Direct oral anticoagulant concentrations and adherence in stroke patients.

No therapeutic ranges linking drug concentrations of apixaban and rivaroxaban to clinical outcomes have been defined. We investigated whether direct oral anticoagulant (DOAC) concentrations among patients admitted to hospital with symptoms of stroke differed between those later verified to suffer an ischaemic cerebrovascular event (stroke or transient ischaemic attack) and those having other diagnoses (control group). Serum concentrations in 102 patients on DOAC for atrial fibrillation (84%) and thromboembolic disease (16%) were measured within 24 h of the acute event, employing ultra-high performance liquid chromatography with tandem mass spectrometry. We converted all concentrations to standardized trough levels. DOAC concentrations were lower in the 64 patients with verified ischaemic cerebrovascular event than in the 30 controls, 255 ± 155 versus 329 ± 144 nmol/L (p = 0.029), despite no statistically significant difference in self-reported adherence and daily dosages. Calculated concentrations were 5.4-596 nmol/L (median = 229 nmol/L) in the ischaemic stroke group and 41-602 nmol/L (median = 316 nmol/L) in controls. CHA2 DS2 -VASc score was significantly higher in the ischaemic stroke group than in controls (4.9 ± 1.6 versus 4.1 ± 1.7; p = 0.007). These results may suggest that patients with high cerebrovascular risk might benefit from higher DOAC levels than those with a lower risk.

Serum or Plasma for Quantification of Direct Oral Anticoagulants?

BACKGROUND: Direct oral anticoagulants are increasingly replacing vitamin K antagonists for prevention of stroke in patients with atrial fibrillation, partly owing to the lack of a need for routine monitoring. Therapeutic drug monitoring may still be warranted under certain circumstances. It is generally assumed that serum and plasma can be interchangeably used for this purpose. The aim of this study was to investigate possible differences between the serum, citrate-plasma, and ethylenediaminetetraacetic acid (EDTA)-plasma concentrations of apixaban and rivaroxaban in a larger patient group and their relation to factor X measurements. METHODS: Plasma and serum samples were drawn during the same venipuncture from patients treated with apixaban or rivaroxaban. Drug levels were measured using ultrahigh-performance liquid chromatography combined with tandem mass spectrometry. Three sample matrices were obtained from 8 healthy volunteers for measurement of factor X antigen and activity. RESULTS: Mean concentrations of apixaban and rivaroxaban were 16.8% and 36.6% higher in serum than in citrate-plasma, respectively (both P < 0.001). The corresponding differences in serum versus EDTA-plasma were 4.5% for apixaban and 13.1% for rivaroxaban (both P < 0.001). Factor X antigen measurements in citrate-plasma, EDTA-plasma, serum with clot activator, and serum without additives yielded comparable results, and factor X activity was significantly higher in serum than in plasma. CONCLUSIONS: Apixaban and rivaroxaban concentrations were significantly higher in serum than in plasma. The difference was more pronounced with rivaroxaban and was larger between serum and citrate-plasma than between serum and EDTA-plasma. Higher factor X activity in serum may explain the observed concentration differences. The choice of matrix is, thus, important when interpreting therapeutic drug monitoring results and in research involving analyses of direct oral anticoagulants. The authors recommend citrate-plasma as the preferred matrix.

Severe Neurological Sequelae after a Recreational Dose of LSD.

A young man with an unremarkable medical history suffered a seizure with subsequent cardiorespiratory arrest and severe neurological sequelae after ingesting a blotter. Analysis of a similar blotter and a serum sample obtained 3 h after the event detected lysergic acid diethylamide (LSD) at an amount of 300 µg in the blotter and at a concentration of 4.0 ng/mL (12.4 nmol/L) in the serum. No other drugs were present in concentrations which may confer significant effects. In addition, no individual traits which would make the patient particularly susceptible to adverse LSD effects have subsequently been identified. This suggests that LSD may confer toxic effects in previously healthy individuals.

[New biomarkers for assesing alcohol consumption]. / Nye markører for påvisning av alkoholbruk.

Alcohol abuse has significant medical, social and socioeconomic consequences. Alcohol biomarkers may serve as a useful tool in identifying individuals with excessive alcohol consumption in medical as well as medico-legal contexts.

Incidence of inflammatory bowel disease in Malta between 1993 and 2005: a retrospective study.

BACKGROUND: The primary aim of the study was to estimate the incidence of Crohn's disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD), in Malta in a well-defined population during a 13-year study period. METHODS: Diagnostic criteria for CD and UC were defined. A diagnosis of IBD was obtained from the histopathology reports at St. Luke's Hospital, Malta, between January 1993 and December 2005. The date of diagnosis was defined as the date of the first histopathology report revealing signs of IBD. RESULTS: Incidence rates were standardized using the direct method on the European Standard Population. The mean incidence of UC in males was 8.16 per 100,000 per year and for females was 7.59 per 100,000 per year, while that for CD in males was 0.96 per 100,000 per year and for females 1.622 per 100,000 per year. Using linear regression, in UC there is an almost significant (P = 0.069) increasing trend with time but no difference by gender (P = 0.591). On the other hand, in CD there is no significant trend with time (P = 0.555) but almost a significant difference by gender (P = 0.078). CONCLUSIONS: This is the first Maltese study in which the incidence of IBD has been recorded. In Malta the incidence of UC is similar to the overall incidence of other European countries while the incidence of CD is lower. In fact, the incidence rates of CD are among the lowest in Europe, similar to other southern European countries.