Comparison of local International Sensitivity Index calibration and ''Direct INR'' methods in correction of locally reported International Normalized Ratios: an international study

BACKGROUND: It is no longer feasible to check local International Normalized Ratios (INR) by the World Health Organization International Sensitivity Index (ISI) calibrations because the necessary manual prothrombin time technique required has generally been discarded. OBJECTIVES: An international collaborative study at 77 centers has compared local INR correction using the two alternative methods recommended in the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis guidelines: local ISI calibration and 'Direct INR'. METHODS: Success of INR correction by local ISI calibration and with Direct INR was assessed with a set of 27 certified lyophilized plasmas (20 from patients on warfarin and seven from normals). RESULTS: At 49 centers using human thromboplastins, 3.0% initial average local INR deviation from certified INR was reduced by local ISI calibration to 0.7%, and at 25 centers using rabbit reagents, from 15.9% to 7.5%. With a minority of commercial thromboplastins, mainly 'combined' rabbit reagents, INR correction was not achieved by local ISI calibration. However, when rabbit combined reagents were excluded the overall mean INR deviation after correction was reduced further to 3.9%. In contrast, with Direct INR, mean deviation using human thromboplastins increased from 3.0% to 6.6%, but there was some reduction with rabbit reagents from 15.9% to 10% (12.3% with combined reagents excluded). CONCLUSIONS: Local ISI calibration gave INR correction for the majority of PT systems but failed at the small number using combined rabbit reagents suggesting a need for a combined reference thromboplastin. Direct INR correction was disappointing but better than local ISI calibration with combined rabbit reagents. Interlaboratory variability was improved by both procedures with human reagents only.     

Prothrombotic gene variation and new vascular events after cerebral ischemia of arterial origin

Summary. Background: Several genetic variants involved in hemostasis have been associated with ischemic stroke or myocardial infarction (MI). Stroke patients who carry a prothrombotic genotype may also be at increased risk for subsequent vascular events. Patients and methods: We included 887 patients with non‐disabling cerebral ischemia of arterial origin, who were referred to the University Medical Center Utrecht in the Netherlands between 1995 and 2005 and followed them for the occurrence of ischemic stroke, MI or death. The primary outcome was a composite of death from all vascular causes, non‐fatal ischemic stroke, non‐fatal MI, whichever happened first. We selected 22 prothrombotic variants in 14 genes that were previously associated with ischemic stroke or MI or had evidence of functionality. Results: During a 4.6‐year mean follow‐up period new vascular events occurred in 135 patients (annual event rate 3.3%). None of the 22 variants was associated with the occurrence of new vascular events. Eight additional analyses with secondary outcomes or among subgroups revealed four associations that were likely to be false positive after accounting for multiple testing. Conclusions: In this cohort, prothrombotic genetic variants do not affect the risk of new vascular events after cerebral ischemia of arterial origin. This study does not support the use of prothrombotic genetic variants to identify stroke patients at increased risk for new vascular events or to guide antithrombotic treatment.     

Assessing pain at wound dressing-related procedures

This article is an abstract from a new guide, Principles of Best Practice: Minimising Pain at Wound Dressing-Related Procedures. It is an educational initiative of the World Union of Wound Healing Societies (WUWHS). The guide has been inspired by two seminal documents: the European Wound Management Association's position document, Pain at Wound Dressing Changes (EWMA, 2002), and Practical Treatment of Wound Pain and Trauma: A Patient-centred Approach (Reddy et al, 2003). As an international educational initiative, the WUWHS document is aimed at anyone involved in dressing-related procedures anywhere in the world. This article summarises the section on best practice in the assessment of wound pain.     

A New Pacing Algorithm for Overdrive Suppression of Atrial Fibrillation

Constant rapid pacing may suppress arrhythmias, but it is usually poorly tolerated in the long term. We report a pilot study of a new pacing algorithm for overdrive suppression of atrial premature complexes (APCs) and atrial fibrillation (AF), which prevents postextrasystolic pauses and varies the pacing rate in response to the frequency of APCs. The algorithm was tested in a multiple crossover study for 24 hours in dual chamber pacemakers implanted in 70 patients. Comparison was made on ambulatory recordings between the number of atrial arrhythmias commencing with the algorithm active and inactive. In all cases, the algorithm functioned as designed. No patient was aware of its operation, and no malignant arrhythmias were induced. The 36 recordings that showed atrial arrhythmia were included for analysis. The effects of the algorithm were: APCs (estimated from pacemaker statistics) reduced in 18 patients, increased in 8 (P = 0.02); atrial salvos reduced in 12, increased in 4 (P = 0.041); and AF reduced in 11, increased in 8 (P = NS). In all patients with frequent AF (> 5 episodes in total), fewer episodes occurred when the algorithm was active. We conclude that the algorithm is safe and well tolerated, reduces atrial ectopic activity, and may reduce the frequency of sustained atrial fibrillation.     

Epidemiology of venous thromboembolism after lower limb arthroplasty: the FOTO study

BACKGROUND: In view of recent substantial changes in the management of orthopedic surgery patients, a study was performed in order to update data on the epidemiology of venous thromboembolism (VTE) in patients undergoing lower limb arthroplasty according to contemporary practise. METHODS: We performed a prospective observational study of a cohort of consecutive patients hospitalized for total hip or knee replacement in June 2003. The primary study outcome was the incidence of symptomatic VTE at 3 months. All events were adjudicated by an independent critical event committee. RESULTS: Data from 1080 patients (mean age 68.0 years) were available; 63.2% were undergoing total hip replacement and 36.8% total knee replacement. Pharmacological thromboprophylaxis was administered for a mean time of 36 days. Injectable antithrombotics were used in more than 99% of patients, irrespective of the type of surgery. The incidence of the primary study outcome was 1.8% (20 events; 95% CI: 1.0-2.6%). The incidences were 1.3% and 2.8% in hip and knee surgery patients, respectively. There were two pulmonary embolisms, both in knee surgery patients; neither was fatal. Thirty-five per cent of VTEs occurred after hospital discharge. An age of at least 75 years and the absence of ambulation before hospital discharge were the only significant (P < 0.05) predictors of VTE. The rate of clinically significant bleeding was 1.0% and the rate of death was 0.9%. CONCLUSIONS: The incidence of symptomatic VTE after lower limb arthroplasty is low, even if there is still a need to improve thromboprophylaxis, notably in patients undergoing knee arthroplasty.     

The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials

To comprehend the results of a randomized, controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through complete transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Con solidated S tandards o f R eporting T rials) statement to help authors improve reporting by using a checklist and flow diagram. The revised CONSORT statement presented in this paper incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Discussion. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting the information is associated with biased estimates of treatment effect or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from four stages of a trial (enrollment, intervention allocation, follow-up, and analysis). The diagram explicitly includes the number of participants, for each intervention group, that are included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have performed an intention-to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.     

Fitness, fatness, and cardiovascular risk factors in type 2 diabetes: look ahead study

PURPOSE: Most studies comparing the effects of fitness and fatness on cardiovascular (CVD) risk have been done with young, healthy participants with low rates of obesity and high levels of fitness. The present study examined the association of cardiorespiratory fitness and obesity with CVD risk factors in an ethnically diverse sample of overweight/obese individuals with type 2 diabetes. METHOD: Baseline data from Look AHEAD, a study of 5145 overweight or obese individuals with type 2 diabetes, were used to examine the association of BMI categories (overweight, class I, II, or III obesity) and cardiorespiratory fitness (assessed with a maximal graded exercise test and categorized by age- and gender-specific quintiles) on cardiovascular risk factors and on the odds of having hypertension, hyperlipidemia, or HbA1c > or = 7%. RESULTS: BMI categories and fitness quintiles were highly associated with each other (P < 0.0001), with the heaviest participants being the least fit. Only 2-3% of participants had class III obesity and were in the two fittest quintiles or, conversely, were overweight and in the two least-fit quintiles. When fitness and BMI were included in the same model (adjusting for age, smoking, diabetes duration, and race), HbA1c, ankle/brachial index (ABI), and Framingham risk score were most strongly associated with fitness. Systolic blood pressure was most strongly associated with BMI category. Similar results occurred when waist circumference and fitness were considered together. CONCLUSION: In this large, ethnically diverse sample of overweight/obese individuals with type 2 diabetes, fitness and fatness were highly related to each other but seemed to have different impact on specific CVD risk factors.