BMJ: British Medical Journal

17 March 2007 (Vol 334, No 7593 , pp. 543-591)

Editor's choice Editor's choice: Real impact Trish Groves BMJ 2007;334, doi:10.1136/bmj.39154.666528.43

US editor's choice: It's all about being first Elizabeth Loder BMJ 2007;334, doi:10.1136/bmj.39155.711400.43

Editorials Why the UK's Medical Training Application Service failed Tony Delamothe BMJ 2007;334:543-544, doi:10.1136/bmj.39154.476956.BE (published 14 March 2007)

Indwelling stents after ureteroscopy Colin H Wilson, David A Rix BMJ 2007;334:544-545, doi:10.1136/bmj.39149.561134.80

Perinatal death in twins Philip Steer BMJ 2007;334:545-546, doi:10.1136/bmj.39146.541100.80

Caring for the oldest old Domhnall MacAuley, Zoe Slote Morris BMJ 2007;334:546-547, doi:10.1136/bmj.39141.534190.80

Reed Elsevier's arms trade Charles Young, Fiona Godlee BMJ 2007;334:547-548, doi:10.1136/bmj.39153.580023.80

Letters This week's letters

MMC: Raging against MTAS (UK Medical Training Application Service) Morris J Brown BMJ 2007;334:549, doi:10.1136/bmj.39150.444340.BE

Regulation: Australia shows benefits of an independent tribunal Peter C Arnold BMJ 2007;334:549, doi:10.1136/bmj.39150.379676.BE

Regulation: Clinical governance can become oppressive D B Double BMJ 2007;334:549, doi:10.1136/bmj.39150.389919.BE

Specialist centres: Haematologists should be treat sickle cell disease Piotr Szawarski BMJ 2007;334:549-550, doi:10.1136/bmj.39150.403877.BE

Specialist centres: US cancer centres show the way Malcolm R Kell BMJ 2007;334:550, doi:10.1136/bmj.39150.413461.BE

Postpartum depression: NICE may be discouraging detection of postpartum depression James C Coyne, Alex J Mitchell BMJ 2007;334:550, doi:10.1136/bmj.39150.424896.BE

Diagnosing hyponatraemia: Urine tests are often unhelpful Mat Davies BMJ 2007;334:550, doi:10.1136/bmj.39150.453854.BE

Publisher boycott: We must challenge war Marion Leighton BMJ 2007;334:550, doi:10.1136/bmj.39150.465984.BE

News Fracture risk a class effect of thiazolidinediones in women Robert Short BMJ 2007;334:551, doi:10.1136/bmj.39154.373889.DB

UK report recommends better planning for phase I drug trials Susan Mayor BMJ 2007;334:551, doi:10.1136/bmj.39153.352234.DB

Lilly's challenge to Australia's drug rationing scheme fails Bob Burton BMJ 2007;334:552, doi:10.1136/bmj.39150.417951.DB

Laughter, learnt of friends Annabel Ferriman BMJ 2007;334:552, doi:10.1136/bmj.39153.711065.DB

Exempt MRI scanners from new EU rules, say campaigners Rory Watson BMJ 2007;334:552, doi:10.1136/bmj.39153.368021.DB

WHO confronts Chinese company over malaria drug Anne Glusker BMJ 2007;334:553, doi:10.1136/bmj.39154.358762.DB

Tuberculosis and AIDS researchers fail to work together, article says Michael Day BMJ 2007;334:553, doi:10.1136/bmj.39153.348264.DB

In Brief: News BMJ 2007;334:553, doi:10.1136/bmj.39153.609039.4E

More evidence shows better outcomes for vascular surgery at high volume hospitals Roger Dobson BMJ 2007;334:554, doi:10.1136/bmj.39153.349167.DB

Audit identifies the most read BMJ research papers Susan Mayor BMJ 2007;334:554-555, doi:10.1136/bmj.39153.350174.DB

Reid wrong about comfort of smoking, research shows Roger Dobson BMJ 2007;334:555, doi:10.1136/bmj.39153.351042.DB

Two thousand health staff sign petition calling for euthanasia to be decriminalised Brad Spurgeon BMJ 2007;334:555, doi:10.1136/bmj.39153.492789.DB

Organ transplant recipients may die when insurance for immunosuppressants runs out Fred Charatan BMJ 2007;334:556, doi:10.1136/bmj.39150.435058.DB

Spending watchdog slates provision of doctors out of hours care in England Lynn Eaton BMJ 2007;334:556, doi:10.1136/bmj.39153.526794.4E

MPs broadly welcome proposals for health research in UK Zosia Kmietowicz BMJ 2007;334:556-557, doi:10.1136/bmj.39154.497674.4E

Doctor's licence suspended after he admitted removing ova without consent Judy Siegel-Itzkovich BMJ 2007;334:557, doi:10.1136/bmj.39150.494271.DB

More mutated genes involved in cancer than previously thought Zosia Kmietowicz BMJ 2007;334:557, doi:10.1136/bmj.39147.543449.4E

UK's chief medical adviser proposes global health strategy Susan Mayor BMJ 2007;334:557, doi:10.1136/bmj.39153.404375.4E

Heathrow airport doctor struck off medical register Owen Dyer BMJ 2007;334:557, doi:10.1136/bmj.39154.584780.DB

Government told to revise guidance on payments for continuing care Adrian O'Dowd BMJ 2007;334:557, doi:10.1136/bmj.39154.575556.DB

Shortcuts from other journals: Primary care fails people with anxiety BMJ 2007;334:558, doi:10.1136/bmj.39153.560833.80

Shortcuts from other journals: Screening for lung cancer must wait for better evidence BMJ 2007;334:558, doi:10.1136/bmj.334.7593.558-a

Shortcuts from other journals: Thailand reduces child deaths and health inequality BMJ 2007;334:558, doi:10.1136/bmj.334.7593.558-b

Shortcuts from other journals: Occipital nerve stimulation for chronic cluster headache BMJ 2007;334:558-559, doi:10.1136/bmj.334.7593.558-c

Shortcuts from other journals: Atkins still best for weight loss BMJ 2007;334:559, doi:10.1136/bmj.334.7593.559

Shortcuts from other journals: ECG abnormalities predict cardiovascular disease in older women BMJ 2007;334:559, doi:10.1136/bmj.334.7593.559-a

Shortcuts from other journals: Abandon chemoprevention for colorectal cancer BMJ 2007;334:559, doi:10.1136/bmj.334.7593.559-b

Shortcuts from BMJPG journals: Tuberculosis in London is rising BMJ 2007;334:560, doi:10.1136/bmj.334.7593.560

Shortcuts from BMJPG journals: Topical azithromycin is effective for conjunctivitis BMJ 2007;334:560, doi:10.1136/bmj.39140.628600.BE

Shortcuts from BMJPG journals: New guidelines for hand osteoarthritis BMJ 2007;334:560, doi:10.1136/bmj.334.7593.560-b

Shortcuts from BMJPG journals: More on the "date rape" myth BMJ 2007;334:560, doi:10.1136/bmj.334.7593.560-c

Shortcuts from BMJPG journals: Surgery helps athletes with hamstring tears BMJ 2007;334:560, doi:10.1136/bmj.334.7593.560-d

Feature How impact factors changed medical publishing—and science Hannah Brown BMJ 2007;334:561-564, doi:10.1136/bmj.39142.454086.AD

Should we ditch impact factors? Gareth Williams BMJ 2007;334:568, doi:10.1136/bmj.39146.549225.BE

Should we ditch impact factors? Richard Hobbs BMJ 2007;334:569, doi:10.1136/bmj.39146.545752.BE

Observations Atlantic crossing: The trouble with US military medicine Uwe E Reinhardt BMJ 2007;334:565, doi:10.1136/bmj.39153.611111.59

Medicine and the media: "We saw human guinea pigs explode" L Stobbart, M J Murtagh, T Rapley, G A Ford, S J Louw, H Rodgers BMJ 2007;334:566-567, doi:10.1136/bmj.39150.488264.47

Analysis Who will care for the oldest people in our ageing society? Jean-Marie Robine, Jean-Pierre Michel, François R Herrmann BMJ 2007;334:570-571, doi:10.1136/bmj.39129.397373.BE

Research Outcomes of stenting after uncomplicated ureteroscopy: systematic review and meta-analysis Ghulam Nabi, J Cook, J N'Dow, S McClinton BMJ 2007;334:572, doi:10.1136/bmj.39119.595081.55 (published 20 February 2007)

Birth order of twins and risk of perinatal death related to delivery in England, Northern Ireland, and Wales, 1994-2003: retrospective cohort study Gordon C S Smith, Kate M Fleming, Ian R White BMJ 2007;334:576, doi:10.1136/bmj.39118.483819.55 (published 2 March 2007)

Clinical review Generalised anxiety disorder Christopher Gale, Oliver Davidson BMJ 2007;334:579-581, doi:10.1136/bmj.39133.559282.BE

Practice Asthma in pregnancy Evelyne Rey, Louis-Philippe Boulet BMJ 2007;334:582-585, doi:10.1136/bmj.39112.717674.BE

Views & reviews Personal views: Advice to a new editor Christopher Martyn BMJ 2007;334:586, doi:10.1136/bmj.39142.475799.AD

Review of the week: Celebrating the medical past, again Balaji Ravichandran BMJ 2007;334:587, doi:10.1136/bmj.39153.707465.59

From the frontline: The poverty of expectation Des Spence BMJ 2007;334:588, doi:10.1136/bmj.39153.513646.59

Drug tales and other stories: Hidden extras Ike Iheanacho BMJ 2007;334:588, doi:10.1136/bmj.39153.595660.59

Between the lines: The foul taste of medicine Theodore Dalrymple BMJ 2007;334:589, doi:10.1136/bmj.39153.458403.59

Medical classics: The Doctor David Memel BMJ 2007;334:589, doi:10.1136/bmj.39150.724063.4E

Obituaries This week's obituaries

Job Joab Bwayo Peter Moszynski BMJ 2007;334:590, doi:10.1136/bmj.39125.581713.FA

David Ivor Bowen David I Bowen BMJ 2007;334:591, doi:10.1136/bmj.39147.944398.BE

Stuart Harvey Green Alan Craft, Tony Hockley BMJ 2007;334:591, doi:10.1136/bmj.39147.965868.BE

Patricia Mary Leeson R M Mishra BMJ 2007;334:591, doi:10.1136/bmj.39125.428356.80

Peter Ogilvie Leggat John Hodgson BMJ 2007;334:591, doi:10.1136/bmj.39147.995231.BE

Nicholas Taptiklis Theodore Taptiklis BMJ 2007;334:591, doi:10.1136/bmj.39143.650127.FA

Ethel Hunter Waddy Sam Waddy BMJ 2007;334:591, doi:10.1136/bmj.39125.623009.80

Minerva Minerva BMJ 2007;334:592, doi:10.1136/bmj.39150.569653.471

Minerva E J Ben-Eliezer BMJ 2007;334:592, doi:10.1136/bmj.39150.569653.47

Fillers Heredity BMJ 2007;334:575, doi:10.1136/bmj.39106.737535.F7

When I use a word: No effect Jeff Aronson BMJ 2007;334:578, doi:10.1136/bmj.39125.598310.DE

Unsafe driving Peter Simmons BMJ 2007;334:585, doi:10.1136/bmj.39125.626019.DE

For the full versions of these articles and the references see bmj.com EDITORIALS

Why the UK’s Medical Training Application Service failed No convincing validation of the new process was provided

Stung by near universal condemnation of its new proc- not in the context of the rest of the form. Blind to pre- ess for short listing junior doctors for specialty train- vious employment history, they could not act on the ing posts,1 the UK government acted. On Tuesday 6 premise that the best predictor of future performance March it announced a review and by Friday 9 March is past performance. Answers to a series of hypotheti- it had accepted the review’s first round of recommen- cal questions about clinical practice were weighted dations. more heavily than verifiable, relevant achievements These recommendations were that the first round (thereby reducing the incentives for future doctors to of interviews should continue as planned, but with a work towards them). “strengthened” interview process. Applicants not short The most serious charge against the new system is listed for interview can have their application form that it apparently lacked any validation. Did the appli- reviewed by a trained adviser, which might result in cation form ask about the sorts of things we consider the offer of a first round interview. Applicants could relevant? Did it cover all aspects we want to measure? now include CVs and portfolios to support their appli- Was the overall score related to other variables in the Tony Delamothe cation. way we would expect? Was the assessment repeatable deputy editor, BMJ [email protected] The review also promised major changes to the sec- and sufficiently objective to give similar results for 4 Competing interests: My wife, ond round, including changes to the application form different observers? who is an obstetrician and and the scoring system. The revised approach will We don’t know—but we needed to know before the gynaecologist, has short listed and be fully tested and agreed with stakeholders before old system was jettisoned. Unfortunately, the process will be interviewing ST1 candidates 2 for the London Deanery. it is introduced. The review expects to make its final was shrouded in the utmost secrecy—even the ques- Provenance and peer review: report by the end of the month. tions and the scoring system were kept under wraps Commissioned; not externally peer While the response has been commendably fast, for as long as possible. (One short lister filed a bogus reviewed. it begs the question as to why if the flaws in the new application just to get a look at the questions.) BMJ 2007;334:543-4 proposals were so easily spotted—and rectified—they The review is changing all this. It has recommended doi: 10.1136/bmj.39154.476956.BE weren’t noticed earlier. All parties to the hastily con- that ratios of numbers of applicants to jobs should be vened review—the government, the royal colleges, and made available by specialty, entry level, and geog- the British Medical Association—were represented dur- raphy. It should also recommend the publication of ing the more leisurely deliberations over the original the numbers of interviews offered to each successful proposals. applicant. If the anecdotes are correct, and the “best” Yet this is an episode with many more questions candidates are being offered four, then deaneries can than answers, and deciding how to apportion blame better calculate how many interviews they will need will have to wait until the system is fixed. In the mean- to offer to fill all their available positions. time, we are stuck in the middle of a process, with no To know how to react to claims that there are 8000 final outcome to evaluate, awash with anecdote. more applicants than jobs we need to know whether That some of the best and brightest of their genera- there are more, fewer, or the same number of jobs as tion of junior doctors had not been short listed for beforehand, and where the doctors come from (the interview was cited as incontrovertible evidence that United Kingdom, the European Economic Area, or the new process needed fixing. Although numerous elsewhere). Is the process being “swamped” by appli- anecdotes support this, others support the opposite, cations from non-UK doctors? This is the elephant in with senior doctors believing that, “among their jun- the room, which no one except the international medi- iors, the best are those with most interviews and those cal graduates themselves seem ready to talk about.5 with no offers are the least able.”3 Will the final appointments be made totally on merit, Undoubtedly, there were technical problems with they wonder, or will the interviewing panel feel com- processing so many applications, especially as a big promised by the fact that UK taxpayers have contrib- bang computerised approach was preferred over a uted £250 000 (€370 000; $480 000) towards training few closely observed pilots. Some people doing the the not quite so good UK doctor in front of them? short listing were insufficiently trained. Short listing It’s early days, but it looks like the review is favour- timescales were absurdly short and coincided with ing a return to what existed before—presumably on the half term holidays (just as the interviews will conflict grounds that it was tried and tested. But the little test- with Easter holidays). ing that has been done suggested that the old ways had Short listers saw the responses to a single question, their own biases. Yet the recent past is already being

BMJ | 17 March 2007 | Volume 334 543 EDITORIALS

constructed as a golden age, with everyone getting the at how other countries (and other doctors within their job in the specialty they wanted, in the region they own country) manage to fit applicants to positions. wanted, and with spouses being welcomed into jobs in They should avoid looking back. the same deanery—which is of course nonsense. Coincidentally, this is the week when the Match 1 Combes R. How specialist training reform sparked crisis of confidence. BMJ 2007:334:508-9. (the United States’ annual scheme for matching medi- 2 Department of Health. Review of the Medical Training Applications cal graduates to residency programmes) releases its Service selection process—government response to concerns. Press results, something that has been happening without release 10 March 2007. www.gnn.gov.uk/environment/fullDetail. asp?ReleaseID=270216&NewsAreaID=2&NavigatedFromDepart much rancour since 1952. Closer to home, UK general ment=False. practitioners have devised machine readable tests (sat 3 Eccles SJA. In defence of MMC and MTAS. Rapid response by all applicants on the same day) as the gateway to to Coombes R. How specialist training reform sparked crisis of confidence. BMJ 2007;334:508-9. www.bmj.com/cgi/ selection interviews. eletters/334/7592/508#162034. For the time being, UK junior hospital doctors and 4 Bland JM, Altman DG. Validating scales and indexes. BMJ those who administer their selection into training posi- 2002:324:606-7. 5 Rapid responses to: Coombes R. How specialist training reform tions may feel too traumatised to look forward to any sparked crisis of confidence. BMJ 2007;334:508-9. www.bmj.com/ radically new proposals. But they might look sideways cgi/eletters/334/7592/508#162034.

Indwelling stents after ureteroscopy Can cause significant postoperative morbidity and should be used with caution

In this week’s BMJ, Nabi and colleagues1 present a nificant difference was seen in stone passage, stricture, meta-analysis of randomised controlled trials of the formation, readmission rates, or emergency surgery. insertion of indwelling stents after uncomplicated ure- The review highlights the paucity of well designed teroscopy. During the past quarter of a century the trials, the heterogeneity of the procedures performed, development and use of endoscopic equipment in and the lack of definition of the label “uncomplicated urology has increased. Semirigid and flexible instru- ureteroscopy.” It also found a lack of evidence for the ments have been developed with working channels use of any particular size or composition of ureteric to allow passage of biopsy forceps, baskets, and laser stent with regard to outcome. fibres. Stones in the ureter, and even within the pel- Pain from stents is usually related to mechanical vis and peripheral calyces of the kidney, can now be bladder irritation and is felt in the suprapubic and fragmented and extracted. Upper tract transitional cell genital area. Alternatively, pain may be felt over the

SPL carcinomas can be diagnosed and, where indicated, kidney itself. In our own meta-analysis of the use of treated endoscopically. stents in recipients of renal transplants, pain was not an research p 572 There remains controversy, however, about whether important feature of their use. This may be because the Colin H Wilson indwelling stents should be routinely inserted after transplanted kidney has no connection to the recipi- specialist registrar these procedures. Balloon dilatation of the ureteric ent’s nervous system, and the ureteric orifice of the The Freeman Hospital, Newcastle upon Tyne NE7 7DN orifice, stone fragmentation and basket retrieval of transplant is high on the anterior wall, away from the David A Rix fragments, biopsy, and destruction of mucosal lesions sensitive trigone.4Interestingly, Nabi and colleagues consultant in urological and renal can all cause trauma to the ureter. In patients without found no significant difference in flank pain between transplant surgery [email protected] stents this trauma can result in postoperative obstruc- the groups with and without stents. tion of the ureter, which requires emergency upper Another problem is that stents can be forgotten, Competing interests: None tract decompression. As an alternative to an indwelling which can result in blocked kidneys, intractable infec- declared. stent, postoperative drainage of the upper tract can tions, or unpleasant urinary symptoms. Fail safe sys- Provenance and peer review: temporarily be achieved with a fine bore catheter. This tems must be in place to record the details of patients Commissioned; not externally peer reviewed avoids the need for a second procedure to remove with stents in situ. In a randomised controlled trial of the stent, but does require the patient to be admitted the use of stents in India, 7% of patients discharged BMJ 2007;334:544��-5 overnight at least. with stents either failed to attend for routine follow-up doi: 10.1136/bmj.39149.561134.80 Nabi and colleagues found that people who had or their stents were forgotten and they presented late stents inserted were significantly more likely to have with encrustation and infection.5 In such cases, open haematuria (relative risk 2.18, 95% confidence inter- stent removal may be needed. At least two cases of val 0.72 to 6.61), and lower urinary tract symptoms nephrectomy have been reported when stents became (dysuria: 2.25, 1.14 to 4.43; frequency and urgency: blocked and could not be separated from the ureter.6 2.00, 1.11 to 3.62) than people without stents.2 For So what should clinicians do in the light of the avail- the outcome of flank pain, significant heterogeneity able evidence? The decision to insert a stent at the between trials precluded pooling of results. No sig- end of a ureteroscopic procedure is a balance between

544 BMJ | 17 March 2007 | Volume 334 EDITORIALS

the known morbidity of stents and the perceived risk retrieval methods with different sizes and materials of of ureteric obstruction if a stent is not inserted. As stents should help guide future practice. Nabi and colleagues point out, the spectrum of ure- 1 Nabi G, Cook J, N’Dow J, McClinton S. Outcomes of stenting after teric trauma after ureteroscopy is wide. An accepted uncomplicated ureteroscopy: systematic review and meta-analysis. grading system, based on operative and radiological BMJ 2007 doi: 10.1136/bmj.39119.595081.55. findings, would greatly improve the ability of clinicians 2 Huffman JL, Bagley DH, Lyon ES. Extending cystoscopic techniques into the ureter and renal pelvis. Experience with ureteroscopy and to compare results and techniques, and ultimately to pyeloscopy. JAMA 1983;250:2002-5. produce validated guidelines for the use of stents. 3 Wilson CH, Bhatti AA, Rix DA, Manas DM. Routine intraoperative ureteric stenting for kidney transplant recipients. Cochrane Database However, such a grading system may prove difficult Syst Rev 2005(4):CD004925. to define and has hitherto eluded the urological 4 Kumar A, Verma BS, Srivastava A, Bhandari M, Gupta A, Sharma R. community. Evaluation of the urological complications of living related renal transplantation at a single centre during the last ten years: impact of As technology advances, we may be able to reduce the double J stent. Transplantation 2000;164:657-60. the trauma of ureterorenoscopy and potentially reduce 5 Kumar A, Kumar R, Bhandari M. Significance of routine JJ stenting in living related renal transplantation: a prospective randomised study. the need for stent insertion and its associated morbi‑ Transplant Proc 1998;30:2995-7. dity. Further well designed trials in people with stones 6 Dominguez J, Clase CM, Mahalati K, MacDonald AS, McAlister of various size and anatomical position, assessing VC, Belitsky P, et al. Is routine ureteric stenting needed in kidney transplantation? A randomized trial. Transplantation 2000;70:597-601.

Perinatal death in twins Should all term multiple pregnancies be delivered by elective caesarean section?

Twin pregnancies are becoming more common because any potential increase in risk to the mother. The use of the increasing use of assisted reproduction technolo- of regional anaesthesia, prophylactic antibiotics, and gies.1 They are associated with an eight to tenfold thromboprophylaxis, plus improved suture materi- increase in the perinatal mortality rate,2 mainly because als and techniques for controlling haemorrhage have 40-70% of twins are born preterm.3 However, the safety improved safety. Recently, a working party of the of term vaginal delivery for twins has long been of con- National Institutes of Health in the United States10 found cern; some large epidemiological studies have suggested no evidence that elective caesarean section increased that the second twin is at especially high risk of death.4 risk to a healthy mother having her first delivery com- Complications associated with the second twin include pared with planned vaginal birth. They highlighted that

ER/SPL the longer second stage, compound presentation lead- critics of high caesarean section rates often compare I

/AST ing to trauma during delivery, cord prolapse, and pre- successful vaginal births with all caesareans, including p i 5

bs mature separation of the placenta. However, the only those performed in an emergency during labour. The randomised controlled trial identified by a Cochrane consensus group stated, “the evidence consistently indi- research p 576 review6 of caesarean section compared with vaginal cates a lower risk of surgical complications in elective Philip Steer delivery in twins7 and other small retrospective studies8 cesarean delivery than in unplanned cesarean deliv- professor have not confirmed clinicians’ subjective impressions ery resulting from attempted vaginal delivery. Among Chelsea and Westminster Hospital, London SW10 9NH of poor outcome in the second twin. planned vaginal delivery. . .there is a significantly higher [email protected] The study by Smith and colleagues in this week’s rate of obstetric trauma than among planned cesarean BMJ is welcome for the light it sheds on this topic.9 delivery. The net direction of the evidence thus favors Competing interests: None They studied twin pregnancies in the United Kingdom planned cesarean delivery.” declared. from 1994 to 2003 in which one of the twins died dur- Overall, caesarean section rates continue to rise across Provenance and peer review: ing or after labour for reasons other than congenital the globe11 and now exceed 25% in many places. In Commissioned; not externally peer abnormality (1377 pregnancies). Before 37 weeks’ of high and medium income countries, higher caesarean reviewed. gestation, the two babies were at equal risk, but at term section rates are not associated with higher maternal BMJ 2007;334:545-6 the risk of death was higher in second twins (odds ratio mortality, and in low income countries, those with the doi: 10.1136/bmj.39146.541100.80 2.3, 95% confidence interval 1.7 to 3.2, P<0.001). This highest caesarean section rates have the lowest levels of was even more marked for deaths due to “intrapartum maternal and neonatal mortality.12 A large randomised anoxia” or trauma (3.4, 2.2 to 5.3). Vaginally delivered trial of elective caesarean section for term breech pres- second twins had a fourfold higher risk than first twins entation found a reduction in perinatal mortality of of death due to intrapartum anoxia. The authors sug- two thirds, with no increase in adverse outcomes in gest that these deaths might be prevented by planned mothers.12 13 These findings rapidly changed practice elective caesarean section for all term twin pregnancies. in many countries, with beneficial results.14 Should this be adopted as routine practice? In relation to twin pregnancies, in the UK obstetri- Before recommending routine caesarean delivery to cians already seem to be voting with their scalpels. In reduce risk to the baby, we must balance this against the northwest London database of about 40 000 births

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each year, the overall proportion of caesarean sec- multiple pregnancy in European countries participating in the PERISTAT project. Br J Obstet Gynaecol 2006;113:528-35. tions in term pregnancies rose from 10.5% in 1988 4 Wen SW, Fung Kee FK, Oppenheimer L, Demissie K, Yang Q, to 20.8% in 2000. In parallel, the overall proportion Walker M. Neonatal mortality in second twin according to cause of death, gestational age, and mode of delivery. Am J Obstet Gynecol of caesarean sections in term twin pregnancies rose 2004;191:778-83. from 22.5% in 1988 to 60% in 2000 (more than half of 5 Neilson JP, Bajoria R. Multiple pregnancy. In: Chamberlain G, Steer PJ, eds. Turnbull’s obstetrics. 3rd ed. London: Churchill Livingstone, these being elective). At the Chelsea and Westminster 2001:229-46. Hospital during 2006, 114 sets of twins were born at 6 Crowther CA. Caesarean delivery for the second twin. Cochrane greater than 36 weeks’ gestation; 92 (81%) were deliv- Database Syst Rev 2000;(2):CD000047. 7 Rabinovici J, Barkai G, Reichman B, Serr DM, Mashiach S. Randomized ered by caesarean section, and 70 (76%) of these were management of the second nonvertex twin: vaginal delivery or elective. This is an international trend; as long ago as cesarean section. Am J Obstet Gynecol 1987;156:52-6. 8 Usta IM, Nassar AH, Awwad JT, Nakad TI, Khalil AM, Karam KS. 1995-2000 in Beirut the caesarean section rate had Comparison of the perinatal morbidity and mortality of the presenting reached 76.8% in twins born after in vitro fertilisa- twin and its co-twin. J Perinatol 2002;22:391-6. 15 9 Smith GC, Fleming KM, White IR. Birth order of twins and risk of tion and 58% in spontaneous twins, while a recent perinatal death related to delivery in England, Northern Ireland, paper from Thailand reported an overall rate between and Wales, 1994-2003: retrospective cohort study. BMJ 2007 doi: 10.1136/bmj.39118.483819.55. 1993 and 2004 of 73.9% (90.6% after in vitro fertilisa- 10 National Institutes of Health state-of-the-science conference tion and 71.3% for spontaneous pregnancies.16 A ran- statement: cesarean delivery on maternal request March 27-29, 2006. Obstet Gynecol 2006;107:1386-97. domised controlled trial of elective caesarean section 11 Althabe F, Sosa C, Belizan JM, Gibbons L, Jacquerioz F, Bergel E. for twin pregnancies is currently under way, coordi- Cesarean section rates and maternal and neonatal mortality in low-, medium-, and high-income countries: an ecological study. Birth nated by the University of Toronto maternal infant and 2006;33:270-7. reproductive health research unit (which carried out 12 Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR. Planned caesarean section versus planned vaginal birth for breech the term breech trial). On the basis of Smith and col- presentation at term: a randomised multicentre trial. Term Breech Trial leagues’ study, the results are likely to show a similar Collaborative Group. Lancet 2000;356:1375-83. benefit from caesarean section as in the breech trial; 13 Su M, Hannah WJ, Willan A, Ross S, Hannah ME. Planned caesarean section decreases the risk of adverse perinatal outcome due to both however, it is important that we obtain evidence from labour and delivery complications in the term breech trial. Br J Obstet randomised controlled trials before caesarean section Gynaecol 2004;111:1065-74. 14 Rietberg CC, Elferink-Stinkens PM, Visser GH. The�� effect of the term for twin pregnancies at term becomes universal and a breech trial on medical intervention behaviour and neonatal outcome trial becomes impossible. in the Netherlands: an analysis of 35 453 term breech infants. Br J Obstet Gynaecol 2005;112:205-9. 15 Nassar AH, Usta IM, Rechdan JB, Harb TS, Adra AM, Abu-Musa 1 El Toukhy T, Khalaf Y, Braude P. IVF results: optimize not maximize. Am J AA. Pregnancy outcome in spontaneous twins versus twins who Obstet Gynecol 2006;194:322-31. were conceived through in vitro fertilization. Am J Obstet Gynecol 2 Luke B, Brown MB. The changing risk of infant mortality by gestation, 2003;189:513-8. plurality, and race: 1989-1991 versus 1999-2001. Pediatrics 16 Kor-anantakul O, Suwanrath C, Suntharasaj T, Getpook C, Leetanaporn 2006;118:2488-97. RJ. Outcomes of multifetal pregnancies. Obstet Gynaecol Res 3 Blondel B, Macfarlane A, Gissler M, Breart G, Zeitlin J. Preterm birth and 2007;33:49-55.

Caring for the oldest old As the population ages the costs of care will rise

analysis p 570 When a 70 year old woman collects a prescription The future is probably somewhere between the two. from the pharmacist, no one is surprised. But, it is Coronary heart disease may have declined, but cancer, Domhnall MacAuley primary care editor for her mother. And she must rush back because her dementia, and HIV are increasing. And although coro- BMJ, Tavistock Square, London mother doesn’t see very well, is a little confused, and nary heart disease and cancer will still cause death, they WC1H 9JR her daughter doesn’t like to leave her for too long on will also become chronic managed diseases. Death from [email protected] Zoe Slote Morris her own. Times change. We are all getting older and heart attack will be superseded by associated chronic Nuffield fellow in health policy living longer so our traditional age structured model of conditions, such as angina and chronic health failure.3 Judge Business School, University of society has had to evolve. No longer are people young, The World Health Organization estimates a doubling of Cambridge, Cambridge CB2 1AG middle aged, and old, but increasingly they are also the chronic disease in the over 65s by 2030.4 And a recent 5 Competing interests: None “oldest old.” In this week’s BMJ, Robine and colleagues report commissioned by the Alzheimer’s Society esti- declared. present a “four age population model,” whereby the mates that by 2025 more than a million people in the Provenance and peer review: future long term care needs of the oldest people can be United Kingdom will have dementia, and by 2050 this Commissioned; not externally peer estimated.”1 These frail elderly people, whom we are figure will reach 1.7 million. This increase will create reviewed likely to become, are increasingly important as consum- even greater demand for acute care, management of BMJ 2007;334:546-7 ers of health resources and a focus for future care. chronic disease, and social care with the inevitable doi: 10.1136/bmj.39141.534190.80 The irony of longer life is an increasing burden of increase in costs. . health. We do not know how ageing will affect health. Caring is expensive. Informal care in the community Two competing theories exist. The first is the compres- is often unseen and unmeasured, yet the people who sion of morbidity,2 where we will live longer with fewer provide this care carry the greatest burden of all. We years of disability before we die. The second suggests an need to face up to the huge cost of care in both the for- ageing population with more than one chronic condition. mal and informal sector. In England it is estimated that

546 BMJ | 17 March 2007 | Volume 334 EDITORIALS

restructuring mean that families are increasingly fragmented. Hundreds of miles often separate parents and children. If no family is available there are two alternatives: neglect or formal care. Robine and colleagues are right to argue that policy makers need to anticipate trends in the number of oldest people. Demand for care is not about age in itself, and they point out that their cut off age of 85 and above is arbitrary. Forecasting care needs has less to do with how old people are than with who they are and how old they will be when they are expected to die. Major differences in rates of mortality and morbidity still occur between groups—for example, according to social class, sex, ethnic origin, and geographical region—and the oldest people in each group will vary in age. Those most in 8.5 million people provided informal care in 2000, 3.4 need of care will need care at an earlier age. 6 million of whom cared for people over 65 years. This These problems are important not only in Switzer- is a huge economic investment and these people do not land and the United States but also in the UK and most appear in any economic balance sheet. Furthermore, as Western states where life expectancy is increasing. Social the retirement age increases and people have to work change and economic wellbeing mean that wealthy longer hours, this social capital will soon reach its limits. countries have postponed their healthcare liabilities And with the crisis in pensions, there will be less money until later. First world countries have swapped infant for people to buy additional care. mortality and childhood illness for the burden of care In the United Kingdom, an estimated 3.5 million of the elderly. Caring for the oldest old is the price of more carers will be needed by 2037 to care for those affluence. aged 75 and over.7 Robine and colleagues, in their proposed four age model, introduce the concept of the old- 1 Robine J-M, Michel J-P, Herrmann FR. Who will care for the oldest people in our ageing society? BMJ 2007 doi: 10.1136/ est old support ratio. They make the assumption that the bmj.39129.397373.BE. “sandwich age cohort”—the young retired—will care for 2 Fries JF. Aging, natural death, and the compression of morbidity. the oldest people. The statistical model is attractive and N Engl J Med 1980;303:130-6. 3 Bellaby P. Can they carry on working? Later retirement, health, and social is one measure of the burden of caring. inequality in an aging population. Int J Health Serv 2006;36:1-23. What this paper cannot tell us is if this generation will 4 Batty D. Reid unveils chronic care plans. Guardian 11 March 2004. be around to help, or indeed, will be willing to help. The http://society.guardian.co.uk/health/story/0,7890,1167386,00. html. responsibility usually falls to families first of all, and the 5 Alzheimer’s Society. Major new report shows impact of dementia in reality is that the carer is usually a daughter or daughter the UK. www.alzheimers.org.uk/index.htm. in law. But women have changing aspirations, and geo- 6 Beesley L. Informal care in England. London: King’s Fund, 2006. 7 Carers UK. (2004). Ten facts about caring. www.carersuk.org/ graphical and social mobility together with household Aboutus/Whoarecarers/Tenfactsaboutcaring.

Reed Elsevier’s arms trade Scientific communities must work together to prevent the sale of arms

Charles Young In a recent editorial in the Journal of the Royal Society Reed Elsevier’s purpose in publishing the Lancet and editor BMJ Clinical Evidence, BMA of Medicine, Richard Smith drew attention once again other health related journals is not to covertly support House, London WC1H 9JR to the paradoxical and disturbing association between arms trade revenues. Reed Elsevier, like any other [email protected] Fiona Godlee Reed Elsevier, a huge global publishing company, and company, aims to make money through business activi- editor BMJ�� the international arms trade.1 While promoting world ties that have diversified over time. But its activities in [email protected] health through its publications, including the Lancet, organising exhibitions for the arms trade are only a Competing interests: CY was Reed Elsevier also organises international trade fairs for small part (we believe about 1%) of its turnover. Why previously an executive editor at the Lancet. FG is the editor of the the arms industry. By facilitating the sale of armaments, would Reed Elsevier risk alienating the essential part BMJ. She is paid a fixed salary and Reed Elsevier is directly implicated in causing untold of its money making business—the health, science, and does not benefit personally from damage to health. This hypocrisy is well illustrated by education sector—to allow a continued association with advertising or reprint revenues that may result from article submissions Smith’s “absurd” example of an imaginary tobacco a much smaller asset—the arms trade? to the BMJ. company that publishes health journals to increase For alienation is what’s happening. In the short term, Provenance and peer review: tobacco sales. Sadly, his example is neither absurd nor the publicity surrounding this controversy may be good Commissioned, not externally peer reviewed. imaginary. In 2005, an article in the Lancet reported for Reed Elsevier, if all publicity really is good public- BMJ 2007;334:547-8 undisclosed relations between the tobacco industry and ity. In the long term, however, the consequences of the doi: 10.1136/bmj.39153.580023.80 the health related journal Indoor and Built Environment.2 debate could be disastrous for the company’s reputation

BMJ | 17 March 2007 | Volume 334 547 EDITORIALS ACOU/REX I TONY KYRTONY

and profits, and, if journals do more good than harm, wary of being disloyal I urge you not to be. You do for world health. nothing but good for the Lancet and the other journals In September 2005, when the Lancet first highlighted by speaking up.”6 So the BMJ joins the Journal of the Reed Elsevier’s links with the arms trade, there was an Royal Society of Medicine in calling for action against Reed appropriate outcry from the journal’s international advi- Elsevier. sory board and global opinion leaders.3 4 More recently, The scientific and health communities with which condemnation of Reed Elsevier has come in a letter to Reed Elsevier is linked in a symbiotic relationship have the Times signed by 140 prominent academics,5 in rapid a clear opportunity to exert their influence. As a group, responses to a BMJ news article,6 and via an online these communities have the power to influence corpo- petition that has collected approaching 1000 signatures rate strategy. They must sign petitions such as the one (http://idiolect.org.uk/elsevier/petition.php). identified here, the societies for which Reed Elsevier This continued and growing negative publicity could publishes journals must look for alternative publish- have several possible effects. The inevitable damage to ers, and editors of journals must express their disgust Reed Elsevier’s global corporate reputation will proba- at the company’s arms trade activities through collec- bly lead to lost business opportunities and thus reduced tives such as the World Association of Medical Editors profits. Damage to the reputation of Reed Elsevier pub- (http://www.wame.org/). Furthermore, academic and lications, such as the Lancet, may lead to fewer high industry funded researchers should now agree not to profile submissions, for which journals fiercely com- submit their high profile randomised control trials to pete, and so a reduction in essential revenue derived Reed Elsevier journals until links with the arms trade from the sale of reprints. Furthermore, damage to the are ended. They should make these decisions public, reputations of health journals including the Lancet could thus ending their tacit support for the company’s links have a negative impact on global health, which these with the arms trade. Direct loss of revenue in this way journals strive so hard to improve. would quickly identify to Reed Elsevier that the scien- It has not been a straightforward decision to speak tific world will no longer tolerate its warmongering and out directly on this issue. The BMJ is often seen as being health damaging business activities. in competition with the Lancet and might be seen to be cashing in on the Lancet’s discomfort. But the BMJ has 1 Smith R. Reed-Elsevier’s hypocrisy in selling arms and health. J R Soc Med 2007;100:114-6. no wish to see the Lancet diminished. The two publica- 2 Garne D, Watson M, Chapman S, Byrne F. Environmental tobacco tions are in many ways complementary, and together smoke research published in the journal Indoor and Built Environment and associations with the tobacco industry. Lancet they represent important evidence of the continuing 2005;365:804-9. influence of British publishing and science around the 3 Feder G, Rohde J, Sebastian M, et al. ��Reed Elsevier and the world. Collaborations between the BMJ and the Lancet international arms trade. Lancet 2005;366:889. 4 The Lancet and the Lancet’s International Advisory Board. Reed have repeatedly helped raise awareness of important Elsevier and the arms trade. Lancet 2005;366:868. issues in health care and research, 7-10 and more are 5 Times higher education supplement. Ethics before arms. www.thes. co.uk/search/story.aspx?story_id=2035528. planned. Anyone interested in global health should 6 Dyer O. Boycott publisher because of holdings in arms trade, readers want the Lancet to continue to thrive unhampered by told. BMJ 2007;334:389. 7 Farthing M, Horton R, Smith R. Research misconduct: Britain’s failure such disastrous bedfellows. As Smith says in his recent to act. BMJ 2000;321:1485-6. rapid response to a BMJ news article on this subject, 8 Godlee F, Horton R, Smith R. Global information flow. BMJ “Are people not bothered or are they scared to speak 2000;321:776-7. 9 Horton R, Smith R. Time to register randomised trials. BMJ up? Or perhaps people think that it would be disloyal 1999;319:865-6. to the journals, which include the Lancet. If people are 10 Horton R, Smith R. Time to redefine authorship. BMJ 1996;312:723.

548 BMJ | 17 March 2007 | Volume 334 We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they letters refer. Letters are thus an early selection of rapid responses on a particular topic. Readers should consult the website for the full list of responses and any authors’ replies, which usually arrive after our selection.

modernisation. We are passionate about structures can facilitate fair and effective quality, rigour, and humanity. action locally. Morris J Brown professor of clinical pharmacology Clinical governance must be University of Cambridge, Cambridge CB2 2QQ implemented in a facilitative and [email protected] On behalf of 25 senior consultants listed at www.bmj.com/cgi/eletters/333/7579/0-f#161670 non-oppressive way. The belief that Competing interests: None declared. medical errors are necessarily due to 1. Modernising Medical Careers. Wikipedia. http:// incompetence, carelessness, or recklessness en.wikipedia.org/wiki/Modernising_Medical_Careers 2. Brown MJ, et al. Raging against MTAS. Electronic for which naming, blaming, and shaming response to: Godlee F. Jam tomorrow. Editor’s choice. BMJ are appropriate responses is perhaps the SCOTT CAMAZINE/ALAMY SCOTT 2006;333:0-f. (2 December.) greatest obstacle to improving patient MMC safety.3 NHS organisations can also be Regulation idiosyncratic, self serving, and autocractic, Raging against MTAS so they react to problems in arbitrary and A suggested definition of MTAS (Medical Australia shows benefits of an sometimes capricious ways.4 Training Application Service) for independent tribunal Independence may not be sufficient to Modernising Medical Careers (MMC) for limit the potentially oppressive nature of Wikipedia1: “Appointment of doctors by UK doctors should welcome the transfer of governance when things go wrong.5 The lottery, plagiarism and creative writing; judging and deregistering doctors from the government needs to support a credible sacrifice of skill and track record at the altar General Medical Council to an independent and effective quality improvement system of political correctness. Like a bad dream, tribunal comprising legal, medical, and lay that meets the needs of patients and health consultants desert patients for days on end to personnel.1 This change, demanded by the professionals. read fragments of applications and interview profession in New South Wales in 1986, D B Double consultant�� psychiatrist ��Norfolk and Waveney candidates without cvs; while the juniors resulted in legislative amendments setting up Mental Health Partnership NHS Trust, Norwich NR6 5BE mind the shop until one day a website tells just such a tribunal under the chairmanship [email protected] Competing interests: None declared. them their career hopes are ended—wrecked of a district court judge. Parties have a right 1. Bruce DA. Regulation of doctors. BMJ 2007;334:436-7. (3 by MMC.” of appeal to the NSW supreme court. March.) This nightmare must stop. It is self Advantages to the public and profession 2. Secretary of State for Health. Trust, assurance and safety—the regulation of health professionals in the 21st indulgent to scream and rage, because time are that it is transparently clear that century. London: Stationery Office, 2007. is now pressing2; but junior doctors must unpopular doctors are not scapegoated 3. Reason J. Resisting cultural change. In: Lugon M, Secker- know that consultants are, at last, roused by and that misdemeanours of leaders of the Walker J, eds. Clinical governance in a changing NHS. London: Royal Society of Medicine Press, 2006. their fate. We need facts and action. How profession are not swept under the carpet. 4. Hittinger R, Fielding LP. Organizational culture: cultural many UK graduates were not shortlisted? The tribunal has the trust of all. indicators as a tool for performance improvement. In: Lugon M, Secker-Walker J, eds. Clinical governance in a How many places will remain in the second An advantage for the NSW Medical changing NHS. London: Royal Society of Medicine Press, round? How many juniors of distinction, Board (equivalent to the GMC) is that, 2006. deserving their first choice career, will be since 1987, it has not had to face public 5. King M. Community psychiatry inquiries must be fair, open and transparent. Times 4 Dec 2006. sacrificed if interviews of a more fortunate opprobrium about being too lenient or too majority are not aborted? severe, as has been the case for the GMC. Our leaders have pressed MMC and Peter C Arnold former deputy president, NSW Medical Board, Specialist centres ministers hard for changes before the Sydney, Australia [email protected] Competing interests: None declared. second round. Will politicians deliver when Haematologists should treat 1. Johnson J. Will we be getting good doctors and safer the news agenda has moved on? We fear patients? BMJ 2007;334:451. (3 March.) sickle cell disease movement of the deckchair variety, and that something titanic will hit the profession I understand the case for dedicated sickle if MTAS is not removed or reinvented Clinical governance can cell centres,1 but we should be wary of altogether. Thirty five thousand applicants— become oppressive centralising services for these patients. Day and the new UK medical schools have yet to centres are excellent, but during weekends produce a doctor. Bruce mentions the climate of fear and or nights patients may find access difficult. It is time for the mass of consultants to the culture of defensive practice created Also, these patients may come under the find voice. Please register your views at by increasing regulation of doctors.1 The care of non-haematology specialists in http://www.cai.cam.ac.uk/people/mjb14. government white paper on which his district general hospitals. The key to care You decide whether we call for a temporary editorial is based recognises that there has for patients in these circumstances is active halt, a back-to-the-drawing-board halt, been managerial over-reaction in NHS involvement of haematologists. Just as or complete resignation of the architects trusts.2 It also concedes that more should intensive care has adopted the “without of MMC. We are not against change or be done to ensure clinical governance walls” approach with readily available

BMJ | 17 MARCH 2007 | Volume 334 549 letters

outreach services, patients with sickle cell and anhedonia is more stringent than that Secondly, measurement of urinary disease should receive expert haematology for a formal diagnosis of depression. A sodium and urinary osmolality is unlikely input on a daily basis wherever they are in recent meta-analysis3 found that requiring to be informative in patients with renal the hospital. Support for non-haematology both symptoms to be endorsed caused many impairment, as interpretation of these tests staff—including good communication and depressed patients to be missed. Adding the assumes normal renal tubular function 24 hour availability of advice—would help help question can only make matters worse. to allow deductions to be made about them understand the problems and their Uptake of treatment in depressed pregnant underlying water or sodium homoeostasis. management and increase their experience and postpartum women is already low.4 In addition, measurement of urinary sodium and confidence. Women may be reluctant to seek help content is unlikely to be informative in Piotr Szawarski specialist registrar in anaesthesia because they have not had the opportunity patients taking natriuretic drugs (furosemide Queen Elizabeth Hospital, London SE18 4QH to discuss treatment options, including and enalapril in this case), as deductions [email protected] the relative risks and benefits of drugs, about underlying sodium homeostatic Competing interests: None declared. particularly in the context of any individual mechanisms are obscured by iatrogenic 1. Serjeant G. The case for dedicated sickle cell centres. BMJ 2007;334:477. (3 March.) risk associated with a personal or family tubular dysfunction. These two factors history of prolonged, severe, or otherwise will probably apply to many patients with impairing depression. The NICE guidelines hyponatraemia and will limit the clinical US cancer centres show the way may deny these women the chance to make usefulness of these urinary tests. an informed choice between psychotherapy Mat Davies consultant�� nephrologist The ethos of a true cancer centre seems to and drugs.5 University Hospital of Wales, Cardiff CF14 4XW [email protected] have been lost on the groups concerned.1 James C Coyne professor of psychology in psychiatry Competing interests: None declared. The US model of a cancer centre, overseen University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA [email protected] 1. Smellie WSA, Heald A. Hyponatraemia and by the National Cancer Institute, is a facility hypernatraemia: pitfalls in testing. BMJ 2007;334:473-6. with true expertise in medical oncology, Alex J Mitchell consultant in liaison psychiatry (3 March.) Leicester General Hospital, Leicester LE5 4PW surgical oncology, and radiation oncology Competing interests: None declared. with a multidisciplinary approach and all Publisher boycott Editorial p 547 necessary ancillary support. These centres 1. Mayor S. Guidance recommends asking pregnant women about mental health. BMJ 2007;334:445. (3 March.) are staffed by personnel with specific 2. National Institute for Health and Clinical Excellence. We must challenge war training and offer extensive fellowship Antenatal and postnatal mental health: clinical management and service guidance. London: NICE. www. programmes to develop the national cancer nice.org.uk/guidance/CG45. It is all very well for publishers of medical programme. The centres offer the index 3. Mitchell AJ, Coyne JC. Do ultra-short screening instruments journals, drug companies, and even level of cancer care. It seems bizarre that accurately detect depression in primary care? A pooled private healthcare institutions to say they analysis and meta-analysis of 22 studies. Br J Gen Pract several royal colleges should be dismayed 2007;57:144-51. are involved in the “legitimate defence that non-specialist centres may lose control 4. Flynn HA, Blow FC, Marcus SM. Rates and predictors industry,”1 but arms fairs also sell torture of depression treatment among pregnant women of cancer services in the United Kingdom; in hospital-affiliated obstetrics practices. Gen Hosp equipment and traders have no qualms the primary endpoint of cancer care should Psychiatry 2006;28:289-95. about selling equipment to regimes that be excellence in clinical care with patient 5. Bonari L, Koren G, Einarson TR, Jasper JD, Taddio A, might be seen as less than legitimate or Einarson A. �U��se of antidepressants by pregnant women: outcome reflecting this. It is imperative that Evaluation of perception of risk, efficacy of evidence legal. How “legal” is most oppression and cancer centres in the UK have appropriate based counseling and determinants of decision making. does legality reflect morality? “Legitimate staffing with experts in clinical care to ensure Arch Women’s Ment Health 2005;8:214-20. defence” in the modern world seems to this happens. involve many more civilians than soldiers; Malcolm R Kell consultant�� surgeon ��Breastcheck, Eccles Unit, Diagnosing hyponatraemia hospitals and humanitarian organisations are Dublin 7, Republic of Ireland [email protected] in the direct firing line and much of it seems Competing interests: None declared. Urine tests are often unhelpful to go on in someone else’s country. 1. Eaton L. Experts call for close scrutiny of new cancer centres. If we, as healthcare professionals, are BMJ 2007;334:447. (3 March.) In their discussion of the management of serious about improving the lot of humanity, hyponatraemia in primary care, Smellie and I think it is our duty to encourage the firms Postpartum depression Heald correctly emphasise the importance we work with to think twice about their of investigating sudden changes in serum moral decisions. If profit at any cost is NICE may be discouraging sodium, but the investigational strategy the bottom line, then we may as well give detection they advocate is incorrect.1 Firstly, they up now. If we continue to support these advocate submitting a sample for urine companies, then we have a direct line of National Institute for Health and Clinical osmolality measurement after discussion responsibility to the child maimed by the Excellence (NICE) recommends these with the laboratory of the serum osmolality unexploded cluster bomb. questions for routinely screening pregnant on a prior sample. However, measurement Those of us working in health care have a and postpartum women for depression: of serum and urine osmolality must be moral imperative to speak out and directly has she been sad or blue for at least two contemporaneous to be meaningful, as challenge any involvement in war. weeks; has she had anhedonia for that urine osmolality may be labile in response Marion Leighton medical registrar,Wellington Hospital, period; has she sought help for these to changes in hydration status. The likely Wellington, New Zealand [email protected] problems?1 The NICE website offers no timescale of obtaining a second sample in Competing interests: None declared. 2 1. Dyer O. Boycott publisher because of holdings in arms empirical support for these criteria. The primary care makes this strategy unworkable trade, readers told. BMJ 2007;334:389-c. (24 February, requirement that women endorse sadness and the results uninterpretable. online.)

550 BMJ | 17 MARCH 2007 | Volume 334 For the full versions of articles in this section see bmj.com UK NEWS Spending watchdog slates doctors’ provision for out of hours care, p 556 news World NEWS F�rench�� doctors sign petition for euthanasia to b�e�� decrim�inalised��,�� p 555 bmj.com M�ore�� m�utated�� genes involved in cancer than previously thought�� Fracture risk is a class effect of glitazones

Robert Short London Treatment with thiazolidinediones (glitazones) for type 2 diabetes has been found to increase the risk of fractures in women. Pioglitazone has now joined rosiglitazone, as the subject of a US Food and Drug Adminis- tration alert for fracture risk. Takeda, the makers of pioglitazone (contained in Actos, Actosplusmet, and Duetact), and GlaxoSmithKline, the makers of rosiglitazone (contained in Avandia and Avandamet), have contacted US healthcare professionals setting out the evidence on fracture risk and recommending that they consider this risk when starting or treating women with type 2 diabetes with these agents. ex The statement on pioglitazone was posted R

on 9 March as an FDA MedWatch safety ayer/ l information alert. Takeda reported findings from an analysis of its clinical trial database, comparing patients treated with pioglitazone JonathanP (more than 8100 patients) with a comparator (more than 7400 patients given placebo UK report recommends better or active agent). The analysis showed an increased risk of fractures in women taking pioglitazone compared with women taking planning for phase I drug trials a comparator. Most of the excess fractures were in the Susan Mayor London Stephen Senn, professor should include quantitative distal upper limb (forearm, hand, and wrist) The first trials of new drugs in of statistics at the University justification of the starting or distal lower limb (foot, ankle, fibula, and humans should be planned of Glasgow and chairman of dose based on appropriate tibia). much more carefully, with the working party, said, “The preclinical studies and The incidences of fractures in the piogli- the same clarity of purpose, fact that so many volunteers relevant calculations; tazone and comparator groups were 1.9 design, and analysis as for simultaneously suffered severe assessment of the risk level and 1.1 per 100 patient years. The excess studies supporting drug reactions clearly signalled that for the recommended study risk of fractures for women in this dataset licensing, a report published the design of the TGN1412 trial dose; and appraisal of the is, therefore, 0.8 fractures per 100 patient this week recommends. might have been deficient.” uncertainty about these years of use. The report, published by He considered that many early recommendations. The fracture side effect with a thiazoli- a working party of the Royal phase studies lack clear aims or Documentation of this dinedione was first discovered in Decem- Statistical Society, was plans for analysis. “Researchers information should be given ber 2006 in the ADOPT study (a diabetes prompted by the TGN1412 are uncertain about what they to the ethics committee, study outcome progression trial; N Engl J Med drug trial last year in which six are going to find, so they don’t participants, and insurers. 2006;355:2427-43). healthy volunteers, including document in detail the study Volunteers taking part in The primary goal of the study was to Navneet Modi (above) design or how they will analyse trials should be fully informed compare glycaemic control with rosiglita- experienced severe immune what they find.” about possible risks. See zone relative to metformin and to glyburide reactions (BMJ 2005;332:683). The working party Observations, p 566-7. monotherapies in 4360 randomised patients. It found that “the trial design recommended that phase I, The Report of the Working Party In a late finding published as a “note added was not well suited to its “first in man,” studies should on Statistical Issues in First-in- in proof,” however, more women in the ros- objectives of testing the safety be designed and described Man Studies is at www.rss.org. iglitazone group had upper limb fractures and tolerability of the drug.” much more carefully. This uk/first-in-man-report. involving the humerus and hand.

BMJ | 17 March 2007 | Volume 334 551 NEWS

If Lilly’s drug teriparatide had been approved under the scheme, patients would Lilly’s challenge to Australia’s have paid a maximum of $A30.70 per prescription, with the government paying the rest drug rationing scheme fails of the cost. A year’s supply of the drug costs about $A10 000 (£4000; €5900; $7800). Bob Burton Canberra whether a change, introduced through the In June 2003 and March 2004 the commit- Eli Lilly Australia has failed to overturn the Australia-US free trade agreement, would tee rejected the company’s applications for repeated rejection of its osteoporosis drug make it easier to overturn decisions made the approval of teriparatide as a second line teriparatide (Forteo) from being included in by the Pharmaceutical Benefits Advisory treatment after the failure of antiresorptive the government’s drug subsidy scheme. An Committee. That committee decides which therapy. In July 2005 Lilly’s request that the independent review, requested by the com- drugs are included in Australia’s pharmaceu- drug be approved for treating severe forms pany, dismissed the clinical data in Lilly’s tical benefits scheme, under which patients of vertebral fractures was also rejected, as submissions as inadequate. receive them at a subsidised rate (BMJ was Lilly’s later request that it be approved The review was seen as a test case on 2006;333:1239). for treating severe fractures.

Exempt MRI scanners from new EU rules, say campaigners Rory Watson Brussels to the EU legislation, to Medical specialists, patients’ address the problem. groups, and European Gabriel Krestin, professor parliamentarians launched a of radiology at Erasmus campaign last week to ensure University Medical Center that new EU health and safety in Rotterdam, estimates that legislation will not restrict the the new restrictions might use of magnetic resonance affect up to eight million imaging (MRI). MRI examinations in the The Alliance for MRI European Union every year. fears that new Europe-wide He calculates these would measures, which are designed include 400 000 procedures to protect employees from involving children or very ill short term exposure to people and 80 000 patients electromagnetic fields, will under anaesthesia. He thinks inadvertently make it harder the legislation will make the to use equipment to diagnose examination of many patients and treat illnesses from cancer with life threatening illnesses and heart attacks to strokes and practically impossible. brain tumours. Nicholas Gourtsoyiannis, The legislation will limit the president of the European time that operators may spend Society of Radiology, which is near MRI machines when in one of the alliance’s founding h/photofusion c use. The alliance warns that members, said at the launch, this will make it more difficult “It is essential that this libbywel for medical staff to help major advance in healthcare patients such as children and technology is not threatened by Laughter, learnt of friends elderly people during scans burdensome legislation when and would stop the use of MRI concerns can be addressed Annabel Ferriman bmj for surgical procedures. through responsible guidance.” Claire Holland (left) and Tracey Butler are friends and colleagues who work The European Commission The Alliance for MRI points for a company called Raise! Mental Health, a training company dedicated to is writing to EU governments out that this important medical raising awareness of mental health issues. Tracey is Claire’s boss. to inform them that it is closely tool has been used safely for 25 All company members have, or have had, a mental health problem—in monitoring the situation. It years. It wants implementation Claire’s case bipolar disorder and in Tracey’s case schizophrenia. confirmed to the BMJ this of the legislation, which is due The pair has been photographed for a poster, entitled Laughter, by week that if new substantial to operate from April 2008, to Stephen Rowell to celebrate mental health action week (8-14 April). The evidence emerged that medical be frozen until the findings of a week is being organised by the Mental Health Foundation. procedures could be unduly European Commission impact To order free copies of the posters or booklets email [email protected]. affected it would consider assessment are known later this ways, including an amendment year.

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and publicly traded on the Shanghai Stock WHO confronts Exchange, is refusing to halt sales, which in brief Chinese company amounted to $5m (£2.6m; €3.8m) in 2004, Poorer women fare worse with breast according to the Wall Street Journal (http:// cancer: Women from more deprived over malaria drug online.wsj.com, 6 Mar, “China’s pride on backgrounds are likely to wait longer to line in malaria clash”). be seen and are diagnosed with more Anne Glusker Geneva The confrontation may prove awkward for advanced breast cancer than women from The World Health Organization is asking a Margaret Chan, the newly elected director more affluent backgrounds, a study by Chinese pharmaceutical company to stop general of WHO, who is from Hong Kong. Cancer Research UK has found (British Journal of Cancer 2007;96:836-40). The making a malaria drug that earns millions One of the questions raised about Chan’s study looked at 13 000 women and found of dollars annually in revenues. candidacy was whether or not she would be that those from the most deprived areas The move is part of a campaign to combat able to stand up to China when necessary. were less likely to have a lumpectomy and increasing resistance to antimalarials and to Kunming’s drug is based on artemisinin, radiotherapy and had a lower five year promote use of combination treatments. The which is derived from a plant used in survival than women from richer areas. drug’s manufacturer, Kunming Pharmaceu- Chinese traditional medicine for centuries. tical, which is owned by the Holley Group Chinese scientists developed the drug, and Hospital restrictions on mobile Mobile Kunming introduced its product in the phones should be lifted: telephones do not interfere with medical 1980s. equipment when used normally in “This is not fair to China,” Yu Zelin, hospitals, according to a study in the general director of international trade at Mayo Clinic Proceedings (2007;82:282- Kunming, told the Wall Street Journal. “We 5). The investigators, who call for a have developed the drug ourselves. We have revision of restrictions on their use, made so much effort.” examined telephones from two different But with resistance to malaria drugs such service providers in patients’ rooms containing a total of 192 medical as chloroquine, sulfadoxine-pyrimethamine, devices such as electrocardiographs, and amodiaquine on the rise, and between ventilators, and ultrasound imaging ho

W 300 and 500 million cases of malaria (and a machines. In 300 tests, they found no million deaths) a year, WHO’s malaria chief, instances of interference. Two personal erre/ F

c Arata Kochi, has stepped up the campaign digital assistants tested 40 times near ar

M to stop drug companies selling monothera- 24 medical devices caused no problems either. ean- J pies, which WHO believes lead to drug Will Dr Margaret Chan be able to stand up to China? resistance. Global fund saves 1.5 million lives: The Global Fund to Fight AIDS, Tuberculosis and Malaria has announced that the lives of more than 1.5 million TB and AIDS researchers fail to people worldwide have been saved as a result of programmes supported by the fund during its first five years in existence. work together, article says For country by country details see www. theglobalfund.org/en/in_action/events/ tgf_5years. Michael Day London A leading concern among doctors in A rift between doctors in the HIV and tuber- the field is an emerging condition called Hungarian hospitals face closure: culosis communities is undermining the fight immune reconstitution inflammatory syn- Hungary is to close three major hospitals against both diseases, an article in Nature drome (IRIS) in patients with tuberculosis and reorganise many others, saving Medicine has claimed (2007;13:268-70). who receive anti-HIV drugs, which affects 10�� 000 hospital beds and cutting As HIV infection rates continue to rise about 20% of them. thousands of healthcare jobs. The and Africa witnesses the alarming spread of These patients develop serious stomach closures announced by the health minister Lajos Molnár will affect Svábhegy extensively drug resistant tuberculosis (XDR abscesses and brain lesions and some die. Children’s Hospital, the National TB), the two research communities are fail- “Nobody knows how to deal with it,” said Psychiatry and Neurology Centre, and ing to combine forces against what is effec- Robert Wilkinson, of the University of Cape Schöpf-Merei Ágost Hospital, all in tively a dual epidemic in many parts of the Town. Budapest. developing world. Paul Nunn, of the World Health Organiza- Tuberculosis is the leading cause of death tion’s Stop TB programme, is more dismiss- Government launches inquiry into among people infected with HIV, and in ive: “This is what you find when you talk to deaths of people with learning some African countries about 60% of people academic researchers whose job it is to go difficulties: The UK Department of Health is holding an inquiry after the charity with tuberculosis are also HIV positive. and look for problems,” he told Nature Medi- Mencap highlighted six deaths of people Despite this, the report in Nature Medicine cine, adding that IRIS had yet to be properly with learning disabilities in NHS care. says that HIV and tuberculosis researchers defined either clinically or in terms of its glo- Mencap says there is a lack of training and are failing to collaborate—and cannot even bal impact. understanding in the NHS of how to care agree on the extent of the threat posed by See www.nature.com/nm/index.html, www. for people with learning difficulties. side effects to the treatments they provide. unaids.org/en, and www.who.int/tb/about/en.

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More evidence shows better outcomes for vascular surgery at high volume hospitals

Roger Dobson Abergavenny (2007 Mar 14, doi: 10.1002/ used hospital episode statistics financial implications for the Patients with abdominal aortic bjs.5725). for 2000-5 to investigate the funding of surgery, pressure aneurysms have better chances “Our research adds to the relation between the annual on intensive care beds and the of survival when they are evidence that concentrating number of repairs done by transfer costs of emergency operated on at hospitals that surgical resources in large a hospital and the outcomes patients,” say the authors. handle large numbers of cases, a centres of excellence can of surgery. The results show They add, “Although hospital new report shows. provide great benefit to that between April 2000 and volume and surgeon volume Having elective surgery patients. A bad outcome in March 2005 there were 112 527 were independent predictors of at hospitals with the greatest this type of surgery is death, diagnoses or repairs of aortic death, with an additive effect, volume—those doing more than and specialist centres are best aneurysms (pictured) in the for other vascular procedures 32 repairs a year—reduced the placed to prevent it,” said the United Kingdom. it has been demonstrated odds of mortality by a third lead author, Peter Holt, of the The researchers then that low-volume surgeons compared with the lowest Vascular Institute at St George’s quantified the effects of can achieve similar results volume centres, say researchers Hospital, London. transferring services to higher to high-volume surgeons in the British Journal of Surgery In the study, the authors volume hospitals and the when operating in a high- number of excess deaths with volume hospital, suggesting the current arrangement of that hospital infrastructure services: “Elective surgery is a key component in this at hospitals that performed relationship.” fewer than 32 repairs per year A second paper (doi: resulted in 46 excess deaths per 10.1002/bjs.5710) reports the annum, or 15 per 1000 cases,” findings of a meta-analysis they say. and systematic review that For urgent repairs, a identified data from 26 studies, significant reduction in mainly from the United States, mortality was also seen with which together involved more greater annual volume. than 350 000 patients. However, there was no The paper indicates that a reduction in mortality, centre needs to be performing complication rate, or duration surgery on at least 43 of hospital stay with increased abdominal aortic aneurysms annual volume for ruptured a year before it could provide aneurysms. significantly greater chances of “There is an argument success.

l that volume criteria should Results show that mortality p s be established for elective fell as the number of operations SM/ I and urgent abdominal aortic increased: “This suggests that aneurysm surgery in the UK. surgery should be performed

Sovereign, There would be significant only at higher-volume centres.” Audit identifies the most read BMJ research papers Susan Mayor London Sara Schroter, the BMJ’s senior researcher, The online version of this paper was accessed Research studies on the side effects of analysed research papers using three measures: 42 505 times in the first year after publication. commonly prescribed drugs constituted the the number of citations a paper received, the It received 28 rapid responses and was cited 97 three most read papers published by the BMJ number of times it was accessed on the web, and times in 2005 and 2006. in 2005, according to an internal audit that the number of rapid responses it generated. At the time, there was widespread interest in the assessed their use by readers. The top scoring paper was a case-control study cardiovascular safety of COX 2 inhibitors after the Studies that showed increased risk of that showed greater risk of myocardial infarction withdrawal of Vioxx and the publication of several myocardial infarction in patients taking cyclo- in patients taking the COX 2 inhibitor rofecoxib papers on the risk associated with these agents. oxygenase-2 (COX 2) inhibitors and that explored (Vioxx) and in patients taking diclofenac and A meta-analysis of drug company data that the link between selective serotonin reuptake ibuprofen (2005;330:1366-9, doi: 10.1136/ showed no evidence that selective serotonin inhibitors and suicide came top. For the audit bmj.330.7504.1366). reuptake inhibitors increase the risk of suicide

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Doctors sign petition calling for euthanasia to be decriminalised Brad Spurgeon Paris More than 2000 doctors, nurses, and other health workers have published a petition in a French news magazine admitting to having assisted the deaths of terminally ill patients at some time in their careers (Le Nouvel Observateur 2007 March 8:98). ion s The petition was published four days before a trial opened in Perigueux, in south hotofu

P west France, of a doctor and a nurse accused ch/ l of killing a 65 year old patient who was terminally ill with pancreatic cancer by admin-

LibbyWe istering a lethal dose of potassium in August 2003. If they are found guilty, the two risk Reid wrong about comfort of up to 30 years in prison. The petition (www.nouvelobs.com) calls for an immediate end to the legal pursuit smoking, research shows of health workers for euthanasia; an immediate change in the law, to decriminalise Roger Dobson Abergavenny To see whether pleasure and better qual- euthanasia and allow it under certain cir- Smoking is not associated with better quality ity of life were associated with smoking, cumstances, as in Switzerland, Belgium, and of life or increased pleasure. the team from Peninsula Medical School in the Netherlands; and a call for appropriate Results from a study that investigated links Exeter and Cambridge University analysed methods to accompany patients at the end of between smoking and pleasure and quality of data from a study of 9176 men and women life, whether it be in the home, hospitals, or life showed no evidence to support a contro- aged 50 years or more who took part in the retirement homes, and with dignity. versial comment by the former health secre- health survey for England. “We, medical workers, have, consciously, tary John Reid (now the home secretary) that The survey data they used included details medically assisted patients to die with for some people their only enjoyment was about past and present smoking habits and decency,” said the petition. It added that having a cigarette (Public Health 2007 Mar 2, household wealth as a marker for socioeco- while not all medical workers are confronted doi: 10.1016/j.puhe.2007.01.005) nomic position. A quality of life test included with such a dramatic situation, the majority of “We found no evidence to support a claim items assessing pleasure. Typical statements them do regularly help their patients die, using that smoking is associated with heightened that participants were invited to agree or dis- “chemical substances that speed up an end to levels of pleasure, either in low socioeco- agree with were “I look forward to each day” life that is otherwise too cruel, knowing full nomic groups or in the general population. and “I enjoy the things that I do.” well that this is currently against the law.” In fact, our results suggest the opposite… The odds ratio for experiencing lower The petition comes during the country’s “As a group, smokers have lower levels than median levels of pleasure for smokers presidential election campaign, at a time of pleasure and quality of life than those in low socioeconomic groups was 1.42 (95% when both leading candidates, Nicolas who have never smoked, with ex-smokers confidence interval 1.16 to 1.74), and for all Sarkozy and Ségolène Royal, vowed to open in between,” say the authors. smokers it was 1.33 (1.17 to 1.51). the debate on euthanasia if elected. The petition was led by Dr Denis Labayle, of a hospital in Courcouronnes, near Paris, but found weak evidence of increased risk of self practical issues, including a trial of calcium and it recognises the improvements brought harm was ranked second (2005;330:385-10, doi: and cholecalciferol for prevention of about by the Leonetti law of April 2005, 10.1136/bmj.330.7488.38). This was accessed fractures (2005;330:1003-6, doi: 10.1136/ which allows doctors under certain circum- almost 24 000 times and was cited 78 times in bmj.330.7498.1003), a prospective study stances to stop treatment and let patients die. 2005 and 2006. of cannabis use and psychotic symptoms in It said that the Leonetti law does not go far In third place was a systematic review that young people (2005;330:11-4, doi: 10.1136/ enough (BMJ 2004;329:1307, 4 December showed an association between suicide bmj.38267.664086.63), and a review of how doi: 10.1136/bmj.329.7478.1307). attempts and the use of selective serotonin well B-type natriuretic peptide predicts The French Society for Accompaniment reuptake inhibitors and that highlighted death and cardiac events in patients and Palliative Care launched an immediate p photo p limitations in the reporting of suicides with heart failure (2005;330:625-7, doi: a counterattack on the petition with another in clinical trials (330:396-403, doi: 10.1136/bmj.330.7492.625). petition on the internet at www.sfap.org. hizer/

10.1136/bmj.330.7488.396). Competing interests: SM writes regularly ls That petition calls for signatures from health hu Other studies in the top 10 addressed for the BMJ and is paid for her contributions. l professionals and organisations that oppose nie a

d euthanasia.

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Organ recipients may Spending watchdog slates die when insurance for drugs runs out doctors’ out of hours provision Fred Charatan Florida Lynn Eaton London tive to opt out—in that they could do a lot Young transplant recipients who lose their Doctors were the only winners from changes less work for a small loss of income. insurance coverage are more likely to in 2004 to out of hours provision, states a “To cap it all, the cost of the new out of stop taking essential anti-rejection drugs, report from the government’s spending hours service is around £70 million a year which can increase their risk of organ loss watchdog, the Public Accounts Committee. more than was expected. That’s the last thing and death, a new study shows (Pediatric As far as patients are concerned, they lost the primary care trusts need at this time of Transplantation 2007;11:127-31). out—not only because of a reduction in the increasing financial pressure.” “Kids with transplanted kidneys who quality of the service, but because of the According to the committee, about nine lose their insurance have a nine times additional financial burden on them as tax- million patients receive urgent primary out greater chance of dying than those payers, says the report. of hours care in England every year between who don’t,” said leading author Mark The findings, published on Wednesday, 6 30 pm and 8 am on weekdays, at all times Schnitzler, associate professor in the look at the changes in GP out of hours cover during weekends, and on public holidays. departments of internal medicine and introduced in 2004. Before then, GPs pro- The report criticises the Department of community health at St Louis University. vided the cover themselves, either by pool- Health for failing to explain to PCTs whether “Immunosuppressive drugs that prevent ing together to operate as a cooperative when the service was for urgent cases only or for organ rejection are incredibly expensive; their surgeries were closed or by paying for all requests for help. And it says the £6000 sometimes more than $13 000 (£6700; a commercial deputising service. After 2004, annual fee for doctors who chose to let their €9900) a year. Even for families with they were able to opt out of this arrangement. PCT provide cover was a “serious underes- insurance, the co-payments can be a huge Instead they paid £6000 a year to their local timate” of the likely costs—even when it was financial burden,” he primary care trust (PCT), which took over partly topped up by the health department. “It is critical that added. responsibility for the provision. An additional Hamish Meldrum, chairman of the BMA’s we find a way In the United amount was paid to PCTs from the Depart- General Practitioners Committee, comment- to offer lifetime States, Medicare ment of Health towards the service. ing on the report, said, “Family doctors had access to these pays for most But preparations for the new arrange- been taken advantage of for years, working children” organ transplants. ment were shambolic, says the committee. long hours on the cheap. When, with the However, coverage Although the service is starting to improve, full agreement of the government, primary of immunosuppressant drugs ends 36 to 44 performance against key targets, such as the care organisations took over responsibility months after surgery, or when the patient time taken before patients are seen by the for providing the [out of hours] service and reaches adulthood. Only about 30% of doctor, is still low. And it is costing £70m in some places failed to make a good job of young adults have health insurance. For (€102m; $135m) a year more than expected, it—they try to blame the GPs. It’s not right people who have employer sponsored or says the report. and it’s not acceptable. private health insurance, coverage ends “The Department of Health thoroughly “We want patients to have high quality, once a patient reaches a lifetime maximum mishandled the introdution of the new sys- safe services around the clock, staffed by amount stipulated by their policies. tem of out of hours care,” said Edward Leigh doctors who are not worn out from having As a result of these factors, many organ MP, chairman of the committee. done a full day’s work before they start an recipients stop taking immunosuppressant He said doctors were given a strong incen- evening or weekend shift. drugs; transplanted organs are rejected and patients’ lives are shortened. Dr Schnitzler and his team studied the medical records of 1001 children who received a donor MPs broadly welcome proposals for health research in United Kingdom kidney between 1995 and 2001, half of whom lost their health insurance. Zosia Kmietowicz London Dr Schnitzler said: “It is critical that we A review by MPs of proposals on how £1bn find a way to offer lifetime access to these (€1.5bn; $1.9bn) worth of publicly funded children and their families so that our health research should be allocated in the United society does not continue to prematurely Kingdom has raised concerns about introducing targets to set research priorities. lose this promising pool of young adults.” pics “Pediatric transplant recipients have m The cross party Science and Technology every desire to become independent and Committee has broadly welcomed the conclusions

useful members of society.” ickett/pa/e reached by Sir David Cooksey in his review R He and his colleagues concluded that published in December (BMJ 2006;333:1239, 16

new public policies requiring lifetime Martin Dec) on how healthcare research can be improved healthcare coverage for organ transplant Phil Willis wants to ensure that money meant for to bring more tangible benefits to patients. recipients would be cost effective, and research is not diverted to other purposes The committee says it has reservations about would prolong patients’ lives.

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1996 and 1999 he took hundreds of ova from private patients undergoing fertility treatments—without their permission. He produced extra ripened eggs in some of them by using hormones to overstimulate the women’s ovaries, which can be dangerous. In 2000, he was also caught paying $20 000 (£10�� 400; €15�� 000) to a man who posed as a policeman in exchange for promises that the criminal file against him would be closed. Professor Ben-Raphael removed 232 ova from one l woman without her permission and used 155 of them for in vitro fertilisation of 33 infertile women. In another case, 53

Motta & Makabe/sp& Motta eggs were surgically removed, and 30 were used. Doctor’s licence suspended after he admitted He took 256 ova from a third patient, and 181 of them were removing hundreds of ova without consent used for fertility treatments in 34 women. Even when women Judy Siegel-Itzkovich JeRusalem a department head of the Rabin women not undergoing fertility agreed to donate extra eggs, he One of Israel’s leading fertility Medical Centre-Beilinson treatments themselves to removed more of them than experts and a former chief of Campus, will be punished donate ova altruistically, has he said he would. In none of gynaecology at one of its largest following a ruling by retired dragged on for seven years. these cases was the taking of public hospitals will lose his Jerusalem District Court The process, which never eggs recorded in medical files. medical licence for two and president Judge Vardi Zeiler, went to court, included a plea In total, six women filed police a half years after admitting who is responsible for deciding bargain with the state attorney’s complaints against him. that he removed hundreds of cases after medical personnel office in which Professor Ben- Ameliorating circumstances ova from private patients at appear before a health ministry Raphael admitted guilt. The cited by Judge Zeiler for the the Herzliya Medical Centre disciplinary panel. case was one of the country’s relatively mild punishment without permission and without The case, which induced most serious involving a included the fact that the registering the procedures in the government to alleviate gynaecologist. doctor had given years of their medical records. the shortage of donor ova The 57 year old doctor “impressive service” to the Zion Ben-Raphael, formerly by changing the law to allow admitted that between Israel Defense Forces.

MPs broadly welcome proposals for health research in United Kingdom

some aspects of the proposals, however, and will Coordination of Health Research, will be the always been the case in the past with NHS funding. be taking “a close interest in reviewing progress central coordinating body for all health research, “The Cooksey Review proposals offer a sound and how the new institutional arrangements will responsible for setting the research budget and basis for the implementation of the single fund for work in practice.” identifying projects that address unmet needs. health research.” In his review, which was commissioned by It will bid for treasury money and allocate it as it The committee expressed concern, however, Gordon Brown, the chancellor of the exchequer, sees fit to the Medical Research Council and the that the Office for Strategic Coordination of Health Sir David proposed creating two new bodies to National Institute for Health Research. The other Research (OSCHR) would set targets and objectives deliver a research strategy that brings together the body—the Translational Medicine Funding Board— for the Medical Research Council and the National two separate funding streams for public health will direct money towards projects that promise Institute for Health Research to define research research in the UK—the Medical Research Council heath benefits and innovation. priorities. MPs were worried that the office would (MRC) and the NHS’s National Institute for Health Phil Willis, chairman of the committee, said, “The adopt a top down approach. Research. committee wishes to see all funding allocated to The Cooksey Review is available at www. One of the new bodies, the Office for Strategic health research used for that purpose. This has not parliament.uk/s&tcom.

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SHORT CUTS

What’s new in the other general journals Alison Tonks, associate editor, BMJ [email protected]

Primary care fails people with Screening for lung cancer must wait Randomised trials under way in Europe for better evidence and the US should tell doctors and smokers anxiety exactly what they need to know about the Anxiety disorders are common, disabling, EFFECT OF CT SCREENING FOR LUNG CANCER risks and benefits of lung cancer screening and costly. But so far they have received with CT. In the meantime, even enthusiasts Detected on CT Predicted Number at risk only meagre attention from researchers and should reserve their judgment. Surgical resections for lung cancer policy makers. This neglect is particularly 160 3500 k JAMA 2007;297:995-7 serious in primary care populations, where JAMA 2007;297:953-61 ents (n) ents 120 2625 No at ris at No anxiety disorders tend to go unnoticed and Ev

untreated, say commentators from Seattle. 80 1750 The situation is different for depression, Thailand reduces child deaths and although the two mental health problems 40 875 often coexist. health inequality Two new screening tools may help. Both 0 0 In 1990, 27 of each 1000 children born in

ask patients how many days in the past two After CT screening Predicted Number at risk Thailand died before reaching their fifth weeks they have been bothered by symp- Deaths from lung cancer birthday. By 2000, this figure had fallen toms such as uncontrolled worry, fear, 160 3500 k by a third to just under 19. Importantly,

nervousness, or irritation. The short version ents (n) 120 2625 death rates fell fastest among the poor. An No at ris at No has just two items, the longer has seven, so Ev analysis of data from two national censuses neither should take long. Both were reason- 80 1750 shows that in 1990 the poorest fifth of the ably good at picking up anxiety disorders in Thai population had a mortality rate among people attending primary care in the United 40 875 under 5s that was three times higher than States (pp 317-25). They worked best for the richest fifth. By 2000 the mortality gap 0 0 general anxiety disorder. Overall, nearly one 0 1 2 3 4 5 6 between rich and poor had halved. How Years in five primary care patients in the sample Adapted from JAMA 2007;297:953-61 did they do it? had at least one common anxiety disorder. Economic development certainly helped, Many had several. All were associated with Screening for lung cancers with computed say the authors. During the 10 years under significant functional impairment. Only 41% tomography (CT) remains an experimen- study, people in Thailand got richer and (77/188) of the affected patients were being tal and unproved intervention that may do the benefits of the economic boom were treated. more harm than good, says an editorial. well distributed, which reduced economic These findings and others, “indicate a seri- There’s no consistent evidence that screening inequality. At the same time, a series of ous failure in the management of anxiety in saves lives, even when offered only to heavy health insurance programmes made health the primary care setting” say the commenta- smokers. But it does increase the chance of care affordable, primary clinics were estab- tors. Screening and diagnosis are only part of invasive tests, biopsies, or even a resection. lished in every village, and the number of the solution. Patients also need much better Mortality after lung resections is about 5% healthcare visits quadrupled. Family plan- access to treatments that have been proved in the United States. ning, skilled birth attendants, and childhood to be effective, such as cognitive therapy. The editorial’s authors were comment- vaccinations all became widely available. Ann Intern Med 2007;146:390-2 ing on a cohort study of 3246 current or By the end of the 1990s women were hav- Ann Intern Med 2007;146:317-25 ex-smokers who had at least three annual ing fewer children, and 90% of them were CT scans (pp 953-61). The scans detected being vaccinated against diphtheria, pertus- NUMBER OF DISORDERS three times as many cancers as would have sis, tetanus, measles, and poliomyelitis. AND WORSENING FUNCTION been expected without screening (relative Unlike many other countries, Thai- Pain Role Social risk 3.2, 95% CI 2.7 to 3.8), and resulted land is now on track to meet the 4th mil- Physical General Mental in 10 times as many resections (10.0, 8.2 to lennium development goal and reduce 0 11.9). But screening did not reduce the risk childhood deaths by two thirds by 2015 -0.5 of an advanced cancer and had no overall Lancet 2007;369:850-5. impact on mortality (1.0, 0.7 to 1.3). -1.0 This kind of study is always a compro- -1.5 mise, however. The researchers had no con- Occipital nerve stimulation for trol group, so they used a prediction model -2.0 chronic cluster headache Functional score: effect size to guess what would have happened without -2.5 1 2 3-4 screening. It’s possible the model was biased, Chronic cluster headaches don’t always Anxiety disorders (n) and the researchers warn that their findings respond to traditional medical treatments Adapted from Ann Intern Med 2007;146:317-25 are preliminary. such as verapamil and lithium, leaving some

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patients with frequent, intense, and disabling tudes, relationships, and nutrition), and the disease or death (hazard ratio 2.34, 95% CI headaches. Researchers are currently inves- Ornish diets—worked about as well as each 1.80 to 3.05). tigating occipital nerve stimulation as a other. Women on these diets lost 1.6-2.6 kg In this cohort of more than 14 000 possible rescue treatment and two separate on average compared with 4.7 kg for women women, developing a new abnormality teams now report that it can work well in on the Atkins diet. The difference between was also risky. Women who started the selected patients. Atkins and the others was significant after study with a normal ECG but developed Both teams treated eight patients who had only two months and peaked at six months evidence of ischaemia, atrial fibrillation or had chronic cluster headaches for between (P<0.05 for all comparisons). flutter, ventricular hypertrophy, abnormal two and 12 years. Five of the eight patients The researchers chose these diets because excitation, or repolarisation were more given unilateral stimulation from implanted they form a continuum of weight loss strate- than two and a half times more likely to electrodes said their headaches improved gies, with the Atkins diet (low in carbohy- develop clinical cardiovascular disease more than 90% during the first two years of drate and high in fats and protein) at one than women whose ECGs stayed normal. treatment. Only two of the eight given bilat- end and the Ornish diet (high in carbohy- The women were all enrolled in a pla- eral stimulation had such dramatic improve- drate and very low in fat) at the other. Nei- cebo controlled trial of combined hor- ments, although three others said their ther diet restricts calories. mone replacement therapy (the women’s headaches got at least moderately better. These findings should reassure women health initiative), but findings from the When treatment was successful, it reduced that the Atkins diet is unlikely to harm their ECG analysis were independent of any both the intensity and frequency of attacks. health in the short term, say the authors. But hormones they took. An ECG is a quick, When the stimulator failed or the batteries don’t expect dramatic results. The women in cheap, and widely available source of ran out the attacks quickly returned in both this trial lost only 5% of their body weight. valuable prognostic information for post- groups of patients. JAMA 2007;297:969-77 menopausal women, say the authors. With only a handful of patients treated JAMA 2007;297:978-85 and no clinical trials, it’s still too early to say whether this treatment is the answer to this ECG abnormalities predict cardio- particularly thorny problem. More invasive Abandon chemoprevention for neurosurgical solutions have not helped or vascular disease in older women colorectal cancer have left patients disabled or dead. Lead ECG ABNORMALITIES AND RISK migration and battery failure were the only OF CARDIOVASCULAR DISEASE The US preventive services task force has adverse events reported in these two prelimi- Coronary heart disease warned doctors not to prescribe aspirin or 0.16 nary reports of occipital nerve stimulation. Major baseline ECG abnormalities non-steroidal anti-inflammatory drugs to pre- Lancet doi: 10.16/S0140-6736(07)60377-8 Minor baseline ECG abnormalities 0.12 vent colorectal cancer. The recommendation Lancet Neurol doi: 10.1016/S1474- Normal follows two systematic reviews showing that 4422(07)70058-3 0.08 the risks of primary prevention with any drug, Cumulative hazard including cyclo-oxygenase-2 inhibitors, out- 0.04 weigh the benefits (pp 365-75, pp 376-89). Low dose aspirin does not seem to protect Atkins still best for weight loss 0 people at average risk from colorectal cancer. Cardiovascular disease WEIGHT CHANGE 0.16 A higher dose taken for up to 12 years reduces the risk by about 22% (relative Zone LEARN Ornish Atkins 0.12 risk 0.78, 95% CI 0.63 to 0.97), but it 0 also causes gastrointestinal bleeding and 0.08

-2 Cumulative hazard possibly haemorrhagic stroke. Non-steroidal 0.04 anti-inflammatory drugs probably help -4 prevent colorectal cancer, although the 0 0 1 2 3 4 5 6 7 task force describes the evidence as fair. -6

Mean weight change (kg) Time (years) It’s still unclear whether any of these -8 Adapted from JAMA 2007;297:978-85 agents save lives. The evidence weighing Baseline 2 4 6 8 10 12 in on the other side is good: non-steroidal Time (months) What can an electrocardiogram (ECG) tell anti-inflammatory drugs cause gastro‑ Adapted from JAMA 2007;297:969-77 you about the likelihood of cardiovascular intestinal bleeding and renal impairment, Further evidence supporting the Atkins disease in apparently healthy postmeno- while cyclo-oxygenase2 inhibitors increase diet has emerged from a randomised trial pausal women? In a new study, women the risk of cardiovascular disease. in overweight and obese American women. with even minor abnormalities were more In its new guidelines, the task force says Women following the Atkins diet for 12 likely than other women to have a heart primary chemoprevention should be aban- months lost more weight than women fol- attack, a stroke, or to die from heart dis- doned for anyone with an average risk of lowing three other popular diets. Their lipid ease in the next five years. Minor abnor- colorectal cancer, including people with a profiles and other cardiovascular risk fac- malities included first or second degree family history of cancer not associated with tors got no worse, and their systolic blood heart block and frequent premature beats. familial adenomatous polyposis. pressure came down significantly during the Major abnormalities such as left or right Ann Intern Med 2007;146:361-4 year. The other three diets—known as the bundle branch block were also linked Ann Intern Med 2007;146:365-75 Zone, the LEARN (lifestyle, exercise, atti- to an increased risk of cardiovascular Ann Intern Med 2007;146:376-89

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The Emergency Medicine Journal (EMJ) is a leading international journal of developments short cuts extra and advances in emergency medicine. With an increasing impact factor, EMJ includes a What’s new in BMJ journals dedicated pre-hospital section every month as well as the usual high quality emergency Harvey Marcovitch, BMJ syndication editor [email protected] medicine papers. www.emj.bmj.com

Tuberculosis in London is rising and 89.4% for tobramycin. The only adverse (Rohypnol) or gamma-hydroxybutyrate event was a burning sensation on application: (GHB). TUBERCULOSIS NOTIFICATION IN LONDON four patients complained of this. Alcohol concentrations of >160 mg/dl The authors recommend the new prepara- were found in 65% of the 34 patients whose London (enhanced tuberculosis surveillance) London (notification of infectious diseases) tion, especially for children, because of its blood was analysed for the presence of Rest of England, and Wales (notification of reduced dosage regimen—twice daily for alcohol. Five samples showed recreational infectious diseases) 50 three days only—rather than one drop of drugs—amphetamine, opiates, and cocaine. tobramycin every two hours for the first two Despite 14 patients having made allegations 40 days, followed by four times daily for five to the police, the authors conclude that the 30 days. The trial was funded by Laboratoires group’s symptoms were the result of excess

20 Théa, the manufacturer of the eye drops alcohol, not drinks spiked with central nerv- used in the study. ous system depressants. 10 Br J Ophthalmol Oct 2006; doi: 10.1136/ Emerg Med J 2007;24:89-91 Rate per 100 000 population 0 bjo.2006.103556

1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 Year Surgery helps athletes with New guidelines for hand hamstring tears The rate of tuberculosis notifications has dou- osteoarthritis bled in London since the late 1980s, from Distal hamstring tears in athletes can be about 20 cases per 100 000 persons in 1987 Evidence based recommendations for treat- treated successfully by surgery. Eighteen to 41.3 cases per 100 000 persons in 2003. ing hand osteoarthritis have been published athletes injured when sprinting or running The capital accounts for 45% of the total UK by the European League Against Rheuma- complained of pain and stiffness of the burden of tuberculosis; 86% of people with tism. A 21 strong international guideline posterior thigh and weakness in flexion or tuberculosis in London are non-white, and development group, including 16 rheuma- instability at the knee joint. Most tears were three quarters were born abroad. The highest tologists, searched databases for acceptable at the myotendinous junction. Thirteen rate—283/100 000—is in black African peo- trials, finding 309 studies of treatment of tears were repaired by suturing after exci- ple. Hospitals report coinfection with HIV hand osteoarthritis in humans. sion of scar tissue (as in a tendinous tear of of 17-25%. Multidrug resistant tuberculosis The systematic search was followed by a the biceps femoris) and two by tenotomy. accounts for about 2% of cases. Delphi exercise that negotiated 11 proposi- Two patients with avulsions required tendon The authors propose screening residents tions involving 17 treatment modules. In reinsertion. of hostels for refugees, asylum seekers, general, the paucity of clinical trials meant Fourteen athletes were able to return to and homeless people; improved access that levels of evidence were low (expert their preinjury sporting level after an aver- to primary care; and better diagnosis of committee reports or opinion) except for age of four months; three resumed only coinfection. They also emphasise the need topical non-steroidal anti-inflammatory recreational sport. A professional dancer, for treatment continuity and completion, as drugs (NSAIDs), topical capsaicin, low who had surgery twice six years after injury, recommended by recently published guide- dose short duration oral NSAIDs, and, had an outcome that was classified by the lines from the UK National Institute for possibly, intra-articular corticosteroids for researchers as “poor” (described as “occa- Health and Clinical Excellence. painful flares in the trapeziometacarpal sional disturbing symptoms even in activities Thorax 2007;62:162-7 joint. of daily living”). The group highlighted eight areas for Br J Sports Med 2007;41:80-3 future research. Topical azithromycin is effective for Ann Rheum Dis 2007;66:377-88 conjunctivitis A three day course of a new preparation of More on the “date rape” myth azithromycin (1.5% eye drops (Azyter)) is as effective and safe as seven days of tobramycin Doctors in Wales investigated all 75 patients 3% in treating purulent bacterial conjunctivitis. (51 women) attending an accident and emer- A multicentre, randomised, single blind trial gency department over a year who claimed recruited 1043 children and adults, of whom their drinks had been covertly contaminated 471 had an initial positive bacterial culture with drugs (a practice known as “spiking”). and no major deviation from protocol. On They found no evidence on urine and blood an intention to treat analysis, the clinical cure testing of agents reputed to be used in this

rate at days 8-10 was 87.8% for azithromycin way—in particular, no trace of flunitrazepam arnededet/dpa/empics

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How impact factors changed medical publishing—and science

Hannah Brown investigates the use and abuse of journal rankings

eorge Lundberg spent the early derived from citations, Dr Lundberg rea- 11, while those of the Annals of Internal Med- 1980s lamenting the loss of his soned that chasing high profile authors and icine and the BMJ rose only slightly in the journal’s once great reputation. institutions could help boost JAMA’s rank same time. JAMA (the Journal of the American and, therefore, its reputation. He instructed Since Dr Lundberg took the decision to Medical Association), which he had his editorial team to seek out studies that had embrace impact factors in the 1980s, these Gtaken over in 1982, had been in decline since the potential to become staple references in indices have grown into something of an its peak of popularity in the 1960s. And a other papers and try to woo the authors into obsession among editors of medical journals. new set of rankings that pitted medical jour- submitting to JAMA. “We were looking for Editorial strategies designed to get the best nals against each other on the basis of article prestige,” Dr Lundberg recalls. impact factor results by chopping, mixing, citations now seemed to confirm thatJAMA At the time the strategy was implemented, and categorising content in different ways was a long way behind the best. To make his JAMA had a lot of ground to make up in the have become the norm. But Dr Lundberg— editorship successful, Dr Lundberg needed a impact factor stakes. “When we started, JAMA who says his dedication to impact factors recovery strategy. and the BMJ were roughly similar at around extended only as far as getting a respectable, So, while other medical journals contin- four, the Lancet was higher, and NEJM rather than an outstanding, number—believes ued to dismiss as an irrelevance their citation [New England Journal of Medicine] and Annals the now central importance of this ranking to rankings—labelled “impact factor” by the data [of Internal Medicine] were higher still,” Dr many editors has distorted the fundamental crunching company that devised and com- Lundberg explains. “But then JAMA started character of their journals, forcing them to piled the system—Dr Lundberg seized the rising and it never stopped,” he says. Over focus more and more on citations and less opportunity to make them work in JAMA’s several years, Dr Lundberg successfully and less on readers. favour. Recognising that impact factors were raised the journal’s impact factor to around According to Dr Lundberg, research shows

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little correlation between papers that are cited Top 15 journals by impact factor, 2005 did not necessarily pick the best studies. He a lot and those that are considered landmark suggested that dividing the number of times a articles by panels of experts decades later. Journal Total cites Impact factor journal is cited by the number of articles that So medical journals that aim to pull in only CA 4 218 49.794 it publishes would eliminate the bias towards Annual Review of 14 745 47.400 those papers likely to be highly cited—at the Immunology big journals and produce a meaningful meas- expense of potentially less citeable but impor- New England Journal of 167 894 44.016 ure of the importance of a journal—the impact tant work—may be doing science, and their Medicine of an average paper published. readers, a disservice in the long run. Annual Review of 16 313 33.456 In 1975, ISI started publishing an annual Whether the popularity of impact factors Biochemistry summary of citations in journals including itself has distorted editorial decisions during Nature Reviews: Cancer 9 823 31.694 the impact factor calculation, primarily as an Science 345 991 30.927 the past decade’s frenzy has become a well aid for librarians making budget decisions Nature Reviews: 8 686 30.458 rehearsed debate. But such concerns as the Immunology who needed to choose the most cost effective fact that a bad paper may be cited because of Reviews of Modern 19 446 30.254 journals to buy. The process involved load- its infamous errors and that a journal’s rank Physics ing the references from each published paper has no bearing on the quality of individual Nature Reviews: 11 438 29.852 onto the science citation index database and papers it publishes, has not stopped this neat Molecular Cell Biology then, to get the impact factor for each journal, Cell 132 371 29.431 metric capturing a growing army of devotees adding up the numbers of citations published Nature 372 784 29.273 outside journal publishing. The impact factor Nature Medicine 40 386 28.878 in all journals in the current year to articles now has a worrying influence not just on pub- Physiology Reviews 14 943 28.721 published in the journal of interest over the lication of papers but on the science behind Nature Immunology 16 989 27.011 two previous years and dividing that total by them too. Nature Genetics 52 387 25.797 the number of “scholarly” items published Attracted by an apparently simple meas- in the previous two years. The result was a ure of quality, academic employers, funding number that quantified the average number bodies, and even governments have begun Counting citations of citations accrued by a paper published in using the impact factor of journals in which So how did a simple calculation become so a particular journal during a given year—the researchers most frequently publish to guide influential? The impact factor was first pro- impact factor. decisions on appointments, grant allocations, posed in the early 1960s by information scien- Three decades later, an almost identical sys- and science policy. This trend has been par- tist Eugene Garfield, now chairman emeritus tem underlies the Journal Citation Reports still ticularly noticeable in the UK, where impact of the multinational information company produced by ISI, which is now subsumed by factors have been used heavily in the research Thomson Scientific. It was conceived as a way Thomson Scientific. Rather than ranking just assessment exercise, a regular evaluation of to make better use of the reams of data that the 152 top journals Dr Garfield began with, research activity that determines the alloca- resulted from his Science Citation Index, set ISI now produces yearly impact factor lists, tion of part of the higher education budget. up in the 1950s to track the “subsequent his- grouped by specialty, for the 6088 journals in One consequence has been to make univer- tory” of scientific ideas through their citations their science citation index, which is growing sities prioritise laboratory based life sciences in future publications. by an astonishing 200 journals every year. that produce research published in the high- With the hundreds of thousands of refer- Inclusion in the index is something of a est impact factor journals, causing substantial ences from scientific journals Dr Garfield and badge of honour for new journals, which must damage to the clinical research base. Impact his team at the Institute of Scientific Informa- pass ISI’s stringent assessment procedure factors, it seems, have a lot to answer for. tion (ISI) collected and categorised for their before being incorporated. Suitable candi- index, they were able to analyse the dates have to meet basic publishing standards publication histories of indi- and have a fairly good chance of influencing vidual authors, identify papers the scientific record. “We take a look at what that caught the imagination of they have been able to do since the beginning other scientists, and, impor- of the year and whether the journal can attract tantly for publishing, rank jour- authors that make an impact. If it passes that nals according to their talent for test we go on to quantitative analysis,” says picking popular papers. James Testa, senior director of editorial devel- Although initial efforts at jour- opment for Journal Citation Reports. nal rankings simply totted up the But whereas the theory hasn’t changed in 40 numbers of mentions each pub- years, the mechanics of the calculation have. lication received in the refer- ISI has to take into account changes in the ence lists of future papers, Dr nature of scientific publishing from print only Garfield quickly realised that to an increasing proportion of electronic pub- this method favoured jour- lications. “We index everything from print to nals that published a lot but direct feed to FTP files,” says Marie McVeigh,

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senior manager of Journal Citation Reports. And data can be, according to Mabel Chew, for- Dr Garfield thinks that a lot of work goes into keeping up with the merly deputy editor of the Medical Journal of although these strate- journals’ changing editorial content. “It’s six Australia and now a BMJ associate editor, a gies can force small months of pretty non-stop work,” she says. tortuous process. Even in cases where there increases in impact “We have begun the first preparatory steps for have been obvious errors—such as the errone- factor, since the year 2006 now and we’ll be publishing [this ous classification of news articles published by index is essentially a year’s impact factors] in mid to late June.” CMAJ during the 1990s as citable items, which measure of quality, For ISI, one of the most difficult aspects of caused the journal’s impact factor to drop sig- “the best thing the the indexing process is deciding which arti- nificantly—ISI takes months to respond to publisher can do is cles from each journal should count as part of editors’ queries. Dr Chew believes the proc- to publish good arti- the scholarly record and should therefore be ess could be made fairer if ISI committed cles.” The striking added into the denominator for calculating to transparency about its indexing process, stability of the impact the impact factor. Many scientific journals— enabling journal editors to see for themselves factor rankings over time supports Dr Gar- and medical journals are particularly bad why changes in their impact factors are occur- field’s view. “The same set of journals tends to offenders in this respect—publish an eclectic ring. “ISI could make public its policies on appear top year in year out,” he says. “Nature mix of article types that marry journalism with the steps it takes to determine whether some- and Science are not ‘Johnny come latelys’; research, narrative reviews with clinical cases. thing is considered a citable item or not and they have always been at the top and they Editorial policy changes that create new sec- say these are the steps we take when we come will remain there.” tions, alter numbers of references, or reorgan- across a funny article type,” she says. “They Journals’ minor manipulation of content in ise article types are made with what seems could be more transparent about how they their jostle for better ranking positions is not like—at least from ISI’s perspective—dizzying do things.” the issue that causes most concern, however. frequency. All of them can affect the eventual Despite the fact that the index has now existed impact factor. Working the system for 30 years, there remains a worrying lack David Tempest, associate director of This system of negotiations—or, as ISI’s Ms of awareness about the other scientific uses research academic relations for the scientific McVeigh prefers it “discussions or clarifica- to which impact factors can appropriately be publisher Elsevier, which publishes the Lancet, tions”—has made journals far more cognisant applied—and situations where it is completely says the denominator is a difficult thing for of how editorial decisions can affect impact inappropriate. This ignorance about what the ISI to get right. “BMJ, JAMA, and the Lancet factors. As well as monitoring cases in which impact factor can and cannot do has persisted might not have the same article types, and ISI ISI gets it wrong, editors are using this knowl- while journals’ increasing tendency to tout has to work out what should be included,” he edge to their advantage. By keeping the num- their numbers on promotional material has explains. bers of scholarly articles as small as possible, helped disseminate the concept to wider audi- But whereas in the 1970s journals were un‑ journals can maximise their ences. Dr Lundberg suggests interested enough in their rankings to let ISI ranking. “Every time you get a The best thing the the impact factor’s meteoric do its calculations unimpeded— “they ignored number you get people work- publisher can do is to rise is simply a question of them”, says Dr Garfield—editors and publishing out how to make it work publish good articles nomenclature: “Because the ers are now active participants, helping ISI to their advantage,” admits Dr impact factor has that word make sure their numbers are correct at every Lundberg. Several artefacts can influence a ‘impact’ it has got in people’s heads that this is step of the way. Tempest says he and his col- publication’s ranking in journal lists. Review something that is really important,” he says. leagues count the number of scholarly articles articles or letters are generally cited more than When used properlythat is, to describe in Elsevier’s journals to highlight any possi- research papers, so boosting review content the use of scientific information by other sci- ble misclassifications by ISI. “What we try to can make journals perform better in the rank- entists within a particular field, it is a useful do is work with ISI to get the citable items, ing. Inclusion of news articles, editorials, and and powerful measure. But, as Dr Garfield the dominator, to be as accurate as possible. media reviews that are among articles consid- emphasises, the impact factor’s only real Things like news items and conference listings ered “non-source” by ISI can win a journal value is in assessing the relative importance don’t get a lot of citations, so they are seen as citations without increasing the denominator. of papers published in one journal compared non-citable by ISI. We work together to get And journals can, of course, deliberately try with those published in another of similar the best outcome for journals”, he explains. to inflate self citations by asking authors to content. It is not an absolute measure and But for many journal editors, particularly reference papers in their journal. should not be used for comparing journals those outside the big publishing houses, check- “There are ridiculous things that people from different fields. Michael Mabe, chief ing on the accuracy of ISI’s indexing of their do to boost their impact factors,” says Dr executive of the International Association of own journal’s content is no easy task. The Garfield. “There were one or two German Scientific, Technical, and Medical Publishers, first difficulty is ascertaining from ISI which journals that listed all the articles that had explains: “There is a common misunderstand- articles have been counted as “citable,” and appeared in the journal in the past year, and ing that the actual impact factor has meaning, therefore contribute to the denominator in that increased the citation count by enough but it doesn’t. In fundamental life sciences, the impact factor calculation. Getting these to boost the impact up a notch,” he says. But for example, a typical impact factor is 3 or

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4 while in maths it is 0.4. But you wouldn’t Impact factor for general medical journals 2005 vidual researchers’ work by analysing the dis- assume that mathematicians are eight times tribution of citations of all their work. And more stupid than life scientists, would you?” Journal Total citations Impact factor the Journal Performance Indicator, which is New England Journal of 167 894 44.016 Medicine like the impact factor but excludes citations Distorting influence? Lancet 131 616 23.878 to non-scholarly articles, gives a better indi- For these reasons, the trend towards use of JAMA 95 715 23.494 cation of long term performance of journals. impact factors to guide decisions on research Annals of Internal 38 396 13.254 This would theoretically better suit ranking of funding is worrying. “People are looking at Medicine clinical journals, whose research publications it, studying it, using it in ways that it really Annual Review of 3 517 10.383 may take years to filter through into practice, Medicine shouldn’t be used,” Mr Mabe says. In the UK, than the impact factor, which favours the BMJ 59 516 9.052 many universities’ obsession with selectively PLoS Medicine 519 8.389 short timeline from publication to impact in encouraging research that achieves publica- Archives of Internal 28 432 8.016 basic life sciences journals. Both measures, tion in high impact factor journalsa result of Medicine however, are languishing in relative obscurity a heavy reliance on impact factors within the CMAJ 7 272 7.402 among the many bibliometric calculations research assessment exercisehas, according Medicine 4 372 5.057 that have failed to catch academics’ and edi- to Michael Rees, who chairs the BMA’s medi- American Journal of 21 513 4.388 tors’ imaginations. “There is only so much cal academic staff committee, introduced a Medicine ISI can do to make people aware of all these Journal of Internal 5 168 4.040 bias against important fields in which few Medicine databases,” says Dr Garfield. “The impact journals boast an exceptional figure. Mayo Clinic Proceedings 7 190 3.933 factor is available and known whereas the Universities trying to second guess the Annals of Medicine 2 694 3.848 others not everybody gets.” It comes down research assessment exercise, focus on exactly British Medical Bulletin 2 273 3.179 to the fundamental problem that people want the kind of cross-specialty comparison of American Journal of 4 725 3.167 a simple, easy to calculate number to do their impact factors that Dr Garfield and Mr Mabe Preventive Medicine comparisons. Complicated maths is just not caution against. Academic medicine has been Journal of General 5 086 3.013 so appealing. Internal Medicine particularly badly affected. There has been a Current Medical 1 801 2.945 In both publishing and science, the impact haemorrhage of clinical academic staff from Research and Opinion factor’s ubiquity has definitely distorted pri- universities during the past 10 years—mirror- QJM 4 407 2.829 orities during the past 10 years, concur Mr ing the existence of the research assessment European Journal of 4 199 2.684 Mabe and Professor Rees. And a side effect exercise—and wide ranging cuts in specialist Clinical Investigation of this change has been that many medical teaching available in medical schools, with journals have dispensed with their traditional some subjects now completely absent. Pro- metrics (although not necessarily the impact measures of success, such as subscriber num- fessor Rees says 1000 members of staff have factor) might play an even greater part in deci- bers and readership. “If you want something been lost from medical schools, most of them sions as universities demand less bureaucratic read by the clinical community you would clinical researchers. He attributes this damag- ways of assessing research quality. want to go to the most widely read journal, ing decline to the fact that papers reporting According to Dr Garfield, use of the impact the impact factor doesn’t mean anything,” laboratory based research get published in factor as a general surrogate to aid decision says Dr Garfield. journals with generally higher impact factors making is not necessarily bad. “It is perfectly But is this change a bad one? What jour- than their clinical counterparts, so universi- OK to use impact data in a general way. I nals, editors, and funders should really be ties selectively return those sorts of papers always like to point out 20 years ago when prioritising, reckons Dr Lundberg, is what for departmental evaluations in the research the Soros Foundation had to make quick judg- matters most to them. “It all depends on the assessment exercise and funding for clinical ments on who to give grants to in the Rus- goals of the journal and what the publisher investigation decreases as a result. sian Federation. They would give priority to wants,” he explains. “You set plans for what Professor Rees believes that because impact scientists that had published in a jour- you are trying to achieve and you measure factors reflect only the immediate response nal with an impact factor above a against those plans. If the publisher’s goal of research communities to a journal’s con- certain number,” he says. “It was a is to attract authors to communicate with tent they are not wholly suitable for judging good measure . . . It is the mindless others in their field, then the impact factor clinical research, whose true impact can take a use of citation data and impact factors that is a good measure to use. But if the goal is decade or more to emerge. The next research gets people upset.” to earn money by selling subscriptions, assessment exercise, planned for 2008, will be But why this particular measure? ISI’s Web then it is irrelevant.” One thing he is sure the first to deliberately reduce the contribution of Science database can be used as a start- about is that the impact factor will not wane of impact factors, and Professor Rees hopes it ing point to calculate plenty of alternative anytime soon. “Everyone loves a number,” will reverse the downward spiral in academic bibliometrics that are better aids to decision he says. clinical research. However, a just finished con- making in various circumstances. The Hirsch Hannah Brown freelance journalist Cambridge sultation on the shape of research assessment index, for instance, which ISI also calculates, [email protected] after 2008 indicates that in the future biblio- is a good way of assessing the impact of indi- Competing interests: None declared.

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Atlantic crossing Uwe E Reinhardt The trouble with US military medicine Squalour at the Walter Reed Army Hospital shows how out of touch America’s elites really are

For over a week now, America has social cost of moral hazard, market the military bureaucracy that oversees been forced to look into the mirror oriented American policy makers, the care of the wounded. The sorry to discover that it has egg on its notably President Bush, favour health conditions of some facilities at Walter presumably noble face. According insurance policies with a high degree Reed and the mindless and often to several recent reports in the of cost sharing by patients. cruel bureaucracy routinely visited on Washington Post, seriously wounded Moral hazard exists in the conduct wounded soldiers, for example, were soldiers at Walter Reed Army Hospital of foreign policy as well. When those fully known to the army sergeants in are housed in rodent infested with the power to lead a nation into charge of these facilities, as well as facilities with holes in the ceilings war are effectively shielded from to their superiors. They should have and paint peeling off the walls—right the blood and fiscal cost of fighting been known to the general in charge in the nation’s capital, less than that war, they enjoy the analogue of as well. six miles from the White House. having the best health insurance. A distinction must also be made Meanwhile, a flood of Should cost sharing by decision between the various branches of reports from wounded soldiers and makers be introduced here as well? With few the military. As vice admiral Donald veterans elsewhere suggests that With few exceptions, America’s “exceptions, Arthur observed in testimony before America, in too many instances, government, financial, academic, and America’s Congress, “The marines have been fails its wounded warriors and business elites are routinely shielded government, very, very forthcoming and forward veterans in general. against the blood cost of war, as few financial, academic, leaning in taking care of their own Americans never tire of professing of their offspring volunteer to serve and business marine casualties.” In fact, so in words their gratitude to the in the military. Unlike in earlier wars concerned are marines over the fate brave men and women who fight in America’s history, that elite has elites are routinely of their wounded that they station the nation’s wars. Automobiles been carefully shielded also from the shielded against a small detachment of marines at are adorned with $3 magnetic negative fiscal consequences of war, the blood cost of the army run Landstuhl US Military ribbons—made in China—exhorting through a series of major tax cuts. The war, as few of their Hospital in Germany for the sole the citizenry to “Support our Troops.” war is effectively paid for with debt offspring volunteer purpose of assuring that their Immense praise is lavished on our financing from Asia. to serve in the wounded comrades are treated at warriors in virtually every speech by It is perhaps understandable, if not military marine corps standards. politicians or corporate executives forgivable, that an elite so carefully Conditions in US military medicine of all ideological stripes. Finally, shielded from the physical and fiscal will not change until its entire anyone who would dare question the consequences of war, and so self bureaucratic system, from the top administration’s war strategy and absorbed in accumulating wealth and civilian echelon of the Pentagon on management is harshly accused of power, will almost innocently neglect ” down through the ranks, is imbued undermining the morale of the its wounded soldiers, taking it on with the idea that wounded soldiers troops. faith that “someone” will take good no longer are pieces of human capital, With all that touching, rhetorical care of them, without ever bothering so to speak, that are rented by the support for America’s troops, what to check whether it is so. Meanwhile, Pentagon on non-cancelable leases can account for the dissonance the incessant flood of verbal praise and that can be pushed around as if between professed sentiment and and gratitude professed for our they were government property, but actual deed? One can think of at least troops gushes forth, because it is so that they are fellow human beings two explanations: “moral hazard,” cheap. worthy of our utmost gratitude and and callousness within the ranks of The army itself must shoulder part compassion, in deeds and in words. the army itself. of the blame, and indeed several high More generous budgets alone will not In economics, “moral hazard” ranking officials have stood down, bring about that change. refers to situations in which a including, this week, Lieutenant Conditions in US military medicine decision maker does not bear the General Kevin C Kiley, the army will not change until its entire full negative consequences of his or surgeon general. Here a distinction bureaucratic system is imbued with her actions. Well insured patients must be made between the military’s the idea that wounded soldiers no and their doctors, for example, medical personnel—many of them longer are pieces of human capital make treatment decisions under brave, skilful and deeply caring Uwe E Reinhardt is James Madison moral hazard, because they visit souls who accompany their buddies professor of political economy, Princeton the cost of the chosen therapy on a into the firefight or care for them at University, Princeton, NJ, United States common risk pool. To mitigate the bedside in the field or at home—and [email protected]

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MEDICINE and the media “We saw human guinea pigs explode” L Stobbart and colleagues examine newspaper coverage of adverse events in the TGN1412 trial

with death and disfigurement. Science fiction or cinematic imagery is often used to add potency to detailed and gruesome descriptions—although no pictures were printed of the victims’ deformities, references such as “his face now resembled that of the Elephant Man” (Daily Star, 16 March) were used with effect. P/EMPICS

A Good science, bad science /

TH TGN1412 was being developed to treat conditions such as arthritis, leukaemia, and multiple sclerosis. In media descriptions of these condi- Y WIGGLESWOY

T tions, the terms “chronic” and “devastating”

KIRS were instrumental in emphasising the drug’s potential value in eliminating suffering. By The story “human tragedy,” “good science, bad sci- using these terms the media aimed to con- On 13 March 2006 eight men took part ence,” and “engagement in science.” Rep- vince readers that the research was worth- in a “first in man” phase 1 clinical trial of resentative quotes are shown in the boxes while and public involvement was vital. TGN1412, a humanised agonistic anti-CD28 on p 567. If the volunteers are the “heroes” of this monoclonal antibody being developed by story then scientists and doctors may be seen TeGenero to treat various diseases in which Human tragedy as the “villains.” But conflicting and conflated T cells are involved, such as chronic inflam- Initial headlines such as “Drug trial men in images of these groups were juxtaposed matory disorders or haematological malignan- intensive care” and “Drug trial leaves six throughout the coverage. Recent healthcare cies. Within hours those receiving the drug men seriously ill” (Daily Mail and Guardian, scandals such as those of Shipman and Alder experienced serious side effects caused by a 15 March) introduced relatively brief accounts Hey have led to media descriptions of an ero- severe inflammatory response, resulting in of the events but soon began to focus on the sion of trust in medical and scientific author- multiorgan failure due to a “cytokine storm,” volunteers and their friends and families. ity. Doctors’ and scientists’ actions, advice, for which they were managed in intensive Approximately 60% of articles reviewed car- and opinions are no longer considered unim- care; some spent more than three months ried a headline emphasising the “human trag- peachable, but we still look to these profes- in hospital. Longer term effects for all of the edy,” such as the Sun’s “We saw human guinea sionals to develop treatments and cures. volunteers remain unknown. The story broke pigs explode.” Experts were pitted against each other: a in the printed media on 15 March, although The TGN1412 story fulfils many recog- researcher defended his work, saying “I don’t radio news bulletins late the previous evening nised criteria of “newsworthiness,” including want to come across as a crazy scientist” but carried the first reports. Headlines were ini- frequency, threshold, unambiguity, meaning- “we are not going to give up” (Mirror, 25 tially conservative but became more dramatic fulness, unexpectedness, continuity, person- March). Others questioned his enthusiasm. as the story quickly attained “scandal status.” alisation, and negativity. Unfolding daily, the The Sunday Times quoted an expert from story lent itself to regular updates, and per- a London research institute who claimed: Analysis of press coverage sonalisation of the story was used to render “The danger is that they are messing around We searched LexisNexis, a database of all it more meaningful to the reader. Volunteers with T regulator cells and we don’t know UK newspapers, for the period 14 March to were stereotypically identified as students or what all the T regulator subsets do.” 21 April 2006, using the search term “drug low paid staff, implying vulnerability, and Placing the drug “at the heroic edge of trial.” We selected nine national newspapers our sympathy was sought by drawing atten- medicine,” the Guardian (17 March) ech- for further exploration: the Daily Star; the tion to their motives in volunteering for this oed coverage of other medical and scien- Daily Mail, the Express; the Guardian; the Inde- research. tific advances hailed as “miracle cure” or pendent; the Daily Mirror; the Observer; the Sun; TGN1412 was novel; its effects were “magic bullet,” bestowing the discoveries and the Times (including Sunday editions). We unexpected and were described in hor- and their creators with supernatural or considered various formats including news rific and lurid detail. Media representations superhuman powers. Paradoxically, while reports, comment and editorials, and readers’ suggested that death and disease had been “life” has become increasingly medicalised published letters and emails. “sequestered away from the majority of and expectations of science and medicine The search yielded more than 200 articles people’s everyday experience.” Events such have increased, trust and respect for medical referring to this phase 1 study. Analysis of as this fulfil an element of voyeurism and and scientific authority have allegedly dimin- press coverage yielded three main themes: schadenfreude, feeding readers’ fascination ished. When things go well doctors’ lab coats

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and clinical detachment are a sign of profes- ies and is discussed at conferences, seminars, media coverage of the TGN1412 trial on vol- sionalism and take on almost angelic sym- and research meetings. It is also referred to unteer and patient participation in other trials bolism, but with errors and setbacks they by clinicians when they explain the content of remains to be determined. help convey a mad scientist image. information documents, particularly the concept of potentially unforeseen side effects. L Stobbart, department of health research capacity Engagement in science When the Medicines and Healthcare Pro development research fellow; M J Murtagh, lecturer Having gained the public’s attention with lurid ducts Regulatory Agency released its final in social science and public health; T Rapley, research and dramatic headlines of a human and per- report on 25 May 2006, press coverage of associate, Institute of Health and Society, Newcastle sonal nature, the media soon said that there the report was limited. Following the interim University, Newcastle upon Tyne NE2 4HH may be a “backlash after trials catastrophe” report of the Expert Scientific Group in July, G A Ford, professor of pharmacology of old age, Stroke even though headlines simultaneously pro- changes had already been made to the way Research Group, Institute for Ageing and Health, claimed: “Tests on humans vital for our safety” in which “first in man” phase 1 studies are Clinical Research Facility, Royal Victoria Infirmary, (Independent and Mirror, 16 March). reviewed and conducted, effectively illustrat- Newcastle upon Tyne NE1 4LP Much of the coverage focused on paying the effects of the “controversy machine” S J Louw, consultant physician; H Rodgers, reader in ments to volunteers and whether or not this whereby crisis cases and “moral panic” pre- stroke medicine, Newcastle upon Tyne Hospitals NHS represented inducement. Payments for partici- cipitate regulatory change. Released on 7 Foundation Trust, Department of General Internal pation in clinical trials are intended to com- December 2006, the final report of the Expert Medicine, Freeman Hospital, Newcastle upon Tyne pensate volunteers for their time rather than to Scientific Group on Phase One Clinical Tri- NE7 7DN induce them to participate or to minimise the als was published with 22 recommendations Correspondence to: M J Murtagh m.j.murtagh@newcastle. significance of potential risk. Reports stated to increase the safety of future clinical trials ac.uk that volunteers could earn “anything between involving first human exposure to agents with Competing interests: None declared. £100 and £3500 for taking part” and that the potential high risk. Compared with media A full version of this article with references is available on student and backpacking communities were a coverage of the trial itself, the report raised bmj.com good source of volunteers. modest media interest. The full impact of the See News, p 551

Implications for clinical research and Box 1 | Human tragedy “science” Detailed and emotive descriptions encouraging the reader to identify with the “victims”: Many of the newspaper reports that we examined constructed a reality in which sci- Mr Wilson, from London, said the tips of most of his toes were “basically dead” and at least half of his big toe had already rotted away. A keen footballer, he also faces an agonising wait to see whether the ence and scientists were out of control, the infection will spread, forcing doctors to amputate his feet and hands.—Daily Mail quest for scientific knowledge and progress may overshadow public safety, and our capac- “His head had swollen to three times its normal size. His neck was the same. It was wider than his head ity for innovation increasingly outstrips the and his skin had turned a dark purple. At first none of us recognised him. His nose was spread across his “know-how of the relevant experts” in dealing face like it had been squashed. He had tubes in his nose and mouth and was hooked up to a machine with associated risks. This media-constructed helping him breathe and to a kidney dialysis machine. His eyes had been taped up and he had been reality is also one in which innocent and vul- sedated. Our fear is that he may never wake up.”—Daily Star nerable members of the public were coerced into risking their health, and possibly their Box 2 | Good science, bad science lives, in irresponsibly conducted research, Doctors and scientists presented as saviours and purveyors of medical miracles, while simultaneously and where advances in scientific capabilities vilified as irresponsible, uncaring and untrustworthy: were not matched by new and safe means of Miss Marshall, 35, called on the international scientific community for emergency assistance. Solicitor testing. Ann Alexander, who is representing her critically ill boyfriend, said: “She wishes that there should be Such coverage could result in a decline in the widest possible attention to this tragedy in the hope that members of the scientific and medical the number of volunteers for clinical research. community around the world will come forward with suggestions for treatment to help the doctors at The Medical Research Council, the British Northwick Park who are doing a magnificent job.”—Daily Mail Heart Foundation, and commercial clinical research organisations expressed this con- We should examine the extent to which the public can trust all the parties involved. Do we trust cern, and were reported as being surprised TeGenero whose chief scientific officer has been very open with the media, yet which has never brought a product to market before? Do we trust the research company Parexel, still recruiting healthy volunteers when inquiries about participation increased. for other trials? Do we trust the research ethics committee that agreed this study could take place? And It remains to be seen whether this surge in do we trust the motives of the NHS in allowing such a contract research organisation to exist on NHS interest has translated to an actual increase in premises—for gain?—Independent/Independent on Sunday recruitment. This incident has already taken on the Box 3 | Engagement in science qualities of an apocryphal event. It is referred Discussions of the validity of informed consent and debate concerning level of payment, inducement, to by patients both when framing questions and coercion: about research involvement and as rationale for declining to participate. Organisations car- Parexel—which launched the trial on behalf of the German drug company TeGenero, the manufacturers rying out clinical trials have fielded inquiries of TGN1412—may have breached guidelines laid down by the Association of British Pharmaceutical from potential volunteers attracted by details Industries over the offering of inducements. “Neither payment, nor the level thereof, should be of financial recompense; the incident is noted mentioned in a public notice,” these state. Yet Parexel”s website for enrolling volunteers to its TGN1412 trials clearly states that recruits would be “paid for your time and inconvenience.”—Observer within ethical review of other, unrelated stud-

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Should we ditch impact factors?

Gareth Williams dean Faculty of Medicine and Dentistry, fatally flawed. Every scientist knows that the like the music charts. Unfortunately, some University of Bristol, Bristol BS2 8DZ vagaries of peer review can push a “not so accord it an importance that can do real [email protected] good” paper into a “good” journal and vice damage. Nowadays, many applicants for Proper measurement of versa. It is patently absurd to believe that jobs or promotion tag their publications the quality of research the intrinsic value of a piece of research is with the journal’s impact factor, and there yes requires a thorough under- increased just because the editor of a “good” is a risk that impressionable assessors might standing of the subject, balanced evalua- journal takes a shine to it. Even the basic take this seriously. Of much greater concern tion of evidence (which may take years to mathematics don’t add up: numerous stud- is evidence that the impact factor profile of acquire), and ultimately consensus among ies have found that as few as 10-20% of a individual academics is used by universities experts. All in all, a tall order—as shown by journal’s papers can account for most of its and funding bodies to determine employ- the decades which the Nobel Prize commit- citations3 9 10; 10-50% of articles may never ability and grant support11 12—even though tee may take to recognise achievement and be cited at all. Thus, the impact factor ena- this is scientifically indefensible. by the controversy which often follows its bles research that has made no detectable As academics, we should have all the skills decisions. impression on the academic community to needed to evaluate the quality of our work. Enter the impact factor, which at first steal prestige from more conspicuous articles The impact factor is a pointless waste of sight is a welcome solution to this conun- that happen to appear in the same journal. time, energy, and money, and a powerful drum.1 The impact factor has become the driver of perverse behaviours in people who global currency for a journal’s scientific Every scientist knows that the should know better. It should be killed off, standing and, by implication, of the papers vagaries of peer review can push a and the sooner the better. Academics should it publishes. Available at the click of a “not so good” paper into a “good” now acknowledge that we have been conned mouse (http://scientific.thomson.com/isi/) journal and vice versa for long enough, and the academic commu- from the Institute of Scientific Information nity as a whole should now agree to consign and updated every year, the impact factor Over the years, the pseudoscientific ration- the impact factor to the dustbin. Crucially, has three decimal place precision and an ale of the impact factor has been comprehen- the journals and libraries which have kept impressive range from close to zero to over sively demolished, notably by Per Seglen.2 the citation industry alive should follow suit. 30. Some journals delight in flaunting their Of the first 50 references listed by Google Perhaps Nature could lead the way? impact factors, and when the big names such Scholar (accessed on 27 February 2007), 33 Competing interests: None declared. as Nature do this you could be forgiven for were critical of one or more aspects of the believing that the impact factor is both cred- impact factor’s validity. Even though 10 of ible and important. the other references listed were by Eugene Sadly, this is not the case. Even superfi- Garfield, one of the progenitors of the cial scratching beneath the hype shows this impact factor,1 none of the substantive criti- currency to be so seriously debased that cisms seems to have been adequately rebut- only the naive could attach any value to it. ted. The inescapable conclusion is therefore A journal’s impact factor is derived as the that the impact factor is worthless. So why, total number of citations of all its eligible in this age of critical, evidence based analy- articles (full papers and reviews) published sis, is it still around? during the previous two years, divided by Part of the answer is that it is produced the total number of eligible articles. The as a commercial venture, driven by profits basic assumption that this ratio reflects the milked from the academic community. In journal’s scientific quality has been chal- 2003, the Institute of Scientific Information lenged on many counts, including the heavy mounted a vigorous legal defence against a citation of reviews, self citation, and period potential competitor, which suggests that the of measurement.2-8 It doesn’t even matter if citation industry must generate big bucks. a paper turns out to be rubbish—or even if Ultimately, though, the impact factor sur- the only reason for citing it is to point this vives only because of the acquiescence and out—because all citations count and contrib- support of the academic community. Even ute equally to the journal’s impact factor. worse, it feeds off three attributes that no academic could be proud of—gullibility, Research quality intellectual sloppiness, and (for those who The further leap of faith, that the stature of enjoy surfing this particular wave) vanity. an individual paper equates to the impact It could be argued that the impact fac- factor of the journal in which it appears, is tor is just a harmless numerical distraction,

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Even advocates of impact factors admit that they are a flawed measure of quality. Gareth Williams believes we should get rid of them whereas Richard Hobbs thinks refinement is the answer

Richard Hobbs head of primary care Department referenced for a short time (enhancing scores We want journals to publish material of Primary Care and General Practice, University of in the limited two year window); journals that has been filtered to ensure it Birmingham, Birmingham B15 2TT that publish weekly get more citations than [email protected] is reliable, interesting, relevant, or monthly (probably because they are more important and that reading it results From 2008, state funding widely read); specialist clinical journals are for academic research in the cited less than non-specialist; selective cita- in some wider benefit No UK will be calculated differ- tion occurs, through within country bias ently. The research assessment exercise, (most notably in the US),2 within discipline produce too many papers creates a market which is based substantially on (high inten- bias,2 and general gaming. for journals, but at an intellectual, material, sity, high cost) peer review, will transfer to Despite these problems we need a meas- and environmental cost. bibliometric scoring.1 Such metrics include ure of quality. We want journals to publish We should be attempting to encourage journal impact factors, published annually material that has been filtered to ensure it is more complete work, of a higher quality, in in Journal Citation Reports. The impact fac- reliable, interesting, relevant, or important a reduced number of journals that are more tor is based on the average number of cita- and that reading it results in some wider widely read and cited. It would be nice to tions of individual “source” articles (original benefit. And surely, if we are sufficiently think that a handful of practice changing papers, research reports, and reviews) pub- influenced by the work, we would want to research papers or thought provoking reviews lished in that journal during the preceding acknowledge the source through citation? were a worthwhile career objective rather two years. Citation scores are therefore capable of rec- than 200 papers of average to low quality. Of course, as with most routinely col- ognising some value, some quality, of those Electronic publication of preliminary work lected data, there are problems. Some of articles that persuade us through argument could stimulate further iterative study and them are basic—only 2.5% of journals are or data. critical response without influencing citation tracked2 and not all disciplines routinely cite So rather than just discarding impact fac- scores. The journals with higher impact fac- others’ work. Numerous other non-quality tors we should consider solutions to the tors currently produce expanded electronic factors drive article citations and therefore problems. For example, extend the citation versions of papers that, if freely available, the impact: reviews cite other articles the surveillance period beyond two years or widen readership and influence. This system 3 most ; basic sciences routinely cite many adjust for citation bulge in rapid turnover is also potentially more carbon friendly—we more references than clinical sciences; short disciplines. Weightings could be applied to print off fewer articles, probably only those turnover science (principally basic) is widely adjust for the average number of references 15% that account for most citations. across journals (which will be discipline All of this is not to say that the articles dependent) or for national versus interna- representing the citation tail in journals with tional citation; or we could consider scor- some impact factor should be disregarded. ing journals on only their most important However, quality measures that focus on a papers, since the most cited 15% of articles reduced number of papers in fewer journals account for 50% of citations and the most should be encouraged. cited 50% of articles account for 90% of the So, yes, it’s easy to criticise bibliometrics, 4 citations. Why not measure only those that but we should attempt to refine them and really influence rather than include the tail? debate in parallel how we can track aca- After all, development of more complex demic careers and encourage fewer, but bet- citation scoring was advocated (to avoid cit- ter studies that affect the wider community. ing unreliable studies and deepen historical After all, as Oscar Wilde said, “The�� only meaning) by Eugene Garfield, the father of 5 thing to do with good advice is pass it on. impact factors, in his original 1955 paper. It is never any use to oneself,” although he failed to reference Publilius Syrus’s maxim: Fewer, better papers “Many receive advice, few profit by it.” So An even more compelling reason to meas- cite freely when citation is merited and let ure and publicise the quality of journals is adjusted metrics profit those, fewer, journals that there are simply too many of them. An that meet a quality threshold. They might estimated 126 000 journals6 in a world that also help save the planet. is struggling to cope with waste is ridiculous. Competing interests: RH is a career academic dedicated Who reads them all? How many journals to evidence based care and regularly attempts to publish exist merely to meet the inexorable drive quality papers in quality journals and to get a high research to “publish at all costs,” regardless of qual- assessment exercise score. ity? Too much pressure on academics to References are in the full version on bmj.com

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Who will care for the oldest people? The number of informal carers for frail elderly people is set to fall steeply. Jean-Marie Robine and colleagues propose a way to assess the trend that should help policy makers plan for the deficit

Medical journals usually focus on the most dramatic Jean-Marie Robine research as the oldest old are expected to make up an increasing consequences of population ageing,1-4 such as the effect director proportion of the number of retired people.15 on financing of health care.5 6 Many people fear that Jean-Pierre Michel professor These significant changes in the population age struc- population ageing will generate a demand for long term of geriatrics medicine ture will have a big effect on intergenerational relation- care that will outpace the supply of formal care.7 8 Of François R Herrmann ships. As the three age group population model cannot course, unremitting prevention of disability could reduce deputy head physician reflect this, it is time to move to a four age group popula- demand,9 but the effect of a decline in disability on the Department of Rehabilitation tion model comprising young people, those of working solvency of social security programmes is still debated.10 and Geriatrics, Geneva age, younger retired people, and the oldest people. This debate does not consider the quality of long term Medical School and University care or the availability of families to care for frail elderly Hospitals, 1226 Thonex- Oldest old support ratio people.11 12 We describe an indicator to monitor potential Geneva, Switzerland Extending previous work,16 17 we propose to introduce informal care resources using American and Swiss data Correspondence to: the oldest old support ratio as the ratio of people aged as examples. F Herrmann 50-74 to those aged ≥85 for monitoring changes in the [email protected] age structure. This ratio provides information on the Population ageing number of people potentially available to care for one Most studies of population ageing use demographic indica- person aged ≥85. tors based on a three age group population model—young In practice, not all grown-up children, especially people, those of working age, and elderly people. This men, provide informal care for their parents. Spouses of model does not reflect the current population changes.13 dependent people significantly contribute as long as they Indeed, the demographic dependency ratio (the ratio of are able to provide such help, but studies have shown young and elderly people to working people) will start to the key role of women aged 50-74. Middle aged women fall steeply only around 2010, as a result of ageing of the not only care for their parents or in-laws but also have an baby boomer generation (born after the second world important role in educating their grandchildren and sup- war).14 This indicator cannot properly reflect the large porting their children, thus having a pivotal role within increase in the numbers of frail elderly people who may the family.15 On the other hand, not all people aged ≥85 be highly dependent on others in their daily life. require help with their everyday needs. For instance, The consequences of the demographic transition according to the US national long term care survey only that occurred during the 20th century in Europe and about half of Americans aged 85 or older are depend- North America were largely ignored. Population age- ent on others to perform personal care or instrumental ing is characterised by changes in the proportions of the activities of daily living.18 different age groups. The sequence of changes begins Since it provides information on the numerical bal- with a decrease in the proportion of young people and a ance between the middle aged and oldest people, the large increase in the working age group before leading oldest old support ratio is a rough indicator of informal later to an inescapable increase in the oldest age group. care resources for very elderly people, complementing Within this group, younger retired people contribute the demographic dependency ratio. The main concep- increasingly to the long term care of very elderly people tual difference with the oldest old support ratio is that by providing informal care to their parents. This active people aged 50-74 are not available to care for anyone retired generation, called the “sandwich” or “pivotal” except their relatives. However, this more personal rela- generation, will have to play a greater part in the future tionship between care givers and receivers does not question the necessity to monitor changes at the population level. Participation in the workforce among the 50-74 age group, especially women, might be limited in the future by the necessity of providing informal long term care to relatives.

Trends in Switzerland and the United States To illustrate the new indicator, we use data from the Human Mortality Database (www.mortality.org) and demographic forecasts from the International Data Base (www.census.gov /ipc/www/idbnew.html) for Switzer- land and the United States. In Switzerland, where data on population age structure are available from 1876, the

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Change over time in dependency ratio and oldest old support ratio in Switzerland and United independence could include home modification or mov- States ing to housing that offers high tech facilities such as safety sensors and personal helper robots. Trends in marital Dependency ratio* Oldest old support ratio† status among both young and very elderly people will Year Switzerland United States Switzerland United States 1890 0.90 NA 139.7 NA also matter, as will the development of private and pub- 1910 0.87 NA 111.8 NA lic insurance for long term care. 1930 0.68 NA 101.0 NA 1940 0.64 NA 96.0 NA Starting debate 1950 0.67 NA 68.9 NA The oldest old support ratio is built on two age groups: 1970 0.73 0.92 37.9 30.9 50-74 and ≥85 years. In essence it is arbitrary, but 1990 0.62 0.70 16.2 16.8 these age groups are the most used when defining 2010‡ 0.65 0.69 8.7 9.9 care givers as well as the oldest age groups. The use of 2030‡ 0.82 0.88 6.6 8.1 this new ratio should help make governments realise 2050‡ 0.98 0.91 3.5 4.1 the implications of the substantial intergenerational *Dependency ratio=(number of people aged 0-19+number aged ≥65)/number aged 20-64. changes that are occurring and aid policy makers to †Oldest old support ratio =number of people aged 50-74/number aged ≥85. ‡Forecasted values. formulate adequate policies. Such a readily available, easy to use, indicator will also be useful in emerging dependency ratio has greatly improved, although the countries such as China, where the same transitions proportion of the population aged ≥65 has increased. are currently taking place at a much faster pace. The decrease in the proportion of young people has not We thank Anne Scherrer Herrmann and Carol Jagger for editorial help. been fully compensated for by the increase in people Contributors and sources: JMR is a demographer with research experience aged ≥65. This trend, also observed in the United States in longevity and health expectancy, JPM is a geriatrician with a strong over the past 40 years, masks a substantial increase in the interest in health issues, and FRH has a wide research expertise combining number of very elderly people as well as large changes in geriatrics, biostatistics, and clinical computing. This article arose from the the ratio of the number of younger retired people to the observation that families of elderly people admitted to our department are quite old themselves and subsequent discussions among the authors, who oldest retired group. In Switzerland, the oldest old sup- all participated in the writing of the manuscript. JMR and FRH took care of the port ratio has fallen from 139.7 in 1890 to 13.4 in 2003 data preparation and are the guarantors. (table). The same trend applies in the United States. The Competing interests: None declared. oldest old support ratios are expected to decrease to 3.5 1 Evans JG. Long term care in later life. BMJ 1995;311:644. in Switzerland and 4.1 in the US by 2050 (table). 2 Raleigh VS. The demographic timebomb. BMJ 1997;315:442-3. These forecasts highlight the large fall in the poten- 3 Angus DC, Kelley MA, Schmitz RJ, White A, Popovich J Jr, Committee tial pool of informal carers. Although this may lead to on Manpower for Pulmonary and Critical Care. Current and projected workforce requirements for care of the critically ill and patients with an increase in the use of formal care services, informal pulmonary disease: can we meet the requirements of an aging care cannot be easily replaced by the less flexible and population? JAMA 2000;284:2762-70. much more expensive formal services. Such services 4 Public health and aging: trends in aging—United States and worldwide. JAMA 2003;289:1371-3. also require a large number of qualified staff, who are 5 Cutler DM. Disability and the future of Medicare. N Engl J Med currently unavailable. Gerontologists are aware of these 2003;349:1084-5. 6 Dyer O. UK is urged to rethink funding of long term care of elderly people. issues but are health policy makers? Failure to anticipate BMJ 2006;332:1052. the consequences of these expected trends today will be 7 Ebrahim S. Disability in older people: a mass problem requiring mass a mistake that will be heavily paid for tomorrow. solutions. Lancet 1999;353:1990-2. 8 The coming crisis of long-term care. Lancet 2003;361:1755. 9 Stuck AE, Beck JC, Egger M. Preventing disability in elderly people. Alternative futures Lancet 2004;364:1641-2. Summary points 10 Chernew ME, Goldman DP, Pan F, Shang B. Disability and health Several studies suggest that disability is falling among care spending among Medicare beneficiaries. Health Aff (Millwood) older people.18-20 We therefore explored the effect of an Current demographic 2005;24(suppl 2):W5R42-52. improved functioning on the demand for long term care. change projects a 11 Heath I. Long term care for older people. BMJ 2002;324:1534-5. decrease in informal care 12 Morris J, Beaumont D, Oliver D. Decent health care for older people. BMJ This exercise shows that we would need to reduce the 2006;332:1166-8. decrease in scores for activities of daily living and instru- givers 13 Robine JM, Michel JP. Looking forward to a general theory on population mental activities of daily living disabilities by 1-2% a year A four age group aging. J Gerontol A Biol Sci Med Sci 2004;59:M590-7. population model will 14 World Health Organization. The world health report 2006— working to compensate for the deficit of younger elderly people. together for health. Geneva: WHO, 2006. better anticipate the 15 Spillman BC, Pezzin LE. Potential and active family caregivers: changing Improving the level of functioning of the oldest people future long term care 7 9 networks and the “sandwich generation.” Milbank Q 2000;78:347-74. and preventing disability is undoubtedly difficult, but needs 16 Ogawa N, Kondo M, Matsukura R. Japan’s transition from the strong public health policies providing more research The oldest old support demographic bonus to the demographic onus. Asian Popul Stud 2005;1:207-26. and resources would help healthcare professionals to ratio corresponds to 17 Singer BH, Manton KG. The effects of health changes on projections of meet this challenge. the number of people health service needs for the elderly population of the United States. Proc Alternative interventions include greater family aged 50-74 potentially Natl Acad Sci USA 1998;95:15618-22. available to care for one 18 Spillman BC. Changes in elderly disability rates and the implications for involvement in long term care, particularly among hus- health care utilization and cost. Milbank Q 2004;82:157-94. bands and sons. Is this a realistic solution? In future the person aged ≥85 19 Freedman VA, Martin LG, Schoeni RF. Recent trends in disability and oldest people, having benefited from higher education Such an indicator will functioning among older adults in the United States: a systematic aid local, national, and review. JAMA 2002;288:3137-46. and better working and living conditions and being more 20 Manton KG, Gu X. Changes in the prevalence of chronic disability in the supranational planning wealthy, may prefer to pay for formal care rather than United States black and nonblack population above age 65 from 1982 of care to 1999. Proc Natl Acad Sci USA 2001;98:6354-9. rely on family support. Individual strategies to maintain

BMJ | 17 march 2007 | Volume 334 571 RESEARCH

Outcomes of stenting after uncomplicated ureteroscopy: systematic review and meta-analysis

Ghulam Nabi, clinical lecturer,1 J Cook, statistician,2 J N’Dow, professor of urology,1 S McClinton, consultant urological surgeon1

1Academic Urology Unit, Institute of ABSTRACT INTRODUCTION Applied Health Sciences, College of Objective To investigate the potential beneficial and The surgical management of ureteric stones has chan- Life Sciences and Medicine, University of Aberdeen, Health adverse effects of routine ureteric stent placement after ged over the past few decades because of advances in 1 Sciences Building, Aberdeen AB25 ureteroscopy. instruments and techniques. Extracorporeal shock 2ZD Design Systematic review and meta-analysis of wave lithotripsy (ESWL) and ureteroscopy are cur- 2Health Services Research Unit, randomised controlled trials. rently the most common treatment options in clinical Institute of Applied Health practice. The routine placement of ureteric stents after Sciences, College of Life Sciences Data sources Cochrane controlled trials register (2006 and Medicine, University of fragmentation and retrieval of ureteroscopic stones is issue 2), Embase, and Medline (1966 to 31 March 2006), Aberdeen questionable.w1 w2 The main advantages of stenting are without language restrictions. Correspondence to: G Nabi g. the prevention of ureteric obstruction and renal pain [email protected] Review methods We included all randomised controlled that may develop as a result of ureteric oedema from doi: 10.1136/bmj.39119.595081.55 trials that reported various outcomes with or without balloon dilation or stone manipulation during uretero- stenting after ureteroscopy. Two reviewers independently scopy. Ureteric stents may aid in the passage of residual extracted data and assessed quality. Meta-analyses used stone fragments secondary to the passive ureteric dila- both fixed and random effects models with dichotomous tion that occurs with an indwelling ureteric stent2 and data reported as relative risk and continuous data as a may prevent delayed formation of ureteric stricture. weighted mean difference with 95% confidence intervals. Routine placement of ureteric stents, however, is Results Nine randomised controlled trials (reporting 831 accompanied by recognised potentially troublesome participants) were identified. The incidence of lower urinary symptoms or morbidity, or both.34 Related urinary tract symptoms was significantly higher in complications such as migration, infection, pyelone- participants who had a stent inserted (relative risk 2.25, phritis, breakage, encrustation, and stone formation 5 95% confidence interval 1.14 to 4.43, for dysuria; 2.00, are not uncommon. Placement of ureteric stents 1.11 to 3.62, for frequency or urgency) after ureteroscopy. results in additional costs. Furthermore, unless a pull There was no significant difference in postoperative string is routinely used at the distal end of the stent, requirement for analgesia, urinary tract infections, stone secondary cystoscopy is required to remove the stent, free rate, and ureteric strictures in the two groups. which has cost implications and the potential to add to ’ Because of marked heterogeneity, formal pooling of data the disruption of patients lives. was not possible for some outcomes such as flank pain. A Ureteroscopy is now performed with small calibre pooled analysis showed a reduced likelihood of endoscopes and better intracorporeal lithotripsy devices such as holmium laser so that most patients unplanned medical visits or admission to hospital in the can be treated without ureteric dilation. As a result, group with stents (0.53, 0.17 to 1.60), although this the need for a postprocedural stent remains question- difference was not significant. None of the trials reported able. on health related quality of life. Cost reported in three We determined the evidence that outcome with rou- randomised controlled trials favoured the group without tine ureteric stent placement after uncomplicated ure- stents. The overall quality of trials was poor and reporting teroscopy is inferior to that without stent placement. of outcomes inconsistent. Conclusions Patients with stents after ureteroscopy have METHODS significantly higher morbidity in the form of irritative lower Search strategy urinary symptoms with no influence on stone free rate, We obtained relevant trials from the Cochrane renal rate of urinary tract infection, requirement for analgesia, group’s specialised register of randomised controlled or long term ureteric stricture formation. Because of the trials; the Cochrane central register of controlled trials marked heterogeneity and poor quality of reporting of the 2006; Medline and PreMedline (1966 to 31 January included trials, the place of stenting in the management 2006); Embase (1980 to 31 January 2006); reference of patients after uncomplicated ureteroscopy remains lists of urology textbooks, review articles, and relevant unclear. trials; and abstracts of conference proceedings. BMJ | ONLINE FIRST | bmj.com page 1 of 7

To be included randomised controlled trials had to compare stenting with no stenting after uncomplicated Potentially relevant trials identified and screened (n=34) ureteroscopy in adults with a clinical diagnosis of ure- Trials excluded: not randomised controlled trial teric stone who required intervention or who were or no comparison of stents v no stents (n=24) undergoing diagnostic or therapeutic ureteroscopy for upper tract transitional cell carcinoma and had at Retrieved for more detailed evaluation (n=10) least one of the predetermined outcomes of interest. Trials excluded: no randomisation (n=1) Outcome measures Trials included in meta-analysis (n=9) Outcomes of interest were pain rated by patients on a validated scale, need for analgesia, lower urinary tract symptoms, unplanned medical visits or admission to Fig 1 | Flow of studies in the systematic review hospital, complications related to the stent (such as migration, encrustation, fragmentation, ureteric ero- more detailed evaluation and excluded one that did sion, and fistulas), return to normal physical activities, not meet our inclusion criteria,8 leaving nine trials for participants’ satisfaction, health economics and health the review.w1-w9 related quality of life. Trials reporting on pain were classified into two groups: those that reported pain Study characteristics score within or at three days or those that reported The nine trials were conducted in eight countries, pain at or after day seven after the procedure. reported on 831 participants, and were published in 2001-4 (table 1). The reported length of hospital stay Quality assessment and data abstraction after ureteroscopy varied from a few hours as an Two reviewers (GN, SMcC) independently assessed outpatientw1 w4 to two to three days.w7 w9 In two trials study quality using the checklist developed for the hospital stay varied on a case-to-case basis,w3 w6 but ure- Cochrane renal group.6 Discrepancies were resolved teroscopy was mostly an outpatient procedure with a by discussion and arbitration by a third party if neces- few patients requiring overnight hospital stay. Two sary. They assessed concealment of allocation, inten- trials reported hospital stays of one day.w2 w5 One trial tion to treat analysis, completeness of follow-up, and did not report on postoperative hospital stay.w8 blinding of investigators, participants, and outcome Seven studies included participants irrespective of assessors. the site of stones in the ureterw1 w2 w4-w8 and a few selec- They screened identified titles and abstracts inde- tively recruited participants with stones in the lower pendently. Potentially relevant trials were retained ureter.w3 w9 There was no significant difference in and the full text examined. The reviewers indepen- stone size between the groups that did or did not dently extracted data. When important data were not receive a stent. Participants with intraoperative ure- reported, we tried to contact the authors. teric perforation or any other complications that otherwise would have required postprocedural placement Study characteristics and quantitative data synthesis of a ureteric stent were specifically excluded from the Whenever possible, we classified the studies by size trials. One trial included participants after diagnostic and site of stones and type of ureteroscope and intra- or therapeutic ureteroscopy for transitional cell carci- corporeal lithotripsy device used. When two or more noma of ureter or pelvicalyceal system.w4 studies reported on the same outcome we quantita- One trial mentioned the material of the ureteric tively combined results. We calculated relative risks stents used.w2 Size of stents used varied from 6 French for dichotomous data and weighted mean differences, gaugew2 w3 w4 w6 w9 to 7 French gauge,w5 w7 but two stu- with 95% confidence intervals, for continuous data. A dies did not specify size.w1 w8 All trials except two fixed effects model (Mantel-Haenszel) was used unless used semirigid or rigid ureteroscopes ranging in size there was evidence of substantial statistical heterogene- from 6.0 to 9.5 French gauge. One trial routinely ity, in which case we used the DerSimonian and Laird used a 7.4 French gauge flexible ureteroscope for random effects model. Statistical heterogeneity of upper ureteric stonesw1 while another did so treatment effects between studies was formally tested occasionally.w4 Two studies carried out ureteral dilata- with Cochran’s test for heterogeneity (P<0.1). The I 2 tion in both groups before the introduction of the statistic was also examined.7 We explored possible ureteroscope.w3 w9 One study excluded participants sources of heterogeneity (participants, treatments, who required dilatation.w4 In three trials ureteral dila- study quality). When we could not combine data quan- tation to facilitate ureteroscopy was not titatively they were assessed qualitatively. All meta- required.w5 w6 w8 Different sources of intracorporeal analyses were performed using RevMan software (ver- lithotripsy were used for fragmentation of large calculi, sion 4.2.8). including holmium:YAG (yttrium-aluminium-garnet) laser,w1 w3 w4 w6 electromechanical,w7 w9 RESULTS electrohydraulic,w5 and ultrasonic lithotrite.w8 Of 34 potentially relevant studies, we excluded 24 after Most of the included trials failed to meet our quality reviewing abstracts (fig 1). We retrieved 10 articles for criteria because of lack of information rather than page 2 of 7 BMJ | ONLINE FIRST | bmj.com RESEARCH

Table1 | Characteristics ofincluded studies comparing stenting (intervention) versus no stenting regard to ureteroscope sizes, intracorporeal lithotripsy (control) after uncomplicated ureteroscopy devices, postoperative analgesia, and outcome assessment and reporting. Only one trial reported on blind- Interven- Stone Study tion/control location Outcomes Notes ing (table 2). Borboroglu w3 53/60 Distal Pain scores preoperatively Day care procedure, except 10 USA and postoperatively at 48 without and 7 with stents. Patients’ outcomes hours and 1 and 4 weeks, Ureteroscopes 6.0 to 9.5 Patients’ pain scores—Five trials measured pain scores at symptoms on 0-100 scale. French gauge. Multicentre, w9 Analgesia requirement. stents removed at 3-10 days. variable intervals after the procedure: at day one, Excretory urography, CT, or Holmium:Yag laser used for days one and three,w6 only at day three,w5 at days ultrasound at 4 weeks fragmentation three, seven, and 15,w2 and at one, six, and 12 weeks. w4 Byrne USA 38/22 Variable Pain and lower urinary tract Semirigid and 7.5Frenchgauge w1 They all used a 10 cm visual analogue scale with 0 symptoms by questionnaire flexible ureteroscope used. on postoperative days 0, 1, Both holmium laser or representing no pain and 10 representing severe pain. and 6 pneumatic lithotripsy used. Experimental studies in minipigs have reported persis- Participants with transitional tent mechanical ureteric oedema and urinary tract cell carcinoma of upper tract 9 included (holmium laser) obstruction up to 96 hours after dilatation, suggesting Chenw5 Taiwan 30/30 Variable Pain on scale of 0-10 before All participants kept overnight, that the cause of flank pain in the first three days after and after operation, lower electrohydraulic energy for ureteroscopy is multifactorial and not caused by stents urinary tract symptoms, fragmentation. Ureteroscopes alone. Two trials reported no significant difference in unplanned medical visits, of 6 French gauge pyuria, KUB radiography and pain scores within three days of the procedure between renograms before and 3, 7, the groups,w5 w9 whereas one trial favoured those with- and 28 days after operation. out stents within three days of the procedure.w2 There Unplanned visits, return to normal activity was evidence of substantial heterogeneity between stu- Cheungw6 29/29 Variable Pain scores on scale of 0-10, Ureteral trauma and oedema dies for pain scores between both immediate (within or Hong Kong symptoms and UTIs, excretory assessed intraoperatively on a at three days) and delayed (seven days) postoperative urography at 3 months, scale of 0-2. Participants with periods. Because of the large degree of heterogeneity renogram if required for perforation excluded from ureteric strictures study. Sample size calculated we could not pool data. One trial reported a signifi- Damianow2 52/52 Variable Pain scores on scale of 0-10; Ureteral trauma and oedema cantly higher pain score at four weeks in those with w3 Italy lower urinary tract symptoms assessed intraoperatively on stents, whereas two trials reported no significant dif- and urinary tract infections, scale of 0-2. All participants ference at two and 12 weeks after the procedure.w1 w2 In KUB radiography. Ultrasound stayed overnight. Antibiotics in immediate postoperative used preoperatively and for two studies the reported data were not suitable for w3 w4 period and at 1 and 3 months. 5-7 days postoperatively. inclusion in the meta-analysis, with both trials Excretory urography at Pneumatic lithotripsy for reporting a higher pain score in participants with 6 months fragmentation. Ureteroscopes of 8.9 French gauge stents. In one other trial the method of pain measurement was not clear,w7 though it reported no significant Denstedtw1 29/29 Variable Pain scores on scale of 0-10; Sample size calculated. 7.5 Canada analgesia requirement, lower French gauge flexible difference in pain perception between groups. urinary tract symptoms, UTIs ureteroscopy used for upper Requirement of analgesia—Four trials reported on the assessed at 1, 6, and stones. Stents removed at first requirement for analgesia after ureteroscopic removal 12 weeks. KUB radiography at visit. Mainly holmium:YAG w1 w6-w8 each postoperative visit and laser used for fragmentation of ureteric stones. None of these studies found ultrasound at 3 months any significant difference in the proportion of partici- Jeongw7 Korea 23/22 Variable Pain and lower urinary tract Participants admitted to pants who required analgesia after ureteroscopy with symptoms assessed as mild, hospital for 2-3 days, or without stents. Only two trials gave data suitable for moderate, and severe electromechanical w4 w7 depending on duration and fragmentation, 7 French gauge meta-analysis. There was no difference in use of requirement of medications. stents used analgesics between the two groups (relative risk 1.03, UTIs and KUB radiography at 7 95% confidence interval 0.73 to 1.47). and 28 days Lower urinary tract symptoms—Eight trials reported on Nettow8 Brazil 133/162 Variable Pain and postoperative Antibioticsused preoperatively analgesia requirement, lower and for 5-7 days lower urinary tract symptoms at various lengths of fol- urinary tract symptoms on postoperatively. Cost of low-up.w1-w7 w9 Combined analysis of four of these stu- modified international procedure assessed. dies that reported urinary frequency or urgency prostatic symptoms score, Ultrasound fragmentation. plain radiography at Ureteroscopes of 7.5 French showed a higher rate in participants with stents (2.00, immediate postoperative gauge 1.11 to 3.62; fig 2). There was also a higher rate of hae- period and ultrasound at maturia (2.18, 0.72 to 6.61) and dysuria (2.25, 1.14 to 2-3 months 4.43) in those with stents. Data from three trials, which Srivastavaw9 26/22 Distal ureter Operative time, postoperative Pneumatic lithotripsy for India pain score, analgesic fragmentation. Distal ureteric could not be used for meta-analysis, also showed requirement, symptoms stones treated. 8.5 semirigid higher rates of lower urinary tract symptoms in those relatedtostent,riskofureteral ureteroscopes used with stents.w1 w3 w4 stricture formation at — 3 months Urinary tract infections Three trials (210 participants) reported on urinary tract infections.w2 w6 w9 The CT=computed tomography; UTI=urinary tract infection; KUB=kidney, ureter, and bladder. pooled analysis showed no significant difference between the two groups (1.09, 0.48 to 2.47; fig 3). explicit reporting of methods that did not conform to One trial reported significantly more pyuria in the the criteria. The trial designs were heterogeneous with initial postoperative period in those with stents. This BMJ | ONLINE FIRST | bmj.com page 3 of 7 RESEARCH

w2-w4 Table 2 | Assessment of quality criteria for trials reporting on stenting versus no stenting after patients required another stent. The pooled analy- ureteroscopic retrieval of stones sis showed a reduced likelihood of unplanned medical visits or admissions to hospital in the patients with a Allocation Completeness Study concealment Intention to treat analysis of follow-up Blinding* stent (0.53, 0.17 to 1.60; fig 4). One of the studies Borborogluw3 Adequate Six participants randomised to group Reported N/A reported a significantly higher rate of unplanned without stents removed from protocol and admission in the patients without stents.w2 This was analysis because of intraoperative injury attributed to the use of a pneumatic intracorporeal w4 Byrne N/A N/A Reported N/A lithotripsy device used for the fragmentation of stones, w5 Chen Adequate N/A Reported N/A which has been shown to leave larger residual frag- Cheungw6 Inadequate N/A Reported N/A ments compared with the holmium:YAG laser10 used Damianow2 Adequate N/A Reported N/A in other studies. The only other trial that used similar Denstedtw1 Adequate 13 participants excluded from study Reported N/A sources of energy for intracorporeal lithotripsy did not because of intraoperative balloon dilatation report a significant difference in the two groups of w7 Jeong N/A N/A Reported N/A participants.w9 Because of the large clinical heterogene- w8 Netto N/A N/A Reported Surgeon ity in the use of intracorporeal lithotripsy devices w9 Srivastava Adequate N/A Reported N/A between trials we could not do a pooled analysis to N/A=not available (insufficient information provided). assess the effect of energy sources. *None of the trials provided sufficient information to determine blinding of participants or outcome assessors. Return to physical activity—One trial reported no significant difference in the reported return to normal resolved, however, and there was no significant differ- physical activities between the groups (25 (83%) v 24 ence between groups by day 28.w5 (80%) at day one after the procedure).w5 Unplanned medical visits and admission to hospital—Of the participants in seven trials, 7% (34/483) required Efficacy outcomes unplanned medical visits or admission to Ureteric strictures/stone free rate—Of the nine trials, six hospital.4 w2-w6 w9 Most participants were managed con- reported on the rate of ureteric stricture servatively, except in three trials in which 9/134 formation.w1-w3 w6 w8 w9 There was no difference in the

Study With stent Without stent Relative risk Weight Relative risk (n/N) (n/N) (random) (95% CI) (%) (random) (95% CI) Dysuria Cheungw6 23/29 2/29 11.69 11.50 (2.98 to 44.37) Srivastava w9 18/26 5/22 21.40 3.05 (1.35 to 6.86) Damiano w2 28/52 22/52 33.12 1.27 (0.85 to 1.91) Jeongw7 20/23 13/22 33.79 1.47 (1.00 to 2.16)

Subtotal (95% CI) 130 125 100.00 2.25 (1.14 to 4.43) Total events: 89 (with stent), 42 (without stent) Test for heterogeneity: χ2=15.24, df=3, P=0.002, I 2=80.3% Test for overall effect: z=2.34, P=0.02

Urinary frequency/urgency Chenw5 25/30 4/30 17.81 6.25 (2.48 to 15.78) Srivastava w9 16/26 7/22 23.58 1.93 (0.98 to 3.83) Damiano w2 30/52 24/52 32.31 1.25 (0.86 to 1.82) Jeongw7 15/23 9/22 26.31 1.59 (0.89 to 2.86)

Subtotal (95% CI) 131 126 100.00 2.00 (1.11 to 3.62) Total events: 86 (with stent), 44 (without stent) Test for heterogeneity: χ2=11.36, df=3, P=0.01, I 2=73.6% Test for overall effect: z=2.31, P=0.02

Haematuria Cheungw6 16/29 1/29 10.34 16.00 (2.27 to 112.87) Damiano w2 10/52 8/52 32.34 1.25 (0.54 to 2.91) Jeongw7 23/23 15/22 57.32 1.47 (1.10 to 1.95)

Subtotal (95% CI) 104 103 100.00 2.18 (0.72 to 6.61) Total events: 49 (with stent), 24 (without stent) Test for heterogeneity: χ2=9.96, df=2, P=0.007, I 2=79.9% 0.1 0.2 0.5 1 2 5 10 Test for overall effect: z=1.37, P=0.17 Favours Favours treatment control Fig 2 | Lower urinary tract symptoms in patients with and without stents after ureteroscopy page 4 of 7 BMJ | ONLINE FIRST | bmj.com RESEARCH

Study With stent Without stent Relative risk Weight Relative risk (n/N) (n/N) (random) (95% CI) (%) (random) (95% CI)

Srivastava w9 1/26 0/22 5.66 2.56 (0.11 to 59.75) Cheungw6 1/29 1/29 10.48 1.00 (0.07 to 15.24) Damiano w2 8/52 8/52 83.86 1.00 (0.41 to 2.46)

Total (95% CI) 107 103 100.00 1.09 (0.48 to 2.47) Total events: 10 (with stent), 9 (without stent) Test for heterogeneity: χ2=0.32, df=2, P=0.85, I 2=0% 0.10.2 0.5 1 2 5 10 Test for overall effect: z=0.20, P=0.84 Favours Favours treatment control Fig 3 | Urinary tract infections proved by culture in patients with and without stents after ureterosopy

proportion of participants developing strictures with or DISCUSSION without stents. Similarly, none of the trials reported Principal findings significant differences in the stone free rates between In this systematic review we found that stenting after participants with or without a stent. ureteroscopy is associated with increased lower urinary tract symptoms such as dysuria and frequency or Health related quality of life urgency. We evaluated the benefits, harms, and costs None of the trials reported on the quality of life of par- of stenting after uncomplicated ureteroscopy, most ticipants. One of the trials assessed participants’ prefer- commonly for the management of ureteric stones. ence by asking those who received a stent whether they Unplanned medical visits and admissions to hospital would prefer to undergo ureteroscopy without place- were more common in the group without stents, ment of a stent if they needed one in the future.w9 though the differences were not significant. The clinical implication of these findings needs further research Around two thirds of participants in the stented as the present level of evidence is based on trials with group said they would prefer not to have stents after marked clinical heterogeneity because of the use of dif- any future ureteroscopy. ferent sizes of ureteroscopes, different intracorporeal Health economics lithotripsy devices, and variation in practice and experience. Moreover, the definition of “uncompli- Three studies reported on the cost per patient with or cated ureteroscopy” varied between studies. We w4 w8 w9 without a stent. Though costs were higher for could not ascertain whether there was a difference in the group with stents in all the three trials, the meth- postoperative pain because of the small number of stu- ods used to estimate costs were not well described dies reporting on this and the varied results. and it is unclear how appropriate any of the costs We found no significant difference between the estimates were and whether any were transferable groups with and without stents in the need for postpro- to other settings. In one trial, the reported costs per cedural analgesia, urinary tract infection, stone clear- patient were based on hospital charges but had been ance rates, and ureteric stricture development. These incorrectly calculated.w8 The operation time (min- outcomes, however, were not reported consistently utes), a key cost driver, was consistently longer in across the studies. None of the trials reported on health the group with stents (weighted mean difference related quality of life. No trials investigated the impact 5.37, 95% confidence interval 2.37 to 8.36, I 2=0, of stent design and material on outcome, especially as fig 5).w1-w6 w9 related to quality of life. In a randomised study Joshi et

Study With stent Without stent Relative risk Weight Relative risk (n/N) (n/N) (random) (95% CI) (%) (random) (95% CI)

Chenw5 0/30 1/30 9.62 0.33 (0.01 to 7.87) Srivastava w9 1/26 0/22 9.67 2.56 (0.11 to 59.75) Borboroglu w3 0/53 4/54 11.00 0.11 (0.01 to 2.05) Damiano w2 0/52 12/52 11.57 0.04 (0.00 to 0.66) Denstedt w1 1/29 1/29 12.05 1.00 (0.07 to 15.24) Byrne w4 1/22 2/28 14.92 0.64 (0.06 to 6.57) Cheungw6 6/29 5/29 31.17 1.20 (0.41 to 3.50)

Total (95% CI) 241 244 100.00 0.53 (0.17 to 1.60) Total events: 9 (with stent), 25 (without stent) Test for heterogeneity: χ2=9.12, df=6, P=0.17, I 2=34.2% 0.1 0.2 0.5 1 2 5 10 Test for overall effect: z=1.13, P=0.26 Favours Favours treatment control Fig 4 | Unplanned medical visits or admission to hospital in patients with and without stents after ureteroscopy

BMJ | ONLINE FIRST | bmj.com page 5 of 7 RESEARCH

Study N With stent N Without stent Weighted mean difference Weight Weighted mean difference Mean (SD) Mean (SD) (fixed) (95% CI) (%) (fixed) (95% CI)

Byrne w4 22 54.70 (17.30) 28 42.60 (15.30) 10.64 12.10 (2.91 to 21.29) Denstedt w1 29 36.00 (20.00) 29 34.00 (14.00) 11.38 2.00 (-6.89 to 10.89) Cheungw6 29 35.90 (19.20) 29 34.20 (14.20) 11.89 1.70 (-6.99 to 10.39) Damiano w2 52 42.00 (15.00) 52 37.00 (20.00) 19.45 5.00 (-1.79 to 11.79) Srivastava w9 26 37.88 (10.72) 22 32.14 (3.61) 46.64 5.74 (1.35 to 10.13)

Total (95% CI) 158 160 100.00 5.37 (2.37 to 8.36) Test for heterogeneity: χ2=3.34, df=4, P=0.50, I 2=0% Test for overall effect: z=3.51, P=0.0004 -10 -50 510 Favours Favours treatment control Fig 5 | Operation time (minutes) in patients with and without stents during ureteroscopy

al showed no difference in the impact on patients’ qual- altered our findings. Some trials allowed withdrawal ity of life between ureteric stents composed of firm or after randomisation because of intraoperative soft polymer.11 This trial, however, did not have a con- complications,w2 w3 leading to potential reporting bias. trol group of participants without stents. In a non-ran- The longest follow-up was only six months.w2 domised study, up to 80% of participants experienced Quality of reporting—The general quality of trials was urinary symptoms and pain associated with indwelling poor (table 2). Some participants were excluded from ureteric stents, which interfere with daily activities and the analysis in a few trials because of intraoperative result in a reduced quality of life.3 Chen et al reported complications, making it difficult to assess the true return to normal physical activity in 80% of partici- effect of intervention. Most of the trials had small sam- pants on the day after the procedures in both ple sizes. groups.w5 A few trials reported on cost implications. Not sur- Implications for practice prisingly, there was a higher cost associated with use of As stent placement after ureteroscopy seems to cause ureteric stents, but none of the trials reported on the undesirable lower urinary tract symptoms maybe it cost effectiveness of this intervention. should not be a standard practice. There are, however, many unanswered questions, and any recommenda- Limitations tions would be potentially flawed because of a lack of Lack of definition of uncomplicated ureteroscopy—Because standardisation of outcome measures, marked clinical of a lack of standardisation of the definition of “uncom- heterogeneity, withdrawal after randomisation, impre- plicated ureteroscopy,” the decision not to insert a stent cision in measurement of outcomes (large confidence can be difficult. This was evident from the included intervals), and poor reporting of published clinical trials. This decision is often affected by the technique, trials. technology used, and experience of the operating surgeon. Denstedt et al defined uncomplicated uretero- Implications for research scopy as no evidence of perforation or lack of Research efforts should now be concentrated on higher clinically important oedema.w1 They did not, however, quality, more rigorous randomised trials. As a mini- propose any objective criteria to assess the clinical mum, these should use predefined ideally standardised importance of any oedema after the procedure but sug- measures of outcome and be multicentred to ensure gested that free flow of contrast into the bladder on that the studies give sufficiently precise estimate of retrograde pyelography should rule it out. Other stu- the various outcomes. Trials should be protocol driven dies used an endoscopic, non-validated grading of ure- and a detailed protocol of how the project is to be con- teric trauma and oedema on a scale of 0 (mild) to 2 ducted should be agreed before the start. The protocol (severe).2w6 should state the research objectives, reasons for the study, issues related to recruitment (inclusion and Performance and reporting of studies—There was a lack exclusion criteria), information to be collected at of standardisation of outcome measures, length of trial, entry to the study, and interventions of interest, and and duration of stenting. The use of preprocedural there should be an agreed follow-up protocol. Out- antibiotics, trial design, stent material, patient popula- come measures must include outcomes assessed by tion, assessment of health related quality of life, and patients and ideally health economic outcome mea- cost-effectiveness data were all inconsistent. Studies sures. The impact of variations in stent design, size, reported pain scores as means with variance, although and material, and the effect of different types of intra- it is well recognised that data from visual analogue corporeal lithotripsy sources on the requirement for scales are often skewed and therefore may be more stents need to be examined. accurately analysed as medians. We were unable to access data from individual patients to assess whether This review was conducted with substantial support and advice from the comparison of medians rather than means may have members of Cochrane Incontinence Group, Aberdeen. The health services page 6 of 7 BMJ | ONLINE FIRST | bmj.com RESEARCH

2 Ryan PC, Lennon GM, McLean PA, Fitzpatrick JM. The effects of acute WHAT IS ALREADY KNOWN ON THIS TOPIC and chronic JJ stent placement on upper urinary tract motility and Stenting after ureteroscopy may lead to undesirable lower urinary tract symptoms with calculus transit. Br J Urol 1994;74:434-9. limited benefits to patients 3 Joshi HB, Newns N, Stainthorpe A, MacDonagh RP, Keeley FX Jr, Timoney AG. Ureteral stent symptom questionnaire: development WHAT THIS STUDY ADDS and validation of a multidimensional quality of life measure. JUrol 2003;169:1060-4. Stent placement after ureteroscopy results in considerable morbidity in the form of irritative 4 Duvdevani M, Chew BH, Denstedt JD. Minimizing symptoms in lower urinary tract symptoms patients with ureteric stents. Curr Opin Urol 2006;16:77-82. It does not seem to influence stone free rate, rate of urinary tract infection, requirement for 5 Singh I, Gupta NP, Hemal AK, Aron M, Seth A, Dogra PN. Severely analgesia, or long term ureteric stricture formation encrusted polyurethane ureteral stents: management and analysis of potential risk factors. Urology 2001;58:526-31. The role of stenting in uncomplicated ureteroscopy remains unclear 6 Willis NS MR, Craig JC. Renal group. Cochrane library.Issue4. Chichester: Wiley, 2003. 7 Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring research unit is core funded by the Chief Scientist Office of the Scottish inconsistency in meta-analyses. BMJ 2003;327:557-60. Executive Health Department. 8 Ali W A-DM, Al-Bareeq R, Samiei MR, Al-Mutawa S. The evaluation of not stenting after uncomplicated ureteroscopy: a randomized prospective study. Bahrain Medical Bulletin 2004;26:3-5. Contributors: GN, SMcC, and JN’D contributed to the idea and designed the 9 Boddy SA, Nimmon CC, Jones S, Ramsay JW, Britton KE, Levison DA, review protocol. GN and SMcC undertook screening of articles, data extraction, ’ et al. Acute ureteric dilatation for ureteroscopy. An experimental and quality assessment. JN D contributed to the drafting and critical revision of study. Br J Urol 1988;61:27-31. the report. JC performed the statistical analyses. All authors contributed to 10 Teichman JM, Vassar GJ, Bishoff JT, Bellman GC. Holmium:YAG drafting the manuscript and approved the final version. GN is guarantor. lithotripsy yields smaller fragments than lithoclast, pulsed dye laser Funding:None. or electrohydraulic lithotripsy. JUrol1998;159:17-23. Competing interests: None declared. 11 Joshi HB, Chitale SV, Nagarajan M, Irving SO, Browning AJ, Biyani CS, Ethical approval: Not required. et al. A prospective randomized single-blind comparison of ureteral stents composed of firm and soft polymer. JUrol2005;174:2303-6. 1 Gettman MT, Segura JW. Management of ureteric stones: issues and controversies. BJU Int 2005;95(suppl 2):85-93. Accepted: 10 January 2007

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RESEARCH

Birth order of twins and risk of perinatal death related to delivery in England, Northern Ireland, and Wales, 1994- 2003: retrospective cohort study

Gordon C S Smith, professor of obstetrics and gynaecology,1 Kate M Fleming, senior data analyst,2 Ian R White, senior scientist3

1Department of Obstetrics and ABSTRACT showed a significantly increased risk of intrapartum Gynaecology, Cambridge Objective To determine the effect of birth order on the risk stillbirth or neonatal death among second twins born University, Box 223, The Rosie of perinatal death in twin pregnancies. 2 Hospital, Cambridge CB2 2QQ at term, but included only nine such deaths. A follow- Design Retrospective cohort study. 2Confidential Enquiry into up study of the same data source over a more pro- Maternal and Child Health, Setting England, Northern Ireland, and Wales, 1994- longed period (1985 to 2001) showed a similar associa- London NW1 5SD 2003. tion but included only 36 deaths at term.3 A subsequent 3Medical Research Council Participants 1377 twin pregnancies with one intrapartum analysis of US data found no variation in the risk of Biostatistics Unit, Institute of Public Health, Cambridge CB2 stillbirth or neonatal death from causes other than neonatal death related to birth order among twins 2SR congenital abnormality and one surviving infant. and concluded that the increased perinatal mortality Correspondence to: G C S Smith Main outcome measures The risk of perinatal death in the among second twins was “merely an artefact of mortal- [email protected] first and second twin estimated with conditional logistic ity comparisons.”4 Data from multiple sources, how- doi: 10.1136/bmj.39118.483819.55 regression. ever, indicate an increased risk of morbidity for the Results There was no association between birth order and second twin at term: a large scale study from Sweden the risk of death overall (odds ratio 1.0, 95% confidence found that second twins had a fourfold risk of an Apgar interval 0.9 to 1.1). However, there was a highly score <7 at five minutes,5 and a recent analysis of data significant interaction with gestational age (P<0.001). from Nova Scotia found a threefold risk of morbidity There was no association between birth order and the risk for the second twin delivered vaginally but no excess of death among infants born before 36 weeks’ gestation risk for those delivered by planned caesarean section.6 but there was an increased risk of death among second It remains unclear, therefore, whether attempted vagi- twins born at term (2.3, 1.7 to 3.2, P<0.001), which was nal delivery of the second twin at term is associated stronger for deaths caused by intrapartum anoxia or with an increased risk of perinatal death. We studied trauma (3.4, 2.2 to 5.3). Among term births, there was a the association between birth order and the risk of peri- trend (P=0.1) towards a greater risk of the second twin natal death among twin pregnancies in England, dying from anoxia among those delivered vaginally (4.1, Northern Ireland, and Wales, 1994-2003. 1.8 to 9.5) compared with those delivered by caesarean section (1.8, 0.9 to 3.6). METHODS Conclusions In this cohort, compared with first twins, Data on perinatal death in England, Northern Ireland, second twins born at term were at increased risk of and Wales have been collected nationally since 1994. perinatal death related to delivery. Vaginally delivered This is currently coordinated by the Confidential second twins had a fourfold risk of death caused by Enquiry into Maternal and Child Health (CEMACH) intrapartum anoxia. and had previously been done by the Confidential Enquiry into Stillbirths and Deaths in Infancy INTRODUCTION (CESDI). A network of local clinicians and health pro- Though vaginal delivery of a second twin is recognised fessionals at hospital level notify regional offices of as a time of obstetric risk, we do not know whether perinatal deaths. Coroners’ officers, child health sys- second twins are at increased risk of perinatal death. tems, and congenital anomaly registers also report Many studies on the association between birth order deaths. Regional managers then code the death accord- and the risk of death have methodological flaws, speci- ing to the information provided, which includes fically, the failure to identify deaths truly related to autopsy results (if performed). From 1995, data from delivery, the failure to use paired statistical tests to England and Wales were linked to the Office for compare the outcome of first and second twins, and National Statistics’ registry of death certifications, the failure to stratify analyses by gestational age.1 An ensuring 100% ascertainment of all registered still- analysis of nationally collected data on pregnancy and births and neonatal deaths. In 1994, the dataset was perinatal death from Scotland in 1992 and 1997 about 95% complete when compared with national BMJ | ONLINE FIRST | bmj.com page 1 of 5 RESEARCH

death registrations. The death registry was compiled order and both maternal and obstetric characteristics nationally at the inquiry’s central office in London, with interaction terms and assumed significance at and the CEMACH database includes all records P<0.05. The characteristics tested for interaction obtained by CESDI. We used the registry of deaths were gestational age, maternal age (expressed as a con- for 1994-2003 for our analyses. tinuous variable), maternal ethnicity (white versus all The data source included only information on others), and method of delivery. Interactions were deaths. We obtained the total number of twin births expressed as odds ratios with 95% confidence inter- over the period of time from the Office of National vals. The latter illustrates the power of the study to Statistics and the Northern Ireland Statistics and exclude a given degree of effect modification and is Research Agency. However, these lack any detailed preferable to post hoc power calculations.8 All statisti- obstetric data. Hence, we had no information from cal analysis was performed with Stata version 8.2 (Sta- cases where both twins survived and, in cases where taCorp, College Station, TX). only one twin died, we had no information on the characteristics of the survivor. We could still study the asso- RESULTS ciation between birth order and the risk of death, The database had records for 5758 twin pregnancies in however, as statistical methods for comparison of a 1994-2003 where death of one or both infants was dichotomous outcome (such as death) in pairs uses recorded. In 4221 of these, one infant died and the only those instances that are discordant for the out- other survived. From these, we excluded eight records come of interest (see below and elsewhere for review1 (0.2%) that did not document birth order, 55 (1.3%) ). Our analyses with this study design, however, were where the gestational age at birth was missing, 450 limited to the relative risk of death for the second twin (10.7%) where delivery was before 24 weeks, 178 referent to the first and determination of whether the (4.7%) where a therapeutic abortion was performed, relative risk of death for the second twin varies in rela- 1975 (46.8%) where death was classed as stillbirth tion to any characteristic common to both, such as and the timing of fetal death was before labour or gestational age and maternal characteristics. unknown, and 752 (17.8%) where the infant had a We classified events using a series of fields in the lethal or severe congenital abnormality. A total of available database. Firstly, we classified deaths as still- 2844 records (67.4%) had one or more of these exclu- birth, early neonatal death, and late neonatal death. A sions, leaving a study group of 1377 in which there was further field documented whether death of the infant one intrapartum stillbirth or neonatal death but the took place before or after the onset of labour or other twin survived. The table shows the characteris- whether the time of death was unknown. Intrapartum tics of this group (table). Over the same period of time, stillbirth was defined as a birth when the infant was the Office for National Statistics documented a total of born showing no signs of life and the death was docu- 96 116 certified twin pregnancies in England and mented as occurring during labour. Neonatal death Wales and the Northern Ireland Statistics and was defined as death of a liveborn infant within the Research Agency recorded 3482, giving a total of first four weeks of life. We classified cause of death 99 598 twin pregnancies as our denominator. Further according to a modified version of the Wigglesworth details of the denominator, such as gestational age at system into one of nine categories: congenital defect/ birth and method of delivery, were not available. malformation; unexplained antepartum fetal death; Birth order was not associated with the overall risk of death from intrapartum “asphyxia,”“anoxia,” or perinatal death related to delivery: the odds ratio for “trauma”; immaturity; infection; other specific causes; the second twin was 1.0 (95% confidence interval 0.9 to injury or non-intrapartum trauma; sudden infant 1.1). There were no significant interactions between death; and unclassifiable.7 We excluded those deaths birth order and maternal age (odds ratio for interaction where the cause was stated to be a lethal or severe con- 0.9, 0.7 to 1.1, P=0.2) or white ethnicity (1.2, 0.9 to 1.5, genital abnormality and classified all other intrapartum P=0.2). There was, however, a highly significant inter- stillbirths and neonatal deaths as perinatal deaths action with gestational age (P<0.001). There was no related to delivery. We also analysed anoxic deaths as association between birth order and the risk of death a subgroup of these events, which we defined as those among infants born before 36 weeks’ gestation (fig 1), where the cause was classified as “death from intra- but there was an increased risk of death among second partum asphyxia, anoxia, or trauma.” As the study twins born at term (2.3, 1.7 to 3.2, P<0.001). When we used wholly anonymised data and data collection was confined the analysis to deaths caused by anoxia, there part of a national clinical audit, we did not require indi- was a weak association with being a second twin for all vidual consent. births (1.4, 1.1 to 1.8, P=0.02). Again, there was a highly significant interaction with gestational age Statistics (P<0.001). When we stratified by gestational age, we We used conditional logistic regression to estimate the found no association between birth order and the risk odds ratio of death for the second twin referent to the of death caused by anoxia before 36 weeks (fig 1) but a first. The method ignores concordant pairs (that is, strong association for births at and beyond 36 weeks where both twins survived or both twins died) and is (3.4, 2.2 to 5.3). therefore appropriate in a dataset containing data on We then assessed the risk of perinatal death related deaths only. We tested for interactions between birth to delivery among second twins born at term in page 2 of 5 BMJ | ONLINE FIRST | bmj.com RESEARCH

Characteristics of the study cohort. Figures are numbers Weeks' gestation No of deaths first twin/second twin (percentage) unless stated otherwise All deaths

Data 24-27 359/344 28-31 192/175 Maternal age (years): 32-35 74/56 Median (IQR) 29 (25-33) ≥36 53/124 Missing 55 (4.0) All 678/699 Ethnicity: White 1118 (81.2) Anoxia Black 88 (6.4) 24-27 24/17 Other 124 (9.0) 28-31 24/17 Missing 47 (3.4) 32-35 29/21 Gestational age (weeks): ≥36 25/85 24-27 703 (51.0) All 102/140 28-31 367 (26.7) 0.25 0.5 1248 32-35 130 (9.4) Odds ratio of death of second twin ≥36 177 (12.9) Presentation†: Fig 1 | Odds ratio for perinatal death related to delivery of second twin for all causes and deaths caused by anoxia, Cephalic 471 (34.2) stratified by gestational age. Numbers of deaths are actual Breech 327 (23.8) numbers of losses of first and second twins, confined to births Other 77 (5.6) where other twin survived Missing* 502 (36.5) Mode of delivery†: those delivered vaginally (fig 2). There were only 19 Spontaneous vaginal 343 (24.9) twin pairs delivered by planned caesarean section at Assisted vaginal 114 (8.3) term where one died and the other survived. Among Elective caesarean 74 (5.4) this group, the odds ratio for any perinatal death of the Emergency caesarean 442 (32.1) second twin related to delivery was 1.4 (0.6 to 3.4) and Other/missing* 404 (29.3) 1.0 (0.1 to 7.1) for death caused by anoxia. Sex of infant†: Male 786 (57.1) Sensitivity analyses Female 587 (42.6) We performed two sensitivity analyses. Firstly, we Missing 4 (0.3) repeated the analysis excluding eligible births from Birth weight (g)†: 1994 (n=178), when the dataset was less complete. Median (IQR) 970 (730-1440) The results were similar to the main analysis, with a Missing 14 (1.0) significant interaction between birth order and gesta- Cause of death: tional age (P<0.001) and no significant association Asphyxia, anoxia, or trauma 242 (17.6) between birth order and the risk of death at preterm Immaturity 735 (53.5) gestations but a significantly increased risk of all Infection 164 (11.9) cause death for the second twin at term (2.4, 1.7 to Other specific 187 (13.6) 3.5) and for death caused by anoxia (3.3, 2.0 to 5.4). Injury 4 (0.3) Secondly, we repeated the analysis including cases Unexplained‡ 39 (2.8) Missing or unclassifiable 6 (0.4) Method of delivery No of deaths first twin/second twin IQR=interquartile range. All deaths *Recorded only from 1996 onwards; 93.8% of missing records for mode of delivery and 74.7% of missing records for presentation were for births Caesarean 23/42 before 1996. Vaginal 18/38 †For infant who died; data were not available for the survivor. All 41/80 ‡Includes in utero and neonatal deaths.

Anoxia relation to method of delivery in the 121 twin pairs for Caesarean 12/21 whom we had this information. When we looked at all Vaginal 7/29 causes of perinatal death related to delivery we found All 19/50 no significant difference in those delivered by caesar- 0.25 0.5 1 2 4 8 ean section (odds ratio for interaction term 0.9, 0.4 to Odds ratio of death of second twin 1.8, P=0.7). When we confined the analysis to deaths caused by intrapartum anoxia we found an interaction Fig 2 | Odds ratio for perinatal death related to delivery of second twin at term gestation for all deaths and deaths of borderline significance between birth order and cae- = caused by anoxia, stratified by method of delivery. Numbers of sarean section (0.4, 0.1 to 1.3, P 0.1). The odds ratio for deaths are actual numbers of losses of first and second twins, the second twin was 1.8 (0.9 to 3.6) among those deliv- confined to births where the other twin survived (excludes ered by caesarean section and 4.1 (1.8 to 9.5) among cases with missing record of method of delivery) BMJ | ONLINE FIRST | bmj.com page 3 of 5 RESEARCH

where the baby was stillborn but the timing of death in —namely, the failure to use paired statistical compar- relation to the onset of labour was documented as ison of first and second twins, the known shortcomings “unknown” (n=179). The results were similar to the of the US birth and death certification databases,11 12 main dataset, with a significant interaction between and stratification by birth weight rather than gesta- birth order and gestational age (P<0.001) and no sig- tional age. Moreover, other analyses of the same data nificant association between birth order and the risk of source suggested an increased risk of death of the sec- death at preterm gestations but a significantly ond twin related to delivery: the risk of neonatal death increased risk of all cause death for the second twin at of the second twin was lower when both babies were term (2.3, 1.8 to 3.0) and for death caused by anoxia delivered by caesarean section compared with those (3.3, 2.1 to 5.0). delivered vaginally.910 The US data also lack information on whether death of the infant occurred before or DISCUSSION during labour and cannot, therefore, address the effect In this retrospective cohort study we found an of birth order on the risk of intrapartum stillbirth. The increased risk of death of second twins compared strengths of our study are the use of more appropriate with first twins born at term in England, Northern Ire- statistical methods and that data were available for a land, and Wales, 1994-2003. There was an interaction large number of losses, including detailed information between the effect of birth order and gestational age. on both the timing and cause of perinatal death. There was no association between birth order and the Our results are consistent with those of several pre- risk of death among infants born at preterm gestations, vious studies of birth order and perinatal morbidity. but we found a strong association between birth order These have shown an increased risk of a depressed and the risk of death at term. The interaction between five minute Apgar score in the second twin.513 We birth order and gestational age is unlikely to be a found no association between birth order and the risk chance finding. Firstly, it was highly significant of perinatal death at preterm gestations, whereas other (P<0.001). Secondly, we had previously observed studies have shown an increased risk of fetal distress or 2 such an interaction in another population, and the pre- morbidity for second twins born preterm.13 Our inter- sence of an interaction was a prior hypothesis. Thirdly, pretation of these findings is that labour and delivery it is biologically plausible. The risk of death at term is are associated with risks to the second twin at all gesta- low and a small absolute risk of complications for the tions. The major determinant of perinatal death at pre- second twin will result in a much greater relative risk of term gestations, however, is the degree of prematurity. death (when compared with the first twin) than at pre- Hence, a small additional risk to the second twin dur- term gestations, where the background risk of death is ing vaginal birth has no significant effect on the relative 2 high for both. The association between birth order risk of death, except at term. Other studies with data on and the risk of perinatal death at term was stronger both twins have identified risk factors for death of the for deaths attributed to intrapartum anoxia. These second twin, including discordant birth weights,2 deliv- findings clearly show an increased risk for death of ery by a means other than planned caesarean section,3 the second twin delivered at term, principally because operative vaginal delivery of the first twin (when com- of complications of labour and delivery. pared with spontaneous vaginal delivery of the first twin),14 and a prolonged interval between delivery of Comparison with other research the first twin and delivery of the second.13 A previous observational study found a lower risk of The findings of this and other studies suggest that death of either twin with planned caesarean delivery.3 planned caesarean section may be beneficial for all Consistent with this, the risk of anoxic death of the sec- twins. Direct evidence for a protective effect of caesar- ond twin was lower among those delivered by caesarean section would require a randomised controlled ean section than those delivered vaginally, although trial, although statistical power might be a problem.2 not significantly so. The data source we used was con- This and previous studies have important lessons for fined to infants who died so we did not know how the any randomised controlled trial of planned caesarean surviving twin had been delivered. In some cases where the second twin died after a caesarean delivery, the first twin may have been delivered vaginally. This WHAT IS ALREADY KNOWN ON THIS TOPIC delivery combination is known to increase the risk of Vaginal delivery of the second twin is recognised as a time of 910 death for the second twin. It is likely, therefore, that high risk the protective effect of caesarean delivery would be Recent studies of the effect of birth order on the risk of greater than our results suggest. The number of perinatal death have produced inconsistent results planned caesarean sections in the present analysis was too small to confirm or exclude a significant asso- WHAT THIS STUDY ADDS ciation between birth order and the risk of perinatal There was no association between birth order and the death with this method of delivery. relative risk of perinatal death related to delivery among preterm twins A large scale study of US birth and death certifications (1995-7) published in 2004 found no significant At term, the second twin had a greater than twofold risk of perinatal death related to delivery and a greater than difference in the risk of neonatal death among second threefold risk of death caused by intrapartum anoxia twins.4 The analysis, however, had several weaknesses page 4 of 5 BMJ | ONLINE FIRST | bmj.com RESEARCH

section for all twin pregnancies. Inclusion of preterm 4 Sheay W, Ananth CV, Kinzler WL. Perinatal mortality in first- and second-born twins in the United States. Obstet Gynecol births may mask a protective effect of caesarean section 2004;103:63-70. on perinatal mortality if the principal effect of caesar- 5 Thorngren-Jerneck K, Herbst A. Low 5-minute Apgar score: a population-based register study of 1 million term births. Obstet ean section is to reduce the risk of complications for the Gynecol 2001;98:65-70. second twin. Moreover, this and previous studies 6ArmsonBA,O’Connell C, Persad V, Joseph KS, Young DC, Baskett TF. showed that it is a minority of all perinatal deaths of Determinants of perinatal mortality and serious neonatal morbidity in the second twin. Obstet Gynecol 2006;108:556-64. twins that are related to complications during labour 7 Hey EN, Lloyd DJ, Wigglesworth JS. Classifying perinatal death: fetal and delivery. Failure to exclude losses that are largely and neonatal factors. Br J Obstet Gynaecol 1986;93:1213-23. 8 Goodman SN, Berlin JA. The use of predicted confidence intervals independent of method of delivery, including antepar- when planning experiments and the misuse of power when tum stillbirth and deaths caused by congenital abnorm- interpreting results. AnnInternMed1994;121:200-6. ality or prematurity, may mask a protective effect of 9 YangQ,WenSW,ChenY,KrewskiD,FungKF,WalkerM.Neonatal death and morbidity in vertex-nonvertex second twins according to caesarean delivery. mode of delivery and birth weight. Am J Obstet Gynecol 2005;192:840-7. Contributors: GCSS had the original idea and is guarantor. All authors 10 Yang Q, Wen SW, Chen Y, Krewski D, Fung KF, Walker M. Neonatal discussed the study design and analytic approach. GCSS and KMF performed mortality and morbidity in vertex-vertex second twins according to mode of delivery and birth weight. JPerinatol2006;26:3-10. the statistical analysis. GCSS drafted the article and all authors contributed to 11 Lydon-Rochelle MT, Cardenas V, Nelson JL, Tomashek KM, and approved the final version. Mueller BA, Easterling TR. Validity of maternal and perinatal risk Funding: None. factors reported on fetal death certificates. Am J Public Health Competing interests: None declared. 2005;95:1948-51. Ethical approval: The directors of CEMACH approved the study. 12 Cahill AG, Macones GA. Vital considerations for the use of vital statistics in obstetrical research. Am J Obstet Gynecol 2006;194:909-10. 1 Smith GCS. Estimating risks of perinatal death. Am J Obstet Gynecol 13 Hartley RS, Hitti J. Birth order and delivery interval: analysis of twin 2005;192:17-22. pair perinatal outcomes. J Matern Fetal Neonatal Med 2 Smith GCS, Pell JP, Dobbie R. Birth order, gestational age, and risk of 2005;17:375-80. delivery related perinatal death in twins: retrospective cohort study. 14 Yang Q, Walker MC, Chen XK, Krewski D, Fung Kee FK, Wen SW. BMJ 2002;325:1004. Impacts of operative delivery for the first twin on neonatal outcomes 3 Smith GCS, Shah I, White IR, Pell JP, Dobbie R. Mode of delivery and in the second twin. Am J Perinatol 2006;23:381-6. the risk of delivery-related perinatal death among twins at term: a retrospective cohort study of 8073 births. BJOG 2005;112:1139-44. Accepted: 18 January 2007

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Generalised anxiety disorder

Christopher Gale,1 Oliver Davidson2

1Department of Psychological Generalised anxiety disorder is a syndrome of ongoing Summary points Medicine, Dunedin School of Medicine, University of Otago, PO anxiety and worry about many events or thoughts that Generalised anxiety disorder is a syndrome of ongoing Box 913, Dunedin, New Zealand, the patient generally recognises as excessive and inap- anxiety and worry about many events or thoughts that and Mental Health Services, Otago propriate. However, the nature of “generalised worry” has the patient generally recognises as excessive and District Health Board, Dunedin inappropriate 2 been hard to describe in a categorical manner. The criteria Department of Psychological Most people with generalised anxiety disorder also have Medicine, Dunedin School of required for making a diagnosis are evolving: these criteria Medicine, University of Otago, PO clearly increase or decrease markedly the threshold for other mood and anxiety disorders Box 913, Dunedin, New Zealand, diagnosis.1 Several treatment efficacy trials have been conducted and Psychology Associates, About 1-5% of the general population report having but few effectiveness trials with generally representative Dunedin samples generalised anxiety disorder. Many of these people also Correspondence to: C Gale Cognitive behaviour therapy is more efficacious than non- christopher.gale@stonebow. have other disorders, and those with generalised anxiety directive psychotherapy or no treatment otago.ac.nz disorder report a considerable level of disability. Long Anxiety management treatment is also better than no term follow-up studies suggest that generalised anxiety treatment and its efficacy may equal that of cognitive BMJ 2007:334:579-81 disorder is a condition that worsens the prognosis for any doi: 10.1136/bmj.39133.559282.BE behaviour therapy other condition, and that people who have only gener- Antidepressants, benzodiazepines, buspirone, and alised anxiety disorder are likely to develop further con- kava are efficacious but often have clinically significant ditions. The availability of and evidence for efficacious adverse effects treatments has increased in the past five years. is half that in womenw1 and is lower in older people.w2 A Sources and selection criteria review of 20 observational studies in younger and older We used the Clinical Evidence database2 then searched for adults suggested that autonomic arousal to stressful tasks community surveys, randomised controlled trials, and was lower in older people and that older people became systematic reviews—using the term “generalised anxiety accustomed to stressful tasks more quickly than younger disorder”—in Medline, Embase, and the Cochrane Library people.w3 up to June 2006. How do people with the disorder pesent? Who is likely to get generalised anxiety disorder? Anyone presenting with a mood or anxiety disorder may Most of the recent literature uses DSM-IV criteria for have generalised anxiety disorder. Most screening ques- generalised anxiety disorder; the ICD-10 criteria place tionnaires for the condition ask if the person is a worrier, greater weight on somatic symptoms and explicitly limit if they worry overmuch about many things, and then ask comorbidity (box). if they have somatic symptoms of anxiety. As people with The table lists recent community surveys using DSM- generalised anxiety disorder may develop other mood IV. These have shown that 1-5% of the population have and anxiety syndromes over time, it is important to screen reported generalised anxiety disorder in the past 12 for these too, particularly depressive disorder. months. The disorder is more common in women, and often occurs alongside mood disorders, anxiety disorders, How can the effect of treatment be measured? somatoform disorders, and medical conditions.3-8 In clinical trials the most commonly used clinician rating A review found that the rate of generalised anxiety scale is the Hamilton anxiety scale,w4 a 14 item instru- disorder was significantly higher (odds ratio 3.3 (95% ment that places an emphasis on somatic symptoms. The confidence interval 2.0 to 5.5)) in those who had been most used self report measures are the state trait anxiety invloved in civilian trauma (such as a dam collapse or inventory,w5 the Beck anxiety inventory,w6 and the Penn toxic chemical spill).9 Reviews have linked the disorder state worry questionnairew7; the first and last of these four e

t 10 e with bullying (or peer victimisation) and an increase in scales are in the public domain. l the number of life events.11 Two reviews of family studies Treatment response is generally defined as a 50% reduc- comp

k show an increased risk of the disorder in first degree relation in baseline score. Clinical recovery is often defined oc t tives of patients.12 13 as a score of less than 7 on the Hamilton anxiety scale or w8 coms The incidence of generalised anxiety disorder in men a score of 1 or 2 on the clinical global impression scale.

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Prevalence of generalised anxiety disorder* in previous 12 months, and comorbidity, according to national community surveys. Values are percentages unless stated otherwise

Singapore3 Germany4 Australia5 US4 US5 Europe6 Age (years) (No of participants) 20-59 (n=2847) 18-64 (n=7124) >18 (n=10 641) >18 (n=9282) >18 (n=2657) >18 (n=21 425) Instrument SCAN M-CIDI CIDI 2.1 CIDI 3.0 AUADIS CIDI 3.0 Proportion of participants with GAD 3.0 1.5 3.6 3.1 4.1 1.0 Proportion of men (women) 1.0 (3.6) 1.0 (2.1) 3.2 (4.0) Not reported 2.8 (5.3) 0.5 (1.3) Of those with a diagnosis of GAD: Proportion with any comorbidity Not reported 93.1 67.8 85 69.4 Mood disorder Not reported 70.6 44.9 Not reported Not reported Not reported Anxiety Not reported 55.9 37.4 Not reported Not reported Not reported Somatoform Not reported 48.1 Not reported Not reported Not reported Not reported Substance misuse Not reported Not reported 13.3 Not reported 23.0 Not reported Medical condition 53.9 Not reported Not reported Not reported Not reported Not reported

CIDI=Composite international diagnostic interview; M-CIDI was based on CIDI; 2.1 and 3.1 were later versions of CIDI. AUADIS=Alcohol use associated disorder interview schedule. SCAN= Schedule of clinical assessment in neuropsychiatry. *As diagnosed according to the DSM-IV criteria.

What is the outcome for patients? causes anxiety. Cognitive restructuring involves challeng- Evidence on long term prognosis is sparse. At 12-year ing the dysfunctional thought processes and the underly- follow-up of adults at an anxiety clinic, 42% of patients ing assumptions that may be related to the symptoms. had recovered from generalised anxiety disorder, but the Systematic reviews and subsequent randomised tri- disorder was a marker for poor outcome for those patients als found that cognitive behaviour therapy significantly who had another anxiety disorder.14 In a similar cohort improved anxiety and depression over four to 12 weeks of 68 people with generalised anxiety disorder alone (as compared with the waiting list control group, anxiety defined by DSM-III criteria) at initial assessment and fol- management alone, relaxation alone, or non-directive lowed over 12 years, two had the disorder alone after 12 psychotherapy. 16 17 w9-w11 Patients randomised to anxiety years, 28 no longer had a diagnosis, 12 had developed management therapy also fare better than waiting list con- dysthymic disorder, and 10 had developed depression; trols, and the efficacy of this treatment may equal that of the rest had been lost to follow up.15 cognitive therapy.2 w12 w13

Which psychological treatments can help? Which drug treatments can help? Both cognitive therapy and anxiety management therapy Two systematic reviews found that antidepressants (imi- are efficacious, and cognitive behaviour therapy may pramine, paroxetine, and venlafaxine) improved symp- be more efficacious than anxiety management therapy toms over four to 28 weeks compared with placebo.18 19 alone. Clinical trials have found no significant differences among Anxiety management therapy is a structured therapy clinical responses to these antidepressantsw14 or between involving education, relaxation training, and exposure but antidepressants and benzodiazepinesw15 or antidepres- does not include cognitive restructuring; cognitive behav- sants and buspirone.w16 In a systematic review buspirone iour therapy adds to this a cognitive restructuring element. improved symptoms over four to nine weeks compared Relaxation involves practising techniques that lead to with placebo.20 One systematic review found that benzo- muscular or bodily relaxation. Exposure entails (over a diazepines reduced symptoms over two to nine weeks period of time) graded, repeated confrontation (through compared with placebo.21 A clinical trial found no sig- visualisation, image, or the stimulus) with a stimulus that nificant difference in symptoms over three to eight weeks between benzodiazepines, between benzodiazepines and A patient’s perspective buspirone, hydroxyzine, or abecarnil (not available in the w17 w18 As a child, I was excessively worried and nervous. I tended to over-analyse situations, was United Kingdom or New Zealand). In a system- fidgety, and found it difficult to relax. At age 18, I had my first intense anxiety experience, after atic review Kava extract significantly reduced symptoms which my anxiety became significantly worse. Fearful of social and physical situations, compared with placebo (according to scores on the Ham- I avoided potential anxious situations and often used alcohol to deal with social situations. ilton anxiety scale).21 There have been some case reports, My anxieties could change overnight and manifest into a seemingly unsolvable problem. however, of severe hepatic compromise in patients receiv- I often worried about my mental state and felt I had to hide my emotions and thoughts from ing kava.w19 w20 Evidence from clinical trials indicates that strangers, friends, family, and doctors. hydroxyzinew21 w20 and pregabalinw23 may be efficacious. I forced myself to talk to my general practitioner as my anxiety would not subside. For over two years I used medication, which helped significantly. However, I also wished to seek psychological advice to understand what the future might hold for me. I was told by a clinical What further research should be done? psychologist that with the right tools and training I would probably be able to change my The evidence base for generalised anxiety disorder has thought patterns, which had became irrational and negative, and my coping behaviour. It was grown in recent years. The development of standard a great relief to know there could be a better future. methods for conducting and reporting such trials means Understanding the errors in my thinking and implementing better coping strategies has that the newer trials are of a higher quality and are reason- reduced my anxiety levels considerably. And this has therefore enabled me to live a much ably comparable. more balanced and normal life. There are still, however, few trials of clinical effective- Martin, aged 37 ness. More are needed because most patients with gen-

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ADDITIONAL EDUCATIONAL RESOURCES of comorbid conditions and be designed to run over a longer period of time than previous trials. Furthermore, Resources for health professionals some treatment options such as benzodiazepines should • Treatment Protocol Project. Management of mental disorders. 4th ed. Darlinghurst, NSW: be examined by meta-analysis of efficacy before further World Health Organization Collaborating Centre for Evidence in Mental Health Policy, 2004. trials are considered. • Clinical Research Unit for Anxiety and Depression (www.crufad.com/cru_index.htm)— We thank our patient, Martin (see “A patient’s perspective” box), for his description Contains information on anxiety plus a computerised intervention, which currently needs of his generalised anxiety disorder. to be prescribed by a general practitioner Contributors: CG was involved in the development of the search strategy, the • British Association for Behavioural and Cognitive Psychotherapies (www.babcp.com)—Has resource selection, and the drafting of the paper; he is also the guarantor. OD a list of therapists, training resources, and general information for patients about anxiety helped with resource collection, the patient description, and drafting the paper. Kate and cognitive behaviour therapy Thompson helped to develop the search strategy. Keren Skegg and Richard Mullen • Gale C. Generalised anxiety disorder. Clin Evidence. www.clinicalevidence.com/ceweb/ reviewed the paper before publication. conditions/meh/1002/1002.jsp Competing interests: CG has given talks for Lilly Pharmaceuticals and has attended conferences paid for by Lilly and Jannsen Pharmaceuticals. He has no Resources for patients shares, has not been a consultant to, or an investigator in clinical trials funded by, • Bourne E. The anxiety and phobia workbook. 4th ed. Oakland, CA: New Harbinger, 2005. any pharmaceutical company. (For use as a supplement for anxiety management training.) Provenance and peer review: Commissioned and peer reviewed. 1 Slade T, Andrews G. DSM-IV and ICD-10 generalized anxiety disorder: discrepant diagnoses and associated disability. Soc Psychiatry Psychiatr Current diagnostic criteria for generalised anxiety disorder Epidemiol 2001;36(1):45-51. 2 Gale C. Generalised anxiety disorder. Clin Evidence. www. Diagnostic and statistical manual of mental disorders (DSM-IV-TR) clinicalevidence.com/ceweb/conditions/meh/1002/1002.jsp • Excessive anxiety and worry (apprehensive expectation), occurring more days than not 3 Lim L, Ng TP, Chua HC, Chiam PC, Won V, Lee T, et al. Generalised anxiety for at least six months, about a number of events or activities (such as work or school disorder in Singapore: prevalence, co-morbidity and risk factors in a multi- performance) ethnic population. Soc Psychiatry Psychiatr Epidemiol 2005;40:972-9. 4 Carter RM, Wittchen HU, Pfister H, Kessler RC. One year prevalence of • The person finds it difficult to control the worry subthreshold and threshold DSM-IV generalized anxiety disorder in a • The anxiety and worry are associated with three or more (only one for children) of the nationally representative sample. Depress Anxiety 2001;13:78-88. following six symptoms, with at least some symptoms present for more days than not for 5 Hunt C, Issakidis C, Andrews G. DSM-IV generalized anxiety disorder in the Australian national survey of mental health and well-being. Psychol Med the past six months): restlessness or feeling keyed up or on edge; being easily fatigued; 2002;32;649-59. difficulty concentrating or mind going blank; irritability; muscle tension; and sleep 6 Kessler R, Chui W, Demler O, Walters E. Prevalence, severity and disturbance comorbidity of 12-month DSM-IV disorders in the national comorbidity • Anxiety and worry owing to panic disorder, social phobia, obsessive compulsive disorder, survey replication. Arch Gen Psychiatry 2005;62:617-27. 7 Conway K, Compton W, Stinson F, Grant B. Lifetime comorbidity of DSM-IV and separation anxiety disorder are excluded mood and anxiety disorders and specific drug use disorder: results from International statistical classification of disease and related health problems, 10th revision the national epidemiologic survey of alcohol and related conditions. J Clin Psychiatry 2006;67:247-57. (ICD-10) 8 Alonso J, Angermeyer MC, Bernert S, Bruffaerts R, Brugha TS, Bryson H, The patient must have experienced at least six months with predominant tension, worry, and et al. 12-Month comorbidity patterns and associated factors in Europe: feelings of apprehension about everyday events and problems. At least four of the symptoms results from the European Study of the Epidemiology of Mental Disorders below must be present (at least one of which from the first group) (ESEMeD) project. Acta Psychiatr Scand Suppl 2004;420:28-37. 9 Brown ES, Fulton MK, Wilkeson A, Petty F. The psychiatric sequelae of Autonomic arousal symptoms civilian trauma. Compr Psychiatry 2000;41:19-23. Palpitations or pounding heart, or accelerated heart rate; sweating; trembling or shaking; dry 10 Hawker DSJ, Boulton MJ. Twenty years’ research on peer victimisation and psychosocial maladjustment: a meta-analytic review of cross-sectional mouth (not due to medication or dehydration) studies. J Child Psychol Psychiatr 2000;41:441-5. Symptoms involving chest and abdomen 11 Seivewright N, Tyrer P, Ferguson B, Murphy S, Johnson T. Longitudinal Difficulty breathing, feeling of choking, chest pain or discomfort, nausea or abdominal study of the influence of life events and personality status on diagnostic distress (such as churning in stomach) change in three neurotic disorders. Depress Anxiety 2000;11:105-13. 12 Middeldorf CM, Cath CD, van Dyck R, Boomsa DI. The co-morbidity of Symptoms involving mental state anxiety and depression in the perspective of genetic epidemiology: A Feeling dizzy, unsteady, faint, or light-headed; feeling that objects are unreal (derealisation) review of twin and family studies. Psychol Med 2005;35:611-24. 13 Hettema JM, Neale MC, Kendler KS. A review and meta-analysis or that the self is “not really here” (depersonalisation); a feeling of losing control, “going of the genetic epidemiology of anxiety disorders. Am J Psychiatry crazy,” or passing out; fear of dying 2001;158:1568-78. 14 Bruce SE, Yonkers KA, Otto MW, Eisen JL, Weisberg RB, Pagano M, et General symptoms al. Influence of psychiatric comorbidity on recovery and recurrence in Hot flushes or cold chills; numbness or tingling sensations; muscle tension or aches and generalized anxiety disorder, social phobia, and panic disorder: a 12-year pains; restlessness and inability to relax; feeling keyed up, on edge, or mentally tense; a prospective study. Am J Psychiatry 2005;162:1179-87. sensation of a lump in the throat or difficulty in swallowing 15 Tyrer P, Seivewright H, Johnson T. The Nottingham study of neurotic disorder: predictors of 12-year outcome of dysthymic, panic and Other non-specific symptoms generalized anxiety disorder. Psychol Med 2004;34:1385-94. Exaggerated response to minor surprises or being startled; difficulty in concentrating or mind 16 Gould RA, Otto MW, Pollack MH, Yap L. Cognitive behavioural and pharmacological treatment of generalized anxiety disorder: a preliminary “going blank” because of worrying or anxiety; persistent irritability; difficulty in getting to meta-analysis. Behavior Therapy 1997;28:285-305. sleep because of worrying 17 Westen D, Morrison K. A multidimensional meta-analysis of treatments Panic disorder, phobic anxiety disorder, obsessive-compulsive disorder, or hypochondrical for depression, panic and generalized anxiety disorder: an empirical disorder criteria must not be met. If the symptoms are due to a physical disorder or organic examination of the status of empirically supported therapies. J Consult Clin Psychol 2001;69:875-89. mental condition or a substance related disorder, generalised anxiety disorder is excluded 18 Mitte K, Noack P, Steil R, Hautzinger M. A meta-analytic review of the efficacy of drug treatment in generalized anxiety disorder. J Clin Psychopharmacol 2005;25:141-50. eralised anxiety disorder have other mood and anxiety 19 Kapczinski F, Lima MS, Souza JS, Cunha A, Schmitt R. Antidepressants disorders too and are affected for a prolonged period14 and for generalized anxiety disorder. Cochrane Database Syst Rev 2003;(2): because the nature of comorbid conditions can change CD003592. 20 Gammans RE, Stringfellow JC, Hvisdos AJ, Seidehamel RJ, Cohn JB, 15 over time. These trials should compare the following: the Wilcox CS, et al. Use of buspirone in patients with generalized anxiety efficacious psychotherapies; the efficacious medications; disorder and coexisting depressive symptoms: a meta-analysis of eight randomized, controlled studies. Neuropsychobiology 1992;25:193-201. and psychotherapies versus medications. Any such trial 21 Pittler M, Ernst E. Efficacy of kava extract for treating anxiety: systematic design should be sufficiently powered to allow for analysis review and meta-analysis. J Clin Psychopharmacology 2000;20(1):84-9.

BMJ | 17 march 2007 | Volume 334 581 PRACTICE For the full versions of these articles see bmj.com

Pregnancy plus Asthma in pregnancy

Evelyne Rey,1 Louis-Philippe Boulet2

1 Departments of Medicine and Doctors often encounter pregnant patients who have Box 1 | Physiological factors affecting asthma in Obstetrics and Gynaecology, asthma but have limited knowledge of asthma and its Faculty of Medicine, University of pregnancy optimal treatment (see Scenario box). After treating an Montreal, CHU Ste-Justine, 3175 • Increase in free cortisol levels may protect against Côte-Ste-Catherine, Montreal, QC, acute episode in a presenting patient, the doctor should inflammatory triggers Canada H3T 1C5 advise her about asthma, its impact on pregnancy, and 2 • Increase in bronchodilating substances (such as Institut de cardiologie et de the best way to manage her asthma. pneumologie de l’Université Laval, progesterone) may improve airway responsiveness Hôpital Laval, 2725 Chemin Sainte- • Increase in bronchoconstricting substances (such as Foy, Québec City, QC, Canada How common is asthma in pregnancy? prostaglandin F2 α) may promote airway constriction G1V 4G5 Asthma is a serious health problem worldwide, and • Placental 11 β hydroxysteroid dehydrogenase type 2 Correspondence to: E Rey w1 [email protected] its prevalence has increased in the past two decades. decreased activity is associated with an increase in With 3.4%-12.4% of pregnant women having placental cortisol concentration and low birth weight BMJ 2007:334:582-5 asthma, it is the most common chronic condition in • Placental gene expression of inflammatory cytokines may doi: 10.1136/bmj.39112.717674.BE pregnancy.w2 w3 The many national and international promote low birth weight guidelines on the management of asthma apply also • Modification of cell mediated immunity may influence to pregnant women.1 2 w4-w6 maternal response to infection and inflammation

Does pregnancy affect asthma? Some historical cohort and prospective studies have pregnancy the condition is more likely to deterio- found that during pregnancy the severity of asthma rate in women with severe asthma (52%-65%) than remains stable in a third of women, worsens in another in those with mild asthma (8%-13%).3 4Exacerbations third, and improves in the remaining third.w7 w8 are most likely to occur between 24 and 36 weeks of Two prospective studies showed, however, that during pregnancy.3 w9 In a prospective study Murphy et al observed that respiratory viral infections were the most common precipitants of exacerbations (34%), followed Scenario by non-adherence to inhaled corticosteroid medication A 30 year old woman presented to the emergency (29%).3 Another small prospective study showed that department complaining of breathlessness. She was 22 among pregnant women, those with severe asthma were weeks pregnant, and her pregnancy had been complicated by nausea and gastric pain. She had had asthma since more likely to have respiratory or urinary tract infec- childhood, had visited the emergency room at least once a tions (69%) than those with mild asthma (31%) or those year in the previous three years, but had not been followed without asthma (5%).w10 Thus, women with asthma need up regularly. She had used inhaled budesonide irregularly to be closely followed during pregnancy, regardless of in the past and stopped this medication when she became the severity of the disease. Box 1 outlines the physi- pregnant. She had been having flu-like symptoms in the ological factors affecting asthma in pregnancy. previous week and used inhaled salbutamol three or four times a day with partial relief. Does asthma affect pregnancy? On examination, we observed a low grade temperature, Few data exist on how asthma control before preg- normal blood pressure, tachycardia (120 beats/min), nancy affects pregnancy outcomes. In a nested case- tachypnoea (28 breaths/min), expiratory wheezes on chest auscultation, and a normal fetal heart rate. Her oxygen control study including 1808 asthmatic women, Martel saturation was 96% and spirometry showed a forced et al observed that markers of poor asthma control expiratory volume in one second of 42% predicted. and severity before pregnancy were associated with an The initial treatment was inhaled salbutamol, oxygen at 5 l/ increased risk of hypertension during pregnancy.w11 This is the first in a series of min, and oral prednisone 40 mg. She improved sufficiently Conflicting data exist on the effects of asthma on occasional articles about how to manage a pre-existing within 24 hours to be discharged with prednisone for a pregnancy outcomes, due mainly to different study medical condition during week, in addition to regular budesonide and (on demand) designs, different severity and management of asthma, pregnancy. If you would like to terbutaline, medication which was used until delivery. She and inadequate control for confounders. Adverse asso- suggest a topic for this series was referred to an asthma educator and regular medical ciations, for example, were more common in historical please email Kirsten Patrick follow-up appointments were scheduled. ([email protected]) studies than in prospective studies with active

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5 management. The many studies on the effects of Box 3 | Main differential diagnoses in pregnant women asthma on pregnancy outcomes have been analysed with dyspnoea in detail recently.5 6 7 w12 Low birth weight or intrauterine growth restriction • Asthma—Acute or progressive dyspnoea with wheezing and cough, more often with a history of asthma and have been reported in historical studies in pregnant 6 w7 precipitating factors; diagnosis confirmed by pulmonary women with asthma but not in large prospective function tests studies.8 w9 w13 However, two recent, large, well con- • Physiological dyspnoea of pregnancy—Hyperventilation ducted prospective studies did report that low birth due mainly to increased progesterone; may occur early in weight was more common in women who specifically pregnancy and does not interfere with daily activities had daily symptoms of moderate asthma9 or a low expiratory flow, than in women without asthma.w14 • Pulmonary embolism—Acute respiratory distress or gradually progressive dyspnoea with or without A systematic review found an increase in low birth tachycardia, cough, chest pain, haemoptysis, or signs weight in 1453 asthmatic women (four studies) not of deep venous thrombosis; diagnosis established by using inhaled corticosteroids (relative risk 1.55; 95% scintigraphic ventilation perfusion scan, computed confidence interval 1.28 to 1.87).5 Another systematic tomographic angiography, or pulmonary angiography review, which included three studies and 934 asth- • Pulmonary oedema—Acute or progressive respiratory matic women, found that asthma exacerbations during distress in the presence of heart disease, hypertension, pregnancy significantly increased the risk of low birth embolic disease, tocolytic therapy, aggressive fluid weight compared with non-asthmatic women (2.54; replacement, or sepsis; diagnosis confirmed by chest 1.52 to 4.25) and women without exacerbations (2.27; radiography 1.29 to 3.97).6 • Peripartum cardiomyopathy—Dyspnoea caused by A large prospective study of 1739 asthmatic women dilated cardiomyopathy occurring during the final found no increase in preterm delivery,8 a finding con- month of pregnancy to six months after delivery; firmed by a meta-analysis on the impact of asthma exac- signs and symptoms of heart failure confirmed by erbations (four studies, 1438 women).6 However, Schatz echocardiographic evaluation et al reported an association between prematurity and • Amniotic fluid embolism—Acute respiratory distress low respiratory flow in a large prospective study.w14 occurring more often during the evacuation of the uterus Historical studies have reported an association and which may be complicated by hypotension, seizure, disseminated intravascular coagulation, and cardiac between asthma and hypertension during pregnancy.5 arrest Two large, multicentre, prospective, well conducted studies reported an increase in gestational hypertension in women with daily asthma symptoms9 or with Management of asthma in pregnancy a low respiratory flow.w14 A systematic review that The general principles of the management and treat- included two studies and 966 asthmatic women found ment of asthma are the same in pregnant women that asthma exacerbations were not a risk factor for as in non-pregnant women and in men.1 2 w4-w6 Some pre-eclampsia (1.37; 0.65 to 2.92).6 Historical and precautions should be taken, however, in managing prospective studies have reported a higher frequency asthma exacerbation in pregnancy (box 4). Reports of caesarean section in asthmatic compared with from a large prospective study including 1739 non-asthmatic women.8 w7 w9 asthmatic women indicated that adequate manage- All these data suggest that asthma severity and ment of asthma in pregnancy decreases adverse suboptimal control are associated with adverse preg- maternal and fetal morbidity.4 8 The intensity of ante- nancy outcomes. Box 2 suggests special management natal fetal surveillance (fetal ultrasonography and approaches for pregnant women with asthma, and box non-stress test) should be based on the severity of 3 outlines the main differential diagnoses in pregnant asthma, the risk of intrauterine growth retardation, women with dyspnoea. and pre-eclampsia.

Education Box 2 | Special considerations in pregnant women with asthma Pregnancy is a good time to review the patient’s basic • Ensure optimal asthma control throughout pregnancy understanding of asthma and its management, including trigger avoidance, asthma control, and adequate • Manage asthma exacerbations aggressively use of devices, medication, and personal action • Avoid delay in diagnosis and treatment plans. Women and doctors should be vigilant for the • Assess medication needs and response to therapy frequently presence of environmental factors such as allergens • Ensure adequate patient education and acquisition of self management skills that may need to be tackled during pregnancy. Useful • Treat rhinitis, gastric reflux, and other comorbidities adequately information is available on the websites of national • Encourage smoking cessation pulmonary societies and international organisations, • Assess pulmonary function (expiratory flow) with spirometry at least monthly and patients can be referred to these if they seek • Offer a multidisciplinary team approach additional information.2 Furthermore, whenever • Do not give flu vaccination until after 12 weeks of pregnancy possible, the educational intervention that started in • Be aware of the risk of pre-eclampsia and intrauterine growth retardation the doctor’s surgery should be continued by an asthma educator.

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Box 4 | Management of acute asthma in pregnancy Large prospective and case-control studies have found that oral corticosteroids are associated with pre- • Intervene rapidly term delivery and pre-eclampsia.1 9 w11 w21 Importantly, • Closely monitor the woman and assess fetal wellbeing prednisone is inactivated at 90% by the placenta, which continuously limits fetal exposure to the active drug and the risk of • Maintain oxygen saturation >95% fetal withdrawal.w22 • Avoid PaCO2 >40 mm Hg Inhaled corticosteroids remain the cornerstone • Place woman in a left lateral position of treatment for persistent asthma, regardless of its • Provide ample hydration with intravenous fluid (isotonic severity. They are safe in pregnancy, and large pro- saline 125 ml/h) if drinking is impossible spective studies, case-control studies, and systematic • Avoid hypotension with adequate position, hydration, reviews have shown that they are not associated with and treatment fetal malformations or perinatal morbidity.5 10 w11 w17 w18 • Use adrenaline (epinephrine) only in the context of an Large prospective studies and randomised trials have anaphylactic reaction also shown that inhaled corticosteroids prevent asthma 10 w9 w23 w24 • Consider intubation earlier than usual and call an exacerbations in pregnancy. Most studies on expert if intubation is required as it can be more inhaled corticosteroids in pregnancy have been con- difficult in pregnant women owing to the oedema of the ducted with budesonide, but the corticosteroid that oropharyngeal mucosa was used successfully before pregnancy should be continued into childbirth.w25 Pharmacological treatment in pregnancy Prospective, observational, and case-control studies

Many mothers and their doctors are concerned about have shown that cromolyn sodium and short acting β2 the potential effects of asthma drugs—on their babies agonists are safe during pregnancy.9 10 w11 w21 w26

as well as on the women themselves. In a recent large Few data exist on long acting β2 agonists used alone cohort study, Enriquez et al reported that asthmatic or in combination with inhaled corticosteroids. Sal‑ women decreased their use of inhaled corticosteroids meterol and formoterol at high doses are associated

by 23%, of short acting β2 agonists by 13%, and of addi- with fetal malformations in animals, but these drugs tional oral corticosteroids for exacerbations by 54% did not cause fetal malformations, preterm delivery, or when becoming pregnant.w15 Cydulka et al found that low birth weight in the limited number of women using in emergency departments doctors were less likely to them in prospective studies.9 w27 w28 As is the case out-

prescribe corticosteroids both initially and on discharge side pregnancy, long acting β2 agonists should always to pregnant women than to non-pregnant women (ini- be used together with an inhaled corticosteroid, ideally tially, 44% v 66%; on discharge, 38% v 64%).w16 in a combination product.w29 It is safer, however, to take asthma drugs in preg- Data are scarce on the safety of leukotriene modi- nancy than to leave asthma uncontrolled as large fiers in pregnancy. No fetal malformation or adverse prospective studies have shown that adverse perinatal outcomes in pregnancy were seen in nine women outcomes are associated with uncontrolled asthma and exposed to a leukotriene modifier in the prospective reduced expiratory flow.9 w14 Moreover, prospective study by Bracken et al9 or in 176 women exposed to studies, case-control studies, and systematic reviews montelukast (145 in the first trimester) according to the have shown that inhaled corticosteroids, theophylline, manufacturer.w30

and short acting β2 agonists do not increase the risk Animal studies show no teratogenicity with montelu- of fetal congenital malformations, pre-eclampsia, pre- kast or zafirlukast but do show such risk with zileuton term delivery, or low birth weight.10 w11 w17 w18 There- (not licensed in the United Kingdom).w22 In the absence fore, treatment for achieving and maintaining adequate of strong data on the safety of these drugs it seems rea- asthma control should be prescribed and compliance sonable to replace them with an inhaled corticosteroid

regularly assessed. at the start of pregnancy or with a long acting β2 agonist Although pregnancy modifies the absorption rate (if this is used as an “add on” therapy). and pharmacokinetics of some medications, the dose Theophylline has been reported to be safe in human or regimen of asthma medications do not usually need pregnancy at recommended doses.1 w21 w24 Serum theo- to be changed in pregnancy. Case-control studies have phylline levels should be monitored because drug found that systemic decongestants used in the first metabolism changes in pregnancy. Theophylline is trimester are associated with small increases in risk rarely used now in asthma, however, and it remains a of fetal gastrochisis, intestinal atresia, and hemifacial last treatment option in moderate or severe asthma. microsomia.w19 Epidemiological studies have shown that oral corti- Does asthma affect labour and delivery? costeroids in the first trimester are associated with an Labour and delivery are not usually affected by increased risk of fetal cleft lip or palate.w20 However, asthma, but prospective studies have shown that as the increased incidence is small (rising from 0.1% to 10%-20% of women experience an exacerbation dur- 0.3%) compared with the benefits of using such medica- ing labour.w8 w9 The drugs should be continued and tion to regain asthma control quickly, the practitioner adjusted according to need during this period. Box 5 should not refrain from using oral corticosteroids in outlines procedures and medications for women with severe asthma and life threatening situations. asthma during labour.

584 BMJ | 17 march 2007 | Volume 334 PRACTICE

Box 5 | Procedures and medications during labour Conclusions Asthma may be influenced by pregnancy, but the out- • Continue medications and give short acting β2 agonists or corticosteroids, or both, if asthma is not well controlled come and prognosis of most asthmatic mothers and their newborn infants are usually favourable, particu- • Provide ample hydration with intravenous fluid larly if the women’s asthma is well controlled in preg- • Evaluate pulmonary status and oxygen saturation on nancy. Exacerbations should be prevented by optimal admission, and later as needed asthma management, and if they occur they should • Favour lumbar epidural analgesia to provide adequate be treated aggressively. Women’s drug treatment needs pain relief (which decreases bronchospasm) and to reduce should be regularly assessed in the light of asthma con- oxygen consumption and minute ventilation trol criteria, including measures of expiratory flow. • Give stress dose of corticosteroids (such as 50-75 mg a w31 day of hydrocortisone equivalent for one to two days ) if Contributors: Both authors performed the literature search. ER wrote the systemic corticosteroids have been taken within previous first version of the manuscript, which was revised many times by both months authors. ER is the guarantor of the paper. • Avoid bronchoconstrictor agents for management Competing interests: None declared. of abortion or labour (such as prostaglandin F2 α) or Provenance: Commissioned and peer reviewed. for postpartum haemorrhage (such as ergonovine, methylergonovine (neither is licensed in the UK), and 1 National Asthma Education and Prevention Program Working carboprost) Group. Managing asthma during pregnancy: recommendations for pharmacologic treatment—2004 update. Expert panel report. J Allergy Clin Immunol 2005;115:34-46. 2 Global Initiative for Asthma (www.ginasthma.com) 3 Murphy VE, Gibson P, Talbot PI, Clifton VL. Severe asthma exacerbations Does asthma affect postpartum period and during pregnancy. Obstet Gynecol 2005;106:1046-54. breast feeding? 4 Schatz M, Dombrowski MP, Wise R, Thom EA, Landon M, Mabie W, et al. Asthma morbidity during pregnancy can be predicted by severity The postpartum period is not associated with an classification. J Allergy Clin Immunol 2003;112:283-8. increased rate of asthma exacerbations. In women 5 Murphy VE, Gibson PG, Smith R, Clifton VL. Asthma during pregnancy: mechanisms and treatment implications. Eur Respir J 2005;25:731-50. who experienced a change of severity during 6 Murphy VE, Clifton VL, Gibson PG. Asthma exacerbations during pregnancy, the severity reverts to pre-pregnancy pregnancy: incidence and association with adverse pregnancy level within three months after the birth.w8 Few outcomes. Thorax 2006;61:169-76. 7 Gluck JC, Gluck PA. Asthma controller therapy during pregnancy. Am J data are available on the safety of asthma drugs Obstet Gynecol 2005;192:369-80. in breastfed neonates. Most drugs are considered 8 Dombrowski MP, Schatz M, Wise R, Momirova V, Landon M, Mabie W, et al. Asthma during pregnancy. Obstet Gynecol 2004;103:5-12. to be safe, but irritability or sleepiness have been 9 Bracken MB, Triche EW, Belanger K, Saftlas A, Beckett WS, Leaderer BP. reported in the breastfed neonates of women taking Asthma symptoms, severity, and drug therapy: a prospective study of theophylline and antihistamines.w22 w32 Non-steroidal effects on 2205 pregnancies. Obstet Gynecol 2003;102:739-52. 10 Schatz M, Dombrowski MP, Wise R, Momirova V, Landon M, Mabie W, et anti-inflammatory drugs should be avoided in women al. The relationship of asthma medication use to perinatal outcomes. J intolerant to aspirin. Allergy Clin Immunol 2004;113:1040-5.

Unsafe driving

Early in my medical career my aged car—which I had one would do anything about it because of the cost of bought with my first month’s wages—had broken down, the contract with the taxi company. I did not, therefore, and the hospital arranged to pay a minicab driver to formally report this, but nowadays I would. take me to another hospital. I am obliged to breach confidentiality under General The minicab driver, who seemed to be in his late 30s, Medical Council guidelines several times a year. I made an illegal right turn to speed the wrong way up have to inform the medical adviser at the Driver and a short one-way street. I asked him if he was in a rush, Vehicle Licensing Agency that a patient with dementia, because I was not. He told me that he was: this was his who is incapable of understanding advice not to drive last job of the day, and he wanted to get to his general and insists on continuing to do so, is unsafe to drive. practitioner as he had high blood pressure, and it The result is usually revocation of licence, a distressed needed to be checked. patient, relieved family, and arguably maintained public I wondered whether to advise him that if he cut his safety. speed and avoided driving the wrong way up a one-way Many such patients tell me that they are safer drivers street, then his high blood pressure might improve. I than younger drivers who drive badly. I sometimes doubted whether his general practitioner would know as agree with them that they may be right but add that I much about this man’s driving as he or she did about his still must follow GMC guidelines. I find it strange that blood pressure. I am obliged to breach confidentiality for this small I remained silent until we completed our journey, keen minority of patients, when I do not report the far more to keep the driver’s concentration on driving rather than numerous instances of unsafe driving I see outside work, speaking. I was pleased to reach my destination without by young people who are not my patients. anyone getting injured. I told a senior colleague of my Peter Simmons consultant psychiatrist, Queen Elizabeth II Hospital, concern that any patients or staff transported by this Welwyn Garden City cab driver could be at risk, but her reply was that no [email protected]

BMJ | 17 march 2007 | Volume 334 585 views & REVIEWS

Advice to a new editor PERSONAL VIEW Christopher Martyn

Dear Hermione, Scientific, and they are derived from readers like them and find them both Congratulations on your appointment citations of papers published two and three educational and entertaining, but they are as editor of the Journal of Amazing Medical years earlier. It will be 2009 before anything rarely cited and they are usually counted Advances. I’m sure that you have already you’ve done as editor begins to have an as citable by Thompson Scientific. And try gathered an enthusiastic new editorial team influence. not to publish papers in areas where there is and that you’re bursting with ideas for You probably already know that the little research activity. Resist any sympathy improving the journal. The last thing that impact factor is calculated by dividing you feel when a paper is submitted on an I want to do is to dampen that enthusiasm the number of citations that your journal unfashionable condition such as deafness but, as someone who has played the receives by the number or itch. You may admire publishing game for a while, I felt a word of of citable papers that you Concentrate on raising the researchers for tackling warning might be useful. published. Increasing the your impact factor . . . common, unromantic illnesses, You’ll find, if you haven’t done so number of citations, of course, there’s no time to lose but there aren’t many scientists already, that the first thing potential authors raises the impact factor. But so working on these conditions so ask you about the journal you edit is: can reducing the number of citable papers. the constituency available to cite them is too “What’s its impact factor?” Indeed, it will You should think about both approaches. small for you to bother with. usually be the only thing they ask you. If The most reliable way of increasing the On the other hand, if you can pull it off, you can reply with a double digit figure, number of citations is to do it yourself. It’s it’s an excellent idea to publish a paper they’ll immediately try to interest you in easy to find ways of citing papers in your in a well researched area that contains a a manuscript they are writing. If you have own journal. You can, for example, write serious mistake. People will seize on the to admit a low number, your plans to an introductory article, under a title such error, referring to it in their own papers and liven up the book reviews and to redesign as Editor’s Choice, for each issue. It’s not writing refutations that you can publish in the journal’s website won’t be enough to much effort to make a few banal remarks your correspondence columns. The trick is compensate. Potential authors will make about the papers published that month in ensuring that the mistake isn’t so obvious an excuse and walk away. If you think I and, if you flag the articles you mention that publishing the paper reflects on your exaggerate how much notice authors take with superscripts and a list of references competence as an editor. of impact factors, take a look at the trouble underneath, Thompson Scientific’s search Now, it’s well known that, as a measure some journals take to make them known. engine will pick them up and count them of a journal’s worth, the impact factor is The Lancet makes a feature of its impact as citations. Commissioning commentaries seriously deficient. Perhaps you’ll take the factor on its home page. Brain’s website on papers and encouraging correspondence view that editors ought to have better things gives its impact factor to three decimal also helps because this too provides an to do than spend time and effort trying to places. opportunity for self citation. Some editors influence such a flawed indicator. Perhaps Forget most of your current plans. The have gone so far as to ask authors of papers you would rather concentrate on producing redesign and book reviews can wait. You that they are about to accept to add papers a journal that is useful to your readers need to concentrate on raising your impact previously published in their journal to the instead of grinding away at stratagems to factor, and there’s no time to lose. Impact list of references. But I don’t recommend raise your position in a league table that no factors are updated annually by Thompson this; it’s just too obvious. one but a fool would take seriously. You The other part of your strategy should be might even feel that journal editors as a NEJM 44.016 to reduce the denominator of citable papers. species have been involved in a collective Unfortunately, Thompson Scientific doesn’t dereliction of duty in the way they have Nature Medicine publish the criteria they use to decide what allowed this malignant number to dominate 28.878 Lancet 23.878 constitutes a citable paper. It’s not even biomedical publishing. I do hope not. clear if there are explicit criteria or if they Although you’ll probably produce a journal

PloS Medicine are applied consistently. Nevertheless, if that’s widely read and enjoyed, you’ll never 8.389 articles are short, lack abstracts, and don’t impress the sort of people who prefer a

JAMA BMJ 9.052 contain too many references they probably number to thinking for themselves. 23.494 won’t be counted as citable themselves. I wish you the best of luck whatever you Journal of General CMAJ Internal Medicine This is why you can publish commentaries decide. 7.402 4.040 and editorials. Christopher Martyn is asso��c�iate�� ed�itor��, BMJ QJM 2.829 Don’t publish case reports. I know that [email protected]

586 BMJ | 17 MARCH 2007 | Volume 334 VIEWS & REVIEWS

A film that has a lot to teach all doctors p 589 review of the week Celebrating the medical past, again

Do we need another 400 minute radio series on the history of medicine, however excellent this one is, asks Balaji Ravichandran

The history of medicine, it seems, must always be No prizes for guessing the heroes of Cunningham’s progressive and be celebrated. Recently, though, it story—Hippocrates, Galen, Paracelsus, Vesalius, has become fashionable to write accusatory histories— Harvey, Sydenham, Jenner, Pasteur, Koch, Magendie, consider, for example, Bad Medicine by David Wootton Morton, Lister, Nightingale, and Fleming—nor for the (review BMJ 2006;333:606). Yet the common thread of milestones and the background themes that define each progressivism binds them all, and Andrew Cunning‑ of his episodes: anatomical progress, establishment of ham’s radio series is another case in point. hospitals, clinical medicine, experimental physiology, Modern medicine, the argument usually goes, is scien‑ microbiology, anaesthesia, tropical medicine, nutrition, tific. For most of human history, it wasn’t: from the days antibiotics, and transplantation. As a welcome relief, of Hippocrates and Galen, the patient centred approach there are episodes on the entry of women into medicine, The Making of Modern to medicine was more of an art than a science, and this the development of clinical medicine, and the establish‑ Medicine viewpoint dominated medical thinking till the late 18th ment of the UK’s National Health Service. Written and narrated by century. But in the aftermath of the French Revolution Cunningham’s series richly enjoys the benefits of Andrew Cunningham scientific discoveries, particularly microbiological ones, hindsight and charitable interpretation. He also says BBC Audiobooks, £25 were slowly yet systematically adopted by practitioners that modern scientific medicine is superior to all other Broadcast as 30 part of Western medicine. Medicine, therefore, has moved practices of medicine, past or present. Wootton, also series on Radio 4, from strength to strength, and is likely to move on in the progessivist in distributing praise and allocating blame, weekdays at 3 45 pm, same direction in the foreseeable future. would largely agree, though Cunningham tries to make starting 5 February 2007 Accusations of viewing the medical past through rose sense of the past in its own terms. He is not entirely suc‑ www.bbc.co.uk/radio4/ tinted spectacles abound—often, rightly so. Dissenters cessful, but he makes a genuine case for understanding science/medicine reject this and have suggested that doctors have done why doctors of the past behaved the way they did. Rating: **** much more harm than good. Undoubtedly, most The problem with most celebratory accounts of medi‑ advances weren’t medical at all, but scientific; refusing cal history is that they are largely unreflective. They to embrace new scientific discoveries, doctors contin‑ might make you feel good and might throw in some ued to favour treatments that had nothing more than interesting facts and legendary stories. In this radio a placebo effect. series, which, with its great many quotations, sounds David Wooton says that the history of modern rather like the reading of a popular history textbook, medicine begins with the discovery of antisepsis by you have familiar anecdotes about Morton’s discov‑ Joseph Lister and its incorporation into surgical proce‑ ery of anaesthesia and the etymology of vitamins and dures. Since then, of course, medicine has progressed, tuberculosis, as well as Osler’s aphorism on the clinical as scientific advances have gone hand in hand with importance of syphilis. advances in medical education and practice. Other his‑ In tune with modern medicine, Cunningham even torians, like Roy Porter (and including Andrew Cun‑ talks at length about sanitation and tropical medicine, at ningham), may not exactly agree, but they would urge the expense of cutting edge medical technologies involv‑ readers to view the past in its own context and to inter‑ ing radiology, biotechnology, and pharmacology. Again, pret events with empathy. the dichotomy between reflective academic (unread‑ Ironically, the works of dissenters have more in com‑ able) history and unreflective popular celebratory his‑ mon with celebratory histories of medicine by Porter tory looms large. and Cunningham than one would think. The working Length matters. More and more medical history hits formula behind dissenting writings is woefully familiar. the market every year, whether in books or in radio The problem with Divide 2000 years of history into discrete, convenient and television programmes. So, why make another periods; give each its own discoveries and heroes (or 400 minute series on the history of medicine that dif‑ celebratory accounts villains); and show that from humble (and even repug‑ fers little from its predecessors, unless to inspire the few of medicine is that nant) beginnings, medicine has progressed farther than who might consider a career in medicine? they are largely anyone could have predicted. Balaji Ravichandran is editor, studentBMJ [email protected] unreflective

BMJ | 17 MARCH 2007 | Volume 334 587 VIEWS & REVIEWS

The poverty of expectation

FROM THE My father went bankrupt in 1972. I eventually resigned myself gives our lives shape, camaraderie, FRONTLINE My family was sent tumbling to signing people off, even if and purpose. Work and routine are down into a black financial abyss. they were capable of work. I the elixir of a contented life. Des Spence We fell, but rather than hit the rationalised that I was not an I see generations of poor bottom, we were caught in a instrument of the benefits system families who have never worked. safety net—the welfare state. This and was not equipped to police Their material deprivation educated me, fed me, clothed me, incapacity benefit. pales in comparison with the housed me, paid for my university Currently, some 2.7 million absolute poverty of expectation education, and supported my people claim incapacity benefit. that is killing them. They are studies. A debt of gratitude to Welfare reform, therefore, is disarticulated from broader society lives with me everyday. important and overdue. This society and trapped in a cycle of There is nothing that I would not is not an economic debate, but subsistence benefits. do to protect our welfare state—for fundamentally a medico-social The welfare state is failing our me it is what passes as my faith. issue. For incapacity benefit is a most deprived populations and Welfare reform is back on the key ingredient in the speedball needs to be reformed for the agenda. Entrenched opinions have that is social deprivation. health of our nation. We must get already started shelling each other We might all hate work at people back to work using both with insults. This is nothing new. times—lying under our duvets incentives and sanctions. Doctors When I first started as a general scheming how to use our medical can play an important role but practitioner I tried to limit medical knowledge to feign the kind must be ready to wrap up against certification. But this compromised of sickness that brings early the wind that will surely blow. my relationship with patients, retirement. But we get up and go. Des Spence is a general practitioner, who simply sidestepped me. It is the very drudgery of work that Glasgow [email protected] Hidden extras DRUG TALES AND Last weekend The Food Magazine published research on highlighted in a medicine’s product literature or other OTHER STORIES over-the-counter medicines for young children (www. guidance; but, even so, a lack of awareness may prevent foodcomm.org.uk/latest_medicines_Mar07.htm). the prescriber from averting or promptly spotting them. Ike Iheanacho Its conclusion that some of these treatments contain Clinical reactions are not the only problem. People with inappropriate additives has caused understandable specific religious or lifestyle principles can feel justifiably anxiety among parents and healthcare professionals. But aggrieved if not forewarned of, or offered alternatives to, this has overshadowed wider issues about the content medicines that contain animal derivatives such as pork of medicines, particularly those less safe than over-the- or beef gelatin. counter treatments. None of this should undermine the importance of Every working day, a doctor may unknowingly excipients. They may be crucial in making, stabilising, prescribe dozens of substances. This represents neither distinguishing, storing, and taking medicines. And incompetence nor carelessness. Far from it: each there is clearly a balance to be struck between avoiding prescription might be wholly appropriate and accurately unjustified paranoia in the prescriber and patient, while documented. Nevertheless, it may still obscure exactly ensuring both are well informed about the therapies what the patient is being invited to take. they use. But achieving this compromise is difficult, not This is because of the ragbag of other substances least because doctors are usually taught little or nothing incorporated in a prescribed medicine with the so- about excipients. This knowledge gap can leave them called active ingredient. Possibilities include coatings, hamstrung to critically appraise a medicine’s content, as colourants, printing inks, preservatives, sweeteners, they would clinical data about the treatment. flavourings, fillers, agents to facilitate binding or Oddly enough, another type of prescriber is better disintegration, lubricants and flow-enhancers—a non- placed to make this sort of assessment. The development exhaustive list. These excipients (and even this umbrella of prescribing by pharmacists in the UK has been greeted term may be unfamiliar to some prescribers) are typically rather sniffily in certain quarters. Yet their training and an under-recognised part of treatment. Until something experience of may confer advantages over doctors in goes wrong, that is. some prescribing decisions. It is hard to believe this A common misconception is that excipents are differential expertise will not have tangible benefits for completely inert substances not worth worrying about. patients. It might do something for the sniffing, too. In reality, these supposedly innocent bystanders can Ike Iheanacho is editor, Drug and Therapeutics Bulletin cause significant casualties. Such effects may well be [email protected]

588 BMJ | 17 MARCH 2007 | Volume 334 VIEWS & REVIEWS

Medical classics The foul taste of medicine The Doctor I was one of the expressed a general Film released 1991 many middle class BETWEEN pessimism about the This film is a classic portrayal of a doctor’s children whose ton‑ THE LINES gustatory quality of transformation as a result of his own experience of sils were sacrificed medicines that has, illness. Like a lot of Hollywood movies, it shows the hero Theodore Dalrymple overcoming adversity and coming out a better person; to the need of ear, on the whole, been it also a reflection on the different aspects of being a nose, and throat borne out by expe‑ doctor. surgeons to increase rience: “And yet William Hurt plays Dr Jack McKee, a cardiac surgeon, their incomes. I am [the potion] must who is lively and technically competent, but also not in the least bitter be taken, for health: arrogant, and who has appalling doctor-patient about it because of neither could it be communication skills. Why is it always the surgeons that the ice cream I was / wholesome, if it seem to be this way? Maybe there is some truth in what Dr McKee says on his ward round with his subservient given to eat after the were less unpleas‑ junior staff, that a surgeon needs to be quick and operation, though I ing; neither could it decisive, and that concentrating on the patient’s agenda did dive down to the make me / whole, if can be distracting. His big fear seems to be that if he bottom of the bed it did not first make becomes sensitive to the patients’ needs and fears, he and spit out the foul me sick.” will be paralysed into inactivity. tasting medicine I For the good Dr McKee develops an irritating cough, and eventually was also given. bishop, it is divinely after coughing up blood he goes to see an ear, nose, The ward sister ordained that what and throat surgeon in his own hospital, the glamorous The healthfulness Dr Lesley Abbott. There is brilliant acting here by William rebuked me sternly is good for us can of the unpleasant is Hurt, as he portrays a patient having a laryngoscope for my bad behav‑ a metaphor for the only be unpleas‑ shoved down his choking throat and then being told iour, but I had my human condition ant, at the very bluntly by Dr Abbott, “You’ve got a growth, doctor.” She, revenge when my least a denial of our rather like Margaret Thatcher, seems to feel that she has mother gave me a fleshly inclinations. to be as tough as the men to survive in her professional box of chocolate The healthfulness world. letters that I distributed to all the staff of the unpleasant is a metaphor for We follow Jack McKee trying to come to terms with with the conspicuous exception of the the human condition: “Why do I not his illness, while also carrying on his work as a heart surgeon, and we see just how difficult it is to be both a ward sister. cheerfully take, and quaff up that bit‑ doctor and a patient, especially when you are playing Medicine has always tasted foul, of ter cup of / affliction, which my wise both roles in the course; indeed, the fouler the better. God hath mixed for the health of my same hospital. The Joseph Hall, DD (1574-1656) reflected / soul?” best scenes show the on this in one of his Occasional The reaction of Lord Bishop of powerlessness and Meditations, which he entitled “On a Exeter (later of Norwich) to his medi‑ frustrations of being medicinal potion”: cine was precisely mine 50 years ago: a patient, from nearly “How loathsome a draught is this! “Why do I then turn away my head, being given a barium SNAP/REX Transformation: Hurt as McKee enema intended for a How offensive, both to the eye, / and and make faces, and shut mine / eyes, neighbouring patient, to the endless waiting around and to the scent, and to the taste? Yea, the and stop my nostrils, and nauseate and poor staff communication. very thought of it, is a / kind of sick‑ abhor to take the / harmless potion for The film is much less effective when straying away from ness: and, when it is once down, my health?” the medical arena to portray Jack’s close relationships. very disease is / not so painful for Why, he goes on to ask, make such Finding difficulty communicating with his wife, he seeks the time, as my remedy. How doth a fuss when “we have seen mounte‑ solace with a fellow radiotherapy patient, who is dying it turn the / stomach, and wring the banks, to swallow dismembered toads, from a brain tumour. Despite being terminally ill, she is beautiful and elegant with her shaven hair, and they run entrails; and works a worse distemper, and drink the poisonous brother after away together, dancing into the sunset in the Nevada / than that, whereof I formerly com‑ them, only for a little ostentation and desert. Pure Hollywood schmaltz! plained?” gain?” Jack discards his female ENT surgeon for a more Reading this, I confess, I thought At the time of my tonsillectomy I sensitive male colleague whom he had previously of my time in a malarious country had a friend who used to drink the ridiculed for being a nerd, but now clearly recognises in Africa, where I recommended water in puddles and swallow earth‑ as the sort of doctor he needs. He survives surgery and proguanil as prophylaxis and grew worms, only for a little ostentation (to the temporary loss of his voice, and is finally reconciled angry when my patients did not take appal the adults) and gain (we paid with his long suffering wife. He returns to work as a much more caring and effective doctor, able to successfully it, although I did not take it myself him three pence to do it). I certainly combine the technical and human qualities of being a because it nauseated me so. wasn’t prepared, then, to swallow foul doctor. Better, I thought, malaria than a life tasting medicine for that most trivial I use this film extensively when teaching medical of gastritis; and to this day, 20 years and uncoupling of all reasons, my own students, but it has a lot to teach all doctors, at all stages later, yea, the very thought of it is a good. of their careers. kind of sickness. Theodore Dalrymple is a writer and retired David Memel, general practitioner, and senior teaching The Right Reverend Dr Hall doctor fellow, University of Bristol [email protected]

BMJ | 17 MARCH 2007 | Volume 334 589 OBITUARIES For the full versions of articles in this section see bmj.com

As KAVI’s lead scientist, Bwayo was STD/AIDS and as a senior member of the just concluding one of the first trials of World Health Organization’s collaborative a candidate AIDS vaccine designed to centre for STD/HIV research training. prevent HIV/AIDS caused by multiple He eventually became one of Africa’s subtypes in east Africa. His investigations most renowned AIDS researchers, whose into the role of truck drivers as a vector work was critical in shaping HIV vaccine for the HIV virus led to his seminal policy across east Africa and giving Kenya research in discovering an apparent natural a key position in the global HIV vaccine immunity among a small group of Nairobi research arena, particularly through his sex workers, which has been key to much innovative development of partnerships to contemporary vaccine development. bring African and international capabilities He recently said: “The development together. of the vaccine dates back to 1985 when “This is a devastating loss for the entire we started to study a group of female AIDS vaccine field,” said Seth F Berkley, e

p commercial sex workers in Nairobi. president of the International AIDS During follow-up, we found out that a Vaccine Initiative. “Professor Bwayo was , euro, i

v small percentage, 5% of the women, a talented scientist, working diligently to ia remained uninfected, even though they find a final solution to the AIDS crisis. Job Joab Bwayo continued to be exposed to HIV.” Under his stewardship, KAVI has played a His research discovered that the leading role in driving research for AIDS Pioneering researcher on AIDS uninfected women had developed very vaccines globally. He was a renowned high numbers of killer T cells, a crucial leader in the AIDS community, in the vaccines component of the immune system. This AIDS vaccine development field, and in observation contributed to the decision to his own country, understanding that Kenya The senseless death of Professor Job Joab create a vaccine designed to boost T cell was at the forefront of AIDS research.” Bwayo, one of Africa’s leading research numbers. Born to Joseph and Margaret K Bwayo scientists, in a violent carjacking in Nairobi “We know that in the search for an AIDS in 1948 in the Bungoma district of western has sent shockwaves across Kenya and vaccine, many different vaccines will need Kenya, Bwayo completed high school caused consternation and dismay among his to be tested. Kenyan scientists are proud education in western Kenya before going fellow researchers world wide. to have had long term experience with on to the University of Nairobi Medical The head of the Kenya Medical this research, and to be on the forefront School. On completing his bachelor’s Research Institute, Dr Davy Koech, of promising new vaccine candidates,” he degree in medicine in the mid-1970s, described Professor Bwayo as “one commented last year. he continued his research and graduate of Africa’s most distinguished and An eloquent teacher as well as studies at the University of Nairobi while accomplished career scientists of his time.” formidable researcher, one of his working full time at the Kenyatta National Dr Kevin M De Cock, director of HIV/ favourite expressions was: “HIV vaccine Hospital, completing his doctorate in AIDS at the World Health Organization, development is a marathon, not a sprint immunology in 1985. told the BMJ: “Professor Job Bwayo was a and—as we all know—Kenyans are very Bwayo’s untimely demise was the result respected, committed scientist who made good at marathons.” of the latest in a wave of high profile car important contributions to HIV vaccine Among his recent achievements were jackings in Nairobi, which on 7 February research. His senseless and tragic death helping to conduct the first five AIDS 2007 prompted the US Embassy to issue is a great loss to his family, Kenya and vaccine trials in Kenya; building a world a travel advisory warning of the dangers Africa, and HIV/AIDS science.” class, accredited laboratory facility and of visiting Kenya, as well as calls for a His former collaborator Professor scientific infrastructure to prepare for crackdown on gun crime by the Kenyan Andrew McMichael, director of John larger scale trials; establishing rigorous press and government. Radcliffe Hospital’s Weatherall Institute quality control programmes; and Bwayo leaves an American born wife, of Molecular Medicine, commented: contributing to Kenya’s national AIDS Elizabeth (who was badly injured in the “Professor Bwayo built the capacity for vaccine plan. attack), and four children. Kenyans to conduct high quality vaccine In addition to heading Kenya’s AIDS Peter Moszynski trials, founding the internationally respected vaccine initiative, Bwayo was former Kenya AIDS Vaccine Initiative (KAVI). He chairman of the Department of Medical Job Joab Bwayo, leading researcher on AIDS and was trying to help young Kenyans, and it is Microbiology, College of Health Sciences. tropical diseases Nairobi (b 1948; q Nairobi around tragic that young carjackers should gun him He also served as co-director of the 1975; PhD), died from gunshot wounds during an down in this way.” Regional AIDS Training Network for armed robbery on 4 February 2007.

590 BMJ | 17 March 2007 | Volume 334 OBITUARIESobituaries

paediatric neurologists in the Navy after a dramatic escape David Ivor Bowen United Kingdom and was a Peter Ogilvie Leggat from occupied Greece. In 1947 founder member, secretary, and he emigrated to New Zealand, president of the British Paediatric where he qualified again. In Neurology Association. He was 1952 he established a general a senior lecturer at Birmingham practice in Tauranga, but in 1963 University and a consultant at the he started his research into Birmingham Children’s Hospital. cancer. He was appointed the He was an exceptionally hard Meres senior student in medical worker and an excellent teacher. research at St John’s College, Time was of little importance: Cambridge, becoming a senior his well-attended teaching member of the Department of Former consultant ophthalmologist ward rounds often ended after Former consultant physician the Regius Professor of Physic Harrogate District Hospital (b 1937; midnight. His special interests Northern Regional Hospital Authority and supervisor at St John’s. After q Cambridge/St Thomas’ Hospital, were neuro-ophthalmology, (b 1917; q Aberdeen 1941; MD, retirement in 1977 he was general London, 1961), died from cancer on 5 metabolic diseases affecting FRCP), died from congestive heart medical officer for the US army in February 2007. the developing nervous system, failure/ischaemic heart disease on 5 Mannheim for five years. He leaves After house jobs at St Thomas’ and adrenoleucodystrophy. He February 2007. a wife, Barbara, and 23 direct Hospital, David Bowen travelled was kind, generous, popular, Peter enlisted as a doctor in the descendants, although he was round the world as a ship’s and notoriously disorganised. Royal Air Force in 1942, leaving in the sole male descendant of the doctor, staying in Australia for He lectured frequently on Jewish 1946 a squadron leader. He was Taptiklis line. some months before returning medical ethics, combining three consultant physician in the Northern Theodore Taptiklis to St Thomas’ to start a career things he loved: his religion, Regional Hospital Authority from in ophthalmology. He became a medicine, and talking. He leaves a 1953 and clinical lecturer at the lecturer at St Paul’s Eye Hospital in wife, Margaret, and two sons. University of Newcastle upon Tyne Ethel Hunter Waddy Liverpool. Appointed consultant Alan Craft from 1966 until his retirement in in 1972, he spent the rest of Tony Hockley 1981. He readily acknowledged Former anaesthetist Northampton his career working in Harrogate that his medical vocation would Manfield Hospital and Kettering in NHS and private practice. not have been realised without the General Hospital (b 1906; q Sheffield He was secretary and later Patricia Mary Leeson support of his wife and family. He 1930), d 30 December 2006. president of the North of England retired to West Looe, East Cornwall, After qualifying, Ethel Hunter Ophthalmological Society, and Former consultant physician where he indulged his passions for Waddy worked in general practice in president of the Harrogate Medical medicine for the elderly Southern fishing, local history, archaeology, Leamington Spa until she married Society. He was a keen distance Derbyshire Acute Hospitals NHS and, in his final years, information her first cousin Francis Fisher Waddy runner in his middle years and Trust (b 1927; q Trinity College technology. He regularly kept up in 1931 and moved to Northampton. enjoyed golf, fell walking, classical Dublin 1951; FRCP), died from with medicine at the local hospital During the war she trained in music, and poetry. Twice married, disseminated cancer on 11 October library, and latterly, as his eyesight anaesthesia and continued his second wife, Clare, died 2006. and health failed, through the practising as an anaesthetist for soon after he retired in 2001. Patricia (“Pat”) Mary Leeson internet. He leaves a wife, Denise, several years after the war. They He leaves four children and two expected the highest possible and two daughters. moved to Great Brington in 1945, grandchildren. standard of care for her patients. John Hodgson when she took up horse riding, David I Bowen She was impervious to flattery— and horses remained her life long only hard work and sincerity held passion. Reasonably active to the sway with her. After qualifying, Nicholas Taptiklis last she died peacefully at home just Stuart Harvey Green she did various research and eight days before her 101st birthday. clinical jobs before becoming Predeceased by her husband, consultant physician in geriatric Francis, she leaves two sons and medicine in 1966. She took over three grandchildren. 700 beds spread over five different Sam Waddy hospitals with no junior staff, no Advice personal secretary, and no office, We will be pleased to receive but she built up an efficient and obituary notices of around 250 comprehensive department with words. In most cases we will be able 60 new acute beds in Derby City to publish only about 100 words in General Hospital. Pat loved horses Former Meres senior student in the printed journal, but we can run a Former paediatric neurologist and farm life and was keenly medical research St John’s College, fuller version on our website. We will Birmingham (b 1939; q Cambridge/ involved in the affairs of her home Cambridge (b 1918; q Athens 1940, take responsibility for shortening. We do not send proofs. Please give Middlesex 1963; FRCP, FRCPCH), died village of Mackworth. She never Otago 1950; PhD), d 1 September a contact telephone number and, from a stroke on 21 November 2006. married but was close to her 2006. where possible, supply the obituary Stuart Harvey Green was brother’s family. Nicholas Taptiklis (“Nick”) served on a disk or by email to obituaries@ one of the first generation of R M Mishra as a doctor in the Royal Hellenic bmj.com

BMJ | 17 March 2007 | Volume 334 591