Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis.

BACKGROUND: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. METHODS: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0-3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. RESULTS: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5-73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. CONCLUSIONS: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03178864.

A Qualitative Evaluation of Young People's, Parents' and Carers' Experiences of a National and Specialist CAMHS Dialectical Behaviour Therapy Outpatient Service.

(1) Background: Dialectical Behaviour Therapy (DBT) is the recommended treatment for Borderline Personality Disorder (BPD) symptoms in adults, however, research investigating the effectiveness of DBT for adolescents is limited. The present study explores the experiences of young people and their parents/carers of a DBT service using qualitative methodology. (2) Methods: Young people and their parents/carers, who completed DBT within the National and Specialist Child and Adolescent Mental Health DBT Service based at the Maudsley Hospital in London, were asked questions regarding their experience of the service. Data was collected from young people who completed treatment between July 2019 and July 2020 (n = 18) and their parents and carers (n = 7). (3) Results: Amongst young people, the themes identified were: a new way of living, better understanding of self, new skills, person-centred approach, and relationships with others. Parent and carer interviews revealed themes of improved relationships, feeling supported, improved quality of life, and time/timing. (4) Conclusions: Young people reported improvements in emerging BPD symptomology after completing DBT. Parents and carers reported improvements in their young person and families since starting DBT. A longer DBT programme, earlier DBT intervention, and the time-consuming nature of DBT were highlighted as areas for improvement.

A Meta-Analysis of Case Fatality Rates of Recurrent Venous Thromboembolism and Major Bleeding in Patients with Cancer.

BACKGROUND: Knowing the case fatality rates of recurrent venous thromboembolism (VTE) and major bleeding is important for weighing the relative risks and benefits of anticoagulation and deciding on the duration of anticoagulant therapy, but these rates are uncertain in patients with cancer-associated thrombosis. METHODS: We performed a systematic review and a meta-analysis to determine the incidence of recurrent VTE and major bleeding and their respective case fatality rates in patients with cancer-associated VTE. RESULTS: Our analysis included 29 studies (15 prospective cohort studies and 14 randomized controlled trials) from 1980 to January 2019. Data from 8,000 cancer patients with 4,786 patient-years of follow-up were summarized. Rates of recurrent VTE and fatal recurrent VTE were 23.7 (95% confidence interval [CI]: 20.1-27.8) and 1.9 (95% CI: 0.8-4.0) per 100 patient-years of follow-up, respectively, with a case fatality rate of 14.8% (95% CI: 6.6-30.1%). The rates of major bleeding and fatal major bleeding events were 13.1 (95% CI: 10.3-16.7) and 0.8 (95% CI: 0.3-2.1) per 100 patient-years of follow-up, respectively, with a case fatality rate of 8.9% (95% CI: 3.5-21.1%). While the estimates of case fatality vary by anticoagulation regimen and study design, the differences between them were not statistically significant. CONCLUSION: In cancer patients receiving anticoagulation, the case fatality rate of recurrent VTE is higher than the case fatality rate of major bleeding. These findings may help to inform decisions regarding the management of anticoagulation in patients with active cancer and VTE.

Patient characteristics and long-term outcomes beyond the first 6 months after a diagnosis of cancer-associated venous thromboembolism.

INTRODUCTION: Little is known about the clinical course and treatment decisions in patients with cancer-associated venous thromboembolism (VTE) beyond the initial treatment period of 3 to 6 months. This information is important for clinicians and patients to inform their decisions regarding duration of anticoagulation. MATERIALS AND METHODS: We reviewed health records from consecutive patients referred to our institution for cancer-associated VTE management between 2013 and 2015 to describe their clinical course and outcomes from 6 to 24 months following their index VTE. Details on patient and cancer characteristics, objectively documented recurrent venous thromboembolism (rVTE), clinically relevant bleeding (CRB) and overall mortality were captured. RESULTS: 524 patients met eligibility criteria and 322 were alive at 6 months after the index VTE. At 6 months, anticoagulation was continued in 222 patients (68.9%). During follow-up, there were 33 rVTE events in 30 patients (1-year cumulative incidence of 8.2%; 95% CI: 5.5%-11.6%), and 16 CRB events in 15 patients (1-year cumulative incidence of 4.1%; 95% CI: 2.3%-6.7%); 20 (60.6%) rVTE events and 13 (81.3%) CRB events occurred while on anticoagulation. One-year survival beyond 6 months was 73.7% (95% CI: 68.5%-78.2%). A higher proportion of patients with advanced cancer and receiving cancer treatment was found among those who continued anticoagulation beyond 6 months compared to those who stopped anticoagulation. CONCLUSIONS: Patients with cancer-associated VTE who are alive at 6 months after VTE diagnosis remain at high risk of rVTE, CRB and death.