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We performed a review of cost-effectiveness of elderly pneumococcal vaccination to prevent invasive disease. It concerns studies in the USA, Canada, Netherlands and Spain and a multinational study of five European countries. Cost-effectiveness of elderly vaccination against invasive pneumococcal infections varies from cost-saving to EUR 33,000 per life-year gained. The Dutch study estimates cost-effectiveness at EUR 10,100 per life-year gained (price level: 1995). This is below the level that has recently been defined for treatment of high cholesterol (EUR 20,000 per life-year gained) and may therefore be considered as favorable. Almost all studies base their estimate of vaccine efficacy on the same case-control study from the USA. We identify a need for a systematic review on the efficacy of the pneumococcal vaccine. Also, we suggest further analysis with respect to potential effects on cost-effectiveness of extended influenza vaccination for the Dutch elderly in recent years and inclusion of pneumococcal re-vaccination. Pending this additional information, we conclude that cost-effectiveness of vaccination against invasive pneumococcal infections for Dutch elderly is favorable (as in several other countries) and justifies implementation from a pharmacoeconomic point of view.

In accordance with World Health Organization guidelines, the Dutch Ministry of Health, Welfare and Sports designed a national plan to minimize effects of pandemic influenza. Within the scope of the Dutch pandemic preparedness plan, we were asked to estimate the magnitude of the problem in terms of the number of hospitalizations and deaths during an influenza pandemic. Using scenario analysis, we also examined the potential effects of intervention options. We describe and compare the scenarios developed to understand the potential impact of a pandemic (i.e., illness, hospitalizations, deaths), various interventions, and critical model parameters. Scenario analysis is a helpful tool for making policy decisions about the design and planning of outbreak control management on a national, regional, or local level.

Asthma is an important chronic disease among children. This study reviews the cost effectiveness of interventions in the long-term care of asthmatic children and compares these results with treatment advice in four current guidelines. Cost-effectiveness studies were searched for in Medline, Embase, Healthstar, Biosis, and the Office of Health Economics-Health Economic Evaluations Database (OHE-HEED), and the Cochrane Library was searched for meta-analyses of clinical trials. In the four reviewed guidelines, cost effectiveness is not explicitly used as a criterion. The cost-effectiveness studies show sufficient evidence for the cost effectiveness of treatment with inhaled steroids and for self-management programs for severe asthmatic patients. Inclusion of these results in the guidelines would not lead to significant changes in current treatment advice. The effectiveness of various measures for trigger avoidance is not fully proven, and hence neither is their cost effectiveness. Available information on the cost effectiveness of cromolyn could be used to focus the guidelines. Finally, evidence exists that organizational interventions, e.g., the employment of asthma nurses, can result in cost savings, but it is unclear to what extent these results can be generalized. More cost-effectiveness studies are needed, especially on long-acting bronchodilators and self-management programs for mild and moderate asthma, in order to help make the guidelines more informative and reduce the differences between them., (Copyright 2002 Wiley-Liss, Inc.)

Objective: To assess the cost-effectiveness of vaccination to prevent invasive pneumococcal disease in the elderly., Design: Review of the literature., Methods: Articles in Dutch or English reporting studies into the cost-effectiveness of vaccination for the prevention of invasive pneumococcal infection in persons over 65 years of age were retrieved from Medline (1980-2000; search terms: 'pneumococcal' and 'vaccine' in combination with 'costs' or 'economics') and on the basis of the reference lists in the articles found. The following aspects of the selected studies were assessed: the net costs per year of life gained, the incidence of invasive pneumococcal disease in the elderly, the mortality due to invasive pneumococcal infections, the effectiveness of the vaccine in the prevention of invasive pneumococcal infections, and the costs of the vaccine and its administration. Attention was also given to specific age categories and to the effects of varying certain crucial assumptions., Results: We retrieved a total of five studies: one each for the USA, Canada, the Netherlands and Spain and a multinational study for five European countries. The cost-effectiveness of vaccination of the elderly against invasive pneumococcal infections varied from cost savings to [symbol: see text] 33,000,-per life-year gained. The Dutch study estimated the cost-effectiveness at [symbol: see text] 10,100,-per life-year gained (price level 1995). Almost all the studies selected based their estimate of the effectiveness of vaccination on the same case-control study from the USA. The potential effects on cost-effectiveness of more extensive influenza vaccination and of the inclusion of re-vaccination against pneumococci were not included in the analyses., Conclusion: The cost-effectiveness of vaccination against invasive pneumococcal infections in persons over 65 years of age (in the Netherlands as well as in several other countries) was below the previously accepted threshold of [symbol: see text] 20,000,-.

A favourable pharmacoeconomic profile has been well established for influenza vaccination in the elderly. For employers relevant benefits seem to exist for vaccinating healthy working adults to avert absenteeism and related production losses. From a pharmacoeconomic point of view it is relevant to consider whether societal benefits of vaccination for healthy working adults is worthwhile given the costs of vaccination for the community. We searched Medline and Embase using the key words influenza (vaccination) in combination with cost, cost-benefit, cost-effectiveness, efficiency, economic evaluation, health-policy and pharmacoeconomics. From this primary search, we selected 11 studies concerned with the group of healthy working adults. We reviewed these studies according to several criteria: benefit-to-cost (B/C) ratio;vaccine effectiveness, influenza incidence, number of days of work absence due to illness; and relative cost of the vaccine. Three studies on vaccinating healthy working adults found costs exceeding the benefits (B/C-ratio <1). The remaining eight pharmacoeconomic studies found a B/C-ratio of almost two or more. Cost savings are strongly related to the inclusion of indirect benefits related to averted production losses. After exclusion of indirect costs and benefits of production gains/losses, only one of the eight studies remains cost saving. Considering the available pharmacoeconomic evidence, vaccination of healthy working adults in Western countries may be an intervention with favourable cost-effectiveness and cost-saving potentials if indirect benefits of averted production losses are included. Excluding indirect benefits and costs of production losses/gains, cost-saving potentials are limited. Recent international guidelines for pharmacoeconomic research advise the inclusion of production gains and losses in the preferred societal perspective. Hence, on the basis of the available evidence, influenza vaccination of healthy working adults may be recommended from pharmacoeconomic point of view. Pharmacoeconomics do, however, present only one argument for consideration aside from ethical issues, budgetary limits and psychosocial aspects.

The cost-effectiveness of universal vaccination of infants with a new hexavalent meningococcal B outer-membrane vesicle vaccine is projected for The Netherlands by applying decision analysis. The societal perspective is taken and direct and productivity costs (friction costs method) are considered. Future costs and effects are discounted at 4% (base year 1998). In this simulation model, vaccination would prevent 19 deaths and eight cases with severe long-term sequelae per year, rendering 526 additional quality adjusted life years (QALYs) per year. Yearly costs of acute phase of illness due to meningococcal infections in children are estimated at 1,426,634, while the future costs due to sequelae are estimated at 3,801,121 per year. Of all these costs, the vaccination program could prevent 3,334,052 per year. The program costs of meningococcal vaccination are estimated at 11,601,356, resulting in a cost-effectiveness ratio (CER) of 15,721 per QALY. These results are sensitive to the vaccine dose price (conservatively estimated at 10), efficacy, and coverage of meningococcal sero-subtypes.

Objective: To assess the cost effectiveness (net costs per life year gained) of pneumococcal vaccination of elderly individuals aged 65 years and over in The Netherlands., Design and Setting: A pharmacoeconomic analysis was conducted from the healthcare perspective in The Netherlands. The gender- and age-specific modelling framework linked epidemiological aspects of invasive pneumococcal disease (e.g. incidence, mortality, life years lost) to vaccination and hospital resource use. To derive 90% confidence limits for net costs per life year gained a stochastic analysis was performed., Intervention: Pneumococcal vaccination in the elderly with the 23-valent vaccine. Effectiveness of the vaccine in preventing invasive pneumococcal disease was derived from international studies., Main Outcome Measures and Results: Pneumococcal vaccination in the elderly was not found to be cost saving. At baseline, stochastic and univariate sensitivity analysis net costs per life year gained were estimated to be between 6000 and 16,000 euro (EUR) [EUR1 = 1.1 US dollars; cost level 1995]. A scenario analysis on alternative age-dependent vaccination strategies indicated even higher net costs per life year gained, up to EUR28,000 for vaccinating only those elderly aged 85 years and over., Conclusions: Pneumococcal vaccination is associated with net costs per life year gained of EUR10,100 (at baseline assumptions). These costs are higher than those for influenza vaccination (EUR5500). Our pharmacoeconomic approach, which needs to be considered in conjunction with social, psychological and budgetary issues, is intended to contribute to rational decision-making in healthcare policy.

Objective: To estimate the cost-effectiveness of antenatal screening for Chlamydia trachomatis., Design: Pharmaco-economic model analysis., Method: The risks of C. trachomatis infection during pregnancy and of complications of the infection as well as the cost of screening for complications (pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, infertility and neonatal pneumonia) and of treatment were estimated. Assumed were a ligase chain reaction on urine and treatment of identified infected cases with erythromycin or amoxicillin (second choice). Cost-effectiveness was calculated and presented in net direct and indirect costs per major complication averted., Results: For C. trachomatis prevalences in pregnancy above 4% benefits exceed the costs. For prevalences between 2.82% and 4.00% net costs are positive, but a major complication averted costs less than f 1000.-. Considering sensitivity analysis as well, screening for C. trachomatis at prevalences above 3% costs less than f 1000.-per major complication averted and might even save costs. No recent Dutch data on C. trachomatis prevalence in pregnancy are published however., Conclusion: Given the current information, antenatal C. trachomatis screening can be recommended from a pharmaco-economic perspective if C. trachomatis prevalence in pregnancy is 3% or more.

Screening for sexually transmitted diseases (STDs) in early pregnancy is included in routine antenatal care for several infectious agents in many western European countries. Pharmaco-economics of these interventions have been evaluated. Currently, reconsideration of antenatal screening is ongoing, with explicit attention given to extending the STD testing to some other infectious agents, such as HIV and Chlamydia trachomatis (CT). This paper examines the socio-economics of such extensions for the Netherlands and the UK. Based on pharmaco-economic investigations in the UK and the Netherlands, we argue that serious consideration should be given to expanding antenatal STD screening to include universal testing for HIV and CT. Further research should be directed to the economic aspects of paediatric HIV infection and the epidemiology of CT in pregnancy.

Background: Recently the Department of Health announced the introduction in England of voluntary universal HIV screening in early pregnancy to prevent vertical transmission. New data have shown the importance of HIV infection in infants born to mothers who were HIV-negative in early pregnancy and who acquired HIV later in pregnancy or during lactation. This requires consideration of repeat testing in late pregnancy and testing of partners of pregnant women (expanded antenatal HIV testing)., Objective: To estimate cost effectiveness of expanded antenatal HIV testing in London (England) within the framework of universal voluntary HIV screening in early pregnancy., Design: Incremental cost-effectiveness analysis., Methods: Cost estimates of service provision for HIV-positive children and adults by stage of HIV infection were combined with estimates of health benefits for infants and parents and with costs of counselling and testing (testing costs). In a pharmacoeconomic model cost effectiveness was estimated for expanded antenatal HIV testing in London for universal and selective strategies., Results: Testing costs in the plausible range of pounds sterling 4 to pounds sterling 40 translate into favourable incremental cost-effectiveness estimates for expanded antenatal HIV testing in London which is already at low numbers of vertical transmissions averted per 100000 pregnant women who test HIV-negative in early pregnancy. Favourable cost effectiveness for universal expanded testing would require testing costs in the lower range, whereas selective expanded testing may produce favourable cost effectiveness at testing costs close to pounds sterling 40., Conclusion: Based on pharmaco-economic considerations, the authors believe that implementation of expanded HIV testing in London should be considered.

Background: Models commonly used for the economic assessment of chlamydial screening programs do not consider population effects., Goal: To develop a novel dynamic approach for the economic evaluation of chlamydial prevention measures and to determine the cost-effectiveness of a general practitioner-based screening program., Study Design: The dynamic approach was used to estimate the cost-effectiveness of a screening program for the first 10 years of screening in The Netherlands. Screening involved a ligase chain reaction test on urine followed by standardized therapies and partner referral. Eligible persons were sexually active, 15 to 24 years, visited a general practitioner, and had no symptoms of sexually transmitted diseases. The heterosexual model population, which consisted of persons 15 to 64 years, had a total chlamydial prevalence of 4.1% before screening. Screening effects on chlamydial incidence were computed by using a population-based stochastic simulation model. Incidence data were connected with a decision analysis model to determine the health effects of the program. The net costs of the program were calculated (investment costs minus averted costs, in 1997 US$) from a societal perspective and expressed per major outcome averted (symptomatic pelvic inflammatory disease, chronic pelvic pain, ectopic pregnancy, infertility, neonatal pneumonia)., Results: Unlike the standard static approach, our model adequately addresses dynamic processes such as chlamydial transmission and the impact of screening programs on chlamydial incidence in the population. During the first 10 years of screening, the investigated program yields savings of US $492 or US $1,086 per major outcome averted, excluding or including indirect costs, respectively. These results depend on chlamydial prevalence and partner referral., Conclusions: The cost-effectiveness of chlamydial screening programs seems best to be determined by using dynamic modeling on a population basis. In addition to preventing negative health outcomes, the investigated screening program may save costs.

Objectives: To adapt and improve methodology for back-calculation of AIDS in Europe and to examine the feasibility of estimating past HIV incidence by birth cohort., Methods: Empirical Bayesian back-calculation (EBBC) used Markov disease progression models, modified to allow for three diseases added to the AIDS case definition in 1993 and for pre-AIDS mortality, and estimation by penalized maximum likelihood with a neighbour prior. EBBC by 5-year birth cohort assumed a minimum age at infection and age-dependent progression rates; three versions, with varying age effects, were investigated using AIDS cases diagnosed prior to the introduction of highly active antiretroviral therapies (HAART)., Results: Compared with the no age-effect version, EBBC by birth cohort tended to produce flattened HIV incidence curves in country-exposure groups with < 1000 AIDS cases, reflecting effects of the neighbour prior when data become sparse. Otherwise, birth cohort analysis, with moderate effects of age on progression, gave initially increasing incidence curves and consistent patterns across countries, with the 1960-1964 cohort most affected. In the European Union, incidence is estimated to have peaked in 1983 among homosexual men and in 1988 among injecting drug users; 460000 persons were estimated to be living with HIV/AIDS at the end of 1995., Conclusions: Our improved methodology deals effectively with the change in AIDS case definition and has allowed quantitative assessments of the HIV epidemic by birth cohort using all AIDS cases diagnosed before 1996, thus providing a sound basis for public health policy at a time when estimation of more recent prevalence is compromised by the effects of HAART.

Most western countries have influenza vaccination programmes for citizens aged > or = 65 years. This paper reviews the available evidence on whether elderly influenza vaccination is worthwhile from a pharmacoeconomic point of view. A search on Medline and EMBASE resulted in a primary selection of approximately 100 studies on the pharmacoeconomics of influenza vaccination in the elderly. Further selection of studies to be included in the review was based on several criteria such as original research paper, cost-benefit or cost-effectiveness analysis. influenza vaccination in the elderly, and publication between 1980 and 1999. The 10 studies included in the final selection were evaluated regarding 3 main aspects: benefit-cost ratio and cost-effectiveness ratio; vaccine effectiveness; and relative costing of the vaccine. In general, differences in benefit-cost ratios could be explained by differences in effectiveness and relative costing of the vaccine. Considering the available pharmacoeconomic evidence, influenza vaccination of the elderly in western countries is an intervention with favourable cost-effectiveness in terms of net costs per life-year gained and even has cost-saving potential. In particular, influenza vaccination among elderly people at higher risk, such as the chronically ill elderly, is generally found to be cost saving. Relatively favourable cost-effectiveness among non-high-risk elderly justifies universal influenza vaccination of the elderly from a pharmacoeconomic point of view.

Objective: To estimate the cost effectiveness of universal screening for HIV of pregnant women in Amsterdam., Design: Pharmaco-economic model calculation., Method: An estimate was made of the minimal and maximal prevalences of undiagnosed HIV infection during pregnancy for the whole of Amsterdam, based on epidemiological data from observation among pregnant women in two Amsterdam hospitals and one obstetrical practice. The calculation was based on universal screening with an ELISA test. The interventions after screening comprised pharmacotherapy during pregnancy, delivery by caesarean section and breast-milk substitution. The issues of pharmaco-economic analysis were whether or not costs were reduced and net costs per year of life gained; the question was also studied at what lifetime costs of care for HIV infected children the net costs would be nil (costs equal benefits)., Results: Universal HIV screening in Amsterdam required a total investment of about Dfl 300,000.-per annum. In many of the analysed options for HIV screening the financial profits exceeded the investment. Variation of assumptions showed that the net costs of HIV screening under all conditions investigated would remain below Dfl 1,200.-per life year gained., Conclusion: Universal HIV screening of pregnant women in Amsterdam showed a favourable cost effectiveness. The calculations indicated a possibility of reducing costs.

This paper compares AIDS hospital care in several European-Union countries. For this purpose hospital-care utilisation studies on inpatient days and outpatient contacts were analysed in a generic approach controlling for severity stages of AIDS. Lifetime hospital-care needs for AIDS are derived, providing useful information for health-care policy makers. In a next step, lifetime estimates are linked to estimated annual new cases of AIDS, resulting from standardised epidemiological modelling. These results on AIDS impact at the population level are reported including statistical confidence limits. Both lifetime hospital-care needs at the patient level and AIDS impact at the population level are compared between countries and related to characteristics of the national AIDS epidemics and health-care systems. A person with AIDS has a contact--either inpatient day or outpatient visit--with the hospital in 14% (UK) to 24% (France) of the days spent in the AIDS stage. Related to the national AIDS epidemics (epidemiological impact), Italy and Greece have high levels of outpatient contacts per million population. Estimated hospital-bed needs for AIDS in 1995 are up to 2.13% (in Spain) of total national acute-care hospital beds available. Estimated per-capita needs for outpatient visits in 1995 are highest in Italy, corresponding to 108 doctor full-time equivalents. In a case-study for Greece and The Netherlands, differences in hospital-care utilisation patterns were assessed to correspond with differences in their health-care systems (number of hospital beds, doctors and nurses per capita and some qualitative characteristics of medical care in both countries). International comparison of AIDS hospital care is possible using standardised analysis of national hospital-care utilisation data and standardised epidemiological modelling. Estimates of lifetime hospital-care needs are an essential input for cost-effectiveness analyses used to aid health-care policy decision-making.

The role of reinfection and the importance of partner treatment were added to a pharmacoeconomic model for the analysis of a GP-based opportunistic screening programme for Chlamydia trachomatis (CT) in sexually active women in Amsterdam. A favourable cost-effectiveness was found for partner treatment. Partner treatment was cost saving and overall net costs per major outcome averted by the screening programme were reduced by 40% or more due to partner treatment. From a pharmacoeconomic point of view partner treatment should be routinely provided in the framework of a CT screening programme for Amsterdam women.

The aim of this study was to estimate the healthcare costs of asthma and chronic obstructive pulmonary disease (COPD), in the Netherlands, in 1993. Also studied was the future development of these costs, as a result of ageing and possible changes in smoking behavior. A prevalence-based cost-of-illness approach was used to estimate direct medical costs. Age- and gender-specific data were obtained from representative national registries and large, representative surveys. To model future costs, cost estimates were linked to an epidemiological model based on a dynamic multi-state lifetable. It describes 1 yr changes, from one state to another, that result from ageing, birth, migration, incidence, recovery from asthma and death due to asthma, COPD or other causes, and starting or quitting smoking. Three different scenarios were modelled: 1) a reference scenario which primarily predicts the impact of ageing. 2) an 'attainable' smoking reduction scenario and 3) an 'extreme' smoking reduction scenario. Direct medical costs were estimated to be $US 346 million in 1993. With increasing age, the relative importance of asthma in total asthma and COPD costs decreased from 91% to less than 4%. Annual costs per patient were estimated to be $US 499 for asthma and $US 876 for COPD. The breakdown of costs differed considerably between asthma and COPD. The reference scenario predicted the costs to increase by 60% to reach $US 555 million by 2010, COPD prevention as modelled in the second and the third scenario reduced the projected cost increase from 60%, to 57% and 48%, respectively. Together, the direct costs of asthma and COPD represent 1.3% of the Dutch health care budget. The breakdown of the costs shows different patterns for asthma and COPD. The costs of these diseases are expected to increase by 60% in the near future. In the short run the impact of smoking reduction on reducing this increase is relatively small, but it will be greater in the long run.

Objective: To estimate the cost effectiveness of universal, voluntary HIV screening of pregnant women in England., Design: Cost effectiveness analysis. Cost estimates of caring for HIV positive children were based on the stage of HIV infection and calculated using data obtained from a London hospital between 1986 and 1996. These were combined with estimates of the health benefits and costs of antenatal screening so that the cost effectiveness of universal, voluntary antenatal screening for HIV infection in England could be estimated., Main Outcome Measures: Lifetime, direct costs of medical care of childhood HIV infection; life years gained as a result of the screening programme; net cost per life year gained for different pretest counselling costs; and different prevalence rates of pregnant women who were unaware that they were HIV positive., Results: Estimated direct lifetime medical and social care costs of childhood HIV infection were pound178 300 using a 5% discount rate for time preference (1995-6 prices). In high prevalence areas screening pregnant women for HIV is estimated to be a cost effective intervention with a net cost of less than pound4000 for each life year gained. For areas with comparatively low prevalence rates, cost effectiveness could be less than pound20 000 per life year gained, depending on the number of pregnant women who are unaware that they are infected and local screening costs., Conclusions: Our results confirm recent recommendations that universal, voluntary antenatal HIV screening should be implemented in the London area. Serious consideration of the policy should be given for other areas in England depending on local prevalence and screening costs.

Objective: To estimate the cost effectiveness of Chlamydia trachomatis (CT) screening of young women visiting general practitioners., Design: Economic model analysis., Methods: Data on the health care needs for CT complications were derived from various sources; costing was done using estimated cost prices, charges and the friction cost method; epidemiological data were derived from a pilot study among 22 general practices in Amsterdam, the Netherlands. The analyses were carried out assuming screening with ligase chain reaction test of a urine sample and treatment of identified cases of infection with single-dose azitromycin. The model intervention consisted of screening all heterosexually active women aged 15-19, 15-24, 15-29, or 15-34 years (strategies 1, 2, 3 and 4, respectively). Cost effectiveness was presented in net direct and indirect costs per woman cured and per major outcome averted (pelvic inflammatory disease (PID), chronic pelvic pain, ectopic pregnancy, infertility and pneumonia of newborns)., Results: The first two strategies were cost saving. For the third strategy net costs per woman cured and per major outcome averted were almost 110.- Dutch guilders (DFL) and over DFL 300, respectively. The last strategy costs over DFL 320 per woman cured and over DFL 910 per major outcome averted. The cost effectiveness was sensitive to the assumed probability of progression of CT infection to PID., Conclusion: Universal implementation of the screening programme investigated in Amsterdam for women aged 15-24 years would result in approximately equal savings and costs. Screening of all 15-29-year-old women would require a net investment of DFL 350,000.

Objective: The objective of this study was to determine the costs associated with influenza and the cost effectiveness (net costs per life-year gained) of influenza vaccination in The Netherlands., Design and Setting: The economic evaluation comprised a cost-of-illness assessment and a cost-effectiveness analysis, both of which were conducted from the healthcare perspective in The Netherlands. The modelling framework for the economic evaluation linked epidemiological aspects of influenza (e.g. incidence, mortality, years of life lost) to vaccination coverage and healthcare resource use. Healthcare resource use was specified for hospitalisations, general practitioner visits and drugs., Intervention: The intervention assessed in the cost-effectiveness analysis was influenza vaccination., Main Outcome Measures and Results: The costs of influenza were estimated to be 31 million euros (EUR) for the influenza season 1995/96 in The Netherlands (EUR1 approximately $US1.1). For the extended programme in 1997/98, i.e. all elderly people, the cost-effectiveness ratio was estimated at EUR1820 per life-year gained. Sub-group analysis demonstrated that the programme had a more favourable cost effectiveness among the chronically ill elderly population (cost saving) than among the rest of the elderly population (EUR6900 per life-year gained)., Conclusion: Influenza vaccination has a cost-effectiveness ratio that is better than or comparable to that of other implemented Dutch programmes in the prevention of infectious diseases.

The purpose of this study was to examine the impact of influenza on hospitalization in The Netherlands. Two methods were applied to estimate this effect: (a) regression analysis and (b) comparison of hospitalization in epidemic years with non-epidemic years. Hospital discharge rates in 1984-93 have been considered. The study shows that, during the period studied, on average, almost 2700 people were hospitalized for influenza per annum, and that influenza was diagnosed as the main cause for hospitalization in only a fraction of these hospitalizations (326: 12%). From an economic perspective, these results imply that the cost-effectiveness of vaccination against influenza may be severely underestimated when looking only at changes achieved in the number of hospitalizations attributed to influenza.

Objectives: To study trends in AIDS incidence in Europe by age and year of birth., Design: Age-period-cohort analyses were adopted to distinguish the different time factors of calendar year, age and year of birth., Methods: Non-aggregate AIDS incidence data from 12 European countries (1978-1994) were adjusted for reporting delay and expressed per unit of population (per 100000 persons or 100000 person-years). Age-specific incidence patterns (absolute level and rate of increase) were compared between 5-year birth cohorts for homo-/bisexual men, injecting drug users (IDU) and heterosexual contact cases., Results: Mean age at diagnosis increased strongly amongst IDU, but less so among homo-/bisexual men and heterosexual contact cases. Of a total 110646 reported cases (116311 after adjustment for reporting delay), 87167 (78.8%) were among people born in 1950-1974 [91951 (79.1%) after adjustment for reporting delay]. The relative impact on specific birth cohorts differed strongly by exposure group. Incidences at age ranges of 20-24 and 25-29 years among cohorts born in 1965 and after were about the same level (homo-/bisexual men, IDU) or higher (heterosexual contact cases) than older birth cohorts when these were in the same age range; rates of increase were less among homo-/bisexual men and IDU, but higher among heterosexuals. There were large differences between counties., Conclusions: Overall, AIDS incidence among cohorts born in 1965 and after is about the same level (homo-/bisexual men, IDU) or higher (heterosexual contact cases) than older cohorts when these were in the same age range. Rates of increase of AIDS incidence curves suggest reduced HIV transmission amongst the most recent cohorts of homo-/bisexual men and IDU, but among young heterosexuals the epidemic is still expanding.

This paper addresses the economic relevance of appropriately staging progression of disease for cost assessment and projection. Illustrations are drawn from two Dutch cost-of-illness studies for Diabetes Mellitus (DM) and AIDS. Our disease-staging specifies a separate late stage to capture terminal high-intensity care for end-stage complications. Data are used from a registration of national hospital resource utilization for DM and from a detailed database on AIDS hospital care and costs. In particular, differences in average length of hospital stay for several potential DM end-stage complications are compared with non-DM patients. Neglecting the separation of a specific late stage is estimated to possibly miscalculate 15-20% of the hospital bed needs for DM and AIDS in the Netherlands. In particular, confidence intervals of future projections for AIDS hospital beds--using respectively staged and non-staged models--do not overlap. AIDS hospital costs are overprojected by almost 11% in the non-staged model. Our estimation of DM hospital bed needs raises the percentage in total Dutch hospital beds from 1.7% (neglecting a specific late stage) to 2.0%. For DM and AIDS an appropriate disease-staging averts structural biases in estimations of bed needs and costs, and therefore benefits the planning of hospital care facilities. Obviously, gathering comparable information and developing similar methodology on other diseases, such as respiratory disease, cardiovascular disease and cancer, is needed and could benefit planning in these fields.

This study estimates the current and future hospital resources for AIDS patients in the European Union (EU), using multinational scenario analysis (EU Concerted Action BMH1-CT-941723). In collaboration with another EU-project ('Managing the Costs of HIV Infection'), six national European studies on the utilization of hospital care for AIDS have been selected to provide the data for our analysis. The selection criteria involve recentness, quality, comparability, accessibility and representativeness. Baseline hospital resource utilization is estimated for hospital inpatient days and outpatient contracts, using a standardized approach controlling for two severity stages of AIDS (chronic stage and late stage). The epidemiological part of the study is based on standard models for backcalculating HIV incidence and projecting AIDS incidence, prevalence and mortality. In the next step, baseline resource utilization is linked to epidemiological information in a mixed prevalence and mortality-based approach. Several scenarios render different future epidemiological developments and hospital resource needs. For the year 1999, hospital bed needs of 10,000-12,700 in the EU are indicated, representing an increase of 20-60% compared to the estimated current (1995) level. The projected range for 1999 corresponds to a maximum of 0.65% of all hospital beds available in the EU. The growth in the number of outpatient hospital contacts is projected to possibly exceed that of inpatient days up to 1.82 million in 1999. Our methodology illustrates that estimation of current and future hospital care for AIDS has to be controlled for severity stages, to prevent biases. Further application of the multinational approach is demonstrated through a 'what-if' analysis of the potential impact of combination triple therapy for HIV/AIDS. Estimation of the economic impact of other diseases could as well benefit from the severity-stages approach.

The objectives of the European Commission Biomed AIDS Programme are to enable Europe to pool its intellectual and financial resources in the control, treatment and prevention of HIV infection and AIDS. In order to facilitate this aim the Commission has allocated 40 to 50 million ECU over the past 6 years for concerted action of the Biomed projects on AIDS by the countries of the European Union. This is only a small proportion of the real cost spent by the member countries on this epidemic.

We explored the relationship between the incidence of hospitalization and disease progression in a group of 140 symptomatic, HIV infected patients by linking hospitalizations to the time of diagnosis, the time of death, or both. The relationship could best be described by positively skewed U-patterns or (weak) J-patterns with a high use of resources immediately following diagnosis and preceding death. The lifetime hospitalization profiles differed according to the type of insurance, age, the initial diagnosis in the CDC-IV stage and the length of survival. The results not only confirm general hypotheses posed by other research groups, but also demonstrate the existence of variations among subgroups of patients. The results can be used to improve economic assessments of the impact of AIDS in The Netherlands and the European Union. The method used has the advantage of being based on a bottom-up approach to resource utilization, involving the use pf prospective data for the patients' full lifespans, and can easily be applied to other areas of health services research.

Objective: To assess the economic impact of HIV/AIDS on the health care system in The Netherlands., Data and Methods: Two types of data are used: (i) routine surveillance data on AIDS incidence and (ii) information on hospital resource utilisation and corresponding monetary costs. Progression of disease is modelled using a multi-stage model, with stages corresponding to clinical classifications and to different phases of health care need. Economic impact is analysed for all stages in three scenarios: the reference and two alternative scenarios., Results: In the year 2000 hospital bed need would reach 220 beds if yearly new HIV infections in the 1990s remain at the level estimated for the end of the 1980s, and if the intensity of hospital care remains constant. A minimum need of 125 beds is projected if no new HIV infections occur in the 1990s. Hospital costs in 1993 are estimated to amount to 33.8 million ECUs. Scenarios indicate a range of 26.7-50.7 million ECUs for the year 2000 (price level: 1993). The proportion of the costs of hospital inpatient care and cure in total hospital costs increases, whereas the proportion for outpatient services decreases., Conclusions: Projected hospital bed need of 125-220 for HIV/AIDS in the year 2000 is limited compared to the projections for coronary heart disease and stroke, but approaches that for lung cancer, pneumonia and diabetes. We estimate hospital costs to have been 85% of total health care costs for HIV/AIDS in 1993. In 1993, the estimated proportions in hospital costs are 41% for inpatient care, 20% for inpatient cure and 39% for outpatient facilities. Our scenarios indicate a decreasing share of outpatient costs--possibly to 30% of total hospital costs for HIV/AIDS in 2000--illustrating the growing relative importance of the AIDS stage for the hospital costs. We project hospital costs for HIV/AIDS in 2000 to reach up to 0.53% of projected hospital costs for all diseases. A present value of 38 million ECUs (23%) of hospital costs projected in the reference scenario might be avoidable, during the period 1994-2000. However, with unchanged treatment patterns a present value of 127 million ECUs for hospital costs during the same period is projected to represent unavoidable costs (discount rate: 5%). In The Netherlands, data needs in the field of economic impact assessment of HIV/AIDS especially refer to registrations of non-hospital outpatient resource utilisation and costs.

Patterns in the costs of hospital in-patient care and in-patient drug treatment of 121 symptomatic, HIV-infected patients are described for a university hospital between 1987 and 1991. Trend analyses have been performed on quarterly and yearly data using parametric and non-parametric statistical techniques. During the 5-year study period the demand for hospital beds almost quadrupled despite a constant number of admissions per person-year and a 40% decrease in the average length of stay. The demand for beds was highest in the autumn and winter months. The impact of female and/or heterosexual subgroups on the yearly utilization of resources increased and reasons for hospitalization became more diverse; there were fewer hospitalizations for Pneumocystis carinii pneumonia infection. Antimicrobial drug treatment accounted for the increased drug treatment costs. The implications for AIDS-treating specialists, hospital managers, and scenario analysts are discussed.

A combined sexual network and lifecourse perspective is proposed as a basis for reconstructing the sexological infrastructure of HIV dissemination. Necessary data are drawn from a representative sample survey of 1001 adults (age range 18-50 years) in the Netherlands. Heterosexual respondents' behavioural risk level, expressed in the number of unprotected sexual interconnections with primary and secondary partners, is found to be related to both age and relational status, though these variables cannot fully predict risk. While those under 24 years of age are over-represented in the larger components of sexual networks, above 32 years of age there is a small group who follow a lifestyle of regularly changing sexual partners.

We study a model for pair formation and separation with two types of pairs which differ in average duration. A fraction f of all newly formed pairs have a long duration (denoted by "steady"), the remaining fraction 1-f have a short duration ("casual"). This distinction is motivated by data about the survival times of partnerships in a sociological survey. In this population we consider a sexually transmitted disease, which can have different transmission rates in steady and in causal partnerships. We investigate under which conditions an epidemic can occur after introduction of the disease into a population where the process of pair formation and separation is at equilibrium. If there is no recovery we can compute an explicit expression for the basic reproduction ratio R0; if we take recovery into account we can derive a condition for the stability of the disease-free equilibrium which is equivalent to R0 < 1. We discuss how R0 depends on various model parameters.

Objective: Description of the epidemiology and transmission categories of AIDS in the Netherlands., Design: Descriptive., Setting: The Netherlands., Method: Analysis of all registered AIDS patients until 31 December 1993. Trends in the composition of this population were studied with respect to age and sex, risk groups, geographic distribution across the country, heterosexual transmission, AIDS-defining diseases and reporting pattern., Results: From the first patient in 1982 until December 31, 1993, a cumulative total of 2912 patients was diagnosed and reported in the Netherlands (2995 when corrected for reporting delay). The numbers of reported AIDS cases in the Netherlands are smaller than previously predicted by mathematical models. The proportion of homosexual men in the incidence of AIDS dropped from 89 to 73 per cent, the proportions of intravenous drug users and heterosexual transmission rose to 11 per cent each. Patients in the category of heterosexual transmission are mainly individuals from countries where heterosexual contact is the dominant mode of transmission and their sex partners, and to a lesser extent the sex partners of intravenous drug users (whether or not in relation to prostitution). The proportion of women is rising (229 patients or 8 per cent by December 1993), with most cases transmitted initially by intravenous drug use but later by heterosexual contact., Conclusion: The number of AIDS cases in all risk groups combined is levelling off. However, more detailed analysis shows that the numbers of cases of heterosexual transmission and those in young homosexual men are still rising. For a better quantitation of the quality of the AIDS data, specific research into underreporting and non-diagnosis of AIDS cases in the Netherlands is warranted.

Trends in the utilization of various hospital resources by HIV-infected persons between January 1987 and June 1990 have been studied to support health care planning. Data on 126 asymptomatic and symptomatic HIV-infected persons have been recorded at a patient level and analyzed at half-yearly intervals. At a hospital level, increasing utilization trends were observed. At the patient level, a decreasing utilization intensity was measured for admissions, inpatient days, inpatient diagnostic examinations, and outpatient consultations. Increasing utilization intensity was measured for care during admissions. A constant utilization intensity was observed for outpatient diagnostic examinations and inpatient medication days. Use of interventions tended to increase at the end of the study period. Discriminating between trends in the utilization of different hospital resources can improve the management of hospital health care demands of HIV-infected people.

Objective: To underpin multinational public-health HIV/AIDS strategy planning in the European Community (EC) by integrating national studies on HIV/AIDS in scenario analysis., Method: Three types of data are used: routine surveillance data, information on disease progression and observational studies on the economic impact. The HIV/AIDS epidemic is simulated using two models (MIDAS and PC-Based AIDS Scenarios). Selected simulations, consistent with surveillance data, are connected to economic impact (hospital-bed needs and annual hospital costs for AIDS patients). Parameter values expressing per person-year economic impacts are derived from a structured review of publications on economic aspects of AIDS., Results: Evaluation of published studies on hospital resource use and costs in EC countries shows that there are significant differences between both countries and studies, even after conversion to similar measures (for example, using purchasing power parities). These differences are partly due to factors such as the composition of the patient population. Differences in methodology may also have influenced the results. Economic impact is analysed for combinations of three factors; survival time after AIDS diagnosis, hospital inpatient days needed per person-year and corresponding hospital costs per person-year. All scenarios indicate 1995 hospital-bed needs above the 1990 level of 5400 beds. Hospital cost projections for 1995 vary (up to US$1050 million)., Conclusions: (1) For economic impact assessment, there are important gaps in epidemiological and economic data, and in the methods for linking these. (2) Standardization of studies on the resource use and costs of HIV/AIDS is necessary to provide a sound basis for multinational scenarios. (3) Preliminary multinational scenarios show that by 1995 hospital-bed needs for AIDS might reach 0.45% of all hospital beds available in the EC, and that hospital cost projections for AIDS in that year will range from 0.15% to 0.30% of EC health-care expenditure.

Objective: Comparison of the quality of life of asymptomatic (n = 24) and symptomatic (n = 20) HIV-infected patients and description of the changes in quality of life during the symptomatic stage., Design: Prospective study., Setting: University Hospital Utrecht., Method: Every four months questionnaires on quality of life were completed by 44 of 55 consecutive HIV-infected patients., Results: Physically, asymptomatic HIV-infected patients were better off than symptomatic HIV-infected patients; psychologically, however, both groups of patients showed similar responses. During the symptomatic stage the patients' physical functioning diminished further, but feelings of anxiety or depression showed no marked change; self-evaluations of health conditions became slightly more negative with time.

Several methods exist for short term projection of the numbers of AIDS cases. Some use extrapolation of empirical curves fitted to data up to a given time, whereas others such as the popular method of 'back projection' or actuarial methods also use information about the process. In this paper we describe a dynamic model based on a distributed modelling technique allowing for variability both in infectiousness and in age distribution of the population at risk. Some model parameters are taken from the literature, others are estimated from AIDS incidence data from the homo/bisexual population in Amsterdam. The model described here simulates prevalence and incidence of HIV infection. We present prediction intervals for two years from January 1990 onwards. We discuss three scenarios based on the estimated model, two of which consider early treatment with anti-viral drugs. Given the model and the state of the epidemic in Amsterdam, early treatment intervention must be combined with very drastic measures for reducing infectivity in order to have any serious impact on the course of the epidemic.

We report a case of gastro-intestinal bleeding caused by jejunal diverticulosis, in which preoperative diagnosis could be achieved by selective angiography. Even though the small bowel is a rare localisation of bleeding (1% of all cases), this part of intestine should be included into diagnostic considerations. Jejunal diverticulosis only requires operative treatment after occurrence of complications, small bowel resection is regarded as treatment of choice in these cases.

In the Netherlands by the 1st of January 1990 1074 AIDS patients have been reported to the Department of the Chief Medical Officer. In the last few years the proportion of intravenous drug users increased and the proportion of homo/bisexual men decreased. After adjustment for the effect of delay in reporting the total number of AIDS patients by 1st January 1990 is estimated to be 1173. It appears that the reporting delay outside Amsterdam is longer than in this city. The time required for doubling of the half-yearly incidence of new AIDS patients (doubling time, dt) increased from 9 months in the beginning of the epidemic to 34 months. It is expected on the assumption of constant dt that 1120 new AIDS patients will be diagnosed in 1990 and 1991 together. The present growth among the homo/bisexual men (dt 34 months) is smaller than the one among the intravenous drug users (dt 23 months). The growth in Amsterdam (dt 36 months) is less than that in the rest of the Netherlands (dt 32 months). Based on the course of the AIDS epidemic the number of HIV infected (including the AIDS patients) is estimated as 9,000-12,000 by the 1st of January 1990.

A multigroup transmission model is described to study the spread of the human immunodeficiency virus (HIV) in linked risk groups. The model permits simultaneous investigation of the increase in the number of persons infected with HIV in three main risk groups: promiscuous homo/bisexual men (two levels of promiscuity), intravenous drug users (men and women) and promiscuous heterosexual men and women. Three modes of transmission are considered: anal and vaginal intercourse and needle sharing. The high dimensional parameter space is connected with the HIV incidence through a transmission matrix. This matrix summarizes the annual effective contact rates due to the three transmission modes. The model helps to clarify which data are needed to disentangle the relative contribution of the within- and between-group transmission routes. The model can be used to perform theoretical experiments. Given a specification of a baseline, the potential use of the model is illustrated by a simulation describing the effect of blocking the transmission through needle sharing. Reference is made to the HIV/AIDS epidemic in The Netherlands. The results of the study show that the model can play a part in the classification of HIV prevalence patterns in linked risk groups, in the study of the interaction between the main risk groups and in the theoretical evaluation of intervention measures.

The results are reported of AIDS monitoring in Amsterdam in the period 1982-1988. Males with homosexual contacts are the principal risk group followed by the fast-growing group of users of intravenous drugs. Transmission of the human immunodeficiency virus to the heterosexual population will occur mostly via sexual contacts with users of drugs. An investigation of the degree of underreporting in Amsterdam revealed 23 unreported patients (5.7% of the cumulative total). The median duration of survival of AIDS patients increased: 1982-1985, 9 months, 1986, 12 months, 1987, 16 months. Two-year survival of patients in the periods 1986 and 1987 was practically the same, however. It is assumed that at the end of 1991, 1124 AIDS patients domiciled in Amsterdam will have been diagnosed.

Precise data on the utilization of health care facilities by HIV infected patients are generally not available. Nor are there data on the related cost, effectiveness and efficiency of the treatment provided. This is due mainly to the lack of a suitable method for recording demographic, medical and financial data on individual patients in hospitals. For this reason we have been developing a system of data collection, which provides a detailed cost record of each patient. The application of this system for 52 patients with HIV infection treated in a university hospital over a two-year period showed that for a patient with AIDS the mean cost of inpatient and outpatient hospital services was $19,507 per person-year. For patients with HIV infections other than AIDS the mean costs ranged from $1,769 for CDC III patients to $2,064 for CDC II patients (expressed in 1987 US dollars). Continued operation of the registration system will make it possible to analyze the causal background of costs as well as the cost-effectiveness of the treatment.

In a retrospective study the two-lined continuous suture for the repair of femoral hernia was examined. From 1.12. 1985 till 31.5. 1988 the femoral defect was closed by a continuous two-lined suture 33 times in 31 patients. In almost 50% (16 cases) the hernia was incarcerated, in total 10 surgeons took part. Postoperatively occurred one wound infection and one serom. During a postoperative observation time of 1-28 months up to now no recurrence has been seen. Thus the two-lined continuous suture of femoral hernia seems to use a sure, simple and practical operation technique, that can be used very well in the every-day-practice, also in case of incarcerated hernia.

This study is motivated by the time lag between date of diagnosis of AIDS cases and date of reporting, which results in incomplete data about the epidemic. A maximum likelihood procedure has been developed to adjust the actual numbers of diagnosed AIDS cases for reporting delay. If a parametric function for describing past and future incidence is assumed, its parameters and the adjustment for reporting delay can be estimated simultaneously. Data from the WHO Collaborating Centre on AIDS, Paris, are used. Practical problems related to data collection are dealt with.

Plasma ampicillin concentrations were determined in a cross-over trial involving five cows after single intramuscular or intra-abdominal administration of sodium ampicillin (10 mg/kg) and ampicillin anhydrate (40 mg/kg). After injection of sodium-ampicillin, high plasma concentrations were reached within 10 min; Cmax following intramuscular injection was 9.1 micrograms/ml and after intra-abdominal injection 7.5 micrograms/ml. Urine concentrations of ampicillin were low after 24 h (1-1.5 micrograms/ml). No significant changes in blood leucocyte numbers, plasma zinc, iron or fibrinogen levels occurred. After injection of ampicillin anhydrate 1 h elapsed before maximum plasma levels were obtained; Cmax was 5.4 micrograms/ml after intramuscular and 6.7 micrograms/ml after intra-abdominal administration. Urine concentrations were very high (238-303 micrograms/ml) after 24 h and stayed above 1 microgram/ml for 6 days. After administration of ampicillin anhydrate a significant increase in blood neutrophils (P less than 0.01) and a significant increase in plasma fibrinogen was measured after intramuscular and intra-abdominal injection (P less than 0.05). A significant decrease in plasma zinc concentration after intra-abdominal injection occurred (P less than 0.05). In abdominal surgery in cows in which contamination cannot be prevented, and practical objections inhibit preoperative administration, intramuscular or intra-abdominal administration during surgery of sodium ampicillin seems justified. Ampicillin anhydrate should not be used intra-abdominally.

Cultivation of microorganisms under growth limitation is a widely used technique in microbiology. The relevant investigations, though seemingly based on straightforward experiments, have generated conflicting results, e.g., concerning molar growth yields. The purpose of this paper is to show that discrepancies in the literature could be solved if more attention were paid to methodology, especially statistics. New experimental results, concerning growth limitations in Paracoccus denitrificans, will exemplify this. They include the following items. Two limitations, one of them being succinate limitation, were established in the present study. Molar growth yields on succinate were 41 g X mol-1 for succinate limitation (95% confidence limits were 38 and 44) and 32 g X mol-1 for the other limitation (95% confidence limits were 29 and 35). The latter result is compatible with sulphate limitation, but the present experimental design does not really permit this conclusion.