In-hospital left ventricular thrombus following ST-elevation myocardial infarction.

BACKGROUND: In-hospital left ventricular (LV) thrombus following acute ST-elevation myocardial infarction (STEMI) has not been evaluated on a national scale and was the focus of this investigation. METHODS: We used the 2003 to 2013 Nationwide Inpatient Sample database to identify adults ≥18 years old with a principal diagnosis code of ST-elevation myocardial infarction. Patients were divided into two groups defined by the presence or absence of LV thrombus. Clinical characteristics and in-hospital outcomes were studied using relevant statistics. Multiple linear and logistic regression models were conducted to identify factors associated with LV thrombus. RESULTS: Of 1,035,888 STEMI patients hospitalized in the U. S from 2003 to 2013, 1982 (0.2%) developed acute in-hospital LV thrombus. Compared to no LV thrombus, patients with LV thrombus were more likely to have in-hospital complications; acute ischemic and hemorrhagic stroke, acute renal failure, gastrointestinal bleed, cardiogenic shock, in-hospital cardiac arrest and mortality. They also had longer mean length of stay and higher hospital charges. Factors associated with LV thrombus included: anterior/anterolateral STEMI, acute or chronic heart failure with reduced ejection fraction, atrial fibrillation, LV aneurysm, Left heart valvular disease, acute or chronic deep venous thrombosis/pulmonary embolism and alcohol abuse. Patients with LV thrombus were less likely to be female [AOR 0.66, 95% CI (0.51-0.84)]. CONCLUSION: The identification of factors associated with early development of LV thrombus following STEMI, will help direct resources for specific high-risk group and prompt cost-effective therapies. Gender variability in LV thrombus development warrants further investigations.

Incidence, Prevention, and Management of Periprocedural Complications of Left Atrial Appendage Occlusion.

Major procedural complications related to left atrial appendage occlusion (LAAO) are relatively infrequent but may be associated with major morbidity and mortality. LAAO operators should be knowledgeable about these potential complications. Prompt recognition and treatment are necessary to avoid rapid deterioration and dire consequences. With stringent guidelines on operator training, competency requirements, and procedural-technical refinements, LAAO can be performed safely with low complication rates. This article focuses on commonly used devices, as well as prevention, treatment, and management of complications of LAOO.

Assessment and Management of the Left Atrial Appendage Thrombus in Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Intracardiac thrombi arising in the left atrial appendage (LAA) are the principal cause of stroke in nonvalvular atrial fibrillation (AF). Predicting the presence of LAA thrombi is of vital importance in stratifying patients that would need further LAA imaging prior to cardioversion or AF ablation. METHODS: We comprehensively searched PubMed from its inception to November 2017 for randomized controlled trials, cohort and case control studies, as well as for case series on LAA thrombi risk factors, imaging, prevention, and anticoagulation management in atrial fibrillation. RESULTS: A systematic review of the literature identified 106 articles that investigated the presence of LAA thrombi in AF patients. We classified the articles according to topic and reported on: (1) risk factors; (2) diagnostic imaging modalities; (3) prevention strategies before cardioversion; (4) prevention strategies before AF ablation; and (5) management of detected LAA thrombi. CONCLUSIONS: Integration of clinical, biomarker, and imaging risk factors can improve overall prediction for the presence of LAA thrombi, translating into improved patient selection for imaging. The gold standard for the diagnosis of LAA thrombi remains transesophageal echocardiography, although intracardiac ultrasound, cardiac computed tomography, and cardiovascular magnetic imaging are promising alternative modalities. When LAA thrombi are discovered, the treatment regimen remains variable, although direct oral anticoagulants might have efficacy similar to vitamin K antagonists. Future trials will help further elucidate direct oral anticoagulant use for the treatment of LAA thrombi.

Left Ventricular Thrombi in Takotsubo Syndrome: Incidence, Predictors, and Management: Results From the GEIST (German Italian Stress Cardiomyopathy) Registry.

BACKGROUND: Left ventricular (LV) thrombi during Takotsubo syndrome represent a potential complication and can be associated with cerebrovascular embolic events. The aim of this study was to evaluate the exact incidence, predictors, and management strategies of LV thrombi in patients with Takotsubo syndrome. METHODS AND RESULTS: We enrolled 541 consecutive patients in a multicenter international registry. Clinical features and echocardiographic data at admission, during hospitalization, and after 3 months were evaluated. Survival rates for long-term follow-up (mean 984±908 days) were recorded. Twelve Takotsubo syndrome patients (2.2%) developed LV thrombi (all female presenting with apical ballooning pattern). All patients with LV thrombi were treated with oral anticoagulation therapy; however, 2 (17%) had a stroke before treatment initiation. These patients were characterized by a higher prevalence of ST-elevation (56% versus 16%; P<0.001) and higher troponin I levels (10.8±18.3 ng/mL versus 3.5±4.3 ng/mL; P=0.001) as compared with those without LV thrombi. At multivariate analysis including age, sex, LV ejection fraction, ST-elevation at admission, and apical ballooning pattern, troponin I level >10 ng/mL was the only predictor for LV thrombosis (hazard ratio 6.6, confidence interval, 1.01-40.0; P=0.04). After 3 months all LV thrombi disappeared. Oral anticoagulation therapy was interrupted in all patients except 1. At long-term follow-up, the survival rate was not different between patients with and without LV thrombi (84% versus 85%; P=0.99). CONCLUSIONS: LV thrombi have a relatively low incidence among patients with Takotsubo syndrome and were detected in female patients with apical ballooning pattern and increased troponin levels. Oral anticoagulation therapy for 3 months seems reasonable in these high-risk patients.

Zenith Bifurcated Iliac Side Branch Device: Mid-term Results and Assessment of Risk Factors for Intraoperative Thrombosis.

BACKGROUND: The aim of this study is to evaluate the short- and mid-term results of the Zenith bifurcated iliac side branch device (ZBIS) in the treatment of common iliac artery (CIA) aneurysms, and to assess risk factors for intraoperative internal iliac artery (IIA) thrombosis. METHODS: All patients who underwent endovascular treatment of either an isolated CIA aneurysm or an aortoiliac aneurysm using the ZBIS device in the departments of vascular surgery of Strasbourg (France) and Lausanne (Switzerland) between January 2010 and December 2014 were retrospectively collected. RESULTS: Thirty-one implantations were performed: 30 patients underwent 31 endovascular CIA aneurysm treatments with the ZBIS device. Mean operative time was 188 min. Technical success was obtained in 26 implantations (84%). In 5 implantations (16%), the final angiogram revealed an IIA thrombosis. Thirty-day mortality was 3.2%. Thirty-day morbidity was 13.3%. Mean follow-up was 15 months. Overall survival was 96% at 1 year and 89% at 2 years. In intention-to-treat analysis, primary patency of the internal iliac side branch was 84% at 1 year and 76% at 2 years (5 peroperative IIA occlusions and 1 late occlusion). Freedom from reintervention was 89% at 1 and 2 years. One case of type III endoleak and 2 cases of type II endoleaks were identified. Only type III endoleak required an additional intervention with a covered stent. Aneurysm diameter decreased in 15 implantations (48%) and remained stable in 16 implantations (52%). Clinical, radiological, and peroperative parameters were analyzed to identify risk factor for intraoperative thrombosis of the internal iliac side branch. Notion of intraoperative difficulties (any additional procedure that was not initially planned and increasing the operating time) appeared as a risk factor in multivariate analysis (P < 0.01, standard deviation 1.27, odds ratio 30.6). CONCLUSIONS: The main findings of our study is that the procedure can be difficult to perform in particular conditions and can lead to peroperative failure in these cases, highlighting the need for adequate patients screening. When technical success is obtained, outcomes can be considered as satisfactory.

Global Burden of Thrombosis: Epidemiologic Aspects.

Thromboembolic conditions were estimated to account for 1 in 4 deaths worldwide in 2010 and are the leading cause of mortality. Thromboembolic conditions are divided into arterial and venous thrombotic conditions. Ischemic heart disease and ischemic stroke comprise the major arterial thromboses and deep-vein thrombosis and pulmonary embolism comprise venous thromboembolism. Atrial fibrillation is a major risk factor for stroke and systemic arterial thromboembolism. Estimates of the global burden of disease were obtained from Global Burden of Disease Project reports, recent systematic reviews, and searching the published literature for recent studies reporting measures of incidence, burden, and disability-adjusted life-years. Estimates per 100 000 of the global incidence rate (IR) for each condition are ischemic heart disease, IR=1518.7; myocardial infarction, IR=139.3; ischemic stroke, IR=114.3; atrial fibrillation, IR=77.5 in males and 59.5 in females; and venous thromboembolism, IR=115 to 269. Mortality rates (MRs) for each condition are ischemic heart disease, MR=105.5; ischemic stroke, MR=42.3; atrial fibrillation, MR=1.7; and venous thromboembolism, MR=9.4 to 32.3. Global public awareness is substantially lower for pulmonary embolism (54%) and deep-vein thrombosis (44%) than heart attack (88%) and stroke (85%). Over time, the incidence and MRs of these conditions have improved in developed countries, but are increasing in developing countries. Public health efforts to measure disease burden and increase awareness of symptoms and risk factors need to improve, particularly in low- and middle-income regions to address this leading cause of morbidity and mortality.

Reflections after the Diane affair.

The Pharmacovigilance Centre Lareb received 621 reports of possible adverse drugs reactions on Diane-35® . Of all reports, 388 were received after media attention. Of the 309 reports of thromboembolic adverse drugs reactions, 18 cases were fatal. In 31 cases the thromboembolic adverse drugs reaction was initially not recognized as such. The analysis and the turmoil of the 'Diane affair' gave rise to the following reflections: Reflection 1. Continuous awareness and attention of risk of medicines is needed, also for known risks, for timely recognition of adverse drugs reactions. Reflection 2. Reporting side effects should be part of the professional attitude. Reports play a pivotal role in the detection of new adverse drugs reactions and the conditions under which known adverse drugs reactions occur. Reflection 3. Improvement of adequate use of drugs. Pharmacovigilance not only has the aim to improve knowledge on risk of medicines, but also the aim of getting this knowledge into Health Care practice.

Geographic differences in outcomes in outpatients with established atherothrombotic disease: results from the REACH Registry.

AIMS: There are major differences in the prevalence and management of patients with atherothrombotic disease including coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD) across different geographical regions. There is, however, little data allowing comparisons of management and outcomes across broad geographic regions. We aimed to describe geographical differences in baseline characteristics, management and outcomes in stable outpatients with established atherothrombotic disease. METHODS AND RESULTS: From the REACH Registry of atherothrombosis, patients with documented CAD, PAD or CVD and with 4-year follow-up were included. Baseline characteristics, treatments and 4-year outcomes were recorded. Event rates were compared between geographical regions and were adjusted for risk scores predicting ischemic and bleeding events. The analyses of baseline characteristics and medications according to geographical region showed marked differences. For the composite primary outcome (cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke), rates ranged from 12.1% in Japan to 18.2% in Eastern Europe. After adjustment, substantial variations remained: taking North America as a reference, patients from Western Europe and Japan had a lower risk of primary outcome event (hazard ratio (HR) 0.93; p = 0.045, and HR = 0.67; p < 0.001 respectively) whereas patients from Eastern Europe had a higher risk (HR = 1.24; p < 0.001). There were no obvious differences between patients from North America and those from Latin America, the Middle East and Asia. CONCLUSION: There are important variations in the outcomes of patients with atherothrombotic across geographic regions. These observations have important implications for public health and clinical research.

Warfarin for stroke prevention following anterior ST-elevation myocardial infarction.

OBJECTIVES: To assess the benefit of vitamin K antagonist (VKA) therapy for prevention of ischemic stroke following anterior ST-elevation myocardial infarction (STEMI) in patients with reduced ejection fraction. METHODS: A prospective institutional-based registry was used to identify survivors of anterior STEMI with a post-STEMI ejection fraction of 40% or less over a 10-year period. Clinical and procedural characteristics were collected from medical records and vital status from the Social Security Death Index. Outcomes were compared on the basis of VKA use. The primary outcome was a composite of ischemic stroke, death, and clinically relevant bleeding. A secondary analysis examined the effects of low-molecular-weight heparin bridging therapy. RESULTS: The primary outcome occurred in 24.7% (40/162) of VKA patients and 20.5% (22/107) of non-VKA patients [adjusted hazard ratio (HR), 1.30; 95% confidence interval (CI), 0.71-2.31]. Ischemic stroke occurred in 2.5 and 0.9% of VKA patients and non-VKA patients, respectively (adjusted HR, 2.81; 95% CI, 0.31-25.1). There was no significant difference in the rate of bleeding or death between groups. The addition of a low-molecular-weight heparin bridge to VKA therapy was associated with increased bleeding events (adjusted HR, 2.55; 95% CI, 1.04-6.24). CONCLUSION: Ischemic stroke was infrequent in the 6 months following anterior STEMI irrespective of VKA treatment status. The routine use of anticoagulation for prevention of stroke following anterior STEMI may not be warranted.

Assessment of causes of early death after twenty years of liver transplantation.

BACKGROUND: Postoperative poor graft function is a serious complication that can lead to graft loss requiring retransplantation or even death. The postoperative complications of primary nonfunction (PNF), early graft dysfunction (EGD), bleeding due to coagulopathy, and hepatic artery thrombosis (HAT) can lead to graft loss requiring retransplantation or even death. We determined the causes of death after liver transplantation. METHODS: This was an observational descriptive study on adult liver transplant recipients from September 1991 to December 2011. The cutoff for the definition of death was 30 days after surgery. We included patients older than 18 years of age who underwent liver grafts using the piggyback technique, excluding those who had retransplantations or liver-kidney transplantations. RESULTS: We analyzed 561 liver transplantations through chart review. After application of exclusion criteria we had 81 patients for analysis. Overall mortality was classified into 3 main causes: PNF (34/81; 42%), EGD (10/81; 12%), and abdominal bleeding due to coagulopathy (9/81; 11%). CONCLUSION: Despite advances, mortality in the first 30 days after surgery is still high, mainly related to the occurrence of PNF and EGD, whose causality was associated with red blood cell transfusion (>5 U).

The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients.

BACKGROUND: Among trauma patients who survive to reach hospital, exsanguination is a common cause of death. A widely practicable treatment that reduces blood loss after trauma could prevent thousands of premature deaths each year. The CRASH-2 trial aimed to determine the effect of the early administration of tranexamic acid on death and transfusion requirement in bleeding trauma patients. In addition, the effort of tranexamic acid on the risk of vascular occlusive events was assessed. OBJECTIVE: Tranexamic acid (TXA) reduces bleeding in patients undergoing elective surgery. We assessed the effects and cost-effectiveness of the early administration of a short course of TXA on death, vascular occlusive events and the receipt of blood transfusion in trauma patients. DESIGN: Randomised placebo-controlled trial and economic evaluation. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial co-ordinating centre staff) were masked to treatment allocation. All analyses were by intention to treat. A Markov model was used to assess cost-effectiveness. The health outcome was the number of life-years (LYs) gained. Cost data were obtained from hospitals, the World Health Organization database and UK reference costs. Cost-effectiveness was measured in international dollars ($) per LY. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results to model assumptions. SETTING: Two hundred and seventy-four hospitals in 40 countries. PARTICIPANTS: Adult trauma patients (n = 20,211) with, or at risk of, significant bleeding who were within 8 hours of injury. INTERVENTIONS: Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo. MAIN OUTCOME MEASURES: The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury and other. RESULTS: Patients were allocated to TXA (n = 10,096) and to placebo (n = 10,115), of whom 10,060 and 10,067 patients, respectively, were analysed. All-cause mortality at 28 days was significantly reduced by TXA [1463 patients (14.5%) in the TXA group vs 1613 patients (16.0%) in the placebo group; relative risk (RR) 0.91; 95% confidence interval (CI) 0.85 to 0.97; p = 0.0035]. The risk of death due to bleeding was significantly reduced [489 patients (4.9%) died in the TXA group vs 574 patients (5.7%) in the placebo group; RR 0.85; 95% CI 0.76 to 0.96; p = 0.0077]. We recorded strong evidence that the effect of TXA on death due to bleeding varied according to the time from injury to treatment (test for interaction p < 0.0001). Early treatment (≤ 1 hour from injury) significantly reduced the risk of death due to bleeding [198 out of 3747 patients (5.3%) died in the TXA group vs 286 out of 3704 patients (7.7%) in the placebo group; RR 0.68; 95% CI 0.57 to 0.82; p < 0.0001]. Treatment given between 1 and 3 hours also reduced the risk of death due to bleeding [147 out of 3037 patients (4.8%) died in the TXA group vs 184 out of 2996 patients (6.1%) in the placebo group; RR 0.79; 95% CI 0.64 to 0.97; p = 0.03]. Treatment given after 3 hours seemed to increase the risk of death due to bleeding [144 out of 3272 patients (4.4%) died in the TXA group vs 103 out of 3362 patients (3.1%) in the placebo group; RR 1.44; 95% CI1.12 to 1.84; p = 0.004]. We recorded no evidence that the effect of TXA on death due to bleeding varied by systolic blood pressure, Glasgow Coma Scale score or type of injury. Administering TXA to bleeding trauma patients within 3 hours of injury saved an estimated 755 LYs per 1000 trauma patients in the UK. The cost of giving TXA to 1000 patients was estimated at $30,830. The incremental cost of giving TXA compared with not giving TXA was $48,002. The incremental cost per LY gained of administering TXA was $64. CONCLUSIONS: Early administration of TXA safely reduced the risk of death in bleeding trauma patients and is highly cost-effective. Treatment beyond 3 hours of injury is unlikely to be effective. Future work [the Clinical Randomisation of an Antifibrinolytic in Significant Head injury-3 (CRASH-3) trial] will evaluate the effectiveness and safety of TXA in the treatments of isolated traumatic brain injury (http://crash3.lshtm.ac.uk/). TRIAL REGISTRATION: Current Controlled Trials ISRCTN86750102, ClinicalTrials.gov NCT00375258 and South African Clinical Trial Register DOH-27-0607-1919. FUNDING: The project was funded by the Bupa Foundation, the J P Moulton Charitable Foundation and the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 10. See HTA programme website for further project information.

Risk assessment for cancer-associated thrombosis: what is the best approach?

Venous thromboembolism (VTE) is an increasingly frequent complication of cancer and its treatments. One in five cancer patients are estimated to develop venous and arterial events during the natural history of their illness. However, the risk for VTE varies widely between various subgroups of cancer patients and even in the same cancer patient over time. This narrative review focuses on risk factors, biomarkers and risk assessment tools and attempts to clarify approaches to risk stratification. Clinical risk factors include primary site of cancer, chemotherapy, anti-angiogenic therapy, surgery and hospitalization. Predictive and candidate biomarkers include platelet and leukocyte counts, hemoglobin, D-dimer and tissue factor. However, single risk factors or biomarkers have not, in general, been able to identify sufficiently high-risk populations. A clinical risk score, incorporating 5 simple clinical and laboratory variables, has now been studied in over 10,000 patients and can successfully categorize patients at low- and high-risk for VTE. Recent trials have shown that outpatient prophylactic anticoagulation is both safe and effective, but event rates have been highly variable. Targeted thromboprophylaxis provides an optimal risk-benefit ratio and the best opportunity to reduce the burden of VTE and its consequences for patients with cancer.

Prognosis of hepatocellular carcinoma with portal vein tumor thrombus:assessment based on clinical and computer tomography characteristics.

Patients with hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus (PVTT) have an extremely poor prognosis. It is important to select adequate therapeutic options based on reliable prognostic factors using imaging studies and clinical data. Prognostic factors were analyzed in patients with HCC with PVTT in the first branch or main trunk of the portal vein. From 2000 to 2007, 107 consecutive patients with HCC with PVTT in the major portal vein were reviewed, and diagnostic images and clinical characteristics were retrospectively observed. Thirty-eight possible prognostic factors for survival were analyzed by the log-rank test and multivariate analysis using Cox's proportional hazards model. Median overall survival was 14 months following PVTT diagnosis. Survival rates at 6 months, 1, 2, and 3 years were 72.1%, 52.6%, 32.6%, and 29.6%, respectively. Independent prognostic factors for longer survival included:patient age < 65 years, Child-Pugh classification A/B, PVTT treatment, accumulation of Lipiodol in the PVTT after TACE, initial radical treatment for HCC, HCC located in a single lobe of the liver, and no invasion of HCC to the hepatic vein or bile duct. Survival was associated with liver function, tumor extension, and treatment for HCC and PVTT.

Assessment of levels of vascular endothelial growth factor in patients with ESRD and its possible role in cardiovascular morbidity and mortality.

Patients with end-stage renal disease (ESRD) are known to have an elevation of a variety of abnormal thrombotic and inflammatory markers associated with high cardiovascular mortality. Vascular endothelial growth factor (VEGF) is also dysregulated in ESRD but not much is known about the serum levels of VEGF in patients with ESRD. Published reports suggest that elevated levels of VEGF may be protective to the kidney during periods of acute injury and may maintain local glomerular function. Impaired production of VEGF may lead to proteinuria, hypertension, and thrombotic microangiopathy. However, its role in chronic kidney disease or ESRD remains undefined. In our study, we analyzed blood samples of 52 patients with ESRD on stable hemodialysis regimen and measured predialysis serum levels of VEGF and compared these with blood samples obtained from 50 healthy volunteers in order to study differences between baseline levels of VEGF and also attempted to determine its role in ESRD-related cardiovascular mortality.

Assessment of atherothrombosis and its treatment in Mexico: first-year data of the REACH Registry.

BACKGROUND: Atherothrombosis, a generalized and progressive process, is currently a major healthcare problem in Mexico. METHODS: The worldwide Reduction of Atherothrombosis for Continued Health (REACH) registry aimed to evaluate risk factors for atherosclerosis, long-term cardiovascular (CV) event rates, and current management of either patients with established symptomatic atherosclerotic disease or asymptomatic subjects with multiple risk factors for atherothrombotic disease. One-year follow-up of the global REACH database was available for 64 977 outpatients. This report includes the Mexican subregistry wherein 62 internists, cardiologists, and neurologists evaluated baseline patient characteristics, risk factors, medications, and CV event rates as primary outcomes at 1-year follow-up. RESULTS: Complete 1-year follow-up data were available for 837 Mexicans. We observed a high prevalence of diabetes (47.1%), hypertension (74.7%), and hypercholesterolemia (57.8%). Antiplatelet, antihypertensive and/or glucose-lowering agents, and lipid-lowering drugs were used in 87.6%, 84.1%, and 61% of patients, respectively. The all-cause mortality rate was 3.3%. The composite outcome CV death/myocardial infarction/stroke/hospitalization for atherothrombotic events was higher in the symptomatic group (14.6%) than in asymptomatic subjects with multiple risk factors (5.1%; P = 0.01), similar to Latin American results of the global REACH report. The highest CV event rate occurred among symptomatic atherothrombotic patients with 3 vascular disease locations (30.2%), followed by those with 2 (21.9%) and 1 location (13.4%; P = 0.0006). CONCLUSIONS: Prevalence of risk factors and CV event rates including hospitalization in Mexican atherothrombotic patients was high despite the current medication use, which suggests it is necessary to have more aggressive risk-factor management.

Impact of pancreatic allograft function on 1-year survival rates after simultaneous pancreatic-renal transplant.

OBJECTIVES: Simultaneous pancreatic-renal transplant is an effective treatment for insulin-dependent patients with chronic renal failure. We sought to identify the main influences on pancreatic and patient survival rates after simultaneous pancreas-kidney transplants. PATIENTS AND METHODS: The 1-year patient and pancreas survival rates of 150 patients who had undergone simultaneous pancreas-kidney transplant were analyzed by the Cox proportional hazards regression model and the Kaplan-Meier method. Uni and multivariate analyses were performed in terms of transplant-, recipient-, and donor-related risk factors. RESULTS: At 1 year, patient and pancreatic allograft survival rates were 82% and 76.7%, respectively. Delayed graft function in the kidney (P = .001, HR 5.41), acute kidney rejection (P = .016, HR 3.36), and intra-abdominal infection (P < .0001, HR 4.15) were the main factors related to 1-year patient survival. Pancreatic allograft survival at 1 year was related to intra-abdominal infection (P < .0001, OR 12.83), vascular thrombosis (P = .002, OR 40.55), acute kidney rejection (P = .027, OR 3.06), donor sodium greater than 155 mEq/L (P = .02, OR 3.27), and dopamine administration exceeding 7.6 microg/kg/min (P = .046, OR 2.85). CONCLUSIONS: Delayed kidney allograft function and intra-abdominal infection had an important effect on both patient and pancreatic allograft survival rates.

Heparin-induced thrombocytopenia (HIT): clinical and economic outcomes.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction that occurs following exposure to unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). HIT with thrombosis (HITT) can cause devastating venous thromboembolism or arterial clots, prolonged hospitalization, and increased costs. To explore the economic and clinical implications of HIT and HITT, we initiated a single-center patient registry. In this report, we describe patient characteristics, comorbidities, management strategies, clinical outcomes, and costs. We enrolled 349 hospitalized patients with an enzyme immunoassay-confirmed diagnosis of HIT over a 40-month period. Patients were assessed for the primary outcome of 30-day mortality, as well as baseline characteristics, development of thrombosis, and the economic impact of HIT. The primary outcome measure was 30-day mortality and occurred in 58 (16.6%) patients, 40 (15.3%) in the HIT group versus 18 (20.7%) in the HITT group (p = 0.25). The frequency of HIT was greater in patients exposed to UFH than in patients exposed to LMWH (0.8% vs. 0.2%, respectively, p < 0.001). Both HIT and HITT patients who were exposed to UFH had higher hospital costs than those exposed to LMWH ($113,100 vs. $56,352, respectively, p < 0.001). HIT remains an important clinical problem with a high mortality rate and significant cost, regardless of development of thrombosis. Prospective controlled trials need to be conducted to determine the optimal strategy to reduce the frequency of HIT.

Clinical effectiveness and cost-effectiveness of different models of managing long-term oral anticoagulation therapy: a systematic review and economic modelling.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of self-testing and self-management of oral anticoagulation treatment compared with clinic-based monitoring. DATA SOURCES: Major electronic databases were searched up to September 2005. REVIEW METHODS: A systematic review was undertaken of relevant data from selected studies. Results about complication events and deaths were pooled in meta-analyses using risk difference (RD) as the outcome statistic. Heterogeneity across trials and possible publication bias were statistically measured. Subgroup analyses (post hoc) were conducted to compare results of self-testing versus self-management, low versus high trial quality, trials conducted in the UK versus trials in other countries and industry versus other sponsors. A Markov-type, state-transition model was developed. Stochastic simulations using the model were conducted to investigate uncertainty in estimated model parameters. RESULTS: In the 16 randomised and eight non-randomised trials selected, patient self-monitoring of oral anticoagulation therapy was found to be more effective than poor-quality usual care provided by family doctors and as effective as good-quality specialised anticoagulation clinics in maintaining the quality of anticoagulation therapy. There was no significant RD of major bleeding events between patient self-monitoring and usual care controls and pooled analyses found that compared with primary care or anticoagulation control (AC) clinics, self-monitoring was statistically significantly associated with fewer thromboembolic events. However, the reduction in complication events and deaths was not consistently associated with the improvement of AC; in some trials this may be due to alternative explanations, including patient education and patient empowerment. Also, the improved AC and the reduction of major complications and deaths by patient self-monitoring were mainly observed in trials conducted outside the UK. According to UK-specific data, for every 100 eligible patients, 24% would agree to conduct self-monitoring, 17 of the 24 patients (70%) could be successfully trained and able to carry out self-monitoring and only 14 of these (80%) would conduct long-term self-monitoring. Seven cost-effectiveness studies were identified and the study that provided the most relevant UK data found that patient self-management was more expensive than current routine care (417 pounds versus 122 pounds per patient-year) and concluded that using a cost-effectiveness threshold of 30,000 pounds per quality-adjusted life-year (QALY) gained, patient self-management does not appear to be cost-effective. De novo modelling for this report found that the incremental cost per QALY gained by patient self-monitoring is 122,365 pounds over 5 years and 63,655 pounds over 10 years. The estimated probability that patient self-monitoring is cost-effective (up to 30,000 pounds/QALY) is 44% over a 10-year period. Wide adoption of patient self-monitoring of anticoagulation therapy would cost the NHS an estimated additional 8-14 million pounds per year. CONCLUSIONS: For selected and successfully trained patients, self-monitoring is effective and safe for long-term oral anticoagulation therapy. In general, patient self-management (PSM) is unlikely to be more cost-effective than the current specialised anticoagulation clinics in the UK; self-monitoring may enhance the quality of life for some patients who are frequently away from home, who are in employment or education, or those who find it difficult to travel to clinics. Further research is needed into alternative dosing regimes, the clinical effectiveness and cost-effectiveness of patient education and training in long-term oral anticoagulation therapy, UK-relevant cost-effectiveness, the effectiveness of PSM in children, and the potential future developments of near-patient testing devices.