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Ayahuasca is a plant concoction containing N,N-dimethyltryptamine (DMT) and certain β-carboline alkaloids from South America. Previous research in naturalistic settings has suggested that ingestion of ayahuasca can improve mental health and well-being; however, these studies were not placebo controlled and did not control for the possibility of expectation bias. This naturalistic observational study was designed to assess whether mental health changes were produced by ayahuasca or by set and setting. Assessments were made pre- and post-ayahuasca sessions in 30 experienced participants of ayahuasca retreats hosted in the Netherlands, Spain, and Germany. Participants consumed ayahuasca (N = 14) or placebo (N = 16). Analysis revealed a main effect of time on symptoms of depression, anxiety, and stress. Compared to baseline, symptoms reduced in both groups after the ceremony, independent of treatment. There was a main treatment × time interaction on implicit emotional empathy, indicating that ayahuasca increased emotional empathy to negative stimuli. The current findings suggest that improvements in mental health of participants of ayahuasca ceremonies can be driven by non-pharmacological factors that constitute a placebo response but also by pharmacological factors that are related to the use of ayahuasca. These findings stress the importance of placebo-controlled designs in psychedelic research and the need to further explore the contribution of non-pharmacological factors to the psychedelic experience.

Purpose: Many patients diagnosed with advanced cancer have malignant pleural effusion that does not respond to chemotherapy or radiation therapy. These patients often have respiratory symptoms, especially dyspnea. In order to relieve these symptoms, various procedures including chemical pleurodesis have been performed. Although talc is the most widely used and effective sclerosing agent, there it has various adverse effects. The objective of this study was to determine whether Viscum (ABNOVA Viscum® Fraxini Injection, manufactured by ABNOVA GmbH, Germany) could be used as an agent to replace talc in clinical practice., Methods: Data of 56 patients with malignant pleural effusion who received chemical pleurodesis after tube thoracostomy from January 2003 to December 2017 were retrospectively reviewed to analyze clinical course and response after pleurodesis with each agent., Results: After pleurodesis, changes in numeric rating scale (NRS) was 1.4 ± 1.6 in the talc group and 0.5 ± 1.5 in the Viscum group (p = 0.108). Changes in white blood cell counts after pleurodesis were 4154.8 ± 6710.7 in the talc group and 3487.3 ± 6067.7 in the Viscum group (p = 0.702). Changes in C-reactive protein (CRP) were 9.03 ± 6.86 in the talc group and 6.3 ± 7.5 in the Viscum group (p = 0.366). The success rate of pleurodesis was 93.3% in the talc group and 96% in the Viscum group (p = 0.225)., Conclusion: Viscum pleurodesis showed comparable treatment results with talc pleurodesis while its adverse effects such as chest pain and fever tended to be relatively weak.

Background: The Birch Allergoid, Tyrosine Adsorbate, Monophosphoryl Lipid A (POLLINEX ® Quattro Plus 1.0 ml Birch 100%) is an effective, well-tolerated short course subcutaneous immunotherapy. We performed 2 phase II studies to determine its optimal cumulative dose., Methods: The studies were conducted in Germany, Austria and Poland (EudraCT numbers: 2012-004336-28 PQBirch203 and 2015-000984-15 PQBirch204) using a wide range of cumulative doses. In both studies, subjects were administered 6 therapy injections weekly outside the pollen season. Conjunctival Provocation Tests were performed at screening, baseline and 3-4 weeks after completing treatment, to quantify the reduction in Total Symptom Scores (as the primary endpoint) with each cumulative dose. Multiple Comparison Procedure and Modeling analysis was used to test for the dose response, shape of the curve and estimation of the median effective dose (ED 50 ), a measure of potency., Results: Statistically significant dose responses (P < .01 & .001) were seen, respectively. The highest cumulative dose in PQBirch204 (27 300 standardized units [SU]) approached a plateau. Potency of the PQBirch was demonstrated by an ED 50 2723 SU, just over half the current dose. Prevalence of treatment-emergent adverse events was similar for active doses, most being short-lived and mild. Compliance was over 85% in all groups., Conclusion: Increasing the cumulative dose of PQBirch 5.5-fold from 5100 to 27 300 SU achieved an absolute point difference from placebo of 1.91, a relative difference 32.3% and an increase in efficacy of 50%, without compromising safety. The cumulative dose response was confirmed to be curvilinear in shape., (© 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.)

Background: Subcutaneous allergen immunotherapy with grass pollen allergoids has been proven to be effective and safe in the treatment of patients with allergic rhinoconjunctivitis. Based on the extensive cross-reactivity among Pooideae species, it has been suggested that grass pollen extracts could be prepared from a single species, rather than from a multiple species mixture., Objective: To find the optimal dose of a Phleum pratense (P. pratense) allergoid preparation and compare its efficacy and safety to a 6-grass pollen allergoid preparation., Methods: In this double-blind, placebo-controlled study (EudraCT: 2011-000674-58), three doses of P. pratense allergoid (1800 therapeutic units (TU), standard-dose 6000 TU and 18 000 TU) were compared with placebo and the marketed 6-grass pollen allergoid (6000 TU). In a pre-seasonal dosing regimen, 102 patients were randomized to five treatment groups and received nine subcutaneous injections. The primary efficacy endpoint was the change in weal size (late-phase reaction [LPR]) in response to the intracutaneous testing (ICT) before and after treatment, comparing the active allergoids to placebo. Secondary outcomes were the change in Total Nasal Symptom Score (TNSS) assessed in the allergen exposure chamber (AEC), the changes in P. pratense-serum-specific IgG 4 and the incidence of adverse events (AEs)., Results: All three doses of the P. pratense and the 6-grass pollen allergoid preparations were significantly superior to placebo for the primary outcome, whereas there were no significant differences in the change in TNSS. Compared to the standard-dose, the high-dose of P. pratense did not produce any additional significant benefit, but showed a slight increase in AEs. Yet this increase in AEs was lower than for the 6-grass pollen preparation., Conclusions & Clinical Relevance: The standard-dose of the new P. pratense allergoid was comparable to the marketed 6-grass pollen preparation at equal dose for the parameters measured., (© 2017 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.)

Background. Nonperception of efficacy ranks among the most commonly cited causes for nonadherence to sublingual immunotherapy (SLIT). Quality of life (QoL) in patients is a determining factor influencing adherence. We investigated QoL and adherence separately in SLIT patients at one pediatric practice in Germany. Methods. We conducted a noninterventional, cross-sectional, retrospective, quality-of-life survey among pediatric patients treated with SLIT. QoL was assessed using the generic SF-12 health survey in German. The items contained in the SF-12 health survey are weighted, added up, and converted to obtain a physical component score (PCS) and a mental component score (MCS). Each component score ranges from 0 to 100; the higher the score, the better the QoL perceived. Results. 201 surveyed patients who had undergone SLIT showed PCS-12 of 49.3 (± 7.0) and MCS-12 of 52.6 (± 7.2). These figures correlate strongly with those reported for the German general population (n = 2453): PCS-12 of 49.6 (± 8.7) and MCS-12 of 52.3 (± 8.0). 70.2% (73) of 104 patients were adherent at this practice. Conclusions. QoL in the SLIT patients surveyed here appears as good as that of the general population. Adherence to SLIT at this practice was remarkably better than that reported elsewhere.

Background: Intratumoral (IT) injection of European mistletoe (Viscum album L) preparations might induce local tumor response through combined cytotoxic and immunomodulatory actions of the preparations. Although promising in vitro and in vivo data, along with clinical case studies suggest the need for validation of this hypothesis in prospective trials, the safety of IT mistletoe injections has yet to be thoroughly assessed., Methods: The present study summarizes the practice and safety of off-label IT mistletoe therapy within the Network Oncology, a conjoint clinical registry of German hospitals and outpatients specialized in anthroposophic and integrative medicine. Demographic, diagnosis and treatment data of cancer patients who received IT mistletoe applications between 2007 and 2013 were assessed. Suspected adverse drug reactions (ADRs) were analyzed in terms of type, frequency, severity, seriousness and potential risk factors., Results: A total of 123 cancer patients received 862 IT mistletoe injections (preparations from Abnoba, Helixor and Iscucin). The most commonly applied preparations were Abnoba viscum Fraxini (71 patients) and Helixor Mali (54 patients). Of the total patients, 26 patients (21.1%) experienced 74 ADRs. All ADRs were in response to either Abnoba viscum Fraxini (25.4% of exposed patients) or Helixor Mali (18.5% of exposed patients). ADRs were mostly body temperature or immune related and of mild (83.8%) or moderate (14.9%) intensity. Only one possible ADR was described as severe (hypertension) and no serious ADRs occurred. The frequency of ADRs to IT mistletoe injections was 3 times and 5 times higher than has previously been found for subcutaneous and intravenous applications of mistletoe, respectively., Conclusion: IT injection of mistletoe preparations resulted in a relatively high frequency of ADRs. Nearly all ADRs were mild to moderate however, and no serious ADRs occurred. Furthermore, it is possible that immune-related ADRs such as pyrexia and local inflammatory reactions might be critical for tumor response. In light of these results, IT mistletoe therapy seems to be safe and prospective trials are recommended., (© The Author(s) 2014.)

Objectives: The side effects, nonresponse, and prejudices against conventional pharmacological treatments call for complementary or alternative medical treatments (CAM) for ADHD. One possible treatment, at least for cognitive problems, might be the administration of Ginkgo biloba, though evidence is currently rare. This study tests the clinical efficacy of a Ginkgo biloba special extract (EGb 761®) and its correlation with brain electrical activity in children with ADHD combined type according to DSM-IV., Method: In this open clinical pilot study, EGb 761® was administered to 20 children with ADHD over 3 to 5 weeks. Dosage was increased to a maximum of 240 mg daily if attention problems persisted. Possible drug side effects were assessed using the Side Effect Rating Scale. Efficacy was assessed in a multilevel approach including clinical assessment, quality of life (QoL), as well as performance and preparatory brain-electrical activity evoked during a Continuous Performance Test (Cue-CNV in the CPT)., Results: A very low rate of mild adverse effects occurred during the observation period. Following EGb 761® administration, possible improvements in QoL, ADHD core symptoms as well as CPT performance were detected. Improved core symptoms were positively related to elevated CNV amplitude., Conclusion: This preliminary evidence suggests that EGb 761® at a maximal dosage of 240 mg daily might be a clinically useful alternative treatment for children with ADHD, but further evidence is required before firm conclusions can be made.

Context: Painful oral mucositis is an almost inevitable side effect of radiotherapy of head and neck tumors that simultaneous chemotherapy intensifies and that is notoriously difficult to treat. In a previous study, chemotherapy-induced stomatitis in children undergoing bone marrow transplantation responded well to the homeopathic complex remedy Traumeel S., Objective: To evaluate the efficacy of Traumeel S in the management of radiation-induced oral mucositis in patients with head and neck tumors., Design: The research team designed a nonrandomized, prospective, observational study with matched pairs., Setting: The research team performed the study in a tertiary cancer-care center at the Institute of Radiotherapy and Special Oncology, Medical School Hanover, Germany., Participants: The participants were 20 patients who were receiving radiotherapy or radiochemotherapy for head and neck tumors., Intervention: Five times per day during the observational period, participants self-administered daily mouth rinses with either sage tea (Salvia officinalis, control group) or Traumeel S solution (intervention group)., Outcome Measures: Two independent physicians determined the grade of oral mucositis at least once per week, and the research team derived the degree of oral pain from diaries that participants kept., Results: Both groups were comparable in terms of tumor and treatment characteristics. The research team could not confirm any appreciable specific effect of Traumeel S on the primary endpoints; the limited reduction in pain for the intervention group compared to the control group was not significant, and the more frequent analgesia in the Traumeel S group most likely explained that reduction. Among the secondary endpoints, loss of taste and swallowing difficulty responded to Traumeel S to some extent., Conclusions: Traumeel S may have some potential in the treatment of radiation-induced oral mucositis, but its possible effects need confirmation by further studies. This article discusses some methodological requirements.

Background: The effectiveness of injection therapy for low-back pain is still debatable. We compared the efficacy of local injections of the homeopathic preparation Disci/Rhus toxicodendron compositum (verum) with placebo injections and with no treatment in patients with chronic low back pain., Methodology/principal Findings: In a randomized controlled partly double blind multicenter trial patients with chronic low back pain from 9 German outpatient clinics were enrolled and randomly allocated in a 1∶1∶1 ratio to receive subcutaneous injections (verum or placebo) into painful sites on the lower back over 12 treatment sessions within eight weeks, or no treatment (rescue pain medication with paracetamol or NSAIDs). All trial personnel and participants were masked to treatment allocation. The primary outcome measure was the average pain intensity over the last seven days on a visual analogue scale (0-100 mm, 0 = no pain, 100 = worst imaginable pain) after eight weeks. Follow-up was 26 weeks. Primary analysis was by intention to treat. Between August 2007 and June 2008, 150 patients were randomly allocated to three groups (51 verum, 48 placebo and 51 no treatment). The mean baseline-adjusted low back pain intensity at week eight was: verum group 37.0 mm (97.5% CI 25.3;48.8), no treatment group 53.0 (41.8;64.2), and placebo group 41.8 (30.1;53.6). The verum was significantly superior to no treatment (P = 0.001), but not to placebo (P = 0.350). No significant side effects were reported., Conclusions/significance: The homeopathic preparation was not superior to placebo. Compared to no treatment injections resulted in significant and clinical relevant chronic back pain relief., Trial Registration: ClinicalTrials.gov NCT00567736.

Aim: The Nasal Spray Evaluation Questionnaire is a standardized means to evaluate hedonicity of nasal sprays in the English speaking countries. To date, there is no such questionnaire for German speaking patients. The here presented study aimed at evaluating the translated questionnaire. Three nasal sprays were tested and the questionnaire was used to estimate sensory hedonicity. Finally, the questionnaire was improved and can now serve as a standardized means to measure nasal sensory perceptions., Material and Methods: The questionnaire was literally translated from English to German. There were three groups of 60 patients each presenting with the sensation of a 'dry nose' to a secondary medical center with a board certified otolaryngologist. The ingredients of the three different nasal sprays varied only in one phytotherapeutic addition. The first evaluation of the nasal spray was conducted immediately after application of the nasal spray, and two minutes after application. A third and optional telephone survey was performed several days later after continuous use of the spray., Results: The different evaluations of nasal sprays were already lined out after the first questionnaire. It could serve as a new, reliable and reproduceable tool for the evaluation of nasal sensory perceptions., Discussion: The questionnaire served as an adequate tool to estimate hedonicity of nasal sprays. First results of the German version show, however, that it could facilitate the evaluation by restructuring the questionnaire. Continuously marking good grades with high points (maximum 100) and negative answers with low points (minimum 0 points) will unify and simplify the questionnaire., Conclusion: The translation of the Nasal Spray Evaluation Questionnaire into a German version can serve as a new standard tool for measuring nasal sensation., (Georg Thieme Verlag KG Stuttgart * New York.)

Objectives: This a priori subgroup analysis was conducted to assess patients' experience with a compliance device for the administration of sublingual specific immunotherapy for grass pollen-induced rhinoconjunctivitis., Methods: The present paper reports the results of a subgroup analysis of a multicenter, randomized, controlled, open-label European study in which adults with grass pollen-induced rhinoconjunctivitis received once-daily treatment with grass allergen tablets with or without a device to aid compliance. Treatment was given approximately 6 to 12 weeks before the grass pollen season, during the season (approximately 8-10 weeks), and for up to 2 weeks after the end of the season. In the subgroup analysis, patients from Germany and the Netherlands who had been randomized to receive the compliance device were asked to complete a brief questionnaire at the final study visit. The questionnaire included 6 items concerning patients' use of the device and whether it helped them remember to take their tablets., Results: Of the 91 patients from Germany and the Netherlands who were randomized to use the compliance device along with grass allergen tablets, 71 returned the questionnaire. Among responders, 58 of 71 (82%) reported using the device sometimes or always, 50 of 63 (79%) found the device easy to use, 32 of 69 (46%) found that the device made it easier to remember to take tablets, and 43 of 71 (61%) indicated that they would consider using the device again., Conclusion: Most patients in this subgroup analysis used the compliance device as a medication reminder and rated it easy to use.

Background and Aims: The objective of this study was to investigate the effect of Boswellia serrata extract (BSE) on symptoms, quality of life, and histology in patients with collagenous colitis., Materials and Methods: Patients with chronic diarrhea and histologically proven collagenous colitis were randomized to receive either oral BSE 400 mg three times daily for 6 weeks or placebo. Complete colonoscopy and histology were performed before and after treatment. Clinical symptoms and quality of life were assessed by standardized questionnaires and SF-36. The primary endpoint was the percentage of patients with clinical remission after 6 weeks (stool frequency

Objective: To investigate the efficacy of the special extract ERr 731 from the roots of Rheum rhaponticum compared with placebo on anxiety, health state, and general well-being in perimenopausal women., Design: This study is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical trial, in which 109 perimenopausal women with climacteric complaints and anxiety received either 1 enteric coated tablet of ERr 731 (n=54) or placebo (n=55) daily for 12 weeks. The Hamilton Anxiety Scale, the Menopause Rating Scale II, the Women's Health Questionnaire, and the Psychological General Well-Being Index were used to measure anxiety, health state, and subjective psychological well-being., Results: The results demonstrate that ERr 731 is highly effective in reducing anxiety in perimenopausal women compared with placebo. After 12 weeks, the Hamilton Anxiety Scale total score decreased significantly with ERr 731 (from 27.5+/-6.8 to 9.4+/-4.2 points) compared with placebo (from 25.1+/-6.0 to 21.6+/-8.6 points). ERr 731 also reduced the Hamilton Anxiety Scale factor scores for somatic and psychic anxiety. After 12 weeks, a reduction in the severity of anxiety from "moderate" or "severe" to "slight" was observed in 33 of 39 ERr 731 women completing the double-blind phase, which correlated well with the reduction in number and severity of hot flushes. This was reflected by a high rate of ERr 731 women reporting a marked improvement in health state and general well-being., Conclusions: ERr 731 is an effective medication for women with menopause-related anxiety and improves their health state and general well-being.

For centuries the roots of Pelargonium sidoides DC have been used in South African ethno-medicine for the treatment of respiratory diseases. In Germany, a medicinal product containing a special extract of this substance is among the group of self-medication products most widely bought at chemist's shops. In December 2005, the Federal Institute for Drugs and Medical Devices (BfArM, Bonn) approved a new license for its use as a drug. The following review focuses on the current pharmacological, toxicological and clinical data covering the efficacy and innocuousness of this drug when administered for the treatment of acute bronchitis.

This randomised, double-blind, bicenter, placebo-controlled clinical trial investigated the effect of a daily application of 6g Kytta-Salbe f (3 x 2 g) over a 3 week period with patients suffering from painful osteoarthritis of the knee. The two hundred and twenty patients examined consisted of 153 women and 67 men of an average age of 57.9 years. On average, the complaints relating to osteoarthritis of the knee had persisted for 6.5 years. Two hundred and twenty patients were included in the Full Analysis Set (FAS) and safety collective, 186 (84.5%) in the Valid Case Analysis Set (VCAS) collective. In the course of the trial, the visual analog scale (VAS) total score (primary target value) in the verum group dropped by 51.6 mm (54.7%) and in the placebo group by 10.1 mm (10.7%). The average difference between the groups of 41.5 mm (95% confidence interval=34.8 to 48.2 mm) or 44.0% is significant (p<0.001). The significance is confirmed through the evaluation of the diary, the VCAS evaluation and the separate assessment of the two centres. This also applies to the separate assessment of the VAS total score following pain at rest and on movement. The WOMAC (Western Ontario and McMaster Universities) total score (secondary target value) also improved similar to the VAS total score. At the end of the trial, a reduction by 60.4 mm (58.0%) was recorded for the verum group and a reduction of 14.7 mm (14.1%) for the placebo group. The average group difference of 45.7 mm (95% confidence interval=37.1 to 54.3 mm) or 43.9% is significant (p<0.001). The difference between the treatment groups increased systematically and significantly, in parallel with the duration of the treatment. Thus, the superiority of the treatment with Kytta-Salbe f over that with the placebo is proven, even by means of the multi-factorial multivariate analysis for repetitive measurements. In respect of the explorative secondary target values SF-36 (quality of life), angle measurement (mobility of the knee), CGI (clinical global impression) and global assessment of efficacy by the physician and the patient, a significant superiority (p<0.001 each) of the verum group over the placebo group was also proven. The results suggest that the comfrey root extract ointment is well suited for the treatment of osteoarthritis of the knee. Pain is reduced, mobility of the knee improved and quality of life increased.

Acute bronchitis, although mostly caused by viral infections, is commonly treated with antibiotics. As antibiotics should only be prescribed upon strict indication, treatment options like a liquid herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) gain more and more interest. To evaluate the efficacy and safety of treatment with EPs 7630 in patients with acute bronchitis, a multi-centre, prospective, open observational study was conducted in 440 study sites located in Germany. A total of 2099 patients aged 0-93 years with productive cough for less than six days without indication for treatment with antibiotics were given EPs 7630-solution in an age-dependent dosage for 14 days. The primary outcome criterion was the mean change of the Bronchitis Severity Score (BSS: cough, sputum, rales/rhonchi, chest pain at cough, dyspnoea) from baseline to patient's individual last observation. During treatment, the mean BSS of all patients decreased from 7.1+/-2.9 points at baseline to 1.0+/-1.9 points at patients' individual last visit. Subgroup analysis for children showed a decrease of mean BSS from 6.3+/-2.8 points to 0.9+/-1.8 points and analysis of children younger than three years showed a decrease of mean BSS from 5.2+/-2.5 points to 1.2+/-2.1 points. Adverse events occurred in 26/2099 (1.2%) patients. Serious adverse events were not reported. In conclusion, EPs 7630 is an effective and well tolerated treatment of acute bronchitis in adults, children and infants outside the strict indication for antibiotic treatment.

An open post-marketing surveillance study was conducted to examine the treatment effect and safety of EPs 7630-solution in the treatment of acute bronchitis in children. This study included a total of 742 children (aged between 0 and 12 years) with acute bronchitis (83.4%) or acute exacerbations of chronic bronchitis (14.3%), who were treated with different doses of the herbal drug for up to 14 days. Five bronchitis specific symptoms (BSS) were summed up to give an overall measure of disease severity. Non-specific disease symptoms (loss of appetite, diarrhoea, headache, vomiting, and fever) were also recorded, together with adverse events and overall ratings of efficacy and tolerability. The overall BSS score decreased during treatment from 6.0+/-3.0 points at baseline to 2.7+/-2.5 points after 7 days and to 1.4+/-2.1 points after 14 days. Remission or improvement in at least 80% of patients was recorded for all the individual component symptoms. The proportion of patients suffering from non-specific symptoms also substantially improved during treatment. For example, loss of appetite was present in 65.8% of patients at study begin, but only in 27.6% at the time point of last observation visit. In 88.3% of cases, the responsible physician rated the treatment as successful. Adverse events were minor and transitory. In conclusion, EPs 7630-solution was shown to be a safe and an effective treatment option for acute bronchitis or acute exacerbations of chronic bronchitis in children.

Acute bronchitis is one of the most common diagnoses in ambulatory care medicine. Although the benefit of antibiotics for acute bronchitis, which is mostly virally induced, is disputed, they are often prescribed. A therapeutic option for respiratory tract infections that do not fall within the strict indication range for antibiotic administration is the liquid herbal drug preparation from the roots of Pelargonium sidoides, EPs 7630 (Umckaloabo), which has been tested against placebo in double-blind clinical trials. EPs 7630 has both antibacterial and immuno-modulating properties. The efficacy and tolerability of EPs 7630 was investigated in a prospective, open, multicentric outcomes study with 205 patients suffering from acute bronchitis or acute exacerbation of chronic bronchitis. The main outcome measure was the change in the total score of five symptoms typical for bronchitis (cough, expectoration, wheezing/whistling on expiration, chest pain during coughing, and dyspnoea), which were each rated using a 5-point scale (from 0=not present to 4=extremely pronounced). Further symptoms (hoarseness, headache, aching limbs and fatigue) were assessed using a four-point scale (from 0=not present to 3=very pronounced). The total score of the typical bronchitis symptoms amounted to 6.1+/-2.8 points on average at the start of treatment and decreased by 3.3+/-3.8 points to 2.8+/-2.6 points by the final examination on day 7. About 60.5% of the patients assessed their health condition at the end of the study as much improved or free from symptoms. The onset of action appeared after two days on average. Adverse events occurred in a total of 16 patients. There were no serious adverse events. Altogether, 78% of the patients were satisfied or very satisfied with the treatment.

Purpose: To compare the effects of cannabis extract (CE), delta-9-tetrahydrocannabinol (THC), and placebo (PL) on appetite and quality of life (QOL) in patients with cancer-related anorexia-cachexia syndrome (CACS)., Patients and Methods: Adult patients with advanced cancer, CACS, weight loss (> or = 5% over 6 months), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2 were randomly assigned (2:2:1) to receive CE (standardized for 2.5 mg THC and 1 mg cannabidiol) or THC (2.5 mg) or PL orally, twice daily for 6 weeks. Appetite, mood, and nausea were monitored daily with a visual analog scale (VAS); QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (composite score: questions 29 and 30). Cannabinoid-related toxicity was assessed every 2 weeks., Results: Of 289 patients screened, 243 were randomly assigned and 164 (CE, 66 of 95 patients; THC, 65 of 100 patients; and PL, 33 of 48 patients) completed treatment. At baseline, groups were comparable for age (mean, 61 years), sex (54% men), weight loss (32% > or = 10%), PS (13% ECOG = 2), antineoplastic treatment (50%), appetite (mean VAS score, 31/100 mm), and QOL (mean score, 30/100). Intent-to-treat analysis showed no significant differences between the three arms for appetite, QOL, or cannabinoid-related toxicity. Increased appetite was reported by 73%, 58%, and 69% of patients receiving CE, THC, or PL, respectively. An independent data review board recommended termination of recruitment because of insufficient differences between study arms., Conclusion: CE at the oral dose administered was well tolerated by these patients with CACS. No differences in patients' appetite or QOL were found either between CE, THC, and PL or between CE and THC at the dosages investigated.

Objective: To investigate endometrial safety by assessment of endometrial biopsy samples and the tolerability and efficacy of the special Actaea or Cimicifuga racemosa extract (CR BNO 1055)., Design: Four hundred postmenopausal women with symptoms related to estrogen deficiency were enrolled into a prospective, open-label, multinational, multicenter study. Treatment duration (daily dose corresponds to 40 mg of herbal drug) was 52 weeks. To determine the probability of endometrial hyperplasia and more serious adverse endometrial outcome, the point estimator and upper limit of 95% CI were calculated. Descriptive statistics was used to assess the secondary endpoints., Results: Endometrial safety has been proven because no case of hyperplasia or more serious adverse endometrial outcome occurred (point estimate: 0.0; upper limit of 95% CI: 0.011). Endometrial thickness, which was measured by endovaginal ultrasonography, did not show an increase. The number and intensity of hot flushes were markedly decreased. The dropout rate was less than 10%. The overall tolerability was good., Conclusions: The lack of endometrial proliferation and improvement of climacteric complaints as well as only few gynecologic organ-related adverse events are reported for the first time after a treatment period of 1 year. Due to the improved benefit:risk ratio, it must be assumed that the Cimicifuga racemosa special extract BNO 1055 is a safe alternative for treatment of climacteric complaints.

Efficacy and tolerability of a combined valerian/lemon balm preparation were investigated in an open, multicentre study in children less than 12 years suffering from restlessness and nervous dyskoimesis. Patients were dosed individually by the investigators. In total, 918 children were evaluated for therapeutic efficacy and tolerability. A distinct and convincing reduction in severity was found for all symptoms in the investigators' and parents' ratings. The core symptoms dyssomnia and restlessness were reduced from "moderate/severe" to "mild" or "absent" in most of the patients. In total, 80.9% of the patients who suffered from dyssomnia experienced an improvement for this symptom and 70.4% of the patients with restlessness improved clearly. For the other listed symptoms the total improvement was 37.8% on average. Both, parents and investigators assessed efficacy as to be "very good" or "good" (60.5% and 67.7%, respectively). The tolerability of Euvegal forte was considered as "good" (in 96.7% of the patients it was judged to be "very good" or "good"). No study medication-related adverse events occurred. In conclusion, Euvegal forte was effective in the treatment of younger children with restlessness and dyssomnia and it was very well tolerated.

Background: The clinical efficacy and safety of a six-grass pollen allergoid has been studied. The advent of more exacting clinical guidelines and a better appreciation of the possible mechanisms of treatment prompted this reappraisal., Methods: A 2-year double-blind multicentre placebo-controlled phase 3 clinical trial was undertaken in 154 patients suffering symptoms of rhinoconjunctivitis with or without asthma (GINA I or II). Therapy comprised two consecutive preseasonal short-courses of subcutaneous injections using a grass pollen allergoid adsorbed to aluminium hydroxide., Results: A combined symptom and medication score (SMS) was used as the primary end-point for clinical efficacy. SMS from the first year showed a significant difference of 26.6% between the two study groups (P=0.026) and this was improved after the second year when there was a 48.4% difference in SMS between active and placebo treatment in favour of the allergoid (P = 0.018). Highly significant increases in grass pollen allergen-specific IgG1 and IgG4 antibody concentrations were measured in association with active treatment. Allergen tolerance was increased as judged by a conjunctival provocation test and significant improvements in quality of life were documented using a standardized questionnaire. The allergoid was well tolerated., Conclusions: The grass pollen allergoid was shown to be safe and clinically efficacious in the management of hay fever with or without asthma (GINA I or II).

Comfrey (Symphytum officinale L.) is a medicinal plant with anti-inflammatory, analgesic and tissue regenerating properties. In a double-blind, multicenter, randomized, placebo-controlled, group comparison study on patients suffering from unilateral acute ankle sprains (n = 142, mean age 31.8 years, 78.9% male), the percutaneous efficacy of an ointment of comfrey extract (Kytta-Salbe f, four treatments per day for 8 days) was confirmed decisively. Compared to placebo, the active treatment was clearly superior regarding the reduction of pain (tonometric measurement, p<0.0001, as the primary efficacy variable) and ankle edema (figure-of-eight method, p = 0.0001). Statistically significant differences between active treatment and placebo could also be shown for ankle mobility (neutral zero method), and global efficacy. Under active treatment, no adverse drug reactions were reported. The good local and global tolerance of the trial medication could also be confirmed. The study results are consistent with the known pre-clinical and clinical data concerning comfrey.

Unipolar major depression is often a chronic disease that may require lifelong prophylaxis. Recovery from an acute episode is followed by 4-6 months of relapse prevention. After that, long-term maintenance treatment is administered to avoid recurrence. We present the rationale and design of an ongoing double-blind, randomized, placebo-controlled trial investigating the efficacy of Hypericum extract WS 5570 in relapse prevention in recurrent unipolar depression. An estimated sample of 425 adults with recurrent, mild to moderate major depression (ICD-10 and DSM-IV criteria), > or = 3 previous episodes (last 5 years) and a total score > or = 20 points on the 17-item Hamilton Rating Scale for Depression (HAMD) will be included. After a one-week wash out patients receive 3 x 300 mg/day WS 5570 single-blind for 6 weeks. Responders are randomized to 26 weeks of double-blind continuation treatment with 3 x 300 mg/day WS 5570 or placebo. Patients completing continuation treatment without relapse enter 52 weeks of doubleblind maintenance treatment, where those treated with WS 5570 are re-randomized to 3 x 300 mg/day WS 5570 or placebo. The primary outcome measure is the time to relapse during continuation treatment (HAMD > or = 16, clinical diagnosis of depression, or premature treatment termination for inefficacy). Hypericum extract, with its favourable tolerability profile, could be an interesting option for long-term prophylaxis. The trial was designed according to current consensus and guidance. Notably, it includes long-term prophylactic treatment with the same drug and the same therapeutic dose applied during acute treatment, uses well-defined outcome measures and provides a clear distinction between relapse and recurrence.

Preparations made from the secondary tubers of Devil's claw (Harpagophytum procumbens) are successfully used in patients with rheumatic diseases (arthrosis and low back pain). In order to add data on the efficacy and long-term safety of an aqueous extract (Doloteffin; 2400 mg extract daily, corresponding to 50 mg harpagoside), which has been tested successfully in patients with low back pain, an uncontrolled multicentre drug surveillance study for about 12 weeks was conducted in 75 patients with arthrosis of the hip or knee. To standardize the assessment of treatment effects, the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index (10 point scale) as well as the 10 cm VAS pain scale were used. The results of the study revealed a strong reduction of pain and the symptoms of osteoarthritis. There was a relevant improvement of each WOMAC subscale as well as of the total WOMAC index: 23.8% for the pain subscale, 22.2% for the stiffness subscale and 23.1% for the physical function subscale. The WOMAC total score was reduced by 22.9%. VAS pain scores were decreased by 25.8% for actual pain, 25.2% for average pain, 22.6% for worst pain and 24.5% for the total pain score. The physicians reported a continuous improvement in typical clinical findings such as 45.5% for pain on palpation, 35% for limitation of mobility and 25.4% for joint crepitus. Only two cases of possible adverse drug reactions were reported (dyspeptic complaints and a sensation of fullness). Although this was an open clinical study, the results suggest that this Devil's claw extract has a clinically beneficial effect in the treatment of arthrosis of the hip or knee., (Copyright 2003 John Wiley & Sons, Ltd.)

The efficacy and tolerability of 150 mg/d Kava special extract WS 1490 were investigated in a randomized, placebo-controlled, double-blind multicenter study in patients suffering from neurotic anxiety (DSM-III-R diagnoses 300.02, 300.22, 300.23, 300.29, or 309.24). 141 adult, male and female out-patients received 3 x 1 capsule of 50 mg/d WS 1490 or placebo for four weeks, followed by two weeks of observation without study-specific treatment. During randomized treatment the total score of the Anxiety Status Inventory (ASI) observer rating scale showed more pronounced decreases in the WS 1490 group than in the placebo group. Although a treatment group comparison of the post-treatment ASI scores was not significant (p > 0.05), an exploratory analysis of variance across the differences between treatment end and baseline, with center as a second factor, showed superiority of the herbal extract over placebo (p < 0.01, two-sided). 73% of the patients treated with WS 1490 exhibited ASI score decreases > 5 points versus baseline, compared to 56% for placebo. Significant advantages for WS 1490 were also evident in a structured well-being self-rating scale (Bf-S) and the Clinical Global Impressions (CGI), while the Erlangen Anxiety, Tension and Aggression Scale (EAAS) and the Brief Test of Personality Structure (KEPS) showed only minor treatment group differences. Although the results show consistent advantages for WS 1490 over placebo in several psychiatric scales and indicate significant improvements in the patients' general well-being, the differences versus placebo were not as large as in previous trials which employed 300 mg/d of the same extract. WS 1490 was well tolerated, with no influence on liver function tests and only one trivial adverse event (tiredness) attributable to the study drug.

Objective: An 8-week randomized, reference-controlled, double-blind, multi-centre clinical trial investigated Kava-Kava LI 150 in Generalized Anxiety Disorder (GAD; ICD-10: F41.1)., Method: 129 out-patients received either 400 mg Kava LI 150, 10 mg Buspirone or 100 mg Opipramol daily for 8 weeks. At week 9, subjects were seen to check for symptoms of withdrawal or relapse. Primary outcome measures comprised the HAMA scale and the proportion of responders at week 8. Secondary measures were the Boerner Anxiety Scale (BOEAS), SAS, CGI, a self-rating scale for well-being (Bf-S), a sleep questionnaire (SF-B), a quality-of-life questionnaire (AL) and global judgements by investigator and patients., Results: In 127 patients (ITT) no significant differences could be observed regarding all efficacy and safety measures. About 75% of patients were classified as responders (50% reduction of HAMA score) in each treatment group, about 60% achieved full remission., Conclusion: Kava-Kava LI150 is well tolerated and as effective as Buspirone and Opipramol in the acute treatment of out-patients suffering from GAD.

Background: New evidence-based treatment options are required to avoid antibiotic overuse in acute bronchitis and to replace potentially inefficacious initial antibiotic treatment., Objective: To evaluate the efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) compared to placebo in patients with acute bronchitis., Design: Randomized, double-blind, placebo-controlled trial using a multi-stage adaptive design., Setting: 36 primary care physicians (investigators) at the out-patient care setting., Patients: 468 adults with acute bronchitis present < or = 48 hours, Bronchitis Severity Score (BSS) > or = 5 points, and informed consent., Intervention: EPs 7630 or placebo (30 drops three times daily) for 7 days., Measurement: The primary outcome criterion was the change of BSS on day 7., Results: The decrease of BSS from baseline to day 7 was 5.9 +/- 2.9 points under EPs 7630 (n = 233), and 3.2 +/- 4.1 points under placebo (n = 235). The 95% CI for the difference of effects between the two treatment groups (EPs 7630 minus placebo) was calculated as [-3.359; -2.060] showing a significant superiority of EPs 7630 compared to placebo on day 7 (p < 0.0001). Working inability decreased to 16% in the EPs 7630 group compared to 43% in the placebo group (p < 0.0001). In addition, the duration of illness was significantly shorter for patients treated with EPs 7630 compared to placebo (p < 0.001). Within the first four days, onset of treatment effect was recognized in 53.6% of patients under EPs 7630 compared to 36.2% of patients under placebo, only (p < 0.0001). Adverse events (AEs) occurred in 36/468 patients (EPs 7630: 20/233 patients, placebo: 16/235 patients). All events were assessed as non-serious., Conclusion: EPs 7630 was superior in efficacy compared to placebo in the treatment of adults with acute bronchitis. Treatment with EPs 7630 clearly reduced the severity of symptoms and shortened the duration of working inability for nearly 2 days.

Depressive disorders in comorbidity with anxiety disorders represent an frequently diagnostic and therapeutic problem. The studies quoted here prove that the symptoms associated with anxiety that severely afflict patients can be clearly improved more quickly with a combination therapy of St John's wort extract and valerian extract than with St John's wort monotherapy. The combination therapy was well tolerated, no significant side-effects occurred. Further studies are necessary to compare the combination treatment with other forms of therapy (serotonin- and noradrenalin re-uptake inhibitors).

Objectives: To compare the effects of a proprietary extract of willow bark (Assalix) and a selective inhibitor (rofecoxib) of the enzyme cyclo-oxygenase-2 (COX-2)., Methods: An open, randomized, post-marketing study was carried out in an out-patients clinic on two groups of patients aged 18 to 80 yr presenting over a 6-month period with acute exacerbations of low back pain. Using computer-generated random list, 114 patients were allocated to receive a daily dose of herbal extract containing 240 mg of salicin [PAID (phyto-anti-inflammatory drug) group] and 114 were allocated to receive 12.5 mg of the synthetic COX-2 inhibitor rofecoxib [NSAID (non-steroidal anti-inflammatory drug) group]. The doses were chosen according to existing recommendations. All patients were free to use whatever additional conventional treatments were thought necessary. The outcome measures were a modified Arhus index, its pain component and the Total Pain Index., Results: Groups were well matched. After 4 weeks of treatment, the Arhus index had improved by about 20%, its pain component by about 30% and the Total Pain Index by about 35%. The number of pain-free patients (visual analogue scale score <2) was about 20 in each group. About 60% of the patients in each group responded well to the treatment (as judged by an improvement of >/=30% in the Total Pain Index relative to its baseline). The improvement was also reflected reasonably well in the physicians' and patients' judgements of the effectiveness of treatment, which were largely concordant. Few patients of either group resorted to the additional conventional treatment options. The incidence of adverse events was similar in the two groups. Treatment with rofecoxib was about 40% more expensive than that with Assalix., Conclusion: There was no significant difference in effectiveness between the two treatments at the doses chosen. Treatment with Assalix was less expensive.