Randomized comparison of ultrasound surveillance and clinical monitoring on arteriovenous graft outcomes.

Arteriovenous graft thrombosis is a frequent event in hemodialysis patients, and usually occurs in grafts with significant underlying stenosis. Regular surveillance for graft stenosis, with pre-emptive angioplasty of significant lesions, may improve graft outcomes. This prospective, randomized, clinical trial allocated 126 hemodialysis patients with grafts to either clinical monitoring alone (control group) or to regular ultrasound surveillance for graft stenosis every 4 months in addition to clinical monitoring (ultrasound group). The two randomized groups were closely matched with respect to demographic, clinical, and graft characteristics, with the exception of a lower frequency of diabetes in the ultrasound group. The primary outcome was graft survival, and the secondary outcome was thrombosis-free graft survival. The frequency of pre-emptive graft angioplasty was 64% higher in the ultrasound group than in the control group (1.05 vs 0.64 events per patient-year, P<0.001), whereas the frequency of thrombosis was not different (0.67 vs 0.78 per patient-year, P=0.37). The median time to permanent graft failure was similar between the two groups (38 vs 37 months, P=0.93). Likewise, the median time to graft thrombosis or failure did not differ (22 vs 25 months, P=0.33). There was no significant association between diabetes and time to graft failure (P=0.93) or time to graft thrombosis or failure (P=0.88). In conclusion, the addition of regular ultrasound surveillance for graft stenosis to clinical monitoring increases the frequency of pre-emptive angioplasty, but may not decrease the likelihood of graft failure or thrombosis.

Adverse cardiac events after surgery: assessing risk in a veteran population.

OBJECTIVE: To establish rates of and risk factors for cardiac complications after noncardiac surgery in veterans. DESIGN: Prospective cohort study. SETTING: A large urban veterans affairs hospital. PARTICIPANTS: One thousand patients with known or suspected cardiac problems undergoing 1,121 noncardiac procedures. MEASUREMENTS: Patients were assessed preoperatively for important clinical variables. Postoperative evaluation was done by an assessor blinded to preoperative status with a daily physical examination, electrocardiogram, and creatine kinase with MB fraction until postoperative day 6, day of discharge, death, or reoperation (whichever occurred earliest). Serial electrocardiograms, enzymes, and chest radiographs were obtained as indicated. Severe cardiac complications included cardiac death, cardiac arrest, myocardial infarction, ventricular tachycardia, and fibrillation and pulmonary edema. Serious cardiac complications included the above, heart failure, and unstable angina. MAIN RESULTS: Severe and serious complications were seen in 24% and 32% of aortic, 8.3% and 10% of carotid, 11.8% and 14.7% of peripheral vascular, 9.0% and 13.1% of intraabdominal/intrathoracic, 2.9% and 3.3% of intermediate-risk (head and neck and major orthopedic procedures), and 0.27% and 1.1% of low-risk procedures respectively. The five associated patient-specific risk factors identified by logistic regression are: myocardial infarction < 6 months (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.9 to 12.9), emergency surgery (OR, 2.6; 95% CI, 1.2 to 5.6), myocardial infarction > 6 months (OR, 2.2; 95% CI, 1.4 to 3.5), heart failure ever (OR, 1.9; 95% CI, 1.2 to 3.0), and rhythm other than sinus (OR, 1.7; 95% CI, 0.9 to 3.2). Inclusion of the planned operative procedure significantly improves the predictive ability of our risk model. CONCLUSIONS: Five patient-specific risk factors are associated with high risk for cardiac complications in the perioperative period of noncardiac surgery in veterans. Inclusion of the operative procedure significantly improves the predictive ability of the risk model. Overall cardiac complication rates (pretest probabilities) are established for these patients. A simple nomogram is presented for calculation of post-test probabilities by incorporating the operative procedure.

Surveillance colonoscopy or chemoprevention with COX-2 inhibitors in average-risk post-polypectomy patients: a decision analysis.

OBJECTIVES: Clinical trials are currently underway evaluating the efficacy of COX-2 inhibitors in decreasing the incidence of adenomas and colorectal carcinoma in 'average' risk individuals. AIM: To use decision analysis to compare the cost-effectiveness of celecoxib to surveillance colonoscopy in 'average' risk patients who had undergone prior adenoma resection. METHODS: A model of the natural history of adenomas after endoscopic polypectomy was constructed using probabilities from the literature. Cost estimates were obtained from available Medicare reimbursement rates and supplemented by the literature. Three strategies were evaluated: (i) no surveillance; (ii) colonoscopic surveillance; and (iii) celecoxib chemoprevention. We compared total costs and performed cost-effectiveness analysis between these strategies. The outcome measures were years of life saved and 'high-grade' adenoma prevented. Sensitivity analyses were performed on selected variables. RESULTS: Our base-case analysis assumed a 50% risk reduction in the incidence of adenomas among patients using celecoxib. No surveillance was associated with a cost of $1014 per patient, and colonoscopic surveillance with a cost of $1572 per patient, whereas celecoxib use was associated with a total cost of $11,503. Ten years after the index colonoscopy, 15% of patients in the no surveillance strategy developed 'high-grade' lesions compared to 13% of patients in the colonoscopic surveillance group and 6% in the celecoxib group. There was a small gain in years of life saved (0.006) favouring celecoxib over colonoscopic surveillance. The incremental cost-effectiveness ratio of celecoxib vs. colonoscopy was $141 871 per 'high-grade' adenoma prevented and $1,715,199 per year of life saved. The most important variables in determining the cost-effectiveness of celecoxib were its cost and its efficacy. CONCLUSION: Chemoprevention with COX-2 inhibitors in 'average-risk' postpolypectomy patients is a more expensive strategy compared to colonoscopic surveillance.

What is heartburn worth? A cost-utility analysis of management strategies.

OBJECTIVE: To determine the best treatment strategy for the management of patients presenting with symptoms consistent with uncomplicated heartburn. METHODS: We performed a cost-utility analysis of 4 alternatives: empirical proton pump inhibitor, empirical histamine2-receptor antagonist, and diagnostic strategies consisting of either esophagogastroduodenoscopy (EGD) or an upper gastrointestinal series before treatment. The time horizon of the model was 1 year. The base case analysis assumed a cohort of otherwise healthy 45-year-old individuals in a primary care practice. MAIN RESULTS: Empirical treatment with a proton pump inhibitor was projected to provide the greatest quality-adjusted survival for the cohort. Empirical treatment with a histamine2 receptor antagonist was projected to be the least costly of the alternatives. The marginal cost-effectiveness of using a proton pump inhibitor over a histamine2-receptor antagonist was approximately $10,400 per quality-adjusted life year (QALY) gained in the base case analysis and was less than $50,000 per QALY as long as the utility for heartburn was less than 0.95. Both diagnostic strategies were dominated by proton pump inhibitor alternative. CONCLUSIONS: Empirical treatment seems to be the optimal initial management strategy for patients with heartburn, but the choice between a proton pump inhibitor or histamine2-receptor antagonist depends on the impact of heartburn on quality of life.

Cost-effectiveness of low-molecular-weight heparin in the treatment of proximal deep vein thrombosis.

OBJECTIVE: To estimate the cost-effectiveness of low-molecular-weight heparin (LMWH) in the treatment of proximal lower extremity deep venous thrombosis. DESIGN: Cost-effectiveness analysis that includes the treatment of the index case and simulated 3-month follow-up. SETTING: Acute care facility. PATIENTS AND PARTICIPANTS: Hypothetical cohorts of 1,000 patients who present with proximal deep venous thrombosis. INTERVENTIONS: Intravenous unfractionated heparin (UH), LMWH (40% at home, 60% in hospital), or selective UH/LMWH (UH for hospitalized patients and LMWH for patients treated at home). MEASUREMENTS AND MAIN RESULTS: The outcomes were recurrent thrombosis, mortality, direct medical costs, and marginal cost-effectiveness ratios from the payer's perspective. At the base-case and under most assumptions in the sensitivity analysis, the LMWH and the selective UH/LMWH strategies dominate the UH strategy i.e., they result in fewer cases of recurrent thrombosis and fewer deaths, and they save resources. The savings occur primarily by decreasing the length of stay. The LMWH strategy resulted in lower costs as compared with the UH strategy when the proportion of patients treated at home was more than 14%. Treating 1, 000 patients with the LMWH strategy as compared with the UH/LMWH strategy would result in 10 fewer cases of recurrent thrombosis, 1.2 fewer deaths, at an additional cost of $96,822; the cost-effectiveness ratio was $9,667 and $80,685 per recurrent thrombosis or death prevented, respectively. CONCLUSIONS: Treatment with LMWH leads to savings and better outcomes as compared with UH in patients with lower extremity deep venous thrombosis. The selective UH/LMWH strategy is an alternative option.

The status of the clinicopathologic conference in academic medical centers.

To determine the current level of use, characteristics, and perceived value of the clinicopathologic conference (CPC), we sent a 22-item survey questionnaire to the program directors of internal medicine residency training programs. Of the 278 residency training programs that returned questionnaires, 221 (80%) indicated that they held CPCs regularly. The conference received a mean rating (Likert scale 1 = best to 5 = worst) of 2.2 (95% confidence interval 2.2, 2. 3) for both its perceived educational value and its popularity. The CPC remains widely used in internal medicine training programs. Although relatively few programs have rigorous guidelines for preparation and evaluation of their presentations, the CPC is generally viewed as being popular and having sound educational value.

Choice of long-term strategy for the management of patients with severe esophagitis: a cost-utility analysis.

BACKGROUND & AIMS: Omeprazole has shown remarkable efficacy and safety in the treatment of patients with gastroesophageal reflux disease (GERD); similarly, laparoscopic techniques have allowed less morbidity in patients undergoing fundoplication procedures. Concerns about the long-term cost and safety of both strategies have prompted a debate of their role in long-term management of patients with severe erosive esophagitis. METHODS: A cost-utility analysis was performed to compare two strategies: laparoscopic Nissen fundoplication (LNF) vs. omeprazole. A two-stage Markov model was used to obtain cost and efficacy estimates; all estimates were discounted at 3% per year. The time horizon was 5 years. Sensitivity analyses were performed on all relevant variables. RESULTS: Both strategies were similarly effective (4.33 quality-adjusted life years per patient), with omeprazole less expensive than LNF ($6053 vs. $9482 per patient). At 10 years, LNF and omeprazole costs were similar. Efficacy estimates were extremely sensitive to changes in quality of life associated with postoperative symptoms and long-term use of medication. CONCLUSIONS: Medical therapy is the preferred treatment strategy for most patients with severe erosive esophagitis. Individuals with a long life expectancy are good candidates for LNF if postoperative morbidity is low and GERD symptoms remain abated for many years.

Validation of a clinical prediction rule for the differential diagnosis of acute meningitis.

OBJECTIVE: To attempt to validate a previously reported clinical prediction rule derived to assist in distinguishing between acute bacterial meningitis and acute viral meningitis. DESIGN: Retrospective chart review of patients treated at five hospitals between 1981 and 1990. The criterion standard for bacterial meningitis was a positive cerebrospinal fluid (CSF) or blood culture or a positive test for bacterial antigen in the CSF. For viral meningitis, the criterion standard was a positive viral culture from CSF, stool, or blood or a discharge diagnosis of viral meningitis with no other etiology evident. SETTING: Two Department of Veterans Affairs (VA) hospitals, two county hospitals, and one private hospital, each affiliated with one of two medical schools. PATIENTS: All persons aged more than 17 years who were hospitalized over a ten-year period at one of five academically affiliated hospitals for the management of acute meningitis. MEASUREMENTS AND MAIN RESULTS: Sixty-two cases of bacterial meningitis and 98 cases of viral meningitis were confirmed. With all patients included, the discriminatory power of the model as measured by the area under the receiver operating characteristic curve (AUC) was 0.977 (95% CI, 0.957-0.997), compared with the AUC of 0.97 in the derivation set of the original publication. The AUCs (95% CIs) for data subsets were: Dallas cases 0.994 (0.986-1.0). Milwaukee cases 0.912 (0.834-0.990); ages 18-39 years 0.952 (0.892-1.0), ages 40-59 years 0.99 (0.951-1.0), and age > or = 60 years 0.955 (0.898-1.0). CONCLUSIONS: The authors conclude that the clinical prediction rule proved robust when applied to a geographically distinct population comprised exclusively of adults. There was sustained performance of the model when applied to cases from each city and from three age strata. Prospective validation of this prediction rule will be necessary to confirm its utility in clinical practice.

Combination drug therapy for hypercholesterolemia. The trade-off between cost and simplicity.

BACKGROUND: The National Cholesterol Education Program recommends achievement of a defined target level of low-density lipoprotein cholesterol (LDL-C) for the treatment of hypercholesterolemia. They endorse the use of niacin and/or sequestrants as the first line of therapy to achieve such target LDL-C level. This recommendation has not been compared with the use of lovastatin as initial therapy if multidrug regimens are required to achieve goal LDL-C. METHODS: Prospectively collected data on tolerance and effectiveness for niacin, sequestrants, and lovastatin were obtained from a lipid clinic at a large midwestern Veterans Affairs medical center. We used a decision tree to compare the complexity and cost of three sequential drug algorithms used for the following initial LDL-C levels: 4.14, 4.91, 5.69, and 6.47 mmol/L (160, 190, 220, and 250 mg/dL). Algorithm 1 was niacin followed by a sequestrant and then lovastatin; algorithm 2, a sequestrant followed by niacin and then lovastatin; and algorithm 3, lovastatin followed by niacin and a sequestrant. Drug and laboratory costs were obtained from the pharmacy and pathology services at the same institution. Sensitivity analyses were performed on the tolerance and effectiveness of each drug as well as drug and laboratory cost estimates. RESULTS: The probability of achieving target LDL-C level (3.36 mmol/L [130 mg/dL]) decreased as initial LDL-C level increased. As a rule, algorithm 3 required fewer drugs in combination to achieve the target level for all initial LDL-C levels modeled. In addition, the use of lovastatin was high across all algorithms at all initial LDL-C levels modeled. Algorithm 1 was less expensive than algorithm 2 or 3 at a low initial LDL-C level (4.14 mmol/L [160 mg/dL]), with an average cost of $375 vs $454 vs $585, respectively. At all other initial LDL-C levels (4.91, 5.69, and 6.47 mmol/L [190, 220, and 250 mg/dL]), algorithm 2 was slightly less expensive than algorithm 1. Algorithm 3 became relatively less expensive as initial LDL-C level increased: 56% more expensive than algorithm 1 at an initial LDL-C level of 4.14 mmol/L (160 mg/dL) as compared with 7% more expensive than algorithm 1 at an initial LDL-C level of 6.47 mmol/L (250 mg/dL). CONCLUSIONS: Fulfillment of the target LDL-C approach recommended by the National Cholesterol Education Program often requires the use of multiple drugs. When lovastatin is used initially, the regimen becomes simpler, albeit more expensive. At initial LDL-C levels of 4.91 mmol/L (190 mg/dL) or higher, this difference in cost becomes progressively smaller (7% at 6.47 mmol/L [250 mg/dL]), making algorithm 3 the better alternative; at low initial LDL-C levels (4.14 mmol/L [160 mg/dL]), a niacin-first regimen is reasonably simple and substantially less expensive. At moderate and severe initial LDL-C levels (4.91 and 5.69 mmol/L [190 and 220 mg/dL]), the lovastatin-first regimen may be advantageous.

Preventing restenosis with fish oils following coronary angioplasty. A meta-analysis.

BACKGROUND: No medical therapy has been shown to reduce the rate of restenosis following percutaneous transluminal coronary angioplasty. We examined the existing evidence for the use of omega-3 fatty acids in this capacity with the tool of meta-analysis. METHODS: A computerized search and a bibliographic review of published articles were performed. Abstracts were identified through journals, Index Medicus, and an unpublished listing of recent requests for fish oil for experimental use. All English-language randomized clinical trials with available reports were included in the analysis. The quality, design differences, and outcomes were evaluated for each study. RESULTS: For four studies that used angiography to define coronary restenosis, the absolute difference in restenosis rates between treatment and control groups was 13.9% (95% confidence interval [CI], 3.2% to 24.5%). Furthermore, regression analysis revealed a positive linear relationship between the dose of omega-3 fatty acids used and the absolute difference in restenosis rates (r = .99, P < .03). When three studies that used stress testing as a means of determining restenosis rates were added to the four studies that used angiography, the risk difference was 5.1% (95% CI, -3.8% to 13.9%). CONCLUSIONS: Restenosis after coronary angioplasty is reduced by supplemental fish oils, and the extent of the observed benefit may be dependent on the dose of omega-3 fatty acids used.