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.

Pulmonary Function Testing in Elderly Patients Treated for a Myasthenia Gravis Exacerbation.

BACKGROUND AND PURPOSE: Pulmonary function testing is a standard part of care for patients admitted to hospital with a myasthenia gravis exacerbation. It may inform clinicians' decisions to intubate patients. It is known that pulmonary function declines with age in healthy adults. We studied the effect of age on pulmonary function and serious respiratory events, including intubation, in patients admitted to hospital for a myasthenia gravis exacerbation. METHODS: Single center, retrospective cohort of consecutive patients treated for a myasthenia gravis exacerbation. Demographics, pulmonary function tests (PFTs), and respiratory events requiring intubation or emergency respiratory therapy were recorded for each encounter. Relationship of PFTs to age was analyzed using age as a continuous and as a dichotomous (cut-value 70 years) variable. RESULTS: Forty-nine encounters from 39 patients were included. Slow vital capacity (SVC) was negatively correlated with age (R 0.46, P value .002). Maximum inspiratory pressure (MIP) and SVC were significantly reduced in elderly versus nonelderly patients (MIP-20.0 vs -30.0 cm H2O, P value .004; SVC 16.5 vs 23.4 mL/kg, P value .013). The incidence of respiratory events did not significantly differ between elderly and nonelderly patients (χ2 P value .08). CONCLUSIONS: In patients treated for a myasthenia gravis exacerbation, pulmonary function values are significantly reduced in elderly patients compared to nonelderly patients. Despite very low SVC and MIP values most elderly patients do not require intubation however they do require intensive monitoring for serious respiratory complications.

Approaches to the field recognition of potential thrombectomy candidates.

Systems of care for acute ischemic stroke are being challenged to implement processes that ensure rapid access to endovascular thrombectomy. Optimizing existing regionalized stroke thrombolysis programs for endovascular thrombectomy will require accurate field recognition of treatment candidates. We begin with a review of the development of early clinical tests for ischemic stroke, illustrating challenges relevant to future field tests for large vessel occlusion. Second, we discuss aspects of diagnosis, eligibility, feasibility, and system organization that are potentially relevant to the development and implementation of field tests and diversion criteria. These considerations may influence the choice and parametrization of field tests in individual jurisdictions. Third, we review the literature evaluating eight clinical tests for the field identification of probable large vessel occlusion. All candidate tests include evaluations for focal weakness, and six evaluate for cortical signs such as aphasia or gaze deviation. Most appear roughly comparable to the NIH Stroke Scale, but direct comparison between studies is inappropriate because of major methodological differences. Finally, we discuss our jurisdiction's approach to the field recognition of thrombectomy candidates. We contextualize diagnostic, eligibility, and system considerations within distinct metro and rural environments and propose a screen-and-consult model for the rural setting.