A non-interventional, observational study of a fixed combination of pepsin and amino acid hydrochloride in patients with functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a gastrointestinal disorder characterized by recurrent and diverse symptoms and pathophysiology that remains unexplained following routine clinical investigation. Enzynorm®f is a pharmaceutical preparation comprising fixed amounts of pepsin of biological origin and organically bound acid in the form of amino acid hydrochloride. It is traditionally used as a mild agent to support gastric function and to stimulate the stomach's proteolytic activities in FD. METHODS: In a non-interventional, observational, post-marketing surveillance study, patients with an established diagnosis of FD were treated with a fixed combination of pepsin and amino acid hydrochloride taken as tablets three times daily for 6 weeks. The primary objective of this study was to assess the change in symptoms using the validated Gastrointestinal Symptom Score (GIS©). Secondary objectives included patients' assessment of their gastrointestinal symptoms as well as treatment safety and tolerability. RESULTS: A total of 97 patients (mean age 58.4 ± 13.9 years; 63.2% females) were included in the study, with 72 data having GIS© score data at baseline and at 6 weeks, and 34 also at 3 weeks. The overall GIS© sum score decreased by 4.1 (p < 0.0001) from 11.6 (±4.8) at baseline to 7.4 (± 4.6) reflecting an improvement of clinical symptomatology after 6 weeks of treatment. In a subgroup of 70 patients who had FD meeting the Rome III criteria a GIS© score reduction of ≥50% was observed after 3 weeks treatment in 24% and in 30.8% after 6 weeks. Adverse events were mostly gastrointestinal in nature and consistent with the underlying disease; no unexpected adverse reactions were reported. Twenty-seven patients discontinued the study, mostly because of gastrointestinal symptoms. CONCLUSION: The results of this study support the efficacy of a fixed combination of pepsin and amino acid hydrochloride for the treatment of patients with FD and also suggest good to moderate treatment tolerability. These findings should be further explored in a randomised, placebo-controlled clinical trial. CLINICAL TRIAL REGISTRATION: This study has been retrospectively registered in the ClinicalTrials.gov registry, trial identifier NCT03076411 .

Safety and compliance of a complex homeopathic drug (Contramutan N Saft) in the treatment of acute respiratory tract infections: A large observational (non-interventional) study in children and adults focussing on homeopathy specific adverse reactions versus adverse drug reactions.

BACKGROUND: This non-interventional study was performed to generate data on safety and treatment effects of a complex homeopathic drug (Contramutan N Saft). PATIENTS AND METHODS: 1050 outpatients suffering from common cold were treated with the medication for 8days. The study was conducted in 64 outpatient practices of medical doctors trained in CAM. Tolerability, compliance and the treatment effects were assessed by the physicians and by patient diaries. Adverse events were collected and assessed with specific attention to homeopathic aggravation and proving symptoms. Each adverse effect was additionally evaluated by an advisory board of experts. RESULTS: The physicians detected 60 adverse events from 46 patients (4.4%). Adverse drug reactions occurred in 14 patients (1.3%). Six patients showed proving symptoms (0.57%) and only one homeopathic aggravation (0.1%) appeared. The rate of compliance was 84% in average for all groups and the global assessment of the treatment effects attributed to "good" and "very good" in 84.9% of all patients. CONCLUSIONS: The homeopathic complex drug was shown to be safe and effective for children and adults likewise. Adverse reactions specifically related to homeopathic principles are very rare. All observed events recovered quickly and were of mild to moderate intensity.

High prevalence but limited evidence in complementary and alternative medicine: guidelines for future research.

The use of complementary and alternative Medicine (CAM) has increased over the past two decades in Europe. Nonetheless, research investigating the evidence to support its use remains limited. The CAMbrella project funded by the European Commission aimed to develop a strategic research agenda starting by systematically evaluating the state of CAM in the EU. CAMbrella involved 9 work packages covering issues such as the definition of CAM; its legal status, provision and use in the EU; and a synthesis of international research perspectives. Based on the work package reports, we developed a strategic and methodologically robust research roadmap based on expert workshops, a systematic Delphi-based process and a final consensus conference. The CAMbrella project suggests six core areas for research to examine the potential contribution of CAM to the health care challenges faced by the EU. These areas include evaluating the prevalence of CAM use in Europe; the EU cititzens' needs and attitudes regarding CAM; the safety of CAM; the comparative effectiveness of CAM; the effects of meaning and context on CAM outcomes; and different models for integrating CAM into existing health care systems. CAM research should use methods generally accepted in the evaluation of health services, including comparative effectiveness studies and mixed-methods designs. A research strategy is urgently needed, ideally led by a European CAM coordinating research office dedicated to fostering systematic communication between EU governments, the public, charitable and industry funders, researchers and other stakeholders. A European Centre for CAM should also be established to monitor and further a coordinated research strategy with sufficient funds to commission and promote high quality, independent research focusing on the public's health needs and pan-European collaboration. There is a disparity between highly prevalent use of CAM in Europe and solid knowledge about it. A strategic approach on CAM research should be established to investigate the identified gaps of knowledge and to address upcoming health care challenges.

No clinically relevant CYP3A induction after St. John's wort with low hyperforin content in healthy volunteers.

OBJECTIVE: Induction of CYP3A by St. John's wort (SJW) products with high hyperforin content is well described. Since CYP3A induction is mediated by hyperforin in a concentration-dependent manner, and SJW preparations differ significantly in hyperforin content, the aim of the study was to evaluate the effect of an SJW powder with low hyperforin content on CYP3A function. METHODS: Twenty healthy male volunteers received an SJW powder with low hyperforin content for 2 weeks. Midazolam plasma concentration time profiles were characterized after a single oral dose of 7.5 mg midazolam on the day before and on the 14th day of SJW medication. RESULTS: Midazolam AUC(0-infinity) slightly decreased from 124.0 +/- 62.5 ng/ml.h at baseline to 105.6 +/- 53.2 ng/ml.h after SJW (P < 0.05), representing a mean 11.3% decrease (95% CI: -22.8 to 0.21). No significant change in midazolam C(max), t(1/2) and t(max) was observed. For all pharmacokinetic parameters, the 90% CI for the geometric mean ratio of treatment over baseline were within the no-effect boundaries of 0.70-1.43. CONCLUSION: Administration of an SJW product with low hyperforin content resulted in a mild induction of CYP3A not considered clinically relevant.

Brachialgia paraesthetica nocturna can be relieved by "wet cupping"--results of a randomised pilot study.

BACKGROUND: Centuries ago cupping was one of the most used medical therapies worldwide but it is now regarded as an antiquated and unsafe treatment. Nevertheless it is widely used especially in Germany and China. OBJECTIVE: To investigate the effectiveness of "wet cupping" of a defined connective tissue area (over the Musculus trapezius) in patients suffering from brachialgia paresthetica nocturna. DESIGN: Monocenter, randomised, controlled, sequential clinical trial. SETTING: Section of pain management at the District Hospital of Rüdersdorf, Germany. PATIENTS: Brachialgia-patients of both sexes without age restictions were eligible if they suffered from chronical tonsillar irritations and showed pathologic indurations of the connective tissue area. INTERVENTIONS: The active group was "wet cupped" once, i.e. the skin first was scarified and then blood was drawn by applying vacuum cupping glasses. The control group was left untreated. MAIN OUTCOME MEASURE: Pre- to post-treatment change of brachialgia severeness, calculated from 1-week averages of the means of three subscales (pain, tingling and numbness), each assessed on a 0-10 numeric analogue scale. RESULTS: N=20 patients were randomised (13 women, median age 47 years). Treatment effects can be found in the active (-2.3+/-1.9 score points) but not in the control group (+0.5+/-1.0 points; p=0.002; triangle test). The results are supported by secondary outcome criteria. Adverse events were not documented in any patient. CONCLUSIONS: This study suggests short-term effects of a single wet cupping therapy, which remain at least for 1 week. As the trial lacks of an adequate and blinded placebo therapy the findings are potentially biased.

Hyperforin content determines the magnitude of the St John's wort-cyclosporine drug interaction.

OBJECTIVE: Hyperforin (HYF) has been discussed as a potential cause of the reduction in the bioavailability of numerous drugs seen with St John's wort (SJW) comedication. This study compared the effects of 2 SJW preparations with high and low HYF content on the pharmacokinetics of cyclosporine (INN, ciclosporin) (CSA). METHODS: In a crossover study, 10 renal transplant patients were randomized into 2 groups and received SJW extract (900 mg/d) containing low or high concentrations of HYF for 14 days in addition to their regular regimen of CSA. After a 27-day washout phase, patients were crossed over to the other SJW treatment for 14 days. Blood concentrations of CSA were measured by immunoassay. RESULTS: The study showed a significant difference between the effects of the 2 SJW preparations on CSA pharmacokinetics (area under the plasma concentration-time curve within one dosing interval [AUC 0-12 ], P < .0001, ANOVA). AUC 0-12 values (monoclonal) with high-HYF SJW comedication were 45% lower (95% confidence interval [CI], -37% to -54%; P < .05, Student-Newman-Keuls test) than for low-HYF SJW. The dose-corrected AUC 0-12 for CSA (monoclonal) decreased significantly compared with baseline by 52% (95% CI, -46% to -56%; P < .05) after 2 weeks of comedication with high-HYF SJW. Values of peak concentration in plasma and drug concentration at the end of one dosing interval were affected to a similar extent, with reductions by 43% (95% CI, -36% to -48%) and 55% (95% CI, -48% to -60%), respectively. In addition, a 65% (95% CI, 53% to 85%; P < .05) increase in daily CSA doses was required during high-HYF SJW treatment. In contrast, coadministration of low-HYF SJW did not significantly affect CSA pharmacokinetics and did not require CSA dose adjustments compared with baseline. CONCLUSION: HYF content of SJW extracts significantly affects the extent of the pharmacokinetic interaction between CSA and SJW.

Effect of St John's wort dose and preparations on the pharmacokinetics of digoxin.

BACKGROUND AND OBJECTIVE: St John's wort preparations vary in composition, main constituents, formulation, and daily dose administered. The aim of the study was to evaluate the possible pharmacokinetic interaction of marketed St John's wort formulations and doses with digoxin. METHODS: A randomized, placebo-controlled, parallel-group study was performed in 96 healthy volunteers in 3 study parts. A 7-day loading phase with digoxin was followed by 14 days of comedication with placebo or one of 10 St John's wort products varying in dose and formulation. The pharmacokinetics of digoxin was determined before comedication and on day 14 of comedication. RESULTS: Comedication comprised traditionally used Hypericum products; 2 g powder without hyperforin, tea, juice, oil extract, and placebo had no significant interaction with digoxin nor did hyperforin-free extract (Ze 117) or low daily doses of hyperforin-containing Hypericum powder (1 g, 0.5 g). However, comedication with the high-dose hyperforin-rich extract LI 160 resulted in a reduction of digoxin area under the curve from time 0 to 24 hours (AUC(0-24)) of -24.8% (95% confidence interval [CI], -28.3 to -21.3), a reduction in digoxin maximal plasma concentration (C(max)) of -37% (95% CI, -42 to -32), and a reduction in digoxin plasma concentration at 24 hours after previous dosing (C(trough)) of -19% (95% CI, -27 to -11). Comedication with 4 g Hypericum powder with comparable hyperforin content resulted in a reduction in digoxin AUC(0-24) of -26.6% (95% CI, -37.3 to -15.9), a reduction in digoxin C(max) of -38% (95% CI, -48 to -18), and a reduction in digoxin C(trough) of -19% (95% CI, -27 to -10). Two grams of Hypericum powder with half the hyperforin content resulted in a less prominent reduction in AUC(0-24) of -17.7% (95% CI, -21.6 to -13.7), C(max) (-21%; 95% CI, -40 to -2), and C(trough) (-13%; 95% CI, -21 to -5). CONCLUSIONS: The interaction of St John's wort and digoxin varies within St John's wort preparations and doses and seems to be correlated with the dose, particularly of hyperforin.

[A research roadmap for complementary and alternative medicine - what we need to know by 2020].

BACKGROUND: The CAMbrella coordination action was funded within the Framework Programme 7. Its aim is to provide a research roadmap for clinical and epidemiological research for complementary and alternative medicine (CAM) that is appropriate for the health needs of European citizens and acceptable to their national research institutes and healthcare providers in both public and private sectors. One major issue in the European research agenda is the demographic change and its impact on health care. Our vision for 2020 is that there is an evidence base that enables European citizens to make informed decisions about CAM, both positive and negative. This roadmap proposes a strategic research agenda for the field of CAM designed to address future European health care challenges. This roadmap is based on the results of CAMbrella's several work packages, literature reviews and expert discussions including a consensus meeting. METHODS: We first conducted a systematic literature review on key issues in clinical and epidemiological research in CAM to identify the general concepts, methods and the strengths and weaknesses of current CAM research. These findings were discussed in a workshop (Castellaro, Italy, September 7­9th 2011) with international CAM experts and strategic and methodological recommendations were defined in order to improve the rigor and relevance of CAM research. These recommendations provide the basis for the research roadmap, which was subsequently discussed in a consensus conference (Järna, Sweden, May 9­11th 2012) with all CAMbrella members and the CAMbrella advisory board. The roadmap was revised after this discussion in CAMbrella Work Package (WP) 7 and finally approved by CAMbrella's scientific steering committee on September 26th 2012. RESULTS: Our main findings show that CAM is very heterogenous in terms of definitions and legal regulations between the European countries. In addition, citizens' needs and attitudes towards CAM as well as the use and provision of CAM differ significantly between countries. In terms of research methodology, there was consensus that CAM researchers should make use of all the commonly accepted scientific research methods and employ those with utmost diligence combined in a mixed methods framework. CONCLUSIONS: We propose 6 core areas of research that should be investigated to achieve a robust knowledge base and to allow stakeholders to make informed decisions. These are: Research into the prevalence of CAM in Europe: Reviews show that we do not know enough about the circumstances in which CAM is used by Europeans. To enable a common European strategic approach, a clear picture of current use is of the utmost importance. Research into differences regarding citizens' attitudes and needs towards CAM: Citizens are the driver for CAM utilization. Their needs and views on CAM are a key priority, and their interests must be investigated and addressed in future CAM research. Research into safety of CAM: Safety is a key issue for European citizens. CAM is considered safe, but reliable data is scarce although urgently needed in order to assess the risk and cost-benefit ratio of CAM. Research into the comparative effectiveness of CAM: Everybody needs to know in what situation CAM is a reasonable choice. Therefore, we recommend a clear emphasis on concurrent evaluation of the overall effectiveness of CAM as an additional or alternative treatment strategy in real-world settings. Research into effects of context and meaning: The impact of effects of context and meaning on the outcome of CAM treatments must be investigated; it is likely that they are significant. Research into different models of CAM health care integration: There are different models of CAM being integrated into conventional medicine throughout Europe, each with their respective strengths and limitations. These models should be described and concurrently evaluated; innovative models of CAM provision in health care systems should be one focus for CAM research. We also propose a methodological framework for CAM research. We consider that a framework of mixed methodological approaches is likely to yield the most useful information. In this model, all available research strategies including comparative effectiveness research utilising quantitative and qualitative methods should be considered to enable us to secure the greatest density of knowledge possible. Stakeholders, such as citizens, patients and providers, should be involved in every stage of developing the specific and relevant research questions, study design and the assurance of real-world relevance for the research. Furthermore, structural and sufficient financial support for research into CAM is needed to strengthen CAM research capacity if we wish to understand why it remains so popular within the EU. In order to consider employing CAM as part of the solution to the health care, health creation and self-care challenges we face by 2020, it is vital to obtain a robust picture of CAM use and reliable information about its cost, safety and effectiveness in real-world settings. We need to consider the availability, accessibility and affordability of CAM. We need to engage in research excellence and utilise comparative effectiveness approaches and mixed methods to obtain this data. Our recommendations are both strategic and methodological. They are presented for the consideration of researchers and funders while being designed to answer the important and implicit questions posed by EU citizens currently using CAM in apparently increasing numbers. We propose that the EU actively supports an EU-wide strategic approach that facilitates the development of CAM research. This could be achieved in the first instance through funding a European CAM coordinating research office dedicated to foster systematic communication between EU governments, public, charitable and industry funders as well as researchers, citizens and other stakeholders. The aim of this office would be to coordinate research strategy developments and research funding opportunities, as well as to document and disseminate international research activities in this field. With the aim to develop sustainability as second step, a European Centre for CAM should be established that takes over the monitoring and further development of a coordinated research strategy for CAM, as well as it should have funds that can be awarded to foster high quality and robust independent research with a focus on citizens health needs and pan-European collaboration. We wish to establish a solid funding for CAM research to adequately inform health care and health creation decision-making throughout the EU. This centre would ensure that our vision of a common, strategic and scientifically rigorous approach to CAM research becomes our legacy and Europe's reality. We are confident that our recommendations will serve these essential goals for EU citizens.

[The Tibetan formula Padma Lax in medical practice: a retrospective case series study in constipation including 174 patients]. / Die Tibetische Rezeptur Padma Lax in der ärztlichen Praxis: Eine retrospektive Fallstudie bei Obstipation mit 174 Patienten.

BACKGROUND: The Tibetan Medicine Padma Lax has been approved in Switzerland for the treatment of constipation and bloating for over 40 years. In this study, data on the application in medical practice, as well as on effectiveness in various constipation-related symptoms and on safety and tolerability, were collected and assessed. MATERIAL AND METHODS: Physicians practicing in Switzerland documented retrospectively the course of treatment for chronic constipation, using an especially developed questionnaire. In addition to defecation frequency, data on the intensity of 12 specific symptoms of constipation were collected. RESULTS: 17 participating physicians provided data from a total of 174 patient cases, about 30% of which originated from gynecological practices. Among others, lifestyle factors and various underlying diseases, e.g. neurological or hormonal disturbances, were indicated as causes of the constipation. Safety and tolerability were very good; only 1 adverse event (a worsening of flatulence) was reported. The frequency of defecation increased significantly during treatment and 97% reached a frequency of >2 per week. On average, the frequency and intensity of all symptoms decreased, with the exception of the symptom soft/loose stools, which increased in as many patients as it decreased. The overall intensity of all symptoms decreased from a mean of 15.8 by 63% to 5.8. The proportion of patients with severe complaints (overall intensity score >20) decreased from 20.1% to 1.7%, and as a result, the group with hardly any complaints (overall intensity score ≤ 5) rose from 1.2% to 57%. 86% of the physicians and the patients rated the efficacy as good. CONCLUSIONS: Padma Lax was used in constipation of different causes and in a broad spectrum of patients. Efficacy and safety were assessed as good or very good. In spite of the limitation of the retrospective study design, the data indicate that Padma Lax is an effective and well-tolerated treatment option for chronic constipation from different causes, especially also in gynecological practice, in geriatric patients, and in patients with neurogenic constipation.

Therapeutic fasting in patients with metabolic syndrome and impaired insulin resistance.

BACKGROUND: In this study, we evaluated whether a short- to mid-term fasting therapy (7-18 days) might improve insulin resistance according to the homeostasis model assessment for insulin resistance (HOMA-IR), measured during mid-term (80 days) follow-up observation in patients with metabolic syndrome. METHODS: In this open label observational study in inpatients, criteria of metabolic syndrome were defined. Before medically controlled Buchinger fasting, a wash-out period for hypoglycemic agents was conducted. Further evaluation was carried out on day 80. RESULTS: 25 patients (13 males, 12 females, mean age 61.3 years) were included in this study (mean fasting duration 11.5 days). Out of 16 inpatients with type 2 diabetes, 4 had been treated with metformin, 3 with insulin, and 1 with glimepiride before the intervention. After therapy, body mass index (BMI), fasting insulin, fasting glucose, and HOMA-IR were all significantly reduced. Compared to baseline, HOMA-IR decreased by 33% in all patients, by 38% in patients with type 2 diabetes, and by 23% in patients without diabetes. At day 80, BMI further improved, while other parameters showed complete (insulin) or partial (glucose, HOMA-IR) rebound. At this time, HOMA-IR values showed an only insignificant improvement in 15% of all patients, in 20% of patients with type 2 diabetes, and in 6% of patients without diabetes. There was no correlation between change in BMI and change in HOMA-IR (r(2) = 0.008, baseline minus day 80). No serious side effects were observed. CONCLUSIONS: Fasting as a safe and acceptable procedure may cause short- and mid-term improvement of increased insulin resistance (HOMA-IR). Patients with type 2 diabetes benefit more than those without diabetes. A possible clinical significance of this effect should be explored in larger and controlled clinical trials.

The history of inpatient care in german departments focussing on natural healing.

We describe historic developments of inhouse facilities for natural healing in this paper, which were mainly located in German speaking regions. The naturopathic movement is a relabeling of the hydropathic movement in Germany, which was supported by a considerable proportion of the population in Germany during the mid 19th century. Due to the fact that hydropathic treatments were provided by nonmedical healers, discriminated as "quacks", there was continuous hostility between hydropathy/naturopathy and medicine. However, among the many establishments providing inhouse treatment for acute and chronic diseases over weeks there were some which were controlled by medical doctors in the 20th century and some which were implemented by government. In many of the establishments there were approaches for measuring usefulness of the treatments, some of which have been initiated explicitly for that purpose.

Clay jojoba oil facial mask for lesioned skin and mild acne--results of a prospective, observational pilot study.

BACKGROUND: External application of clay facial masks is a cosmetic procedure generally used to reduce skin lesions and to improve overall skin condition. OBJECTIVE: Collecting pilot data about self-treatment with clay jojoba oil masks on participants with acne-prone, lesioned skin and acne. METHODS: Open, prospective, observational pilot study: Participants received written information, instructions, and questionnaires without direct contact with the study physician. For 6 weeks, they applied the masks 2-3 times per week. The primary outcome is the difference of skin lesions: baseline vs. after 6 weeks. RESULTS: 194 participants (192 female, 2 male, mean age (± SE) (32.3 ± 0.7 years) returned questionnaires and diaries. 133 of these participants returned complete and precise lesion counts (per-protocol (PP) collective). A 54% mean reduction in total lesion count was observed after 6 weeks of treatment with clay facial mask. Both inflammatory and non-inflammatory skin lesions were reduced significantly after treatment compared to baseline: Median counts (MC) of pustules per affected participant were reduced from 7.0 ± 0.9 to 3.0 ± 0.5 (mean individual reduction (MIR) = 49.4%), the MC of the papules from 3.5 ± 2.2 to 1.0 ± 0.4 (MIR = 57.3%), the MC of cysts from 2.0 ± 0.8 to 0.5 ± 0.4 (MIR = 68.6%) and the MC of comedones from 26.5 ± 6.3 to 16.0 ± 4.0 (MIR = 39.1%). DLQI-average score decreased from 5.0 ± 4.5 (mean ± SE) before to 2.1 ± 2.8 after treatment. CONCLUSIONS: The present study gives preliminary evidence that healing clay jojoba oil facial masks can be effective treatment for lesioned skin and mild acne vulgaris.

Are the correct herbal claims by Hildegard von Bingen only lucky strikes? A new statistical approach.

BACKGROUND: Ancient and medieval herbal books are often believed to describe the same claims still in use today. Medieval herbal books, however, provide long lists of claims for each herb, most of which are not approved today, while the herb's modern use is often missing. So the hypothesis arises that a medieval author could have randomly hit on 'correct' claims among his many 'wrong' ones. METHODS: We developed a statistical procedure based on a simple probability model. We applied our procedure to the herbal books of Hildegard von Bingen (1098- 1179) as an example for its usefulness. Claim attributions for a certain herb were classified as 'correct' if approximately the same as indicated in actual monographs. RESULTS: The number of 'correct' claim attributions was significantly higher than it could have been by pure chance, even though the vast majority of Hildegard von Bingen's claims were not 'correct'. The hypothesis that Hildegard would have achieved her 'correct' claims purely by chance can be clearly rejected. CONCLUSION: The finding that medical claims provided by a medieval author are significantly related to modern herbal use supports the importance of traditional medicinal systems as an empirical source. However, since many traditional claims are not in accordance with modern applications, they should be used carefully and analyzed in a systematic, statistics-based manner. Our statistical approach can be used for further systematic comparison of herbal claims of traditional sources as well as in the fields of ethnobotany and ethnopharmacology.

Towards a pan-European definition of complementary and alternative medicine--a realistic ambition?

BACKGROUND: The terms used for defining complementary and alternative medicine (CAM) including the methods, procedures and therapies vary greatly. The task of the CAMbrella working group on terminology was to explore the existing CAM terminologies and to develop a pragmatic definition of CAM that is acceptable Europe-wide. This can then be used to systematically research, e.g., its prevalence and legal status and to investigate the citizens' demands on CAM and the perspectives of providers of CAM in Europe. METHODS: Terms and definitions were collected from both scientific and non-scientific sources. The terms and definitions identified were analysed and discussed among the CAMbrella working group participants on several occasions with the aim of arriving at a consensus. RESULTS: We developed a proposal for a pragmatic European definition of CAM: 'Complementary and alternative medicine (CAM) utilised by European citizens represents a variety of different medical systems and therapies based on the knowledge, skills and practices derived from theories, philosophies and experiences used to maintain and improve health, as well as to prevent, diagnose, relieve or treat physical and mental illnesses. CAM has been mainly used outside conventional health care, but in some countries certain treatments are being adopted or adapted by conventional health care.' CONCLUSION: Developing a uniform, pragmatic pan-European definition of CAM was complicated by a number of factors. These included the vast diversity of existing definitions, systems, disciplines, procedures, methods and therapies available within the EU.

Key issues in clinical and epidemiological research in complementary and alternative medicine--a systematic literature review.

BACKGROUND: In the last 2 decades there has been a large increase in publications on complementary and alternative medicine (CAM). However, CAM research methodology was heterogeneous and often of low quality. The aim of this systematic review was to investigate scientific publications with regards to general issues, concepts and strategies. We also looked at research priorities and methods employed to evaluate the clinical and epidemiological research of CAM in the past to identify the basis for consensus-based research strategies. METHODS: We performed a systematic literature search for papers published between 1990 and 2010 in 7 electronic databases (Medline, Web of Science, PsychArticles, PsycInfo, CINAHL, EMBASE and Cochrane Library) on December 16 and 17, 2010. In addition, experts were asked to nominate relevant papers. Inclusion criteria were publications dealing with research methodology, priorities or complexities in the scientific evaluation of CAM. All references were assessed in a multistage process to identify relevant papers. RESULTS: From the 3,279 references derived from the search and 98 references contributed by CAM experts, 170 papers fulfilled the criteria and were included in the analysis. The following key issues were identified: difficulties in past CAM research (e.g., randomisation, blinding), utility of quantitative and qualitative research methods in CAM, priority setting in CAM research and specific issues regarding various CAM modalities. CONCLUSIONS: Most authors vote for the use of commonly accepted research methods to evaluate CAM. There was broad consensus that a mixed methods approach is the most suitable for gathering conclusive knowledge about CAM.

A pilot feasibility study of a questionnaire to determine European Union-wide CAM use.

BACKGROUND: No questionnaire specifically measuring the core components of complementary and alternative medicine (CAM) use has been validated for use across European Union (EU) countries. We aimed to determine the face validity, acceptability and the participants' comprehension of a pre-existing questionnaire designed to measure 'CAM use', to provide a comparative, standardised questionnaire for use by health care providers, policy makers and purchasers throughout Europe. METHODS: Established procedures were employed to translate the questionnaire into 4 EU languages. The translated questionnaires were piloted on 50 healthy adults from each country who may never have used CAM. 10 participants per country also took part in audio-recorded think aloud interviews about the questionnaire. The interviews were transcribed and analysed in the language in which they were conducted; findings were summarised in English. Questionnaire data were pooled across countries, and patterns of completion and missing data were analysed. RESULTS: The questionnaire was translated into Italian, Spanish, Dutch and Romanian. The mean age of the participants was 43.6 years. 34% were male, 87.4% were either light or heavy CAM users, and 12.6% were non-users. Qualitative analysis identified common problems across countries including a 'hard-to-read' layout, misunderstood terminology and uncertainty in choosing response options. Quantitative analysis confirmed that a substantial minority of respondents failed to follow questionnaire instructions and that some questions had substantial rates of missing data. CONCLUSIONS: The I-CAM-Q has low face validity and low acceptability, and is likely to produce biased estimates of CAM use if applied in England, Romania, Italy, The Netherlands or Spain. Further work is required to develop the layout, terms, some response options and instructions for completion before it can be used across the EU.

Phytodolor® in musculoskeletal disorders: re-analysis and meta-analysis.

BACKGROUND: Treatment of rheumatic or musculoskeletal disorders (MD) is multi-disciplinary and includes herbal analgesics. Although already reviewed, no quantitative evaluation of efficacy and safety of the herbal combination Phytodolor® (STW1) is available. METHODS: We searched in databases and contacted authors and the manufacturer to identify randomized controlled trials (RCTs) examining STW1 in patients with MD. We made a reanalysis of raw data of eligible published and unpublished RCTs and pooled the results for meta-analysis according to Cochrane guidelines and intention-to-treat. Primary outcome measure was patient global assessment of efficacy, secondary outcome measure was pain at rest and on movement. Results were stratified according to treatment groups. RESULTS: Patient data of 11 RCTs were eligible for pooling. In the entire population, STW1 was significantly superior compared to placebo in patients' global assessment of efficacy (group difference for rating very good/good: 20%; placebo 48.9% and STW1 69.1%; p < 0.001; OR 0.43; 95% CI 0.28-0.65) and in the subpopulation 'other rheumatic diseases' (placebo 45.4%; STW1 72.3%; p < 0.001; OR 0.32; 95% CI 0.2-0.52), but not in the subpopulation 'gonarthrosis'. STW1 did not differ significantly compared to non-steroidal anti-inflammatory drugs (NSAIDs), neither in the entire population nor the subpopulations. Similar results were found for pain at rest and on movement. No serious adverse events (AE) but minor AE were reported (placebo 8.1%; STW1 14.2%; NSAIDs 18.9%). CONCLUSION: According to the analysed data, STW1 showed a better pain reduction than placebo in patients with pain due to MD, probably equivalent to NSAIDs, and was well tolerated.

EU FP7 project 'CAMbrella' to build European research network for complementary and alternative medicine.

BACKGROUND: The status of complementary and alternative medicine (CAM) within the EU needs clarification. The definition and terminology of CAM is heterogeneous. The therapies, legal status, regulations and approaches used vary from country to country but there is widespread use by EU citizens. A coordination project funded by the EU has been launched to improve the knowledge about CAM in Europe. OBJECTIVES AND METHODS: The project aims to evaluate the conditions surrounding CAM use and provision in Europe and to develop a roadmap for European CAM research. Specific objectives are to establish an EU network involving centres of research excellence for collaborative projects, to develop consensus-based terminology to describe CAM interventions, to create a knowledge base that facilitates the understanding of patient demand for CAM and its prevalence, to review the current legal status and policies governing CAM provision, and to explore the needs and attitudes of EU citizens with respect to CAM. Based on this information a roadmap will be created that will enable sustainable and prioritised future European research in CAM. CAMbrella encompasses 16 academic research groups from 12 European countries and will run for 36 months starting from January 2010. The project will be delivered in 9 work packages coordinated by a Management Board and directed by a Scientific Steering Committee with support of an Advisory Board. OUTPUT: The outcomes generated will be disseminated through the project's website, peer review open access publications and a final conference, with emphasis on current and future EU policies, addressing different target audiences.

A clinical surrogate model for proof of efficacy of external phytomedicines for muscle pain. Results of a randomized, placebo-controlled clinical study in volunteers with muscle pain due to physical training.

PURPOSE: Surrogate models have been postulated for (re-)registration of external remedies for pain, whose active substances are in accordance to monographs. In a new human model, we investigated an ointment consisting of high dosed herbal ingredients. METHODS: We conducted a clinical study in 32 healthy volunteers. Four muscle regions were treated with the ointments (verum on the one side and placebo on the other) in a randomized and doubleblinded manner immediately after a standardized physical exercise with individual intensity, as well as after 1, 2 and 24 h. Acute muscle pain and muscle tension for each region was documented repeatedly during the following two days by visual analogue scale (VAS). Primary outcome parameter was the difference of pain during the follow up given as area under the curve (AUC) of VAS for corresponding right and left regions, treated with verum or placebo. Also the difference of muscle tension was documented and evaluated in an analogous way. RESULTS: 30 out of 32 included patients finished the study, but developed only moderate muscle pain, with highest pain scores for extension muscles of the arm. There was less pain in the course for the verum in 3 of the 4 regions, the mean difference of individual AUCs was at highest for the extension (triceps) muscles of the arm, but between-group differences failed significance. Feeling of muscle tension was higher than that of pain, with smaller mean AUCs of verum in all 4 regions; the differences were significant in total (p<0.02) and in 2 of 4 single regions. CONCLUSIONS: Physical exercise was not intensive enough to exert clear symptoms. Our volunteers with sportive background seem not to show severe symptoms of muscle pain and muscle tension even after an intensive training. Despite low levels of symptoms, verum showed better courses of muscle tension and muscle pain. For future studies it seems better not to use volunteers with sportive background but totally untrained persons in order to achieve pronounced symptoms. The model is feasible, sensitive, inexpensive and is much more clinically relevant than those, focusing on perfusion parameters of skin.