Mechanistic Evidence of Andrographis paniculata (Burm. f.) Wall. ex Nees, Pelargonium sidoides DC., Echinacea Species and a Combination of Hedera helix L., Primula veris L./Primula elatior L. and Thymus vulgaris L./Thymus zygis L. in the Treatment of Acute, Uncomplicated Respiratory Tract Infections: A Systematic Literature Review and Expert Interviews.

Reducing inappropriate antibiotic (AB) use by using effective non-antibiotic treatments is one strategy to prevent and reduce antimicrobial resistance (AMR). Andrographis paniculata (Burm. f.) Wall. ex Nees, Pelargonium sidoides DC., Echinacea species and a combination of ivy (Hedera helix L.), primrose (Primula veris L./Primula elatior L.) and thyme (Thymus vulgaris L./Thymus zygis L.) have promising clinical effects in uncomplicated, acute upper respiratory tract infections (URTI) treatment. However, mechanistic evidence of these herbal treatments is lacking. The objective of this Pstudy is to provide an overview of mechanistic evidence for these effects. Thirty-eight databases were searched. Included studies were mechanistic studies (in vitro, animal, and human studies and reviews) on these herbs; published before June 2021. Non-mechanistic studies or studies on combinations of herbs other than ivy/primrose/thyme were excluded. Furthermore, three experts in traditional, complementary and integrative healthcare (TCIH) research and pharmacognosy were interviewed to collect additional expert knowledge. The results show that A. paniculata acts through immunomodulation and antiviral activity, possibly supplemented by antibacterial and antipyretic effects. P. sidoides acts through antiviral, indirect antibacterial, immunomodulatory and expectorant effects. Echinacea species likely act through immunomodulation. The combination of ivy/primrose/thyme combines secretolytic and spasmolytic effects from ivy with antibacterial effects from thyme. Studies on primrose were lacking. This mechanistic evidence supports the difference-making evidence from clinical studies, contributes to evidence-based recommendations for their use in URTI treatment, and guides future mechanistic studies on URTI treatments.

Anthroposophic Medicinal Products: A Literature Review of Features, Similarities and Differences to Conventional Medicinal Products, Scientific and Regulatory Assessment.

Background: Regulatory assessment of anthroposophic medicinal products (AMPs) can be challenging due to their specific features. Objective: The aim of this paper is therefore to provide adequate scientific information on AMPs for regulatory purposes. Methods: A literature review was executed with database searches in PubMed, Cinahl, Merkurstab, Anthromedics, and https://iaap-pharma.org/. Search terms were: anthroposophic medicinal products, anthroposophic medicines, anthroposophic pharmacy. There was no language restriction; searches were executed from onset until June 11, 2020. In addition, experts were invited to suggest relevant literature. Results: Eighty-seven of 660 identified publications were included. The system of anthroposophic medicine (AM) with its conceptual background and various aspects of AMPs was described: definition, pharmaceutical properties, an example of AMP development, use in clinical practice, similarities with and differences to conventional medicinal products, societal aspects, scientific and regulatory assessment. Conclusion: AMPs are part of the integrative whole medical system of AM. AMPs are manufactured according to Good Manufacturing Practice and national drug regulations and have an excellent safety status; the limited available evidence suggests clinical benefits. Current drug regulation of AMPs in the EU and most European countries does not take the special properties of AMPs into account. Future research should focus on appropriate methodologies for the evaluation of effects of AMPs as part of the AM whole medical system, the scientific quality of its non-atomistic holistic ontological position, and the integration of AM and conventional medicine in clinical practice. Future policies should focus on appropriate ways of addressing regulatory challenges to AMPs.

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.

Corrigendum to "The Contribution of Complementary and Alternative Medicine to Reduce Antibiotic Use: A Narrative Review of Health Concepts, Prevention, and Treatment Strategies".

[This corrects the article DOI: 10.1155/2019/5365608.].

Patient-reported quality of care in anthroposophic and integrative medicine: A scoping review.

OBJECTIVE: To investigate how, and to what extent, patient-reported quality of care is measured in Anthroposophic and Integrative Medicine (AM/IM). METHODS: Scoping review of evaluation studies of patient-reported quality of care and development studies of PREMs and/or PROMs in AM/IM, using five stages of Arksey's methodological framework. SEARCH STRATEGY: Literature search in twelve relevant databases. DATA EXTRACTION: Basic information, added categories: Focus; PREMs/PROMs; Evaluation measures; Patient involvement; Use of results. RESULTS: Sixty-four included studies: 30 quantitative, 20 qualitative and 14 mixed-methods studies. Quantitative studies showed a wide variety of instruments and qualitative studies showed a meaningful list of evaluation themes. Most prevalent themes: Agency & Empowerment; Patient-provider relationship; Perceived effectiveness; Coping & Psychological functioning; Inner awareness; Meaning; and General wellbeing. Seven studies report concrete, coherent, patient-derived evaluation measures with emphasis on PROMs and/or PREMs. CONCLUSION: Patient-reported quality of care was not measured in a standardised way. Knowledge gap: in general, quantitative studies lack patient-derived measures and qualitative studies lack development of concrete evaluation measures. Many AM/IM evaluation aspects connect with patient-centred care. PRACTICE IMPLICATION: The international field of AM/IM would benefit from the development of a core set of validated PROMs and PREMs to further enhance its scientific underpinning.

The Effectiveness of Art Therapy for Anxiety in Adult Women: A Randomized Controlled Trial.

OBJECTIVES: Art therapy (AT) as a treatment option for anxiety is regularly employed in clinical practice, but scientific evidence for its effectiveness is lacking, since this intervention has hardly been studied. The aim was to study the effectiveness of AT on anxiety in adult women. The specific type of AT studied was anthroposophic AT. METHODS: A RCT comparing AT versus a waiting list (WL) condition on anxiety symptom severity, quality of life, and emotion regulation. Factors influencing treatment outcome were additionally explored. Participants were women, aged 18-65 years, diagnosed with generalized anxiety disorder, social anxiety disorder or panic disorder, with moderate to severe anxiety symptoms. The trial was registered in the Dutch Trial Registration (NTR28143). RESULTS: Fifty-nine women were included, of which 47 completed the trial. Both per-protocol and intention-to treat analyses demonstrated effectiveness of AT compared to WL, showing a reduction in anxiety, an increase in subjective quality of life (both with large effects) and an improvement in accessibility of emotion regulation strategies (medium effect). Treatment effects remained after 3 months follow-up. Improved acceptance of emotions and improved goal-oriented action are aspects of emotion regulation that are associated with the decrease in anxiety level. CONCLUSION: AT is effective in reducing anxiety symptoms, improving quality of life and aspects of emotion regulation. Future RCTs should use active controls (treatment as usual) and study cost-effectiveness.

The Contribution of Complementary and Alternative Medicine to Reduce Antibiotic Use: A Narrative Review of Health Concepts, Prevention, and Treatment Strategies.

AIM: The aim of this narrative review was to explore the potential contributions of CAM to reduce antibiotic use. METHODS: We searched PubMed, Embase, and Cochrane Database of Systematic Reviews with a specific, limited set of search terms and collected input from a group of expert CAM researchers to answer the question: What is known about the contribution of CAM health and health promotion concepts, infection prevention, and infection treatment strategies to reduce antibiotic use? Results. The worldview-related CAM health concepts enable health promotion oriented infection prevention and treatment aimed at strengthening or supporting the self-regulating ability of the human organism to cope with diseases. There is some evidence that the CAM concepts of health (promotion) are in agreement with current conceptualization of health and that doctors who practice both CAM and conventional medicine prescribe less antibiotics, although selection bias of the presented studies cannot be ruled out. There is some evidence that prevention and some treatment strategies are effective and safe. Many CAM treatment strategies are promising but overall lack high quality evidence. CONCLUSIONS: CAM prevention and treatment strategies may contribute to reducing antibiotic use, but more rigorous research is necessary to provide high quality evidence of (cost-)effectiveness.

An assessment of the scientific status of anthroposophic medicine, applying criteria from the philosophy of science.

OBJECTIVES: The objective was to evaluate the scientific status of anthroposophic medicine (AM) according to demarcation criteria proposed in contemporary philosophy of science. DESIGN: Criteria for what is science were retrieved from eight publications in the philosophy of science, focusing either on science in medicine or on the demarcation between science and pseudoscience or non-science. Criteria were combined, redundancies were excluded, and the final set of criteria was ordered in a logical sequence. The analysis yielded 11 demarcation criteria (community, domain, problems, goals, axiomatic basis, conceptual basis, quality of concepts, methodology, deontic basis, research products, tradition). RESULTS: Assessing the scientific status of AM according to the 11 criteria, all criteria were fulfilled by AM. DISCUSSION: AM is grounded on the notion that specific non-atomistic holistic formative forces exist and can be empirically and rationally assessed. From a position claiming that such holistic forces cannot possibly exist or cannot be empirically and rationally assessed, the axiomatic and conceptual basis of AM can be contested. However, such an a priori rejection is problematic in the presence of empirical evidence supporting the validity of holistic concepts, as discussed in the paper. Future research should therefore focus on the tenability of the ontological reductionist position in science and on the further validation of AM non-atomistic holistic concepts, methods and practices. CONCLUSION: In this analysis, using criteria from philosophy of science, AM fulfilled all 11 criteria for what is science.

Do NHS GP surgeries employing GPs additionally trained in integrative or complementary medicine have lower antibiotic prescribing rates? Retrospective cross-sectional analysis of national primary care prescribing data in England in 2016.

OBJECTIVE: To determine differences in antibiotic prescription rates between conventional General Practice (GP) surgeries and GP surgeries employing general practitioners (GPs) additionally trained in integrative medicine (IM) or complementary and alternative medicine (CAM) (referred to as IM GPs) working within National Health Service (NHS) England. DESIGN: Retrospective study on antibiotic prescription rates per STAR-PU (Specific Therapeutic group Age-sex weighting Related Prescribing Unit) using NHS Digital data over 2016. Publicly available data were used on prevalence of relevant comorbidities, demographics of patient populations and deprivation scores. SETTING: Primary Care. PARTICIPANTS: 7283 NHS GP surgeries in England. PRIMARY OUTCOME MEASURE: The association between IM GPs and antibiotic prescribing rates per STAR-PU with the number of antibiotic prescriptions (total, and for respiratory tract infection (RTI) and urinary tract infection (UTI) separately) as outcome. RESULTS: IM GP surgeries (n=9) were comparable to conventional GP surgeries in terms of list sizes, demographics, deprivation scores and comorbidity prevalence. Negative binomial regression models showed that statistically significant fewer total antibiotics (relative risk (RR) 0.78, 95% CI 0.64 to 0.97) and RTI antibiotics (RR 0.74, 95% CI 0.59 to 0.94) were prescribed at NHS IM GP surgeries compared with conventional NHS GP surgeries. In contrast, the number of antibiotics prescribed for UTI were similar between both practices. CONCLUSION: NHS England GP surgeries employing GPs additionally trained in IM/CAM have lower antibiotic prescribing rates. Accessibility of IM/CAM within NHS England primary care is limited. Main study limitation is the lack of consultation data. Future research should include the differences in consultation behaviour of patients self-selecting to consult an IM GP or conventional surgery, and its effect on antibiotic prescription. Additional treatment strategies for common primary care infections used by IM GPs should be explored to see if they could be used to assist in the fight against antimicrobial resistance.

Whole Medical Systems versus the System of Conventional Biomedicine: A Critical, Narrative Review of Similarities, Differences, and Factors That Promote the Integration Process.

BACKGROUND: There is an increasing need for a worldwide professional integration of conventional medicine and traditional/complementary whole medical systems (WMSs). However, the integration is perceived by conventional medicine as problematic or unacceptable, because of a supposed lack of evidence for specific effects of WMSs therapies and supposed prescientific or unscientific paradigms of WMSs. OBJECTIVES: To review the literature on the features of WMSs, similarities and differences between conventional medicine and WMSs, and scientific and clinical practice issues that should be dealt with in order to promote the integration process. METHODS: A critical, narrative review of the literature on six WMSs. RESULTS AND CONCLUSIONS: Key factors for the integration of WMSs and conventional medicine are as follows: legal frameworks, quality standards, high-quality research on safety and efficacy of WMS interventions, infrastructure, and financial resources. For scientific assessment of WMSs, there are unresolved ontological, epistemological, and methodological issues and issues of diagnostics, therapy delivery, and outcome assessment in clinical practice. Future research not only should be directed at quality assurance and generating the necessary data on safety and efficacy/effectiveness but also should address more fundamental (ontological, epistemological, and methodological) issues, in order to overcome the differences between WMSs and conventional medicine.

The Contribution of Anthroposophic Medicine to Self-Management: An Exploration of Concepts, Evidence, and Patient Perspectives.

BACKGROUND: In Western healthcare policies, promotion of self-management of patients is an important topic. Currently, there is also a worldwide interest in the integration of complementary and alternative medicine (CAM) and conventional medicine into integrative medicine. This article explores the contribution of anthroposophic medicine (AM) to the promotion of self-management of patients. MATERIAL AND METHODS: The scientific literature on concepts of, evidence on and experiences of patients with AM was explored. RESULTS: The AM approach contributes to: (1) a patient-centered, collaborative promotion of patient self-management by means of application of basic values (equivalence, servitude, and presence of mind) and specific methods; (2) a better coping with health-related issues by providing a spiritual worldview that serves as a coping strategy; by treating patients in such a way that they (further) develop self-regulating functioning, both on the physiological and the psychosocial level, thus enabling the self-management of disease-related symptoms; and by treating with (non-verbal) therapies that improve emotion-focused coping skills; and (3) a better self-monitoring of: one's own activity during treatment and in dealing with treatment- and health-related issues, and the physiological and/or psychological responses to these (self-reflection) activities. CONCLUSION: AM provides specific contributions to promoting self-management of patients.

The Development of an Anthroposophic, Whole Medical System, Healthcare Program for Patients with Depressive Disorders.

OBJECTIVES: The aim of the study was to develop a whole medical system healthcare program as an alternative for group-oriented guidelines and as a basis for future studies on safety and (cost) effects. Mild to moderately severe depressive disorders were chosen as an illustrative example. DESIGN: Literature surveys, monodisciplinary expert interviews, and multidisciplinary panel discussions were employed to describe the whole medical system, its important elements, and the way the important elements are integrated in daily practice. RESULTS: The treatment of depressive disorders consists of four separate treatment phases in which 10 specific treatment goals are identified. Different disciplines may contribute to each goal. This gives an opportunity for the individualization of care. Within each discipline multiple options per goal are identified which leads to additional possibilities to individualize care. CONCLUSIONS: Individualized healthcare for patients with mild to moderately severe depressive disorders can be described in terms of treatment goals and treatment options to allow for personalization. The program may serve as the basis for future measurement of quality, cost effectiveness, and safety of provided care.

Patient-centered outcomes on quality of life and anthroposophic healthcare: a qualitative triangulation study.

PURPOSE: To provide a qualitative investigation of aspects that matter to patients regarding quality of life (QOL) and other perceived treatment effects of anthroposophic healthcare (AH). It is a first step in the development of patient reported outcome measures (PROMs) for AH. Hence, it will contribute to the evaluation of AH quality from patients' perspectives. METHOD: Within-method triangulation of four qualitative data sources is: (1) Survey of 2063 patients of AH general practitioners; single open item; (2) Survey of 34 patients of AH nurses; single open item; (3) and (4) Sixteen semi-structured interviews with patients. The data sources contained patients' qualitative reports on contribution of treatment to QOL, other perceived treatment effects and/or quality of care aspects. Content analysis Construction of items and domains by open, axial and selective coding. RESULTS: Twelve domains regarding quality of life are found: Recovery/Symptom reduction, Active contribution/Autonomy, General well-being, Meaning, Rest/Relaxation, Functioning, Energy/Strength, Care relationship, Natural healing, Mindful inner attitude, Being well informed and Social relations. The interviews demonstrate relations between domains. CONCLUSIONS: The findings give a comprehensive insight into aspects of care that are relevant to patients, providing a first step to develop PROMs for AH. Findings show a broadening of domains compared to existing measurement instruments and show close similarities with the recently developed concept of "positive health." Extending QOL instruments with a broader set of domains would give concrete tools to improve evaluation of quality of care and make this evaluation more in line with aspects that matter to AH patients.

Resistance to Antibiotics and Antifungal Medicinal Products: Can Complementary and Alternative Medicine Help Solve the Problem in Common Infection Diseases? The Introduction of a Dutch Research Consortium.

The increase of antibiotic resistance worldwide, rising numbers of deaths and costs associated with this, and the fact that hardly any new antimicrobial drugs have been developed during the last decade have increased the interest in Complementary and Alternative Medicine (CAM) therapeutic interventions, if proven safe and effective. Observational studies on clinical CAM practices demonstrate positive effects of treatment of infections with CAM therapies (clinical effects, patient satisfaction) in combination with small percentages of antibiotics prescription. However, Cochrane reviews and other studies demonstrate that in most instances the quality of clinical trials on CAM treatment of infections is currently too low to provide sufficient evidence. Therefore a Dutch consortium on (in vitro and clinical) scientific research on CAM and antibiotic resistance has been formed. The aim and objective of the consortium is to establish an enduring partnership and to develop expertise to further develop and investigate safe and effective CAM treatments for infectious diseases of humans (and animals). A first ongoing project on the development of safe and effective biobased CAM antimycotics in women with (recurrent) vaginal candidiasis infection is introduced.

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.

A 6-year comparative economic evaluation of healthcare costs and mortality rates of Dutch patients from conventional and CAM GPs.

OBJECTIVES: To compare healthcare costs and mortality rates of Dutch patients with a conventional (CON) general practitioner (GP) and patients with a GP who has additionally completed training in complementary and alternative medicine (CAM). DESIGN: Comparative economic evaluation. SETTING: Database from the Dutch insurance company Agis. PARTICIPANTS: 1,521,773 patients (98.8%) from a CON practice and 18,862 patients (1.2%) from a CAM practice. MAIN OUTCOME MEASURES: Annual information on five types of healthcare costs for the years 2006-2011: care by GP, hospital care, pharmaceutical care, paramedic care and care covered by supplementary insurance. Healthcare costs in the last year of life. Mortality rates. RESULTS: The mean annual compulsory and supplementary healthcare costs of CON patients are respectively €1821 (95% CI 1813 to 1828) and €75.3 (95% CI 75.1 to 75.5). Compulsory healthcare costs of CAM patients are €225 (95% CI 169 to 281; p<0.001; 12.4%) lower and result mainly from lower hospital care costs (€165; 95% CI 118 to 212; p<0.001) and lower pharmaceutical care costs (€58; 95% CI 41 to 75; p<0.001), especially in the age categories 25-49 and 50-74 years. The costs in the last year of life of patients with CAM, GPs are €1161 (95% CI -138 to 2461; p<0.1) lower. This difference is entirely due to lower hospital costs (€1250; 95% CI 19 to 2481; p<0.05). The mean annual supplementary costs of CAM patients are €33 (95% CI 30 to 37; p<0.001; 44%) higher. CAM patients do not have lower or higher mortality rates than CON patients. CONCLUSIONS: Dutch patients whose GP additionally completed training in CAM on average have €192 (10.1%) lower annual total compulsory and supplementary healthcare costs and do not live longer or shorter than CON patients.

The consumer quality index anthroposophic healthcare: a construction and validation study.

BACKGROUND: Accounting for the patients' perspective on quality of care has become increasingly important in the development of Evidence Based Medicine as well as in governmental policies. In the Netherlands the Consumer Quality (CQ) Index has been developed to measure the quality of care from the patients' perspective in different healthcare sectors in a standardized manner. Although the scientific accountability of anthroposophic healthcare as a form of integrative medicine is growing, patient experiences with anthroposophic healthcare have not been measured systematically. In addition, the specific anthroposophic aspects are not measured by means of existing CQ Indexes. To enable accountability of quality of the anthroposophic healthcare from the patients' perspective the aim of this study is the construction and validation of a CQ Index for anthroposophic healthcare. METHOD: Construction in three phases: Phase 1. Determining anthroposophic quality aspects: literature study and focus groups. Phase 2. Adding new questions and validating the new questionnaire. Research population: random sample from 7910 patients of 22 anthroposophic GPs. DATA COLLECTION: survey, mixed mode by means of the Dillman method. Measuring instrument: experience questionnaire: CQ Index General Practice (56 items), added with 27 new anthroposophic items added and an item-importance questionnaire (anthroposophic items only). STATISTICAL ANALYSES: Factor analysis, scale construction, internal consistency (Chronbach's Alpha), inter-item-correlation, discriminative ability (Intra Class Correlation) and inter-factor-correlations. Phase 3. Modulation and selection of new questions based on results. Criteria of retaining items: general: a limited amount of items, statistical: part of a reliable scale and inter-item-correlation <0,7, and theoretical. RESULTS: Phase 1. 27 anthroposophic items. Phase 2. Two new anthroposophic scales: Scale AntroposophicTreatmentGP: seven items, Alpha=0,832, ICC=4,2 Inter-factor-correlation with existing GP-scales range from r=0,24 (Accessibility) to r=0,56 (TailoredCare). Scale InteractionalStyleGP: five items, Alpha=0,810, ICC=5,8, Inter-factor-correlation with existing GP-scales range from r=0,32 (Accessibility) to r=0,76 (TailoredCare). Inter-factor-correlation between new scales: r=0,50. Phase 3: Adding both scales and four single items. Removing eleven items and reformulating two items. CONCLUSION: The CQ Index Anthroposophic Healthcare measures patient experiences with anthroposophic GP's validly and reliably. Regarding the inter-factor-correlations anthroposophic quality aspects from the patients' perspective are mostly associated with individually tailored care and patient centeredness.

Adverse drug reactions to anthroposophic and homeopathic solutions for injection: a systematic evaluation of German pharmacovigilance databases.

PURPOSE: Medicinal solutions for injection are frequently applied in anthroposophic medicine and homeopathy. Despite their extensive use, there is little data published on the safety of these products. Therefore, we investigated the safety of anthroposophic and homeopathic solutions for injection through a systematic evaluation of adverse drug reactions (ADRs). METHODS: ADRs were extracted from the pharmacovigilance databases of eight German manufacturers. Analysed ADRs included case reports in humans only, (spontaneous) case reports from post-marketing surveillance, literature and clinical/safety trials. RESULTS: Between 2000 and 2009, in total, 303 million ampoules for injection were sold, and 486 case reports were identified, corresponding to a total number of 1180 ADRs. Of all case reports, 71.8% (349/486) included ADRs that were listed (e.g. stated in package leaflet), and 9.5% (46/486) of the reports were classified as serious. The most frequently reported ADRs were pruritus, followed by angioedema, diarrhoea and erythema. A total of 27.3% (322/1180) were localized reactions for example; application or injection site erythema, pain, swelling and inflammation. The overall reporting rate of ADRs associated with injections was less than 4 per 1 million sold ampoules and classified as very rare. CONCLUSIONS: Our systematic evaluation demonstrated that the reporting rate of ADRs associated with anthroposophic and homeopathic solutions for injection is very low. Most reported ADRs were listed, and one quarter consisted of local reactions. These findings suggest a low risk profile for solutions for injection as therapeutically applied in anthroposophic medicine and homeopathy.

Development of systems biology-oriented biomarkers by permuted stepwise regression for the monitoring of seasonal allergic rhinitis treatment effects.

BACKGROUND: The immune system, a complex set of integrated responses, often cannot be explained, predicted, or monitored by examining its separate components as biomarkers. Combining different components may therefore be a suitable approach to develop relevant biomarkers reflecting immune system functioning in an appropriate way. METHODS: Here we compute and test pattern variables that should reflect immune system functioning on the systems level. Computation was based on a dataset (from a randomized controlled trial comparing two routes of administration) of allergen-specifically induced expression levels of cytokines (IL-1ß, IL-5, IL-10, IL-12, IL-13, IL-17, IFN-γ and TNF-α) and symptom severity scores from 22 seasonal allergic rhinitis (SAR) patients measured before and after six weeks of treatment with medicinal products containing Citrus and Cydonia. By means of stepwise regression analyses we explored and tested pattern variables of the immunological data using permuted stepwise regression (PStR) to distinguish optimally between (immunological) baseline and post-baseline data for the whole treatment group (22 patients) and the two separate treatment groups (11 patients in each group). The validity of the stepwise selection method for the computed pattern variables was tested by means of random permutation tests and evaluated with the cross-validated correct rate of classification (CV correct). RESULTS: For the total group a pattern variable was computed with three variables: IL-10 (day 7), TNF-α (day 1) and IL-10 (day 1) (CV correct: 0.91; p<0.001; R(2)=0.66), demonstrating a small improvement from the model with IL-10 (day 7) only (CV correct: 0.84; p<0.001; R(2)=0.47). For the subcutaneous injection group a pattern variable was computed with four variables: IL-10 (day 7), IL-10 (day 1), IL-17 (day 7) and IFN-γ (day 7) (CV correct: 0.90; p<0.01; R(2)=0.78), demonstrating a very small improvement from the model with IL-10 (day 7) only (CV correct: 0.86; p<0.01; R(2)=0.58). For the nasal spray group a pattern variable was computed with three variables: IL-10 (day 7), TNF-α (day 1) and IL-10 (day 1) (CV correct: 0.95; p<0.01; R(2)=0.79), demonstrating a moderate improvement from the model with IL-10 (day 7) only (CV correct: 0.79; p<0.05; R(2)=0.37). CONCLUSION/DISCUSSION: In this study three robust systems biology-oriented biomarkers for the monitoring of SAR were computed that demonstrated small to moderate improvement compared to monitoring of a single cytokine (IL-10 (day 7)) (CV correct improvement: 0.07 (total group), 0.04 (subcutaneous injection group), 0.16 (nasal spray group)). Further computation and biomarker validation with larger datasets, including data from healthy persons and SAR patients, are indicated.