BACKGROUND: Crataegus preparations have been used for centuries especially in Europe. To date, no proper data on their efficacy and safety as an add-on-treatment are available. Therefore a large morbidity/mortality trial was performed. AIM: To investigate the efficacy and safety of an add-on treatment with Crataegus extract WS(R) 1442 in patients with congestive heart failure. METHODS: In this randomised, double-blind, placebo-controlled multicenter study, adults with NYHA class II or III CHF and reduced left ventricular ejection fraction (LVEF</=35%) were included and received 900 mg/day WS(R) 1442 or placebo for 24 months. Primary endpoint was time until first cardiac event. RESULTS: 2681 patients (WS(R) 1442: 1338; placebo: 1343) were randomised. Average time to first cardiac event was 620 days for WS(R) 1442 and 606 days for placebo (event rates: 27.9% and 28.9%, hazard ratio (HR): 0.95, 95% CI [0.82;1.10]; p=0.476). The trend for cardiac mortality reduction with WS(R) 1442 (9.7% at month 24; HR: 0.89 [0.73;1.09]) was not statistically significant (p=0.269). In the subgroup with LVEF>/=25%, WS(R) 1442 reduced sudden cardiac death by 39.7%(HR 0.59 [0.37;0.94] at month 24; p=0.025). Adverse events were comparable in both groups. CONCLUSIONS: In this study, WS(R) 1442 had no significant effect on the primary endpoint. WS(R) 1442 was safe to use in patients receiving optimal medication for heart failure. In addition, the data may indicate that WS(R) 1442 can potentially reduce the incidence of sudden cardiac death, at least in patients with less compromised left ventricular function.

BACKGROUND: In the 'Klinik am Steigerwald'(Gerolzhofen, Germany), founded in 1996 and providing accommodation for 44 patients, European physicians apply methods of traditional Chinese medicine (TCM). OBJECTIVE: To develop an assessment system which is suitable for the evaluation of therapies, can be integrated into daily routine, takes into account the particular therapeutic approach of the hospital, and promotes quality management. PATIENTS AND METHODS: The hospital admits all kinds of patients with chronic and often therapy-resistant diseases. Patients are primarily treated with Chinese phytotherapy and acupuncture. Methods of classical naturopathy and Western medicine complete the therapeutic range. All admitted patients are to be assessed. Exclusions are made according to a previously determined set of criteria. A written consent is mandatory. RESULTS: The assessment system comprises 3 questionnaires; 2 to be filled in by the patients, and 1 to document the physician's evaluation of the therapeutic success, based on his final consultation of the patient. Between January 2000 and December 2004, 2,021 patients were admitted to the hospital and followed-up until 2006. Of these, 1,609 patients met the inclusion criteria; 1,282 of these, again, agreed to participate in the interviewing process. The questionnaires of 1,110 patients were eligible for analysis. The present paper describes the methods of assessment. Its results are to be published in a future paper. CONCLUSION: Over the past 7 years, the assessment system has shown to be effective and appropriate to evaluate the type of therapy in question. It is intended to shorten the questionnaires.

AIM: Efficacy and safety of benfotiamine in treatment of diabetic polyneuropathy. METHODS: Double blind, placebo-controlled, phase-III-study. 181 patients were screened. 165 patients with symmetrical, distal diabetic polyneuropathy were randomised to one of three treatment groups entering the wash-out phase and 133/124 patients were analysed in the ITT/PP analysis: Benfotiamine 600 mg per day (n=47/43), benfotiamine 300 mg per day (n=45/42) or placebo (n=41/39). RESULTS: After 6 weeks of treatment, the primary outcome parameter NSS (Neuropathy Symptom Score) differed significantly between the treatment groups (p=0.033) in the PP (per protocol) population. In the ITT (intention to treat) population, the improvement of NSS was slightly above significance (p=0.055). The TSS (Total Symptom Score) showed no significant differences after 6 weeks of treatment. The improvement was more pronounced at the higher benfotiamine dose and increased with treatment duration. In the TSS, best results were obtained for the symptom "pain". Treatment was well tolerated in all groups. CONCLUSION: Benfotiamine may extend the treatment option for patients with diabetic polyneuropathy based on causal influence on impaired glucose metabolism. Further studies should confirm the positive experiences.

The efficacy of classic homeopathic therapy is scientifically not well proven. Few of the studies available are acceptable from a scientific point of view. In this paper we will describe a study protocol for a trial of classic homeopathy in chronic headache, which not only is in accordance with currently accepted scientific research standards but also accounts for the special needs of homeopathic therapy. The prescribing practioners are allowed to use any homeopathic drug at any potency or dosage, this enables them to ful fill the homeopathic principle of individuality. At the same time, the study is strictly controlled, randomized and double blind. The prescribing physician sends the homeopathic medication selected for a patient to a notary public, who either forwards it to the patient or substitute placebo, according to the randomization plan. Hence, the trial is not testing a specific drug, but the rationale of individual homeopathic drug selection and the efficacy of the selected drugs in headache patients in general. Patients suffering from chronic headaches for at least 1 year and with headaches at least once a week on average are eligible for the study. Exclusion criteria follow the generally accepted standards and account for the special needs of homeopathic therapy. Data are to be recorded in a patient's diary containing the outcome variables occurrence, duration, intensity of headaches and use of analgesic drugs. After a baseline period of at least 6 weeks the first consultation will take place, with the proper remedy selected and sent to the patient via the notary. After 6 weeks a first follow-up will allow the physician to modify the treatment if necessary. After another 6 weeks the final examination will take place. The duration of the homeopathic treatment, then, is 12 weeks. A total of 100 patients in two groups of 50 are to be treated in the study. The study started in the later part of 1991, and is scheduled to last for 2 1/2 years. We expect a critical discussion of the results from conventional medicine or from homeopathy, depending on the outcome of the study. The study protocol is being published in advance to enable the reviewers of the study to check the original study design and the a priori hypotheses adopted.

OBJECTIVE: We conducted a randomized double-blind trial of riluzole in Huntington's disease to investigate the efficacy of this antiexcitotoxic drug in slowing disease progression. METHODS: The study included 537 adult patients with a clinical diagnosis of Huntington's disease confirmed by genotyping. Patients were randomized (2:1) to treatment with riluzole (50mg twice daily) or placebo for 3 years. Concomitant use of antichoreic medication was forbidden, and introduction of such medication was a predefined end point. The primary outcome measure was change in a combined score derived from the motor and total functional capacity subscores of the Unified Huntington's Disease Rating Scale. Safety was also evaluated. RESULTS: A total of 379 patients completed the study (mean age, 47 [standard deviation, 9.5] years; 50% female patients). The principal reason for discontinuation was introduction of antichoreic medication. The median change from baseline in the combined score (primary outcome) for the "per protocol" population was 13.7 (95% confidence interval, 11.1-17.2) in the placebo group and 14.3 (95% confidence interval, 11.7-16.6) in the riluzole group. No intergroup difference in outcome could thus be demonstrated (p = 0.93, Mann-Whitney U test). No differences in secondary efficacy outcome variables were observed except for more frequent recourse to antichoreic medication in the placebo group. No unexpected adverse events were reported, and tolerability was acceptable. INTERPRETATION: No neuroprotective or beneficial symptomatic effects of riluzole in Huntington's disease were demonstrated. Ann Neurol 2007.

The efficacy of a modular education program for adult asthmatics was evaluated in a controlled, randomized multicenter trial under outpatient conditions for six months. The education was performed with material (patient handout and PowerPoint slides) of the MASA Program (i.e. a modular outpatient education program for adult asthmatics) according to the contents list of the NASA Program (i.e. a national education program for adult asthmatics). In total, 75 patients of seven asthma specialists were included. The complete data of 53 patients were obtained and evaluated. All patients had been diagnosed with asthma in the year before, most of them (54%) with moderately severe asthma. The patients in the intervention group attended a two-hour teaching program for three times; the control group once received a short introduction to the use of a peak-flow meter, an asthma diary and asthma emergency instructions. Compared to the control group, the intervention group patients showed significantly less mild asthma attacks. The mean requirement for inhalation of short-acting beta-agonists was 0.18 times vs. 1.5 times per week for the intervention and the control group, respectively (p = 0.0062). Another primary outcome was the number of unscheduled asthma-related visits to the doctor within six months. There was a trend to lower numbers in the intervention group, but due to the small number of patients the results did not reach significance. The same applies to the patients' estimation of their quality of life, measured by the SF-36 questionnaire. Patients in the intervention group had a significantly better knowledge about their disease (improvement in the number of correctly answered questions: 6.7 times in the intervention and 5.5 times in the control group; p = 0.0062) and showed a better adherence to their regular medication. In conclusion, this trial proves the quality of the MASA education program and its feasibility in the outpatient setting of a chest physician's practice, and it demonstrates the efficacy of outpatient education programs for asthmatics.

Objective: Information about adverse drug reactions plays an important role when assessing the benefit/risk profile of a drug. Identifying rare adverse drug reactions, however, is a difficult task. This paper illustrates the advantages of using a prescription database for this purpose. Methods: The mediplus((R)) database used in our analysis covered data from 320,644 outpatients observed between July 1999 and June 2002. The example of bleeding complications during intake of antidementia drugs is used to illustrate this approach. The comparison of cohorts and subgroups is nearly always a problem in surveys. For our analyses we considered a set of patients who had taken a selected medication for a certain period of time and compared the frequency of adverse events with those occurring when the same patients did not take this medication. Hence, the comparison with versus without a certain medication is based on the same set of patients as in a cross-over study. Results: Our evaluations indicate that the rate of bleeding complications is low when taking any of the widely used antidementia drugs, glutamate modulators, cholinesterase inhibitors, calcium antagonists or the phytomedicine Ginkgo biloba. Conclusion: Basing the comparison of the rates of complications during periods with and without intake of a certain drug on the same set of patients may be a useful tool for assessing adverse drug reactions from data reported in prescription databases.

In a randomized, double-blind, placebo-controlled, parallel group, phase III clinical trial efficacy and safety of Korodin, a combination of natural D-camphor and an extract from fresh crataegus berries, was investigated in patients 50 years and older with orthostatic hypotension. At visit 1 eligibility of patients was checked and a placebo medication was given to all patients. At visit 2 orthostatic hypotension had to be reconfirmed, then the patient was randomized either to Korodin or placebo, study medication (25 drops) was applied once and then outcome was measured. After 7 days of home treatment with daily 3 x 25 drops outcome was measured at visit 3. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were documented 10, 5, 2 and 0 min before as well as 1, 3, 5, 8, and 10 min after getting in the upright position at visit 1, at visit 2 before and after application of study medication and at visit 3. Primary outcome was the change of mean arterial blood pressure (MAP) from just before standing up to the nadir within the first 3 min after standing up. Secondary outcome variables were SBP, DBP, HR, quality of life (SF-12) and seven typical signs and symptoms of orthostatic hypotension. The study was performed in a rehabilitation clinic and in two doctor's practices in Germany from November 2002 to May 2003. During this time, 57 patients were admitted to the study, 39 patients were eligible and randomized, 38 patients were treated according to protocol and evaluated, 21 patients with Korodin and 17 patients with placebo. After a single application the median decrease of MAP was 11.4 mmHg for Korodin and 14.0 mmHg for placebo. Compared to baseline, the median MAP improved 4.3 mmHg for Korodin and 0.3 mmHg for placebo. After 1 week of treatment the decrease of median MAP after standing up was 9.3 mmHg for Korodin and 13.3 mmHg for placebo. Compared to baseline, the improvement was 5.9 mmHg for Korodin and 1.6 mmHg for placebo. Efficacy of 1 week treatment was significant. For the single application a superiority of Korodin over placebo was seen; however, it was not significant. All secondary outcome variables confirmed these findings, except for the physical summary score in the quality of life evaluation (SF-12 questionnaire). Only one adverse event occurred, but this was not serious and without relationship to the study medication. The other safety variables (SBP, DBP, HR, ECG, physical examination) did not show any problems. This study demonstrates that Korodin is efficacious for orthostatic hypotension in patients over 50 years.