BACKGROUND: To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV) and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. METHODS: We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN), HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF) scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. RESULTS: Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69-82%) and 69% (60-77%), respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter uncertainty about the natural history of type-specific HPV infection. The uncertainty surrounding the model-predicted reduction in cervical cancer incidence narrowed substantially when vaccination was combined with every-5-year screening, with a mean reduction of 89% and range of 83% to 95%. CONCLUSION: We demonstrate an approach to parameterization, calibration and performance evaluation for a U.S. cervical cancer microsimulation model intended to provide qualitative and quantitative inputs into decisions that must be taken before long-term data on vaccination outcomes become available. This approach allows for a rigorous and comprehensive description of policy-relevant uncertainty about health outcomes under alternative cancer prevention strategies. The model provides a tool that can accommodate new information, and can be modified as needed, to iteratively assess the expected benefits, costs, and cost-effectiveness of different policies in the U.S.

Background: The comparative effectiveness of coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) for patients in whom both procedures are feasible remains poorly understood.

Purpose: To compare the effectiveness of PCI and CABG in patients for whom coronary revascularization is clinically indicated.

Data Sources: MEDLINE, EMBASE, and Cochrane databases (1966-2006); conference proceedings; and bibliographies of retrieved articles.

Study Selection: Randomized, controlled trials (RCTs) reported in any language that compared clinical outcomes of PCI with those of CABG, and selected observational studies.

Data Extraction: Information was extracted on study design, sample characteristics, interventions, and clinical outcomes.

Data Synthesis: We identified 23 RCTs in which 5019 patients were randomly assigned to PCI and 4944 patients were randomly assigned to CABG. The difference in survival after PCI or CABG was less than 1% over 10 years of follow-up. Survival did not differ between PCI and CABG for patients with diabetes in the 6 trials that reported on this subgroup. Procedural strokes were more common after CABG than after PCI (1.2% vs. 0.6%; risk difference, 0.6%; P = 0.002). Angina relief was greater after CABG than after PCI, with risk differences ranging from 5% to 8% at 1 to 5 years (P 0.001). The absolute rates of angina relief at 5 years were 79% after PCI and 84% after CABG. Repeated revascularization was more common after PCI than after CABG (risk difference, 24% at 1 year and 33% at 5 years; P 0.001); the absolute rates at 5 years were 46.1% after balloon angioplasty, 40.1% after PCI with stents, and 9.8% after CABG. In the observational studies, the CABG-PCI hazard ratio for death favored PCI among patients with the least severe disease and CABG among those with the most severe disease.

Limitations: The RCTs were conducted in leading centers in selected patients. The authors could not assess whether comparative outcomes vary according to clinical factors, such as extent of coronary disease, ejection fraction, or previous procedures. Only 1 small trial used drug-eluting stents.

Conclusion: Compared with PCI, CABG was more effective in relieving angina and led to fewer repeated revascularizations but had a higher risk for procedural stroke. Survival to 10 years was similar for both procedures.

We use an empirically calibrated model to estimate the cost-effectiveness of cervical cancer prevention in Brazil, a country with a high cervical cancer burden. Assuming 70% coverage, HPV 16, 18 vaccination of adolescent girls is expected to reduce the lifetime risk of cancer by approximately 42.7% (range, 33.2-53.5%); screening three times per lifetime is expected to reduce risk by 21.9-30.7% depending on the screening test, and a combined approach of vaccination and screening is expected to reduce cancer risk by a mean of 60.8% (range, 52.8-70.1%). In Brazil; provided the cost per vaccinated woman is less than I$ 25, implying a per dose cost of approximately I$ 5, vaccination before age 12, followed by screening three times per lifetime between ages 35 and 45, would be considered very cost-effective using the country's per capita gross domestic product as a cost-effectiveness threshold. Assuming a coverage rate of 70%, this strategy would be expected to prevent approximately 100,000 cases of invasive cervical cancer over a 5-year period. Vaccination strategies identified as cost-effective may be unaffordable in countries with similar socioeconomic profiles as Brazil without assistance; these results can provide guidance to the global community by identifying health investments of highest priority and with the greatest promise.

The primary study objective is to conduct a prospective, randomized controlled clinical trial that compares the effectiveness of two approaches for delivering smoking cessation treatment for veterans with posttraumatic stress disorder (PTSD). An approach where smoking cessation treatment is integrated into mental health care for PTSD and delivered by mental health providers (experimental condition) will be compared to specialized smoking cessation clinic referral (VA's usual standard of care).

Secondary study objectives are to (a) compare the cost outcomes and cost-effectiveness of IC versus USC, (b) identify treatment process variables that explain (mediate) observed differences in smoking abstinence rates for the two study conditions, and (c) determine whether cessation from smoking is associated with worsening of symptoms of PTSD and/or depression.

Background: Thrombolytic therapy is controversial in patients with submassive pulmonary embolism.

Methods: We performed a cost-effectiveness analysis to compare health effects and costs of treatment with alteplase plus heparin sodium vs heparin alone in hemodynamically stable patients with pulmonary embolism and right ventricular dysfunction by developing a Markov model and using data from clinical trials and administrative sources.

Results: Based on data from a recent randomized trial, we assumed that the risk of clinical deterioration requiring treatment escalation was almost 3 times higher in patients who received heparin alone (23.2% vs 7.6%) but that the risk of death was equal in the 2 cohorts (2.7%). Based on registry data, we assumed that the risk of intracranial hemorrhage was approximately 3 times higher in patients who received alteplase plus heparin (1.2% vs 0.4%). Under these and other assumptions, thrombolysis resulted in marginally higher total lifetime health care costs ($43,900 vs $43,300) and was slightly less effective (10.52 vs 10.57 quality-adjusted life-years) than treatment with heparin alone. Thrombolysis was more effective and cost less than $50,000 per quality-adjusted life-year gained when we assumed that the baseline risk of death in the heparin group was 3 times the base-case value (8.1%) and that alteplase reduced the relative risk of death by at least 10%.

Conclusions: Available data do not support the routine use of thrombolysis to treat patients with submassive pulmonary embolism. However, thrombolysis may prove to be cost-effective in selected subgroups of hemodynamically stable patients in whom the risk of death is higher.

Objective:

To assess the effectiveness and cost-effectiveness of treating HIV-infected injection drug users (IDUs) and non-IDUs in Russia with highly active antiretroviral therapy HAART.

Design and Methods:

A dynamic HIV epidemic model was developed for a population of IDUs and non-IDUs. The location for the study was St. Petersburg, Russia. The adult population aged 15 to 49 years was subdivided on the basis of injection drug use and HIV status. HIV treatment targeted to IDUs and non-IDUs, and untargeted treatment interventions were considered. Health care costs and quality-adjusted life years (QALYs) experienced in the population were measured, and HIV prevalence, HIV infections averted, and incremental cost-effectiveness ratios of different HAART strategies were calculated.

Results:

With no incremental HAART programs, HIV prevalence reached 64% among IDUs and 1.7% among non-IDUs after 20 years. If treatment were targeted to IDUs, over 40 000 infections would be prevented (75% among non-IDUs), adding 650 000 QALYs at a cost of USD 1501 per QALY gained. If treatment were targeted to non-IDUs, fewer than 10 000 infections would be prevented, adding 400 000 QALYs at a cost of USD 2572 per QALY gained. Untargeted strategies prevented the most infections, adding 950 000 QALYs at a cost of USD 1827 per QALY gained. Our results were sensitive to HIV transmission parameters.

Conclusions:

Expanded use of antiretroviral therapy in St. Petersburg, Russia would generate enormous population-wide health benefits and be economically efficient. Exclusively treating non-IDUs provided the least health benefit, and was the least economically efficient. Our findings highlight the urgency of initiating HAART for both IDUs and non-IDUs in Russia.

Objectives:

To examine the cost-effectiveness of a quantitative D-dimer assay for the evaluation of patients with suspected pulmonary embolism (PE) in an urban emergency department (ED).

Methods:

The authors analyzed different diagnostic strategies over pretest risk categories on the basis of Wells criteria by using the performance profile of the ELISA D-dimer assay (over five cutoff values) and imaging strategies used in the ED for PE: compression ultrasound (CUS), ventilationperfusion (VQ) scan (over three cutoff values), CUS with VQ (over three cutoff values), computed tomography (CT) angiogram (CTA) with pulmonary portion (CTP) and lower-extremity venous portion, and CUS with CTP. Data used in the analysis were based on literature review. Incremental costs and quality-adjusted-life-years were the outcomes measured.

Results:

Computed tomography angiogram with pulmonary portion and lower-extremity venous portion without D-dimer was the preferred strategy. CUS-VQ scanning always was dominated by CT-based strategies. When CTA was infeasible, the dominant strategy was D-dimer with CUS-VQ in moderate- and high-Wells patients and was D-dimer with CUS for low-Wells patients. When CTP specificity falls below 80%, or if its overall performance is markedly degraded, preferred strategies include D-dimer testing. Sensitivity analyses suggest that pessimistic assessments of CTP accuracy alter the results only at extremes of parameter settings.

Conclusions:

In patients in whom PE is suspected, when CTA is available, even the most sensitive quantitative D-dimer assay is not likely to be cost-effective. When CTA is not available or if its performance is markedly degraded, use of the D-dimer assay has value in combination with CUS and a pulmonary imaging study. These conclusions may not hold for the larger domain of patients presenting to the ED with chest pain or shortness of breath in whom PE is one of many competing diagnoses.