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The cost-effectiveness of preventing AIDS-related opportunistic infections.

CONTEXT: Multiple options are now available for prophylaxis of opportunistic infections related to the acquired immunodeficiency syndrome (AIDS). However, because of differences in incidence rates as well as drug efficacy, toxicity, and costs, the role of different types of prophylaxis remains uncertain. OBJECTIVE: To determine the clinical impact, cost, and cost-effectiveness of strategies for preventing opportunistic infections in patients with advanced human immunodeficiency virus (HIV) disease. DESIGN: We developed a Markov simulation model to compare different strategies for prophylaxis of Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) infection, fungal infections, and cytomegalovirus (CMV) disease in HIV-infected patients. Data for the model were derived from the Multicenter AIDS Cohort Study, randomized controlled trials, and the national AIDS Cost and Services Utilization Survey. MAIN OUTCOME MEASURES: Projected life expectancy, quality-adjusted life expectancy, total lifetime direct medical costs, and cost-effectiveness in dollars per quality-adjusted life-year (QALY) saved. RESULTS: For patients with CD4 cell counts of 0.200 to 0.300 x 10(9)/L (200-300/microL) who receive no prophylaxis, we projected a quality-adjusted life expectancy of 39.08 months and average total lifetime costs of $40288. Prophylaxis for PCP and toxoplasmosis with trimethoprim-sulfamethoxazole for patients with CD4 cell counts of 0.200 x 10(9)/L (200/microL) or less increased quality-adjusted life expectancy to 42.56 months, implying an incremental cost of $16000 per QALY saved. Prophylaxis for MAC for patients with CD4 cell counts of 0.050 x 10(9)/L (50/microL) or less produced smaller gains in quality-adjusted life expectancy; incremental cost-effectiveness ratios were $35000 per QALY saved for azithromycin and $74000 per QALY saved for rifabutin. Oral ganciclovir for the prevention of CMV infection was the least cost-effective prophylaxis ($314000 per QALY saved). Results were most sensitive to the risk of developing an opportunistic infection, the impact of opportunistic infection history on long-term survival, and the cost of prophylaxis. CONCLUSIONS: The cost-effectiveness of prophylaxis against HIV-related opportunistic infections varies widely, but prophylaxis against PCP or toxoplasmosis and against MAC delivers the greatest comparative value. In an era of limited resources, these results can be used to set priorities and explore new alternatives for improving HIV patient care.

AIDS-Related Opportunistic Infections↗

Should clozapine continue to be restricted to third-line status for schizophrenia?: a decision-analytic model.

BACKGROUND: Clozapine is currently restricted to patients who have failed at least two trials of other antipsychotic medications because of concerns that its use as a first-line agent would lead to greater mortality, mainly through agranulocytosis. AIMS OF THE STUDY: We sought to determine the cost-effectiveness of allowing clozapine to be a first-line treatment versus the current policy of restricting clozapine to third-line status. METHODS: We performed a cost-effectiveness analysis using published data from randomized controlled trials and epidemiologic studies. The target population was patients with schizophrenia in an acute psychotic episode, with a lifetime time horizon and societal perspective. Outcome measures included life expectancy, quality-adjusted life expectancy, costs, and cost-effectiveness ratios. RESULTS: Using clozapine as a first agent would lead to modest gains in life-expectancy as well as quality-adjusted life expectancy, relative to restricting its use to patients who failed 2 conventional antipsychotics. The cost-effectiveness ratio of using clozapine first vs. using clozapine third would be $24,100 per quality-adjusted life year (QALY). In 1-way and probabilistic sensitivity analyses, these findings were robust to a variety of assumptions. DISCUSSION: Allowing clozapine to be a first-line agent may lead to small gains in life expectancy at moderate but acceptable costs. IMPLICATIONS: While these results do not shed light on whether clozapine should be the preferred first-line strategy, they do suggest that clozapine should be added to the armamentarium of possible treatments for treatment-sensitive as well as treatment-resistant schizophrenia.

Adult↗

Benefits of colonoscopic surveillance and prophylactic colectomy in patients with hereditary nonpolyposis colorectal cancer mutations.

BACKGROUND: Predisposition genetic testing is now possible for many hereditary cancer syndromes, including hereditary nonpolyposis colorectal cancer. The optimal management of the elevated risk for cancer in carriers of mutations for hereditary nonpolyposis colorectal cancer is unclear. OBJECTIVE: To assess the life expectancy and quality-adjusted life expectancy benefits derived from endoscopic surveillance and prophylactic colectomy for persons who carry a mutation associated with hereditary nonpolyposis colorectal cancer. DESIGN: Decision analysis model. Lifetime risk for colorectal cancer, efficacy of surveillance and colectomy, stage-specific colorectal cancer mortality, and quality of life were included in the model. SETTING: Decision about a cancer prevention strategy at the time of a positive result on genetic testing. PATIENTS: Carriers of a mutation for hereditary nonpolyposis colorectal cancer who were 25 years of age. INTERVENTIONS: Immediate prophylactic colectomy; delayed colectomy on the basis of age, adenoma, or diagnosis of colorectal cancer; and endoscopic surveillance. Prophylactic surgical options were proctocolectomy with ileoanal anastomosis and subtotal colectomy with ileorectal anastomosis. MEASUREMENTS: Life expectancy and quality-adjusted life expectancy. RESULTS: All risk-reduction strategies led to large gains in life expectancy for carriers of a mutation for hereditary nonpolyposis colorectal cancer, with benefits ranging from 13.5 years for surveillance to 15.6 years for prophylactic proctocolectomy at 25 years of age compared with no intervention. The benefits of colectomy compared with surveillance decreased with increasing age and were minimal if colectomy was performed at the time of colorectal cancer diagnosis. When health-related quality of life was considered, surveillance led to the greatest quality-adjusted life expectancy benefit (3.1 years compared with proctocolectomy and 0.3 years compared with subtotal colectomy). CONCLUSIONS: Colonoscopic surveillance is an effective method of reducing risk for cancer in carriers of a mutation for hereditary nonpolyposis colorectal cancer. The individual patient's choice between prophylactic surgery and surveillance is a complex decision in which personal preferences weigh heavily.

Adult↗

Gender differences in quality-adjusted survival using a Health-Utilities Index.

PURPOSE: Women live longer than men but experience high morbidity during later years. We attempt to represent life expectancy with adjustments for quality of life for men and women in the United States. DATA SOURCES: Survival estimates were obtained from Vital Statistics of the United States Life Tables. Quality-of-life data were obtained for 12,220 participants, aged 32-85 years, in the 1982-1984 National Health and Nutrition Examination Survey I Epidemiologic Follow-Up Study (NHEFS). METHOD: Using public data tapes, scores for the Health-Utilities Index (HUI) were imputed for NHEFS. These scores were calculated separately for men and women in the United States population and broken down by age. Using mortality data, the quality-adjusted life expectancy was calculated separately for men and women. RESULTS: The current life expectancy among men aged 32 years was 39.45 years. For women aged 32 years it was 44.83 years, suggesting a 5.38 female life-expectancy advantage. The life expectancy, adjusted for quality of life, was 31.8 years for men versus 33.1 years for women. Adjustment for quality of life reduced the 5.38-year female advantage to 1.3 years. CONCLUSIONS: Although women enjoy longer life expectancies than do men, this advantage is reduced when quality adjustments are used. The finding reflects high levels of morbidity among older women.

Adult↗

The routine use of high-resolution immunological screening of recipients of primary deceased donor kidney allografts is cost-effective.

BACKGROUND: The economic and health benefits of kidney transplantation are dependent on the length of allograft survival. High-resolution immunological screening can identify recipients at increased risk of early graft loss caused by acute rejection, but the use of these tests increases screening costs before transplantation. The objective of this study was to evaluate the cost-effectiveness of routine use of high-resolution flow-cytometry cross-matching and solid-phase screening for all recipients of primary deceased donor kidney transplants. METHODS: A Markov model was constructed to evaluate costs and effects of two different clinical strategies on a simulated cohort of 1,000 transplant recipients: serological screening (SS) only and flow screening (FS) only. Outcomes measures were total cost of patient care over 25 years, life expectancy, quality-adjusted life expectancy, and transplant life expectancy. RESULTS: In the base-case analysis, FS was associated with an average gain of 0.08 life years, 0.25 transplant life years, and 0.08 quality-adjusted life years per patient. SS was associated with a higher cost of CND$6,397 per patient, mostly because of increased use of dialysis in patients who suffered early graft loss under the SS strategy. The results were robust to uncertainty in the majority of variables, and a strategy using FS was cost-effective except under the unlikely scenario where the false-negative rate for SS was <or=2% or the early graft loss rate for flow-positive recipients was <or=7% (compared with 5% for flow-negative recipients). CONCLUSIONS: Routine use of FS in recipients of first-deceased donor kidney transplants is cost-effective.

Cadaver↗