[Surgery in the balance between humanity, ethics and economics]. / Chirurgie im Spannungsfeld "Humanität-Ethik-Ökonomie".

BACKGROUND: The economic pressure in the healthcare system has noticeably increased in the past few years. The manifestation of an "economization in medicine" development raises questions about the compatibility of physicians' duties and economic incentives in the healthcare system. OBJECTIVE: Against this background the article analyzes areas of conflict in the German healthcare system and surgery in particular. The main questions focus on: what lines of conflict can arise between ethical duties and economic requirements and what possibilities for conflict resolution can provide orientation on the macrolevel and microlevel? MATERIAL AND METHODS: The article is based on the analysis of normative regulations, guidelines and statements from the self-administrative institutions and multidisciplinary literature from medicine, medical ethics and health economics. Core issues in the conflict area between "humanity-ethics-economics" are structured and recommendations for action are derived. RESULTS AND DISCUSSION: Superordinate regulatory framework conditions and their subsequent incentives must not conflict with the ethical principles of medical care, especially the primary orientation to patient welfare. Institutional and individual healthcare providers have a responsibility towards patients first and only secondarily for an economically appropriate spending of public resources. The provision of medical care for people must enable an adequate livelihood. Institutional maximization of profits is to be avoided, especially concerning financial investors. In the corona pandemic, economic disincentives are becoming apparent and necessitate readjustments. Possible recommendations for action are the empowerment of the medical profession and management to engage in a qualified exchange.

Acute disseminated encephalomyelitis following Tdap vaccination and bacterial meningoencephalitis.

INTRODUCTION: Association of Acute Disseminated Encephalomyelitis (ADEM) with both recent vaccination and viral infections is well described in current literature. However, the coincidence of ADEM and bacterial infections has been rarely documented. In this report, we present a case of ADEM which occurred after bacterial meningoencephalitis and prior vaccination against tetanus, diphtheria, and pertussis (Tdap). CASE PRESENTATION: A 62-year old woman was hospitalized with an upper respiratory tract infection three weeks after Tdap triple vaccination. A few days after admission, she became somnolent and developed meningism. Cerebrospinal fluid (CSF) analysis revealed pleocytosis and increased protein/lactate levels compatible with bacterial meningoencephalitis. The patient was treated with intravenous antibacterial triple therapy in combination with dexamethasone leading to a significant improvement of clinical symptoms and improvement of CSF parameters. Five days later, the patient's condition worsened again, and she developed aphasia and right-sided hemiparesis. A magnetic resonance imaging (MRI) scan revealed distinct fluid-attenuated inversion recovery sequence (FLAIR)-hyperintense lesions in both hemispheres. Following brain biopsy, the diagnosis of ADEM was made and methylprednisolone pulse therapy was initiated for five days leading to a nearly complete remission of symptoms. CONCLUSION: ADEM is a neurological syndrome which may be associated with bacterial infection of the central nervous system (CNS). We hypothesize that the preceding Tdap triple vaccination may have contributed to the development of ADEM.

[The Trade-Off between Chance of Success and Urgency in Organ Allocation: A Discrete Choice Experiment to Elicit Public Preferences]. / Organallokation im Spannungsfeld zwischen Erfolgsaussicht und Dringlichkeit - Ein Discrete Choice Experiment zur Erhebung von Präferenzen in der Bevölkerung.

OBJECTIVE: According to the German Organ Transplantation Act, donor organs must be allocated with particular regard to chance of success and urgency. However, the objectives of these guiding criteria - the efficient use of available organs and meeting the most urgent need - are in conflict with each other, as success rate of transplantation (TX) ordinarily diminishes when urgency increases. Current allocation guidelines balance these criteria differently depending on the organ. This is only justified in part by medical reasons. Thus, further considerations are essential to develop consistent allocation rules. Therefore, a discussion on the stated trade-off considering the far-reaching consequences of such allocation decisions is indispensable. This also implies taking account of public preferences. METHODS: In this pilot study, preferences of 250 participants were assessed using a Discrete Choice Experiment. Choice-sets for the allocation of a donor organ included 2 patients, who were characterized by 3 success- and 2 urgency-based attributes. Data analysis was performed by Counting Analysis and Hierarchical Bayes estimation as well as Student's t-tests for subgroup analysis. RESULTS: All attributes influenced allocation decisions significantly (p≤0.01). Both, patients with greater chance of success and higher urgency were preferred. As a whole, chance of success and urgency were equally important for the allocation of organs (53 and 47%, respectively). The importance of the success- and urgency-based criteria was quantified as follows: The post-TX 5-year probability of survival was weighted with 31%, the expected post-TX quality of life and the surgery survival rate with 11% each, the pre-TX 3-month mortality with 35% and the pre-TX quality of life with 12%. Subgroup analysis revealed significant differences. CONCLUSION: The pilot study was successful in analyzing the balance of the guiding criteria chance of success and urgency without referring to a specific kind of organ. This type of results allows comparing current allocation rules and public preferences. These results could help decision makers to take into account public preferences developing organ-specific guidelines. A stronger involvement of citizens in decision making could gain confidence in transplantation medicine, increase the willingness to donate and potentially counteract the scarcity of organs and thereby the tragedy of the distributional conflict. Therefore the continuation of this project is advisable.

[The quality of the German health-care system in an international comparison - a systematic review]. / Die Qualität des deutschen Gesundheitswesens im internationalen Vergleich - Ein systematischer Review.

OBJECTIVES: Studies assessing the quality of the German health-care system in an international comparison come to different results. Therefore, this review aims to investigate how the German health-care system is evaluated in comparison to other health-care systems by reviewing international publications. Results show starting points for ways to improve the German health-care system, to maintain and expand its strengths as well as to derive strategies for solving identified problems. METHODS: A systematic review searching different databases [library catalogues, WorldCat (including MEDLINE and OAIster-search), German National Library, Google Scholar and others]. Search requests were addressed to English or German language publications for the time period 2000-2010 (an informal search was conducted in October 2011 for an update). Results of the identified studies were aggregated and main statements derived. RESULTS: In total, 13 publications assessing the German health-care system in an international comparison were identified. These comparisons are based on 377 measures. After aggregation, 244 substantially different indicators remained, which were dedicated to 14 categories. It became apparent that the German health-care system can be characterised by a high level of expenses, a well-developed health-care infrastructure as well as a high availability of personal and material resources. Outcome measures demonstrate heterogeneous results. It can be stated that, particularly in this field, there is potential for further improvement. The utilisation of health-care services is high, the access is mostly not regulated and out of pocket payments can pose a barrier for patients. Waiting times are not regarded as a major weakness. Although civic satisfaction seems to be acceptable, a large portion of the citizens calls for elementary modifications. Especially, more patient-centred health-care delivery should be addressed as well as management of information and the adoption of meaningful electronic assistance systems. CONCLUSION: The presented results show starting points on the way to further improve the German health-care system. It is necessary to maintain and expand its strengths as well as to derive strategies for solving identified weaknesses. This can be done with confidence since, according to Donabedian, a high structural quality represents an important fundament to improve outcome and process measures.

Nitrate Acts as a Signal to Induce Organic Acid Metabolism and Repress Starch Metabolism in Tobacco.

Nia30(145) transformants with very low nitrate reductase activity provide an in vivo screen to identify processes that are regulated by nitrate. Nia30(145) resembles nitrate-limited wild-type plants with respect to growth rate and protein and amino acid content but accumulates large amounts of nitrate when it is grown on high nitrate. The transcripts for nitrate reductase (NR), nitrite reductase, cytosolic glutamine synthetase, and glutamate synthase increased; NR and nitrite reductase activity increased in leaves and roots; and glutamine synthetase activity increased in roots. The transcripts for phosphoenolpyruvate carboxylase, cytosolic pyruvate kinase, citrate synthase, and NADP-isocitrate dehydrogenase increased; phosphoenolpyruvate carboxylase activity increased; and malate, citrate, isocitrate, and [alpha]-oxoglutarate accumulated in leaves and roots. There was a decrease of the ADP-glucose pyrophosphorylase transcript and activity, and starch decreased in the leaves and roots. After adding 12 mM nitrate to nitrate-limited Nia30(145), the transcripts for NR and phosphoenolpyruvate carboxylase increased, and the transcripts for ADP-glucose pyrophosphorylase decreased within 2 and 4 hr, respectively. Starch was remobilized at almost the same rate as in wild-type plants, even though growth was not stimulated in Nia30(145). It is proposed that nitrate acts as a signal to initiate coordinated changes in carbon and nitrogen metabolism.

Tobacco mutants with a decreased number of functional nia genes compensate by modifying the diurnal regulation of transcription, post-translational modification and turnover of nitrate reductase.

Although nitrate reductase (NR. EC 1.6.6.1) is thought to control the rate of nitrate assimilation, mutants with 40-45% of wildtype (WT) NR activity (NRA) grow as fast as the WT. We have investigated how tobacco (Nicotiana tabacum L. cv. Gatersleben) mutants with one or two instead of four functional nia genes compensate. (i) The nia transcript was higher in the leaves of the mutants. However, the diurnal rhythm was retained in the mutants, with a maximum at the end of the night and a strong decline during the photoperiod. (ii) Nitrate reductase protein and NRA rose to a maximum after 3-4 h light in WT leaves, and then decreased by 50-60% during the second part of the photoperiod and the first part of the night. Leaves of mutants contained 40-60% less NR protein and NRA after 3-4 h illumination, but NR did not decrease during the photoperiod. At the end of the photoperiod the WT and the mutants contained similar levels of NR protein and NRA. (iii) Darkening led to a rapid inactivation of NR in the WT and the mutants. However, in the mutants, this inactivation was reversed after 1-3 h darkness. Calyculin A prevented this reversal. When magnesium was included in the assay to distinguish between the active and inactive forms of NR, mutants contained 50% more activity than the WT during the night. Conversion of [15N]-nitrate to organic compounds in leaves in the first 6 h of the night was 60% faster in the mutants than in the WT. (iv) Growth of WT plants in enhanced carbon dioxide prevented the decline of NRA during the second part of the photoperiod, and led to reactivation of NR in the dark. (v) Increased stability of NR in the light and reversal of dark-inactivation correlated with decreased levels of glutamine in the leaves. When glutamine was supplied to detached leaves it accelerated the breakdown of NR, and led to inactivation of NR, even in the light. (vi) Diurnal changes were also investigated in roots. In the WT, the amount of nia transcript rose to a maximum after 4 h illumination and then gradually decreased. The amplitude of the changes in transcript amount was smaller in roots than in leaves, and there were no diurnal changes in NRA. In mutants, nia transcript levels were high through the photoperiod and the first part of the night. The NRA was 50% lower during the day but rose during the night to an activity almost as high as in the WT. The rate of [15N]-nitrate assimilation in the roots of the mutants resembled that in the WT during the first 6 h of the night. (vii) Diurnal changes were also compared in Nia30(145) transformants with very low NRA, and in nitrate-deficient WT plants. Both sets of plants had similar low growth rates. Nitrate reductase did not show a diurnal rhythm in leaves or roots of Nia30(145), the leaves contained very low glutamine, and NR did not inactivate in the dark. Nitrate-deficient WT plants were watered each day with 0.2 mM nitrate. After watering, there was a small peak of nia transcript NR protein and NRA and, slightly later, a transient increase of glutamine and other amino acids in the leaves. During the night glutamine was low, and NR did not inactivate. In the roots, there was a very marked increase of nitrate, nia transcript and NRA 2-3 h after the daily watering with 0.2 mM nitrate. (viii) It is concluded that WT plants have excess capacity for nitrate assimilation. They only utilise this potential capacity for a short time each day, and then down-regulate nitrate assimilation in response, depending on the conditions, to accumulation of the products of nitrate assimilation or exhaustion of external nitrate. Genotypes with a lower capacity for nitrate assimilation compensate by increasing expression of NR and weakening the feedback regulation, to allow assimilation to continue for a longer period each day.