Novel Echinacea formulations for the treatment of acute respiratory tract infections in adults-A randomized blinded controlled trial.

Background: Echinacea purpurea has clinical antiviral activity against respiratory viruses and modulates immune functions. In this study, we compared higher doses of new Echinacea formulations with conventional formulations at lower, preventive doses for therapy of respiratory tract infections (RTIs). Methods: In this randomized, blinded, controlled trial, healthy adults (n = 409) were randomized between November 2018 and January 2019 to one of four Echinacea formulations, which were taken in case of an RTI for up to 10 days. New formulations A (lozenges) and B (spray) delivered an increased dose of 16,800 mg/d Echinacea extract during days 1-3 and 2,240-3,360 mg/d afterward; as controls, conventional formulations C (tablets) and D (drops) delivered a lower daily dose of 2,400 mg, usually taken for prevention. The primary endpoint was time to clinical remission of first RTI episodes based on the Kaplan-Meier analysis of patient-reported, investigator-confirmed, respiratory symptoms assessed for up to 10 days. In a sensitivity analysis, the mean time to remission beyond day 10 was calculated by extrapolating the treatment effects observed on days 7 to 10. Results: A total of 246 participants (median age 32 years, 78% female participants) were treated for at least one RTI. Recovery by day 10 (complete absence of symptoms) was achieved in 56 and 44% of patients with the new and conventional formulations, respectively, showing a median time to recovery of 10 and 11 days, respectively (p = 0.10 in intention-to-treat analysis, p = 0.07 in per-protocol analysis). In the extrapolated sensitivity analysis, new formulations resulted in a significantly shorter mean time to remission (9.6 vs. 11.0 days, p < 0.001). Among those with an identified respiratory virus, viral clearance until day 10 based on real-time PCR from nasopharyngeal swabs was more frequent with new formulations (70 vs. 53%, p = 0.046). Tolerability and safety (adverse events: 12 vs. 6%, p = 0.19) were good and similar between formulations. There was one severe adverse event with a potential hypersensitivity reaction in a recipient of the novel spray formulation. Conclusion: In adults with acute RTI, new Echinacea formulations with higher doses resulted in faster viral clearance than conventional formulations in prophylactic dosages. The trend for faster clinical recovery was not significant by day 10 but became so upon extrapolation. A dose increase during acute respiratory symptoms might improve the clinical benefits of orally administered Echinacea formulations. Trial registration: The study was registered in the Swiss National Clinical Trials Portal (SNCTP000003069) and on ClinicalTrials.gov (NTC03812900; URL https://clinicaltrials.gov/ct2/show/NCT03812900?cond=echinacea&draw=3&rank=14).

Echinacea reduces antibiotic usage in children through respiratory tract infection prevention: a randomized, blinded, controlled clinical trial.

BACKGROUND: In children, up to 30% of viral respiratory tract infections (RTIs) develop into bacterial complications associated with pneumonia, sinusitis or otitis media to trigger a tremendous need for antibiotics. This study investigated the efficacy of Echinacea for the prevention of viral RTIs, for the prevention of secondary bacterial complications and for reducing rates of antibiotic prescriptions in children. METHODS: Echinaforce® Junior tablets [400 mg freshly harvested Echinacea purpurea alcoholic extract] or vitamin C [50 mg] as control were given three times daily for prevention to children 4-12 years. Two × 2 months of prevention were separated by a 1-week treatment break. Parents assessed respiratory symptoms in children via e-diaries and collected nasopharyngeal secretions for screening of respiratory pathogens (Allplex® RT-PCR). RESULTS: Overall, 429 cold days occurred in NITT = 103 children with Echinacea in comparison to 602 days in NITT = 98 children with vitamin C (p < 0.001, Chi-square test). Echinacea prevented 32.5% of RTI episodes resulting in an odds ratio of OR = 0.52 [95% CI 0.30-0.91, p = 0.021]. Six children (5.8%) with Echinacea and 15 children (15.3%) with vitamin C required 6 and 24 courses of antibiotic treatment, respectively (reduction of 76.3%, p < 0.001). A total of 45 and 216 days of antibiotic therapy were reported in the two groups, respectively (reduction of 80.2% (p < 0.001). Eleven and 30 events of RTI complications (e.g., otitis media, sinusitis or pneumonia) occurred with Echinacea and vitamin C, respectively (p = 0.0030). Echinacea significantly prevented influenza (3 vs. 20 detections, p = 0.012) and enveloped virus infections (29 vs. 47 detections, p = 0.0038). Finally, 76 adverse events occurred with Echinacea and 105 events with vitamin C (p = 0.016), only three events were reported possibly related with Echinacea. CONCLUSIONS: Our results support the use of Echinacea for the prevention of RTIs and reduction of associated antibiotic usage in children. Trial registration clinicaltrials.gov, NCT02971384, 23th Nov 2016.

Lithium and Therapeutic Targeting of GSK-3.

Lithium salts have been in the therapeutic toolbox for better or worse since the 19th century, with purported benefit in gout, hangover, insomnia, and early suggestions that lithium improved psychiatric disorders. However, the remarkable effects of lithium reported by John Cade and subsequently by Mogens Schou revolutionized the treatment of bipolar disorder. The known molecular targets of lithium are surprisingly few and include the signaling kinase glycogen synthase kinase-3 (GSK-3), a group of structurally related phosphomonoesterases that includes inositol monophosphatases, and phosphoglucomutase. Here we present a brief history of the therapeutic uses of lithium and then focus on GSK-3 as a therapeutic target in diverse diseases, including bipolar disorder, cancer, and coronavirus infections.

Safety and Dose-Dependent Effects of Echinacea for the Treatment of Acute Cold Episodes in Children: A Multicenter, Randomized, Open-Label Clinical Trial.

Background: Due to the frequency and severity of cold symptoms in children, and the risk of associated complications, effective treatments are urgently needed. Here we evaluated the safety profile and treatment benefits of Echinacea in children with acute cold and flu symptoms. Methods: A total of 79 children (4-12 years) were randomized to a treatment regimen of three or five times daily Echinaforce Junior tablets (total of 1200 or 2000 mg Echinacea extract, EFJ) for the prospective treatment of upcoming cold and flu episodes at first signs. Parents recorded respiratory symptoms daily during episodes in their child and physicians and parents subjectively rated tolerability. Results: EFJ was used to treat 130 cold episodes in 68 children and was very well tolerated by more than 96% positive physician's ratings. EFJ-treated cold episodes lasted 7.5 days on average, with nine out of 10 episodes being fully resolved after 10 days. Five EFJ tablets daily reduced the average episode duration by up to 1.7 days (p < 0.02) in comparison to three EFJ tablets daily regimen. Effective symptom resolution finally contributed to a low antibiotic prescription rate in this study of 4.6%. Conclusions: EFJ tablets present a valuable option for the treatment of acute cold episodes in children showing a wide safety margin and increased therapeutic benefits at five tablets daily.

The Multicomponent, Multitarget Therapy SUC in Cats with Chronic Kidney Disease: A Multicenter, Prospective, Observational, Nonrandomized Cohort Study.

BACKGROUND: We compared the natural multicomponent, multitarget therapy SUC (Solidago compositum ad us. vet., Ubichinon compositum and Coenzyme compositum, Heel GmbH, Baden-Baden, Germany) to the well-known angiotensin-converting enzyme inhibitor benazepril in a prospective, observational, nonrandomized, two-arm cohort study of cats with chronic kidney disease (CKD). The objective was to assess the tolerability and the effectiveness of SUC in cats with CKD. MATERIAL AND METHODS: One hundred thirty-six cats were screened for CKD, and 70 cats were eligible for the study. Thirty-three cats were assigned to the SUC treatment, and 35 cats received benazepril. All cats were diagnosed with CKD. The follow-up period was 168 days. Response was assessed as an improved or stable serum creatinine from baseline to the end of the study. Additionally, a clinical summary score, as measure of quality of life, was evaluated. RESULTS: Serum creatinine remained close to baseline in both study groups with slightly improved values in the SUC group. The clinical summary score improved significantly in the SUC group on days 3, 7, 28, 56 and 112, but not on day 168. CONCLUSIONS: Within the limitations of the study, the results carry implications for the usefulness of SUC as an interesting new treatment option for feline CKD. The results indicate that SUC might be more effective if given at least twice weekly.

Tenuous Inhibitory GABAergic Signaling in the Reticular Thalamus.

Maintenance of a low intracellular Cl- concentration ([Cl-]i) is critical for enabling inhibitory neuronal responses to GABAA receptor-mediated signaling. Cl- transporters, including KCC2, and extracellular impermeant anions ([A]o) of the extracellular matrix are both proposed to be important regulators of [Cl-]i Neurons of the reticular thalamic (RT) nucleus express reduced levels of KCC2, indicating that GABAergic signaling may produce excitation in RT neurons. However, by performing perforated patch recordings and calcium imaging experiments in rats (male and female), we find that [Cl-]i remains relatively low in RT neurons. Although we identify a small contribution of [A]o to a low [Cl-]i in RT neurons, our results also demonstrate that reduced levels of KCC2 remain sufficient to maintain low levels of Cl- Reduced KCC2 levels, however, restrict the capacity of RT neurons to rapidly extrude Cl- following periods of elevated GABAergic signaling. In a computational model of a local RT network featuring slow Cl- extrusion kinetics, similar to those we found experimentally, model RT neurons are predisposed to an activity-dependent switch from GABA-mediated inhibition to excitation. By decreasing the activity threshold required to produce excitatory GABAergic signaling, weaker stimuli are able to propagate activity within the model RT nucleus. Our results indicate the importance of even diminished levels of KCC2 in maintaining inhibitory signaling within the RT nucleus and suggest how this important activity choke point may be easily overcome in disorders such as epilepsy.SIGNIFICANCE STATEMENT Precise regulation of intracellular Cl- levels ([Cl-]i) preserves appropriate, often inhibitory, GABAergic signaling within the brain. However, there is disagreement over the relative contribution of various mechanisms that maintain low [Cl-]i We found that the Cl- transporter KCC2 is an important Cl- extruder in the reticular thalamic (RT) nucleus, despite this nucleus having remarkably low KCC2 immunoreactivity relative to other regions of the adult brain. We also identified a smaller contribution of fixed, impermeant anions ([A]o) to lowering [Cl-]i in RT neurons. Inhibitory signaling among RT neurons is important for preventing excessive activation of RT neurons, which can be responsible for generating seizures. Our work suggests that KCC2 critically restricts the spread of activity within the RT nucleus.

Effect of an Echinacea-Based Hot Drink Versus Oseltamivir in Influenza Treatment: A Randomized, Double-Blind, Double-Dummy, Multicenter, Noninferiority Clinical Trial.

BACKGROUND: Echinacea has antiviral activity against influenza viruses in vitro and has traditionally been used for treatment of colds and flu. OBJECTIVES: This randomized, double-blind, double-dummy, multicenter, controlled clinical trial compared a new echinacea formulation with the neuraminidase inhibitor oseltamivir, the gold standard treatment for influenza. METHODS: Following informed consent, 473 patients with early influenza symptoms (≤48 hours) were recruited in primary care in the Czech Republic and randomized to either 5 days of oseltamivir followed by 5 days of placebo, or 10 days of an Echinacea purpurea-based formulation called Echinaforce Hotdrink (A. Vogel Bioforce AG, Roggwil, Switzerland). The proportion of recovered patients (influenza symptoms rated as absent or mild in the evening) was analyzed for noninferiority between treatment groups using a generalized Wilcoxon test with significance level α = 0.05 (2-sided) and using a CI approach in the per-protocol sample. RESULTS: Recovery from illness was comparable in the 2 treatment groups at 1.5% versus 4.1% after 1 day, 50.2% versus 48.8% after 5 days, and 90.1% versus 84.8% after 10 days of treatment with Echinaforce Hotdrink and oseltamivir, respectively. Noninferiority was demonstrated for each day and overall (95% CI, 0.487-0.5265 by generalized Wilcoxon test). Very similar results were obtained in the group with virologically confirmed influenza virus infections and in a retrospective analysis during the peak influenza period. The incidence of complications was lower with Echinaforce Hotdrink than with oseltamivir (2.46% vs 6.45%; P = 0.076) and fewer adverse events (particularly nausea and vomiting) were observed with Echinaforce Hotdrink. CONCLUSIONS: Echinaforce Hotdrink is as effective as oseltamivir in the early treatment of clinically diagnosed and virologically confirmed influenza virus infections with a reduced risk of complications and adverse events. It appears to be an attractive treatment option, particularly suitable for self-care. Clinical trial identifier: Eudra-CT: 2010-021571-88. (Curr Ther Res Clin Exp. 2015; 77:66-72).

Echinacea reduces the risk of recurrent respiratory tract infections and complications: a meta-analysis of randomized controlled trials.

INTRODUCTION: Respiratory tract infections are common, and these infections occur frequently in children, susceptible adults, and older persons. The risk for recurrences and complications relates not only to the presence of viruses but also to immune function. Therefore, modulation of the immune system and antiviral interventions such as echinacea might reduce the risk of recurrences and possibly the development of complications. METHODS: MEDLINE, EMBASE, CAplus, BIOSIS, CABA, AGRICOLA, TOXCENTER, SCISEARCH, NAHL, and NAPRALERT were searched for clinical trials that studied recurrent respiratory infections and complications on treatment with echinacea extracts in a generally healthy population. Two independent reviewers selected randomized, placebo-controlled studies of high methodological quality and a Jadad score of ≥4. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated according to a fixed effect model. RESULTS: Six clinical studies with a total of 2458 participants were included in the meta-analysis. Use of echinacea extracts was associated with reduced risk of recurrent respiratory infections (RR 0.649, 95% CI 0.545-0.774; P < 0.0001). Ethanolic extracts from echinacea appeared to provide superior effects over pressed juices, and increased dosing during acute episodes further enhanced these effects. Three independent studies found that in individuals with higher susceptibility, stress or a state of immunological weakness, echinacea halved the risk of recurrent respiratory infections (RR 0.501, 95% CI 0.380-0.661; P < 0.0001). Similar preventive effects were observed with virologically confirmed recurrent infections (RR 0.420, 95% CI 0.222-0.796; P = 0.005). Complications including pneumonia, otitis media/externa, and tonsillitis/pharyngitis were also less frequent with echinacea treatment (RR 0.503, 95% CI 0.384-0.658; P < 0.0001). CONCLUSION: Evidence indicates that echinacea potently lowers the risk of recurrent respiratory infections and complications thereof. Immune modulatory, antiviral, and anti-inflammatory effects might contribute to the observed clinical benefits, which appear strongest in susceptible individuals.

Perfil de eficacia y seguridad de Echinacea purpurea en la prevención de episodios de resfriado común: estudio clínico aleatorizado, doble ciego y controlado con placebo / Safety and efficacy profile of Echinacea purpurea to prevent common cold episodes: a randomized, double-blind, placebo-controlled trial

Objetivo: Investigar la seguridad y la eficacia de un extracto de Echinacea purpurea en la prevención del resfriado común en una amplia población durante un período de 4 meses. Método: 755 sujetos sanos recibieron un extracto etanólico de E. purpurea(95% parte aérea florida y 5% de raíz) fresca o placebo. A los participantes se les solicitó registrar en un diario los acontecimientos adversos y evaluar los síntomas relacionados con el resfriado, durante todo el período del estudio. Se tomaron muestras de las secreciones nasales de los participantes que padecieron resfriados agudos y fueron examinadas en busca de virus. Resultados: Ocurrieron un total de 293 acontecimientos adversos en el grupo al que se le asignó la equinácea y 306 en el grupo placebo. El 9% de los participantes experimentó acontecimientos adversos, que se consideraron al menos posiblemente, relacionados con el extracto (reacciones adversas), frente al 10% en el grupo placebo. Por lo tanto, la seguridad de la equinácea no fue inferior a la del placebo. La equinácea redujo el número total de episodios de resfriados, los días acumulados de resfriado y los episodios comedicados con analgésicos y antiinflamatorios. Asimismo inhibió los resfriados virales confirmados por deteccion del virus y previno especialmente las infecciones de los virus con membrana (p<0,05) La equinácea demostró mayor eficacia en las infecciones recurrentes y los efectos preventivos aumentaron cuando se cumplió estrictamente con el tratamiento y con el protocolo. Conclusión: La toma profiláctica de E. purpurea durante un período de 4 meses proporcionó una relación beneficio/riesgo positiva (AU)

Objective: To investigate the safety (risk) and efficacy (benefit) of Echinacea purpurea extract in the prevention of common cold episodes in a large population over a 4-month period. Methods: 755 healthy subjects were allocated to receive either an alcohol extract from freshly harvested E. purpurea (95% herba and 5% root) or placebo. Participants were required to record adverse events and to rate cold-related issues in a diary throughout the investigation period. Nasal secretions were sampled at acute colds and screened for viruses. Results: A total of 293 adverse events occurred with Echinacea and 306 with placebo treatment. Nine and 10% of participants experienced adverse events, which were at least possibly related to the study drug (adverse drug reactions).Thus, the safety of Echinacea was noninferior to placebo. Echinacea reduced the total number of cold episodes, cumulated episode days within the group, and pain-killer medicated episodes. Echinacea inhibited virally confirmed colds and especially prevented enveloped virus infections (p < 0.05). Echinacea showed maximal effects on recurrent infections, and preventive effects increased with therapy compliance and adherence to the protocol. Conclusions: Compliant prophylactic intake of E. purpurea over a 4-month period appeared to provide a positive risk to benefit ratio (AU)

Effectiveness of the homeopathic preparation Neurexan compared with that of commonly used valerian-based preparations for the treatment of nervousness/restlessness - an observational study.

Mild anxieties, nervousness, and restlessness are common in the general population and are commonly treated by complementary and alternative medical (CAM) therapies. A prospective, nonrandomized, noninterventional, observational study, using conventional or CAM practices, was conducted in 49 German practices. Each practice could include up to 15 subjects treated with either the homeopathic preparation Neurexan or with combination formulations based on valerian extracts. There was no placebo group. Choice and doses of study therapies were at the respective physician's discretion. The planned treatment duration was 2 weeks. A total of 826 subjects were included in the study and 777 (553 Neurexan and 224 valerian) subjects were available for the final examination. Subjects receiving Neurexan tended to weigh less, to have fewer concomitant illnesses and slightly milder severity of nervousness/restlessness, and were likelier to be female than the subjects receiving valerian therapies. The summary score for nervousness/restlessness was reduced from 19.0 +/- 6.1 at baseline to 7.4 +/- 6.8 at the end of the observation period in the Neurexan group, a reduction of 11.5 +/- 7.3 score units. In the valerian group, the summary score was reduced from 21.4 +/- 6.0 to 12.6 +/- 7.3, a reduction of 9.0 +/- 6.6 score units. The changes from baseline and the differences between the groups were statistically significant. Similar significant differences in effects were seen on the subscores and on the subjects' assessments of effectiveness. Both study therapies were well tolerated. Neurexan appears to be an effective and well-tolerated alternative to valerian-based combination therapies for the treatment of nervousness/restlessness in subjects favorable towards a CAM-based therapy.

The homeopathic preparation Neurexan vs. valerian for the treatment of insomnia: an observational study.

Insomnia is prevalent and complementary therapies are common, but data are lacking on the effectiveness and tolerability of preparations beyond valerian. Here we report on an open-label, prospective cohort study in 89 German centers offering both conventional and complementary therapies. Subjects received the homeopathic preparation Neurexan or valerian for 28 days. Doses were at physicians' judgments. Sleep duration and latency were evaluated based on patients' sleep diaries over 14 days; sleep quality was evaluated at 28 +/- 1 days. A total of 409 subjects were enrolled. The groups were balanced at baseline for age, sex, weight, and sleep disturbances. At day 14, both groups reported improved sleep latency and duration; latency was reduced from baseline by 37.3 +/- 36.3 min with Neurexan and by 38.2 +/- 38.5 min with valerian. The duration of sleep increased by 2.2 (+/-1.6) h in the Neurexan group and by 2.0 (+/-1.5) h in the valerian group. Differences between the groups in improvement on sleep duration were significantly in favor of Neurexan therapy at days 8, 12, and 14. At day 28, quality of sleep was improved in both groups with no significant differences between the treatments. Significantly more patients reported lack of daytime fatigue with Neurexan than with valerian therapies (49% vs. 32%; p < 0.05 for the comparison). For patients favorable towards a CAM-based therapy, Neurexan might be an effective and well-tolerated alternative to conventional valerian-based therapies for the treatment of mild to moderate insomnia.

Effects of Spascupreel versus hyoscine butylbromide for gastrointestinal cramps in children.

BACKGROUND: Gastrointestinal spasms and cramps are common in children as well as in adults. Alternative medical practices such as chiropractice and homeopathy are becoming increasingly popular in Europe and the USA. The effectiveness and tolerability of the homeopathic preparation Spascupreel was compared with that of hyoscine butylbromide treatment in children <12 years of age. METHODS: An observational cohort study in 204 children <12 years was conducted over a 1 week treatment period. The efficacy of the respective therapies were evaluated on the effect on severity of spasms and clinical symptoms (pain/cramps, sleep disturbances, distress, eating or drinking difficulties and frequent crying). Compliance was evaluated on a four-point scale from 'very good' to 'low'. Evaluation was done by the practitioner based on information given by the patient or minder. RESULTS: The analysis showed comparative improvements with the homeopathic preparation and hyoscine butylbromide therapy on severity of spasms, pain/cramps, sleep disturbances, eating or drinking difficulties, and frequent crying, all as evaluated by the practitioner. Both treatments were very well tolerated. CONCLUSIONS: For patients opting for a homeopathic therapy, Spascupreel seems to be an effective and well tolerated alternative to conventional therapies in children suffering from gastrointestinal spasms.

A complex homeopathic preparation for the symptomatic treatment of upper respiratory infections associated with the common cold: An observational study.

BACKGROUND: The use of complementary medicines is large and growing in both the United States and Europe. OBJECTIVE: To compare the effects of a complex homeopathic preparation (Engystol; Heel GmbH, Baden-Baden, Germany) with those of conventional therapies with antihistamines, antitussives, and nonsteroidal antiinflammatory drugs on upper respiratory symptoms of the common cold in a setting closely related to everyday clinical practice. DESIGN: Nonrandomized, observational study over a treatment period of maximally two weeks. SETTING: Eighty-five general and homeopathic practices in Germany. PARTICIPANTS: Three hundred ninety-seven patients with upper respiratory symptoms of the common cold. INTERVENTIONS: Engystol-based therapy or common over-the-counter treatments for the common cold. Patients receiving this homeopathic treatment were allowed other short-term medications, but long-term use of analgesics, antibiotics, and antiinflammatory agents was not permitted. Patients were allowed nonpharmacological therapies such as vitamins, thermotherapies, and others. MAIN OUTCOME MEASURES: The effects of treatment were evaluated on the variables fatigue, sensation of illness, chill/tremor, aching joints, overall severity of illness, sum of all clinical variables, temperature, and time to symptomatic improvement. RESULTS: Both treatment regimens provided significant symptomatic relief, and this homeopathic treatment was noninferior in a noninferiority analysis. Significantly more patients (P < .05) using Engystol-based therapy reported improvement within 3 days (77.1% vs 61.7% for the control group). No adverse events were reported in any of the treatment groups. CONCLUSION: This homeopathic treatment may be a useful component of an integrated symptomatic therapy for the common cold in patients and practitioners choosing an integrative approach to medical care.

Echinacea in the prevention of induced rhinovirus colds: a meta-analysis.

BACKGROUND: The therapeutic effectiveness of Echinacea in the treatment and the prevention of colds has been debated. Studies of naturally occurring colds are hampered by variability in time from onset of symptoms to treatment and by heterogeneity in trial design. Experimental infection studies allow for the standardization of time to initiation of treatment, virus type and dose, and immune competence of volunteers. OBJECTIVE: To determine whether the negative results obtained in previous studies of Echinacea were a consequence of efficacy or of inadequate sample size, we performed a meta-analysis of experimental rhinovirus infection studies on the efficacy of Echinacea extracts to prevent symptomatic development of an experimentally induced cold. METHODS: We carried out a systematic search of English- and German-language literature using the MEDLINE, EMBASE, CAplus, BIOSIS, CABA, AGRICOLA, TOXCENTER, SCISEARCH, NAHL, and NAPRALERT, databases and the search terms Echinacea, black Sampson, coneflower, and Roter Sonnenbut. Matching documents were then searched for > or = 1 of the following terms: rhinovirus, RV, inoculation, Inokulation, induced, induziert, artificial, and artifiziell. Suitable studies were identified and pooled for analysis. The primary end point was the development of symptomatic clinical colds, as defined by the authors of the original studies. Results were reported as differences in the proportion of subjects with symptomatic episodes of a common cold, expressed as odds ratios (ORs) and 95% CIs. The secondary outcome was the difference in total symptom severity scores between treatment groups (assessed daily by integrating the severity scores of 8 individual cold-related symptoms that were rated on a scale from 0 [absent] to 4 [very severe]). RESULTS: A total of 234 articles were identified through the literature search; 231 were excluded from the analysis because they related to studies of spontaneous common colds. Three suitable studies were selected for pooling of data. Based on the analysis, the likelihood of experiencing a clinical cold was 55% higher with placebo than with Echinacea (OR, 1.55 [95% CI, 1.02-2.36]; P<0.043). The absolute difference in total symptom scores between groups was -1.96 (95% CI, -4.83 to 0.90; P=NS). CONCLUSIONS: This meta-analysis suggests that standardized extracts of Echinacea were effective in the prevention of symptoms of the common cold after clinical inoculation, compared with placebo. Further prospective, appropriately powered clinical studies are required to confirm this finding.

[Treatment of inflammatory diseases of the upper respiratory tract -- comparison of a homeopathic complex remedy with xylometazoline]. / Behandlung von Entzündungen im Bereich der oberen Atemwege -- Vergleich eines homöopathischen Komplexpräparates mit Xylometazolin.

INTRODUCTION: The primary objective of treatment of inflammatory diseases of the upper respiratory tract (rhinitis, uncomplicated sinusitis) with local decongestants is to relieve obstruction and to improve associated symptoms. Restoration of unrestricted respiration and drainage of the nasal sinuses reduce the risk of further complications (i.e. chronicity). OBJECTIVE: To determine whether the therapeutic effects of the homeopathic complex remedy Euphorbium compositum nasal drops SN are comparable to those of xylometazoline with respect to efficacy and tolerability. METHODS: Open, multicenter, prospective, active-controlled cohort study in patients with inflammatory processes and diseases of the upper respiratory tract. The primary outcome was to demonstrate non-inferiority of the homeopathic complex remedy to xylometazoline. RESULTS: Clinically relevant reductions in the intensities of disease-specific symptoms were observed with both therapies. Non-inferiority of the homeopathic complex remedy to xylometazoline could be shown for all studied variables and in no case did the lower boundary of the 95% confidence interval cross the threshold of 0.5 score points. Tolerability was good with for both therapies. CONCLUSIONS: This cohort study indicates a comparable efficacy and tolerability profile of the homeopathic complex remedy Euphorbium compositum nasal drops SN and the reference substance xylometazoline in patients with inflammatory processes and diseases of the upper respiratory tract.

The homeopathic preparation Vertigoheel versus Ginkgo biloba in the treatment of vertigo in an elderly population: a double-blinded, randomized, controlled clinical trial.

OBJECTIVE: Alternative medical practices are common in the treatment of vertigo. This study compared the effects of Ginkgo biloba treatment with the homeopathic remedy Vertigoheel (Biologische Heilmittel Heel GmbH, Baden-Baden, Germany). DESIGN: Randomized, double-blinded, parallel group study. SUBJECTS: One hundred and seventy (170) patients, ages 60-80 years, with atherosclerosis-related vertigo. INTERVENTIONS: Patients were randomly allocated to receive treatment with either Vertigoheel (n = 87) or G. biloba (n = 83). OUTCOME MEASURES: The results were analyzed for the non-inferiority of Vertigoheel to G. biloba on the combined endpoint of changes from baseline to week 6 in dizziness score (assessed by questionnaire), frequency, duration, and intensity of vertigo episodes (recorded in patient diaries). RESULTS: Both treatments improved vertigo status. From a baseline mean value of 26.1 +/- 5.2 (on a 50-point scale) in the Vertigoheel group, the dizziness questionnaire score improved by -10.6 +/- 10.0, and by -10.7 +/- 9.0 from 25.8 - 4.7 in the G. biloba group. Statistical analysis of this endpoint showed that Vertigoheel was not inferior to G. biloba. The 95% confidence interval for the difference between treatment did not reach the inferiority threshold of 0.36 at any of the time points tested. The results were supported by the results of a line walking test, Unterberger's stepping test, and patient and physician global assessments of therapeutic effect. Both treatments were well tolerated. CONCLUSIONS: Vertigoheel is an appealing alternative to established G. biloba therapy for atherosclerosis-related vertigo.

Treatment of vertigo with a homeopathic complex remedy compared with usual treatments: a meta-analysis of clinical trials.

The increasing interest in alternative medical practices has led to a number of controlled studies on herbal and homeopathic agents. This paper presents the results of a meta-analysis of four recent clinical trials evaluating the homeopathic preparation Vertigoheel (VH) compared with usual therapies (betahistine, Ginkgo biloba extract, dimenhydrinate) for vertigo in a total of 1388 patients. Two trials were observational studies and the other two were randomised double-blind controlled trials. The duration of treatment (6-8 weeks) and dosage were comparable in all studies. Treatments were evaluated for the variables "number of vertigo episodes", "intensity of episodes" and "duration of episodes". As the studies differed in the age of patients and in the baseline values of vertigo, the individual reductions of number, intensity and duration of episodes were adjusted on equal age and baseline values (total means). An analysis of variance (with studies as random effects) showed no relevant influence of studies on the adjusted reductions and no relevant interaction between studies and treatment effects. The meta-analysis of all four trials showed equivalent reductions with VH and with control treatment: mean reduction of the number of daily episodes 4.0 for VH and 3.9 for control (standard error 0.11 for both groups); mean reduction of the duration (on a scale 0-4) for VH 1.1 and for the control 1.0 (standard error 0.03 for both groups); mean reduction of the intensity (on a scale 0-4) for VH 1.18 and for the control 1.8 (standard error 0.03 for both groups). In the non-inferiority analysis from all trials, VH was non-inferior in all variables. The results show the applicability of meta-analyses on the data from studies with homeopathicdrugs and support the results from the individual studies indicating good efficacy and tolerability of VH in patients with vertigo.

The effects of a complex homeopathic medicine compared with acetaminophen in the symptomatic treatment of acute febrile infections in children: an observational study.

CONTEXT: Children frequently suffer infections accompanied by fever, which is commonly treated with acetaminophen (paracetamol), a use not devoid of risk. OBJECTIVE: The effect of a complex homeopathic medicine (Viburcol, Heel Belgium, Gent, Belgium) was compared with that of acetaminophen in children with infectious fever. DESIGN: Non-randomized observational study. SETTING: Thirty-eight Belgian centers practicing homeopathy and conventional medicine. PATIENTS: Children <12 years old. INTERVENTIONS: Viburcol (drops) or acetaminophen (pills, capsules, or liquid form) for a maximum of 2 weeks. MAIN OUTCOME MEASURES: Fever, cramps, distress, disturbed sleep, crying, and difficulties with eating or drinking. Symptoms were graded by the practitioner on a scale from 0 to 3. Severity of infection was evaluated on a scale from 0 to 4. Data were captured on body temperature, subjective impression of health status, time to first improvement of symptoms, and global evaluation of treatment effects. Tolerability and compliance were monitored. RESULTS: Both treatment groups improved during the treatment period. Body temperature was reduced by 1.7 degrees C +/- 0.7 degrees C with Viburcol and by 1.9 degrees C +/- 0.9 degrees C with acetaminophen; fever score (scale from 0 to 3) from 1.7 +/- 0.6 to 0.1 +/- 0.2 with Viburcol and from 1.9 +/- 0.7 to 0.2 +/- 0.5 with acetaminophen (all values mean +/-SD). The overall severity of infection (scale from 0 to 4) decreased from 2.0 +/- 0.5 to 0.0 +/- 0.2 with Viburcol and from 2.2 +/- 0.7 to 0.2 +/- 0.6 with acetaminophen. There were no statistically significant differences between treatment groups in time to symptomatic improvement. Viburcol was noninferior to acetaminophen on all variables evaluated. Both treatments were very well tolerated, but the Viburcol group had a significantly greater number of patients with the highest tolerability score. CONCLUSIONS: In this patient population, Viburcol was an effective alternative to acetaminophen treatment and significantly better tolerated.

A homeopathic ointment preparation compared with 1% diclofenac gel for acute symptomatic treatment of tendinopathy.

CONTEXT: The incidence of tendon injuries and tendinopathy has risen substantially in the past decades. OBJECTIVE: To assess the noninferiority of therapy based on the homeopathic preparation Traumeel S ointment (Heel GmbH, Baden-Baden, Germany) compared with treatment based on diclofenac 1% gel in patients with tendinopathies of varying etiology. DESIGN: Nonrandomized, observational study. SETTING: Ninety-five homeopathy and conventional medical practices in Germany. PATIENTS: Three hundred fifty-seven patients aged 18 to 93 years with tendinopathy of varying etiology based on excessive tendon load rather than inflammation. INTERVENTIONS: Traumeel S ointment or diclofenac 1% gel for a maximum of 28 days. MAIN OUTCOME MEASURES: Efficacy was measured on a four-degree scale on pain-related variables, on variables related to motility, and on overall treatment outcome. Tolerability was monitored as adverse events. Compliance was assessed by practitioner and patient on a four-degree scale. RESULTS: The patients groups were comparable at baseline. The changes in summary score of all pain-related variables were -5.3 +/- 2.7 (all values means +/- SD) in the Traumeel group and -5.0 +/- 2.7 in the control group. Changes for all motility-related variables were -4.2 +/- 3.8 with Traumeel and -3.7 +/- 3.4 with control therapy. The summary scores for all clinical variables were reduced by -9.5 +/- 5.7 with Traumeel therapy and by -8.7 +/- 5.4 with diclofenac-based treatment. Homeopathic therapy was noninferior to diclofenac therapy on all variables. For motility-related variables, there was a trend toward superiority of Traumeel. Treatments were well tolerated with no treatment-related adverse events. CONCLUSIONS: The results suggest that Traumeel ointment is an effective alternative to nonsteroidal antiinflammatory drugs therapy for the acute symptomatic treatment of patients with tendinopathy.

Lysophosphatidic acid acyltransferase-beta: a novel target for induction of tumour cell apoptosis.

Phosphatidic acid (PA) is a component of cellular membranes that is also a mediator of certain cell signalling functions associated with oncogenesis. These include ras/raf/Erk and Akt/mTor [1-3]. The authors have investigated whether it would be possible to interrupt these known oncogenic pathways through the inhibition of lysophosphatidic acid acyltransferase (LPAAT), an enzyme that catalyses the biosynthesis of PA. The expression and activity of the LPAAT-beta isoform are elevated in human tumours, and the respective gene displays transforming capacity when overexpressed in vitro. Inhibition by either genetic means or by isoform-specific small molecules results in a block to cell signalling pathways and apoptosis. Furthermore, the small-molecule inhibitors of LPAAT-beta are not cytotoxic to a number of normal cell types, including primary bone marrow progenitors, indicating a differential dependence of tumour cells on LPAAT-beta function. These discoveries indicate that LPAAT-beta represents a potential novel cancer therapy target.