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Biomedical subjects

Andy Vail

Publications and source records attributed to Andy Vail.

14 recordsLinked to original sources

Outcome prediction in trauma.

BACKGROUND: In the Trauma Audit and Research Network (TARN), currently the largest trauma network in Europe, outcome prediction is performed using the TRISS methodology since 1989. Its database contains 200,000 hospital admissions from 110 hospitals over the country, but a large amount of data is lost for the modelling because of missing data. To improve some of the shortcomings of TRISS a new model was developed. METHODS: The data for modelling consisted of 100,399 hospital trauma admissions over the period 1996 to 2001. Using the Glasgow Coma Score (GCS) instead of RTS has dramatically reduced the number of missing cases. Gender and its interaction with age have also been included in the model. The model was tested on different subsets of cases traditionally excluded, such as children, those with penetrating injuries, and ventilated and transferred patients. The new model included all those subsets using age, a transformation of ISS, GCS, gender and gender by age interaction as predictors. RESULTS: The model has shown a good discriminant ability tested by the area under the receiver operating characteristic (AROC) curve. The values of the AROC for the new model were 0.947 (95% CI: 0.943-0.951) on the prediction set and 0.952 (95% CI: 0.946-0.957) on the validation set compared respectively with 0.937 (95% CI: 0.932-0.943) and 0.941 (95% CI: 0.936-0.952) for TRISS. CONCLUSION: The new model has enabled us to include most of the cases that were excluded under the TRISS's inclusion criteria, less missing data are incurred and the predictive performance was significantly better than that of the TRISS model as shown by the AROC curves.

Adolescent↗

Variability of the systemic acute phase response after ischemic stroke.

Despite apparent relationships between ischemic stroke and the acute phase response (APR), considerable variation in the APR exists between individuals. We therefore performed post-hoc analysis of individual APR profiles in 31 patients with ischemic stroke in relation to volume of brain infarction. Patients with ischemic stroke had serial blood samples taken within 12 h, and up to 12 months of symptom onset, for analysis of plasma C-reactive protein (CRP) and interleukin-6 (IL-6). Computed tomography (CT) brain infarct volume was measured at 5 to 7 days (median 23.9 cm(3)). An increase in plasma CRP after the admission sample was evident in 94% of patients by day 5 to 7 (median increase 558% of admission value). CRP response, assessed as area under the curve between admission and day 5 to 7, correlated strongly (r=0.62, p<0.001) with CT infarct volume. Those with greater infarct volumes had more evidence of infection, either prior to or during the first week after stroke. The pattern of response was similar for IL-6, although only 77% showed an increase in plasma IL-6 after the admission sample (median increase 148% of admission value). These data suggest that, although infection and other factors may contribute to systemic inflammation, the extent of acute brain injury after ischemic stroke is a major factor influencing the magnitude and variability of the APR.

Acute-Phase Reaction↗

Evidence of improving quality of reporting of randomized controlled trials in subfertility.

BACKGROUND: The quality of randomized controlled trials (RCTs) in subfertility and their suitability for inclusion in meta-analyses have been assessed in the past and found to be insufficient. Our aim was to assess whether this quality has improved over time, particularly since the publication of the Consolidated Standards of Reporting Trials (CONSORT) statement, and to assess what proportion of trials could be included in the meta-analyses of pregnancy outcomes such as those included in Cochrane Reviews. METHODS: A selection of subfertility trials published in 1990, 1996 and 2002 was collected from the Cochrane Menstrual Disorder and Subfertility Group (MDSG) database. Only trials published in English as full journal articles, claiming to be randomized and reporting on pregnancy outcomes, were included. RESULTS: One hundred and sixty-four trials met our inclusion criteria. Twenty-four (15%) were found not to be randomized, despite claims, and only 10 trials (6%) provided adequate details on the methods of randomization and allocation concealment. Of these, only three had sufficient details extractable to allow for an intention-to-treat analysis of the outcome 'live birth'. CONCLUSIONS: Although an improvement in some subfertility-specific issues was observed, the quality of reporting of RCTs still needs to improve to make them suitable for inclusion in meta-analyses such as those in the Cochrane Library.

Female↗

Rapid elimination of protein S-100B from serum after minor head trauma.

Protein S-100B is released into the circulation after traumatic brain injury, and its serum concentration relates to measures of injury severity and outcome. These properties have led to interest in its development as a marker for clinical use, particularly in the prediction of adverse outcome for those with apparently trivial injuries. Before it can be used in populations of patients with head injuries, however, more needs to be understood about its release and elimination. This study was designed to estimate the elimination half-life of S-100B from the circulation after minor head trauma. We studied 14 patients with minor head injuries and measured serum S-100B serially after initial assessment in the Emergency Department of an inner city teaching hospital. We used curve-fit analysis to estimate the elimination constant that best fitted our data, and from this estimated the elimination half-life of protein S-100B. We estimated the mean half-life in this setting to be 97 min (95% confidence interval [CI] of 75-136 min). S-100B is cleared rapidly, relative to the time elapsed between injury and initial assessment in the Emergency Department. Variation in the time elapsed between injury and sampling is likely to influence the accuracy of head injury outcome prediction based on S-100B concentrations in serum, and should be considered when designing future studies.

Adult↗

Pitfalls in systematic reviews.

PURPOSE OF REVIEW: The term 'evidence-based medicine' means integrating individual clinical expertise with the best available external clinical evidence from systematic research. An important source for those who wish to practise evidence-based medicine is the systematic review. Systematic reviews, however, are not without their pitfalls. This review will consider the problems and challenges for researchers and users of systematic reviews. RECENT FINDINGS: Failure to adequately assess study quality, funding bias, publication bias, reliance on outcomes that provide no help in clinical decision-making, analysis errors and the incorrect use of evidence statements are all common pitfalls in systematic reviews. SUMMARY: There are several steps in completing a systematic review. These include developing the clinical question, searching for all available literature, study selection, assessment of study quality, data extraction, data analysis, interpreting the results, implications for practice and further research, and finally updating the review in a timely manner. Authors of systematic reviews need to be aware of these problems and attempt to address them so that research evidence may be of clinical value to both providers and consumers of healthcare.

Evidence-Based Medicine↗

A new approach to outcome prediction in trauma: A comparison with the TRISS model.

BACKGROUND: The Trauma Audit & Research Network (TARN) has been using the TRISS methodology since 1989. Its database contains 200,000 hospital admissions from 110 hospitals over the country. To improve outcome prediction, a revision of the current model became necessary. Our model tried to overcome some of the concerns of the trauma community, namely missing data, functional form of the predictors, inclusion criteria and patient's death within 30 days. METHODS: The data for modeling consisted of 100,399 anonymized hospital trauma admissions during the period 1996 to 2001. Cross validation was performed on this data set, and a multiple logistic regression model was derived using the prediction set and then its prediction ability was tested on the validation set. Fractional polynomials modeling showed that the linear functional form of the Injury Severity Score (ISS) in the model was not satisfactory. Using the Glasgow Coma Score (GCS) instead of the revised trauma score (RTS) has dramatically reduced the number of missing cases. Sex and its interaction with age have also been included in the model. The model was tested on different subsets of cases, traditionally excluded, such as children, those with penetrating injuries, and ventilated and transferred patients. The new model included all those subsets using age, a transformation of ISS, GCS, sex, and sex by age interaction as predictors. RESULTS: The model has shown a good discriminant ability tested by the Area under the Receiver Operating Characteristic (AROC) curve. The values of the AROC for the new model were 0.947 (95% confidence interval [CI]: 0.943-0.951) on the prediction set and 0.952 (95% CI: 0.946-0.957) on the validation set compared, respectively, with 0.937 (95% CI: 0.932-0.943) and 0.941 (95% CI: 0.936-0.952) for TRISS. CONCLUSION: The new model has enabled us to include most of the cases that were excluded under the TRISSs inclusion criteria, less missing data are incurred and the predictive performance was significantly better than that of the TRISS model as shown by the AROC curves.

Adolescent↗

Brain temperature and outcome after severe traumatic brain injury.

INTRODUCTION: In humans, raised body temperature is linked to poor outcome after brain injury. Because deviations between brain and body temperature have been reported after severe traumatic brain injury (TBI), the aim of this study was to explore the relationship between initial and mean brain temperature and survival at 3 months. METHODS: Intraparenchymal temperature was measured 3 - 4 cm within white matter. Logistic regression was used to explore linear and quadratic relationships between initial and average brain temperature and survival at 3 months. RESULTS: In 36 patients, initial brain temperatures ranged from 33.5 to 39.2 degrees C (median 37.4 degrees C). There was no evidence of an association between initial brain temperature and risk of death, either linear (odds ratio [OR] 95% confidence interval [CI] = 1.3 [0.68 to 2.5], p = 0.42) or quadratic ( p = 0.26). Assuming a linear relationship, patients with higher mean brain temperatures were less likely to die: OR (95% CI) for death per 1 degrees C was 0.31 (0.09 to 1.1), p = 0.06. However, by fitting the quadratic relationship, there was a suggestion that both high and low temperatures were associated with increased risk of death: p = 0.06. CONCLUSION: Initial brain temperature measured shortly after admission did not predict outcome. There is a suggestion that patients with "middle range" temperatures were less likely to die.

Adult↗

Reliability of a semi-automated technique of cerebral infarct volume measurement with CT.

BACKGROUND: A reliable method of infarct volume measurement is needed if infarct volume is to be used as an outcome measure in clinical stroke trials. We investigated the reproducibility of a semi-automated method of computed tomography (CT) infarct volume measurement amongst three stroke research fellows with no formal neuroradiology training and two consultant neuroradiologists. METHODS: CT brain scans for volumetric analysis were performed at 5 to 7 days in 34 patients with acute ischaemic stroke, of which 28 scans showed visible recent infarction. Five observers independently traced the infarct boundary on digitised images with a cursor. Volumetric analysis incorporated pixel thresholding with preset Hounsfield thresholds. One of the observers repeated the analyses on 21 of the scans in order to assess intraobserver variation. RESULTS: Median infarct volume was 35.7 cm3 (range 0.2-318 cm3). The closest limits of observed agreement (mean +/- 1.96 SD) between pairs of observers were between a research fellow and neuroradiologist (-29 to 21 cm3). The widest limits of agreement were between a different research fellow and the same neuroradiologist (-39.1 to 41.4 cm3). The limits of agreement between infarct volumes measured on two separate occasions by one of the research fellows were -7 to 8 cm3. CONCLUSIONS: Intraobserver reliability of CT infarct volume measurements performed by a stroke research fellow was superior to interobserver reliability between any pair of observers. The wide limits of agreement between different observers using manual tracing may not be acceptable in multicentre trials of acute ischaemic stroke treatment, but volume measurement by a single observer appears to be more reliable.

Aged↗

Peak plasma interleukin-6 and other peripheral markers of inflammation in the first week of ischaemic stroke correlate with brain infarct volume, stroke severity and long-term outcome.

BACKGROUND: Cerebral ischaemia initiates an inflammatory response in the brain and periphery. We assessed the relationship between peak values of plasma interleukin-6 (IL-6) in the first week after ischaemic stroke, with measures of stroke severity and outcome. METHODS: Thirty-seven patients with ischaemic stroke were prospectively recruited. Plasma IL-6, and other markers of peripheral inflammation, were measured at pre-determined timepoints in the first week after stroke onset. Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score (mRS) at 3 months and computed tomography (CT) brain infarct volume. RESULTS: Peak plasma IL-6 concentration correlated significantly (p < 0.001) with CT brain infarct volume (r = 0.75) and mRS at 3 months (r = 0.72). It correlated similarly with clinical outcome at 12 months or stroke severity. Strong associations were also noted between either peak plasma C-reactive protein (CRP) concentration or white blood cell (WBC) count, and all outcome measures. CONCLUSIONS: These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke, and clinical outcome.

Aged↗

Comparison of academic, application form and social factors in predicting early performance on the medical course.

OBJECTIVES: To compare the relative importance of social, academic and application form factors at admission in predicting performance in the first 3 years of a medicine course. DESIGN: Retrospective cohort study. SETTING: A single UK medical school. PARTICIPANTS: A total of 738 students who entered medical school between 1994 and 1997. MAIN OUTCOME MEASURE: Performance in Year 3 objective structured clinical examination (OSCE). RESULTS: School-leaving grades were significant predictors of success in the OSCE. Non-academic activities as assessed from the application form were associated with poorer performance. Mature students performed extremely well, and male and ethnic minority students performed less well. Socioeconomic status and type of school attended were not found to affect performance on the course. CONCLUSIONS: The relatively poor performance of male and ethnic minority students urgently needs further investigation. Our results carry no suggestion that, other things being equal, widening access to medical school for mature students and those from less affluent backgrounds would result in poorer performance.

Clinical Competence↗

An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis.

Central nervous system and peripheral inflammation is important in the responses to ischaemic stroke, and may also predispose to its development. We aimed to identify (1) the extent to which a peripheral inflammatory response is activated in patients following acute stroke, and (2) whether there was evidence for preexisting peripheral inflammation. Thirty-six patients with ischaemic stroke within 12 h of onset of symptoms had serial blood samples taken up to 12 months for analysis of markers of inflammation. Thirty-six control subjects, individually matched for age, sex and degree of atherosclerosis, were also studied. Median C-reactive protein (CRP) was elevated, relative to controls (2.08 mg/l), from admission (4.31 mg/l) (p</=0.001) until 3 months (2.90 mg/l) (p</=0.01), the greatest elevation occurring at 5-7 days (17.67 mg/l) (p</=0.001). Elevations were also seen in erythrocyte sedimentation rate (ESR) and white blood cell (WBC) count until 3 months. Median plasma IL-6 was also elevated, relative to controls (9 pg/ml), by 24 h after onset of symptoms (22 pg/ml) (p</=0.01), and remained elevated at 5-7 days (23 pg/ml) (p</=0.01), but not at 3 months. Less marked elevations in these markers were seen in patients without evidence of infection except for IL-6, which was not increased in the absence of infection. These data provide evidence of an early and sustained peripheral inflammatory response to acute ischaemic stroke in patients with or without evidence of infection. The very early increase in concentrations of inflammatory markers after stroke may either be induced by stroke itself, or may indicate a preexisting inflammatory condition in stroke patients which may contribute to the development of stroke.

Acute Disease↗

Systolic hypertension and the response to blunt trauma in infants and children.

OBJECTIVES: To describe age-related systolic blood pressures and pulse rates in children following blunt injury. To compare these variables with standard reference values for uninjured children at rest and with reference ranges from the Advanced Paediatric Life Support (APLS) guidelines. DESIGN: Secondary analysis of a prospective cohort. SETTING: Emergency departments throughout England and Wales. PARTICIPANTS: 12906 children presenting with acute blunt traumatic injury from August 1989 to September 1998. MAIN OUTCOME MEASURES: Systolic blood pressure and pulse rate on arrival. RESULTS: Injured children had higher systolic blood pressures than the standard quoted 'norms'. Standard reference values of systolic blood pressure for children at rest always appeared below the 50th percentile for our cohort of injured children (range 7th-27th percentiles). Pulse rates for children at rest were always towards the mid-range for injured children (range 41st-54th percentiles). These results appeared unrelated to injury severity. Age related APLS reference ranges for systolic blood pressure and pulse rate resembled the standard reference values for uninjured children at rest. CONCLUSIONS: Injured children have a relative systolic hypertension compared with children at rest. Pulse rates in the two groups are comparable. Following injury, children with apparently 'normal' age-specific systolic blood pressures on arrival in the Emergency Department are relatively hypotensive and should be carefully assessed.

Adolescent↗

Meta-analyses involving cross-over trials: methodological issues.

BACKGROUND: Meta-analysis of randomized controlled trials (RCTs) is usually based on trials where patients are randomized individually into two different, parallel, treatment groups. This paper concentrates on RCTs of a different design-two-period, two-treatment cross-over trials. METHODS: The characteristics of these trials are outlined, with detailed examples of methods for analysis for both continuous and binary data. These case studies are then extended into the context of a meta-analysis. The Cochrane Library was surveyed to assess current practice for synthesis. RESULTS: Methods are described for continuous and binary data for use both when the necessary paired data are given and also when they need to be calculated or imputed, and some suggestions are provided to help people wishing to synthesize data from cross-over trials into meta-analyses. The survey suggested that about 8% of the trials in the Cochrane library were cross-over trials and 18% of the reviews referred to such trials, although there was no consistent approach to their inclusion into the reviews. CONCLUSIONS: Methods do exist for including valuable information from two-period, two-treatment cross-over trials into quantitative reviews. However, poor reporting of cross-over trials will often impede attempts to perform a meta-analysis using the available methods.

Cross-Over Studies↗