Willow bark extract STW 33-I in the long-term treatment of outpatients with rheumatic pain mainly osteoarthritis or back pain.

STUDY OBJECTIVE: Efficacy and safety of willow bark extract for pain reduction in patients suffering from musculoskeletal disorders (MSD) has been shown in clinical short term trials. Therefore this observational study over 6 months should evaluate patterns of treatments like mono- or combinations therapy, dosage and safety during long-term treatment under pragmatic conditions with the aqueous willow bark extract STW 33-I, (Proaktiv(®); drug-extract-ratio 16-23:1). PATIENTS AND METHODS: The patients were treated with STW 33-I; comedication with other NSAIDs and opioids was allowed. An extensive case report form including pain questionnaires and patient diary was used for outcome evaluation. RESULTS: Four hundred and thirty-six patients with rheumatic pain mainly due to osteoarthritis (56.2%) and back pain (59.9%) were included. During the study the mean reductions from baseline value 58.4±22.6-31.8±22.5 after 24 weeks in the pain intensity scale (VAS 0-100mm) were significant even after 3 weeks with a reduction by 26 mm (45.6% of the baseline value) at the end of the study. The relative reductions of the weekly means of the daily patient self-rated scores of the pain (6-point Likert-scales) were between 33% and 44% of the baseline values during the course of the study. We present results of subgroups according their analgetic/antiphlogistic comedication. The distribution and specification of the main adverse events and the ratings of the treatment showed a good tolerability. No relevant drug interactions were reported. CONCLUSION: These data suggest that STW 33-I can be used as a basic treatment in the long-term therapy of painful musculoskeletal disorders and that it can be combined with NSAIDs and opioids if necessary.

Phase II trial on the effects of Silexan in patients with neurasthenia, post-traumatic stress disorder or somatization disorder.

Silexan, a novel lavender oil preparation for oral use, has been authorized in Germany for the treatment of states of restlessness during anxious mood. An open-label, exploratory trial was performed to assess the potential of the medicinal product in the treatment of restlessness caused by anxiety as related to several disorders. Outcome measures included the Symptom Checklist-90-Revised (SCL-90-R), von Zerssen's Depression Scale (D-S), the 36-item Short Form Health Survey Questionnaire (SF-36), and a sleep diary. 50 male and female patients with neurasthenia (ICD-10 F48.0), post-traumatic stress disorder (PSD; F43.1), or somatization disorder (F45.0, F45.1) were included to receive 1 × 80 mg/day Silexan over 6 weeks; 47 could be analyzed for efficacy as full analysis set. At baseline, patients suffered from restlessness (96%), depressed mood (98%), sleep disturbances (92%), or anxiety (72%). Of those, resp. 62%, resp. 57%, resp.51%, resp. 62% showed improvements during treatment (p < 0.001). For all patients, mean D-S score decreased by 32.7% and SCL-90-R Global Severity Index by 36.4% as compared to baseline, (p < 0.001), while the SF-36 Mental Health Score increased by 48.2% (p < 0.001). Waking-up frequency (p = 0.002), Waking-up duration (p < 0.001) and morning tiredness (p = 0.005) were reduced, while efficiency of sleep (p = 0.018) and mood (p = 0.03) improved. Patients suffering from neurasthenia or PSD showed comparable improvements with most outcomes. The results in this trial justify to further investigate Silexan in disorders with accompanying restlessness caused by sub-threshold anxiety. Adverse reactions, predominantly gastrointestinal complaints, were judged as mild or moderate.

Silicea gastrointestinal gel improves gastrointestinal disorders: a non-controlled, pilot clinical study.

Aim. To investigate efficacy and tolerability of Silicea Gastrointestinal Gel in patients with gastrointestinal disorders. Methods. Open, prospective pivotal phase IV study with oral Silicea Gastrointestinal Gel over 6 weeks. Symptom score was part 1 of the Nepean Dyspepsia Index: 15 questions addressing intensity, frequency and impact of upper abdominal symptoms. 10 lower abdominal symptoms were asked analogously. A responder showed reduction of score of >50%. Results. 62 of 90 patients were evaluated per protocol. Upper and lower abdomen sum scores decreased already in the first three weeks (P < 0.001), which continued the following three weeks (P < 0.01). Mean symptom score for upper abdomen decreased from 52.2 ± 31.0 to 33.7 ± 28.7 (or by 35.4%; responder rate 37%); for lower from 39.6 ± 24.7 to 22.6 ± 21.7 (by 42.9%; responder rate 46%). Subgroups with diarrhea, IBS and GERD presented highest responder rates. 6% of patients reported adverse reactions with probable or possible relationship to the test product. Conclusions. Silicea Gastrointestinal Gel seems suitable beyond infectious acute gastrointestinal disorders. Responses are relevant for chronic functional disorders, but it remains unclear, how much of that might be placebo-effect. Controlled studies are recommended in gastrointestinal syndromes like IBS or GERD.

Randomised controlled trial with medical leeches for osteoarthritis of the knee.

OBJECTIVES: To evaluate the possible efficacy of medical leeches (Hirudo medicinalis) in the treatment of patients with active osteoarthritis of the knee. DESIGN: Unblinded, randomised controlled trial with outpatients in a crossover design with single interventions of either leeches or transcutaneous electrical nerve stimulation (TENS) as comparator. MAIN OUTCOME MEASURES: Change in Lequesne's combined index for pain and function and change (L.I.) and overall assessment of complaints by visual analog scale (VAS). Cross-over at day 42, with further observation period of 21 days. RESULTS: 52 out of 72 screened patients were randomised (intent to treat) to initial treatment with either eight leeches (group 1: 27 patients) or TENS (group 2: 25 patients). Due to phase effects, confirmatory evaluation had to be restricted to the first period. Between days 0 and 21, we observed highly significant (p<0.001) improvements for means of Lequesne's index from 12.07 to 9.37 and for VAS from 5.89 to 4.16 cm for leeches, but no significant differences for TENS. Effect size as group difference was -2.50 for L.I. (95% confidence interval -3.88 to -1.11), resp. -1.86 cm for VAS (95% confidence interval -2.85 to -0.87 cm). 12 patients (5 group 1, 7 group 2) did not finish the trial, mostly due to non-compliance (6). No serious adverse effects were observed. CONCLUSIONS: Single leech therapy showed significant, relevant and sustaining effects, comparable to other trials with leeches. The method deserves further research, esp. into mechanisms of possible specific effects and optimization of dosing by number of leeches and possible repeats.

Cholesterol reduction using psyllium husks - do gastrointestinal adverse effects limit compliance? Results of a specific observational study.

PURPOSE: Despite known cholesterol lowering effects the use of psyllium husk (Plantaginis ovatae testa) in Germany for hypercholesterolemia is limited compared to their use as a laxative. To investigate whether use in hypercholesterolemia is limited due to adverse effects on the gastrointestinal system, a prospective observational study was conducted. METHODS: Sixty-two outpatients with documented hypercholesterolemia and complaints of constipation were identified from an academic clinical center. Treatment with 3.5g psyllium husk preparation administered three times daily was initiated and patients were monitored at weekly intervals. Gastrointestinal symptoms were quantified using a validated Nepean Dyspepsia Index modified to identify both upper and lower abdominal symptoms. Diaries and study medication records were used to evaluate compliance. RESULTS: Fifty-four of 62 patients enrolled in the study completed the study protocol with 4 subjects discontinuing due to adverse reactions associated with psyllium husks. Total cholesterol was significantly decreased from 252+/-39mg/dl before treatment to 239+/-37mg/dl after 3 weeks of treatment. Similarly, low density lipoprotein (LDL)-cholesterol decreased from 174+/-34 to 162+/-31mg/dl during the study. Triglycerides and high density lipoprotein (HDL) were unchanged. Gastrointestinal symptoms were rated lower at the end than at the beginning of the study. In week 1 most of the patients reported gastrointestinal symptoms and also gastrointestinal adverse reactions, which however, showed a decrease from week 1 to weeks 2 and 3 in the diaries. Patient response to study medication was positive for patients completing the study. CONCLUSIONS: Psyllium husk preparations may be a therapeutic option for patients with mild to moderately elevated cholesterol levels. Adverse gastrointestinal symptoms associated with the preparation appear to be transient in some of the patients. Compliance may be optimized with adequate patient counseling.

Self-medication in Germany.

We introduce the legal background of self-medication with OTC-drugs in Germany with regard to the pharmacy, drug store and health food shop distribution channels and the qualifications of the sales personnel. We give an overview of the frequency of self-medication and discuss risk/benefit in a pharmacoepidemiological context.

Pharmacokinetics and bioavailability of quercetin glycosides in humans.

Due to its potentially beneficial impact on human health, the polyphenol quercetin has come into the focus of medicinal interest. However, data on the bioavailability of quercetin after oral intake are scarce and contradictory. Previous investigations indicate that the disposition of quercetin may depend on the sugar moiety of the glycoside or the plant matrix. To determine the influence of the sugar moiety or matrix on the absorption of quercetin, two isolated quercetin glycosides and two plant extracts were administered to 12 healthy volunteers in a four-way crossover study. Each subject received an onion supplement or quercetin-4'-O-glucoside (both equivalent to 100 mg quercetin), as well as quercetin-3-O-rutinoside and buckwheat tea (both equivalent to 200 mg quercetin). Samples were analyzed by HPLC with a 12-channel coulometric array detector. In human plasma, only quercetin glucuronides, but no free quercetin, could be detected. There was no significant difference in the bioavailability and pharmacokinetic parameters between the onion supplement and quercetin-4'-O-glucoside. Peak plasma concentrations were 2.3 +/- 1.5 microg x mL(-1) and 2.1 +/- 1.6 microg x mL(-1) (mean +/- SD) and were reached after 0.7 +/- 0.2 hours and 0.7 +/- 0.3 hours, respectively. After administration of buckwheat tea and rutin, however, peak plasma levels were--despite the higher dose-only 0.6 +/- 0.7 microg x mL(-1) and 0.3 +/- 0.3 microg x mL(-1), respectively. Peak concentrations were reached 4.3 +/- 1.8 hours after administration of buckwheat tea and 7.0 +/- 2.9 hours after ingestion of rutin. The terminal elimination half-life was about 11 hours for all treatments. Thus, the disposition of quercetin in humans primarily depends on the sugar moiety. To a minor extent, the plant matrix influences both the rate and extent of absorption in the case of buckwheat tea administration compared with the isolated compound. The site of absorption seems to be different for quercetin-4'-O-glucoside and quercetin-3-O-rutinoside. The significance of specific carriers on the absorption of quercetin glycosides, as well as specific intestinal beta-glucosidases, needs to be further evaluated.