Glasgow Coma Scale (GCS) scores and pupil responses are key indicators of the severity of traumatic brain damage. The aim of this study was to determine what information would be gained by combining ...these indicators into a single index and to explore the merits of different ways of achieving this.
METHODS Information about early GCS scores, pupil responses, late outcomes on the Glasgow Outcome Scale, and mortality were obtained at the individual patient level by reviewing data from the CRASH (Corticosteroid Randomisation After Significant Head Injury; n = 9,045) study and the IMPACT (International Mission for Prognosis and Clinical Trials in TBI; n = 6855) database. These data were combined into a pooled data set for the main analysis. Methods of combining the Glasgow Coma Scale and pupil response data varied in complexity from using a simple arithmetic score (GCS score range 3-15 minus the number of nonreacting pupils 0, 1, or 2), which we call the GCS-Pupils score (GCS-P; range 1-15), to treating each factor as a separate categorical variable. The content of information about patient outcome in each of these models was evaluated using Nagelkerke's R
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Separately, the GCS score and pupil response were each related to outcome. Adding information about the pupil response to the GCS score increased the information yield. The performance of the simple GCS-P was similar to the performance of more complex methods of evaluating traumatic brain damage. The relationship between decreases in the GCS-P and deteriorating outcome was seen across the complete range of possible scores. The additional 2 lowest points offered by the GCS-Pupils scale (GCS-P 1 and 2) extended the information about injury severity from a mortality rate of 51% and an unfavorable outcome rate of 70% at GCS score 3 to a mortality rate of 74% and an unfavorable outcome rate of 90% at GCS-P 1. The paradoxical finding that GCS score 4 was associated with a worse outcome than GCS score 3 was not seen when using the GCS-P.
A simple arithmetic combination of the GCS score and pupillary response, the GCS-P, extends the information provided about patient outcome to an extent comparable to that obtained using more complex methods. The greater range of injury severities that are identified and the smoothness of the stepwise pattern of outcomes across the range of scores may be useful in evaluating individual patients and identifying patient subgroups. The GCS-P may be a useful platform onto which information about other key prognostic features can be added in a simple format likely to be useful in clinical practice.
Summary Background Pathological waves of spreading mass neuronal depolarisation arise repeatedly in injured, but potentially salvageable, grey matter in 50–60% of patients after traumatic brain ...injury (TBI). We aimed to ascertain whether spreading depolarisations are independently associated with unfavourable neurological outcome. Methods We did a prospective, observational, multicentre study at seven neurological centres. We enrolled 109 adults who needed neurosurgery for acute TBI. Spreading depolarisations were monitored by electrocorticography during intensive care and were classified as cortical spreading depression (CSD) if they took place in spontaneously active cortex or as isoelectric spreading depolarisation (ISD) if they took place in isoelectric cortex. Investigators who treated patients and assessed outcome were masked to electrocorticographic results. Scores on the extended Glasgow outcome scale at 6 months were fitted to a multivariate model by ordinal regression. Prognostic score (based on variables at admission, as validated by the IMPACT studies) and spreading depolarisation category (none, CSD only, or at least one ISD) were assessed as outcome predictors. Findings Six individuals were excluded because of poor-quality electrocorticography. A total of 1328 spreading depolarisations arose in 58 (56%) patients. In 38 participants, all spreading depolarisations were classified as CSD; 20 patients had at least one ISD. By multivariate analysis, both prognostic score (p=0·0009) and spreading depolarisation category (p=0·0008) were significant predictors of neurological outcome. CSD and ISD were associated with an increased risk of unfavourable outcome (common odds ratios 1·56 95% CI 0·72–3·37 and 7·58 2·64–21·8, respectively). Addition of depolarisation category to the regression model increased the proportion of variance in outcome that could be attributed to predictors from 9% to 22%, compared with the prognostic score alone. Interpretation Spreading depolarisations were associated with unfavourable outcome, after controlling for conventional prognostic variables. The possibility that spreading depolarisations have adverse effects on the traumatically injured brain, and therefore might be a target in the treatment of TBI, deserves further research. Funding US Army CDMRP PH/TBI research programme.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In a trial comparing decompressive craniectomy with medical therapy in patients with traumatic brain injury and raised intracranial pressure refractory to medical therapy, decompressive craniectomy ...resulted in lower mortality and higher rates of vegetative state and severe disability.
After traumatic brain injury (TBI), intracranial pressure can be elevated owing to a mass effect from intracranial hematomas, contusions, diffuse brain swelling, or hydrocephalus.
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Intracranial hypertension can lead to brain ischemia by reducing the cerebral perfusion pressure.
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Intracranial hypertension after TBI is associated with an increased risk of death in most studies.
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The monitoring of intracranial pressure and the administration of interventions to lower intracranial pressure are routinely used in patients with TBI, despite the lack of level 1 evidence.
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Decompressive craniectomy is a surgical procedure in which a large section of the skull is removed and the underlying . . .
CONTEXT A low ankle brachial index (ABI) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events. Screening for a low ABI can identify an asymptomatic higher risk ...group potentially amenable to preventive treatments. OBJECTIVE To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population. DESIGN, SETTING, AND PARTICIPANTS The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind randomized controlled trial conducted from April 1998 to October 2008, involving 28 980 men and women aged 50 to 75 years living in central Scotland, free of clinical cardiovascular disease, recruited from a community health registry, and had an ABI screening test. Of those, 3350 with a low ABI (≤0.95) were entered into the trial, which was powered to detect a 25% proportional risk reduction in events. INTERVENTIONS Once daily 100 mg aspirin (enteric coated) or placebo. MAIN OUTCOME MEASURES The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization. Two secondary end points were (1) all initial vascular events defined as a composite of a primary end point event or angina, intermittent claudication, or transient ischemic attack; and (2) all-cause mortality. RESULTS After a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1000 person-years, 95% confidence interval CI, 12.2-15.0). No statistically significant difference was found between groups (13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group; hazard ratio HR, 1.03; 95% CI, 0.84-1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1000 person-years; 95% CI, 21.0-24.8) and no statistically significant difference between groups (22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group; HR, 1.00; 95% CI, 0.85-1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77-1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1000 person-years) in the aspirin group and 20 (1.5 per 1000 person-years) in the placebo group (HR, 1.71; 95% CI, 0.99-2.97). CONCLUSION Among participants without clinical cardiovascular disease, identified with a low ABI based on screening a general population, the administration of aspirin compared with placebo did not result in a significant reduction in vascular events. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN66587262
In this randomized trial involving patients with traumatic brain injury and elevated intracranial pressure, therapeutic hypothermia plus standard care to reduce intracranial pressure did not result ...in outcomes better than those with standard care alone.
In Europe, traumatic brain injury is the most common cause of permanent disability in people younger than 40 years of age, with the annual cost exceeding €33 billion (approximately $37.5 billion in U.S. dollars).
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Recent statistics show a 21% increase in the incidence of traumatic brain injury during the past 5 years — three times greater than the increase in population. Despite this, management of traumatic brain injury has been underrepresented in medical research as compared with other health problems.
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Consequently, there are few data to support the commonly used stage 2 interventions (Figure 1) for the management of . . .
Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed ...distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis.
We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios.
For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally performed better than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials gave superior results.
Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median) reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or variability summary statistics within meta-analyses.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diaphragm dysfunction worsens outcomes in mechanically ventilated patients, but the clinical impact of potentially preventable changes in diaphragm structure and function caused by mechanical ...ventilation is unknown.
To determine whether diaphragm atrophy developing during mechanical ventilation leads to prolonged ventilation.
Diaphragm thickness was measured daily by ultrasound in adults requiring invasive mechanical ventilation; inspiratory effort was assessed by thickening fraction. The primary outcome was time to liberation from ventilation. Secondary outcomes included complications (reintubation, tracheostomy, prolonged ventilation, or death). Associations were adjusted for age, severity of illness, sepsis, sedation, neuromuscular blockade, and comorbidity.
Of 211 patients enrolled, 191 had two or more diaphragm thickness measurements. Thickness decreased more than 10% in 78 patients (41%) by median Day 4 (interquartile range, 3-5). Development of decreased thickness was associated with a lower daily probability of liberation from ventilation (adjusted hazard ratio, 0.69; 95% confidence interval CI, 0.54-0.87; per 10% decrease), prolonged ICU admission (adjusted duration ratio, 1.71; 95% CI, 1.29-2.27), and a higher risk of complications (adjusted odds ratio, 3.00; 95% CI, 1.34-6.72). Development of increased thickness (n = 47; 24%) also predicted prolonged ventilation (adjusted duration ratio, 1.38; 95% CI, 1.00-1.90). Decreasing thickness was related to abnormally low inspiratory effort; increasing thickness was related to excessive effort. Patients with thickening fraction between 15% and 30% (similar to breathing at rest) during the first 3 days had the shortest duration of ventilation.
Diaphragm atrophy developing during mechanical ventilation strongly impacts clinical outcomes. Targeting an inspiratory effort level similar to that of healthy subjects at rest might accelerate liberation from ventilation.
Summary Traumatic brain injury (TBI) is a heterogeneous condition that encompasses a broad spectrum of disorders. Outcome can be highly variable, particularly in more severely injured patients. ...Despite the association of many variables with outcome, prognostic predictions are notoriously difficult to make. Multivariable analysis has identified age, clinical severity, CT abnormalities, systemic insults (hypoxia and hypotension), and laboratory variables as relevant factors to include in models to predict outcome in individual patients. Advances in statistical modelling and the availability of large datasets have facilitated the development of prognostic models that have greater performance and generalisability. Two prediction models are currently available, both of which have been developed on large datasets with state-of-the-art methods, and offer new opportunities. We see great potential for their use in clinical practice, research, and policy making, as well as for assessment of the quality of health-care delivery. Continued development, refinement, and validation is advocated, together with assessment of the clinical impact of prediction models, including treatment response.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Background Cerebral cavernous malformations (CCMs) can cause symptomatic intracranial haemorrhage (ICH), but the estimated risks are imprecise and predictors remain uncertain. We aimed to ...obtain precise estimates and predictors of the risk of ICH during untreated follow-up in an individual patient data meta-analysis. Methods We invited investigators of published cohorts of people aged at least 16 years, identified by a systematic review of Ovid MEDLINE and Embase from inception to April 30, 2015, to provide individual patient data on clinical course from CCM diagnosis until first CCM treatment or last available follow-up. We used survival analysis to estimate the 5-year risk of symptomatic ICH due to CCMs (primary outcome), multivariable Cox regression to identify baseline predictors of outcome, and random-effects models to pool estimates in a meta-analysis. Findings Among 1620 people in seven cohorts from six studies, 204 experienced ICH during 5197 person-years of follow-up (Kaplan-Meier estimated 5-year risk 15·8%, 95% CI 13·7–17·9). The primary outcome of ICH within 5 years of CCM diagnosis was associated with clinical presentation with ICH or new focal neurological deficit (FND) without brain imaging evidence of recent haemorrhage versus other modes of presentation (hazard ratio 5·6, 95% CI 3·2–9·7) and with brainstem CCM location versus other locations (4·4, 2·3–8·6), but age, sex, and CCM multiplicity did not add independent prognostic information. The 5-year estimated risk of ICH during untreated follow-up was 3·8% (95% CI 2·1–5·5) for 718 people with non-brainstem CCM presenting without ICH or FND, 8·0% (0·1–15·9) for 80 people with brainstem CCM presenting without ICH or FND, 18·4% (13·3–23·5) for 327 people with non-brainstem CCM presenting with ICH or FND, and 30·8% (26·3–35·2) for 495 people with brainstem CCM presenting with ICH or FND. Interpretation Mode of clinical presentation and CCM location are independently associated with ICH within 5 years of CCM diagnosis. These findings can inform decisions about CCM treatment. Funding UK Medical Research Council, Chief Scientist Office of the Scottish Government, and UK Stroke Association.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Diaphragm atrophy and dysfunction have been reported in humans during mechanical ventilation, but the prevalence, causes, and functional impact of changes in diaphragm thickness during routine ...mechanical ventilation for critically ill patients are unknown.
To describe the evolution of diaphragm thickness over time during mechanical ventilation, its impact on diaphragm function, and the influence of inspiratory effort on this phenomenon.
In three academic intensive care units, 107 patients were enrolled shortly after initiating ventilation along with 10 nonventilated intensive care unit patients (control subjects). Diaphragm thickness and contractile activity (quantified by the inspiratory thickening fraction) were measured daily by ultrasound.
Over the first week of ventilation, diaphragm thickness decreased by more than 10% in 47 (44%), was unchanged in 47 (44%), and increased by more than 10% in 13 (12%). Thickness did not vary over time following extubation or in nonventilated patients. Low diaphragm contractile activity was associated with rapid decreases in diaphragm thickness, whereas high contractile activity was associated with increases in diaphragm thickness (P = 0.002). Contractile activity decreased with increasing ventilator driving pressure (P = 0.01) and controlled ventilator modes (P = 0.02). Maximal thickening fraction (a measure of diaphragm function) was lower in patients with decreased or increased diaphragm thickness (n = 10) compared with patients with unchanged thickness (n = 10; P = 0.05 for comparison).
Changes in diaphragm thickness are common during mechanical ventilation and may be associated with diaphragmatic weakness. Titrating ventilatory support to maintain normal levels of inspiratory effort may prevent changes in diaphragm configuration associated with mechanical ventilation.
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