Standard-risk medulloblastoma treated by adjuvant chemotherapy followed by reduced-dose craniospinal radiation therapy: a French Society of Pediatric Oncology Study.

OBJECTIVE: The primary objective of this study was to decrease the late effects of prophylactic radiation without reducing survival in standard-risk childhood medulloblastoma. PATIENTS AND METHODS: Inclusion criteria were as follows: children between the ages of 3 and 18 years with total or subtotal tumor resection, no metastasis, and negative postoperative lumbar puncture CSF cytology. Two courses of eight drugs in 1 day followed by two courses of etoposide plus carboplatin (500 and 800 mg/m(2) per course, respectively) were administered after surgery. Radiation therapy had to begin 90 days after surgery. Delivered doses were 55 Gy to the posterior fossa and 25 Gy to the brain and spinal canal. RESULTS: Between November 1991 and June 1998, 136 patients (median age, 8 years; median follow-up, 6.5 years) were included. The overall survival rate and 5-year recurrence-free survival rate were 73.8% +/- 7.6% and 64.8% +/- 8.1%, respectively. Radiologic review showed that 4% of patients were wrongly included. Review of radiotherapy technical files demonstrated a correlation between the presence of a major protocol deviation and treatment failure. The 5-year recurrence-free survival rate of patients included in this study with all optimal quality controls of histology, radiology, and radiotherapy was 71.8% +/- 10.5%. In terms of sequelae, 31% of patients required growth hormone replacement therapy and 25% required special schooling. CONCLUSION: Reduced-dose craniospinal radiation therapy can be proposed in standard-risk medulloblastoma provided staging and radiation therapy are performed under optimal conditions.

Treatment of high risk medulloblastomas in children above the age of 3 years: a SFOP study.

AIM: Improvement of EFS of children older than 3 years with high risk medulloblastoma. METHODS: Between 1993 and 1999, 115 patients (3-18 years, mean 8 years) with high risk medulloblastoma were included. After surgery treatment consisted of chemotherapy ('8in1' and etoposide/carboplatin) before and after craniospinal radiotherapy. RESULTS: Patients were staged using Chang-criteria (PF residue only, M1 and M2/M3) by local investigator as well as by central review panel (82.4% concordance). Chemotherapy was well tolerated without major delays in radiotherapy. With a mean follow up of 81 months (9-119), 5-year EFS was 49.8% and OS 60.1%. In detail according to subgroups EFS was 68.8% for PF residue only, 58.8% for M1 disease and 43.1% for M2/M3. CONCLUSION: M1 patients are legitimate high risk patients. Survival rates are still very low for high risk medulloblastoma patients and future trials should therefore focus on more intensive (chemotherapy/radiotherapy) treatment.

Costs and outcomes of liver transplantation in adults: a prospective, 1-year, follow-up study. GRETHECO study group.

BACKGROUND: Orthotopic liver transplantation (OLT) is widely used to treat patients with end-stage liver disease. However, data on the cost of the procedure are fragmentary. We evaluated the costs, as calculated from resource use, and outcomes of OLT in adults, from registration on the transplant waiting list to the end of the 1st-year of follow-up after the transplant. METHODS: Two parallel cohort studies were conducted from 1994 to 95. All patients ages 18 years and older, on the waiting list (n=33) according to national criteria or having undergone transplants (n=38) were followed for 1 year or until either the transplant (waiting list cohort) or death (waiting list and transplantation cohorts). RESULTS: Eighty percent of the patients undergoing transplants were alive after 1 year, and no patient died while on the waiting list. However, the estimated cost of the procedure was high: more than 55,000 pound silver for the 1st year after OLT, to be added to 5,500 pound silver for evaluation and further costs motivated by the planned transplant during an average 6.5 months on the waiting list. Age over 40 and a baseline Child-Pugh score of 10 and over were predictive of high costs. The proportion of costs associated with immunosuppressive therapy and rejection were very high. CONCLUSIONS: This medical and economic cohort study suggests that OLT is still expensive; the study identifies sources of extra cost that could be limited either by improved selection of patients or, in the future, by technological advances in immunosuppressive therapy that help avoid medical complications. It also suggests the situation is precarious, with outcomes and costs being very sensitive to variation in graft availability.

Contrasted diffusion and the use of CT scanner equipment in France.

During the last 4 years, there has been a rapid catching-up in the distribution level of CT-scanners in France. In a survey of CT-scanner utilization, data from all machines operating in the PACA Region in 1986, showed that the mean activity was 6,080 examinations per machine. The co-existence of both private and public medicine led to different use of materiel (5,500 to 5,800 exams per machine in the public versus 8,600 in the private sector and a higher productivity in the profit-making establishments. This difference was not explained by procedural variations in carrying out the technique, which appeared to be similar and standardized everywhere, but probably reflected patient selection (80% of ambulatory patients in the private sector, 25 to 50% in PTH).

Cost-effectiveness of HIV screening of pregnant women in hospitals of the Paris area. The Paris-Tours study group of antenatal transmission of HIV, Group '9 maternites'.

In the context of an epidemiologic multicentric study about perinatal transmission of HIV, screening was systematically proposed to all pregnant women attending nine maternities clinics of the Paris region (n = 7600, between August 1987 and July 1988) at their first prenatal visit. Among them, 2145 had already been tested and 45 were known to be HIV positive. So, 5660 tests were performed during the first 6 months (period 1), and 17 pregnant women were discovered to be positive. The total cost of screening has been estimated between FF. 720,000 and 775,000, resulting in a mean cost per pregnant woman found to be HIV positive of about FF. 42,000 to 45,000. A similar calculation over the following 5 months (period 2) gave a mean cost of between FF. 165,000 and 178,000. Since the women, before being screened, had to answer a short questionnaire about risk factors; cost and effectiveness of a selective screening strategy could be simulated. The preference of systematic screening to selective screening enabled the discovery of two HIV positive cases in each period, the marginal cost, i.e., cost per extra pregnant woman found to be HIV positive was thus FF. 303,320 to 327,540 for period 1, and FF. 572,240 to 619,000 for period 2. Although these figures seem high, an estimation of the cost-effectiveness does not allow us to conclude whether it is in society's interest to devote the funds necessary to move away from selective screening towards systematic screening.(ABSTRACT TRUNCATED AT 250 WORDS)

Social perception of AIDS in the general public: a French study.

The paper presents the results of the first national survey about social perception of AIDS in a representative sample of the French general public (which was carried out in June 1987). A large majority of the French public (73.1% of respondents) support mandatory screening for HIV, and a significant part (21.9% of respondents) even favours isolation of AIDS patients. Results show the relations between false beliefs on transmission of AIDS by casual contact and willingness to agree with measures that carry a great danger of stigmatization for AIDS patients and HIV carriers; but strong correlations between support of coercive measures for prevention of AIDS and similar opinions on other controversial issues suggest that, for a fraction of the public, attitudes about AIDS are rather determined by a priori ideological and ethical values than by risk perception of the disease per se. Results also suggest that any ambiguity in scientific information about AIDS may increase social pressure, even among the most educated part of the population, for unnecessary measures. Tentative conclusions for public policy on prevention and information about AIDS are drawn.

Cost-effectiveness of monolayers and human papillomavirus testing compared to that of conventional Papanicolaou smears for cervical cancer screening: protocol of the study of the French Society of Clinical Cytology.

The French Society of Clinical Cytology is conducting a study to compare the cost-effectiveness of monolayers and human papillomavirus (HPV) testing with that of conventional Papanicolaou (Pap) smears for cervical cancer screening. The protocol of this study is presented. It includes 3,000 women who will be evaluated by the three methods (conventional Pap smears, or monolayers with or without HPV testing) and by the reference method: colposcopy followed, in cases with abnormalities, by cervical biopsy. Efficacy or performance of the methods will be compared on the basis of sensitivity. Cost comparisons and cost-effectiveness modeling will be based on the costs associated with methods themselves and also the costs of "false positives." This will require specific collection of data concerning the costs of the three methods, as these costs have not previously been accurately documented. Patient recruiting and data collection started in September 1999 and will be complete in June 2000. The first results are expected to be available in spring 2001.

[Cost-effectiveness analysis of the treatment of chronic hepatitis C]. / Analyse coût-efficacité du traitement de l'hépatite chronique C.

OBJECTIVES: Chronic active hepatitis C is an important public health issue because of its prevalence, evolution, and overall cost. Treatment by recombinant alpha-interferon is both expensive and exacting and its effectiveness is limited. We report the results of a cost-effectiveness analysis of alpha-interferon treatment in patients with chronic active hepatitis C. METHODS: Direct medical costs of caring for patients with chronic active hepatitis C and its complications, based on treatment or no treatment, were assessed with retrospective data collected from the files of 137 hospital patients. Seventy-seven patients were treated with alpha-interferon between 1988 and 1994. The overall costs of caring for chronic active hepatitis C patients, without treatment or with alpha-interferon treatment (3 millions units three times a week) for 6 months (strategy A), 12 months (strategy B), or 12 months but discontinuing treatment when there was no response (strategy C), was reported and compared to the respective effectiveness of each. RESULTS: With an actualization rate of 5%, the real overall cost of caring for a chronic active hepatitis C patient was 143290 FF. Considering the contraindication rate (15%), the treatment acceptance (85%), the response rate to treatment (50%), and the prolonged response rate (25 to 30%), treating patients with strategy A induced a real overall cost of caring to 140731 FF to avoid 0.11 cases of cirrhosis, to 150277 FF to avoid 0.13 cases of cirrhosis with strategy B, and to 136947 FF to avoid 0.13 cases of cirrhosis with strategy C. CONCLUSION: Alpha-interferon treatment in patients with chronic active hepatitis C provides a long-term saving compared to cases which receive no treatment. Strategy C was the most cost-effective, inducing the reduction of both the number of cases of cirrhosis and the cost of care.

[Model for evaluation of occupational mortality related to asbestos (the case of the asbestos industry in France between 1950 and 1980)]. / Un modèle d'évaluation de la mortalité professionnelle liée à l'amiante (Le cas de l'industrie de l'amiante en France entre 1950 et 1980).

This article presents an evaluation model of the mortality attributed to asbestos occupational exposure. French workers exposed at least ten years between 1950 and 1979 constitute the population studied. Exposure-risk relations are used to estimate mortality from lung cancer, mesothelioma, or asbestosis, and the associated reduction of life expectancy among 76 groups (about 18,500 workers) defined by their level of asbestos exposure. The most important results are presented and discussed as are the main hypotheses regarding historical exposure parameters.

[Prevention of occupational carcinogens: perspectives opened by the evaluation of risks and preventive actions]. / La prévention des cancérogènes professionnels: les perspectives ouvertes par l'évaluation des risques et des actions de prévention.

The first part of the review deals with the present situation in terms of prevention against potential carcinogenic substances in France. A significant effort should be devoted to the measurement of contaminants--not only carcinogenic substances--in the workplace. This is a prerequisite for setting a data base in terms of potential occupational risk. Moreover gaps exist also as far as the definition of the technical means aimed at the reduction of risk is concerned. These conclusions put into light the importance of the contribution that "industrial hygienists" would bring in France. In the second part of the review, the methodological content of the risk assessment and risk management procedures is described and illustrated. Risk assessment of carcinogens deals: with the identification of potential carcinogens through epidemiology, animal bio-assays and short term tests; with the quantitative estimation of the magnitude of the potential carcinogenic risk among the exposed workers. It appears necessary to carry out systematic surveys of the number of workers exposed to the carcinogenic substances. The risk assessment procedure is applied to 5 substances BCME, MOCA, Acrylonitrile, Chromium, Nickel and some compounds of these metals. The number of potential excess cancers related to a unit lifelong exposure to Nickel compounds is estimated. This requires exposure-response models which are critically analysed. Risk management is devoted to the choice of primary health care policies. The methodology of risk management consists of: identifying various control policies; quantitative estimation of their efficiency--indicators of the efficiency are discussed--and of their cost; choice among these policies with the help of a cost-effectiveness analysis when necessary. The procedure is illustrated in the case of Acrylonitrile control in a facility.

[Economic analysis of neonatal screening for drepanocytosis in metropolitan France]. / Analyse économique du dépistage néonatal de la drépanocytose en France métropolitaine.

There is indisputable evidence that mortality and morbidity can be significantly reduced by programmes that screen newborns for sickle cell disease. But in the French epidemiological context, national decision regarding generalization of local screening programmes to all newborns must take into account economic considerations as at-risk populations represent, in most geographic areas, a few percent of the total population. Targeted screening can be considered but raises ethical and practical issues. In order to compare alternative screening strategies, a cost-effectiveness analysis has been performed. The analysis is based on a screening programme of newborns conducted in the south-eastern suburb of Paris. Strategies have been defined in terms of laboratory procedures (isoelectrofocalisation, electrophoresis on citrate agar, high pressure liquid chromatography, BIORAD technique,...) and methods for blood collection (dried paper, micro-tube). An evaluation of all the necessary costs have been performed for each strategy in the biochemistry laboratory in charge of the neonatal programme. Costs have been estimated from detailed observation of physical quantities of capital and labour involved in each case. Evolution of unit and marginal costs according to the level of annual production has been assessed. Effectiveness has been measured in terms of number of sickle cell cases detected. Screening of at-risk babies in Paris region would permit detection of 80 to 215 babies each year at a unit cost per case found varying from 1 to 2,800 US$ (according to hypothesis of prevalence). When compared with other programmes of prevention, results of selected screening of newborns in whole metropolitan France suggest that this action might be discussed by public health authorities.

[Economic evaluation of interventions in public health: potentials and limitations]. / L'évaluation économique des interventions en santé publique: principes et limites.

One of the main principles of economic evaluation refers to the scarcity of resources. So, choices must and will be made concerning the commitment of these resources to one use instead another. Economic evaluation can assume different methodological forms regarding the kind and complexity of programme to be assessed and the issue of outcome valuation, but each analytic technique compares the resources consumed by different relevant alternatives with the health improvements and other consequences arising from them. From a pragmatic point of view, four types of economic evaluation can be distinguished associated with different measurement and valuation of consequences: cost-minimization, cost-effectiveness, cost-utility and cost-benefit analysis. A first step of economic appraisal is definition and description of each competing alternative. Then, there are difficulties associated with measurement and valuation of both costs and effectiveness of alternatives. The assessment of public health interventions poses some special problems in terms of time profiles of cost and consequences. Most of the costs of a health programme incurred in the present while benefits will come later in the future. Therefore, cost and consequences must be discounted to reflect the existence of time preference. The last important point concerns the assessment of health consequences. Ideally, evaluation of efficacy takes the form of a well controlled randomized trial designed for this purpose. But, in many situations, this approach is not relevant, appropriate or feasible and efficacy appraisal must be developed on the basis of available data and "realistic" assumptions. So, every evaluation will contain some degree of uncertainty or imprecision and a sensibility analysis must be performed in order to test sensitivity of the results to alternative assumptions and uncertainty.

[Methodologic contribution to determining maximum occupational exposure levels for asbestos. Exposure-risk relation and economic criteria]. / Contribution méthodologique à la détermination de valeurs limites d'exposition professionnelle à l'amiante. Relation exposition-risque et critères économiques.

It is not easy to set exposure limits for industrial carcinogens when only biological and epidemiological criteria are used. Hence, criteria should also include relevant social and economical considerations. This paper, using asbestos exposure as an example, explains how the economic aspects of prevention may be taken into account. The methodology includes three stages: use of the exposure-risk models in order to estimate the residual health effects associated with asbestos, according to various exposure limits, evaluation of costs of preventive measures required by these exposure limits, discussion of the exposure limits--a synthesis of the two preceding stages.

[Evaluation of the cost-effectiveness of school screening for hereditary hemoglobin abnormalities: prospective study in Bouches-du-Rhône. School screening for hemoglobinopathies]. / Evaluation coût-efficacité du dépistage scolaire des anomalies héréditaires de l'hémoglobine: une étude prospective dans les Bouches-du-Rhône. Dépistage scolaire des hémoglobinoses.

Screening in schools for heterozygote carriers of haemoglobinopathies traits has been carried out experimentally in southeast France ("Bouches du Rhône", the Marseille region) since 1977. The study compares, in cost-effectiveness terms, the screening strategy now followed with 27 alternative strategies in all the pupils (14-16 years). Although the frequency of heterozygote carriers in this school population as a whole is only 7.9% carriers for beta-thalassaemia gene and 2.5% carriers for HbS, prospective costs per diagnosis still seem reasonable: from 1544 to 4997 French francs (1987) depending on the strategy, and 2099 to 7380 francs if beta-thalassaemia alone is screened. In comparison with the current screening strategy, cost-effectiveness ratios could be improved by using haemoglobin electrophoresis as a preselection test, or a blood count if beta-thalassaemia alone is screened. Further improvement of cost-effectiveness ratios could be obtained by limiting screening to ethnic groups most "at risk"; but such strategies raise ethical and acceptability issues.

[Evaluation of the policies for detection of pulmonary tuberculosis in France]. / Contribution à l'évaluation de la politique de dépistage de la tuberculose pulmonaire en France.

A survey of 984 cases of pulmonary tuberculosis was carried out to assist French public health authorities in determining policies for pulmonary tuberculosis detection. The adjusted sample was representative of the totality of pulmonary tuberculosis cases reported. The survey made it possible to define the economic and socio-demographic characteristics (age, nationality, lack of social security coverage, living conditions) which, when combined, represent high-risk attributes with regard to pulmonary tuberculosis. Nonetheless, over half the subjects studied presented no risk factors. Systematic X-ray screening of an undifferentiated population permits detection of about 23% of reported cases; among them, 26 or 50% (depending on the definition of contagiousness chosen) were contagious. In 1982, 9 million systematic X-ray screenings were performed and about 13,100 cases of pulmonary tuberculosis reported. When extrapolated to these 1982 figures, our survey conclusions point to an effectiveness rate for systematic X-ray screening of 33.7 per 100,000 for the overall tuberculosis population, and between 8.9 and 17.4 per 100,000 for contagious cases. On the other hand, high-risk groups (female immigrants, the aged, etc.) do not seem to be particularly well covered by systematic X-ray screening. Thus, maintaining such a program no longer appears justified either in terms of the overall tuberculosis population or that of high-risk subgroups.

[Medical and economic evaluation of organ transplantation in France. The example of liver transplantation]. / L'évaluation médico-économique des greffes d'organe en France. L'exemple de la transplantation hépatique.

BACKGROUND: Organ transplantation is an expensive and risky medical procedure. Estimating the cost is difficult because the care is complex and involves many actors. We present a methodological framework for the economic evaluation of organ transplantation in France which include a detailed collection of all the direct costs and the simultaneous analysis of health status. It was applied to evaluate the cost of liver transplantation in France. METHODS: All consecutive adults transplanted or placed on the waiting list of liver transplantation in the Department of Surgery of Cochin Hospital, Paris, between 1994 and 1996 were included. All resource use was measured during one year: staff wages, pharmacy and blood, laboratory and radiology, supplies, overhead hospital services. Mean quality of life was estimated by the survival weighted by the Karnofsky index. RESULTS: Transplantation: 38 patients were included. The first year mean cost after transplantation was 561,000FF (included rehospitalizations cost of 120,000FF). Care outside the hospital induced 10% of the total cost. Mean quality of life was 63% (from 0% to 93%) and increased with time, whereas cost decreased. Waiting list: 26 of 33 patients on waiting list were transplanted. The first year mean cost was 95,000FF (included 32,000FF for first evaluation) and increased with time. 44% of cost was supported by another hospital than the transplanting one. Sickness allowance added 20% to the cost. The mean quality of life was 56% during the first year. CONCLUSIONS: This complete approach of organ transplantation cost respected the medical procedure over the time. Detailed costs take into account the care outside the hospital. This method can be used in other countries and generalised to all surgical or medical procedure as heavy as the organ transplantation.

[Cost-benefit analysis of amniocentesis in the prenatal diagnosis of chromosome abnormalities]. / Analyse coût-bénéfice du diagnostic prénatal des anomalies chromosomiques par amniocentèse.

The article presents a cost-benefit analysis of amniocentesis for detection of chromosomal anomalies based on data (1985/87) collected in the Marseille area. In this geographic area, it is possible to confront, in an exhaustive manner, pregnant women's access to amniocentesis and incidence of fetal anomalies due to chromosomal aberrations. Results show that prenatal diagnosis is highly cost-beneficial, the average cost of one "avoided" case of Down's syndrome being lower than the lifelong costs of care for such a child. However, the study emphasizes that the cost-benefit ratio is highly sensitive to the implicit value society affects to the loss of "normal" fetuses through spontaneous abortions provoked by amniocentesis and because of terminations of pregnancy following diagnosis of minor fetal anomalies. The study also shows that lowering maternal age limit for access to free-of-charge amniocentesis from the current 38 years of age to 35 would have been cost-beneficial. Such lowering of the maternal age limit is discussed and compared with other indications which might be used for systematic access to amniocentesis.

[Cost-benefit analysis of prenatal screening for trisomy 21 through analysis of HCG in maternal blood]. / Analyse coût-bénéfice du dépistage prénatal de la trisomie 21 par dosage de l'hCG sérique maternelle.

Introduction of maternal serum markers for prenatal screening of Down's syndrome implies a redefinition of the criteria used for identifying at risk women for screening by amniocentesis, which are currently based on maternal age. On the basis of the first French prospective study of human chorionic gonadotropin measurement in maternal serum as a predictor of Down's syndrome, this paper shows that a screening policy combining maternal age with hCG measurement was more cost-effective than one relying on maternal age alone. A cost-benefit analysis (using the "avoided" lifelong costs of care for a trisomic 21 child that are allowed by prenatal screening) would justify lower hCG cut-off values and an higher detection rate of Down's syndrome (74.5%) than other decision rules based on alternative principles such as: equalization to 1% of fetal risk of Down's syndrome for access to amniocentesis at all maternal ages or equalization to 1/1000 of fetal risk of Down's syndrome among women not undergoing amniocentesis. However, results of the cost-benefit analysis are very sensitive to other factors such as the cost associated with loss of a normal fetus due to iatrogenic risk of amniocentesis (false positives of hCG). Ethical and value-laden issues that necessarily underlie economic evaluation of screening programmes, as well as other decision rules based on equalization of acceptable risk for each maternal age, are discussed.

[Medical costs associated with the risk of maternal-fetal contamination by HIV. Results of a prospective survey]. / Coûts médicaux associés au risque de contamination maternofoetale par le VIH. Résultats d'une enquête prospective.

BACKGROUND: Assessment of economic implications of pediatric HIV infection allows to document efforts which are devoted by health care system to the care of children born to HIV infected women. This paper presents the results of the first analysis, in the French health care context, of direct medical costs related to HIV mother-to-child risk of transmission. MATERIAL AND METHODS: Statistical prospective analysis was performed on 853 files concerning 152 children followed in three medical centers. Because the medical consumptions data were linked to clinical status, average direct medical costs per medical contact could be defined for each center. RESULTS: Results were consistent with the hypothesis that more medical care is necessary when the clinical picture is uncertain (indeterminate status) or reflects health state deterioration. However, results are very different according to HIV clinical status and disparities may be so large that costs per clinical status hierarchy may be disrupted. Explicative factors for these variabilities are expressed in terms of patient recruitment, medical uncertainty management and resources disponibility.

[The practice of x-ray computed tomography during a period of rapid growth. A survey on the Provence-Alpes-Côte d'Azur region in 1986]. / La pratique de la tomodensitométrie en période de croissance rapide du parc. Enquête dans la région Provence-Alpes-Côte d'Azur en 1986.

From May to September 1986, a sample of 748 CT-scanner examinations, representative of the total annual activity, has been collected in Provence-Alpes-Côte d'Azur Region. The regional activity of CT-scanner has been estimated to 91,200 examinations in 1986 (total France: 628,500 in 1985) or 22.7 procedures per 1,000 inhabitants (total France: 11,4 in 1985). CT-scanner is now a routine diagnostic imaging device with an annualized average of 6,080 procedures per machine (5,770 in public sector and 8,415 in the for-profit private one). The mean effective utilization time for a machine in one year was 2,700 hours in a regional, public, teaching hospital (PTH) and 3,100 in private, for-profit establishment (PPE). The number of procedures per machine-use hour was 2,4 in PTH and 2.8 PPE. No procedural difference has been observed between the two sectors in carrying out the technique. CT-Scanner diffusion in the private for profit sector has meant: - an increase in the demand from general medical practionners (more than 1/4 examinations); - a larger range of indications concerning less serious health conditions.