Safety of Anthroposophic Medicinal Products: An Analysis of Adverse Drug Reactions from German Pharmacovigilance Databases.

BACKGROUND: Anthroposophic medicinal products (AMPs) are widely used in Europe and world-wide. OBJECTIVE: To determine the frequency of reported adverse drug reactions (ADRs) from all AMPs on the market, in absolute numbers and relative to the maximum daily administration doses (MDADs). PATIENTS AND METHODS: Retrolective safety analysis of AMP-related ADRs in pharmacovigilance databases of four AMP Marketing Authorisation Holders in Germany. For each ADR, information about the patient, outcome, causality and AMP was retrieved. Primary outcome was the frequency of reported ADRs relative to MDADs sold. RESULTS: In the period 2010-2017, a total of 5506 ADRs were reported that had occurred in 2765 different patients, comprising 370 different AMPs. A total of 104 ADRs (1.9%) were classified as serious. The frequency of ADRs for all AMPs was 1.50 per million MDADs. For serious ADRs the frequency was 0.03 per million MDADs. ADRs were more frequently reported with parenteral AMP administration (injections) than with oral or local administration (18.85 vs. 0.59 vs. 1.61 ADRs per million MDADs, respectively; p < 0.0001). The large majority of users (91.9%) had recovered or were recovering from the ADRs and there were no reports with a fatal outcome. Most frequently reported ADR symptom was injection site inflammation for parenteral AMPs (4.66 ADRs per million MDADs), nausea for oral AMPs (0.03 ADRs per million MDADs), and eye irritation for locally administered AMPs (0.23 ADRs per million MDADs). CONCLUSIONS: In this retrolective safety analysis of pharmacovigilance data, the frequency of ADRs to AMPs was 1.50 per million MDADs. Notably, the ADR frequency in this study based on spontaneous reporting is not directly comparable to frequencies in prospective clinical studies nor to frequencies based on other measures of patient exposure than MDADs.

Mapping Physicians' Experiences with Medicinal Products from Whole Medical Systems: A Descriptive Analysis of the Vademecum of Anthroposophic Medicines.

BACKGROUND: Therapy in whole medical systems involves a large number of medicinal products. One source of knowledge of clinical properties of such products is the experience of therapy providers. A systematic approach to documentation, assessment, and aggregation of physicians' experiences with anthroposophic medicinal products (AMPs) has been developed: the Vademecum of Anthroposophic Medicines. MATERIAL AND METHODS: The Vademecum contains structured information on AMPs, including therapeutic rationale, indications, and therapy recommendations. The information is based on a 17-item questionnaire of physicians' therapy experiences, which is peer-reviewed by an interdisciplinary editorial board. We conducted a descriptive analysis of the Vademecum, 4th edition. RESULTS: The Vademecum comprised 799 different AMPs, used for 1,773 indications, based on 2,543 questionnaires submitted by 274 physicians from 19 countries. The 799 AMPs comprised 52.6% of all AMPs marketed in Germany in 2015-2016. The 1,773 indications corresponded to 544 different ICD-10 three-digit codes, amounting to 29.3% (n = 544/1,854) of all three-digit codes. A total of 30.6% (n = 542/1,773) of indications were supported by ≥2 questionnaires. CONCLUSIONS: The current Vade-mecum covers more than half of all AMPs, used for more than one fourth of all ICD-10 three-digit codes. The Vademecum approach may be relevant for medicinal products from other whole medical systems.

Use and Safety of Anthroposophic Medicinal Products: An Analysis of 44,662 Patients from the EvaMed Pharmacovigilance Network.

BACKGROUND: There is a need for data on the clinical safety of anthroposophic medicinal products (AMPs). OBJECTIVES: The main objective of this analysis was to determine the frequency of adverse drug reactions (ADRs) to AMPs, relative to the number of AMP prescriptions. METHODS: EvaMed (Evaluation of Anthroposophic Medicine) was a prospective pharmacovigilance study with the patients of 38 physicians in outpatient care in Germany. Diagnoses and prescriptions were extracted from the electronic medical records. All physicians documented ADRs of Grades III-IV and serious ADRs, seven 'prescriber physicians' also documented non-serious ADRs of any intensity. Patients were eligible for this analysis if they had one or more AMP prescription in the years 2001-2010, followed by one or more physician visit. RESULTS: A total of 44,662 patients with 311,731 AMP prescriptions, comprising 1722 different AMPs, were included. One hundred ADRs to AMPs occurred, caused by 83 different AMPs. ADR intensity was mild, moderate, and severe in 50% (n = 50/100), 43%, and 7% of cases, respectively; one ADR was serious. Among patients of prescriber physicians, ADRs of any intensity occurred in 0.071% (n = 67/94,734) of AMP prescriptions and in 0.502% (n = 65/12,956) of patients prescribed AMPs. In subgroup analyses according to age, specific AMPs or AMP groups, dosage forms, and concentrations (altogether 11 groups), the highest ADR frequency was 0.290% of prescriptions (for one specific AMP). Among all patients, serious ADRs occurred in 0.0003% (n = 1/311,731) of prescriptions and 0.0022% (n = 1/44,662) of patients. CONCLUSION: In this analysis from a large sample, ADRs to AMP therapy in outpatient care were rare; ADRs of high intensity as well as serious ADRs were very rare.

Antibiotic Use in Children with Acute Respiratory or Ear Infections: Prospective Observational Comparison of Anthroposophic and Conventional Treatment under Routine Primary Care Conditions.

Children with acute respiratory or ear infections (RTI/OM) are often unnecessarily prescribed antibiotics. Antibiotic resistance is a major public health problem and antibiotic prescription for RTI/OM should be reduced. Anthroposophic treatment of RTI/OM includes anthroposophic medications, nonmedication therapy and if necessary also antibiotics. This secondary analysis from an observational study comprised 529 children <18 years from Europe (AT, DE, NL, and UK) or USA, whose caregivers had chosen to consult physicians offering anthroposophic (A-) or conventional (C-) treatment for RTI/OM. During the 28-day follow-up antibiotics were prescribed to 5.5% of A-patients and 25.6% of C-patients (P < 0.001); unadjusted odds ratio for nonprescription in A- versus C-patients 6.58 (95%-CI 3.45-12.56); after adjustment for demographics and morbidity 6.33 (3.17-12.64). Antibiotic prescription rates in recent observational studies with similar patients in similar settings, ranged from 31.0% to 84.1%. Compared to C-patients, A-patients also had much lower use of analgesics, somewhat quicker symptom resolution, and higher caregiver satisfaction. Adverse drug reactions were infrequent (2.3% in both groups) and not serious. Limitation was that results apply to children of caregivers who consult A-physicians. One cannot infer to what extent antibiotics might be avoided in children who usually receive C-treatment, if they were offered A-treatment.

Overview of the Publications From the Anthroposophic Medicine Outcomes Study (AMOS): A Whole System Evaluation Study.

Anthroposophic medicine is a physician-provided complementary therapy system that was founded by Rudolf Steiner and Ita Wegman. Anthroposophic therapy includes special medicinal products, artistic therapies, eurythmy movement exercises, and special physical therapies. The Anthroposophic Medicine Outcomes Study (AMOS) was a prospective observational multicenter study of 1631 outpatients starting anthroposophic therapy for anxiety disorders, asthma, attention deficit hyperactivity disorder, depression, low back pain, migraine, and other chronic indications under routine conditions in Germany. AMOS INCORPORATED TWO FEATURES PROPOSED FOR THE EVALUATION OF INTEGRATIVE THERAPY SYSTEMS: (1) a sequential approach, starting with the whole therapy system (use, safety, outcomes, perceived benefit), addressing comparative effectiveness and proceeding to the major system components (physician counseling, anthroposophic medicinal products, art therapy, eurythmy therapy, rhythmical massage therapy) and (2) a mix of different research methods to build an information synthesis, including pre-post analyses, prospective comparative analyses, economic analyses, and safety analyses of individual patient data. AMOS fostered two methodological innovations for the analysis of single-arm therapy studies (combined bias suppression, systematic outcome comparison with corresponding cohorts in other studies) and the first depression cost analysis worldwide comparing primary care patients treated for depression vs depressed patients treated for another disorder vs nondepressed patients. A total of 21 peer-reviewed publications from AMOS have resulted. This article provides an overview of the main research questions, methods, and findings from these publications: anthroposophic treatment was safe and was associated with clinically relevant improvements in symptoms and quality of life without cost increase; improvements were found in all age, diagnosis, and therapy modality groups and were retained at 48-month follow-up; nonrespondent bias, natural recovery, regression to the mean, and adjunctive therapies together could explain a maximum of 37% of the improvement.

La medicina antroposófica es un sistema terapéutico complementario proporcionado por el médico que fue fundada por Rudolf Steiner e Ita Wegman. La terapia antroposófica incluye productos medicinales especiales, terapias artísticas, ejercicios de movimiento eurítmico y terapias físicas especiales. El estudio de los resultados de la medicina antroposófica (Anthroposophic Medicine Outcomes Study, AMOS) consistió en un estudio prospectivo observacional multicéntrico de 1631 pacientes ambulatorios que comenzaban la terapia antroposófica para trastornos de ansiedad, asma, trastorno de hiperactividad y déficit de atención, depresión, dolor lumbar, migraña y otras indicaciones crónicas bajo condiciones rutinarias en Alemania.AMOS incorporaba dos características propuestas para la evaluación de sistemas terapéuticos integrales: (1) un enfoque secuencial, comenzando con el sistema terapéutico completo (uso, seguridad, resultados, ventaja percibida), que aborda la eficacia comparativa y continúa con los componentes principales del sistema (asesoramiento del médico, productos medicinales antroposóficos, terapia artística, terapia eurítmica, terapia de masaje rítmico) y (2) una combinación de diferentes métodos de investigación para crear una síntesis de información, que incluye análisis previos y posteriores, análisis comparativos prospectivos, análisis económicos y análisis de la seguridad de los datos del paciente individual. AMOS fomentaba dos innovaciones metodológicas para el análisis de los estudios terapéuticos de un grupo único (supresión del sesgo combinado, comparación sistemática de resultados con las cohortes correspondientes en otros estudios) y el primer análisis a nivel mundial del coste de la depresión comparando pacientes de atención primaria tratados de depresión frente a pacientes deprimidos tratados por otro trastorno frente a pacientes no deprimidos.Ha resultado en un total de 21 publicaciones revisadas por expertos de AMOS. Este artículo proporciona una visión general de las principales cuestiones de investigación, métodos y los resultados de estas publicaciones: el tratamiento antroposófico era seguro y se asociaba a mejoras clínicamente relevantes en los síntomas y la calidad de vida sin aumento de los costes; se observaron mejoras en todos los grupos de edad, diagnóstico y modalidad de terapia y se mantuvieron en el seguimiento de 48 meses; el sesgo ajeno a los entrevistados, la recuperación natural, la regresión a la media y las terapias adyuvantes juntos podían explicar un máximo del 37 % de la mejoría.

Long-term outcomes of anthroposophic treatment for chronic disease: a four-year follow-up analysis of 1510 patients from a prospective observational study in routine outpatient settings.

BACKGROUND: Anthroposophic treatment includes special artistic and physical therapies and special medications. We here report an update to a previously published study of anthroposophic treatment for chronic diseases, including more patients and a longer follow up. The Anthroposophic Medicine Outcomes Study (AMOS) was a prospective observational cohort study of anthroposophic treatment for chronic indications in routine outpatient settings in Germany. Anthroposophic treatment was associated with improvements of symptoms and quality of life. Previous follow-up-analyses have been performed after 24 months or, in subgroups of patients enrolled in the period 1999-2001, after 48 months. We conducted a 48-month follow-up analysis of all patients enrolled in AMOS in the period 1999-2005. METHODS: 1,510 outpatients aged 1-75 years, starting anthroposophic treatment for chronic conditions in routine German outpatient settings, participated in a prospective cohort study. Main outcomes were Symptom Score (primary outcome, mean symptom severity on numerical rating scales), SF-36 Physical and Mental Component scores in adults, and disease-specific outcomes in the six most common diagnosis groups: asthma, anxiety disorders and migraine (numerical rating scales), depression (Center for Epidemiological Studies Depression Scale), attention deficit hyperactivity symptoms (FBB-HKS Total score), and low back pain (Hanover Functional Ability Questionnaire, Low Back Pain Rating Scale). RESULTS: Median disease duration at baseline was 3.5 years. From baseline to 48-month follow-up all ten outcomes improved significantly (p < 0.001 for all pre-post comparisons). Standardised Response Mean effect sizes were large (range 0.84-1.24 standard deviations) for seven comparisons, medium for two comparisons (SF-36 Mental Component: 0.60, Low Back Pain Rating Scale: 0.55), and small for one comparison (SF-36 Physical Component: 0.39). Symptom Score improved significantly with large effect sizes in adults and children, and in the four main anthroposophic therapy modality groups (art therapy, eurythmy therapy, rhythmical massage therapy, medical therapy). CONCLUSIONS: This 48-month follow-up analysis confirmed previous analyses from the AMOS study. Outpatients receiving anthroposophic treatment for chronic indications had sustained, clinically relevant improvements of symptoms and quality of life.

[Clinical research on anthroposophic medicine:update of a health technology assessment report and status quo]. / Klinische Forschung zur Anthroposophischen Medizin - update eines «Health Technology Assessment¼-Berichts und status quo.

BACKGROUND AND OBJECTIVE: In 2005 a Health Technology Assessment (HTA) report analyzed efficacy, effectiveness, safety, utilization and costs of Anthroposophic Medicine (AM). After a recent referendum of the 'Swiss Population pro Complementary Medicine' (May 2009) this HTA report was updated. DESIGN: Update of the HTA report by a systematic review. METHODS: Methods corresponded to the existing HTA report and the guidelines of the Swiss Federal Office of Public Health. For clinical studies four databases and a specialized journal were searched, and extensive expert consultations were used. Studies were selected according to predefined inclusion criteria, data were extracted, and methodological quality was assessed individually. RESULTS: 70 new clinical studies were found. Altogether, 265 clinical studies investigated efficacy and effectiveness of AM: 38 randomized controlled trials, 36 prospective and 49 retrospective non-randomized controlled trials as well as 90 prospective and 52 retrospective trials without control groups. They investigated a wide spectrum of AM treatments in a multitude of diseases; the whole AM system in 38 trials, non-pharmacological therapies in 10 trials, AM mistletoe products in cancer therapy in 133 trials, and other AM medication treatments in 84 trials. Most studies showed a positive result for AM. Methodological quality differed substantially; some studies showed major limitations, others were reasonably well conducted. Trials with better quality still showed a positive result. External validity was usually high. Side effects or other risks were rare and usually described to be mild or moderate. Studies regarding safety showed a good tolerability altogether. CONCLUSION: Trials of varying design and quality in a variety of diseases predominantly describe good clinical outcomes for AM, only marginal side effects, high satisfaction of patients with regard to results and safety and presumably slightly less costs. Further high-quality evaluations are desirable.

Pulpa dentis D30 for acute reversible pulpitis: A prospective cohort study in routine dental practice.

BACKGROUND: Pulpa dentis D30 (PD: dental pulp of the calf, prepared in a homeopathic D30 potency) has been used in acute reversible pulpitis for pain relief and to avoid or postpone invasive dental treatment. PRIMARY STUDY OBJECTIVE: To study short-term clinical outcomes of PD therapy for acute reversible pulpitis in routine dental practice. METHODS/DESIGN: Prospective, observational, open-label, single-arm cohort study. SETTING: Eleven dental primary care practices in Germany. PARTICIPANTS AND INTERVENTION: Thirty-two patients starting monotherapy with PD for acute reversible pulpitis without visible or radiological abnormalities. PD was applied as 1-mL submucous injections into the mucobuccal fold, repeated daily as needed. PRIMARY OUTCOME MEASURES: Avoidance of invasive dental treatment (pulp capping, root canal therapy, tooth extraction) and remission of pain, measured on a 0-10 point scale (partial remission: reduction by > or =3 points; complete remission: reduction from > or =4 points to 0-1 points) during the 10-day follow-up period. RESULTS: Median pain duration was 14.0 days. The patients received a median of two PD applications (range 1-7). A total of 81% (n=26/32) of patients did not require invasive dental treatment, and 19% (n= 6) had root canal therapy. Remission status was evaluable in 24 patients. Of these, 63% (n = 15/24) achieved pain remission, 58% (n = 14) remitted without invasive dental treatment (complete remission: n=12, partial remission: n=2), and 29% (n= 7) had a close temporal relationship between PD and remission (ratio "time to remission after first PD application vs pain duration prior to first PD application" <1:10). CONCLUSION: In this study of PD for acute reversible pulpitis, 58% of evaluable patients achieved pain remission without invasive dental treatment. The open-label pre-post design does not allow for conclusions about comparative effectiveness. However, more than one-fourth of evaluable patients remitted with a close temporal relationship between the first PD application and pain remission, suggesting a causal relationship between therapy and remission.

Anthroposophic therapy for attention deficit hyperactivity: a two-year prospective study in outpatients.

BACKGROUND: Anthroposophic treatment for attention deficit hyperactivity disorder (ADHD) includes special artistic and physical therapies and special medications. METHODS: We studied 61 consecutive children starting anthroposophic treatment for ADHD symptoms under routine outpatient conditions. Primary outcome was FBB-HKS (a parents' questionnaire for ADHD core symptoms, 0-3), and secondary outcomes were disease and symptom scores (physicians' and parents' assessment, 0-10) and quality of life (KINDL(®) total score, 0-100). RESULTS: A total of 67% of patients fulfilled the DSM-IV criteria for ADHD, 15% had an exclusion diagnosis such as pervasive developmental disorders, while 18% did not fulfill ADHD criteria for another reason. Anthroposophic treatment modalities used were eurythmy therapy (in 56% of patients), art therapy (20%), rhythmical massage therapy (8%), and medications (51%). From baseline to six-month follow-up, all outcomes improved significantly; average improvements were FBB-HKS total score 0.30 points (95% confidence interval [CI]: 0.18-0.43; P < 0.001), FBB-HKS inattention 0.36 (95% CI: 0.21-0.50; P < 0.001), FBB-HKS hyperactivity 0.29 (95% CI: 0.14-0.44; P < 0.001), FBB-HKS impulsivity 0.22 (95% CI: 0.03-0.40; P < 0.001), disease score 2.33 (95% CI: 1.84-2.82; P < 0.001), symptom score 1.66 (95% CI: 1.17-2.16; P < 0.001), and KINDL 5.37 (95% CI: 2.27-8.47; P = 0.001). Improvements were similar in patients not using stimulants (90% of patients at months 0-6) and were maintained until last follow-up after 24 months. CONCLUSION: Children with ADHD symptoms receiving anthroposophic treatment had long-term improvement of symptoms and quality of life.

Predictors of outcome after 6 and 12 months following anthroposophic therapy for adult outpatients with chronic disease: a secondary analysis from a prospective observational study.

BACKGROUND: Anthroposophic medicine is a physician-provided complementary therapy system involving counselling, artistic and physical therapies, and special medications. The purpose of this analysis was to identify predictors of symptom improvement in patients receiving anthroposophic treatment for chronic diseases. METHODS: 913 adult outpatients from Germany participated in a prospective cohort study. Patients were starting anthroposophic treatment for mental (30.4% of patients, n = 278/913), musculoskeletal (20.2%), neurological (7.6%), genitourinary (7.4%) or respiratory disorders (7.2%) or other chronic indications. Stepwise multiple linear regression analysis was performed with the improvement of Symptom Score (patients' assessment, 0: not present, 10: worst possible) after 6 and 12 months as dependent variables. 61 independent variables pertaining to socio-demographics, life style, disease status, co-morbidity, health status (SF-36), depression, and therapy factors were analysed. RESULTS: Compared to baseline, Symptom Score improved by average 2.53 points (95% confidence interval 2.39-2.68, p < 0.001) after six months and by 2.49 points (2.32-2.65, p < 0.001) after 12 months. The strongest predictor for improvement after six months was baseline Symptom Score, which alone accounted for 25% of the variance (total model 32%). Improvement after six months was also positively predicted by better physical function, better general health, shorter disease duration, higher education level, a diagnosis of respiratory disorders, and by a higher therapy goal documented by the physician at baseline; and negatively predicted by the number of physiotherapy sessions in the pre-study year and by a diagnosis of genitourinary disorders. Seven of these nine variables (not the two diagnoses) also predicted improvement after 12 months. When repeating the 0-6 month analysis on two random subsamples of the original sample, three variables (baseline Symptom Score, physical function, general health) remained significant predictors in both analyses, and three further variables (education level, respiratory disorders, therapy goal) were significant in one analysis. CONCLUSION: In adult outpatients receiving anthroposophic treatment for chronic diseases, symptom improvement after 6 and 12 months was predicted by baseline symptoms, health status, disease duration, education, and therapy goal. Other variables were not associated with the outcome. This secondary predictor analysis of data from a pre-post study does not allow for causal conclusions; the results are hypothesis generating and need verification in subsequent studies.

Anthroposophic therapy for migraine: a two-year prospective cohort study in routine outpatient settings.

BACKGROUND AND METHODS: Anthroposophic treatment for migraine is provided by physicians and includes special artistic and physical therapies and special medications. We conducted a prospective cohort study of 45 consecutive adult outpatients (89% women) starting anthroposophic treatment for migraine under routine conditions. Main outcomes were Average Migraine Severity (physician and patient ratings 0-10, primary outcome), Symptom Score (patient rating, 0-10), and quality of life (SF-36); main follow-up time point was after six months. RESULTS: The anthroposophic treatment modalities used were medications (67% of patients), eurythmy therapy (38%), art therapy (18%), and rhythmical massage therapy (13%). Median therapy duration was 105 days. In months 0-6, conventional prophylactic antimigraine medications were used by 14% (n=5/36) of evaluable patients. From baseline to six-month follow-up, physician-rated Average Migraine Severity improved by 3.14 points (95% confidence interval 2.40-3.87, p<0.001); patient-rated Average Migraine Severity improved by 2.82 points (2.05-3.64, p<0.001); and Symptom Score improved by 2.32 points (1.68-2.95, p<0.001). In addition, three SF-36 scales (Social Functioning, Bodily Pain, Vitality), the SF-36 Physical Component summary measure, and the SF-36 Health Change item improved significantly. All improvements were maintained at last follow-up after 24 months. Patients not using conventional prophylactic antimigraine medications had improvements similar to the whole cohort. CONCLUSIONS: Patients with migraine under anthroposophic treatment had long-term improvement of symptoms and quality of life. Although the pre-post design of the present study does not allow for conclusions about comparative effectiveness, study findings suggest that anthroposophic therapies may be useful in the long-term care of patients with migraine.

Health costs in patients treated for depression, in patients with depressive symptoms treated for another chronic disorder, and in non-depressed patients: a two-year prospective cohort study in anthroposophic outpatient settings.

We studied costs of healthcare and productivity loss in 487 German outpatients starting anthroposophic treatment: Group 1 was treated for depression, Group 2 had depressive symptoms but were treated for another chronic disorder, while Group 3 did not have depressive symptoms. Costs were adjusted for socio-demographics, comorbidity, and baseline health status. Total costs in groups 1-3 averaged euro7,129, euro4,371, and euro3,532 in the pre-study year (P = 0.008); euro6,029, euro3,522, and euro3,353 in the first year (P = 0.083); and euro4,929, euro3,792, and euro4,031 in the second year (P = 0.460). In the 2nd year, costs were significantly reduced in Group 1. This study underlines the importance of depression for health costs, and suggests that treatment of depression could be associated with long-term cost reductions.

Outcome of anthroposophic medication therapy in chronic disease: a 12-month prospective cohort study.

BACKGROUND: Anthroposophic medications (AMED) are prescribed in 56 countries. OBJECTIVE: To study clinical outcomes in patients prescribed AMED for chronic disease. DESIGN: Prospective cohort study. SETTING: 110 medical practices in Germany. PARTICIPANTS: 665 consecutive outpatients aged 1-71 years, prescribed AMED for mental, respiratory, musculoskeletal, neurological, genitourinary, and other chronic diseases. MAIN OUTCOMES: Disease and Symptom Scores (physicians' and patients' assessment, 0-10) and SF-36. RESULTS: During the first six months, an average of 1.5 AMED per patient was used, in total 652 different AMED. Origin of AMED was mineral (8.0% of 652 AMED), botanical (39.0%), zoological (7.2%), chemically defined (13.0%), and mixed (33.0%). From baseline to six-month-follow-up, all outcomes improved significantly: Disease Score improved by mean 3.15 points (95% confidence interval 2.97-3.34, p < 0.001), Symptom Score by 2.43 points (2.23-2.63, p < 0.001), SF-36 Physical Component Summary by 3.04 points (2.16-3.91, p < 0.001), and SF-36 Mental Component Summary by 5.75 points (4.59-6.92, p < 0.001). All improvements were maintained at 12-month follow-up. Improvements were similar in adult men and women, in children, and in patients not using adjunctive therapies. CONCLUSION: Outpatients using AMED for chronic disease had long-term reduction of disease severity and improvement of quality of life.

Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research.

BACKGROUND: Viscum album L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment. METHODS: Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and breast cancer. Search of databases, reference lists and expert consultations. Criteria-based assessment of methodological study quality. RESULTS: 19 randomized (RCT), 16 non-randomized (non-RCT) controlled studies, and 11 single-arm cohort studies were identified that investigated VAE treatment of breast or gynaecological cancer. They included 2420, 6399 and 1130 patients respectively. 8 RCTs and 8 non-RCTs were embedded in the same large epidemiological cohort study. 9 RCTs and 13 non-RCTs assessed survival; 12 reported a statistically significant benefit, the others either a trend or no difference. 3 RCTs and 6 non-RCTs assessed tumour behaviour (remission or time to relapse); 3 reported statistically significant benefit, the others either a trend, no difference or mixed results. Quality of life (QoL) and tolerability of chemotherapy, radiotherapy or surgery was assessed in 15 RCTs and 9 non-RCTs. 21 reported a statistically significant positive result, the others either a trend, no difference, or mixed results. Methodological quality of the studies differed substantially; some had major limitations, especially RCTs on survival and tumour behaviour had very small sample sizes. Some recent studies, however, especially on QoL were reasonably well conducted. Single-arm cohort studies investigated tumour behaviour, QoL, pharmacokinetics and safety of VAE. Tumour remission was observed after high dosage and local application. VAE application was well tolerated. 34 animal experiments investigated VAE and isolated or recombinant compounds in various breast and gynaecological cancer models in mice and rats. VAE showed increase of survival and tumour remission especially in mice, while application in rats as well as application of VAE compounds had mixed results. In vitro VAE and its compounds have strong cytotoxic effects on cancer cells. CONCLUSION: VAE shows some positive effects in breast and gynaecological cancer. More research into clinical efficacy is warranted.

Anthroposophic therapy for children with chronic disease: a two-year prospective cohort study in routine outpatient settings.

BACKGROUND: Many children with chronic disease use complementary therapies. Anthroposophic treatment for paediatric chronic disease is provided by physicians and differs from conventional treatment in the use of special therapies (art therapy, eurythmy movement exercises, rhythmical massage therapy) and special medications. We studied clinical outcomes in children with chronic diseases under anthroposophic treatment in routine outpatient settings. METHODS: In conjunction with a health benefit program, consecutive outpatients starting anthroposophic treatment for any chronic disease participated in a prospective cohort study. Main outcome was disease severity (Disease and Symptom Scores, physicians' and caregivers' assessment on numerical rating scales 0-10). Disease Score was documented after 0, 6, and 12 months, Symptom Score after 0, 3, 6, 12, 18, and 24 months. RESULTS: A total of 435 patients were included. Mean age was 8.2 years (standard deviation 3.3, range 1.0-16.9 years). Most common indications were mental disorders (46.2% of patients; primarily hyperkinetic, emotional, and developmental disorders), respiratory disorders (14.0%), and neurological disorders (5.7%). Median disease duration at baseline was 3.0 years (interquartile range 1.0-5.0 years). The anthroposophic treatment modalities used were medications (69.2% of patients), eurythmy therapy (54.7%), art therapy (11.3%), and rhythmical massage therapy (6.7%). Median number of eurythmy/art/massage therapy sessions was 12 (interquartile range 10-20), median therapy duration was 118 days (interquartile range 78-189 days).From baseline to six-month follow-up, Disease Score improved by average 3.00 points (95% confidence interval 2.76-3.24 points, p < 0.001) and Symptom Score improved by 2.41 points (95% confidence interval 2.16-2.66 points, p < 0.001). These improvements were maintained until the last follow-up. Symptom Score improved similarly in patients not using adjunctive non-anthroposophic therapies within the first six study months. CONCLUSION: Children under anthroposophic treatment had long-term improvement of chronic disease symptoms. Although the pre-post design of the present study does not allow for conclusions about comparative effectiveness, study findings suggest that anthroposophic therapies may play a beneficial role in the long-term care of children with chronic illness.

Long-term outcomes of anthroposophic therapy for chronic low back pain: A two-year follow-up analysis.

BACKGROUND: Anthroposophic treatment for chronic low back pain (LBP) includes special artistic and physical therapies and special medications. In a previously published prospective cohort study, anthroposophic treatment for chronic LBP was associated with improvements of pain, back function, and quality of life at 12-month follow-up. These improvements were at least comparable to improvements in a control group receiving conventional care. We conducted a two-year follow-up analysis of the anthroposophic therapy group with a larger sample size. METHODS: Seventy-five consecutive adult outpatients in Germany, starting anthroposophic treatment for discogenic or non-specific LBP of ≥6 weeks' duration participated in a prospective cohort study. Main outcomes were Hanover Functional Ability Questionnaire (HFAQ; 0-100), LBP Rating Scale Pain Score (LBPRS; 0-100), Symptom Score (0-10), and SF-36 after 24 months. RESULTS: Eighty-five percent of patients were women. Mean age was 49.0 years. From baseline to 24-month follow-up all outcomes improved significantly; average improvements were: HFAQ 11.1 points (95% confidence interval [CI]: 5.5-16.6; p < 0.001), LBPRS 8.7 (95% CI: 4.4-13.0; p < 0.001), Symptom Score 2.0 (95% CI: 1.3-2.8; p < 0.001), SF-36 Physical Component Summary 6.0 (95% CI: 2.9-9.1; p < 0.001), and SF-36 Mental Component Summary 4.0 (95% CI: 1.1-6.8; p = 0.007). CONCLUSION: Patients with chronic LBP receiving anthroposophic treatment had sustained improvements of symptoms, back function, and quality of life, suggesting that larger multicenter rigorous studies may be worthwhile.

Anthroposophic therapy for asthma: A two-year prospective cohort study in routine outpatient settings.

BACKGROUND: Anthroposophic treatment for asthma includes special artistic and physical therapies and special medications. METHODS: We studied consecutive outpatients starting anthroposophic treatment for asthma under routine conditions in Germany. Main outcomes were average asthma severity (0-10, primary outcome); symptoms (1-4); and asthma-related quality of life at 12-month follow-up (Asthma Quality of Life Questionnaire [AQLQ] overall score, 1-7, for adults; KINDL Questionnaire for Measuring Health-Related Quality of Life in Children and Adolescents, asthma module, 0-100, for children) at 12-month follow-up. RESULTS: Ninety patients (54 adults, 36 children) were included. Anthroposophic treatment modalities used were medications (88% of patients, n = 79/90); eurythmy therapy (22%); art therapy (10%); and rhythmical massage therapy (1%). Median number of eurythmy/art/massage sessions was 12 (interquartile range 10-20), median therapy duration was 120 days (84-184). From baseline to 12-month follow-up, all outcomes improved significantly (P < 0.001 for all comparisons). Average improvements were: average asthma severity 2.61 points (95% confidence interval CI: 1.90-3.32); cough 0.93 (95% CI: 0.60-1.25); dyspnea 0.92 (95% CI: 0.56-1.28); exertion-induced symptoms 0.95 (95% CI: 0.64-1.25); frequency of asthma attacks 0.78 (95% CI: 0.41-1.14); awakening from asthma 0.90 (95% CI: 0.58-1.21); AQLQ overall score 1.44 (95% CI: 0.97-1.92); and KINDL asthma module 14.74 (95% CI: 9.70-19.78). All improvements were maintained until last follow-up after 24 months. CONCLUSIONS: Patients with asthma under anthroposophic treatment had long-term improvements of symptoms and quality of life.

Combined bias suppression in single-arm therapy studies.

RATIONALE, AIMS AND OBJECTIVES: For therapy evaluation studies, control groups are sometimes not feasible. In single-arm studies, various bias factors apart from the test therapy can affect clinical outcomes. The objective of this analysis was to improve the methods to minimize bias in single-arm studies. METHOD: We present a procedure for combined suppression of several bias factors, using two methods: sample restriction to patients unaffected by bias, and score adjustment. The procedure was used for a secondary analysis of disease score (doctors' global rating, 0-10) in a cohort of patients receiving anthroposophic therapies for chronic diseases. Four bias factors were suppressed stepwise: attrition bias (by replacing missing values with the baseline value carried forward), bias from natural recovery (by sample restriction to patients with disease duration of >/=12 months), regression to the mean due to symptom-driven self-selection (by replacing baseline scores with scores three months before enrolment) and bias from adjunctive therapies (by sample restriction to patients not using adjunctive therapies). RESULTS: In the cohort analysed, these four bias factors could together explain a maximum of 37% of the 0- to 6-month improvement of disease score. CONCLUSION: Combined bias suppression, using sample restriction and score adjustment, is a transparent procedure to minimize bias in single-arm therapy studies. Further applicability of the procedure should be tested in future studies.

Assessing the order of magnitude of outcomes in single-arm cohorts through systematic comparison with corresponding cohorts: an example from the AMOS study.

BACKGROUND: When a therapy has been evaluated in the first clinical study, the outcome is often compared descriptively to outcomes in corresponding cohorts receiving other treatments. Such comparisons are often limited to selected studies, and often mix different outcomes and follow-up periods. Here we give an example of a systematic comparison to all cohorts with identical outcomes and follow-up periods. METHODS: The therapy to be compared (anthroposophic medicine, a complementary therapy system) had been evaluated in one single-arm cohort study: the Anthroposophic Medicine Outcomes Study (AMOS). The five largest AMOS diagnosis groups (A-cohorts: asthma, depression, low back pain, migraine, neck pain) were compared to all retrievable corresponding cohorts (C-cohorts) receiving other therapies with identical outcomes (SF-36 scales or summary measures) and identical follow-up periods (3, 6 or 12 months). Between-group differences (pre-post difference in an A-cohort minus pre-post difference in the respective C-cohort) were divided with the standard deviation (SD) of the baseline score of the A-cohort. RESULTS: A-cohorts (5 cohorts with 392 patients) were similar to C-cohorts (84 cohorts with 16,167 patients) regarding age, disease duration, baseline affection and follow-up rates. A-cohorts had > or = 0.50 SD larger improvements than C-cohorts in 13.5% (70/517) of comparisons; improvements of the same order of magnitude (small or minimal differences: -0.49 to 0.49 SD) were found in 80.1% of comparisons; and C-cohorts had > or = 0.50 SD larger improvements than A-cohorts in 6.4% of comparisons. Analyses stratified by diagnosis had similar results. Sensitivity analyses, restricting the comparisons to C-cohorts with similar study design (observational studies), setting (primary care) or interventions (drugs, physical therapies, mixed), or restricting comparisons to SF-36 scales with small baseline differences between A- and C-cohorts (-0.49 to 0.49 SD) also had similar results. CONCLUSION: In this descriptive analysis, anthroposophic therapy was associated with SF-36 improvements largely of the same order of magnitude as improvements following other treatments. Although these non-concurrent comparisons cannot assess comparative effectiveness, they suggest that improvements in health status following anthroposophic therapy can be clinically meaningful. The analysis also demonstrates the value of a systematic approach when comparing a therapy cohort to corresponding therapy cohorts.

Anthroposophic art therapy in chronic disease: a four-year prospective cohort study.

BACKGROUND: Anthroposophic art therapy (painting, clay modeling, music, and speech exercises) is used in 28 countries but has not yet been studied in primary care. OBJECTIVE: To study clinical outcomes in patients treated with anthroposophic art therapy for chronic diseases. DESIGN: Prospective cohort study. SETTING: Fifty-four medical practices in Germany. PARTICIPANTS AND INTERVENTIONS: One hundred sixty-one consecutive outpatients (primary care: n = 150), aged 5-71 years, were treated by 52 different art therapists. MAIN OUTCOME MEASURES: Disease and symptom scores (physician and patient assessment, respectively, 0-10) and quality of life (adults: SF-36 Health Survey, children: KINDL Questionnaire for Measuring Health-Related Quality of Life in Children and Adolescents). Outcomes were measured after 3, 6, 12, 18, and 24 months; SF-36 and symptom scores were also measured after 48 months. RESULTS: Most common indications were mental disorders (60.9% of patients, primarily depression, fatigue, and anxiety) and neurological diseases (6.8%). The median number of therapy sessions was 15; median therapy duration was 161 days. All outcomes except KINDL improved significantly between baseline and all subsequent follow-ups. Improvements from baseline to 12 months were: disease score from (mean +/- standard deviation) 6.69 +/- 1.72 to 2.46 +/- 1.90 (P < .001), symptom score from 5.99 +/- 1.69 to 3.40 +/- 2.08 (P < .001), SF-36 physical component summary measure from 44.12 +/- 10.03 to 48.68 +/- 9.47 (P < .001), and SF-36 mental component summary measure from 35.07 +/- 12.23 to 42.13 +/- 11.51 (P < .001). All these improvements were maintained until last follow-up. CONCLUSION: Patients receiving anthroposophic art therapy had long-term reduction of chronic disease symptoms and improvement of quality of life.