Prediction modelling for trauma using comorbidity and 'true' 30-day outcome.

BACKGROUND: Prediction models for trauma outcome routinely control for age but there is uncertainty about the need to control for comorbidity and whether the two interact. This paper describes recent revisions to the Trauma Audit and Research Network (TARN) risk adjustment model designed to take account of age and comorbidities. In addition linkage between TARN and the Office of National Statistics (ONS) database allows patient's outcome to be accurately identified up to 30 days after injury. Outcome at discharge within 30 days was previously used. METHODS: Prospectively collected data between 2010 and 2013 from the TARN database were analysed. The data for modelling consisted of 129 786 hospital trauma admissions. Three models were compared using the area under the receiver operating curve (AuROC) for assessing the ability of the models to predict outcome, the Akaike information criteria to measure the quality between models and test for goodness-of-fit and calibration. Model 1 is the current TARN model, Model 2 is Model 1 augmented by a modified Charlson comorbidity index and Model 3 is Model 2 with ONS data on 30 day outcome. RESULTS: The values of the AuROC curve for Model 1 were 0.896 (95% CI 0.893 to 0.899), for Model 2 were 0.904 (0.900 to 0.907) and for Model 3 0.897 (0.896 to 0.902). No significant interaction was found between age and comorbidity in Model 2 or in Model 3. CONCLUSIONS: The new model includes comorbidity and this has improved outcome prediction. There was no interaction between age and comorbidity, suggesting that both independently increase vulnerability to mortality after injury.

Clinical article: mortality associated with severe head injury in the elderly.

BACKGROUND: Age is an important factor in determining prognosis following severe head injury (SHI), although mortality in patients > or =65 years is poorly reported. The aim of this study was to document mortality in patients with SHI > or =65 years. METHODS: A retrospective analysis of prospectively collected data from the TARN (Trauma Audit and Research Network) database (1996-2004) was performed. Six hundred and sixty-nine patients aged > or =65 with a GCS <9 after a head injury were identified, and mortality at 3 months was recorded. FINDINGS: Mortality was 71% in 65- to 70-year-old patients (n = 137) (CI, 64-79), 75% for patients aged 70-75 years (n = 147) (CI, 68-82), 85% in patients aged 75-80 years (n = 160) (79-91), and 87% for patients >80 years (n = 225) (CI, 83-91). Mortality for all patients > or =65 years with a GCS 3-5 was >80%. A better outcome was observed in patients with a GCS = 6-8 [65-70 years, 47% (CI, 30-64); 70-75 years, 56% (CI, 43-69); 75-80 years, 73% (CI, 62-85); >80 years, 79% (CI, 70-87)]. CONCLUSIONS: SHI-related mortality continues to increase with age. Overall, these data support a conservative approach to the severely head-injured elderly patient; however, patients presenting with a GCS = 6-8 and below the age of 75 may represent a group where more aggressive therapy may be indicated.

LXR ligand lowers LDL cholesterol in primates, is lipid neutral in hamster, and reduces atherosclerosis in mouse.

Liver X receptors (LXRs) are ligand-activated transcription factors that coordinate regulation of gene expression involved in several cellular functions but most notably cholesterol homeostasis encompassing cholesterol transport, catabolism, and absorption. WAY-252623 (LXR-623) is a highly selective and orally bioavailable synthetic modulator of LXR, which demonstrated efficacy for reducing lesion progression in the murine LDLR(-/-) atherosclerosis model with no associated increase in hepatic lipogenesis either in this model or Syrian hamsters. In nonhuman primates with normal lipid levels, WAY-252623 significantly reduced total (50-55%) and LDL-cholesterol (LDLc) (70-77%) in a time- and dose-dependent manner as well as increased expression of the target genes ABCA1/G1 in peripheral blood cells. Statistically significant decreases in LDLc were noted as early as day 7, reached a maximum by day 28, and exceeded reductions observed for simvastatin alone (20 mg/kg). Transient increases in circulating triglycerides and liver enzymes reverted to baseline levels over the course of the study. Complementary microarray analysis of duodenum and liver gene expression revealed differential activation of LXR target genes and suggested no direct activation of hepatic lipogenesis. WAY-252623 displays a unique and favorable pharmacological profile suggesting synthetic LXR ligands with these characteristics may be suitable for evaluation in patients with atherosclerotic dyslipidemia.

Unexpected mortality in patients discharged from the emergency department following an episode of nontraumatic chest pain.

BACKGROUND: Chest pain is the second most common presenting complaint seen in the emergency department. Following evaluation in the emergency department, many of these patients are discharged with a diagnosis of nonspecific chest pain. Our hypothesis is that this group of patients has a high prevalence of ischaemic heart disease. METHODS: This was a prospective follow-up study of mortality in 786 patients who presented to an emergency department in the UK with an episode of nontraumatic chest pain and were discharged without further inpatient assessment. Observed mortality was compared with expected mortality in age-matched and sex-matched local population. RESULTS: The observed mortality of the study group was consistently higher than expected throughout the study period. The 5-year mortality rates for men and women under the age of 65 years were more than double the expected rates for the local population [relative risk of 2.1 (95% confidence interval: 1.4-2.8) and 2.6 (1.4-3.8), respectively]. This increase was less marked in male and female patients aged 65 years or more [relative risk of 1.2 (0.9-1.5) and 1.5 (1.2-1.8), respectively]. Ischaemic heart disease accounted for almost 50% of male deaths in the study group. This compared with an expected rate of less than 30% of male deaths in the local population. An excess of cardiac deaths was not seen in women. INTERPRETATION: Patients discharged from the emergency department following an episode of acute chest pain have significantly reduced 5-year survival. We conclude that further evaluation of this group to establish the prevalence of risk factors is important to support the strategic implementation of appropriate prevention programmes.

The effect of pre-existing medical conditions and age on mortality after injury.

BACKGROUND: Pre-existing medical conditions (PMCs) have been shown to increase mortality after trauma even after adjustment for the effect of chronological aging. It has been suggested that there is an interaction between injury severity and physiologic reserve, such that diminished physiologic reserve will have an adverse effect on survival at lower injury severity, but that at higher levels of injury severity, physiologic reserve will have much less of an impact. METHODS: Records of 65,743 patients, admitted after trauma, were extracted from the database of the United Kingdom Trauma Network to explore the impacts of age, gender and PMCs on mortality, and modification of these effects by severity of injury. RESULTS: PMCs were categorized as absent (23%), present (23%), or unrecorded (54%). There was an increase in mortality with increasing age at all levels of injury severity. Presence of a PMC was associated with a marked increase in mortality of patients with minor injuries (odds ratio [OR] = 5.9, 95% confidence interval [CI] 4.4, 8.0) or moderate injuries (OR = 2.0, 95% CI 1.4, 2.9), but not in those with more severe injuries (OR = 1.1, 95% CI 0.9, 1.4). The impact of age and male gender were also somewhat more pronounced for patients with less severe injuries. CONCLUSION: These findings support the hypothesis of an interaction between physiologic reserve and injury severity, where PMCs are associated with increased mortality when combined with low to moderate severity injuries, but not when combined with more severe injuries.

Abdominal injury due to child abuse.

Diagnosis of abuse in children with internal abdominal injury is difficult because of limited published work. We aimed to ascertain the incidence of abdominal injury due to abuse in children age 0-14 years. 20 children (identified via the British Paediatric Surveillance Unit) had abdominal injuries due to abuse and 164 (identified via the Trauma Audit and Research Network) had injuries to the abdomen due to accident (112 by road-traffic accidents, 52 by falls). 16 abused children were younger than 5 years. Incidence of abdominal injury due to abuse was 2.33 cases per million children per year (95% CI 1.43-3.78) in children younger than 5 years. Six abused children died. 11 abused children had an injury to the gut (ten small bowel) compared with five (all age >5 years) who were injured by a fall (relative risk 5.72 [95% CI 2.27-14.4]; p=0.0002). We have shown that small-bowel injuries can arise accidentally as a result of falls and road-traffic accidents but they are significantly more common in abused children. Therefore, injuries to the small bowel in young children need special consideration, particularly if a minor fall is the explanation.

Abnormalities on magnetic resonance imaging seen acutely following mild traumatic brain injury: correlation with neuropsychological tests and delayed recovery.

Mild traumatic brain injury (MTBI) is a common reason for hospital attendance and is associated with significant delayed morbidity. We studied a series of 80 persons with MTBI. Magnetic resonance imaging (MRI) and neuropsychological testing were used in the acute phase and a questionnaire for post-concussion syndrome (PCS) and return to work status at 6 months. In 26 subjects abnormalities were seen on MRI, of which 5 were definitely traumatic. There was weak correlation with abnormal neuropsychological tests for attention in the acute period. There was no significant correlation with a questionnaire for PCS and return to work status. Although non-specific abnormalities are frequently seen, standard MRI techniques are not helpful in identifying patients with MTBI who are likely to have delayed recovery.

Effect of alcohol on the lactate/pyruvate ratio of recently injured adults.

OBJECTIVE: To compare the ability of plasma (lactate) and the plasma lactate/pyruvate (L/P) ratio to predict shock-related outcome after injury and also to examine the influence of plasma ethanol on any relationships found. DESIGN: Prospective observational study. SETTING: Emergency departments in the UK and the Republic of South Africa. PATIENTS: Blood samples were taken at presentation from 232 adult patients 1-23 hrs (median, 3.5 hrs) after sustaining an injury or injuries deemed sufficiently severe to require inpatient care. MEASUREMENTS: Plasma concentrations of lactate, pyruvate, and ethanol, anatomical severity of injury, development of multiple organ failure, and 30-day survival were determined. RESULTS: At 90% specificity for predicting subsequent mortality and/or multiple organ failure, plasma lactate >or=3.85 mmol/L was 23% (5% to 41%) more sensitive than an L/P ratio of >or=42.76. At 90% sensitivity for ruling out morbidity, plasma lactate <1.6 mmol/L is 6% (-1% to 13%) more specific than an L/P ratio of <14.08. High L/P ratios were noted to be associated with a detectable plasma alcohol level. A post hoc regression analysis showed that alcohol-positive/-negative status was a much stronger predictor of the L/P ratio than was anatomical severity of injury, shock, or time after injury. CONCLUSIONS: Plasma lactate alone is a better predictor than the L/P ratio of shock-related outcome after injury. The interpretation of L/P ratios after injury is confounded in the presence of elevated plasma ethanol.