Evaluation of a decision support system for initiation and control of oral anticoagulation in a randomised trial.

OBJECTIVE: To determine whether a computerised decision support system for initiation and control of oral anticoagulant treatment improves quality of anticoagulant control achieved by trainee doctors. DESIGN: Randomised controlled trial. SETTING: District general hospital in North London. SUBJECTS: 148 inpatients requiring start of warfarin treatment. INTERVENTIONS: Management by trainee doctors (to achieve therapeutic range of international normalised ratio of 2 to 3) with indirect assistance from computerised decision support system (intervention group) or without such assistance (control group). MAIN OUTCOME MEASURES: Median time to therapeutic range, stable dose, and first pseudoevent (excessive international normalised ratio after therapeutic range has been reached) and person time spent in the therapeutic range. RESULTS: 72 patients were randomised to the intervention group and 76 to control group. Median time to reach international normalised ratio of > or = 2 was not significantly different in the two groups (3 days). Median time to achieve a stable dose was significantly lower in intervention group than in controls (7 days v 9 days, P = 0.01) without excessive overtreatment or undertreatment with anticoagulant. Patients in intervention group spent greater proportion of time in therapeutic range, both as inpatients (59% v 52%) and outpatients (64% v 51%). CONCLUSION: The computerised decision support system was safe and effective and improved the quality of initiation and control of warfarin treatment by trainee doctors.     

Fixed minidose warfarin: a new approach to prophylaxis against venous thrombosis after major surgery.

A prospective study was carried out to see whether a small fixed dose of warfarin (1 mg daily) given before operation (mean 20 days) would prevent deep vein thrombosis in patients having major gynaecological surgery. One hundred and four patients were randomised into three groups: fixed minidose warfarin; full dose oral anticoagulation; and no treatment (controls). There was a significantly lower incidence of deep vein thrombosis in the minidose warfarin and full dose anticoagulant treatment groups (9% (3/32) and 3% (1/35) respectively) than in the controls (30%; 11/37) but no significant difference between the two anticoagulant treatment groups. Prothrombin time and the activated partial thromboplastin time were normal on the day of surgery in the warfarin treatment group, whereas times were prolonged in the group given full dose anticoagulation. Mean haemoglobin concentrations fell in all three groups after operation but the fall was significantly less in the minidose warfarin treatment group than after full dose anticoagulation. The benefit from full dose oral anticoagulant prophylaxis, based on a preoperative international normalised ratio of 1.5-2.5 with rabbit brain Manchester reagent, was similar to the protection achieved in an oral anticoagulant treatment group controlled with human brain Manchester comparative reagent at a similar level of anticoagulation. The lack of disturbance of normal haemostasis at the time of operation together with a significant reduction in deep vein thrombosis may encourage surgeons to introduce minidose prophylaxis with warfarin.     

Effectiveness of long term oral anticoagulation treatment in preventing venous thrombosis in hereditary protein S deficiency.

In eight of 14 patients who were deficient in protein S and who belonged to two unrelated families thrombosis presented as thrombophlebitis in seven and deep vein thrombosis in six, complicated by pulmonary embolism in four and leg ulcers in two. In four patients superficial thrombophlebitis preceded deep vein thrombosis by one to 11 years. Post-thrombotic varicose veins and venous insufficiency had developed in four patients. In three of those and in a fourth patient symptomatic superficial thrombophlebitis, deep vein thrombosis, and pulmonary embolism did not recur while they were taking oral anticoagulant treatment for six to 12 years. The anticoagulation intensity corresponded to international normalised ratio values of over 2.5. It is concluded that the benefits of anticoagulant treatment for patients with congenital thrombotic disease are great, and thus it is necessary to make an early diagnosis and treat patients at risk of developing thrombosis.     

Molecular surveillance of the antifolate-resistant mutation I164L in imported african isolates of Plasmodium falciparum in Europe: sentinel data from TropNetEurop

Background

Malaria control programmes utilising indoor residual spraying are only effective if a high coverage of targeted structures is achieved and an insecticide that is effective against the specific mosquito vector is correctly applied. Ongoing monitoring of spraying operations is essential to assure optimal programme performance and early corrective action, where indicated.

Methods

Successful development and application of a computerised spraying operations management system in Mpumalanga Province, South Africa during 1998 resulted in its adaptation and introduction in neighbouring Maputo Province, southern Mozambique during 2000. The structure and components of this computerised management system are described, and its' operational benefit in southern Mozambique, where community-based spray operators apply intradomiciliary insecticide, are reviewed.

Conclusions

The computerised management system allowed malaria programme management and field supervisors to monitor spraying coverage, insecticide consumption and application rates on an ongoing basis. The system supported a successful transition to community-based spraying, while assuring correct insecticide application and spraying completion according to schedule.     

Guidelines on anticoagulant treatment in atrial fibrillation in Great Britain: variation in content and implications for treatment.

OBJECTIVE: To describe the content of guidelines on the use of anticoagulant treatment in patients with atrial fibrillation and the impact of variations in guidelines on treatment. DESIGN: Postal survey of guidelines, semistructured interview with lead developers of guidelines, and application of guidelines to patient sample. SUBJECTS: 15 lead developers of the 20 guidelines identified in the postal survey were interviewed. 100 patients over 65 with atrial fibrillation to whom the guidelines were applied. MAIN OUTCOME MEASURES: Evaluation of guidelines and the methods of dissemination, implementation, review, and evaluation; proportion of patients recommended for anticoagulant treatment by each guideline; and level of agreement between guidelines. RESULTS: There was considerable variation in whether anticoagulant treatment was recommended for subjects (range 13% to 100%, kappa = 0.12). Guidelines varied greatly in advice on treatment by age, the use of echocardiography, and the target value or range of the international normalised ratio (8 of the 20 guidelines included values unlikely to be effective). Development was unsystematic; evidence based approaches were rarely used, 9 of the 15 lead developers had developed the guidelines themselves, and the 6 guidelines developed by groups relied on informal consensus. Methods to support effective dissemination, implementation, and evaluation were limited. CONCLUSION: The widespread non-systematic production of guidelines has led to considerable variation with implications for the quality of care and clinical decision making. There is a need for a central, well funded programme of guideline development to ensure that valid guidelines are produced and disseminated.     

Venous thromboembolism and anticoagulant therapy in pregnancy

Background:Venous thromboembolism (VTE) is a leading cause of maternal mortality in western countries. Many of these deaths could be prevented by optimal prophylaxis and management.Objective:The aim of this study was to examine the current literature to assess the risk of VTE in pregnant women and to identify the most effective and safe anticoagulant therapy.Methods:A search was conducted using the major electronic databases of PubMed and MEDLINE 1996–October 2005 using the following key words: Pregnancy, venous thrombosis, thrombophilia, prosthetic heart valves, anticoagulants, heparin, low-molecular-weight heparin, coumarin, and warfarin.Results:The common risk factors for VTE during pregnancy are age >35 years, obesity, operative delivery, thrombophilia, and a family or personal history of VTE. Coumarins are unsuitable for use during pregnancy because of embryopathy and risk of fetal bleeding. Low-molecular-weight heparins (LMWHs), such as enoxaparin and dalteparin, are safer and more convenient than unfractionated heparin (UFH). LMWH is now the agent of choice for pharmacologic thromboprophylaxis and treatment of VTE during pregnancy. Women with a suspected VTE should receive anticoagulant therapy until an objective diagnostic test is performed, unless there is a clear contraindication to anticoagulation. If a VTE is confirmed, anticoagulant treatment should be continued throughout pregnancy. These patients usually, require at least 6 months of anticoagulation, and treatment should be continued until at least 6 weeks postpartum. Management of women with prosthetic heart valves in pregnancy is controversial; while coumarin treatment is more effective than UFH for thromboprophylaxis in the mother, UFH is associated with a better outcome for the fetus. Coumarin embryopathy can be avoided if heparin is substituted by 6 weeks' gestation. The limited data on LMWH in women with prosthetic heart valves suggest that it compares favorably with UFH.Conclusions:LMWH is now the anticoagulant of choice for the treatment and prevention of VTE in pregnancy. However, the management of women with prosthetic heart valves requiring anticoagulation in pregnancy remains controversial as coumarins appear safer for the mother, but heparin is associated with less fetal morbidity and data on LMWH are limited.     

Occurrence and quality of anticoagulant treatment of chronic atrial fibrillation in primary health care in Sweden: a retrospective study on electronic patient records

Background  

Chronic atrial fibrillation is a prevalent cardiac disorder. The literature indicates varying proportions of those treated with anticoagulants, and varying intensity of anticoagulation. Electronic patient records are providing us with clinical data concerning management of anticoagulant treatment in real-life practice that is useful for audits. We aimed to assess warfarin treatment for chronic atrial fibrillation in primary health care with regard to prevalence, incidence, the proportion treated and the quality of anticoagulation control.     

Diet as prophylaxis and treatment for venous thromboembolism?

Background

Both prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored.

Methods and Findings

The literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment. Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using anticoagulants as VTE prophylaxis. For both prophylaxis and treatment of VTE, we propose RCTs comparing standard anticoagulation with low VTE risk diets, and we discuss the statistical considerations for an example of such a trial.

Conclusions

Because of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials.     

Training and Experience of Physicians in the Management of Adequate Anticoagulant Therapy

In a group of seven physicians engaged on a full-time basis in the anticoagulant unit of a teaching hospital, it was demonstrated that errors occur frequently in the management of anticoagulant therapy and that the incidence of such errors decreases during the course of the physician''s training period. Expert supervision and proper organization of the unit permit detection and correction of a high percentage of these errors.     

Target Specific Anticoagulant Peptides: A Review

Anticoagulant drugs are of crucial importance for the treatment and prophylaxis of thrombotic disorders. The use of traditional anticoagulants like heparin and warfarin is majorly associated with bleeding complications. In the quest for safer anticoagulation therapy, the interest for the isolation of novel anticoagulant compounds has shifted towards natural sources. Peptides can be considered as better alternative due to their therapeutic potential in the treatment of diseases. Peptides from hematophagous (blood-feeding) and venomous organisms have been recognized as potential anticoagulant agents. Of late, peptides derived from the hydrolysis of food proteins, including edible seaweeds, milk and seed proteins, have also shown to possess promising in vitro anticoagulant activity. To overcome the problems associated with regular anticoagulants, peptides targeting vital steps in the clotting cascade have been studied. This review focuses on anticoagulant peptides with known targets, inhibiting crucial factors in the coagulation cascade such as FXa, FXIa, FXIIa and FVIIa/TF complex, as well as peptides with unknown targets.     

Implications of Using Different Methods to Characterise Anticoagulant Control in Patients with Second Generation Mechanical Heart Valve Prostheses

Objective

Characterisation of anticoagulant control is fundamental to investigations of its association with clinical outcome. Anticoagulant control depends on several factors. This paper aims to illustrate the implications of different methods for measuring and analysing anticoagulant control in patients with second generation mechanical heart valve prostheses.

Methods

International normalised ratio (INR) data collected during the 10-year follow-up of a randomised controlled trial were analysed. We considered the influence of: 3 different target INR ranges; anticoagulant control expressed as the proportion of INR readings (PoR) vs. anticoagulant control follow-up time (PoT); 3 ways of describing the profile of anticoagulant control over time.

Results

Different target INR ranges dramatically influenced derived measures of anticoagulant control; the PoT within the target range varied from 88% for the widest to 28% for narrowest range. Overall distributions of PoR and PoT observations were similar but differed by up to ±20% for individuals; PoT exceeded PoR when control was good but was less than PoR when control was poor. Classifying PoT outside the target range showed that widely varying combinations of PoT too high and too low are possible across individuals.

Conclusions

Researchers'' choices about methods for measuring and quantifying anticoagulant control markedly influence the values derived from INR readings. The use of different methods across studies makes it difficult or impossible to compare findings and to establish an evidence base for clinical practice. Methods for quantifying anticoagulant control should be standardised.     

Patterns of Asian and non-Asian morbidity in hospitals.

On the basis of surname, 6418 Asians were identified out of a total of 109 187 deaths and discharges of Leicestershire residents who had been treated in hospitals in the Trent Regional Health Authority over two years. After linkage to Hospital Activity Analysis computerised records, hospital morbidity in Asians and non-Asians was compared. Asian patients in certain age groups were more likely than non-Asian patients to be diagnosed as having asthma; leukaemia; diabetes mellitus; blood, thyroid, and eye disorders; certain forms of heart disease; and spontaneous and other types of abortion (excluding therapeutic abortion). The well recognised excess of cases of tuberculosis among Asians was also confirmed. Conversely, for some age groups, Asians were less likely than non-Asians to fall into particular diagnostic categories. Exploring such apparent differences can serve as the basis for aetiological inquiry and service planning. The patient''s name is now probably the most reliable indicator of Asian ethnic origin in health records.     

Snake Bite in South Asia: A Review

Snake bite is one of the most neglected public health issues in poor rural communities living in the tropics. Because of serious misreporting, the true worldwide burden of snake bite is not known. South Asia is the world''s most heavily affected region, due to its high population density, widespread agricultural activities, numerous venomous snake species and lack of functional snake bite control programs. Despite increasing knowledge of snake venoms'' composition and mode of action, good understanding of clinical features of envenoming and sufficient production of antivenom by Indian manufacturers, snake bite management remains unsatisfactory in this region. Field diagnostic tests for snake species identification do not exist and treatment mainly relies on the administration of antivenoms that do not cover all of the important venomous snakes of the region. Care-givers need better training and supervision, and national guidelines should be fed by evidence-based data generated by well-designed research studies. Poorly informed rural populations often apply inappropriate first-aid measures and vital time is lost before the victim is transported to a treatment centre, where cost of treatment can constitute an additional hurdle. The deficiency of snake bite management in South Asia is multi-causal and requires joint collaborative efforts from researchers, antivenom manufacturers, policy makers, public health authorities and international funders.     

Antidote-mediated control of an anticoagulant aptamer in vivo

Patient safety and treatment outcome could be improved if physicians could rapidly control the activity of therapeutic agents in their patients. Antidote control is the safest way to regulate drug activity, because unlike rapidly clearing drugs, control of the drug activity is independent of underlying patient physiology and co-morbidities. Until recently, however, there was no general method to discover antidote-controlled drugs. Here we demonstrate that the activity and side effects of a specific class of drugs, called aptamers, can be controlled by matched antidotes in vivo. The drug, an anticoagulant aptamer, systemically induces anticoagulation in pigs and inhibits thrombosis in murine models. The antidote rapidly reverses anticoagulation engendered by the drug, and prevents drug-induced bleeding in surgically challenged animals. These results demonstrate that rationally designed drug-antidote pairs can be generated to provide control over drug activities in animals.     

A microcomputer record system for diabetic patients

A computerised medical records system for diabetic patients has been developed on a Vector Graphics MZ microcomputer using programs written in UCSD-Pascal. The system allows addition or deletion of patient records, alteration of records, alphabetical listing of recorded patients' names, and printing of individual records in a concise format. The amount of information capable of being stored in each record makes the easy to use system a useful device in the clinical management of diabetic patients.     

Evaluation of etiology and pregnancy outcome in recurrent miscarriage patients

The purpose of this study was to evaluate etiology and pregnancy outcome of recurrent miscarriage women. The enrolled patients (280) were evaluated for Triiodothyronine, Thyroxine, Thyroid stimulating hormone, prolactin, chromosomal analysis, Haemoglobin A1C, blood sugar, Magnetic resonance imaging, 3D-ultrasound, auto-antibodies profile (antiphospholipid antibodies, anticardiolipin antibodies, lupus anticoagulant, antinuclear antibodies, anti-thyroid antibodies and β2 glycoprotein1), torch profile (Toxoplasmo gondii, rubella, cytomegalo virus and herpes simplex virus), blood vitamin D3 levels, psychological factors, Body mass index and thrombotic factors (protein S and C deficiency, Prothrombin G20210A mutation, anti-thrombin III, Factor V Leiden and Methylenetetrahydrofolate reductase mutation), uterosalpingography (hysteronsalpingography) and hysteroscopy. The therapeutic regimens either singly or combined were employed for the treatment of recurrent miscarriage patients on the basis of etiology (single or multiple) and include intravenous immunoglobulin, low molecular weight heparin, low dose aspirin, levothyroxine, progesterone, folic acid, human chorionic gonadotrophin, vitamin D3, psychotherapy, genetic counselling. However, patients with idiopathic recurrent miscarriage were treated with progesterone supplementation, anticoagulation and/or immune modulatory agents. The incidence of primary recurrent miscarriage was highest and most of the women experienced recurrent miscarriage during first trimester. Endocrinological disorders (39%) were found as the major pathological factor for recurrent miscarriage. Other factors include uterine abnormalities (5.7%), vitamin D3 deficiency (3.5%), psychological factors (3.2%) infection (3.6%), autoimmune abnormalities (1.8%) and protein S deficiency (1.8%). However, 40% cases were idiopathic. The overall live birth rate achieved after the management of recurrent miscarriage patients was 75.7%. Enocrinopathy was the major cause of recurrent miscarriage. The overall live birth rate achieved was 75.7% with highest pregnancy outcome in secondary recurrent miscarriage patients after the management.     

Complex Compound of Heparin and Glutamic Acid: Synthesis and Effect on Hemostatic Indices in vitro and in vivo

A complex compound of high-molecular heparin and glutamic acid has been synthesized. This compound has anticoagulant, fibrinolytic, and antithrombotic properties in vitro. Single intravenous or chronic peroral introduction of the complex in normal animals imitates the activation of anticoagulation system. When the anticoagulation system in depressed, the complex restores or even activates the anticoagulant–fibrinolytic background of the serum it. The obtained data are discussed in physiological terms.     

基于最优实践的国家公园管理能力评价方法体系研究

建立国家公园体制对我国自然保护地体系改革以及生态文明建设具有重要意义。然而,我国国家公园建设却面临着创新管理体制、确定资源权属、健全法律体系等诸多挑战。对标国际先进经验将有助于识别我国现有基础与最优目标之间的差距,发现国家公园建设与管理的薄弱环节与努力方向,推动适合我国国情的国家公园建设路径与管理模式的探索。为此,系统梳理了世界上不同国家的国家公园管理经验,并对国际上国家公园管理的最优实践进行了归纳总结。在此基础上,综合考虑我国国家公园建设的自身特点,构建了包含体制建设、保障机制、资源环境管理、社区管理和科普教育5方面共18项指标的国家公园管理能力评价指标体系,并对各项指标的最优标准进行了界定。基于该指标体系,提出了国家公园管理能力综合评价方法。该方法运用层次分析法和专家打分法确定各项指标权重及得分,通过加权求和得到国家公园管理能力的综合评分。基于最优实践的国家公园管理能力评价方法体系,在短期内将有助于判断国家公园体制试点的管理基础与建设潜力,为我国国家公园的甄别与遴选提供科学依据,在长期将为国家公园管理有效性评估体系的构建奠定基础,为我国国家公园管理质量的提升提供技术支撑。