Safety of higher dosages of Viscum album L. in animals and humans - systematic review of immune changes and safety parameters

<p>Abstract</p> <p>Background</p> <p><it>Viscum album </it>L extracts (VAE, mistletoe) and isolated mistletoe lectins (ML) have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects.</p> <p>Methods</p> <p>Systematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (<it>Viscum album </it>> 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg) and assessing immune parameters or infections or adverse drug reactions.</p> <p>Results</p> <p>69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, <it>Viscum album </it>was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 μg/kg in humans and in animals up to 14 μg/kg subcutaneously, 50 μg/kg nasally and 500 μg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS), fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases.</p> <p>Conclusions</p> <p>Application of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages.</p

Health costs in anthroposophic therapy users: a two-year prospective cohort study

BACKGROUND: Anthroposophic therapies (counselling, special medication, art, eurythmy movement, and rhythmical massage) aim to stimulate long-term self-healing processes, which theoretically could lead to a reduction of healthcare use. In a prospective two-year cohort study, anthroposophic therapies were followed by a reduction of chronic disease symptoms and improvement of quality of life. The purpose of this analysis was to describe health costs in users of anthroposophic therapies. METHODS: 717 consecutive outpatients from 134 medical practices in Germany, starting anthroposophic therapies for chronic diseases, participated in a prospective cohort study. We analysed direct health costs (anthroposophic therapies, physician and dentist consultations, psychotherapy, medication, physiotherapy, ergotherapy, hospital treatment, rehabilitation) and indirect costs (sick leave compensation) in the pre-study year and the first two study years. Costs were calculated from resource utilisation, documented by patient self-reporting. Data were collected from January 1999 to April 2003. RESULTS: Total health costs in the first study year (bootstrap mean 3,297 Euro; 95% confidence interval 95%-CI 3,157 Euro to 3,923 Euro) did not differ significantly from the pre-study year (3,186 Euro; 95%-CI 3,037 Euro to 3,711 Euro), whereas in the second year, costs (2,771 Euro; 95%-CI 2,647 Euro to 3,256 Euro) were significantly reduced by 416 Euro (95%-CI 264 Euro to 960 Euro) compared to the pre-study year. In each period hospitalisation and sick-leave together amounted to more than half of the total health costs. Anthroposophic therapies and medication amounted to 3%, 15%, and 8% of total health costs in the pre-study year, first year, and second study year, respectively. The cost reduction in the second year was largely accounted for by a decrease of inpatient hospitalisation, leading to a hospital cost reduction of 519 Euro (95%-CI 377 Euro to 904 Euro) compared to the pre-study year. CONCLUSION: In patients starting anthroposophic therapies for chronic disease, total health costs did not increase in the first year, and were reduced in the second year. This reduction was largely explained by a decrease of inpatient hospitalisation. Within the limits of a pre-post design, study findings suggest that anthroposophic therapies are not associated with a relevant increase in total health costs

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 ≥ 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 ≥ 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.</p> <p>Conclusion</p> <p>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.</p

Eurythmy therapy in chronic disease: a four-year prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Many patients with chronic diseases use complementary therapies, often provided by their physicians. In Germany, several physician-provided complementary therapies have been reimbursed by health insurance companies as part of health benefit programs. In most of these therapies, the patient has a predominantly passive role. In eurythmy therapy, however, patients actively exercise specific movements with the hands, the feet or the whole body. The purpose of this study was to describe clinical outcomes in patients practising eurythmy therapy exercises for chronic diseases.</p> <p>Methods</p> <p>In conjunction with a health benefit program, 419 outpatients from 94 medical practices in Germany, referred to 118 eurythmy therapists, participated in a prospective cohort study. Main outcomes were disease severity (Disease and Symptom Scores, physicians' and patients' assessment on numerical rating scales 0–10) and quality of life (adults: SF-36, children aged 8–16: KINDL, children 1–7: KITA). Disease Score was documented after 0, 6 and 12 months, other outcomes after 0, 3, 6, 12, 18, 24, and (SF-36 and Symptom Score) 48 months.</p> <p>Results</p> <p>Most common indications were mental disorders (31.7% of patients; primarily depression, fatigue, and childhood emotional disorder) and musculoskeletal diseases (23.4%). Median disease duration at baseline was 3.0 years (interquartile range 1.0–8.5). Median number of eurythmy therapy sessions was 12 (interquartile range 10–19), median therapy duration was 119 days (84–188).</p> <p>All outcomes improved significantly between baseline and all subsequent follow-ups (exceptions: KITA Psychosoma in first three months and KINDL). Improvements from baseline to 12 months were: Disease Score from mean (standard deviation) 6.65 (1.81) to 3.19 (2.27) (p < 0.001), Symptom Score from 5.95 (1.75) to 3.49 (2.12) (p < 0.001), SF-36 Physical Component Summary from 43.13 (10.25) to 47.10 (9.78) (p < 0.001), SF-36 Mental Component Summary from 38.31 (11.67) to 45.01 (11.76) (p < 0.001), KITA Psychosoma from 69.53 (15.45) to 77.21 (13.60) (p = 0.001), and KITA Daily Life from 59.23 (21.78) to 68.14 (18.52) (p = 0.001). All these improvements were maintained until the last follow-up. Improvements were similar in patients not using diagnosis-related adjunctive therapies within the first six study months.</p> <p>Adverse reactions to eurythmy therapy occurred in 3.1% (13/419) of patients. No patient stopped eurythmy therapy due to adverse reactions.</p> <p>Conclusion</p> <p>Patients practising eurythmy therapy exercises had long-term improvement of chronic disease 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 eurythmy therapy can be useful for patients motivated for this therapy.</p