Immunological differences between insect venom-allergic patients with and without immunotherapy and asymptomatically sensitized subjects.

BACKGROUND: Currently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy (VIT) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings. METHODS: We included 77 asymptomatically sensitized subjects, 85 allergic patients with acute systemic sting reactions, and 61 allergic patients currently treated with VIT. Levels of sIgE and sIgG4 to bee and vespid venom, rApi m 1, and rVes v 5 were measured immediately after allergic sting reactions or before sting challenges and 4 weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT inhibition and ELIFAB assay. RESULTS: Median sIgG4 levels were 96-fold higher in VIT patients (P < .001) while sIgE/sIgG4 ratios were consistently lower (P < .001). The ELIFAB assay was paralleled by low sIgE/sIgG4 ratios in VIT patients, showing markedly higher allergen-blocking capacity (P < .001). An almost complete inhibition of the basophil response was seen in all patients treated with vespid venom, but not in those treated with bee venom. Four weeks after the sting, sIgE and sIgG4 levels were increased in allergic and asymptomatically sensitized patients, but not in VIT patients. CONCLUSION: Immunological responses after stings varied in bee and vespid venom-allergic patients. In patients under VIT, sIgE and sIgG4 remained completely stable after sting challenges. Monitoring VIT efficacy was only possible in vespid venom allergy, and the sIgG4 threshold for rVes v 5 had the highest sensitivity to confirm tolerance. The BAT inhibition test was the most reliable tool to confirm tolerance on an individual basis.

Requirements for the implementation of open door policies in acute psychiatry from a mental health professionals' and patients' view: a qualitative interview study.

BACKGROUND: Treating legally committed patients on open, instead of locked wards is controversially discussed and the affected stakeholders (patients, mental health professionals) have ambiguous views on the benefits and disadvantages. The study aims to assess the opinions and values of relevant stakeholders with regard to the requirements for implementing open wards in psychiatric hospitals. METHODS: Semi-structured interviews were conducted with 15 psychiatrists, 15 psychiatric nurses and 15 patients, and were analyzed using qualitative content analysis. RESULTS: The interviewees identified conceptual, personnel and spatial requirements necessary for an open door policy. Observation and door watch concepts are judged to be essential for open wards, and patients appreciate the therapeutic value they hold. However, nurses find the door watch problematic. All groups suggest seclusion or small locked divisions as a possible way of handling agitated patients. All stakeholders agree that such concepts can only succeed if sufficient, qualified staff is available. They also agree that freedom of movement is a key element in the management of acutely ill patients, which can be achieved with an open door policy. Finally, the interviewees suggested removing the door from direct view to prevent absconding. CONCLUSIONS: For psychiatric institutions seeking to implement (partially) open wards, the present results may have high practical relevance. The stakeholders' suggestions also illustrate that fundamental clinical changes depend on resource investments which - at least at a certain point - might not be feasible for individual psychiatric institutions but presumably require initiatives on the level of mental health care providers or policy makers.

Treatment recommendations within the leeway of clinical guidelines: A qualitative interview study on oncologists' clinical deliberation.

BACKGROUND: Recommending the optimal treatment for an individual patient requires a well-balanced consideration of various medical, social and ethical factors. The interplay of these factors, interpretation of the patient's situation and understanding of the existing clinical guidelines can lead to divergent therapy recommendations, depending on the attending physician. Gaining a better understanding of the individual process of medical decision-making and the differences occurring will support the delivery of optimal individualized care within the clinical setting. METHODS: A case vignette of a 64-year-old patient with locally advanced pancreatic adenocarcinoma was discussed with oncologists in 14 qualitative, semi-structured interviews at two academic institutions. Relevant factors that emerged were ranked by the participants using the Q card sorting method. Qualitative data analysis and descriptive statistics were performed. RESULTS: Oncologists recommend different therapeutic approaches within the leeway of the relevant clinical guidelines. One group of participants endorses a rather aggressive and potentially curative approach with a combination chemotherapy following the FOLFIRINOX protocol to provide the patient with the best chances of resectability. The second group suggests a milder chemotherapy approach with gemcitabine, highlighting the palliative approach and the patient's quality of life. Clinical guidelines are generally seen as an important point of reference, but are complicated to apply in highly individual cases. CONCLUSION: The physician's individual assessment of factors, such as biological age, general condition or prognosis, plays a decisive role in treatment recommendations, particularly in those cases which are not fully covered by guidelines. Judgment and discretion remain crucial in clinical decision-making and cannot and should not be fully ruled out by evidence-based guidelines. Therefore, a more comprehensive reflection on the interaction between evidence-based medicine and the physician's estimation of each individual case is desirable. Knowledge of existing barriers can enhance the implementation of guidelines, for example, through medical education.

[Rationing in German health care with particular consideration of oncology: view points of German stakeholders--a qualitative interview study]. / Rationierung im deutschen Gesundheitswesen unter besonderer Berücksichtigung der Onkologie: Sichtweisen deutscher Entscheidungsträger--eine qualitativen Interviewstudie.

AIM: Germany is at the beginning of a discussion about possible rationing in the health-care system. Cancer treatment, which is often cost-intensive but not always cost-effective, is frequently considered as a field for rationing. METHODS: Against this background, we conducted semi-structured, guideline-based interviews with different stakeholders of the German health-care system and analysed them with the help of grounded theory techniques. The goal of the study was to collect the experiences and opinions of members of the German Medical Review Board of the Statutory Health Insurance Funds (MDK), leading officials in central administrations of the German health-care sector and health politicians (members of the Parliamentary Committee for Health of the Federal German Parliament, the Bundestag) regarding cost-considerations in treatment decisions in health care with a special focus on oncology. RESULTS: (1) Cost-considerations have a limited role in the daily routine of the interviewed experts; (2) the interviewed personnel of the MDK were open to discuss rationing, while the group of leading officials was ambivalent and the health politicians rejected rationing and its discussion altogether; (3) the awareness of the opportunity costs of medical services varied with the profession of the interviewee: the members of the MDK saw opportunity costs primarily within the field of medicine, the leading officials noted the opportunity costs for other social services, and the health policy makers interpreted opportunity costs under fiscal budgetary aspects; (4) according to the interviewees, decisions on rationing require a legal basis, which should be based on a broad public discussion and an interdisciplinary debate among experts; (5) defining criteria for rationing was regarded as being outside of the professional competence of the interviewees; however, a preference with regard to the criterion of cost-effectiveness became apparent. CONCLUSIONS: The results of this study indicate that the strongest opposition to a debate on rationing in Germany does not stem from the medical, but rather from the political sector. The criteria for rationing suggested in the theoretical debate are in need of a context-sensitive examination and specification for the field of oncology. A possible approach to constructively promote the debate on rationing is a stronger focus on social opportunity costs of health care. The exact role of experts in a discourse on rationing, which was emphasised by the interviewees, requires a thorough determination. It is necessary to differentiate between the roles of impartial experts and stakeholders. Decisions on rationing can ultimately only be legitimised politically by parliament.

[Compulsory treatment in psychiatry: an ethical analysis of the new legal regulations for clinical practice]. / Zwangsbehandlungen in der Psychiatrie : Eine ethische Analyse der neuen Rechtslage für die klinische Praxis.

BACKGROUND: The new legal regulations of compulsory treatment in Germany require a change in clinical psychiatric practice as well as an ethical analysis of the consequences for those involved. MATERIALS AND METHODS: The new legal regulations are reported and via ethical analysis new problematic fields, such as consequences of the new law are identified and discussed in the context of psychiatry and law. RESULTS: The main ethical identified problems are care of mentally ill with mental competence who refuse medical treatment, the different normative assessment of compulsory treatment and mechanical fixation, the ambivalent role of the conversation between psychiatrist and patient in order to change the natural will of the patient to avoid compulsory measures, the ethical consequences of questionable financial incentives in the context of compulsory treatment and the contradictive legal regulations in the field. CONCLUSIONS: The ethical analysis of the new law on compulsory treatment in Germany shows chances for improvement of clinical psychiatric practice as well as normative problematic regulations and fields of conflicts.

[The new financial compensation system PEPP: an ethical analysis]. / Das neue pauschalierende Entgeltsystem PEPP : Eine ethische Analyse.

BACKGROUND: The new compensation system for psychiatric and psychosomatic institutions (German acronym: PEPP) not only constitutes a change in billing practices, but also necessitates an ethical investigation and analysis of possible consequences of the new legislation for those affected in practice. MATERIAL AND METHODS: Following the presentation of the new PEPP and its consequences for psychiatric practice, problems and areas of conflict will be analyzed from an ethical perspective and discussed. RESULTS: Ethical conflicts exist in the following areas: (1) in the attempt to standardize inpatient care and invoicing for mental illnesses, (2) in poorer treatment for severely ill patients in view of degressive per diem rates, (3) in false incentives due to threshold values e.g. for 1:1 health professional-patient ratios in the case of coercive measures and (4) due to the inappropriate use of a supposed normative neutral quantitative economic model for a qualitative work area that often takes place in human border zones such as complex inpatient care of severely mentally ill patients. CONCLUSION: The ethical analysis of PEPP reveals that apart from the limited opportunities to improve efficiency, there is a considerable ethical risk of loss of quality in psychiatric inpatient care in particular for severely and chronically mentally ill patients.

'One also needs a bit of trust in the doctor ... ': a qualitative interview study with pancreatic cancer patients about their perceptions and views on information and treatment decision-making.

BACKGROUND: Information about diagnosis, treatment options and prognosis has been emphasized as a key to empower cancer patients to make treatment decisions reflecting their values. However, surveys indicate that patients' preferences regarding information and treatment decision-making differ. In this qualitative interview study, we explored pancreatic cancer patients' perceptions and preferences on information and treatment decision-making. PATIENTS AND METHODS: Qualitative in-depth interviews with patients with pancreatic cancer. Purposive sampling and qualitative analysis were carried out. RESULTS: We identified two stages of information and treatment decision-making. Patients initially emphasize trust in their physician and indicate rather limited interest in details about surgical and medical treatment. In the latter stage of disease, patients perceive themselves more active regarding information seeking and treatment decision-making. All patients discuss their poor prognosis. Reflecting on their own situation, all patients interviewed pointed out that hope was an important driver to undergo further treatment also in advanced stages of the disease. Interviewees unanimously emphasized the difficulty of anticipating the time at which stopping cancer treatment would be the right decision. CONCLUSIONS: The findings can serve as starting point for reflection on professional decision-making in pancreatic cancer and larger representative surveys on ethical issues in treatment decision-making in pancreatic cancer.

[Advance directives in patients with mental disorders. Scope, prerequisites for validity, and clinical implementation]. / Patientenverfügungen von Menschen mit psychischen Störungen. Gültigkeit, Reichweite, Wirksamkeitsvoraussetzung und klinische Umsetzung.

Since 1 September 2009, advance directives are regulated by law in Germany. This article discusses ethical challenges of advance directives in patients with mental disorders. Besides concrete information on the preferred medical treatment in concrete clinical situations, the mental capacity of the patient at the time of issuing the directive is essential. The "Decisional Competence Assessment Tool for Psychiatric Advance Directives" and empirical studies from the USA on advance directives in patients with mental disorders and the assessment by the treating psychiatrists of these patient directives are discussed. Ethical conclusions are drawn for handling advance directives in psychiatric practice.

Information provision and decision-making in assisted reproduction treatment: results from a survey in Germany.

BACKGROUND: The objective of this study was to investigate the views of patients and experts in Germany on information provision and decision-making in assisted reproduction treatment (ART). METHODS: Standard questionnaire techniques were used for interviewing Reproductive Physicians (n= 230), Psychosocial Counsellors (n = 66) and Patients (n = 1590). Descriptive data analyses and non-parametric tests for significance were performed. RESULTS: Higher scores were assigned for information on the chances for treatment success and on direct, physical risks of fertility treatment than for information on the risks and burden of multiple pregnancies and on the emotional risks and burden associated with infertility treatment. Three-quarters (74%) of the Patients (P) reported that they had experienced an overwhelming desire for a child at some point during their treatment, and half (47%) stated that they had experienced the feeling of losing control over the situation. According to 25% of the Reproductive Physicians (RP) and 47% of the Psychosocial Counsellors (PC), patients are often or very often limited in their capacity to decide when to stop the treatment. CONCLUSIONS: A significant number of patients in reproductive care in Germany are not well informed on all the aspects that are relevant for treatment decision-making, are overwhelmed by their desire for a child, lose control over the situation, and are limited in their capacity to end unsuccessful treatment. Information provision should be ensured and monitored during treatment by standardized safeguards. A strategy for stopping ART and embarking on alternative ways of coping with infertility should be installed from the outset of every treatment.

Who should pay for assisted reproductive techniques? Answers from patients, professionals and the general public in Germany.

BACKGROUND: Financing ART is variously regulated in the different countries of Europe. In Germany, coverage of assisted reproduction by statutory health insurances was restricted to 50% in 2004. We conducted a national survey among patients, professionals (physicians and other academics in IVF centres, psychosocial counsellors, medical ethicists, social lawyers, health politicians) and the general public in Germany regarding their opinions on financing ART. METHODS: Standard questionnaire techniques (paper and pencil interviewing, computer-aided web interviewing, computer-aided telephone interviewing) were used. RESULTS: The vast majority of all groups supported public coverage of ART. Co-payments by patients were considered appropriate by about one-third of the patients, two-third of the physicians and three quarters of all other groups. According to the respondents, the amount of co-payment should cover 15-25% of the costs, considerably less than what patients actually have to pay (50%). Support for public coverage was strongly correlated with the views (i) of infertility as a disease, (ii) that there is a need for assisted reproduction for infertile couples and (iii) that every human should have the opportunity to have children. The respondents had varying opinions on whether to increase medical insurance premiums in order to cover ART. Reducing services in other areas of health care in favour of reproductive medicine was supported only by the group of reproductive physicians. Financial incentives for oocyte sharing were rejected by most groups as was a money-back guarantee for unsuccessful treatments. CONCLUSIONS: Experts and the general public in Germany accept moderate co-payments for ART. No clear pattern of opinion emerged regarding the question of how public co-funding should be financed.

Under which conditions are changes in the treatment of people under involuntary commitment justified during the COVID-19 pandemic? An ethical evaluation of current developments in Germany.

The COVID-19 pandemic poses significant challenges in psychiatric hospitals, particularly in the context of the treatment of people under involuntary commitment. The question arises at various points in the procedure for and process of involuntary commitment whether procedural modifications or further restrictive measures are necessary to minimise the spread of COVID-19 and protect all people involved from infection. In the light of current developments in Germany, this article examines under which conditions changes in the treatment of people under involuntary commitment are ethically justified in view of the COVID-19 pandemic. Among others, we discuss ethical arguments for and against involuntary commitments with reference to COVID-19, the use of different coercive interventions, the introduction of video hearings, an increased use of video surveillance and interventions based on the German Infection Protection Act. We argue that strict hygiene concepts, the provision of sufficient personal protective equipment and frequent testing for COVID-19 should be the central strategies to ensure the best possible protection against infection. Any further restrictions of the liberty of people under involuntary commitment require a sound ethical justification based on the criteria of suitability, necessity and proportionality. A strict compliance with these criteria and the continued oversight by external and independent control mechanisms are important to prevent ethically unjustified restrictions and discrimination against people with the diagnosis of a mental disorder during the COVID-19 pandemic.

Ethical opinions and personal attitudes of young adults conceived by in vitro fertilisation.

BACKGROUND: Today in vitro fertilisation (IVF) is a widespread and important technique of reproductive medicine. When the technique was first used, it was considered ethically controversial. This is the first study conducted of adult IVF-offspring in order to learn about their ethical opinions and personal attitudes towards this medical technology. METHODS: We recruited the participants from the first cases of in vitro fertilisation in Germany at the Gynaecological Clinic of the University Hospital Erlangen. Our qualitative interview study consisted of in-depth, face-to-face interviews with 16 adults who had been conceived by IVF. Our data was analysed with methods of Grounded Theory. RESULTS: For these adults, the most important factor influencing their personal attitudes towards IVF was the knowledge that they were deeply wanted children. The artificiality of their conception seemed irrelevant for their ethical opinion. All participants mentioned that it was important for them to be informed about the circumstances of their conception by their parents. CONCLUSIONS: IVF seems to be a medical technique which, although it affects intimate aspects of human existence, can be integrated into the lives of the affected persons without any great difficulties. The findings suggest that parents should inform their children about their fertilisation at an early age and as part of a process over time, not only on a single occasion. Physicians should advise IVF-parents accordingly.

Information and participation in decision-making about treatment: a qualitative study of the perceptions and preferences of patients with rheumatoid arthritis.

OBJECTIVES: To elicit the perceptions and preferences of patients with rheumatoid arthritis regarding information and participation in treatment decision-making. To analyse the patients' narratives on the background of the ethical discourse on various approaches to treatment decision-making. DESIGN: In-depth interviews with themes identified using principles of grounded theory. PARTICIPANTS: 22 patients with long-standing rheumatoid arthritis. MAIN OUTCOME MEASURES: Qualitative data on patients' perceptions and preferences regarding information and participation in decision-making about treatment. RESULTS: Decision-making about treatment has been described by the patients as a process consisting of different stages with shifting loci of control and responsibility. Patients initially received one treatment recommendation and were not aware of alternative treatment options. Those participants in this study who wanted information about negative effects of a treatment cited "interest in one's own health" and the potential "use of information" as reasons for their preference. The physicians' expert knowledge and clinical experience regarding the effects of medication were cited as arguments by patients for a treatment recommendation. CONCLUSIONS: The patients' accounts of decision-making about treatment differ from models of physician-patient relationship that have been put forward in ethical discourse. These differences may be relevant with respect to the starting point of an ethical analysis of treatment decision-making. Patients' accounts with respect to a lack of information on treatment alternatives point to ethically relevant challenges regarding treatment decision-making in clinical practice.

[End-of-life practices of physicians in Germany]. / Ärztliche Handlungspraxis am Lebensende.

BACKGROUND: Ethical questions at the end of life are at the centre of scientific and public debates. Up to the present there is scarcity of empirical data regarding physicians' end-of-life practices in Germany. METHODS: Cross-sectional study among a random sample of German physicians by means of the questionnaire of the EURELD Consortium with additional questions on experiences and attitudes regarding physician assisted suicide. RESULTS: 734 physicians from five state chambers of physicians responded (response rate 36.9 %). 403 physicians reported about end-of-life practices regarding adult patients. Alleviation of symptoms took place in 86.7 % of cases and in 50.7 % medical treatment had been withheld. In three cases death was the consequence of a drug which was provided or administered by respondents. 20.7 % of respondents had been requested to perform physician-assisted suicide (PAS). 41.7 % of participants could not imagine participating in PAS, whereas 40.2 % could imagine this under certain circumstances. A prohibition of PAS by professional law war rejected by 33.7 %, 25.0 % support such a ban and 41.4 % were undecided. CONCLUSION: Physicians in Germany perform a broad spectrum of end-of-life practices. The empirical findings can serve as a starting point for the reflection about an appropriate normative framework for physicians' end-of-life practices.

Sleep deprivation combined with consecutive sleep phase advance as a fast-acting therapy in depression: an open pilot trial in medicated and unmedicated patients.

OBJECTIVE: The authors' goal was to test the hypothesis that the antidepressant effect of total sleep deprivation can be maintained by initially avoiding sleep during a supposedly "critical" time period in the early morning. METHOD: They studied 33 inpatients with major depression, melancholic type, all of whom responded positively to total sleep deprivation. Twelve of the patients were men and 21 were women; their mean age was 46.7 years (SD = 13.7). After total sleep deprivation, the patients started a sleep schedule from 5:00 p.m. to 12:00 midnight, which then was shifted back by 1 hour each day until a sleep time of 11:00 p.m. to 6:00 a.m. was reached. RESULTS: Twenty (61%) of the 33 patients who responded to total sleep deprivation with an improved state of mood maintained this improvement during sleep phase advance therapy. Drug-free and medicated patients did not differ from each other. CONCLUSIONS: The rapid amelioration of mood observed with total sleep deprivation can be preserved with a succeeding phase shift of the sleep period.

Determination of the material properties of microstructures by laser based ultrasound.

In most applications of MEMS the mechanical properties of the used materials are key parameters for the perfect working of the microsystems. Measuring bulk acoustic waves excited in MEMS structures with ultra-short laser pulses is a powerful method for the accurate and non-destructive evaluation as well as for the characterization of material properties. The pump-probe laser-based acoustic method generates bulk acoustic waves in a thermo-elastic way by absorbing the pump laser pulses. The acoustic waves are partly reflected at any discontinuity of the acoustic impedance. At the surface of the specimen the reflected acoustic pulses cause changes of the optical reflection coefficient, which are measured with the probe laser pulses. Thin membranes are part of numerous microelectromechanical systems (MEMS) like sensors, activators and bulk acoustic wave (BAW) filters for example. The described non-destructive and non-contact method is the right approach for testing such thin and brittle structures like membranes. Results of measurements on freestanding aluminium-silicon nitride multi-layer membranes with total thicknesses in the order of several hundred nanometers are presented and compared with thermo-elastic models and with measurements of the supported case. The measured results are used for the determination of the moduli of the membranes.

Ultrasonic wave propagation in focussing tips with arbitrary geometries.

Pulsed laser acoustic experiments have the advantage of very high temporal resolution. However, the lateral resolution amounts to several wavelengths of light. To improve the lateral resolution a focussing tip in which the mechanical waves are focussed is introduced. The combination of high resolution in time and space domain leads to a new potential time resolved scanning probe method. Therefore several axi-symmetric structures are investigated numerically using a finite difference method. The ultrasonic wave propagation in different tips is discussed. By varying the geometry of the tip, the displacement at the sharp end is maximized. The numerically calculated results are verified experimentally on structures having macroscopic dimensions. Scaling effects are considered in order to translate the results into the microscopic scale where arbitrary geometries are much more challenging to implement.

Informed consent in human experimentation before the Nuremberg code.

The issue of ethics with respect to medical experimentation in Germany during the 1930s and 1940s was crucial at the Nuremberg trials and related trials of doctors and public health officials. Those involved in horrible crimes attempted to excuse themselves by arguing that there were no explicit rules governing medical research on human beings in Germany during the period and that research practices in Germany were not different from those in allied countries. In this context the Nuremberg code of 1947 is generally regarded as the first document to set out ethical regulations in human experimentation based on informed consent. New research, however, indicates that ethical issues of informed consent in guidelines for human experimentation were recognised as early as the nineteenth century. These guidelines shed light on the still contentious issue of when the concepts of autonomy, informed consent, and therapeutic and non-therapeutic research first emerged. This issue assumes renewed importance in the context of current attempts to assess liability and responsibility for the abuse of people in various experiments conducted since the second world war in the United States, Canada, Russia, and other nations.

[Do ethics committees hinder progress in medicine?]. / Behindern Ethikkommissionen den Fortschritt in der Medizin?

Research Ethics Committees are instruments which allow the medical profession to control the research with human subjects. In this context, some medical researchers criticize the increasing bureaucracy and the hindrance of research which interfere with the ability to compete in international research. On the other hand, the public criticizes the missing transparency, independence and democratic legitimization of Research Ethics Committees as well as the possible conflicts of interests of their members. The medical research with human subjects who are incompetent to give informed consent serves as an example to show the necessity of quality control and standardized criteria of assessment. By comparison with the development of Institutional Review Boards in the United States, ideas for the necessary changes of Research Ethics Committees in Germany regarding their work, assembly and transparency are developed.

[Advance directives in clinical practice]. / Patientenverfügungen in der klinischen Praxis.

DEFINITIONS: In the United States advance directives were developed since the late 60s in order to improve patients' medical decision making in case of incompetence in the future. In Germany 3 types of advance directives exist: 1. "Patientenverfügungen". 2. "Berreuungsverfügugen" and 3. "Vorsorgevollmachten". EMPIRICAL STUDIES: In empirical studies, mostly from the US, the implementation of advance directives into clinical practice and the attitude of physicians, patients, relatives and the general population have been examined. This review article provides results of theses studies in text and tables. CONCLUSION: Against the will of patients and of the general population advance directives are not often used in clinical practice. Physicians talk with patients about treatment procedures more often than they talk about end of life decisions. Informing patients about advance directives opens the chance to improve palliative care and respects their choices and values at the end of their lives.