Monitored isoniazid prophylaxis for low-risk tuberculin reactors older than 35 years of age: a risk-benefit and cost-effectiveness analysis

BACKGROUND: Isoniazid chemoprophylaxis effectively prevents the development of active infectious tuberculosis. Current guidelines recommend withholding this prophylaxis for low-risk tuberculin reactors older than 35 years of age because of the risk for fatal isoniazid-induced hepatitis. However, recent studies have shown that monitoring for hepatotoxicity can significantly reduce the risk for isoniazid-related death. OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of monitored isoniazid prophylaxis for low-risk tuberculin reactors older than 35 years of age. DESIGN: A Markov model was used to compare the health and economic outcomes of prescribing or withholding a course of prophylaxis for low-risk reactors 35, 50, or 70 years of age. Subsequent analyses evaluated costs and benefits when the effect of transmission of Mycobacterium tuberculosis to contacts was included. MEASUREMENTS: Probability of survival at 1 year, number needed to treat, life expectancy, and cost per year of life gained for individual persons and total population. RESULTS: Isoniazid prophylaxis increased the probability of survival at 1 year and for all subsequent years. For 35-year old, 50-year-old, and 70-year-old tuberculin reactors, life expectancy increased by 4.9 days, 4.7 days, and 3.1 days, respectively, and costs per person decreased by $101, $69, and $11, respectively. When the effect of secondary transmission to contacts was included, the gains in life expectancy per person receiving prophylaxis were 10.0 days for 35-year-old reactors, 9.0 days for 50-year-old reactors, and 6.0 days for 70-year-old reactors. Costs per person for these cohorts decreased by $259, $203, and $100, respectively. The magnitude of the benefit of isoniazid prophylaxis is moderately sensitive to the effect of isoniazid on quality of life. The hypothetical provision of isoniazid prophylaxis for all low-risk reactors older than 35 years of age in the U.S. population could prevent 35,176 deaths and save $2.11 billion. CONCLUSIONS: Monitored isoniazid prophylaxis reduces mortality rates and health care costs for low-risk tuberculin reactors older than 35 years of age, although reductions for individual patients are small. For the U.S. population, however, the potential health benefits and economic savings resulting from wider use of monitored isoniazid prophylaxis are substantial. We should consider expanding current recommendations to include prophylaxis for tuberculin reactors of all ages with no contraindications.     

Evaluating the potential cost-effectiveness of stenting as a treatment for symptomatic single-vessel coronary disease. Use of a decision-analytic model

BACKGROUND: Coronary stenting appears to provide more predictable immediate results and lower rates of restenosis than conventional balloon angioplasty for selected lesion types, but its hospital costs are significantly higher. This study was designed to evaluate the potential cost-effectiveness of Palmaz-Schatz coronary stenting relative to conventional balloon angioplasty for the treatment of patients with symptomatic, single-vessel coronary disease. METHODS AND RESULTS: We developed a decision-analytic model to predict quality-adjusted life expectancy and lifetime treatment costs for patients with symptomatic, single-vessel coronary disease treated by either Palmaz-Schatz stenting (PSS) or conventional angioplasty (PTCA). Estimates of the probabilities of overall procedural success (PTCA, 97%; PSS, 98%), abrupt closure requiring emergency bypass surgery (PTCA, 1.0%; PSS, 0.6%), and angiographic restenosis (PTCA, 37%; PSS, 20%) were derived from review of the literature published as of September 1993. Procedural costs were based on the true economic (ie, variable) costs of each procedure at Boston's Beth Israel Hospital. On the basis of these data, coronary stenting was estimated to result in a higher quality-adjusted life expectancy than conventional angioplasty but to incur additional costs as well. Compared with conventional angioplasty, stenting had an estimated incremental cost-effectiveness ratio of $23,600 per quality-adjusted life year gained. Although the cost-effectiveness ratio for stenting changed with variations in assumptions about the relative costs and restenosis rates, it remained less than $40,000 per quality-adjusted year of life gained--and thus was similar to many other accepted medical treatments--unless the stent angiographic restenosis rate was > 23%, the angioplasty restenosis rate was < 34%, or the cost of stenting (including vascular complications) exceeded that of conventional angioplasty by more than $3000. The alternative strategy of secondary stenting (initial angioplasty followed by stenting only for symptomatic restenosis) was estimated to be both less effective and less cost-effective than primary stenting over a wide range of plausible assumptions and thus does not appear to be cost-effective when primary stenting is also an option. CONCLUSIONS: Decision-analytic modeling can be used to evaluate the potential cost-effectiveness of new coronary interventions. Our analysis suggests that despite its higher cost, elective coronary stenting may be a reasonably cost-effective treatment for selected patients with single-vessel coronary disease. Primary stenting is unlikely to be cost-effective for lesions with a low probability of restenosis (eg, < 30%) or for patients for whom the cost of stenting is expected to be much higher than usual (eg, because of a high risk of vascular complications). Given the sensitivity of the cost-effectiveness ratios to even modest variations in the relative restenosis rates and cost estimates, future studies will be necessary to determine more precisely the cost-effectiveness of coronary stenting for specific patient and lesion subsets.     

Epigastric antinociception by cervical dorsal column lesions in rats

OBJECTIVE: The purpose was to determine the optimal treatment protocol for women with a cervical vaginal diagnosis of atypical squamous cells of undetermined significance. STUDY DESIGN: By means of decision analysis, 8 strategies were compared in terms of cost, life expectancy, cost-effectiveness, and the number of cancers and complications from treatment. Data were obtained from the medical literature and the University of Iowa Hospitals and Clinics. RESULTS: Compared with more aggressive strategies, such as those that use immediate colposcopy, strategies featuring repeated smears were less expensive and carried fewer complications but had lower life expectancies per patient and more cancers. The strategy of repeating a smear annually had a lower cost per patient than did the other strategies, ranging from $112 to $989, and had a similar discounted life expectancy to that of the strategy with the longest discounted life expectancy. CONCLUSIONS: In most clinical scenarios strategies that used repeated smears were the most cost-effective.     

Endoscopic assessment of variceal volume and wall tension in cirrhotic patients: effects of pharmacological therapy

BACKGROUND & AIMS: Variceal rupture is believed to occur when variceal wall tension is excessive. The combined use of endosonography, allowing the objective measurement of variceal radius, and endoscopic measurement of transmural variceal pressure may enable assessment of this important parameter. The aim of this study was to assess the effects on variceal hemodynamics of drugs acting through different mechanisms: decreasing portocollateral blood flow (propranolol) or resistance (isosorbide-5-mononitrate [ISMN]). METHODS: Repeated measurements of variceal radius, volume (by endosonography), and transmural pressure (using endoscopic gauge) were performed in 27 cirrhotic patients at baseline and 40 minutes after double-blind administration of placebo (n = 9), propranolol (n = 9), or ISMN (n = 9). RESULTS: Placebo had no effect. Propranolol significantly reduced variceal volume (-32% +/- 26%; P = 0.01), radius (-12% +/- 9%; P < 0.005), and pressure (-26% +/- 10%; P < 0.0001). The resulting decrease in wall tension (-34% +/- 13%; P < 0.0005) exceeded that in transmural pressure (P < 0.01). ISMN reduced transmural variceal pressure (-26% +/- 21%; P < 0.005), but not radius (-3% +/-14%; NS) and volume (-9% +/- 31%; NS). CONCLUSIONS: The combination of endosonography and endoscopic measurement of transmural variceal pressure allows quantitative estimation of variceal wall tension. Propranolol and ISMN reduce similarly transmural variceal pressure. Propranolol, but not ISMN, reduces variceal volume and radius. Therefore, despite similar decreases in variceal wall tension, propranolol may offer a greater therapeutic effect than ISMN in portal hypertension.     

Medical prophylaxis of haemorrhage from oesophageal varices in patients with liver cirrhosis

Haemorrhage from oesophageal varices is a life-threatening event in patients with liver cirrhosis. About 40-80% of patients surviving the first bleeding suffer a recurrence within 1 year. This high recurrence rate substantially contributes to the mortality in patients with liver cirrhosis. Therefore, various treatment regimens in both primary and secondary prophylaxis were studied. Most experience in medical primary prophylaxis was collected with beta-blockers, mainly propranolol. Treating patients with oesophageal varices with propranolol significantly reduces the incidence of first variceal bleeding. However, the effect on mortality is marginal, and primary prophylaxis is generally not recommended in these patients. Several studies support the hypothesis that medical prophylaxis with beta-blockers is more effective in reducing the rate of first oesophageal bleeding in patients with a high risk of haemorrhage, such as those with very large varices with red spots. A score to assess an individual patient's risk of variceal bleeding would be helpful, but until such a score has been validated, no general rule for this treatment decision can be given. In secondary prophylaxis, both beta-blockers and endoscopic therapy (sclerotherapy or ligation of the varices) are effective in lowering the rate of rebleeding. However, the effect on mortality was not significant in most studies. Several studies comparing the efficacy of medical prophylaxis and endoscopic treatment showed advantages of the endoscopic therapy with a greater reduction in recurrent bleeding episodes. However, medical prophylaxis with beta-blockers has the important advantage of being immediately effective, whereas endoscopic procedures provide the best protection against recurrent bleeding after complete obliteration of the varices. Therefore, in the first weeks and months of endoscopic therapy, additional treatment with beta-blockers may further reduce the risk of rebleeding. Only half of all studies on this topic reported a significant advantage with this combined therapy. Therefore, it seems reasonable to restrict this approach to patients with a high risk of rebleeding, such as patients with large sclerotherapy-derived oesophageal ulcers.     

Modulation of excision repair cross complementation group 1 (ERCC-1) mRNA expression by pharmacological agents in human ovarian carcinoma cells

CONTEXT: ThinPrep, AutoPap, and Papnet are 3 new technologies that increase the sensitivity and cost of cervical cancer screening. OBJECTIVE: To estimate the cost-effectiveness of these technological enhancements to Papanicolaou (Pap) tests. DESIGN: We estimated the increase in sensitivity from using these technologies by combining results of 8 studies meeting defined criteria. We used published literature and additional sources for cost estimates. To estimate overall cost-effectiveness, we applied a 9-state time-varying transition state model to these data and information about specific populations. SETTING: A hypothetical program serving a cohort of 20- to 65-year-old women who begin screening at the same age and are representative of the US population. RESULTS: The new technologies increased life expectancy by 5 hours to 1.6 days, varying with the technology and the frequency of screening. All 3 technologies also increased the cost per woman screened by $30 to $257 (1996 US dollars). AutoPap dominated ThinPrep in the base case. At each screening interval, AutoPap increased survival at the lowest cost. The cost per year of life saved rose from $7777 with quadrennial screening to $166000 with annual screening. Papnet produced more life-years at a higher cost per year of life saved. However, when used with triennial screening, each of them produced more life-years at lower cost than conventional Pap testing every 2 years. The cost-effectiveness ratio of each technology improved with increases in the prevalence of disease, decreases in the sensitivity of conventional Pap testing, and increases in the improvement in sensitivity produced by the technology. CONCLUSIONS: Technologies to increase the sensitivity of Pap testing are more cost-effective when incorporated into infrequent screening. Increases in sensitivity and decreases in cost may eventually make each technology more cost-effective.     

Cost-effectiveness of a community-level HIV risk reduction intervention

OBJECTIVES: The authors evaluated the cost-effectiveness of a community-level HIV prevention intervention that used peer leaders to endorse risk reduction among gay men. METHODS: A mathematical model of HIV transmission was used to translate reported changes in sexual behavior into an estimate of the number of HIV infections averted. RESULTS: The intervention cost $17,150, or about $65,000 per infection averted, and was therefore cost-saving, even under very conservative modeling assumptions. CONCLUSIONS: For this intervention, the cost of HIV prevention was more than offset by savings in averted future medical care costs. Community-level interventions to prevent HIV transmission that use existing social networks can be highly cost-effective.     

Analytical decision model for the cost-effective management of solitary pulmonary nodules

PURPOSE AND METHODS: Multiple strategies are currently being used to manage patients who present with indeterminate solitary pulmonary nodules (SPN). We have used decision-analysis models to assess the cost-effectiveness of various strategies for the diagnosis and management of SPN. Four decision strategies were compared: a wait and watch strategy, a surgery strategy, a computed tomography (CT)-based strategy, and a CT-plus-positron emission tomography (PET) strategy. An incremental cost-effectiveness ratio (ICER) was used to compare all strategies to the wait and watch strategy. RESULTS: A CT-plus-PET strategy was the most cost-effective over a large pretest likelihood (probability of having a malignant nodule), with a range of 0.12 to 0.69. Furthermore, within this likelihood range, the potential cost savings of using the CT-plus-PET strategy over the CT strategy ranged from $91 to $2,200 per patient. This translates to a yearly national savings of approximately $62.7 million. CONCLUSION: Decision-analysis modeling indicates the potential cost-effectiveness of [18F]2-fluoro-2-deoxy-D-glucose (FDG)-PET in the management of SPN. Furthermore, the decision trees developed can be used to model various features of the management of SPN, including modeling the cost-effectiveness of other newly emerging technologies.     

Localization of the APECED protein in distinct nuclear structures

The effect of changes in cytology laboratory costs, including the costs of new technologies, on the cost-effectiveness of cervical cancer prevention has not been studied. Using University of Iowa laboratory detection rates and costs, a decision model determined the cost-effectiveness of the laboratory with and without new technologies. Compared with not performing a cervicovaginal smear, the cost to increase the discounted life expectancy per patient by 1 year was $2,805 for the laboratory component alone and $19,655 for the entire cervical cancer prevention strategy. In moderate- to high-risk women, cervical cancer screening was cost-effective even at high cytology laboratory costs (eg, $75 per smear). New technologies were cost-effective only if they resulted in a substantial increase in the detection of high-grade squamous intraepithelial lesions (eg, an additional 236 high-grade squamous intraepithelial lesions per 10,000 women). New technologies have not demonstrated these increased detection rates.     

Cost-analysis of prophylactic antibiotics in spontaneous bacterial peritonitis

BACKGROUND & AIMS: Antibiotic prophylaxis has been shown to decrease the incidence of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites. The aim of this study was to test whether antibiotic prophylaxis for SBP is cost-effective and to compare the costs associated with different patient groups and treatment strategies. METHODS: A cost-effectiveness analysis was performed using a Markov chain model. The costs incurred during 1-year treatment with prophylactic antibiotics vs. no prophylaxis in patients with cirrhosis and ascites were calculated. The incidence rates of primary and recurrent SBP and the mortality rate of SBP were obtained from the literature. Total direct costs of SBP treatment were determined from the wholesale price of drugs and from disbursements by the Health Care Financing Administration. RESULTS: Norfloxacin prophylaxis resulted in savings between $2216 and $8545 per patient per year, depending on the patient group studied. Trimethoprim-sulfamethoxazole prophylaxis resulted in savings between $2934 and $9251 per patient per year. The groups that benefited most from prophylaxis were patients with an ascitic fluid total protein concentration of < or = 1 g/dL and those with a previous history of SBP. CONCLUSIONS: The use of prophylactic antibiotics to decrease the incidence of SBP is a cost-saving strategy in patients with cirrhosis and ascites.     

Investigation of milk-borne Streptococcus zooepidemicus infection associated with glomerulonephritis in Australia

OBJECTIVES: The aim of this study was to estimate the cost-effectiveness of antihypertensive treatment in elderly people based on the results of the Swedish Trial in Old Patients with Hypertension (STOP Hypertension). DESIGN: The STOP Hypertension study was a randomized trial comparing active antihypertensive treatment with a placebo. The risk of stroke, cardiovascular disease and total mortality was significantly reduced in the actively treated group compared to placebo. SETTING: One hundred and sixteen primary health care centres in Sweden. SUBJECTS: A total of 1627 hypertensive patients aged 70-84. No patient was lost to follow-up. INTERVENTIONS: Antihypertensive treatment with beta blockers and diuretics for a mean follow-up of 25 months. MAIN OUTCOME MEASURE: The cost-effectiveness ratio estimated as the net cost (the treatment cost minus saved costs of reduced cardiovascular morbidity) divided by the number of life-years gained (the increase in life expectancy from treatment). RESULTS: The cost per life-year gained was estimated as SEK 5000 for men and SEK 15,000 for women ($1 = SEK 6; 1 pound = SEK 10). The cost per life-year gained did not exceed SEK 100,000 in any of the sensitivity analyses. CONCLUSIONS: It is concluded that treatment of elderly hypertensive patients with beta blockers and/or diuretics is cost-effective according to the results of the STOP Hypertension study.     

Cost effectiveness of low-molecular weight heparin versus warfarin following hip replacement surgery

Little information is available on the efficacy of low-molecular-weight heparin (enoxaparin) versus warfarin for treatment of deep vein thrombosis and pulmonary embolism following hip replacement surgery. Still less is known of the comparative cost effectiveness of these two therapies. A retrospective study was done on 56 patients who underwent elective hip surgery at an urban medical center between 1991 and 1996. All patients received enoxaparin or warfarin for purposes of thromboprophylaxis. An analysis of medication cost, therapy, laboratory monitoring, and bleeding events of the two antithrombolytic agents was undertaken. Total savings with enoxaparin averaged $1253 per patient, or $137,886 over the study period. The incidence of deep vein thrombosis or pulmonary embolism was 0% with enoxaparin and 3% with warfarin. These data indicate that enoxaparin is a more cost-effective and efficacious regimen for thromboprophylaxis following hip replacement surgery than warfarin.     

Cost-effectiveness of thrombolytic therapy for acute myocardial infarction

OBJECTIVE: To estimate the cost-effectiveness of thrombolytic therapy versus no thrombolytic therapy for patients following acute myocardial infarction, focusing on the impact of time to treatment on outcome. METHODS: A decision model was developed to assess the benefits, risks, and costs associated with thrombolytic therapy for treatment of acute myocardial infarction compared with standard nonthrombolytic therapy. The model used pooled data from a recent study of nine large randomized, controlled clinical trials and 12-month outcome data from a recently published meta-analysis of thrombolytic therapy trial data. Outcomes were expressed in terms of survival to hospital discharge and survival to 1 year after discharge. The risks of treatment that led to death, morbidity, or added costs were estimated. The model determined excess and marginal costs per death averted to hospital discharge and at 1 year. Results were also estimated in terms of cost per year of life saved. Sensitivity analyses included variations in time to treatment and drug cost. RESULTS: The marginal cost of thrombolytic therapy per death averted at 1 year was $222,344, or $14,438 per year of life saved. For patients treated within 6 hours of acute myocardial infarction, the marginal cost per death averted was $181,536 at 1 year, or $11,788 per year of life saved. CONCLUSIONS: Thrombolytic therapy is significantly more cost-effective than many other cardiovascular interventions and compares favorably with other forms of medical therapy. Results suggest that shortening the time to treatment has a critical impact on the cost-effectiveness of thrombolytic therapy.     

Cost-effectiveness of extending screening mammography guidelines to include women 40 to 49 years of age

BACKGROUND: Screening mammography is recommended for women 50 to 69 years of age because of its proven efficacy and reasonable cost-effectiveness. Extending screening recommendations to include women 40 to 49 years of age remains controversial. OBJECTIVE: To compare the cost-effectiveness of screening mammography in women of different age groups. DESIGN: Cost-effectiveness analysis done using Markov and Monte Carlo models. PATIENTS: General population of women 40 years of age and older. INTERVENTIONS: Biennial screening from 50 to 69 years of age was compared with no screening. Screening done every 18 months from ages 40 to 49 years, followed by biennial screening from ages 50 to 69 years, was compared with biennial screening from ages 50 to 69 years. MEASUREMENTS: Life-expectancy, costs, and incremental cost-effectiveness. RESULTS: Screening women from 50 to 69 years of age improved life expectancy by 12 days at a cost of $704 per woman, resulting in a cost-effectiveness ratio of $21,400 per year of life saved. Extending screening to include women 40 to 49 years of age improved life expectancy by 2.5 days at a cost of $676 per woman. The incremental cost-effectiveness of screening women 40 to 49 years of age was $105,000 per year of life saved. On the basis of a multiway sensitivity analysis, there is a 75% chance that screening mammography in women 50 to 69 years of age costs less than $50,000 per year of life saved, compared with a 7% chance in women 40 to 49 years of age. CONCLUSION: The cost-effectiveness of screening mammography in women 40 to 49 years of age is almost five times that in older women. When breast cancer screening policies are being set, the incremental cost-effectiveness of extending mammographic screening to younger women should be considered.     

Parenteral antibiotic prophylaxis of bacterial infections does not improve cost-efficacy of oral norfloxacin in cirrhotic patients with gastrointestinal bleeding

OBJECTIVE: Selective intestinal decontamination with norfloxacin is useful in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. However, bleeding cirrhotic patients with ascites, encephalopathy, or shock are at high risk to develop bacterial infections in spite of prophylactic norfloxacin. The aim of this study was to assess whether the addition of intravenous ceftriaxone could improve the efficacy of prophylaxis with norfloxacin in these patients. METHODS: Fifty-six cirrhotic patients with gastrointestinal hemorrhage and ascites, encephalopathy, or shock were randomized into two groups: Group 1 (n = 28) received oral norfloxacin 400 mg/12 h for 7 days, and group 2 (n = 28) received norfloxacin plus intravenous ceftriaxone 2 g daily during the first 3 days of admission. RESULTS: Ten patients were excluded because of community-acquired infection, surgery, or death within the first 24 h. The incidence of bacterial infections during hospitalization was 18.1% in group 1 and 12.5% in group 2 (p = NS). The incidence of severe infections (spontaneous bacterial peritonitis, bacteremia, or pneumonia) was also similar in both groups: 9% in group 1 versus 8.3% in group 2 (p = NS). There were no statistical differences between the two groups with respect to duration of hospitalization or mortality. The cost of antibiotic therapy (including prophylaxis and treatment of infections) was significantly higher in group 2. CONCLUSION: These results suggest that the addition of intravenous ceftriaxone during the first 3 days of hospitalization does not improve the cost-efficacy of oral norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding and high risk of infection.     

The cost and cardioprotective effects of enalapril in hypertensive patients with left ventricular dysfunction

This study examined the effect of enalapril on survival, resource use, and cost of care in patients with left ventricular dysfunction and hypertension using a retrospective analysis of patients who participated in the Studies of Left Ventricular Dysfunction (SOLVD). Among the 6797 SOLVD participants, 1917 patients had either elevated systolic (> or = 140 mm Hg) or diastolic (> or = 90 mm Hg) blood pressure. Therapy with enalapril was associated with a significant relative risk reduction for mortality (RR = 0.819, 95% CI: 0.68 to 0.98; P = .03). This resulted in a gain of 0.11 years (95% CI: 0.00 to 0.20 years) of survival during the average 2.8 year follow-up for this subgroup and was projected to result in a gain of 2.14 years (95% CI: 0.05 to 4.21 years) during the patient's lifetime. Enalapril significantly reduced the risk of first hospitalization for heart failure by 37%. For all types of hospitalizations, there was an average reduction of 32 hospitalizations per 100 patients treated with enalapril during the trial period (95% CI: 11.8 to 52.2 hospitalizations avoided per 100 patients), resulting in an estimated net savings of $1656 per patient during the trial period (95% CI: increased cost of $191 to savings of $3502). Although the projected lifetime net savings of $1456 was not significant (95% CI: increased cost of $9243 to saving of $12,527), evaluation of the cost per life year saved indicated that enalapril represented a cost-effective strategy. The estimated clinical benefit of enalapril among the hypertensive subgroup in SOLVD supports the recommendation that angiotensin converting enzyme (ACE) inhibitors should be considered as first line pharmacologic therapy for hypertensive patients with left ventricular dysfunction. From both the clinical and economic viewpoints, ACE inhibitors provide important clinical benefits and are cost-effective.     

Cost-effectiveness of hepatitis A vaccination in healthcare workers

OBJECTIVE: To study the cost-effectiveness of vaccination for hepatitis A. SETTING: Hypothetical analysis of students currently enrolled in medical school in the United States. METHOD: A Markov-based model was developed using data from the literature, actual hospital costs, and an annual discount rate of 5%. The incidence rate was based on the lowest annual rate for the US population during the past decade. RESULTS: Over the lifetimes of students currently in medical school, the model estimated that there would be 286 hepatitis A cases with four deaths and 107 lost years of life. With routine vaccination, these numbers would decrease to 17, 0.3, and 6, respectively. The costs per life-year saved and quality adjusted life-year saved were $58,000 and $47,000, respectively. Serologic screening prior to vaccination was less cost-effective than universal vaccination. If the incidence of hepatitis A was underestimated by a factor of 5, the cost per life-year saved would decrease to $5,500. If the incidence of hepatitis was underestimated by a factor of 10, vaccination would result in a net cost savings. CONCLUSION: We conclude that the cost per life-year saved by routine hepatitis A vaccination was similar to many other standard medical modalities. For routine vaccination of medical students to be cost-saving, the incidence rate for hepatitis A must be at least 10 times higher than the rate presently reported for the general population. Serological screening prior to vaccination was not cost-effective.     

Cost effectiveness of inpatient initiation of antiarrhythmic therapy for supraventricular tachycardias

This study assessed the cost effectiveness of inpatient antiarrhythmic therapy initiation for supraventricular tachycardias using a metaanalysis of proarrhythmic risk and a decision analysis that compared inpatient to outpatient therapy initiation. A MEDLINE search of trials of antiarrhythmic therapy for supraventricular tachycardias was performed, and episodes of cardiac arrest, sudden or unexplained death, syncope, and sustained or unstable ventricular arrhythmias were recorded. A weighted average event rate, by sample size, was calculated and applied to a clinical decision model of therapy initiation in which patients were either hospitalized for 72 hours or treated as outpatients. Fifty-seven drug trials involving 2,822 patients met study criteria. Based on a 72-hour weighted average event rate of 0.63% (95% confidence interval, 0.2% to 1.2%), inpatient therapy initiation cost $19,231 per year of life saved for a 60-year-old patient with a normal life expectancy. Hospitalization remained cost effective when event rates and life expectancies were varied to model hypothetical clinical scenarios. For example, cost-effectiveness ratios for a 40-year-old without structural heart disease and a 60-year-old with structural heart disease were $37,510 and $33,310, respectively, per year of life saved. Thus, a 72-hour hospitalization for antiarrhythmic therapy initiation is cost effective for most patients with supraventricular tachycardias.     

Comparison of isolated hepatocytes and tissue slices for study of liver hypothermic preservation/reperfusion injury

BACKGROUND/AIMS: Effective protection from the risk of variceal bleeding is achieved when the hepatic venous pressure gradient is reduced to 12 mmHg or at least by 20% of baseline values. Such a marked decrease is rarely achieved with propranolol, and new agents or combinations of them are now being explored. The present randomized study investigated whether chronic treatment with the combination of propranolol plus molsidomine, a preferential venous dialator that reduces hepatic venous pressure gradient and does not cause pharmacological tolerance, achieves greater reduction in hepatic venous pressure gradient than propranolol alone. METHODS: A hemodynamic study was performed in 34 patients with cirrhosis with portal hypertension in baseline conditions and after 3 months of chronic oral treatment with propranolol alone (n = 19) or propranolol plus molsidomine (n = 15). RESULTS: Propranolol produced a significant reduction in hepatic venous pressure gradient (-16%, p < 0.01). Propranolol plus molsidomine also caused a slight but significant decrease in hepatic venous pressure gradient (-9%, p < 0.05). Hepatic blood flow and the hepatic and intrinsic clearance of indocyanine green were significantly reduced by propranolol. The combined administration of propranolol+molsidomine significantly reduced hepatic blood flow but not hepatic and intrinsic clearance of indocyanine green. Both treatment groups produced similar reduction in azygos blood flow, heart rate and cardiac output. However, contrary to propranolol alone, propranolol plus molsidomine did not increase cardiopulmonary pressures. CONCLUSIONS: The current study shows that although the combined administration of propranolol plus molsidomine prevents some of the adverse effects of propranolol on liver function and cardiopulmonary pressures, it does not achieve a greater reduction in hepatic venous pressure gradient than propranolol alone and therefore, does not support the use of this combined therapy for the pharmacological treatment of portal hypertension.