID lozenge Yes Yes (33 36) Yes (34,35) Yes (33,34) Yes (33 36) Faster action than systemic treatments (30) Can relieve pain in 2 min and last up to 4 6 h (35,35) Local NSAID spray/gargle Yes Yes (37) Yes (37) No Yes (37) Faster action than systemic treatments (28) Gargles are often swallowed and the active ingredients do not reach the throat (38) Antiseptic/anaesthetic lozenge Antiseptic/anaesthetic spray/gargle Antiseptic/anaesthetic ear drops Yes Yes (39) No Yes (39) Yes (39) Faster action than systemic treatments (30) Lozenges dissolve slowly to release active ingredients (30) Yes Yes (30,40) No No Yes (30) Faster action than systemic treatments (30) Yes Yes (41) No No Yes (30) Acidic agent preferred for acute early stage disease compared with topical/oral antimicrobial agents (35) Cough syrup Yes No No Yes (30) Yes Provides a cough suppressant (antitussive) effect (39) a prescription for antibiotics and patient satisfaction; however, satisfaction was associated with patients understanding their illness and the physician spending enough time with them, confirming the importance of effective communication and explanation. Many patients lack awareness of when antibiotics are appropriate. A useful strategy on which to focus is the effect treatment has on symptoms, rather than explaining bacterial or viral aspects. Nonetheless, it is important to state that antibiotics will not clear a viral infection, reduce symptoms or help the patient recover more quickly even in most cases of bacterial infection; moreover, antibiotics may do more harm than good by causing side effects (23). Many patients are also not aware of the connection between overuse of antibiotics and antibiotic resistance (18). Healthcare providers need to inform patients that antibiotic resistance can have serious consequences both for the individual patient and for the community, owing to the spread of resistant bacteria to family members, work colleagues and friends (19). In addition to providing patient education about the appropriate use of antibiotics, healthcare providers and patients should work together to agree on a treatment plan around patients individual needs and concerns. The use of non-paternalistic, patient-centred language by both prescribers and pharmacy staff is a key to the process of establishing such a partnership approach. Communicating with empathy reassures patients that their concerns have been taken seriously and supports confidence in self-care. Patients will be more likely to accept the rationale for a symptomatic treatment approach and understand the risks of antibiotic use. To be a participating partner in the management of their sore throat symptoms, patients should be empowered to: Assess their symptoms, Beat their symptoms and Care for themselves. In practice, this means that patients should be encouraged to assess their symptoms to be able to give their primary care provider a good description of their condition and any concerns. In addition, patients should be encouraged to seek the best medicines for their specific symptoms. To help them in this process, primary care providers need to help patients understand that there is a wide range of therapeutic options available that provide symptomatic relief and that pharmacy staff can help in determining the medicines and formulations that best suit their needs and preferences. Finally, patients should be encouraged to take care of themselves. Besides advice on effective symptomatic relief, rest and/or staying home from school or work can possibly be advised.

14 Sore throat: encourage self-care, reduce antibiotic use A successful intervention may then mean that the patient will be able to self-manage sore throat symptoms in future. Local education and support for primary care providers: the 1,2,3 toolkit The campaign towards appropriate use of antibiotics for the management of sore throat will only be effective if the outlined strategies are implemented in line with local needs, with a consistent approach from healthcare providers. There is a strong need for targeted education of primary care providers in line with local management, advice and prescribing practice. Secondly, patients visiting the GP or pharmacy should be informed with written information about non-antibiotic management of sore throat. Finally, commitment from government and/or local health authorities is required to support and promote the benefits of self-management by symptomatic care and the concept of antibiotic stewardship when managing acute throat infections. Nationwide recommendations and media campaigns for appropriate use of antibiotics in URTIs can be used as tools to communicate this issue to patients. At the end of the 1990s, Finland demonstrated that the campaign reduced not only the amount of antibiotics prescribed but also decreased the rate of erythromycin resistance (27). It is also desirable to promote local educational programmes where healthcare providers can share data about prescription and consumption of therapies for URTIs, and find out about the evidence and information strategies that should be adopted. Healthcare providers should use consistent communication with patients to promote patient confidence in the advice they are given. Incongruent messages among healthcare providers would likely result in patients seeking a second opinion from another healthcare provider, which could result in ineffective management of the URTI and frustration. To provide practical support in this complex process, the GRIP team has developed a toolkit (Figure 1) with template materials for healthcare providers and patients that can be adapted to meet local needs. The materials include: A continuing professional development module for primary care teams A pharmacy education tent cart (flip chart-style booklet), which can be used by pharmacists when training pharmacy staff, or serve as a general resource on the management of URTIs for pharmacy teams Various patient-oriented materials (leaflet and poster) providing guidance on URTIs including expected duration of symptoms and information on self-management A patient pressure conversation guide with pictograms to support the text, for prescribers when Figure 1 GRIP Toolkit including template materials for healthcare providers and patients that can be adapted to meet local needs

Sore throat: encourage self-care, reduce antibiotic use 15 explaining to patients the non-prescribing of antibiotics A non-prescription tear-off pad to be used by prescribers to offer patients general information, as well as individualised advice The toolkit materials and further information on GRIP are available on the GRIP website (www. GRIP-initiative.com). Conclusions To address the problem of inappropriate antibiotic use in primary care, many countries are now promoting a self-care approach for the management of self-limiting illnesses (4,23). Sore throat is a prime example as the condition is caused by a virus in the majority of patients, resolves within one week without the need for antibiotics, and effective treatment options are available to provide symptomatic relief. As the first port of call for patients who seek medical attention for sore throat, and other self-limiting URTIs, primary care physicians and pharmacy team members need to take an active approach to direct patients towards self-management strategies. They have an important role in educating patients on the appropriate use of antibiotics; providing reassurance that the condition is not serious, but self-limiting; and advising that symptomatic treatment is the most appropriate course of action. They need to work with patients to create a personal self-management plan in line with patient preferences. For this purpose, patients expectations and concerns should be identified and addressed and serious infection must be ruled out. A structured approach to patient consultations (i) Address patient s concerns; (ii) Be vigilant; assess severity; (iii) Counsel on effective selfmanagement will help healthcare providers to take a consistent approach to the management of sore throat and to put the patient at the centre of the consultation. This approach, complemented by the use of written patient information, will help to drive patient confidence in self-care and, ultimately, augment efforts to reduce antibiotic prescribing in primary care for URTIs. Disclosures Publication of this supplement article was supported as part of an unrestricted educational grant by Reckitt Benckiser Group PLC. Editorial assistance during the development and revision of this manuscript was provided by Mash Health Limited and supported by Reckitt Benckiser Group PLC. Author contributions The authors provided substantial contributions to the development and revision of the manuscript and approved the final version of the manuscript. References 1 Centor RM, Samlowski R. Avoiding sore throat morbidity and mortality: when is it not just a sore throat?. Am Fam Physician 2011; 83(26): 28. 2 Oxford JS, Goossens H, Schedler M, Sefton A, Sessa A, van der Velden A. Factors influencing inappropriate antibiotic prescription in Europe. Educ Prim Care 2013; 24: 291 3. 3 Worrall GJ. Acute sore throat. Can Fam Physician 2007; 53: 1961 2. 4 National Institute for Health and Clinical Excellence (NICE). Clinical Guideline 69. Respiratory tract infections antibiotic prescribing. Prescribing of antibiotics for self-limiting respiratory tract infections and in adults and children in primary care, July 2008. http://www.nice.org.uk/cg069 (accessed 12 September 2013). 5 Francis NA, Butler CC, Hood K, Simpson S, Wood F, Nuttall J. Effect of using an interactive booklet about childhood respiratory tract infections in primary care consultations on reconsulting and antibiotic prescribing: a cluster randomised controlled trial. BMJ 2009; 339: b2885. 6 Centers for Disease Control and Prevention. Adult appropriate antibiotic use summary. http://www. cdc.gov/getsmart/campaign-materials/info-sheets/ adult-approp-summary.pdf (accessed September 2013). 7 Spinks A, Glasziou P, Del Mar CB. Antibiotics for sore throat. Cochrane Database Syst Rev 2006; (4) Art. No.: CD000023. DOI: 10.1002/14651858. CD000023.pub3. 8 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. 9 Aalbers J, O Brien KK, Chan WS et al. Predicting streptococcal pharyngitis in adults in primary care: a systematic review of the diagnostic accuracy of symptoms and signs and validation of the Centor score. BMC Med 2011; 9: 67. 10 Shephard A, Smith G, Aspley S, Schachtel B. Efficacy of Flurbiprofen 8.75 Mg Lozenges for Streptococcal and Non-Streptococcal Sore Throat: Pooled Analysis of Two Randomised, Placebo-Controlled Studies. Berlin, Germany: ECCMID, 2013; P2085. 11 Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH. Diagnosis and management of group A streptococcal pharyngitis: a practice guideline. Infectious Diseases Society of America. Clin Infect Dis 1997; 25: 574 83. 12 Pelucchi C, Grigoryan L, Galeone C et al. Guideline for the management of acute sore throat. Clin Microbiol Infect 2012; 18(Suppl. 1): 1 28. 13 van Duijn HJ, Kuyvenhoven MM, Schellevis FG, Verheij TJ. Illness behaviour and antibiotic prescription in patients with respiratory tract symptoms. Br J Gen Pract 2007; 57: 561 8. 14 Borchardt RA, Rolston KV. Respiratory tract infections: emerging viral pathogens. JAAPA 2012; 25: 19 20. 15 Cals JW, Butler CC, Hopstaken RM, Hood K, Dinant GJ. Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial. BMJ 2009; 338: b1374. 16 Kenealy T, Arroll B. Antibiotics for the common cold and acute purulent rhinitis. Cochrane Database Syst Rev 2013; 6: CD000247. 17 Wilton L, Kollarova M, Heeley E, Shakir S. Relative risk of vaginal candidiasis after use of antibiotics compared with antidepressants in women: postmarketing surveillance data in England. Drug Saf 2003; 26: 589 97. 18 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. 19 Hildreth CJ, Burke AE, Glass RM. JAMA patient page. Inappropriate use of antibiotics. JAMA 2009; 302: 816. 20 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.

16 Sore throat: encourage self-care, reduce antibiotic use 21 van Gageldonk-Lafeber AB, Heijnen ML, Bartelds AI, Peters MF, van der Plas SM, Wilbrink B. A case-control study of acute respiratory tract infection in general practice patients in The Netherlands. Clin Infect Dis 2005; 41: 490 7. 22 van der Velden A, Duerden MG, Bell J et al. Prescriber and patient responsibilities in treatment of acute respiratory tract infections essential for conservation of antibiotics. Antibiotics 2013; 2: 316 27. 23 NPS. NPS News 63: Managing expectations for antibiotics in respiratory tract infections. June 2009. http://www.nps.org.au/ data/assets/pdf_file/0009/ 71478/news_63.pdf (accessed 12 September 2013). 24 Hamm RM, Hicks RJ, Bemben DA. Antibiotics and respiratory infections: are patients more satisfied when expectations are met? J Fam Pract 1996; 43: 56 62. 25 Welschen I, Kuyvenhoven M, Hoes A, Verheij T. Antibiotics for acute respiratory tract symptoms: patients expectations, GPs management and patient satisfaction. Fam Pract 2004; 21: 234 7. 26 Little P, Gould C, Williamson I, Warner G, Gantley M, Kinmonth AL. Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. BMJ 1997; 315: 350 2. 27 Sepp al a H, Klaukka T, Vuopio-Varkila J et al. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. Finnish Study Group for Antimicrobial Resistance. N Engl J Med 1997; 337: 441 6. 28 Burian M, Geisslinger G. COX-dependent mechanisms involved in the antinociceptive action of NSAIDs at central and peripheral sites. Pharmacol Ther 2005; 107: 139 54. 29 Rainsford KD. Ibuprofen: from invention to an OTC therapeutic mainstay. Int J Clin Pract Suppl 2013; 178: 9 20. 30 Oxford JS, Leuwer M. Acute sore throat revisited: clinical and experimental evidence for the efficacy of over-the-counter AMC/DCBA throat lozenges. Int J Clin Pract 2011; 65: 524 30. 31 Graham GG, Scott KF. Mechanism of action of paracetamol. Am J Ther 2005; 12: 46 55. 32 Derry S, Moore RA, McQuay HJ. Single dose oral codeine, as a single agent, for acute postoperative pain in adults. Cochrane Database Syst Rev 2010; (4). Art. No.: CD008099. DOI: 10.1002/146518 58.CD008099.pub2. 33 Blagden M, Christian J, Miller K, Charlesworth A. Multidose flurbiprofen 8.75 mg lozenges in the treatment of sore throat: a randomised, double-blind, placebo-controlled study in UK general practice centres. Int J Clin Pract 2002; 56: 95 100. 34 Watson N, Nimmo WS, Christian J, Charlesworth A, Speight J, Miller K. Relief of sore throat with the anti-inflammatory throat lozenge flurbiprofen 8.75 mg: a randomised, double-blind, placebo-controlled study of efficacy and safety. Int J Clin Pract 2000; 54: 490 6. 35 Benrimoj SI, Langford FH, Christian F, Charlesworth A, Steans A. Efficacy and tolerability of the anti-inflammatory throat lozenges Flurbiprofen 8.75mg in the treatment of sore throat. A randomised, double-blind, placebo-controlled study. Clin Drug Invest 2001; 21: 183 93. 36 Schachtel BP, Aspley S, Sternberg M et al. Onset of demulcent and analgesic activity of flurbiprofen lozenge. Int J Clin Pharm 2012; 34: 143 258. 37 Passali D, Volonte M, Passali GC, Damiani V, Bellussi L, Group MIS. Efficacy and safety of ketoprofen lysine salt mouthwash versus benzydamine hydrochloride mouthwash in acute pharyngeal inflammation: a randomized, single-blind study. Clin Ther 2001; 23: 1508 18. 38 Limb M, Connor A, Pickford M et al. Scintigraphy can be used to compare delivery of sore throat formulations. Int J Clin Pract 2009; 63: 606 12. 39 Wade AG, Morris C, Shephard A, Crawford GM, Goulder MA. A multicentre, randomised, double-blind, single-dose study assessing the efficacy of AMC/DCBA Warm lozenge or AMC/DCBA Cool lozenge in the relief of acute sore throat. BMC Fam Pract 2011; 12: 6. 40 Buchholz V, Leuwer M, Ahrens J, Foadi N, Krampfl K, Haeseler G. Topical antiseptics for the treatment of sore throat block voltage-gated neuronal sodium channels in a local anaesthetic-like manner. Naunyn Schmiedebergs Arch Pharmacol 2009; 380: 161 8. 41 Prasad S, Ewigman B. Use anesthetic drops to relieve acute otitis media pain. J Fam Pract 2008; 57: 370 3. Paper received September 2013, accepted September 2013