Integrative medicine during the intensive phase of chemotherapy in pediatric oncology in Germany: a randomized controlled trial with 5-year follow up.

BACKGROUND: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients. METHODS: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales. RESULTS: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up. DISCUSSION: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown.

Comparative analysis of resource utilization in integrative anthroposophic and all German pediatric inpatient departments.

BACKGROUND: Integrative Medicine (IM) combines conventional and complementary therapies. It aims to address biological, psychological, social, spiritual and environmental aspects of patients' health. During the past 20 years, the use and request of IM in children and adults has grown. Anthroposophic Medicine (AM) is an IM approach frequently used in children in Germany. From both public health and health economic perspectives, it is relevant to investigate whether there are differences in the resource utilization between integrative pediatric departments (IPD) and the entirety of all pediatric departments. METHODS: Standard ward documentation data from all German integrative anthroposophic pediatric departments (2005-2016; N = 29,956) is investigated and systematically compared to data of the entirety of all pediatric departments in Germany derived from the Institute for the Hospital Reimbursement System (2005-2016, N = 8,645,173). The analyses focus on: length of stay, Diagnosis Related Groups (DRG), Major Diagnosis Categories (MDC), and effective Case Mix Index (CMI). RESULTS: The length of stay in the IPD (M = 5.38 ± 7.31) was significantly shorter than the DRG defined length of stay (M = 5.8 ± 4.71; p < .001; d = - 0.07) and did not exceed or undercut the DRG covered length of stay. Compared to the entirety of all pediatric departments (M = 4.74 ± 6.23) the length of stay was significantly longer in the in the IPD (p <. 001; d = 0.12). The effective CMI in IPD and all pediatric departments were identical (M = 0.76). The frequencies of DRG and MDC differed between IPD and all pediatric departments, with higher frequencies of DRGs and MDCs associated with chronic and severe illnesses in the IPD. CONCLUSIONS: Treatment within integrative anthroposophic pediatric departments fits well in terms of the DRG defined conditions concerning length of stay, even though integrative pediatric patients has an increased length of stay of averagely 1 day, which is most likely associated to time consuming, complex integrative treatment approaches and to a certain extend to higher amount of chronic and severe diseases.

Information and Training Needs of Pediatric Oncologists in Complementary and Integrative Medicine: A Cross-Sectional Study.

More than one third of all German pediatric patients with cancer use complementary and integrative medicine (CIM). Parents want to discuss the topic of CIM with their pediatric oncologists (POs); however, POs mostly do not feel confident discussing these topics. POs report openness to receiving further information and training, but CIM training opportunities in medical education seem rare. We investigated POs' information and training needs and preference patterns regarding CIM training content with a paper-based or online survey. A total of 101 POs from Germany completed the survey. Only 11.4% agreed to being sufficiently informed of CIM. The participants stated needing further CIM information very often (8.6%), often (38.7%), or occasionally (44.1%). They considered an overview of CIM therapies and information about relaxation methods, herbal remedies, and acupuncture for cancer-related symptoms such as lack of appetite, nausea, or vomiting as most important in CIM training material, and also the topics of adverse effects and summary of evidence. Finally, POs reported on clinical situations in which a need for further information on CIM emerged. The results of our study indicate that there is a need for a structured training that offers knowledge and skills on the subject of patient counseling on CIM in pediatric oncology.

Preclinical Evaluation of Antitumoral and Cytotoxic Properties of Viscum album Fraxini Extract on Pediatric Tumor Cells.

In Europe, especially in German-speaking countries, administration of mistletoe extracts is the most common and popular complementary and alternative therapy approach reported in oncology. Mistletoe therapy is applied to children with cancer for curative and palliative therapeutic regimes with increasing frequency, but at the same time, there are only a few studies on the effectiveness of this therapy. Therefore, we have investigated the response of various pediatric cell lines (acute myeloid leukemia, Ewing's sarcoma, hepatocellular carcinoma, medulloblastoma, neuroblastoma, and osteosarcoma) to mistletoe extract, abnobaVISCUM Fraxini. Effects on cell proliferation, cell cycle distribution as well as on mitochondrial integrity and caspase-mediated apoptosis were investigated in neuroblastoma cell lines, SH-SY5Y and Kelly. Additionally, in vitro tumor cell migration and invasion were studied. In vivo effects of the mistletoe extract were investigated in a syngeneic neuroblastoma mouse model. We could show that tumor cell lines were from 5- to 640-fold more sensitive to abnobaVISCUM Fraxini treatment than non-tumorigenic fibroblasts, whereby neuroblastoma cell lines were the most sensitive. For two neuroblastoma cell lines, SH-SY5Y and Kelly, induction of caspase-9-mediated apoptosis, a decrease of mitochondrial integrity as well as attenuation of migration and invasion were observed. In vivo experiments revealed a reduction of tumor growth and a prolonged survival of tumor-bearing animals. In summary, we can state that these results provide the first preclinical data for cytotoxic activities of abnobaVISCUM Fraxini for a broad panel of pediatric tumor cell lines, in particular, neuroblastoma cells. Thus, it might be a potential remedy for the supportive treatment of neuroblastoma.

Do patients of integrative anthroposophic pediatric inpatient departments differ? Comparative analysis to all pediatric inpatients in Germany considering demographic and clinical characteristics.

BACKGROUND: Integrative medicine (IM) is a patient-centered, evidence-based, therapeutic paradigm which combines conventional and complementary approaches. The use of IM in pediatrics has increased in the past two decades and parents' demand for it is growing. An IM whole systems approach is anthroposophic medicine. Considering the growing demand for integrative approaches in children, it is relevant from a public health perspective to find out which kind of children use IM in Germany and whether they differ from the entirety of pediatric inpatients in Germany. Moreover, it would be interesting to known, whether these patients are willing to travel a longer distance to gain integrative treatment. METHODS: The present study investigates the standard ward documentation datasets of 29,956 patients of all German integrative anthroposophic pediatric inpatient wards from 2005 to 2016 and compares them systematically to collect data of the entirety of all pediatric inpatient wards in Germany. Apart from patients' age and gender, and the ICD-10 admission diagnoses, the geographical catchment area of the hospitals were analyzed. RESULTS: Sociodemographic characteristics of pediatric inpatients in the integrative anthroposophic departments (IAH) did not differ from the entirety of all pediatric inpatients. Regarding clinical characteristics, higher frequencies were found for endocrine, nutritional and metabolic diseases (IAH: 7.24% vs. 2.98%); mental, behavioral, and neurodevelopmental disorders (IAH: 9.83% vs. 3.78%) and nervous diseases (IAH: 8.82% vs. 5.16%) and lower frequencies for general pediatric diseases such as respiratory diseases (IAH: 17.06% vs. 19.83%), digestive diseases (IAH: 3.90% vs. 6.25%), and infectious and parasitic diseases (IAH: 12.88% vs. 14.82%) in comparison to the entirety of all pediatric inpatients in Germany. The IAH showed a broad catchment area, with most patients being from former, Western federal republic of Germany. Large catchment areas (> 100 km) for the IAH are merely covered by severe and chronic diseases. CONCLUSION: Pediatric inpatients of IAH do not differ from the entirety of pediatric inpatients in Germany regarding sociodemographic characteristics but show differences regarding clinical characteristics. Parents are willing to travel further distance to get specialized integrative anthroposophic medical care for children with severe and chronic diseases.

Differences of Medical Care for Acute Severe Viral Bronchiolitis in Two Urban Areas in Europe.

BACKGROUND: Acute viral bronchiolitis is a frequent disease in infancy. There is little knowledge on medical care of severely affected infants in different European countries. PATIENTS: Infants (n=146) with bronchiolitis requiring respiratory support in winter season 2015/2016 treated in either one of two regions in Central Europe: South of greater Paris region in France (group 1) and Ruhr area in Germany (group 2). METHODS: Retrospective chart review. Primary outcome parameter was duration of respiratory support. RESULTS: Infants in group 1 (n=96) were younger, suffered less frequently from neurologic disorders and had lower respiratory rates than in group 2 (n=50). CO2 levels and dyspnea score were similar. Ninety percent of infants in group 1 were treated by nasal Continuous Airway Pressure CPAP, while 80% of infants in group 2 were treated by High Flow Nasal Cannula HFNC. Duration of respiratory support was significantly shorter in group 1. Infants in group 2 received more frequently infusion therapy, more antibiotics and more inhalation therapy. DISCUSSION: Our results show better outcome for infants with viral bronchiolitis treated in France. Striking differences were the practice of respiratory support (nasal CPAP vs. HFNC) and the prescription of supportive treatments. CONCLUSION: Treatment approaches in severe acute viral bronchiolitis differ widely between a French and a German urban region.

Students with an autonomous role in hospital care - patients perceptions.

BACKGROUND: There have been calls to enhance clinical education by strengthening supported active participation (SAP) of medical students in patient care. This study examines perceived quality of care when final-year medical students are integrated in hospital ward teams with an autonomous relationship toward their patients. METHODS: We established three clinical education wards (CEWs) where final-year medical students were acting as "physician under supervision". A questionnaire-based mixed-method study of discharged patients was completed in 2009-15 using the Picker Inpatient Questionnaire complemented by specific questions on the impact of SAP. Results were compared with matched pairs of the same clinical specialty from the same hospital (CG1) and from nationwide hospitals (CG2). Patients free-text feedback about their hospital stay was qualitatively evaluated. RESULTS: Of 1136 patients surveyed, 528 (46.2%) returned the questionnaire. The CEWs were highly recommended, with good overall quality of care and patient-physician/student-interaction, all being significantly (p < 0.001) higher for the CEW group while experienced medical treatment success was similar. Patient-centeredness of students was appreciated by patients as a support to a deeper understanding of their condition and treatment. CONCLUSION: Our study indicates that SAP of final-year medical students is appreciated by patients with high overall quality of care and patient-centeredness.

Contributing factors and outcomes of treatment refusal in pediatric oncology in Germany.

BACKGROUND: In Germany, about 1,800 new cases of pediatric cancer under 15 years of age are diagnosed each year and survival rates approach 80%. Although treatment is covered by health insurance and is thus available for all patients at no cost, treatment refusal and treatment discontinuation have been observed. However, no data providing numbers and outcomes for developed countries have been published thus far. PROCEDURE: A questionnaire-based survey was performed among German pediatric oncology centers to ascertain the number of treatment refusals among pediatric patients who were diagnosed between January 2008 and December 2009 in Germany. RESULTS: Questionnaires from 70 of 73 centers were available, and of these 13 centers reported a total of 15 cases of treatment refusal or discontinuation within this 2-year period. Five of the 15 patients died, 7 of 15 were still alive, and the current status of 3 of 15 patients was unknown. Diseases were heterogeneous. Six of the 15 parents refused treatment for their children initially, 8 of 15 discontinued during the course of treatment. Five patients were treated after parental custody had been withdrawn due to the lack of compliance. All these five patients survived. Parents' reasons given for refusal or discontinuation of treatment were related to personal health beliefs and coping strategies. CONCLUSIONS: Although treatment refusal or discontinuation is rare, it is accompanied by a high mortality rate. Parents' personal health beliefs play a primary role in treatment refusal or discontinuation in Germany. This emphasizes the importance of sustaining a functioning and mutually communicative physician-parent-patient relationship.

Use of complementary and alternative medicine by pediatric oncology patients during palliative care.

PURPOSE: Although the popularity of complementary and alternative medicine (CAM) has risen in the last decade, information about its use by pediatric patients in palliative care is still scarce. The purpose of the study was to assess the frequency and types of CAM administered by parents with children suffering from cancer during the palliative phase. METHODS: All parents who lost their child due to cancer in the federal state North Rhine Westfalia/Germany were eligible for the study. The first group of eligible parents was contacted in 1999-2000 and a second group of parents in 2005-2006. Upon agreement, parents were asked to complete a semi-structured questionnaire about the frequency of CAM use and the specific treatments that had been used. The types of CAM were categorized according to the National Center for Complementary and Alternative Medicine (NCCAM). RESULTS: A total of 96 parents participated in the study (48 in each cohort). Forty-three percent of all parents in both groups reported CAM use. The results show an increase of CAM use from 38 % in the first group to 49 % in the second cohort of pediatric patients during palliative care. The most common types of CAM used in both groups were homeopathy and treatment with mistletoe preparations. CONCLUSIONS: The study provides information about usage of CAM in children suffering from cancer during the palliative phase of the disease. Further research is required to investigate benefits, potential adverse effects, and the potential efficacy of CAM in this population.

Expert consensus-based clinical recommendation for an integrative anthroposophic treatment approach to acute tonsillitis in childhood.

BACKGROUND: Medical guidelines are an important basis for qualitative and cost-effective patient care. However, there is a lack of clinical recommendations in anthroposophic medicine (AM), an integrative medicine approach frequently practised in Europe. Acute tonsillitis, which includes tonsillopharyngitis, is a common childhood disease. that is mostly caused by a viral infection. Symptomatic treatment is therefore of high importance, and AM can offer several therapy options. METHODS: 53 physicians from Germany, Spain, Netherlands, Switzerland, Austria, and Hungary with at least one year of experience in anthroposophic paediatric medicine were invited to participate in an online Delphi process. The process comprises five survey rounds starting with open-ended questions and ending with final statements, which need 75% agreement of experts to reach consensus. Expert answers were evaluated by two independent reviewers using MAXQDA and Excel. RESULTS: Response rate was between 28% and 45%. The developed recommendation included 15 subtopics. These covered clinical, diagnostic, therapeutic and psychosocial aspects of acute tonsillitis. Six subtopics achieved a high consensus (>90%) and nine subtopics achieved consensus (75-90%). CONCLUSION: The clinical recommendation for acute tonsillitis in children aims to simplify everyday patient care and provide decision-making support when considering and prescribing anthroposophic therapies. Moreover, the recommendation makes AM more transparent for physicians, parents, and maybe political stakeholders as well.

Evaluation of a guideline for supportive anthroposophic therapies for hospitalised children with acute gastroenteritis - A prospective case series study.

OBJECTIVE: Even though several German children's hospitals offer integrative, anthroposophic medical therapies in addition to the standard medical care, guidelines for these anthroposophic therapies are still rare. Therefore, we investigated the feasibility of implementing a published, consensus-based guideline for the treatment of children with acute gastroenteritis (aGE) with anthroposophic therapies in the community hospital Herdecke. DESIGN: A prospective case series of paediatric patients (≤18 years) with an aGE admitted to the department of integrative paediatrics of the community hospital Herdecke was conducted. Demographic, clinical and therapeutic data was recorded at initial presentation and at follow-up visits. Physicians were surveyed with a questionnaire to evaluate feasibility of implementing the guideline. RESULTS: Sixty-two patients (0-15 years; 22 male, 40 female) were included in the case series. All patients received some form of anthroposophic therapy. The most frequently used remedies were Geum urbanum, Nux vomica and Bolus alba comp. Treating physicians showed a high adherence to the expert-based consensus guideline in their prescribed therapies. All physicians stated that they were familiar with the guideline and used the recommendation to inform their therapy decision. Suitability for daily use and effectiveness in treating the main symptoms of aGE were highly scored by the physicians. CONCLUSION: The consensus-based guideline of anthroposophic therapies for aGE in children was successfully implemented and found to be useful for physicians in clinical practice.

Complementary and alternative medicine in the (symptomatic) treatment of acute tonsillitis in children: A systematic review.

BACKGROUND: Acute tonsillitis (including tonsillopharyngitis) in childhood is a common disease with a peak of illness in school-age. Most of these cases have a viral origin and antibiotic therapy is not indicated, therefore, effective symptomatic therapy is required. For this reason, complementary, alternative and integrative medicine therapies might be a solution. OBJECTIVE: The aim of this review is to demonstrate study status of such therapies. METHODS: The databases PubMed, Cochrane Library, OVID, CAMbase, CAM-QUEST® and Anthromedics were systematically screened for studies investigating complementary, alternative and integrative therapy approaches in paediatric cohorts. Studies were analyzed by therapy approach, study design, cohort and outcome, using the PRISMA 2020 checklist. RESULTS: The systematic literature search resulted in 321 articles. Five publications corresponded to the search criteria and were assigned to the following specific therapeutic categories: herbal medicine (3), homeopathy (1) and ayurvedic medicine (1). Clinical trials were found for the herbal compounds BNO 1030 (Impupret®) and EPs® 7630 (Umckaloabo), the homeopathic complex Tonzolyt® and the ayurvedic medicine Kanchnara-Guggulu and Pratisarana of Tankana­Madhu. Antimicrobial effects of essential oils and carvacrol as single agents as well as in combination with erythromycin were analysed in an in vitro study. CONCLUSION: Clinical studies indicate an improvement of symptoms and a good tolerability of all investigated remedies of complementary, alternative and integrative medicine in the treatment of tonsillitis in childhood. Nevertheless, quality and quantity of the studies were insufficient to make a reliable conclusion regarding effectiveness. Therefore, more clinical trials are urgently needed to achieve a meaningful result.

Pediatric oncologists' perspectives on the use of complementary medicine in pediatric cancer patients in Switzerland: A national survey-based cross-sectional study.

BACKGROUND: There is a widespread use of complementary therapies among pediatric cancer patients. Previous studies provided evidence that communication between pediatric oncologists (POs) and patients/families about the use of these therapies is often incomplete. Furthermore, nationwide studies on this topic are rare. AIMS: We assessed POs' perspectives on the use of complementary medicine (CM) in Switzerland, on the basis of an edited survey previously used in a nationwide study. METHODS AND RESULTS: A link to an online survey was sent by e-mail to each of the fifty-two eligible pediatric oncologists in all nine Swiss Pediatric Oncology Group (SPOG) centers. Eligible respondents were board-certified (Switzerland or abroad) POs currently working at a SPOG center. The survey was available for a total period of 2 months. We received 29 filled questionnaires (overall response rate: 56%). Most POs (59%) indicated that they ask more than 50% of their patients about CM use. Frequent reasons for not asking about the use of CM were i) forgetting to ask (55%), ii) lack of knowledge on the subject (31%), and iii) lack of time (24%). More than every second PO (55%) reported having a lack of knowledge on the subject. A majority of POs (66% to 76%) indicated interest in learning more about specific CM topics (cannabinoids, hypnosis and relaxation, music therapy, herbal medicine, acupuncture, meditation, and yoga). More information and specific training opportunities on the use of CM was deemed important by 76% to 97% of POs. CONCLUSION: POs working in Switzerland identify complementary therapies as an important subject. Swiss POs are willing to acquire more knowledge on CM. More training seems to be necessary in order to increase awareness about the topic, to enhance communication about complementary therapies and thus to improve patient care.

Warming up for a better fever: a randomized pilot study in pediatric oncology.

BACKGROUND: Fever in children is a major problem in pediatric oncology. Usual management leads to immediate antibiotic and antipyretic therapy, although there is consensus that antipyretic therapy should not be utilized with the sole aim of reducing body temperature. Increased body temperature during fever appears to be an effective modifier in terms of viral replication and enhanced host defense mechanisms against pathogens. Therefore, it might be beneficial to support febrile patients by applying gentle heat during the onset of fever to help the body to reach its new thermoregulatory set point. METHODS: A randomized pilot study over 6 months will be conducted in a pediatric oncology department in an academic hospital in Germany. This study is a preparation for a multicenter clinical trial with two parallel groups concerning the efficacy of heat application vs. treatment as usual. One of the inclusion criteria is body temperatures ≥ 38.0 °C in n = 24 cases of patients receiving chemotherapy aged 18 months to 17 years. The first intervention consists of gentle heat application with hot water bottles at any sign of illness and onset of fever. The aim is to achieve a warm periphery equilibrated to trunk temperature of less than 0.5 °C. The second intervention is the avoidance of antipyretics. The control group receives the standard antipyretic treatment from the participating hospital. The purposes of this pilot study are proof of principle of intervention, evaluation of safety, feasibility, definition of endpoints, and to receive basic data for sample size calculation and needed resources. DISCUSSION: The main goal is to improve the care of children with cancer by providing the best possible support for febrile episodes. If fever support by heat reduces discomfort, administration of antipyretics and maybe even antibiotics, this would be an advancement in oncological fever management. This pilot study is intended to provide a basis for a main, multicenter, randomized trial and demonstrate the practicability of heat application in febrile patients in pediatric oncology. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00028273 . Registered on 14 April 2022.

[Präklinische Untersuchungen von Wechselwirkungen zwischen Mistel und Radio- oder Chemotherapie auf pädiatrische Tumorzellen]. / Preclinical Investigations of Interactions between Mistletoe and Radio- or Chemotherapy on Pediatric Tumor Cells.

Hintergrund: Mistelanwendungen werden als komplementäre Therapien häufig in der pädiatrischen Onkologie zusammen mit einer Radio- oder Chemotherapie verabreicht. Wechselwirkungen bei simultaner Applikation sind gerade in der Pädiatrie von großer Bedeutung, sie sind allerdings nach wie vor unzureichend untersucht. Material und Methoden: Zytotoxische Effekte des Mistelextraktes abnobaVISCUM Fraxini (aVF) auf LAN-1 Neuroblastomzellen und deren Etoposid- bzw. Cisplatin-resistente Subzelllinien wurden mittels Viabilitätstest untersucht, sowie mögliche Synergieeffekte zwischen aVF und den Chemotherapeutika durch die Softwareprodukte Combenefit und CompuSyn analysiert. Effekte einer Kombinationstherapie aus aVF und Bestrahlung auf SH-SY5Y Zellen wurden mittels Koloniebildungstest untersucht und Auswirkungen auf die Reparatureffizienz strahleninduzierter Doppelstrangbrüche mit Hilfe durchflusszytometrischer Quantifizierungen von γ-H2AX-Foci nach PI/FITC Doppelfärbung analysiert. Ergebnisse: Die Chemotherapie-resistenten LAN-1 Subzelllinien erwiesen sich als resistenter gegenüber der Mistelbehandlung als die Ursprungszelllinie. Auf Basis vier verschiedener Referenz-modelle konnten vor allem synergistisch/additive Effekte zwischen aVF und den Zytostatika Etoposid und Cisplatin berechnet werden. Die Kombination aus Mistelbehandlung und Bestrahlung führte zu einer Verringerung der Koloniebildung und zu einer Verzögerung der Reparaturgeschwindigkeit von strahleninduzierten Doppelstrangbrüchen. Schlussfolgerung: Die präklinischen Daten könnten darauf hinweisen, dass die Verwendung des Mistelextraktes, aVF, eine unterstützende Wirkung auf Radio- und Chemotherapien hat. BACKGROUND: Mistletoe therapies belong to the field of complementary medicines and are often administered simultaneously or successive to conventional radio- or chemotherapy. Drug-herb interactions are of great significance, especially in pediatrics, but are still insufficiently investigated. MATERIAL AND METHODS: Cytotoxic effects of the mistletoe extract, abnobaVISCUM Fraxini (aVF), on LAN-1 neuroblastoma cell line and their chemotherapy-resistant (cisplatin; etoposide) subclones were investigated by cell viability assays. Potential synergistic or antagonistic effects of the co-treatment of aVF and cisplatin or etoposide, respectively, were analyzed by Combenefit and CompuSyn software. Combinational effects of mistletoe and irradiation were assessed by colony formation assays and repair efficiency of irradiation-induced double strand breaks was investigated by flow cytometric analyses of γ-H2AX foci after PI/FITC double staining. RESULTS: Chemotherapy-resistant subclones were more resistant to mistletoe therapy than the parental cells. Based on four different reference models, primarily synergistic/additive effects between aVF and the cytostatic drugs could be calculated. Simultaneous application of mistletoe extract and irradiation led to a delay of irradiation-induced double strand break repair in neuroblastoma cells and a decreased colony formation compared to irradiation monotherapy. CONCLUSION: The preclinical data may indicate that the use of aVF has a supportive effect on radio- and chemotherapies.

Anticancer Effects of Viscum album Fraxini Extract on Medulloblastoma Cells in vitro.

BACKGROUND: Mistletoe therapy is frequently administered as a supportive treatment in diverse pediatric cancer entities including brain tumors. Medulloblastoma is the most common brain tumor in childhood. Its high risk to metastasize and its long-term sequelae caused by aggressive chemo- or radiotherapies are still challenging. MATERIAL AND METHODS: Effects of a lectin-rich mistletoe extract, abnobaVISCUM Fraxini, were investigated in two medulloblastoma cell lines (Daoy and ONS-76). Responsiveness of tumor cells was assessed by cell viability assays and xCELLigence real-time analyses. Moreover, impacts on proliferation, cell cycle and apoptosis were investigated. Apoptosis was studied by staining of vital mitochondria and assessing the involvement of caspases. In addition, effects on migration and invasion were analyzed. RESULTS: Both medulloblastoma cell lines were more susceptible to treatment with the mistletoe extract than a nontumorigenic fibroblast cell line. In mistletoe-sensitive Daoy cells, reduction of proliferation and induction of caspase-mediated apoptosis were observed upon administration of 0.05 and 0.5 mg/mL abnobaVISCUM Fraxini treatment, respectively. Furthermore, mistletoe extract inhibited migration and invasion properties in Daoy and significantly impaired invasive capabilities of ONS-76 cells. CONCLUSION: AbnobaVISCUM Fraxini has cell line dependent antitumoral effects in medulloblastoma models. These results call for further investigations, to reveal mechanistic insights into antitumorigenic properties of mistletoe extracts.

Expert consensus-based clinical recommendation for an integrative anthroposophic treatment of acute bronchitis in children: A Delphi survey.

BACKGROUND: Acute bronchitis is one of the most common pediatric diseases. In addition to conventional therapies, a frequent use of complementary and alternative medicine (CAM) has been stated. Anthroposophic medicine (AM) is one of the most practiced complementary and integrative medicine (CIM) approaches in Central Europe but hitherto no consensus-based clinical recommendations or guidelines are available. Therefore, a consensus-based recommendation leading to an informed and reasonable use of AM in the treatment of acute bronchitis in pediatrics was developed. METHODS: A total of 61 physicians in Germany with expertise in the field of anthroposophic pediatrics was invited to complete an online multistep Delphi process. Two independent reviewers quantitatively and qualitatively evaluated the results. The survey was completed when >75 % consensus was achieved. RESULTS: The clinical recommendation comprises 15 subitems related to treatment as well as clinical and psychosocial aspects. All items reached strong consensus (>90 %; N = 9) or consensus (75-90 %; N = 6). CONCLUSION: The comprehensive clinical recommendation creates a scientific base for the anthroposophic integrative treatment of acute bronchitis in children in Germany. It will make the anthroposophic approach more applicable, understandable and comparable to a wider public of physicians and other health professionals in Germany.

Antitumoral Effects of Curcumin (Curcuma longa L.) and Thymoquinone (Nigella sativa L.) on Neuroblastoma Cell Lines.

INTRODUCTION: Overall survival of high-risk neuroblastoma patients is still poor, emphasizing the need for novel therapeutic options. There is evidence for anti-cancer properties of the herbal substances thymoquinone and curcumin. These substances are isolated from Nigella sativa L. and Curcuma longa L., respectively, which are used in traditional medicine. OBJECTIVE: We investigated cytotoxic effects of thymoquinone and curcumin on neuroblastoma cell lines NLF, NB69, and SK-N-BE(2), in vitro. METHODS: Cytotoxicity of compounds was investigated by MTT cell viability assays. For analyzing effects on cell proliferation BrdU assays were employed and induction of apoptosis was detected by Cell Death ELISA assays. RESULTS: Both substances showed cytotoxic effects in all three neuroblastoma cell lines, whereby primary human fibroblast cells reacted less sensitively. Overall, lower IC50 values could be calculated for curcumin (3.75-7.42 µM) than for thymoquinone (5.16-16.3 µM). Decreased proliferation and increased apoptosis rates were observed under treatment. CONCLUSIONS: Both substances showed anti-tumoral properties on neuroblastoma cell lines and should be further investigated as therapeutic agents.

Accidental intakes of remedies from complementary and alternative medicine in children--analysis of data from the Swiss Toxicological Information Centre.

The use of complementary and alternative medicine (CAM) in Switzerland is rather high, and therefore, the occurrence of accidental intakes of CAM remedies by children and associated intoxications is to be expected. In the present study, the inquiries to the Swiss Toxicological Information Centre that took place from 1998 until 2007 and concerned accidental, unintended intakes of CAM remedies by children were analysed. Inquiries for information were performed by concerned care-givers, physicians, pharmacists and others in case of acute accidental intake of CAM remedies. Feedbacks from physicians about paediatric patients with acute intoxication possibly associated with the accidental ingestion of CAM remedies were as well considered. During the study period, 3,158 accidental intakes of CAM remedies (1,015 of herbal and 2,143 of homeopathic remedies) were reported, corresponding to 8.6% of all reported accidental intakes of pharmaceutical products by children. No significant increase of the yearly number of accidental intakes of CAM remedies was detected during the study period. There was no accidental intake of CAM remedies leading to severe signs or symptoms. Concerning the herbal remedies, three intoxications of moderate and 28 of minor severity were reported. Nine children with intoxication from homeopathic remedies were reported, with minor symptoms only. All other accidental intakes of CAM remedies did not lead to intoxications and evolved without manifestations. The data show that accidental, unintended intake of CAM remedies happened in children, but developed mostly harmlessly. Comparing herbal with homeopathic remedies, accidental intakes with homeopathic remedies were more common, but intoxications associated with manifestations were observed more frequently with herbal remedies.