MD, PhD, FMedSci, FRSB, FRCP, FRCPEd.

Monthly Archives: August 2021

Research on glucosamine, one of the most popular dietary supplements, shows anti-inflammatory and anti-cancer benefits with minimal adverse effects. An international team of researchers aimed to explore the relationship between the use of glucosamine and the risk of lung cancer and lung cancer mortality based on data from the large-scale nationwide prospective UK Biobank cohort study.

Participants were enrolled between the years 2006 and 2010 and followed up to 2020. The Cox proportion hazards model was used to assess the relationship between glucosamine use and the risk of lung cancer and lung cancer mortality. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings.

A total of 439,393 participants (mean age: 56 years; 53% females) with a mean follow-up of 11 years were included for analyses. There were 82,603 (18.80%) participants reporting regular use of glucosamine at baseline. During follow-up, there were 1,971 (0.45%) lung cancer events documented. Glucosamine use was significantly associated with a decreased risk of lung cancer (hazard ratio=0.84, 95% CI: 0.75-0.92, p<0.001) and lung cancer mortality (hazard ratio=0.88, 95% CI: 0.81-0.96, p=0.002) in fully adjusted models. A stronger association between glucosamine use and decreased lung cancer risk was observed in participants with a family history of lung cancer when compared to those without a family history.

The authors concluded that regular use of glucosamine was significantly related with decreased risk of lung cancer and lung cancer mortality, based on data from this nationwide prospective cohort study.

A previous analysis of the same data concluded that regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases. The new analysis shows a strong association with lung cancer.

This is certainly interesting, but does it prove a causal relationship?

The answer is no.

Correlation is not causation!

What would be helpful in testing whether we are dealing with a cause-effect relationship?

  1. We need data from other studies. Several other epidemiological investigations indicated that glucosamine use might play a role in the prevention of cancer.
  2. We require to know the strength of the association. The new analysis suggests that it is indeed strong.
  3. We need a mode of action. Might the anti-inflammatory action of glucosamine explain the effect?
  4. We should ask whether there is a dose-response relationship. As far as I know, this has not been addressed as yet.
  5. Ideally, we would require a randomized trial to test the hypothesis. But I fear that such a study might be too difficult to conduct and will thus not be forthcoming.

And what if glucosamine should one day be proven to reduce the cancer risk? Would it become the first ALTERNATIVE measure to prevent cancer?

Certainly not!

It would automatically become a conventional method of cancer prevention. All the research into the subject has been entirely conventional and is unrelated to the alternative medicine movement. Or, to put it bluntly, alternative cancer prevention is a contradiction in terms. Either it works in which case it is conventional medicine, or it doesn’t in which case it is not even an alternative but at best so-called alternative medicine.

 

This study aimed to assess the feasibility of a future definitive trial, with a preliminary assessment of differences between effects of individualized homeopathic (IH) medicines and placebos in the treatment of cutaneous warts.

A double-blind, randomized, placebo-controlled trial (n = 60) was conducted at the dermatology outpatient department of the Homoeopathic Medical College and Hospital, West Bengal. Patients were randomized to receive either IH (n = 30) or identical-looking placebos (n = 30). The primary outcome measures were numbers and sizes of warts; the secondary outcome measure was the Dermatology Life Quality Index (DLQI) questionnaire measured at baseline, and every month up to 3 months. Group differences and effect sizes were calculated on the intention-to-treat sample.

Attrition rate was 11.6% (IH, 3; placebo, 4). Intra-group changes were significantly greater in the IH group than in the placebo group. Inter-group differences were statistically non-significant (all > 0.05, Mann-Whitney U tests) with small effect sizes, both in the primary outcomes (number of warts after 3 months: IH median [interquartile range; IQR] 1 [1, 3] vs. placebo 1 [1, 2]; p = 0.741; size of warts after 3 months: IH 5.6 mm [2.6, 40.2] vs. placebo 6.3 [0.8, 16.7]; p = 0.515) and in the secondary outcomes (DLQI total after 3 months: IH 4.5 [2, 6.2] vs. placebo 4.5 [2.5, 8]; p = 0.935). Thuja occidentalis (28.3%), Natrum muriaticum (10%), and Sulphur (8.3%) were the most frequently prescribed medicines. No homeopathic aggravations or serious adverse events were reported.

The authors concluded that, as regards efficacy, the preliminary study was inconclusive, with a statistically non-significant direction of effect favoring homeopathy. The trial succeeded in showing that an adequately powered definitive trial is both feasible and warranted.

Partly the same group of authors recently published another trial of homeopathy with similar findings. At the time, I commented as follows:

We have come across this terminology before; homeopaths seem to like it. It prevents them from calling a negative trial by its proper name: A NEGATIVE TRIAL. In their view

  • a positive trial is a study where homeopathy yields better results than placebo,
  • a negative trial is a study where placebo yields better results than homeopathy,
  • an inconclusive trial is a study where homeopathy yields results that are not significantly different from placebo.

Is this silly?

Yes, it is completely bonkers!

Is it dishonest?

Yes, in my view, it is.

Why is it done nonetheless?

Perhaps a glance at the affiliations of the authors provides an answer. And here is the list of the affiliations of the trialists of the present cutaneous wart study:

  • 1Department of Repertory, D.N. De Homoeopathic Medical College and Hospital, Govt. of West Bengal, Tangra, Kolkata, West Bengal, India.
  • 2D.N. De Homoeopathic Medical College and Hospital, Govt. of West Bengal, Tangra, Kolkata, West Bengal, India.
  • 3Department of Organon of Medicine and Homoeopathic Philosophy, The Calcutta Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India.
  • 4Department of Practice of Medicine, The Calcutta Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India.
  • 5Department of Repertory, National Institute of Homoeopathy, Ministry of AYUSH, Govt. of India, Kolkata, West Bengal, India.
  • 6Department of Organon of Medicine and Homoeopathic Philosophy, D.N. De Homoeopathic Medical College and Hospital, Govt. of West Bengal, Tangra, Kolkata, West Bengal, India.
  • 7Department of Pediatrics, National Institute of Homoeopathy, Ministry of AYUSH, Govt. of India, Salt Lake, Kolkata, West Bengal, India.
  • 8Department of Organon of Medicine and Homoeopathic Philosophy, State National Homoeopathic Medical College and Hospital, Lucknow, Uttar Pradesh.
  • 9Independent Researcher; Champsara, Baidyabati, Hooghly, West Bengal, India.
  • 10Independent Researcher, Shibpur, Howrah, West Bengal, India.

And, as before, this paper also contains this statement:

Conflict of interest statement

None declared.

Bromelain, papain and chymotrypsin are proteolytic enzymes. They can be found in fruits such as pineapple or papaya, but also in the human body, namely in the pancreas. Besides their enzymatic functions, they have long been said to have a wide range of positive health effects. For instance, it is claimed that they reduce side effects and even improve the outcome of cancer therapies. This systematic review examined the existing evidence on the role that these enzymes which are available as food supplements might play in cancer treatment.

A total of 15 studies with 3,008 patients could be included in this systematic review. Patients treated with enzymes were diagnosed with various entities of gastrointestinal, gynecologic, head and neck, and lung cancer as well as hematological malignancies. The therapy concepts included mainly oral intake of enzymes in addition to conventional therapies. Investigated outcomes were:

  • side-effects of anticancer therapy,
  • quality of life,
  • anticancer effects,
  • survival rates.

Due to conflicting results and moderate quality of the included studies, the evidence is insufficient to attribute positive effects to enzymes in terms of better tolerability of the various antineoplastic therapies or even improvement in treatment efficacy. In most cases, enzyme therapy was well tolerated; side-effects were mainly gastrointestinal complaints such as diarrhea or meteorism.

The authors concluded that there is no clear therapeutic benefit of enzymes neither as supportive therapy nor as part of antineoplastic therapy.

I fully agree with this conclusion. In fact, in my new book that is just being published, I summarised the evidence for enzyme therapy (and many more alternative cancer therapies) in very similar terms: the evidence to suggest that enzyme therapy might be an effective treatment for any type of cancer is less than convincing.

I find it highly irresponsible to claim otherwise. Cancer patients are vulnerable and can easily be tempted to opt for one of the many quack treatments that are said to be both effective and free of nasty adverse effects. If they do try such options, they usually pay dearly, and not just in monetary terms.

Pre-hypertension, or stage 1 hypertension as it is also called, is usually defined as a systolic pressure reading between 120 mmHg and 139 mmHg, or a diastolic reading between 80 mmHg and 89 mmHg. It remains a significant public health challenge and appropriate intervention is required to stop its progression to hypertension and cardiovascular diseases.

This double-blind, randomized, two parallel arms, placebo-controlled study tested the effects of individualized homeopathic medicines (IH) against placebo in intervening with the progression of pre-hypertension to hypertension.

Ninety-two patients with pre-hypertension were randomized to receive either IH (n = 46) or identical-looking placebo (n = 46). Both IH or placebo were applied in the mutual context of lifestyle modification (LSM) advice including dietary approaches to stop hypertension (DASH) and brisk exercises.

The primary endpoints were systolic and diastolic blood pressures (SBP and DBP); secondary endpoints were Measure Yourself Medical Outcome Profile version 2.0 (MYMOP-2) scores. All endpoints were measured at baseline, and every month, up to 3 months.

After 3 months of intervention, the number of patients having progression from pre-hypertension to hypertension between groups was similar without any significant differences in between the groups. Reduction in BP and MYMOP-2 scores were also not significantly different. Lycopodium clavatum, Thuja occidentalis and Natrum muriaticum were the most frequently prescribed medicines. No serious adverse events were reported from either group.

The authors concluded that there was a small, but non-significant direction of effect favoring homeopathy, which ultimately rendered the trial as inconclusive.

We have come across this terminology before; homeopaths seem to like it. It prevents them from calling a negative trial by its proper name: A NEGATIVE TRIAL. In their view

  • a positive trial is a study where homeopathy yields better results than placebo,
  • a negative trial is a study where placebo yields better results than homeopathy,
  • an inconclusive trial is a study where homeopathy yields results that are not significantly different from placebo.

Is this silly?

Yes, it is completely bonkers!

Is it dishonest?

Yes, in my view, it is.

Why is it done nonetheless?

Perhaps a glance at the affiliations of the authors provides an answer:

  • 1Dept. of Organon of Medicine and Homoeopathic Philosophy, D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, affiliated to The West Bengal University of Health Sciences, Govt. of West Bengal, India. Electronic address: drsouvikdutta@gmail.com.
  • 2Dept. of Organon of Medicine and Homoeopathic Philosophy, D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, affiliated to The West Bengal University of Health Sciences, Govt. of West Bengal, India.
  • 3Principal and Administrator D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, affiliated to The West Bengal University of Health Sciences, Govt. of West Bengal, India.
  • 4Dept. of Practice of Medicine, D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, affiliated to The West Bengal University of Health Sciences, Govt. of West Bengal, India.
  • 5Dept. of Practice of Medicine, Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Howrah, Govt. of West Bengal, affiliated to The West Bengal University of Health Sciences, Govt. of West Bengal, India.
  • 6Dept. of Organon of Medicine and Homoeopathic Philosophy, National Institute of Homoeopathy, Block GE, Sector III, Salt Lake, Kolkata 700106, West Bengal, India; affiliated to The West Bengal University of Health Sciences, Govt. of West Bengal, India.
  • 7Dept. of Organon of Medicine and Homoeopathic Philosophy, State National Homoeopathic Medical College and Hospital, Lucknow, Govt. of Uttar Pradesh, affiliated to Dr. Bhimrao Ramji Ambedkar University, Agra, Govt. of Uttar Pradesh), India.
  • 8Dept. of Repertory, D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, affiliated to The West Bengal University of Health Sciences, Govt. of West Bengal, India.

Despite these multiple conflicts of interest, the article carries this note:

“Declaration of Competing Interest: None declared.”

During the last few days, we were entertained by one of the more fanatical specimen of the lunatic fringe. From the outset, ‘ASTRO’ was out to provoke, insult, and foremost state utter nonsense. Within just a few hours ‘ASTRO’ posted dozens of comments, one more hilarious than the next.

As always, I let it pass for a while because this sort of thing usually is very amusing and mildly instructive. Then, when my fun was over, I told him or her that my conversation with him or her was finished, thereafter I sent ‘ASTRO’ my usual hint to indicate that my patience was wearing thin (an overdose of nonsense, fun, and hilarity might be toxic) and now I have blocked ‘ASTRO’.

This little incident is a mere triviality, of course. Yet, it is also a most welcome reminder to demonstrate what is needed to get blocked by me. Here are a few selected ‘bon mots’ posted by ‘ASTRO’ which all contributed to his or her dismissal from this blog:

  • Lenny is an intellectual terrorist
  • you manipulate data
  • you are nobody in the scientific world
  • I’m very sorry for your lack of education
  • I don’t hate you for lying, I pity you
  • With all sincerity, and seeing that you don’t have a single scientific publication, I recommend that mounts a business for atheists resentful and sell cheap products with the face of Carl Sagan or James Randi in a coffe cup or pins, I assure you that the media will make of your business, earn some money and you’ll be able to publish a book trash like Ben Goldacre, with his “Bad science” or the Steven Novella. Poor quality is a typical sign of skeptical pseudoscientists.
  • your “letter to the editor” is based on manipulating data and making false accusations, everything
  • you only have an opinion based on your belief and denial that may well be a projection of your lack of knowledge
  • I’m disappointed that you have very superficial knowledge, no wonder Mathie will ignore you
  • Your comments again reflect that you haven’t the slightest idea
  • your lack of reading comprehension is evident
  • You are very ignorant
  • your aggressiveness and lack of empathy tell a lot about your profile of atheist resentful of life
  •  these” verdicts ” that Ernst quotes in his pamphlets are at best a fraud
  • in reality you, Grams and the team of the anti-homeopathy propaganda network have no idea what you’re talking about
  • Ernst,” friend, ” you’re still pretty aggressive, maybe you need some joy in your life. Now I understand why the pseudoscientific skeptical atheist community is so childish and so toxic
  • anyone who questions Edzar’s sacred dogmas is a troll
  • Thank you for confirming that you are a sectarian
  • your obsessive behavior borders on harassment
  • Magazines like Skepter are very popular with immature gentlemen who believe they are the world or with teenagers who are just out of college who believe that science is done with whims
  • don’t be like Lenny and try to grow up
  • real science is in the objective pursuit and not in harassment campaigns orchestrated by a few clowns who believe James Randi is unquestionable
  • every time I read your entries I feel sorry that your level of logic is so low and lousy
  •  Your naivety and superficial knowledge in philosophy of science (and that of most of those who follow you) is very pitiful
  • you are the example of a pseudo-sceptic, a rude and cowardly skeptic who can’t tolerate criticism
  • your friends are a sect, possibly a group based on coertion
  • it doesn’t look like “Lenny” has a single scientific article published, not to mention your colleagues in the “About” section that the few who look like scientists are mediocre in their fields, the rest are small-time activists. No wonder, so much envy, so much anger, so much hatred, that’s what leaves fanatical atheism. They’re talibans of science, not scientists
  • you with your age presume a lot and I only see you being interviewed by mainstream media that talk nonsense against homeopathy
  • You had to control that aggressiveness, you feel more nervous and angry, maybe you’re a relative of the troll Lenny
  • The obsessive behavior of Aust trying to refute Frass already looks like that of a stalker, similar of the journalist Christian Kreil who invented a whole string of nonsense in a German public media trying to link Frass to a questionable company, the media does not even mention Frass’s refutation to Kreil

One thing we cannot accuse ‘ASTRO’ of is that he or she was not industrious. You might ask why I did not stop his aggressive stupidity earlier after it had stopped being funny. Perhaps I should have – but, to be honest, these trolls do amuse me a great deal. More importantly, they might teach us important lessons:

  • The fun one can have with fanatics is usually short-lasted.
  • Some weirdos are very well misinformed, i.e. they read a lot and misunderstand even more.
  • The minds of heavily deluded people are beyond productive discussions.
  • Any hope to educate them will be disappointed.
  • If we allow them to, they swiftly make themselves ridiculous.
  • Their pseudo-arguments are strikingly similar.
  • Their aggressiveness can be considerable.

And finally, the little ‘ASTRO’ interlude tells you something else:

It really does need a lot to get banned from my blog.

By guest blogger Ken McLeod

RICHARD MICHAEL NILSSON is the owner of Colloidal Minerals Australia Pty Ltd, ACN 003 484 955, of Wyongah New South Wales (NSW), Australia. On August 13 he was convicted in the Wyong Court, after pleading guilty to offences including intimidation with intent to cause fear of physical or mental harm.

Nilsson is a prolific antivaxxer, deluging unlucky politicians, journalists, health officials, etc with emails containing misinformation about vaccines and warning of the dire consequences to come to anyone involved in vaccination programs. He has been known to harass and threaten. Usually recipients have better things to do than engage with a crank, but he has been known to go too far.

As the Sydney Daily Telegraph reported on 14 August 2021: “Anti-vaccine activist Richard Nilsson pleads guilty to sending death threats.”

“A Central Coast anti-vaccine campaigner who sent death threats to The Sunday Telegraph journalist Jane Hansen has pleaded guilty to the charge of using intimidation to unlawfully influence a person.

“Richard Nilsson, 66, from Wyongah, sent an email to Ms Hansen’s work email address on the evening of February 27.

“The subject of the email was “WHEN IS A MURDER WARRANTED? YOURS, YES?”

The contents of the email read: ‘I am proposing that your murder might well be a celebration of not life but death! And what a celebrated and glorious one at that!

‘I know ten thousand that would do it, but of course it only needs one and you will never know until it is too late!

‘I expect you might meet your maker, maybe in the near future … the sooner the better, yes?’

“Ms Hansen has reported widely on vaccination since 2013 when The Sunday Telegraph launched the No Jab No Play campaign, and more recently has reported on the vaccine rollout for Covid-19.

“On February 27, the evening the email was sent, Sky News re-ran a documentary made by Ms Hansen called Big Shots, which looked at anti-vaccine activity in relation to the pandemic and the vaccine rollout.

“Mr Nilsson followed up his email with another with the subject line: “WHEN IS SLUT NOT A SLUT AND IS A SELECTIVE SLUT STILL A SLUT?” before launching into a barrage of abuse.

“Mr Nilsson, who runs a business selling colloidal silver, faced Wyong Court on August 11 and pleaded guilty to a charge of use intimidation/violence to unlawfully influence a person.

“He received an 18-month Community Corrections Order to be of good behaviour.

“Ms Hansen said threats to journalists who write on the subject of vaccination were not unusual but Mr Nilsson’s emails were unsettling in their violence.

‘All journalists get abused on occasion, especially on the currently highly emotive topic of vaccination, and mostly it is best ignored but this email was next level and no one should have to put up with such vile abuse,’ she said.

“Mr Nilsson is well known by politicians, who have also received numerous emails from him suggesting all manner of conspiracies, including that Covid vaccination is a mass depopulation exercise.”

Nilsson appeared before His Honour Ian Guy in case number 2021/00159728, R V Richard Michael Nilsson. He was convicted of stalking or intimidation with intent to cause fear of physical or mental harm, an offence under section 13 of the Crimes (Domestic and Personal Violence) Act 2007 (NSW). This attracts a maximum penalty of 5 years imprisonment and/or $5,500. He could also have been convicted of using a carriage service to menace, harass or cause offence, an offence under section 474.17 of the Criminal Code Act 1995 (Commonwealth of Australia). That carries a maximum penalty of 3 years imprisonment.

He was sentenced to a Community Corrections Order requiring him to be of good behaviour.

A rational person would have thought themselves lucky that they had avoided years of a high-fibre low-calorie diet of porridge and baked beans, but we are not dealing with a rational person here.

Hardly was the ink dry on the Court file, than on the 15th, two days after he was found guilty, Nilsson pounded his foam-flecked keyboard and sent another rant in an email to 130 people and organisations, including politicians, Skeptics groups, a Radiation Oncologist, government departments, doctors, political parties, people in the horse-racing industry, scientists, journalists, lobby groups including climate and conservation organisations, mental health groups, the National Security Hotline, and a coal mining company.

It reads: “Subject: FW: The Hidden Victims of the Covid Vaccine and why I included you all in this email…

“When will it be that enough lives have been ruined and enough have been murdered? And when will the maiming and the killing end?

“My hope is that some of you here own up and confess (I know who among you are in this group and I suspect in time you will all pay a heavy price for your crimes and transgressions), while others it is incumbent upon you to inform all those you purport to represent that the maiming and killing that has transpired and of course is inevitably and scheduled to transpire will continue until such time we say: f_ ck you!

“I know, and some of you know too, who the traitors are. Scott Morrison is just one and Greg Hunt is another and of course Jane Halton, Brendan Murphy and Paul Kelly are other worthless humans and are included and we know they are just tools – plasticised and fake as they are.

“I have an incomplete list of those who need to answer for their crimes and it does not include all I have included in this email.

“Add a Mr Skerrit. His evilness is seen in his face and in his utterings and communications and his connection with Jane Halton and the WHO and the so-called, Australian Health (sickness proliferation) Dep’t and Event 201 should not be lost on anyone with brain cells that still operate and are able to coordinate.

“Wake the f_ _k up!”

 

All emphases and redactions above are as in Nilsson’s email. Scott Morrison is the Prime Minister, Greg Hunt the Commonwealth Minister for Health, Brendan Murphy is a former Chief Medical Officer (CMO) of Australia and now Secretary of the Department of Health. Paul Kelly is the current Chief Medical Officer, the “Mr Skerrit” he refers to is Adjunct Professor John Skerritt, Deputy Secretary, Health Products Regulation Group, Therapeutics Goods Administration. “Jane Halton” is a former Secretary of the Commonwealth Dept of Health, now Council Member of the Australian Strategic Policy Institute.

The “Event 201” that Nilsson refers to was a tabletop exercise conducted in October 2019 by the Johns Hopkins Center for Health Security (CHS), the World Economic Forum and the Bill and Melinda Gates Foundation in New York City. According to the CHS, “[t]he exercise illustrated areas where public/private partnerships will be necessary during the response to a severe pandemic in order to diminish large-scale economic and societal consequences”.

Event 201 simulated the effects of a fictional coronavirus originating in bats but passing to humans via pigs. Claims that Event 201 was a rehearsal for the COVID-19 pandemic have been debunked by fact-checking outlets such as USA Today and FullFact, but facts have never matter to antivax conspiracy theorists and other assorted cranks. All emergency response authorities and health bureaucracies conduct exercises to identify threats and to develop and improve response plans. There was nothing unusual in “Event 201” except in the fevered imaginations of nutters and fruitloops.

Does Nilsson, with no qualifications whatsoever, really think that he knows more about emergency response and immunology than those distinguished experts, and all the scientists researching Covid19 and vaccines? How does 20 minutes reading email conspiracy theories trump PhDs, professorships and Nobel Prizes? How conceited does someone have to be to imagine that? Where is the boundary between conceit and dementia? So does accusing honourable people of ‘crimes and transgressions,’ ‘maiming and killing,’ being ‘traitors,’ are evil tools, ‘who need to answer for their crimes’ constitute the good behaviour that the Court imposed? And coming within hours of the Court hearing?

 

Watch this space.

In their 2019 systematic review of spinal manipulative therapy (SMT) for chronic back pain, Rubinstein et al included 7 studies comparing the effect of SMT with sham SMT.

They defined SMT as any hands-on treatment of the spine, including both mobilization and manipulation. Mobilizations use low-grade velocity, small or large amplitude passive movement techniques within the patient’s range of motion and control. Manipulation uses a high-velocity impulse or thrust applied to a synovial joint over a short amplitude near or at the end of the passive or physiological range of motion. Even though there is overlap, it seems fair to say that mobilization is the domain of osteopaths, while manipulation is that of chiropractors.

The researchers found:

  • low-quality evidence suggesting that SMT does not result in a statistically better effect than sham SMT at one month,
  • very low-quality evidence suggesting that SMT does not result in a statistically better effect than sham SMT at six and 12 months.
  • low-quality evidence suggesting that, in terms of function, SMT results in a moderate to strong statistically significant and clinically better effect than sham SMT at one month. Exclusion of an extreme outlier accounted for a large percentage of the statistical heterogeneity for this outcome at this time interval (SMD −0.27, 95% confidence interval −0.52 to −0.02; participants=698; studies=7; I2=39%), resulting in a small, clinically better effect in favor of SMT.
  • very low-quality evidence suggesting that, in terms of function, SMT does not result in a statistically significant better effect than sham SMT at six and 12 months.

This means that SMT has effects that are very similar to placebo (the uncertain effects on function could be interpreted as the result of residual de-blinding due to a lack of an optimal placebo or sham intervention). In turn, this means that the effects patients experience are largely or completely due to a placebo response and that SMT has no or only a negligibly small specific effect on back pain. Considering the facts that SMT is by no means risk-free and that less risky treatments exist, the inescapable conclusion is that SMT cannot be recommended as a treatment of chronic back pain.

By guest blogger Wolfgang Denzer

Most pseudoscientific studies related to the explanation of the proposed mechanisms of homeopathy used tadpoles, wheat, or watercress as models. Results of these studies, e.g. those by Endler, Baumgartner & Co., were published in dedicated SCAM (So-Called Alternative Medicine) journals where the peers who review manuscripts have a clear tendency to support non-evidence-based studies in particular those that deal with homeopathy. In recent years several papers were published in reputable journals (see below) that purport the efficacy of ultrahigh dilution (UHD). None of these publications relates directly to homeopathy or even uses the term “homeopathy”. One thing the publications have in common is that they were either sponsored by the Russian OOO [sometimes LLC] “npf” Materia Medica Holding or co-authored by staff of that company. Materia Medica Holding produces and markets ultra-high diluted remedies that are called ‘release-active’ drugs (RA-drugs). The company founder rigorously states that their remedies are not homeopathy and that „homeopathy is doomed to have a marginal position in the modern system of therapy“. (see interview link at the end). Already a few years ago Panchin et al. (2018) analyzed several papers that involved Materia Medica Holding in one way or the other and published an article in BMJ Evidence-Based Medicine (Drug discovery today: no molecules required. http://dx.doi.org/10.1136/bmjebm-2018-111121). His remarkable conclusion was as follows: “Surprisingly, these innovative “drugs” contain no active molecules and can be considered a new brand of homeopathy. This indicates one of two possibilities: either we are at the brink of a revolution in medicine or that something went wrong with research published in numerous academic journals.” Of course, the latter assumption is correct.

The difficulty to uncover the use of an ultra-high diluted homeopathic (oops) remedy instead of proper medication published in a study is best shown by having a look at the following publication co-authored by the founder of Materia Medica Holding Oleg I. Epstein and two of his employees:

Pathogenetic approach to the treatment of functional disorders of the gastrointestinal tract and their intersection: results of the Russian observation retrospective program COMFORT (BMC Gastroenterol. 2020; 20: 2. Published online 2019 Dec 31. doi: 10.1186/s12876-019-1143-5).

The study deals with a retrospective analysis of the effectiveness of Kolofort, “a release-active drug” produced by Materia Medica Holding. The only statement regarding the composition of the drug reads as follows: “For the treatment of FGID [functional gastrointestinal disorders], the combination of released-active form of antibodies [RAF of Abs] to S-100 protein, TNF-α and histamine (RAF of Abs to S 100, Abs to TNF-α and Abs to H), a pathogenetically targeted drug Kolofort, was developed by the Research and Production Company Materia Medica Holding (LLC NPF” MATERIA MEDICA HOLDING”) Moscow, Russia and introduced into practical medicine. The RAF of Abs in the drug provides an anti-inflammatory, spasmolytic, and anxiolytic effect ” (notations in square brackets by me). The two following paragraphs provide information (and citations of two publications in Russian) related to the clinical trials of Kolofort. At no point in the publication are the concentrations of the active components of Kolofort mentioned! Only a web search provides further information about the composition of Kolofort (see screenshot). The three active ingredients, RAF of Abs to S-100 protein, TNF-α, and histamine, are only present at concentrations of C12, C30, and C200, respectively, i. e. they are absent. Perhaps a better notation for the remedy should be RAF in Abs of histamine, meaning release-active form in absence of histamine.

Judging from the composition of Kolofort no physiological or therapeutical reaction is to be expected. Still the authors claim that “The COMFORT program has demonstrated the positive effect of treatment [with Kolofort] in the majority of patients with IBS and FD and their combination in real clinical practice”. The authors arrived at these results by analyzing a questionnaire that had been specially developed for the assessment of gastrointestinal disorders. The questionnaire is called “7*7” [seven symptoms in seven days], but not further discussed or explained in the publication. Although there exists at least one publication from 2016 where the questionnaire was used to assess symptoms of gastrointestinal ailments (Ivashkin et al. RZHGGK. 2016;3(S):24-33. https://doi.org/10.22416/1382-4376-2016-26-3-24-33) the actual validation was not published until November 2018 (online, print June 2019) which is after the Kolofort study had already terminated (November 01, 2017, through March 30, 2018). Please note that the validation was done by one of the co-authors (V. Ivashkin) of the Kolofort study. There is certainly a good explanation for post-validating a tool used in earlier studies, but I just can’t think of one right now.

There exist several more (if not dozens) of publications by this group of authors that have already been investigated. It appears that the Materia Medica Holding director Oleg I. Epstein is heavily involved in a competition of who is capable of producing the highest number of retracted publications. Here are a few of them:

Retraction: Novel Approach to Activity Evaluation for Release-Active Forms of Anti-Interferon-Gamma Antibodies Based on Enzyme-Linked Immunoassay

The PLOS ONE Editors. Published: May 3, 2018

https://doi.org/10.1371/journal.pone.0197086

Retraction notice to “Efficacy of novel antibody-based drugs against rhinovirus infection: In vitro and in vivo results” [Antiviral Research 142 (2017) 185–192]

https://doi.org/10.1016/j.antiviral.2019.02.010

Retraction notice to “Activity of ultra-low doses of antibodies to gamma-interferon against lethal influenza A(H1N1)2009 virus infection in mice” [Antiviral Research 93 (2012) 219–224]

https://doi.org/10.1016/j.antiviral.2019.02.011

Retraction Note: Release-Active Dilutions of Diclofenac Enhance Anti-inflammatory Effect of Diclofenac in Carrageenan-Induced Rat Paw Edema Model

https://doi.org/10.1007/s10753-013-9705-0

Retraction: Activity of ergoferon against lethal influenza A (H3N2) virus infection in mice

https://www.intmedpress.com/journals/avt/article.cfm?id=3325&pid=48&sType=AVT

Retraction Note: Effects of chronic treatment with the eNOS stimulator Impaza on penis length and sexual behaviors in rats with a high baseline of sexual activity

https://www.nature.com/articles/s41443-020-0321-x

There are probably more retractions out there, but to make it onto the current Retraction Watch Leader Board (https://retractionwatch.com/the-retraction-watch-leaderboard/) a minimum of 25 retractions is required to take over rank 30. You have to work harder Dr. O. I. Epstein!

Last but not least there is an interview with Epstein available online (https://pharmaboardroom.com/interviews/interview-with-oleg-epstein-general-director-materia-medica/) where he claimed that „We proved that we [Materia Medica] are not a homeopathy company, and 1.5 years ago, the Ministry of Public Health decreed that our drugs will no longer be classified as homeopathic.“ Wow! How?

So, what does all this tell us? There exists a pool of authors, somehow connected to Materia Medica Holding, who manage to get articles, that are nothing else but homeopathy in disguise, past the peer review of reputable academic journals. It would be easy to blame the reviewers for their not soo stringent approach. But as the Kolofort paper shows, only in-depth research may actually reveal the truth. Let’s not forget, even the retracted papers made it through to publication and only a later review scrutinized their scientific merit.

It can be assumed that Materia Medica will not stop promoting their remedies through the publication of further studies. There are already publications out there that do not include any company staff as co-authors but were sponsored by the company. Judging from the rate of already retracted paper, reputation does not appear to matter. These authors possibly work along a submission-rejection-resubmission to a different journal approach until a paper gets published.

So far the homeopathy community hasn’t taken much notice of any of the beforementioned studies, most probably for two reasons: nowhere does the term “homeopathy” appear nor were the papers published in SCAM journals but rather in academic journals above the radar of homeopaths. But it can be assumed that in future, if it fits their purpose, such studies will feature among their usual dubious double blindfolded placebo trials.

Keep your eyes open for more of this stuff and please get in touch with the editorial team of the journal concerned if you discover yet another “UHD” or “RAF” publication!

This systematic review assessed the effect of spinal manipulative therapy (SMT), the hallmark therapy of chiropractors, on pain and function for chronic low back pain (LBP) using individual participant data (IPD) meta-analyses.

Of the 42 RCTs fulfilling the inclusion criteria, the authors obtained IPD from 21 (n=4223). Most trials (s=12, n=2249) compared SMT to recommended interventions. The analyses showed moderate-quality evidence that SMT vs recommended interventions resulted in similar outcomes on

  • pain (MD -3.0, 95%CI: -6.9 to 0.9, 10 trials, 1922 participants)
  • and functional status at one month (SMD: -0.2, 95% CI -0.4 to 0.0, 10 trials, 1939 participants).

Effects at other follow-up measurements were similar. Results for other comparisons (SMT vs non-recommended interventions; SMT as adjuvant therapy; mobilization vs manipulation) showed similar findings. SMT vs sham SMT analysis was not performed, because data from only one study were available. Sensitivity analyses confirmed these findings.

The authors concluded that sufficient evidence suggest that SMT provides similar outcomes to recommended interventions, for pain relief and improvement of functional status. SMT would appear to be a good option for the treatment of chronic LBP.

In 2019, this team of authors published a conventional meta-analysis of almost the same data. At this stage, they concluded as follows: SMT produces similar effects to recommended therapies for chronic low back pain, whereas SMT seems to be better than non-recommended interventions for improvement in function in the short term. Clinicians should inform their patients of the potential risks of adverse events associated with SMT.

Why was the warning about risks dropped in the new paper?

I have no idea.

But the risks are crucial here. If we are told that SMT is as good or as bad as recommended therapies, such as exercise, responsible clinicians need to decide which treatment they should recommend to their patients. If effectiveness is equal, other criteria come into play:

  • cost,
  • risk,
  • availability.

Can any reasonable person seriously assume that SMT would do better than exercise when accounting for costs and risks?

I very much doubt it!

Guest post by Norbert Aust and Viktor Weisshäupl

Imagine you recently published an excellent and rigorous trial providing solid evidence that a certain therapy is able to help patients suffering from some inevitably fatal condition. You proved that your therapy is able to significantly prolong the patients’ lifetime, much longer than with the current state-of-the-art therapeutic approach. But the patients not only live considerably longer, but they also do so with a much better quality of life (QoL) and subjective well-being. In short: this therapy marks some progress that would otherwise take years or decades of scientific effort.

And then someone comes forward and points out your data apparently were manipulated. Essential parameters of this trial were modified sometime after data collection was completed, with the patients’ outcome and first analyses available. Thus the results were biased in a certain direction and the critics show that the results as published in your study show characteristics that such manipulations would evoke. After all, this holds an implication of scientific misconduct that could, if verified, ruin your academic reputation more or less completely.

What would you do?

Ignore the preposterous concerns because you know your methods and performance were rigorous and solid? After all, anytime some real academic criticism arises you are ready to prove your findings are well-founded results of accepted scientific methods. Or would you publish data or documents that your critics were too ignorant to find or to understand, and thus to stop such rumours once and for all? Maybe you could even clarify some of the issues raised by those critics, maybe add some follow-up information or data to ensure no more misunderstandings occur. Or would you try to find some clues for a libel lawsuit?

Well, we thought some of the above would happen after we contacted the authors of the recent study on adjunct homeopathy in non-small cell lung cancer. On that date, we forwarded our detailed analysis to the lead author and all the co-authors.

Of course, we even considered the possibility, not very likely though, that we would receive some explanation for the numerous exclusion criteria while other serious conditions that coincide with advanced age did not preclude enrollment. Or an updated CONSORT diagram accounting for the patients excluded. Or some explanation just why the numerous amendments to the protocol were necessary but not important enough to mention them in the published paper.

But nothing of this happened as yet (July 2021). Instead on June 14 and 16, 2021, not two weeks after our messages to the authors, the registration data at ClinicalTrials were updated once again and a new version of the protocol was uploaded [3]. And this update looks pretty much like it is meant to cover up and blur the former data that we based our analysis on. Of course, these data and the former version of the protocol are available still – just one layer further down, and you have to scroll to the bottom of the page to find the small link “history of changes”. Maybe not many visitors will do that.

In contrast to the versions before, now the uploaded data are in line with the study as published, namely, they include a full list of the exclusion criteria and the reduced observation time for QoL, which was the primary outcome. Note: throughout the trial until the end of data assessment those parameters were set with pregnancy as the only exclusion criterion and two years follow up time, only to be amended in the protocol uploaded two months after data collection was complete and analysis presumably was well underway.

In addition, there is a new version of the study protocol, this one dated Feb. 6, 2014. Of course, this protocol is fairly new, in spite of the date it carries. Why would the older version allegedly from January 2011 be uploaded to the register in September 2019, if this more actual version already had existed and was available?

Contrary to the prior version all the clues are removed that would indicate that this document was finished at a much later point in time than given in its date: References to some future software versions that were released years after the protocol was allegedly compiled are dropped. And this strange literature reference “25” that corresponds to the reference list in the final study as published but is pointless in the protocol without any reference list, is removed too. And of course, again contrary to the prior version, the exclusion criteria are identical with the final study as is the shortened follow-up time for QoL.

New to the protocol is a section “Bringing in the patient’s voice”, where the authors disclose how they want to “systematically research the ethical, legal, socio-political, and science theoretical dimensions of homeopathy as in the case of lung cancer (non-small-cell lung carcinoma) exemplified” in some “integral social scientific study”, where some “focus groups” of 4 to 10 participants together with their relatives, friends and caregivers included should be used to study “interactions between individuals, collectively shared and uncontested assumptions, and the emergence of collective meaning”.

But from all of this more or less meaningless but very sciency sounding socio-speak, not a single word found its way into the study. Nothing. So it is pointless to try to figure out what the content of this part of the investigation is all about.

Why then was this chapter added? This “integral social scientific study” was to start after the “third or fourth homeopathic treatment” (But why should patients not be included in this “research” from the very first beginning?). Is it perhaps to give some rationale why the follow-up time for QoL was to end after the third homeopathic treatment?

So what we see, when we look up the study at ClinicalTrials now, is a perfectly matching set of data and a protocol that corresponds to the study as published and looks as if it was published at a time where the trial was underway and the patients were still blinded. If you do not look very closely everything now appears to be perfect.

And here we would like to forward some critique to the register: The purpose of the study register is to prevent not only publication bias but misleading manipulation from happening as well. They do quite a good job in preserving former versions of data and documents and keeping them available to the public. Many national study registers do not offer this service. But you must be of a suspicious mind and of some persistence to actively search and find and check the history of modifications. Thus, a cover-up like the one we are witnessing here might well prove successful. We, therefore, propose to improve the presentation of the registration: If vital amendments occurred that may affect the outcomes – such as protocol changes, extensions of exclusion criteria, modifications of follow-up time – this should be indicated upfront in the study’s record instead of some small hint to “history of changes” at the very bottom of the page.

In conclusion, there appears to be no proof that the results of the study were produced using rigorous scientific methods. And the issues we raised in our report to the authors remain unresolved.

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