Fibrinogen; a predictor of injury severity and mortality among patients with traumatic brain injury in Sub-Saharan Africa: a prospective study.

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John Baptist Ssenyondwa, Joel Kiryabwire, Martin Kaddumukasa, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2596161/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction Fibrinogen levels drop quicker than any other factors in severe trauma such as Traumatic Brain Injury (TBI). Contemporaneous studies show that fibrinogen concentrations < 2 g/L are strongly related to mortality. However, little is known regarding fibrinogen levels and TBI severity as well as mortality in sub-Saharan Africa. We therefore set out to determine whether fibrinogen levels are associated with TBI severity and seven days outcomes. Objectives To determine the sensitivity and specificity of fibrinogen levels and the association with severity and mortality among TBI patients at Mulago Hospital. Methods We prospectively enrolled 213 patients with TBI aged between 13 and 60 years of age and presenting within 24hrs of injury. Patients with pre-existing coagulopathy, concurrent use of anticoagulant or antiplatelet agents, pre-existing hepatic insufficiency, diabetes mellitus and who were pregnant were excluded. Fibrinogen levels were determined using the Clauss fibrinogen assay. Results Majority of the patients were male (88.7%) and nearly half were aged 30 or less (48.8%). Fibrinogen levels less than 2g/L were observed in 74 (35.1%) of the patients while levels above 4.5 g/L were observed in 30(14.2%) of the patients. The average time spent in the study was 3.7 ± 2.4 days. The sensitivity and specificity using fibrinogen < 2g/L was 56.5% and 72.9% respectively. Fibrinogen levels predict TBI severity with an AUC = 0.656 (95% CI 0.58–0.73: p = 0.000) Fibrinogen levels < 2g/L (hypofibrinogenemia) were independently associated with severe TBI. (AOR 2.87 CI,1.34–6.14: p = 0.007). Levels above 4.5g/L were also independently associated with injury severity (AOR 2.89, CI 1.12–7.48: p < 0.05) Fibrinogen levels more than 4.5g/L were independently associated with mortality (OR 4.5, CI;1.47–13.61, p < 0.05). Conclusions The fibrinogen level is a useful tool in predicting severity including mortality of TBI in our settings. We recommend the routine use of fibrinogen levels in TBI patient evaluations as levels below 2g/L and levels above 4.5g/L are associated with severe injuries and mortality Traumatic Brain Injury Fibrinogen Outcomes Mortality Figures Figure 1 Figure 2 Introduction Trauma accounts for 11% of the world’s disability adjusted life years (DALYs) with 90% of these occurring in Low and Middle Income Countries.( 1 ) Traumatic Brain Injury (TBI) per se is a major cause of disability globally with an incidence rate of 200 per 100 000 people per year( 2 ) In Uganda, head injuries with TBI are the commonest type of injuries accounting for 44% of trauma admissions at hospitals in Kampala( 3 ) and mortality rate of 220/100,000.( 4 ) The morbidity and mortality due to TBI is higher in low-income and middle-income countries( 5 , 6 ) despite advancements in the clinical evaluation of patients with TBI using standardized protocols such as the Advanced Trauma Life Support (ATLS) protocols.( 7 , 8 ) Evidence from prior studies shows that deaths from trauma can be prevented if adequate and timely identification of the problem is done and the appropriate line of management is decided early.( 9 ) In low and middle income settings where there is limited access to prompt investigation modalities for TBI victims, clinicians often find themselves relying on trauma algorithms, trauma assessment tools and clinical examination findings to diagnose and direct TBI management. Some of the trauma assessment tools employed in the evaluation of TBI patients include; Abbreviated Injury Score(AIS), Trauma Injury Severity Score (TRISS) and the Glasgow Coma Scale (GCS) specifically for TBI.( 10 ) These assessment tools have been found to have considerable limitations and that they may not correlate well with severity of injury.( 11 ) Among these, the GCS remains the commonest tool used to assess TBI severity in Sub-Saharan Africa.( 12 , 13 ) Despite its wide utility, the GCS does not provide specific parametric clinical information about the pathophysiologic abnormalities in TBI which are the targets of our interventions.( 14 ) One example of a pathophysiologic event is intracranial bleeding which is also associated with poor clinical outcomes such as mortality and disability.( 15 ) Fibrinogen, which is a positive acute phase protein( 16 ) as well as a haemostatic protein ( 17 ) has been retrospectively studied as a prognostic indicator among TBI patients as well as a predictor of in hospital mortality( 18 – 20 ). Following trauma, fibrinogen levels deteriorate more frequently and earlier than other routine coagulation parameters.( 21 , 22 ) Additionally hypofibrinogenemia has been described as a common occurrence in TBI possibly due to trauma induced coagulopathy.( 19 , 21 , 23 ) A recent study showed that fibrinogen concentrations less than 2g.L were associated with poor outcomes including mortality in contrast to concentrations above 2.5g/L that are associated with favourable outcomes.( 18 , 19 ) Current guidelines also emphasize that fibrinogen concentrations be maintained over 1.5–2.0 g/L in severe trauma patients( 22 ) Fibrinogen, therefore has a pivotal role in TBI; however, little is known regarding its sensitivity and specificity in diagnosis of severe TBI in sub-Saharan Africa. We therefore set out to study the predictive ability of fibrinogen levels in determining TBI severity and predicting clinical outcomes in TBI as a step in improving prompt diagnosis and management of TBI victims. The aims of the study were to determine the sensitivity and specificity of low fibrinogen levels in predicting severity of traumatic brain injuries, to describe the association of fibrinogen levels with TBI severity and 7-day outcomes among TBI patients at Mulago Hospital. We hypothesized that plasma fibrinogen levels are associated with severity and short-term clinical outcomes in TBI patients. Materials And Methods Study design and setting. We prospectively studied 213 randomly selected TBI patients admitted to the Casualty unit at Mulago National Referral Hospital (MNRH) between December 2021 and May 2022. MNRH is the biggest public hospital in Uganda at approximately 5 kilometres from the city centre and it receives 75% of injured victims in Kampala.( 24 ) The Casualty unit of the hospital is the entry point for all trauma cases presenting to the hospital. Study population and sampling. The inclusion criteria were as follows: patients aged 13 to 60 years with a clinical diagnosis of TBI documented using Computed Tomography (CT) or Glasgow Coma Scale (GCS) score by clinician and admitted within 24Hrs of TBI occurrence. The age range of 13 to 60 years was used in consideration of the altered metabolism of fibrinogen that occurs at the young and elderly extremes of age.( 25 – 27 ) TBI in this study was defined as any alteration of brain function or presence of other evidence of brain pathology based on the GCS or head CT scan in a patient, caused by an external force such as accidents, assault, falls and burns.( 28 ) Patients on concurrent use of anticoagulant or antiplatelet agents, medical diagnosis of liver disease, hypertension, and Diabetes mellitus, patients admitted after 24hrs of the injury occurrence and pregnant women were excluded. To achieve our first objectives, we used the proportion of patients with low fibrinogen from a prior study ( 19 ) and level of precision of 7% at 95% confidence interval to determine a sample size of 186 patients using the Kish and Leslie formula.( 29 ) To study the relationship of fibrinogen with outcomes, we calculated the sample size using formula for cohort studies based on comparison of two proportions representing the event rates in both the exposed and the non-exposed groups.( 30 ) Using proportions from the study by Lv et al.( 31 ), with 95% CI and power of 80%, we determined a sample size of 140 patients for the cohort. Adjusting upwards for losses to follow up, we estimated the sample size to be 200 patients. We therefore enrolled a total of 213 patients using systematic random sampling to answer our objectives. All patients were evaluated and treated according to the local protocol. Informed consent was obtained from the patients included in the study and for the unconscious patients, waiver of informed consent was obtained from the Research Ethics Committee of Makerere University and Mulago Hospital Ethics committee. Study procedure and data Collection. Data obtained included demographic information such as age, sex, occupation, time of injury, level of education, mechanism of injury and type of head injury. Clinical data including, blood pressure, pulse oximetry, temperature, pupillary reaction, CT scan results, GCS score and fibrinogen levels taken at time of admission were also obtained. The severity of injury was determined by the GCS score obtained by the neurosurgical team. The GCS score of ≤ 8 was categorized as severe TBI and scores 9–15 as non-severe TBI. (Fig. 1 ) Fibrinogen levels were measured by the Clauss fibrinogen assay using the “ Yumizen G FIB 5 ” reagent. The test was carried out on fresh decalcified venous blood obtained from the participants. On admission, 5 milliliters of venous blood were drawn from each of the participants into 3.2% sodium citrate vacutainers and transported to the laboratory within 60 minutes of collection for analysis. Samples were centrifuged to obtain plasma that was prepared for analysis as a 1:10 dilution with Yumizen G IMIDAZOL buffer. The prepared sample was then analysed using an automated analyser and results recorded in g/L. We obtained levels < 1g/L as well as those above 5g/L that were retested at 1:5 dilution and 1:20 dilution respectively to obtain final results. The fibrinogen levels were categorized as: normal fibrinogen levels between 2 and 4.5g/L.( 32 ) A fibrinogen level of 4.5 g/L as high according to standard laboratory reference values. The patients were followed up daily for 7 days and outcomes documented. The clinical outcome studied was in hospital mortality within 7 days of admission. The 11 patients lost to follow up were not analysed for outcomes. (Fig. 1 ) They were however included in the analysesis for the association between fibrinogen and injury severity on admission to the hospital. Statistical analysis. All study data collected was entered in Epidata version 4.6 software, cleaned and exported to STATA version 14 for analysis. Continuous variables were summarised as means with standard deviation. Categorical variables are expressed as percentages. Bivariate analyses of categorical variables were performed using Pearson’s chi test and presented as p values. A Receiver Operating Characteristic (ROC) curve is used to describe the predictive ability of fibrinogen levels in TBI. The sensitivity ± positive predictive value and specificity ± negative predictive value of fibrinogen levels were calculated using a 2˟2 table. Binary logistic regression models were used to describe the relationship between categorical variables between the patient groups with GCS ≤ 8 and that with GCS ≥ 9. Following bivariate analyses, logistic regression multivariate models were used to evaluate the association between fibrinogen and TBI severity as well as in-hospital mortality. All patients with missing data were excluded from the analyses. The models were tested for multiple collinearities, goodness of fit and all independent variables with correlation coefficient above ± 0.4 were excluded from the logistic regression model. The relationship is presented as odds ratio with 95% confidence intervals. All statistical analyses were performed using Stata statistical software, StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP. For all analysis, the level of statistical significance was considered when p < 0.05. Results A total of 213 TBI patients were included in the analysis. Road Traffic Crashes (RTCs) were responsible for TBI in 72.3% (n = 154) of the patients followed by assault (n = 45, 21.13%). 101 (47.42%) of the participants had severe TBI while 112(52.58%) had non severe TBI. The majority of the participants were male (n = 189, 88.73%, M: F = 189:24) and aged 30 or less (n = 104, 48.83%). Most of the participants were casual labourers (n = 65, 30.52) and educated to primary school level (n = 99, 46.48%). The average age of the study population was 32.42 ± 11.98 years with the minimum age of 13 and maximum age of 60. The majority of patients had closed head injuries (n = 115, 53.99%). The peak time of injury among the patients was during the evening hours between 1700hrs and 2300hrs with 51.5% (n = 103) of injuries during this time of the day. The average time spent in the study by the participants was 3.7 ± 2.4 days. (Table 1 ) The average length of time spent in hospital before discharge was 4 (± 1.79) days. The majority 66(31%) of the patients were discharged within 4 days of stay while 21 (10%) of the participants were discharged after 4 days. The average time spent in study before death occurred was 2.1 (± 1.98) days. In the majority (107, 50.71%) of the patients, the fibrinogen levels were between 2-4.5g/L. The maximum level observed was 7.81g/L. The minimum values were as low as < 1g/L. Levels 4.5 g/L were observed in 30(14.22%) of the patients. The 7-day mortality rate was 34.3%. Forty-seven patients (47,64.38%) died at Casualty within 24hrs of admission, 14 (19.18%) died in the Neurosurgery unit and 12(16.44%) in the ICU. Table 1. Baseline characteristics of the study population. GCS SCORE GCS 9-15 n (%) GCS 3-8 n (%) p [1] value N 112(52.58) 101(47.42) Age (years)[2] 13-30 63(58.88) 41(46.59) 0.0870 31-60 44(41.12) 47(53.41) Sex Male 100(89.29) 89(88.12) 0.7880 Female 12(10.71) 12(11.88) Type of Head Injury Closed head injury 58(51.79) 57(56.44) 0.4966 Open head injury 54(48.21) 44(43.56) SBP 90-139mmhg 85(75.89) 58(57.43) 0.0001 140mmhg 18(16.07) 41(40.59) Oximetry[3] 90-100% 100(91.74) 76(76.77) 0.0028 <90% 9(8.26) 23(23.23) Temperature(ºC) 36-38 66(58.93) 52(51.49) 0.0064 38 21(18.75) 37(36.63) Fibrinogen[4] 2-4.5g/L 70(63.06) 37(37.00) 0.0003 4.5g/L 15(13.51) 15(15.00) Cause of trauma[5] RTC 84(75.68) 70(70.71) 0.7713 Assault 21(18.92) 24(24.24) Falls 4(3.60) 4(4.04) Others 2(1.80) 1(1.01) Hospital stay (days) Mean (SD) Mean (SD) Length of stay 3.8 (±2.1) 3.5 (±2.7) [1] P value from comparative analysis between severe and non-severe TBI groups. Statistical significance p <0.05 [2] Missing 18 [3] Missing 5 [4] Missing 2 [5] Unspecified cause 3; RTC Road Traffic Crash Table 2. Two by two table showing fibrinogen association with TBI severity. GCS score Bivariate analysis Fibrinogen [1] GCS≤8 GCS>8 Total COR [2] 95% CI p [3] value 4.5g/L 15(15.00) 15(13.51) 30 1.892 0.834-4.292 0.127 Total 100 111 211 The sensitivity using fibrinogen <2g/L was SN =56.5%, PPV=64.9%, (p< 0.001) The specificity using fibrinogen <2g/L was SP =72.9%, NPV=61.7% (p< 0.001). (Table 2) Fibrinogen levels predict TBI severity with an AUC = 0.656, 95% CI (0.58-0.73) p=0.000. (Figure 2) [1] Missing 2 [2] Crude Odds ratio: Unadjusted for other variables. [3] Statistical significance determined by chi square test. Values in Bold are statistically significant. On bivariate analysis, fibrinogen levels were significantly associated with injury severity. SBP and pulse oximetry were also significantly associated with TBI severity. Without adjustment, TBI patients with fibrinogen levels < 2g/L were 3 times more likely to have severe TBI than in participants with fibrinogen levels of 2-4.5g/L. Further multivariate analysis with logistic regression showed a strong association between fibrinogen levels and TBI severity. When adjusted for age, systolic blood pressure, temperature and oximetry; fibrinogen levels < 2g/L (hypofibrinogenemia) were independently associated with severe TBI. (AOR 2.87 CI,1.34–6.14: p = 0.007) Levels above 4.5g/L were also independently associated with injury severity (AOR 2.89, CI 1.12–7.48: p 140mmHg, oxygen saturation 38º C were also associated with severe TBI. (Table 3 ) On bivariate analysis, fibrinogen levels were significantly associated with mortality. Other factors viz SBP, temperature and oximetry were also significantly related to mortality. (Table 4 ) After adjusting for patient age, hypoxia levels, and hemodynamic status on multivariate analysis, fibrinogen levels more than 4.5g/L were independently associated with mortality (OR 4.5, CI;1.472–13.607, p 38ºC, SBP and oximetry were also associated with mortality. (Table 4 ) Table 3. Clinical parameters associated with TBI severity GCS SCORE n (%) Bivariate analysis Multivariate analysis Parameter GCS 9-15 GCS 3-8 COR[1] (95%CI) p AOR[2] (95% CI) p Age (years) [3] 13-30 63(58.88) 41(46.59) 1(Reference) 1(reference) 31-60 44(41.12) 47(53.41) 1.64(0.93-2.90) 0.088 1.47(0.75-2.89) 0.261 Sex Male 100(89.29) 89(88.12) 1(Reference) Female 12(10.71) 12(11.88) 1.12(0.48-2.63) 0.788 Head injury Closed 58(51.79) 57(56.44) 1(Reference) Open 54(48.21) 44(43.56) 0.83 (0.48-1.42) 0.497 SBP 90-139mmHg 85(75.89) 58(57.43) 1(Reference) 1(reference) 140mmHg 18(16.07) 41(40.59) 3.34(1.75-6.38) 0.000 4.46(1.99-10.00) 0.000 Oximetry[4] 90-100% 100(91.74) 76(76.77) 1(Reference) 1(reference) <90% 9(8.26) 23(23.23) 3.36 (1.47-7.68) 0.004 2.87(1.02-8.06) 0.046 Temperature 36-38º C 66(58.93) 52(51.49) 1(Reference) 1(reference) 38ºC 21(18.75) 37(36.63) 2.24 (1.17-4.27) 0.015 2.80(1.18-6.64) 0.02 Fibrinogen[5](g/L) 2-4.5 70(63.06) 37(37.00) 1(Reference) 1(reference) 4.5 15(13.51) 15(15.00) 1.89 (0.83-4.29) 0.127 2.89(1.12-7.48) 0.029 [1] Crude Odds Ratio [2] Adjusted Odds ratio. Adjusted for age, Systolic Blood Pressure (SBP) Oximetry, temperature. Values in bold italic are statistically significant. [3] Missing age 18 [4] Missing oximetry 5 [5] Missing fibrinogen 2 Table 4. Factors associated with mortality in TBI. Bivariate analysis Multivariate analysis Parameter Survived n (%) Died n (%) COR[1] [95% CI] p AOR[2]. [95% CI] p Age(years) [3] 13-30 55(60.44) 28(44.44) 1(reference) 1(reference) 31-60 36(39.56) 35(55.56) 1.91(1.00-3.66) 0.051 1.78(0.80-3.97) 0.157 Sex Male 83(89.25) 63(86.30) 1(reference) Female 10(10.75) 10(13.70) 1.32 (0.52-3.36) 0.564 Head Injury Closed Injury 53(56.99) 38(52.05) 1(reference) Open injury 40(43.01) 35(47.95) 1.22(0.66-2.26) 0.526 SBP (mmHg) 90-139 73(78.49) 42(57.53) 1(reference) 1(reference) 140 14(15.05) 30(41.10) 3.72(1.78-7.80) 0.000 4.59 (1.80-11.66) 0.001 Temperature ºC 36-38 61(65.59) 34(46.58) 1(reference) 1(reference) 38 13(13.98) 30(41.10) 4.14(1.91-8.98) 0.000 4.19 (1.49-11.75) 0.007 Oximetry[4] 90-100% 88(96.70) 51(72.86) 1(reference) 1(reference) <90% 3(3.30) 19(27.14) 10.93(3.08-38.74) 0.000 9.15 (2.17-38.68) 0.003 Fibrinogen[5](g/L) 2-4.5 54(58.06) 25(34.72) 1(reference) 1(reference) 4.5 10(10.75) 16(22.22) 3.46(1.36-8.69) 0.008 4.48(1.47-13.61) 0.008 [1] Crude Odds Ratio [2] Adjusted Odds ratio Adjusted for age, Systolic Blood Pressure (SBP) Oximetry, temperature. Values in bold italic are statistically significant [3] Missing age 18 [4] Missing oximetry 5 [5] Missing Fibrinogen 2 Discussion This study set out to determine the specificity and sensitivity of fibrinogen levels and the association with severity and mortality among TBI patients at Mulago Hospital. There are no studies addressing this topic from sub-Saharan Africa and this is the first study in Uganda to describe this relationship. Despite numerous evidence available regarding the predictability of fibrinogen in the prognosis of TBI outcomes from prior studies( 19 , 33 ), little is known concerning its predictive ability in the diagnosis of severe TBI. The sensitivity using fibrinogen < 2g/L(hypofibrinogenemia) was 56.5% with a positive predictive value of 64.9%. The specificity was 72.9% with a negative predictive value of 61.7%. In addition, hypofibrinogenemia (fibrinogen levels < 2g/L) was common in TBI patients occurring in 35.07% of TBI patients on admission. This is similar to 38.6% found in a previous study done by Lv, et al.( 19 ) Our study also found that 20.4% of patients with TBI had high levels of fibrinogen(> 4.5g/L). Recent research showed that for patients admitted with severe TBI, fibrinogen levels < 2g/L on admission are strongly related to increased mortality.( 19 ) In addition, studies have demonstrated that in severe trauma, fibrinogen is reduced to critical levels. ( 21 , 34 ) The debate about the critical value of fibrinogen in trauma is an ongoing matter of contention.( 35 ) Floccard et’al defined critical levels as being ≤ 1.0g/L and abnormal levels being 1.0–1.8 g/L all of which have been reported in patients with severe Trauma.( 36 ). By contrast, high fibrinogen levels have been described as being protective in patients with multiple trauma.( 35 ) Furthermore, previous studies have demonstrated that TBI is associated with abnormalities in clot formation due to differences in fibrinogen levels among victims.( 37 ) Fibrinogen could therefore be used as a marker or predictor of TBI severity. The study found that low fibrinogen levels (< 2 g/L) were fairly predictive of TBI severity with an AUC = 0.656, sensitivity of 56.5% and specificity of 72.9%. Therefore, absence of hypofibrinogenemia in TBI patients found in this study was associated with milder forms of TBI. This is consistent with what previous studies have described in severe trauma. This study shows that the likelihood of having a severe form of TBI increases with low levels of fibrinogen(< 2g/L). Possible explanations for the above relationship stem from the presence of intracranial bleeding which is a common occurrence in TBI as noted in the CRASH trial.( 38 ) Trauma induced coagulopathy is a crucial element in severe TBI especially when compounded with intracranial bleeding. The consumption of clotting factors and platelets in response to intracranial bleeding further lowers fibrinogen levels.( 39 ) TBI is also associated with systemic hyperfibrinolysis which occurs in as much as 20% of critical trauma patients hence lowering fibrinogen levels further. ( 40 , 41 ) In addition, prior studies have shown that fibrinogen levels drop drastically and most rapidly during haemorrhage.( 34 ) Therefore, the association of low fibrinogen levels with severe TBI is possibly due to a combination of haemorrhage and trauma induced coagulopathy that occurs in severe TBI.( 42 ) Much as there is a stronger association of severity with low fibrinogen levels, high fibrinogen levels (> 4.5g/L) were also associated with severe TBI. This could be due to the inflammation that accompanies major trauma and disruption of the blood brain barrier with release of procoagulant molecules.( 37 , 43 ) A study done by Samuels et al found that TBI patients commonly presented with a spectrum ranging from hypocoagulability to hypercoagulability.( 37 ) It is therefore likely that severe TBI without intracranial haemorrhage leads to high fibrinogen levels while severe TBI with haemorrhage lowers the fibrinogen levels. Unlike prior research findings, ( 19 ) this study showed that fibrinogen levels > 4.5g/L were strong predictors of mortality. A possible explanation of this observation starts with trauma induced disruption of the Blood Brain Barrier that incites an extensive inflammatory response.( 16 , 44 ) Such extensive inflammation can be caused by neural cell death with resultant secondary brain oedema.( 43 ) Diffuse Axonal Injury is of utmost importance here since it is characterized by an intense inflammatory response.( 45 ) It is this inflammatory process that is responsible for the elevated fibrinogen levels. Organ dysfunction then ensues from this trauma induced systemic inflammatory state.( 46 ) The development of organ dysfunction is related to the intensity of the trauma induced inflammatory response.( 47 ) Hence, a severe systemic inflammatory response due to a disrupted blood brain barrier causes early organ dysfunction and later multiple organ failure which leads to death.( 47 , 48 ). This possibly explains the high fibrinogen levels found to be associated with mortality. While one of the strengths of our study is that it was carried out prospectively in a high-volume trauma center, some limitations need to be acknowledged. This was a single centre study with a rather small sample size and with limited duration allocated to conduct the study due to specified time frames for research activities. Secondly, fibrinogen is not a routine test in Mulago Hospital for TBI patients and replacement therapy is not currently part of the management protocols in patients with TBI; hence, despite the identification of abnormalities among the participants, correction therapy with concentrate was not possible for the participants. Patients with coagulopathies however received other supplements such as tranexamic acid and Fresh frozen plasma. Additional prospective studies with larger sample size and longer study duration are needed to confirm the predictability of TBI severity and clinical outcomes using fibrinogen levels. Conclusions In conclusion, we established that fibrinogen is a useful tool in predicting severity of TBI and mortality. The study reveals that the sensitivity of fibrinogen levels < 2g/L is 56.5% and the specificity is 72.9%. Fibrinogen fairly predicts TBI severity with an AUC of 0.656. Fibrinogen levels may be used as an additional tool to screen TBI patients for injury severity. Low fibrinogen levels ( 4.5g/L are also predictors of TBI severity. A fibrinogen level of > 4.5g/L is a strong predictor of mortality in TBI patients. Integrating fibrinogen as a biomarker in TBI management could therefore provide critical information about trauma physiology and ultimately influence clinical decisions. Additional larger prospective studies are needed to confirm these findings. Abbreviations AOR Adjusted Odds ratio ATC Acute Traumatic Coagulopathy ATLS Advanced Trauma Life Support. bpm beats per minute COR Crude Odds ratio DALYs Disability Adjusted Life Years. DVT Deep Vein Thrombosis EDH Extradural Hematoma GCS Glasgow Coma Scale ICU Intensive Care Unit INR International Normalized Ratio. IPH Intraparenchymal Haemorrhage. IVH Intraventricular Haemorrhage LAR Legally Acceptable Representative LMIC Low- and Middle-Income Country LNMP Last Normal Menstrual Period. MOF Multiple Organ Failure RTC Road Traffic Crash SBP Systolic Blood Pressure. SDH Subdural Hematoma TBI Traumatic Brain Injury TRISS Trauma and Injury Severity Score. Declarations Ethics approval and consent to participate The School of Medicine Ethics and Research Committee and Mulago Hospital Ethics and Research Committee approved the study in October 2021 with reference number; Mak-SOMREC-2021-126. Informed consent was obtained from each patient or legally acceptable representative of the patient before participation in the study. All methods were carried out in accordance with the Declaration of Helsinki. Consent for publication Not Applicable. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to confidentiality agreements but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests Funding This research was supported by the National Institute of Neurological Disorders and Stroke and Stroke of the under-award Number D43NS118560. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health. Authors’ contributions Study concept and design: S.J.B. Drafting of the Manuscript: S.J.B., M.K., J.K., M.T.K., M.S. Statistical Analysis: S.J.B., W.F Interpretation of data: S.J.B., M.T.K., W.F., K.J., L.K.K. Revision of Manuscript: M.T.K., K.J., M.D., M.K. Administrative and Technical Support: M.T.K., K.J., M.D., M.G., M.K., K.J., M.S. Supervision: M.T.K., K.J., M.D., M.G., M.K. Acknowledgements The authors extend gratitude to the Dr. Walugembe Fred for their useful input during the preparation of the manuscript Authors' information S.J.B.: MBChB, General Surgery Resident, Makerere University, College of Health Sciences. M.T.K.: MBChB, MMED, Senior Lecturer, Makerere University, College of Health Sciences Department of Surgery. K.J.: MBChB, MMED, FCS NEURO.Neurosurgeon, Mulago National Specialized Hospital. M.G.: MBChB, MMED, MHPE, Associate Professor and Head of Department, Surgery Makerere University College of Health Sciences. M.D.: M.D, Professor of Neurology Case Western Reserve University School of Medicine. M.K.[1]: MBChB, MMED, Neurologist, Mulago National Referral Hospital M.K.[2]: MBChB, MMED, Associate Professor of Medicine, Department of Medicine, College of Health Sciences Makerere University L.K.K: MBChB, Neurosurgery resident, Makerere University, College of Health Sciences. M.S.: MD, Professor of Psychiatry and of Neurology, Case Western Reserve University School of Medicine [1] Martin Kaddumukasa [2] Mark Kaddumukasa. References Bickler SN, Weiser TG, Kassebaum N, Higashi H, Chang DC, Barendregt JJ, et al. Global Burden of Surgical Conditions. In: Debas HT, Donkor P, Gawande A, Jamison DT, Kruk ME, Mock CN, editors. Essential Surgery: Disease Control Priorities, Third Edition (Volume 1). Washington (DC): The International Bank for Reconstruction and Development / The World Bank © 2015 International Bank for Reconstruction and Development. / The World Bank.; 2015. Bryan-Hancock C, Harrison J. 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A systematic review and meta-analysis. PLoS ONE. 2021;16(12):e0261831. Saatman KE, Duhaime AC, Bullock R, Maas AI, Valadka A, Manley GT. Classification of traumatic brain injury for targeted therapies. J Neurotrauma. 2008;25(7):719–38. Perel P, Roberts I, Shakur H, Thinkhamrop B, Phuenpathom N, Yutthakasemsunt S. Haemostatic drugs for traumatic brain injury.Cochrane Database Syst Rev. 2010(1):Cd007877. Schultz DR, Arnold PI. Properties of four acute phase proteins: C-reactive protein, serum amyloid A protein, alpha 1-acid glycoprotein, and fibrinogen. Semin Arthritis Rheum. 1990;20(3):129–47. van den Herik EG, Cheung EY, de Lau LM, den Hertog HM, Leebeek FW, Dippel DW, et al. Fibrinogen γ' levels in patients with intracerebral hemorrhage. Thromb Res. 2012;129(6):807–9. Sawamura A, Hayakawa M, Gando S, Kubota N, Sugano M, Wada T, et al. Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality. Thromb Res. 2009;124(5):608–13. Lv K, Yuan Q, Fu P, Wu G, Wu X, Du Z, et al. Impact of fibrinogen level on the prognosis of patients with traumatic brain injury: a single-center analysis of 2570 patients. World J Emerg Surg. 2020;15(1):54. McCully SP, Schreiber MA. Traumatic brain injury and its effect on coagulopathy. Semin Thromb Hemost. 2013;39(8):896–901. Hayakawa M, Gando S, Ono Y, Wada T, Yanagida Y, Sawamura A. Fibrinogen level deteriorates before other routine coagulation parameters and massive transfusion in the early phase of severe trauma: a retrospective observational study. Semin Thromb Hemost. 2015;41(1):35–42. Hayakawa M. Dynamics of fibrinogen in acute phases of trauma. J Intensive Care. 2017;5(1):1–6. Sørensen B, Larsen OH, Rea CJ, Tang M, Foley JH, Fenger-Eriksen C. Fibrinogen as a hemostatic agent. Semin Thromb Hemost. 2012;38(3):268–73. Kobusingye OC, Lett RR. Hospital-based trauma registries in Uganda. J Trauma. 2000;48(3):498–502. Hager K, Felicetti M, Seefried G, Platt D. Fibrinogen and aging. Aging (Milano). 1994;6(2):133–8. Ignjatovic V, Ilhan A, Monagle P. Evidence for age-related differences in human fibrinogen. Blood Coagul Fibrinolysis. 2011;22(2):110–7. Fu A, Nair KS. Age effect on fibrinogen and albumin synthesis in humans. Am J Physiol. 1998;275(6):E1023–30. McKee AC, Daneshvar DH. The neuropathology of traumatic brain injury. Handb Clin Neurol. 2015;127:45–66. Kish L, SAMPLING ORGANIZATIONS AND, GROUPS OF UNEQUAL SIZES. Am Sociol Rev. 1965;30:564–72. Khaled Fahim N, Negida A. Sample Size Calculation Guide - Part 2: How to Calculate the Sample Size for an Independent Cohort Study. Adv J Emerg Med. 2019;3(1):e12. Lv K, Yuan Q, Fu P, Wu G, Wu X, Du Z, et al. Impact of fibrinogen level on the prognosis of patients with traumatic brain injury: a single-center analysis of 2570 patients. World J Emerg Surg. 2020;15(1):1–9. Fenger-Eriksen C, Ingerslev J, Sørensen B. Fibrinogen concentrate–a potential universal hemostatic agent. Expert Opin Biol Ther. 2009;9(10):1325–33. Spahn DR, Bouillon B, Cerny V, Duranteau J, Filipescu D, Hunt BJ, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care. 2019;23(1):98. Levy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion. 2014;54(5):1389–405. quiz 8. Fries D, Martini WZ. Role of fibrinogen in trauma-induced coagulopathy. Br J Anaesth. 2010;105(2):116–21. Floccard B, Rugeri L, Faure A, Saint Denis M, Boyle EM, Peguet O, et al. Early coagulopathy in trauma patients: an on-scene and hospital admission study. Injury. 2012;43(1):26–32. Samuels JM, Moore EE, Silliman CC, Banerjee A, Cohen MJ, Ghasabyan A, et al. Severe traumatic brain injury is associated with a unique coagulopathy phenotype. J Trauma Acute Care Surg. 2019;86(4):686–93. Roberts I, Yates D, Sandercock P, Farrell B, Wasserberg J, Lomas G, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004;364(9442):1321–8. Chhabra G, Rangarajan K, Subramanian A, Agrawal D, Sharma S, Mukhopadhayay AK. Hypofibrinogenemia in isolated traumatic brain injury in Indian patients. Neurol India. 2010;58(5):756–7. Kushimoto S, Shibata Y, Yamamoto Y. Implications of fibrinogenolysis in patients with closed head injury. J Neurotrauma. 2003;20(4):357–63. Stettler GR, Moore EE, Nunns GR, Chandler J, Peltz E, Silliman CC, et al. Rotational thromboelastometry thresholds for patients at risk for massive transfusion. J Surg Res. 2018;228:154–9. Hiippala ST, Myllylä GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth Analg. 1995;81(2):360–5. Shi K, Zhang J, Dong JF, Shi FD. Dissemination of brain inflammation in traumatic brain injury. Cell Mol Immunol. 2019;16(6):523–30. Engler R. [Acute-phase proteins in inflammation]. C R Seances Soc Biol Fil. 1995;189(4):563–78. Humble SS, Wilson LD, Wang L, Long DA, Smith MA, Siktberg JC, et al. Prognosis of diffuse axonal injury with traumatic brain injury. J Trauma Acute Care Surg. 2018;85(1):155–9. Chakraborty RK, Burns B. Systemic Inflammatory Response Syndrome. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2022. StatPearls Publishing LLC.; 2022. Sauaia A, Moore FA, Moore EE. Postinjury Inflammation and Organ Dysfunction. Crit Care Clin. 2017;33(1):167–91. Baker CC, Oppenheimer L, Stephens B, Lewis FR, Trunkey DD. Epidemiology of trauma deaths. Am J Surg. 1980;140(1):144–50. Additional Declarations No competing interests reported. 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Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Joel","middleName":"","lastName":"Kiryabwire","suffix":""},{"id":179216568,"identity":"7ec3feb5-7050-4588-aca1-883430a914b0","order_by":2,"name":"Martin Kaddumukasa","email":"","orcid":"","institution":"College of Health Sciences Makerere University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Martin","middleName":"","lastName":"Kaddumukasa","suffix":""},{"id":179216569,"identity":"86525de2-f43a-4de3-aa91-a416bcea233a","order_by":3,"name":"Devereaux Michael","email":"","orcid":"","institution":"Neurological and Behavioral Outcome Center, University Hospitals, Case Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Devereaux","middleName":"","lastName":"Michael","suffix":""},{"id":179216570,"identity":"de68bc71-17ef-4617-a554-78d357f49a1b","order_by":4,"name":"Larrey Kasereka Kamabu","email":"","orcid":"","institution":"College of Health Sciences Makerere University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Larrey","middleName":"Kasereka","lastName":"Kamabu","suffix":""},{"id":179216571,"identity":"f84cd57a-4523-4714-b426-6d7fd3b31a35","order_by":5,"name":"Moses Galukande","email":"","orcid":"","institution":"College of Health Sciences Makerere University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Moses","middleName":"","lastName":"Galukande","suffix":""},{"id":179216572,"identity":"e5b02740-6070-450f-8b5e-aa968ec0f43c","order_by":6,"name":"Mark Kaddumukasa","email":"","orcid":"","institution":"College of Health Sciences Makerere University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mark","middleName":"","lastName":"Kaddumukasa","suffix":""},{"id":179216573,"identity":"2a8ec904-c4cb-4f54-af37-c01c494a24ea","order_by":7,"name":"Martha Sajatovic","email":"","orcid":"","institution":"Neurological and Behavioral Outcome Center, University Hospitals, Case Medical Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Martha","middleName":"","lastName":"Sajatovic","suffix":""},{"id":179216574,"identity":"884153c2-3113-4081-ba45-754714e7e336","order_by":8,"name":"Timothy Kabanda Makumbi","email":"","orcid":"","institution":"College of Health Sciences Makerere University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Timothy","middleName":"Kabanda","lastName":"Makumbi","suffix":""}],"badges":[],"createdAt":"2023-02-16 18:59:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2596161/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2596161/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":33637820,"identity":"47348693-6900-4072-ab72-ec5d84e45a4b","added_by":"auto","created_at":"2023-03-01 16:51:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":401662,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart showing study procedure and follow up\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2596161/v1/0c323d40984505c36eb2047c.png"},{"id":33637819,"identity":"2c4ad269-3d6d-48e9-b82a-4814259c2ccd","added_by":"auto","created_at":"2023-03-01 16:51:40","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":8893,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve showing predictability of fibrinogen levels in TBI severity\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-2596161/v1/7a7f70b494bcdd0ebbfa3a73.png"},{"id":35760137,"identity":"e705055f-6740-428d-97e9-d674bba064aa","added_by":"auto","created_at":"2023-04-14 10:14:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":579744,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2596161/v1/923586aa-50c9-4885-8d61-6739958feef3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fibrinogen; a predictor of injury severity and mortality among patients with traumatic brain injury in Sub-Saharan Africa: a prospective study.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTrauma accounts for 11% of the world\u0026rsquo;s disability adjusted life years (DALYs) with 90% of these occurring in Low and Middle Income Countries.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) Traumatic Brain Injury (TBI) per se is a major cause of disability globally with an incidence rate of 200 per 100 000 people per year(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) In Uganda, head injuries with TBI are the commonest type of injuries accounting for 44% of trauma admissions at hospitals in Kampala(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) and mortality rate of 220/100,000.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The morbidity and mortality due to TBI is higher in low-income and middle-income countries(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) despite advancements in the clinical evaluation of patients with TBI using standardized protocols such as the Advanced Trauma Life Support (ATLS) protocols.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e) Evidence from prior studies shows that deaths from trauma can be prevented if adequate and timely identification of the problem is done and the appropriate line of management is decided early.(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) In low and middle income settings where there is limited access to prompt investigation modalities for TBI victims, clinicians often find themselves relying on trauma algorithms, trauma assessment tools and clinical examination findings to diagnose and direct TBI management. Some of the trauma assessment tools employed in the evaluation of TBI patients include; Abbreviated Injury Score(AIS), Trauma Injury Severity Score (TRISS) and the Glasgow Coma Scale (GCS) specifically for TBI.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) These assessment tools have been found to have considerable limitations and that they may not correlate well with severity of injury.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Among these, the GCS remains the commonest tool used to assess TBI severity in Sub-Saharan Africa.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Despite its wide utility, the GCS does not provide specific parametric clinical information about the pathophysiologic abnormalities in TBI which are the targets of our interventions.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) One example of a pathophysiologic event is intracranial bleeding which is also associated with poor clinical outcomes such as mortality and disability.(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eFibrinogen, which is a positive acute phase protein(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) as well as a haemostatic protein (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) has been retrospectively studied as a prognostic indicator among TBI patients as well as a predictor of in hospital mortality(\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Following trauma, fibrinogen levels deteriorate more frequently and earlier than other routine coagulation parameters.(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) Additionally hypofibrinogenemia has been described as a common occurrence in TBI possibly due to trauma induced coagulopathy.(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) A recent study showed that fibrinogen concentrations less than 2g.L were associated with poor outcomes including mortality in contrast to concentrations above 2.5g/L that are associated with favourable outcomes.(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) Current guidelines also emphasize that fibrinogen concentrations be maintained over 1.5\u0026ndash;2.0 g/L in severe trauma patients(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) Fibrinogen, therefore has a pivotal role in TBI; however, little is known regarding its sensitivity and specificity in diagnosis of severe TBI in sub-Saharan Africa.\u003c/p\u003e \u003cp\u003eWe therefore set out to study the predictive ability of fibrinogen levels in determining TBI severity and predicting clinical outcomes in TBI as a step in improving prompt diagnosis and management of TBI victims. The aims of the study were to determine the sensitivity and specificity of low fibrinogen levels in predicting severity of traumatic brain injuries, to describe the association of fibrinogen levels with TBI severity and 7-day outcomes among TBI patients at Mulago Hospital. We hypothesized that plasma fibrinogen levels are associated with severity and short-term clinical outcomes in TBI patients.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003cp\u003e \u003cb\u003eStudy design and setting.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eWe prospectively studied 213 randomly selected TBI patients admitted to the Casualty unit at Mulago National Referral Hospital (MNRH) between December 2021 and May 2022. MNRH is the biggest public hospital in Uganda at approximately 5 kilometres from the city centre and it receives 75% of injured victims in Kampala.(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) The Casualty unit of the hospital is the entry point for all trauma cases presenting to the hospital.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStudy population and sampling.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe inclusion criteria were as follows: patients aged 13 to 60 years with a clinical diagnosis of TBI documented using Computed Tomography (CT) or Glasgow Coma Scale (GCS) score by clinician and admitted within 24Hrs of TBI occurrence. The age range of 13 to 60 years was used in consideration of the altered metabolism of fibrinogen that occurs at the young and elderly extremes of age.(\u003cspan additionalcitationids=\"CR26\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) TBI in this study was defined as any alteration of brain function or presence of other evidence of brain pathology based on the GCS or head CT scan in a patient, caused by an external force such as accidents, assault, falls and burns.(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) Patients on concurrent use of anticoagulant or antiplatelet agents, medical diagnosis of liver disease, hypertension, and Diabetes mellitus, patients admitted after 24hrs of the injury occurrence and pregnant women were excluded.\u003c/p\u003e \u003cp\u003eTo achieve our first objectives, we used the proportion of patients with low fibrinogen from a prior study (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) and level of precision of 7% at 95% confidence interval to determine a sample size of 186 patients using the Kish and Leslie formula.(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) To study the relationship of fibrinogen with outcomes, we calculated the sample size using formula for cohort studies based on comparison of two proportions representing the event rates in both the exposed and the non-exposed groups.(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) Using proportions from the study by Lv et al.(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), with 95% CI and power of 80%, we determined a sample size of 140 patients for the cohort. Adjusting upwards for losses to follow up, we estimated the sample size to be 200 patients. We therefore enrolled a total of 213 patients using systematic random sampling to answer our objectives. All patients were evaluated and treated according to the local protocol. Informed consent was obtained from the patients included in the study and for the unconscious patients, waiver of informed consent was obtained from the Research Ethics Committee of Makerere University and Mulago Hospital Ethics committee.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStudy procedure and data Collection.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eData obtained included demographic information such as age, sex, occupation, time of injury, level of education, mechanism of injury and type of head injury. Clinical data including, blood pressure, pulse oximetry, temperature, pupillary reaction, CT scan results, GCS score and fibrinogen levels taken at time of admission were also obtained. The severity of injury was determined by the GCS score obtained by the neurosurgical team. The GCS score of \u0026le;\u0026thinsp;8 was categorized as severe TBI and scores 9\u0026ndash;15 as non-severe TBI. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) Fibrinogen levels were measured by the Clauss fibrinogen assay using the \u0026ldquo;\u003cem\u003eYumizen G FIB 5\u003c/em\u003e\u0026rdquo; reagent. The test was carried out on fresh decalcified venous blood obtained from the participants. On admission, 5 milliliters of venous blood were drawn from each of the participants into 3.2% sodium citrate vacutainers and transported to the laboratory within 60 minutes of collection for analysis. Samples were centrifuged to obtain plasma that was prepared for analysis as a 1:10 dilution with Yumizen G IMIDAZOL buffer. The prepared sample was then analysed using an automated analyser and results recorded in g/L. We obtained levels\u0026thinsp;\u0026lt;\u0026thinsp;1g/L as well as those above 5g/L that were retested at 1:5 dilution and 1:20 dilution respectively to obtain final results. The fibrinogen levels were categorized as: normal fibrinogen levels between 2 and 4.5g/L.(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) A fibrinogen level of \u0026lt;\u0026thinsp;2 g/L was considered as being low and a level of \u0026gt;\u0026thinsp;4.5 g/L as high according to standard laboratory reference values. The patients were followed up daily for 7 days and outcomes documented. The clinical outcome studied was in hospital mortality within 7 days of admission. The 11 patients lost to follow up were not analysed for outcomes. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) They were however included in the analysesis for the association between fibrinogen and injury severity on admission to the hospital.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis.\u003c/h2\u003e \u003cp\u003eAll study data collected was entered in Epidata version 4.6 software, cleaned and exported to STATA version 14 for analysis. Continuous variables were summarised as means with standard deviation. Categorical variables are expressed as percentages. Bivariate analyses of categorical variables were performed using Pearson\u0026rsquo;s chi test and presented as \u003cem\u003ep\u003c/em\u003e values. A Receiver Operating Characteristic (ROC) curve is used to describe the predictive ability of fibrinogen levels in TBI. The sensitivity\u0026thinsp;\u0026plusmn;\u0026thinsp;positive predictive value and specificity\u0026thinsp;\u0026plusmn;\u0026thinsp;negative predictive value of fibrinogen levels were calculated using a 2˟2 table. Binary logistic regression models were used to describe the relationship between categorical variables between the patient groups with GCS\u0026thinsp;\u0026le;\u0026thinsp;8 and that with GCS\u0026thinsp;\u0026ge;\u0026thinsp;9. Following bivariate analyses, logistic regression multivariate models were used to evaluate the association between fibrinogen and TBI severity as well as in-hospital mortality. All patients with missing data were excluded from the analyses. The models were tested for multiple collinearities, goodness of fit and all independent variables with correlation coefficient above \u0026plusmn;\u0026thinsp;0.4 were excluded from the logistic regression model. The relationship is presented as odds ratio with 95% confidence intervals. All statistical analyses were performed using Stata statistical software, StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP. For all analysis, the level of statistical significance was considered when p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 213 TBI patients were included in the analysis. Road Traffic Crashes (RTCs) were responsible for TBI in 72.3% (n\u0026thinsp;=\u0026thinsp;154) of the patients followed by assault (n\u0026thinsp;=\u0026thinsp;45, 21.13%). 101 (47.42%) of the participants had severe TBI while 112(52.58%) had non severe TBI. The majority of the participants were male (n\u0026thinsp;=\u0026thinsp;189, 88.73%, M: F\u0026thinsp;=\u0026thinsp;189:24) and aged 30 or less (n\u0026thinsp;=\u0026thinsp;104, 48.83%). Most of the participants were casual labourers (n\u0026thinsp;=\u0026thinsp;65, 30.52) and educated to primary school level (n\u0026thinsp;=\u0026thinsp;99, 46.48%). The average age of the study population was 32.42\u0026thinsp;\u0026plusmn;\u0026thinsp;11.98 years with the minimum age of 13 and maximum age of 60. The majority of patients had closed head injuries (n\u0026thinsp;=\u0026thinsp;115, 53.99%). The peak time of injury among the patients was during the evening hours between 1700hrs and 2300hrs with 51.5% (n\u0026thinsp;=\u0026thinsp;103) of injuries during this time of the day. The average time spent in the study by the participants was 3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 days. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) The average length of time spent in hospital before discharge was 4 (\u0026plusmn;\u0026thinsp;1.79) days.\u003c/p\u003e \u003cp\u003eThe majority 66(31%) of the patients were discharged within 4 days of stay while 21 (10%) of the participants were discharged after 4 days. The average time spent in study before death occurred was 2.1 (\u0026plusmn;\u0026thinsp;1.98) days. In the majority (107, 50.71%) of the patients, the fibrinogen levels were between 2-4.5g/L. The maximum level observed was 7.81g/L. The minimum values were as low as \u0026lt;\u0026thinsp;1g/L. Levels\u0026thinsp;\u0026lt;\u0026thinsp;2g/L were observed in 74 (35.07%) of the patients. Levels of fibrinogen\u0026thinsp;\u0026gt;\u0026thinsp;4.5 g/L were observed in 30(14.22%) of the patients. The 7-day mortality rate was 34.3%. Forty-seven patients (47,64.38%) died at Casualty within 24hrs of admission, 14 (19.18%) died in the Neurosurgery unit and 12(16.44%) in the ICU.\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;1. Baseline characteristics of the study population.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"586\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"50%\"\u003e\n \u003cp\u003eGCS SCORE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003eGCS 9-15\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003eGCS 3-8 \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003cstrong\u003e[1]\u003c/strong\u003e\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e112(52.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e101(47.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eAge (years)[2]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e13-30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e63(58.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e41(46.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e0.0870\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003e31-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e44(41.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e47(53.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"45.22184300341297%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e100(89.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e89(88.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e0.7880\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e12(10.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e12(11.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eType of Head Injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.406143344709896%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" width=\"53.58361774744027%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eClosed head injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e58(51.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e57(56.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e0.4966\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003eOpen head injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e54(48.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e44(43.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eSBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.406143344709896%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" width=\"53.58361774744027%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e90-139mmhg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e85(75.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e58(57.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u003cem\u003e0.0001\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003e\u0026lt;90mmhg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e9(8.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e2(1.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003e\u0026gt;140mmhg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e18(16.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e41(40.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eOximetry[3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.406143344709896%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" width=\"53.58361774744027%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e90-100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e100(91.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e76(76.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u003cem\u003e0.0028\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003e\u0026lt;90%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e9(8.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e23(23.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eTemperature(\u0026ordm;C)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.406143344709896%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" width=\"53.58361774744027%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e36-38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e66(58.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e52(51.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u003cem\u003e0.0064\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e\u0026lt;36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e25(22.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e12(11.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e\u0026gt;38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e21(18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e37(36.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eFibrinogen[4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.406143344709896%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" width=\"53.58361774744027%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e2-4.5g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e70(63.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e37(37.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u003cem\u003e0.0003\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003e\u0026lt;2g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e26(23.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e48(48.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003e\u0026gt;4.5g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e15(13.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e15(15.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"100%\"\u003e\n \u003cp\u003eCause of trauma[5]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eRTC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e84(75.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e70(70.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e0.7713\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003eAssault\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e21(18.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e24(24.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003eFalls\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e4(3.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e4(4.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"36.7170626349892%\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.6133909287257%\"\u003e\n \u003cp\u003e2(1.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"30.669546436285096%\"\u003e\n \u003cp\u003e1(1.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003e\u0026nbsp;Hospital stay (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"29.01023890784983%\"\u003e\n \u003cp\u003eLength of stay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"25.7679180887372%\"\u003e\n \u003cp\u003e3.8 (\u0026plusmn;2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.2320819112628%\"\u003e\n \u003cp\u003e3.5 (\u0026plusmn;2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.98976109215017%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cdiv id=\"ftn1\"\u003e\n \u003cp\u003e[1] P value from comparative analysis between severe and non-severe TBI groups. Statistical significance \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn2\"\u003e\n \u003cp\u003e[2] Missing 18\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn3\"\u003e\n \u003cp\u003e[3] Missing 5\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn4\"\u003e\n \u003cp\u003e[4] Missing 2\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn5\"\u003e\n \u003cp\u003e[5] Unspecified cause 3; RTC Road Traffic Crash\u003c/p\u003e\n\u003c/div\u003e\u003cp\u003eTable\u0026nbsp;2. Two by two table showing fibrinogen association with TBI severity.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"633\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003eGCS score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.976377952755906%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"32.75590551181102%\"\u003e\n \u003cp\u003e\u003cem\u003eBivariate analysis\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.968503937007874%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003eFibrinogen\u003csup\u003e\u003csup\u003e[1]\u003c/sup\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003eGCS\u0026le;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003eGCS\u0026gt;8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.976377952755906%\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003eCOR\u003csup\u003e\u003csup\u003e[2]\u003c/sup\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.968503937007874%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003csup\u003e\u003cstrong\u003e\u003csup\u003e[3]\u003c/sup\u003e\u003c/strong\u003e\u003c/sup\u003e\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003e\u0026lt;2g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e48(48.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003e26(23.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.976377952755906%\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e3.493\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e1.876-6.504\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.968503937007874%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003e2-4.5g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e37(37.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003e70(63.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.976377952755906%\"\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e1(Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.968503937007874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003e\u0026gt;4.5g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e15(15.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003e15(13.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.976377952755906%\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e1.892\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e0.834-4.292\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.968503937007874%\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.960629921259843%\"\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.976377952755906%\"\u003e\n \u003cp\u003e211\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.37795275590551%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.968503937007874%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;The sensitivity using fibrinogen \u0026lt;2g/L was SN =56.5%, PPV=64.9%, (p\u0026lt; 0.001) The specificity using fibrinogen \u0026lt;2g/L was SP =72.9%, NPV=61.7% (p\u0026lt; 0.001). (Table 2) Fibrinogen levels predict TBI severity with an AUC = 0.656, 95% CI (0.58-0.73) p=0.000. (Figure 2)\u003c/p\u003e\n\u003cdiv id=\"ftn1\"\u003e\n \u003cp\u003e[1] Missing 2\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn2\"\u003e\n \u003cp\u003e[2] Crude Odds ratio: Unadjusted for other variables.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn3\"\u003e\n \u003cp\u003e[3] Statistical significance determined by chi square test. Values in Bold are statistically significant.\u003c/p\u003e\n\u003c/div\u003e \u003cp\u003eOn bivariate analysis, fibrinogen levels were significantly associated with injury severity. SBP and pulse oximetry were also significantly associated with TBI severity. Without adjustment, TBI patients with fibrinogen levels\u0026thinsp;\u0026lt;\u0026thinsp;2g/L were 3 times more likely to have severe TBI than in participants with fibrinogen levels of 2-4.5g/L. Further multivariate analysis with logistic regression showed a strong association between fibrinogen levels and TBI severity. When adjusted for age, systolic blood pressure, temperature and oximetry; fibrinogen levels\u0026thinsp;\u0026lt;\u0026thinsp;2g/L (hypofibrinogenemia) were independently associated with severe TBI. (AOR 2.87 CI,1.34\u0026ndash;6.14: p\u0026thinsp;=\u0026thinsp;0.007) Levels above 4.5g/L were also independently associated with injury severity (AOR 2.89, CI 1.12\u0026ndash;7.48: p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) SBP\u0026thinsp;\u0026gt;\u0026thinsp;140mmHg, oxygen saturation\u0026thinsp;\u0026lt;\u0026thinsp;90% and temperature\u0026thinsp;\u0026gt;\u0026thinsp;38\u0026ordm; C were also associated with severe TBI. (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eOn bivariate analysis, fibrinogen levels were significantly associated with mortality. Other factors viz SBP, temperature and oximetry were also significantly related to mortality. (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eAfter adjusting for patient age, hypoxia levels, and hemodynamic status on multivariate analysis, fibrinogen levels more than 4.5g/L were independently associated with mortality (OR 4.5, CI;1.472\u0026ndash;13.607, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Temperature\u0026thinsp;\u0026gt;\u0026thinsp;38\u0026ordm;C, SBP and oximetry were also associated with mortality. (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;3. Clinical parameters associated with TBI severity\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"662\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 23.7159%;\" valign=\"top\" width=\"24.20574886535552%\"\u003e\n \u003cp\u003eGCS SCORE n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 29.3484%;\" valign=\"top\" width=\"27.68532526475038%\"\u003e\n \u003cp\u003eBivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 13.1475%;\" valign=\"top\" width=\"29.95461422087746%\"\u003e\n \u003cp\u003eMultivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003eGCS 9-15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003eGCS 3-8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003eCOR[1] (95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.5676%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003eAOR[2] (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eAge (years)\u003csup\u003e\u003csup\u003e[3]\u003c/sup\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"13.61573373676248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e13-30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e63(58.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e41(46.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e1(Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e31-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e44(41.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e47(53.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e1.64(0.93-2.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e1.47(0.75-2.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e0.261\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"13.61573373676248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e100(89.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e89(88.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e1(Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e12(10.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e12(11.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e1.12(0.48-2.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e0.788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eHead injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"13.61573373676248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eClosed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e58(51.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e57(56.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e1(Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eOpen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e54(48.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e44(43.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e0.83 (0.48-1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e0.497\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eSBP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"13.61573373676248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e90-139mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e85(75.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e58(57.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e1(Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026lt;90mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e9(8.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e2(1.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e0.33\u0026nbsp;(0.07-1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e0.29(0.05-1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e0.165\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026gt;140mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e18(16.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e41(40.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e3.34(1.75-6.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e4.46(1.99-10.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eOximetry[4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"13.61573373676248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e90-100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e100(91.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e76(76.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e1(Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026lt;90%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e9(8.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e23(23.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e3.36 (1.47-7.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.004\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e2.87(1.02-8.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.046\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eTemperature\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"13.61573373676248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e36-38\u0026ordm; C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e66(58.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e52(51.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e1(Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026lt;36\u0026ordm;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e25(22.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e12(11.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e0.61 (0.28-1.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e0.212\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e0.76(0.31-1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e0.534\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026gt;38\u0026ordm;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e21(18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e37(36.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e2.24 (1.17-4.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.015\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e2.80(1.18-6.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.02\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.15431164901664%\"\u003e\n \u003cp\u003eFibrinogen[5](g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.10287443267776%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"13.61573373676248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.984871406959153%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"17.700453857791224%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1899%;\" valign=\"top\" width=\"9.833585476550681%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e2-4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e70(63.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e37(37.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e1(Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026lt;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e26(23.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e48(48.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e3.49 (1.88-6.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e2.87(1.34-6.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.007\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 16.8976%;\" valign=\"top\" width=\"18.12688821752266%\"\u003e\n \u003cp\u003e\u0026gt;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.4508%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e15(13.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.265%;\" valign=\"top\" width=\"12.084592145015106%\"\u003e\n \u003cp\u003e15(15.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0103%;\" valign=\"top\" width=\"17.673716012084594%\"\u003e\n \u003cp\u003e1.89 (0.83-4.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3381%;\" valign=\"top\" width=\"9.969788519637461%\"\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.4529%;\" valign=\"top\" width=\"18.580060422960724%\"\u003e\n \u003cp\u003e2.89(1.12-7.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.0852%;\" valign=\"top\" width=\"11.48036253776435%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.029\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cdiv id=\"ftn1\"\u003e\n \u003cp\u003e[1] Crude Odds Ratio\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn2\"\u003e\n \u003cp\u003e[2] Adjusted Odds ratio. Adjusted for age, Systolic Blood Pressure (SBP) Oximetry, temperature. Values in bold italic are statistically significant.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn3\"\u003e\n \u003cp\u003e[3] Missing age 18\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn4\"\u003e\n \u003cp\u003e[4] Missing oximetry 5\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn5\"\u003e\n \u003cp\u003e[5] Missing fibrinogen 2\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\u003cp\u003eTable\u0026nbsp;4. Factors associated with mortality in TBI.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"680\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 27.0925%;\" valign=\"top\" width=\"26.431718061674008%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eBivariate analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 10.6613%;\" valign=\"top\" width=\"30.54331864904552%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMultivariate analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eParameter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003eSurvived\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003eDied\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026nbsp;COR[1] [95% CI]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;p\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.5446%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e\u0026nbsp;AOR[2]. [95% CI]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eAge(years)\u003csup\u003e\u003csup\u003e[3]\u003c/sup\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"6.461086637298091%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.152716593245227%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e13-30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e55(60.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e28(44.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e31-60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e36(39.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e35(55.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1.91(1.00-3.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e1.78(0.80-3.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"6.461086637298091%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.152716593245227%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e83(89.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e63(86.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.59324522760646%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e10(10.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e10(13.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1.32 (0.52-3.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e0.564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.59324522760646%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eHead Injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"6.461086637298091%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.152716593245227%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eClosed Injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e53(56.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e38(52.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.59324522760646%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eOpen injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e40(43.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e35(47.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1.22(0.66-2.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e0.526\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.59324522760646%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eSBP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"6.461086637298091%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.152716593245227%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e90-139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e73(78.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e42(57.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026lt;90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e6(6.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e1(1.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e0.29(0.03-2.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e0.259\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e0.24(0.02-2.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e0.265\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026gt;140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e14(15.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e30(41.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e3.72(1.78-7.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e4.59 (1.80-11.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.001\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eTemperature \u0026ordm;C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"6.461086637298091%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.152716593245227%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e36-38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e61(65.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e34(46.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026lt;36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e19(20.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e9(12.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e0.85(0.35-2.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e0.722\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e1.02 (0.35-2.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e0.977\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026gt;38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e13(13.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e30(41.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e4.14(1.91-8.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e4.19 (1.49-11.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.007\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eOximetry[4]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"6.461086637298091%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.152716593245227%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e90-100%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e88(96.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e51(72.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026lt;90%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e3(3.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e19(27.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e10.93(3.08-38.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.000\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e9.15\u0026nbsp;(2.17-38.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.003\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003eFibrinogen[5](g/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"6.461086637298091%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.8162%;\" valign=\"top\" width=\"16.152716593245227%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e2-4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e54(58.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e25(34.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e1(reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026lt;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e29(31.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e31(43.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e2.31(1.15-4.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.018\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e1.64(0.66-4.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e0.288\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e\u0026gt;4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e10(10.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3015%;\" valign=\"top\" width=\"12.481644640234949%\"\u003e\n \u003cp\u003e16(22.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.72%;\" valign=\"top\" width=\"18.061674008810574%\"\u003e\n \u003cp\u003e3.46(1.36-8.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3725%;\" valign=\"top\" width=\"8.370044052863436%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.008\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.5986%;\" valign=\"top\" width=\"19.383259911894275%\"\u003e\n \u003cp\u003e4.48(1.47-13.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.9834%;\" valign=\"top\" width=\"11.160058737151248%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e0.008\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cdiv id=\"ftn1\"\u003e\n \u003cp\u003e[1] Crude Odds Ratio\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn2\"\u003e\n \u003cp\u003e[2] Adjusted Odds ratio Adjusted for age, Systolic Blood Pressure (SBP) Oximetry, temperature. Values in bold italic are statistically significant\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn3\"\u003e\n \u003cp\u003e[3] Missing age 18\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn4\"\u003e\n \u003cp\u003e[4] Missing oximetry 5\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn5\"\u003e\n \u003cp\u003e[5] \u0026nbsp;Missing Fibrinogen 2\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study set out to determine the specificity and sensitivity of fibrinogen levels and the association with severity and mortality among TBI patients at Mulago Hospital. There are no studies addressing this topic from sub-Saharan Africa and this is the first study in Uganda to describe this relationship. Despite numerous evidence available regarding the predictability of fibrinogen in the prognosis of TBI outcomes from prior studies(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e), little is known concerning its predictive ability in the diagnosis of severe TBI.\u003c/p\u003e \u003cp\u003eThe sensitivity using fibrinogen\u0026thinsp;\u0026lt;\u0026thinsp;2g/L(hypofibrinogenemia) was 56.5% with a positive predictive value of 64.9%. The specificity was 72.9% with a negative predictive value of 61.7%. In addition, hypofibrinogenemia (fibrinogen levels\u0026thinsp;\u0026lt;\u0026thinsp;2g/L) was common in TBI patients occurring in 35.07% of TBI patients on admission. This is similar to 38.6% found in a previous study done by Lv, et al.(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) Our study also found that 20.4% of patients with TBI had high levels of fibrinogen(\u0026gt;\u0026thinsp;4.5g/L).\u003c/p\u003e \u003cp\u003eRecent research showed that for patients admitted with severe TBI, fibrinogen levels\u0026thinsp;\u0026lt;\u0026thinsp;2g/L on admission are strongly related to increased mortality.(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) In addition, studies have demonstrated that in severe trauma, fibrinogen is reduced to critical levels. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e) The debate about the critical value of fibrinogen in trauma is an ongoing matter of contention.(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e) Floccard et\u0026rsquo;al defined critical levels as being \u0026le;\u0026thinsp;1.0g/L and abnormal levels being 1.0\u0026ndash;1.8 g/L all of which have been reported in patients with severe Trauma.(\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). By contrast, high fibrinogen levels have been described as being protective in patients with multiple trauma.(\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e) Furthermore, previous studies have demonstrated that TBI is associated with abnormalities in clot formation due to differences in fibrinogen levels among victims.(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e) Fibrinogen could therefore be used as a marker or predictor of TBI severity.\u003c/p\u003e \u003cp\u003eThe study found that low fibrinogen levels (\u0026lt;\u0026thinsp;2 g/L) were fairly predictive of TBI severity with an AUC\u0026thinsp;=\u0026thinsp;0.656, sensitivity of 56.5% and specificity of 72.9%. Therefore, absence of hypofibrinogenemia in TBI patients found in this study was associated with milder forms of TBI. This is consistent with what previous studies have described in severe trauma.\u003c/p\u003e \u003cp\u003eThis study shows that the likelihood of having a severe form of TBI increases with low levels of fibrinogen(\u0026lt;\u0026thinsp;2g/L). Possible explanations for the above relationship stem from the presence of intracranial bleeding which is a common occurrence in TBI as noted in the CRASH trial.(\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e) Trauma induced coagulopathy is a crucial element in severe TBI especially when compounded with intracranial bleeding. The consumption of clotting factors and platelets in response to intracranial bleeding further lowers fibrinogen levels.(\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e) TBI is also associated with systemic hyperfibrinolysis which occurs in as much as 20% of critical trauma patients hence lowering fibrinogen levels further. (\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e) In addition, prior studies have shown that fibrinogen levels drop drastically and most rapidly during haemorrhage.(\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e) Therefore, the association of low fibrinogen levels with severe TBI is possibly due to a combination of haemorrhage and trauma induced coagulopathy that occurs in severe TBI.(\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eMuch as there is a stronger association of severity with low fibrinogen levels, high fibrinogen levels (\u0026gt;\u0026thinsp;4.5g/L) were also associated with severe TBI. This could be due to the inflammation that accompanies major trauma and disruption of the blood brain barrier with release of procoagulant molecules.(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e) A study done by Samuels et al found that TBI patients commonly presented with a spectrum ranging from hypocoagulability to hypercoagulability.(\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e) It is therefore likely that severe TBI without intracranial haemorrhage leads to high fibrinogen levels while severe TBI with haemorrhage lowers the fibrinogen levels.\u003c/p\u003e \u003cp\u003eUnlike prior research findings, (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) this study showed that fibrinogen levels\u0026thinsp;\u0026gt;\u0026thinsp;4.5g/L were strong predictors of mortality. A possible explanation of this observation starts with trauma induced disruption of the Blood Brain Barrier that incites an extensive inflammatory response.(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e) Such extensive inflammation can be caused by neural cell death with resultant secondary brain oedema.(\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e) Diffuse Axonal Injury is of utmost importance here since it is characterized by an intense inflammatory response.(\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e) It is this inflammatory process that is responsible for the elevated fibrinogen levels. Organ dysfunction then ensues from this trauma induced systemic inflammatory state.(\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e) The development of organ dysfunction is related to the intensity of the trauma induced inflammatory response.(\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e) Hence, a severe systemic inflammatory response due to a disrupted blood brain barrier causes early organ dysfunction and later multiple organ failure which leads to death.(\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e). This possibly explains the high fibrinogen levels found to be associated with mortality.\u003c/p\u003e \u003cp\u003eWhile one of the strengths of our study is that it was carried out prospectively in a high-volume trauma center, some limitations need to be acknowledged. This was a single centre study with a rather small sample size and with limited duration allocated to conduct the study due to specified time frames for research activities. Secondly, fibrinogen is not a routine test in Mulago Hospital for TBI patients and replacement therapy is not currently part of the management protocols in patients with TBI; hence, despite the identification of abnormalities among the participants, correction therapy with concentrate was not possible for the participants. Patients with coagulopathies however received other supplements such as tranexamic acid and Fresh frozen plasma. Additional prospective studies with larger sample size and longer study duration are needed to confirm the predictability of TBI severity and clinical outcomes using fibrinogen levels.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, we established that fibrinogen is a useful tool in predicting severity of TBI and mortality. The study reveals that the sensitivity of fibrinogen levels\u0026thinsp;\u0026lt;\u0026thinsp;2g/L is 56.5% and the specificity is 72.9%. Fibrinogen fairly predicts TBI severity with an AUC of 0.656.\u003c/p\u003e \u003cp\u003eFibrinogen levels may be used as an additional tool to screen TBI patients for injury severity. Low fibrinogen levels (\u0026lt;\u0026thinsp;2g/L) are predictors of TBI severity. High fibrinogen levels\u0026thinsp;\u0026gt;\u0026thinsp;4.5g/L are also predictors of TBI severity. A fibrinogen level of \u0026gt;\u0026thinsp;4.5g/L is a strong predictor of mortality in TBI patients. Integrating fibrinogen as a biomarker in TBI management could therefore provide critical information about trauma physiology and ultimately influence clinical decisions. Additional larger prospective studies are needed to confirm these findings.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdjusted Odds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eATC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute Traumatic Coagulopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eATLS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdvanced Trauma Life Support.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ebpm\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ebeats per minute\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCrude Odds ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDALYs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDisability Adjusted Life Years.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDVT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDeep Vein Thrombosis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEDH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eExtradural Hematoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGCS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlasgow Coma Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntensive Care Unit\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eINR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational Normalized Ratio.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIPH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntraparenchymal Haemorrhage.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntraventricular Haemorrhage\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLAR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLegally Acceptable Representative\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLMIC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLow- and Middle-Income Country\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLNMP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLast Normal Menstrual Period.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMOF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMultiple Organ Failure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRTC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRoad Traffic Crash\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSBP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSystolic Blood Pressure.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSDH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSubdural Hematoma\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTBI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTraumatic Brain Injury\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTRISS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTrauma and Injury Severity Score.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe School of Medicine Ethics and Research Committee and Mulago Hospital Ethics and Research Committee approved the study in October 2021\u0026nbsp;with reference number; Mak-SOMREC-2021-126. Informed consent was obtained from each patient or\u0026nbsp;legally acceptable representative of the patient before participation in the study. All methods were carried out in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to confidentiality agreements but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by the National Institute of Neurological Disorders and Stroke and Stroke of the under-award Number D43NS118560. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy concept and design: S.J.B.\u003c/p\u003e\n\u003cp\u003eDrafting of the Manuscript: S.J.B., M.K., J.K., M.T.K., M.S.\u003c/p\u003e\n\u003cp\u003eStatistical Analysis: S.J.B., W.F\u003c/p\u003e\n\u003cp\u003eInterpretation of data: S.J.B., M.T.K., W.F., K.J., L.K.K.\u003c/p\u003e\n\u003cp\u003eRevision of Manuscript: M.T.K., K.J., M.D., M.K.\u003c/p\u003e\n\u003cp\u003eAdministrative and Technical Support: M.T.K., K.J., M.D., M.G., M.K., K.J., M.S.\u003c/p\u003e\n\u003cp\u003eSupervision: M.T.K., K.J., M.D., M.G., M.K.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors extend gratitude to the Dr. Walugembe Fred for their useful input during the preparation of the manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eS.J.B.: MBChB, General Surgery Resident, Makerere University, College of Health Sciences.\u003c/p\u003e\n\u003cp\u003eM.T.K.: MBChB, MMED, Senior Lecturer, Makerere University, College of Health Sciences Department of Surgery.\u003c/p\u003e\n\u003cp\u003eK.J.:\u0026nbsp;MBChB, MMED, FCS NEURO.Neurosurgeon, Mulago National Specialized Hospital.\u003c/p\u003e\n\u003cp\u003eM.G.:\u0026nbsp;MBChB, MMED,\u0026nbsp;MHPE,\u0026nbsp;Associate Professor and Head of Department, Surgery Makerere University College of Health Sciences.\u003c/p\u003e\n\u003cp\u003eM.D.: M.D, Professor of Neurology Case Western Reserve University School of Medicine.\u003c/p\u003e\n\u003cp\u003eM.K.[1]: MBChB, MMED, Neurologist, Mulago National Referral Hospital\u003c/p\u003e\n\u003cp\u003eM.K.[2]: MBChB, MMED, Associate Professor of Medicine, Department of Medicine, College of Health Sciences Makerere University\u003c/p\u003e\n\u003cp\u003eL.K.K: MBChB, Neurosurgery resident, Makerere University, College of Health Sciences.\u003c/p\u003e\n\u003cp\u003eM.S.: MD, Professor of Psychiatry and of Neurology, Case Western Reserve University School of Medicine\u003c/p\u003e\n\u003cdiv id=\"ftn1\"\u003e\n \u003cp\u003e[1] Martin Kaddumukasa\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"ftn2\"\u003e\n \u003cp\u003e[2] Mark Kaddumukasa.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBickler SN, Weiser TG, Kassebaum N, Higashi H, Chang DC, Barendregt JJ, et al. 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World J Emerg Surg. 2020;15(1):1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFenger-Eriksen C, Ingerslev J, S\u0026oslash;rensen B. Fibrinogen concentrate\u0026ndash;a potential universal hemostatic agent. Expert Opin Biol Ther. 2009;9(10):1325\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSpahn DR, Bouillon B, Cerny V, Duranteau J, Filipescu D, Hunt BJ, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition. Crit Care. 2019;23(1):98.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLevy JH, Welsby I, Goodnough LT. Fibrinogen as a therapeutic target for bleeding: a review of critical levels and replacement therapy. Transfusion. 2014;54(5):1389\u0026ndash;405. quiz 8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFries D, Martini WZ. Role of fibrinogen in trauma-induced coagulopathy. Br J Anaesth. 2010;105(2):116\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFloccard B, Rugeri L, Faure A, Saint Denis M, Boyle EM, Peguet O, et al. Early coagulopathy in trauma patients: an on-scene and hospital admission study. Injury. 2012;43(1):26\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSamuels JM, Moore EE, Silliman CC, Banerjee A, Cohen MJ, Ghasabyan A, et al. Severe traumatic brain injury is associated with a unique coagulopathy phenotype. J Trauma Acute Care Surg. 2019;86(4):686\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoberts I, Yates D, Sandercock P, Farrell B, Wasserberg J, Lomas G, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet. 2004;364(9442):1321\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChhabra G, Rangarajan K, Subramanian A, Agrawal D, Sharma S, Mukhopadhayay AK. Hypofibrinogenemia in isolated traumatic brain injury in Indian patients. Neurol India. 2010;58(5):756\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKushimoto S, Shibata Y, Yamamoto Y. Implications of fibrinogenolysis in patients with closed head injury. J Neurotrauma. 2003;20(4):357\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStettler GR, Moore EE, Nunns GR, Chandler J, Peltz E, Silliman CC, et al. Rotational thromboelastometry thresholds for patients at risk for massive transfusion. J Surg Res. 2018;228:154\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHiippala ST, Myllyl\u0026auml; GJ, Vahtera EM. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. 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StatPearls Publishing LLC.; 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSauaia A, Moore FA, Moore EE. Postinjury Inflammation and Organ Dysfunction. Crit Care Clin. 2017;33(1):167\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaker CC, Oppenheimer L, Stephens B, Lewis FR, Trunkey DD. Epidemiology of trauma deaths. Am J Surg. 1980;140(1):144\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Traumatic Brain Injury, Fibrinogen, Outcomes, Mortality","lastPublishedDoi":"10.21203/rs.3.rs-2596161/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2596161/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e\n\u003cp\u003eFibrinogen levels drop quicker than any other factors in severe trauma such as Traumatic Brain Injury (TBI). Contemporaneous studies show that fibrinogen concentrations \u0026lt; 2 g/L are strongly related to mortality. However, little is known regarding fibrinogen levels and TBI severity as well as mortality in sub-Saharan Africa. We therefore set out to determine whether fibrinogen levels are associated with TBI severity and seven days outcomes.\u003c/p\u003e\n\u003ch2\u003eObjectives\u003c/h2\u003e\n\u003cp\u003eTo determine the sensitivity and specificity of fibrinogen levels and the association with severity and mortality among TBI patients at Mulago Hospital.\u003c/p\u003e\n\u003ch2\u003eMethods\u003c/h2\u003e\n\u003cp\u003eWe prospectively enrolled 213 patients with TBI aged between 13 and 60 years of age and presenting within 24hrs of injury. Patients with pre-existing coagulopathy, concurrent use of anticoagulant or antiplatelet agents, pre-existing hepatic insufficiency, diabetes mellitus and who were pregnant were excluded. Fibrinogen levels were determined using the Clauss fibrinogen assay.\u003c/p\u003e\n\u003ch2\u003eResults\u003c/h2\u003e\n\u003cp\u003eMajority of the patients were male (88.7%) and nearly half were aged 30 or less (48.8%). Fibrinogen levels less than 2g/L were observed in 74 (35.1%) of the patients while levels above 4.5 g/L were observed in 30(14.2%) of the patients. The average time spent in the study was 3.7 ± 2.4 days. The sensitivity and specificity using fibrinogen \u0026lt; 2g/L was 56.5% and 72.9% respectively. Fibrinogen levels predict TBI severity with an AUC = 0.656 (95% CI 0.58–0.73: p = 0.000) Fibrinogen levels \u0026lt; 2g/L (hypofibrinogenemia) were independently associated with severe TBI. (AOR 2.87 CI,1.34–6.14: p = 0.007). Levels above 4.5g/L were also independently associated with injury severity (AOR 2.89, CI 1.12–7.48: p \u0026lt; 0.05) Fibrinogen levels more than 4.5g/L were independently associated with mortality (OR 4.5, CI;1.47–13.61, p \u0026lt; 0.05).\u003c/p\u003e\n\u003ch2\u003eConclusions\u003c/h2\u003e\n\u003cp\u003eThe fibrinogen level is a useful tool in predicting severity including mortality of TBI in our settings. We recommend the routine use of fibrinogen levels in TBI patient evaluations as levels below 2g/L and levels above 4.5g/L are associated with severe injuries and mortality\u003c/p\u003e","manuscriptTitle":"Fibrinogen; a predictor of injury severity and mortality among patients with traumatic brain injury in Sub-Saharan Africa: a prospective study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-03-01 16:51:35","doi":"10.21203/rs.3.rs-2596161/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0f7a8306-f594-4c1e-b238-022e383e678f","owner":[],"postedDate":"March 1st, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-04-14T10:14:15+00:00","versionOfRecord":[],"versionCreatedAt":"2023-03-01 16:51:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2596161","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2596161","identity":"rs-2596161","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}