Validation of the CoaguChek XS international normalised ratio point-of-care analyser in patients at Charlotte Maxeke Johannesburg Academic Hospital, South Africa

Background. Measurement of the international normalised ratio (INR) is essential in the management of patients on long-term warfarin therapy. The CoaguChek XS portable coagulometer is a point-of-care test for INR measurement. It offers the advantage of improved patient accessibility, particularly in peripheral clinics.Objectives. To evaluate the clinical utility of the CoaguChek XS for monitoring of patients on standard warfarin therapy (INR 2 - 3) as well as those with mechanical heart valve replacements (INR 2.5 - 3.5).Methods. We compared the performance of the CoaguChek XS device with that of the STAGO laboratory analyser with regard to accuracy and precision in 304 patients referred for routine testing.Results. The mean INR value of the CoaguChek XS of 2.75 (standard deviation (SD) 1.18) was comparable to that of the STAGO (2.65 (SD 1.04)). The Bland Altman difference plot revealed good agreement. Bias between the two methods was small, and the imprecision was within acceptable limits. Within the target range (2.0 - 3.5), 93.9% of the CoaguChek XS INR readings were within 0.5 units of the standard laboratory method result. There was, however, an increase in the variability of the differences between the two test methods when the INR was >3.6.Conclusion. The CoaguChek XS point-of-care device can be used to provide accurate and precise INR measurements over a wide range for monitoring of valvular and non-valvular patients on long-term warfarin therapy

Thrombo-embolic and bleeding complications in patients with mechanical valve replacements - a prospective observational study

Background and objectives. Long-term anticoagulation therapy is essential to prevent thrombo-embolic events in patients with mechanical valve replacements. In order to offer indigent patients mechanical heart valve replacement surgery, dedicated anticoagulation clinics are necessary for follow-up. This study assessed the safety and efficacy of lifelong oral anticoagulation therapy in Johannesburg General Hospital mechanical heart valve replacement recipients. The incidence of bleeding and thrombo-embolic complications was documented in three groups of patients with mechanical valve replacements. The groups included patients with aortic valve replacements (AVRs), mitral valve replacements (MVRs) and double (aortic and mitral) valve replacements (DVRs). Materials and methods. A prospective observational study was conducted over a 4-month period. Data on 306 patients attending the Johannesburg General Hospital anticoagulation clinic between 2000 and 2005 were analysed. Of the total patients selected, 205 were assigned to the mechanical valve replacement group (which included 63 patients with AVRs, 93 with MVRs and 49 with DVRs); a control group of 101 nonmechanical valve replacement patients were also included. At each visit the level of anticoagulation was assessed from the international normalised ratio (INR) values, and the presence of bleeding and / or thrombo-embolic complications was documented. Results. There were a total of 51 bleeding and thrombo-embolic complications in the study population. Patients with DVRs had a higher proportion of combined complications (30.61%) than patients with single valve replacements (14.29% in the AVR group and 18.05% in the MVR group) and patients in the control group (12.87%). There were 38 bleeding complications, 30 minor and 8 major. Twelve thrombo-embolic events were documented. Individually, there was no significant difference in thrombo-embolic and bleeding complications between the subgroups. Eighty-two per cent of patients in the mechanical valve replacement group were within the therapeutic range for anticoagulant control (INR 2.5 - 3.5) v. 54% in the control group (INR 2.0 - 3.0). Anticoagulant control was of a high quality and was not a contributing factor to the incidence of bleeding and / or thrombo-embolic complications. Conclusion. The finding of a low incidence of bleeding and thrombo-embolic complications in patients with mechanical valve replacements supports the continued placement of mechanical valves in our setting and use of oral anticoagulation therapy at an INR of 2.5 - 3.5. However the increased risk of both bleeding and thrombo-embolic complications in the DVR group is cause for great concern and warrants further investigation. South African Medical Journal Vol. 96(8) 2006: 710-71

Erythrocyte sedimentation rate as a marker of inflammation and ongoing coagulation in stroke and transient ischaemic attack

No abstract. South African Medical Journal Vol. 95 (8) 2005: 607-61

Lipid accumulation and alkaline phosphatase activity in human preadipocytes isolated from different body fat depots

Background: Alkaline phosphatase (ALP) controls intracellular lipid accumulation in human preadipocytes, but it is not known whether ALP is expressed in all body fat depots, or whether it has a similar role at all sites.Design: Cross-sectional.Setting and subjects: Subjects undergoing breast reduction and abdominal fat biopsies operations at Charlotte Maxeke Johannesburg Academic Hospital.Outcome measures: This study compared intracellular lipid accumulation and ALP activity in the presence and absence of ALP inhibitors in preadipocytes that were obtained from different adipose depots. Abdominal and mammary gland preadipocytes were isolated from women and induced to differentiate in culture. ALP activity and intracellular lipid levels were measured at baseline and after 12 days of differentiation in the presence and absence of the ALP inhibitors, histidine and levamisole.Results: ALP activity was detected in nondifferentiated abdominal (134 ± 7.5 mU/mg protein) and mammary gland (136 ± 9.6 mU/mg protein) preadipocytes. Its activity had increased significantly (p-value < 0.0005 for both) by day 12 of differentiation (388 ± 55 for abdominal and 278 ± 28 mU/mg protein for mammary). Preadipocytes treated with histidine had lower fat accumulation (p-value < 0.0005) and ALP activity (p-value < 0.005) than nontreated cells on day 12, while those treated with levamisole had lower fat accumulation (p-value < 0.005), but elevatedALP activity (p-value < 0.05), compared to nontreated cells. Lipid  accumulation (p-value < 0.005) and ALP activity (p-value < 0.05) were higher in abdominal than mammary gland preadipocytes by day 12.Conclusion: ALP is involved in the control of intracellular lipid accumulation in human preadipocytes that are isolated from both adipose depots. The ability of levamisole to inhibit this process while activating ALP, suggeststhat this molecule acts via an ALP-independent pathway, while histidine attenuates both lipid deposition and ALP activity

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Impact of patient selection in clinical trials: application of ROCKET AF and ARISTOTLE criteria in GARFIELD-AF.

BACKGROUND: The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)-the landmark trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular AF-were influenced by differences in their protocols is debated. The potential influence of selection criteria on trial results was assessed by emulating these trials in data from the Global Anticoagulant Registry in the Field (GARFIELD)-AF registry. METHODS: Vitamin K antagonist (VKA) and non-vitamin K oral antagonist (NOAC) users from GARFIELD-AF were selected according to eligibility for the original ARISTOTLE or ROCKET AF trials. A propensity score overlap weighted Cox model was used to emulate trial randomisation between treatment groups. Adjusted HRs for stroke or systemic embolism (SE) within 2 years of enrolment were calculated for each NOAC versus VKA. RESULTS: Among patients on apixaban, rivaroxaban and VKA, 2570, 3560 and 8005 were eligible for ARISTOTLE, respectively, and 1612, 2005 and 4368, respectively, for ROCKET AF. When selecting for ARISTOTLE criteria, apixaban users had significantly lower stroke/SE risk versus VKA (HR 0.57; 95% CI 0.34 to 0.94) while no reduction was observed with rivaroxaban (HR 0.98; 95% CI 0.68 to 1.40). When selecting for ROCKET AF criteria, safety and efficacy versus VKA were similar across the NOACs. CONCLUSION: Apixaban and rivaroxaban showed similar results versus VKA in high-risk patients selected according to ROCKET AF criteria, whereas differences emerged when selecting for the more inclusive ARISTOTLE criteria. Our results highlight the importance of trial selection criteria in interpreting trial results and underline the problems faced in comparing treatments across rather than within clinical trials

Association of Epstein-Barr virus antibody titers with a human IL-10 promoter polymorphism in Japanese women

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