Change in stem cell source for hematopoietic stem cell transplantation (HSCT) in Europe: a report of the EBMT activity survey 2003.

This EBMT activity survey presents the status of hematopoietic stem cell transplantation (HSCT) in Europe 2003 and focuses on changes in stem cell source over the last decade. There were 21 028 first HSCT, 7091 allogeneic (34%), 13 937 autologous (66%) and 4179 additional re- or multiple transplants reported from 597 centers in 42 European countries in the year 2003. Main indications were leukemias (6613 (31%; 78% allogeneic)); lymphomas (11 571 (55%; 93% autologous)); solid tumors (1792 (9%; 92% autologous)) and nonmalignant disorders (898 (5%; 93% allogeneic)). In 1991, the vast majority of autologous and all allogeneic HSCT were still bone marrow (BM) transplants. Stem cell source changed rapidly to peripheral blood (PB) for autologous HSCT between 1992 and 1996. In 2003, 97% of autologous HSCT were PB derived. The change to PB for allogeneic HSCT followed 3 years later and occurred at a lower rate. In 2003, 65% of all allogeneic HSCT were PB derived. The change in stem cell source was not homogeneous. It was associated with donor type, main diagnosis, disease stage and it differed between European countries. In 2003, bone marrow remains a significant source of stem cells in some European countries for autologous HSCT and for nonmalignant disorders in allogeneic HSCT.

Haematopoietic stem cell transplantation (HSCT) in Europe 2002. Changes in indication and impact of team density. A report of the EBMT activity survey.

This 2002 European Group for Blood and Marrow Transplantation (EBMT) activity survey concentrates on current status, increase and decrease in haematopoietic stem cell transplantation (HSCT) activity in Europe and investigates the association of transplant rates with team density. In 2002, there were 20 207 HSCT, 6915 allogeneic (34%), 13 292 autologous (66%) and 3947 additional re- or multiple transplants collected from 586 centres in 39 European countries. Main indications were leukaemias (6523 (32%; 76% allogeneic)); lymphomas (10 760 (53%; 92% autologous)); solid tumours (1913 (9%; 92% autologous)) and nonmalignant disorders (874 (4%; 92% allogeneic)). Compared to 2001, there were increases (>10%) for AML, ALL 1st CR, CML not 1st cP, MDS, SAA and CLL in allogeneic HSCT and for MDS, Ewing's sarcoma, soft-tissue sarcoma and ovarian cancer in autologous HSCT. Decreases (>10%) were observed in autologous HSCT for acute leukaemias beyond 1st CR, CML cP, glioma, breast cancer and lung cancer. Correlation of transplant rates (number of transplants per 10 million inhabitants) with team density (number of transplant teams per 10 million inhabitants) suggests different diffusion patterns for autologous compared to allogeneic HSCT. These data describe current practice for blood and marrow transplantation in Europe and give some hints about mechanisms involved in HSCT rates.

Salvia divinorum: an hallucinogenic mint which might become a new recreational drug in Switzerland.

Salvia divinorum Epling & Jativa is an hallucinogenic mint traditionally used for curing and divination by the Mazatec Indians of Oaxaca, Mexico. Young people from Mexican cities were reported to smoke dried leaves of S. divinorum as a marijuana substitute. Recently, two S. divinorum specimens were seized in a large-scale illicit in-door and out-door hemp plantation. Salvinorin A also called divinorin A, a trans-neoclerodane diterpene, was identified in several organic solvent extracts by gas chromatography-mass spectrometry. The botanical identity of the plant was confirmed by comparing it to an authentic herbarium specimen. More plants were then discovered in Swiss horticulturists greenhouses. All these data taken together suggest that many attempts exist in Switzerland to use S. divinorum as a recreational drug. This phenomenon may be enhanced because neither the magic mint, nor its active compound are banned substances listed in the Swiss narcotic law.

The challenge of identification following the tragedy of the Solar Temple (Cheiry/Salvan, Switzerland).

On October 5, 1994, 48 members of the Sect of the Solar Temple were found dead at two different locations in Switzerland: 23 victims in Cheiry and 25 victims in Salvan. Our Institute was commissioned to solve the forensic problems presented by this tragedy. Our goals were to establish the time of death, determine its causes, help elucidate the surrounding circumstances and identify the victims. This work presented us with the following challenges. This catastrophe was of an 'open' type: there was no list of 'passengers'; the victims were of five different nationalities and many had just arrived in Switzerland to participate in this event; family ties were very complex within this group; half of the victims were burned and sometimes charred; the exceptionally intense media converage of the story put a lot of pressure on the investigators and our Institute. In spite of these difficulties, all the victims were positively identified within 1 month. In the present report, we describe the steps realized to progress in our work. A special section describes our relationship with the journalists and their invaluable help in our investigations. The importance of being prepared for such an event is discussed.

Economic analysis of terminal care for patients with malignant osteolytic bone disease and pain treated with pamidronate.

The goals of this study were the assessment (1) of all costs of terminal care of patients with osteolytic bone disease and pain and (2) of the economic consequences of the pamidronate treatment as observed in a prospective clinical trial on the effectiveness of pamidronate. A total of 70 patients were recruited, who were all suffering from advanced tumour diseases (60% breast cancer, 21% multiple myeloma, and 19% other tumours). In a single-institution study the patients were randomly assigned to receive, in a double-blinded setting, pamidronate 60 mg i.v. or 90 mg i.v. every 3 weeks for a maximum of six cycles. Perception of pain intensity was recorded by self-assessment, using a linear analogue scale. Follow-up lasted 6 months after treatment. All elements of direct costs of in-patient and out-patient care were recorded in cooperation with the hospital administration and the health insurance companies [Krankenkassen]. Average monthly direct costs amounted to ECU 1,290 (+/-410) and 1,050 (+/- 430) during the treatment phase and follow-up, respectively. Average in-patient costs were about three times the out-patient costs. Significantly higher costs (by a factor of 2) were observed for terminal care in hospital (last 3 months before death) than for continued care (of patients surviving the study period). The treatment with pamidronate reduced pain significantly but did not add noticeably to the costs. The study showed that it is practicable and quite efficient to combine a pharmaco-economic evaluation with a clinical trial, although it may be difficult (depending on the setting and availability of information) to assess true costs, i.e. total resource usage.

Exit association-mediated suicide: toxicologic and forensic aspects.

The Swiss German chapter of the Exit Association provides conditional assistance to individuals wishing to end their own lives. The Exit Association advocates death with dignity and fights for the right to freely choose the timing of one's own death. According to the Swiss criminal code (articles 114 and 115), altruistic assistance to suicide is not punishable. Active euthanasia is punished by imprisonment. An individual commits active euthanasia if he or she is driven by honorable motives (e.g., pity) and causes the death of another person wishing to die who seriously and insistently requests such action. Based on our information, the preparation for suicide and its completion relies on a well-defined protocol. First, the candidate's eligibility for Exit Association assistance is verified. The candidate then writes a farewell declaration that explicitly confirms the will to terminate his or her own life. A written report describes the events during the suicide procedure. Depending on the circumstances, the investigative judge requests a forensic autopsy and toxicologic analyses. The results of the forensic investigations conducted in the cases presented here are in agreement with the scenario described in the reports of the Exit Association, namely, suicide by massive ingestion of pentobarbital.

[Socioeconomic aspects of the changed mortality rate of coronary disease in Switzerland 1988-1993]. / Sozioökonomische Aspekte der veränderten Mortalität der koronaren Herzerkrankung in der Schweiz; 1988-1993.

Mortality from ischemic heart disease (ICD 410-414) is changing. Remarkable decreases have been observed in the age groups from 35-64 years, while overall mortality (all age groups) has remained approximately stable. In Switzerland this has meant a gain of some 4700 life years in the period 1988 to 1993 in the working population (35-64 years). The object of this study was to assess the associated change in indirect costs (productivity losses) due to premature death, using the human capital approach. The indirect costs were CHF 519 million (CHF 7.5 million per 100,000 population) in 1993. This represents approximately half of all indirect costs (and 25% of the total costs generated by the disease). Compared with the year 1988, a decrease in productivity losses due to premature death was observed amounting to CHF 46 million (-11%) in constant Swiss francs. Society benefits from this decrease in indirect costs, a desirable development hardly ever mentioned.

An economic analysis of ischaemic heart disease in Switzerland.

AIMS: Direct and indirect costs of ischaemic heart disease were assessed in Switzerland, for the period 1988-1993, in order to evaluate the economic consequences of more intensive treatment of the disease and of the decreasing mortality from ischaemic heart disease in the working population. METHODS AND RESULTS: A societal perspective was taken for a prevalence-based assessment of the direct (total resources consumed by outpatients and inpatients) and indirect (due to morbidity, invalidity, and premature death, using the human capital approach) costs. The results showed the total costs were 21 million US dollars per 100000 population in the year 1993 (47% direct, 53% indirect costs). The largest components were the direct costs of inpatient care and indirect costs due to premature death (each approximately 25% of the total). Trends showed a large increase in direct costs (+9% per year, constant dollars). Indirect costs stabilized or decreased slightly due to the reduction of work losses. CONCLUSIONS: Today's medicine and preventive measures have proven effective for ischaemic heart disease, although such remedies have required increasingly large financial resources. However, society benefits because indirect costs decrease, although this gain does not compensate for all direct costs.

Forensic diaphanoscopy: how to investigate invisible subcutaneous hematomas on living subjects.

A significant proportion of subcutaneous hematomas remain undetected after external visual examination of the body. In the case of a cadaver such hematomas can be easily identified through a cutaneous incision but in living persons the diagnosis becomes more complicated. The usual methods, based on diagnostic imaging, do not combine sufficient reliability and feasibility. The results of our investigations demonstrated that forensic diaphanoscopy is a highly sensitive (95%) and specific (97%) means to determine the presence or absence of subcutaneous invisible hematomas. In addition, it is possible to locate such hematomas with great precision, to draw their shape and evaluate their magnitude. The lower limit of detection is of the order of 1 mm. The advantages of this method lie in the fact that it is reliable, non-invasive, has no side effects, is simple to carry out and allows real time scanning.

[Cost-benefit analysis of screening for congenital toxoplasmosis]. / Kosten-Nutzen-Analyse des Screenings auf kongenitale Toxoplasmose.

A comprehensive cost-benefit analysis of possible screening strategies for congenital toxoplasmosis is necessary as a basis for the decision whether or not screening is efficient and socially desirable. The total costs of the disease in Switzerland were calculated for the year 1990. Direct costs (all diagnostic and therapeutic interventions, including care of handicapped children) and indirect costs (partial and total work losses in the future) were taken into account. Today, the direct costs amount to approx. SFr. 20 mio per year (i.e. approx. SFr. 2.8 mio per million population). The indirect costs were calculated at SFr. 4 mio per year. Moreover, the costs incurred with three possible screening programs (1 test with all pregnant women, with 1, 2 or 5 additional tests, depending on the strategy) were estimated, together with the concomitant cost savings. The financial resources needed for the screenings would amount to SFr. 7 mio-18 mio per year, depending on the strategy chosen. However, the possible savings would be in the range of SFr. 4 mio-12 mio only. The possible savings are, in any case, of the same order of magnitude as the costs for screening. Screening would become cost-efficient if costs for the serological tests could be lowered.

Fatal intoxication due to an unexpected presence of carbon dioxide.

A fatal accident which occurred in a tank containing a sludge made of wine and activated charcoal is described. Similar accidents in the wine industry seem to have never been reported before. Initially, the cause of death was not obvious and became clear only after the autopsy confirmed the presence of a very high concentration of carbon dioxide in blood. It is shown in this paper how the concentration of carbon dioxide in the tank could be estimated from its solubility in water, assuming a realistic content of this gas in the wine remaining in the sludge. Moreover the accident was analysed by the fault tree method which revealed that, as well as the deficiencies in risk management of such companies, the unsuspected presence of carbon dioxide played a significant role.

Economic evaluation of pharmaceuticals: a European perspective.

In recent years there has been a large increase in the number of economic evaluations of pharmaceuticals. Many of these studies have been commissioned by individual pharmaceutical companies, in support of new or existing products. In 2 countries, Australia and Canada (in the province of Ontario), draft guidelines issued by the government have outlined the requirements for economic evaluations to be submitted in support of requests for reimbursement (government subsidy) of particular products. One consequence of the guidelines is that they clarify what is required, and in specifying the procedure for submission of dossiers, identify a clear audience for the economic evaluation. In contrast, the situation in Europe is diverse. A wide range of healthcare systems exist, including national health services and more liberal systems, involving a wide range of insurers and providers. European countries also differ widely in their approach to the pricing and reimbursement of pharmaceuticals. Because of this diversity, the nature, conduct and impact of economic evaluation in Europe is not clear. It is therefore difficult for pharmaceutical companies to develop appropriate strategies for economic evaluation and for analysts to decide on appropriate study methodology. This article reviews the nature of any official guidance or requirements for economic evaluation, the potential for use of economic evaluation, the range of studies carried out and the identifiable impacts. There is currently no official guidance in any country, although some countries are considering issuing guidelines. In some countries there is official encouragement to pharmaceutical companies to undertake studies, and where economic data have been presented they have been considered by the relevant committees. The potential uses of economic evaluation vary widely from country to country. These can be classified in terms of a potential role in undertaking national price negotiations, deciding on reimbursement status or copayment level, deciding on inclusion in local formularies or in treatment guidelines, or in improving prescribing decisions. Approximately 80 economic evaluations of pharmaceutical products have been conducted to date in Europe, covering a wide range of clinical areas. There are relatively few examples of identifiable effects of such studies. In part this is because it is often difficult to assess the part played by various items of data. Nevertheless, the overriding conclusion is that economic evaluation of medicines is likely to be more relevant in Europe in the future. The problem for the pharmaceutical industry is in determining when and how.

Cost-benefit analysis of hepatitis-B vaccination. A computerized decision model for Spain.

The availability and efficacy of recombinant deoxyribonucleic acid yeast-derived hepatitis-B vaccine, at a price much lower than the previously available plasma-derived hepatitis-B vaccines against hepatitis-B virus infections, motivate a new cost-benefit analysis of hepatitis-B vaccination. Spanish data were used to calculate direct and indirect costs of hepatitis-B infection and the costs and benefits of different vaccination strategies in defined risk groups of the Spanish population. A vaccination program will reduce direct expenditures for hepatitis B if the attack rate in the target population is higher than 4.9%. If indirect costs are included, the threshold for cost saving is reduced to 0.9%. The results are sensitive to the price of the vaccine, the duration of protection, assumptions about consequences for quality of life, and to indirect costs.

[Cost benefit analysis of ulcer therapy]. / Kosten-Nutzen-Analyse der Ulkustherapie.

Duodenal ulcer (DU) disease, one of the "common diseases" of economic importance, is widespread among the population. Epidemiological data indicate that in Germany (FRG) 400,000 patients underwent treatment in 1980. Some 625,000 ulcer attacks can be estimated for the total population, and 56,900 patients had to be hospitalized because of the disease. The overall effect of DU on the national economy was close to DM 1 billion (943.5 million). The average loss of working time cost DM 514 million (54.5%), and medical costs amounted to DM 429.5 million (45.5% for hospitalization and ambulatory care). Cimetidine, the H2-blocking agent, introduced in the FRG in 1977 as an antiulcer drug, has resulted in an economic gain of over DM 200 million to the national economy. If one deducts DM 43.1 million for additional expenditures caused by DU treatment with cimetidine, the net benefit of the drug in Germany in 1980 was DM 170.5 million, which corresponds to a cost-benefit ratio of 4:1. In addition, intangible medical and social benefits have been generated which cannot be expressed in monetary terms, e.g. a gain in 40-50 pain-free weeks per 100 patients treated with cimetidine.

[Determination and analysis of cost and production measures in physicians' practices and hospitals for the objective evaluation of medical measures]. / Erfassung und Analyse des Kosten- und Leistungsaufwandes in Arztpraxen und Spitälern zur objektiven Bewertung von medizinischen Massnahmen.

The complete data on 7200 practising physicians in Switzerland were analyzed in the first phase of the project. The 2600 GP's and the 4600 specialists (in 18 medical specialties) were categorized as to year of graduation and geographic regions (population centres). The distributions of the practising physician of the different specialties over the population centres (defined by 30-min. catchment area) areas were evaluated. Trends towards specialization in larger settlement areas were analyzed. The results are being used as a basis for formation of samples for further studies. The inventories of medical technical equipment and medical procedures are in the process of systematization.

The concept of intensive medicine. A systems approach of importance to medical engineers.

The paper demonstrates how planning, organizing, equipping, and running all Intensive Care Unit (ICU) should be carried out, using a systems approach, and by keeping in mind that quality and degree of overall performance is a function of effectiveness and efficiency. The interactions of the ICU with its "environment" are discussed; a method of estimating the size of the ICU is mentioned. Then, the elements determining performance are analyzed: personnel, pathophysiologic states of the patients, financial and material resources. Furthermore, the problem of goal-oriented systems synthesis is outlined and suggestions for more detailed studies on the structure of some of the "subsystems" are put forward. The paper summarizes some important consequences for medical engineering as applied to intensive medicine.