Antiretroviral drugs as a public health intervention for pregnant HIV-infected women in rural South Africa: an issue of cost-effectiveness and capacity

OBJECTIVE: To estimate cost-effectiveness and capacity requirements for providing antiretroviral drugs to pregnant HIV-infected women in rural South Africa. SETTING: Hlabisa health district, where HIV prevalence among pregnant women was 26.0% in 1997. METHODS: Calculation of the number of paediatric HIV infections averted under three scenarios, and their cost. No intervention was compared with scenario A (zidovudine delivered within current infrastructure), scenario B (zidovudine delivered through enhanced infrastructure), and scenario C (short-course zidovudine plus lamivudine delivered through enhanced infrastructure). Cost-effectiveness was defined as cost per infection averted and cost per potential life-year gained. Capacity was determined in terms of staff and infrastructure required to effectively implement the scenarios. RESULTS: With no intervention, 657 paediatric HIV infections were projected for 1997. In scenario A this could be reduced by 15% at a cost of US$ 574 825, in scenario B by 42% at US$ 1520770, and in scenario C by 47% at US$ 764901. In scenario C, drugs accounted for 76% of costs, whereas additional staff accounted for 18%. Cost per infection averted was US$ 2492 and cost per potential life-year gained (discounted at 3%) was US$ 88. Cost of scenario C was equivalent to 14% of the 1997 district health budget. At least 12 extra counsellors and nurses and one laboratory technician, together with substantial logistical and managerial support, would be needed to deliver an effective intervention. CONCLUSION: Although antiretrovirals may be relatively cost-effective in this setting, the budget required is currently unaffordable. Developing the capacity required to deliver the intervention would pose both a major challenge, and an opportunity, to improve health services.     

Improving the prediction of visual field progression in glaucoma using spatial processing

AIMS: To estimate the cost of population screening for haemochromatosis in Australia and to compare the cost of alternative screening strategies. METHODS: The costs of screening for haemochromatosis were analysed in a hypothetical study using transferrin saturation as the primary screening test, with confirmation of the diagnosis by either liver biopsy or DNA testing for the recently-described haemochromatosis gene. RESULTS: Screening, with confirmation of the diagnosis by liver biopsy, would cost between US$5079 and US$8813 per case detected (excluding administrative costs), depending on the screening strategy (Aust$ = US$0.80). If a DNA test were used instead of liver biopsy, the cost would be reduced to an estimated US$3954-US$4410 per case. This would be further reduced to US$2457 by detection of additional cases by screening family members. The least costly strategy utilised a transferrin saturation threshold of 55% and DNA testing for confirmation of the diagnosis; however, a transferrin saturation threshold of 45% increased the cost only marginally. The initial screening step (transferrin saturation) accounted for 74%-94% of the estimated cost of the screening programme. CONCLUSIONS: Screening for haemochromatosis using transferrin saturation involves relatively modest costs which may be recovered if complications of haemochromatosis can be prevented by early detection and treatment. The most cost-effective strategies utilised transferrin saturation for initial screening, followed by DNA testing. Reduction in the cost of transferrin saturation would lead to a significant reduction in total screening costs. Additional benefits of a screening programme include detection of other iron overload disorders and iron deficiency.     

The direct and indirect costs of cardiovascular disease in South Africa in 1991

BACKGROUND: In South Africa, cardiovascular disease (CVD) is the leading cause of death among all population groups, other than blacks, among whom it ranks third. CVD therefore has a severe impact on the South African economy. OBJECTIVES: To ascertain the availability and quality of South African data on the cost of CVD and to estimate the impact of CVD on the South African economy during 1991. METHODS: The direct health care costs and the indirect costs related to loss of productivity were estimated. Where no direct or complete detailed South African data were available, projections were made based on reasonable assumptions of data and models developed in other countries; these were applied to the limited available South African data. The major disease outcomes considered for this cost estimation were: expenditure on ischaemic heart disease, cerebrovascular disease (stroke), venous thrombosis and embolism, and peripheral vascular diseases and related conditions. These diseases are responsible for the majority of fatal cases of CVD reported in South Africa. RESULTS: The estimated total cost of CVD in South Africa in 1991 was between R4.135 billion and R5.035 billion. This does not include the cost of rehabilitation and follow-up of CVD patients since the necessary data were not available to estimate it. About three-quarters of the direct health care costs were carried by the private sector. The direct health care costs were estimated to be approximately 42% of the total cost. The rest reflects the indirect cost of earnings foregone as a result of premature morbidity and mortality. CONCLUSION: To determine accurately the total economic burden of CVD on the South African economy, additional data will have to be collected. The estimated economic burden of CVD in South Africa clearly highlights the need for a broad-based population strategy, part of an overall national effort to prevent, diagnose and cost-effectively treat CVD.     

Effect of pharmacist interventions on medication use and cost in hospitalized patients with or without HIV infection

Pharmacotherapeutic interventions and drug acquisition costs in HIV-positive and HIV-negative patients on a hospital medical service were studied. In November and December 1995, HIV-positive and HIV-negative patients were randomly selected and matched on the basis of admission date. Pharmacotherapeutic interventions were recorded by a pharmacist until the time of discharge. Drug acquisition costs were obtained through records of medications ordered. The two patient groups were compared with respect to length of stay (LOS), number and cost of medications, and number of interventions. HIV-positive patients had significantly more medication orders and required more interventions than HIV-negative patients. Mean LOS was not significantly different. HIV status and number of medications were significantly associated with requiring five or more interventions. Drug acquisition costs were significantly higher in the HIV-positive group. The mean pharmacist-attributed cost saving per patient was $134 for HIV-positive patients and $27 for HIV-negative patients. HIV-positive patients required more interventions and consumed more medication resources than HIV-negative patients. Pharmacist interventions produced drug acquisition cost savings for both groups, with more savings being realized for positive patients.     

Financing HIV service provision in England: estimated impact of the cost of antiretroviral combination therapy

The objective of this study was to provide population-based estimates on the cost of HIV service provision in England and the use of dual or triple antiretroviral combination therapy. Contemporary cost estimates of treating HIV-infected individuals by clinical stage of HIV infection (indexed to 1995/96 prices) were linked to the number of diagnosed HIV-infected individuals using statutory medical services in England during 1996. Two cost measures were used: the first one was based on average hospital prices derived from a number of English HIV units. These results were compared with those estimated using standard unit costs obtained through specific costing studies performed at a national HIV referral centre. Overall annual expenditure on HIV service provision was estimated for different treatment scenarios as was expenditure by clinical stage of HIV infection. Using hospital prices, in 1996 the total annual cost estimate for HIV service provision amounted to pound sterling 131 m (range pound sterling 83 m to pound sterling 233 m), or pound sterling 150 m (95% CI pound sterling 126 m to pound sterling 173 m) using standard costs, if all patients with HIV disease were treated with AZT monotherapy. For all eligible patients to be treated with dual therapy, cost estimates amounted to pound sterling 161 m (range pound sterling 126 m to pound sterling 173 m) per year using hospital prices or pound sterling 180 m (95% CI pound sterling 156 m to pound sterling 203 m) when using standard cost estimates, while for triple therapy annual estimated expenditure amounted to pound sterling 204 m per year (range pound sterling 157 m to pound sterling 306 m) when using hospital prices or pound sterling 223 m (95% CI pound sterling 199 m to pound sterling 246 m) using standard costs. Increasingly costs will be more evenly distributed across the 3 stages of HIV infection, with a greater proportion of costs generated by HIV-infected individuals before the onset of AIDS. Using non-standardized hospital prices may systematically underestimate the real cost of service provision. Monitoring prospectively the use, cost and outcome of HIV service provision in a standardized format will provide information on the actual cost impact over the next 2-3 years of combination therapy compared with the scenario-based estimates produced in this paper.     

Neandertal capitate-metacarpal articular morphology

The cost effectiveness of several modes of family planning service delivery based on the cost per couple-year of protection (CYP), including commodity costs, is assessed for 1991-92 using programme and project data from fourteen developing countries (five in Africa, four in Asia, three in Latin America and two in the Middle East). More than 100 million CYP were provided through these family planning services during the 12 months studied. Sterilisation services provided both the highest volume (over 60% of total) and the lowest cost per CYP ($1.85). Social marketing programmes (CSM), delivering almost 9 million CYPs, had the next lowest cost per CYP on average ($2.14). Clinic-based services excluding sterilisation had an average cost of $6.10. The highest costs were for community-based distribution projects (0.7 million CYPs), which averaged $9.93, and clinic-based services with a community-based distribution component (almost 6 million CYPs), at a cost of $14.00 per CYP. Based on a weighted average, costs were lowest in the Middle East ($3.37 per CYP for all modes of delivery combined) and highest in Africa ($11.20).     

Diagnosis of breast cancer by measuring nuclear disorder using planar graphs

The purpose of this study was to determine the incidence of non-traumatic lower extremity amputations (LEAs) in diabetic and non-diabetic subjects in Madrid, Spain, and their direct cost. All patients who underwent LEAs between the 1st of January 1994 and the 31st of December 1996, and who had lived in area 7 of the city (569,307 inhabitants) for at least the last 6 months, were identified through operating theatre records cross-checked with Vascular Surgery Department discharge records. In addition, the direct cost of LEAs per year was estimated, taking into account the length of the hospital stay, the period of rehabilitation in the outpatient clinic after discharge, and the use of artificial limbs and their maintenance. The incidence of LEAs was 1.6 (95% CI: 1.1-2.2) per 10(5) non-diabetic subjects and 46.1 (95% CI: 34.5-57.6) per 10(5) diabetic patients. Relative risk was 28. Total direct costs associated with LEAs per year were US$ 56,131 in the diabetic population and US$ 30,765 in the non-diabetic population. Thus, potential cost savings associated with excess amputations in the diabetic population was estimated at US$ 541,353 per year of US$ 94,736 per 10(5) inhabitants. It is concluded that the incidence of LEAs in both diabetic and non-diabetic populations in area 7 is the lowest reported in European countries. The potential cost savings per 10(5) inhabitants and per year is estimated at US$ 94,736.     

Protease inhibitor and triple-drug therapy: cellular immune parameters are not restored in pediatric AIDS patients after 6 months of treatment

OBJECTIVE: To assess whether treatment of HIV-positive children by antiretroviral drugs for a 6-month period would improve immune function significantly. DESIGN AND METHODS: Immunological assessment of 89 HIV-positive children who received protease inhibitor monotherapy for 12-16 weeks as part of phase I/II studies, followed by triple antiretroviral therapy for an additional 12 weeks, was conducted. Immunological parameters were assessed in vitro at four time points (at enrollment, at weeks 2-4, at weeks 12-16, and at weeks 24-28). Assessments included: cytokine production by monocytes, T-cell proliferation to mitogen or recall antigens (including an HIV antigen) and apoptotic cell death. Plasma levels of tumor necrosis factor (TNF)-alpha and soluble TNF receptor (sTNF-R) were also measured, in addition to CD4+ T-lymphocyte counts and viral load. In addition, limited analyses were performed on samples from 17 children after 120 weeks of therapy, including 104 weeks of triple therapy. RESULTS: At enrollment, the 89 children exhibited severe immune defects. Antiretroviral therapy raised CD4+ T-lymphocyte counts significantly and decreased viral loads. In contrast, the in vitro immune parameters studied were not improved, except for plasma levels of sTNF-RII which decreased in parallel with the decrease in viral load. In addition, there was a trend towards increased skin test reactivity for the ritonavir-treated children. No differences were seen in the immune parameters whether the patients were treated with mono- or triple therapy. Results obtained after 120 weeks of therapy demonstrated that defective interleukin-12 production was not restored by long-term therapy. CONCLUSIONS: After 6 months of therapy, with the exception of decreased sTNF-RII levels, and a trend towards increased skin test reactivity, restoration of several defective cellular immune responses did not occur despite significantly decreased viral loads and increased CD4+ T-lymphocyte counts.     

Eradication of Helicobacter pylori: an objective assessment of current therapies

The purpose of the present review was to determine objectively the optimal treatment for the eradication of H. pylori amongst the currently used regimens. A comprehensive literature search provided a data-base relating to the following treatments: dual therapy with an anti-secretory drug plus either amoxycillin or clarithromycin; standard triple therapy, with or without additional anti-secretory drugs; proton pump inhibitor triple therapy; and H2-receptor antagonist triple therapy. Emphasis was placed on intention-to-treat analyses of eradication rates using all of the available evidence. The criteria used to select the optimal treatment were efficacy (eradication rates), frequency of side-effects, simplicity of the regimen (number of tablets per day and duration of treatment) and cost. The analysis showed that proton pump inhibitor triple therapy (that is, a proton pump inhibitor plus any two of amoxycillin, clarithromycin or a nitroimidazole) was the preferred treatment for the eradication of H. pylori. In particular, the 1-week, low-dose regimen with omeprazole plus clarithromycin plus tinidazole produced the highest eradication rates (> 90%) with the lowest frequency of side-effects and at only modest cost.     

Costs of asthma according to the degree of severity

An increase in asthma-related morbidity and mortality has been reported recently, resulting in a substantial increase in the economic impact of this condition. Little information is available relating to the costs of asthma depending on the degree of severity of the disease. Total, direct and indirect costs generated by asthma patients who sought medical care for asthma control over a one-year period in a northern area of Spain were determined. Data were obtained from the patients themselves and severity of illness was classified into mild, moderate and severe according to the International Consensus Report on Diagnosis and Treatment of Asthma, 1992. The average total annual asthma-derived cost was estimated at US$2,879 per patient, with averages of US$1,336 in mildly asthmatic patients, US$2,407 in moderate asthma and US$6,393 in severe asthma. At all levels of severity, indirect costs were twice as high as direct costs, and at the same degree of severity, direct costs due to medication and hospitalization were higher among females than males. A minority of severe asthmatics incurred some 41% of the total costs. The cost of asthma was surprisingly high and varied substantially depending on the degree of severity of the disease. Further knowledge of the costs of asthma across various levels of severity will contribute to a better characterization of optimal intervention strategies for asthma care.     

Increased left ventricular muscle mass after long-term altitude training in athletes

STUDY OBJECTIVES: To compare the costs and effectiveness of directly observed therapy (DOT) vs self-administered therapy (SAT) for the treatment of active tuberculosis. DESIGN: Decision analysis. SETTING: We used published rates for failure of therapy, relapse, and acquired multidrug resistance during the initial treatment of drug-susceptible tuberculosis cases using DOT or SAT. We estimated costs of tuberculosis treatment at an urban tuberculosis control program, a municipal hospital, and a hospital specializing in treating drug-resistant tuberculosis. OUTCOME MEASURES: The average cost per patient to cure drug-susceptible tuberculosis, including the cost of treating failures of initial treatment. RESULTS: The direct costs of initial therapy with DOT and SAT were similar ($1,206 vs $1,221 per patient, respectively), although DOT was more expensive when patient time costs were included. When the costs of relapse and failure were included in the model, DOT was less expensive than SAT, whether considering outpatient costs only ($1,405 vs $2,314 per patient treated), outpatient plus inpatient costs ($2,785 vs $10,529 per patient treated), or outpatient, inpatient, and patients' time costs ($3,999 vs $12,167 per patient treated). Threshold analysis demonstrated that DOT was less expensive than SAT through a wide range of cost estimates and clinical event rates. CONCLUSION: Despite its greater initial cost, DOT is a more cost-effective strategy than SAT because it achieves a higher cure rate after initial therapy, and thereby decreases treatment costs associated with failure of therapy and acquired drug resistance. This cost-effectiveness analysis supports the widespread implementation of DOT.     

Changes in use of antiretroviral therapy in regions of Europe over time. EuroSIDA Study Group

OBJECTIVES: To analyse use of antiretroviral therapy within Europe between 1994 and 1997. DESIGN: From September 1994, the EuroSIDA study (cohorts I-III) has prospectively followed unselected HIV-infected patients from 50 clinical centres in 17 European countries (total, 7230). METHODS: Patients under follow-up at half-year intervals from September 1994 (n=2871) to September 1997 (n=3682) were classified according to number of drugs currently used (none, one, two, three, four or more). Use of antiretroviral therapy was stratified by CD4 cell count (< 200 versus > or = 200 x 10(6)/l) and by region of Europe (south, central, or north). Frequency data were compared by chi2 test and logistic regression modelling. RESULTS: The proportion of patients on antiretroviral monotherapy diminished over time (1994, 42%; 1997, 3%), as did the proportion of patients without therapy (from 37 to 9%). Over time, the proportion of patients on triple (from 2 to 55%) and quadruple (from 0 to 9%) therapy increased, whereas use of dual therapy peaked in 1996 and subsequently fell. In the three regions of Europe, changes in use of antiretroviral therapy differed substantially. However, as of September 1997, only minor differences persisted. The proportion of patients on dual, triple, and quadruple therapy were as follow: south, 33, 52 and 5%, respectively; central, 23, 55 and 14%, respectively; north, 16, 59 and 10%, respectively. In September 1997, odds for use of three or more drugs including at least one protease inhibitor did not differ significantly between regions. CONCLUSIONS: Use of antiretroviral therapy in Europe has changed dramatically towards combination treatment in the last few years. Regional differences in use of antiretroviral therapy have decreased, and by September 1997 only minor differences remained. Antiretroviral therapy with three or more drugs and use of protease inhibitors has become more common in all regions of Europe.     

Cost-effectiveness of chemoprophylaxis after occupational exposure to HIV

OBJECTIVES: To assess the economic efficiency of recent US Public Health Service recommendations for chemoprophylaxis with a combination of antiretroviral drugs following high-risk occupational exposure to human immunodeficiency virus (HIV). To provide a framework for evaluating the relative effectiveness and costs associated with candidate postexposure prophylaxis (PEP) regimens. METHODS: Standard techniques of cost-effectiveness and cost-utility analysis were used. The analysis compares the costs and consequences of a hypothetical, voluntary combination-drug PEP program consisting of counseling for all HIV-exposed health care workers, followed by chemoprophylaxis for those who elect it vs an alternative in which PEP is not offered. A societal perspective was adopted and a 5% discount rate was used. Hospital costs of recommended treatment regimens (zidovudine alone or in combination with lamivudine and indinavir) were used, following the dosing schedules recommended by the US Public Health Service. Estimates of lifetime treatment costs for HIV and acquired immunodeficiency syndrome were obtained from the literature. Because the effectiveness of combination PEP has not been established, the effectiveness of zidovudine PEP was used in the base-case analyses. MAIN OUTCOME MEASURES: Net PEP program costs, number of HIV infections averted, cost per HIV infection averted, and cost-utility ratio (net cost per discounted quality-adjusted life-year saved) for zidovudine, lamivudine, and indinavir combination PEP. Lower bounds on the effectiveness required for combination regimens to be considered incrementally cost saving, relative to zidovudine PEP alone, were calculated. Multiple sensitivity and threshold analyses were performed to assess the impact of uncertainty in key parameters. RESULTS: Under base-case assumptions, the net cost of a combination PEP program for a hypothetical cohort of 10,000 HIV-exposed health care workers is about $4.8 million. Nearly 18 HIV infections are prevented. The net cost per averted infection is just less than $400,000, which exceeds estimated lifetime HIV and acquired immunodeficiency syndrome treatment costs. Although combination PEP is not cost saving, the cost-utility ratio (about $37,000 per quality-adjusted life-year in the base case) is within the range conventionally considered cost-effective, provided that chemoprophylaxis is delivered in accordance with Public Health Service guidelines. Small incremental improvements in the effectiveness of PEP are associated with large overall societal savings. CONCLUSIONS: Under most reasonable assumptions, chemoprophylaxis with zidovudine, lamivudine, and indinavir following moderate- to high-risk occupational exposures is cost-effective for society. If combination PEP is minimally more effective than zidovudine PEP, then the added expense of including lamivudine and indinavir in the drug regimen is clearly justified.     

A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study

CONTEXT: Current guidelines recommend that individuals infected with the human immunodeficiency virus type 1 (HIV-1) be treated using combinations of antiretroviral agents to achieve sustained suppression of viral replication as measured by the plasma HIV-1 RNA assay, in the hopes of achieving prolonged remission of the disease. However, until recently, many drug combinations have not led to sustained suppression of HIV-1 RNA. OBJECTIVE: To compare the virologic effects of various combinations of nevirapine, didanosine, and zidovudine. DESIGN: Double-blind, controlled, randomized trial. SETTING: University-affiliated ambulatory research clinics in Italy, the Netherlands, Canada and Australia (INCAS). PATIENTS: Antiretroviral therapy-naive adults free of the acquired immunodeficiency syndrome with CD4 cell counts between 0.20 and 0.60x10(9)/L (200-600/microL). INTERVENTION: Patients received zidovudine plus nevirapine (plus didanosine placebo), zidovudine plus didanosine (plus nevirapine placebo), or zidovudine plus didanosine plus nevirapine. MAIN OUTCOME MEASURE: Plasma HIV-1 RNA. RESULTS: Of the 153 enrolled patients, 151 were evaluable. At week 8, plasma HIV-1 RNA levels had decreased by log 2.18, 1.55, and 0.90 in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.05). The proportions of patients with plasma HIV-1 RNA levels below 20 copies per milliliter at week 52 were 51%, 12%, and 0% in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively (P<.001). Viral amplification was attempted in 59 patients at 6 months. Viral isolation was unsuccessful in 19 (79%) of 24, 10 (53%) of 19, and 5 (31%) of 16 patients in the triple drug therapy, zidovudine plus didanosine, and zidovudine plus nevirapine groups, respectively. Among patients from whom virus could be amplified, resistance to nevirapine was found in all 11 patients receiving zidovudine plus nevirapine and in all 5 patients receiving triple drug therapy. Rates of disease progression or death were 23% (11/47), 25% (13/53), and 12% (6/51) for the zidovudine plus nevirapine, zidovudine plus didanosine, and triple drug therapy groups, respectively (P=.08). CONCLUSIONS: Triple drug therapy with zidovudine, didanosine, and nevirapine led to a substantially greater and sustained decrease in plasma viral load than the 2-drug regimens studied. Our results also suggest that suppression of viral replication, as demonstrated by a decrease in the plasma HIV-1 RNA load below the level of quantitation of the most sensitive test available, may at least forestall the development of resistance.     

Cost-effectiveness of post-exposure prophylaxis following sexual exposure to HIV

OBJECTIVES: To assess the cost-effectiveness, relative to other health-related interventions in the U.S., of post-exposure prophylaxis (PEP) following potential HIV exposure through sexual contact with a partner who may or may not be infected, and to compare the relative cost-effectiveness of dual- and triple-combination PEP. METHODS: Standard techniques of cost-utility analysis were used to assess the cost-effectiveness of PEP with a four-week regimen of zidovudine and lamivudine, or zidovudine, lamivudine, and indinavir. Due to a lack of empirical data on the effectiveness of PEP with combination drug regimens, the analysis assumed that combination PEP was no more effective than PEP with zidovudine alone. The main outcome variable is the cost per quality-adjusted life year (QALY) saved by the program. RESULTS: Providing PEP to a cohort of 10,000 patients who report receptive anal intercourse with a partner of unknown HIV status (who is assumed to be infected with probability equal to 0.18) would prevent about 20 infections, at an average net cost of about US$ 70,000 per infection averted. The cost-utility ratio, US$ 6316 per QALY saved, indicates that PEP is highly cost-effective in this instance. Moreover, triple-combination PEP would need to be about 9% more effective than dual-combination PEP for the addition of indinavir to the regimen to be considered cost-effective. Prophylaxis following receptive vaginal exposure is cost-effective only when it is nearly certain that the partner is infected; PEP for insertive anal and vaginal intercourse does not appear to be cost-effective. CONCLUSIONS: From a purely economic standpoint, PEP should be restricted to partners of infected persons (e.g., serodiscordant couples), to patients reporting unprotected receptive anal intercourse (including condom breakage), and possibly to cases where there is a substantial likelihood that the partner is infected. Providing PEP to all who request it does not appear to be an economically efficient use of limited HIV prevention and treatment resources.     

Cost-effectiveness comparison of sequential ofloxacin versus standard switch therapy

OBJECTIVE: To compare the cost-effectiveness of sequential intravenous-to-oral ofloxacin versus intravenous-to-oral standard switch therapy for the treatment of patients with sepsis who are hospitalized with bacterial infections. DESIGN: Cost-effectiveness analysis from a provider perspective, including resources important to an integrated healthcare network, of a randomized, open-label, controlled, clinical trial. SETTING: Millard Fillmore Health System, Buffalo, NY. PATIENTS: Hospitalized adults requiring parenteral antibiotics for a complicated urinary tract infection, lower respiratory tract infection, or skin and soft tissue infection. INTERVENTIONS: Sequential intravenous-to-oral ofloxacin or standard intravenous-to-oral switch antibiotics. OUTCOME MEASURES: Clinical outcomes and direct costs associated with hospitalization, primary physician services, specialist physician services, and outpatient care. RESULTS: Eighty-two of 89 patients randomized into the two treatment groups were evaluable. Standard switch therapy failed with 12 patients versus 10 patients receiving ofloxacin. Complete economic data were available for 74 patients. Sequential ofloxacin therapy resulted in a 1-day-shorter antibiotic-related hospitalization without evidence of recurrent infection during the posttherapy follow-up evaluations. An average cost savings of $399 per patient was achieved in the sequential ofloxacin group. Although this difference did not attain statistical significance (probably due to the large variance), it is an economically significant finding. The cost-effectiveness ratios were $5735 per successful outcome for the standard switch therapy group versus $5126 per successful outcome in the sequential ofloxacin group. CONCLUSIONS: Sequential ofloxacin was as effective and consistently less expensive than standard switch antibiotics in the initial evaluation and in the sensitivity analysis of room cost and drug acquisition cost. Standard switch therapy would have to be greater than 25% more effective than sequential ofloxacin therapy to change the economic decision.     

Autoimmunity and its treatment in aplastic anemia

A pilot survey of men aged 35 and over in Buenos Aires indicated that many had one or more risk factors for chronic diseases. A low response rate hampered the investigation: on average it proved necessary to visit several homes in order to obtain one interview. Furthermore, at the cost of US$ 10 incurred per interview, large prospective investigations would be precluded in most developing countries, but case-control studies assessing tobacco use and other risk factors retrospectively would be a good alternative.     

Cost-effectiveness of new treatments for overactive bladder: the example of tolterodine, a new muscarinic agent: a Markov model

Economic analyses of interventions for chronic diseases require evaluations over a long timeframe to illustrate the benefits and costs of treatments. Clinical trials are generally short and carried out in strictly controlled conditions. They are therefore of limited value for economic evaluation aimed at facilitating decisions about resource allocation. The objective of this study was to develop a simulation model that allows integration of data from different sources to calculate the incremental cost-effectiveness and cost-utility of new treatments for overactive bladder. The model compares tolterodine, a new treatment that aims at alleviating symptoms and improving patients' quality of life, to no treatment. Simulations for Sweden are presented as an example. The Markov model combines clinical, observational, and economic data. Markov states are defined based on severity of symptoms of overactive bladder (frequency of voids and leaks). Specific costs for drug treatment and use of sanitary protections as well as utilities are assigned for each state. The effectiveness of tolterodine is based on controlled clinical trials and open long-term extensions of these trials. Outcome is measured as quality-adjusted life years (QALYs) and as the number of months spent in a state with no or very limited symptoms. During the course of 1 year, patients treated with tolterodine spend more time in states with no or limited symptoms compared to those receiving no treatment. Tolterodine-treated patients having a better quality of life during the year. The mean utility of the treated cohort is 0.70, compared to 0.67 in the no-treatment cohort, which is equivalent to the entire cohort moving by one level to a state with less severe symptoms. Mean total costs per patient in the tolterodine arm are SEK8,595 (US $1,131; 1 US$ = 7.6 SEK) compared to SEK3,286 (US$432) in the no-treatment arm. The extra cost due to tolterodine is SEK380 (US$50) per month, which falls within the range of monthly amounts that patients were willing to pay out of pocket for a 25 or 50% improvement of their symptoms in a previous study. The cost for pads is reduced by 23%. The marginal cost per QALY gained with tolterodine is estimated at SEK213,000 (US$28,000). Based on this simulation model, it appears that treatment of overactive bladder with a well-tolerated pharmacological treatment such as tolterodine is cost-effective.     

Individual prognoses of long-term responses to antiretroviral treatment based on virological, immunological and pharmacological parameters measured during the first week under therapy

OBJECTIVE: To predict long-term (12 weeks or longer) virological responses to antiretroviral treatment from measurements made during the first few days on therapy. METHODS: Forty-one HIV-1-infected children were treated with ritonavir for 12 weeks followed by triple drug combination treatment, and the kinetics of virus decay in plasma, ritonavir concentration and CD4 cell counts were measured. A robust multivariate pattern recognition method was used for prediction of the longterm virological responses. RESULTS: The virus decay rate constants calculated from measurements of plasma viral RNA concentrations on the first, second, third, fourth and seventh day on therapy, the drug concentrations in the plasma on day seven, and the pretreatment levels of viral RNA and CD4 cell counts, correlated with long-term levels of plasma HIV-1 RNA. The combination of these parameters contained sufficient information for correct and robust prediction of the long-term response in 88% of the treated children. The predictions of individual responses were stable as demonstrated by a cross-validation analysis, which was highly statistically significant (r=0.87) and specific. CONCLUSION: These results demonstrate that multiple parameters determine the response to antiretroviral therapy and offer a very early measure of individual long-term responses, suggesting that treatment could be optimized after few days of therapy.     

Impact of antiretroviral combination therapies on AIDS surveillance reports in Switzerland. Swiss HIV Cohort Study

BACKGROUND: AIDS reporting in Switzerland is mandatory by law. For the first time since the beginning of the epidemic, health authorities observed a decline in AIDS surveillance reports, from 545 new cases in 1995 to 459 in 1996, a decrease of 86 cases. OBJECTIVE: To examine the extent to which this decline in AIDS surveillance reports is attributable to the introduction of antiretroviral combination therapy. Patients and setting: Swiss HIV Cohort Study, a multicentre cohort of adult HIV-infected patients with national coverage. Participants at risk of developing a first AIDS-defining event, defined as persons with a CD4 cell count below 200 x 10(6)/l or in clinical stage B, were studied. METHODS: A parametric statistical survival model was used to estimate the number of AIDS cases expected in the absence of combination therapies. Taking reporting delays into account, the effect of the introduction of combination therapies in the cohort on national AIDS reports was estimated from the difference between the number of expected and observed cases. RESULTS: A total of 4915 participants contributed 10755 person-years and 2366 initial AIDS events. Between 1990 and 1994, about 35% received antiretroviral therapy, predominantly monotherapy. In 1995 and 1996, the prevalence of antiretroviral therapy increased steadily due to the introduction of dual and triple combinations. The mid-year prevalence of use of combination therapies was 6% in 1994, 13% in 1995, and 48% in 1996. The difference between expected and observed cases per half-year increased from 12 in the first 6 months of 1994 to 69 in the second half of 1996. Taking reporting delays into account, we estimated that 43 (95% confidence interval, 17-69) of the deficit of 86 reports could be attributed to combination therapies. CONCLUSION: The introduction of antiretroviral combination therapies in a single cohort study explained 50% of the decline in national AIDS surveillance reports. Monitoring the use and effectiveness of antiretroviral therapy must become an important component of AIDS surveillance systems.