A comparative analysis of tranexamic acid dosing strategies in traumatic major hemorrhage.

INTRODUCTION: Tranexamic acid (TXA) is a life-saving treatment for traumatic hemorrhage, but the optimal dosing regimen remains unknown. Different doses and treatment strategies have been proposed, including single bolus, repeated bolus, or bolus plus infusion. The aim of this study was to determine the effect of different TXA dosing strategies on clinical outcomes in bleeding trauma patients. METHODS: Secondary analysis of a perpetual cohort study from a UK Level I trauma center. Adult patients who activated the local major hemorrhage protocol and received TXA were included. The primary outcome was 28-day mortality. Secondary outcomes were 24-hour mortality, multiple organ dysfunction syndrome, venous thromboembolism, and rotational thromboelastometry fibrinolysis. RESULTS: Over an 11-year period, 525 patients were included. Three dosing groups were identified: 1 g bolus only (n = 317), 1 g bolus +1 g infusion over 8 hours (n = 80), and 2 g bolus (n = 128). Demographics and admission physiology were similar, but there were differences in injury severity (median Injury Severity Score, 25, 29, and 25); and admission systolic blood pressure (median Systolic Blood Pressure, 99, 108, 99 mm Hg) across the 1-g, 1 g + 1 g, and 2-g groups. 28-day mortality was 21% in each treatment group. The incidence of multiple organ dysfunction syndrome was significantly higher in the bolus plus infusion group (84%) vs. 1 g bolus (64%) and 2 g bolus (62%) group, p = 0.002, but on multivariable analysis was nonsignificant. Venous thromboembolism rates were similar in the 1-g bolus (4%), 2 g bolus (8%) and bolus plus infusion groups (7%). There was no difference in rotational thromboelastometry maximum lysis at 24 hours: 5% in both the 1-g and 2-g bolus groups vs. 4% in bolus plus infusion group. CONCLUSION: Clinical outcomes and 24-hour fibrinolysis state were equivalent across three different dosing strategies of TXA. Single bolus administration is likely preferable to a bolus plus infusion regimen. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Nationwide analysis of prehospital tranexamic acid for trauma demonstrates systematic bias in adherence to treatment guidelines: a retrospective cohort study.

BACKGROUND: Prehospital (PH) tranexamic acid (TXA) improves survival from trauma haemorrhage. Injury mechanism, physiology, and sex demographics vary with patient age. The authors hypothesised that these factors influence TXA guideline compliance and examined national trends in PH use to identify any systematic biases in bleeding management. MATERIALS AND METHODS: The UK Trauma Audit and Research Network data for TXA eligible patients admitted to major trauma centres were divided into two cohorts: 2013-2015 ( n =32 072) and 2017-2019 ( n =14 974). Patients were stratified by PH, emergency department or no TXA use. Logistic regression models explored interaction between PH variables and TXA administration. Results are presented as odds ratios with a 95% CI. RESULTS: PH TXA use increased from 8% to 27% over time ( P <0.001). Only 3% of eligible patients who fell less than 2 m received PH TXA versus 63% with penetrating injuries ( P <0.001). Older patients eligible for PH TXA were less likely to receive it compared to younger patients [≥65 years old: 590 (13%) vs. <65 years old: 3361 (33%), P <0.001]. There was a significant interaction between age and sex with fewer older women receiving PH TXA. In shocked patients, one third of females compared to a fifth of men did not receive TXA ( P <0.001). There was a decrease in PH TXA use as age increased ( P <0.001). CONCLUSIONS: Despite a threefold increase in use, treatment guidance for PH TXA is not universally applied. Older people, women, and patients with low energy injury mechanisms appear to be systematically under treated. Training and education for PH providers should address these potential treatment biases.

Global burden of active smoking among people living with HIV on antiretroviral therapy: a systematic review and meta-analysis.

BACKGROUND: Although the high burden of both active smoking and human immunodeficiency virus (HIV) is clearly known, the relationship between them is still not well characterized. Therefore, we estimated the global prevalence of active smoking in people living with HIV (PLHIV) on antiretroviral therapy (ART) and investigated the association between exposure to active smoking and risk for suboptimal adherence to ART. Main text: We searched PubMed, Embase, and Web of Science to identify articles published until September 19, 2019. Eligible studies reported the prevalence of active smoking in PLHIV on ART or investigated the association between active smoking and ART adherence; or enough data to compute these estimates. We used a random-effects model to pool data and quantified heterogeneity (I2). The global prevalence of active smoking was 36.1% (95% CI: 33.7-37.2; 329 prevalence data; 462 104 participants) with substantial heterogeneity. The prevalence increased with level of country income; from 10.1% (95% CI: 6.8-14.1) in low-income to 45.2% (95% CI: 42.7-47.7) in high-income countries; P < 0.0001. With regards to the Joint United Nations Programme on HIV/AIDS (UNAIDS) regions, the prevalence was higher in West and Central Europe and North America 45.4% (42.7-48.1) and lowest in the two UNAIDS regions of sub-Saharan Africa: Eastern and Southern Africa 10.7% (95% CI: 7.8-14.0) and West and Central Africa 4.4% (2.9-6.3); P < 0.0001. Globally, we estimated that there were 4 110 669 PLHIV on ART who were active smokers, among which the highest number was from Eastern and Southern Africa (35.9%) followed by Asia and the Pacific (25.9%). Active smoking was significantly associated with suboptimal ART adherence: pooled odds ratio 1.57 (95% CI: 1.37-1.80; I2 = 56.8%; 19 studies; 48 450 participants); even after considering adjusted estimates: 1.67 (95% CI: 1.39-2.01; I2 = 53.0%; 14 studies). CONCLUSIONS: This study suggests a high prevalence of active smoking in PLHIV on ART and an association between active smoking and ART suboptimal adherence. As such, healthcare providers and policy makers should focus on adopting and implementing tobacco harm reduction strategies in HIV care, especially in sub-Saharan Africa known as epicenter of HIV pandemic with highest number of active tobacco smoking among PLHIV on ART.

The impact of prehospital TXA on mortality among bleeding trauma patients: A systematic review and meta-analysis.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic drug associated with improved survival among trauma patients with hemorrhage. Tranexamic acid is considered a primary hemostatic intervention in prehospital for treatment of bleeding alongside blood product transfusion. METHODS: A systematic review and meta-analysis was conducted to investigate the impact of prehospital TXA on mortality among trauma patients with bleeding. A systematic search was conducted using the National Institute for Health and Care Excellence Healthcare Databases Advanced Search library which contain the following of databases: EMBASE, Medline, PubMed, BNI, EMCARE, and HMIC. Other databases searched included SCOPUS and the Cochrane Central Register for Clinical Trials Library. Quality assessment tools were applied among included studies; Cochrane Risk of Bias for randomized control trials and Newcastle-Ottawa Scale for cohort observational studies. RESULTS: A total of 797 publications were identified from the initial database search. After removing duplicates and applying inclusion/exclusion criteria, four studies were included in the review and meta-analysis which identified a significant survival benefit in patients who received prehospital TXA versus no TXA. Three observational cohort and one randomized control trial were included into the review with a total of 2,347 patients (TXA, 1,169 vs. no TXA, 1,178). There was a significant reduction in 24 hours mortality; odds ratio (OR) of 0.60 (95% confidence interval [CI], 0.37-0.99). No statistical significant differences in 28 days to 30 days mortality; OR of 0.69 (95% CI, 0.47-1.02), or venous thromboembolism OR of 1.49 (95% CI, 0.90-2.46) were found. CONCLUSION: This review demonstrates that prehospital TXA is associated with significant reductions in the early (24 hour) mortality of trauma patients with suspected or confirmed hemorrhage but no increase in the incidence of venous thromboembolism. LEVEL OF EVIDENCE: Systematic review and meta-analysis. Level I.