A ten-year comparison of treatment and outcomes of cancer-associated thrombosis to non-cancer venous thromboembolism: from traditional anticoagulants to direct oral anticoagulants.

DOACs have emerged as first-line treatment in most cancer-associated thrombosis (CAT), representing a paradigm shift in its management. However, CAT management remains challenging and requires careful risk-benefit considerations. A retrospective analysis of CAT presentations to a tertiary referral centre from January 2011 to December 2020. Outcomes in CAT patients were compared to VTE patients without malignancy. Subgroup analysis was also conducted for CAT according to anticoagulation type. 514 CAT cases from 491 patients were identified from 3230 total VTE cases. CAT patients had higher rates of major VTE (PE and/or proximal DVT) compared to patients without malignancy (78.4% vs. 66.8%, p < 0.001). CAT patients also had higher rates of VTE recurrence (HR 1.66, 95%CI 1.23-2.26), major bleeding (HR 3.41, 95%CI 2.36-4.93), VTE-related mortality (HR 2.59, 95%CI 1.46-4.62) and bleeding-related mortality (HR 2.66, 95%CI 1.05-6.73). There were no significant differences in rates of VTE recurrence, major bleeding, VTE-related mortality or fatal bleeding between CAT patients treated with DOACs, enoxaparin or warfarin. In the subgroup of CAT treated with DOACs, there was no significant difference in rates of GI bleeding compared to the enoxaparin subgroup (HR 0.17, 95%CI 0.02-1.26). CAT was associated with a larger clot burden and higher rates of VTE recurrence, major bleeding and mortality compared to VTE patients without malignancy in this large real-world study. This study demonstrated no significant differences in complication rates for CAT patients treated with DOACs over enoxaparin, suggesting that DOACs can be safely used in most cases of CAT.

Management of venous thromboembolism in morbidly obese patients: a 10-year review.

Obesity is a known risk factor for venous thromboembolism (VTE) and poses a unique set of challenges in anticoagulation management. We report a 10-year experience of VTE management in morbidly obese patients. We conducted a retrospective analysis of VTE presentations to Northern Health, Victoria, Australia, from January 2011 to December 2020, with median follow-up of 44 months. Morbidly obese patients (defined as weighing > 120 kg) were compared to those ≤ 120 kg. Patients with active malignancy were excluded. 194 VTE cases with weight > 120 kg were compared to 2168 cases weighing ≤ 120 kg. Patients > 120 kg were more likely to present with unprovoked VTE (59.3% vs. 45.2%, p < 0.001) and major VTE (74.7% vs. 67.4%, p = 0.028). Overall, patients > 120 kg were more likely to develop VTE recurrence after anticoagulation cessation (7.80 vs. 3.92 per 100-patient-years, HR 1.97, 95%CI 1.29-3.00), while there were no significant differences in major bleeding or 30-day all-cause mortality. There were no significant differences in outcomes in patients > 120 kg treated with warfarin compared to direct oral anticoagulants (DOAC), or when comparing those treated with an uncapped (1 mg/kg BD) vs. capped (< 1 mg/kg) enoxaparin dosing regimen. Morbid obesity is associated with increased clot burden at presentation and VTE recurrence following anticoagulation cessation, without significant differences in bleeding compared to those ≤ 120 kg. There were no significant differences in morbidly obese patients' outcomes when treated with warfarin or DOAC, or when treated with an uncapped or capped enoxaparin dosing strategy. Larger randomised controlled trials evaluating the safety of DOACs and different enoxaparin dosing strategies in patients > 120 kg are warranted.

A ten-year review of the impact of the transition from warfarin to direct oral anticoagulant - Has venous thromboembolism treatment become safer?

BACKGROUND: The introduction of direct oral anticoagulants (DOAC) has resulted in a paradigm shift in the management of venous thromboembolism (VTE). We evaluate the impact of the transition to DOAC, over the last decade, on overall VTE clinical outcomes including in first unprovoked major VTEs. METHOD: A retrospective analysis of all VTE admissions in non-cancer patients from January 2011 to December 2020 at Northern Health, Victoria, Australia. "Warfarin era" included events that occurred between January 2011 and December 2014 and "DOAC era" from January 2016. RESULTS: There were 2687 cases involving 2508 patients (45.9 % males; median age 63 years). 98 % were symptomatic and 1261 events (47 %) were unprovoked. 1003 events occurred during the warfarin era (79 % warfarin, 6 % DOAC) and 1479 during the DOAC era (18 % warfarin, 70 % DOAC). While recurrent thrombosis during the acute phase of treatment was comparable, there were fewer recurrences during the long-term preventative phase of treatment in the DOAC era compared to warfarin era (HR 0.602, 95 % CI: 0.393-0.924, p0.020). Clinically significant bleeding events were lower in the DOAC era (HR 0.623, 95 % CI: 0.395-0.985, p = 0.043). A subanalysis of first unprovoked major VTE events (n = 602) demonstrated a significant reduction in recurrent VTE during the long-term preventative phase of treatment in the DOAC era (HR 0.296, 95 % CI: 0.097-0.901, p = 0.032) with no difference in clinically significantly bleeding rates (HR 0.529, 95 % CI 0.219-1.280, p = 0.158) between the eras. CONCLUSION: Treatment outcomes for VTE appear to have improved over time with reduced rate of thrombotic and clinically significant bleeding complications in the DOAC era.

Ameloblastoma: A succinct review of the classification, genetic understanding and novel molecular targeted therapies.

Ameloblastomas are benign but locally invasive neoplasms which may grow to massive proportions and cause significant morbidity. Although some types of ameloblastoma can be treated predictably with aggressive surgical treatment, recurrent ameloblastoma and metastasising ameloblastoma are still difficult to treat. Recent studies have identified recurrent somatic and activating mutations in the mitogen-activated protein kinase (MAPK) and sonic hedgehog (SHH) signalling pathways in ameloblastoma. This development provided a possibility that molecular targeted therapies can be used as neoadjuvant treatment. In this review, we provide a summary of the latest WHO classification of ameloblastoma, the current understanding of genetic mutations and novel molecular targeted therapies arising from the recent developments.

A narrative review of heart rate and variability in sepsis.

Clinicians face challenges in the timely diagnosis and management of pediatric sepsis. Pediatric heart rate has been incorporated into early warning systems and studied as a predictor for critical illness. We aim to review: (I) the role of heart rate in pediatric warning systems and (II) the role of heart rate variability (HRV) in adult and neonatal sepsis, with a focus on its potential applications in pediatrics. We conducted a literature search for papers published up to December 2019 on the utility of heart rate and HRV analysis in the diagnosis and management of sepsis, using four medical databases: PubMed, Google Scholar, EMBASE and Web of Science. This review demonstrates that the clinical utility of pediatric heart rate in predicting clinical deterioration is limited by the lack of consensus among warning systems, consensus-based guidelines, and evidence-based studies as to what constitutes abnormal heart rate in the pediatric age group. Current studies demonstrate that abnormal heart rate itself does not adequately discriminate children with sepsis from those without. HRV analysis provides a quick and non-invasive method of assessment and can provide more information than traditional heart rate. HRV analysis has the potential to add value in identification and prognostication of adult and neonatal sepsis. With further studies to explore its role, HRV analysis has the potential to add to current tools in the diagnosis and prognosis of pediatric sepsis.

Novel anticoagulants in atrial fibrillation stroke prevention.

This review article evaluates novel oral anticoagulants in comparison with warfarin for thromboembolism prophylaxis in patients with atrial fibrillation (AF). AF is the most frequently diagnosed arrhythmia in the United States. The most serious side effect of AF is stroke. Warfarin has several decades of proven efficacy in AF-related stroke prevention but the drug's numerous drawbacks make its implementation difficult for practitioners and patients. The difficulties of warfarin have prompted the development of alternative anticoagulants for AF-related stroke prevention with better efficacy, safety, and convenience. The oral direct thrombin inhibitor, dabigatran, and the oral factor Xa inhibitors, rivaroxaban and apixaban, have been evaluated in a large phase III trial. Dabigatran, rivaroxaban and apixaban were shown to be noninferior compared with warfarin in the prevention of stroke. Dabigatran and apixaban were found to be statistically superior to warfarin. All three may also have a better safety profile than warfarin. In conclusion, novel anticoagulants have a different pharmacologic profile compared with warfarin that may eliminate many of the treatment inconveniences. Practitioners must also be aware of the disadvantages these new drugs possess when choosing a management strategy for their patients. Drug selection may become clearer as these new drugs are used more extensively.