D F Signorini

The University of Edinburgh, Edinburgh, Scotland, United Kingdom

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Publications (38)193.71 Total impact

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    ABSTRACT: Hemorrhagic transformation of cerebral infarction (HTI) occurs spontaneously but its frequency and risk factors are uncertain with mixed results in previous studies. We aimed to determine the overall frequency of and risk factors for HTI. We performed a systematic review according to Cochrane Collaboration methods of published reports of HTI with reliable, systematic follow-up with computed tomography or magnetic resonance imaging. In all, 28 observational studies and 19 randomized controlled trials in stroke were identified that included follow-up imaging data. Problems with inconsistent definitions or small and biased patient populations limited detailed interpretation. The overall frequency of any HTI in untreated patients was 8.5% (95% confidence interval 7%-10%). Severe HTI (i.e., HTI accompanied by neurologic deterioration or parenchymal hematoma formation) occurred in 1.5% (95% confidence interval 0.8%-2.2%). The frequency of HTI increased markedly with increasing use of antithrombotic or thrombolytic drugs. Magnetic resonance imaging detected more HTI than did computed tomography. The published data were generally inadequate to undertake more detailed analysis of risk factors. However, in the 8 studies that did provide the information, HTI was associated with large infarcts, mass effect, hypodensity observed early after the stroke, and age older than 70 years, but not hypertension or cardioembolic stroke. Severe HTI is uncommon in patients not receiving antithrombotic or thrombolytic agents. The methods used to assess the frequency of and risk factors for HTI, particularly a standard of definitions in future prospective studies, could be improved.
    Full-text · Article · Nov 2004 · Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association
  • D.F. Signorini · M.C. Jones
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    ABSTRACT: We present a rather thorough investigation of the use of kernel-based nonparametric estimators of the binary regression function in the case of a single covariate. We consider various versions of Nadaraya-Watson and local linear estimators, some involving a single bandwidth and others involving two bandwidths. The locally linear logistic estimator proves to be a good single-bandwidth estimator, although the basic Nadaraya-Watson estimator also fares quite well. Two-bandwidth methods show great potential when bandwidths are selected with knowledge of the target function, but much of their potential vanishes when data-based bandwidths are used. Likelihood cross-validation and plug-in approaches are the data-based bandwidth selection methods tested; both prove quite useful, with a preference for the latter. Adaptive two-bandwidth methods retain particularly good performance only in certain special situations (and separate estimation of the two bandwidths as for optimal density estimation is never recommended). We therefore propose a hybrid estimation procedure in which the local linear logistic estimator is used unless the ratio of (robust) variances of the covariate in the success and failure groups is greater than 2, in which case we switch to a two-bandwidth Nadaraya-Watson-type estimator, each using plug-in bandwidth selection.
    No preview · Article · Feb 2004 · Journal of the American Statistical Association
  • B. U. Park · W. C. Kim · D. Ruppert · M. C. Jones · D. F. Signorini · R. Kohn
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    ABSTRACT: We propose and investigate two new methods for achieving less bias in non- parametric regression. We show that the new methods have bias of order h4, where h is a smoothing parameter, in contrast to the basic kernel estimator’s order h2. The methods are conceptually very simple. At the first stage, perform an ordinary non-parametric regression on {xi, Yi} to obtain m^(xi) (we use local linear fitting). In the first method, at the second stage, repeat the non-parametric regression but on the transformed dataset {m^(xi, Yi)}, taking the estimator at x to be this second stage estimator at m^(x). In the second, and more appealing, method, again perform non-parametric regression on {m^(xi, Yi)}, but this time make the kernel weights depend on the original x scale rather than using the m^(x) scale. We concentrate more of our effort in this paper on the latter because of its advantages over the former. Our emphasis is largely theoretical, but we also show that the latter method has practical potential through some simulated examples.
    No preview · Article · Dec 2001 · Scandinavian Journal of Statistics
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    N U Weir · P. A. G. Sandercock · S C Lewis · D F Signorini · C P Warlow
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    ABSTRACT: This study describes the large variations in outcome after stroke between countries that participated in the International Stroke Trial and seeks to define whether they could be explained by variations in case mix or by other factors. We analyzed data from the 15 116 patients recruited in Argentina, Australia, Italy, the Netherlands, Norway, Poland, Sweden, Switzerland, and the United Kingdom: We compared crude case fatality and the proportion of patients dead or dependent at 6 months; we used logistic regression to adjust for age, sex, atrial fibrillation, systolic blood pressure, level of consciousness, and number of neurological deficits. We used the frequency of prerandomization head CT scan and prescription of aspirin at discharge to indicate quality of care. The differences in outcome (all treatment groups combined) between the "best" and "worst" countries were very large for death (171 cases per 1000 patients) and for death or dependency (375 cases per 1000 patients). The differences were somewhat smaller after adjustment for case mix (160 and 311 cases per 1000 patients, respectively). Process of care may have accounted for some but not all of the residual variation in outcome. Adjustment for case mix explained only some of the variation in outcome between countries. The residual differences in outcome were too large to be explained by variations in care and most likely reflect differences in unmeasured baseline factors. These findings demonstrate the need to achieve balance of treatment and control within each country in multinational randomized controlled stroke trials and the need for caution in the interpretation of nonrandomized comparisons of outcome after stroke between countries.
    Full-text · Article · Jul 2001 · Stroke
  • D Hilton · N Iman · G.J. Burke · A Moore · G O'Mara · D Signorini · D Lyons · A.K. Banerjee · D Clinch
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    ABSTRACT: In a retrospective study we reported absence of abdominal pain in 35% of elderly patients with peptic ulcer disease. We now report a prospective study on this question. Patients undergoing upper GI endoscopy were systematically questioned before endoscopy. A reproducible method for identifying the location of symptoms was used. Among patients referred for upper endoscopy, there was no selection of patients for study purposes as all had strong indications, such as pain, dyspepsia, GI bleeding, weight loss, or anemia. Patients were divided into two groups according to age: A younger group consisting of patients <50 yr (mean, 33.6 yr) and an older group >60 yr (mean, 70.9 yr). A total of 277 patients were included in the study. There was no significant difference in reported use of medications, alcohol, or cigarette use between the groups. Of the 106 patients with peptic ulcer, 15 (14.2%) had not experienced pain. Abdominal pain was absent in 5 (6.9%) of the younger patients and 10 (29.4%) of the older patients. The difference was significant using the chi2 method (p = 0.004). A trend toward an even higher proportion of pain-free peptic ulcer disease was noted in the elderly female group (37.5%), but it did not reach statistical significance. Absence of abdominal pain is confirmed in approximately 30% of elderly patients with peptic ulcer disease.
    No preview · Article · Mar 2001 · The American Journal of Gastroenterology
  • N U Weir · D F Signorini · M S Dennis · P S Murdoch
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    ABSTRACT: To determine how far the difference in published stroke case fatality between the Western General Hospital (WGH), Edinburgh and the Falkirk and District Royal Infirmary (FDRI) for the period 1990-93 can be explained by adjusting more fully for casemix. The cases were ascertained and followed prospectively at the WGH and retrospectively at the FDRI; casemix correction was performed using a validated logistic regression model. The WGH is a teaching hospital and the FDRI a district general hospital. Four hundred and thirty seven patients with a verified acute stroke at the WGH; 471 patients assigned a cerebrovascular disease discharge diagnostic code at the FDRI. Thirty day case fatality. About half of the difference in the two hospitals' published stroke case fatality could be accounted for by variation in measured casemix. The residual difference in adjusted case fatality might have been due to differences in the structure of stroke care or simply to remaining differences in casemix. Full investigation of the cause was prevented by the destruction of the deceased patients records. Comparisons of routinely collected stroke outcomes will remain difficult to interpret unless casemix is properly accounted for and deceased patients' records stored for several years.
    No preview · Article · Aug 2000 · Health bulletin
  • D J Hellawell · D F Signorini · B Pentland
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    ABSTRACT: The relative's questionnaire (RQ) was developed to assess outcome after brain injury. The present study investigated its test-retest reliability when used in a postal survey. Hospital records were used to identify and contact 288 surviving patients treated for brain injury five to seven years earlier. Patients were sent a copy of the RQ (RQ1) and one month later a second copy (RQ2) was sent to those who returned RQ1. Two hundred and eleven patients were successfully contacted, of whom 128 (61%) returned RQ1, and 94 of these (73%) returned RQ2. The reliability of items was variable, with most having a kappa value of > 0.6 suggesting 'substantial agreement' or better. The data presented suggest that the RQ is a reliable instrument in collecting outcome information in brain-injured patients by postal survey. Further research is recommended to test the suitability of the RQ for the use as a telephone interview.
    No preview · Article · Aug 2000 · Disability and Rehabilitation
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    ABSTRACT: The aim of this project was to determine whether histological features of 'active' plaque as described in the coronary circulation following acute myocardial infarction were similar in the carotid circulation, and whether these factors could be detected ultrasonically. Endarterectomy specimens were prospectively collected, and examined histologically and assessed by two observers for ulceration, inflammation, size of necrotic core, thickness of fibrous cap, haemorrhage and luminal thrombosis. Ultrasound of the plaque obtained preoperatively was similarly coded (blind to pathology) and compared with the pathology. In 42 endarterectomy specimens, there was a highly significant relationship between a thin fibrous cap and a large necrotic core (P<0.002), irregular plaque contour (P<0.05) and ulceration (P<0.01) and between a large necrotic core (P<0.002) and ulceration and inflammation (P<0.05). Increasing amounts of necrosis were associated with more surface thrombosis (P<0.02). Ultrasound detected the thickness of the fibrous cap and 'any necrosis or haemorrhage' with some reliability (kappas are 0.53 and 0.5, respectively), but not ulceration, necrosis or haemorrhage on their own. Features corresponding to active atheromatous plaque are similar in the carotid and coronary arteries, and some of these, namely lucent areas in the plaque (corresponding to necrosis or haemorrhage) and the thickness of the fibrous cap, can be determined reliably with ultrasound.
    No preview · Article · Jun 2000 · European Journal of Ultrasound
  • D J Hellawell · D F Signorini · B Pentland
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    ABSTRACT: To evaluate alternative methods of determining Glasgow Outcome Scale scores, a postal survey was made of 288 general practitioners and 128 relatives of patients who had sustained acute brain injuries 5-7 years previously. The Glasgow Outcome Scale score from the general practitioner and relative were compared with that calculated from questionnaire information by an experienced rater. There was poor agreement between general practitioner and rater (K = 0.17) and relative and rater (K = 0.35) scores. Both general practitioners and relatives indicated more favourable outcomes than the rater, with a higher level of agreement (K = 0.61) between them. When Glasgow Outcome Scale scores are used, the methods employed should be valid and reliable; failure to ensure this may be responsible for a considerable proportion of variability in reported studies of brain injury outcome.
    No preview · Article · Apr 2000 · Scandinavian Journal of Rehabilitation Medicine
  • G Gubitz · C Counsell · P Sandercock · D Signorini
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    ABSTRACT: Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention with anticoagulant therapy could have a significant impact on patient survival, disability and recurrence of stroke. The objective of this review was to assess the effect of anticoagulant therapy in the early treatment of patients with acute ischaemic stroke. We searched the Cochrane Stroke Group trials register (most recent search: March 1999) and consulted MedStrategy (1995). We also contacted drug companies. Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in patients with acute presumed or confirmed ischaemic stroke. Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. Twenty-one trials involving 23,427 patients were included. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Based on eight trials (22,450 patients) there was no evidence that anticoagulant therapy reduced the odds of death from all causes (odds ratio 1.05, 95% confidence intervals 0.98-1.12). Similarly, based on five trials (21, 846 patients), there was no evidence that anticoagulants reduced the odds of being dead or dependent at the end of follow-up (odds ratio 0.99, 95% confidence intervals 0.94-1.05). Although anticoagulant therapy was associated with about 9 fewer recurrent ischaemic strokes per 1000 patients treated, it was also associated with a similar sized 9 per 1000 increase in symptomatic intracranial haemorrhages. Similarly, anticoagulants avoided about 4 pulmonary emboli per 1000, but this benefit was offset by an extra 9 major extracranial haemorrhages per 1000. Sensitivity analyses did not identify a particular type of anticoagulant regimen or patient characteristic associated with net benefit. Immediate anticoagulant therapy in patients with acute ischaemic stroke is not associated with net short- or long-term benefit. The data from this review do not support the routine use of any type of anticoagulant in acute ischaemic stroke.
    No preview · Article · Feb 2000 · Cochrane database of systematic reviews (Online)
  • I Piper · A Spiegelberg · I Whittle · D Signorini · L Mascia
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    ABSTRACT: A new automated method of compliance measurement has been developed which may overcome some of the problems of the manual method. Measurement of craniospinal compliance in brain-injured patients offers the potential for early detection of raised intracranial pressure (ICP) before it rises to levels that may damage brain parenchyma. However, limitations of the existing manual volume pressure techniques have meant few centres routinely perform compliance testing. We report on the results of testing this new method against a manual volume pressure response method (VPR) in 10 patients with hydrocephalus. In this comparison study, 19 pairs of compliance measurements were obtained from 10 patients. The compliance values obtained ranged from 0.141 to 1.407 ml/mmHg. There was a good correlation between the two methods (r2 = 0.8508). The average bias in compliance between the two methods was 0.111 ml/mmHg (95% CL for the bias = 0.0438, 0.1788) with the new method reading higher compliance than the manual method. These results indicate that the new automatic method of compliance measurement correlates well with an independent and classical measurement of compliance, and defines the bias and limits of agreement by which the new method measures craniospinal compliance in patients with hydrocephalus. Further work is needed to validate this device over a wider compliance range, especially at the lower compliance range often found in head injured patients. Studies are also required to determine the normal range of compliance values in the patient populations who undergo ICP monitoring. Research into determining which patient populations may benefit from continuous compliance measurement is warranted.
    No preview · Article · Jan 2000 · British Journal of Neurosurgery
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    J J Nissen · PA Jones · D F Signorini · L S Murray · G M Teasdale · J D Miller
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    ABSTRACT: Using an independent data set, the utility of the Glasgow Head Injury Outcome Prediction Program was investigated in terms of possible frequency of use and reliability of outcome prediction in patients with severe head injury, or haematoma requiring evacuation, or coma lasting 6 hours or more, in whom outcome had been reliably assessed at 6 to 24 months after injury. Predictions were calculated on admission, before evacuation of a haematoma, or 24 hours, 3 days, and 7 days after onset of coma lasting 6 hours or more. Three hundred and twenty four patients provided 426 predictions which were possible in 76%, 97%, 19%, 34%, and 53% of patients on admission, before operation, 24 hours, 3 days, and 7 days respectively. Major reasons for non-feasible predictions were that patients were paralysed/ventilated as part of resuscitation or management. Overall, 75.8% of predictions were correct, 14.6% were pessimistic (outcome better than predicted), and 9.6% optimistic (outcome worse than predicted). Of 197 patients (267 predictions) whose eventual outcome was good or moderate, 84.3% of predictions were correct. For death or vegetative survival (96 patients with 110 predictions), 83.6% of predictions were correct but for severe disability (31 patients with 49 predictions), only 12.2% were correctly predicted. The utility of the Glasgow Head Injury Outcome Prediction Program compares favourably with other outcome prediction algorithms for patients with head injury.
    Preview · Article · Jan 2000 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: The most common neuropathological substrates of dementia are Alzheimer's disease, cerebrovascular disease, and dementia with Lewy bodies. A preliminary, retrospective postmortem analysis was performed of the relative burden of each pathology in 25 patients with predominantly Alzheimer's disease-type dementia. Log linear modelling was used to assess the relations between ApoE genotype, Alzheimer's disease, and cerebrovascular disease pathology scores. Sixteen of 18 cases (89%) with a Braak neuritic pathology score </=4 had, in addition, significant cerebrovascular disease, or dementia with Lewy bodies, or both. There was a significant inverse relation between cerebrovascular disease and Braak stage (p=0.015). The frequency of the ApoE-epsilon4 allele was 36.4%. No evidence was found for an association between possession of the ApoE-epsilon4 allele and any one pathological variable over another. In this series most brains from patients with dementia for which Alzheimer's disease is the predominant neuropathological substrate also harboured significant cerebrovascular disease or dementia with Lewy bodies. The data suggest that these diseases are perhaps pathogenetically distinct, yet conspire to produce the dementing phenotype.
    Full-text · Article · Dec 1999 · Journal of Neurology Neurosurgery & Psychiatry
  • J M Wardlaw · P J Dorman · L Candelise · D F Signorini
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    ABSTRACT: Thrombolysis increases case fatality but reduces the proportion of disabled survivors in recent trials in acute ischaemic stroke, although some trials show much higher mortality rates than others. One possible explanation for the different outcomes between trials is that the treatment effect with thrombolysis varies with baseline prognostic factors such as stroke severity. We examined the interaction between baseline risk and thrombolysis on outcome using individual patient data from the Multicentre Acute Stroke Trial-Italy (MAST-I). A multiple logistic regression of the MAST-I data was performed to identify which factors, identifiable at randomisation, most strongly predict a poor functional outcome. We then stratified the patients into those with severe strokes and those with mild strokes and examined the effect of thrombolysis on (a) case fatality and (b) dependency at 6 months after the stroke in the 157 patients who received streptokinase alone and the 156 controls. Streptokinase was found to cause an absolute increase of about 3% in case fatality in both "severe" and "mild" strokes; however, there was a 12% reduction in the number of dead or dependent "mild" strokes but a 6% increase in "severe" strokes. The number of patients was small, and therefore neither finding was statistically significant. In this exploratory analysis, the hazard with streptokinase appears similar in "severe" and "mild" strokes, but the benefit may be greater in "mild" strokes. Thrombolysis may be more effective in patients with "mild" strokes, but more information is required to confirm this hypothesis.
    No preview · Article · Dec 1999 · Journal of Neurology
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    ABSTRACT: Thrombolysis increases case fatality but reduces the proportion of disabled survivors in recent trials in acute ischaemic stroke, although some trials show much higher mortality rates than others. One possible explanation for the different outcomes between trials is that the treatment effect with thrombolysis varies with baseline prognostic factors such as stroke severity. We examined the interaction between baseline risk and thrombolysis on outcome using individual patient data from the Multicentre Acute Stroke Trial–Italy (MAST-I). A multiple logistic regression of the MAST-I data was performed to identify which factors, identifiable at randomisation, most strongly predict a poor functional outcome. We then stratified the patients into those with severe strokes and those with mild strokes and examined the effect of thrombolysis on (a) case fatality and (b) dependency at 6 months after the stroke in the 157 patients who received streptokinase alone and the 156 controls. Streptokinase was found to cause an absolute increase of about 3% in case fatality in both “severe” and “mild” strokes; however, there was a 12% reduction in the number of dead or dependent “mild” strokes but a 6% increase in “severe” strokes. The number of patients was small, and therefore neither finding was statistically significant. In this exploratory analysis, the hazard with streptokinase appears similar in “severe” and “mild” strokes, but the benefit may be greater in “mild” strokes. Thrombolysis may be more effective in patients with “mild” strokes, but more information is required to confirm this hypothesis.
    No preview · Article · Nov 1999 · Journal of Neurology
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    ABSTRACT: Many of the important clinical decisions we make on a daily basis in stroke medicine are not supported by adequate evidence. This leads to variations in practice. If practice influences outcome, this must be regarded as unacceptable since it implies that many patients are receiving sub-optimal treatment. Where the advantages of certain treatment policies over others are only moderate, large randomised clinical trials provide the most reliable evidence of effectiveness. However, only a tiny proportion of patients with stroke are randomised in trials. Instead, the majority are exposed to treatments allocated haphazardly, rather than randomly, which serves only to delay the emergence of evidence concerning the relative merits of alternative treatment approaches. We suggest that we might increase the proportion of patients who contribute to advancing our knowledge by developing 'families' of trials. A 'family' would comprise a series of randomised trials into which patients with stroke may be enrolled either simultaneously or sequentially into one or more of the trials which would share common systems for randomisation and follow-up. Such a system would facilitate large, simple, randomised trials, reduce research costs, increase the generalisability of trial results and allow clinicians and patients to contribute to advancing our knowledge whenever they are uncertain about the best treatment. In this article, we discuss the advantages of this approach, some of the problems and their potential solutions.
    No preview · Article · Oct 1999 · Cerebrovascular Diseases
  • J M Wardlaw · D F Signorini · I Marshall

    No preview · Article · May 1999 · Magnetic Resonance Imaging
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    ABSTRACT: Objectives: Prediction of patient outcome can be useful as an aid to clinical decision making, to explore possible biological mechanisms, and as part of the clinical audit process. Many studies have constructed predictive models for survival after traumatic brain injury, but these have often used expensive, time consuming, or highly specialised measurements. The aim of this study was to develop a simple easy to use model involving only variables which are rapidly and easily clinically achievable in routine practice. Methods: All consecutive patients admitted to a regional trauma centre with moderate or severe head injury were enrolled in the study. Basic demographic, injury, and CT characteristics were recorded. Patient survival at 1 year was used to construct a simple predictive model which was then validated on a very similar patient group. Results: 372 patients were included in the study, of whom 365 (98%) were followed up for survival at 1 year. Multiple logistic regression resulted in a model containing age (p<0.001), Glasgow coma scale score (p<0.001), injury severity score (p<0.001), pupil reactivity (p=0.004), and presence of haematoma on CT (p=0.004) as independently significant predictors of survival. The model was validated on an independent set of 520 patients, showing good discrimination and adequate calibration, but with a tendency to be pessimistic about very severely injured patients. It is presented as an easy to use nomogram. Conclusions: All five variables have previously been shown to be related to survival. All variables in the model are clinically simple and easy to measure rapidly in a centre with access to 24 hour CT, resulting in a model that is both well validated and clinically useful.
    Full-text · Article · Feb 1999 · Journal of Neurology Neurosurgery & Psychiatry
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    ABSTRACT: Secondary intracranial hypertension has been linked to leukocytosis. We examined our data bank containing physiologic recordings and outcome data of severely head injured patients to investigate the relationship between delayed increases in intracranial pressure (ICP), defined as occurring after a 12-hr period of normal ICP values, and leukocytosis. A retrospective study of observational data. Regional neurosurgical unit and intensive care unit. Sixty-four patients suffered increased ICP >20 mm Hg. Thirty-five patients fulfilled selection criteria for delayed increases in ICP (group 1). Twenty-nine patients with increased ICP with no preceding or intervening periods of normal ICP were selected as a comparison group (group 2). Comparison of 12-month outcome revealed that 11% of group 1 patients died, with 49% remaining severely disabled, in contrast to group 2, where 35% of patients died and 14% were left severely disabled (p = .021). The pattern of outcome was independent of monitoring time, or injury severity. Regression modeling was performed for prediction of delayed increase in ICP. Of 46 patients with an initial increase then decrease in leukocyte count in the first 48 hrs, 65% experienced delayed increases in ICP, as compared with 18% of the 11 patients without this pattern p = .01 1). Patients with delayed increases have a significantly different pattern of outcome. Change in leukocyte count from admission to day 2 is a significant predictor of such a delayed increase.
    No preview · Article · Feb 1999 · Critical Care Medicine
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    D F Signorini · N U Weir

    Full-text · Article · Feb 1999 · BMJ Clinical Research