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Inappropriate use of randomised trials to
evaluate complex phenomena: case study of

vaginal breech delivery
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A correction has been published for this article. The contents of the have been appended to the original article in this reprint. The correction is also available online at: To order reprints of this article go to: Eisenberg JM. Globalize the evidence, localize the decision: evidence- 10 McIntosh HM, Olliaro P. Artemisinin derivatives for treating uncompli- based medicine and international diversity. Health Aff 2002;21:166-8.
cated malaria. Cochrane Database Syst Rev 2000(2):CD000256.
Clarke M, Chalmers I. Discussion sections in reports of controlled trials 11 Smith H. Better Births Initiative in South Africa. British Journal of published in general medical journals: islands in search of continents? 12 Thomson O’Brien MA, Oxman AD, Haynes RB, Davis DA, Freemantle N, Global Programme on Evidence for Health Policy. Guidelines for WHO Harvey EL. Local opinion leaders: effects on professional practice and guidelines (EIP/GPE/EQC/2003.1.). Geneva: WHO, 2003 ( health care outcomes. Cochrane Database Syst Rev 2000(2):CD000125.
medicines/organization/par/edl/expcom14/guid_for_guid.pdf) 13 Smith H, Brown H, Hofmeyr GJ, Garner P. Evidence-based obstetric care GRADE Working Group. Grading quality of evidence and strength of in South Africa—influencing practice through the ‘Better Births recommendations. BMJ 2004;328:1490.
Initiative.’ S Afr Med J 2004;94:117-20.
Kim Y, Hahn S, Garner P. Reduced osmolarity oral rehydration solution 14 Jamtvedt G, Young JM, Kristoffersen DT, Thomson O’Brien MA, Oxman for treating dehydration caused by acute diarrhoea in children. CochraneDatabase Syst Rev 2001(2):CD002847. Update in: Cochrane Database Syst AD. Audit and feedback: effects on professional practice and health care outcomes. Cochrane Database Syst Rev 2003(3):CD000259.
Child and Adolescent Health Development, WHO. Oral rehydration salts 15 Plsek P, Wilson T. Complexity, leadership, and management in healthcare (ORS): a new reduced osmolarity formulation. organisations. BMJ 2001;323:746-9.
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improvement projects. Qual Saf Health Care 2003;12:210-4.
Inappropriate use of randomised trials to evaluate
complex phenomena: case study of vaginal breech
Andrew Kotaska
As randomised trials continue to ascend in the evolution of evidence based medicine, we mustrecognise and respect their limitations when examining complex phenomena in heterogeneouspopulations Randomised controlled trials have greatly improved the quality of evidence guiding clinical practice, but when applied to complex phenomena, they have important limitations. Complex patient populations with poorly quantifiable variations between individuals present one area of difficulty; complex procedures requiring skill and clinical judgment present another.
A large, well designed, and well executed randomised controlled trial of breech presentation at term, the “term breech trial,” by Hannah et al rapidly dictated a new standard of care for the management of breechdeliveries around the world.1 Yet this trial failed to adequately appreciate both the complex nature of vaginal breech delivery and the complex mix of opera- tor variables necessary for its safe conduct. Widespread acceptance of this trial’s results has breached the limits Hannah et al’s trial showed a significant increase in perinatal mortality and morbidity in women ran-domised to a trial of labour compared with electivecaesarean section.1 The trial’s methodological flaws have been examined,2–4 but the intrinsic limitations of applying large scale randomisation to complexphenomena have received little attention. These limitations are the focus of this paper.
Bias of licence
Vaginal breech delivery is a complex procedure Many of the term breech trial’s 121 centres were inNorth America, where 13% of breech presentations atterm were delivered vaginally.5 The study achieved a breech delivery at baseline were not reported, but successful vaginal delivery rate of 57% by asking those many would have tripled their vaginal delivery rate centres with vaginal birth rates under 40% in the labour group to increase the rate or withdraw from The vaginal delivery of a breech baby involves risk.
participation.6 Individual centres rates of vaginal Cord prolapse and trapped fetal parts are unpredict- BMJ VOLUME 329 30 OCTOBER 2004
able complications. Every practitioner knows this; and surgery and because some surgeons lack the skill or the literature, the courts, and the low baseline rate of experience to support a safe, high vaginal hysterec- such deliveries in North America highlight caution.
tomy rate. Case selection depends on diagnosis, parity, Maternity units with interest and skill in delivering size and mobility of the uterus, and operator skill, breech babies vaginally have achieved higher rates: which together determine a safe baseline rate. Increas- 24% in the United States, 36% in Sweden, 38% in ing the rate arbitrarily and randomising such a Israel, 38% in Switzerland, 39% in France, and 53% in complex mix of patient and operator characteristics would compromise safety, yet this is what happened in selected women for a trial of labour using various safety criteria and showed lower mortality and morbid-ity associated with vaginal breech delivery than in the Homogenising populations and
term breech trial. Few obstetrical units other than Løv- clinicians
set’s have published vaginal delivery rates as high as theterm breech trial.12 Randomisation improves the internal validity of trials Statistical power required a high vaginal delivery by homogenising study and control populations rate to enhance the trial’s ability to detect small differ- thereby avoiding bias from differences between the ences in outcome. With this aim, the researchers two. Clinically important factors that are variable encouraged practitioners to increase their vaginal within populations are, however, homogenised as well.
breech delivery rate beyond their previous comfort Their importance to the outcome is lost, and the trial level. Despite being difficult to quantify, comfort level loses external validity for individuals within subsets of (or “practitioner comfort level”) plays a pivotal part in the population. Results represent the mean outcome the safety of complex procedures. Protected from for all participants and are not applicable to subgroups medicolegal liability by the equipoise of a randomised at lower risk. Although subgroup analysis, found in the trial, some practitioners must have pushed their term breech trial, can potentially identify subpopula- comfort levels with vaginal breech delivery. This tions in which a procedure may be safer, it is statistically constitutes a significant bias: one of licence. The trial weak. When phenomena are complex, many patient protocol’s liberal labour guidelines allowed 0.5 cm and practitioner characteristics influence outcome, dilation/h and 3.5 hours for the second stage. This is rendering individual subgroups small and meaningful considerable licence, and few obstetricians from centres with proved safety in vaginal breech delivery A major limit of evidence based medicine is the dif- ficulty in applying the results of randomised trials toindividual patients. For example, most would agree that A discriminating procedure
a multiparous woman in advanced labour at 38 weekswith a 3000 g fetus in a frank breech presentation with Human skill varies. This is particularly evident when flexed head and no nuchal cord represents a low risk tasks are complex, require careful judgment, and have subgroup of all breech presentations. By studying a narrow margins for error. Increasingly complex tasks heterogeneous group of women, the term breech trial are discriminating, with more effort and skill required lacks the external validity needed to guide us with the to master them. The safe vaginal delivery of a breech management of such women. Yet experienced baby requires considerable skill and is a discriminating obstetricians will now press for an emergency obstetrical procedure. Skill is required in multiple are- caesarean, not trusting their clinical judgment to nas: not just in the delivery technique, but in discern low risk situations, because all women with a ultrasound assessment, the selection of cases, intra- breech presentation have been assigned a similar risk partum fetal surveillance, the conduct of labour, and status by a randomised controlled trial.
paediatric support. A coordinated, well functioning Multicentre trials can also lead to homogenisation of the intervention. Previous randomised trials of breech presentations were too small to detect clinically include carotid endarterectomy, where surgical skill is meaningful differences in outcome, so a large one of the strongest predictors of the operation’s multicentre trial was required to improve statistical utility;13 14 surgery for cancer, where additional surgical power. Yet despite the interest, altruism, and self refer- training improves outcome;15 16 and vaginal hysterec- ential experience of the practitioners, the involvement tomy. Rates of vaginal hysterectomy vary greatly of 121 centres resulted in an average level of care.
among surgeons, and the learning curve to increase an Encouraging practitioners to exceed their comfort individual surgeon’s rate takes years.17 It has been sug- level with vaginal breech delivery lowered that gested that “encouraging more surgeons to perform more vaginal hysterectomies may result initially in an If generic levels of care had always been accepted as increasing complication rate because it is technically the ideal, none of the surgical subspecialties would have arisen. The standard of care shown by the term In the United Kingdom and in North America, the breech trial is not the best we can offer. Although baseline vaginal hysterectomy rate for non-malignant breech deliveries commonly occur under average con- disease is 20%. Encouraging a group of surgeons to ditions, it does not mean that committed centres are suddenly increase their rate from 20% to 60% would unable to offer better than average care. Collectively we not be a meaningful way to evaluate the safety of the have been improving our “mean” level of care for years, procedure compared with abdominal hysterectomy.
and the perinatal risk associated with breech delivery Nor should all women have an abdominal hysterec- has continued to drop despite stabilisation of the tomy because some are poor candidates for vaginal BMJ VOLUME 329 30 OCTOBER 2004
Simplified risk reduction
Historically, the greatest decrease in perinatal mortality Summary points
from vaginal breech deliveries was reported by Brachtin 1938.20 Other techniques recommended to enhance the safety of vaginal breech delivery include routine randomised trials have important limitations determination of fetal weight, head attitude, andnuchal or presenting cord using ultrasonography; con- Vaginal breech delivery is a complex procedure tinuous fetal monitoring; radiological pelvimetry; cau- that is poorly amenable to the methods of large tious attention to the progress of labour; and preparing for emergency symphysiotomy should fetalparts become trapped.21 Although poorly amenable to One randomised controlled trial has dictated a scientific analysis, some of these techniques are likely new standard of care for vaginal breech deliveries to be important for safe vaginal breech delivery. None were included in the term breech trial.
The use of a short term combined end point It is impractical for a large, multicentre trial to use overstated any true risk of planned vaginal complex risk reducing strategies. Meaningful quality delivery to longer term neurodevelopmental control in 121 centres is impossible, and more caution would have meant fewer vaginal deliveries, increasingthe number of participants needed to achieve similarstatistical power. Therefore, the researchers chose asimple labour protocol with few risk avoidance deliveries and 0.4% of women undergoing elective strategies. The lack of proved effectiveness of other caesareans. Mortality was not significantly different strategies ostensibly justified their exclusion; yet our (3 of 511 or 0.6%) in the planned vaginal delivery current inability to analyse safe vaginal breech delivery group compared with zero in the planned caesarean does not preclude its existence. The resulting standard group. One of these deaths, included in the intention of care, arguably reasonable for a large, multicentre to treat analysis, occurred before the onset of labour in trial, falls short of its designation as the definitive study a cephalic twin weighing 1150 g, highlighting concerns about the adequacy of case selection and Since publication of the term breech trial, the onus raising questions about the appropriateness of has been placed on individual obstetrical units to ret- intention to treat analysis at all cost. Regardless, the rospectively examine their experience with vaginal impact of the trial’s results was due primarily to an breech delivery and to show safety. Several have done excess of short term morbidity in the planned vaginal so and continue to offer vaginal breech delivery.11 22 23 Safety in these specific centres is due to heterogeneity Long term outcomes in breech babies are hard to of human skill, not to statistical anomaly, and vaginal assess epidemiologically, but were retrospectively breech delivery in those units should be studied and shown to be equivalent in 1645 children, irrespective emulated. For complex phenomena, a large, ran- of the planned mode of delivery.25 Researchers domised, multicentre trial does not overrule demon- from the term breech trial have published details on death or abnormal neurodevelopment over two years In the case of carotid endarterectomy, it should ide- in a subgroup of 923 children from the term breech ally be performed at a centre and by a surgeon with a trial.26 They found a similar incidence: 2.8% in the perioperative stroke rate of 3%, not 6%. If unavailable, planned vaginal delivery group and 3.1% in the a patient might elect medical treatment, as the risks elective caesarean section group. The use of a short could outweigh the benefits. Similarly, a woman with term combined end point seems to have been an average breech presentation and access to average care may decide that a caesarean section is safer than atrial of labour; yet even that conclusion is potentiallyflawed: without a bias of licence, the maternity unit car- The limits of evidence based medicine
ing for her may well have a low, safe, baseline vaginal Delivering a breech presentation vaginally is a skill: guided by science, its safety relies on the experience ofpractitioners and caution. In the term breech trial, Short term combined end points
large scale randomisation, which homogenised boththe study population and clinical intervention, Randomised trials often utilise short term end points resulted in an average level of care in an average because they are easier to measure than longer term population, limiting the trial’s external validity in cen- outcomes. It is also easier to show a statistical tres showing above average skill and in women of difference in a combined end point rather than a sin- below average risk. Encouraging practitioners to gle end point. Yet combined end points can be exceed their comfort level ensured a high vaginal misleading.24 In the term breech trial, the end point delivery rate and adequate statistical power, but intro- included perinatal mortality and various short term duced a bias of licence and compromised safety. Using morbidities, including hypotonia, transient brachial a combined short term end point overstated any true plexus injury, and isolated low arterial cord pH or effect on long term neurodevelopment.
base excess, whose lasting significance is unclear. In The philosophical limits of evidence based countries with low perinatal mortality, this combined medicine include failing to appreciate and cultivate the end point occurred in 5.7% of planned vaginal complex nature of sound clinical judgment, failing to BMJ VOLUME 329 30 OCTOBER 2004
appreciate the relevance of poorly quantifiable clinical 11 Kayem G, Goffinet F, Clement D, Hessabi M, Cabrol D. Breech presenta- tion at term: morbidity and mortality according to the type of delivery at phenomena that are obscured by randomisation, and Port Royal Maternity hospital from 1993 through 1999. Eur J Obstet devaluing the intangible differences between individu- Gynecol Reprod Biol 2002;102:137-42.
als, thus potentially devaluing them (patients and care 12 Albrechtsen S, Rasmussen S, Reigstad H, Markestad T, Irgens LM, Dalaker K. Evaluation of a protocol for selecting fetuses in breech providers).27 The condemnation of vaginal breech presentation for vaginal delivery or cesarean section. Am J Obstet Gynecol delivery by one randomised controlled trial and its 13 Tu JV, Hannan EL, Anderson GM, Iron K, Wu K, Vranizan K, et al. The sweeping effect on clinical practice show how each of fall and rise of carotid endarterectomy in the United States and Canada.
these philosophical limits can be exceeded.
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14 Barnett HJ, Taylor DW, Eliasziw M, Fox AJ, Ferguson GG, Haynes RB, et al. Benefit of carotid endarterectomy in patients with symptomatic mod- The author thanks Ewart Woolley, whose skill in vaginal breech erate or severe stenosis. North American Symptomatic Carotid Endarter- deliveries inspired him, and Robert Liston and Michael Klein ectomy Trial Collaborators. N Engl J Med 1998;339:1415-25.
15 Mayer AR, Chambers SK, Graves E, Holm C, Tseng PC, Nelson BE, et al.
Ovarian cancer staging: does it require a gynecologic oncologist. Gynecol 16 Tingulstad S, Skjeldestad F, Hagen B. The effect of centralization of pri- mary surgery on survival in ovarian cancer patients. Obstet Gynecol2003;102:499-505.
17 Varma R, Tahseen S, Lokugamage A, Kunde D. Vaginal route as the norm when planning hysterectomy for benign conditions: change in practice.
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Planned cesarean section versus planned vaginal birth for breech 18 Maresh M, Metcalfe M, McPherson K, Overton C, Hall V, Hargreaves J, et presentation at term: a randomised multicentre trial. Term Breech Trial al. The VALUE national hysterectomy study: description of the patients Collaborative Group. Lancet 2000;356:1375-83.
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Hauth JC, Cunningham FG. Vaginal breech delivery is still justified. Obstet 19 Albrechtsen S, Rasmussen S, Irgens LM. Secular trends in peri- and neo- natal mortality in breech presentation; Norway 1967-1994. Acta Obstet Keirse MJ. Evidence-based childbirth only for breech babies? Birth Gynecol Scand 2000;79:508-12.
20 Bracht E. Zur Behandlung der Steisslage. Zentralblatt Gynaecol 1938; Halmesmaki E. Vaginal term breech delivery—a time for reappraisal? Acta Obstet Gynecol Scand 2001;80:187-90.
21 Menticoglou SM. Symphysiotomy for the trapped aftercoming parts of Lee KS, Khoshnood B, Sriram S, Hsieh HL, Singh J, Mittendorf R. Rela- the breech: a review of the literature and a plea for its use. Aust NZ J Obstet tionship of cesarean delivery to lower birth weight-specific neonatal mor- tality in singleton breech infants in the United States. Obstet Gynecol 22 Giuliani A, Schoell W, Basver A, Tamussino K. Mode of delivery and out- come of 699 term singleton breech deliveries at a single center. Am J University of Toronto Maternal, Infant and Reproductive Health Obstet Gynecol 2002;187:1694-8.
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23 Alarab M, Regan C, O’Connell MP, Keane DP, O’Herlihy C, Foley ME.
Sanchez-Ramos L, Wells TL, Adair CD, Arcelin G, Kaunitz AM, Wells DS.
Singleton vaginal breech delivery at term: still a safe option. Obstet Gyne- Route of breech delivery and maternal and neonatal outcomes. Int J 24 Julian D. What is right and what is wrong about evidence-based Lindqvist A, Lindeberg SN, Hanson U. Perinatal mortality and route of medicine? J Cardiovasc Electrophysiol 2003:14(Suppl);S2-5.
delivery in term breech presentations. Br J Obstet Gynaecol 1997; 25 Danielian P, Wang J, Hall M. Long term outcome by method of delivery of fetuses in breech presentation at term: population based follow up.
Schiff E, Friedman SA, Mashiach S, Hart O, Barkai G, Sibai BM. Maternal and neonatal outcome of 846 term singleton breech deliveries: 26 Whyte H, Hannah M, Saigal S. Outcomes of children at 2 years of age in the seven-year experience at a single center. Am J Obstet Gynecol 1996;175: term breech trial. Am J Obstet Gynecol 2003;Suppl 189(6). [Abstract No 7.] 27 Tonelli MR. The philosophical limits of evidence-based medicine. Acad 10 Irion O, Almagbaly PH, Morabia A. Planned vaginal delivery versus elec- tive cesarean section: a study of singleton term breech presentations. Br JObstet Gynaecol 1998;105:710-7.
Effect of postnatal depression on other members of the mother’s family
In a situation of mild stress (the threat of losing a deal in a Does anyone know of any journals or sites with information on competitive children’s card game), 5 year old children of how postnatal depression affects the rest of the family, not just the depressed mothers were more likely to express depressive cognitions (hopelessness, pessimism, and low self worth) than Oliver Mallon, student nurse, Queens University, Belfast children of well mothers. The association between depressivecognitions and recent exposure to maternal depression was in part accounted for by current maternal hostility to the child.
Different effects appear at different stages of child development.
Sinclair D, Murray L. Effects of postnatal depression on children’s The leading figure in UK research in Professor Lynn Murray. Shehas been publishing in the area of effects of postnatal depression adjustment to school. Teacher’s reports. Br J Psychiatry 1998;172: on child development for about 15 years. Here are details of three of her characteristic studies.
Murray L. The impact of postnatal depression on infant Family social class and the child’s sex had the greatest influences development. J Child Psychol Psychiatry 1992;33:543-61.
on 5 year old children’s behavioural adjustment. However, bothpostnatal and recent maternal depression were associated with Infants of postnatally depressed mothers performed worse on significantly raised levels of child disturbance, particularly among object concept tasks, were more insecurely attached to their boys and those from lower social class families.
mothers, and showed more mild behavioural difficulties. Postnatal Woody Caan, professor of public health, APU, Chelmsford depression had no effect on general cognitive and languagedevelopment, but seemed to make infants more vulnerable toadverse effects of lower social class and male sex.;69637 Murray L, Woolgar M, Cooper P, Hipwell A. Cognitive This exchange was posted on the Q&A section of If you want to vulnerability to depression in 5-year-old children of depressed respond to the question, or ask a new question of your own, follow the mothers. J Child Psychol Psychiatry 2001;42:891-9.
link above or go to BMJ VOLUME 329 30 OCTOBER 2004
13 Rasbash J, Browne W, Goldstein H. A user’s guide to MLwiN Version 2.1.
London: Institute of Education, University of London, 2000.
Funding: Medical Research Council (research costs); NHS in 14 Fenwick E, Claxton K, Sculpher M. Representing uncertainty: the role of England, Northern Ireland, Scotland, and Wales (excess cost-effectiveness acceptability curves. Health Econ 2001;10:779-87.
treatment and service support costs).
15 Fenwick E, O’Brien BJ, Briggs AH. Cost-effectiveness acceptability Competing interests: LL, JM, MU, MV, and KW have received curves—facts, fallacies and frequently asked questions. Health Econ2004;13:405-15.
salaries from the MRC. MU has received fees for speaking from 16 Raftery J. NICE: faster access to modern treatments? Analysis of guidance Menarini Pharmaceuticals, the manufacturers of dexketoprofen on health technologies. BMJ 2001;323:1300-3.
and ketoprofen, and Pfizer, the manufacturers of celecoxib and valdecoxib. The other 12 authors have nothing to declare.
Ethical approval: The Northern and Yorkshire multicentreresearch ethics committee and 41 local research ethics commit-tees approved the trial protocol.
Corrections and clarifications
Klaber Moffett J, Torgerson D, Bell-Syer S, Jackson D, Llewlyn-Phillips H,Farrin A, et al. Randomised controlled trial of exercise for low back pain: Inappropriate use of randomised trials to evaluate clinical outcomes, costs, and preferences. BMJ 1999;319:279-83.
complex phenomena: case study of vaginal breech Malmivaara A, Hakkinen U, Heinrichs M, Koskenniemi L, Kuosma E, Lappi S, et al. The treatment of acute low back pain—bed rest, exercises, In the final stage of production of this Education or ordinary activity? N Engl J Med 1995;332:351-5.
Skargren EI, Carlsson PG, Oberg BE. One-year follow-up comparison of and Debate article by Andrew Kotaska, human the cost and effectiveness of chiropractic and physiotherapy as primary error conspired with an electronic glitch to management for back pain. Spine 1998;23:1875-84.
produce two correspondence addresses—only one Meade TW, Dyer S, Browne W, Townsend J, Frank AO. Low back pain of of which was correct (30 October, pp 1039-42). As mechanical origin: randomised comparison of chiropractic and hospitaloutpatient treatment. BMJ 1990;300:1431-7.
well as publishing Kotaska’s email address, we UK BEAM Trial Team. United Kingdom back pain exercise and manipu- wrongly inserted the email address for the lation (UK BEAM) randomised trial: effectiveness of physical treatments corresponding author (P Garner) of the preceding for back pain in primary care. BMJ 2004;329:1377-81.
article (although that email address also appeared Kind P. The EuroQoL instrument: an index of health-related quality oflife. In: Spilker B, ed. Quality of life and pharmacoeconomics in clinical trials.
in the correct place, attached to Garner’s article).
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Kind P, Hardman G, Macran S. UK population norms for EQ-5D. York: Centre for Health Economics, University of York, 1999. (Discussion paper We failed to spot a spelling mistake and an Chartered Institute of Public Finance and Accountancy. The health service consultation” article by H U Rehman and T A database 2002. Croydon: CIPFA, 2002.
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Bajwa (27 November, p 1271). It should be carpal Canterbury: Personal Social Services Research Unit, University of Kent, recommended international non-proprietary name 10 BUPA Hospitals UK. How much will it cost? (rINN) of the treatment for hypothyroidism is asp/paying/priceguides.asp (accessed 17 Nov 2004).
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In retrospect, my belief in serendipity began in the summer of Subsequent distractions of examinations and surgical training 1951. I was between my first and second years as a clinical meant that I knew little of him again until I became a consultant in medical student at the Welsh National School of Medicine when I Cardiff in 1966 and was able to meet him on more equal terms. By was attracted to a medical secretary working in the MRC unit at this time he had become an international figure on healthcare policy, which was later crystallised in his 1972 classic monograph She told me that the unit was looking for two medical students Effectiveness and Efficiency: Random Reflections on Health Services. To who, for a modest stipend, would assist in an MRC survey of coal my mind, this remains the definitive work on the functioning of the miners’ chest diseases in one of the South Wales mining valleys.
NHS and, at only 92 pages, should be compulsory reading for all Apart from the attractions of the secretary, no stipend was too clinicians and managers who work in it.
modest for me at that time, and I applied. Having been I cannot now remember much about the medical secretary, but interviewed by Archie Cochrane, who was running the survey, I I remain most grateful to her for telling me about that holiday job was the third choice of the four who applied. One of the first two in 1951. Because of it, I came to know a really remarkable man and, to a certain extent, to understand what made him tick. He During that long distant summer, I cannot recall having been given any important duties beyond arranging x ray envelopes in died in 1988. I feel sure that all the current talk of “integrated alphabetical order. But I do remember many hours in the medicine” must be making him turn in his grave.
company of Archie Cochrane. It was a small team, and we spent David Crosby retired surgeon, University Hospital of Wales, Cardiff long hours classifying chest x rays and poring over the data,which were well beyond my comprehension. We also spent time We welcome articles up to 600 words on topics such as in his Jaguar car, of which he was quite proud, visiting individual A memorable patient, A paper that changed my practice, My most miners in their homes who for many diverse and interesting unfortunate mistake, or any other piece conveying instruction, reasons did not wish to be x rayed. Considerable energy was pathos, or humour. Please submit the article on http:// expended in ensuring that the survey should be 100%. Permission is needed from the patient or a Once or twice he had a migraine, which meant a longer session relative if an identifiable patient is referred to. We also welcome the next day. To me, he was kind and quizzical. I doubt that I ever contributions for “Endpieces,” consisting of quotations of up to gave him any of the answers he wanted, but he tried hard to make 80 words (but most are considerably shorter) from any source, ancient or modern, which have appealed to the reader.


SemEval-2010 Task 8: Multi-Way Classificationof Semantic Relations Between Pairs of NominalsIris Hendrickx∗ , Su Nam Kim† , Zornitsa Kozareva‡ , Preslav Nakov§ ,O S´eaghdha¶, Sebastian Pad´o , Marco Pennacchiotti∗∗,Lorenza Romano††, Stan Szpakowicz‡‡dataset for each of seven relations. We have definedSemEval-2010 Task 8 as multi-way classification,where the label for ea


Peter H Andersen Department of Dermatology Marselisborg Hospital P.P Orumsgade 11 DK-8000 Ärhus C. Title: Treatment of recurrent herpes labialis (cold sores) using trans-cutaneous electrical nerve stimulation Purpose: To investigate if recurrent attacks of herpes labialis may be prevented or the severity diminished using trans-cutanneous electrical nerve stimulation (TCNS)

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