[Pharmaco-economic evaluations of new drugs: potential key to a more efficient allocation of the health care budget]. / Farmaco-economische evaluaties van nieuwe geneesmiddelen: mogelijk de sleutel tot een doelmatiger verdeling van het gezondheidszorgbudget.

In the light of rising expenditure on drugs and health care, a transparent, rational and careful decision-making process is required for the reimbursement of drugs. In the Netherlands, the Ministry of Health intends using pharmaco-economics in this process, i.e., new drugs will not only be judged on their clinical efficacy but also on their cost-effectiveness. Guidelines for pharmaco-economic research in the Netherlands have been published. According to these guidelines, a pharmaco-economic study must contain a cost-effectiveness analysis and/or a cost-utility analysis. In addition, a budgetary impact analysis is required. By 2005, all new drugs with therapeutic added value must supply a pharmaco-economic evaluation in order to apply for reimbursement. It will be the Minister of Health who decides whether a new drug will be reimbursed.

A population-based longitudinal study on the incidence and disease burden of gastroenteritis and Campylobacter and Salmonella infection in four regions of The Netherlands.

The aim of this study was to estimate the incidence of gastroenteritis and Campylobacter and Salmonella infection in the Dutch population, the disease burden, and the percentage of patients with gastroenteritis that consults a general practitioner. A sample of 6243 persons was invited to participate in the study, i.e. completing a questionnaire and submitting stool samples. The follow-up period was 17 weeks. In total, 2206 persons participated (= 35%), contributing 660 person years. The incidence (standardised by age and gender) of first episodes of gastroenteritis was 45 per 100 person years. Among patients with gastroenteritis, Salmonella and Campylobacter were cultured in 1.6 and 4.5%, respectively. The standardised incidence of first Campylobacter infections was 9 per 100 person years, of first Salmonella infections 4 per 100 person years. For 22% of the episodes of gastroenteritis, a general practitioner was consulted (either by phone or by practice visit). For 52% of the episodes, medicine were used. For 34% of the episodes, absence from school was reported and for 15%, absence from work was reported. Despite of possible biases, we can conclude that the incidence of gastroenteritis is very high and causes considerable use of medication, consultation of general practitioners and absence from work and school.

Resistance in Campylobacter species: increased resistance to fluoroquinolones and seasonal variation.

To identify epidemiological features of culture-proven campylobacter infections and to determine resistance rates, we conducted a 4-year demographic survey of culture-proven campylobacteriosis in one Dutch region. Examination of 24,435 fecal specimens revealed 1,315 cases of campylobacteriosis (5.4%). The ofloxacin-resistance rate among Campylobacter isolates increased from 11% to 29%. Resistance against tetracycline fluctuated between 7% and 15%, and resistance against erythromycin remained low. Resistance against fluoroquinolones was seasonally influenced, with relatively high rates during winter. We conclude that resistance of Campylobacter isolates to fluoroquinolones is still rising, probably because of the use of fluoroquinolones (enrofloxacin) in animal husbandry.

[Infections and bacterial resistance in the community]. / Infecties en bacteriële resistentie in de open bevolking.

The frequency of resistance to antibiotics among community acquired pathogens and the number of drugs to which they are resistant are increasing world wide. Antimicrobial resistance in the Netherlands is still low. Resistance to antimicrobial drugs is clearly linked to consumption of antibiotics within and outside of the hospital. Use of antibiotics in veterinary medicine may also contribute to the occurrence of antimicrobial resistance in human pathogens. Strategies to limit the spread of resistant strains should include encouraging the judicious use of antimicrobial agents. Guidelines for antibiotic therapy should be based on results derived from well designed surveillance studies.

[European strategy for control of resistance to antibiotics]. / Europese strategie voor het beheersen van antibioticaresistentie.

The problem of international spread of bacterial resistance requires development of a strategy at worldwide or at least at European level. Clinically relevant monitoring systems for resistance and use of antibiotics have to be implemented to support the guidelines on prescription of antibiotics. Every hospital should establish an 'antibiotics team' controlling the prescription of antimicrobials and the observance of local formulary agreements. Veterinary use of growth promoting antimicrobials related to substances used in human medicine should be terminated. Future research should be aimed at resolving the problem of resistance to antimicrobials.

EU conference 'The Microbial Threat'.

A global or European strategy should be developed to deal with increasing antimicrobial resistance. This strategy includes surveillance of antimicrobial resistance and monitoring of the use of antimicrobial agents in animals and humans. In animals, surveillance should be focussed on potential transfer of resistant, zoonotic, food-born pathogens and resistance genes to humans. In humans the surveillance should be clinically relevant. Guidelines for rational therapy should be implemented and 'antibiotic teams' should be installed in each hospital to evaluate the prescription of antibiotics and its compliance with guidelines. Keeping animals for food production involves the responsibility for their well being. This includes treatment of infections. However, the use of feed additive, growth-promoting antimicrobials related to therapeutics in human medicine, should be banned immediately. Research aimed at intervention strategies for antimicrobial resistance should be given a high priority with adequate financing both nationally and in Europe. Well co-ordinated European research programmes should have priority; this includes the need to install a European multidisciplinary scientific advisory group.

Surveillance of respiratory pathogens and influenza-like illnesses in general practices - The Netherlands, winter 1997-98.

The Netherlands Institute of Primary Health Care (NIVEL) has coordinated the activities of a sentinel surveillance network of 43 general practices since 1970. These practices care for 1% of the Dutch population, a sample representative of the national pop

European Antimicrobial Resistance Surveillance System (EARSS): objectives and organisation.

Effective European surveillance must have the agreement and active involvement of all participants, concluded a European Union (EU) conference on the need for surveillance of resistant microorganisms (the microbial threat), held in September 1998 in De

Economic evaluation of influenza vaccination. Assessment for The Netherlands.

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.

An age-period-cohort analysis of 50,875 AIDS cases among injecting drug users in Europe.

BACKGROUND: The long average incubation time from HIV infection to AIDS makes it difficult to estimate recent HIV transmission from AIDS incidence data. Age-period-cohort (APC) analysis can separate out the effects of age, calendar time and birth cohort to provide a clearer picture of transmission trends. METHODS: AIDS incidence data from 1981 to 1994 among intravenous drug users (IDU) for 12 Western European countries were used. Yearly incidences per 100,000 population or 100,000 person-years were calculated by age at diagnosis and 5-year birth cohort (1950-1954, 1955-1959, 1960-1964, 1965-1969 and 1970-1974), and corrected for reporting delay. Incidence patterns were compared between birth cohorts and countries. RESULTS: For most countries the impact was greatest on the cohort born 1960-1964. Comparing incidence patterns in the 1965-1969 to 1960-1964 cohorts suggest the epidemic has plateaued at low to intermediate levels in Austria, Greece and the North-Western European countries, and at high levels in France, Italy and Switzerland. For most countries transmission amongst the 1970-1974 as compared to the 1965-1969 cohorts could not be assessed due to small numbers and short follow-up time. In Spain the epidemic was uncontrolled with a high incidence among recent birth cohorts. In Portugal the epidemic was still at an early and expanding phase. CONCLUSIONS: The APC analysis revealed large country differences in the dynamics of the HIV/AIDS epidemic among IDU. Full interpretation of these differences is dependent on information from other sources about the local public health response and trends in drug injecting behaviours. Earlier introduction of the virus and higher prevalence of injecting drug use may explain some of the generally higher incidence in Southern European countries, but the larger part of it is most likely explained by local characteristics of drug users, such as younger age and more frequent sharing of needles and syringes, and a less effective public health response.

[Surveillance of communicable diseases in the European Union]. / Surveillance van infectieziekten in de Europese Unie.

Important developments are taking place in the Public Health framework in the European Union (EU). A number of international surveillance networks have been developed between the countries of the EU. The European Commission has initiated horizontal and disease specific programmes in the field of infectious disease surveillance. These have stimulated European co-operation for prevention and control of infectious diseases. Much topical information can be found on several Internet pages. The challenge is to set up networks for all public health relevant infectious diseases.

[More information on infectious diseases provided by a national information system]. / Meer informatie over infectieziekten door landelijk systeem.

The Infectious Diseases Information System (ISIS) was established to improve the exchange of information about infectious diseases among those combating these diseases. Information about infectious diseases is obtained from municipal health services by means of a data processing system elaborated by the National Institute for Public Health and the Environment. After adjustment to the new Act on Combating and Tracing of Infectious Diseases it will be introduced nation-wide in 1998. Information about pathogens is obtained from medical microbiological laboratories (MMLs) through automatic storage of positive and negative results in a central data bank. After a pilot project had shown that the data from one MML, Arnhem, were complete and reliable, the MMLs of Roermond and Tilburg were also connected. For feedback of information to medical microbiologists and infectious diseases specialists, but also to, for instance, GPs, data from the whole country are presented daily on a public Internet site (http:/(/)www.isis.rivm.nl).

Estimating influenza-related hospitalization in The Netherlands.

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.

Risk of gastroenteritis among triathletes in relation to faecal pollution of fresh waters.

BACKGROUND: We conducted a prospective cohort study among endurance athletes to investigate the effects of microbiological water quality on the risk of gastroenteritis after bathing in fresh waters that meet current water quality standards. We aimed to establish quantitative relationships, in order to evaluate current bathing water standards. METHODS: The study was spread over two summers, during which 827 triathletes (swimmers) in seven Olympic distance triathlons and 773 participants in 15 run-bike-runs (non-swimming controls) participated. Intensive water quality monitoring was used to assess exposure to faecal indicator organisms and detailed questionnaires were used to collect data on the occurrence of health complaints and potential confounding factors. RESULTS: The microbiological water quality at the time of the triathlons met current Dutch and European bathing water standards. Dependent on the case definition studied, gastroenteritis developed in 0.4-5.2% of swimmers and 0.1-2.1% of non-swimmers in the week following exposure (odds ratio [OR] = 1.6-2.3). Attack rates and burden of disease varied with the case definition used. Among swimmers, the attack rate of gastroenteritis was significantly increased when the geometric mean concentration of thermotolerant coliforms in the water at the time of exposure was > or = 220/100 ml or the geometric mean concentration of Escherichia coli was > or = 355/100 ml (OR comparing high versus low exposure 2.9-4.7 dependent on the case definition studied). Thermotolerant coliform concentrations at these triathlons ranged from 100/100 ml (the EU guide level) to 960/100 ml (the EU imperative level is 2000/100 ml). Below the threshold levels attack rates were comparable with attack rates among non-swimmers. A relation with other indicators of faecal pollution was not observed. CONCLUSIONS: We observed that swimming in fresh waters that met the European imperative level for thermotolerant coliforms but failed the European guide level was associated with a significant risk of gastroenteritis among triathletes. This means that the current European imperative level for thermotolerant coliforms provides insufficient protection to gastrointestinal illness for those who are comparable with triathletes.

Influenza vaccination in 22 developed countries: an update to 1995.

This study expands and updates through 1995 our earlier report on influenza vaccine use in 18 developed countries. Five of the six countries with high levels of vaccine use in 1992 (> or = 130 doses/1000 population) showed little change or slight declines over the subsequent 3 years. The exception was the United States, where a new federal program for vaccination reimbursement for the elderly helped to increase vaccine distribution from 144 to 239 doses/1000 population. The six countries with medium levels of vaccine use in 1992 (76-96 doses/1000 population) increased to > or = 100 doses/1000 population by 1995. Among the six low-use countries in 1992 (< or = 65 doses/1000 population), only Finland showed substantial improvement (96 doses/1000 population) in 1995. Four new countries were added to the study. In Germany, vaccine use increased to 80 doses/1000 population in 1995, but in Ireland it remained at a low level (48 doses/1000 population). In Korea, vaccine use increased from 17 to 95 doses/ 1000 population during the period 1987-1995. In Japan, very high levels of vaccine use (approximately 280 doses/1000 population) in the early 1980s were associated with vaccination programs for school children. However, vaccine use fell precipitously when these programs were discontinued, and only 2 and 8 doses/1000 population were used in 1994 and 1995, respectively. In all 22 countries, higher levels of vaccine use were associated with vaccination reimbursement programs under national or social health insurance and were not correlated with different levels of economic development. Excluding Japan, in 1995 there was still a greater than fourfold difference between the highest and lowest levels of vaccine use among the other 21 countries in the study. Given its well established clinical effectiveness and cost-effectiveness, none of these countries has yet achieved the full benefits of its programs for influenza vaccination.

[Cost-effectiveness of influenza vaccination The Netherlands]. / Kosteneffectiviteit van influenzavaccinatie in Nederland.

OBJECTIVE: To determine the cost-effectiveness of influenza vaccination of all people aged 65 or over in the Netherlands. DESIGN: Model calculations. SETTING: National Institute of Public Health and Environment, Bilthoven, the Netherlands. METHOD: The cost-effectiveness of vaccination strategies was calculated using a mathematical model, with which the epidemiological effects in terms of morbidity and mortality as well as the direct costs of care of an influenza epidemic can be determined. The cost-effectiveness of non-intervention, of the current vaccination scenario for risk groups, and of an alternative scenario involving vaccination of all persons aged 65 or over and of all younger persons in risk groups, was calculated. RESULTS: Influenza-related care (the number of GP contacts and hospital days) and related costs decreased more with the alternative than with the current risk group scenario. Although the costs of care decreased when more people were vaccinated, the cost of vaccination increased more so that total net costs rose (55 million guilders versus 24 million). In the alternative scenario yearly 1115 life years more were won than with the current practice. CONCLUSION: Vaccinating all risk groups and all persons aged 65 or more has a favourable cost-effect ratio in comparison with other preventive intervention programmes.

[Indications for influenza vaccination in children with lung disorders. Dutch Association for Pediatric Medicine]. / Indicaties voor influenzavaccinatie bij kinderen met longaandoeningen. Nederlandse Vereniging voor Kindergeneeskunde.

The Dutch Association for Paediatric Medicine has formulated guidelines regarding influenza vaccination of children with pulmonary disease. Influenza virus is the most frequent cause of airway infections in humans over two years of age. It may lead to serious morbidity in children with pulmonary disease: exacerbations, (transient) disturbances in pulmonary function, and symptoms lasting weeks, but mortality is probably very low. The effects of influenza vaccination of children with pulmonary disease are similar to those in normal healthy children. A positive long-term effect on the asthma has never been demonstrated. It is advised that children with moderate to severe asthma who require treatment to be vaccinated against influenza every year. If the first vaccination ever occurs before the age of six years, it should be followed by a booster vaccination after four weeks. In both instances, a full vaccination dose should be administered.