for severe head injury

sEDiCAL LIBRARY

321 E. 15tb Eo; ? Y. CITY,321 E. ~~~1ou,Mal of Neurology, Neurosurgery, and Psychiatry, 1980, 43, 289-295

Treatment for severe head injuryB JENNETT, G TEASDALE, J FRY, R BRAAKMAN, J MINDERHOUD,J HEIDEN, AND T KURZE

From the Department ofNeurosurgery, Institute ofNeurological Sciences, Southern General Hospital, Glasgow,Department ofNeurosurgery, Academisch Ziekenhuis Rotterdam-Dijkzigt, Erasmus University, Rotterdam,Department ofNeurology, University Hospital, Groningen, Department of Neurological Surgery, Universityof Southern California Medical School, Los Angeles, California

SUMMARY Difficulties in establishing the value of certain treatments for head injury are reviewed.An analysis of 1000 severely head injured patients, managed by varying7methods in three differentcountries, showed that certain treatments were more often used in the most severely injured patients.Even when the severity of injury was taken account of, it appeared that the use of steroids andtracheostomy did not affect outcome; but that patients undergoing mechanical ventilation hadoutcomes which were worse than expected. The value of treatments proposed for severe headinjury needs rigorous scrutiny.

"As soon as a new, but still unproved, method oftreatment is adopted by even a minortiy of themedical profession, it becomes virtually impossibleto conduct the controlled trial that alone can furnishtruly reliable evaluation of its effectiveness and itshazards."'

This comment by a British neurologist applieswith particular force to therapy for severe headinjuries. Whilst the risk that new drugs will do moreharm than good have diminished because of recentstatutory restrictions on widespread adoption beforeadequate trials, there are no limits to the applicationof therapeutic methods which involve surgicalprocedures, mechanical ventilation and variousregimens of drugs already in common use.The last 20 years have seen the adoption of a

number of therapeutic techniques designed tocontrol events which threaten life after severe headinjury. In 1958 a dramatic reduction in mortalitywas attributed to the introduction of what wouldnow be called respiratory intensive care (tracheostomyand suction).2 A decade later controlled ventilationwas reported to have further improved outcome.3Corticosteroids have been widely used for manyyears, in spite of a lack of specific evidence for theirvalue; there are recent reports that a very large doseimproves outcome.4 Claims for the value of largebony decompressions have been made,5 6 and

Address for reprint requests: Professor B Jennett, Institute ofNeurological Sciences, Southern General Hospital, Glasgow G5 1 4TF.

Accepted 6 December 1979

retracted.7 Several years ago there was a vogue forusing hypothermia to reduce cerebral metabolism,but this is now seldom used. There have been recentreports,8 9 that the use of large doses of barbituratesmay be beneficial for these patients.

In spite of all these efforts Langfitt10 recentlyconcluded that there had been little change inmortality from severe head injury over the last 50years; but he drew attention to the recent reports ofBecker etall'and ofBruce et al,12 which he considereddid indicate an improvement in outcome; to thesehas been added the series of Marshall et al.8 13

However, there has been considerable discussionabout the validity of the claims for these methods,which are very demanding of personnel, time andfacilities.

There are several reasons why it is difficult toestablish the efficacy of treatment for severe headinjury; these can be conveniently grouped aspractical, ethical and statistical problems. Amongpractical problems are that treatment regimensusually include several components (for examplesurgery, controlled ventilation, osmotics, steroidsand other drugs); and that decisions about theinitiation of therapy have to be made rapidly.Because of the need for rapid decision-making thereis little time to evaluate the degree of brain damageand to estimate accurately what the prognosiswould be without the particular therapeutic modalityunder consideration. In trials of therapy for manyother conditions there is time for analysis of dataabout an individual patient, and for discussion

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between members of therapeutic teams and trialcoordinators about which combination of methodsto use in a particular case.An ethical problem is perceived by many clinicians

because of the high mortality rate of this condition,and of its predominant occurrence in young patients.This might be regarded as emotional rather thanethical-but it is a fact that doctors faced with thiscondition frequently consider that every possiblemeasure must be used which might assist recovery,even if the efficacy of some of these methods isunproven. Doubts about the ethics of controlledtrials for conditions associated with a high mortalityhave recently been expressed.14 15The statistical problems are not unique to this

condition. However, several of the circumstancesthat create difficulties in proving the efficacy oftherapy in any branch of medicine tend to occurtogether after severe head injury, and these combineto frustrate attempts to reach a satisfactory con-clusion. To begin with, the definition of severitydepends crucially on when, where and by whomassessment is made, as well as on the criteria adopted.Moreover, any method of treatment will have a

proportion of "successes", and a considerabledifference in outcome will be needed before astatistically significant change is detected. Con-sidering the number of variables which can influenceoutcome, large numbers of patients must be studiedbefore a significant effect is likely to be evident fromthe application of alternative treatments to sets ofsimilar cases.

In spite of the prevalence of head injury, only afraction of patients admitted to hospital are severe-and these tend to be widely dispersed. Only thelargest services can accumulate a sizeable series ofpatients, and few of these admit many more than 50patients a year. For a result to be obtained within a

reasonable time period, multicentre data collectionis therefore required, with all the difficulties whichthis entails.

International Data Bank Study

It seemed to us that unless outcome could bepredicted reliably, in at least a proportion ofidentifiable patients, it was unlikely that the influenceof alternative forms of management on outcomecould be detected. This led us to initiate a systematicapproach to this problem, with the intention ofevolving standardised ways of assessing initialseverity and ultimate outcome after severe headinjury, so that the relationship between these twocould be explored, as a basis for prediction. Thisstudy began in Glasgow 12 years ago, and lateracquired data also from the Netherlands and Los

B Jennett, G Teasdale, J Fry et al

Angeles. Data collection and analysis are stillproceeding, but already it has proved possible topredict outcome in many individual patients on thebasis of clinical data available during the first weekafter injury.16 Although methods of assessment werestrictly standardised in this data bank there was noattempt to impose uniform treatment regimens onthe collecting centres, but the methods used werealways recorded. In the event there were markeddifferences between the three countries in the relativefrequency with which various therapeutic measureswere used. This makes it possible to make someobservations about the effects of certain forms oftreatment on outcome.

Patients studied

These were collected prospectively from Glasgow(since 1968), from Rotterdam and Groningen (since1972) and from Los Angeles (since 1974) usingstandardised methods of assessment and recording.Details of the collecting centres, of the indicators ofseverity used, and of the features of the first 1000patients, have been published.15 The present analsyisof treatment methods is based on 1250 patients,collected between 1968 and 1977 inclusive; 118patients treated during 1968 and 1969 in Glasgow,which were included in previous published papers,were treated before the Glasgow neurosurgical unitmoved into the city from its country location atKillearn, are excluded from the analysis in this paper.Patient selection was by one criterion only-thepersistence of coma for more than 6 hours. Comawas defined as not opening the eyes at all, notobeying commands and not uttering any words.

Indicators of severity

From analysis of the relationship between clinicalfeatures in the first week and the outcome 6 monthsafter injury we were able to identify indicators ofseverity.17 Features which were associated with aworse outcome indicated a more severe injury, andthese included depth of coma, nonreacting pupils,impairment of spontaneous and reflex eye move-ments, and abnormal patterns of movement in thelimbs. One of the most useful single indicators ofseverity is the state of responsiveness on the GlasgowComa Scale"8 19; this can be summarised by thecoma score or sum, made up by adding the scores oneach of the three components to give a figure whichranges from 3 (deepest coma) to 15. As describedelsewhere20 this provides a less accurate indicator ofseverity than does the exact composition of thescore-but nonetheless it is a useful means ofcomparing approximate severity, and is now widely



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Table 1 Severity and age in three countries indifferent years

Glasgow Netherlands LA531 302 224

Coma Sum 3-5*70-71 25%72-73 21% 40%74-75 20% 42% 24%76-77 31 % 26% 29%

Average 70-77 25% 36% 27%Non-reacting pupils*

70-71 16%72-73 17% 17%74-75 15% 31 % 29%76-77 26% 21% 28%

Average 70-77 19 % 26% 29%Age < 20 years

70-71 60%72-73 37% 47%74-75 33% 40% 19%76-77 27% 41% 21%

Average 70-77 36% 41 % 20%Intracranial haematoma

70-71 42%72-73 52% 26%74-75 59% 36% 62%76-77 57% 35% 50%

Average 70-77 54% 34% 56%

*Best state in first 24 hours

used in reports of head injured patients. Age is alsosignificantly related to outcome.

Patients in three countries

Although these patients were all of similar minimumseverity (coma at least 6 hours), there were differencesamong the three countries in the proportion ofpatients with various features (table 1). Anotherdifference was that fewer patients were admitted tothe neuro-service within 6 hours of injury in Glasgow.There was relatively little change in the characteristicsof the patients from year to year during the period inany one centre of data collection.The outcome 6 months after injury was very

similar in each country, both for the series as a

whole and for subsets matched for various features(table 2). Again there was little change during theyears of data collection.

Different therapeutic measures

The management of severely head injured patients,some of them with multiple injuries, is a complexaffair, and it is particularly difficult to compare

overall standards of care. We chose to compare thefrequency with which six separate components oftherapy were used and to study the relationshipbetween their use and outcome. The modalities were

those about the value of which there is currentcontroversy, or at least doubt.

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Table 2 % Dead/vegetative at 6 months in differentcountries and years

Glasgow Netherlands LA

All cases70-71 43%72-73 46% 47%74-75 44% 52% 53%76-77 51% 46% 54%

Average 70-77 46% 50% 54%With intracranial haematoma

70-71 52%72-73 50% 50%74-75 51% 54% 61%76-77 57% 66% 72%

Average 70-77 53% 58% 66%No haematoma

< 72 32%72-73 41% 48%74-75 34% 48% 39%76-77 43% 31% 36%

Average 70-77 37% 42% 37%

1 Steroids were given as dexamethazone 4 mg 6hourly or its equivalent. Treatment was started onthe first day after injury in 86% of those cases inwhich it was employed, but the exact intervalbetween injury and commencement within thisperiod was not recorded. Treatment was continuedin survivors for several days in decreasing doses. Aminority of patients with pulmonary complicationsreceived lower doses of steroids, and have not beenincluded in the steroid treated group. No patients inthe present analysis received "mega-dose" steroids.42 Osmotics consisted of one or more doses ofmannitol, usually a 20% solution over 10-30minutes to a total dose varying from 0-3 g/kg to1-0 g/kg. The indication for giving mannitol wasoften the demonstration ofa high level of intracranialpressure during continuous monitoring. There were,however, other patients in whom the indicationswere empirical; patients awaiting surgery forintracranial haematoma sometimes received man-nitol, and it was continued postoperatively whenbrain swelling had been noted at the end of opera-tion. Sometimes the indication was deterioration ina patient's clinical state, irrespective of whether thepatient had a haematoma.

Decompressive craniectomy

It was not the practice in any centre to employ largedeliberate decompressions by hemicraniectomy,6circumferential craniotomy5 or bifrontal craniotomy.The usual method for dealing with an acute intra-cranial haematoma was by a generous fronto-temporal craniotomy. The bone flap was sometimesleft out in patients whose brain appeared swollen atthe end of operation.



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Endotracheal tube and tracheostomy

Tracheostomy was usually performed when it was

evident that there was likely to be a prolonged needfor endotracheal intubation; it was rarely donewithin the first day or two of injury unless there wereassociated facial or chest injuries. Differences in therate of intubation in the three centres partly reflectsvariations in the reliance upon this measure as ameans of ensuring an adequate airway and gas

exchange, but is also related to the more frequentemployment of assisted ventilation in two of thecentres.

Mechanical ventilation

The cases classified in this group did not includethose in whom ventilation was used only terminallyin fatal cases, nor those in whom mechanicalassistance was triggered by the patient. Respiratoryinsufficiency was usually the indication for controlledmechanical ventilation, but in some cases thepurpose was to provide the brain with the supposedbenefits of hypocapnia.3

Frequency of use of different treatments

When the three countries were compared there wasfor each of the six therapeutic techniques one countrywhich differed in its use of it, as compared with theother two countries; each country was equallyoften the "odd one out" (table 3). During theperiod of data collection there were changes in thefrequency with which some methods were used inGlasgow (for which the period of study is longest).

Table 3 Treatment in three countries (1970-1977)

Glasgow Netherlands L A531 302 224

Steroids 24% 34% 99%Osmotics-No haematoma 28% 19% 28%

Haematoma 53% 31% 64%Bone flap out(% of craniotomies) 28% 92% 93%Tracheostomy (any time) 10% 15% 66%Mechanical ventilation 18% 28% 13%ET tube or tracheostomy(first 3 days) 38% 61% 70%

Table 4 Treatment over 8 years (531 cases in Glasgow)

Years Steroids Tracheostomy Deadl Vegat 6 months

70-71 52% 23% 43%72-73 26% 9% 46%74-75 20% 6% 44%76-77 15% 8% 51%

B Jennet, G Teasdale, J Fry et al

Table 5 Therapy and outcome (all centres (70-77),all coma scores)

Therapy Without this With thistherapy therapyn %D/VS n %D/VS

Steroids 588 49 447 51Osmotics 651 43 386 60Bone flap removal(% of craniotomies) 190 44 185 67Tracheostomy (ever) 811 48 248 51ET/tracheostomy (first 3 days) 410 30 649 61Mechanical ventilation 732 40 327 68

Steroids are now less frequently used, as is tracheos-tomy; but more patients are intubated in the first3 days and there is a small increase in the use ofcontrolled ventilation (table 4); there were nosignificant difference in outcome associated withthese changes in treatment.

Treatment and outcome

When patients who did or did not receive variouskinds of treatment were compared as a whole therewas no evidence of a better outcome in the treatedgroup; where there was a difference the treatedpatients had a higher mortality. It seemed that thismight reflect the tendency noticeable in all threecountries, for each of these therapies to be used moreoften for patients whowere more severely affected.Therefore it was considered important tomake allow-anceforthe severity of braindamagewhen comparingthe outcome of patients who did, with those who didnot, receive each of these various treatments.

Patients were therefore divided into three gradesof severity on the basis of the best state on theComa Scale in the first 24 hours, and comparisonsthen made between those who did or did not receiveeach treatment modality within these severity grades.In the most severely affected patients there was littledifference between treated and untreated patients,both having a high mortality (table 6). In the other

Table 6 Severity of injury, therapy and outcome at 6months

Coma sum ° Dead or vegetative24 hour best Steroids No steroids

3/5 77% 82%6/7 47% 48%>8 20% 23%

All levels 50% 50%

Tracheostomy No tracheostomy

3/5 72% 83%6/7 45% 47%> 8 39% 22%

All levels 53% 48%



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Table 7 Effect of therapy on outcome (stratifyingfor age, coma sum, pupils, haematoma, country)

Therapy Number of deathsWithout this therapy With therapyExpected Observed Expected Observed

Steroids 232.4 232 193.6 194Ventilation 274.9 249 152.1 178Tracheostomy 320.2 319 106.8 108

patients outcomes were less good in the treatedpatients, except for those treated with steroids; nodifference could be found between patients who didor did not have steroids. This might suggest that thecoma sum was an inadequate means of matchingpatients, and that other factors might be associatedboth with a poor outcome and with a tendency toattract more intensive treatment. A further analysiswas therefore undertaken which allowed not only forcoma sum but also for pupil reaction, the presence ofintracranial haematoma, the patient's age and thecountry in which he was treated.The statistical technique used was based on that

described by Peto and Pike,22 and previously used byone of us.22 First the data were divided into n strata,a stratum being one combination of levels of eachrelevant variable. Within each stratum the treatmentwas divided into different groups, ie airwaymanagement was divided into 3 groups. Group 1 hadendotracheal intubation; group 2 had tracheostomyand group 3 had neither. If Oj and Sj representrespectively the number of survivors observed andthe total munber studied in group j, the expectednumber of survivors, Ej, can be computed assumingmortality independent of treatment group. Fromthis the deviation Dj-Oj-Ej was calculated andsummed over all strata. These total deviations(which sum identically to zero) were then tested forsignificant departure from the null hypothesis bytaking the quadratic form X2 = dA-1d to beasympotically distributed as chi-squared on m-1degrees of freedom, where d is the vector formed bythe first m-l total deviations (m = total number ofgroups for the treatment), and A is their covariancematrix, the formula for which is given by Peto andPike.22 When this analysis was done there was usuallyno difference in outcome between treated anduntreated patients; when there was a difference,again the outcome was less good in the treatedgroups.

Discussion

The patients reported here were all managed in wellequipped and well staffed specialised centres, and thefact that many of these severely affected patients

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survived and became independent reflects the benefitof this treatment. Given this good general manage-ment, however, it seems from this study that certaincomponents of therapy, which are commonly usedin intensive care units, do not markedly affect theoutcome in patients who are brain damaged enoughto be in coma for 6 hours or more. It is interestingthat we should have reached this conclusion aboutsteroids, using our method of comparison, when tworecent controlled trials have also shown that steroidsdo not have an effect-even in high doses.24 25 Thissuggests that our conclusions about other measuresmay also be valid. The study did not (directly)investigate the importance of the interval afterinjury (within the first day after injury) at whichtreatment was started. We have elsewhere emphasisedthe importance of measures designed to preventsecondary brain damage which may lead to coma ofthe duration which qualified patients for inclusionin the present study.26 27Whenever outcome proves to be similar in groups

of patients who have received different treatment,three interpretations are possible:

1 the treatments are not effective in influencingoutcome;

2 treatment is effective only if instituted soonenough, or

3 only for some types of patient (of a certain agegroup, or with particular kinds or grades ofseverity of injury).

In that event the beneficial effect may be obscuredby failure to take sufficient account of the intervalbefore treatment, or ofcertain features ofthe patients.For example, this study confirms that there is agroup of patients so severely affected that the out-come is uniformly bad, regardless of treatment;there is also evidence that the most severely affectedpatients tend to be the most intensively treated.However, we have carried out analyses which allowfor various seveiity factors, for age, and for whetheror not neurosurgical care began within 6 hours; wewere still unable to demonstrate a beneficial effectfor the measures under consideration.When the outcome is better in one group of

patients than another, several explanation3 arepossible:1 the treatment of one group has been moreeffective. Most regimens used after severe headinjury comprise several modalities and it may bedifficult to discern which component is in factcontributing to an improved result.2 specialised care (in general) has been startedsooner after injury in the patients with a betteroutcome, and it is this rather than particular com-ponents of treatment which accounts for the betteroutcome.



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3 assessment of initial severity or of outcome, or

both, has not been well enough standardised betweenthe two patient populations being compared. Theimportance of rigorous attention to the standardisa-tion of methods of assessment cannot be over-

emphasised. The comparisons in this paper are basedupon data collected prospectively according tomethods which were carefully agreed and standard-ised in advance; this was not always the case in somestudies with which the results of this data bank havebeen compared. The minimum criteria of coma for6 hours applied in this study seems not to have beenmet in all cases in other series. Moreover, in one

study"' observations were originally made accordingto a different system for assessing responsiveness,but the patients were re-analysed retrospectively inan attempt to apply the criteria of the data bank.4 Other factors have not been sufficiently carefullymatched in the groups of patients under analysis.These include features known to influence outcome,such as the age distribution of the series, and hiddenvariables, not yet recognised as affecting outcome,and therefore not taken into account. Thus thecomparison between the series of children mean age7 years reported by Bruce et al'2 and the data bank(mean age 33 years) is invalid. Likewise the seriesreported by Marshall et at8 13 from San Diego was

unusual in that 75% of patients with high intra-cranial pressure did not have a haematoma. In mostother centres raised intracranial pressure is usually a

sequel of the damage associated with an intracranialhaematoma.5 Statistical factors may account for the appear-ance of improved outcome-which is in fact notsignificant. The commonest reason for this isinadequate sample size; but the distribution in thetwo populations of various features which affectoutcome may also be crucial even though thereappears to be comparability by simpler measure ofsimilarity. Those various factors are discussedelsewhere.20 2130

Another approach to investigating the efficacy ofdifferent therapies is to use the methods currentlybeing evolved for predicting outcome on the basis ofdata available soon after injury.21 28 An effectivetreatment would be one that led to a "better thanpredicted" outcome in a significant number ofpatients, when predictions were based on a trainingset of patients not treated by the method underexamination. Such an analysis has not yet beencompleted for all the treatment methods discussedin this paper.

In a quarter of patients in the data bank it becomesclear at an early stage that they will do well withconventional intensive management; another quarterare obviously destined to die because of brain

B Jennet, G Teasdale, J Fry et al

damage so severe that survival is inconceivable, nomatter what management is applied. Prediction ofoutcome soon after injury would make it possible torecognise these patients, and attention could then befocussed on those whose outcome was in doubt, andtherefore liable to be influenced. In this way theefficacy of a particular therapeutic technique wouldlikely be detected much more rapidly because itsbenefit would not be submerged or obscured by itsuse in many patients whose outcome was alreadydetermined.

Treatment of severe head injury is not the onlyform of intensive therapy about which there iscurrent controversy about efficacy. Colleagues study-ing patients in coma due to nontraumatic lesionsfound no better outcome in those who had beenmore intensively investigated and treated.29 Recentcomments on the paucity ofevidence for the effective-ness of special coronary units in reducing mortalityfrom myocardial infarction might be considered toapply also to claims about certain regimens forseverely head injured patients. One editorial3l con-cludes "We should no longer accept sweeping claimsfor a substantial reduction of mortality, since hard-won experience tells us that a true reduction of thismagnitude is very unlikely to be produced so readily.The apparent mortality rate of patients admitted toa coronary care unit can be altered drastically byminor variations in the age structure, infarct-timing,and general health of the patients. Claims for a majoralteration in mortality cannot therefore be acceptedwithout an assurance that like is being comparedwith like."As new methods are devised and introduced, the

supposed benefits of each need to be subject torigorous scrutiny and analysis, according to agreedmethods of assessment. We should obey Pasteur'sinjunction to "keep your enthusiasm but let strictverification be its constant companion."

References

1 Miller H. Medicine and Society. London: OxfordUniversity Press, 1973.

2 Maclver IN, Frew IJC, Matheson JG. The role ofrespiratory insufficiency in the mortality of severehead injuries. Lancet 1958; i:390-3.

3 Gordon E. Controlled ventilation in the manage-ment of patients with severe head injury. Scand JRehab Med 1972; 4:21-3.

4 Gobiet W. Advances in management of severe headinjury in children. Acta Neurochir 1977; 39:207-10.

5 Clark K, Nash TM, Hutchison GL. The feature ofcircumferential craniotomy in adult traumaticcerebral swelling. J Neurosurg 1968; 29:361-71.

6 Ransahoff J, Benjamin MV, Gage EL, Epstein F.Hemicraniectomy in the management of acutesubdural haematoma. J Neurosurg 1971; 34:70-6.



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7 Cooper PR, Rovit RL, Ransahoff J. Hemicraniec-tomy in the treatment of acute subdural haematoma:a re-appraisal. Surg Neurol 1976; 5:25-8.

8 Marshall LF, Smith RW, Shapiro HM. The outcomewith aggressive treatment in severe head injuries.Part 1: The significance of intracranial pressuremonitoring. J Neurosurg 1979a; 50:20-5.

9 Shapiro JM, Wyte SR, Loeser J. Barbiturate-augmented hypothermia for reduction of persistentintracranial hypertension. J Neurosurg 1979; 40:90-100.

10 Langfitt TW. Measuring the outcome from headinjuries. J Neurosurg 1978; 48:673-8.

11 Becker DP, Miller JD, Ward JD, Greenberg RP,Young HF, Sakalas R. The outcome from severehead injury with early diagnosis and intensivemanagement. J Neurosurg 1977; 47:491-502.

12 Bruce DA, Schut L, Bruno LS, Wood JH, SuttonLN. Outcome following severe head injuries inchildren. J Neurosurg 1978; 48:679-88.

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Knill-Jones R. Predicting outcome in individualpatients after severe head injury. Lancet 1976;1:1031-4.

17 Jennett B, Teasdale G, Braakman R, Minderhoud J,Heiden J, Kurze T. Prognosis in series of patientswith severe head injury. Neurosurg 1979; 4:283-8

18 Teasdale G, Jennett B. Assessment of coma andimpaired consciousness. Lancet 1974; ii:81-4.

19 Jennett B, Teadale G. Aspects of coma after severehead injury. Lancet 1977; 1:878-81.

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21 Teasdale G, Parker L, Murray G, Jennett B. Oncomparing series of head injured patients. ActaNeurochir 1979b; Supplementum 28:205-8.

22 Peto R, Pike MC. Conservatism of the approxima-tion e(O-E)2I/E in the Log Rank Test for SurvivalData or Tumor Incidence Data. Biometrics 1973;29:579-84.

23 Hawthorne VM, Fry JS. Smoking and health; theassociation between smoking behaviour, totalmortality and cardiorerpiratory disease in WestCentral Scotland. J Epidemiol Comm Hlth 1978;32:260-6.

24 Cooper PR, Moody S, Clark WK, Kirkpatrick J,Maravilla K, Gould AL, Drane W. Dexamethasoneand severe head injury. A prospective double-blindstudy. J Neurosurg 1979; 51:307-16.

25 Gudeman SK, Miller JD, Becker DP. Failure ofhigh-dose steroid therapy to influence intracranialpressure in patients with severe head injury. J Neuro-surg 1979; 51:301-6.

26 Rose J, Valtonen S, Jennett B. Avoidable factorscontributing to death after head injury. Br Med J1977; 2:615-8.

27 Jennett B, Carlin J. Preventable mortality andmorbidity after head injury. Injury 1978; 10:31-9.

28 Murray GD, Parker LS, Skene AM, SpiegelholterDJ, Titterington DM, Gilphe GJ, Habbema JDF.Comparison of Discrimination Techniques appliedto a Complex Data Set. J Roy Statist Soc 1979;in press.

29 Bates D, Caronna JJ, Cartlidge NEF, Knill-JonesRP, Levy DE, Shaw DA, Plum F. A prospectivestudy of non-traumatic coma: Methods and resultsin 310 patients. Ann Neurol 1977; 2:211-20.

30 Teasdale G, Parker L, Murray G, Jennett B. Oncomparing series of head injured patients. A ctaNeurochir 1979; Supplementum 28:205-8.

31 Anti-dysrhythmic treatment in acute myocardialinfarction. Lancet 1979b; i:193.



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