Primary care

Reducing antibiotic use for acute bronchitis inprimary care: blinded, randomised controlled trial ofpatient information leafletJohn Macfarlane, William Holmes, Philip Gard, David Thornhill, Rosamund Macfarlane,Richard Hubbard

AbstractObjective To assess whether sharing the uncertaintyof the value of antibiotics for acute bronchitis in theform of written and verbal advice affects thelikelihood of patients taking antibiotics.Design Nested, single blind, randomised controlledtrial.Setting Three suburban general practices inNottinghamParticipants 259 previously well adults presentingwith acute bronchitis.Intervention In group A, 212 patients were judged bytheir general practitioner not to need antibiotics thatday but were given a prescription to use if they gotworse and standard verbal reassurance. Half of them(106) were also given an information leaflet. Allpatients in group B (47) were judged to needantibiotics and were given a prescription andencouraged to use it.Main outcome measures Antibiotic use in the nexttwo weeks. Reconsultation for the same symptoms inthe next month.Results In group A fewer patients who received theinformation leaflet took antibiotics compared withthose who did not receive the leaflet (49 v 63, riskratio 0.76, 95% confidence interval 0.59 to 0.97,P = 0.04). Numbers reconsulting were similar (11 v14). In group B, 44 patients took the antibiotics.Conclusion Most previously well adults with acutebronchitis were judged not to need antibiotics.Reassuring these patients and sharing the uncertaintyabout prescribing in a information leaflet supportedby verbal advice is a safe strategy and reducesantibiotic use.

IntroductionAcute bronchitis is a common condition that results innearly 2 million consultations in England and Waleseach year.1 2 General practitioners prescribe antibioticsin three quarters of such consultations, even thoughthere is little evidence to justify it.2 3 The widespreadbelief among patients with acute bronchitis thatinfection is the problem and antibiotics the solution hasconsiderable influence on prescribing of antibiotics by

general practitioners, even when their clinical judgmentis that antibiotics are not definitely indicated.3–5 This is afactor in the overuse of antibiotics and the increasingprevalence of drug resistance, adverse effects, and cost.6

As a major reason for the use of antibiotics in acutebronchitis seems to be the expectations of patients, weconducted a randomised, controlled, clinical trail todetermine the impact of a patient information leafleton the use of antibiotics in patients with this condition.

MethodsRecruitment and initial assessment of participantsParticipants for the trial were recruited from three gen-eral practices in Nottingham familiar with research inthis topic.3 4 7–9 Between September 1999 and August2000 (excluding a month over Christmas and themillennium period), we recruited consecutive adultspresenting with “acute bronchitis,” defined as a “new,acute lower respiratory tract illness in a previously welladult,” using previously reported definitions (box 1).4 8–11

The study was approved by the Nottingham CityHospital ethics committee, and all participantsprovided written consent.

Each general practitioner managed the patientsaccording to their usual clinical practice and based ontheir clinical judgment divided them into two groups:group A, in which antibiotics were not definitelyindicated that day, and group B, in which antibiotics

Box 1: Definitions for recruitment• Patients aged >16 years who were previously well

and not under supervision or management for anunderlying disease (for example, no pre-existingasthma, chronic obstructive pulmonary disease,heart disease, and diabetes)• Lower respiratory tract illness required all of:

Acute illness present for 21 days or lessCough as the main symptomAt least one other lower respiratory tract symptom(sputum production, dyspnoea, wheeze, chestdiscomfort or pain)No alternative explanation (for example, notsinusitis, pharyngitis, a new presentation ofasthma)

RespiratoryMedicine,Nottingham CityHospital NG5 1PBJohn Macfarlaneconsultant physician

Sherrington ParkMedical Practice,NottinghamNG5 2EJWilliam Holmesprincipal in generalpractice

Arnold HealthCentre, Arnold,NottinghamNG5 7BPPhilip Gardprincipal in generalpractice

Stenhouse MedicalCentre, Arnold,NottinghamNG5 7BPDavid Thornhillprincipal in generalpractice

RespiratoryInfection ResearchGroup, NottinghamCity HospitalRosamundMacfarlaneresearchadministrator

University ofNottingham,Clinical SciencesBuilding,Nottingham CityHospitalRichard Hubbardsenior lecturer inclinical epidemiology

Correspondence to:J Macfarlanejohn.macfarlane@tinyworld.co.uk

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were definitely indicated that day. This decision wasmade without additional guidance or investigations.

Antibiotic prescriptions and randomisationAll patients were given a prescription for an antibiotic,the choice of which was left to the general practitioner,and a sealed envelope containing a two week diary cardwith instructions, pen, and a stamped, addressed returnenvelope. Patients in group B were advised to take theantibiotics.

For all patients in group A the general practitionerprovided verbal information based on a prompt card(box 2). These patients were then randomised by usingpermuted blocks of four to receive or not receive apatient information leaflet about the natural course oflower respiratory tract symptoms and the advantagesand disadvantages of antibiotic use (fig 1). The patientinformation leaflet was in the sealed envelope, blindedfrom the general practitioner by means of a blank leaf-let, together with the diary card and return envelope.

Fig 1 Information leaflet given to patients

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Patients were asked to open and read the contents ofthe envelope after the consultation.

End points and follow upThe primary end point was whether the patient tookthe antibiotics they had been prescribed. Thisinformation was obtained from the symptom diary,which included a space to record daily antibiotic use,and by telephone contact. Patients were contacted bytelephone at around one week and two weeks after theconsultation by research assistants blinded to thegrouping of the patients. Answers to structuredquestions regarding antibiotic use were recorded.

The secondary outcome was whether patients initi-ated a further consultation for the same symptomswithin the next month. Patients were not asked toreturn routinely by the general practitioner. We havepreviously reported that reconsultation is an easilymeasured and consistent end point for acute bronchi-tis and relates to persistent cough and patient dissatis-faction with their progress.8 9 11 12

We carried out a pilot study of 33 consecutivepatients with acute bronchitis to develop consistency ofdata collection by the general practitioners andtelephone follow up by the research assistants.

Statistical analysisOur primary hypothesis was that the proportion ofpatients in group A who would take antibiotics duringthe two week follow up period would be lower in thosewho received the leaflet than in those in the controlgroup. We calculated the risk ratio and 95% confidenceinterval using EpiInfo and used a ÷2 test with Yates’scorrection for the hypothesis test. Using these data wecalculated the number need to treat as the reciprocal ofthe absolute difference in antibiotic uptake betweenthe two groups.

To calculate sample size we set a minimumdifference of 20% in primary outcome between the twointervention arms in group A and a discriminatorypower of 80%. The required number in group A was206.

To look for possible confounding by age, sex,surgery, smoking status, description of cough, durationof cough, and the presence of chest signs we used aseries of bivariate logistic regression models withinStata (version 5). We also examined whether the impactof the leaflet on antibiotic uptake was modified by anyof these variables by fitting a series of multiplicative

interaction terms and comparing the nested modelsusing the likelihood ratio test.

We constructed a Kaplan-Meier plot from the daysbetween consultation and the day antibiotics werestarted and calculated the rate ratio using a Coxregression model within Stata. We tested the propor-tional hazard assumption of this model using the diag-nostic section within Stata (ph1test).

ResultsParticipantsDuring the study, the general practitioners saw 280patients with acute bronchitis, 259 of whom agreed toparticipate in the study (table, fig 2). Of the 212 patientsin group A, 106 received the patient information leaf-let and 106 did not. Among patients who were giventhe leaflet, two were lost to follow up, and 49 (47%)took their antibiotics. For patients in the control groupfive were lost to follow up, and 63 (62%) took their anti-biotics (risk ratio 0.76, 95% confidence interval 0.59 to0.97, P = 0.04; number needed to treat 6.7).

Within the logistic regression model we found noevidence of confounding by age, sex, smoking status,whether patients paid for their prescriptions, descrip-tion of cough or sputum, duration of cough, presenceof chest signs, or general practice. In addition there wasno evidence of significant effect modification by any ofthese variables.

Figure 3 shows the Kaplan-Meier plot. The rateratio for the intervention group compared with thecontrol group was 0.66 (0.46 to 0.96). The reconsulta-tion rates were similar for all patients in group A(table). For the 47 patients in group B (20% of allpatients), all of whom were told by their doctor that

Box 2: Prompt card for verbal informationgiven to patient by general practitioners

“I have examined you and I am happy there is no signof serious disease which definitely needs antibioticstoday. Most chesty illnesses get better on their own,although the cough may take a long time to gocompletely.Antibiotics don’t seem to make much difference tohow quickly most people recover. However, if you feelyou are getting worse after a while, considering takingantibiotics then would be reasonable.So, here is a prescription for an antibiotic for you tokeep at home. You are quite likely not to need it, butuse your judgment whether to get them in duecourse.”

Details of patients with acute bronchitis for whom generalpractitioners thought that antibiotics were not definitely indicatedon day of consultation, according to whether patient receivedwritten information. Figures are numbers of patients unless statedotherwise with denominators shown when data were incomplete

Patientsreceived

leaflet (n=106)

Patients didnot receive

leaflet (n=106)

Median (range) age (years) 45 (16-84) 44 (17-84)

Women 60 64

Smokers:

Current 26 29

Former 28 31

Never 52 46

Sputum:

None 13 19

Clear 22 28

Discoloured 71 59

Median (range) duration of cough (days) 7 (1-21) 7 (1-21)*

Results of chest examination:

Clear 85 84

General signs 19 18

Focal signs 2 4

Taking antibiotics 49/104 63/101

Reconsulted within four weeks 11/104 14/105

Received antibiotics at reconsultation 4 6

Antibiotic prescribed:

Amoxicillin 102 101

Macrolide 8 4

Cephalosporin 0 1

*Not known for one patient.

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antibiotics were definitely indicated, 44 (94%) tooktheir antibiotics.

DiscussionUse of antibiotics by patients with acute bronchitis canbe reduced by providing patients with a simpleinformation leaflet about the use of antibiotics and thenatural course of acute bronchitis and givingreassurance after a consultation and examination thattheir condition is not serious. The use of the patientinformation leaflet reduced the use of antibiotics bynearly a quarter. If these results are extrapolated tonational figures, about 750 000 fewer courses of antibi-otics could be prescribed each year.

This may underestimate the true efficacy of theleaflet as all patients were also reassured verbally bytheir general practitioner that antibiotics were not defi-nitely indicated at the time of the consultation. Theeffect of the leaflet was seen not only at the time of theconsultation but continued over the following twoweeks of observation. By contrast, when the generalpractitioner recommended that antibiotics were defi-nitely indicated, nearly all patients said they did takethem, emphasising the strong influence of doctors’advice on patient compliance.

Prescribing and management strategies for acutebronchitisMost episodes of acute bronchitis resolve on their own,and how to identify those few patients who may benefitfrom antibiotics is not clear.2 13 Prescribing antibioticsfor patients with such self limiting conditions can becounterproductive as it reinforces the belief thatantibiotics are beneficial and encourages futureconsultations.10 13

Providing patients with information and using adelayed prescription have been advanced by theNational Prescribing Centre of the NHS13 and theStanding Medical Advisory Committee of the Depart-ments of Health14 as strategies for reducing antibioticuse in the community. Open studies of managinguncomplicated respiratory infection in adults15 andsore throat and otitis media in children in primarycare16–18 have shown that such strategies result in fewerpeople taking antibiotics. Our study supports thisapproach for adults with acute bronchitis. There arenearly three million consultations for acute bronchitisannually in England and Wales1 and an incidence of upto 70 per 1000 for a practice population of previouslywell adults.8 Reducing antibiotic use by a quarter wouldsubstantially influence antibiotic use in the community,as currently up to three quarters of UK adults whoconsult with acute bronchitis receive antibiotics, andthe figures are even higher in some other Europeancountries.10–13

Further studies could assess whether reassuranceand sharing information and prescribing decisionswould lead to longer term benefits for individuals andthe community in terms of less dependence on antibi-otics.10 13 19 Little et al showed that prescribing antibiot-ics for sore throat and otitis media increased thelikelihood of consultations during future episodes.18 20

For acute bronchitis, we have shown that pressures athome and work and concerns about the seriousness ofthe problem are also associated with the likelihood ofseeking medical attention.21

The strategy of verbal and written informationseems practical and safe. The leaflet was cheap andsimple to produce, and the study was conductedduring normal consultations by general practitioners.Most patients seemed happy with the approach. Fewdeclined to take part in the study or expressed concernabout sharing the prescribing decision with their doc-tor. Rates of reconsultation were no higher in the leaf-let group, and no patients required referral to hospitalfor respiratory illness during follow up. A similar studyon management of acute cough also showed that aninformation leaflet led to fewer future consultations forminor coughs and no delays in consultations for moreserious respiratory symptoms.19 We developed ourleaflet from one we used successfully to reduce recon-sultation rates in a previous study of acute bronchitis(that is, acute lower respiratory tract illness in apreviously well adult).9 Our results support thedevelopment of a more robust study in which no pre-scription would be offered.

Study weaknessesWe did not measure antibiotic use directly, a problemshared with other studies.15–18 We have previouslyreported on a simple technique using a bioassay onurine to check whether patients in the community are

Patients with lower respiratorytract illness who fulfilled thestudy entry criteria (n=280)

Group APatients for whom GP thoughtantibiotics were not definitely

indicated (n=212)

Group BPatients for whom GP thought

antibiotics were definitelyindicated (n=47)

Patients whodeclined toenter study

(n=19)

Patientsexcludedbecause

antibioticsprescribedfor anotherindicationduring trial

(n=2)

Patients entered into study (n=261)

Did notreceive leaflet

(n=106)

Receivedleaflet

(n=106)

Antibioticfollow up data

(n=104)

No antibioticfollow up data

(n=2)

No of patients studied (n=259)

Antibioticfollow up data

(n=46)

No antibioticfollow up data

(n=1)

Antibioticfollow up data

(n=101)

No antibioticfollow up data

(n=5)

Fig 2 Flow of patients through whole study and nested trial ofinformation leaflet

Days after consultation

Prob

abili

ty o

f not

taki

ng a

ntib

iotic

s

0 2 4 6 8 10 12 140

0.2

0.4

0.6

0.8

1.0LeafletNo leaflet

Fig 3 Kaplan-Meier plot of number of days between consultationand day of taking antibiotics for those who did and did not receiveinformation leaflet

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using their prescriptions for antibiotics.22 However, inthe current study we could not devise a method of col-lecting urine from the patients in an informed mannerwithout compromising our objectives. We consideredleaving the filled out prescription with the practicereceptionist and recording the number collected, amethod used in previous studies.15 16 18 However, thisdoes not record antibiotic consumption and is moreinconvenient for both the patient and the practice thanour approach. Arguably, it is also less representative oftypical practice and can lead to patients with acutecough feeling dissatisfied and less empowered.15

Our practices were used to doing research in thistopic, which may make the doctors and patients unrep-resentative. This may have encouraged the generalpractitioners to include more patients in the groupthought not to need antibiotics and hence provide asterner test of the information strategy we used.

How this study helps general practitionersOf course some patients with an acute lower respiratorytract illness do benefit from antibiotics.23 In our studynearly one in five patients were thought to needantibiotics, a figure consistent with that found inprevious studies.10 Further research would identify thosepatients most likely to benefit from antibiotics.2 We haveshown that investigating patients for infection either atfirst presentation or when they reconsult is not a usefulstrategy for better targeting of antibiotic treatment.7 8 Forthe many patients (around 80%) for whom the generalpractitioner thinks that antibiotics are not definitelyindicated, we have shown that sharing uncertainty aboutprescribing openly and honestly with the patient is safeand effective and also reduces antibiotic use.

We thank the general practitioners who participated in thestudy: Gina Bajek, Stephen Bolsher, Anne Cockburn, FionaCoutts, Mike Elliott, Andrew Flewitt, Phil Gard, Brian Hammers-ley, Bill Holmes, Richard Howard, Christine Leiper, Elaine Mad-dock, Fiona McCracken, Suresh Patel, Peter Pavier, Kathy

Scahill, David Thornhill, and P Wilson. We also thank the prac-tice staff, in particular Dawn Hill, Jill Moon, and Karen Gloverwho coordinated the study in each practice, Susan Allen andTracy Broadhurst for performing the patient telephone followup, and Jennie Etches for help with data entry.

Contributors: JM had the original idea for the study and allauthors were involved in the design and planning. RMcoordinated the study logistics throughout and WH, PG, and DTliaised with their colleagues and staff in the three practices andmonitored reconsultations. RM and RH performed the dataanalysis. The paper was written by JM, who acts as guarantor(with RH as guarantor for data analysis), with input from allauthors.

Funding: British Lung Foundation.Competing interests: JM has received consultancy fees from

Pfizer, Abbott, Hoechst Marion Roussel, Trinity, GlaxoWellcome; research funding from Hoechst Marion Roussel,Rhone Poulenc Rorer, and Bayer; lecture fees from Astra-Zeneca, Hoechst Marion Roussel, and Pfizer; and support forattending conferences from Astra, Pfizer, Allen and Hanbury,and 3M. WH has received consultancy fees from GlaxoWellcome, Schering Plough, Boehringer Ingleheim, HoechstMarion Roussel, Astra, 3M, Zeneca, and Rhone Poulenc Rorer;research funding from 3M and Rhone Poulenc Rorer; and sup-port for attending conferences or courses from GlaxoWellcome, Schering Plough, Zeneca, and 3M. RH received sup-port from Bayer for attending two scientific meetings and tosupport a research project.

1 Office of Population Censuses and Surveys. Morbidity statistics from generalpractice: fourth national study 1991-1992. London: HMSO, 1995 (series MB5;3).

2 Arroll B, Kenealy T. Antibiotics for acute bronchitis. BMJ 2001;322:939-40.

3 Macfarlane JT, Lewis SA, Macfarlane RM, Holmes WF, et al. Contempo-rary use of antibiotics in 1089 adults presenting with acute lower respira-tory tract illness in general practice in the UK: implications fordeveloping management guidelines. Respir Med 1997;91:427-34.

4 Macfarlane J, Holmes, Macfarlane R, Britten N. Influence of patients’expectations on antibiotic management of acute lower respiratory tractillness in general practice: questionnaire study. BMJ 1997;315:1211-4.

5 Cockburn J, Pit S. Prescribing behaviour in clinical practice: patients’expectations and doctors’ perceptions of patients’ expectations—aquestionnaire study. BMJ 1997;315:520-3.

6 Audit Commission. A prescription for improvement. Towards more rationalprescribing in general practice. London: HMSO, 1994.

7 Macfarlane J, Prewett J, Rose D, Gard P, Guion A, Cunningham R, et al.Prospective, case-control study of the role of infection in patients whoreconsult after initial antibiotic treatment for lower respiratory tractinfection in primary care. BMJ 1997;315:1206-10.

8 Macfarlane J, Holmes W, Gard P, Macfarlane R, Rose D, Weston V, et al.Prospective study of the incidence, aetiology and outcome of lower respi-ratory tract illness in the community. Thorax 2001;56:109-14.

9 Macfarlane JT, Holmes WF, Macfarlane RM. Reducing reconsulations foracute lower respiratory tract illness with an information leaflet: arandomized controlled study of patients in primary care. Br J Gen Pract1997;47:719-22.

10 Macfarlane J, Holmes WF, Macfarlane R. Do hospital physicians have arole in reducing antibiotic prescribing in the community? Thorax2000;55:153-8.

11 Holmes WF, Macfarlane JT, Macfarlane RM, Hubbard R. Symptoms,signs, and prescribing for acute lower respiratory tract illness. Br J GenPract 2001;51:177-81.

12 Holmes WF, Macfarlane JT, Macfarlane RM, Lewis S. The influence ofantibiotics and other factors on reconsultation for acute lower respiratorytract illness in primary care. Br J Gen Pract 1997;47:815-8.

13 Anon. Antibiotic prescribing: a challenge for primary care. MeReC Bulle-tin 2000;11:1-4.

14 Standing Medical Advisory Committee. Subgroup on AntimicrobialResistance. The path to least resistance. London: Department of Health,1988.

15 Dowell J, Pitkethly M, Bain J, Martin S. A randomised controlled trial ofdelayed prescribing as a strategy for managing uncomplicatedrespiratory tract infection in primary care. Br J Gen Pract 2001;51:200-5.

16 Little P, Williamson I, Warner G, Gould C, Gantley M, Kinmonth AL.Open randomised trial of prescribing strategies in managing sore throat.BMJ 1997;314:722-7.

17 Cates C. An evidence based approach to reducing antibiotic use in chil-dren with acute otitis media: controlled before and after study. BMJ1999;318:715-6.

18 Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey J.Pragmatic randomised controlled trial of two prescribing strategies forchildhood acute otitis media. BMJ 2001;322:336-42.

19 Rutten G, Van Eijk J, Beek M, Van der Velden H. Patient education aboutcough: effect on the consulting behaviour of general practice patients. BrJ Gen Pract 1991;41:289-92.

20 Little P, Gould C, Williamson I, Warner G, Gantley M, Kinmonth AL.Reattendance and complications in a randomised trail of prescribingstrategies for sore throat: the medicalising effect of prescribingantibiotics. BMJ 1997;315:350-2.

What is already known on this topic

Most adults with acute bronchitis who consulttheir general practitioner will receive antibiotics

For most patients antibiotics do not modify thenatural course of the symptoms

The widespread belief among patients thatinfection is the problem and antibiotics thesolution has considerable influence on prescribingby general practitioners, even when they judgethat antibiotics are not definitely indicated

What this study adds

General practitioners judged that about four infive adults with acute bronchitis did not definitelyneed antibiotics on the day they consulted

Antibiotic use was reduced by a quarter in suchpatients, who received verbal and writteninformation and reassurance in addition to aprescription for antibiotics

Sharing with the patient the uncertainty about thedecision to prescribe seems safe and effective

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21 Holmes WF, Macfarlane RM, Macfarlane JT. Why do patients attend theirphysician with lower respiratory tract illness and what do they think oftheir treatment and infection? Am J Resp Crit Care Med 1998;157:A500.

22 Lim WS, Garner S, Finch RG, Macfarlane JT. A novel method for collect-ing and detecting amoxycillin in urine: a tool for testing antibiotic com-pliance in the community. J Antimicrob Chemother 2000;46:835-7.

23 Gonzales R, Sande M. What will it take to stop physicians from prescrib-ing antibiotics in acute bronchitis? Lancet 1995;345:665-6.

(Accepted 20 September 2001)

Commentary: More self reliance in patients and fewer antibiotics:still room for improvementChris van Weel

The study of Macfarlane et al examines the oldproblem of overprescribing of antibiotics, but itapproaches the problem in a highly original way. Towhat extent can their findings be applied to routinecare in general practice.

Firstly the reduction of antibiotic use. Theempirical findings of acute bronchitis in general prac-tice can in all probability be generalised: manyprescriptions for antibiotics are given for episodes ofillness that usually are self limiting. Use of antibioticsunder these circumstances is often spurious and doesnot contribute to patients’ wellbeing. Undue use ofantibiotics may at the same time contribute to thegrowing concerns about resistance. These are soundprofessional arguments for the restriction of prescrib-ing.

But patients influence prescribing, and there is astrong perception among practitioners—whether trueor not—that patients in general value a prescription forantibiotics. Macfarlane et al focused their interventionon the interaction between professional opinion andpatients’ values. The intervention of inviting patientsnot to use the prescribed antibiotics is something mostgeneral practitioners do most days. They offer reassur-ance and encouragement to the patient to await thenatural, benign course of an infection, without remov-ing the possibility of antibiotic treatment. Theadvantages are obvious. The procedure takes away thepower struggle between the patient and the generalpractitioner, who is in charge of prescribing, andfocuses the patient’s decision on the content of theadvice. This paper shows that general practitioners can

distinguish between those in need of antibiotictreatment and those who can do without it and cansubstantially reduce the reliance on antibiotics. But it isimportant to note that about half of the patients stillused the antibiotics that their general practitionerthought they could do without. So there is substantialroom for improvement.

One problem with the authors’ intervention is themessage it gives to the patients, and here the approachused may not be as easy to transfer to routine care. Theexplicit message (“antibiotics are not required”) wasaccompanied by the handing out of a prescription thatimplied a totally different message. This inconsistencymay trigger doubt and lack of confidence in theproposed self reliance, particularly in patients whovalue medical as opposed to self treatment and preferexternal powers to deal with their problems. Thisgroup is particularly at risk of medicalisation, includingrepeated prescriptions of for unnecessary antibioticsfor self limiting infections.

The medical setting is not a harmless placebo andcan have positive and negative effects. Macfarlane et alshould be complimented on their way of bringing thissetting into the test of effectiveness. An obviousalternative way to test their current intervention wouldbe to examine the patient and give advice to come backin a couple of days if the predicted wearing off of theirsymptoms did not occur. Continuity of care is not apanacea, but I would not be surprised if it were able toreduce such unnecessary use of antibiotics by morethan half.

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Department ofGeneral Practice,University MedicalCentre St Radboud,Nijmegen,NetherlandsChris van Weelprofessor

c.vanweel@hsv.kun.nl

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