Listerine® Products: An Update on the Efficacy and Safety.

UNLABELLED: In the 19th century, the mouthwash Listerine® was formulated from four essential oils. Later, the oils were replaced by their marker substances. To keep them in solution, 24-27% ethanol was added as a vehicle. This is an update of our previous review on the efficacy and safety of Listerine®. METHOD: PubMed was searched for clinical studies on the therapeutic benefits and safety of Listerine® from the end of 2011 to the end of October 2015. RESULTS: Sixteen studies were found and extracted. Three of the four 6-month studies were of sound confirmatory design. Two of these investigated Listerine® and one Listerine Zero®. The evidence of effectiveness for Listerine®, based on the bulk of three confirmatory studies and numerous exploratory studies carried out so far, is strong, but only moderate for Listerine® Zero and poor for Listerine® Cool Blue. In the three safety studies identified, we found methodological flaws that biased the results. CONCLUSIONS: Evidence is accumulating that Listerine® is effective in improving oral health, but the absence of systematic toxicological studies means that an accurate safety assessment cannot be made.

Paramedian vertical palatal bone height for mini-implant insertion: a systematic review.

Paramedian insertion of orthodontic mini-implants is increasingly used to anchor molar distalizers. The aim of this review was to systematically examine the available measurements of vertical palatal bone height (VBH). PUBMED, MEDLINE and the Cochrane Controlled Trials Register were searched using specific search terms. Hand searches of bibliographies of articles were also performed to identify studies measuring VBH or bone thickness in the human palate. Sixteen studies were included, arising from 19 published articles. Repeat presentations were excluded. Ten of the 11 computed tomogram (CT)-based studies presented data from 956 orthodontic patients on average VBH and its variation at a range of palatal sites. Individual data were not available, and pooling of data was not feasible because of heterogeneity of subjects, different measurement sites, different CT methods and their associated software. The compilation of data did indicate that the region 3-4mm behind the incisive foramen and 3-9mm lateral to the midpalatal suture should normally provide sufficient VBH to anchor molar distalizers. The risks of unwanted effects during distalization should be small, but the limitations listed above and the small numbers of studies available impair the precision of the estimates and do not allow the results to be generalized. Paramedian anchorage in the anterior palate can be recommended for molar distalization but, given the great inter-individual variability of the palatal bone height, it must be preceded by reliable CT-based imaging in patients identified by routine investigations as being at risk.

[German version of a validated instrument to measure the quality of life in patients with hypertension]. / Deutsche Version eines validierten Instruments zur Messung der Lebensqualität bei Patienten mit Bluthochdruck.

The aim of this study was to prepare according to standardised criteria a German version of the validated short instrument for the quality of life in patients suffering from hypertension. This instrument is appropriate for clinical trials investigating the effectiveness of antihypertensive treatments. But also in the daily routine this instrument enables one to identify any impairment of life quality due to antihypertensive treatment as early as possible, especially sexual dysfunction, and to react appropriately with treatment adaptations.

Micro-morphometrical assessment of the effect of Harpagophytum procumbens extract on articular cartilage in rabbits with experimental osteoarthritis using magnetic resonance imaging.

In vitro effects indicate a putative beneficial effect of Harpagophytum procumbens on cartilage turnover, however, in vivo protective effects on cartilage have yet to be demonstrated. A 7.1T MRI scanner was used to derive measurements of thickness, surface area and volume of the tibial condylar cartilage and to assess their precision (in the case of volume also accuracy) against the volumes of dissected cartilage measured by water displacement. Quantitative measurements were made in 16 rabbits, 6 months after unilateral medial meniscectomy and transection of the anterior cruciate ligament, after which eight of these were given a proprietary extract of Harpagophytum procumbens (HP). A semiquantitative MRI-based grading of the tibial cartilage was also compared with a 'macroscopic' grading based on direct visual inspection of dissected joints. The test-retest precision for MRI-based measurement was ≤6.4%. MRI-based measurements correlated well with volumes of surgically resected cartilage (r = 0.97, pair-wise random difference 4.2%). The medial tibial cartilage thickness and volume were about 35% smaller in the operated knees than in the non-operated contralateral knees (p < 0.05). The findings suggest that MRI is a precise and accurate tool for evaluating cartilage in a rabbit model of OA. The difference between the intact and operated knee in thickness and volume of the medial tibial cartilage was slightly but not significantly smaller in the HP-treated group than in the non-treated group.

Willow species and aspirin: different mechanism of actions.

Many believe that willow is the natural source of aspirin. However, willow species contain only a low quantity of the prodrug salicin which is metabolized during absorption into various salicylate derivatives. If calculated as salicylic acid, the daily salicin dose is insufficient to produce analgesia. Salicylic acid concentrations following an analgesic dose of aspirin are an order of magnitude higher. Flavonoids and polyphenols contribute to the potent willow bark analgesic and anti-inflammatory effect. The multi-component active principle of willow bark provides a broader mechanism of action than aspirin and is devoid of serious adverse events. In contrast to synthetic aspirin, willow bark does not damage the gastrointestinal mucosa. An extract dose with 240 mg salicin had no major impact on blood clotting. In patients with known aspirin allergy willow bark products are contraindicated.

Effectiveness and safety of topical capsaicin cream in the treatment of chronic soft tissue pain.

Topical capsaicin is an established treatment option for various pain conditions. In a randomized double-blind multi-centre study, 281 patients suffering from chronic soft tissue pain were treated either with a cream containing capsaicin 0.05% ('Finalgon® CPDWärmecreme', n = 140) or placebo (n = 141). Of these, 151 were excluded from the ITT analysis, as they had in addition to their soft-tissue pain, pain of other origin. The primary outcome measure was a positive treatment response, defined as a pain sum score reduction of 30% or more. After 3 weeks of treatment, the median pain sum score had decreased by 49% (capsicum group) and 23% (placebo group) (ITT analysis, p = 0.0006). The odds ratio of the responders in favour for capsaicin was 4.3 (CI 97.5% lower limit 1.9, p < 0.0001). Improvements in the secondary efficacy measures confirmed the results. Likewise, all outcome measures had significantly more improved in the capsaicin-treated compared with the placebo-treated chronic back pain sufferers. All patients were included in the safety assessments. More adverse events occurred in the capsicum group (n = 13) than in the placebo group (n = 6). The capsaicin cream was generally well tolerated. The results indicate that capsaicin cream is useful in patients with chronic soft tissue pain and is also efficacious in patients with chronic back pain for which effectiveness was already demonstrated in earlier clinical trials.

The clinical effectiveness of chokeberry: a systematic review.

Products derived from the black chokeberry, Aronia melanocarpa, are claimed to be beneficial in disorders or diseases associated with oxidative stress. The claims are based on evidence from in vitro studies and animal experiments. The active principle--a mixture of procyanidins, anthocyanins and phenolic acids--constitutes one of the most potent natural antioxidants. A systematic review was carried out of the quality of the clinical trials on chokeberry products that had been published up to December 2009, and conventionally established criteria were used to assess the strength of the evidence for their clinical effectiveness. Thirteen studies were identified. The quality of most of the trials and, correspondingly, the evidence of effectiveness for Aronia products is poor. Though laboratory and clinical data indicate that chokeberry products may well be useful as 'functional food' for disorders or diseases related to oxidative stress, these promising indications need to be confirmed in more rigorous studies before putative therapeutic uses can be confidently recommended for chokeberry products.

A systematic review on the sambuci fructus effect and efficacy profiles.

The berries of European elder are used in traditional German medicine for various complaints. Due to insufficient research data, elderberry fruit was not monographed by the German Commission E at the end of the last century. A comprehensive review of the literature was conducted to summarize the pharmacological and clinical effects of elderberry fruit. Several databases and other sources were searched to identify in vitro and animal studies, and clinical trials investigating elderberry fruit preparations. For the latter, the level of evidence was evaluated as described previously. Elderberry fruit preparations may provide antioxidant, antiviral and antiproliferative effects in vitro. One animal experiment and one clinical trial were able to back the antioxidative impact in terms of a weak antilipidemic effect. Antibacterial and antiinflammatory effects seem possible, but need further support. In rats, an aqueous elderberry fruit extract produced central depression and analgesia and an ethanol fruit extract improved acetic acid-induced colitis. Several in vitro studies together with two exploratory studies in humans and one open study in chimpanzees indicate that the aqueous elderberry extract Sambucol may be useful for the treatment of viral influenza infections. These promising effects of elderberry fruit preparations from experimental and clinical studies should be backed by more rigorous studies before these preparations are recommended in the prevention of diseases and in treatment schedules.

Medicinal use of potato-derived products: a systematic review.

In the traditional medicine of Europe, raw potatoes are used for gastrointestinal disorders, and topical potato preparations as a hot pack for pain or for softening furuncles. The aim of this study was to review the literature and summarize the data on the medicinal use of potato-derived products. Several databases and other sources were searched to identify clinical trials investigating potato-derived preparations. The trials were analysed for quality. Five trials were identified; two open uncontrolled studies, two open controlled studies and one double-blind study. These results stimulate further investigation of oral potato juice concentrate in patients with dyspeptic complaints, of potato proteinase inhibitor II for weight reduction, and of topical potato proteins for preventing protease-induced perianal dermatitis. We recommend that future studies have a confirmatory design.

A systematic review on the effectiveness of willow bark for musculoskeletal pain.

Since ancient times preparations from Salix species have been used to alleviate pain. The aim of this study was to update the evidence of the effectiveness of willow bark products in the treatment of musculoskeletal pain. OVID(MEDLINE), PUBMED, Silverplatter, and CENTRAL and manual searches were used to identify clinical trials investigating Salix preparations. Authors SC and JEV extracted the data independently and discussed disagreements. Seven manuscripts were identified, reporting four trials with confirmatory and four with exploratory study designs. Three manuscripts presented the same trial data: repetitious reports were excluded. One confirmatory and two exploratory studies indicate a dose-dependent analgesic effect not inferior to rofecoxib in patients with low back pain. In one exploratory and one confirmatory study conflicting results were achieved in participants with osteoarthritis. No significant effect was seen in a confirmatory study in patients with rheumatoid arthritis, but this study was grossly underpowered. All studies investigated ethanolic extracts with daily doses up to 240 mg salicin over periods of up to six weeks. Minor adverse events occurred during treatment. The review provides moderate evidence of effectiveness for the use of ethanolic willow bark extract in low back pain. Further studies are required to find out if treatment of osteoarthritis and rheumatoid arthritis requires extract with higher doses than 240 mg salicin per day.

Retrospective evaluation of biopsychosocial determinants and treatment response in patients receiving devil's claw extract (doloteffin).

In a retrospective evaluation of patients taking part for 2 months in a postmarketing surveillance study on the effectiveness and safety of Harpagophytum procumbens, associations were found to known explanators of pain, disability and depression. Therefore, treatment non-responders might best be referred to a multimodal pain relief program that deals with fear avoidance beliefs, enhances experiences that decrease perceptions linking disability and pain and forces the patients to rethink the way they deal with the problem. However, during treatment with the aqueous Harpagophytum extract, this decision might reasonably be postponed to the end of month 4, since it has been shown that the maximum pain relief occurs after 3-4 months.

Phytochemical composition and in vitro pharmacological activity of two rose hip (Rosa canina L.) preparations.

The aim of the present study was to compare powdered rose hip with and without fruits (Rosae pseudofructus cum/sine fructibus, Rosa canina L., Rosaceae) with regard to their phytochemical profile and their in vitro anti-inflammatory and radical-scavenging properties. The two powders were subsequently extracted with solvents of increasing polarity and tested for inhibition of cyclooxygenase (COX-1, COX-2) and of 5-LOX-mediated leukotriene B(4) (LTB(4)) formation as well as for DPPH-radical-scavenging capacity. While the water and methanol extracts were inactive in the COX-1, COX-2 and LTB(4) inhibition assays, the n-hexane and the dichloromethane extracts inhibited all three enzymes. In the active extracts, the triterpenoic acids ursolic acid, oleanolic acid and betulinic acid were identified, although only in minute amounts. Furthermore, oleic, linoleic and alpha-linolenic acid were identified apart from several saturated fatty acids. Even though unsaturated fatty acids are known to be good inhibitors of COX-1, COX-2 and LT formation, no clear correlation between their concentration in the extracts and their activity was found. We suggest that other, yet unidentified, lipophilic constituents might play a more important role for the observed in vitro inhibitory activity on arachidonic acid metabolism. Some of the extracts also showed considerable DPPH radical scavenging activity, the methanolic extracts being most potent. The radical scavenging activity of the extracts correlated very well with their total phenolic content, while ascorbic acid contributes only little to the radical-scavenging activity due to its low concentration present in the extracts. In summary, extracts derived from powdered rose hip without fruits were more effective in all assays carried out compared with extracts derived from powdered rose hip with fruits.

A one-year survey on the use of a powder from Rosa canina lito in acute exacerbations of chronic pain.

This pilot surveillance included 152 patients with acute exacerbations of chronic pain, 124 (Back group) with non-specific low back pain (NSLBP), 20 with NSLBP overridden by osteoarthritic pain (Knee-Hip group), and eight with specific LBP (included in the safety analysis). Patients were recommended the rose hip and seed powder Litozin at a dose providing up to 3 mg of galactolipid/day for up to 54 weeks. Clinical symptoms and well-being were assessed every 6 weeks. The patients also kept a diary of their pain and the requirement for rescue medication. Data were analysed by intention to treat with last observation carried forward. Only 77 patients completed the year of surveillance. Multivariate analysis suggested an appreciable overall improvement during the surveillance, irrespective of group, and this was reflected for most of the individual measures in repeated measures ANOVA. The degree and time-course of improvement echoed that seen in similar surveillances of patients receiving an aqueous extract of Harpagophytum. Multiple regression analyses indicated that percentage changes from baseline tended to be greater in patients with greater degrees of pain and disability, but were otherwise largely unrelated to the patients' characteristics. There were no serious adverse events. The rose hip and seed powder, Litozin, seems to deserve further, more definitive studies as a possible option in long-term management of NSLBP with or without osteoarthritic pain.

Systematic review on the safety of Harpagophytum preparations for osteoarthritic and low back pain.

Harpagophytum products are a treatment option for osteoarthritic and low back pain. The aim of this study was to review the safety of treatment with Harpagophytum procumbens. The databases OVID(MEDLINE), PUBMED and COCHRANE COLLABORATION LIBRARY were searched back to 1985 for studies with Harpagophytum procumbens. Twenty-eight clinical trials were identified of which 20 stated adverse events. In none of the double-blind studies was the incidence of adverse events during treatment with Harpagophytum procumbens higher than during placebo treatment. Minor adverse events occurred in around 3% of the patients, mainly gastrointestinal adverse events. A few reports of acute toxicity were found but there were no reports on chronic toxicity. Since the dosage used in most of the studies is at the lower limit and since long-term treatment with Harpagophytum products is advisable, more safety data are urgently needed.

Impact of herbal medicines on physical impairment.

The usefulness of recording physical impairment during intervention studies in chronic low back patients has been questioned. A re-analysis of all of our studies investigating aqueous extracts of Harpagophytum procumbens and a proprietary ethanolic Salix extract for chronic non-specific low back pain revealed that the "physical impairment" component of the Arhus low back pain index changed very little during treatment despite appreciable changes in the other two components, "pain" and "disability", over time. For comparison, we also extracted data from the literature on the topical use of capsaicin, which showed the same thing. There may be little to lose from omitting the time-consuming assessments of "physical impairment" in studies of the (primarily analgesic) effectiveness of herbal preparations.

Patient-perceived benefit during one year of treatment with Doloteffin.

We recruited 114 patients (56 with chronic nonspecific low back pain, 37 with osteoarthritic knee and 21 with osteoarthritic hip pain) into a surveillance of the effects of taking Doloteffin at a dose providing 60 mg harpagoside per day for up to 54 weeks. Their symptoms and well-being were monitored at 4-6 week intervals by disease-specific and generic outcome measures, and the patients also kept a diary of their pain and requirement for rescue medication. The principal analyses were on the basis of Intention to Treat (ITT) with Last Value Carried Forward (LOCF). A Multivariate Analysis of Variance (MANOVA) indicated an appreciable overall improvement during the surveillance, similar in the Back, Knee and Hip groups. In separate ANOVAs, most of the individual outcome scores decreased significantly over time. Multiple regression analyses indicated that changes from baseline were independent of patients' characteristics. Additional analgesic requirements (which were very modest) declined during the year of surveillance. "Response during treatment", assessed according to criteria adapted from joint proposals of the Outcome Measures in Rheumatoid Arthritis Clinical Trials group and the Osteoarthritis Research Society International group, was achieved in 75% of patients, and was reflected in the percentages who rated the treatment as "good" or "very good". Adverse events were few and none were serious.

Evidence of effectiveness of herbal antiinflammatory drugs in the treatment of painful osteoarthritis and chronic low back pain.

Treatment with herbal medicines is very popular in Europe. In order to get information on the evidence of effectiveness of oral herbal medicines in the treatment of pain in the joints or lower back, OVID(MEDLINE), PUBMED and COCHRANE COLLABORATION LIBRARY were searched back to 1985 for systematic reviews. The level of evidence of effectiveness was defined as strong - at least two confirmatory studies demonstrating a clinical relevant effect, moderate - one confirmatory study with a clinical relevant effect and/or multiple exploratory studies of good quality; otherwise the evidence was insufficient or conflicting in the case of inconsistent findings. Fifteen systematic reviews were identified. The evidence of effectiveness was strong for a proprietary unsaponifiable avocado soybean fraction and Harpagophytum preparations containing > 50 mg harpagoside in the daily dosage, moderate for ginger and a proprietary rose hip and seed powder, insufficient for Boswellia serrata gum resin and other herbal preparations and inconsistent for a proprietary willow bark extract. Further rigorous studies are required to confirm the usefulness of herbal medicines in the treatment of osteoarthritic complaints and chronic low back pain in order to enable acceptance of the herbal medicines into the treatment guidelines.

Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine: a systematic review.

The objective of this review was to evaluate the strength of evidence of effectiveness for Petasites hybridus in the prophylaxis of migraine. Several databases and other sources were searched to identify randomised-controlled trials investigating P. hybridus preparations. Two trials totalling 293 patients (60 and 233 patients) were included in this review. Both trials investigated the proprietary Petasites root extract Petadolex. The trials were described in narrative way, taking into consideration methodological quality scores. Pooling of data was not carried out due to the heterogeneity of the results. The extract at higher dose (150 mg) showed a greater decreased frequency of migraine attacks and a greater number of responders (improvement>50%) after treatment over 3-4 months than the extract at lower dose (100 mg) and placebo. Moderate evidence of effectiveness is, thus, available for a higher than the recommended dose of the proprietary Petasites root extract Petadolex in the prophylaxis of migraine. Further rigorous studies are required to confirm effectiveness and safety in long-term use before treatment with Petasites root extract can be recommended as an alternative option in the treatment schedule for the prophylaxis of migraine.