Intention to treat analysis is related to methodological quality

Analgesic effects of sweet solutions and pacifiers in term neonates

Suckling at the breast is better than sweetsolutions and pacifiers

Editor—A breastfeeding mother spontane-ously comforts her distressed infant byputting him or her to the breast. It is a pitythat Carbajal et al, when assessing theanalgesic effects of orally administeredglucose and sucrose in healthy termneonates, did not include a comparisongroup of infants given breast milk, which isrich in lactose and naturally sweet.1 It wouldalso have been appropriate to compare theanalgesic effect of using a pacifier with thatof suckling at the breast before and immedi-ately after the painful procedure.

Pacifiers and sugar solutions givenunnecessarily to healthy neonates are notproved to be “simple and safe interventions,”as Carbajal et al state. Exclusive breast feeding(for about the first six months) is the WorldHealth Organization’s recommendation.2

Two of the evidence based “ten steps tosuccessful breastfeeding,” developed by theWHO/Unicef Baby Friendly Hospital Initia-tive, are step 6 (“Give newborn infants nofood or drink other than breast milk, unlessmedically indicated”) and step 9 (“Give noartificial teats or pacifiers, also called dum-mies or soothers, to breastfeeding infants”).3

Anything that may interfere with theestablishment of lactation or undermine themother’s confidence in breast feeding is tobe avoided. I hope that this flawed piece ofresearch will not result in either pacifiers orsugar solutions being “widely used for minorprocedures in neonates.”1

Carol Campbell clinical medical officerCommunity Paediatric Department, Foyle HSSTrust, Londonderry BT47 [email protected]

1 Carbajal R, Chauvet X, Couderc S, Olivier-Martin M.Randomised trial of analgesic effects of sucrose, glucose,and pacifiers in term neonates. BMJ 1999;319:1393-7.(27 November.)

2 World Health Organization. The World Health Organiza-tion’s infant-feeding recommendation. WHO Wkly Epide-miol Rec 1995;17:117-220.

3 Vallenas C, Savage F. Evidence for the ten steps to successfulbreastfeeding. Geneva: World Health Organization, 1998.

Use of pacifier may modify responsesmeasured on rating scale

Editor—Carbajal et al conclude that theanalgesic effects of both pacifiers and sweetsolutions are clinically apparent and thatpacifiers are more effective than sweetsolutions alone.1 As a measure of pain theyused a rating scale, douleur aiguë dunouveau-né (DAN), which has beendescribed previously.2

This scale uses facial expression, limbmovements, and vocal expression to give ascore between 0 and 10. Low scores meanno or little pain, and higher scores mean thatthe infant experiences more pain. It isapparent that the results in the two groupstreated with pacifier alone and with pacifiercombined with sweet solution differ fromthe results in the other groups in two ways:the groups whose treatment included apacifier have a lower mean score and show aless varied response to the stimulus ofvenepuncture.

I would suggest that the less variedresponse to the stimulus is due to the pacifieritself. The ability to express a range of facialexpressions will be modified by sucking on apacifier in a way that reduces the possibleresponses on the rating scale. It would beinteresting to see ratings of infants who donot have venepuncture and their ratings onthe rating scale with and without pacifier.S Blomstrand paediatricianDepartment of Paediatrics, Borås Hospital, S-50182 Borås, [email protected]


2 Carbajal R, Paupe A, Hoenn E, Lenclen R, Olivier-MartinM. DAN: une échelle comportementale d’évaluation de ladouleur aiguë du nouveau-né. Arch Pédiatr 1997;4:623-8.

Surely evidence is not needed to justifycuddling babies in pain

Editor—The results of Carbajal et al’s trialwere not surprising.1 The study concludedthat non-nutritive sucking on a pacifier(dummy) was more successful in producinganalgesia in neonates during venepuncturethan the use of glucose or sucrose solutions.

In the accompanying editorial Choonarastates that “parents know that a crying babyneeds comforting and will hold their infantclose. Breastfeeding mothers will give theirinfants the opportunity to breast feed, even ifthey are not hungry.”2 Choonara tells us howthe study confirms that these actions ofmothers are appropriate, but I questionwhether we need a scientific study to supportdeeply engrained human responses that havebeen witnessed to work throughout the ages.

The paper’s authors comment that themechanism by which pacifiers induce analge-sia is unknown. I would offer instinct andconditioning as two possible mechanisms.Most parents know to hold their distressedoffspring, but it is equally true that children

naturally seek proximity to their attachmentfigures when in pain or distress. The pacifiermimics the breast, and psychobiologicalprocesses associated with the mother-childrelationship and reduction in distress are per-haps triggered in the infant; the relationbetween reduction in distress and reductionin perception of pain is well recognised.

A growing body of evidence suggeststhat disruption of the natural, instinctive“knowledge” and interaction betweenmother and child can have detrimentaleffects on emotional development; the effectof postnatal depression is an example.3 Wecan all recognise a basic need for safety andsecurity, and it seems unsurprising that chil-dren need the same to develop emotionally.

Choonara believes that the use ofinterventions including cuddling for paincontrol needs to be evidence based. Why? Ashe acknowledges, parents will not changetheir behaviour in the face of research find-ings. They would be right not to: they knowthat cuddling works. Science does not offerus absolute truths; instead it offers usanswers with a given degree of certainty.This certainty will never be large enough tojustify attempted suppression of the natural,magical responses evoked in a mother byher distressed baby.Mark Morris senior house officer, general psychiatryWotton Lawn, Horton Road, Gloucester GLI [email protected]


2 Choonara I. Why do babies cry? BMJ 1999;319:1381.(27 November.)

3 Cooper PJ, Murray L. Postnatal depression. BMJ 1998;316:1884-6.

Measures of pain must be validated inyoung children

Editor—Using a behavioural pain score(facial expression, movement, and vocalexpression), Carbajal et al concluded thatoral sugar solutions and non-nutritive suck-ing were analgesic in neonates.1 Their studyshows not analgesia but a reduced behav-ioural response to pain in neonates.

There are two main problems: firstly,what is meant by the term analgesia, and,secondly, how can you check the validity of apain scoring system? Analgesia is defined asthe absence of pain on noxious stimulation,and pain is defined as always a subjectiveexperience.2 Subjective self report measuresof pain that are used in adults are impossibleto use in children before they can talk.Therefore proxy responses such as behav-iour (loudness and duration of cry, facialexpression, body posture, mobility, alert-

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Website: bmj.comEmail: [email protected]

1002 BMJ VOLUME 320 8 APRIL 2000 bmj.com

ness), physiology (heart rate, blood pressure,respiratory rate, palmar sweating, oxygena-tion, intracranial pressure), and endocrineresponses (concentrations of cortisol, cat-echolamine, glucose) are used. The difficultyis that these are all non-specific markers andare influenced by factors such as fear,anxiety, and medical problems.

The sole use of behaviour as a measureof pain can be misleading.3 “Sweet flavouredpacifiers can calm a crying baby but shouldnever be regarded as providing majoranalgesia.”3 Likewise measurement of theendocrine response alone is inadequate.4 Anexample is that dummies (pacifiers) reducethe behavioural response to pain (sleep,alertness, crying) but do not reduce theendocrine response (cortisol concentra-tion).5 Colloquially, we do not use the termanalgesia to describe techniques such as dis-traction or rubbing of a sore leg, whichinfluence only one dimension of pain.

The second problem is that scoring sys-tems can be tested for internal validity suchas consistency between different observersand showing that there is an increasedresponse to what is perceived as increas-ingly painful circumstances. Rarely, painscores are validated against other pain scor-ing systems, but we have no gold standardfor comparison.

This is more than semantics. We need tovalidate our clinical scoring systems againstall dimensions of pain, including behaviour,physiology, endocrine response, develop-ment, culture, and environment. Until wehave better measures of pain in childrenbefore they have can talk we should be waryof concluding more than the evidenceshows. If all that sugar and sucking does isreduce the external expression of pain thenwe are treating ourselves, the carers, ratherthan the children.Richard Rogers consultant anaesthetistNuffield Department of Anaesthetics, John RadcliffeHospital, Oxford OX3 [email protected]


2 International Association for the Study of Pain (Subcom-mittee on Taxonomy). Pain terms: a list with definitionsand notes on usage. Pain 1979;6:249-52.

3 Pacifiers, passive behaviour, and pain. Lancet 1992;339:275-6.

4 Wolf AR. Treat the babies not their stress responses. Lancet1993;342:319-20.

5 Gunnar MR, Fisch RO, Malone, S. The effects of apacifying stimulus on behavioral and adrenocorticalresponses to circumcision in the newborn. J Am Acad ChildPsychiatry 1984;23:34-8.

Trial of drug treatment to alleviate painin neonatal intubation is needed

Editor—Carbajal et al address the issue ofneonatal pain relief,1 and in the accompany-ing editorial by Choonara health profes-sionals are encouraged to study the painful-ness of clinical procedures and use measuresto prevent pain.2

Neonatologists agree on the importanceof pain relief for newborn babies undergo-ing invasive procedures, such as placementof a chest drain. Analgesia decreases theincidence of accidental extubation and pro-

vides pain relief for ventilated newbornbabies.3 Yet for the most painful procedure—intubation—neonatologists in the UnitedKingdom have been cautious. American andAustralian neonatal intensivists have beenusing intravenous drugs for some time whenpatients need intubation.

Evidence suggests that intubation donewhen the neonate is awake is associated withhigher spikes in intracranial pressure thanthat done when general anaesthesia is given.4

Even awake neonates who have beenparalysed have shown significant increases inmean arterial blood pressure and intracranialpressure, indicating the effect of pain.

Adequate anaesthesia prevents swings inblood pressure and thus potentially thedevelopment of intracranial haemorrhage.Although one study showed that there wasno hypertensive response in neonates whowere intubated while awake, changes inintracranial pressure were not measured.5

So that we know whether or not tofollow the practice used abroad, a trial ofdrug treatment to prevent pain in neonatalintubation is necessary.Asrar Rashid specialist registrar in paediatricsBirmingham Heartlands Hospital, BirminghamB9 [email protected]


2 Choonara I. Why do babies cry? BMJ 1999;319:1381.(27 November.)

3 Levene MI, Quinn MW. Use of sedatives and muscle relax-ants in newborn babies receiving mechanical ventilation.Arch Dis Child 1992;67:870-3.

4 Friesen RH, Honda AT, Thieme RE. Changes in anteriorfontanel pressure in preterm neonates during trachealintubation. Anesth Analg 1987;66:874-8.

5 Charlton AJ, Greenhough SG. Blood pressure response ofneonates to tracheal intubation. Anaesthesia 1988;43:744-6.

Authors’ reply

Editor—Currently, most minor proceduresin neonates are performed with little or noanalgesia. We found that pacifiers can effec-tively relieve pain and that the analgesiceffect is synergetic with sucrose. To ourknowledge, this latter effect, which has prac-tical implications, had not been reportedbefore our study. Recently, Blass and Wattreported the same effect.1

Campbell wonders why we did notinclude breast milk or suckling at the breastbefore and immediately after painful proce-dures. Our study included six groups, and itwould have been difficult to add more—firstly, because of the masking constraintsimposed by a randomised double blindstudy, and, secondly, because we aimed tocompare the analgesic effects of non-nutritive sucking with those of sugarysolutions. A single study cannot answerseveral questions at once.

Analgesia induced by milk has beenshown in newborn infants.2 This effect wasnot related to lactose and was modestcompared with that of sugar. We do notagree with Campbell when she states thatpacifiers and sugar solutions given for anal-gesic purposes are given unnecessarily. Weadhere to the “ten steps to successful breast-

feeding” and consider that, with regard tostep 6, relief of neonatal pain with pacifiersand sugar solutions is medically indicated.We do not think that occasional use of paci-fiers or small volumes of sterile glucose orsucrose solutions for a painful procedureshould be regarded as equivalent to frequentor routine use.

Blomstrand suggests that the less variedresponse to venepuncture in infants treatedwith a pacifier may be due to these infants’inability to express a range of facialexpressions during the treatment. Thishypothesis can be rejected for at least tworeasons. Firstly, when one evaluates facialexpressions on the rating scale that we usedthe modification of only one of eye squeeze,brow bulge, or nasolabial furrow is enoughto determine the intensity of this item. Eyesqueeze and brow bulge are not incompat-ible with sucking. Secondly, infants who sucka pacifier make several pauses betweensucking bursts, which gives them the oppor-tunity to express grimacing.

Morris asks if evidence is needed to jus-tify cuddling a baby in pain. Obviously not.However, studies that determine the efficacyof behavioural interventions in preventingpain in neonates are welcome for, asChoonara states,3 they can encourage healthprofessionals to modify their behaviour.Morris’s hypothesis offering instinct andconditioning to explain the mechanism bywhich pacifiers induce analgesia is interest-ing. Blass and Watt have suggested that anti-nociception and pain blockades induced byorogustatory and orotactile mechanisms arelikely to be occurring at the level of thedorsal horn of the spinal cord.1

Rogers’s concern about the differencebetween analgesia and reduced behaviouralresponse to pain is theoretically valid. As hestates, pain has been defined as a subjectiveexperience. This definition has led to manyadvances, but it challenges our understand-ing of pain because it does not apply toliving organisms that are incapable of selfreport. This includes neonates and olderinfants and many adult patients.4

The biological and behavioural reactionsto pain are evident in term and pretermneonates. The fact that neonates’ expressionof unpleasantness does not fit within the strictdefinition of pain contributes to the failure torecognise and aggressively treat pain inchildren.4 Increasing evidence supports thespecificity of facial expressions as a manifesta-tion of pain in neonates. As we stated in ourpaper, we assumed that the more pro-nounced the facial expressions, limb move-ments, and vocal expressions the greater thepain in the neonates.

Rashid makes an important point.Endotracheal intubation is a powerfulnoxious stimulus with potential adverseeffects. Although premedication is manda-tory for endotracheal intubation in adults,most neonatal units do not sedate neonatesbefore intubating them. Recently, Bhutada etal showed that the heart rate and bloodpressure of neonates who are premedicatedwith thiopental before intubation remain

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1003BMJ VOLUME 320 8 APRIL 2000 bmj.com

nearer to baseline values than do those ofsimilar infants not given premedication.5

Ricardo Carbajal [email protected]

Sophie Couderc paediatricianMarie Olivier-Martin paediatricianPoissy Hospital, 78300 Poissy, France

1 Blass EM, Watt LB. Suckling- and sucrose-induced analge-sia in human newborns. Pain 1999;83:611-23.

2 Blass EM. Milk-induced hypoalgesia in human newborns.Pediatrics 1997;99:825-9.

3 Choonara I. Why do babies cry? BMJ 1999;319:1381.4 Anand KJS, Craig KD. New perspectives on the definition

of pain. Pain 1996;67:3-6.5 Bhutada A, Sahni R, Rastogi S, Wung JT. Randomised con-

trolled trial of thiopental for intubation in neonates. ArchDis Child Fetal Neonat Ed 2000;82:F34-7.

Diagnose and be damned

Corroboration is important whenchildren’s illnesses are diagnosed

Editor—Marcovitch’s arguments abouttreatment of the chronic fatigue syndrome(myalgic encephalomyelitis) in children areillogical.1 He writes of the “hatchet job”performed by Panorama in the programme of8 November and refers to the WashingtonPost’s policy that news requires corroboration.

One of the responses to his article, byWessely [published here, p 1005], states,“contrary to the message of the programme,the management of chronic fatigue syn-drome in children is not contentious.”2 Inreferring to a case reported by PanoramaMarcovitch states that “parents’ views andthose of the local medical team were in con-flict.” Yet the programme made clear that thedispute was between the parents supportedby their own medical advisers and the localmedical team, so perhaps there is greaterdisagreement than has been asserted.

Marcovitch discussed at length Mun-chausen’s syndrome by proxy; Panoramalabelled one of the cases of myalgicencephalitis as being a case of thissyndrome. No one likes receiving emotional,intemperate outbursts, even from peoplewho think they have been wrongly accused.But what is sauce for the goose is surelysauce for the gander. Even doctors some-times make mistakes, yet Marcovitch disre-gards the possibility that parents, knowingthemselves innocent, may feel themselves tohave been receiving exactly the same type ofvituperative attack that he objects to whendoctors are on the receiving end. Such alle-gations turn on fact rather than clinicalopinion so should be subject to Marcovitch’sown test of corroboration.

Innocent people are made angry byaccusations that, if made without justificationin any other context, could end in High Courtactions for defamation. They often reactvigorously to them, to give paramountimportance to the interests of their childrenand to preserve the integrity of their families.Clinical opinion may be highly speculative innature. Yet alone of professionals, somedoctors seem to regard their opinions asparamount, even when they fly in the face ofthe facts. Lawyers may form professionalopinions about cases but expect to see them

challenged during legal proceedings. Journal-ists, as Marcovitch himself has suggested,should seek corroboration of their views.

Much heat could be taken out of thesituation if some doctors approached thecare of children with myalgic encephalomy-elitis with greater humility and understand-ing. They should attempt to build the type ofpartnership with parents that is clearly bestpractice and in line with the intentions oflegislation on child care.Derek Pheby directorUnit of Applied Epidemiology, University of theWest of England, Bristol BS16 [email protected]

1 Marcovitch H. Diagnose and be damned. BMJ 1999;319:1376-7. (20 November.)

2 Wessely S. Confrontational TV programme harmschildren [electronic response to Marcovitch H. Diagnoseand be damned]. bmj.com 1999;319 (www.bmj.com/cgi/eletters/319/7221/1376#EL1).

Doctors must remember their rights andobligations to infants and children

Editor—Marcovitch’s article on doctors whohave exposed cases of child abuse is unfair.1

The NHS inquiry into some of the work car-ried out by the department headed by Profes-sor Southall was set up to investigateconcerns with research that we had raisedthrough our member of parliament. To dateno one has been able to refute our allegationsor alleviate our concerns. All our evidence iswritten by the researchers themselves, and wehave never accused any clinician of anythingwe could not substantiate.

The complaint about continuous nega-tive pressure ventilation has never been acampaign directed at Southall or childprotection issues. We have attacked a systemthat allows maverick clinicians to conductresearch in an ungoverned manner and theculture of subterfuge that surrounds thegaining of consent and the patient infor-mation given. We have attacked the handlingof complaints and the attitudes of the trusts,which close ranks.

Doctors should be accountable for theiractions and should be able to justify theirdecisions to their patients. Patients are oftenforced to look to the media to expose theirplight because of the lack of cooperationand misleading information from the trusts.

The Guardian was probably the onlynewspaper to write an article based on theBMA’s and Southall’s press release about acampaign to obstruct his child protectionwork2—the other newspapers realised itsinaccuracies. The Guardian quickly made apublic apology after publishing the article,and the BMA, which also published it,2 isconsidering its position after we suggestedthat Southall’s statement in the press releasecould be libellous.

If Southall had made it clear to Channel4 that he could not discuss the use ofcontinuous negative pressure ventilationbefore the broadcast, why did he thenproceed to answer questions around theissue? He was not obliged to and could haverefused. Indeed, his own hospital was nothappy that he should be involved with anymedia that pre-empted the various inquiries

about research in general and morespecifically his own work.

Marcovitch ends by saying that it is timethe profession hit back. Surely now is thetime for the medical profession and thepublic to work together. Scandals haveevolved because of self regulation and dam-age limitation. This outdated “them and us”attitude has no place in a modern system ofpublic involvement and working in partner-ship. Openness, transparency, and account-ability are the only way forward.Carl Henshall parent/carerDeborah Henshall parent/carer6 Melville Court, Clayton, Newcastle-under-Lyme,Staffordshire ST5 [email protected]


2 BMA. Leading paediatrician hits back at orchestratedcampaign to obstruct child protection work. (Press release1999 Oct 11.) (www.bma.org.uk)

Inquiry should be held into doctorsinvolved in child abuse investigations

Editor—Since the publication of Marco-vitch’s article on doctors who have exposedchild abuse1 and my initial electronicresponses to it (published here, in thefollowing cluster)2 there have been severaldevelopments. Professor Southall and DrSamuels (one of his colleagues) weresuspended without prejudice during investi-gations into their child protection work.3

The expert opinion given by Professor SirRoy Meadow in a murder trial was criticisedby colleagues,4 5 and concerns are to beincorporated into an inquiry into Mun-chausen’s syndrome by proxy by the RoyalCollege of Paediatrics and Child Health(L Tyler, secretary of the college, personalcommunication). The BMA’s press release6

was withdrawn. With inquiries under wayMarcovitch might have been wiser to waitrather than to offer hostages to fortune.

Marcovitch claims that doctors who workwith cases of child abuse are being hounded.But most doctors work unobtrusively, andwithout generating complaints, to protectchildren from abuse within the frameworklaid down by parliament after the “Clevelandscandal,” when child abuse was reported inCleveland. He should ask why a very smallproportion of doctors—paediatricians for themost part—have exposed themselves tosustained complaints. The answer is that theywould not accept after the Cleveland scandalthat child protection was a multiagency taskand that doctors must not use untested diag-noses before they had been accepted by theprofession.7 The diagnosis that has led to somuch reaction—Munchausen’s syndrome byproxy—may at last be given proper scientificreview.

When Marcovitch says: “Southall . . . hasreceived threats of violence, and . . . his chari-ty’s equipment has been destroyed. There is,however, no evidence to link this darker sideof campaigning to Morgan or the public facesof the movement. . . .” I have to speculate thatthe second sentence was inserted on legaladvice, because what follows (“Surely Chan-nel 4 News, the Sunday Times, the Independent,and others have been barking up the wrong

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tree. The real story is what drives Morgan andothers like him, how the ‘loose network’ isfunded, the backgrounds of its supporters,and whether its campaign has destroyedsome children’s protection”) suggests thatthere is after all a sinister side.

Marcovitch’s suggestion is a two edgedsword; he and the colleagues he defendsmust submit to an investigation as well. Iwould welcome an inquiry by the healthselect committee into the part played bypaediatricians and child and adolescent psy-chiatrists in child abuse investigations in thedecade after the Cleveland scandal. Theinquiry should also look at the quality of evi-dence given by medical experts behind theclosed doors of family courts in secretproceedings under the Children Act 1989.Brian Morgan freelance journalist4 Rawden Place, Riverside, Cardiff CF11 [email protected]


2 Morgan B. Damned diagnosis [electronic response to Mar-covitch H. Diagnose and be damned]. bmj.com 1999;319(www.bmj.com/cgi/eletters/319/7221/1376#EL16).

3 Laurance J. Doctors in child abuse detection suspended.Independent 1999 Dec 10:2.

4 Edwards J. Murder case “cot-deaths” [electronic responseto Green MA and Limerick S. Time to put “cot death” tobed?]. bmj.com 1999;319 (www.bmj.com/cgi/eletters/319/7211/697#EL8).

5 Watkins SJ. Conviction by mathematical error? BMJ2000;320:2-3. (1 January.)

6 BMA. Leading paediatrician hits back at orchestratedcampaign to obstruct child protection work. (Press release1999 Oct 11.) (www.bma.org.uk)

7 Butler-Sloss E. Report of the inquiry into child abuse in Cleve-land 1987. London: HMSO, 1988.

Management of CFS in children is notcontentious

Editor—I congratulate Marcovitch on hisexposition of the methods used by someactivists to hound those paediatricians whoare prepared to consider that parents do notalways act in the best interests of theirchildren.1 He draws attention to an edition ofPanorama on the equally contentious subjectof the chronic fatigue syndrome in children.This was a particularly biased and perniciousaccount of an area where balance and reasonare needed, not polemic and distortion.

Contrary to the message of the pro-gramme, the management of the chronicfatigue syndrome in children is not conten-tious. Programmes of rehabilitation rathersimilar to those now shown to be effective inadults—including some form of support,encouragement, behavioural management,and activation—are now the mainstay oftreatment in virtually all centres helpingchildren with the syndrome and theirfamilies. Indeed, it is hard to find dissentingvoices in the professional literature.

Such programmes, including the onerun at King’s College Hospital, necessarilyinvolve collaboration, not confrontation,with both the child and the family.Colleagues and I will shortly be presentingan uncontrolled case series, adding to theliterature showing both the effectiveness andthe acceptability of such approaches. Wehave just started a randomised controlledtrial as part of the normal process ofshowing efficacy in the most scientificfashion.

Any parent who watched the one sidedPanorama programme might be forgiven forthinking that management of the chronicfatigue syndrome in children involvescoercion and the courts and might bediscouraged from seeking help. Of coursecases of parents harming their children—even, occasionally, with good intentions—doexist. Some appear nowadays under theguise of the chronic fatigue syndrome orbizarre allergic disorders,2 and when adoctor believes that this is happening he orshe has statutory duties to fulfil. But suchcases are fortunately extremely rare—wehave not yet encountered such a problem atKing’s—and tell us little about the generalmanagement of the syndrome.Simon Wessely professor of liaison andepidemiological psychiatryKing’s College Hospital, London SE5 [email protected]


2 Taylor D. Outlandish factitious illness. In: David T, ed.Recent advances in paediatrics. Edinburgh: Churchill Living-stone, 1992:63-76.

“Correcting” bmj.com

What happened to the false allegation inbmj.com?

Editor—Several months ago I received anemail from a reader puzzled by a referencethat I had made in an earlier rapid response1

to Marcovitch’s article on doctors who haveexposed child abuse2 [a shortened version ofthat earlier response is published here as thethird letter in the previous cluster, p 1004]. Ihad written that Marcovitch had made a falseallegation of perjury, but the reader was puz-zled because there was no such falseallegation when he came to read theresponse.

Soon after I wrote my response a “rapidcorrection” was made and a retraction of theallegation posted. The reader was not toknow this, for soon after that, and before heread the response, the allegation was deletedfrom the text in bmj.com and the correctionwas also deleted. The correction appeared inbmj.com on the same day that Marcovitch’sarticle was published in the paper journal.Any readers who see only bmj.com would bepuzzled because both Marcovitch’s allega-tion and bmj.com’s correction have beendeleted from bmj.com.

The allegation and the correction appearin the printed BMJ, which must be assumed tobe the definitive text. The trend now istowards electronic versions of biomedicaljournals having different content from theprinted ones, by design, and there beingonline journals with no printed version. Isthere no one who shares my concern thatinternet publications should have the samepermanent authenticity as printed ones?

If publishers may remove text, or evenadd text, what evidentiary value do suchdocuments have as source materials?Brian Morgan freelance journalist4 Rawden Place, Riverside, Cardiff CF11 [email protected]

1 Morgan B. Damned diagnosis [electronic response to Mar-covitch H. Diagnose and be damned]. bmj.com 1999;319(www.bmj.com/cgi/eletters/319/7221/1376#EL16).


Editor’s reply

Morgan raises an important question. It isclearly impossible to correct errors in thepaper journal after publication by correct-ing every copy. It is, however, possible to cor-rect bmj.com by deleting the error orcorrecting it. But should we do that?

We have decided not to in general.Instead, we will correct errors as we usuallydo by publishing a correction. That correc-tion is then linked to the piece it iscorrecting, so that anybody reading it will beaware that there is a correction. Theelectronic medium does thus have anadvantage over the paper medium.

We have adopted this policy to leave atrail of errors and corrections. They may wellprove to be important at some future time.There is something unnerving—andtotalitarian—about “rewriting” history.

An exception to our policy is when alawyer tells us to remove something, which iswhat happened in the case that Morgan iswriting about. Perhaps lawyers and the lawwill eventually take a different view.Richard Smith Editor, BMJ

How much to do at theaccident scene?

Paramedic agrees with most of commentsabout prehospital care

Editor—I agree with most of Cooke’s com-ments about prehospital care by paramedicsin the United Kingdom1 but would like toraise a few points. As a paramedic inLondon, I realise that my remarks may nothave national generalisability, but theiressence should travel across regionalboundaries.

Cooke is correct in his assertion that“Changes are needed if the paramedic is tobe an independent practitioner.” Paramedicsare the product of doctors; we are what theymade us. The idea of having extended roleambulance staff began during the 1970s and’80s. Unfortunately, the original aspirationsof our worthy fathers were overtaken bypolitical posturing.

The original concept was for a smallcadre of highly trained paramedics whowould be targeted at the small percentage of999 calls where the patient would benefitfrom extended skills before reaching hospital.The emphasis was initially on calls forpatients with cardiac problems; later this wasextended to patients with trauma. When theambulance dispute in 1989 was eventuallyconcluded a promise was made that therewould be a paramedic in each vehicle. Thiswent against the original concept of sendinga paramedic to every call made about a lifethreatening condition—which would haverequired accurate and effective assessmentand deployment.2

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Cooke is correct that paramedics needthe underpinning knowledge to make appro-priate decisions about patients’ treatment.Degree programmes will help provide thisknowledge, along with experiential learning.The proposed development of practitionersin emergency care will certainly address thisissue.3 Education alone, however, will not altersome of the problems currently encounteredin the prehospital phase:

(1) Paramedics need to question whatmore can reasonably be done for theirpatient after securing the airway and check-ing breathing at the scene. Problems withcirculation should be dealt with on the wayto hospital.4

(2) The choice of hospital needs to beaddressed. Preventable deaths may beavoided by transporting the patient to themost appropriate multidisciplinary hospital,not the nearest hospital.5

(3) The fact that little direct communi-cation occurs between the receiving hospitaland the ambulance crew needs to be consid-ered.

Research into prehospital care is neededand should include input from paramedics;they could be part of the research team. Theold maxims of “stay and play” and “load andgo” could perhaps be replaced with “playwhile running” to the most appropriate hos-pital. That way we might be able to make areal, quantifiable difference.John Warwick paramedic/work based trainerLondon Ambulance Service NHS Trust, LondonSE1 [email protected]

1 Cooke MW. How much to do at the accident scene? BMJ1999;319:1150. (30 October.)

2 Cocks RA, Glucksman E. What does London need from itsambulance service? BMJ 1993;306:1428-9.

3 Joint Royal Colleges and Ambulance Liaison Committee-Ambulance Service Association. The future role andeducation of paramedic ambulance service personnel. London:JCALC, 2000.

4 Deakin CD, Hicks IR. AB or ABC: pre-hospital fluid man-agement in major trauma. J Accid Emerg Med 1994;11:154-7.

5 Royal College of Surgeons of England. The management ofpatients with major injuries. London: RCS, 1988.

Anaesthetists are best people to provideprehospital airway management

Editor—Although I agree with Cooke’sgeneral conclusions that airway and breath-ing problems must be treated at the roadsideand circulation ones in hospital, I disagreewith his statement that the airway can beeasily secured at the scene.1

Two studies examining prehospitaldeaths from trauma in the United Kingdomhave shown significant morbidity andmortality from airway obstruction. Hussainand Redmond concluded that up to 85% ofpatients who die with survivable injuriesbefore reaching hospital may do so becauseof airway obstruction.2 In another studyairway obstruction was thought to have con-tributed to death from major trauma in 28%of patients treated by ambulance crew.3

These figures do not support the assump-tion that the airway can easily be secured atthe scene.

The airway is often compromisedbecause of limited skilled help; poor

lighting; a difficult patient position; blood,vomit, and debris in the upper airway; andpoor views at laryngoscopy due to stabilisa-tion of the cervical spine; in addition, thepatient must be managed in a movingambulance. Prehospital airway managementis therefore difficult, even for anaesthetistswith extensive experience in airway manage-ment. Paramedics in the United Kingdomwho start in this environment havingperformed just 20 intubations do not havesufficient training to manage many of themore difficult cases. Furthermore, becauseparamedics are not trained to use neuro-muscular blocking drugs, the only patientswith trauma who are sufficiently obtundedto tolerate endotracheal intubation by themhave invariably got non-survivable injuries(G Davies, personal communication).

Having completed training in endotra-cheal intubation, an average paramedic willintubate only about eight patients a year, andnot all ambulance services undertake formalrefresher training in airway management. Dif-ficult clinical scenarios and limited trainingmay explain why only 63% of attempts atintubation by paramedics are successful.3

Paramedics do not have the necessaryskills to deal with the airway in patients withmajor trauma. Prehospital airway manage-ment must be undertaken by those withmuch greater experience than 20 intubations.Graduate courses will not improve airwaymanagement; what is required is much morepractical training in airway skills. Currentlythe only group able to provide advanced pre-hospital airway management are anaesthet-ists, who have practical experience and canuse neuromuscular blocking drugs andinduction agents. The United Kingdom is theonly country in Europe that does notroutinely employ this standard of prehospitalcare; until it changes its practice, inadequateairway management will continue to contrib-ute to the unacceptable prehospital morbid-ity and mortality of patients with trauma.Charles D Deakin consultant anaesthetistShackleton Department of Anaesthetics,Southampton General Hospital, SouthamptonSO16 [email protected]


2 Hussain LM, Redmond AD. Are prehospital deaths fromaccidental injury preventable? BMJ 1994;308:1077-80.

3 Nicholl J, Hughes S, Dixon S, Turner J, Yates D. The costsand benefits of paramedic skills in pre-hospital traumacare. Health Technol Assess 1998;2.

Prehospital interventions prolongprehospital time

Editor—The question of how much pre-hospital care to give to patients (“scoop andrun” versus “stay and play”)1 is very relevantin Denmark, where the ministry of health isconsidering extending the ambulance tech-nicians’ curriculum. We have carried out aprospective study (unpublished) of therelation between prehospital interventionsand time at the scene.

The study was of all 5571 patients withacute conditions transported to hospital byambulances from two ambulance stations inthe county of Roskilde in 1998. No selection

of patients took place. The ambulancescover a mixed urban/rural area with roughly150 000 inhabitants. Prehospital interven-tions took place for a wide variety of indica-tions: 2479 of the patients received oxygenat the scene or in the ambulance, and ambu-lance technicians carried out electrocardio-graphy on 1131 patients. The median timeat the scene was 8.0 minutes, and the mediantransport time to hospital was 12.0 minutes.

Despite the variety of indications forprehospital interventions the technicianshad relatively little experience. In 1998 eachtechnician was present, on average, on 7.9occasions when drugs were given for angina,on 4.0 occasions when drugs were given forasthma, at 3.4 cardiopulmonary resuscita-tions, and at 3.0 defibrillations.

For most prehospital interventions thereis little evidence of a positive effect onoutcome,2 while shorter total prehospitaltime may be an important factor in survivalfor patients with trauma.3 We found that useof each kind of prehospital interventionimplied a prolonged time at the scene andthat there was a direct correlation betweenthe number of basic prehospital interven-tions used and the time at the scene.

When the scope of the ambulance tech-nicians’ curriculum is considered, severalfactors should be borne in mind: the limitedexperience of the technicians, the lack ofevidence of a positive effect on outcome ofmost prehospital interventions, and the pro-longation of the time at the scene. Newinterventions will usually be technicallydemanding, their use will rarely be indi-cated, and the skills requiring the most tech-nical knowledge deteriorate the fastest.4

Hans Okkels Birk health [email protected]

Lars Onsberg Henriksen chief medical officerDepartment of Hospitals, County of Roskilde,Postboks 170, 4000 Roskilde, Denmark


2 Callaham M. Quantifying the scanty science of prehospitalemergency care. Ann Emerg Med 1997;30:785-90.

3 Feero S, Hedges JR, Simmons E, Irwin L. Doesout-of-hospital time affect trauma survival? Am J EmergMed 1995;13:133-5.

4 Skelton MB, McSwain NE. A study of cognitive and techni-cal skill deterioration among trained paramedics. JACEP1977;6:436-8.

Predicted impact ofintravenous thrombolysis

Patients who died or recovered fullyshould have been included in analysis

Editor—Jørgensen et al report a simulationof the impact of intravenous thrombolysis onprognosis for a general population of strokepatients.1 Although we do not argue withtheir conclusion that comparatively fewpatients with acute ischaemic stroke will ben-efit from thrombolytic treatment, we believethat their analysis of the data is flawed.

During their retrospective analysisJørgensen et al identified patients whofulfilled the criteria for thrombolysis andthen excluded patients who died or had a

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full recovery. They subsequently excludedthe same groups of patients from the idealscenario in which all patients were admittedwithin the time window for thrombolysis.Had thrombolysis actually been given, theoutcomes for these patients would havebeen unknown at the time of administration.These patients should therefore have beenincluded in the analysis.Joris Berwaerts lecturer in clinical pharmacologyDepartment of Medicine and Therapeutics,University of Aberdeen, Aberdeen AB25 2ZD

Andrew McDonald Johnston cardiovascularresearch fellowAcute Stroke Unit, Aberdeen Royal Infirmary,Aberdeen AB25 [email protected]

Mary-Joan Macleod lecturer in clinical pharmacologyDepartment of Medicine and Therapeutics,University of Aberdeen, Aberdeen AB25 2ZD

1 Jørgensen HS, Nakayama H, Kammersgaard LP, RaaschouHO, Olsen TS. Predicted impact of intravenous throm-bolysis on prognosis of general population of strokepatients: simulation model. BMJ 1999;319:288-9. (31 July.)

Another trial is needed

Editor—The paper by Jørgensen et alprovides a small counterbalance to theenormous propaganda behind an expen-sive, minimally tested, and potentially harm-ful intervention.1 The real ratio of benefit torisk of thrombolytics for stroke may even befar worse than Jørgensen et al calculate, forthe following reasons.

Firstly, even fewer stroke patients in com-munity practice would qualify for treatmentwith alteplase if a strict three hour cut-offpoint for completion of all diagnosticactivities and initiation of the drug were used.

Secondly, inclusion of even a few ofthose patients with seizure, tumour, infec-tion, etc, whose condition mimics stroke andwho constitute perhaps 15-25% of patientsdiagnosed as having “stroke” in communitypractice but were rare in the expert basedNational Institute of Neurological Disordersand Stroke (NINDS) trial,2 could easily over-whelm any benefits of alteplase, since suchpatients cannot possibly benefit from treat-ment but can certainly be harmed.

Thirdly, treatment of even a few patientswith subtle haemorrhage, undetectedbecause the computed tomography scan wasnot read by a neuroradiologist, would havethe same effect—and there is good evidencethat very few general radiologists, neurolo-gists, or emergency physicians are able toidentify most or all such haemorrhages.

Fourthly, treatment outside the special-ised environments used in NINDS, and with-out the experts participating in such studies,could lead to far more harm when a drug thatproduces such a high rate of intracranialhaemorrhage under ideal conditions is used.

Fifthly, of seven trials of lytics in stroke todate, only the fairly small NINDS trial hashad positive results—the results of the sixthat have been either neutral or negative(including several with dramaticallyincreased mortality in patients treated withthrombolytics) are typically ignored.

“Another trial is needed” is a generoussummary of the available evidence. Given the

extremely limited evidence of efficacy, themarginal nature of that efficacy (under thebest of circumstances), and the stronglikelihood that such efficacy will not translateinto effectiveness in community practice—aswell as the real potential for harm—approvalof this drug in the United Kingdom, for thetreatment of stroke should be withheld unlessand until far more definitive evidence (foreffectiveness as well as for efficacy) isforthcoming.Jerome R Hoffman professor of medicineUCLA School of Medicine, Los Angeles, CA 90077,[email protected]

1 Jørgensen HS, Nakayama H, Kammersgaard LP, RaaschouHO, Olsen TS. Predicted impact of intravenous throm-bolysis on prognosis of general population of strokepatients: simulation model. BMJ 1999;319:288-9. (31 July.)

2 National Institute of Neurological Disorders and Strokert-PA Stroke Study Group. Tissue plasminogen activatorfor acute ischemic stroke. N Engl Med J 1995;333:1581-7.

Author’s reply

Editor—Our simulation model of intra-venous thrombolysis (using alteplase) inpatients with acute stroke model had twopurposes: firstly, to estimate the target popu-lation for intravenous thrombolysis in anunselected population of patients with acutestroke; and, secondly, to estimate thenumber of patients who would actually ben-efit from this treatment—provided that theresults of the only trial with positive reults sofar, the National Institute of NeurologicalDisorders and Stroke (NINDS) trial,1 can bereproduced.

In the study we included the 1197patients from the Copenhagen stroke study, acommunity based study in which all patientswith acute stroke from a well definedcatchment area of Copenhagen had all theiracute treatment and rehabilitation in onelarge stroke unit regardless of their age, theseverity of the stroke, and their comorbidityprior to stroke. In the first part of our analysiswe estimated the target population foralteplase treatment using the inclusion crite-ria from the NINDS trial. We includedpatients who eventually died or who recov-ered fully. A disappointing rate of only 4% ofthe patients fulfilled the inclusion criteria.

To estimate the number of patients whowould have benefited from intravenousthrombolysis we excluded the patients whoeither recovered fully and had no functionaldisability after completed rehabilitation orwho died during hospital stay. Berwaerts et alargue that these patients should have beenincluded as the outcomes for them wouldhave been unknown at the time of drugadministration. We believe, however, that itwas justified to exclude them from the analy-sis of the number of patients who would actu-ally benefit from alteplase treatment. None ofthese patients would have benefited fromtreatment because they either had a completerecovery without thrombolysis or they died.As the NINDS trial shows, alteplase treatmenthas no effect on overall mortality.

The results of our study in combinationwith the arguments offered by Hoffmanshould raise serious questions about the

approval of intravenous thrombolysis inpatients with acute stroke. The possible, butnot proved, marginal benefit of intravenousthrombolysis in a very small number ofpatients (1 out of 160 patients in our simula-tion model) should be considered incontrast to the marked benefit of treatmentand rehabilitation of unselected patients inspecialised stroke units,2–5 regardless of theirage, sex, severity of stroke, and comorbidity.Economic resources are limited and shouldbe used where they benefit most patients inthe most effective way—in this case byproviding early, intensive rehabilitation to allpatients in dedicated stroke units.Henrik Stig Jørgensen consultantDepartment of Neurology, Bispebjerg Hospital,Bispebjerg bakke 23, DK-2400 Copenhagen, NV,Denmark

1 National Institute of Neurological Disorders and Strokert-PA Stroke Study Group. Tissue plasminogen activatorfor acute ischemic stroke. N Engl Med J 1995;333:1581-7.

2 The Stroke Unit Trialists’ Collaboration. Collaborative sys-tematic review of the randomised trials of organised in-patient (stroke unit) care after stroke. BMJ1997;315:1151-9.

3 Jørgensen HS, Nakayama H, Raaschou HO, Larsen K,Hübbe P, Olsen TS. The effect of a stroke unit: reducesmortality, discharge to nursing home, length of hospitalstay and cost. A community-based study. Stroke 1995;26:1178-82.

4 Jørgensen HS, Kammersgaard LP, Nakayama H, RaaschouHO, Larsen K, Hübbe P, et al. Treatment and rehabilitationon a stroke unit improves 5-year survival. A community-based study. Stroke 1999;30:930-3.

5 Jørgensen HS, Kammersgaard LP, Houth JG, NakayamaH, Raaschou HO, Larsen K, et al. Who benefits from treat-ment and rehabilitation on a stroke unit? A community-based study. Stroke 2000;31;434-9.

Intention to treat analysis isrelated to methodologicalqualityEditor—In their survey of all randomisedcontrolled trials published in 1997 in fourmajor medical journals, Hollis and Campbellfound that only 48% of the reports explicitlymentioned intention to treat analysis.1 In aconsiderable proportion it was insufficientlydescribed and sometimes inadequatelyapplied. Their results are confirmed by ourassessment of all randomised controlled trialspublished between 1993 and 1995 in thesame four journals.2 In addition to our assess-ment of ethical issues, we calculated theproportion of randomised controlled trialsreporting intention to treat analysis inaccordance with different descriptive andmethodological characteristics.

In our review of 608 randomisedcontrolled trials, we found that 290 of thetrials (47.7%) explicitly mentioned that theyapplied the principle of intention to treatanalysis. The reporting of this issueincreased slightly between 1993 and 1995(although the increase was not significant).Trials with a greater number of participantsand those funded by the pharmaceuticalindustry were more likely to report theapplication of the intention to treat princi-ple (table). In the multivariable logisticregression analysis, when we controlled forthe general characteristics previouslydescribed, we found that trials with survivalof patients as the principal outcome were

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more frequently reported to follow theintention to treat principle. In addition,those randomised controlled trials that gaveno information about sample size were lesslikely to report the use of this principle(table). Randomised controlled trials notreporting the number of withdrawals orlosses to follow up and those not reportinginformation about compliance with treat-ment were also less likely to report theintention to treat principle, although theseresults were not significant.

Our data support the relation between ahigher methodological quality of the trials

and the reporting of the intention to treatanalysis. Our results reinforce the conclu-sions of Hollis and Campbell that the appli-cation of this principle still needs toimprove because it seems that there hasbeen no improvement between 1993 and1997.1 A joint effort of editors and research-ers is needed to meet the CONSORTguidelines3 and the authors’ recommenda-tions favouring intention to treat analysis.1

A better quality of reporting will help read-ers to assess the design, conduct, and analy-sis of randomised controlled trials morecritically.

Miguel Ruiz-Canela assistant professorDepartment of Biomedical Humanities andDepartment of Epidemiology and Public Health,School of Medicine, University of Navarra, E 31080Pamplona, [email protected]

Miguel Angel Martínez-González acting chairJokin de Irala-Estévez associate professorDepartment of Epidemiology and Public Health,School of Medicine, University of Navarra

1 Hollis S, Campbell F. What is meant by intention to treatanalysis? Survey of published randomised controlled trials.BMJ 1999;319:670-4. (11 November.)

2 Ruiz-Canela M, Martínez-González MA, Gómez Gracia E,Fernández-Crehuet Navajas J. Informed consent andapproval by institutional review board in published clinicaltrials. N Engl J Med 1999;340:1114-5. (Erratum N Engl JMed 1999;341:460.)

3 Begg C, Cho M, Eastwood S, Horton R, Moher D, Olkin I,et al. Improving the quality of reporting of randomizedcontrolled trials. The CONSORT statement. JAMA1996;276:637-9.

Using anticoagulation oraspirin to prevent stroke

Research was methodologically flawed

Editor—The paper by Hellemons et al isnot justified in concluding that aspirin is theprophylactic choice in primary care foratrial fibrillation, if there is no clearindication for full anticoagulation.1

The study is methodologically flawed. Asclinicians, we ask ourselves: “Which patientin atrial fibrillation should be given anti-coagulants?” This is a statistical questionabout the risks and benefits of aspirin orwarfarin for that individual patient.

In the power calculation Hellemons et alasked whether low anticoagulation (inter-national normalised ratio 1.1-1.6) or aspirinshould be used—but this is the wrongquestion. The choice should have beenbetween aspirin and standard anticoagula-tion (INR 2.5-3.5). The increased incidenceof major intracranial bleeding in the aspiringroup compared with the anticoagulatedgroups (0.75% per patient year v 0.35%)calls into question the sagacity of using onetailed statistical tests.

As the study was underpowered, thequestion of whether standard anticoagula-tion or aspirin was better in preventingmajor cerebral infarction cannot beanswered. Although there is a trend towardsfull anticoagulation (hazard ratio 0.67), the95% confidence intervals are so wide (0.11to 4.1) that the result is meaningless.

The arbitrary exclusion from standardanticoagulation of all people who were 78years or older also undermines the study, foralthough it may have reduced the complica-tion rate from anticoagulation, it will havealso reduced the potential benefit.

This paper highlights the problems inreporting “negative” or “no difference” stud-ies. It has failed to show “no difference”between standard anticoagulation and aspi-rin prophylaxis in atrial fibrillation, asclinically important differences could wellexist within the confidence limits. The studyadds little to previous work that doesdemonstrate benefit from anticoagulation2

and may be misinterpreted as an excuse for

Reporting of intention to treat analysis in published clinical trials (1993-5)

Total No

No (%)reporting

intention totreat

Crude odds ratio fornot reporting the useof intention to treat

(95% CI)

Logistic regressionmultivariable modeladjusted odds ratio

(95% CI)

Odds ratio (95% CI)adjusted fordescriptive

characteristics

All sample 608 290 (47.7)

Descriptive characteristics of the trials

Journal:

N Engl J Med 219 122 (55.7) 1 1

JAMA 81 37 (45.7) 1.50 (0.90 to 2.50) 1.64 (0.92 to 2.92)

BMJ 105 44 (41.9) 1.74 (1.09 to 2.79) 1.80 (0.96 to 3.39)

Lancet 203 87 (42.9) 1.68 (1.14 to 2.46) 1.54 (0.95 to 2.50)

Year of publication:

1995 211 108 (51.2) 1 1

1994 195 92 (47.2) 1.17 (0.79 to 1.73) 1.20 (0.78 to 1.86)

1993 202 90 (44.6) 1.30 (0.89 to 1.92) 1.14 (0.73 to 1.77)

Country of authors:

Europe (except UnitedKingdom)

164 86 (52.4) 1 1

United Kingdom 127 61 (48.0) 1.19 (0.75 to 1.90) 0.90 (0.52 to 1.55)

United States 240 120 (50.0) 1.10 (0.74 to 1.64) 1.24 (0.75 to 2.07)

Other 77 23 (29.9) 2.59 (1.45 to 4.60) 2.59 (1.38 to 4.85)

Main specialty of authors:

Medical specialties 432 213 (49.3) 1 1

Surgery ormedical-surgical

106 45 (42.5) 1.32 (0.86 to 2.02) 1.23 (0.76 to 1.99)

Intensive or emergencycare

37 18 (48.6) 1.03 (0.52 to 2.01) 1.08 (0.51 to 2.29)

Public health 16 7 (43.8) 1.25 (0.46 to 3.42) 1.60 (0.54 to 4.74)

Other 17 7 (41.2) 1.39 (0.52 to 3.72) 1.29 (0.44 to 3.82)

Number of participating subjects:

>500 171 109 (63.7) 1 1

51 to 500 322 167 (51.9) 1.63 (1.11 to 2.39) 1.68 (1.12 to 2.53)

<50 115 14 (12.2) 12.66 (6.68 to 24.10) 12.43 (6.24 to 24.36)

Source of funding:

Pharmaceutical industry 206 129 (62.6) 1 1

Public agency 165 73 (44.2) 2.11 (1.39 to 3.20) 2.11 (1.34 to 3.34)

Other 126 52 (41.3) 2.38 (1.52 to 3.75) 2.01 (1.22 to 3.30)

Not reported 111 36 (32.4) 3.49 (2.14 to 5.68) 2.35 (1.34 to 4.10)

Methodological characteristics of the trials

Outcome:

Survival 142 104 (73.2) 1 1

Other 466 186 (39.9) 4.12 (2.72 to 6.24) 2.86 (1.77 to 4.60)

Sample size estimation:

Shown 281 167 (59.4) 1 1

Not shown 327 123 (37.6) 2.43 (1.75 to 3.37) 2.28 (1.55 to 3.37)

Compliance with treatment:

Stated 532 261 (49.1) 1 1

Not stated 76 29 (38.2) 1.56 (0.95 to 2.56) 1.71 (0.98 to 2.99)

Reporting follow up or withdrawals:

Reporting the number ofpatients withdrawn or lostto follow up

194 100 (51.5) 1 1

Not giving informationabout number of patientslost to follow up

414 190 (45.9) 1.25 (0.89 to 1.76) 1.45 (0.98 to 2.14)

A higher odds ratio means a higher probability of not reporting the use of the intention to treat principle.

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a nihilistic approach to the prevention ofembolic episodes in primary care.Simon J Ellis consultant [email protected]

Renu Hans senior house officerNeurosciences Trust, North Staffordshire RoyalInfirmary, Keele University, Stoke on Trent ST4 7LN

1 Hellemons BSP, Langenberg M, Lodder J, Vermeer F,Schouten HJA, Lemmens Th, et al. Primary prevention ofarterial thromboembolism in non-rheumatic atrial fibrilla-tion in primary care: randomised controlled trial compar-ing two intensities of coumarin with aspirin. BMJ 1999;319:958-64. (9 October.)

2 Petersen P, Boysen G, Godtfredsen J, Andersen ED,Andersen B. Placebo-controlled, randomised trial ofwafarin and aspirin for prevention of thromboemboliccomplications in chronic atrial fibrillation. The Copenha-gen AFASAK study. Lancet 1989;1:175-9.

Study does not have the power to showthat aspirin is as good as anticoagulation

Editor—We welcome the data provided byHellemons et al on the relative merits of anti-coagulation or aspirin for stroke preventionin atrial fibrillation in a primary care popula-tion.1 However, we feel that their interpret-ation of the data is misleading, and that thestudy raises more questions than it answers.

The arm comparing standard anticoagu-lation with aspirin involved 272 patientsfollowed up for an average of three years,during which time there were 22 primaryoutcome events. The hazard ratio was 0.78(95% confidence interval: 0.34 to 1.8) infavour of anticoagulation. The wide confi-dence interval does not exclude a potentiallyimportant advantage of anticoagulation overaspirin. Taken with the existing evidence forthe superiority of anticoagulation over aspi-rin, this inadequately powered study providesno evidence to support the authors’ conclu-sion that aspirin should be preferred tostandard anticoagulation in primary care.2 3

Patients aged 78 years or more wereexcluded from standard anticoagulation andwere randomised to receive low intensity cou-marin or aspirin. Because half of patients withatrial fibrillation are older than 75 years, acrucial question is how people over this ageshould be treated.4 Hellemons et al have con-firmed the finding of the Stroke Prevention inAtrial Fibrillation Investigators that lowintensity anticoagulation is ineffective,5 andtheir study had (just) sufficient power for test-ing this comparison. However, the studyavoids the more important and unansweredquestion of whether standard anticoagulationshould be used for patients in this age group,in whom the risk of stroke is higher, butpossibly so is the risk of haemorrhage.

We will shortly begin recruiting to ageneral practice based trial, the Birminghamatrial fibrillation treatment assessment study,which will specifically address this issue, ran-domising patients aged 75 years or over toreceive warfarin (target international nor-malised ratio 2.5) or aspirin (75 mg).Jonathan Mant senior [email protected]

David Fitzmaurice senior lecturerEllen Murray research fellowRichard Hobbs professorDepartment of Primary Care and General Practice,Medical School, University of Birmingham,Birmingham B15 2TT


2 Atrial Fibrillation Investigators. Risk factors for stroke andefficacy of anti-thrombotic therapy in atrial fibrillation.Arch Intern Med 1994;154:1449-57.

3 Atrial Fibrillation Investigators. The efficacy of aspirin inpatients with atrial fibrillation: analysis of pooled data fromthree randomised trials. Arch Intern Med 1997;157:1237-40.

4 Feinberg WM, Blackshear JL, Laupacis A, Kronmal R, HartRG. Prevalence, age distribution and gender of patientswith atrial fibrillation. Arch Intern Med 1995;155:469-73.

5 Stroke Prevention in Atrial Fibrillation Investigators.Adjusted dose warfarin versus low intensity, fixed dosewarfarin plus aspirin for high risk patients with atrial fibril-lation: stroke prevention in atrial fibrillation III ran-domised clinical trial. Lancet 1996;348:633-8.

Anticoagulation has a major role inprimary prevention of stroke in generalpractice

Editor—The paper by Hellemons et al1

emphasises the conclusions of the StrokePrevention in Atrial Fibrillation Investiga-tors,2 that not all patients with non-rheumatic atrial fibrillation benefit fromtherapeutic anticoagulation with warfarin.Their study population included a high pro-portion of patients (40%) with lone atrialfibrillation, who would not be expected tobenefit from anticoagulation. Excludingpatients with chronic heart failure and notrandomising patients who were more than78 years old to the standard anticoagulationlimb would further reduce the power of theirstudy to detect a reduced number of eventsin patients given warfarin.

The decision to prescribe anticoagulantsrequires careful assessment of the patients’risk of stroke and bleeding (including compli-ance difficulties and risk of falling). We arereassured by the low rate of bleeding ( < 1%)in the anticoagulation arm of the trial whichused local anticoagulation services.

It is important not to draw the conclusionthat aspirin is as effective as an adjusted doseof warfarin for primary prevention in allpatients with atrial fibrillation. Anticoagula-tion has a major role in managing patientswith atrial fibrillation who are at high risk ofstroke, but it requires more than the blanketapproach of “atrial fibrillation thereforewarfarin”3 There is good evidence that warfa-rin is underused in clinical practice, whichmay be because consensus is lacking on whobenefits from treatment.4 Guidelines exist forrational use of aspirin and anticoagulation inatrial fibrillation.5 These should be appliedwhen assessing patients for prophylactic anti-thrombotic treatment.Andy Evans clinical [email protected]

Iñigo Perez research fellowLallit Kalra professorDepartment of Stroke Medicine, Guy’s, King’s andSt Thomas’s School of Medicine, London SE5 9PJ


2 Stroke Prevention in Atrial Fibrillation Investigators. War-farin versus aspirin for prevention of thromboembolism inatrial fibrillation: stroke prevention in atrial fibrillation IIstudy. Lancet 1994;343:687-91.

3 Hart RG, Halperin JL. Atrial fibrillation and thromboem-bolism: a decade of progress in stroke prevention. AnnIntern Med 1999;131:688-95.

4 Perez I, Melbourn A, Kalra L. Use of antithrombotic meas-ures for stroke prevention in atrial fibrillation. Heart1999;82:570-4.

5 Laupacis A, Albers G, Dalen J, Dunn MI, Jacobsen AK,Singer DE. Antithrombotic therapy in atrial fibrillation.Chest 1998;114:579-89S.

Results of the study cannot be generalisedto the general practice population

Editor—Hellemons et al studied antithrom-botic treatment in patients with non-rheumatic atrial fibrillation in general prac-tice.1 By using a screening method (checkingthe pulse) they were able to find morepatients with atrial fibrillation than are usuallyknown to the general practitioner. In a previ-ous article about this study, they mentioned aprevalence of atrial fibrillation of 5.1% inpatients aged 60 years or over.2 This iscomparable to the prevalence of 4.7% foundby Sudlow et al in a community study inpeople aged 65 years and older.3 In studies ingeneral practice prevalence is about 50%lower. In our study conducted in generalpractice in the Netherlands we found a preva-lence of 2.4% in patients aged 55 years ormore (unpublished data). A general practicestudy in the United Kingdom found the sameprevalence in patients aged 50 years or over.4

Thus a considerable proportion (50%)of the population with atrial fibrillation inthe study by Hellemons et al had not previ-ously been diagnosed with atrial fibrillation,whereas the other 50% were known to havesuch a diagnosis. It seems plausible that thecardiovascular risk profile of the previously“unknown” patients with atrial fibrillation ismore advantageous than that of those with“known” atrial fibrillation. The inclusion ofmany low risk patients with atrial fibrillationcould be the cause of the low cardiovascularevent rate in the present study and of thelack of difference in efficacy between aspirinand coumarin treatment. We are thereforehesitant to generalise the results of this studyto the general practice population, incontrast to the authors. In addition we won-der whether the power of Hellemons et al’sstudy allows for the conclusion that aspirinis equivalent to coumarin. The confidencelimits are rather wide.

We are interested to know whether theauthors analysed the “known” and“unknown” patients with atrial fibrillationseparately, whether there was a difference inprognostic determinants between these twogroups, and whether this influenced thetreatment effect. A difference could explainthe contrasting results with other ran-domised controlled trials conducted inreferred patients.Frans H Rutten general practitionerEelko Hak epidemiologistArno W Hoes professor of epidemiology in generalpracticeJulius Centre for General Practice andPatient-oriented Research, University MedicalCentre Utrecht, PO Box 80045, 3508 TA Utrecht,Netherlands

1 Hellemons BSP, Langenberg M, Lodder J, Vermeer F,Schouten HJA, Lemmens Th, et al. Primary prevention ofarterial thromboembolism in non-rheumatic atrial fibrilla-

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tion in primary care: randomised controlled trial compar-ing two intensities of coumarin with aspirin. BMJ 1999;319:958-64. (9 October.)

2 Langenberg M, Hellemons BSP, van Ree JW, Vermeer F,Lodder J, Schouten HJA, et al. Atrial fibrillation in elderlypatients: prevalence and comorbidity in general practice.BMJ 1996;313:1534.

3 Sudlow M, Thomson R, Thwaites B, Rodgers H, Kenny RA.Prevalence of atrial fibrillation and eligibility for anti-coagulants in the community. Lancet 1998;352:1167-71.

4 Lip GY, Golding DJ, Nazir M, Beevers DG, Child DL,Fletcher RI. A survey of atrial fibrillation in generalpractice: the West Birmingham atrial fibrillation project. BrJ Gen Pract 1997;47:285-9.

Patients should be assessed for riskfactors before deciding on prophylaxis

Editor—Hellemons et al reported thatstandard adjusted dose oral anticoagulationwas no more beneficial than aspirin inprimary care for patients with non-rheumatic atrial fibrillation.1 As 30% ofpatients in this study were excluded from thetrial because they were already taking oralanticoagulants, and patients at high risk ofstroke (those aged more than 78 years) andhypertensive patients were excluded fromthe randomisation to dose adjusted warfa-rin, the results apply to only about 20% ofpatients with atrial fibrillation seen inprimary care.

With only a 1% annual rate of strokerecorded in the study for patients aged lessthan 78 years, it is not surprising that no dif-ference was observed in the treatment arms.The results from this preselected group ofpatients should not be applied to mostpatients with atrial fibrillation in thecommunity. In the low risk group 3% ofpatients randomised to receive aspirin had astroke, whereas 10% of the higher risk grouphad strokes. This illustrates the need forimproving prophylaxis for high riskpatients—the very patients excluded frombeing treated with an adjusted dose ofanticoagulant. Furthermore, the risk of seri-ous haemorrhage in the group treated withaspirin needs to be emphasised. As 3% ofthese patients had a major haemorrhage orcerebral bleed, aspirin should not beassumed to be a safer option.

Large hospital based clinical trialscomparing dose adjusted anticoagulationwith low dose warfarin and aspirin treat-ment have shown a consistent reduction inthe rate of stroke in favour of dose adjustedoral anticoagulation, with no increase inbleeding complications. The third trial onstroke prevention in atrial fibrillation lookedat high risk patients for stroke,2 and theCopenhagen atrial fibrillation, aspirin andanticoagulation 2 study3 and recent Italianstudies4 did not exclude patients at high riskfor adverse events (in contrast to Hellemonset al’s study). The patients most at risk fromstroke are those with a history of thrombo-embolic disease, diabetes, hypertension, andcardiac failure and those female patientsmore than 75 years old. Most of the patientsin primary care with atrial fibrillation fallinto this category, with the treatment ofchoice being adjusted dose warfarin toachieve an international normalised ratio of2-3. Hellemons has shown that somepatients with non-rheumatic atrial fibrilla-tion are at low risk of stroke. The conclusion

that this may be the first choice for patientswith atrial fibrillation in general practice ismisleading. A proper clinical risk assessmentfor stroke and haemorrhage is required forall patients with atrial fibrillation before thebest approach to prophylaxis is decided on.The report should not be used in primarycare to justify the routine use of aspirin inpreference to standard anticoagulation,however onerous monitoring warfarin treat-ment might seem.P E Rose consultant haematologistPathology Laboratory, Warwick Hospital, WarwickCV34 5BJ


2 Stroke Prevention in Atrial Fibrillation Investigators.Adjusted dose warfarin versus low intensity, fixed dosewarfarin plus aspirin for high risk patients with atrial fibril-lation: stroke prevention in atrial fibrillation III ran-domised clinical trial. Lancet 1996;348:633-8.

3 Gullov AL, Koefoed BG, Petersen P. Bleeding during war-farin and aspirin therapy in patients with atrial fibrillation:the AFASAK 2 study. Atrial fibrillation, aspirin and antico-agulation. Arch Intern Med 1999;159(12):1322-8.

4 Pengo V, Zasso A, Babero F, Banzato A, Nante G, ParissentiL, et al. Effectiveness of fixed mini dose warfarin in the pre-vention of thromboembolism and vascular death innon-rheumatic atrial fibrillation. Am J Cardiol 1998;82:433-7.

Aspirin is the logical choice fornon-rheumatic atrial fibrillation

Editor—Hellemons et al’s randomised con-trolled trial is one of only a handful of “headto head” comparisons of anticoagulationwith aspirin.1 The trial shows that aspirin isat least as good as anticoagulation inpatients with non-rheumatic atrial fibrilla-tion. However, anticoagulation is widely rec-ommended as the best treatment forpatients with non-rheumatic atrial fibrilla-tion, on the grounds that the risk of stroke isreduced by 62% in comparison withplacebo.2 Aspirin is viewed as a suitablealternative only if anticoagulation is con-traindicated, because aspirin is less effectivein reducing the risk of stroke—22% in com-parisons with placebo.2 However, risk reduc-tions are less impressive if all vascular deathsare considered.

Referral rates to anticoagulation clinicshave increased dramatically over the pastdecade.3 Hellemons et al’s evaluation ofstandard anticoagulation versus aspirinshows no significant difference in theprimary outcome. As shown in table 2, thehazard ratio comparing standard anticoagu-lation with aspirin for the primary outcomeis 0.78 (95% confidence interval 0.34 to1.80), which is equivalent to standard antico-agulation being 66% worse than aspirin andas much as 80% better than aspirin. But howmuch better would anticoagulation have tobe to make it the treatment of choice? A lookat cost effectiveness may help in making adecision. As a policy of widespread anti-coagulation costs 15 times the use of aspirinalone,4 anticoagulation would have to be 15times as effective as aspirin and cause noadverse effects to achieve equal costeffectiveness. At the baseline rate of vascularevents on aspirin of those eligible for stand-

ard anticoagulation in Hellemons et al’s trial(2% a year), this translates to an event rate onanticoagulation of 0.13% a year. Hellemonset al’s trial was more than adequatelypowered to detect such a difference and,taken with previous studies, indicates that a15-fold advantage of anticoagulation overaspirin is extremely unlikely.

A preliminary systematic review of alltrials comparing antiplatelet drugs withanticoagulants, including Hellemons et al’sfindings, gives a pooled relative risk ofvascular deaths on anticoagulation of 0.97(95% confidence interval: 0.73 to 1.27), sug-gesting that there is little to choose betweenthese two options in terms of efficacy. If costand safety are considered, then it is clear thataspirin is the logical choice.5

Fiona Clair Taylor clinical trials coordinatorBristol Heart Institute, University of Bristol, BristolRoyal Infirmary, Bristol BS2 [email protected]

Shah Ebrahim professor in epidemiology of ageingDepartment of Social Medicine, University ofBristol, Bristol BS8 2PR

1 Hellemons BSP, Langenberg M, Lodder J, Vermeer F,Schouten HJA, Lemmens Th, et al. Primary prevention ofarterial thromboembolism in non-rheumatic atrial fibrilla-tion in primary care: randomised controlled trial compar-ing two intensities of coumarin with aspirin. BMJ1999;319:958-64. (9 October.)

2 Hart R, Benavente M, Renton A, Cohen H. Antithrombo-lytic therapy to prevent stroke in patients with atrial fibril-lation: a meta-analysis. Ann Intern Med 1999;131:492-501.

3 Taylor F, Ramsay M, Renton A, Cohen H. Methods formanaging the increased workload in anticoagulant clinics.BMJ 1996;307:297.

4 Ebrahim S, Harwood RH. Stroke: epidemiology, evidence, andclinical practice. Oxford: Oxford University Press, 1999.

5 Taylor F, Ebrahim S, Cohen H. Risks and benefits of long-term anticoagulation versus antiplatelet treatment inocclusive vascular disease: a systematic review. Br J Haema-tol 1998;102:266.

Authors’ reply

Editor—Ellis and Hans conclude that in theprimary prevention of arterial thromboem-bolism in non-rheumatic atrial fibrillationstudy only 20% of the targeted general prac-tice patients with non-rheumatic atrial fibril-lation were studied. We did not include thegroup of patients who had already had astroke or who had rheumatic heart diseasebecause these patients do not represent aproblem of prevention to the generalpractitioner in the context of our studyquestion. A few patients refused to partici-pate because they did not want to take cou-marin.

Our population had less comorbiditycompared with other atrial fibrillationstudies (lone atrial fibrillation percentagewas high). Based on population studies wecould not have predicted the low incidencewe found in our younger patients nor such ahigh prevalence in our elderly patients. Weasked general practitioners to screen theirpopulation using pulse counts, and thesepatients might not be found in otherstudies.1

Thrombosis services in the Netherlandshave a lot of clinical experience and arereluctant to give coumarin regularly topatients aged over 80 years for indicationssuch as non-rheumatic atrial fibrillation, soour trial limited this treatment to patientsaged 80 years or less.2 In our prevalence

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study the enhanced comorbidity showedthat the risk of interfering comedication wasrealistic, as confirmed by the relatively highincidence of bleeding in the aspirin arm inpatients > 80 years.3 Ellis and Hans noticedthe important problem of bleeding, particu-larly in elderly patients.

Our data show that in general practice,for patients with atrial fibrillation who havelittle comorbidity, the benefit of coumarindoes not outweigh potential haemorrhagicrisks and that aspirin may suffice. For out-patients aspirin is a better option in terms oflogistics rather than safety, as our studyshowed. From our trial we cannot concludethat low intensity coumarin solves this prob-lem. Ellis and Hans state that the conclusionfrom our study that aspirin suffices forprimary care patients is false, because we didnot investigate the high risk patients. At thesame time they state that our patients wereat the same risk as patients in AFASAK,stroke prevention in atrial fibrillation III4

and the trial by Pengo et al.5 The rate ofevents in our study differed, as did baselinemeasurements (more elderly patients, differ-ent comorbidity).

Which patient should be given preven-tive therapy with regular dose coumarin(international normalised ratio 2.5-3.5): aman of 61 years with lone atrial fibrillation?A woman aged 95 years? A woman aged 76with rheumatic disease and nervousness,who occasionally falls and uses non-steroidanti-inflammatory drugs frequently? Theproper clinical risk assessment for strokeand haemorrhage is needed here, as is moreevidence that in certain patients a regulardose of coumarin is indicated.

We regret that our results could lead to anihilistic approach for prevention in pri-mary care, because primary prevention ofstroke and thromboembolism is an impor-

tant task for the general practitioner.Conclusions from investigations withreferred patients are biased towards includ-ing patients with a higher degree of comor-bidity than is expected in general practice.So these conclusions cannot always beapplied to the general practice population,as may be concluded from our study.

We welcome the initiative of theBirmingham atrial fibrillation treatmentassessment group to perform a study on aregular dose of coumarin in elderly out-patients, because there is not enoughevidence to justify the use of this dose ofcoumarin in these patients. We hope thatMant and colleagues will succeed in recruit-ing enough patients in this age group.Beppie Hellemons general [email protected]

Machteld Langenberg general practitionerJan van Ree professorAndré Knottnerus professorDepartment of General Practice, University ofMaastricht, PO Box 616, 6200 MD Maastricht,Netherlands

Jan Lodder neurologistDepartment of Neurology, University of Maastricht

Frank Vermeer cardiologistDepartment of Cardiology, University of Maastricht

Hubert Schouten clinical biostatisticianDepartment of Methodology and Statistics,University of Maastricht

1 Atrial Fibrillation Investigators. The efficacy of aspirin inpatients with atrial fibrillation: analysis of pooled data fromthree randomised trials. Arch Intern Med 1997;157:1237-40.

2 Van der Meer FJ, Rosendaal FR, Vandenbroucke JP, Briet E.Bleeding complications in oral anticoagulant therapy. Ananalysis of risk factors. Arch Intern Med 1993;153:1557-62.

3 Langenberg M, Hellemons BSP, van Ree JW, Vermeer F,Lodder J, Schouten HJA, et al. Atrial fibrillation in elderlypatients: prevalence and comorbidity in general practice.BMJ 1996;313:1534.

4 Stroke Prevention in Atrial Fibrillation Investigators.Adjusted dose warfarin versus low intensity, fixed dosewarfarin plus aspirin for high risk patients with atrial fibril-lation in atrial fibrillation III randomised clinical trial.Lancet 1996;348:633-8.

5 Pengo V, Zasso A, Barbero F, Banzato A, Nante G,Parissenti L, et al. Effectiveness of fixed minidose warfarinin the prevention of thromboembolism and vascular deathin nonrheumatic atrial fibrillation. Am J Cardiol1998;82:433-7.

Evidence of a CJD epidemicmay still be missedEditor—The United Kingdom faces thepossibility of an epidemic of new variantCreutzfeldt-Jakob disease as a result ofbovine spongiform encephalopathy,1 butthe referral of brain tissue to neuropatholo-gists to determine the cause of degenerativediseases of the brain has virtually stopped.Public concerns over the retention of tissuesfor investigation after postmortem exam-ination make it is easy to see how this hashappened.2

In the United Kingdom most postmor-tem examinations on adults are performedbecause they are directed by law. The mainreason is to ascertain a natural medicalcause of death for certification, therebyremoving the need for an inquest. In thepast, retaining the brain for examination wasa routine part of the practice of pathologists,but it is now clear that many relatives of thedeceased person may not have been aware

of this. Because of concerns over thelegitimacy of organ retention the true causeof a degenerative brain disease is now hardlyever being established after a postmortemexamination, even though the brain hasbeen examined by the inadequate methodof slicing during the necropsy. Simply certi-fying that a person has died of a disease suchas pneumonia, in the face of a decline as aresult of a degenerative brain disease, is giv-ing a mechanism of death rather than itstrue cause. This has implications for estimat-ing misclassification rates in epidemiologicalstudies.3 I suspect that many families will beconcerned that they were not given theopportunity to benefit from appropriateinvestigations. Guidelines from the RoyalCollege of Pathologists (www.rcpath.org) willbe released soon, but medical and publicconfidence has already been lost.

So far, the cases of new variantCreutzfeldt-Jakob disease have been in a dis-tinct subset of the population.1 We have noknowledge of the ways in which new variantCreutzfeldt-Jakob disease may becomemanifest, especially in elderly people. Unlessa positive statement is made to reassurethe public, medicolegal authorities, andpathologists, the situation of “not looking”will prevail and we run the risk of missingany emerging epidemic.James Lowe professorSchool of Clinical Laboratory Sciences, Division ofPathology, University of Nottingham MedicalSchool, Nottingham NG7 [email protected]

Competing interests: Professor Lowe recieves fund-ing from the UK Department of Health forsurveillance of the incidence of Creutzfeldt-Jakobdisease. He is a member of the council of the RoyalCollege of Pathologists and has contributed to theformulation of its document Guidelines for the Reten-tion of Tissues at Post-mortem Examination.

1 Collinge J. Variant Creutzfeldt-Jakob disease. Lancet1999;354:317-23.

2 Woodman R. Storage of human organs prompts threeinquiries. BMJ 2000;320:77. (8 January.)

3 Majeed A, Lehmann P, Kirby L, Knight R, Coleman M.Extent of misclassification of death from Creutzfeldt-Jakobdisease in England 1979-96: retrospective examination ofclinical records. BMJ 2000;320:145-7. (15 January.)

Correction

Stages of change model for smoking preventionand cessation in schoolsAn editorial error occurred in this authors’reply by Paul Aveyard and others (5 February,p 447). “Smoking cessation” was omitted inthe last sentence of the second paragraph,which should have read: “On this basis, itseems more likely that the smoking cessationexpert system for adults, the only one that canbe compared with the system for adults,should be more successful and require fewersessions, yet we found no effect.”

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Intention to treat analysis is related to methodological quality

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