clinical trial
Ever since I published a post about the irresponsible and aggressive advertising campaign of LYMA (“the world’s 1st super-supplement”), I am pursued by them with emails informing me about the wonders of this supplement. Here is one I received recently:
Here at LYMA we are firm believers that optimal productivity depends on good quality sleep and your day is only as good as the previous night.
Suffering from bad sleep is debilitating whether it’s ourselves or we’re watching someone we love suffer, the search for good rest is something we’re all united in.
Energy levels, positive mindset and strong cognitive function all come from sleep, which is why we spent so long formulating the LYMA supplement. Our patented KSM-66® Ashwagandha is the highest-quality, zero toxicity, concentrated Ashwagandha root in the world. The hefty combination of purity and potency make it unrivalled in its ability to reduce inflammation, neutralise anxiety and promote deep, restful sleep, night after night.
Thousands of customers have told us that after years of bad sleep, they’re finally getting the rest they need and feeling transformed as a result. In fact, it’s one of the very first benefits most people notice. We’re happy to hear it.
And the knock-on effects of a good night’s sleep in how we feel, how we perform and our overall health are far reaching. Which is why we are so delighted to welcome Michael Grandner, world-renowned sleep expert and Director of the Behavioural Sleep Medicine Clinic, Arizona to the LYMA team.
Michael is one of the most cited sleep experts in the world and has himself published over 175 articles on issues relating to sleep and health. We plan on tapping into every area of his expertise to understand our own sleep habits and how we can all become the best at rest.
To introduce Michael to the LYMA community we’re hosting a seminar dedicated to understanding sleep on Tuesday 22nd June…
I was tempted to discard all this as rather pathetic advertising hype. But then I had second thoughts. This text does after all make several medical claims, and the question is: ARE THEY SUPPORTED BY EVIDENCE?
It claims that KSM-66® Ashwagandha:
- is the highest-quality, zero toxicity, concentrated Ashwagandha root in the world.
- That the hefty combination of purity and potency makes it unrivalled in its ability to reduce inflammation.
- That the product neutralises anxiety.
- That it promotes deep, restful sleep, night after night.
I ran a few searches to find out whether there is any sound evidence for any of these claims.
- There seem to be several supplements that contain,KSM-66® Ashwagandha’. The impression that LYMA is the only one is thus wrong. Zero toxicity must also be wrong; not even water has zero toxicity. In fact, epigastric pain/discomfort and loose stools were reported as most common (>5%); and giddiness, drowsiness, hallucinogenic, vertigo, nasal congestion (rhinitis), cough, cold, decreased appetite, nausea, constipation, dry mouth, hyperactivity, nocturnal cramps, blurring of vision, hyperacidity, skin rash and weight gain have all been associated with the herbal remedy. Moreover, if it is true that Ashwagandha stimulates the immune system, it might cause problems for people with autoimmune diseases.
- I found no compelling evidence from clinical trials to show that KSM-66® Ashwagandha reduces inflammatory conditions in humans.
- I found a study concluding that Ashwagandha given as an adjunct offered some potential advantages as a safe and effective adjunctive therapy to SSRIs in GAD. Yet, I found no compelling evidence from clinical trials to show that KSM-66® Ashwagandha as a single supplement reduces anxiety in otherwise healthy individuals.
- A 2021 study suggested that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Yet the authors cautioned that additional clinical trials are required to generalize the outcome.
So, what does that tell us?
It could mean that:
- My searches were not sufficiently thorough and that I have missed compelling evidence. If so, I would appreciate, if the LYMA promoters would show me their evidence so that I can assess it.
- The LYMA people are irresponsible and mislead the public with untenable claims.
I am looking forward to their response.
Qigong can be described as a mind-body-spirit practice that improves one’s mental and physical health by integrating posture, movement, breathing technique, self-massage, sound, and focused intent. But does it really improve health?
The purpose of this review was to evaluate the effectiveness of Qigong in improving the quality of life and relieving fatigue, sleep disturbance, and cancer-related emotional disturbances (distress, depression, and anxiety) in women with breast cancer.
The PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Sinomed, Wanfang, VIP, and China National Knowledge Infrastructure databases were searched from their inceptions to March 2020 for controlled clinical trials. Two reviewers selected relevant trials that assessed the benefit of Qigong for breast cancer patients independently. A methodological quality assessment was conducted according to the criteria of the 12 Cochrane Back Review Group for risk of bias independently. A meta-analysis was performed using Review Manager 5.3.
A total of 17 trials were found in which 1236 cases were enrolled. The quality of the included trials was generally low, as only 5 of them were rated high quality. 14 studies were conducted in China. The types of qigong included Baduanjin Qigong (9 trials), Chan-Chuang Qigong (1 trial), Goulin New Qigong (2 Trials), Tai Chi Qigong (2 Trials), and Kuala Lumpur Qigong (1 trial). The course of qigong ranged from 21 days to more than 6 months. Four trials compared qigong to no treatment, one sham Qigong, seven compared to other types of exercise, and 6 to usual care.
The results showed significant positive effects of Qigong on quality of life (n = 950, standardized mean difference (SMD), 0.65, 95 % confidence interval (CI) 0.23–1.08, P = 0.002). Depression (n = 540, SMD = −0.32, 95 % CI −0.59 to −0.04, P = 0.02) and anxiety (n = 439, SMD = −0.71, 95 % CI −1.32 to −0.10, P = 0.02) were also significantly relieved in the Qigong group. There was no significant benefit on fatigue (n = 401, SMD = −0.32, 95 % CI 0.71 to 0.07, P = 0.11) or sleep disturbance relief compared to that observed in the control group (n = 298, SMD = −0.11, 95 % CI 0.74 to 0.52, P = 0.73). 
The authors concluded that this review shows that Qigong is beneficial for improving quality of life and relieving depression and anxiety; thus, Qigong should be encouraged in women with breast cancer.
No, this review does not show that Qigong is beneficial for improving quality of life and relieving depression and anxiety!
Why?
- Most primary studies were of very poor quality.
- Most were from China, and we know (and have often discussed) that such trials are most unreliable.
- No trial even attempted to control for placebo effects.
A better conclusion would therefore be something like this:
Even though most trials conclude positively, the value of Qigong can, for a range of reasons, not be determined on the basis of the evidence available to date.
On 7/10/2020, I discussed a study suggesting that homeopathy improves the quality of life and survival of cancer patients. Now, these data have been carefully scrutinized by a group of members of the „INH“ and „Initiative für Wissenschaftliche Medizin“.
By guest bloggers Norbert Aust and Viktor Weisshäupl
Abstract
The first impression of the results of the study on the adjunctive homeopathic treatment of patients with non-small cell lung cancer (NSCLC) is that of a seemingly rigorous trial with valid results. But a more thorough review yields different insights:
- The methods and definitions were pre-determined in a protocol and seem to have been maintained up to the end. But the date given in the document pointing at some point in time before enrollment began is wrong and misleading: This protocol was first published by uploading it to the register only two months after data assessment was completed with outcomes presumably available.
- The data initially saved to the register are not in agreement with the information given in the published paper: important definitions were subjected to considerable modifications while the study was underway. None of these modifications are mentioned in the paper, neither a rationale nor a comment of their impact on the results was provided.
- Some of the modifications with presumably heavy impact on the results were introduced with the upload of the protocol only, that is two months after data collection was completed. These were (a) a massive extension of the exclusion criteria: the number increased from 1 during initial registration to 20 in the final paper. and (b) an equally massive reduction of the follow-up time for the primary endpoint from two years to 18 weeks.
- The paper discloses no reason why the additional exclusion criteria were introduced. Their selection seems arbitrary without any apparent necessity arising from the trial itself.
- The patients who did not meet the added criteria and were thus excluded are not mentioned in the publication. The CONSORT flow chart does not give information either of their number or of the point in time when they were excluded.
- The survival curves of the placebo and verum groups show some aspects that arise if the inter-group difference was due to the exclusion of unfavorable data.
- It is hard to imagine that, in this trial, the homeopathic preparations had strong effects on the patients’ health, while other rigorous studies or systematic reviews failed to notice such effects.
Altogether, it seems much more plausible to assume that the positive results were achieved by post hoc data manipulation, namely by omitting patients with unfavorable outcomes, than by rigorous and valid science. A retraction of the paper seems the only appropriate measure to avoid misleading the public.
Introduction
Due to its outstanding results, the study about adjunct homeopathic treatment of non-small cell lung cancer patients was met among homeopaths with enthusiasm. However, in this article, we will show that the enthusiasm is unjustified because the results may not be based on a rigorous trial meeting established scientific criteria. Crucial definitions were modified, while the study was underway or even after data collection was completed. It stands to reason that this introduced bias in favor of homeopathy.
For this analysis, we considered the following sources of information :
- the text of the published paper (link)
- the data that were uploaded during registration (link)
- the history of changes of the registered data (link)
- the study protocol included in the registration (link)
As all of this information is readily available on the internet, it is easy to double-check our findings and verify our statements. We also submitted a letter to the editor of the Oncologist, the journal where the paper was published which has not yet been published (status 06-06-2021).
The study
At first glance, the study meets the requirements for reliable evidence.
- There is a study protocol dated January 11, 2011, well before recruiting of participants started. It provides definitions that were used until the end.
- The study was registered at ClinicalTrials.gov before recruiting started.
- The methods of randomization and blinding are suitable to meet the requirements for a low risk of bias rating.
- The presentation of the paper follows the principles set out in the CONSORT-Statement.
- The paper was published in a peer-reviewed journal of some reputation.
The study yielded formidable results in favor of homeopathy: In the group that received the adjunctive homeopathic treatment, the quality of life improved continuously throughout the follow-up time, while the patients in the placebo group deteriorated. In addition, the median survival time was only about two-thirds compared to the patients in the homeopathy group. However, the impression of a valid study does not stand up to closer scrutiny when the history of changes is taken into account.
Changes in study parameters
Between the initial registration and data upload in January 2012 (Link), shortly before recruiting started in February 2012, and the publication in October 2020, multiple changes in essential study parameters occurred:
| Registration January 2012 | Publication October 2020 | |
| Number of participants | 600 | 150 |
| Number of study arms | 2 | 3 |
| Number of exclusion criteria | 1 | 20 |
| Follow-up time for Quality of life | 104 weeks (*) | 18 weeks |
| Number of cancer types | 3 | 1 |
| (*) Derived from “Time Frame: 7 Years” minus the recruitment period of 5 years. | ||
Note the drastic reduction in the follow-up time for quality of life by more than 80 % which was defined as the primary endpoint. Furthermore, note the substantial increase in the number of exclusion criteria. Both issues will be discussed in more detail below.
In contrast to the requirements for a rigorous and valid trial, these modifications are not mentioned in the published paper, and no rationale is given as to why they became necessary. As a consequence, the authors do not discuss the possible impact these modifications may have had on the results.
The study protocol
A study protocol is available in the registration database. It was first uploaded on September 18, 2019, about two months after the end of data collection in July 2019 (Link). The document itself is dated January 11, 2011, which would place it about a year before the study was registered. However, this date is obviously wrong: there are substantial discrepancies between the parameters specified in the protocol and the data provided one year later during initial registration:
| Protocol, allegedly January 2011 | Registration January 2012 | |
| Number of participants | 300 | 600 |
| Number of study arms | 3 | 2 |
| Number of exclusion criteria | 9 | 1 |
| Follow-up time for Quality of life | 18 weeks | 104 weeks (*) |
| Number of cancer types | 1 | 3 |
| (*) Derived from “Time Frame: 7 Years” minus the recruitment period of 5 years. | ||
We see no sensible explanation why the parameters given in the study protocol allegedly compiled in January 2011 are in line with the publication nine years later, but not with the registration only one year after the protocol was compiled. The only sensible conclusion seems to be that this protocol was not completed on the date indicated, but at a much later point in time, maybe just shortly before its upload (September 2019). This impression is corroborated by the information presented in the document that was not available on the date given: On page 10 the software package used in data analysis is referenced as “IBM SPSS statistics 25.0” while, at the beginning of 2011, when the protocol was allegedly compiled, the current version number of this package was 19 only.
A second clue: Also on page 10 there is a reference “(EORTC-QLQ-C30 remaining dimensions; SF-36; subjective well-being)25.” with the number 25 indicating some reference. And some references that is, but not in the protocol – this does not have any references – but in the published paper, where the 25 indicates a paper on the SF-36 questionnaire. So it stands to reason that the number in the protocol originates from some messed up copy and paste procedure from the draft of the paper. Which would indicate that the paper and the protocol were at least partially developed in parallel.
It seems therefore reasonable to assume, that the protocol was finished only shortly before it being uploaded in September 2019, that is two months after data collection was completed.
However, the obviously inaccurate date given in the protocol supports the impression that the study parameters were set a year before the study began and were consistently maintained during the course of the trial, which is not the case, as the above tables show.
Change in exclusion criteria
The initial registration data list pregnancy as the only exclusion criterion. But with the upload of the protocol, which took place two months after data collection was completed, the number of exclusion criteria was increased to nine, only to be enlarged once again in the final publication to the final number of twenty. It is beyond any doubt that at least the final increase of eleven criteria took place after the data collected from the patients were available. But all this is neither disclosed in the final paper nor is there any rationale given for this action.
The patients excluded by the additional criteria never appear anywhere, they are not included in the CONSORT-flow-chart, Fig 3 in the study. It is obvious that some patients were excluded: What was the reason to define such an abundance of criteria, if they were not to be applied? As a consequence, the CONSORT diagram seems to be incomplete which would be in violation of the CONSORT statement.
Thus, an unknown number of patients seems to have been excluded from the study by criteria defined at a time after data collection was completed with outcomes available. After all, eleven of the exclusion criteria were established even after the protocol had been uploaded, at least those were established well after the patients’ results were available.
This raises the question of why these exclusion criteria were introduced. One would assume that an intervention to treat stage III and stage IV lung cancer patients should be effective under the conditions that are usually present in such patients. One would expect that patients somewhat advanced in age, like in this study, usually suffer from some health problems, regardless of their cancer condition. What is the sense of excluding patients with hematological, hepatic, or renal pathology, with coronary heart disease or rheumatism? Homeopathy is claimed to be able to treat comorbidities based on the assessment of symptoms independent of what disease they belong to. And this apparently was the idea at the start of the trial where only pregnancy was specified as an exclusion criterion, while it was understood that elderly patients to be enrolled in the study would suffer from some additional medical problems.
On the other hand, not all health conditions that are associated with advanced age were excluded. Diabetes, hypertension, gastrointestinal diseases, or COPD were no reason to exclude any patient from participation. Only very few of the criteria are somewhat self-explanatory as to why they were defined as exclusion criteria, e.g. if a patient was unwilling to give her informed consent.
Altogether, the assumption seems reasonable that more patients had participated in the trial than accounted for in the publication, and that an unknown number of them were excluded according to criteria that were not present until after data collection was completed. If so, a substantial bias was introduced.
Median survival time
Here, we will focus on the comparison between the homeopathy and placebo groups and leave aside the third group not receiving any additional treatment at all.
If the favorable result in survival really was established by dropping unfavorable data, this might be recognized in some characteristics of the survival curves. Therefore, we modeled this situation starting with two random distributions somewhat tweaked to resemble the typical shape of natural survival functions.
This graph shows the two distributions (n = 80) defined in the range of 0 to 200 as thin lines. Both are very similar to each other with median survival at 27 weeks. If 15 of the 20 patients with the shortest survival are dropped from the thin blue line this would result in the solid blue line (“Hom”). If, on the other hand, 15 out of 20 patients with the longest survival are dropped from the other distribution this would yield the solid red line (“Plac”).
The new functions show some characteristic properties:
- In the red line, median survival drops by 8 weeks to 19 weeks.
- In the blue line median survival rises by 12 Weeks to 39 weeks.
- The difference between the two functions arises from of the first 12 weeks alone. With the blue line, 8 people died, with the red line 23 people died during the first 12 weeks. After week 12 up to week 80, the same number of fatalities occur in both groups (blue: 36, red: 37).
After week 80, the two functions start to converge, which is due to the fact that at some future point all the patients of both groups will be dead. The survival functions that are reported in the study show the same characteristics.
Assuming that homeopathy did not have any effect, both groups should show more or less identical survival functions. In the paper 10.1 months = 303 days is cited from literature as to be expected under conventional care, maybe with some margin to the better because the data that yielded this value of 10.1 months were more than six years old at the time of the trial. The survival functions allegedly found in the trial show:
- Median survival time with the placebo group is reduced by 46 days compared to conventional care alone.
- Median survival time with the homeopathy group is increased by 132 days compared to conventional care alone.
- The advantage of homeopathy arises within the first 9 weeks alone, where only two patients died (out of 51) in the homeopathy group compared to 11 (out of 47) in the placebo group. After this initial phase, the groups developed in parallel: By the end of the two-year follow-up time an additional 26 patients died with homeopathy, and about the same, namely 25 patients died with placebo.
The inevitable convergence of both functions apparently started outside the two-year follow-up. In other words, the survival functions given in the study for placebo and homeopathy treatments show characteristics that match what you would be expected, if two very similar functions were manipulated by dropping unwanted results, i.e. “good” survival data from placebo and “bad” survival data from homeopathy functions. After week 9, the two functions develop parallel to each other, indicating a lack of effect of homeopathy even though the treatment continued until the death of the patient or the end of the study. However, with ongoing effective treatment, the functions should continue to diverge. It seems implausible that homeopathy should be effective on a short time basis only, with a sudden complete loss of effectiveness later on.
Reduction of observation time
Quality of life was defined as the primary endpoint. On initial registration, it was specified that patients should be observed for the entire seven-year duration of the study which, allowing for the recruitment period of five years, results in a follow-up time of two years or 104 weeks for each individual patient. According to the information provided in the study, this was indeed done: “Patients were followed up every nine weeks until death” (or until the end of the study, of course), and questionnaires were completed to determine the quality of life.
The reduction of follow-up time from 104 to 18 weeks was first introduced when the protocol was uploaded. So it is obvious that this substantial reduction occurred after data collection was completed and that data from more than 80 % of the originally defined follow-up were omitted.
Incomplete outcome reporting, especially when a larger scope was defined at the beginning of the study, is considered a source of substantial bias and a major shortcoming in clinical trials: Maybe patients initially experienced an improvement in their quality of life due to whatever effect – but what were the results after this initial phase? Why were they omitted? Perhaps because they got worse than in the placebo group? The long-term development would have been a vital aspect for the evaluation of efficacy – and the study originally was designed to evaluate such long-term effects. Yet, the authors’ conclusions on the quality of life – notably: the primary outcome criterion – are based on less than 20 % of the follow-up in which a positive effect may have occurred due to bias or by chance. To extrapolate from this short time to the total period is not justified and may be misleading. A detailed review of the quality of life results is meaningless: they do not disclose any long-term effects and they are subject to bias caused by the post hoc exclusion of patients anyway.
Study results
The overall evidence on the effectiveness of homeopathy is not encouraging. The quintessence of all systematic reviews that have looked at homeopathy as a whole is that some marginal effect may be found, if all studies are included in the review, regardless of their quality. But this result is questionable due to the generally low quality of the primary studies (Link, in German). However, when quality is taken into account, the systematic reviews do not produce robust evidence for any positive effect beyond placebo. In addition, no review could identify a single condition in which homeopathy is of well-established therapeutic benefit.
This study on NSCLC contradicts the long-established and often-confirmed evidence. During the follow-up time for the patients who actually received the prescribed homeopathic preparations, the quality of life improved steadily in all subscales – even down to the patients’ financial situation – whereas the opposite was observed in the placebo patients. In addition, the mean survival time was about two-thirds longer for the homeopathy patients than for the placebo group.
After 200 years of clinical research into homeopathy, it seems unlikely that such a powerful effect of homeopathy should not have been noticed before. Another scenario seems to be much more plausible:
- The survival times of the placebo group were worse than the data from the literature. This could be due to the fact that patients with relatively good outcomes were excluded by the introduction of additional exclusion criteria.
- The survival times of the homeopathy group were considerably better than expected. This could also be due to the additional exclusion criteria, in that patients with poor outcomes were excluded retrospectively.
- The long time frame where the survival functions run in parallel from week 9 onwards until the end of the two years observation period indicates the lack of effect of the homeopathic treatment. The advantage occurring in the first nine weeks alone seems to be the result of unwanted data being dropped.
- In the case of quality of life (after all, not a “hard” criterion, but based on information from the patients ), the advantage in survival would have initially created a positive effect for the homeopathy group. Then, reporting was discontinued, once the initial positive effects presumably caused by the selective omission of patients had ended.
In conclusion, it seems likely that the substantial modifications of crucial study parameters that occurred after the study had been started and results had become available biased the results in favor of homeopathy. Therefore, this study does not meet strict scientific standards that were established to exclude any confounding factors or biases. If our analysis is correct, the results of this study are invalid, and the authors’ conclusions are not justified. Retraction of this study seems to be appropriate.
Reference
[1] Frass M, Lechleitner P, Gründling C et al. Homeopathic Treatment as an Add-On Therapy May Improve Quality of Life and Prolong Survival in Patients with Non-Small Cell Lung Cancer: A Prospective, Randomized, Placebo-Controlled, Double-Blind, Three-Arm, Multicenter Study. The Oncologist 2020;25:e1930–e1955 https://theoncologist.onlinelibrary.wiley.com/doi/epdf/10.1002/onco.13548Tai chi is a form of exercise that combines deep breathing and relaxation with meditative, slow movements. Originally developed as a martial art in 13th-century China, tai chi is now practised around the world as a health-promoting exercise. Despite its popularity, its therapeutic value is not clear. 
This randomized, assessor-blinded trial examined the therapeutic efficacy of tai chi for the management of central obesity. A total of 543 participants with central obesity were randomly assigned in a 1:1:1 ratio to:
- a control group with no exercise intervention (n = 181),
- conventional exercise consisting of aerobic exercise and strength training (EX group) (n = 181),
- a tai chi group (TC group) (n = 181). Interventions lasted 12 weeks.
Outcomes were assessed at baseline, week 12, and week 38. The primary outcome was waist circumference (WC). Secondary outcomes were body weight; body mass index; high-density lipoprotein cholesterol (HDL-C), triglyceride, and fasting plasma glucose levels; blood pressure; and incidence of remission of central obesity.
The adjusted mean difference in WC from baseline to week 12 in the control group was 0.8 cm (95% CI, -4.1 to 5.7 cm). Both intervention groups showed reductions in WC relative to control (adjusted mean differences: TC group vs. control, -1.8 cm [CI, -2.3 to -1.4 cm]; P < 0.001; EX group vs. control: -1.3 cm [CI, -1.8 to -0.9 cm]; P < 0.001); both intervention groups also showed reductions in body weight (P < 0.05) and attenuation of the decrease in HDL-C level relative to the control group. The favorable changes in WC and body weight were maintained in both the TC and EX groups, whereas the beneficial effect on HDL-C was only maintained in the TC group at week 38.
The authors concluded that Tai chi is an effective approach to reduce WC in adults with central obesity aged 50 years or older.
This is a decent trial with an odd conclusion: it is not just the Tai chi intervention but both types of exercise that yield significantly positive effects on the primary outcome measure. So, why did the authors not conclude exercise is an effective approach to reduce WC in adults with central obesity aged 50 years or older?
Could it be that such a conclusion would have meant stating the obvious?
The integration of so-called alternative medicine (SCAM) into cancer care may reduce the adverse effects of anti-neoplastic treatment but also cause new problems and non-adherence to conventional treatment. Therefore, its net benefit is questionable.
The aim of this randomized controlled study was to investigate the impact of integrative open dialogue about SCAM on cancer patients’ health and quality of life (QoL).
Patients undergoing curative or palliative anti-neoplastic treatment were randomly assigned to standard care (SC) plus SCAM or SC alone. A nurse specialist facilitated SCAM in one or two sessions. The primary endpoint was the
frequency of grade 3–4 adverse events (AE) eight weeks after enrollment. Secondary endpoints were the frequency of grade 1–4 AE and patient-reported QoL, psychological distress, perceived information, attitude towards and use of SCAM 12 and 24 weeks after enrollment. Survival was analyzed post-hoc.
Fifty-seven patients were randomized to SCAM and 55 to SC. No significant differences were found in terms of AEs of cancer patients. A trend towards better QoL, improved survival, and a lower level of anxiety was found in the SCAM group.
The authors concluded that integration of SCAM into daily oncology care is feasible. IOD-CAM was not superior to SC in reducing the frequency of grade 3-4 AEs, but it did not compromise patient safety. Implementation of SCAM
may improve the QoL, anxiety, and emotional well-being of the patients by reducing the level of nausea, vomiting and diarrhea. Finally, SCAM potentially improves the patients’ self-care, which contributes to
increased treatment adherence and improved survival.
This is an interesting paper with a very odd conclusion. The positive trends found failed to be statistically significant. Why employ statistics only to ignore them in our interpretation of the findings?
I can well imagine that the integration of effective treatments into cancer care improves the outcome. I have no problem with this at all – except it is not called INTEGRATIVE MEDICINE but EVIDENCE-BASED MEDICINE!!! If we integrate dubious treatments into cancer care, it’s called INTEGRATIVE MEDICINE, and it’s unlikely to do any good.
In my view, this small study showed just one thing:
Integrative medicine does not reduce adverse effects in cancer patients.
A new study evaluated the effects of yoga and eurythmy therapy compared to conventional physiotherapy exercises in patients with chronic low back pain.
In this three-armed, multicentre, randomized trial, patients with chronic low back pain were treated for 8 weeks in group sessions (75 minutes once per week). They received either:
- Yoga exercises
- Eurythmy
- Physiotherapy
The primary outcome was patients’ physical disability (measured by RMDQ) from baseline to week 8. Secondary outcome variables were pain intensity and pain-related bothersomeness (VAS), health-related quality of life (SF-12), and life satisfaction (BMLSS). Outcomes were assessed at baseline, after the intervention at 8 weeks, and at a 16-week follow-up. Data of 274 participants were used for statistical analyses.
The results showed no significant differences between the three groups for the primary and secondary outcomes. In all groups, RMDQ decreased comparably at 8 weeks but did not reach clinical meaningfulness. Pain intensity and pain-related bothersomeness decreased, while the quality of life increased in all 3 groups. In explorative general linear models for the SF-12’s mental health component, participants in the eurythmy arm benefitted significantly more compared to physiotherapy and yoga. Furthermore, within-group analyses showed improvements of SF-12 mental score for yoga and eurythmy therapy only. All interventions were safe.
Everyone knows what physiotherapy or yoga is, I suppose. But what is eurythmy?
It is an exercise therapy that is part of anthroposophic medicine. It consists of a set of specific movements that were developed by Rudolf Steiner (1861–1925), the inventor of anthroposophic medicine, in conjunction with Marie von Sievers (1867-1948), his second wife.
Steiner stated in 1923 that eurythmy has grown out of the soil of the Anthroposophical Movement, and the history of its origin makes it almost appear to be a gift of the forces of destiny. Steiner also wrote that it is the task of the Anthroposophical Movement to reveal to our present age that spiritual impulse that is suited to it. He claimed that, within the Anthroposophical Movement, there is a firm conviction that a spiritual impulse of this kind must enter once more into human evolution. And this spiritual impulse must perforce, among its other means of expression, embody itself in a new form of art. It will increasingly be realized that this particular form of art has been given to the world in Eurythmy.
Consumers learning eurythmy are taught exercises that allegedly integrate cognitive, emotional, and volitional elements. Eurythmy exercises are based on speech and direct the patient’s attention to their own perceived intentionality. Proponents of Eurythmy believe that, through this treatment, a connection between internal and external activity can be experienced. They also make many diffuse health claims for this therapy ranging from stress management to pain control.
There is hardly any reliable evidence for eurythmy, and therefore the present study is exceptional and noteworthy. One review concluded that “eurythmy seems to be a beneficial add-on in a therapeutic context that can improve the health conditions of affected persons. More methodologically sound studies are needed to substantiate this positive impression.” This positive conclusion is, however, of doubtful validity. The authors of the review are from an anthroposophical university in Germany. They included studies in their review that were methodologically too weak to allow any conclusions.
So, does the new study provide the reliable evidence that was so far missing? I am afraid not!
The study compared three different exercise therapies. Its results imply that all three were roughly equal. Yet, we cannot tell whether they were equally effective or equally ineffective. The trial was essentially an equivalence study, and I suspect that much larger sample sizes would have been required in order to identify any true differences if they at all exist. Lastly, the study (like the above-mentioned review) was conducted by proponents of anthroposophical medicine affiliated with institutions of anthroposophical medicine. I fear that more independent research would be needed to convince me of the value of eurythmy.
Mind-body interventions (MBIs) are one of the top ten so-called alternative medicine (SCAM) approaches utilized in pediatrics, but there is limited knowledge on associated adverse events (AE). The objective of this review was to systematically review AEs reported in association with MBIs in children.
Electronic databases MEDLINE, Embase, CINAHL, CDSR, and CCRCT were searched from inception to August 2018. The authors included primary studies on participants ≤ 21 years of age that used an MBI. Experimental studies were assessed for whether AEs were reported on or not, and all other study designs were included only if they reported an AE.
A total of 441 were included as primary pediatric MBI studies. Of these, 377 (85.5%) did not explicitly report the presence/absence of AEs or a safety assessment. In total, there were 64 included studies: 43 experimental studies reported that no AE occurred, and 21 studies reported AEs. A total of 37 AEs were found, of which the most serious were grade 3. Most of the studies reporting AEs did not report on severity (81.0%) or duration of AEs (52.4%).
The authors concluded that MBIs are popularly used in children; however associated harms are often not reported and lack important information for meaningful assessment.
SCAM is far too often considered to be risk-free. This phenomenon is particularly stark if the SCAM in question does not involve physical or pharmacological treatments. Thus MBIs are seen and often waved through as especially safe. Consequently, many researchers do not even bother to monitor AEs in their clinical trials. This might be understandable, but it is nevertheless a violation of research ethics.
This new review is important in that it highlights these issues. It is high time that we stop giving researchers in SCAM the benefit of the doubt. They may or may not make honest mistakes when not reporting AEs. In any case, it is clear that they are not properly trained and supervised. All too often, we still see clinical trials run by amateurs who have little idea of methodology and even less of ethics. The harm this phenomenon does is difficult to quantify, but I fear it is huge.
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.
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).
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.
The authors concluded that 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.
This conclusion is obviously nonsense! The authors stated that their trial has ‘pilot character’. The study was not designed as an equivalence trial. Thus it is improper to draw conclusions about the comparative effectiveness of Medi-Taping.
Having clarified this crucial point, we might ask, what is this new therapy called Medi-Taping? This is how the authors of the above paper describe the technique:
…sessions started with an assessment of leg length difference. Patients were asked to lie on their back and the legs were slightly stretched by a soft pull at the ankles. Next, a continuous horizontal line was drawn on the inside of both calves indicating the position of the calves relative to each other. Then the patient was asked to sit up with the legs remaining outstretched. This procedure results in a shift of the line between the two calves for most people. This shift was measured in millimeters as leg length difference.
The patient was then asked to stretch out, lying supine, and the therapist palpated any myogeloses (areas of abnormal hardening in a muscle) and tense muscles areas that could be found next to the cervical spine between the base of the skull and seventh cervical vertebra on both sides. After this treatment the leg length difference assessment was repeated. If there was still a substantial difference. The same treatment was also performed on the thoracic and lumbar spine. Also, the mandibular joint was assessed for tense muscles and, if necessary, treated by palpation.
Next, the leg length difference was assessed again and several tapes were applied as follows: First, two parallel tapes were fixed on both sides of the spine above the erector spinae muscles ranging from the base of the skull to the sacrum. For the application patients were asked to bend forward and to lean on a bench. This position stretches the back and its anatomical structure before applying the tape and thus provides the tape with tension before fixing it. Next a star-shaped pattern of tape (three stripes meeting in one point) was placed on the lower back while the patient was still in the same bent position. Thus, the star tape covered the area of the patient’s maximum pain and additionally stabilized the sacroiliac joint. This tape was placed with maximum tension in the middle section by stretching the tape before application, with the ends (approx. 5 cm) applied without tension. If after this procedure there was still residual pain, a third tape was placed at the gluteus maximus muscle. This tape was first fixed distally from the greater trochanter then stretched up to approx. 80% of the possible tension before the other end was placed on the sacrum. On average six tapes were applied for the gluteus tape.
Patients were instructed to keep the tapes on as long as they stuck to the skin. If the patients had recurring low back pain (LBP) within the same week, they were asked to see the therapist again immediately. Otherwise, the second and the third treatment were scheduled once a week for the following 2 weeks, respectively.
(Elsewhere MEDI-Taping is described differently as a technique using an elastic tape. The tape comes in different colors that are used depending on the patient’s need. The fabric and adhesive are made from cotton and other all natural materials. The tape can be ‘stretched’ in order to better support a given joint or muscle. Through the stretch, the underlying areas are relieved of tension, circulation is improved, and as a result injuries are healing faster. While it is applied to the skin, the tape gently massages the affected area as the body is moving. As the tape is applied, an improvement in motor function and pain relief should be felt immediately.)
Considering the above, I think that the most likely explanation of the outcome of this study (if it ever got confirmed in a properly designed equivalence trial) is that Medi-Taping itself is fairly useless. The fact that it did as well as (more precisely perhaps not worse than) standard physiotherapy is due to its exotic and novel flair which raised expectations and thus contributed to a large placebo response.
Whether my speculation is true or not, I don’t feel that Medi-Taping is the solution to back or any other problems.
PS
The senior author of this study is Harad Walach who has been a regular feature on this blog, and I could not help but notice that he now has 4 affiliations:
- Institute for Frontier Areas of Psychology and Mental Health, Freiburg, Germany.
- Pediatric Clinic, Medical University Poznan, Poznan, Poland.
- Department of Psychology and Psychotherapy, University Witten-Herdecke, Witten, Germany.
- CHS Institute, Berlin, Germany.
A low intake of selenium has been associated with increased cardiovascular mortality in some epidemiological studies. This could be reduced by supplementation with selenium and coenzyme Q10. D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease.
The objective of this trial was to examine the impact of selenium and coenzyme Q10 on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years.
All included individuals were low in selenium (mean 67 μg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance, and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer.
In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups.
The authors concluded that supplementation with selenium and coenzyme Q10 in a group of elderly low in selenium and coenzyme Q10 prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.
These results are interesting and potentially important. The authors agree that their study is not fully conclusive: “Even if the size of the study population is small, we regard the results as being interesting from a scientific point of view, and for hypothesis-generating. The included participants represented a relatively narrow age stratum, so it is not possible to extrapolate the results to other age groups without uncertainty. Finally, as the evaluated population consisted of Caucasians who were low in selenium and coenzyme Q10, it is not necessarily true that the obtained results could be extrapolated to another population.” It might furthermore be of interest to note that part of the analysis cost was supported by grants from Pharma Nord Aps, Denmark, the County Council of Östergötland, Linköping University.
What is needed next, I think, are independent replications. Also of interest would be to determine whether the effects are due to the selenium, or the Q10, or both. And finally, one must caution consumers to not overdose on selenium which could have a host of negative effects on health.
Qigong is a branch of Traditional Chinese Medicine using meditation, exercise, deep breathing, and other techniques with a view of strengthening the assumed life force ‘qi’ and thus improving health and prolong life. There are several distinct forms of qigong which can be categorized into two main groups, internal qigong, and external qigong. Internal qigong refers to a physical and mental training method for the cultivation of oneself to achieve optimal health in both mind and body. Internal qigong is not dissimilar to tai chi but it also employs the coordination of different breathing patterns and meditation. External qigong refers to a treatment where qigong practitioners direct their qi-energy to the patient with the intention to clear qi-blockages or balance the flow of qi within that patient. According to Taoist and Buddhist beliefs, qigong allows access to higher realms of awareness. The assumptions of qigong are not scientifically plausible and its clinical effectiveness remains unproven.
The aim of this study was to investigate the effects of internal Qigong for the management of a symptom cluster comprising fatigue, dyspnea, and anxiety in patients with lung cancer.
A total of 156 lung cancer patients participated in this trial, and they were randomized to a Qigong group (6 weeks of intervention) or a waitlist control group receiving usual care. A professional coach with 12 years of experience in teaching Qigong was employed to guide the participants’ training. The training protocol was developed according to the “Qigong Standard” enacted by the Chulalongkorn University, Thailand. The training involved a series of simple, repeated practices including body posture/movement, breathing practice, and meditation performed in synchrony. It mainly consisted of gentle movements designed to bring about a deep state of relaxation and included 7 postures. The symptom cluster was assessed at baseline, at the end of treatment (primary outcome), and at 12 weeks, alongside measures of cough and quality of life (QOL).
The results showed no significant interaction effect between group and time for the symptom cluster, the primary outcome measure of this study, overall and for fatigue and anxiety. However, a significant trend towards improvement was observed on fatigue (P = .004), dyspnea (P = .002), and anxiety (P = .049) in the Qigong group from baseline assessment to the end of intervention at the 6th week (within-group changes). Improvements in dyspnea and in the secondary outcomes of cough, global health status, functional well-being and QOL symptom scales were statistically significant between the 2 groups (P = .001, .014, .021, .001, and .002, respectively).
The authors concluded that Qigong did not alleviate the symptom cluster experience. Nevertheless, this intervention was effective in reducing dyspnea and cough, and improving QOL. More than 6 weeks were needed, however, for detecting the effect of Qigong on improving dyspnea. Furthermore, men benefited more than women. It may not be beneficial to use Qigong to manage the symptom cluster consisting of fatigue, dyspnea, and anxiety, but it may be effective in managing respiratory symptoms (secondary outcomes needing further verification in future research). Future studies targeting symptom clusters should ensure the appropriateness of the combination of symptoms.
I am getting very tired of negative trials getting published as (almost) positive ones. The primary outcome measure of this study did not yield a positive result. The fact that some other endpoints suggested a positive might provide an impetus for further study but does not demonstrate Qigong to be effective. I know the first author of this study is a fan of so-called alternative medicine (SCAM), but this should not stop him from doing proper science.
