Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients.

BACKGROUND: Patients with active cancer are often on chronic anticoagulation and frequently require interruption of this treatment for invasive procedures. The impact of cancer on periprocedural thromboembolism (TE) and major bleeding is not known. PATIENTS AND METHODS: Two thousand one hundred and eighty-two consecutive patients referred for periprocedural anticoagulation (2484 procedures) using a standardized protocol were followed forward in time to estimate the 3-month incidence of TE, major bleeding and survival stratified by anticoagulation indication. For each indication, we tested active cancer and bridging heparin therapy as potential predictors of TE and major bleeding. RESULTS: Compared with patients without cancer, active cancer patients (n=493) had more venous thromboembolism (VTE) complications (1.2% versus 0.2%; P=0.001), major bleeding (3.4% versus 1.7%; P=0.02) and reduced survival (95% versus 99%; P<0.001). Among active cancer patients, only those chronically anticoagulated for VTE had higher rates of periprocedural VTE (2% versus 0.16%; P=0.002) and major bleeding (3.7% versus 0.6%; P<0.001). Bridging with heparin increased the rate of major bleeding in cancer patients (5% versus 1%; P=0.03) without impacting the VTE rate (0.7% versus 1.4%, P=0.50). CONCLUSIONS: Cancer patients anticoagulated for VTE experience higher rates of periprocedural VTE and major bleeding. Periprocedural anticoagulation for these patients requires particular attention to reduce these complications.

Predictors of major bleeding in peri-procedural anticoagulation management.

BACKGROUND: Appropriate periprocedural management for chronically anticoagulated patients requires assessment of patient-specific thrombosis and bleeding risks. However, predictors of post-procedure bleeding are unknown. OBJECTIVES: To determine the 3-month cumulative incidence and independent predictors of peri-procedural bleeding in chronically anticoagulated patients requiring temporary warfarin interruption for an invasive procedure. METHODS: In a protocol driven, cohort study design, all patients referred to the Mayo Clinic Thrombophilia Center for peri-procedural anticoagulation management (1997-2007; n = 2182), were followed forward in time to determine the 3-month cumulative incidence of peri-procedural bleeding (Kaplan-Meier product limit) and potential predictors of bleeding (Cox proportional hazards). Decisions to 'bridge' with low-molecular-weight heparin were based on estimated thromboembolism and bleeding risk. RESULTS: Indications for chronic anticoagulation included venous thromboembolism (38%), atrial fibrillation (30%) and mechanical heart valves (27%). Of these, 1496 (69%) patients received bridging therapy. The 3-month cumulative incidence rates of major and overall bleeding were 2.1% and 5.1%, respectively. Major bleeding occurred more frequently in patients receiving bridging therapy (3% vs. 1%; P = 0.017). Independent predictors (hazard ratio; 95% confidence interval) of major bleeding included mitral mechanical heart valve (2.2; 1.1-4.3), active cancer (1.8; 1.0-3.1), prior bleeding history (2.6; 1.5-4.5) and re-initiation of heparin therapy within 24 h after the procedure (1.9; 1.1-3.4). CONCLUSION: Factors predisposing to peri-procedural bleeding are primarily patient-specific. Premature heparin re-initiation is an avoidable provider-specific variable to consider.

Quality in the technical performance of screening flexible sigmoidoscopy: recommendations of an international multi-society task group.

BACKGROUND: Flexible sigmoidoscopy (FS) is a complex technical procedure performed in a variety of settings, by examiners with diverse professional backgrounds, training, and experience. Potential variation in technical quality may have a profound impact on the effectiveness of FS on the early detection and prevention of colorectal cancer. AIM: We propose a set of consensus and evidence based recommendations to assist the development of continuous quality improvement programmes around the delivery of FS for colorectal cancer screening. RECOMMENDATIONS: These recommendations address the intervals between FS examinations, documentation of results, training of endoscopists, decision making around referral for colonoscopy, policies for antibiotic prophylaxis and management of anticoagulation, insertion of the FS endoscope, bowel preparation, complications, the use of non-physicians as FS endoscopists, and FS endoscope reprocessing. For each of these areas, continuous quality improvement targets are recommended, and research questions are proposed.

Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: a randomized, placebo-controlled trial.

OBJECTIVES: To assess the efficacy of Lactobacillus GG in preventing antibiotic-associated diarrhea (AAD) in adults and, secondarily, to assess the effect of coadministered Lactobacillus GG on the number of tests performed to determine the cause of diarrhea. PATIENTS AND METHODS: In this prospective, randomized, double-blind, placebo-controlled trial conducted from July 1998 to October 1999, 302 hospitalized patients receiving antibiotics were randomized to receive Lactobacillus GG, 20 x 10(9) CFU/d, or placebo for 14 days. Subjects recorded the number of stools and their consistency daily for 21 days. The primary outcome was the proportion of patients who developed diarrhea in the first 21 days after enrollment. Weekly telephone follow-up was also performed. Results were analyzed in an intention-to-treat fashion. RESULTS: Diarrhea developed in 39 (29.3%) of 133 patients randomized to receive Lactobacillus GG and in 40 (29.9%) of 134 patients randomized to receive placebo (P=.93). No additional difference in the rate of occurrence of diarrhea was found between treatment and placebo patients in a subgroup analysis of those treated with beta-lactam vs non-beta-lactam antibiotics. Too few patients had stool cultures, additional laboratory tests for diarrhea, or a positive diagnosis of Clostridium difficile infection to assess between-group differences. CONCLUSION: Lactobacillus GG in a dose of 20 x 10(9) CFU/d did not reduce the rate of occurrence of diarrhea in this sample of 267 adult patients taking antibiotics initially administered in the hospital setting.

A randomized controlled trial of the accuracy of clinical record retrieval using SNOMED-RT as compared with ICD9-CM.

BACKGROUND: Concept-based Indexing is purported to provide more granular data representation for clinical records.1,2 This implies that a detailed clinical terminology should be able to provide improved access to clinical records. To date there is no data to show that a clinical reference terminology is superior to a precoordinated terminology in its ability to provide access to the clinical record. Today, ICD9-CM is the most commonly used method of retrieving clinical records. OBJECTIVE: In this study, we compare the sensitivity, specificity, positive likelihood ratio, positive predictive value and accuracy of SNOMED-RT vs. ICD9-CM in retrieving ten diagnoses from a random sample of 2,022 episodes of care. METHOD: We randomly selected 1,014 episodes of care from the inpatient setting and 1,008 episodes of care from the outpatient setting. Each record had associated with it, the free text final diagnoses from the Master Sheet Index at the Mayo Clinic and the ICD9-CM codes used to bill for the encounters within the episode of care. The free text diagnoses were coded by two expert indexers (disagreements were addressed by a Staff Clinician) as to whether queries regarding one of 5 common or 5 uncommon diagnoses should return this encounter. The free text entries were automatically coded using the Mayo Vocabulary Processor. Each of the ten diagnoses was exploded in both SNOMED-RT and ICD9-CM and using these entry points, a retrieval set was generated from the underlying corpus of records. Each retrieval set was compared with the Gold Standard created by the expert indexers. RESULTS: SNOMED-RT produced significantly greater specificity in its retrieval sets (99.8% vs. 98.3%, p<0.001 McNemar Test). The positive likelihood ratios were significantly better for SNOMED-RT retrieval sets (264.9 vs. 33.8, p<0.001 McNemar Test). The positive predictive value of a SNOMED-RT retrieval was also significantly better than ICD9-CM (92.9% vs. 62.4%, p<0.001 McNemar Test). The accuracy defined as 1 (the total error rate (FP+FN) / Total # episodes queried (20,220)) was significantly greater for SNOMED-RT (98.2% vs. 96.8%, p=0.002 McNemar Test). Interestingly, the sensitivity of the SNOMED-RT generated retrieval set was not significantly different from ICD9-CM, but there was a trend toward significance (60.4% vs. 57.6%, p=0.067 McNemar Test). However, if we examine only the outpatient practice SNOMED-RT produced a more sensitive retrieval set than ICD9-CM (54.8% vs. 46.4%, p=0.002 McNemar Test). CONCLUSIONS: Our data clearly shows that information regarding both common and rare disorders is more accurately identified with automated SNOMED-RT indexing using the Mayo Vocabulary Processor than it is with traditional hand picked constellations of codes using ICD9-CM. SNOMED-RT provided more sensitive retrievals of outpatient episodes of care than ICD9-CM.

Use of low-molecular-weight heparin in the treatment of venous thromboembolic disease: answers to frequently asked questions. The Thrombophilia Center Investigators.

Low-molecular-weight heparins (LMWHs) represent an important therapeutic advance in the treatment of patients with venous thromboembolism. The use of LMWH has potential advantages in comparison with the use of standard unfractionated heparin (UH), including decreased binding to nonanticoagulant-related plasma proteins, greater bioavailability, longer half-life, and lower incidence of the heparin-induced thrombocytopenia syndrome. Because of the predictable anticoagulant response of LMWH when administered subcutaneously, laboratory monitoring is unnecessary, and the drug can be used to treat selected patients with venous thromboembolism in outpatient setting. Numerous studies have shown that the treatment of venous thromboembolism with LMWH is as safe and effective as that with standard UH when both are used appropriately. Allied health personnel can easily teach most patients to self-administer LMWH subcutaneously for home use. Transition of the treatment regimen to oral warfarin anticoagulation necessitates an overlap with heparin (UH or LMWH) for at least 4 to 5 days, and the international normalized ratio should ideally be 2.0 or higher for 2 consecutive days before heparin therapy is discontinued. A practical understanding of the pharmacology, risks, and benefits of LMWH in the treatment of venous thromboembolism will enhance the primary-care physician's ability to care for patients safely and cost-effectively.

Fecal hemoglobin excretion in elderly patients with atrial fibrillation: combined aspirin and low-dose warfarin vs conventional warfarin therapy.

BACKGROUND: Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy. METHODS: To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalization ratio,<1.5] plus 325 mg/d of enteric-coated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin. RESULTS: Among the 63 at high risk of stroke, abnormal values (>2mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean ( +/- SD) values were more for those randomly assigned to receive combined therapy (1.7 +/- 3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0 +/- 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (+/- SD) HemoQuant value of 0.8 +/- 0.7mg of hemoglobin per gram of stool 1 month after entry in the study. CONCLUSIONS: Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.

Management of atrial fibrillation in adults: prevention of thromboembolism and symptomatic treatment.

Because of its prevalence in the population and its associated underlying diseases and morbidity, atrial fibrillation (AF) is an important and costly health problem. Advancing age, diabetes, heart failure, valvular disease, hypertension, and myocardial infarction predict the occurrence of AF within a population. The management of AF is complex and involves prevention of thromboembolic complications and treatment of arrhythmia-related symptoms. Stroke occurs in 4.5% of untreated patients with AF per year. Independent risk factors for stroke in nonrheumatic patients with AF are advanced age; a history of prior embolism, hypertension, or diabetes; and echocardiographic findings of left atrial enlargement and left ventricular dysfunction. Warfarin decreases stroke by two-thirds and death by one-third; aspirin is only about half as effective overall and is insufficient therapy for those with risk factors for stroke. Options for thromboembolic prophylaxis are use of warfarin for all in whom it is safe or, alternatively, warfarin for those with risk factors and aspirin for those without risk factors. One-half of the patients with AF are 75 years of age or older. The uniform applicability and relative safety of warfarin therapy in this age-group are controversial. Specific therapy for the arrhythmia should be dictated by the need to control symptoms. Symptomatic treatments include rate-control medications and strategies designed to terminate and prevent arrhythmia recurrence. Digoxin, beta-adrenergic blockers, verapamil, and diltiazem slow excessive ventricular rates in patients with AF and may favorably manage comorbid conditions. The efficacy of anti-arrhythmic medications is only 40 to 70% per year in preventing recurrences of AF, and these agents, except amiodarone, may increase the risk of sudden death in patients with certain types of organic heart disease and AF. The use of nonpharmacologic symptomatic therapies such as atrioventricular node modification or ablation with a rate-response pacemaker or surgical intervention is increasing.

Current concepts in anticoagulant therapy.

An understanding of the international normalized ratio (INR)--which was developed to standardize reporting of the prothrombin time (PT) and provide consistent regulation of anticoagulation--is important. The recommended therapeutic range for the INR (which is calculated from the patient's PT, a mean control PT, and the international sensitivity index) for oral anticoagulant treatment of most conditions is 2.0 to 3.0. In patients with mechanical cardiac valves, the INR should be at least 2.5 to 3.5. A common cause for progression of venous thromboembolic disease and treatment failure is inadequate heparinization during the first day of treatment. Therefore, an intravenous bolus of 5,000 to 10,000 U of heparin should be administered before a maintenance infusion is initiated. Also during the first day of treatment, warfarin therapy can be implemented. Overlap treatment with heparin and warfarin for 4 or 5 days is recommended. Low-molecular-weight heparins, a new class of anticoagulants, have been shown to be more effective than standard heparin in preventing venous thrombosis in orthopedic surgical patients, but at a higher cost. Patients with mechanical cardiac valves who are receiving anticoagulant therapy and are scheduled for noncardiac operations must have a risk-to-benefit assessment of the need for continuous anticoagulation performed preoperatively. Many of these patients can safely discontinue warfarin therapy for several days as outpatients before the surgical procedure. Preoperative heparin therapy and warfarin withdrawal in the hospital are recommended only for those patients with cardiac valves at high risk for systemic embolization (with a mitral valve prosthesis, cardiomyopathy, or previous thromboembolism). The concurrent use of certain drugs or presence of comorbid conditions can predispose to hemorrhagic complications of anticoagulant therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The macroenzymes: a clinical review.

Macroenzymes are serum enzymes that have a higher molecular mass than the corresponding enzyme normally found in serum under physiologic or pathophysiologic conditions. Although no evidence convincingly indicates that macroenzymes cause disease or necessitate treatment, some patients with immunoglobulin-complexed enzyme disorders have previously been reported to have associated autoimmune diseases or malignant lesions. To address this issue, we reviewed the medical records of 42 patients in whom a macroenzyme had been detected during assessment at the Mayo Clinic between 1986 and 1990. Of these 42 patients, 21 had macro-creatine kinase, 10 had macro-lactate dehydrogenase, 6 had macro-aspartate aminotransferase, and 5 had macroamylase in the serum. Although the study group did not include all Mayo patients with this phenomenon, it represented a sufficient sample size to determine retrospectively whether specific dismissal diagnoses were present concurrently. The most common findings in this group of patients with macroenzymes were (1) advanced age (except for those with macro-aspartate aminotransferase), (2) cardiovascular disease (probably due to sampling bias), (3) malignant lesions (particularly in those with macro-creatine kinase), and (4) rheumatologic disease (in those with macro-lactate dehydrogenase). The immunoglobulin-complexed enzyme disorders are characterized by increased total serum enzyme levels that are often isolated and persistent. Physicians should be aware of the presence of macroenzymes so that invasive or costly procedures are not undertaken unnecessarily to determine the cause of increased serum enzyme levels.

Pancreatic pseudocyst that compressed the inferior vena cava and resulted in edema of the lower extremities.

To our knowledge, edema of the lower extremities has not previously been reported as a sign of a pancreatic pseudocyst. In this case report, we describe a 66-year-old man in whom such a lesion compressed the inferior vena cava and caused pronounced leg swelling. After drainage of the pseudocyst, the edema did not recur. Although the most well-known complications of pancreatic pseudocyst are pain, hemorrhage, rupture, infection, and obstruction of adjacent viscera, bilateral edema of the lower extremities can be the initial manifestation of this lesion.

Renal cell carcinoma associated with sarcoidlike tissue reaction.

A 60-year-old man was referred to our institution with the diagnosis of sarcoidosis. Because of several months' complaint of right flank pain and weight loss, the patient had consulted his local physician. After an extensive workup revealed only cholelithiasis, he underwent a cholecystectomy for presumed chronic cholecystitis. At the time of operation, biopsy of several liver nodules and peripancreatic nodes revealed noncaseating granulomas, consistent with sarcoidosis. On initial examination at our institution, the patient had microhematuria. A chest roentgenogram demonstrated multiple pulmonary nodules, an abdominal computed tomographic scan showed an indeterminate left renal mass, and magnetic resonance imaging of the spine revealed abnormal signals in the body of T-12. Open-lung biopsy showed an adenocarcinoma with clear cell features, likely of renal origin. The patient was diagnosed as having a metastatic renal carcinoma associated with a sarcoidlike tissue reaction. Although noncaseating granulomas have been reported in association with other malignant lesions, to our knowledge this is the first report of such an association with renal carcinoma. In addition, this case illustrates several points. First, sarcoidosis is a multisystem disorder with protean extrapulmonary manifestations. In fact, all our patient's findings could have been attributed to sarcoidosis. Second, noncaseating granulomas occur with many types of processes, including infections, chemical exposures, and, as in this case, neoplasms. Thus, noncaseating granulomas are not pathognomonic for sarcoidosis. Third, sarcoidosis is a clinical diagnosis that cannot be based on histologic findings alone.