Mistletoe, an anthroposophical medicine, is often recommended as a so-callled alternative medicine (SCAM) for cancer patients. But what type of cancer, what type of mistletoe preparation, what dosage regimen, what form of application?
The aim of this systematic analysis was to assess the concept of mistletoe treatment in published clinical studies with respect to indication, type of mistletoe preparation, treatment schedule, aim of treatment, and assessment of treatment results. The following databases were systematically searched: Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL, and “Science Citation Index Expanded” (Web of Science). The researchers assessed all studies for study types, methods, endpoints and mistletoe preparations including their ways of application, host trees and dosage schedules.
The searches revealed 3296 hits. Of these, 102 publications with a total of 19.441 patients were included. The researchers included several study types investigating the application of mistletoe in different groups of participants: cancer patients with any type of cancer were included as well as studies conducted with healthy volunteers and pediatric patients. The most common types of cancer were:
- breast cancer,
- pancreatic cancer,
- colorectal cancer,
- malignant melanoma.
Randomized controlled studies, cohort studies and case reports make up most of the included studies. A huge variety was observed concerning the type and composition of mistletoe extracts (differing pharmaceutical companies and host trees), ways of applications and dosage schedules. Administration varied widely, e. g. between using mistletoe extract as sole treatment and as concomitant therapy to cancer treatment. The researchers found no relationship between the mistletoe preparation used, host tree, dosage, and cancer type.
A variety of different mistletoe preparations was used to treat cancer patients. Due to the heterogeneity of the mistletoe preparations used, no comparability between different studies or within single studies using different types of mistletoe preparations or host trees is possible. Moreover, no relationship between mistletoe preparation and type of cancer can be observed. This results in a severely limited comparability of studies with regard to the different cancer entities and mistletoe therapy in oncology in general. Analyzing the methods sections of all articles, there are no information on how the selection of the respective mistletoe preparation took place. None of the articles provided any argument which type of preparation (homeopathic, anthroposophic, standardized) or which host tree was chosen due to which selection criteria. Considering preparations from different companies, funding may have been the reason of the selection.
Dosage or dosage regimens varied strongly in the studies. Due to the heterogeneity of dosage and dosage regimens within studies and between studies of the endpoints the comparability of the different studies is severely limited. Duration of mistletoe treatment varied strongly in the studies ranging from a single dose given on one day to the application of mistletoe preparations for several years. Moreover, the duration of treatment frequently varied within the studies. Mistletoe preparations were administered by different ways of application. Most frequently, the patients received mistletoe preparations subcutaneously. The second most common way was intravenous administration of mistletoe preparations. According to the respective manufacturers, this type of application is only recommended for Lektinol® and Eurixor®. Other preparations were given as off-label intravenous applications. No dosage recommendations from the respective manufacturers were available. Only in two studies the dose schedules were mentioned: according to the classical phase I 3 + 3 dose escalation schedule or in ratio to the body surface area.
The authors concluded that despite a large number of clinical studies and reports, there is a complete lack of transparently reported, structured procedures considering all fields of mistletoe therapy. This applies to type of mistletoe extract, host tree, preparation, treatment schedules as well as indication with respect of type of cancer and the respective treatment aim. All in all, despite several decades of clinical mistletoe research, no clear concept of usage is discernible and, from an evidence-based point of view, there are serious concerns on the scientific base of this part of anthroposophical treatment.
A long time ago, I worked as a junior doctor in a hospital where we used subcutaneous misteloe injections regularly to treat cancer. I remember being utterly confused: none of my peers was able to explain to me what preparation to use and how to does it. There simply were no rules and the manufacurer’s instructions made little sense. I suspected then that mistletoe therapy was a danerous nonsense. Today, after much research has been published on mistletoe, I do no longer suspect it, I know it.
I would urge every cancer patient to stay well clear of mistletoe and those practitioners who recommend it.
Autogenic training (AT) is a relaxation technique that has garnered attention for its potential to reduce anxiety and improve psychological well-being. This review aimed to synthesize the findings from a diverse range of studies investigating the relationship between AT and anxiety disorder across different populations and settings.
A comprehensive review of 162 studies, including randomised controlled trials (RCTs), non-randomized controlled trials (N-RCTs), surveys, and meta-analysis, was conducted and 29 studies were selected. Participants in the studies were patients with:
- bulimia nervosa,
- coronary angioplasty,
Others were nursing students, healthy volunteers, athletes, etc.
Anxiety levels were measured before and after the AT intervention using a variety of anxiety assessment scales, including the State Trait Anxiety Inventory (STAI) and the Hospital Anxiety and Depression Scale (HADS). The formats, duration, and delivery of the interventions varied, with some studies utilising guided sessions by professionals and other self-administered practises.
The combined findings of these studies revealed consistent trends in the beneficial effects of AT on anxiety reduction. AT was found to be effective in reducing anxiety symptoms across a wide range of populations and settings. Following AT interventions, participants reported reduced anxiety, improved mood states, and improved coping mechanisms. AT was found to be superior to no treatment or a comparable intervention in a number of cases.
The authors conclused that the body of evidence supports autogenic training as a non-pharmacological approach to reducing anxiety and improving psychological well-being. Despite differences in methodology and participant profiles, the studies show that AT has a positive impact on a wide range of populations. The findings merit further investigation and highlight AT’s potential contribution to anxiety management strategies.
I was taught AT many years ago and have practised it occasionally ever since. I have also co-authored several papers of AT that showed encouraging results, e.g.:
- Autogenic training for tension type headaches: a systematic review of controlled trials. Complement Ther Med. 2006 Jun;14(2):144-50.
- Autogenic training for stress and anxiety: a systematic review. Complement Ther Med. 2000 Jun;8(2):106-10.
- Autogenic training to reduce anxiety in nursing students: randomized controlled trial. Kanji N, White A, Ernst E.J Adv Nurs. 2006 Mar;53(6):729-35.
- Autogenic training to manage symptomology in women with chest pain and normal coronary arteries. Menopause. 2009 Jan-Feb;16(1):60-5.
- Autogenic training reduces anxiety after coronary angioplasty: a randomized clinical trial. Am Heart J. 2004 Mar;147(3)
Thus, I feel that the conclusions of this review might be correct.
Several further recent papers seem to support the notion that AT is a treatment worth trying, e.g.:
- A review concluded that as an add-on intervention psychotherapy technique with beneficial outcome on psychophysiological functioning, AT represents a promising avenue towards expanding research findings of brain-body links beyond the current limits of the prevention and clinical management of number of mental disorders.
- A clinical trial showed that AT seems to improve sleep quality and could improve some dimensions of quality of life and other symptoms among people living with HIV. Further studies are needed to confirm these results.
Why then AT is not better studied and more popular? A short paragraph of my next book (to be published in about 6 months) on the inventors of so-called alternative medicines (SCAMs), including the German psychiatry professor Johannes Schulz (1884-1970), inventor of AT, might give you a clue:
Schultz supported the euthanasia program of the Nazis, i.e. the extermination of disabled and other people considered ‘unworthy of living’ during the Third Reich. He passed death sentences on “hysterical women” through his diagnoses. In 1933, Schultz began research on a guide-book on sexual education in which he focused on homosexuality and explored the topics of sterilization and euthanasia. In 1935, he published an essay about the psychological consequences of sterilization and castration among men; in it he supported compulsory sterilization of men in order to eliminate hereditary illnesses. With a diagnostic scheme developed by him in 1940, Schulz advocated the execution of mentally ill patients by stating: “I personally have to align myself with Mr. Hoche […], by recalling the ‘annihilation of life unworthy of life’ and by raising the hope that the madhouses will soon become emptied and remodelled according to this principle.” Schultz was fully aware of the consequences of his diagnostic assessment and even used the term “death sentence in the form of a diagnosis”.
I came across this evidence only years after having published my papers on AT. Would I have developed an interest in AT, if I had known about Schulz’s Nazi past? Probably not.
This systematic review aimed to assess the impact of Tai Chi on individuals with essential hypertension and to compare the effects of Tai Chi with other therapies. The researchers conducted a systematic literature search of the Medline, Scholar, Elsevier, Wiley Online Library, Chinese Academic Journal (CNKI) and Wanfang databases from January 2003 to August 2023. Using the methods of the Cochrane Collaboration Handbook, a meta-analysis was conducted to assess the collective impact of Tai Chi exercise in controlling hypertension. The primary outcomes measured included blood pressure and nitric oxide levels.
A total of 32 RCTs were included. The participants consisted of adults with an average age of 57.1 years who had hypertension (mean ± standard deviation systolic blood pressure at 148.2 ± 12.1 mmHg and diastolic blood pressure at 89.2 ± 8.3 mmHg). Individuals who practiced Tai Chi experienced reductions in systolic blood pressure of 10.6 mmHg, diastolic blood pressure of 4.7 mmHg and an increase in nitric oxide levels.
The authors concluded that Tai Chi can be a viable lifestyle intervention for managing hypertension. Greater promotion of Tai Chi by medical professionals could extend these benefits to a larger patient population.
Tai Chi allegedly incorporates principles rooted in the Yin and Yang theory, Chinese medicine meridians and breathing techniques, and creates a unique form of exercise characterized by its inward focus, continuous flow, the balance of strength and gentleness, and alternation between fast and slow movements. What sets Tai Chi apart from other forms of excercise is the requirement for mindful guidance during practice. This aspect may, according to the authors, be the reason why Tai Chi also outperforms general aerobic exercise in managing hypertension.
I can well imagine that any form of relaxation reduces blood pressure. What I find hard to believe is that Tai Chi is better than any other relaxing SCAMs. The 32 RCTs included in this new review fail to impress me because they are all from China, and – as we have often mentioned before – studies from China are to be taken with a pinch of salt.
Yet, the subject is important enough, in my view, to merit a few rigorous trials conducted by independent researchers. Until such data are available, I think, I prefer to rely on our own systematic review which conculded that the evidence for tai chi in reducing blood pressure … is limited. Whether tai chi has benefits over exercise is still unclear. The number of trials and the total sample size are too small to draw any firm conclusions.
So-called alternative medicine (SCAM) interventions are growing in popularity and are even advocated as treatments for long COVID symptoms. However, comprehensive analysis of current evidence in this setting is still lacking. This study aims to review existing published studies on the use of SCAM interventions for patients experiencing long COVID through a systematic review of randomized controlled trials (RCTs).
A comprehensive electronic literature search was performed in multiple databases and clinical trial registries from September 2019 to January 2023. RCTs evaluating efficacy and safety of SCAM for long COVID were included. Methodological quality of each included trial
was appraised with the Cochrane ‘risk of bias’ tool. A qualitative analysis was conducted due to heterogeneity of included studies.
A total of 14 RCTs with 1195 participants were included in this review. Study findings demonstrated that SCAM interventions could benefit patients with long COVID, especially those suffering from
- neuropsychiatric disorders,
- olfactory dysfunction,
- cognitive impairment,
- mild-to-moderate lung fibrosis.
The main interventions reported were:
- self-administered transcutaneous auricular vagus nerve stimulation,
- dietary supplements,
- olfactory training,
- inspiratory muscle training,
- concurrent training,
- online breathing programs,
- online well-being programs.
The authors concluded that SCAM interventions may be effective, safe, and acceptable to patients with symptoms of long COVID. However, the findings from this systematic review should be interpreted with caution due to various methodological limitations. More rigorous trials focused on CAM for long COVID are warranted in the future.
Such wishy-washy conclusions seem to be popular in the fantasy land of SCAM. Yet, they are, in my view, most ojectionable because:
- they tell us nothing of value;
- that something “MAY BE EFFECTIVE” has been known before and cannot be the result of but is the reason for a systematic review;
- a review of 14 RCTs of almost as many interventions cannot possibly tell us anything about the SAFETY of these treatments;
- it also does not provide evidence of effectiveness and merely indicates a lack of independent replications;
- if the abstract mentions an assessment of the study rigor, one expects that it also informs us about this important aspect.
Once we do come around looking at the methodological quality of the primary studies we realize that it is mostly miserable. This means that the conclusions of the review are not just irritating but plainly misleading. Responsible researchers should have concluded along the following lines:
The quantity and the quality of the evidence are both low. Therefore, the effectiveness and safety of SCAM interventions for long COVID remains unproven.
This project was financially supported by The HEAD Foundation, Singapore and in part by the grant from the NIH R61 AT01218.
Shame on the authors, journal editors, peer-reviewers, and funders of this dangerous nonsense!
Many of you will be familiar with the ‘ALTERNATIVE MEDICINE HALL OF FAME’. It is my creation and meant to honour reserchers who have dedicated much of their professional career to investigating a form of so-called alternative medicine (SCAM) without ever publishing negative conclusions about it. Obviously, if anyone studies any therapy, he/she will occasionally produce a negative finding. This would be the case, even if he/she tests an effective treatment. However, if the treatment in question comes from the realm of SCAM, one would expect negative results fairly regularly. No therapy works well under all conditions, and to the best of my knowledge, no SCAM is a panacea!
This is why researchers who defy this inevitability are remarkable. If someone tests a treatment that is at best dubious and at worst bogus, we are bound to see some studies that are not positive. He/she would thus have a high or normal ‘TRUSTWORTHINESS INDEX‘ (another creation of mine which, I think, is fairly self-explanatory). Conversely, any researcher who does manage to publish nothing but positive results of a SCAM is bound to have a very low ‘TRUSTWORTHINESS INDEX‘. In other words, these people are special, so much so that I decided to honour such ‘geniuses’ by admitting them to my ALTERNATIVE MEDICINE OF FAME.
So far, this elite group of people comprises the following individuals:
- Helge Franke (osteopathy, Germany)
- Tery Oleson (acupressure , US)
- Jorge Vas (acupuncture, Spain)
- Wane Jonas (homeopathy, US)
- Harald Walach (various SCAMs, Germany)
- Andreas Michalsen ( various SCAMs, Germany)
- Jennifer Jacobs (homeopath, US)
- Jenise Pellow (homeopath, South Africa)
- Adrian White (acupuncturist, UK)
- Michael Frass (homeopath, Austria)
- Jens Behnke (research officer, Germany)
- John Weeks (editor of JCAM, US)
- Deepak Chopra (entrepreneur, US)
- Cheryl Hawk (chiropractor, US)
- David Peters (osteopathy, homeopathy, UK)
- Nicola Robinson (TCM, UK)
- Peter Fisher (homeopathy, UK)
- Simon Mills (herbal medicine, UK)
- Gustav Dobos (various SCAMs, Germany)
- Claudia Witt (homeopathy, Germany/Switzerland)
- George Lewith (acupuncture, UK)
- John Licciardone (osteopathy, US)
You will notice that the group does not yet contain a representative of anthroposophic medicine. Today, I intend to rectify this oversight by admitting Helmut Kiene (1952-). He has published plenty of studies and reviews on his pet subject; here are the ones that I found on Medline:
- Anthroposophic therapies in chronic disease: the Anthroposophic Medicine Outcomes Study (AMOS). Eur J Med Res. 2004 Jul 30;9(7):351-60.
- Anthroposophic medical therapy in chronic disease: a four-year prospective cohort study. Hamre HJ, Witt CM, Glockmann A, Ziegler R, Willich SN, Kiene H.BMC Complement Altern Med. 2007 Apr 23;7:10. doi: 10.1186/1472-6882-7-10.
- Anthroposophic art therapy in chronic disease: a four-year prospective cohort study. Hamre HJ, Witt CM, Glockmann A, Ziegler R, Willich SN, Kiene H.Explore (NY). 2007 Jul-Aug;3(4):365-71. doi: 10.1016/j.explore.2007.04.008.
- Rhythmical massage therapy in chronic disease: a 4-year prospective cohort study. Hamre HJ, Witt CM, Glockmann A, Ziegler R, Willich SN, Kiene H.J Altern Complement Med. 2007 Jul-Aug;13(6):635-42. doi: 10.1089/acm.2006.6345
- Anthroposophic vs. conventional therapy for chronic low back pain: a prospective comparative study. Hamre HJ, Witt CM, Glockmann A, Wegscheider K, Ziegler R, Willich SN, Kiene H.Eur J Med Res. 2007 Jul 26;12(7):302-10.
- Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research. Kienle GS, Glockmann A, Schink M, Kiene H.J Exp Clin Cancer Res. 2009 Jun 11;28(1):79. doi: 10.1186/1756-9966-28-79.
- Anthroposophic therapy for children with chronic disease: a two-year prospective cohort study in routine outpatient settings. Hamre HJ, Witt CM, Kienle GS, Meinecke C, Glockmann A, Willich SN, Kiene H.BMC Pediatr. 2009 Jun 19;9:39. doi: 10.1186/1471-2431-9-39
- Predictors of outcome after 6 and 12 months following anthroposophic therapy for adult outpatients with chronic disease: a secondary analysis from a prospective observational study. Hamre HJ, Witt CM, Kienle GS, Glockmann A, Willich SN, Kiene H.BMC Res Notes. 2010 Aug 3;3:218. doi: 10.1186/1756-0500-3-218.
- Pulpa dentis D30 for acute reversible pulpitis: A prospective cohort study in routine dental practice. Hamre HJ, Mittag I, Glockmann A, Kiene H, Tröger W.Altern Ther Health Med. 2011 Jan-Feb;17(1):16-21.
- Use and safety of anthroposophic medications for acute respiratory and ear infections: a prospective cohort study. Hamre HJ, Glockmann A, Fischer M, Riley DS, Baars E, Kiene H.
- [Clinical research on anthroposophic medicine:update of a health technology assessment report and status quo]. Kienle GS, Glockmann A, Grugel R, Hamre HJ, Kiene H.Forsch Komplementmed. 2011;18(5):269-82. doi: 10.1159/000331812. Epub 2011 Oct 4.
- Anthroposophical medicine: a systematic review of randomised clinical trials. Kienle GS, Hamre HJ, Kiene H.Wien Klin Wochenschr. 2004 Jun 30;116(11-12):407-8; author reply 408. doi: 10.1007/BF03040923.
- Eurythmy therapy in chronic disease: a four-year prospective cohort study. Hamre HJ, Witt CM, Glockmann A, Ziegler R, Willich SN, Kiene H.BMC Public Health. 2007 Apr 23;7:61. doi: 10.1186/1471-2458-7-61.
- Long-term outcomes of anthroposophic therapy for chronic low back pain: A two-year follow-up analysis. Hamre HJ, Witt CM, Kienle GS, Glockmann A, Ziegler R, Willich SN, Kiene H.J Pain Res. 2009 Jun 25;2:75-85. doi: 10.2147/jpr.s5922.
- Health costs in anthroposophic therapy users: a two-year prospective cohort study. Hamre HJ, Witt CM, Glockmann A, Ziegler R, Willich SN, Kiene H.BMC Health Serv Res. 2006 Jun 2;6:65. doi: 10.1186/1472-6963-6-65.
- Use and safety of anthroposophic medications in chronic disease: a 2-year prospective analysis. Hamre HJ, Witt CM, Glockmann A, Tröger W, Willich SN, Kiene H.Drug Saf. 2006;29(12):1173-89. doi: 10.2165/00002018-200629120-00008.
- Anthroposophic therapy for chronic depression: a four-year prospective cohort study. Hamre HJ, Witt CM, Glockmann A, Ziegler R, Willich SN, Kiene H.BMC Psychiatry. 2006 Dec 15;6:57. doi: 10.1186/1471-244X-6-57.
- Health costs in patients treated for depression, in patients with depressive symptoms treated for another chronic disorder, and in non-depressed patients: a two-year prospective cohort study in anthroposophic outpatient settings. Hamre HJ, Witt CM, Glockmann A, Ziegler R, Kienle GS, Willich SN, Kiene H.Eur J Health Econ. 2010 Feb;11(1):77-94. doi: 10.1007/s10198-009-0203-0.
- Outcome of anthroposophic medication therapy in chronic disease: a 12-month prospective cohort study. Hamre HJ, Witt CM, Glockmann A, Ziegler R, Kienle GS, Willich SN, Kiene H.Drug Des Devel Ther. 2009 Feb 6;2:25-37.
- Clinical research in anthroposophic medicine. Hamre HJ, Kiene H, Kienle GS.Altern Ther Health Med. 2009 Nov-Dec;15(6):52-5.
- Anthroposophic therapy for attention deficit hyperactivity: a two-year prospective study in outpatients. Hamre HJ, Witt CM, Kienle GS, Meinecke C, Glockmann A, Ziegler R, Willich SN, Kiene H.Int J Gen Med. 2010 Aug 30;3:239-53. doi: 10.2147/ijgm.s11725.
- Anthroposophic therapy for asthma: A two-year prospective cohort study in routine outpatient settings. Hamre HJ, Witt CM, Kienle GS, Schnürer C, Glockmann A, Ziegler R, Willich SN, Kiene H.J Asthma Allergy. 2009 Nov 24;2:111-28.
- Anthroposophic therapy for migraine: a two-year prospective cohort study in routine outpatient settings. Hamre HJ, Witt CM, Kienle GS, Glockmann A, Ziegler R, Rivoir A, Willich SN, Kiene H.Open Neurol J. 2010;4:100-10.
- Antibiotic Use in Children with Acute Respiratory or Ear Infections: Prospective Observational Comparison of Anthroposophic and Conventional Treatment under Routine Primary Care Conditions. Hamre HJ, Glockmann A, Schwarz R, Riley DS, Baars EW, Kiene H, Kienle GS.Evid Based Complement Alternat Med. 2014;2014:243801.
- An assessment of the scientific status of anthroposophic medicine, applying criteria from the philosophy of science. Baars EW, Kiene H, Kienle GS, Heusser P, Hamre HJ.Complement Ther Med. 2018 Oct;40:145-150.
- Anthroposophic vs. conventional therapy of acute respiratory and ear infections: a prospective outcomes study. Hamre HJ, Fischer M, Heger M, Riley D, Haidvogl M, Baars E, Bristol E, Evans M, Schwarz R, Kiene H.Wien Klin Wochenschr. 2005 Apr;117(7-8):256-68. doi: 10.1007/s00508-005-0344-9.
- Long-term outcomes of anthroposophic treatment for chronic disease: a four-year follow-up analysis of 1510 patients from a prospective observational study in routine outpatient settings. Hamre HJ, Kiene H, Glockmann A, Ziegler R, Kienle GS.BMC Res Notes. 2013 Jul 13;6:269. doi: 10.1186/1756-0500-6-269
- Eurythmy Therapy in anxiety. Kienle GS, Hampton Schwab J, Murphy JB, Andersson P, Lunde G, Kiene H, Hamre HJ.Altern Ther Health Med. 2011 Jul-Aug;17(4):56-63
- Mistletoe in cancer – a systematic review on controlled clinical trials. Kienle GS, Berrino F, Büssing A, Portalupi E, Rosenzweig S, Kiene H.Eur J Med Res. 2003 Mar 27;8(3):109-19.
- Anthroposophic therapy of respiratory and ear infections. Hamre HJ, Fischer M, Heger M, Riley D, Haidvogl M, Baars E, Bristol E, Evans M, Schwarz R, Kiene H.Wien Klin Wochenschr. 2005 Jul;117(13-14):500-1. doi: 10.1007/s00508-005-0389-9
- Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts.
Eur J Med Res. 2007 Mar 26;12(3):103-19.
- Review article: Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Kienle GS, Kiene H.Integr Cancer Ther. 2010 Jun;9(2):142-57.
- [Anthroposophic medicine: health technology assessment report – short version].
Forsch Komplementmed. 2006;13 Suppl 2:7-18. doi: 10.1159/000093481. Epub 2006 Jun 26.
- Bilateral Asynchronous Renal Cell Carcinoma With Lung Metastases: A Case Report of a Patient Treated Solely With High-dose Intravenous and Subcutaneous Viscum album Extract for a Second Renal Lesion. Reynel M, Villegas Y, Kiene H, Werthmann PG, Kienle GS.Anticancer Res. 2019 Oct;39(10):5597-5604. doi: 10.21873/anticanres.13754.
- Long-term survival of a patient with an inoperable thymic neuroendocrine tumor stage IIIa under sole treatment with Viscum album extract: A CARE compliant clinical case report. Reynel M, Villegas Y, Werthmann PG, Kiene H, Kienle GS.Medicine (Baltimore). 2020 Jan;99(5):e18990. doi: 10.1097/MD.0000000000018990
- Long-Term Survival of a Patient with Recurrent Dedifferentiated High-Grade Liposarcoma of the Retroperitoneum Under Adjuvant Treatment with Viscum album L. Extract: A Case Report. Reynel M, Villegas Y, Werthmann PG, Kiene H, Kienle GS.Integr Cancer Ther. 2021 Jan-Dec;20:1534735421995258. doi: 10.1177/1534735421995258.
- Intralesional and subcutaneous application of Viscum album L. (European mistletoe) extract in cervical carcinoma in situ: A CARE compliant case report. Reynel M, Villegas Y, Kiene H, Werthmann PG, Kienle GS.Medicine (Baltimore). 2018 Nov;97(48):e13420.
- High-Dose Viscum album Extract Treatment in the Prevention of Recurrent Bladder Cancer: A Retrospective Case Series.
Perm J. 2015 Fall;19(4):76-83. doi: 10.7812/TPP/15-018.
- Disappearance of an advanced adenomatous colon polyp after intratumoural injection with Viscum album (European mistletoe) extract: a case report. von Schoen-Angerer T, Goyert A, Vagedes J, Kiene H, Merckens H, Kienle GS.J Gastrointestin Liver Dis. 2014 Dec;23(4):449-52. doi: 10.15403/jgld.2014.1121.234.acpy.
- Viscum Album in the Treatment of a Girl With Refractory Childhood Absence Epilepsy. von Schoen-Angerer T, Madeleyn R, Kienle G, Kiene H, Vagedes J.J Child Neurol. 2015 Jul;30(8):1048-52. doi: 10.1177/0883073814541473. Epub 2014 Jul 17.
- Improvement of Asthma and Gastroesophageal Reflux Disease With Oral Pulvis stomachicus cum Belladonna, a Combination of Matricaria recutita, Atropa belladonna, Bismuth, and Antimonite: A Pediatric Case Report. von Schoen-Angerer T, Madeleyn R, Kiene H, Kienle GS, Vagedes J.Glob Adv Health Med. 2016 Jan;5(1):107-11. doi: 10.7453/gahmj.2015.019. Epub 2016 Jan 1.
- Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study. Grossarth-Maticek R, Kiene H, Baumgartner SM, Ziegler R.Altern Ther Health Med. 2001 May-Jun;7(3):57-66, 68-72, 74-6 passim
WHAT A LIST!
It makes several things very clear to me:
- Kiene is a productive researcher
- He likes observational studies and case reports
- He dislikes the idea of rigorously testing a hypothesis
- He never publishes a negative finding about anthroposophical medicine
- He certainly deserves to be admitted to the ALTERNATIVE MEDICINE HALL OF FAME!
This review evaluated the magnitude of the placebo response of sham acupuncture in trials of acupuncture for nonspecific LBP, and assessed whether different types of sham acupuncture are associated with different responses. Four databases including PubMed, EMBASE, MEDLINE, and the Cochrane Library were searched through April 15, 2023, and randomized controlled trials (RCTs) were included if they randomized patients with LBP to receive acupuncture or sham acupuncture intervention. The main outcomes included the placebo response in pain intensity, back-specific function and quality of life. Placebo response was defined as the change in these outcome measures from baseline to the end of treatment. Random-effects models were used to synthesize the results, standardized mean differences (SMDs, Hedges’g) were applied to estimate the effect size.
A total of 18 RCTs with 3,321 patients were included. Sham acupuncture showed a noteworthy pooled placebo response in pain intensity in patients with LBP [SMD −1.43, 95% confidence interval (CI) −1.95 to −0.91, I2=89%]. A significant placebo response was also shown in back-specific functional status (SMD −0.49, 95% CI −0.70 to −0.29, I2=73%), but not in quality of life (SMD 0.34, 95% CI −0.20 to 0.88, I2=84%). Trials in which the sham acupuncture penetrated the skin or performed with regular needles had a significantly higher placebo response in pain intensity reduction, but other factors such as the location of sham acupuncture did not have a significant impact on the placebo response.
The authors concluded that sham acupuncture is associated with a large placebo response in pain intensity among patients with LBP. Researchers should also be aware that the types of sham acupuncture applied may potentially impact the evaluation of the efficacy of acupuncture. Nonetheless, considering the nature of placebo response, the effect of other contextual factors cannot be ruled out in this study.
As the authors stated in their conclusion: the effect of other contextual factors cannot be ruled out. I would go much further and say that the outcomes noted here are mostly due to effects other than placebo. Obvious candidates are:
- regression towards the mean;
- natural history of the condition;
- success of patient blinding;
- social desirability.
To define the placebo effect in acupuncture trials as the change in the outcome measures from baseline to the end of treatment – as the authors of the review do – is not just naive, it is plainly wrong. I would not be surprised, if different sham acupuncture treatments have different effects. To me this would be an expected, plausible finding. But such differences just cannot be estimated in the way the authors suggest. For that, we would need an RCT in which patients are randomized to be treated in the same setting with a range of different types of sham acupuncture. The results of such a study might be revealing but I doubt that many ethics committees would be happy to grant their approval for it.
In the absence of such data, the best we can do is to design trials such that the verum is tested against a credible placebo which, for patients, is indistinguishable from the verum, while demonstrating that blinding is successful.
This systematic review and meta-analysis was aimed at analyzing the effectiveness of craniosacral therapy in improving pain and disability among patients with headache disorders.
PubMed, Physiotherapy Evidence Database, Scopus, Cochrane Library, Web of Science, and Osteopathic Medicine Digital Library databases were searched in March 2023. Two independent reviewers searched the databases and extracted data from randomized clinical trials comparing craniosacral therapy with control or sham interventions. The same reviewers assessed the methodological quality and the risk of bias using the PEDro scale and the Cochrane Collaboration tool, respectively. Grading of recommendations, assessment, development, and evaluations was used to rate the certainty of the evidence. Meta-analyses were conducted using random effects models using RevMan 5.4 software.
The searches retrieved 735 papers, and 4 studies were finally included. The craniosacral therapy provided statistically significant but clinically unimportant change on pain intensity (Mean difference = –1.10; 95% CI: –1.85, –0.35; I2: 44%), and no change on disability or headache effect (Standardized Mean Difference = –0.34; 95% CI –0.70, 0.01; I2: 26%). The certainty of the evidence was downgraded to very low.
The authors concluded that very low certainty of evidence suggests that craniosacral therapy produces clinically unimportant effects on pain intensity, whereas no significant effects were observed in disability or headache effect.
I find it strange that researchers seem so frequently unable to formulate their conclusions clearly. Is it political correctness? Or are they somehow favorably inclined (i.e. biased) towards the treatment that they pretend to critically evaluate?
Let’s look at the facts related to this review:
- Craniosacral therapy (CST) is utterly implausible.
- Only 4 RCTs were found.
- They were of poor quality.
- They were published mostly by people who want to promote CST.
- Therefore the overall statistically significant effect is most likely a false-positive result.
- This means that the conclusion should be much more straight forward.
I suggest something along the following lines:
A critical evaluation of the existing RCTs failed to find convincing evidence that CST is an effective treatment for headache disorders.
Exercise is often cited as a major factor contributing to improved cognitive functioning. As a result, the relationship between exercise and cognition has received much attention in scholarly literature. Systematic reviews and meta-analyses present varying and sometimes conflicting results about the extent to which exercise can influence cognition. The aim of this umbrella review was to summarize the effects of physical exercise on cognitive functions (global cognition, executive function, memory, attention, or processing speed) in healthy adults ≥ 55 years of age.
This review of systematic reviews with meta-analyses invested the effect of exercise on cognition. Databases (CINAHL, Cochrane Library, MEDLINE, PsycInfo, Scopus, and Web of Science) were searched from inception until June 2023 for reviews of randomized or non-randomised controlled trials. Full-text articles meeting the inclusion criteria were reviewed and methodological quality assessed. Overlap within included reviews was assessed using the corrected covered area method (CCA). A random effects model was used to calculate overall pooled effect size with sub-analyses for specific cognitive domains, exercise type and timing of exercise.
A total of 20 met the inclusion criteria. They were based on 332 original primary studies. Overall quality of the reviews was considered moderate with most meeting 8 or more of the 16 AMSTAR 2 categories. Overall pooled effects indicated that exercise in general has a small positive effect on cognition (d = 0.22; SE = 0.04; p < 0.01). Mind–body exercise had the greatest effect with a pooled effect size of (d = 0.48; SE = 0.06; p < 0.001). Exercise had a moderate positive effect on global cognition (d = 0.43; SE = 0,11; p < 0,001) and a small positive effect on executive function, memory, attention, and processing speed. Chronic exercise was more effective than acute exercise. Variation across studies due to heterogeneity was considered very high.
The authors concluded that mind–body exercise has moderate positive effects on the cognitive function of people aged 55 or older. To promote healthy aging, mind–body exercise should be used over a prolonged period to complement other types of exercise. Results of this review should be used to inform the development of guidelines to promote healthy aging.
It seems to me that the umbrella review hides the crucial fact that many of the primary studies had major flaws, e.g. in terms of:
- lack of randomisation,
- lack of blinding.
Eleven studies investigated the effects of aerobic exercise on cognition. Only three studies investigated the effects of mind body exercise on cognition, two analysed the effects of resistance exercise, and five investigated the effects of mixed exercise interventions. I am therefore mystified how the authors managed to arrive at such a hyped conclusion in favour of the effectiveness of mind body exercises. Even an optimistic interpretation of the data would allow merely a weak indication that a positive effect might exist. To state that mind body exercises should be promoted for ‘healthy aging’ borders on the irresponsible, in my view. Surely even the most naive researcher must see that, for such a far-reaching recommendation, we would need much more solid evidence.
I strongly suspect that a proper review of the primary studies of mind body exercise with a critical evaluation of the quality of the primary studies would lead to dramatically different conclusion.
Homeopathic remedies are highly diluted formulations without proven clinical benefits, traditionally believed not to cause adverse events. Nonetheless, published literature reveals severe local and non–liver-related systemic side effects. Here is the first series on homeopathy-related severe drug-induced liver injury (DILI) from a single center.
A retrospective review of records from January 2019 to February 2022 identified 9 patients with liver injury attributed to homeopathic formulations. Competing causes were comprehensively excluded. Chemical analysis was performed on retrieved formulations using triple quadrupole gas chromatography-mass spectrometry and inductively coupled plasma atomic emission spectroscopy.
Males predominated with a median age of 54 years. The most typical clinical presentation was acute hepatitis, followed by acute or chronic liver failure. All patients developed jaundice, and ascites were notable in one-third of the patients. Five patients had underlying chronic liver disease. COVID-19 prevention was the most common indication for homeopathic use. Probable DILI was seen in 77.8%, and hepatocellular injury predominated (66.7%). Four (44.4%) patients died (3 with chronic liver disease) at a median follow-up of 194 days. Liver histopathology showed necrosis, portal and lobular neutrophilic inflammation, and eosinophilic infiltration with cholestasis. A total of 29 remedies were consumed between 9 patients, and 15 formulations were analyzed. Toxicology revealed industrial solvents, corticosteroids, antibiotics, sedatives, synthetic opioids, heavy metals, and toxic phyto-compounds, even in ‘supposed’ ultra-dilute formulations.
The authors concluded that homeopathic remedies potentially result in severe liver injury, leading to death in those with underlying liver disease. The use of mother tinctures, insufficient dilution, poor manufacturing practices, adulteration and contamination, and the presence of direct hepatotoxic herbals were the reasons for toxicity. Physicians, the public, and patients must realize that Homeopathic drugs are not ‘gentle placebos.’
The authors also cite our own work on this subject:
A detailed systematic review of homeopathic remedies-induced adverse events from published case reports and case series by Posadzski and colleagues showed that severe side effects, some leading to fatality, are possible with classic and unspecified homeopathic formulations. The total number of patients included was 1159, of which 1142 suffered adverse events directly related to homeopathy. The direct adverse events had acute pancreatitis, severe allergic reactions, arsenical keratosis, bullous pemphigoid, neurocognitive disorders, sudden cardiac arrest and coma, severe dyselectrolytemia, interstitial nephritis, kidney injury, thallium poisoning, syncopal attacks, and focal neurological deficits as well as movement disorders. Fatal events involved advanced renal failure requiring dialysis, toxic polyneuropathy, and quadriparesis. The duration of adverse events ranged from a few hours to 7 months, and 4 patients died. The authors state that in most cases, the mechanism of action for side effects of homeopathy involved allergic reactions or the presence of toxic substances—the use of strong mother tinctures, drug contaminants, adulterants, or poor manufacturing (incorrect dilutions).
When we published our paper back in 2012, it led to a seies of angry responses from defenders of homeopathy who claimed that one cannot ‘have the cake and eat it’; either homeopathic remedies are placebos and thus harmless, or they have effects and thus also side-effects, they claimed. As the new publication by Indian researchers yet again shows, they were mistaken. In fact, homeopathy is dangerous in more than one way:
- the homeopathic remedies can do harm if not diluted or wrongly manufactured;
- the homeopaths can do harm through their often wrong advice in health matters;
- homeopathy erodes rational thinking (as, for instance, the resopnses to our 2012 paper demonstrated).
Manual therapy is considered a safe and less painful method and has been increasingly used to alleviate chronic neck pain. However, there is controversy about the effectiveness of manipulation therapy on chronic neck pain. Therefore, this systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to determine the effectiveness of manipulative therapy for chronic neck pain.
A search of the literature was conducted on seven databases (PubMed, Cochrane Center Register of Controlled Trials, Embase, Medline, CNKI, WanFang, and SinoMed) from the establishment of the databases to May 2022. The review included RCTs on chronic neck pain managed with manipulative therapy compared with sham, exercise, and other physical therapies. The retrieved records were independently reviewed by two researchers. Further, the methodological quality was evaluated using the PEDro scale. All statistical analyses were performed using RevMan V.5.3 software. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment was used to evaluate the quality of the study results.
Seventeen RCTs, including 1190 participants, were included in this meta-analysis. Manipulative therapy showed better results regarding pain intensity and neck disability than the control group. Manipulative therapy was shown to relieve pain intensity (SMD = -0.83; 95% confidence interval [CI] = [-1.04 to -0.62]; p < 0.0001) and neck disability (MD = -3.65; 95% CI = [-5.67 to – 1.62]; p = 0.004). However, the studies had high heterogeneity, which could be explained by the type and control interventions. In addition, there were no significant differences in adverse events between the intervention and the control groups.
The authors concluded that manipulative therapy reduces the degree of chronic neck pain and neck disabilities.
Only a few days ago, we discussed another systematic review that drew quite a different conclusion: there was very low certainty evidence supporting cervical SMT as an intervention to reduce pain and improve disability in people with neck pain.
How can this be?
Systematic reviews are supposed to generate reliable evidence!
How can we explain the contradiction?
There are several differences between the two papers:
- One was published in a SCAM journal and the other one in a mainstream medical journal.
- One was authored by Chinese researchers, the other one by an international team.
- One included 17, the other one 23 RCTs.
- One assessed ‘manual/manipulative therapies’, the other one spinal manipulation/mobilization.
The most profound difference is that the review by the Chinese authors is mostly on Chimese massage [tuina], while the other paper is on chiropractic or osteopathic spinal manipulation/mobilization. A look at the Chinese authors’ affiliation is revealing:
- Department of Tuina and Spinal Diseases Research, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China.
- Department of Tuina and Spinal Diseases Research, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China; Department of Tuina, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: [email protected].
- Department of Tuina and Spinal Diseases Research, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, China; Department of Tuina, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: [email protected].
What lesson can we learn from this confusion?
Perhaps that Tuina is effective for neck pain?
What the abstract does not tell us is that the Tuina studies are of such poor quality that the conclusions drawn by the Chinese authors are not justified.
What we do learn – yet again – is that
- Chinese papers need to be taken with a large pintch of salt. In the present case, the searches underpinning the review and the evaluations of the included primary studies were clearly poorly conducted.
- Rubbish journals publish rubbish papers. How could the reviewers and the editors have missed the many flaws of this paper? The answer seems to be that they did not care. SCAM journals tend to publish any nonsense as long as the conclusion is positive.