Neutrophil gelatinase-associated lipocalin as a biomarker for short-term outcomes among trauma patients: A single-center observational study.

BACKGROUND: Urinary biomarkers for organ dysfunction could predict the outcomes of severe trauma patients. However, the use of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of trauma is not well studied. OBJECTIVES: To evaluate the association between the short-term prognosis of trauma patients and NGAL levels. METHODS: We conducted a single center study and compared predictive performances between NGAL levels and the trauma severity. RESULTS: A total of 104 patients were included in the study. Patients were divided into two groups based on ISS score of 16. There was no significant difference in patient characteristics based on trauma severity. However, the lactate level was significantly higher in the more severe group. There was a significant association between urinary NGAL levels and trauma severity indicators, such as intensive care unit stay (ICU) (p = 0.005) and emergency care unit (ECU) stay (p = 0.049). In addition, receiver operating curve analysis showed that as a predictor, NGAL could be used for detecting severity with moderate precision, especially for short-term outcomes (specificity 70.6 for ICU and 69.0 for ECU stay). CONCLUSION: In this study, we revealed that the level of NGAL could predict the degree of invasiveness in trauma patients with moderate precision and estimate the duration of treatment during the acute phase. It is necessary to examine the validity of the findings of this study using a prospective, cohort, and multi-center collaborative study design.

Urinary markers of oxidative stress respond to infection and late-life in wild chimpanzees.

Oxidative stress (OS) plays a marked role in aging and results from a variety of stressors, making it a powerful measure of health and a way to examine costs associated with life history investments within and across species. However, few urinary OS markers have been examined under field conditions, particularly in primates, and their utility to non-invasively monitor the costs of acute stressors versus the long-term damage associated with aging is poorly understood. In this study, we examined variation in 5 urinary markers of oxidative damage and protection under 5 validation paradigms for 37 wild, chimpanzees living in the Kibale National Park, Uganda. We used 924 urine samples to examine responses to acute immune challenge (respiratory illness or severe wounding), as well as mixed-longitudinal and intra-individual variation with age. DNA damage (8-OHdG) correlated positively with all other markers of damage (F-isoprostanes, MDA-TBARS, and neopterin) but did not correlate with protection (total antioxidant capacity). Within individuals, all markers of damage responded to at least one if not both types of acute infection. While OS is expected to increase with age, this was not generally true in chimpanzees. However, significant changes in oxidative damage were detected within past-prime individuals and those close to death. Our results indicate that OS can be measured using field-collected urine and integrates short- and long-term aspects of health. They further suggest that more data are needed from long-lived, wild animals to illuminate if common age-related increases in inflammation and OS damage are typical or recently aberrant in humans.

Point-of-Care Urinary Biomarker Testing for Risk Prediction in Critically Injured Combat Casualties.

BACKGROUND: Risk prediction is important during combat operations because resources are limited and triage decisions must be rapid and accurate. We evaluated 2 point-of-care urinary biomarker tests for risk prediction in combat casualties. STUDY DESIGN: This was an observational cohort study of critically injured military personnel admitted to Craig Joint Theater Hospital in Afghanistan from October 2012 to December 2013. We collected urine within 3 hours of admission and measured urinary biomarkers with NephroCheck and a neutrophil gelatinase-associated lipocalin dipstick (NGALds) to evaluate their ability to predict a combined end point of need for renal replacement therapy or death. Odds ratios (ORs) were calculated and receiver operator characteristic curves were generated for both tests. RESULTS: A total of 89 patients were included for analysis. The median Injury Severity Score was 18 and the combined end point occurred in 12 (13.5%) patients. NephroCheck was not associated with the combined end point (OR 1.56; 95% CI 0.81 to 3.03; p = 0.19) and the area under the curve of the receiver operator characteristic curve was 0.65. The NGALds was highly associated with the combined end point (OR 4.93; 95% CI 2.18 to 11.14; p < 0.001) and the area under the curve of the receiver operator characteristic curve was 0.84. The NGALds remained significantly associated with the combined end point in a logistic regression model that included Injury Severity Score as a covariate (OR 4.10; 95% CI 1.74 to 9.67; p = 0.001). CONCLUSIONS: Measurement of urinary biomarkers with an NGALds, but not NephroCheck, predicts poor outcomes in combat casualties. An NGALds is a simple urine dipstick that could be deployed to combat zones to prioritize aeromedical evacuation, help with triage decisions, and predict resource use.

Prevalence of cocaine and derivatives in blood and urine samples of trauma patients and correlation with injury severity: a prospective observational study.

PURPOSE: The abuse of cocaine and its derivatives presents a likely risk factor for injury. Trauma incurred by cocaine and derivative abusers may be more severe than that incurred by non-users. OBJECTIVES: To ascertain the presence of cocaine and its derivatives in trauma patients and to correlate RTS (Revised Trauma Score) and ISS (Injury Severity Score) with the presence of cocaine and its derivatives in blood and urine samples. METHODS: All trauma victims treated in an emergency unit between November 11, 2012 and September 15, 2013 were included in the study. Blood and urine samples were collected on admission to hospital. RTS and ISS scores were then compared with the presence or absence of cocaine and its derivatives in the samples. The associations between RTS < 7.84 and ISS > 16 and the independent variables were evaluated by the gross odds ratio values, determined by univariate logistic regression. Multivariate analysis was performed using multivariate logistic regression. RESULTS: Of 453 patients (83.7% male) included in the study, 28.6% presented ISS > 16 and 33.6% presented RTS < 7.84. A total of 435 samples were collected, and 86 (19.8%) provided positive samples for cocaine, 48 (11%) for crack and 69 (15.9%) for cocaethylene. Compared to other patients, drug users showed a greater probability of RTS < 7.84 (2.18 times greater) and a greater probability of ISS > 16 (1.76 times greater). CONCLUSION: For the trauma patients included in our study, the use of cocaine and its derivatives was shown to be associated with more severe traumas, as demonstrated by their RTS and ISS scores.

A Case Study of the NCRP 156 Wound Model of Embedded DU Using Data From Urine Uranium Concentrations of Wounded Veterans.

Depleted uranium (DU) munitions were initially used by the United States (U.S.) military during the first Persian Gulf War in 1991 in order to penetrate heavily armored vehicles. However, as a result of friendly fire, several U.S. military personnel received intakes from DU munitions. One of the ongoing concerns for these wounded veterans is the potential long-term exposure received from DU embedded fragments. The United States Army Institute of Public Health (AIPH) is the first laboratory that analyzes the urine bioassays from Army Soldiers that are injured with DU fragments. The United States Air Force School of Aerospace Medicine also evaluates bioassays from DU injuries. The urine bioassay data collected by AIPH was evaluated using the NCRP 156 wound model coefficients for the DU-Wafer, Fragment, and Particle models. The maximum likelihood method was used in the Integrated Modules for Bioassay Analysis (IMBA-PPAE) to calculate the estimates of intake and tissue doses. Evaluating the three models for wound retention, the DU-Wafer and Fragment model yielded a credible fit to the bioassay data. Comparing the two models, the DU-Wafer model fits the data better than the Fragment model when comparing their autocorrelation coefficient and chi-squared values of (P 1.73 × 10, c 4.83 × 10), (P 2.01 × 10, c 1.09), respectively. This evaluation supports the validity of both the DU-wafer model as well as the default fragmentation model proposed by NCRP 156.

Pharmacokinetic Study of Intravenous Acetaminophen Administered to Critically Ill Multiple-Trauma Patients at the Usual Dosage and a New Proposal for Administration.

The pharmacokinetic profile of intravenous acetaminophen administered to critically ill multiple-trauma patients was studied after 4 consecutive doses of 1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected (during 6-hour intervals between doses) to determine serum and urine acetaminophen concentrations. These were used to calculate the following pharmacokinetic parameters: maximum and minimum concentrations, terminal half-life, area under serum concentration-time curve from 0 to 6 hours, mean residence time, volume of distribution, and serum and renal clearance of acetaminophen. Daily doses of acetaminophen required to obtain steady-state minimum (bolus dosing) and average plasma concentrations (continuous infusion) of 10 µg/mL were calculated (10 µg/mL is the presumed lower limit of the analgesic range). Data are expressed as median [interquartile range]. Twenty-two patients were studied, mostly young (age 44 [34-64] years) males (68%), not obese (weight 78 [70-84] kg). Acetaminophen concentrations and pharmacokinetic parameters were these: maximum concentration 33.6 [25.7-38.7] µg/mL and minimum concentration 0.5 [0.2-2.3] µg/mL, all values below 10 µg/mL and 8 below the detection limit; half-life 1.2 [1.0-1.9] hours; area under the curve for 6 hours 34.7 [29.7-52.7] µg·h/mL; mean residence time 1.8 [1.3-2.6] hours; steady-state volume of distribution 50.8 [42.5-66.5] L; and serum and renal clearance 28.8 [18.9-33.7] L/h and 15 [11-19] mL/min, respectively. Theoretically, daily doses for a steady-state minimum concentration of 10 µg/mL would be 12.2 [7.8-16.4] g/day (166 [112-202] mg/[kg·day]); for an average steady-state concentration of 10 µg/mL, they would be 6.9 [4.5-8.1] g/day (91 [59-111] mg/[kg·day]). In conclusion, administration of acetaminophen at the recommended dosage of 1 g per 6 hours to critically ill multiple-trauma patients yields serum concentrations below 10 µg/mL due to increased elimination. To reach the 10 µg/mL target, and from a strictly pharmacokinetic point of view, continuous infusion may be more feasible than bolus dosing. Such a change in dosing strategy requires appropriate, pharmacokinetic-pharmacodynamic and specific safety study.

Urinary Biomarkers are Associated with Severity and Mechanism of Injury.

Combat-related blast trauma results in massive tissue injury and tends to involve multiple systems. Further, an acute measure of injury severity based on underlying biological mechanisms may be important for the triage and treatment of these types of patients. We hypothesized that urinary biomarkers (UBs) would reflect severity of injury and that they would be elevated for blast injuries compared with gunshot wounds (GSW) in a cohort of combat casualties. We also postulated that UBs would be higher in patients with burns compared with patients with non-burn trauma in a civilian cohort. Among 80 service members who sustained combat-related injuries, we performed generalized estimating equations to compare differences in log-transformed concentrations of the UBs by both injury severity and injury mechanism. Among 22 civilian patients, we performed Kruskal-Wallis tests to compare differences for the UBs stratified by burn and non-burn trauma. In the military cohort, with the exception of IL-18, all UBs were significantly (P <0.05) higher for patients with a severe combat-related injury (Injury Severity Score ≥25). In addition, all crude UBs concentrations were significantly higher for blast versus GSW patients (P < 0.05). After adjusting for injury severity score and time of UB draw, KIM-1 (2.80 vs. 2.31; P = 0.03) and LFABP (-1.11 vs. -1.92; P = 0.02) were significantly higher for patients with a blast mechanism of injury. There were no significant differences in UBs between burn and non-burn civilian trauma patients. Future studies are needed to understand the physiologic response to trauma and the extent that UBs reflect these underlying processes.

Do trauma patients with phencyclidine-positive urine drug screens have increased morbidity or mortality?

BACKGROUND: Phencyclidine (PCP) use is anecdotally associated with agitation and injury and is frequently tested for in the setting of trauma. We sought to determine characteristics of trauma patients with a PCP-positive urine immunoassay drug screen (UDS) and if they had increased levels of care or mortality. METHODS: A 5-year retrospective review of a level 1 trauma center's trauma registry identified patients with a PCP-positive UDS. This group was then compared with 2 randomly selected control groups from the same trauma registry which were matched for age and sex but differed in that one had no sEtOH detected and a negative UDS (drug-free group) whereas the other had sEtOH or an other-than-PCP-positive UDS (other-drug group). Subgroup analysis was performed comparing PCP-positive patients with undetectable sEtOH with other-drug patients with undetectable sEtOH. RESULTS: The registry contained 7770 patients of which 156 met inclusion criteria. The mean age was 33.4years (range, 19-63), and 77% were male (n=121). When compared with the other-drug group, the PCP-positive group had significantly lower injury severity score, rates of intensive care unit admission, and sEtOH. No difference was seen in vital signs, mechanism of injury, ventilator days, intensive care unit days, total hospital days, disposition, or mortality between the 3 groups. This remained true even when subgroups with negative sEtOH were compared. CONCLUSION: This study suggests that a PCP-positive UDS in the setting of trauma is not associated with increased level of care, length of stay, or mortality.

Urinary Glycosaminoglycans Predict Outcomes in Septic Shock and Acute Respiratory Distress Syndrome.

RATIONALE: Degradation of the endothelial glycocalyx, a glycosaminoglycan (GAG)-rich layer lining the vascular lumen, is associated with the onset of kidney injury in animal models of critical illness. It is unclear if similar pathogenic degradation occurs in critically ill patients. OBJECTIVES: To determine if urinary indices of GAG fragmentation are associated with outcomes in patients with critical illnesses such as septic shock or acute respiratory distress syndrome (ARDS). METHODS: We prospectively collected urine from 30 patients within 24 hours of admission to the Denver Health Medical Intensive Care Unit (ICU) for septic shock. As a nonseptic ICU control, we collected urine from 25 surgical ICU patients admitted for trauma. As a medical ICU validation cohort, we obtained serially collected urine samples from 70 patients with ARDS. We performed mass spectrometry on urine samples to determine GAG (heparan sulfate, chondroitin sulfate, and hyaluronic acid) concentrations as well as patterns of heparan sulfate/chondroitin sulfate disaccharide sulfation. We compared these indices to measurements obtained using dimethylmethylene blue, an inexpensive, colorimetric urinary assay of sulfated GAGs. MEASUREMENTS AND MAIN RESULTS: In septic shock, indices of GAG fragmentation correlated with both the development of renal dysfunction over the 72 hours after urine collection and with hospital mortality. This association remained after controlling for severity of illness and was similarly observed using the inexpensive dimethylmethylene blue assay. These predictive findings were corroborated using urine samples previously collected at three consecutive time points from patients with ARDS. CONCLUSIONS: Early indices of urinary GAG fragmentation predict acute kidney injury and in-hospital mortality in patients with septic shock or ARDS. Clinical trial registered with www.clinicaltrials.gov (NCT01900275).

Association of in vivo κ-opioid receptor availability and the transdiagnostic dimensional expression of trauma-related psychopathology.

IMPORTANCE: Exposure to trauma increases the risk for developing threat (ie, fear) symptoms, such as reexperiencing and hyperarousal symptoms, and loss (ie, dysphoria) symptoms, such as emotional numbing and depressive symptoms. While preclinical data have implicated the activated dynorphin/κ-opioid receptor (KOR) system in relation to these symptoms, the role of the KOR system in mediating these phenotypes in humans is unknown. Elucidation of molecular targets implicated in threat and loss symptoms is important because it can help inform the development of novel, mechanism-based treatments for trauma-related psychopathology. OBJECTIVE: To use the newly developed [11C]LY2795050 radiotracer and high-resolution positron emission tomography to evaluate the relation between in vivo KOR availability in an amygdala-anterior cingulate cortex-ventral striatal neural circuit and the severity of threat and loss symptoms. We additionally evaluated the role of 24-hour urinary cortisol levels in mediating this association. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional positron emission tomography study under resting conditions was conducted at an academic medical center. Thirty-five individuals representing a broad transdiagnostic and dimensional spectrum of trauma-related psychopathology, ranging from nontrauma-exposed psychiatrically healthy adults to trauma-exposed adults with severe trauma-related psychopathology (ie, posttraumatic stress disorder, major depressive disorder, and/or generalized anxiety disorder). MAIN OUTCOMES AND MEASURES: [11C]LY2795050 volume of distribution values in amygdala-anterior cingulate cortex-ventral striatal neural circuit; composite measures of threat (ie, reexperiencing, avoidance, and hyperarousal symptoms) and loss (ie, emotional numbing, major depressive disorder, and generalized anxiety disorder symptoms) symptoms as assessed using the Clinician-Administered PTSD Scale, Hamilton Depression Rating Scale, and Hamilton Rating Scale for Anxiety; and 24-hour urinary cortisol levels. RESULTS: [11C]LY2795050 volume of distribution values in an amygdala-anterior cingulate cortex-ventral striatal neural circuit were negatively associated with severity of loss (r = -0.39; 95% CI, -0.08 to -0.66), but not threat (r = -0.03; 95% CI, -0.30 to 0.27), symptoms; this association was most pronounced for dysphoria symptoms (r = -0.45; 95% CI, -0.10 to -0.70). Path analysis revealed that lower [11C]LY2795050 volume of distribution values in this circuit was directly associated with greater severity of loss symptoms and indirectly mediated by 24-hour urinary cortisol levels. CONCLUSIONS AND RELEVANCE: Results of this study suggest that KOR availability in an amygdala-anterior cingulate cortex-ventral striatal neural circuit mediates the phenotypic expression of trauma-related loss (ie, dysphoria) symptoms. They further suggest that an activated corticotropin-releasing factor/hypothalamic-pituitary-adrenal axis system, as assessed by 24-hour urinary cortisol levels, may indirectly mediate this association. These results may help inform the development of more targeted, mechanism-based transdiagnostic treatments for loss (ie, dysphoric) symptoms.

The prevalence of positive drug and alcohol screens in elderly trauma patients.

BACKGROUND: Alcohol and drug abuse are recognized to be significantly prevalent in trauma patients, and are frequent harbingers of injury. The incidence of substance abuse in elderly trauma patients has, however, been limitedly examined. The authors sought to identify the spectrum of positive alcohol and drug toxicology screens in patients ≥65 years admitted to a Level I trauma center. METHODS: Patients ≥65 years old admitted to an American College of Surgeons (ACS) Level I trauma center over a 60--month period were identified from the trauma registry. Demographic data, blood alcohol content (BAC), and urine drug screen (UDS) results at admission were obtained and analyzed. The positive results were compared with individuals below 65 years in different substance categories using Fisher's exact test. RESULTS: In the 5-year period studied, of the 4139 patients ≥65 years, 1302 (31.5%) underwent toxicological substance screening. A positive BAC was present in 11.1% of these patients and a positive UDS in 48.3%. The mean BAC level in those tested was 163 mg/dL and 69% of patients had a level >80 mg/dL. CONCLUSIONS: These data show that alcohol and drug abuse are an issue in patients ≥65 years in our institution, though not as pervasive a problem as in younger populations. Admission toxicology screens, however, are important as an aid to identify geriatric individuals who may require intervention.

Comparison of serum and urinary calcium profile of immobilized and ambulant trauma patients.

BACKGROUND: Hypercalcemia occurs more frequently than is recognized in patients who are immobilized, but most of these patients are asymptomatic. This study is to determine serum and urinary calcium levels, incidence of hypercalcemia and hypercalciuria in immobilized and ambulant trauma patients. METHODS: A prospective comparative study was carried out over a period of seven months. Total serum calcium level and 24-hour urinary calcium output were measured weekly over 4weeks in 55 immobilized trauma patients as study group and 51 ambulant trauma patients as control group. RESULTS: Mean total serum calcium of immobilized patients increased progressively (on admission: 2.315±0.056mmol/l and week 4: 2.552±0.231mmol/l, p<.001) while that of ambulant patients did not change significantly (on admission: 2.306±0.041mmol/l, and week 4: 2.300±0.028mmol/l, p=.348). There is a significant difference in overall mean total serum calcium between immobilized and ambulant patients (p<.001). In immobilized and ambulant patients, mean 24-hour urinary calcium increased progressively from baseline (3.044±0.480mmol/day and 3.056±0.540mmol/day respectively), till the end of the study (8.543±2.142mmol/day and 6.783±1.372mmol/day respectively). Overall mean 24-hour urinary calcium is significantly different between immobilized and ambulant patients {multivariate Pillai F (5,100)=883.124, p<.001}. Incidence of hypercalcemia increased progressively in immobilized patients (end of week 1=7.27% and end of week 4=29.09%) while none of the ambulant patients had hypercalcemia. Incidence of hypercalciuria also increased progressively in immobilized patients (end of week 1=7.27% and end of week 4=63.64%) while ambulant patients only had hypercalciuria at the end of week 3 (9.8%) and week 4 (21.57%). CONCLUSION: Mean total serum calcium increased with increased duration of immobilization in trauma patients. Both immobilized and ambulant trauma patients developed hypercalciuria but it is worse and earlier in the immobilized trauma patients.

Changes in urine composition after trauma facilitate bacterial growth.

BACKGROUND: Critically ill patients including trauma patients are at high risk of urinary tract infection (UTI). The composition of urine in trauma patients may be modified due to inflammation, systemic stress, rhabdomyolysis, life support treatment and/or urinary catheter insertion. METHODS: Prospective, single-centre, observational study conducted in patients with severe trauma and without a history of UTIs or recent antibiotic treatment. The 24-hour urine samples were collected on the first and the fifth days and the growth of Escherichia coli in urine from patients and healthy volunteers was compared. Biochemical and hormonal modifications in urine that could potentially influence bacterial growth were explored. RESULTS: Growth of E. coli in urine from trauma patients was significantly higher on days 1 and 5 than in urine of healthy volunteers. Several significant modifications of urine composition could explain these findings. On days 1 and 5, trauma patients had an increase in glycosuria, in urine iron concentration, and in the concentrations of several amino acids compared to healthy volunteers. On day 1, the urinary osmotic pressure was significantly lower than for healthy volunteers. CONCLUSION: We showed that urine of trauma patients facilitated growth of E. coli when compared to urine from healthy volunteers. This effect was present in the first 24 hours and until at least the fifth day after trauma. This phenomenon may be involved in the pathophysiology of UTIs in trauma patients. Further studies are required to define the exact causes of such modifications.

Trauma activation patients: evidence for routine alcohol and illicit drug screening.

BACKGROUND: Statistics from the National Trauma Data Bank imply that discretionary blood alcohol and urine drug testing is common. However, there is little evidence to determine which patients are appropriate for routine testing, based on information available at trauma center arrival. In 2002, Langdorf reported alcohol and illicit drug rates in Trauma Activation Patients. METHODOLOGY/PRINCIPAL FINDINGS: This is a retrospective investigation of alcohol and illicit drug rates in consecutive St. Elizabeth Health Center (SEHC) trauma patients. SEHC Trauma Activation Patients are compared with the Langdorf Activation Patients and with the SEHC Trauma Nonactivation Patients. Minimum Rates are positive tests divided by total patients (tested and not tested). Activation patients: The minimum alcohol rates were: SEHC 23.1%, Langdorf 28.2%, combined 24.8%. The minimum illicit drug rates were: SEHC 15.7%, Langdorf 23.5, combined 18.3%. The minimum alcohol and/or illicit drug rates were: SEHC 33.4%, Langdorf 41.8%, combined 36.2%. Nonactivation patients: The SEHC minimum alcohol rate was 4.7% and the minimum illicit drug rate was 6.0%. CONCLUSIONS: Alcohol and illicit drug rates were significantly greater for Trauma Activation Patients, when compared to Nonactivation Patients. At minimum, Trauma Activation Patients are likely to have a 1-in-3 positive test for alcohol and/or an illicit drug. This substantial rate suggests that Trauma Activation Patients, a readily discernible group at trauma center arrival, are appropriate for routine alcohol and illicit drug testing. However, discretionary testing is more reasonable for Trauma Nonactivation Patients, because minimum rates are low.

Increased creatinine clearance in polytrauma patients with normal serum creatinine: a retrospective observational study.

INTRODUCTION: The aim of this study, performed in an intensive care unit (ICU) population with a normal serum creatinine, was to estimate urinary creatinine clearance (CLCR) in a population of polytrauma patients (PT) through a comparison with a population of non trauma patients (NPT). METHODS: This was a retrospective, observational study in a medical and surgical ICU in a university hospital. A total of 284 patients were consecutively included. Two different groups were studied: PT (n = 144) and NPT (n = 140). Within the second week after admission to the ICU, renal function was assessed using serum creatinine, 24 h urinary CLCR . RESULTS: Among the 106 patients with a CLCR above 120 mL minute(-1) 1.73 m(-2), 79 were PT and 27 NPT (P < 0.0001). Only 63 patients had a CLCR below 60 mL minute(-1) 1.73 m(-2) with 15 PT and 48 NPT (P < 0.0001). Patients with CLCR greater than 120 mL minute(-1). 1.73 m(-2) were younger, had a lower SAPS II score and a higher male ratio as compared to those having CLCR lower than 120 mL minute(-1). 1.73 m(-2). Through a logistic regression analysis, age and trauma were the only factors independently correlated to CLCR. CONCLUSIONS: In ICU patients with normal serum creatinine, CLCR, is higher in PT than in NPT. The measure of CLCR should be proposed as routine for PT patients in order to adjust dose regimen, especially for drugs with renal elimination.

The relationship between urinary melatonin metabolite excretion and posttraumatic symptoms following traumatic injury.

BACKGROUND: Associations between 24-hour urinary 6-sulphatoxy melatonin excretion and symptoms of posttraumatic stress disorder were assessed 2 days, 1 month and 6 months after traumatic injury requiring hospitalisation. METHODS: Forty-eight participants were recruited following an admission to hospital for an acute traumatic injury. They completed assessments 48h after the accident, 1 month and 6 months later. A 24-hour urine collection was initiated the morning before questionnaires were administered. PTSD symptoms and caseness was determined using the Impact of Event Scale (IES-R) and the Clinician Administered PTSD Scale respectively. Urinary 6-sulphatoxy melatonin was assayed by radioimmunoassay. RESULTS: Mean age of participants was 34 years (SD=12.72) and 75% were males. Ten (27%) participants met the criteria for PTSD 1 month post trauma and 6 (21%) met the criteria for PTSD at 6 months. Four of the six (67%) participants with PTSD at 6 months were also positive for major depression. Significant negative correlations were found between 6-sulphatoxy melatonin excretion at day 2 and all subscales and total score of the IES-R at the six month assessment. Controlling for depression, every one unit decrease in 6-sulphatoxy melatonin excretion was associated with a 13% increase in PTSD risk at six months (OR=1.13, 95% CI 1.00-1.27). However, this association was lost when self-reported pain, gender and employment was added to the model (OR=1.11, 0.93-1.32). CONCLUSION: This study provides preliminary data suggesting disrupted melatonin levels in the first 48h following trauma may place individuals at increased risk of PTSD.

Traumatic and non-traumatic spinal cord-injured patients in Quebec, Canada. Part 2: biochemical profile.

STUDY DESIGN: Community-based, cross-sectional study. OBJECTIVES: This study aimed at examining and comparing biochemical profiles (blood and urine) of traumatic and non-traumatic spinal cord-injured patients (TSCIs vs NTSCIs). SETTING: The Interval Rehabilitation Center, Trois-Rivieres, Province of Quebec, Canada. METHODS: Medical records from a cohort of 175 chronic spinal cord-injured patients (94 TSCI and 81 NTSCI individuals) were thoroughly studied. RESULTS: Augmentations over time of red blood cell (erythrocyte), hematocrit and hemoglobin levels were generally found after spinal cord injury (SCI), specifically in NTSCI patients (late vs early chronic). In contrast, although leukocyte levels generally decreased over time after SCI, higher lymphocyte levels were detected only in NTSCI patients (late vs early chronic). Higher total cholesterol, triglyceride, high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), protein and albumin serum levels were generally found over time after SCI, again, specifically in chronic NTSCI patients (late vs early chronic), whereas increased (twofold) nitrite and decreased (twofold) ubilirogen urine levels were found specifically in TSCI individuals (late vs early chronic). CONCLUSION: Clear differences were reported between subgroups of SCI patients strongly supporting the idea that therapeutic approaches aimed to treat these problems should be specifically designed for each type of patients (that is, NTSCI vs TSCI or early vs late chronic patients).

Urine toxicology screening in Austrian trauma patients: a prospective study.

INTRODUCTION: The question as to whether the patient consumed drugs prior to the trauma and which drugs were consumed, is of prime importance for the anesthesia required during surgery. However, many patients are unwilling or unable (including those with multiple trauma or impaired consciousness, or unconscious patients) to answer this question. The purpose of our prospective multicenter study was to collect data about drug consumption in Austria to determine whether drugs are identifiable in the urine of recently injured individuals and to establish the types of drugs consumed. MATERIALS AND METHODS: This prospective study included severely and moderately injured patients admitted to the Lorenz Boehler Trauma Hospital (Vienna, Austria), the Trauma Hospital Linz (Linz, Austria) and the Department of Trauma Surgery of the General Hospital Horn (Horn, Austria) during an 18-month period (October 2003-March 2005). All patients were suffering from injuries urgently requiring surgery. Urine samples were gained from all patients immediately after admission. Urinary samples were tested by Immuno-Assay (Triage 8 Immuno-Assay, Biosite, San Diego, USA). Urine samples were screened simultaneously for opiates, methadone, cocaine, barbiturates, amphetamines, cannabinoids, benzodiazepines and tricyclic antidepressants. RESULTS: Our prospective study included a total of 664 patients (320 from Vienna, 193 from the city of Linz, and 151 from Horn). Six hundred and forty-two patients were moderately injured (ISS < 16), suffering mostly from injuries to the extremities (504 patients) and 22 patients were severely injured (ISS > 16). Of the 664 patients, 178 (26.8%) tested positive for one or more drugs. The drugs most commonly detected were benzodiazepines (111 patients, 16.7%), cannabinoides (39 patients, 6%), tricyclic antidepressants (28, 4.2%) and opiates (26, 3.9%). CONCLUSION: Drug use is widespread in patients presenting to urban trauma centers in Austria. Physicians should maintain a high index of suspicion that their patients may be intoxicated and should perform drug testing routinely.

Occurrence of alpha- and beta-nortestosterone residues in the urine of injured male cattle.

The administration of anabolic steroids, for the purposes of growth promotion, to food-producing animals is banned in the EU. Among the compounds covered by this prohibition is ss-nortestosterone (beta-NT). This hormone is known to occur naturally in stallions and boars, and its main bovine metabolite, alpha-nortestosterone (alpha-NT), occurs naturally in pregnant cows and neonatal calves. However, neither compound is believed to occur naturally in male cattle. During 2006, the presence of alpha-NT and, on occasion, beta-NT was confirmed in male cattle (bulls and steers) slaughtered in Northern Ireland on welfare grounds, as a result of acute injury. Subsequent investigations revealed no evidence of abuse at any of the farms involved and revealed that the phenomenon also occurred in three other regions of the EU, in similarly injured animals. A hypothetical link to release of the adrenal steroid, dehydroepiandrosterone (DHEA), in response to the stress of the injury was tested. Following the intravenous administration of DHEA to two normal steers, beta-NT (but not alpha-NT) was confirmed in the urine of one steer. Thus, it may be concluded that both beta-NT and, by implication, alpha-NT can occur naturally in male cattle (or a specific cohort thereof) in contrast to previously accepted scientific knowledge.