[Foetal Mortality in Singleton Foetuses at and beyond Term - An Analysis of German Perinatal Data 2004-2013]. / Fetale Mortalität bei Einlingen ab Termin - eine Analyse bundesdeutscher Perinataldaten 2004-2013.

BACKGROUND: Foetal mortality appears to increase in postmature pregnancies. There is debate on the optimal timing of induction of labour vs. watchful waiting. The literature on retrospective analyses of secondary data is inconclusive. Different approaches to calculate foetal risk exist. Recent and relevant data are needed in order to realise an appropriate discussion. MATERIAL AND METHODS: Mortality in singleton foetuses in Germany, between 2004 and 2013 was analysed in relation to gestational age. Risk for foetal death is described comparing stillbirths per 1,000 births at a particular gestational age (GA) vs. stillbirths per 1,000 ongoing pregnancies ("fetus-at-risk" model). Access to German routine perinatal data was granted. We included all stillbirths in singleton foetuses with no malformations after 36+6 weeks gestational age from 2004 until 2013. RESULTS: 5,933,117 births fulfilled our inclusion criteria. Foetal mortality per 1,000 births during that week of pregnancy is lowest between 41+0 and 41+6 days of (0.7/1,000). Mortality then increases to 2.3/1,000 in 42+0 to 42+6 GA. With the "fetus-at-risk" model, mortality is low between 37+0 and 39+6 GA, ranging from 0.2/1,000 ongoing pregnancies, increasing to 0.6/1,000 between 41+0 and 41+6, and 2.3/1,000 in the following week. For pregnancies lasting longer than 42+6 weeks, the stillbirth risk is identical at 6.3/1,000 with both calculation methods. CONCLUSION: Fetal mortality is low until 41+6 weeks of pregnancy. Interpretation of current data does not support a policy of routine IOL before this gestational age in singleton foetuses.

Effects of Lipophilic Extract of Viscum album L. and Oleanolic Acid on Migratory Activity of NIH/3T3 Fibroblasts and on HaCat Keratinocytes.

Viscum album L. lipophilic extract (VALE) contains pharmacologically active pentacyclic triterpenes that are known to exhibit immunomodulatory, antitumor, and wound healing activity. Preliminary clinical observations indicate that VALE was able to influence cutaneous wound healing in vivo. The objective of this study was to investigate wound closure related properties of VALE in vitro. As measured in a wound healing assay, VALE and its predominant triterpene oleanolic acid (OA) significantly and dose dependently promoted the migration of NIH/3T3 fibroblasts in vitro, thereby leading to an enhanced wound closure. Compared to the negative control, maximal stimulation by 26.1% and 26.2%, respectively, was attained with 10 µg/mL VALE and 1 µg/mL OA. Stimulation of proliferation in NIH/3T3 fibroblasts by VALE and OA could be excluded. At higher concentrations both substances affected proliferation and viability of NIH/3T3 fibroblasts and HaCat keratinocytes. In the toxic range of concentrations of VALE and OA, migration of NIH/3T3 fibroblasts was suppressed. The extent of the stimulatory effect on cell migration of VALE quite closely corresponded to the effect expected by the concentrations of OA contained in the crude extract VALE. These data support the casual observation that Viscum album L. lipophilic extract might modulate wound healing related processes in vivo.

[Integrative and personalized health care--requirements for a timely health-care system]. / Integrative und personalisierte gesundheitsversorgung--forderungen für ein zeitgemässes gesundheitssystem.

In medical and public debates, the concept "personalized" or "individualized" medicine (PM) is increasingly used for the orientation of medicine towards individual genetic, molecular and biological characteristics. However, this tunnel view neglects that the human "person" or "individual" encompasses more than just the molecular and biological side, and that patients increasingly call for a more holistic and more person-centred form of health care. Therefore the authors propose to extend the concept of PM in the framework of an integrative health-care concept, so that with respect to a modern and patient-centred health-care system not only the biological, but also the relevant psychological, mental, social, cultural, spiritual, and economic aspects of the human individual are accounted for in health care. The Faculty of Health of Witten/Herdecke University proposes the term "integrative and personalised health care" for such a holistic form of PM.

Effects of changes in colored light on brain and calf muscle blood concentration and oxygenation.

Color light therapy is a therapeutic method in complementary medicine. In color therapy, light of two contrasting colors is often applied in a sequential order. The aim of this study was to investigate possible physiological effects, i.e., changes in the blood volume and oxygenation in the brain and calf muscle of healthy subjects who were exposed to red and blue light in sequential order. The hypothesis was that if a subject is first exposed to blue and then red light, the effect of the red light will be enhanced due to the contrastingly different characteristics of the two colors. The same was expected for blue light, if first exposing a subject to red and then to blue light. Twelve healthy volunteers (six male, six female) were measured twice on two different days by near-infrared spectroscopy during exposure to colored light. Two sequences of colored light were applied in a controlled, randomized, crossover design: first blue, then red, and vice versa. For the brain and muscle, the results showed no significant differences in blood volume and oxygenation between the two sequences, and a high interindividual physiological variability. Thus, the hypothesis had to be rejected. Comparing these data to results from a previous study, where subjects were exposed to blue and red light without sequential color changes, shows that the results of the current study appear to be similar to those of red light exposure. This may indicate that the exposure to red light was preponderant and thus effects of blue light were outweighed.

Spiritual needs of patients with chronic pain diseases and cancer - validation of the spiritual needs questionnaire.

PURPOSE: For many patients confronted with chronic diseases, spirituality/religiosity is a relevant resource to cope. While most studies on patients' spiritual needs refer to the care of patients at the end of life, our intention was to develop an instrument to measure spiritual, existential and psychosocial need of patients with chronic diseases. METHODS: In an anonymous cross-sectional survey, we applied the Spiritual Needs Questionnaire (SpNQ version 1.2.) to 210 patients (75% women, mean age 54 +/- 12 years) with chronic pain conditions (67%), cancer (28%), other chronic conditions (5%). Patients were recruited at the Community Hospital Herdecke, the Institute for Complementary Medicine (University of Bern), and at a conference of a cancer support group in Herten. RESULTS: Factor analysis of the 19-item instrument (Cronbach's alpha +/- .93) pointed to 4 factors which explain 67% of variance: Religious Needs, Need for Inner Peace, Existentialistic Needs (Reflection / Meaning), and Actively Giving. Within the main sample of patients with chronic pain and cancer, Needs for Inner Peace had the highest scores, followed by Self competent Attention; Existentialistic Needs had low scores, while the Religious Needs scores indicate no interest. Patients with cancer had significantly higher SpNQ scores than patients with chronic pain conditions. There were just some weak associations between Actively Giving and life satisfaction (r +/- .17; p +/- .012), and negatively with the symptom score (r +/- -.29; p < .0001); Need for Inner Peace was weakly associated with satisfaction with treatment efficacy (r +/- .24; p < .0001). Regression analyses reveal that the underlying disease (i.e., cancer) was of outstanding relevance for the patients' spiritual needs. CONCLUSION: The preliminary results indicate that spiritual needs are conceptually different from life satisfaction, and can be interpreted as the patients' longing for spiritual well-being. Methods how health care professionals may meet their patients' spiritual needs remain to be explored.

Validation of the brief multidimensional life satisfaction scale in patients with chronic diseases.

OBJECTIVE: We intended to determine the reliability of a brief life satisfaction scale in a sample of patients with chronic diseases, and to analyze its external validity. METHODS: Reliability and factor analysis of the 8-item "Brief Multidimensional Life Satisfaction Scale" (BMLSS) were performed according to standard procedures. The test sample contained 979 individuals (mean age 54+/-11 years). Forty-two percent had cancer, 22% chronic pain conditions, 10% depressive disorders, 6% other chronic diseases, and 20% were healthy. RESULTS: Reliability analysis of the 8-item pool revealed a good internal consistency coefficient (Cronbach's alpha=.869), and a single-factor structure which explains 53% of variance. The BMLSS sum scores significantly differed with respect to the underlying disease, family status, duration of disease, and age. The highest scores were found in healthy individuals, and the lowest in patients with chronic pain conditions and depressive disorders. In cancer patients, the BMLSS correlated negatively with Depression/Anxiety (HADS), Fatigue (CFS-D), and positively with SF-12's mental health and to a weaker content also with physical health. Stepwise regression analyses revealed that life satisfaction can be predicted best by (the absence of) depression, but also by Conscious Living (AKU), which is an active cognitive-behavioral style in terms of adaptive coping. CONCLUSIONS: The evaluation of the BMLSS revealed that the instrument has good psychometric properties and can be regarded as a brief, reliable and valid measure of LS in patients with chronic diseases. The instrument can be an important additive to existing health-related quality of life questionnaires, since it captures dimensions that contribute to quality of life but are not health related.

Growth stimulation of dwarf peas (Pisum sativum L.) through homeopathic potencies of plant growth substances.

BACKGROUND: Efficacy of higher homeopathic potencies is controversial. Universally accepted specific detection assays for homeopathic dilutions do not exist. Basic research has to develop a spectrum of standardized tools to investigate the mode of action and nature of homeopathic potencies. OBJECTIVE: Can the shoot growth reaction of dwarf peas (gibberellin- deficient mutants) be regarded as evidence of treatment with homeopathic potencies of plant growth substances? MATERIALS AND METHODS: Pea seed (Pisum sativum L. cv. Fruher Zwerg) is immersed for 24 hours in homeopathic potency or control solutions for soaking. Plants germinate and grow in a standard cultivation substrate under controlled environmental conditions. Shoot length is measured 14 days after planting. RESULTS: A screening of homeopathic potencies (12x-30x) of four different plant growth substances revealed biological activity of certain potency levels of gibberellin and kinetin (p < 0.05). Growth stimulation through gibberellin 17x (5 x 10(-18 M)) was assessed in six independent replications; results confirmed those of the screening (p < 0.05). The effect of gibberellin 17x seemed to weaken during the course of the experiments. CONCLUSION: The results back the hypothesis that homeopathic potencies of plant growth substances affect pea shoot growth. Dwarf peas might thus be an interesting system model for studying the action of homeopathic potencies. Further work is required to identify all boundary conditions modulating the reactivity of this system.

Socio-demographic and medical characteristics of advanced cancer patients using conventional or complementary medicine.

BACKGROUND: To provide prospective comparative data describing the profiles of two patient populations attending conventional or complementary medicine institutions. PATIENTS AND METHODS: A registration study was set up in an oncology ward at the Institute for Medical Oncology (IMO) of the University Hospital in Bern, and at the Lukas Clinic (LC) for Anthroposophical Cancer Treatment in Arlesheim, Switzerland. The same eligibility criteria were applied to enrol into the study all newly referred or newly diagnosed patients with advanced cancer over a 2-year period. Their socio- demographic and clinical characteristics at presentation have been compared between the two institutions. RESULTS: Patients at LC are primarily females, of higher educational level, and living in an urban environment. Patients at LC are also more frequently of poorer performance status but present with less comorbidity and a longer interval between diagnosis of metastatic disease and accrual into the study. CONCLUSION: This study suggests that the respective merits of these two schools of medicine can be assessed successfully only through a concrete research partnership based on rigorously controlled clinical trials.

[Criteria for assessing benefit with complementary medical methods]. / Kriterien zur Beurteilung des Nutzens von komplementärmedizinischen Methoden.

UNLABELLED: Criteria for Assessing Benefit with Complementary Medical Methods BACKGROUND: The paper was produced by the author at the request of the Swiss Federal Social Insurance Department in a broad-based consensus process involving the principal parties in the health system, discussed with international experts at a public workshop, and finally approved in the form it is presented here by the Services Commission of the Federal Home Office on March 12, 1998. It provides a basis for assessing the efficacy, suitability and financial viability of complementary medical methods in the context of Swiss health insurance legislation. CONTENTS: Evidence-based complementary medicine cannot rest entirely on experimental trials but needs all available methods of obtaining evidence to arrive at a fair assessment, from the empirical judgement of individual medical practitioners to randomized double blind trials. In addition to experimental trials, special emphasis lies on test methods involving no experimental change in the medical intervention and the conditions pertaining to it. In so far as the experimental design on which randomized double blind trials are based takes no account of factors that are integral to holistic and individualized complementary medical treatment (e.g., the individual aspect of the doctor-patient relationship, and motivation), other evaluation concepts are needed that will do justice to these methods, such as evaluation of the overall clinical situation.The same applies when it is a matter not only of the efficacy of a method within the closely defined framework of experimental trials but also of its effectiveness in a wider context in practice and the context-related situation in the target population for the social security system (real world effectiveness). It is important for evaluation to be not primarily design-orientated but problem-orientated, with the design developed accordingly.

Experiences in the realisation of a research project on anthroposophical medicine in patients with advanced cancer.

QUESTIONS UNDER STUDY: To date most of the published studies on the effectiveness of complementary therapies in cancer patients have yielded controversial results because of questionable methodology. Research strategies and methodologies acceptable to both conventional and unconventional medicine are difficult to find due to different belief systems. In this publication we describe the development and implementation of a project conducted as part of National Research Programme 34 (NFP 34). Detailed analysis of our experiences might provide some information on how to deal with practical difficulties in the planning and conduct of further research projects in this field. The project involved the anthroposophical Lukas Clinic in Arlesheim and the Institute of Medical Oncology of the University Hospital, Berne. This interdisciplinary research project was devised to study the relative merits of these two schools of medicine in the care of advanced cancer patients. The project was made up of three components: (1) a registration study aimed at comparing the case mix at the two institutions; (2) a three armed randomised study on the effectiveness of supportive therapy, comparing anthroposophy to psychosocial group therapy, and (3) a longitudinal study to monitor the evaluation of quality of life of patients at the anthroposophical clinic. METHODS: After a brief review of the study protocol, which presents the theoretical framework of the project, problems of its implementation are described. Aspects of accrual, acceptance of randomisation and data availability are presented using simple descriptive statistics and logistic regression. RESULTS: The registration study was duly completed with a total of 567 patients. For several reasons (not meeting inclusion requirements, high refusal rate) the accrual into the randomised study was slower than expected and required modification of the original design specifications with regard to inclusion criteria and data collection schedule. Additionally, a high dropout rate contributed to premature closure of this part of the project. The longitudinal study also suffered from low data availability at follow up. CONCLUSIONS: The study protocol constituted a major effort at compromise without loss of scientific rigour, and this effort demonstrates that it is possible to allow for different views on patients, on clinical interventions and on research strategies when establishing collaboration between different schools of medicine. Despite a theoretically sound framework, the randomised part of the project proved difficult in its practical execution. Some unexpected logistical constraints and some unmet expectations influenced the feasibility of this part of the project. Therefore, careful planning of research projects in this field of medicine should always include an extended analysis of various practical aspects of study implementation.

Commentary on Sommer et al. 'A randomized experiment of the effects of including alternative medicine in the mandatory benefit package of health insurance.

The study by Sommer et al. recently reported in Complementary Therapies in Medicine has been heavily criticised in Switzerland since its original publication. Its major problems are an inadequate reflection of real practice, an inadequate study design relative to the central research objective, questionable value of the applied instrument and procedure for health assessment, methodological and statistical problems, and failure to consider literature relevant to the topic. For these reasons, this experimental study does not allow an answer to its central questions as to costs and effectiveness of complementary medicine made available within Switzerland's mandatory basic health insurance provisions. We propose more practice-related, non-experimental prospective study designs to realistically answer these questions.

Immunomodulatory and clinical effects of Viscum album (Iscador M and Iscador P) in children with recurrent respiratory infections as a result of the Chernobyl nuclear accident.

Ninety-two children 5 to 14 years of age living in areas exposed to the radioactive fallout from Chernobyl with recurrent respiratory infections (RRIs) were treated after randomization with either Viscum album praeparatum mali or pini (Iscador M or P). The dosage was two subcutaneous injections a week for 5 weeks with individual doses of 0.001 mg to 1.0 mg. Both Viscum album preparations were effective in significantly reducing clinical symptoms. One year after a single treatment course, the frequency of RRI relapses decreased by 78% and 73%, respectively. Immunomodulatory effects were assessed by investigation of lymphocyte subsets, natural killer (NK) cell activity, phagocytic and oxidative activity of polymorphonuclear leukocytes, and antiviral activity of serum before and 1 week after treatment. Viscum album therapy resulted in normalization of initial immune indices either below or above the normal ranges. High levels of antiviral activity before treatment were significantly decreased by Viscum album mali. Viscum album treatment should be studied further in children with RRI.

Attitudes and Beliefs towards Disease and Treatment in Patients with Advanced Cancer Using Anthroposophical Medicine.

BACKGROUND: In Switzerland, anthroposophical medicine has a long tradition, offers a special tumor treatment, is frequently used by cancer patients, and has been approved in 1998 by the Swiss government to be reimbursed by health insurances. This popularity contrasts with the fact that to date no sound evidence of the effectiveness of anthroposophical cancer treatments exists. In this study we draw a profile on a population of patients with advanced disease attending treatment at the anthroposophical Lukas Clinic (LC) regarding patients' attitudes, experiences and expectations. PATIENTS AND METHODS: All newly admitted patients with a diagnosis of locally advanced or metastasized breast, gastrointestinal, lung or gynecological cancer were recruited into a registration study. In parallel, a population of patients with the same inclusion criteria attending a conventional institution (Institute of Medical Oncology, University of Bern, IMO) was taken as a reference sample. Data were collected by means of a fully structured interview, and simple descriptive statistics was used for evaluation. RESULTS: 221 and 280 patients accrued at LC and at IMO, respectively. LC patients were mainly women (87%), had a good education (36% with completed college or university education), and were admitted on average 3.5 months after the diagnosis of advanced disease. With respect to their advanced cancer, they put very little hope in the effectiveness of conventional medicine, but expected great help from anthroposophical treatment. Compared with the reference population they cared more for psychological well-being and quality of life, but an important factor for choosing treatment at the LC was clearly the patients' strong belief in the effectiveness of anthroposophical treatment. CONCLUSIONS: With its holistic approach, anthroposophical medicine intends to provide tumor treatment together with supportive care throughout the course of the illness. To some patients this is an attractive alternative to conventional medicine, which too often focuses on tumor treatment only. Conventional medicine should clearly be advised to give higher priority to supportive care already early in the course of the disease. We acknowledge some patients' need for a more holistic approach, but anthroposophical medicine or any other providers of alternative or complementary cancer therapies should evaluate treatment effectiveness more thoroughly according to the principles of evidence-based medicine. Copyright 2000 S. Karger GmbH, Freiburg

[Problems of study designs with randomization, blinding and placebos]. / Probleme von studiendesigns mit randomisation, verblindung und placebogabe.

As randomised double-blind trials are not rarely demanded as a prerequisite for the scientific acceptance of complementary medicine, the author has analysed the soundness of this demand on the basis of the international literature. As a result there appeared a number of methodological, practical and ethical problems which question the theoretically deduced primal value of this study design relative to the needs of medical practice and of health insurance issues. The experimental instruments of randomisation, blinding and placebo deliberately exclude essential therapeutic factors which are integral elements of complementary medical concepts; therefore, it is suggested to supplement quantitatively and collectively oriented experimental research by non-experimental procedures, which adequately reflect the context- and practice-related individual reality.

[Quality of life of patients with metastatic breast or intestinal cancer, treated with anthroposophic medicine or with mainstream medicine, the latter with or without psycho-oncologic or supplementary anthroposophic therapy]. / Untersuchungen der Lebensqualität von Patienten mit metastasierendem Brust- oder Darmkrebs, behandelt in der anthroposophischen Medizin oder in der Schulmedizin, letztere mit oder ohne psychoonkologische oder anthroposophische Zusatztherapie.

This project dealt with two subjects. On the one hand, the measurement of the quality of life of cancer patients which needed to be further refined in order to assess the usefulness and efficacy of a treatment by complementary medicine. On the other hand, it was important to know whether severely ill cancer patients treated in an anthroposophical clinic would differ from equally ill patients in a university hospital in terms of attitude towards their illness and in terms of clinical diagnosis. Finally, an attempt was made to demonstrate an improvement of quality of life in conventionally treated patients of the university hospital, who were offered an additional treatment either with a supportive-expressive group therapy or with an anthroposophical therapy. More than 500 patients participated in the study. There were marked sociodemographic and medical differences between the patients of the anthroposophical clinic and those of the university hospital. In addition, it seems that spiritually oriented and active, problem-oriented coping contribute a lot to the quality of life. It was not possible to truly compare the value of the two additional therapies offered to the patients at the university hospital because patient accrual was much slower than anticipated and many patients left the study too early for health reasons or death.

The cognitive-spiritual dimension--an important addition to the assessment of quality of life: validation of a questionnaire (SELT-M) in patients with advanced cancer.

UNLABELLED: Questions of meaning and challenge by illness, i.e., the spiritual dimension of quality of life (QL) traditionally played an important role in anthroposophically oriented medicine and have gained importance in palliative medicine and supportive care. In the context of a research project on QL in patients with advanced cancer, we therefore investigated the psychometric properties of a questionnaire covering spiritual QL issues, with the aim of providing a module for the assessment of cognitive-spiritual QL. PATIENTS AND METHODS: We investigated 89 patients with advanced breast and gastro-intestinal cancer. Construct validity of a modified version of the SELT (Skalen zur Erfassung von Lebensqualität bei Tumorkranken), the SELT-M was tested by multitrait scaling analysis. Discriminant and convergent validity were also tested. The EORTC QLQ-C30 was used as a standard for validation. Results showed the SELT-M as feasible in administration. Four of the five SELT-M subscales were internally consistent (Cronbach's Alpha = > 0.7). The subscale on spiritual QL showed higher within than outside subscale correlations for six of its eight items. Association of the SELT-M with the EORTC QLQ-C30 was good for the items and subscales covering the same aspects of QL in both questionnaires: emotional (Spearman r = 0.61), physical functioning (r = -0.54) and fatigue (r = -0.75). In accordance with expectations, there was no association between spiritual QL with any EORTC QLQ-C30 subscales. Self-assessed spiritual QL in the SELT-M corresponded well with interviewer assessments (test for trend accross ordered groups, P = 0.0023). CONCLUSIONS: Overall there is confirming evidence for the hypothesised structure of the SELT-M, especially for the newly developed module on spiritual QL. This module may be used as a module together with other cancer specific QL questionnaires.