Thromboelastography (TEG®) compared to conventional coagulation tests in surgical patients – a laboratory evaluation

Abstract

Background. Several methods exist for evaluation of hypocoagulation in patients with perioperative bleeding, e.g. thromboelastography (TEG^®) and conventional methods (platelet count, aPTT, INR and fibrinogen). Considering the vast experience of conventional methods it is important to investigate how well the methods correspond. Methods. Sixty surgical patients were included prospectively and blood samples were taken perioperatively. TEG^® and conventional parameters were analyzed simultaneously. An assessment of coagulopathy, based on a synthesis of the conventional methods, was done by two experienced coagulation specialists, blinded from the results of TEG^® and from the results of each other. Hypocoagulation, defined by TEG^® parameters; reaction time (R-time), angle, maximal amplitude (MA) and fibrinolysis, was evaluated according to a commonly used algorithm. Results. To detect a platelet count below 150 × 10⁹ L^?1, the sensitivity of TEG was 17% (95% CI, 7–36%) with angle and 25% (95% CI, 11–45%) with MA. The sensitivity to detect fibrinogen below 2 g/L was 11% (95% CI, 3–29%) with angle and 21% with MA (95% CI, 8–43%). To detect aPTT more than 40 s and INR more than 1.2 with R-time, the sensitivity was 19% (95% CI, 8–37%) and 0% (95% CI, 0–69%) respectively. The agreement of the evaluator's assessments of hypocoagulation was 100%, but the agreement with the overall TEG^® analysis was poor with a sensitivity of 33% and a specificity of 95%. Conclusion. The agreement between conventional laboratory tests and TEG is poor, but it remains uncertain which type of coagulation tests that best reflects the actual bleeding risk.     

The anticoagulant effect of therapeutic levels of dabigatran in atrial fibrillation evaluated by thrombelastography (TEG®), Hemoclot Thrombin Inhibitor (HTI) assay and Ecarin Clotting Time (ECT)

Monitoring the effect of dabigatran (Pradaxa^®) is challenging. The aim of this study was to evaluate if thrombelastography reaction time (TEG^® R) could detect the anticoagulant effect of dabigatran showing a correlation between TEG^® R, Hemoclot Thrombin Inhibitor (HTI) assay and Ecarin Clotting Time (ECT) in patients with non-valvular atrial fibrillation (NVAF). Blood samples from 35?AF patients receiving either 110?mg (n 19) or 150?mg (n 16) dabigatran twice daily were analyzed with TEG^®, HTI and ECT 2–3?h after dabigatran intake. All patients had prolonged TEG^® R. The patients receiving dabigatran 110?mg ×2 had a TEG^® R mean 14.2?min (range 9.1–25), a mean dabigatran concentration measured by HTI of 268.5?ng/mL (range 54–837?ng/mL) and by ECT of 355.7?ng/mL (range 40–1020?ng/mL). The corresponding numbers for patients receiving dabigatran 150?mg ×2 were TEG^® R mean of 12.5?min (range 9.2–23.2?min), mean dabigatran concentration of 179.2?ng/mL by HTI (range 26–687?ng/mL) and by ECT 225.1?ng/mL (range 42–1020?ng/mL). The two dosage groups had comparable anticoagulation demonstrated by equally prolonged TEG^® R (p?=?.909), HTI (p?=?.707) and ECT (p?=?.567). No difference in creatinine levels in the two dosage groups was observed (p?=?.204) though patients with dabigatran concentration >400?ng/mL had significantly higher creatinine levels (p?=?.001). Large individual variation of the anticoagulant response was observed. Some patients had TEG^® R values up to three times upper normal limit with immediate risk of bleeding. Our data indicate that TEG^® R reflected dabigatran levels in NVAF patients and that TEG^® R correlated to HTI and ECT.     

Enhanced thrombin generation in patients with cirrhosis‐induced coagulopathy

Summary. Background: Prothrombin time (PT) and the international normalized ratio (INR) are still routinely measured in patients with liver cirrhosis to ‘assess’ their bleeding risk despite the lack of correlation with the two. Thrombin generation (TG) assays are global assays of coagulation that are showing promise in assessing bleeding and thrombosis risks. Aim: To study the relationship between the INR and TG profiles in cirrhosis‐induced coagulopathy. Methods: Seventy‐three patients with cirrhosis were studied. All TG parameters were compared with those from a normal control group. Contact activation was prevented using corn trypsin inhibitor. TG was also assayed in the presence of Protac^®. The endogenous thrombin potential (ETP) ratio was derived by dividing the ETP with Protac® by the ETP without Protac®. Results: The INR (mean 1.7) did not correlate with the ETP and the velocity of TG (P > 0.05). There was no difference between the lag time and ETP of the two groups (P > 0.05). The velocity of TG was increased in cirrhosis (67.95 ± 34.8 vs. 45.05 ± 25.9 nM min^?1; P = 0.016) especially in patients with INRs between 1.21 and 2.0. Both the ETP with Protac^® and the ETP ratio were increased in cirrhosis (mean 1074 ± 461.4 vs. 818 ± 357.9 nM min, P = 0.004 and 0.80 ± 0.21 vs. 0.44 ± 0.15, P ≤ 0.0001, respectively). Conclusion: Despite a raised INR, TG parameters are consistent with a hypercoagulable profile in cirrhosis‐related coagulopathy. This confirms that the PT or INR should not be used to assess bleeding risk in these patients, and other parameters, such as TG, need to be explored as clinical markers of coagulopathy.     

Effect of DHA+EPA on oxidative stress and apoptosis induced by ischemia‐reperfusion in rat kidneys

Apoptosis, as well as necrosis, has an important role in post‐ischemic renal pathology. The effect of pretreatment with Docosahexaenoic acid+Eicosapentaenoic acid (DHA+EPA) on renal injury and apoptotic protein expression was evaluated. Right nephrectomy was completed on male Wistar rats (255–300 g). The rats received DHA+EPA (200 mg/kg/day) of distilled water orally for 14 days before ischemia reperfusion (IR) or sham operation. A total of 81 rats were divided into three main groups with 6, 24 and 48 h of post‐operation or reperfusion period. Serum creatinine (SCr), BUN, creatinine clearance (CCr) and fractional excretion of sodium (FE_Na) were measured. Tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) activities, Bax and Bcl‐2 protein expressions and renal histological injury were determined. SCr, BUN and FE_Na increased 6–48 h of reperfusion (P < 0.01). Tissue MDA content and Bax expression increased (P < 0.01) and CAT and SOD activities decreased (P < 0.05) in the IR group. DHA+EPA decreased SCr and BUN, FE_Na, tissue MDA levels (P < 0.05 vs. IR) and increased CAT and SOD activities and Bcl‐2 expression (P < 0.05 vs. IR) for 6–48 h after ischemia. IR induced mild (6 h, P < 0.05) and severe (24–48 h, P < 0.01) tissue damage. Mild‐to‐moderate tissue damage was observed in DHA+EPA groups from 6 to 48 h of reperfusion period (P < 0.05 vs. IR, 24–48 h). In conclusion, the results suggest that pre‐ischemic exposure to DHA+EPA could improve the outcome of early graft function by inhibition of IR‐induced oxidative stress and apoptosis.     

Comparison of bioimpedance and radioisotope methods in the estimation of extracellular water volume before and after coronary artery bypass grafting operation

To estimate extracellular water volume (ECW) changes in connection with coronary artery bypass grafting operation, simultaneous ECW estimations by ⁵¹Cr‐EDTA dilution and whole‐body bioimpedance techniques were performed in 15 patients. The assessments of ECW were compared with patients’ weighing results. Whole‐body bioimpedance‐derived ECW correlated significantly with ⁵¹Cr‐EDTA dilution‐based ECW in the pre‐operative period (r=0·74; P<0·005); the bias was 0·2 ± 1·1 l (±SD). In the post‐operative period, the agreement between these methods was poor, the bias being 0·5 ± 2·5 l, and no significant correlation between the methods was found (r=0·38; P>0·05). Whole‐body bioimpedance‐derived ECW changes correlated significantly with weight changes of the patient induced by the operation (r=0·52; P<0·05). ⁵¹Cr‐EDTA dilution‐based ECW changes correlated neither with weight changes (r=0·33; P>0·05) nor with bioimpedance‐derived ECW changes (r=0·03; P>0·05). Alterations in radioisotope tracer distribution and loss of it due to blood leakage in the post‐operative period were presumed to explain the discrepancy between dilution technique and weighing results. The results suggest that bioimpedance is a useful non‐invasive method for assessment of extracellular volume changes induced by coronary artery bypass grafting operations. ⁵¹Cr‐EDTA dilution‐based ECW determination is not suitable in related conditions.     

Sensory responses to mechanically and chemically induced tendon pain in healthy subjects

This investigation aimed to quantify and compare sensory responses to hypertonic saline‐induced pain in the tendoachilles and the common extensor tendon of the elbow. Healthy subjects (n =14; seven males) received in randomised order, injections of sterile saline (0.5 ml, 5.8% hypertonic or 0.9% isotonic saline) at each tendon bilaterally at two sessions separated by one week. Mechanical sensitivity (pressure pain threshold), muscle pain intensity (visual analogue scale; VAS area‐under‐curve, pain duration, peak pain) and pain distribution were assessed pre, immediately after and post saline injection. Hypertonic saline‐induced pain intensity (VAS area‐under‐curve, duration and peak) was significantly greater compared with control injections (P <0.001) and induced significantly greater VAS area (P <0.01) and longer pain duration (P <0.001) in tendoachilles compared with the common extensor tendon. Regardless of saline type and compared with pre and post injection, mechanical sensitivity increased significantly (P <0.01) immediately after injections at all injected tendon sites. Hypertonic saline‐induced referred pain was infrequent (tendoachilles: n =3 and common extensor tendon: n =4). Significant maximal force attenuation occurred immediately after hypertonic saline injections in both tendons (P <0.001) compared with control injections. The greater induced deep tissue pain and hyperalgesia demonstrated at tendoachilles compared with the common extensor tendon may relate to anatomical differences such as higher nociceptor density or increased vascular perfusion at the injection site. This translational tendon pain model may contribute to the further understanding of pain mechanisms in tendinopathic conditions.     

Aspirin ‘resistance’: role of pre‐existent platelet reactivity and correlation between tests

Summary. Background: Aspirin ‘resistance’ is a widely used term for hyporesponsiveness to aspirin in a platelet function test. Serum thromboxane (TX) B₂ is the most specific test of aspirin’s effect on platelets. Objectives: (i) To examine the role of pre‐existent platelet hyperreactivity in aspirin ‘resistance’. (ii) To determine the correlation between aspirin resistance defined by serum TXB₂ and other assays of platelet function. Methods: To enable pre‐aspirin samples to be drawn, platelet function was measured in normal subjects (n = 165) before and after aspirin 81 mg daily for seven days. Results: The proportion of the post‐aspirin platelet function predicted by the pre‐aspirin platelet function was 28.3 ± 7.5% (mean ± asymptotic standard error) for serum TXB₂, 39.3 ± 6.8% for urinary 11‐dehydro TXB₂, 4.4 ± 7.7% for arachidonic acid‐induced platelet aggregation, 40.4 ± 7.1% for adenosine diphosphate‐induced platelet aggregation, 26.3 ± 9.2% for the VerifyNow Aspirin Assay^®, and 45.0 ± 10.9% for the TEG^® PlateletMapping? System with arachidonic acid. There was poor agreement between aspirin‐resistant subjects identified by serum TXB₂ vs. aspirin‐resistant subjects identified by the other five assays, irrespective of whether the analysis was based on categorical or continuous variables. Platelet count correlated with pre‐aspirin serum TXB₂ and VerifyNow Aspirin Assay, but not with any post‐aspirin platelet function test. Conclusions: (i) Aspirin ‘resistance’ (i.e. hyporesponsiveness to aspirin in a laboratory test) is in part unrelated to aspirin but is the result of underlying platelet hyperreactivity prior to the institution of aspirin therapy. (ii) Aspirin resistance defined by serum TXB₂ shows a poor correlation with aspirin resistance defined by other commonly used assays.     

Plasma angiopoietin-2 levels increase in children following cardiopulmonary bypass

Objective  The aim was to investigate the effects of cardiopulmonary bypass (CPB) on plasma levels of the vascular growth factors, angiopoietin (angpt)-1, angpt-2, and vascular endothelial growth factor (VEGF). Design  The design was a prospective, clinical investigation. Setting  The setting was a 12-bed pediatric cardiac intensive care unit of a tertiary children’s medical center. Patients  The patients were 48 children (median age, 5 months) undergoing surgical correction or palliation of congenital heart disease who were prospectively enrolled following informed consent. Interventions  There were no interventions in this study. Measurements and results  Plasma samples were obtained at baseline and at 0, 6, and 24 h following CPB. Angpt-1, angpt-2, and VEGF levels were measured via commercial ELISA. Angpt-2 levels increased by 6 h (0.95, IQR 0.43–2.08 ng mL⁻¹ vs. 4.62, IQR 1.16–6.93 ng mL⁻¹, P < 0.05) and remained significantly elevated at 24 h after CPB (1.85, IQR 0.70–2.76 ng mL⁻¹; P < 0.05). Angpt-1 levels remained unchanged immediately after CPB, but were significantly decreased at 24 h after CPB (0.64, IQR 0.40–1.62 ng mL⁻¹ vs. 1.99, IQR 1.23–2.63 ng mL⁻¹, P < 0.05). Angpt-2 levels correlated significantly with cardiac intensive care unit (CICU) length of stay (LOS) and were an independent predictor for CICU LOS on subsequent multivariate analysis. Conclusions  Angpt-2 appears to be an important biomarker of adverse outcome following CPB in children.     

Prediction of post‐operative glomerular filtration rate after nephrectomy for renal malignancy

The importance of a correct estimation of contralateral renal function in cases of renal malignancy is obvious, necessitating a conservative approach to tumour resection when function of the contralateral kidney is markedly reduced. The aim of the present study was to determine the accuracy of preoperative gamma camera renography and ⁵¹Cr‐EDTA clearance to predict the glomerular filtration rate (GFR) early and up to 6 months after nephrectomy for renal malignancy. Patients (n=40) underwent both gamma camera renography (^99mTC‐DTPA) and ⁵¹Cr‐EDTA clearance preoperatively, whereas ⁵¹Cr‐EDTA clearance was measured within 1 week and up to 6 months after nephrectomy. The single kidney GFR values of the contralateral kidneys were estimated preoperatively and then compared with the post‐operative ⁵¹Cr‐EDTA clearance values. The predicted GFR values were lower compared with the measured post‐operative ⁵¹Cr‐EDTA clearance values (45 ± 2 vs. 54 ± 3 ml min^–1 1 week after nephrectomy and 53 ± 3 ml min^–1 6 months later, P<0·01, respectively). The difference between the measured and predicted GFR was larger in patients below the median age of 60 years (P<0·05) and confined to patients with a relative uptake of >30% by the tumour affected kidney. Prediction of post‐operative GFR by non‐invasive renal function tests performed prior to surgery for renal malignancy underestimate post‐operative GFR when the function of the tumour affected kidney is preserved, indicating an adaptive GFR increase in these cases.     

Influence of exercise intensity on systemic oxidative stress and antioxidant capacity

The aim of the current study was to examine the influence of exercise intensity on systemic oxidative stress (OS) and endogenous antioxidant capacity. Non‐smoking, sedentary healthy adult males (n = 14) participated in two exercise sessions using an electronically braked cycle ergometer. The first session consisted of a graded exercise test to determine maximal power output and oxygen consumption (VO_2max). One week later, participants undertook 5‐min cycling bouts at 40%, 55%, 70%, 85% and 100% of VO_2max, with passive 12‐min rest between stages. Measures of systemic OS reactive oxygen metabolites (dROM), biological antioxidant potential (BAP), heart rate (HR), VO₂, blood lactate and rating of perceived exertion were assessed at rest and immediately following each exercise stage. Significant (P<0·05) differences between exercise bouts were examined via repeated measures ANOVA and post hoc pairwise comparisons with Bonferroni correction. Increasing exercise intensity significantly augmented HR (P<0·001), VO₂ (P<0·001), blood lactate (P<0·001) and perceived exertion (P<0·001) with no significant effect on dROM levels compared with resting values. In contrast, increasing exercise intensity resulted in significantly (P<0·01) greater BAP at 70% (2427 ± 106), 85% (2625 ± 121) and 100% (2651 ± 92) of VO_2max compared with resting levels (2105 ± 57 μmol Fe²⁺/L). The current results indicate that brief, moderate‐to‐high‐intensity exercise significantly elevates endogenous antioxidant defences, possibly to counteract increased levels of exercise‐induced reactive oxygen species. Regular moderate‐to‐high‐intensity exercise may protect against chronic OS associated diseases via activation, and subsequent upregulation of the endogenous antioxidant defence system.     

Effects of rest intervals and training loads on metabolic stress and muscle hypertrophy

We investigated the effects of volume‐matched resistance training (RT) with different training loads and rest intervals on acute responses and long‐term muscle and strength gains. Ten subjects trained with short rest (30 s) combined with low load (20 RM) (SL) and ten subjects performed the same protocol with long rest (3 min) and high load (8 RM) (LH). Cross‐sectional area (CSA) of the upper arm was measured by magnetic resonance imaging before and after 8 weeks of training. Acute stress markers such as growth hormone (GH) and muscle thickness (MT) changes have been assessed pre and post a single RT session. Only the SL group demonstrated significant increases in GH (7704·20 ± 11833·49%, P<0·05) and MT (35·2 ± 16·9%, P<0·05) immediately after training. After 8 weeks, the arm CSA s in both groups significantly increased [SL: 9·93 ± 4·86% (P<0·001), LH: 4·73 ± 3·01% (P<0·05)]. No significant correlation between acute GH elevations and CSA increases could be observed. We conclude that short rest combined with low‐load training might induce a high amount of metabolic stress ultimately leading to improved muscle hypertrophy while long rest with high‐load training might lead to superior strength increases. Acute GH increases seem not to be directly correlated with muscle hypertrophy.     

Safety and efficacy of protease‐activated receptor‐1 antagonists in patients with coronary artery disease: a meta‐analysis of randomized clinical trials

Summary. Background: Thrombin receptor antagonists blocking protease‐activated receptor‐1 (PAR‐1) on platelets represent a new class of oral antiplatelet agents for patients with atherothrombotic disease manifestations. Objectives: We investigated the safety and efficacy of PAR‐1 antagonists in patients with coronary artery disease (CAD). Patients/Methods: Randomized, placebo‐controlled trials of the PAR‐1 antagonists atopaxar or vorapaxar in CAD patients were identified. The primary safety endpoint was the composite of Thrombolysis In Myocardial Infarction (TIMI) clinically significant bleeding. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke. Results: A total of 41 647 patients from eight trials were included. PAR‐1 antagonists were associated with higher risks of TIMI clinically significant (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.39–1.57, P < 0.001), major (OR 1.46, 95% CI 1.28–1.67, P < 0.001) and minor (OR 1.67, 95% CI 1.40–2.00, P < 0.001) bleeding than placebo in the fixed‐effects model. PAR‐1 antagonists reduced the composite of death, MI or stroke as compared with placebo (OR 0.87, 95% CI 0.81–0.92, P < 0.001), driven by a lower risk of MI (OR 0.85, 95% CI 0.78–0.92, P < 0.001). Conversely, PAR‐1 antagonists and placebo did not differ in terms of risk of death (OR 0.99, 95% CI 0.90–1.09, P = 0.81) or stroke (OR 0.96, 95% CI 0.84–1.10, P = 0.59). Conclusions: PAR‐1 antagonists decrease ischemic events in patients with CAD as compared with placebo, mainly driven by a reduction in MI, at the cost of an increased risk of clinically significant bleeding.     

The effectiveness of a brief motivational nursing intervention to reduce psychoactive substance consumption in entertainment‐sector workers: A transversal,observation, and semi‐experimental study

Checking whether changes in the perception of the quality of life related to health, after the nursing intervention, influence these patients’ motivation to change. This was a two‐staged study undertaken in entertainment‐sector workers in Spain: the first part was transversal and observational, and the second was semi‐experimental. First part undertook in 284 entertainment‐sector workers, selected by non‐probabilistic sampling, while second part undertook in 50 entertainment‐business workers, selected by consecutive sampling from those who consumed substances. A short group‐based motivational intervention session was implemented by nursing staff, and a before and after evaluation was completed. The EuroQol‐5D and Test for the Evaluation of the Quality of Life in Addicts to Psychoactive Substances (TECVASP) were used. The patients’ motivation to change was evaluated through the Stages of Change Readiness and Treatment Eagerness Scale. The results analysis showed that the nursing intervention reduced the participants’ perceptions of their health‐related quality of life (t = 4.23; P = 0.00009) and of their quality of life in addicts to psychoactive substances (t = 3.38; P = 0.00140). There was an increase in the motivation of 6 workers (12%) to seek treatment of their addiction (χ² = 13.02; P = 0.0091). The post‐test contemplation stage score was predicted (F = 6.56; P = 0.003; R = 0.46) with post‐test TECVASP score and pre–post difference in TECVASP score. By reducing the patients’ perception of their quality of life, this brief nursing intervention facilitated a favourable increase in the motivation for change among these workers and was effective in 12% of cases.     

Effects of short‐term detraining following blood flow restricted low‐intensity training on muscle size and strength

We investigated the effects of 3 weeks of detraining on muscle cross‐sectional area (CSA) and one‐repetition maximum strength (1‐RM) in young men who had previously participated in 6 weeks (3 days week^?1) of bench press training [blood flow restricted low‐intensity (LI‐BFR; n = 10, 20% 1‐RM) or high‐intensity (HI; n = 7, 75% 1‐RM)]. Bench press 1‐RM and muscle CSA of triceps brachii (TB) and pectoralis major (PM) were evaluated before (pre) and after training period (post) as well as after detraining period (detraining). Bench press 1‐RM was higher at both post and detraining than at pre for LI‐BFR (P<0·01) and the HI (P<0·01). TB and PM muscle CSA were higher at both post and detraining than at pre for the HI group (P<0·01), while the LI‐BFR group only increased (P<0·01) at post. Relative dynamic strength (1‐RM divided by TB muscle CSA) was higher at both post and detraining than at pre for the HI group (P<0·01), while the LI‐BFR group only increased (P<0·01) at detraining. In conclusion, increased muscle strength following 6 weeks of training with LI‐BFR as well as HI was well preserved at 3 weeks of detraining. HI‐induced muscle strength appears to be dependent upon both neural adaptations and muscle hypertrophy with training and detraining. On the other hand, LI‐BFR‐induced muscle strength appears to be related primarily to muscle hypertrophy with training and to neural adaptations with detraining.     

Effect of Icosapent Ethyl on Gynoid Fat and Bone Mineral Health in the Metabolic Syndrome: A Preliminary Report

PurposeThe metabolic syndrome (MetS) is a systemic disorder associated with reduced atheroprotective gynoid fat and bone mineral content (BMC). The goal of this pilot study was to assess whether administration of icosapent ethyl (IPE), a purified formulation of eicosapentaenoic acid, would maintain gynoid fat and BMC over a 9-month treatment period.MethodsPatients with MetS aged ≥40 years were randomly assigned to receive 4 g daily of IPE (2 g BID with food) or placebo (paraffin oil 2 g BID with food) for 9 months. Data were collected at baseline and 9 months later. The data included anthropometric measures, biochemical analysis, and whole body fat mass, including gynoid fat. Bone mineral density and BMC were measured by using dual-energy X-ray absorptiometry. A two-tailed P value ≤ 0.05 was considered statistically significant.FindingsThe study sample consisted of 13 patients with MetS (mean age, 61.6 years; age range, 44–77 years; 77% female and 23% male). Compared with the IPE group, the placebo group experienced statistically significant mean reductions in percent gynoid fat (pre/post, 46.8%–43.5%; P = 0.02), BMC (pre/post, 2461 g–2423 g; P = 0.02), and bone mineral density (pre/post, 1.24 g/cm² to 1.22 g/cm²; P = 0.05) over the 9-month study period.ImplicationsThe results of this pilot study raise the possibility that IPE supplementation may preserve gynoid fat distribution and bone mineral health in patients with MetS. Larger, randomized longitudinal studies are necessary to determine the potential long-term metabolic benefits of IPE treatment.     

Impact of a modified nursing handover model for improving nursing care and documentation in the emergency department: A pre‐ and post‐implementation study

The aim of this study was to evaluate whether implementation of a new nursing handover model led to improved completion of nursing care activities and documentation. A pre‐ and post‐implementation study, using a survey and document audit, was conducted in a hospital ED in Melbourne. A convenience sample of nurses completed the survey at baseline (n = 67) and post‐intervention (n = 59), and the audit was completed at both time points. Results showed significant improvements in several processes: handover in front of the patient (P < 0.001), patients contributed and/or listened to handover discussions (P < 0.001), and provision of adequate information about all patients in the department (P < 0.001). Nurses also reported a reduction in omission of vital signs (P = 0.022) during handover. Three hundred sixty‐eight medical records were audited in the two study periods: 173 (pre‐intervention) and 195 (post‐intervention). Statistically significant improvements in the completion of two nursing care tasks and three documentation items were identified. The findings suggest that implementation of a new handover model improved completion of nursing care activities and documentation, and transfer of important information to nurses on oncoming shifts.     

Effectiveness of prothrombin complex concentrate for the treatment of bleeding: A systematic review and meta‐analysis

Prothrombin complex concentrate (PCC) is increasingly being used as a treatment for major bleeding in patients who are not taking anticoagulants. The aim of this systematic review and meta‐analysis is to evaluate the effectiveness of PCC administration for the treatment of bleeding in patients not taking anticoagulants. Studies investigating the effectivity of PCC to treat bleeding in adult patients and providing data on either mortality or blood loss were eligible. Data were pooled using Mantel‐Haenszel random effects meta‐analysis or inverse variance random effects meta‐analysis. From 4668 identified studies, 17 observational studies were included. In all patient groups combined, PCC administration was not associated with mortality (odds ratio = 0.83; 95% confidence interval [CI], 0.66‐1.06; P = .13; I² = 0%). However, in trauma patients, PCC administration, in addition to fresh frozen plasma, was associated with reduced mortality (odds ratio = 0.64; CI, 0.46‐0.88; P = .007; I² = 0%). PCC administration was associated with a reduction in blood loss in cardiac surgery patients (mean difference: ?384; CI, ?640 to ?128, P = .003, I² = 81%) and a decreased need for red blood cell transfusions when compared with standard care across a wide range of bleeding patients not taking anticoagulants (mean difference: ?1.80; CI, ?3.22 to ?0.38; P = .01; I² = 92%). In conclusion, PCC administration was not associated with reduced mortality in the whole cohort but did reduce mortality in trauma patients. In bleeding patients, PCC reduced the need for red blood cell transfusions when compared with treatment strategies not involving PCC. In bleeding cardiac surgery patients, PCC administration reduced blood loss.     

Sumatriptan reduces severity of status epilepticus induced by lithium–pilocarpine through nitrergic transmission and 5‐HT1B/D receptors in rats: A pharmacological‐based evidence

Status epilepticus (SE) is a life‐threatening neurologic disorder that can be as both cause and consequence of neuroinflammation. In addition to previous reports on anti‐inflammatory property of the anti‐migraine medication sumatriptan, we have recently shown its anticonvulsive effects on pentylenetetrazole‐induced seizure in mice. In the present study, we investigated further (i) the effects of sumatriptan in the lithium–pilocarpine SE model in rats, and (ii) the possible involvement of nitric oxide (NO), 5‐hydroxytryptamin 1B/1D (5‐HT_1B/1D) receptor, and inflammatory pathways in such effects of sumatriptan. Status epilepticus was induced by lithium chloride (127 mg/kg, i.p) and pilocarpine (60 mg/kg, i.p.) in Wistar rats. While SE induction increased SE scores and mortality rate, sumatriptan (0.001‐1 mg/kg, i.p.) improved it (P < 0.001). Administration of the selective 5‐HT_1B/1D antagonist GR‐127935 (0.01 mg/kg, i.p.) reversed the anticonvulsive effects of sumatriptan (0.01 mg/kg, i.p.). Although both tumor necrosis factor‐α (TNF‐α) and NO levels were markedly elevated in the rats' brain tissues post‐SE induction, pre‐treatment with sumatriptan significantly reduced both TNF‐α (P < 0.05) and NO (P < 0.001) levels. Combined GR‐127935 and sumatriptan treatment inhibited these anti‐inflammatory effects of sumatriptan, whereas combined non‐specific NOS (L‐NAME) or selective neuronal NOS (7‐nitroindazole) inhibitors and sumatriptan further reduced NO levels. In conclusion, sumatriptan exerted a protective effect against the clinical manifestations and mortality rate of SE in rats which is possibly through targeting 5‐HT_1B/1D receptors, neuroinflammation, and nitrergic transmission.     

A comparison of dynamic contrast‐enhanced CT and MR imaging‐derived measurements in patients with cervical cancer

This work is to compare the kinetic parameters derived from the DCE‐CT and ‐MR data of a group of 37 patients with cervical cancer. The modified Tofts model and the reference tissue method were applied to estimate kinetic parameters. In the MR kinetic analyses using the modified Tofts model for each patient data set, both the arterial input function (AIF) measured from DCE‐MR images and a population‐averaged AIF from the literature were applied to the analyses, while the measured AIF was used for the CT kinetic analysis. The kinetic parameters obtained from both modalities were compared. Significant moderate correlations were found in modified Tofts parameters [volume transfer constant(K^trans) and rate constant (k_ep)] between CT and MR analysis for MR with the measured AIFs (R = 0·45, P<0·01 and R = 0·40, P<0·01 in high‐K^trans region; R = 0·38, P<0·01 and R = 0·80, P<0·01 in low‐K^trans region) as well as with the population‐averaged AIF (R = 0·59, P<0·01 and R = 0·62, P<0·01 in high‐K^trans region; R = 0·50, P<0·01 and R = 0·63, P<0·01 in low‐K^trans region), respectively. In addition, from the Bland–Altman plot analysis, it was found that the systematic biases (the mean difference) between the modalities were drastically reduced in magnitude by adopting the population‐averaged AIF for the MR analysis instead of the measured ones (from 51·5% to 18·9% for K^trans and from 21·7% to 4·1% for k_ep in high‐K^trans region; from 73·0% to 29·4% for K^trans and from 63·4% to 24·5% for k_ep in low‐K^trans region). The preliminary results showed the feasibility in the interchangeable use of the two imaging modalities in assessing cervical cancers.