The health technology assessment of the compulsory accident insurance scheme of hand transplantation in Switzerland.

UNLABELLED: Recently the decision-making committee of the compulsory Swiss accident insurance scheme needed to make a basic decision as to whether to fund hand transplantation under that scheme or not. A Health Technology Assessment was commissioned to inform decision-making and gain experience with applicability of the method. The following were main findings from various domains. Compared with prosthesis fitting, the outcome of hand transplantation is satisfactory for function and sensibility. Complications due to immunosuppression are frequent, sometimes severe and potentially life-shortening. The direct medical costs over the entire life span calculated for a 35-year-old unilaterally amputated base case patient were CHF 528,600 (EUR 438,500) higher than for a prosthesis. There are challenging ethical, legal and organizational issues. The committee decided not to reimburse hand transplantation for ethical reasons. The Health Technology Assessment has been shown to be a useful tool for decision-making in the context of Swiss accident insurance. LEVEL OF EVIDENCE: IV.

[Integrated care for patients with heart failure in Switzerland: a cost analysis]. / Vernetzte Betreuung bei Patienten mit Herzinsuffizienz in der Schweiz: Eine Kostenstudie.

UNLABELLED: To assess the treatment costs of patients with heart failure in an integrated care model, we evaluated a Swiss primary care disease-management programme (DMP). METHODS: We compared the direct medical costs per patient before joining the DMP (time interval 1: 365 days) with the direct medical costs per patient during attendance at the programme (time interval 2: 365 days). Possible cost savings were related to the costs of the DMP. RESULTS: In 71 patients with heart failure, the average direct medical costs decreased after attendance at the program by -2'268 CHF (95% CI: -5'922 to +1'386). The average costs of the DMP were 2'100 CHF per patient. CONCLUSION: The assessed DMP will hardly generate net savings in the first year, but may be cost neutral.

[Scientific basis of measuring instruments in public health: on the example of LEP progress in the achievements of nursing]. / Zur Wissenschaftlichkeit von Messinstrumenten im Gesundheitswesen: Am Beispiel der Methode LEP (Leistungs Entwicklung in der Pfledge)

The need for data of professional interventions in public health in general and in nursing in particular has risen sharply over the last years. When it comes to the development and the use of respective measuring instruments, their scientific foundation is normally called into question. The article deals with this problem using as an example the LEP method. The focus lies on questions of methodology and philosophy of science rather than questions concerning the sociology of organization, profession or knowledge. At first the basic problem of measurement in social sciences is outlined using the distinction of first and second order measurements. Then we introduce the construction process of LEP and show, in which way it links the two levels of measurement. In the following paragraphs questions of validity and reliability are addressed as well as the decision to use time as a yardstick. We then show that LEP is not a measuring method to test scientific hypotheses but a valid instrument constructed with the help of social sciences that instructs management decisions. As an information system it combines elements of science, practice and bureaucracy and integrates them at the same time. As a boundary object it provides the basis for a constructive dialogue between the various stakeholder groups.

A novel real-time noise reduction system for the assessment of evoked otoacoustic emissions.

A novel noise reduction method and apparatus to be used in connection with the measurement of evoked otoacoustic emissions (EOAE) are presented. The noise reduction method is based on an adaptive noise canceller and requires a noise-only reference microphone placed in the vicinity of the OAE-probe. The method was implemented in real time on a custom built digital signal processing system using an Analog Devices ADSP-2181 digital signal processor. The system interfaces seamlessly with a commercial EOAE acquisition system. Results of a series of experiments show than noise reductions of 7-8 dB can be reached.

Effect of CAPD dialysate on the release of eicosanoids and cytokines from human peritoneal macrophages.

The effect of fresh peritoneal dialysis (PD) solution and effluent on the generation of eicosanoids and cytokines by human peritoneal macrophages (PMO) was studied in vitro. PMO, isolated by density gradient separation from patients undergoing intermittent peritoneal dialysis (IPD), were incubated for 2 h with PD effluent after dwell periods of 5 to 240 min or fresh PD solution. Supplemented RPMI-1640 medium served as control. PMO were stimulated by calcium ionophore A23187 (10 M). PD solution significantly inhibited the release of prostanoids (PGE2, TXB2, 6-k-PGF1), leukotrienes (LTB4, LTC4), and cytokines (11-6, TNF) from PMO by 60 to 96% (p < 0.05). Addition of A23187 increased the generation of TXB2, LTB4, and LTC4 in PD solution adjusted to pH 7.4 to 2.7 up to 28.6 times the basal level, but was ineffective in PD fluid at pH 5.2. Incubation of PMO with PD effluent of varying dwell times resulted in a rise of all assayed mediators (p < 0.05). The release of IL-6 increased continuously from 80 +/- 10 pg/10(6) PMO (0 min dwell time) to 440 +/- 104 pg/10(6) PMO (4 h dwell time, mean +/- S.E.M.). TNF generation rose from 6.0 +/- 0.1 pg/10(6) PMO (0 min dwell time) to 162 +/- 54 pg/10(6) PMO after 5 min dwell time and remained constant with effluents of longer dwell times (15 to 240 min). Exposure of PMO to PD effluents after 240 min dwell time tended to decrease the median levels of PGE2, TXB2, and 6-k-PGF1.(ABSTRACT TRUNCATED AT 250 WORDS)

Monoclonal antibodies to interferon-gamma inhibit interleukin 2-dependent induction of growth and maturation in lectin/antigen-reactive cytolytic T lymphocyte precursors.

In this study we tested the effect of monoclonal antibodies (moAb) AN-18 to murine IFN-gamma on the generation of cytolytic T cells (CTL) from a homogeneous population of precursor cells (CTL-P). As responder cells, highly purified Lyt-2+ C57BL/6 lymph node T cells were used that had been positively selected by flow cytofluorometry on a cell sorter. Lyt-2+ cells were set up in bulk culture or in limiting dilution (LD) either with Con A or with P815 tumor cells as antigen and recombinant human interleukin 2 (rec.hIL 2) in the presence or absence of moAb AN-18 and tested for growth and development of CTL. The results show that moAb AN-18 but not the unrelated moAb AN-37 diminished or abrogated proliferative and cytolytic responses of Lyt-2+ lymphocytes to lectin and rec.hIL 2 in a dose-dependent manner. The inhibitory activity of the antibodies could be abolished by neutralizing moAb AN-18 with recombinant murine IFN-gamma (rec.mIFN-gamma) before their addition to culture. Kinetic analysis shows that the inhibitory effect of moAb AN-18 is only optimal when added at the beginning of culture or up to 48 hr after initiation. The frequencies of CTL-P responding either to Con A or to P815 tumor cells and rec.hIL 2 were reduced up to 10-fold in the presence of moAb AN-18. The inhibitory capacity of moAb AN-18 was also operative in cultures containing on the average one antigen-specific CTL-P. Together with the finding that activated CTL-P secrete IFN-gamma in response to rec.hIL 2 in a dose-dependent manner, the data suggest that endogenous IFN-gamma collaborates with exogenous IL 2 in the induction of CTL-P. The generation of CTL may therefore represent a case of autocrine growth regulation of normal lymphocytes, in which the same cell synthesizes and responds to its own factor.

Disturbance of phospholipid metabolism during the selective destruction of tumor cells induced by alkyl-lysophospholipids.

Alkyl-lysophospholipids inhibit the growth of Meth A sarcoma cells in vitro. In contrast, murine bone marrow macrophages are not sensitive to the destructive effect of these substances. Since alkyl-lysophospholipids are antimetabolites in the synthesis of 3-sn-phosphatidylcholine, tumor cell destruction can be correlated with the disturbance of this metabolism. A decreased synthesis of 3-sn-phosphatidylcholine is accompanied by an increased degradation of cellular 3-sn-phosphatidylcholine in the presence of alkyl-lysophospholipids. As a consequence, endogeneously formed lysophospholipid accumulates, although the lysophospholipase is found to be stimulated. This accumulation of endogeneous lysophospholipids might be due to the fact that a high percentage of these compounds contain an alkyl bond which cannot be split by a lysophospholipase. On the other hand, the reacylation of the formed lysophospholipids is partially blocked as the lysophosphatidylcholine acyltransferase is inhibited by the added alkyllysophospholipids. An accumulation of potentially cytotoxic lysophospholipids in tumor cells might be an additional factor in the tumor cell destruction by alkyl-lysophospholipids.