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

study design

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When tested rigorously, the evidence for so-called alternatives medicine (SCAM) is usually weak or even negative. This fact has prompted many SCAM enthusiasts to become utterly disenchanted with rigorous tests such as the randomised clinical trial (RCT). They seem to think that, if the RCT fails to generate the findings we want, let’s use different methodologies instead. In other words, they are in favour of observational studies which often yield positive results.

This line of thinking is prevalent in all forms of SCAM, but probably nowhere more so that in the realm of homeopathy. Homeopaths see that rigorous RCTs tend not to confirm their belief and, to avoid cognitive dissonance, they focus on observational studies which are much more likely to confirm their belief.

In this context, it is worth mentioning a recent article where well-known homeopathy enthusiasts have addressed the issue of observational studies. Here is their abstract:

Background: Randomized placebo-controlled trials are considered to be the gold standard in clinical research and have the highest importance in the hierarchical system of evidence-based medicine. However, from the viewpoint of decision makers, due to lower external validity, practical results of efficacy research are often not in line with the huge investments made over decades.

Method: We conducted a narrative review. With a special focus on homeopathy, we give an overview on cohort, comparative cohort, case-control and cross-sectional study designs and explain guidelines and tools that help to improve the quality of observational studies, such as the STROBE Statement, RECORD, GRACE and ENCePP Guide.

Results: Within the conventional medical research field, two types of arguments have been employed in favor of observational studies. First, observational studies allow for a more generalizable and robust estimation of effects in clinical practice, and if cohorts are large enough, there is no over-estimation of effect sizes, as is often feared. We argue that observational research is needed to balance the current over-emphasis on internal validity at the expense of external validity. Thus, observational research can be considered an important research tool to describe “real-world” care settings and can assist with the design and inform the results of randomised controlled trails.

Conclusions: We present recommendations for designing, conducting and reporting observational studies in homeopathy and provide recommendations to complement the STROBE Statement for homeopathic observational studies.

In their paper, the authors state this:

It is important to realize three areas where observational research can be valuable. For one, as already mentioned, it can be valuable as a preparatory type of research for designing good randomized studies. Second, it can be valuable as a stand-alone type of research, where pragmatic or ethical reasons stand against conducting a randomized study. Additionally, it can be valuable as the only adequate method where choices are involved: for instance, in any type of lifestyle research or where patients have very strong preferences, such as in homeopathy and other CAM. This might also lead to a diversification of research efforts and a broader, more realistic, picture of the effects of therapeutic interventions.

My comments to this are as follows:

  1. Observational research can be valuable as a preparatory type of research for designing good randomized studies. This purpose is better fulfilled by pilot studies (which are often abused in SCAM).
  2. Observational research can be valuable as a stand-alone type of research, where pragmatic or ethical reasons stand against conducting a randomized study. Such situations rarely arise in the realm of SCAM.
  3. Observational research can be valuable as the only adequate method where choices are involved: for instance, in any type of lifestyle research or where patients have very strong preferences, such as in homeopathy and other CAM. I fail to see that this is true.
  4. Observational research leads to a diversification of research efforts and a broader, more realistic, picture of the effects of therapeutic interventions. The main aim of research into the effectiveness of SCAM should be, in my view, to determine whether the treatment per se works or not. Observational studies are likely to obscure the truth on this issue.

Don’t get me wrong, I am not saying that observational studies are useless; quite to the contrary, they can provide very important information. But what I am trying to express is this:

  • We should not allow double standards in medical research. The standards and issues of observational research as they exist in conventional medicine must also apply to SCAM.
  • Observational studies cannot easily determine cause and effect between the therapy and the outcome.
  • Observational studies cannot be a substitute for RCTs.
  • Depending on their exact design, observational studies measure the outcome caused by a whole range of factors, including the therapy per se, the placebo-effect, the natural history of the disease, the regression towards the mean.
  • Observational studies are particularly useful in effectiveness research, AFTER the efficacy of a therapy has been established by RCTs.
  • If RCT fail to show that a therapy is effective and observational studies seem to indicate that they work, the therapy in question is probably a placebo.
  • SCAM-enthusiasts’ preference for observational studies is transparently due to motivated reasoning.

Am I the only one who is tired of hearing that, in India, homeopathy is doing wonders for the current pandemic? All of the reports that I have seen are based on little more than hearsay, anecdotes or pseudo-science. If anyone really wanted to find out whether homeopathy works, they would need more than that; in fact, they would need to conduct a clinical trial.

But wait!

As it happens, there are already ~500 clinical trials of homeopathy. Many show positive effects, but the reliable ones usually don’t. Crucially, the totality of the evidence fails to be positive. So, running further studies is hardly a promising exercise. In fact, considering how utterly implausible homeopathy is, it even seems like an unethical waste of resources.

But many homeopaths disagree, particularly those in India. And it has been reported that several trials have been given the go-ahead in India and are now up and running. This regrettable fact is being heavily exploited for swaying public opinion in favour of homeopathy. The way I see it, the situation is roughly this:

  • a few trials of homeopathy are being set up;
  • they are designed by enthusiasts of homeopathy who lack research expertise;
  • therefore their methodology is weak and biased towards generating a false-positive result;
  • while this is going on, the homeopathic propaganda machine is running overtime;
  • when the results will finally emerge, they will get published in a 3rd rate journal;
  • homeopaths worldwide will celebrate them as a triumph for homeopathy;
  • critical thinkers will be dismayed at their quality and will declare that the conclusions drawn by over-enthusiastic homeopaths are not valid;
  • in the end, we will be exactly where we were before: quasi-religious believers in homeopathy will feel vexed because their findings are not accepted in science, and everyone else will be baffled by the waste of time, opportunity and resources as well as by the tenacity of homeopaths to make fools of themselves.

But criticising is easy; doing it properly is often more difficult.

So, how should it be done?

The way I see it, one should do the following:

  • carefully consider the implausibility of homeopathy;
  • thoroughly study the existing evidence on homeopathy;
  • abandon all plans to study homeopathy in the light of the above.

But this hardly is inconceivable considering the current situation in India. If further studies of homeopathy are unavoidable, the following procedure might therefore be reasonable:

  1. assemble a team of experts including trial methodologists, statisticians, epidemiologists and homeopaths;
  2. ask them to design a rigorous protocol of one or two studies that would provide a definitive answer to the research question posed;
  3. make sure that, once everyone is happy with the protocol, all parties commit to abiding by the findings that will emerge from these trials;
  4. conduct the studies under adequately strict supervision;
  5. evaluate the results according to the protocol;
  6. publish them in a top journal;
  7. do the usual press-releases, interviews etc.

In India, it seems that the last point in this agenda came far too early. This is because, in this and several other countries, homeopathy has become more a belief system than a medicine. And because it is about belief, the believers will avert any truly meaningful and rigorous test of homeopathy’s efficacy.

 

 

This was essentially the question raised in a correspondence with a sceptic friend. His suspicion was that statistical methods might produce false-positive overall findings, if the research is done by enthusiasts of the so-called alternative medicine (SCAM) in question (or other areas of inquiry which I will omit because they are outside my area of expertise). Consciously or inadvertently, such researchers might introduce a pro-SCAM bias into their work. As the research is done mostly by such enthusiasts; the totality of the evidence would turn out to be heavily skewed in favour of the SCAM under investigation. The end-result would then be a false-positive overall impression about the SCAM which is less based on reality than on the wishful thinking of the investigators.

How can one deal with this problem?

How to minimise the risk of being overwhelmed by false-positive research?

Today, we have several mechanisms and initiatives that are at least partly aimed at achieving just this. For instance, there are guidelines on how to conduct the primary research so that bias is minimised. The CONSORT statements are an example. As many studies pre-date CONSORT, we need a different approach for reviews of clinical trials. The PRISMA guideline or the COCHRANE handbook are attempts to make sure systematic reviews are transparent and rigorous. These methods can work quite well in finding the truth, but one needs to be aware, of course, that some researchers do their very best to obscure it. I have also tried to go one step further and shown that the direction of the conclusion correlates with the rigour of the study (btw: this was the paper that prompted Prof Hahn’s criticism and slander of my work and person).

So, problem sorted?

Not quite!

The trouble is that over-enthusiastic researchers may not always adhere to these guidelines, they may pretend to adhere but cut corners, or they may be dishonest and cheat. And what makes this even more tricky is the possibility that they do all this inadvertently; their enthusiasm could get the better of them, and they are doing research not to TEST WHETHER a treatment works but to PROVE THAT it works.

In the realm of SCAM we have a lot of this – trust me, I have seen it often with my own eyes, regrettably sometimes even within my own team of co-workers. The reason for this is that SCAM is loaded with emotion and quasi-religious beliefs; and these provide a much stronger conflict of interest than money could ever do, in my experience.

And how might we tackle this thorny issue?

After thinking long and hard about it, I came up in 2012 with my TRUSTWORTHYNESS INDEX:

If we calculated the percentage of a researcher’s papers arriving at positive conclusions and divided this by the percentage of his papers drawing negative conclusions, we might have a useful measure. A realistic example might be the case of a clinical researcher who has published a total of 100 original articles. If 50% had positive and 50% negative conclusions about the efficacy of the therapy tested, his TI would be 1.

Depending on what area of clinical medicine this person is working in, 1 might be a figure that is just about acceptable in terms of the trustworthiness of the author. If the TI goes beyond 1, we might get concerned; if it reaches 4 or more, we should get worried.

An example would be a researcher who has published 100 papers of which 80 are positive and 20 arrive at negative conclusions. His TI would consequently amount to 4. Most of us equipped with a healthy scepticism would consider this figure highly suspect.

Of course, this is all a bit simplistic, and, like all other citation metrics, my TI provides us not with any level of proof; it merely is a vague indicator that something might be amiss. And, as stressed already, the cut-off point for any scientist’s TI very much depends on the area of clinical research we are dealing with. The lower the plausibility and the higher the uncertainty associated with the efficacy of the experimental treatments, the lower the point where the TI might suggest  something  to be fishy.

Based on this concept, I later created the ALTERNATIVE MEDICINE HALL OF FAME. This is a list of researchers who manage to go through life researching their particular SCAM without ever publishing a negative conclusion about it. In terms of TI, these people have astronomically high values. The current list is not yet long, but it is growing:

John Weeks (editor of JCAM)

Deepak Chopra (US entrepreneur)

Cheryl Hawk (US chiropractor)

David Peters (osteopathy, homeopathy, UK)

Nicola Robinson (TCM, UK)

Peter Fisher (homeopathy, UK)

Simon Mills (herbal medicine, UK)

Gustav Dobos (various, Germany)

Claudia Witt (homeopathy, Germany and Switzerland)

George Lewith (acupuncture, UK)

John Licciardone (osteopathy, US)

The logical consequence of a high TI would be that researchers of that nature are banned from obtaining research funds and publishing papers, because their contribution is merely to confuse us and make science less reliable.

I am sure there are other ways of addressing the problem of being mislead by false-positive research. If you can think of one, I’d be pleased to hear about it.

 

Bach-Flower Remedies (BFRs) are often confused with homeopathics. Like them, they contain no active molecule; unlike them, they are not potentised nor used according to the ‘like cures like’ assumption. Both have in common that they are as popular as implausible.

Few studies have tested BFRs; my own systematic review of controlled clinical trials was published in 2010:

Bach flower remedies continue to be popular and its proponents make a range of medicinal claims for them. The aim of this systematic review was to critically evaluate the evidence for these claims. Five electronic databases were searched without restrictions on time or language. All randomised clinical trials of flower remedies were included. Seven such studies were located. All but one were placebo-controlled. All placebo-controlled trials failed to demonstrate efficacy. It is concluded that the most reliable clinical trials do not show any differences between flower remedies and placebos.

Now a new study has emerged. This trial from the Department of Pedodontics and Preventive Dentistry, DY Patil University – School of Dentistry, Navi Mumbai, Maharashtra, India, compared the effects of Bach Flower Therapy (BFT) and music therapy (MT) on the dental anxiety in paediatric patients. A total of 120 children (aged 4-6 years) were selected and randomly allocated to one of three groups:

  • BFT group: Children from this group were administered orally four drops of “rescue remedy” diluted in 40 mL of water 15 min before the treatment. Children were asked to wear headphones without playing any music during the dental treatment
  • MT group: Children from this group were provided with a headphone, and Indian classical instrumental music (Raag Sohni played by Pandit Shiv Kumar Sharma on santoor) was played during the scheduled dental treatment. Children were also given 40 mL plain water to drink 15 min before the treatment
  • Control group: Children from this group were given 40 mL plain water 15 min before the treatment. During the treatment, children were asked to wear the headphone without playing any music.

All children received oral prophylaxis and fluoride treatment (no further details provided). Dental anxiety was evaluated using

  • North Carolina Behavior Rating Scale (NCBRS), the primary outcome measure,
  • Facial Image Scale (FIS),
  • and physiological parameters.

Significantly better behaviour was seen in children from the BFT group as compared to the control group (P = 0.014). FIS scores measured postoperatively did not show significant differences among the groups.

Table 2: Comparison of North Carolina Behavior Rating Scale scores of child's behavior measured during the dental procedure between the three groups

Table 3: Comparison of postoperative patient-reported dental anxiety as measured by Facial Image Scale among the three groups

Children from the BFT and MT groups showed a significant decrease in the pulse rates intraoperatively from the preoperative period. Intraoperative systolic blood pressure in children from the MT group was significantly lower than both the BFT and the control groups. Diastolic blood pressure significantly increased in the control group intra-operatively, whereas other groups showed a decrease.

The authors concluded that the results of this study demonstrate significant effects of both single dose of BFT and exposure to MT, on reduction of dental anxiety in children aged between 4 and 6 years.

I find these findings most puzzling (like all BFRs, Rescue Remedies do not contain a single active molecule that could explain them) and strongly recommend that we wait until we have an independent replication before accepting these results as trustworthy.

Dr. Dhanunjaya Lakkireddy, a cardiologist at the Kansas City Heart Rhythm Institute in the US, has started a trial of prayer for corona-virus infection. The study will involve  1000 patients with COVID-19 infections severe enough to require intensive care. The four-month study will investigate “the role of remote intercessory multi-denominational prayer on clinical outcomes in COVID-19 patients,” according to a description provided to the National Institutes of Health.

Inclusion Criteria:

  • Male or female greater than 18 years of age
  • Confirmed positive for COVID-19
  • Patient admitted to Intensive Care Unit

Exclusion Criteria:

  • Patients admitted to ICU for diagnosis that is not COVID-19 positive

(Not giving informed consent is not listed as an exclusion criterion!)

Half of the patients, randomly chosen, will receive a “universal” prayer offered in five denominational forms, via:

  • Buddhism,
  • Christianity,
  • Hinduism,
  • Islam,
  • Judaism.

The other 500 patients in the control group will not be prayed for by the prayer group. All the patients will receive the standard care prescribed by their medical providers. “We all believe in science, and we also believe in faith,” Lakkireddy claims. “If there is a supernatural power, which a lot of us believe, would that power of prayer and divine intervention change the outcomes in a concerted fashion? That was our question.”

The outcome measures in the trial are

  • the time patients remain on ventilators,
  • the number of patients who suffer from organ failure,
  • the time patients have to stay in intensive care,
  • the mortality rate.

On this blog, we have seen many other ‘corona-quacks’ come forward with their weird ideas. I ask myself why we give them not the opportunity to test their concepts as well? Why do we not spend our resources testing:

In my recent book, I included a short review of the literature on prayer as a medical intervention. This is what I wrote:

  1. Prayer can be defined as the solemn request or thanksgiving to God or other object of worship.
  2. Intercessory prayer is practised by people of all faiths and involves a person or group setting aside time for petitioning god on behalf of another person who is in need. Intercessory prayer is organised, regular, and committed. Those who practise it usually do not ask for payments because they hold a committed belief.
  3. The mechanisms by which prayer might work therapeutically are unknown, and hypotheses about its mode of action will depend to a large extent on the religious beliefs in question. People who believe in the possibility that prayers might improve their health assume that god could intervene on their behalf by blessing them with healing energy.
  4. These assumptions lack scientific plausibility.
  5. Numerous clinical trials have been conducted. Most of them fail to adequately control for bias, and their findings are not uniform.
  6. A systematic review of all these studies is available. It included 10 trials with a total of 7646 patients. The authors concluded that the findings are equivocal and, although some of the results of individual studies suggest a positive effect of intercessory prayer, the majority do not and the evidence does not support a recommendation either in favour or against the use of intercessory prayer. We are not convinced that further trials of this intervention should be undertaken and would prefer to see any resources available for such a trial used to investigate other questions in health care.[1]

[1] https://www.ncbi.nlm.nih.gov/pubmed/19370557

Lakkireddy says he has no idea what he will find. “But it’s not like we’re putting anyone at risk,” he says. “A miracle could happen. There’s always hope, right?”

Personally, I have a pretty good idea what he will find. I also find Lakkireddy not all that honest and think his assumptions are deeply mistaken:

  • Lakkireddy cites an extensive list of references; however, the Cochrane review (usually the most reliable and independent source of evidence) that arrived to the conclusions I quoted above, he somehow ‘forgot’ to mention.
  • As the review-authors tried to indicate, further trials of prayer are a waste of resources.
  • There are many much more promising interventions to be tested, and by conducting this study, he is diverting research funds that are badly needed elsewhere.
  • The study seems to have several ethical problems, e.g. informed consent.
  • Contrary to Lakkireddy’s belief, he will harm in more than one way; apart from wasting resources, his study undermines rational thought and public trust in clinical research.

PERSONALLY, I FIND THIS PROJECT DESPICABLE!

This study investigated the effects of reflexology and homeopathy as an addition to conventional treatment on different markers of airway inflammation in asthma. Eighty-four patients with asthma were randomized to receive one to three different treatments:

  1. conventional treatment alone,
  2. conventional treatment with addition of homeopathy,
  3. conventional treatment plus reflexology.

The study was a single centre, investigator-blinded, controlled trial with a treatment period of one year.

During the study period, patients regularly consulted their general practitioner for evaluation and asthma treatment. At randomization, and after 6 and 12 months, methacholine challenge test and measurement of exhaled nitric oxide were performed. Blood samples were collected for eosinophil count and measurement of serum eosinophil cationic protein.

No significant differences were found between groups for any of the inflammatory markers were demonstrated. Methacholine responsiveness improved in all three groups but improvements were not statistically significant within and between groups.

The authors concluded that this randomized controlled study of reflexology and homeopathy failed to show significant improvement on selected markers of inflammation and airway hyperresponsiveness in asthma.

I would argue that the results imply that homeopathy and reflexology are not merely ineffective but have negative effects on the outcome. As this trial followed the infamous ‘A+B versus B’ design, one would have expected that the two add on treatments generate a placebo response – at least in terms of subjective endpoints. The only such measure is the medication use in this particular trial; it showed no inter-group differences. To me, this implies that homeopathy and reflexology might have generated slightly detrimental effects on subjective outcomes.

Ah yes, do I hear the fans of so-called alternative medicine (SCAM) claim that this study must have been conducted by the enemies of SCAM in order to defame it? For them, this acknowledgement might be enlightening:

This study was supported by The Knowledge and Research Centre for Alternative Medicine, Denmark. The authors thank registered homeopath Anne Hammer Langgaard for homeopathic treatments, registered reflexologists Pia Løbner Jeppesen and Pia Stolarzcyk for reflexology treatments, Pia Pedersen for secretarial assistance and randomization procedure, laboratory technician Anne-Marie Toft for handling blood samples, specialist nurses Anne Dorte Vindelev Kristensen and Jytte Møller Kjemtrup for help with clinical procedures.

Wouldn’t it be wonderful, if we had a treatment that reduces the risk of getting infected with the corona-virus? Well, this paper claims that there is one. Here is its abstract:

Since December 2019, an outbreak of corona virus disease 2019 (COVID-19) occurred in Wuhan, and rapidly spread to almost all parts of China. This was followed by prevention programs recommending Chinese medicine (CM) for the prevention. In order to provide evidence for CM recommendations, we reviewed ancient classics and human studies.

Methods

Historical records on prevention and treatment of infections in CM classics, clinical evidence of CM on the prevention of severe acute respiratory syndrome (SARS) and H1N1 influenza, and CM prevention programs issued by health authorities in China since the COVID-19 outbreak were retrieved from different databases and websites till 12 February, 2020. Research evidence included data from clinical trials, cohort or other population studies using CM for preventing contagious respiratory virus diseases.

Results

The use of CM to prevent epidemics of infectious diseases was traced back to ancient Chinese practice cited in Huangdi’s Internal Classic (Huang Di Nei Jing) where preventive effects were recorded. There were 3 studies using CM for prevention of SARS and 4 studies for H1N1 influenza. None of the participants who took CM contracted SARS in the 3 studies. The infection rate of H1N1 influenza in the CM group was significantly lower than the non-CM group (relative risk 0.36, 95% confidence interval 0.24–0.52; n=4). For prevention of COVID-19, 23 provinces in China issued CM programs. The main principles of CM use were to tonify qi to protect from external pathogens, disperse wind and discharge heat, and resolve dampness. The most frequently used herbs included Radix astragali (Huangqi), Radix glycyrrhizae (Gancao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), and Fructus forsythia (Lianqiao).

Conclusions

Based on historical records and human evidence of SARS and H1N1 influenza prevention, Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population. Prospective, rigorous population studies are warranted to confirm the potential preventive effect of CM.

So, what should we make of this conclusion?

To provide an evidence-based answer, I tried to look up the original studies cited in the article. The links provided by the authors seem to be all dead except one which leads to a paper published in the infamous JCAM. Here is its abstract:

Objectives: To investigate the efficacy of an herbal formula in the prevention of severe acute respiratory syndrome (SARS) transmission among health care workers. The secondary objectives are to investigate quality of life (QOL) and symptomology changes among supplement users, and to evaluate the safety of this formula.

Design: Controlled clinical trial.

Settings: Hong Kong during epidemic of SARS.

Subjects: Two cohorts of health care workers from 11 hospitals in Hong Kong, 1 using an herbal supplement for a 2-week period (n = 1063) and a control cohort comprising all other health care workers who did not receive the supplement (n = 36,111) were compared prospectively.

Interventions: Taking an herbal supplement for a 2-week period.

Outcome measures: SARS attack rates and changes in quality of life and influenza-like symptoms were also examined at three timepoints among herbal supplement users.

Results: None of the health care workers who used the supplement subsequently contracted SARS compared to 0.4% of the health care workers who did not use the supplement (p = 0.014). Improvements in influenza-like symptoms and quality of life measurements were also observed among herbal supplement users. Less than 2% reported minor adverse events.

Conclusion: The results of this pilot study suggest that there is a good potential of using Traditional Chinese Medicine (TCM) supplements to prevent the spread of SARS.

How can I be polite and still say what I think about this article? Perhaps by stating this: THIS STUDY WAS INCAPABLE OF INVESTIGATING THE ‘EFFICACY’ OF ANYTHING AND ITS RESULTS ARE NOT CONVINCING.

So, are the Chinese authors correct when concluding that Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population?

No, I don’t think so! And I even feel that it is irresponsible in the current situation to misguide consumers, patients, scientists and decision-makers into believing that TCM offers an answer to the pandemic.

 

Resveratrol is one of the most popular dietary supplements. It is an antioxidant found in red grape skin, Japanese knotweed, blueberries and other berries. Resveratrol is available as dietary supplements from red wine extracts, grape seed extracts, Japanese knotweed extracts and other plants. The amount and purity of resveratrol in supplements varies significantly; absorption in the gut is low.

While, for many supplements, there is no or very little research, this one has a huge amount. So, has reseveratrol any proven health effects demonstrated in clinical trials?

The answer is encouraging.

This abstract provides a useful summary:

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented in over 244 clinical trials, with an additional 27 clinical trials currently ongoing. Resveretrol is reported to potentially improve the therapeutic outcome in patients suffering from diabetes mellitus, obesity, colorectal cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Alzheimer’s disease, stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The polyphenol is reported to be safe at doses up to 5 g/d, when used either alone or as a combination therapy. The molecular basis for the pleiotropic activities of resveratrol are based on its ability to modulate multiple cell signaling molecules such as cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5′-AMP-activated protein kinase, intercellular adhesion molecule, vascular cell adhesion molecule, sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor 1, insulin-like growth factor-binding protein 3, Ras association domain family 1α, pAkt, vascular endothelial growth factor, cyclooxygenase 2, nuclear factor erythroid 2 like 2, and Kelch-like ECH-associated protein 1. Although the clinical utility of resveratrol is well documented, the rapid metabolism and poor bioavailability have limited its therapeutic use. In this regard, the recently produced micronized resveratrol formulation called SRT501, shows promise. This review discusses the currently available clinical data on resveratrol in the prevention, management, and treatment of various diseases and disorders. Based on the current evidence, the potential utility of this molecule in the clinic is discussed.

This is a comprehensive review but it fails to critically assess the quality of the clinical trials. Once we do that, we are likely to get disappointed. Many studies are just not up to the mark.

And if we consult a Cochrane review, our enthusiasm for resveratrol disappears completely: Currently, research is insufficient for review authors to evaluate the safety and efficacy of resveratrol supplementation for treatment of adults with T2DM [type 2 diabetes mellitus]. The limited available research does not provide sufficient evidence to support any effect, beneficial or adverse, of four to five weeks of 10 mg to 1000 mg of resveratrol in adults with T2DM. Adequately powered RCTs reporting patient-relevant outcomes with long-term follow-up periods are needed to further evaluate the efficacy and safety of resveratrol supplementation in the treatment of T2DM.

So, for the time being, I might just continue to obtain my resveratrol in very small but regular doses from red wine, I think.

 

 

During the last 30 years, I must have read a few thousand studies of so-called alternative medicine (SCAM). Some made me angry because of their methodological flaws or wrong conclusions. A few impressed me. Many made me giggle. But none has ever caused me to laugh out so long as this one entitled ‘A STUDY ON THE PROPHYLACTIC EFFICACY OF HOMOEOPATHIC PREVENTIVE’.

Here is its abstract:

Homoeopathy has established its supremacy in the control of infectious viral diseases. The widespread acclaim in this regard is now supported by this study. The study was conducted in the Chikungunya fever hit areas of Kerala. The genus epidemicus was selected after detailed analysis of the first cases of Chikungunya. This preventive medicine was widely distributed in the disease prevalent areas. A survey was conducted for the evaluation of prophylactic efficacy. The study showed a very high significant effect of Homeopathic medicine in the prevention of Chikungunya fever.

You are, of course, correct to defend the Indian authors: it is unfair to judge a study purely on its abstract. So, let’s have a look at the rest. After a lengthy introduction, the heart of the full paper discloses the amazing details of the study.

Here I present the unabridged text of the study; the only part I have omitted is the introduction:

Aims and Objectives

1. To assess the efficacy of Homoeopathic medicine in the prevention of Chikungunya.
2. To determine the magnitude of incidence, clinical features, mortality , social & economic impact of the Chikungunya epidemic.

Conclusion

The Homoeopathic preventive medicine distributed for Chikungunya epidemic was highly effective.

THAT’S ALL!

The objective of this analysis was to evaluate the impact of chiropractic utilization upon use of prescription opioids among patients with spinal pain. The researchers employed a retrospective cohort design for analysis of health claims data from three contiguous US states for the years 2012-2017.

They included adults aged 18-84 years enrolled in a health plan and with office visits to a primary care physician or chiropractor for spinal pain. Two cohorts of subjects were thus identified:

  1. patients who received both primary care and chiropractic care,
  2. Patients who received primary care but not chiropractic care.

The total number of subjects was 101,221. Overall, between 1.55 and 2.03 times more nonrecipients of chiropractic care filled an opioid prescription, as compared with recipients.

The authors concluded that patients with spinal pain who saw a chiropractor had half the risk of filling an opioid prescription. Among those who saw a chiropractor within 30 days of diagnosis, the reduction in risk was greater as compared with those with their first visit after the acute phase.

Similar findings have been reported before and we have discussed them on this blog (see here, here and here). As before, one has to ask: WHAT DO THEY ACTUALLY MEAN?

The short answer is NOTHING MUCH! And certainly not what many chiros make of them.

They do not suggest that chiropractic care is a substitute for opioids in the management of spinal pain.

Why?

There are several reasons. Perhaps the most important ones are that such analyses lack any clinical outcome data, and that comparing one mistake (opioid-overuse) whith what might be another (chiropractic care) is a wrong apporoach. Imagine a scenario where half to the patients had received, in addition to their usual care, the services of:

  • a paranormal healer,
  • a crystal therapist,
  • a shaman,
  • or a homeopath.

Nobody would be surprised to see a very similar result, particularly if all of these practitioners were in the habit of discouraging their patients from using conventional drugs. Or imagine a scenario where half of all patients suffering from spinal pain are entered into an environment where they receive no treatment at all. Who would not expect that this regimen does not dramatically reduce the risk of filling an opioid prescription? But would that indicate that zero treatment is a good solution for managing spinal pain?

The thing is this:

  • If you want to reduce opioid use, you need to prescribe less opioids (for instance, by re-educating doctors to do as they have been told in med school and curb over-prescribing).
  • If you discourage patients to use opioids (as many other healthcare professionals would), many will not use opioids.
  • If you want to know whether chiropractic is effective in managing spinal pain, you need to conduct a well-designed clinical trial.

Or, to put it simply:

CORRELATION IS NOT CAUSATION!

 

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