Jon Bishop

Improved survival in UK combat casualties from Iraq and Afghanistan: 2003-2012

BACKGROUND The United Kingdom was at war in Iraq and Afghanistan for more than a decade. Despite assertions regarding advances in military trauma care during these wars, thus far, no studies have examined survival in UK troops during this sustained period of combat. The aims of this study were to examine temporal changes of injury patterns defined by body region and survival in a population of UK Military casualties between 2003 and 2012 in Iraq and Afghanistan. METHODS The UK Military Joint Theatre Trauma Registry was searched for all UK Military casualties (survivors and fatalities) sustained on operations between January 1, 2003, and December 31, 2012. The New Injury Severity Score (NISS) was used to stratify injury severity. RESULTS There were 2,792 UK Military casualties sustaining 14,252 separate injuries during the study period. There were 608 fatalities (22% of all casualties). Approximately 70% of casualties injured in hostile action resulted from explosive munitions. The extremities were the most commonly injured body region, involved in 43% of all injuries. The NISS associated with a 50% chance of survival rose each year from 32 in 2003 to 60 in 2012. CONCLUSION An improvement in survival during the 10-year period is demonstrated. A majority of wounds are a result of explosive munitions, and the extremities are the most commonly affected body region. The authors recommend the development of more sophisticated techniques for the measuring of the performance of combat casualty care systems to include measures of morbidity and functional recovery as well as survival. LEVEL OF EVIDENCE Epidemiologic study, level III.

Visual Outcomes after Blunt Ocular Trauma

OBJECTIVE To describe the prognosis and retinal location in patients presenting with acute traumatic maculopathy and extramacular retinal injuries. DESIGN Retrospective, noninterventional case series. PARTICIPANTS AND CONTROLS All patients presenting with commotio retinae or sclopetaria retinae to the Birmingham Midland Eye Centre Eye Casualty from October 1, 2007, to February 23, 2011. METHODS The notes of all patients presenting with ocular trauma in the specified time period were examined to identify suitable patients and demographic and injury data were extracted. MAIN OUTCOME MEASURES Outcome was assessed by visual acuity (VA). RESULTS For macular commotio retinae, 53 patients were identified, of whom 34 had adequate follow-up to determine final VA. The median presenting VA was 20/40; 25 patients (74%) recovered to ≥ 20/30. The median extent of visual recovery was 0.18 logarithm of the minimum angle of resolution (logMAR). For extramacular commotio retinae, 117 patients were identified, of whom 58 had adequate follow-up to determine final VA. The median presenting VA retinae was 20/30; 55 patients (95%) recovered to ≥ 20/30. The median extent of visual recovery was logMAR 0.076. There was 1 case of extramacular sclopetaria retinae. The 3 most common retinal locations of extramacular commotio retinae, in order of frequency, were inferotemporal (37%), temporal (17%), and superotemporal (17%); <5% of cases were in a nasal location. CONCLUSIONS This is the first report on the prognosis of acute traumatic maculopathy and extramacular commotio retinae. After macular injury, 26% of patients were left with a VA of ≤ 20/30, although the proportion with visual impairment is higher than this because (1) a deterioration from 20/15 to 20/30 is significant to many patients; and (2) additional patients are visually impaired by symptomatic paracentral visual field defects despite a normal VA. Reduced VA after extramacular commotio retinae may represent occult macular injury or previously undiagnosed visual impairment in the affected eye. Extramacular commotio occurs mostly in an inferotemporal to temporal location, consistent with direct trauma to the sclera overlying the injured retina. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke: The Stroke Oxygen Study Randomized Clinical Trial

Importance Hypoxia is common in the first few days after acute stroke, is frequently intermittent, and is often undetected. Oxygen supplementation could prevent hypoxia and secondary neurological deterioration and thus has the potential to improve recovery. Objective To assess whether routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation. Design, Setting, and Participants In this single-blind randomized clinical trial, 8003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015). Interventions Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93% or less and at 2 L/min if oxygen saturation was greater than 93%. Main Outcomes and Measures The primary outcome was reported using the modified Rankin Scale score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The modified Rankin Scale score was analyzed by ordinal logistic regression, which yields a common odds ratio (OR) for a change from one disability level to the next better (lower) level; OR greater than 1.00 indicates improvement. Results A total of 8003 patients (4398 (55%) men; mean [SD] age, 72 [13] years; median National Institutes of Health Stroke Scale score, 5; mean baseline oxygen saturation, 96.6%) were enrolled. The primary outcome was available for 7677 (96%) participants. The unadjusted OR for a better outcome (calculated via ordinal logistic regression) was 0.97 (95% CI, 0.89 to 1.05; P = .47) for oxygen vs control, and the OR was 1.03 (95% CI, 0.93 to 1.13; P = .61) for continuous vs nocturnal oxygen. No subgroup could be identified that benefited from oxygen. At least 1 serious adverse event occurred in 348 (13.0%) participants in the continuous oxygen group, 294 (11.0%) in the nocturnal group, and 322 (12.1%) in the control group. No significant harms were identified. Conclusions and Relevance Among nonhypoxic patients with acute stroke, the prophylactic use of low-dose oxygen supplementation did not reduce death or disability at 3 months. These findings do not support low-dose oxygen in this setting. Trial Registration ISRCTN Identifier: ISRCTN52416964

Endotheliopathy of Trauma is an On-Scene Phenomenon, and is Associated with Multiple Organ Dysfunction Syndrome: A Prospective Observational Study

Background: Trauma patients are vulnerable to coagulopathy and inflammatory dysfunction associated with endotheliopathy of trauma (EoT). In vitro evidence has suggested that tranexamic acid (TXA) may ameliorate endotheliopathy. We aimed to investigate how soon after injury EoT occurs, its association with multiple organ dysfunction syndrome (MODS), and whether TXA ameliorates it. Methods: A prospective observational study included 91 trauma patients enrolled within 60 min of injury and 19 healthy controls. Blood was sampled on enrolment and again 4 to 12 h later. ELISAs measured serum concentrations of syndecan-1 and thrombomodulin as biomarkers of EoT. MODS was compared between groups according to biomarker dynamics: persistently abnormal; abnormal to normal; and persistently normal. Timing of EoT was estimated by plotting biomarker data against time, and then fitting generalized additive models. Biomarker dynamics were compared between those who did or did not receive prehospital TXA. Results: Median age was 38 (interquartile range [IQR] 24–55) years; 78 of 91 were male. Median injury severity score (ISS) was 22 (IQR 12–36). EoT was estimated to occur at 5 to 8 min after injury. There were no significant differences in ISS between those with or without prehospital EoT. Forty-two patients developed MODS; 31 of 42 with persistently abnormal; 8 of 42 with abnormal to normal; and 3 of 42 with persistently normal biomarkers; P < 0.05. There were no significant differences between TXA and non-TXA groups. Conclusions: EoT was present at the scene of injury. MODS was more likely when biomarkers of EoT were persistently raised. There were no significant differences between TXA and non-TXA groups. Prehospital interventions aimed at endothelial restoration may represent a clinically meaningful target for prehospital resuscitation.

Endotheliopathy is associated with higher levels of cell-free DNA following major trauma:: A prospective observational study

Background Cell free deoxyribonucleic acid (cfDNA) has been proposed as a biomarker of secondary complications following trauma. Raised thrombomodulin and syndecan-1 levels have been used to indicate endotheliopathy, and are associated with inflammation, coagulopathy, and mortality. The current study aimed to analyse the association between cfDNA and biomarkers of endotheliopathy in a cohort of trauma patients, and whether raised levels of cfDNA were associated with poorer clinical outcomes. Methods Serum thrombomodulin and syndecan-1 were used as biomarkers of endotheliopathy and compared to plasma cfDNA in trauma patients from two prospective longitudinal observational studies. Cohort A (n = 105) had a predicted injury severity score (ISS) >8, and had blood sampled within 1h of injury and at 4–12h. Cohort B (n = 17) had evidence of haemorrhagic shock, and had blood sampled at a median time of 3.5h after injury. Relationships between biomarkers were tested using multivariable linear regression models that included the covariates of gender, age, ISS, Glasgow Coma Scale, lactate, systolic blood pressure, and heart rate. A model was fitted to investigate whether changes in cfDNA were associated with similar changes in endothelial biomarkers. Results The mean age was 41 (SD 19), and the median ISS was 25 (IQR 12–34). There was a significant association between cfDNA levels and both syndecan-1 and thrombomodulin levels (both p<0.001). This was independent of all covariates except for ISS, which significantly correlated with cfDNA levels. 50 ng/ml change in syndecan-1 and 1 ng/ml change in thrombomodulin corresponded to 15% and 20% increases in cfDNA levels respectively (both p<0.001). Patients who died had significantly higher prehospital and in-hospital cfDNA levels (both p<0.05). Conclusions Raised cfDNA levels are associated with markers of endotheliopathy following trauma, and are associated with mortality. This relationship is present within the first hour of injury, and a change in one biomarker level is reflected by similar changes in the others. These findings are in keeping with the hypothesis that circulating DNA and endothelial injury share a common pathway following trauma.

Changes in novel haematological parameters following thermal injury:: A prospective observational cohort study

The mortality caused by sepsis is high following thermal injury. Diagnosis is difficult due to the ongoing systemic inflammatory response. Previous studies suggest that cellular parameters may show promise as diagnostic markers of sepsis. The aim of this study was to evaluate the effect of thermal injury on novel haematological parameters and to study their association with clinical outcomes. Haematological analysis was performed using a Sysmex XN-1000 analyser on blood samples acquired on the day of the thermal injury to 12 months post-injury in 39 patients (15–95% TBSA). Platelet counts had a nadir at day 3 followed by a rebound thrombocytosis at day 21, with nadir values significantly lower in septic patients. Measurements of extended neutrophil parameters (NEUT-Y and NEUT-RI) demonstrated that septic patients had significantly higher levels of neutrophil nucleic acid content. A combination of platelet impedance count (PLT-I) and NEUT-Y at day 3 post-injury exhibited good discriminatory power for the identifying septic patients (AUROC = 0.915, 95% CI [0.827, 1.000]). Importantly, the model had improved performance when adjusted for mortality with an AUROC of 0.974 (0.931, 1.000). A combination of PLT-I and NEUT-Y show potential for the early diagnosis of sepsis post-burn injury. Importantly, these tests can be performed rapidly and require a small volume of whole blood highlighting their potential utility in clinical practice.

Refining the Trauma and Injury Severity Score (TRISS) to Measure the Performance of the UK Combat Casualty Care System

Introduction The Trauma and Injury Severity Score (TRISS) methodology is used in both the UK and US Military trauma registries. The method relies on dividing casualties according to mechanism, penetrating or blunt, and uses different weighting coefficients accordingly. The UK Military Joint Theatre Trauma Registry uses the original coefficients devised in 1987, whereas the US military registry uses updated civilian coefficients, but it is not clear how either registry analyzes explosive casualties according to the TRISS methodology. This study aims to use the UK Military Joint Theatre Trauma Registry to calculate new TRISS coefficients for contemporary battlefield casualties injured by either gunshot or explosive mechanisms. The secondary aim of this study is to apply the revised TRISS coefficients to examine the survival trends of UK casualties from recent military conflicts. Materials and Methods: The Joint Theatre Trauma Registry was searched for all UK casualties injured or killed in Iraq and Afghanistan by explosive or gunshot mechanisms between January 1, 2003 and December 31, 2014. Details of these casualties including injuries and vital signs were reviewed. Logistic regression analysis was performed to devise new TRISS coefficients; these were then used to examine survival over the 12 yr of the study. Results Comparing the predictions from the gunshot TRISS model to the observed outcomes, it demonstrates a sensitivity of 98.1% and a specificity of 96.8% and an overall accuracy of 97.8%. With respect to the explosive TRISS model, there is a sensitivity of 98.6%, a specificity of 97.4%, and an overall accuracy of 98.4%. When this updated and mechanism-specific TRISS methodology was used to measure changes in survival over the study period, survival following these injuries improved until 2012 when performance was maintained for the last 2 yr of the study. Conclusion: This study for the first time refines the TRISS methodology with coefficients appropriate for use within combat casualty care systems. This improved methodology reveals that UK combat casualty care performance appears to have improved until 2012 when this standard was maintained.

Routine low-dose continuous or nocturnal oxygen for people with acute stroke: three-arm Stroke Oxygen Supplementation RCT.

BACKGROUND Stroke is a major cause of death and disability worldwide. Hypoxia is common after stroke and is associated with worse outcomes. Oxygen supplementation could prevent hypoxia and secondary brain damage. OBJECTIVES (1) To assess whether or not routine low-dose oxygen supplementation in patients with acute stroke improves outcome compared with no oxygen; and (2) to assess whether or not oxygen given at night only, when oxygen saturation is most likely to be low, is more effective than continuous supplementation. DESIGN Multicentre, prospective, randomised, open, blinded-end point trial. SETTING Secondary care hospitals with acute stroke wards. PARTICIPANTS Adult stroke patients within 24 hours of hospital admission and 48 hours of stroke onset, without definite indications for or contraindications to oxygen or a life-threatening condition other than stroke. INTERVENTIONS Allocated by web-based minimised randomisation to: (1) continuous oxygen: oxygen via nasal cannula continuously (day and night) for 72 hours after randomisation at a flow rate of 3 l/minute if baseline oxygen saturation was ≤ 93% or 2 l/minute if > 93%; (2) nocturnal oxygen: oxygen via nasal cannula overnight (21:00-07:00) for three consecutive nights. The flow rate was the same as the continuous oxygen group; and (3) control: no routine oxygen supplementation unless required for reasons other than stroke. MAIN OUTCOME MEASURES Primary outcome: disability assessed by the modified Rankin Scale (mRS) at 3 months by postal questionnaire (participant aware, assessor blinded). Secondary outcomes at 7 days: neurological improvement, National Institutes of Health Stroke Scale (NIHSS), mortality, and the highest and lowest oxygen saturations within the first 72 hours. Secondary outcomes at 3, 6, and 12 months: mortality, independence, current living arrangements, Barthel Index, quality of life (European Quality of Life-5 Dimensions, three levels) and Nottingham Extended Activities of Daily Living scale by postal questionnaire. RESULTS In total, 8003 patients were recruited between 24 April 2008 and 17 June 2013 from 136 hospitals in the UK [continuous, n = 2668; nocturnal, n = 2667; control, n = 2668; mean age 72 years (standard deviation 13 years); 4398 (55%) males]. All prognostic factors and baseline characteristics were well matched across the groups. Eighty-two per cent had ischaemic strokes. At baseline the median Glasgow Coma Scale score was 15 (interquartile range 15-15) and the mean and median NIHSS scores were 7 and 5 (range 0-34), respectively. The mean oxygen saturation at randomisation was 96.6% in the continuous and nocturnal oxygen groups and 96.7% in the control group. Primary outcome: oxygen supplementation did not reduce disability in either the continuous or the nocturnal oxygen groups. The unadjusted odds ratio for a better outcome (lower mRS) was 0.97 [95% confidence interval (CI) 0.89 to 1.05; p = 0.5] for the combined oxygen groups (both continuous and nocturnal together) (n = 5152) versus the control (n = 2567) and 1.03 (95% CI 0.93 to 1.13; p = 0.6) for continuous versus nocturnal oxygen. Secondary outcomes: oxygen supplementation significantly increased oxygen saturation, but did not affect any of the other secondary outcomes. LIMITATIONS Severely hypoxic patients were not included. CONCLUSIONS Routine low-dose oxygen supplementation in stroke patients who are not severely hypoxic is safe, but does not improve outcome after stroke. FUTURE WORK To investigate the causes of hypoxia and develop methods of prevention. TRIAL REGISTRATION Current Controlled Trials ISRCTN52416964 and European Union Drug Regulating Authorities Clinical Trials (EudraCT) number 2006-003479-11. FUNDING DETAILS This project was funded by the National Institute for Health Research (NIHR) Research for Patient Benefit and Health Technology Assessment programmes and will be published in full in Health Technology Assessment; Vol. 22, No. 14. See the NIHR Journals Library website for further project information.