Quality of Life in Breast Cancer Patients Treated With Mistletoe Extracts: A Systematic Review and Meta-Analysis.

BACKGROUND: Breast cancer is the most common cancer type in women and quality of life an essential part of patients' well-being. Although the treatment with mistletoe extracts is covered by multiple cancer guidelines and reviews, it is uncertain whether mistletoe extracts can improve the quality of life in breast cancer patients. We therefore performed a systematic review and meta-analysis on this topic. METHODS: This systematic review included randomized clinical trials (RCTs) and non-randomized studies of intervention (NRSIs) comparing the quality of life in breast cancer patients treated with mistletoe extracts as add-on therapy to control groups treated conventionally. We searched previous systematic reviews and multiple databases until January 2023. We conducted a meta-analysis and assessed the risk of bias according to the Cochrane Handbook via RoB 2 and ROBINS-I and the certainty of evidence via GRADE, respectively. RESULTS: Nine RCTs and 7 NRSIs with 833 and 2831 participants, respectively, were included. The pre-post changes for the quality of life resulted in a pooled standardized mean difference for RCTs of SMD = 0.61 (95% CI 0.47-0.75; P < .0001) and for retrospective NRSIs of SMD = 0.46 (95% CI 0.10-0.82; P = .01). The risk of bias was low to high for the RCTs and serious for all NRSIs. The certainty of evidence was moderate for RCTs and very low for NRSIs. DISCUSSION: Our results indicate a clinically relevant, medium-sized effect of mistletoe extracts on the quality of life in breast cancer patients which may be based on the immunomodulating effects of mistletoe extracts during chemotherapy. The limitations of evidence include the risk of bias which is mainly caused by the difficulty of blinding. Further RCTs and real-world evidence need to confirm this result, especially in the setting of neoadjuvant chemotherapy and in breast cancer survivors.

Systematic reviews and meta-analyses in Homeopathy: Recommendations for summarising evidence from homeopathic intervention studies (Sum-HomIS recommendations).

BACKGROUND: Mainly due to the use of different inclusion criteria and quality assessments, systematic reviews (SRs) and meta-analyses (MAs) with homeopathic intervention studies (HOMIS) have shown inconsistent results. We aimed to build recommendations for "Summarizing evidence from Homeopathic Intervention Studies" (Sum-HomIS recommendations) in order to approach standardization. METHODS: Against the background of a framework-project to update the evidence from homeopathic intervention studies, we launched an expert panel on how to assess the quality of HOMIS and how to summarize evidence from HOMIS. The results of a literature review and the expert communications in advance of the panel as well as the consensus from the discussions are presented here. We added specific considerations for homeopathic veterinary research. RESULTS: On top of the general guidelines when planning a review we report five basic Sum-HomIS recommendations. These are: 1) A broad literature search including special archives and consideration of so-called grey-literature; 2) The inclusion of controlled observational studies alongside randomized controlled trials; 3) The choice of a clear clinical research question in the terms that, if possible, the review project includes studies with predominantly homogeneous populations, interventions, comparators and outcomes (PICOs); 4) The use of a global quality assessment including the assessment of external, model and internal validity; 5) A summary of evidence using the GRADE-approach if the body of evidence is sufficiently large and homogenous or a descriptive summary if it is not so. CONCLUSIONS: We present recommendations for designing, conducting, and reporting SRs and MAs with HOMIS.

Bioenergy Treatment for Improving Well-Being: A Meta-Analysis.

BACKGROUND: Bioenergy treatment devices for self-treatment with the aim to improve well-being are widely available, have become popular, and are used by a rather large number of persons. Yet, a systematic analysis of the assumed effect of these devices has not yet been conducted. We meta-analyzed eight very similar studies of the Healy device to assess the joint effect size. METHOD: Eight studies with similar designs, some active controlled and some wait-list controlled, testing the Healy bioenergy device, were meta-analyzed. They were conducted by the producer of the device for quality assurance and further development of the application. An additional literature search revealed no additional, independent studies. RESULT: The overall effect size across studies, combining all active arms and averaging outcome measures, is Hedge's g = 0.757 (random effects model, I2 = 85.8; z = 6.57; p < 0.0001). The stronger active intervention against control yields a heterogeneous g = 0.825 (random effects, I2 = 82.5; z = 7.77; p < 0.0001). Active treatments against each other result in a significant g = 0.29 (fixed effects, I2 = 0.0; z = 8.34; p < 0.0001). DISCUSSION: The highest effect sizes are produced by a measure of coherence, followed by the WHO5 well-being questionnaire, the Perceived Stress Scale, with the Measure Your Own Medical Outcome Profile, resulting in the smallest effect size. Heterogeneity can be partially explained by the type of control, with active control producing smaller and wait-list control producing larger outcomes. Another source of heterogeneity is the sequencing of studies. Effect sizes grew for three studies, which were similar, and then fell and remained very similar for the rest of the studies. A limitation of this analysis is the fact that all studies were conducted by the R and D Department of the producer of the device. CONCLUSION: In this meta-analysis, the Healy device showed considerable effects, improving general well-being in healthy individuals. Nonetheless, an independent confirmation of these findings would be desirable. Moreover, the potential mechanisms of effect of the bioenergy device remain unclear, and further studies addressing this research question are warranted.

Bibliography of Homeopathic Intervention Studies (HOMIS) in Human Diseases.

Objectives: Homeopathy (HOM) is a therapeutic method, which is widely used by patients and medical professionals. The medical conditions as well as the homeopathic medical products investigated vary strongly. There is an extensive amount of research, and this necessitates a bibliography that comprehensively presents the entire body of clinical evidence grouped according to medical conditions. Design: Thirty-seven online sources as well as print libraries were searched for HOM and related terms in eight languages (1980 to March 2021). We included studies that compared a homeopathic medicine or intervention with a control regarding the therapeutic or preventive outcome of a disease (classified according to International Classification of Diseases-10). The data were extracted independently by two reviewers and analyzed descriptively. Results: A total of 636 investigations met the inclusion criteria, of which 541 had a therapeutic and 95 a preventive purpose. Seventy-three percent were randomized controlled trials (n = 463), whereas the rest were non-randomized studies (n = 173). The leading comparator was placebo (n = 400). The type of homeopathic intervention was classified as multi-constituent or complex (n = 272), classical or individualized (n = 176), routine or clinical (n = 161) and isopathic (n = 19), or various (n = 8). The potencies ranged from 1X (dilution of -10,000) to 10 M (100-10.000). The included studies explored the effect of HOM in 223 medical indications. We present the evidence in an online database. Conclusions: This bibliography maps the status quo of clinical research in HOM. The data will serve for future targeted reviews, which may focus on the most studied conditions and/or homeopathic medicines, clinical impact, and the risk of bias of the included studies.

Survival of Cancer Patients Treated with Non-Fermented Mistletoe Extract: A Systematic Review and Meta-Analysis.

BACKGROUND: Mistletoe extracts (ME) are used in integrative cancer care to improve quality of life and to prolong survival. ME are available from different producers and differ in pharmaceutical processing, such as fermentation. In contrast to fermented ME, the impact of unfermented extracts on the survival of cancer patients has not yet been assessed in a meta-analysis. METHODS: We searched the databases Embase, CENTRAL, Europe PMC, Clinicaltrials.gov, Opengrey and Google Scholar, and selected controlled studies on cancer patients treated with non-fermented ME. We included randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs). The risk of bias was assessed with Cochrane's ROB2 and ROBINS-I; a meta-analysis was conducted. RESULTS: Eleven RCTs and eight NRSIs met the inclusion criteria. The studies were heterogeneous and their ROB2 and ROBINS-I displayed a moderate and high risk of bias, respectively. For RCTs, the pooled effect estimate of non-fermented ME on survival was HR = 0.81 (95% CI 0.69-0.95, P = .01). Subgroup analyses as well as the NRSIs estimation support the robustness of the finding. When active comparators are added to the analysis, the effect estimates become non-significant. CONCLUSION: The results may indicate a positive impact of non-fermented ME on the overall survival of cancer patients. High quality RCTs are necessary to substantiate our results. PROSPERO REGISTRATION: CRD42021233177.

Assessment of a taping method combined with manual therapy as a treatment of non-specific chronic low back pain - a randomized controlled trial.

BACKGROUND: Chronic low back pain is the most frequent medical problem and the condition with the most years lived with disability in Western countries. The objective of this study was to assess a new treatment, Medi-Taping, which aims at reducing complaints by treating pelvic obliquity with a combination of manual treatment of trigger points and kinesio taping in a pragmatic RCT with pilot character. METHODS: One hundred ten patients were randomized at two study centers either to Medi-Taping or to a standard treatment consisting of patient education and physiotherapy as control. Treatment duration was 3 weeks. Measures were taken at baseline, end of treatment and at follow-up after 2 months. Main outcome criteria were low back pain measured with VAS, the Chronic Pain Grade Scale (CPGS) and the Oswestry Low Back Pain Disability Questionnaire (ODQ). RESULTS: Patients of both groups benefited from the treatment by medium to large effect sizes. All effects were pointing towards the intended direction. While Medi-Taping showed slightly better improvement rates, there were no significant differences for the primary endpoints between groups at the end of treatment (VAS: mean difference in change 0.38, 95-CI [- 0.45; 1.21] p = 0.10; ODQ 2.35 [- 0.77; 5.48] p = 0.14; CPGS - 0.19 [- 0.46; 0.08] p = 0.64) and at follow-up. Health-related quality of life was significantly higher (p = .004) in patients receiving Medi-Taping compared to controls. CONCLUSIONS: Medi-Taping, a purported way of correcting pelvic obliquity and chronic tension resulting from it, is a treatment modality similar in effectiveness to complex physiotherapy and patient education. TRIAL REGISTRATION: This trial was registered retrospectively on July 24th, 2019 as Number DRKS00017051 in the German Register of Clinical Trials (Deutsches Register Klinischer Studien). URL of trial registry record: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017051 .

Is Homeopathic Arnica Effective for Postoperative Recovery? A Meta-analysis of Placebo-Controlled and Active Comparator Trials.

Background: Homeopathic Arnica montana is used in surgery as prevention or treatment for the reduction of pain and other sequelae of surgery. Our aim was to perform a metaanalysis of clinical trials to assess efficacy of Arnica montana to reduce the inflammatory response after surgery. Method: We conducted a systematic review and metaanalysis, following a predefined protocol, of all studies on the use of homeopathic Arnica montana in surgery. We included all randomized and nonrandomized studies comparing homeopathic Arnica to a placebo or to another active comparator and calculated two quantitative metaanalyses and appropriate sensitivity analyses. We used "Hegde's g," an effect size estimator which is equivalent to a standardized mean difference corrected for small sample bias. The PROSPERO registration number is CRD42020131300. Results: Twenty-three publications reported on 29 different comparisons. One study had to be excluded because no data could be extracted, leaving 28 comparisons. Eighteen comparisons used placebo, nine comparisons an active control, and in one case Arnica was compared to no treatment. The metaanalysis of the placebo-controlled trials yielded an overall effect size of Hedge's g = 0.18 (95% confidence interval -0.007/0.373; p = 0.059). Active comparator trials yielded a highly heterogeneous significant effect size of g = 0.26. This is mainly due to the large effect size of nonrandomized studies, which converges against zero in the randomized trials. Conclusion: Homeopathic Arnica has a small effect size over and against placebo in preventing excessive hematoma and other sequelae of surgeries. The effect is comparable to that of anti-inflammatory substances.

Quality of life in cancer patients treated with mistletoe: a systematic review and meta-analysis.

BACKGROUND: Mistletoe extracts are used as an adjunct therapy for cancer patients, but there is dissent as to whether this therapy has a positive impact on quality of life (QoL). METHODS: We conducted a systematic review searching in several databases (Medline, Embase, CENTRAL, CINAHL, PsycInfo, Science Citation Index, clinicaltrials.gov, opengrey.org ) by combining terms that cover the fields of "neoplasm", "quality of life" and "mistletoe". We included prospective controlled trials that compared mistletoe extracts with a control in cancer patients and reported QoL or related dimensions. The quality of the studies was assessed with the Cochrane Risk of Bias tool version 2. We conducted a quantitative meta-analysis. RESULTS: We included 26 publications with 30 data sets. The studies were heterogeneous. The pooled standardized mean difference (random effects model) for global QoL after treatment with mistletoe extracts vs. control was d = 0.61 (95% CI 0.41-0.81, p < 0,00001). The effect was stronger for younger patients, with longer treatment, in studies with lower risk of bias, in randomized and blinded studies. Sensitivity analyses support the validity of the finding. 50% of the QoL subdomains (e.g. pain, nausea) show a significant improvement after mistletoe treatment. Most studies have a high risk of bias or at least raise some concern. CONCLUSION: Mistletoe extracts produce a significant, medium-sized effect on QoL in cancer. Risk of bias in the analyzed studies is likely due to the specific type of treatment, which is difficult to blind; yet this risk is unlikely to affect the outcome. PROSPERO REGISTRATION: CRD42019137704 .

Recommendations for Designing, Conducting and Reporting Observational Studies in Homeopathy.

BACKGROUND: Randomized placebo-controlled trials are considered to be the gold standard in clinical research and have the highest importance in the hierarchical system of evidence-based medicine. However, from the viewpoint of decision makers, due to lower external validity, practical results of efficacy research are often not in line with the huge investments made over decades. METHOD: We conducted a narrative review. With a special focus on homeopathy, we give an overview on cohort, comparative cohort, case-control and cross-sectional study designs and explain guidelines and tools that help to improve the quality of observational studies, such as the STROBE Statement, RECORD, GRACE and ENCePP Guide. RESULTS: Within the conventional medical research field, two types of arguments have been employed in favor of observational studies. First, observational studies allow for a more generalizable and robust estimation of effects in clinical practice, and if cohorts are large enough, there is no over-estimation of effect sizes, as is often feared. We argue that observational research is needed to balance the current over-emphasis on internal validity at the expense of external validity. Thus, observational research can be considered an important research tool to describe "real-world" care settings and can assist with the design and inform the results of randomised controlled trails. CONCLUSIONS: We present recommendations for designing, conducting and reporting observational studies in homeopathy and provide recommendations to complement the STROBE Statement for homeopathic observational studies.

Power Point Therapy: An Effective and Simple Treatment for Subacute Back Pain - A Randomized Controlled Trial.

OBJECTIVE: Subacute low back pain is a frequent problem with the danger of chronification. Conventional treatment options are not always effective. Power Point therapy (PPT) is a novel approach that uses reflexological insights and can be easily applied by practitioners and patients. METHODS: Randomized, active controlled study comparing 10 units of PPT of 10 min each, with 10 units of standard physiotherapy of 30 min each. Outcomes were functional scores (Roland Morris Disability, Oswestry, McGill Pain Questionnaire, Linton-Halldén - primary outcome) and health-related quality of life (SF-36), as well as blinded assessments by clinicians (secondary outcome). RESULTS: Eighty patients consented and were randomized, 41 to PPT, 39 to physiotherapy. Measurements were taken at baseline, after the first and after the last treatment (approximately 5 weeks after enrolment). Multivariate linear models of covariance showed significant effects of time and group (p < 0.001) and for the quality of life variables also a significant interaction of time by group (p < 0.001). Clinician-documented variables showed significant differences at follow-up (p = 0.05 to p < 0.0001). DISCUSSION: Both physiotherapy and PPT improve subacute low back pain significantly. PPT is likely more effective and should be studied further.

Feldenkrais 'Functional Integration' Increases Body Contact Surface in the Supine Position: A Randomized-Controlled Experimental Study.

Feldenkrais 'Functional Integration' (FI) is a widely used type of body work with a focus on the continuous integration of body sensations and awareness with movement. The method is, amongst others, known for improving balance in aging populations, but also for its ability to relax muscles. With participants treated in the supine position FI is potentially changing the surface area of the body in contact with the surface on which a participant is lying. So far, no prior study has assessed this claim. We evaluated objectively and subjectively if a treatment with FI would induce changes in pressure and contact surface of the body on the mat. Thirty volunteers received an individual treatment with FI, in a randomized order on both sides of the body. Pressure and contact surface was documented with the Xsensor-Measurement-System. Subjective sensations were assessed with a self-report scale. Due to two parallel assessments alpha-level was adjusted to α = 0.025. We found that pressure and contact surface of the body on the mat significantly changed after the treatment (factor time: p < 0.0001, η p 2 = 0.90). We also found that pressure and contact surface increased significantly on the left side for the group that started with the left side first (time × group p = 0.016; η p 2 = 0.62), but less so on the right side for the group that started with the right side first (time × group: p = 0.056) although there was still a substantial effect size ( η p 2 = 0.54). The subjective reports confirmed the physical measurements. In conclusion our results demonstrate for the first time that the treatment with the Feldenkrais method changes muscle tone leading to a more relaxed supine position with respect to pressure and contact surface on the mat.

RegentK and Physiotherapy Support Knee Function after Anterior Cruciate Ligament Rupture without Surgery after 1 Year: A Randomized Controlled Trial.

BACKGROUND: Recent data have opened the debate on whether conservative treatment of anterior cruciate ligament (ACL) rupture might be an alternative treatment option to surgery. In a previous study, such a conservative treatment, i.e. 'Regenerative Therapy According to Mohammed Khalifa' (RegentK), had shown good effects over physiotherapy. METHODS: This was a randomized controlled trial assessing the efficacy of 1 session of RegentK compared to the myofascial mobilization technique (MMT), another type of intensive physiotherapy, in 20 patients with fresh ACL rupture during the previous 4 weeks. The International Knee Documentation Committee (IKDC) 2000 score was measured before, immediately after, and 3 months after treatment, and 1 year later; magnetic resonance imaging (MRI) data were taken before treatment and 1 year after treatment. RESULTS: Both groups were comparable at baseline. A repeated measures analysis of variance showed a strong effect of time (p < 0.0001; partial η2 = 0.81) and no significant interaction or group effect. Both groups reached near full function after 1 year. The IKDC score was 90.9 (standard deviation (SD) 6.7; 95% confidence interval (CI) 86.2-95.6) for the RegentK group and 93.3 (SD 3.1; 95% CI 91.1-95.5) for the MMT group. CONCLUSION: One treatment session of enhanced MMT physiotherapy or RegentK can lead to nearly full function and thus recovery of a ruptured ACL after 1 year.

[Healing of Amyotrophic Lateral Sclerosis: A Case Report].

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating disease leading to death within 3-5 years in most cases. New approaches to treating this disease are needed. Here, we report a successful therapy. CASE REPORT: In a 49-year-old male patient suffering from muscle weakness and fasciculations, progressive muscular atrophy, a variant of ALS, was diagnosed after extensive examinations ruling out other diseases. Due to supposed mercury exposure from residual amalgam, the patient's teeth were restored. Then, the patient received sodium 2,3-dimercaptopropanesulfate (DMPS; overall 86 × 250 mg in 3 years) in combination with α-lipoic acid and followed by selenium. In addition, he took vitamins and micronutrients and kept a vegetarian diet. The excretion of metals was monitored in the urine. The success of the therapy was followed by scoring muscle weakness and fasciculations and finally by electromyography (EMG) of the affected muscles. First improvements occurred after the dental restorations. Two months after starting therapy with DMPS, the mercury level in the urine was increased (248.4 µg/g creatinine). After 1.5 years, EMG confirmed the absence of typical signs of ALS. In the course of 3 years, the patient recovered completely. CONCLUSIONS: The therapy described here is a promising approach to treating some kinds of motor neuron disease and merits further evaluation in rigorous trials.