Correlation between rivaroxaban (Xarelto) plasma activity, patient clinical variables and outcomes in a South African centre.

BACKGROUND: Low-molecular-weight heparin and vitamin K antagonists such as warfarin are the gold standard for prohylaxis and treatment of venous thromboembolic disease (VTED). Direct oral anticoagulants (DOACs) result in predictable anticoagulation with significantly reduced inter- and intra-patient variability. DOAC absorption is rapid, with a short half-life and relatively few drug interactions. DOACs are effective and safe at fixed doses without activity monitoring. However, specific situations may require assessment of accurate drug activity. Rivaroxaban, a DOAC targeting activated coagulation factor X (FXa), is registered for the prevention and treatment of VTED in South Africa. OBJECTIVES: To establish a prophylactic rivaroxaban activity level range and determine any associations with clinical complications, viz. haemorrhage and/or thrombosis. METHODS: Samples from 115 orthopaedic patients were tested 3 hours after a prophylactic oral dose of 10 mg rivaroxaban with STAGO rivaroxaban anti-FXa reagent on an automated coagulation analyser. Patient demographics and clinical outcomes were documented. RESULTS: The mean rivaroxaban anti-FXa level was 105.7 ng/mL. Two patients developed adverse events on therapy. One patient had minor bleeding (menorrhagia) (drug activity level 288.7 ng/mL) and another a deep-vein thrombosis (drug activity level 34.7 ng/mL). Statistical analysis demonstrated an association between drug activity and advancing age (p=0.008), most apparent among those aged ≥65 years. CONCLUSIONS: Measuring rivaroxaban activity levels reduces uncertainty if treatment failure and complications occur. Patients aged ≥65 years should be closely monitored. A local rivaroxaban activity level for patients on rivaroxaban prophylaxis has been established.

Adult deaths and the future: a cause-specific analysis of adult deaths from a longitudinal study in rural Tanzania 2003-2007.

OBJECTIVES: To determine patterns and risk factors for cause-specific adult mortality in rural southern Tanzania. METHODS: The study was a longitudinal open cohort and focused on adults aged 15-59 years between 2003 and 2007. Causes of deaths were ascertained by verbal autopsy (VA). Cox proportion hazards regression model was used to determine factors associated with cause-specific mortality over the 5-year period. RESULTS: Thousand three hundred and fifty-two of 65 548 adults died, representing a crude adult mortality rate (AMR) of 7.3 per 1000 person years of observation (PYO). VA was performed for 1132 (84%) deaths. HIV/AIDS [231 (20.4%)] was the leading cause of death followed by malaria [150 (13.2%)]. AMR for communicable disease (CD) causes was 2.49 per 1000 PYO, 1.21 per 1000 PYO for non-communicable diseases (NCD) and 0.53 per 1000 PYO for accidents/injury causes. NCD deaths increased from 16% in 2003 to 24% in 2007. High level of education was associated with a reduction in the risk of dying from NCDs. Those with primary education (HR = 0.67, 95% CI: 0.49, 0.92) and with education beyond primary school (HR = 0.11, 95% CI: 0.02, 0.40) had lower mortality than those who had no formal education. Compared with local residents, in-migrants were 1.7 (95% CI: 1.37, 2.11) times more likely to die from communicable disease causes. CONCLUSION: NCDs are increasing as a result of demographic and epidemiological transitions taking place in most African countries including Tanzania and require attention to prevent increased triple disease burden of CD, NCD and accident/injuries.

Performance of selected nonparametric tests for discrete longitudinal data under different patterns of missing data.

Comparison of changes over time of a continuous response variable between treatment groups is often of main interest in clinical trials. When the distributional properties of the continuous response variable are not regular enough, or when the response is discrete, nonparametric techniques have been used. The relative performances of selected repeated measures nonparametric two-sample tests proposed by Wei and Lachin, Koziol, Wei and Johnson, and the adapted Wilcoxon Rank-Sum test are compared through simulations based on quality of life data. The Wilcoxon Rank-Sum test is the most powerful and is not significantly affected by the different patterns of missing data.